1 00:00:05,080 --> 00:00:08,480 >> GOOD MORNING, EVERYBODY. 2 00:00:08,480 --> 00:00:11,560 THIS IS DAY 3 OF OUR ANNUAL 3 00:00:11,560 --> 00:00:12,600 SICKLE CELL DEC MEETING AND 4 00:00:12,600 --> 00:00:12,840 WELCOME. 5 00:00:12,840 --> 00:00:18,840 WE HAVE A FULL DAY AND MOST OF 6 00:00:18,840 --> 00:00:20,520 THE TOPICS TODAY WILL BE RELATED 7 00:00:20,520 --> 00:00:23,280 TO SICKLE CELL PAIN, A VERY 8 00:00:23,280 --> 00:00:24,400 IMPORTANT COMPONENT OF SICKLE 9 00:00:24,400 --> 00:00:24,920 CELL DISEASE. 10 00:00:24,920 --> 00:00:31,160 SO BEFORE WE GET STARTED I WILL 11 00:00:31,160 --> 00:00:37,160 LET ALEXANDRA GIVE YOU A LITTLE 12 00:00:37,160 --> 00:00:37,880 LOGISTICS COMPONENTS OF 13 00:00:37,880 --> 00:00:41,120 HOUSEKEEPING SLIDE AND THEN WE 14 00:00:41,120 --> 00:00:43,320 WILL GET STARTED. 15 00:00:43,320 --> 00:00:43,520 ALEX? 16 00:00:43,520 --> 00:00:46,760 >> GOOD MORPING AND WELCOME TO 17 00:00:46,760 --> 00:00:49,320 DAY 3 I WANT TO LET YOU ALL KNOW 18 00:00:49,320 --> 00:00:50,800 WE ARE RECORDING THE MEETING. 19 00:00:50,800 --> 00:00:52,760 DAYS WOB AND 2 HAVE BEEN 20 00:00:52,760 --> 00:00:53,440 RECORDED AS WELL. 21 00:00:53,440 --> 00:00:55,360 WE DO HOPE THAT ATTENDEES WILL 22 00:00:55,360 --> 00:00:57,080 INTERACT WITH THE SPEAKERS. 23 00:00:57,080 --> 00:00:59,320 WE ASK STEANDEES TO INPUT YOUR 24 00:00:59,320 --> 00:01:01,360 QUESTIONS INTO THE Q&A CHAT 25 00:01:01,360 --> 00:01:02,640 WHICH IS LOCATED AT THE BOTTOM 26 00:01:02,640 --> 00:01:06,520 OF YOUR SCREEN AND IF YOU HAVE 27 00:01:06,520 --> 00:01:07,640 ANY SIDE CONVERSATIONS, LET'S 28 00:01:07,640 --> 00:01:09,360 PUT THOSE IN THE CHAT BOX. 29 00:01:09,360 --> 00:01:11,360 ONCE AGAIN, WE ARE RECORDING 30 00:01:11,360 --> 00:01:12,280 THIS. 31 00:01:12,280 --> 00:01:14,200 IF YOU DO NEED LIVE CAPTIONS, IT 32 00:01:14,200 --> 00:01:17,160 IS AVAILABLE AT THE BOTTOM, 33 00:01:17,160 --> 00:01:21,560 PLEASE CLICK LIVE CAPTIONS AND 34 00:01:21,560 --> 00:01:23,320 THEN SHOW SUBSCRIPT. 35 00:01:23,320 --> 00:01:25,960 ONCE AGAIN WE ARE NEEDING ALL 36 00:01:25,960 --> 00:01:27,600 ATTENDEES, TURNING OFF CAMERAS 37 00:01:27,600 --> 00:01:29,560 AND FOR ANY REASON, IT CHANGES 38 00:01:29,560 --> 00:01:30,960 PLEASE TURN OFF YOUR CAMERAS IN 39 00:01:30,960 --> 00:01:32,520 THE MAIN MEETING THROUGHOUT THE 40 00:01:32,520 --> 00:01:32,760 MEETING. 41 00:01:32,760 --> 00:01:34,120 ONCE AGAIN, WE HOPE YOU ALL 42 00:01:34,120 --> 00:01:36,720 ENJOY DAY 3 AND THANK YOU FOR 43 00:01:36,720 --> 00:01:39,640 JOINING US FOR THE LAST 2 DAYS. 44 00:01:39,640 --> 00:01:46,600 WITH THAT, I WILL PASS IT BACK. 45 00:01:46,600 --> 00:01:49,760 >> THANK YOU, ALEX. 46 00:01:49,760 --> 00:01:58,920 OKAY SO WE HAVE IS DR. DAYSAI, 47 00:01:58,920 --> 00:01:59,400 ARE YOU ON? 48 00:01:59,400 --> 00:02:01,040 >> I AM THANK YOU. 49 00:02:01,040 --> 00:02:02,160 >> I WAS TOLD YOU ARE 50 00:02:02,160 --> 00:02:03,720 INTRODUCING THE CHAIRS SO I WILL 51 00:02:03,720 --> 00:02:06,640 LET YOU DO THE HONORS AND LET'S 52 00:02:06,640 --> 00:02:08,520 GET STARTED WITH FIRST COMPONENT 53 00:02:08,520 --> 00:02:12,360 OF SYMPOSIUM 5 WHICH IS 54 00:02:12,360 --> 00:02:13,560 MULTIDISCIPLINARY AND 55 00:02:13,560 --> 00:02:16,840 ALTERNATIVE CHRONIC PAIN 56 00:02:16,840 --> 00:02:17,160 MANAGEMENT. 57 00:02:17,160 --> 00:02:17,760 >> GOOD, MORNING EVERYONE AND 58 00:02:17,760 --> 00:02:18,760 THANK YOU SO MUCH. 59 00:02:18,760 --> 00:02:22,640 I WANTED TO INTRODUCE OUR 60 00:02:22,640 --> 00:02:26,120 DISTINGUISHED PANELISTS, 61 00:02:26,120 --> 00:02:28,760 DR. JJ STROUSE, AND DR. JULIE 62 00:02:28,760 --> 00:02:29,960 KANTER, WHO WILL LEAD THIS 63 00:02:29,960 --> 00:02:30,760 DISCUSSION FOR US TODAY. 64 00:02:30,760 --> 00:02:32,240 I WANT TO THANK THEM FOR COMING 65 00:02:32,240 --> 00:02:34,360 ITTH WITH THIS FANTASTIC 66 00:02:34,360 --> 00:02:36,480 PRESENTATION AND THAT IS VERY 67 00:02:36,480 --> 00:02:37,360 TIMLY ON MULTIDISCIPLINARY 68 00:02:37,360 --> 00:02:41,360 APPROACHES TO PAIN AND I ALSO 69 00:02:41,360 --> 00:02:42,880 WANTED TO MENTION THAT I'M 70 00:02:42,880 --> 00:02:45,920 INTRODUCING THEM AS PRESIDENT OF 71 00:02:45,920 --> 00:02:47,920 SICKLE CELL ADULT PROVIDER 72 00:02:47,920 --> 00:02:49,440 NETWORK, DR. KANTER IS THE HEAD 73 00:02:49,440 --> 00:02:51,160 OF NATIONAL ALLIANCE OF SICKLE 74 00:02:51,160 --> 00:02:52,160 CELL CENTERS AND THIS IS THE 75 00:02:52,160 --> 00:02:54,960 FIRST I HOPE OF VERY MANY 76 00:02:54,960 --> 00:02:55,880 PARTNERSHIPS OF US COMING 77 00:02:55,880 --> 00:02:58,560 TOGETHER AS I GROUP WORKING ON 78 00:02:58,560 --> 00:03:00,040 SICKLE CELL TLGT BOTH ON THE 79 00:03:00,040 --> 00:03:01,480 EDUCATION PIECE AS WELL AS 80 00:03:01,480 --> 00:03:06,240 QUALITY AND ALLIANCE IN TERMS OF 81 00:03:06,240 --> 00:03:06,800 DELIVERING CARE SO THANK YOU 82 00:03:06,800 --> 00:03:07,320 VERY MUCH. 83 00:03:07,320 --> 00:03:14,640 AND I WILL HAND IT OVER TO THEM. 84 00:03:14,640 --> 00:03:18,440 SO WE'RE EXCITED TO BE HERE TO 85 00:03:18,440 --> 00:03:20,320 PRESENT SYMPOSIUM 5, 86 00:03:20,320 --> 00:03:21,040 MULTIDISCIPLINARY AND 87 00:03:21,040 --> 00:03:21,720 ALTERNATIVE CHRONIC PAIN 88 00:03:21,720 --> 00:03:22,960 MANAGEMENT FOR ADULTS WITH 89 00:03:22,960 --> 00:03:23,600 SICKLE CELL DISEASE. 90 00:03:23,600 --> 00:03:26,640 AND YOU CAN SEE OUR SIMLE FOR 91 00:03:26,640 --> 00:03:28,440 THE NATIONAL ALLIANCE AND THE 92 00:03:28,440 --> 00:03:29,440 PROVIDER NETWORK, AND I 93 00:03:29,440 --> 00:03:30,880 ENCOURAGE TO YOU REACH OUT TO 94 00:03:30,880 --> 00:03:36,440 ANY OF US, PARTICULARLY KYLE AND 95 00:03:36,440 --> 00:03:37,640 JULIE IF YOU'RE INTERESTED IN 96 00:03:37,640 --> 00:03:38,440 LEARNING MORE. 97 00:03:38,440 --> 00:03:43,520 SO THE NETWORK WAS ESTABLISHED 98 00:03:43,520 --> 00:03:44,880 TO SUPPORT HEALTHCARE PROVIDERS 99 00:03:44,880 --> 00:03:46,960 AND INVESTIGATORS TO SERVE 100 00:03:46,960 --> 00:03:52,240 ADULTS WITH SICKLE CELL DISEASE 101 00:03:52,240 --> 00:03:54,120 AND IT'S REALLY FOR PEDEIAT 102 00:03:54,120 --> 00:03:55,880 PROVIDERS AND WE ALSO WELCOME 103 00:03:55,880 --> 00:03:57,800 FAMILY MEMBERS LIVING WITHIC 104 00:03:57,800 --> 00:03:59,040 ISLELE DISEASE. 105 00:03:59,040 --> 00:04:00,440 THE NATIONAL ASSOCIATION OF 106 00:04:00,440 --> 00:04:01,400 SICKLE CELL CENTERS IS TO 107 00:04:01,400 --> 00:04:03,320 SUPPORT THEM IN DELIVERING HIGH 108 00:04:03,320 --> 00:04:05,880 QUALITY CARE BY THE FOLLOWING, 109 00:04:05,880 --> 00:04:07,280 SETTING AND PROMOTING THE 110 00:04:07,280 --> 00:04:08,560 ADOPTION OF STANDARDS AND WE 111 00:04:08,560 --> 00:04:12,080 RADIO RECENTLY HAD OUR FIRST 112 00:04:12,080 --> 00:04:13,360 CONFERENCE TO DEVELOP STANDARDS 113 00:04:13,360 --> 00:04:15,920 OF CARE, FOR SICKLE CELL 114 00:04:15,920 --> 00:04:16,560 CENTERS, IDENTIFYING 115 00:04:16,560 --> 00:04:17,680 OPPORTUNITIES AND RESOURCES TO 116 00:04:17,680 --> 00:04:19,160 STRENGTHEN SICKLE CELL CENTERS 117 00:04:19,160 --> 00:04:21,160 AND ADVOCATING FOR ACCESS TO 118 00:04:21,160 --> 00:04:22,440 COMPREHENSIVE SICKLE CELL CARE 119 00:04:22,440 --> 00:04:23,680 TO IMPROVE HEALTH OUTCOMES, 120 00:04:23,680 --> 00:04:25,120 QUALITY OF LIFE AND SURVIVAL FOR 121 00:04:25,120 --> 00:04:29,000 ALL PEOPLE WITH SICKLE CELL 122 00:04:29,000 --> 00:04:29,240 DISEASE. 123 00:04:29,240 --> 00:04:32,240 SO WHAT'S THE CHAL ENK OF TODAY. 124 00:04:32,240 --> 00:04:33,440 TODAY WE'RE TALKING ABOUT SICKLE 125 00:04:33,440 --> 00:04:35,560 CELL AND CHRONIC PAIN, I WILL 126 00:04:35,560 --> 00:04:37,640 FOCUS ON MANY OF CHALLENGES. 127 00:04:37,640 --> 00:04:40,960 WE KNOW THAT NEARLY 30% OF 128 00:04:40,960 --> 00:04:42,760 PEOPLE REPORT PAIN ON GREATER 129 00:04:42,760 --> 00:04:45,240 THAN 95% OF DAYS SO THAT MORE 130 00:04:45,240 --> 00:04:46,400 THAN MEETS THE DEFINITION OF 131 00:04:46,400 --> 00:04:47,840 CHRONIC PAIN, WHICH IS PAINOT 132 00:04:47,840 --> 00:04:50,040 MAJORITY OF DAYS OVER A 6 MONTH 133 00:04:50,040 --> 00:04:51,560 PERIOD FOR PEOPLE WITH SICKLE 134 00:04:51,560 --> 00:04:54,280 CELL DISEASE AND THE ASH SICKLE 135 00:04:54,280 --> 00:04:55,320 CELL PAIN GUIDELINES WHICH I WAS 136 00:04:55,320 --> 00:04:57,200 1 OF THE PEOPLE THAT 137 00:04:57,200 --> 00:04:59,400 PARTICIPATED NONAPOPTOTIC THIS 138 00:04:59,400 --> 00:05:00,320 GUIDELINE PANEL SUGGESTED 139 00:05:00,320 --> 00:05:02,440 AGAINST THE INITIATION OF 140 00:05:02,440 --> 00:05:03,520 CHRONIC THERAPY FOR CHRONIC PAIN 141 00:05:03,520 --> 00:05:06,640 UNLESS THE PAIN IS REFRACTORY TO 142 00:05:06,640 --> 00:05:08,160 OTHER MULTIPLE TREATMENT 143 00:05:08,160 --> 00:05:08,440 MODALITIES. 144 00:05:08,440 --> 00:05:09,920 THERE WAS MOW CERTAINTY FOR THAT 145 00:05:09,920 --> 00:05:10,960 SUGGESTION BUT THAT SUGGESTION 146 00:05:10,960 --> 00:05:13,600 WAS MADE AND ALSO TO SUGGEST THE 147 00:05:13,600 --> 00:05:15,440 SHARED DECISION MAKING ABOUT THE 148 00:05:15,440 --> 00:05:17,840 CONTINUATION OF CHRONIC OPIATE 149 00:05:17,840 --> 00:05:18,840 THERAPY FOR THOSE FUNCTIONING 150 00:05:18,840 --> 00:05:20,800 WELL WITH TREATMENT AND 151 00:05:20,800 --> 00:05:21,840 SUGGESTING DISCONTINUATION AND 152 00:05:21,840 --> 00:05:23,480 THOSE FUNCTIONING POORLY OR AT 153 00:05:23,480 --> 00:05:25,320 HIGH RISK FOR OPIATE USE FOR 154 00:05:25,320 --> 00:05:27,000 TOXICITY AND WE SEE THIS IN OUR 155 00:05:27,000 --> 00:05:28,320 PRACTICE, YOU KNOW WHAT TO DO 156 00:05:28,320 --> 00:05:32,880 FOR PATIENTS THAT OPIATES MIGHT 157 00:05:32,880 --> 00:05:35,040 NOT BE A GREAT CHOICE FOR THEIR 158 00:05:35,040 --> 00:05:35,520 CHRONIC PAIN. 159 00:05:35,520 --> 00:05:37,240 WE WILL TALK ABOUT THAT TODAY 160 00:05:37,240 --> 00:05:39,160 ALONG WITH AN EXCELLENT GROUP OF 161 00:05:39,160 --> 00:05:42,240 SPEAKERS AND ALSO A PANEL 162 00:05:42,240 --> 00:05:42,520 DISCUSSION. 163 00:05:42,520 --> 00:05:45,920 SO THESE ARE OUR SPEAKERS, WE 164 00:05:45,920 --> 00:05:47,800 HAVE 4 SPEAKERS ON TOPICS ON 165 00:05:47,800 --> 00:05:50,440 CHRONIC PAIN AND THEN DR. KANTER 166 00:05:50,440 --> 00:05:55,360 AND I WILL SERVE AS MODERATORS 167 00:05:55,360 --> 00:05:59,920 ON A SPEAKER PANEL AND THEN 168 00:05:59,920 --> 00:06:02,840 DR. WILL PROVIDE CLOSING 169 00:06:02,840 --> 00:06:03,600 REMARKS. 170 00:06:03,600 --> 00:06:05,920 AND THEN FOR THE OTHER HALF WE 171 00:06:05,920 --> 00:06:07,600 HAVE SPEAKERS AREYALATED TO 172 00:06:07,600 --> 00:06:09,000 TOPICS IN SICKLE CELL DISEASE 173 00:06:09,000 --> 00:06:10,840 MOSTLY FOCUSED ON PAIN AND THOSE 174 00:06:10,840 --> 00:06:13,360 WILL BE INTRODUCED BY THE 175 00:06:13,360 --> 00:06:14,920 LEADERSHIP OF OUR SYMPOSIUM. 176 00:06:14,920 --> 00:06:17,520 SO WITH THAT, I WANT TO 177 00:06:17,520 --> 00:06:22,960 INTRODUCE OUR FIRST SPEAKER WHO 178 00:06:22,960 --> 00:06:31,960 IS DR. CHARLES JONASSAINT, WHO 179 00:06:31,960 --> 00:06:37,640 IS A ENTHUSIASTIC ADVOCATE FOR 180 00:06:37,640 --> 00:06:39,040 NONPREKRIPGZ PSYCHOLOGY AND 181 00:06:39,040 --> 00:06:40,240 OTHER MIND-BASED APPROACHES FOR 182 00:06:40,240 --> 00:06:40,520 PAIN. 183 00:06:40,520 --> 00:06:42,840 HE WILL ALSO FOCUS ON OTHER 184 00:06:42,840 --> 00:06:46,200 COGNITIVE BEHAVIORIAL THERAPY 185 00:06:46,200 --> 00:06:46,360 AND. 186 00:06:46,360 --> 00:06:47,200 >> THANK YOU VERY MUCH. 187 00:06:47,200 --> 00:06:48,480 I APPRECIATE THE OPPORTUNITY TO 188 00:06:48,480 --> 00:06:51,480 TALK ABOUT THIS, DOING 189 00:06:51,480 --> 00:06:52,200 NONPHARMACOLOGICAL APPROACHES TO 190 00:06:52,200 --> 00:06:54,920 PAIN MANAGEMENT AND SICKLE SEAL 191 00:06:54,920 --> 00:06:55,280 DISEASE. 192 00:06:55,280 --> 00:06:57,640 FIRST I WOULD LIKE TO TALK A BIT 193 00:06:57,640 --> 00:06:58,920 ABOUT BEHAVIORIAL THERAPY IN 194 00:06:58,920 --> 00:07:00,560 SICKLE CELL, I WILL TELL YOU 195 00:07:00,560 --> 00:07:01,920 RIGHT AWAY I DON'T HAVE GREAT 196 00:07:01,920 --> 00:07:04,920 NEWS ABOUT THE EVIDENCE THAT'S 197 00:07:04,920 --> 00:07:06,840 CURRENTLY AVAILABLE BUT 198 00:07:06,840 --> 00:07:08,160 HOPEFULLY, I CREATE EXPECTATIONS 199 00:07:08,160 --> 00:07:09,320 FOR WHAT'S COMING DOWN THE PIPE. 200 00:07:09,320 --> 00:07:11,640 ONE OF THE BIGGEST THINGS IS THE 201 00:07:11,640 --> 00:07:13,440 ENGAGEMENT WITH OUR DIGITAL 202 00:07:13,440 --> 00:07:14,480 INTERVENTIONS, WE THINK THAT 203 00:07:14,480 --> 00:07:18,840 UPON DIGITAL MIGHT BE THE WAY TO 204 00:07:18,840 --> 00:07:20,640 EXPAND OR SCALE BEHAVIORIAL 205 00:07:20,640 --> 00:07:22,880 INTERVENTIONS FOR PAIN IN SICKLE 206 00:07:22,880 --> 00:07:24,400 CELL DISEASE AND OTHER 207 00:07:24,400 --> 00:07:25,120 UNDERSERVED POPULATIONS AND 208 00:07:25,120 --> 00:07:27,640 THERE ARE PAIRIERS TO GETTING 209 00:07:27,640 --> 00:07:28,400 DIGITAL INTERVENTIONS OUT. 210 00:07:28,400 --> 00:07:30,080 AND THE LAST PIECE I'M GOING TO 211 00:07:30,080 --> 00:07:31,760 PRESENT IS A LITTLE BIT OF WORK 212 00:07:31,760 --> 00:07:33,520 FROM OUR COMMUNITY ENGAGED TRIAL 213 00:07:33,520 --> 00:07:36,280 AND THE LESSONS THAT WE'VE 214 00:07:36,280 --> 00:07:37,840 LEARNED AND HOPEFULLY THINGS WE 215 00:07:37,840 --> 00:07:38,960 CAN CARRY FORWARD TO FUTURE 216 00:07:38,960 --> 00:07:41,720 TRIALS TO SEE IF WE CAN BUILD 217 00:07:41,720 --> 00:07:43,160 ECHEDZ FOR BEHAVIORIAL 218 00:07:43,160 --> 00:07:45,800 INTERVENTIONS IN SICKLE CELL 219 00:07:45,800 --> 00:07:46,120 DISEASE. 220 00:07:46,120 --> 00:07:48,840 NOW, THERE ARE A FEW EXISTING 221 00:07:48,840 --> 00:07:49,840 BEHAVIORIAL THERAPIES IN SICKLE 222 00:07:49,840 --> 00:07:53,960 CELL DISEASE AND UNFORTUNATELY, 223 00:07:53,960 --> 00:07:57,000 THOSE, THEY'VE BEEN HAMPERED BY 224 00:07:57,000 --> 00:07:59,160 SMALL SAMPLE SIZES, POOR 225 00:07:59,160 --> 00:08:00,000 TREATMENT ENGAGEMENT, FOR 226 00:08:00,000 --> 00:08:02,280 OVERALL QUALITY OF EVIDENCE IN 227 00:08:02,280 --> 00:08:03,560 THESE TRIES SO THE EVIDENCE IS 228 00:08:03,560 --> 00:08:06,320 NOT GREAT, THERE'S STUDIES ON 229 00:08:06,320 --> 00:08:07,200 ACUE PURVEGHTURE, MINDFULNESS 230 00:08:07,200 --> 00:08:09,400 AND RECEIPTLY THERE'S STUDIES ON 231 00:08:09,400 --> 00:08:11,440 PROBLEM SOLVING SKILLS, 232 00:08:11,440 --> 00:08:13,120 TRAINING, OUR COLLEAGUES, SAM 233 00:08:13,120 --> 00:08:14,320 ROGERS RECENTLY PUBLISHED ON 234 00:08:14,320 --> 00:08:19,120 MUSIC THERAPY AND SICKLE CELL 235 00:08:19,120 --> 00:08:21,840 DISEASE AND ALL OF THESE HAVE 236 00:08:21,840 --> 00:08:24,640 PROMISE BUT AS HAS BEEN STATED 237 00:08:24,640 --> 00:08:25,920 IN THIS COCHRAN REVIEW THIS, IS 238 00:08:25,920 --> 00:08:27,120 AN OALTDER REVIEW BUT THE STATE 239 00:08:27,120 --> 00:08:28,640 OF THE LITERATURE IS STILL 240 00:08:28,640 --> 00:08:29,960 RELATIVELY THE SAME IS THAT THE 241 00:08:29,960 --> 00:08:31,800 SAMPLE SIZES FOR THESE STUDIES 242 00:08:31,800 --> 00:08:34,640 HAVE BEEN PRETTY SMALL. 243 00:08:34,640 --> 00:08:36,880 AS MANY OF YOU HAVE EXPERIENCED 244 00:08:36,880 --> 00:08:41,160 WITH SICKLE CELL STUDIES IS 245 00:08:41,160 --> 00:08:41,720 ENGAGEMENT IS CHALLENGING. 246 00:08:41,720 --> 00:08:45,040 NOW THERE ARE A FEW CBT STUDIES 247 00:08:45,040 --> 00:08:49,040 AND I WANT TO HILIGHT 2, S SIL 248 00:08:49,040 --> 00:08:50,320 HAS RECENTLY PUBLISHED FOR YOUTH 249 00:08:50,320 --> 00:08:51,720 WITH SICKLE CELL DISEASE WHO 250 00:08:51,720 --> 00:08:54,640 HAVE BEEN REFERRED TO 251 00:08:54,640 --> 00:08:55,160 FACE-TO-FACE COGNITIVE 252 00:08:55,160 --> 00:08:55,760 BEHAVIORIAL THERAPY AND THEY 253 00:08:55,760 --> 00:08:58,680 SHOW THAT THERE IS REDUCTIONS IN 254 00:08:58,680 --> 00:09:01,040 MAIN, LENGTH OF STAY, PAIN 255 00:09:01,040 --> 00:09:01,840 INTENSITY AND DISABILITY, SO 256 00:09:01,840 --> 00:09:03,240 OVERALL THE PATIENTS THAT HAVE 257 00:09:03,240 --> 00:09:07,440 BEEN REFERRED AND HAVE GOTTEN TO 258 00:09:07,440 --> 00:09:08,760 FACE-TO-FACE COGNITIVE 259 00:09:08,760 --> 00:09:10,520 DEHAIEVERRIAL THERAPY DID NO AN 260 00:09:10,520 --> 00:09:12,360 IMPROVEMENT IN PATIENT OUTCOMES. 261 00:09:12,360 --> 00:09:14,440 TONYA PAL EMBRYONIC STEM O 262 00:09:14,440 --> 00:09:18,440 CONDUCTED A LARGE TRIAL OF 263 00:09:18,440 --> 00:09:20,280 COGNITIVE VERSUS DIGITAL VERSUS 264 00:09:20,280 --> 00:09:22,040 EDUCATION IN 1 SEIVET 265 00:09:22,040 --> 00:09:23,440 ADOLESCENTS THEY DID SEE 266 00:09:23,440 --> 00:09:24,840 POSITIVE EFFECTS, OF COURSE 267 00:09:24,840 --> 00:09:26,400 THERE WERE ISSUES WITH 268 00:09:26,400 --> 00:09:27,520 ENGAGEMENT BUT THAT DATA IS 269 00:09:27,520 --> 00:09:29,920 FORTH COMING SO I NOLL PRESENT 270 00:09:29,920 --> 00:09:33,680 TO ANY OF HER DATA HERE. 271 00:09:33,680 --> 00:09:35,800 NOW THIS IDEA OF USING COMPUTER 272 00:09:35,800 --> 00:09:39,040 OR USING A MOBILE DEVICE TO 273 00:09:39,040 --> 00:09:40,640 TREAT PATIENTS WITH THERAPY HAS 274 00:09:40,640 --> 00:09:43,160 BEEN AROUND FOR OVER A COUPLE 275 00:09:43,160 --> 00:09:43,560 DECADES. 276 00:09:43,560 --> 00:09:46,600 AND THIS IS PROMISING JUST 277 00:09:46,600 --> 00:09:49,400 BECAUSE THERE'S A LACK OF 278 00:09:49,400 --> 00:09:50,600 AVAILABLE PROVIDERS, THERE'S 279 00:09:50,600 --> 00:09:53,040 LIMITED ACCESS FOR OUR PATIENTS 280 00:09:53,040 --> 00:09:54,800 AND OVERALL, IT IS JUST 281 00:09:54,800 --> 00:09:56,440 DIFFICULT TO GET PATIENTS INTO 282 00:09:56,440 --> 00:09:58,600 THE CLINIC TO DO BEHAVIORIAL 283 00:09:58,600 --> 00:10:02,080 THERAPY, SO EVEN WITH THESE 284 00:10:02,080 --> 00:10:02,800 EVIDENCE-BASED TREATMENTS, HOW 285 00:10:02,800 --> 00:10:04,680 ARE WE ACTUALLY GOING TO GET IT 286 00:10:04,680 --> 00:10:06,640 TO OUR PATIENTS AND DOING 287 00:10:06,640 --> 00:10:07,840 THERAPY WITHOUT AN ACTUAL 288 00:10:07,840 --> 00:10:10,680 THERAPIST IS 1 OF THAT'S 289 00:10:10,680 --> 00:10:11,200 POTENTIAL AVENUES. 290 00:10:11,200 --> 00:10:14,200 YOU MAY HAVE SEEN MANY OF THE 291 00:10:14,200 --> 00:10:17,040 NEW THERAPY APPS THAT ARE OUT 292 00:10:17,040 --> 00:10:22,640 THERE, WE HAVE HAPPIFY NOOM, 293 00:10:22,640 --> 00:10:27,920 MOOD, TOOLS, MOOD FIT, THERE'S 294 00:10:27,920 --> 00:10:29,920 SEVERAL TYPINGS OF MINDFULNESS 295 00:10:29,920 --> 00:10:30,520 AND BEHAVIORIAL INTERVENTIONS 296 00:10:30,520 --> 00:10:31,880 THAT ARE AVAILABLE AND YOU CAN 297 00:10:31,880 --> 00:10:33,240 DOWNLOAD THEM ON THE APP STORE 298 00:10:33,240 --> 00:10:34,400 AND YOU CAN SIGN UP TO HAVE 299 00:10:34,400 --> 00:10:36,640 LAWEDDER DALE WOULD PROBABLY BE 300 00:10:36,640 --> 00:10:37,840 DEFINED AS STANDARD CBT 301 00:10:37,840 --> 00:10:40,040 TECHNIQUES BUT MOST OF THESE ARE 302 00:10:40,040 --> 00:10:41,160 BEHAVIORIAL RATHER THAN 303 00:10:41,160 --> 00:10:42,240 COGNITIVE SO THAT THEY'RE NOT 304 00:10:42,240 --> 00:10:44,600 TRYING TO WORK ON COGNITIVELY 305 00:10:44,600 --> 00:10:45,960 STRUCTURING BUT MORE LIKELY 306 00:10:45,960 --> 00:10:48,680 BEHAVIORIAL CHANGE OR 307 00:10:48,680 --> 00:10:49,840 BEHAVIORIAL ACTIVATION. 308 00:10:49,840 --> 00:10:51,400 ONE OF THE MOST IMPORTANT 309 00:10:51,400 --> 00:10:52,800 COMPONENTS OF THESE DIGITAL 310 00:10:52,800 --> 00:10:54,040 INTERVENTION SYSTEM THAT YOU 311 00:10:54,040 --> 00:10:56,240 STILL NEED TO HAVE A HUMAN 312 00:10:56,240 --> 00:10:56,520 COMPONENT. 313 00:10:56,520 --> 00:10:58,280 YOU NEED TO HAVE A HEALTH 314 00:10:58,280 --> 00:10:59,560 EXPOACH THERE'S DATA THAT 315 00:10:59,560 --> 00:11:00,840 SUGGESTS WITHOUT A HEALTH COACH 316 00:11:00,840 --> 00:11:02,240 THESE TREATMENTS, THESE DIGITAL 317 00:11:02,240 --> 00:11:03,360 TREATMENTS ARE NOT EFFECTIVE. 318 00:11:03,360 --> 00:11:05,040 NOW THIS IS NOT A SICKLE CELL 319 00:11:05,040 --> 00:11:06,960 THIS, IS JUST A GENERAL 320 00:11:06,960 --> 00:11:07,920 POPULATION, BUT 1 THING I WANT 321 00:11:07,920 --> 00:11:11,280 TO HIGHLIGHT HERE IS THAT THERE 322 00:11:11,280 --> 00:11:13,440 IS A BEHAVIORIAL EFFECT FOR 323 00:11:13,440 --> 00:11:14,960 COGNITIVE BEHAVIOR HAL THERAPY 324 00:11:14,960 --> 00:11:18,240 ON OUTCOMES, THESE ARE MENTAL 325 00:11:18,240 --> 00:11:19,120 HEALTH OUTCOMES, SUPPRESSION, 326 00:11:19,120 --> 00:11:23,040 BUT THE SAME IS TRUE FOR SAME 327 00:11:23,040 --> 00:11:25,120 MENTAL OUTCOMES FOR OTHER 328 00:11:25,120 --> 00:11:25,440 POPULATIONS. 329 00:11:25,440 --> 00:11:26,200 BUT THERE'S OHM 2 OF THESE 330 00:11:26,200 --> 00:11:29,160 STUDIES IN THE U.S., SO MOST OF 331 00:11:29,160 --> 00:11:30,000 THESE DIGITAL THERAPY STUDIES 332 00:11:30,000 --> 00:11:31,760 HAVE BEEN DONE IN THE UK OR 333 00:11:31,760 --> 00:11:32,840 AUSTRALIA AND IN ADDITION TO 334 00:11:32,840 --> 00:11:37,200 THAT, NONE OF THESE STUDIES HAVE 335 00:11:37,200 --> 00:11:38,200 INCLUDED ENOUGH AFRICAN 336 00:11:38,200 --> 00:11:39,880 AMERICANS OR MINORITIES TO 337 00:11:39,880 --> 00:11:42,520 ACTUALLY SEE IF THERE ARE 338 00:11:42,520 --> 00:11:44,840 DIFFERENCES BETWEEN HOW WHITES 339 00:11:44,840 --> 00:11:46,280 RESPOND TO DICK'RE DIGITAL 340 00:11:46,280 --> 00:11:47,440 THERAPY AND HOW AIF I CAN AN 341 00:11:47,440 --> 00:11:49,360 AMERICANS RESPOND TO ADDITIONAL 342 00:11:49,360 --> 00:11:49,680 THERAPY. 343 00:11:49,680 --> 00:11:50,560 SO THERE'S VERY LITTLE ALTHOUGH 344 00:11:50,560 --> 00:11:55,320 WE SEE THERE IS PROMISE FOR A 345 00:11:55,320 --> 00:11:58,760 POTENTIAL FOR DIGITAL CBT, EVEN 346 00:11:58,760 --> 00:12:00,640 IN OUR SICKLE CELL POPULATION, 347 00:12:00,640 --> 00:12:01,840 THERE'S SUCH LIMITED DATA JUST 348 00:12:01,840 --> 00:12:04,120 TO ACTUALLY FIND OUT, DOES 349 00:12:04,120 --> 00:12:06,560 DIGITAL THERAPY EVEN WORK INAC 350 00:12:06,560 --> 00:12:07,800 AFRICAN AMERICANS. 351 00:12:07,800 --> 00:12:09,040 THIS STUDY PUBLISHES PRIMARY 352 00:12:09,040 --> 00:12:10,000 CARE POPULATION AND JUST SHOWING 353 00:12:10,000 --> 00:12:12,560 THAT 1 OF THE FIRST STUDIES TO 354 00:12:12,560 --> 00:12:13,640 SHOW THAT FOR AFRICAN AMERICANS 355 00:12:13,640 --> 00:12:17,240 WE SEE A DECREASE IN DEPRESSION 356 00:12:17,240 --> 00:12:19,160 AND IMPROVEMENT IN PAIN OUTCOMES 357 00:12:19,160 --> 00:12:20,760 FOR AFRICAN AMERICAN SIMILAR TO 358 00:12:20,760 --> 00:12:21,600 THAT FOR WHITES. 359 00:12:21,600 --> 00:12:23,120 SO INDEED, WE'RE FINDING THAT 360 00:12:23,120 --> 00:12:25,120 YOU KNOW AT LEAST IN THE PRIMARY 361 00:12:25,120 --> 00:12:29,360 CARE POPULATION, WE DO SEE THAT 362 00:12:29,360 --> 00:12:32,600 AFRICAN AMERICANS CAN BENEFIT 363 00:12:32,600 --> 00:12:33,640 FROM DIGITAL THERAPY, AT THE 364 00:12:33,640 --> 00:12:35,720 SAME LEVEL OR MORE SO THAN WHITE 365 00:12:35,720 --> 00:12:36,040 PARTICIPANTS. 366 00:12:36,040 --> 00:12:38,400 ONE OF THE ISSUES THOUGH IS 367 00:12:38,400 --> 00:12:38,960 OBVIOUSLY IN ENGAGEMENT. 368 00:12:38,960 --> 00:12:41,560 WE KNOW THAT THERE ARE 369 00:12:41,560 --> 00:12:42,960 CHALLENGES TO GETTING AFRICAN 370 00:12:42,960 --> 00:12:44,640 AMERICANS AND MINORITY 371 00:12:44,640 --> 00:12:45,240 POPULATIONS INTO FACE-TO-FACE 372 00:12:45,240 --> 00:12:47,520 THERAPY AND A LOT OF THOSE 373 00:12:47,520 --> 00:12:48,200 CHALLENGES, USUALLY COME INTO 374 00:12:48,200 --> 00:12:50,240 THE COST OF IT, AND 375 00:12:50,240 --> 00:12:50,960 TRANSPORTATION, JUST BEING ABLE 376 00:12:50,960 --> 00:12:54,040 TO GET TO A THERAPIST OR BEING 377 00:12:54,040 --> 00:12:57,240 ABLE TO ACCESS A CULTURALLY 378 00:12:57,240 --> 00:12:57,680 COMPETENT THERAPIST. 379 00:12:57,680 --> 00:13:00,440 BUT EVEN IN THIS DIGITAL 380 00:13:00,440 --> 00:13:02,240 DELIVERY WHERE A LOT OF THOSE 381 00:13:02,240 --> 00:13:03,600 BARRIERS SHOULD BE OVERCOME, 382 00:13:03,600 --> 00:13:06,360 THERE ARE STILL SOME BARRIERS TO 383 00:13:06,360 --> 00:13:08,120 GETTING ENGAGEMENT WITH DIGITAL 384 00:13:08,120 --> 00:13:11,000 CBT, AS CAN YOU SEE, FOR THE 385 00:13:11,000 --> 00:13:12,040 WHITE POPULATION, 10% DID NOT 386 00:13:12,040 --> 00:13:14,640 EACH START THE DIGITAL CBT 387 00:13:14,640 --> 00:13:16,840 PROGRAM, WHEREAS FOR OUR 388 00:13:16,840 --> 00:13:19,160 MINORITIES 25% DID NOT START THE 389 00:13:19,160 --> 00:13:21,960 DIGITAL CBT PROGRAM, AND WE SEE 390 00:13:21,960 --> 00:13:23,120 THIS PRETTY CONSISTORRENTLY THAT 391 00:13:23,120 --> 00:13:25,880 ENGAGEMENT WITH THE DIGITAL CBT 392 00:13:25,880 --> 00:13:28,680 PROGRAMS IS MUCH LESS FOR 393 00:13:28,680 --> 00:13:29,760 AFRICAN AMERICANS THAN IT IS FOR 394 00:13:29,760 --> 00:13:31,480 WHITES SO IN THIS STUDY WE 395 00:13:31,480 --> 00:13:33,640 SHOWED FOR AFRICAN AMERICANS 396 00:13:33,640 --> 00:13:35,760 THEY COMPLETED 2 AND HALF FEWER 397 00:13:35,760 --> 00:13:37,400 DIGITAL SESSIONS THAN THEIR 398 00:13:37,400 --> 00:13:39,080 WHITE COUNTERPARTS, AND EVEN IN 399 00:13:39,080 --> 00:13:40,640 THE DIFFERENT STUDY WE LOOKEDDA 400 00:13:40,640 --> 00:13:42,200 THE SAME THING AND AGAIN THIS IS 401 00:13:42,200 --> 00:13:44,600 YESTERDAY A GENERAL POPULATION 402 00:13:44,600 --> 00:13:45,800 BUT HOPEFULLY THE APPLICATION IS 403 00:13:45,800 --> 00:13:47,840 RELEVANT BUT CAN YOU SEE THAT 404 00:13:47,840 --> 00:13:50,200 FOR THOSE WHITE PARTICIPANTS IN 405 00:13:50,200 --> 00:13:52,960 THE STUDY, THEY COMPLETED 8 AND 406 00:13:52,960 --> 00:13:54,240 HALF SESSIONS VERSUS 4 SESSIONS 407 00:13:54,240 --> 00:13:55,880 FOR PLAQUE, SO THAT'S HALF THE 408 00:13:55,880 --> 00:13:58,240 NUMBER OF SESSIONS COMPLETED, 409 00:13:58,240 --> 00:13:59,400 TECHNIQUES COMPLOATED AND THOSE 410 00:13:59,400 --> 00:14:01,680 ARE DEEP BREATHING EXERCISES OR 411 00:14:01,680 --> 00:14:03,640 TAKING A NICE WALK IN THE WOODS, 412 00:14:03,640 --> 00:14:05,840 THOSE TECHNIQUES ARE ABOUT 12, 413 00:14:05,840 --> 00:14:08,200 BUT HALF OF THOSE COMPLETED BY 414 00:14:08,200 --> 00:14:10,720 THE BLACK PARTICIPANTS, USAGE 415 00:14:10,720 --> 00:14:12,440 AND MESSAGES ARE A HEALTH COACH 416 00:14:12,440 --> 00:14:12,840 ARE HALF. 417 00:14:12,840 --> 00:14:15,240 SO WE SEE THERE'S A HUGE ISSUE 418 00:14:15,240 --> 00:14:17,960 WITH ENGAGEMENT WITH THE DIGITAL 419 00:14:17,960 --> 00:14:18,880 THERAPY AMONG AFRICAN AMERICANS 420 00:14:18,880 --> 00:14:20,840 AND WE ALSO IN OUR PRELIMINARY 421 00:14:20,840 --> 00:14:23,160 STUDY WE SEE THE SAME CHALLENGES 422 00:14:23,160 --> 00:14:25,640 WITH ENGAGEMENT FOR OUR SICKLE 423 00:14:25,640 --> 00:14:26,160 CELL PATIENTS. 424 00:14:26,160 --> 00:14:27,480 BUT THIS IS 1 OF THE EXAMPLES 425 00:14:27,480 --> 00:14:30,360 THAT I WANT TO PULL OUT JUST 426 00:14:30,360 --> 00:14:31,960 QUICKLY, I'LL SPEED THROUGH THIS 427 00:14:31,960 --> 00:14:34,640 BECAUSE IT'S NOT MUCH TIME BUT 428 00:14:34,640 --> 00:14:37,240 MIKE IS A 55 YEAR-OLD AFFRIC ARN 429 00:14:37,240 --> 00:14:38,280 AMERICAN WITH ANXIOUS, COACH 430 00:14:38,280 --> 00:14:40,040 SAID THIS IS A DIGITAL COACH 431 00:14:40,040 --> 00:14:42,520 THAT IS TEXT MESSAGES TO THIS 432 00:14:42,520 --> 00:14:43,720 INDIVIDUAL, HI, CHECKING IN, HOW 433 00:14:43,720 --> 00:14:45,320 ARE YOU DOING, HE SAYS I'M 434 00:14:45,320 --> 00:14:46,640 DEALING WITH LIFE, CAR BROKE 435 00:14:46,640 --> 00:14:47,920 DOWN, SERIOUS MONEY ISSUES NOT 436 00:14:47,920 --> 00:14:50,720 SURE I WANT TO KEEP DOING THIS 437 00:14:50,720 --> 00:14:51,000 APP. 438 00:14:51,000 --> 00:14:51,920 BEING HONEST, BEING TRUTHFUL 439 00:14:51,920 --> 00:14:54,000 BECAUSE THIS APP REQUIRES WORK, 440 00:14:54,000 --> 00:14:54,960 WORK I'M SOMETIMES I'M NOT 441 00:14:54,960 --> 00:14:56,920 WILLING TO DO BUT I WON'T 442 00:14:56,920 --> 00:14:57,680 BECAUSE I CAN'T. 443 00:14:57,680 --> 00:14:58,960 I'M FRUSTRATED WITH THE COUNTRY 444 00:14:58,960 --> 00:15:01,480 AND THE BELIEF THAT THINGS WILL 445 00:15:01,480 --> 00:15:04,080 NEVER GET BETTER FOR MY SON OR 446 00:15:04,080 --> 00:15:05,600 HIS CHILDREN, IT'S IMPOSSIBLE TO 447 00:15:05,600 --> 00:15:09,680 PLAIN TO A PERSON OF NO COLOR. 448 00:15:09,680 --> 00:15:11,640 JUST NOW JUST THINKING ABOUT 449 00:15:11,640 --> 00:15:12,840 THAT RESPONSE FROM MIKE AND A 450 00:15:12,840 --> 00:15:15,040 PATIENT AND WHAT DOES THE HEALTH 451 00:15:15,040 --> 00:15:16,520 COACH TEXT BACK, I'M SORRY TO 452 00:15:16,520 --> 00:15:19,400 HEAR YOU'RE DEALING WITH SO MANY 453 00:15:19,400 --> 00:15:20,200 DIFFERENT STRESSORS ARE 454 00:15:20,200 --> 00:15:21,640 SOPHISTICATED SO MANY FRONTS, I 455 00:15:21,640 --> 00:15:24,040 HEAR THE FRUSTRATION, I HOPE YOU 456 00:15:24,040 --> 00:15:26,240 WON'T GIVE UP ON THIS APP, 457 00:15:26,240 --> 00:15:27,520 DURING TIMES OF EXTREME STRESS, 458 00:15:27,520 --> 00:15:30,200 THE SECTION ON THE HOME PAGE 459 00:15:30,200 --> 00:15:31,720 LABELED IN THE MOMENT RELIEVE, 460 00:15:31,720 --> 00:15:35,240 CAN BE HELPFUL WAY TOK SESES 2-3 461 00:15:35,240 --> 00:15:43,840 MINUTE AUDIO RECORDING TO HELP 462 00:15:43,840 --> 00:15:44,400 YOU FEEL BETTER. 463 00:15:44,400 --> 00:15:46,560 IF WE'RE NOT DOING THIS IN A WAY 464 00:15:46,560 --> 00:15:48,200 THAT ENGAGE THIS IS SPECIFIC 465 00:15:48,200 --> 00:15:49,760 PATIENT POPULATION, WE WILL HAVE 466 00:15:49,760 --> 00:15:51,480 CHALLENGES. 467 00:15:51,480 --> 00:15:54,240 WE'VE TRIED TO USE A VERY 468 00:15:54,240 --> 00:15:57,440 SIMILAR APPLICATIONS WITH OUR 469 00:15:57,440 --> 00:15:58,480 SICKLE CELL PATIENTS, AND 1 OF 470 00:15:58,480 --> 00:16:00,920 THE THINGS AND FEEDBACK WE GOT 471 00:16:00,920 --> 00:16:02,960 WAS IT WAS COOL BUT IT WASN'T 472 00:16:02,960 --> 00:16:04,440 RELEVANT TO ME. 473 00:16:04,440 --> 00:16:05,960 PATIENTS DID ISN'T SEE SOMEBODY 474 00:16:05,960 --> 00:16:07,360 THAT LOOKED LOAMACYIC THEM AND 475 00:16:07,360 --> 00:16:08,640 SOMETHING WE HEARD FREQUENTLY 476 00:16:08,640 --> 00:16:09,880 FROM THE COMMUNITY IS NOTHING 477 00:16:09,880 --> 00:16:12,080 FOR US WITHOUT US. 478 00:16:12,080 --> 00:16:13,160 AND WE RECOGNIZE IMMEDIATELY 1 479 00:16:13,160 --> 00:16:15,400 OF THE BARRIERS TO US BEING ABLE 480 00:16:15,400 --> 00:16:16,400 TO DELIVER BEHAVIORIAL 481 00:16:16,400 --> 00:16:18,720 INTERVENTIONS FOR PAIN AND 482 00:16:18,720 --> 00:16:21,600 MENTAL HEALTH AND MAKING SURE 483 00:16:21,600 --> 00:16:23,280 THAT THIS--THIS TREATMENT WILL 484 00:16:23,280 --> 00:16:24,600 BE RELEVANT AND REPRESENTATIVE 485 00:16:24,600 --> 00:16:27,240 OF THE POPULATION THAT WE'RE 486 00:16:27,240 --> 00:16:27,640 TRYING TO SERVE. 487 00:16:27,640 --> 00:16:30,480 WHAT WE DID TO ADDRESS THESE 488 00:16:30,480 --> 00:16:34,840 HUGE BARRIERS WAS TOOK 2 489 00:16:34,840 --> 00:16:36,760 EXISTING PROGRAMS, I CAN COPE 490 00:16:36,760 --> 00:16:38,480 SICKLE CELL, THIS IS THE PROGRAM 491 00:16:38,480 --> 00:16:40,640 THAT TONYA PAL EMERGING O TESTED 492 00:16:40,640 --> 00:16:41,800 IN PEDIATRICS AND WE TRIED TO 493 00:16:41,800 --> 00:16:43,240 ADAPT AND TAKE PIECES AND USE IT 494 00:16:43,240 --> 00:16:44,680 FOR ADULTS AND THEN ALSO WORKING 495 00:16:44,680 --> 00:16:46,520 WITH THE COMMUNITY, SICKLE CELL 496 00:16:46,520 --> 00:16:48,240 101 IS A COMMUNITY-BASED 497 00:16:48,240 --> 00:16:49,840 ORGANIZATION THAT HAS BEEN 498 00:16:49,840 --> 00:16:53,120 EDUCATING PASHTS AND THEIR 499 00:16:53,120 --> 00:16:54,520 FAMILY MEMBERS OVER SOCIAL 500 00:16:54,520 --> 00:16:57,320 MEDIA, SOCIAL MEDIA PLATFORMS 501 00:16:57,320 --> 00:16:58,240 LIKE INSTAGRAM, TWITTER, 502 00:16:58,240 --> 00:17:00,040 FACEBOOK, ET CETERA AND CLEARLY, 503 00:17:00,040 --> 00:17:02,440 YOU CAN SEE THAT THE COMMUNITY 504 00:17:02,440 --> 00:17:03,400 BASED ORGANIZATIONS ARE DOING A 505 00:17:03,400 --> 00:17:04,800 MUCH BETTER JOB OF GETTING 506 00:17:04,800 --> 00:17:06,040 EDUCATION TO OUR PATIENT 507 00:17:06,040 --> 00:17:07,520 POPULATION EVEN THAN WE ARE HERE 508 00:17:07,520 --> 00:17:10,480 AT THE IVORY TOWER, SO WHY TRY 509 00:17:10,480 --> 00:17:12,600 TO RECREATE THE WHEEL WHEN WE 510 00:17:12,600 --> 00:17:13,120 LEVERAGE WHAT'S EXISTING. 511 00:17:13,120 --> 00:17:14,520 THE HIGHLIGHT OF THIS IS THAT 512 00:17:14,520 --> 00:17:16,360 WE'RE ABLE TO GET PATIENTS 513 00:17:16,360 --> 00:17:18,080 LIVING WITH SICKLE CELL DISEASE, 514 00:17:18,080 --> 00:17:19,840 ADULTS WITH SICKLE CELL DISEASE 515 00:17:19,840 --> 00:17:23,280 TO ACTUALLY DELIVER THE 516 00:17:23,280 --> 00:17:23,640 INTERVENTION. 517 00:17:23,640 --> 00:17:26,040 SO ALL THE RECORDINGS, ALL THE 518 00:17:26,040 --> 00:17:27,560 MESSAGING, THAT IS DONE BY 519 00:17:27,560 --> 00:17:29,000 ADULTS WITH SICKLE CELL DISEASE, 520 00:17:29,000 --> 00:17:31,560 IT'S NOT COMING FROM DR. CHARLES 521 00:17:31,560 --> 00:17:33,440 WHO THINKS HE KNOWS IT ALL BUT 522 00:17:33,440 --> 00:17:34,840 IT'S COMING FROM PEOPLE WHO HAVE 523 00:17:34,840 --> 00:17:35,880 REAL LIVED EXPERIENCE AND IN 524 00:17:35,880 --> 00:17:37,400 ADDITION TO THE TRAINING AND 525 00:17:37,400 --> 00:17:38,440 TEACHING ON COGNITIVE 526 00:17:38,440 --> 00:17:39,240 BEHAVIORIAL THERAPY AND 527 00:17:39,240 --> 00:17:43,080 EDUCATION, YOU ALSO HAVE WARRIOR 528 00:17:43,080 --> 00:17:44,480 STORIES SO YOU HAVE PATIENT WHO 529 00:17:44,480 --> 00:17:46,240 IS ARE TALKING ABOUT THEIR 530 00:17:46,240 --> 00:17:47,960 EXPERIENCE WITH STRESS AND PAIN 531 00:17:47,960 --> 00:17:49,840 AND WITH EDUCATION AND THE 532 00:17:49,840 --> 00:17:50,200 UPTICK. 533 00:17:50,200 --> 00:17:52,600 WE WERE FUNDED BY PATIENT 534 00:17:52,600 --> 00:17:53,640 CENTERED OUTCOMES RESEARCH 535 00:17:53,640 --> 00:17:54,720 INSTITUTE TO HAVE 6 DIFFERENT 536 00:17:54,720 --> 00:17:58,040 CLINICAL SITES AND NOW WE ADDED 537 00:17:58,040 --> 00:17:59,640 A SEVENTH SITE, VANDERBILT BUT 538 00:17:59,640 --> 00:18:01,840 THE REAL PUSH OR DRIVER OF THE 539 00:18:01,840 --> 00:18:03,720 STUDIES HAVING THESE 540 00:18:03,720 --> 00:18:04,320 COMMUNITY-BASED ORGANIZATIONS 541 00:18:04,320 --> 00:18:06,640 PARTICIPATING WITH US, SICKLE 542 00:18:06,640 --> 00:18:08,720 CELL 101, SICKLE SOLE COMMUNITY 543 00:18:08,720 --> 00:18:10,520 AND CONSORTIUM THEY'VE DONE A 544 00:18:10,520 --> 00:18:11,360 FANTASTIC JOB OF RECRUELTIMENT 545 00:18:11,360 --> 00:18:12,720 AND I WILL SHOW THAT YOU DAT A. 546 00:18:12,720 --> 00:18:16,120 BUT JUST IN BRIEF, THE STUDY IS 547 00:18:16,120 --> 00:18:18,760 RANDOMIZING TO DIGITAL CBT OR 548 00:18:18,760 --> 00:18:19,160 DIGITAL EDUCATION. 549 00:18:19,160 --> 00:18:21,240 OUR GOAL IS TO GET 350 PATIENTS 550 00:18:21,240 --> 00:18:22,760 ALL PATIENTS IN THE STUDY 551 00:18:22,760 --> 00:18:24,240 REGARDLESS OF WHAT ARM THEY'VE 552 00:18:24,240 --> 00:18:25,400 BEEN ANDROGEN ORDER OF 553 00:18:25,400 --> 00:18:26,680 MICRONSIZED TOO WILL GET HELT 554 00:18:26,680 --> 00:18:28,080 COACH SUPPORT, THEY GET HEALTH 555 00:18:28,080 --> 00:18:29,120 COACH SUPPORT FOR 3 MONTHS AND I 556 00:18:29,120 --> 00:18:30,440 WILL TALK ABOUT THE HEALTH 557 00:18:30,440 --> 00:18:31,760 COACHES IN A SECOND. 558 00:18:31,760 --> 00:18:33,280 AND THE PRIMARY OUTCOMES FOR 559 00:18:33,280 --> 00:18:36,040 THIS ARE PAIN INTENSITY, DAILY 560 00:18:36,040 --> 00:18:37,560 PAIN INTENSITY AND PAIN 561 00:18:37,560 --> 00:18:39,280 INTERFERENCE BUT THE OUTCOMES 562 00:18:39,280 --> 00:18:44,040 COME AT 3, 6 AND 12 MONTHS. 563 00:18:44,040 --> 00:18:45,720 NOW JUST A QUICK STORY BOARD OF 564 00:18:45,720 --> 00:18:46,640 HOW PATIENTS GET INTO THE STUDY 565 00:18:46,640 --> 00:18:48,640 BECAUSE WE THINK THIS IS NEW AND 566 00:18:48,640 --> 00:18:49,640 INNOVATIVE AND MIGHT HELP 567 00:18:49,640 --> 00:18:51,040 OVERCOME THE ISSUES WE'VE SEEN 568 00:18:51,040 --> 00:18:52,080 WITH OTHER TRIALS IN TERMS OF 569 00:18:52,080 --> 00:18:54,080 BEING ABLE TO RECRUIT AND 570 00:18:54,080 --> 00:18:54,320 ENGAGE. 571 00:18:54,320 --> 00:18:55,720 IT'S PATIENTS THAT COME INTO THE 572 00:18:55,720 --> 00:18:58,440 CLINIC, THEY ARE GOING TO GET 573 00:18:58,440 --> 00:19:00,200 ACCESS TO AN iPAD KIOSK, IT 574 00:19:00,200 --> 00:19:02,880 WILL HAVE A LITTLE VIDEO ON IT 575 00:19:02,880 --> 00:19:04,520 OR HAS A VIDEO ON IT THAT 576 00:19:04,520 --> 00:19:06,240 EXPLAINS THE STUDY, SO WE'RE NOT 577 00:19:06,240 --> 00:19:07,640 JUST GIVING PEOPLE A CONSENT 578 00:19:07,640 --> 00:19:10,480 FORM, WE HAVE A VIDEO AND IT'S 579 00:19:10,480 --> 00:19:13,160 ENGAGING, WE HAVE A VIDEO THAT 580 00:19:13,160 --> 00:19:14,080 EXPLAINS, THE STUDY TO THE 581 00:19:14,080 --> 00:19:15,400 PATIENTS AND WHAT THEY'RE 582 00:19:15,400 --> 00:19:15,720 GETTING INTO. 583 00:19:15,720 --> 00:19:17,440 WE KNOW YOU HAVE PAIN, WE KNOW 584 00:19:17,440 --> 00:19:18,640 YOU HAVE STRESS, THIS IS THE 585 00:19:18,640 --> 00:19:22,040 STUDY THAT WANTS TO ADDRESS THAT 586 00:19:22,040 --> 00:19:23,440 IN AN NONFARM COLLAGE CALAWAY. 587 00:19:23,440 --> 00:19:24,960 RIGHT THERE ON THE iPAD THEY 588 00:19:24,960 --> 00:19:26,840 CAN SIGN UP FOR THE STUDY AND 589 00:19:26,840 --> 00:19:28,040 COMPLETE THOSE BASE LINE 590 00:19:28,040 --> 00:19:29,200 QUESTIONNAIRES AND THEN ONCE 591 00:19:29,200 --> 00:19:31,240 THEY SIGN UP, EVERYBODY IMETS AN 592 00:19:31,240 --> 00:19:33,240 ALERT ON THEIR PHONE, THE 593 00:19:33,240 --> 00:19:34,320 COORDINATOR CAN GO AND PRESENT 594 00:19:34,320 --> 00:19:36,840 THE STUDY OR HELP THE PATIENT OR 595 00:19:36,840 --> 00:19:38,080 THE PARTICIPANT GET ON TO THE 596 00:19:38,080 --> 00:19:40,280 APP AND GET ON TO THE SYSTEM AND 597 00:19:40,280 --> 00:19:41,640 EXPLAIN ANY DETAILS OF THE STUDY 598 00:19:41,640 --> 00:19:43,400 THAT THEY DIDN'T UNDERSTAND FROM 599 00:19:43,400 --> 00:19:45,480 THE KIOSK AND THEN OF COURSE, 600 00:19:45,480 --> 00:19:46,640 RIGHT AFTER THAT, AS SOON AS 601 00:19:46,640 --> 00:19:48,760 THEY LEAVE THE CLINIC, 602 00:19:48,760 --> 00:19:51,880 EVERYTHING IS REMOTE IS A 603 00:19:51,880 --> 00:19:53,120 COMPLETELY REMOTELY DELIVERED 604 00:19:53,120 --> 00:19:53,480 INTERVENTION. 605 00:19:53,480 --> 00:19:55,600 WITHIN 24 HOURS WE HAVE THE 606 00:19:55,600 --> 00:19:56,760 HEALTH COACH CONTACTED 607 00:19:56,760 --> 00:19:57,960 INDIVIDUAL AND MAKE SURE THEY'RE 608 00:19:57,960 --> 00:19:59,000 CONNECT WIDE THE STUDY AND WITH 609 00:19:59,000 --> 00:20:01,880 THE ISHT VENTION WHICH IS THE 610 00:20:01,880 --> 00:20:03,760 IPAD, WHICH IS THE APP THAT THEY 611 00:20:03,760 --> 00:20:06,360 ACCESS ON THEIR PHONE EMPLOY ALL 612 00:20:06,360 --> 00:20:07,160 THE ASSESSMENTS ARE DONE ON THE 613 00:20:07,160 --> 00:20:08,680 PHONE, THEY DON'T HAVE TO COME 614 00:20:08,680 --> 00:20:10,040 BACK TO CLINIC ABOUT YOU WE 615 00:20:10,040 --> 00:20:12,360 ENCOURAGE THE PARENT TO CONTINUE 616 00:20:12,360 --> 00:20:14,760 USING THE CHARISMA APP OVER THE 617 00:20:14,760 --> 00:20:16,040 COURSE OF THOSE 3 MONTHS, EVERY 618 00:20:16,040 --> 00:20:17,800 DAY AND OF COURSE THEY CAN 619 00:20:17,800 --> 00:20:20,120 INTERACT WITH THESE LESSONS IT'S 620 00:20:20,120 --> 00:20:22,680 AN AUTOMATED CHAT BOX AND IT HAS 621 00:20:22,680 --> 00:20:24,880 THE HIGHLIGHT OF IT OF COURSE 622 00:20:24,880 --> 00:20:26,520 ARE THOSE VIDEO LESSONS THEY 623 00:20:26,520 --> 00:20:30,120 WILL GET AND LEARN ON COGNITIVE 624 00:20:30,120 --> 00:20:31,400 BEHAVIORIAL THERAPY OR ON SICKLE 625 00:20:31,400 --> 00:20:33,160 CELL AND PAIN EDUCATION AND ALL 626 00:20:33,160 --> 00:20:34,920 IT IS DELIVERED BY PATIENTS WITH 627 00:20:34,920 --> 00:20:36,440 LIVING SICKLE CELL DISEASE, I 628 00:20:36,440 --> 00:20:38,360 TRIED TO DO 1 OF THE LESSONS 629 00:20:38,360 --> 00:20:39,560 MYSELF AND WE TOO BEING IT OUT 630 00:20:39,560 --> 00:20:40,440 OF THE PROGRAM BECAUSE PATIENTS 631 00:20:40,440 --> 00:20:42,920 DID NOT LIKE IT, THEY MUCH MORE 632 00:20:42,920 --> 00:20:44,440 PREFER LIVING OTHER PEOPLE 633 00:20:44,440 --> 00:20:46,000 LIVING WITH SICKLE DISEASE. 634 00:20:46,000 --> 00:20:48,040 WITH THE LAST FEW MINUTES 635 00:20:48,040 --> 00:20:55,680 OVERALL, THE STUDY AS OF 636 00:20:55,680 --> 00:20:58,800 JULY 2022, SCREEN OVER 440 637 00:20:58,800 --> 00:21:00,960 INDIVIDUALS WE 277 CONSENTED AND 638 00:21:00,960 --> 00:21:02,880 256 RANDOMIZED AND TO BE 639 00:21:02,880 --> 00:21:04,640 RANDOMIZED PATIENTS NEED TO 640 00:21:04,640 --> 00:21:06,240 COMPLETE THE BASE LINE 641 00:21:06,240 --> 00:21:08,120 QUESTIONNAIRES AND THEN THEY GET 642 00:21:08,120 --> 00:21:09,840 RANDOMIZED TO GET A HEALTH COACH 643 00:21:09,840 --> 00:21:12,960 AND WE'RE TRYING TO GET THAT 644 00:21:12,960 --> 00:21:13,880 NUMBER UP TO 350. 645 00:21:13,880 --> 00:21:15,840 WITH A FEW THINGS AS WITH 646 00:21:15,840 --> 00:21:18,080 EVERYBODY, WE HAD ISSUES WITH 647 00:21:18,080 --> 00:21:19,640 COVID, IT WAS HARD TO GET THE 648 00:21:19,640 --> 00:21:20,760 STUDY STARTED UP AND EVEN ONCE 649 00:21:20,760 --> 00:21:23,600 WE GOT IT STARTED UP, THERE WAS 650 00:21:23,600 --> 00:21:25,720 A 7-MONTH DELAY INET GOING ALL 651 00:21:25,720 --> 00:21:27,720 OF OUR SITES ENROLLING BUT 652 00:21:27,720 --> 00:21:29,480 STILL, WE'RE PUSHING ALONG, BUT 653 00:21:29,480 --> 00:21:31,400 REALLY WE WANTED TO END WITH THE 654 00:21:31,400 --> 00:21:33,880 HIGHLIGHT HERE, IS THE HEALTH 655 00:21:33,880 --> 00:21:34,240 COACHING. 656 00:21:34,240 --> 00:21:35,280 WE STARTED OUT, WE THOUGHT WE 657 00:21:35,280 --> 00:21:37,640 WOULD BE ABLE TO HAVE JUST 2 658 00:21:37,640 --> 00:21:40,240 HEALTH COACHES, BE ABLE TO SERVE 659 00:21:40,240 --> 00:21:41,520 OVER 350 PATIENTS, AND THE 660 00:21:41,520 --> 00:21:43,640 REALITY WAS IS THAT THE HEALTH 661 00:21:43,640 --> 00:21:46,120 COACHING COMPONENT TO THIS WAS 662 00:21:46,120 --> 00:21:48,560 SO POPULAR THAT WE HAD TO GO OUT 663 00:21:48,560 --> 00:21:50,120 AND REKROWT MORE HEALTH COACHES. 664 00:21:50,120 --> 00:21:51,760 IN FACT WE HAD TO STOP THE STUDY 665 00:21:51,760 --> 00:21:53,600 AT 1 POINT BECAUSE WE DID NOT 666 00:21:53,600 --> 00:21:54,720 HAVE ENOUGH HEALTH COACHES TO 667 00:21:54,720 --> 00:21:55,840 SERVE THE NEED. 668 00:21:55,840 --> 00:21:57,760 SO REALLY, I THINK THIS IS A 669 00:21:57,760 --> 00:21:59,240 COMBINATION OF THINGS. 670 00:21:59,240 --> 00:22:01,040 CLEARLY COVID HAS HAD AN IMPACT 671 00:22:01,040 --> 00:22:03,000 ON EVERYBODY AND BEING SHUT-IN 672 00:22:03,000 --> 00:22:04,440 BUT ALSO JUST THE STATE OF 673 00:22:04,440 --> 00:22:05,880 SOCIETY RIGHT NOW AND WHAT IT'S 674 00:22:05,880 --> 00:22:07,200 LIKE TO BEING PLACENTA IN 675 00:22:07,200 --> 00:22:08,120 AMERICA HAS BEEN PARTICULARLY 676 00:22:08,120 --> 00:22:09,360 STRESSFUL FOR OUR PATIENTS BUT 677 00:22:09,360 --> 00:22:11,640 WITH OUR HEALTH COACHES WE HAD A 678 00:22:11,640 --> 00:22:13,960 LOT OF SUCCESS, THEY MADE OVER 679 00:22:13,960 --> 00:22:16,440 ALMOST 15 CONTACTS PER PATIENT 680 00:22:16,440 --> 00:22:18,080 SO THAT'S JUST TEXT MESSAGES AND 681 00:22:18,080 --> 00:22:19,400 PHONE CALLS TRYING TO REACH OUT 682 00:22:19,400 --> 00:22:22,280 WHICH HAS MANY OF YOU KNOW, 683 00:22:22,280 --> 00:22:23,800 HAVING--EVEN THE PATIENTS DON'T 684 00:22:23,800 --> 00:22:25,040 ANSWER THE PHONE, KNOWING THAT 685 00:22:25,040 --> 00:22:26,480 SOMEBODY CARES AND IS REACHING 686 00:22:26,480 --> 00:22:28,360 OUT, CAN BE AN INTERVENTION IN 687 00:22:28,360 --> 00:22:31,000 AND OF ITSELF, WE HAD AT LEAST 1 688 00:22:31,000 --> 00:22:32,720 PHONE SESSION WITH 205 PATIENTS 689 00:22:32,720 --> 00:22:34,080 SO THAT'S 80% OF OUR PATIENTS SO 690 00:22:34,080 --> 00:22:35,640 OUR REACH HAS BEEN REALLY GOOD 691 00:22:35,640 --> 00:22:37,960 AND JUST TO EMPHASIZE THE POINT 692 00:22:37,960 --> 00:22:39,080 OF THE DIGITAL INTERVENTION IS 693 00:22:39,080 --> 00:22:41,360 IMPORTANT AND IT'S CRITICAL 694 00:22:41,360 --> 00:22:44,080 BECAUSE THAT'S WHERE THE ACTIVE 695 00:22:44,080 --> 00:22:46,040 INGREDIENT IS BUT HAVING THAT 696 00:22:46,040 --> 00:22:46,880 HEALTH COACH, THAT REAL LIFE 697 00:22:46,880 --> 00:22:48,440 PERSON IS GOING TO BE CRITICAL 698 00:22:48,440 --> 00:22:49,760 MOVING FORWARD AND THAT'S WHAT 699 00:22:49,760 --> 00:22:51,640 REALLY THE PATIENTS WHO HAVE 700 00:22:51,640 --> 00:22:52,440 PARTICIPATED IN THE TRIAL, 701 00:22:52,440 --> 00:22:54,240 THAT'S BEEN THE PART THAT HAS 702 00:22:54,240 --> 00:22:55,560 BEEN REALLY THE MOST ATTRACTIVE 703 00:22:55,560 --> 00:22:56,000 TO THEM. 704 00:22:56,000 --> 00:22:57,840 AND THEN OF COURSE, OUR HEALTH 705 00:22:57,840 --> 00:23:01,200 COACHES HAVE DONE ABOUT 5 706 00:23:01,200 --> 00:23:03,120 SESSIONS ON AVERAGE WITH THESE 707 00:23:03,120 --> 00:23:03,720 PARTIC PLAN TO ANALYZE BY AGES 708 00:23:03,720 --> 00:23:04,880 AND THOSE CAN BE PHONE OR TEXT, 709 00:23:04,880 --> 00:23:07,000 BUT WE FEEL LIKE THE FIRST PHONE 710 00:23:07,000 --> 00:23:08,680 CALL IS REALLY, REALLY CLITICAL. 711 00:23:08,680 --> 00:23:10,680 ENDING WITH THIS, WE LEARNED SO 712 00:23:10,680 --> 00:23:11,640 FAR, THERE'S SIGNIFICANT MENTAL 713 00:23:11,640 --> 00:23:14,040 HEALTH NEED FOR THE POPULATIONS, 714 00:23:14,040 --> 00:23:15,680 SO, ALL THE PATIENTS HAVE BEEN 715 00:23:15,680 --> 00:23:18,040 ENROLLED IN THIS TRIAL HAVE TO 716 00:23:18,040 --> 00:23:18,480 HAVE CHRONIC PAIN. 717 00:23:18,480 --> 00:23:19,640 THEY'RE NOT GETTING TO THE 718 00:23:19,640 --> 00:23:21,760 THRIEL, BECAUSE OF MENTAL HEALTH 719 00:23:21,760 --> 00:23:24,240 NEEDS BUT WE FOUND OUT THAT VERY 720 00:23:24,240 --> 00:23:27,160 QUICKLY WE HAD THE SUICIDALLITY, 721 00:23:27,160 --> 00:23:28,640 MANAGEMENT SYSTEM, AND IT WOULD 722 00:23:28,640 --> 00:23:31,840 SEND US AN ALERT ANYTIME 723 00:23:31,840 --> 00:23:33,480 SOMEBODY INDICATED THEY FELT 724 00:23:33,480 --> 00:23:35,680 SUICIDAL ON THE PH Q 9 IT WOULD 725 00:23:35,680 --> 00:23:38,720 LEAD THEM THROUGH A SUICIDAL 726 00:23:38,720 --> 00:23:39,880 SEVERITY INDEX, 10%, OVER 10% 727 00:23:39,880 --> 00:23:41,760 NOW OF OUR PATIENT WHO IS HAVE 728 00:23:41,760 --> 00:23:50,960 ENROLLED IN THIS STUDY HAVE 729 00:23:50,960 --> 00:23:53,080 TRIGGERED THE SUICIDALLITY 730 00:23:53,080 --> 00:23:53,600 INDEX. 731 00:23:53,600 --> 00:23:55,440 NOW NO WOAN INDICATED INTENT BUT 732 00:23:55,440 --> 00:23:57,120 JUST THE FACT THAT OUR PATIENTS 733 00:23:57,120 --> 00:23:58,120 MORE THAN PREVIOUSLY HAVE BEEN 734 00:23:58,120 --> 00:23:59,920 THINKING ABOUT DEATH AND DYING 735 00:23:59,920 --> 00:24:01,000 IS REALLY CONCERNING AND I THINK 736 00:24:01,000 --> 00:24:03,480 IT SPEAKS TO THE STATE OF OUR 737 00:24:03,480 --> 00:24:04,640 SOCIETY RIGHT NOW AND OUR 738 00:24:04,640 --> 00:24:15,440 PATIENT POPULATION THAT WE'RE 739 00:24:15,440 --> 00:24:15,960 TRYING TO SERVE. 740 00:24:15,960 --> 00:24:17,800 ONE THING IS WE'VE BEEN TRYING 741 00:24:17,800 --> 00:24:19,880 TO TARGET JUST MENTAL HEALTH AND 742 00:24:19,880 --> 00:24:21,080 ENROLLMENT IS NOT SUCCESSFUL SO 743 00:24:21,080 --> 00:24:23,080 I THINK PATIENTS ARE MORE LIKELY 744 00:24:23,080 --> 00:24:23,960 TO DO BEHAVIORIAL INTERVENTION 745 00:24:23,960 --> 00:24:26,440 FOR PAIN THAN THEY ARE FOR HAD 746 00:24:26,440 --> 00:24:28,400 MENTAL HEALTH AND THEN OF COURSE 747 00:24:28,400 --> 00:24:29,720 THE HEALTH COACHES ARE THE 748 00:24:29,720 --> 00:24:30,880 HIGHLIGHT FOR THIS, AGAIN, I 749 00:24:30,880 --> 00:24:32,080 WANT THINGS TO GO DIGITAL 750 00:24:32,080 --> 00:24:33,600 BECAUSE I THINK THAT'S THE WAY 751 00:24:33,600 --> 00:24:38,160 TO CREATE SCALE BUT THE REMOTE 752 00:24:38,160 --> 00:24:39,000 HEALTH COACHING INTERVENTION IS 753 00:24:39,000 --> 00:24:40,800 SOMETHING THAT COULD BE REALLY 754 00:24:40,800 --> 00:24:42,640 SUCCESSFUL MOVING FORWARD FOR 755 00:24:42,640 --> 00:24:43,960 BEHAVIORIAL INTERVENTIONS TRYING 756 00:24:43,960 --> 00:24:44,600 TO TREAT PAIN. 757 00:24:44,600 --> 00:24:45,680 THEN THE FINAL THING IS, I THINK 758 00:24:45,680 --> 00:24:47,320 THAT WITH ALL OF OUR STUDIES AND 759 00:24:47,320 --> 00:24:49,440 ALL OF OUR BEHAVIORIAL 760 00:24:49,440 --> 00:24:53,520 TREATMENTS, IS SIMPLIFY AND THEN 761 00:24:53,520 --> 00:24:54,040 SIMPLIFY AGAIN. 762 00:24:54,040 --> 00:24:56,240 WE LEARN QUICKLY YOU CAN'T MAKE 763 00:24:56,240 --> 00:24:57,200 THINGS TOO COMPLICATED, KEEPING 764 00:24:57,200 --> 00:24:58,640 IT STRAIGHT FORWARD BUT IF YOU 765 00:24:58,640 --> 00:25:00,120 CAN SIMPLIFY IT, MAKE IT VERY 766 00:25:00,120 --> 00:25:02,320 EASY FOR OUR POPULATION TO 767 00:25:02,320 --> 00:25:04,120 ENGAGE WITH, AND MAKING SURE 768 00:25:04,120 --> 00:25:06,320 THAT IT'S RELEVANT AND RELATABLE 769 00:25:06,320 --> 00:25:08,360 FOR OUR PATIENTS, I THINK WE 770 00:25:08,360 --> 00:25:09,960 WILL FIEBD THESE BEHAVIORIAL 771 00:25:09,960 --> 00:25:10,760 TREATMENTS ARE EFFECTIVE FOR 772 00:25:10,760 --> 00:25:11,160 PAIN. 773 00:25:11,160 --> 00:25:14,440 WE DON'T HAVE THE DATA YET TO BE 774 00:25:14,440 --> 00:25:16,040 ABLE TO RECOMMEND ANY SPECIFIC 775 00:25:16,040 --> 00:25:16,920 BEHAVIORIAL TREATMENTS FOR PAIN 776 00:25:16,920 --> 00:25:18,160 IN SICKLE CELL DISEASE BUT THE 777 00:25:18,160 --> 00:25:19,320 DATA IS COMING AND I LOOK 778 00:25:19,320 --> 00:25:21,120 FORWARD TO MAYBE NEXT YEAR 779 00:25:21,120 --> 00:25:30,400 SHARING MORE OF WHAT'S--WHAT 780 00:25:30,400 --> 00:25:31,440 WE'VE LEARNED. 781 00:25:31,440 --> 00:25:33,840 >> SO THANK YOU VERY MUCH, 782 00:25:33,840 --> 00:25:35,040 CHARLES. 783 00:25:35,040 --> 00:25:36,160 THAT WAS PHENOMENAL, I WANT TO 784 00:25:36,160 --> 00:25:37,440 NOTICE THAT THERE ARE A LOST 785 00:25:37,440 --> 00:25:38,600 DISCUSSIONS IN THE CHAT SO 786 00:25:38,600 --> 00:25:39,640 THAT'S GOING TO BE IMPORTANT FOR 787 00:25:39,640 --> 00:25:40,560 YOU TO LOOK AT. 788 00:25:40,560 --> 00:25:42,680 WE'RE GOING TO SAVE OUR Q&As 789 00:25:42,680 --> 00:25:44,400 TO THE END SO I DON'T WANT 790 00:25:44,400 --> 00:25:45,680 ANYBODY TO THINK WE'RE IGNORING 791 00:25:45,680 --> 00:25:47,240 YOU, WE HAVE A PANEL AT THE END 792 00:25:47,240 --> 00:25:49,560 FOR ALL OF OUR SPEAKERS ISSUES 793 00:25:49,560 --> 00:25:52,640 DON'T WORRY THAT'S COMING UP 794 00:25:52,640 --> 00:25:54,040 SOON. 795 00:25:54,040 --> 00:25:57,840 I'M JULIE KANTER, THANK TO YOU 796 00:25:57,840 --> 00:26:01,400 DR. SAYAI, AND DR. STROUSE, FOR 797 00:26:01,400 --> 00:26:02,560 INTRODUCING OUR PANEL TODAY, WE 798 00:26:02,560 --> 00:26:05,080 COULD TALK ABOUT ALL OF THIS FOR 799 00:26:05,080 --> 00:26:07,040 DAYS, SO WE WILL GOET THROUGH AS 800 00:26:07,040 --> 00:26:08,520 MUCH OF THIS HAS MUCH AS 801 00:26:08,520 --> 00:26:09,720 POSSIBLE AND AS I SAID GET TO 802 00:26:09,720 --> 00:26:11,960 ALL OF YOUR QUESTIONS LATER ON, 803 00:26:11,960 --> 00:26:13,240 I AM REALLY EXCITED TO BE ABLE 804 00:26:13,240 --> 00:26:20,640 TO INTRODUCE OUR NEXT SPEAKER. 805 00:26:20,640 --> 00:26:23,840 DR. SCHLAEGER IS A PABLIST WITH 806 00:26:23,840 --> 00:26:25,320 THE UNIVERSITY OF 807 00:26:25,320 --> 00:26:26,760 ILLINOIS-CHICAGO, SHE HAS AN 808 00:26:26,760 --> 00:26:29,600 EXTENSIVE BACKGROUND AS A 809 00:26:29,600 --> 00:26:30,520 LICENSED ACCUPUNCTURIST WHERE 810 00:26:30,520 --> 00:26:32,520 SHE DEVELOPED RESEARCH IN PAIN, 811 00:26:32,520 --> 00:26:33,840 CERTIFIED MIDWIFE AND SHE IS 812 00:26:33,840 --> 00:26:36,600 JUST REALLY AN AMAZING SPEAKER 813 00:26:36,600 --> 00:26:38,320 AND I'M VERY EXCITED TO SEE WHAT 814 00:26:38,320 --> 00:26:43,600 SHE HAS TO TELL US TODAY SO WITH 815 00:26:43,600 --> 00:26:45,600 THAT I SHOULD ALSO MENTION SHE'S 816 00:26:45,600 --> 00:26:47,040 AMAZINGLY WELL FUNDED AND IF I 817 00:26:47,040 --> 00:26:48,520 WENT TO ALL HER GRANTS WE 818 00:26:48,520 --> 00:26:50,280 WOULDN'T HAVE TIME TO GET 819 00:26:50,280 --> 00:26:51,920 THROUGH HER PRESENTATION, SO 820 00:26:51,920 --> 00:26:52,360 TAKE IT AWAY. 821 00:26:52,360 --> 00:26:55,400 >> THANK YOU FOR THE WONDERFUL 822 00:26:55,400 --> 00:26:55,840 DISTRIBUTION, DOCTOR. 823 00:26:55,840 --> 00:26:58,760 TODAY I WOULD LIKE TO SPEAK WITH 824 00:26:58,760 --> 00:27:00,120 YOU ABOUT NONPHARMACOLOGIC 825 00:27:00,120 --> 00:27:01,160 MODALITIES FOR TREATING SICKLE 826 00:27:01,160 --> 00:27:02,360 CELL PAIN SO WE WILL RUN THROUGH 827 00:27:02,360 --> 00:27:06,400 SOME OF THOSE AND I WILL SHARE 828 00:27:06,400 --> 00:27:10,560 WITH YOU OUR HUGE BABY WHICH IS 829 00:27:10,560 --> 00:27:15,000 OUR GRACE TRIAL WHICH IS LOOKING 830 00:27:15,000 --> 00:27:17,520 AT RELAXATION AS WELL AS 831 00:27:17,520 --> 00:27:18,840 ACCUPUNCTURE FOR THE TREATMENT 832 00:27:18,840 --> 00:27:20,760 OF SICKLE CELL PAIN. 833 00:27:20,760 --> 00:27:22,720 AND WITH NO FURTHER ADO, LET'S 834 00:27:22,720 --> 00:27:23,440 GET GOING HERE. 835 00:27:23,440 --> 00:27:24,880 NEXT, PLEASE. 836 00:27:24,880 --> 00:27:28,360 THE USE OF ACCUPUNCTURE AND 837 00:27:28,360 --> 00:27:29,040 OTHER NONPHARMAICOLOGGIC 838 00:27:29,040 --> 00:27:30,720 MODALITIES TO REDUCE PAIN, 839 00:27:30,720 --> 00:27:32,320 OPIOID USE AND ENABLE THEMSELVES 840 00:27:32,320 --> 00:27:34,120 TO BETTER COPE WITH THEIR PAIN 841 00:27:34,120 --> 00:27:35,440 AND WELL KNOWN. 842 00:27:35,440 --> 00:27:38,280 OUT OF 227 ADULT RESPONDENTS, 843 00:27:38,280 --> 00:27:39,840 92% EXPERIENCE CHRONIC PAIN AND 844 00:27:39,840 --> 00:27:43,440 92% OF THOSE RESPONDED TO USE 845 00:27:43,440 --> 00:27:45,560 SOME FORM OF NONPHARMAICOLOGGIC 846 00:27:45,560 --> 00:27:46,720 THERAPY TO MANAGE CHRONIC PAIN. 847 00:27:46,720 --> 00:27:48,880 A FEW STUDY VS ADEQUATELY 848 00:27:48,880 --> 00:27:51,000 EVALUATED THE EFFECTIVENESS OF 849 00:27:51,000 --> 00:27:54,480 THESE THERAPIES, NEXT, PLEASE. 850 00:27:54,480 --> 00:27:58,040 THERE ARE 2 METAANOLL SIS THAT 851 00:27:58,040 --> 00:27:59,080 WE AS ACCUPUNCTURE 852 00:27:59,080 --> 00:28:02,040 METHODOLOGISTS AND SCIENTISTS 853 00:28:02,040 --> 00:28:03,840 USE TO SUBSTANTIATE USING 854 00:28:03,840 --> 00:28:05,040 ACCUPUNCTURE FOR THE TREATMENT 855 00:28:05,040 --> 00:28:10,720 OF CHRONIC PAIN, BOTH BY VICARS 856 00:28:10,720 --> 00:28:13,480 ET AL, 1 WAS THE META-ANALYSIS 857 00:28:13,480 --> 00:28:15,360 OF ALMOST 21 PATIENTS THAT 858 00:28:15,360 --> 00:28:16,520 SHOWED A STATISTICALLY 859 00:28:16,520 --> 00:28:18,640 SIGNIFICANT DIFFERENCE BETWEEN 860 00:28:18,640 --> 00:28:21,800 THE ACCUPUNCTURE GROUP VERSUS 861 00:28:21,800 --> 00:28:24,440 THE SHAM ACCUPUNCTURE GROUP, FOR 862 00:28:24,440 --> 00:28:27,080 TREATING MUSK LO SKELETAL PAIN, 863 00:28:27,080 --> 00:28:28,840 OFTIO RGTERATEIS EXPOO SHOULDER 864 00:28:28,840 --> 00:28:31,120 AND NECK AND PAIN. 865 00:28:31,120 --> 00:28:38,960 THEY LOOKED AT DURATION OF THE 866 00:28:38,960 --> 00:28:40,240 ACCUPUNCTURE EFFECT ALMOST 6400 867 00:28:40,240 --> 00:28:40,600 PATIENTS. 868 00:28:40,600 --> 00:28:43,600 UP TO 90% OF THE ACCUPUNCTURE 869 00:28:43,600 --> 00:28:46,320 EFFECT WAS PRESENT 1 YEAR AFTER 870 00:28:46,320 --> 00:28:46,600 TREATMENT. 871 00:28:46,600 --> 00:28:47,440 NEXT PLEASE. 872 00:28:47,440 --> 00:28:50,520 IN TERMS OF PHYSIOLOGICAL 873 00:28:50,520 --> 00:28:52,040 EFFECTS OF ACCUPUNCTURE, IT 874 00:28:52,040 --> 00:28:56,040 RELIEVES PAIN BY THE EMILY 875 00:28:56,040 --> 00:28:58,640 CIBOL, NEOCORTICALE SYSTEM, ACT 876 00:28:58,640 --> 00:29:00,600 ACTIVATES RECEPTORS, INCREASES 877 00:29:00,600 --> 00:29:02,640 SERUM, BETA ENDORPHINS, DOWN 878 00:29:02,640 --> 00:29:06,240 REGULATES M1 MACROFAJS, IL1 B, 879 00:29:06,240 --> 00:29:09,600 IL6 AND IL18 AND TNF, 880 00:29:09,600 --> 00:29:11,240 ACCUPUNCTURE REGULATES CENTRAL 881 00:29:11,240 --> 00:29:14,720 AND PERIPHERAL BLOOD FLOW AND 882 00:29:14,720 --> 00:29:19,040 REGULATED THE HBA ACCESS BY 883 00:29:19,040 --> 00:29:23,760 REDUCING ACTHRELEASE FROM THE 884 00:29:23,760 --> 00:29:25,840 ANTERIOR PITUITARYY WITH THE 885 00:29:25,840 --> 00:29:28,680 SUBSEQUENT REDUCTION IN ADRENAL 886 00:29:28,680 --> 00:29:28,920 CORTEX. 887 00:29:28,920 --> 00:29:29,880 NEXT, PLEASE. 888 00:29:29,880 --> 00:29:32,320 IN TERMS OF PEDIATRIC 889 00:29:32,320 --> 00:29:33,720 ACCUPUNCTURE, THERE ARE 4, 1 IS 890 00:29:33,720 --> 00:29:36,200 FOCUSED ON CHRONIC PAIN, 2 ARE 891 00:29:36,200 --> 00:29:38,200 FOCUS ONED ACUTE VOCs AND 1 ON 892 00:29:38,200 --> 00:29:39,240 ACUTE AND CHRONIC PAIN. 893 00:29:39,240 --> 00:29:41,840 THE FIRST WAS A RETROSPECTIVE 894 00:29:41,840 --> 00:29:44,760 CHART REVIEW OF THE 16 YEAR-OLD 895 00:29:44,760 --> 00:29:47,680 GIRL WHO RECEIVED 58 ACUE 896 00:29:47,680 --> 00:29:49,040 PURNGHTURE IN-PATIENT AND 897 00:29:49,040 --> 00:29:50,000 OUT-PATIENT TREATMENT OVER 3 898 00:29:50,000 --> 00:29:50,320 YEARS. 899 00:29:50,320 --> 00:29:52,040 NO PAIN SCORES WERE REPORTED BUT 900 00:29:52,040 --> 00:29:55,640 THERE WAS AN 80% REDUCTION IN ED 901 00:29:55,640 --> 00:29:56,040 VISITS. 902 00:29:56,040 --> 00:29:58,480 FIRST UNCONTROLLED STUDY HAD 903 00:29:58,480 --> 00:30:00,240 ONLY 2 PATIENTS. 904 00:30:00,240 --> 00:30:01,520 THEY BOTH THOUGHT ACCUPUNCTURE 905 00:30:01,520 --> 00:30:02,840 WAS BENEFICIAL FOR THEIR PAIN, 906 00:30:02,840 --> 00:30:04,040 THE SECOND UNCONTROLLED STUDY 907 00:30:04,040 --> 00:30:05,840 WAS FOR ACUTE AND CHRONIC PAIN 908 00:30:05,840 --> 00:30:07,960 IN 12 CHILDREN WHO HAD 909 00:30:07,960 --> 00:30:10,480 ACCUPUNCTURE A TOTAL OF 33 910 00:30:10,480 --> 00:30:10,840 TIMES. 911 00:30:10,840 --> 00:30:12,640 WITHIN GROUP SCORES FOR 912 00:30:12,640 --> 00:30:13,800 ACCUPUNCTURE SHOWED A REDUCTION 913 00:30:13,800 --> 00:30:15,040 IN PAIN, THE ONLY CONTROLLED 914 00:30:15,040 --> 00:30:18,520 STUDY WAS AN RCT WHICH WAS DONE 915 00:30:18,520 --> 00:30:21,280 FOR ACCEPTABILITY, THAT LOOKED 916 00:30:21,280 --> 00:30:23,440 AT ACCUPUNCTURE VERSUS IN 917 00:30:23,440 --> 00:30:24,880 CHILDREN VERSUS CHILDREN 918 00:30:24,880 --> 00:30:26,440 UNINTERESTED IN RECEIVING ACUE 919 00:30:26,440 --> 00:30:29,240 PUVENGHTURE FOR ACUTE VOCs, 920 00:30:29,240 --> 00:30:30,440 ACCUPUNCTURE WAS FOUND TO BE 921 00:30:30,440 --> 00:30:32,040 ACCEPTABLE AND THERE WAS A 922 00:30:32,040 --> 00:30:33,360 REDUCTION WITHIN GROUP PAIN 923 00:30:33,360 --> 00:30:36,160 SCORES IN THE ACCUPUNCTURE 924 00:30:36,160 --> 00:30:36,360 GROUP. 925 00:30:36,360 --> 00:30:38,560 NEXT PLEASE. 926 00:30:38,560 --> 00:30:42,440 FOR ADULT--NEXT SLIDE, PLEASE. 927 00:30:42,440 --> 00:30:44,040 THANK YOU. 928 00:30:44,040 --> 00:30:45,440 FOR ADULT ACCUPUNCTURE, THERE 929 00:30:45,440 --> 00:30:48,520 ARE 3 STUDIES, 2 FOR ACUTE 930 00:30:48,520 --> 00:30:50,760 VOCs, 1 FOR CHRONIC PAIN, ALL 931 00:30:50,760 --> 00:30:51,240 WERE UNCONTROLLED. 932 00:30:51,240 --> 00:30:53,840 THE FIRST STUDY OF 9 IN-PATIENTS 933 00:30:53,840 --> 00:30:56,320 HAD A MEDIAN OF 3 ACCUPUNCTURE 934 00:30:56,320 --> 00:30:58,040 TREATMENTS EACH AND AVERAGE PAIN 935 00:30:58,040 --> 00:31:00,480 REDUCTION OF 2 OUT OF 10. 936 00:31:00,480 --> 00:31:02,040 SECOND EVALUATED 16 ACUTE 937 00:31:02,040 --> 00:31:03,640 PAINFUL CRISIS, EXPERIENCED BY 938 00:31:03,640 --> 00:31:05,240 10 PATIENTS, PATIENTS IN THE 939 00:31:05,240 --> 00:31:07,480 STUDY ACHIEVED PAIN RELIEVE IN 940 00:31:07,480 --> 00:31:11,800 15 OF 16 ACUTE PAIN EPISODES, 941 00:31:11,800 --> 00:31:14,840 AFTER RECEIVING EITHER 942 00:31:14,840 --> 00:31:16,080 ACCUPUNCTURE OR SHAM 943 00:31:16,080 --> 00:31:17,960 ACCUPUNCTURE, THE THIRD WAS A 1 944 00:31:17,960 --> 00:31:22,040 ARM FEASIBILITY AND 945 00:31:22,040 --> 00:31:23,120 ACCEPTABILITY STUDY OF 5 ADULTS 946 00:31:23,120 --> 00:31:27,400 WHO RECEIVED A STANDARD PROTOCOL 947 00:31:27,400 --> 00:31:31,440 FOR 10 SESSIONS, 2 TIMES A WEEK 948 00:31:31,440 --> 00:31:33,520 FOR 5 WEEKS, PAIN INTENSITY AND 949 00:31:33,520 --> 00:31:35,240 PAIN INTERFERENCE WAS REDUCED AS 950 00:31:35,240 --> 00:31:36,560 WELL AS ANXIOUS, DEPRESSION, 951 00:31:36,560 --> 00:31:40,400 ANGER AND SLEEP DISTURBANCE. 952 00:31:40,400 --> 00:31:41,240 NEXT, PLEASE. 953 00:31:41,240 --> 00:31:44,120 THERE WAS 1 RCT AND 2 954 00:31:44,120 --> 00:31:45,400 UNCONTROLLED STUDIES LOOKING AT 955 00:31:45,400 --> 00:31:47,120 MASSAGE IN CHILDREN AND 956 00:31:47,120 --> 00:31:49,320 ADOLESCENCE ALL FOR CHRONIC 957 00:31:49,320 --> 00:31:50,440 PAIN. 958 00:31:50,440 --> 00:31:51,040 THIRTY-FOUR CHILDREN IN 959 00:31:51,040 --> 00:31:52,960 ADOLESCENCE AND THEIR APPARENTS 960 00:31:52,960 --> 00:31:54,880 WERE ASSIGNED TO A MASSAGE 961 00:31:54,880 --> 00:31:56,640 THERAPY OR AN ATTENTION CONTROL 962 00:31:56,640 --> 00:31:57,320 GROUP. 963 00:31:57,320 --> 00:31:58,640 PARENTS PROVIDED NIGHTLY 964 00:31:58,640 --> 00:32:01,160 MASSAGES, THE PARENTS GIVING 965 00:32:01,160 --> 00:32:03,520 MASSAGE HAD INCREASED ANXIETY 966 00:32:03,520 --> 00:32:05,080 AND DEPRESSION, THE CHILDREN 967 00:32:05,080 --> 00:32:09,680 RECEIVING MASSAGE HAD DECREASED 968 00:32:09,680 --> 00:32:11,240 PAIN, ANXIETY AND DEPRESSION, 969 00:32:11,240 --> 00:32:13,000 THE SECOND STUDY EXAMINED 970 00:32:13,000 --> 00:32:15,640 MASSAGE IN 4 CHILDREN AND 1 971 00:32:15,640 --> 00:32:18,080 ADULT, THE NUMBER OF SESSIONS OF 972 00:32:18,080 --> 00:32:20,080 NOT SPEC PIED BUT GROUP PAIN 973 00:32:20,080 --> 00:32:21,160 SCORES WERE REDUCED. 974 00:32:21,160 --> 00:32:22,560 THE THIRD UNCONTROLLED STUDY WAS 975 00:32:22,560 --> 00:32:25,000 A MASSAGE VERSUS A GUIDED 976 00:32:25,000 --> 00:32:25,840 IMAGERY RELAXATION INTERVENTION 977 00:32:25,840 --> 00:32:27,680 FOR THE MASSAGE GROUP WITHIN 978 00:32:27,680 --> 00:32:31,880 GROUP PAIN SCORES WERE ALSO 979 00:32:31,880 --> 00:32:33,360 REDUCED. 980 00:32:33,360 --> 00:32:36,800 NEXT PLEASE. 981 00:32:36,800 --> 00:32:37,320 NEXT, SLIDE, PLEASE. 982 00:32:37,320 --> 00:32:40,400 THERE WERE 2 STUDIES OF YOGA IN 983 00:32:40,400 --> 00:32:42,000 CHILDREN AND ADOLESCENCE, 1 WAS 984 00:32:42,000 --> 00:32:43,960 A FEASIBILITY STUDY, THE OTHER 985 00:32:43,960 --> 00:32:46,160 WAS AN RCT FEASIBILITY AND 986 00:32:46,160 --> 00:32:46,840 ACCEPTABILITY STUDY, THE FIRST 987 00:32:46,840 --> 00:32:49,400 STUDY FIRST PART WAS A SURVEY OF 988 00:32:49,400 --> 00:32:50,640 15 ADOLESCENTS AND THEIR 989 00:32:50,640 --> 00:32:53,240 PATIENTS TO DESCRIBE PAIN 990 00:32:53,240 --> 00:32:54,240 CHARACTERISTICS, ATTITUDES AND 991 00:32:54,240 --> 00:32:57,160 PRACTICES RELATED TO YOGA, AND 992 00:32:57,160 --> 00:32:58,440 POTENTIAL ACCEPTABILITY OF A 993 00:32:58,440 --> 00:33:01,160 YOGA PROGRAM FOR CHRONIC SICKLE 994 00:33:01,160 --> 00:33:02,000 CELL PAIN. 995 00:33:02,000 --> 00:33:03,440 PATIENTS WITH SICKLE CELL AND 996 00:33:03,440 --> 00:33:05,560 CHRONIC PAIN OVERALL HAD A 997 00:33:05,560 --> 00:33:07,240 POSITIVE OPINION OF YOGA, BUT 998 00:33:07,240 --> 00:33:08,640 THERE WERE CHALLENGES WITH 999 00:33:08,640 --> 00:33:11,040 RECRUITMENT AND RETENTION OF 1000 00:33:11,040 --> 00:33:12,640 PARTICIPANTS, AND BARRIERS TO 1001 00:33:12,640 --> 00:33:16,040 FEASIBILITY OF AN IN-PERSON 1002 00:33:16,040 --> 00:33:16,560 GROUP YOGA INTERVENTION. 1003 00:33:16,560 --> 00:33:19,040 THE SECOND STUDY WAS AN RCT OF 1004 00:33:19,040 --> 00:33:22,760 73 CHILDREN OF YOGA, VERSUS 1005 00:33:22,760 --> 00:33:25,280 ATTENTION CONTROL PERFORMED IN 1006 00:33:25,280 --> 00:33:27,560 PATIENT FOR UNCOMPLICATED 1007 00:33:27,560 --> 00:33:28,040 VOCs. 1008 00:33:28,040 --> 00:33:30,520 CHILDREN RANDOMIZED TOIOLA HAD A 1009 00:33:30,520 --> 00:33:31,440 SIGNIFICANTLY GREATER REDUCTION 1010 00:33:31,440 --> 00:33:33,320 IN MEAN PAIN SCORE AFTER 1 YOGA 1011 00:33:33,320 --> 00:33:36,720 SESSION COMPARED TO THE CONTROLS 1012 00:33:36,720 --> 00:33:38,840 THIS STUDY SUGGESTS THAT YOGA IS 1013 00:33:38,840 --> 00:33:41,360 ACCEPTABLE AND FEASIBILITY AND 1014 00:33:41,360 --> 00:33:43,240 MAY REDUCE PAIN IN HOSPITALIZED 1015 00:33:43,240 --> 00:33:51,960 CHILDREN WITH ACUTE VOCs. 1016 00:33:51,960 --> 00:33:52,920 NEXT PLEASE. 1017 00:33:52,920 --> 00:33:54,640 THERE WAS 1 UNCONTROLLED STUDY 1018 00:33:54,640 --> 00:33:56,440 OF 8 CHILDREN RECEIVING 12 1019 00:33:56,440 --> 00:33:58,560 SESSIONS EACH OF BIOFEEDBACK FOR 1020 00:33:58,560 --> 00:33:59,840 CHRONIC PAIN. 1021 00:33:59,840 --> 00:34:02,120 A REPEATED MEASURES OF NOVA 1022 00:34:02,120 --> 00:34:03,240 COMPARED THE FIRST AND LAST 1023 00:34:03,240 --> 00:34:06,200 WEEKS OF TRAINING AND REVEALED A 1024 00:34:06,200 --> 00:34:07,240 SIGNIFICANT REDUCTION IN 1025 00:34:07,240 --> 00:34:09,520 REPORTED PAIN INTENSITY AND THE 1026 00:34:09,520 --> 00:34:10,840 FREQUENCY OF SELF-TREATED VOCs 1027 00:34:10,840 --> 00:34:12,680 FROM THE FIRST 1-4 WEEKS 1028 00:34:12,680 --> 00:34:16,040 COMPARED TO THE LAST 9-12 WEEKS. 1029 00:34:16,040 --> 00:34:16,520 NEXT PLEASE. 1030 00:34:16,520 --> 00:34:18,440 --EXCUSE ME, PARDON ME, 1 MORE, 1031 00:34:18,440 --> 00:34:20,840 THERE WAS A CASE STUDY OF 1 1032 00:34:20,840 --> 00:34:24,240 ADULT LOOKING AT A REHAB THAT 1033 00:34:24,240 --> 00:34:26,440 INCLUDED EXERCISE, STRETCHING, 1034 00:34:26,440 --> 00:34:28,040 AEROBIC AND RELAXATION PROGRAMS 1035 00:34:28,040 --> 00:34:31,680 TWICE PER WEEK FOR 5 WEEKS WITH 1036 00:34:31,680 --> 00:34:33,440 SCORES FOR AVERAGE PAIN AND FOR 1037 00:34:33,440 --> 00:34:36,040 THE SENSORY PAIN INDEX FOR THE 1038 00:34:36,040 --> 00:34:38,400 MIGUEL PAIN QUESTIONNAIRE WERE 1039 00:34:38,400 --> 00:34:38,920 BOTH REDUCED. 1040 00:34:38,920 --> 00:34:40,760 NEXT, PLEASE. 1041 00:34:40,760 --> 00:34:42,400 FOR GUIDED RELAXATION, THERE 1042 00:34:42,400 --> 00:34:44,560 WERE 2 RCTs ARE FEASIBILITY 1043 00:34:44,560 --> 00:34:48,920 AND ACCEPTABILITY OF GUIDED 1044 00:34:48,920 --> 00:34:50,280 RELAXATION, VERSUS ATTENTION 1045 00:34:50,280 --> 00:34:50,800 CONTROL. 1046 00:34:50,800 --> 00:34:52,840 THE FIRST WAS 15 RESULTS WHO 1047 00:34:52,840 --> 00:34:54,720 USED A GUIDE EDUCATIONAL VIDEO 1048 00:34:54,720 --> 00:34:56,400 ONCE PERDAY FOR 2 WEEKS. 1049 00:34:56,400 --> 00:34:58,400 GUIDED RELAXATION WAS FOUND TO 1050 00:34:58,400 --> 00:34:59,040 BE FEASIBILITYIBLE AND 1051 00:34:59,040 --> 00:35:00,840 ACCEPTABLE AND THERE WAS A LARGE 1052 00:35:00,840 --> 00:35:02,640 REDUCTION IN THE COMPOSITE INDEX 1053 00:35:02,640 --> 00:35:11,880 IN THE GUIDED RELAXATION GROUP. 1054 00:35:11,880 --> 00:35:16,760 ONE LOOKED AT A 12 MINNITE VIDEO 1055 00:35:16,760 --> 00:35:19,440 OF RELUXURIATION ON A MOBILE 1056 00:35:19,440 --> 00:35:20,120 DEVICE VERSUS CONTROL. 1057 00:35:20,120 --> 00:35:22,640 FINDINGS SHOW IT WAS IT FEASIBLE 1058 00:35:22,640 --> 00:35:24,840 AND ACCEPTABLE TO DELIVER GUIDED 1059 00:35:24,840 --> 00:35:28,320 RELAXATION ON A COMPUTER TABLET. 1060 00:35:28,320 --> 00:35:28,800 NEXT, PLEASE. 1061 00:35:28,800 --> 00:35:32,240 IN TERMS OF OUR LIMITATIONS AND 1062 00:35:32,240 --> 00:35:35,880 CONCLUSIONS, AS DR. CHARLES HAD 1063 00:35:35,880 --> 00:35:38,560 MENTIONED, THERE'S A PAUCITY OF 1064 00:35:38,560 --> 00:35:41,040 STUDIES OVERALL IN ACCUPUNCTURE 1065 00:35:41,040 --> 00:35:43,080 AND OTHER NONPHARMAICOLOGGIC 1066 00:35:43,080 --> 00:35:43,640 INTERVENTIONS, PRELIMINARY 1067 00:35:43,640 --> 00:35:46,920 STUDIES HAD METHOD LOGIC ISSUES 1068 00:35:46,920 --> 00:35:48,800 HAMPERING GBLIZED ABILITIES, 1069 00:35:48,800 --> 00:35:50,520 WEAKNESSES INCLUDE RELIANCE ON 1070 00:35:50,520 --> 00:35:51,480 RETROSPECTIVE CHART REVIEWS AND 1071 00:35:51,480 --> 00:35:53,240 CASE STUDIES, LACK OF CONTROL 1072 00:35:53,240 --> 00:35:55,640 QUOM PAIR SONS AND SMALL SAMPLE 1073 00:35:55,640 --> 00:35:58,840 SYSTEMS, RESEARCH ON 1074 00:35:58,840 --> 00:35:59,320 ACCUPUNCTURE AND 1075 00:35:59,320 --> 00:36:03,080 UNNONFORMICOLOGGIC MODALITIES 1076 00:36:03,080 --> 00:36:06,120 FOR SICKLE CELL PAIN IS IN ITS 1077 00:36:06,120 --> 00:36:07,280 INFANCY AND ADDITIONAL RESOURCES 1078 00:36:07,280 --> 00:36:09,360 ARE NEED TO REDUCE CHRONIC PAIN 1079 00:36:09,360 --> 00:36:10,840 AND OPIOID USE FOR INDIVIDUALS 1080 00:36:10,840 --> 00:36:12,440 WITH SICKLE CELL. 1081 00:36:12,440 --> 00:36:12,800 NEXT, PLEASE. 1082 00:36:12,800 --> 00:36:15,840 NOW I WOULD LIKE TO SHARE WITH 1083 00:36:15,840 --> 00:36:17,720 YOU OUR CURRENT STUDY FUNDED 1084 00:36:17,720 --> 00:36:20,000 THROUGH NCCIH AND THE NIH 1085 00:36:20,000 --> 00:36:22,280 PRAGMATIC TRIALS COLLABRATORY AS 1086 00:36:22,280 --> 00:36:25,840 WELL AS NIH HEAL INITIATIVE, 1087 00:36:25,840 --> 00:36:26,560 HYBRID EFFECTIVENESS 1088 00:36:26,560 --> 00:36:29,040 IMPLEMENTATION TRIAL OF GUIDED 1089 00:36:29,040 --> 00:36:30,960 RELAXATION AND ACCUPUNCTURE FOR 1090 00:36:30,960 --> 00:36:32,360 CHRONIC SICKLE CELL DISEASE PAIN 1091 00:36:32,360 --> 00:36:36,000 OR THE GRACE TRIAL. 1092 00:36:36,000 --> 00:36:36,320 NEXT, PLEASE. 1093 00:36:36,320 --> 00:36:39,760 THE GRACE TRIAL IS PART OF THE 1094 00:36:39,760 --> 00:36:41,120 NIH PRAGMATIC TRIALS 1095 00:36:41,120 --> 00:36:41,760 COLLABRATORY. 1096 00:36:41,760 --> 00:36:43,760 THE NIH PRAGMATIC TRIALS 1097 00:36:43,760 --> 00:36:45,240 COLLABRATORY WAS INITIATED IN 1098 00:36:45,240 --> 00:36:48,240 THE NIH COMMON FUND IN 20 WITH 1099 00:36:48,240 --> 00:36:48,400 12. 1100 00:36:48,400 --> 00:36:50,760 SELECTED AS THE PRAGMATIC AND 1101 00:36:50,760 --> 00:36:51,920 IMPLEMENTATION STUDY FOR THE 1102 00:36:51,920 --> 00:36:55,240 MANAGEMENT OF PAIN TO REDUCE 1103 00:36:55,240 --> 00:36:57,760 OPIOID PRESCRIBING OR THE PRISM 1104 00:36:57,760 --> 00:37:01,200 FUND RESOURCE COORDINATING 1105 00:37:01,200 --> 00:37:01,640 CENTER IN 2019. 1106 00:37:01,640 --> 00:37:03,600 THE GOAL IS TO STRENGTHEN THE 1107 00:37:03,600 --> 00:37:06,320 NATIONAL CAPACITY TO IMPLEMENT 1108 00:37:06,320 --> 00:37:07,680 COST EFFECTIVE LARGE SCALE 1109 00:37:07,680 --> 00:37:09,880 RESEARCH STUDIES THAT ENGAGE 1110 00:37:09,880 --> 00:37:11,480 HEALTHCARE DELIVERY ORGANIZE 1111 00:37:11,480 --> 00:37:13,240 EGGs AS RESEARCH PARTNERS. 1112 00:37:13,240 --> 00:37:15,520 THE VISION, IS TO SUPPORT THE 1113 00:37:15,520 --> 00:37:19,440 DESIGN AND EXECUTION OF 1114 00:37:19,440 --> 00:37:20,840 INNOVATIVE PRAGMATIC CLINICAL 1115 00:37:20,840 --> 00:37:28,000 TRIAL DEMONSTRATION PROJECTS TO 1116 00:37:28,000 --> 00:37:28,960 ESTABLISH BEST PRACTICES AND 1117 00:37:28,960 --> 00:37:30,000 PROOF OF CONCEPT. 1118 00:37:30,000 --> 00:37:30,320 NEXT, PLEASE. 1119 00:37:30,320 --> 00:37:35,000 THE GRACE TRIAL IS 1 OF 22 1120 00:37:35,000 --> 00:37:38,360 DEMONSTRATION PROJECTS IN THE 1121 00:37:38,360 --> 00:37:39,760 NIH PRAGMATIC TRIALS, AND IF YOU 1122 00:37:39,760 --> 00:37:40,800 NOTICE THE POINTER RIGHT DOWN 1123 00:37:40,800 --> 00:37:44,640 HERE IN THE BOTTOM RIGHT CORNER, 1124 00:37:44,640 --> 00:37:46,360 PRAGMATIC TRIALS EMBEDDED IN 1125 00:37:46,360 --> 00:37:47,440 HEALTHCARE SYSTEMS TO ADDRESS 1126 00:37:47,440 --> 00:37:50,120 QUESTIONS OF MAJOR PUBLIC HEALTH 1127 00:37:50,120 --> 00:37:51,560 IMPORTANCE INCLUDE DEMONSTRATION 1128 00:37:51,560 --> 00:37:51,840 PROJECTS. 1129 00:37:51,840 --> 00:37:53,920 THE PROJECTS SPAN MULTIPLE NIH 1130 00:37:53,920 --> 00:37:55,640 INSTITUTES, CENTERS AND OFFICES. 1131 00:37:55,640 --> 00:37:58,680 THERE'S A 1 YEAR PLANNING PHASE 1132 00:37:58,680 --> 00:37:59,600 FOLLOWED BY IMPLEMENTATION PHASE 1133 00:37:59,600 --> 00:38:06,440 AND ALL OF THESE DEMONSTRATION 1134 00:38:06,440 --> 00:38:13,440 PROGECS. 1135 00:38:13,440 --> 00:38:15,200 NEXT PLEASE. 1136 00:38:15,200 --> 00:38:17,440 PRAGMATIC TRIALS PRODUCING 1137 00:38:17,440 --> 00:38:19,160 RESULTS IN THE REAL WORLD, THEY 1138 00:38:19,160 --> 00:38:21,200 MAY TEST THE SAME INTERVENTION 1139 00:38:21,200 --> 00:38:22,320 AS AN EXPLANATORY TRIAL. 1140 00:38:22,320 --> 00:38:24,920 WE USE TYPICAL PATIENTS, THEY 1141 00:38:24,920 --> 00:38:27,040 USE CLINICIANS WHO MAY NOT BE 1142 00:38:27,040 --> 00:38:29,880 RESEARCHERS, AND THEY MEASURE 1143 00:38:29,880 --> 00:38:31,440 EFFECTIVENESS, HOW WELL THE 1144 00:38:31,440 --> 00:38:34,360 INTERVENTION PERFORMS IN THE 1145 00:38:34,360 --> 00:38:37,320 REAL WORLD. 1146 00:38:37,320 --> 00:38:39,120 NEXT PLEASE. 1147 00:38:39,120 --> 00:38:40,240 EMBEDDED PRAGMATIC CLINICAL 1148 00:38:40,240 --> 00:38:42,280 TRIALS BRIDGE RESEARCH INTO 1149 00:38:42,280 --> 00:38:43,840 CLINICAL CARE. 1150 00:38:43,840 --> 00:38:48,240 EMBEDDED PRAGMATIC CLINICAL 1151 00:38:48,240 --> 00:38:50,000 TRIALS ARE STUDIES WITH INPUT 1152 00:38:50,000 --> 00:38:51,080 FROM STAKEHOLDERS SUCH AS 1153 00:38:51,080 --> 00:38:54,200 PATIENTS AND CLINICIANS AND 1154 00:38:54,200 --> 00:38:55,840 SOMETIMES HOSPITALS 1155 00:38:55,840 --> 00:38:57,000 ADMINISTRATION, DATA IS 1156 00:38:57,000 --> 00:38:59,960 COLLECTED THROUGH EHRs IN THE 1157 00:38:59,960 --> 00:39:00,440 HEALTHCARE SETTINGS. 1158 00:39:00,440 --> 00:39:02,040 AND THE OUTCOMES ARE IMPORTANT 1159 00:39:02,040 --> 00:39:05,600 TO DECISION MAKERS SUCH AS 1160 00:39:05,600 --> 00:39:07,440 POLITICIANS, MEDICARE AND 1161 00:39:07,440 --> 00:39:09,760 MEDICAID AND INTERVENTIONS ARE 1162 00:39:09,760 --> 00:39:12,280 INCORPORATED INTO ROUTINE 1163 00:39:12,280 --> 00:39:14,160 CLINICAL WORK FLOWS, OFTEN THESE 1164 00:39:14,160 --> 00:39:17,400 TRIALS USE DIVERSE 1165 00:39:17,400 --> 00:39:25,320 REPRESENTATIVES, TODAY 1166 00:39:25,320 --> 00:39:28,840 POPULATIONS, NEXT, PRAGMATIC AND 1167 00:39:28,840 --> 00:39:31,000 IMPLEMENTATION STUDIES FOR THE 1168 00:39:31,000 --> 00:39:31,960 PAIN FOR OPIOID PRESCRIBING OR 1169 00:39:31,960 --> 00:39:36,120 AS WE KNOW IT THE PRISON 1170 00:39:36,120 --> 00:39:37,000 PROGRAM. 1171 00:39:37,000 --> 00:39:37,240 NEXT. 1172 00:39:37,240 --> 00:39:38,640 THE PRISM PROGRAM IS FUNDED 1173 00:39:38,640 --> 00:39:41,000 THROUGH THE NIH HEAL INITIATIVE, 1174 00:39:41,000 --> 00:39:43,440 PRISM TRIALS FOCUS ON NONOPIOID 1175 00:39:43,440 --> 00:39:45,280 INTERVENTIONS TO MANAGE PAIN AND 1176 00:39:45,280 --> 00:39:47,400 REDUCE RELIANCE ON OPIOIDS, 1177 00:39:47,400 --> 00:39:49,760 PRISM PRAGMATIC TRIALS SEEK TO 1178 00:39:49,760 --> 00:39:52,280 IDIDN'TIFY EFFECTIVE STRATEGIES 1179 00:39:52,280 --> 00:39:55,240 TO IMPLEMENT EVIDENCE-BASED 1180 00:39:55,240 --> 00:39:56,720 INTERVENTIONS. 1181 00:39:56,720 --> 00:39:57,040 NEXT, PLEASE. 1182 00:39:57,040 --> 00:39:59,440 THE SIGNIFICANCE OF THE GRACE 1183 00:39:59,440 --> 00:40:01,080 TRIAL IS FOUND IN THAT 1184 00:40:01,080 --> 00:40:01,800 INDIVIDUALS WITH SICKLE CELL 1185 00:40:01,800 --> 00:40:04,640 HAVE A HIGH LEVEL OF PAIN, PAIN 1186 00:40:04,640 --> 00:40:08,440 IS THE LEADING CAUSE OF ED 1187 00:40:08,440 --> 00:40:10,200 VISITS AND HOSPITAL ADMISSIONS. 1188 00:40:10,200 --> 00:40:12,480 TREATMENTS FOCUS IS USUALLY ON 1189 00:40:12,480 --> 00:40:16,880 MEDICATION THERAPIES SUCH AS 1190 00:40:16,880 --> 00:40:18,440 OPIOIDS, FEW COMPLIMENTARY 1191 00:40:18,440 --> 00:40:19,600 INTEGRATIVE HEALTH THERAPIES ARE 1192 00:40:19,600 --> 00:40:23,640 TESTED TO REDUCE PAIN AND OPIOID 1193 00:40:23,640 --> 00:40:24,320 USE. 1194 00:40:24,320 --> 00:40:25,400 NEXT, PLEASE. 1195 00:40:25,400 --> 00:40:29,040 IN TERMS OF OUR UG3 UH 3, WHICH 1196 00:40:29,040 --> 00:40:30,840 IS OUR PRAGMATIC TRIAL OR GRACE 1197 00:40:30,840 --> 00:40:34,120 TRIAL, WE ARE A TYPE 1 HIBRIDE 1198 00:40:34,120 --> 00:40:34,720 EFFECTIVENESS IMPLEMENTATION 1199 00:40:34,720 --> 00:40:38,360 TRIAL, SO WE ARE LOOKING MORE AT 1200 00:40:38,360 --> 00:40:39,920 EFFECTIVENESS THAN I. 1201 00:40:39,920 --> 00:40:40,240 ELEMENTATION. 1202 00:40:40,240 --> 00:40:43,360 OUR FIRST NAME IS TO ASSESS THE 1203 00:40:43,360 --> 00:40:44,400 EFFECTIVENESS OF ACCUPUNCTURE 1204 00:40:44,400 --> 00:40:46,600 AND GUIDED RELAXATION IN TREATS 1205 00:40:46,600 --> 00:40:49,640 CHRONIC SICKLE CELL PAIN. 1206 00:40:49,640 --> 00:40:53,120 OUR FOURTH AIM IS TO IDENTIFY 1207 00:40:53,120 --> 00:40:54,640 FACILITATORS, CHALLENGES, AND 1208 00:40:54,640 --> 00:40:55,720 SOLUTIONS FOR SEAMLESS 1209 00:40:55,720 --> 00:40:57,440 INTEGRATION OF THESE CIH 1210 00:40:57,440 --> 00:41:03,120 THERAPIES IN 3 HEALTH SYSTEMS. 1211 00:41:03,120 --> 00:41:03,320 NEXT. 1212 00:41:03,320 --> 00:41:05,000 THE 3 HEALTH SYSTEMS ARE 1213 00:41:05,000 --> 00:41:08,400 UNIVERSITY OF ILLINOIS CHICAGO, 1214 00:41:08,400 --> 00:41:09,240 DUKE UNIVERSITY, AND UNIVERSITY 1215 00:41:09,240 --> 00:41:11,880 OF FLORIDA AT GAINSVILLE, ALL 3 1216 00:41:11,880 --> 00:41:15,040 SITES HAVE LARGE SICKLE CELL 1217 00:41:15,040 --> 00:41:19,320 DISEASE CLINICS. 1218 00:41:19,320 --> 00:41:21,280 NEXT, OUR SAMPLE WILL BE 330 1219 00:41:21,280 --> 00:41:24,360 ADULT PATIENTS WITH SICKLE CELL. 1220 00:41:24,360 --> 00:41:26,000 THEY MUST HAVE TO ENTER THE 1221 00:41:26,000 --> 00:41:27,400 STUDY OF PAIN INTERFERENCE SCORE 1222 00:41:27,400 --> 00:41:29,200 OF AT LEAST 3 OUT OF 10 IN THE 1223 00:41:29,200 --> 00:41:30,280 LAST WEEK. 1224 00:41:30,280 --> 00:41:31,920 THEY MUST HAVE CHRONIC PAIN 1225 00:41:31,920 --> 00:41:34,040 WHICH IS DEFINED AS A POSITIVE 1226 00:41:34,040 --> 00:41:37,240 RESPONSE TO SOME DAYS, MOST 1227 00:41:37,240 --> 00:41:38,760 DAYS, OR EVERY DAY WHEN ASKED AT 1228 00:41:38,760 --> 00:41:41,680 SCREENING IN THE PAST 3 MONTHS 1229 00:41:41,680 --> 00:41:46,040 HOW OFTEN HAVE YOU HAD PAIN. 1230 00:41:46,040 --> 00:41:48,040 NEXT, PLEASE. 1231 00:41:48,040 --> 00:41:51,240 >> OUR DESIGN IS A SEQUENTIAL 1232 00:41:51,240 --> 00:41:52,320 MULTIPLE ASSIGNMENT RANDOMIZED 1233 00:41:52,320 --> 00:41:55,120 TRIAL DESIGN OR A SMART DESIGN. 1234 00:41:55,120 --> 00:41:58,040 THE 3 GROUPS ARE RANDOMIZED 1 TO 1235 00:41:58,040 --> 00:42:03,800 1 TO 1, THAT IS GUIDED 1236 00:42:03,800 --> 00:42:04,560 RELAXATION, ACCUPUNCTURE AND 1237 00:42:04,560 --> 00:42:05,800 USUAL CARE. 1238 00:42:05,800 --> 00:42:08,240 IN TERMS OF IMPLEMENTATION, WE 1239 00:42:08,240 --> 00:42:13,480 ARE USING THE CONSOLIDATED FOR 1240 00:42:13,480 --> 00:42:17,080 IMPLEMENTATION, GUIDED BY CFIR, 1241 00:42:17,080 --> 00:42:20,880 WHICH IS GUIDED BY PATIENTS AND 1242 00:42:20,880 --> 00:42:21,440 SCD CLINICAL PROFESSIONALS. 1243 00:42:21,440 --> 00:42:22,480 HERE'S OUR SMART DESIGN. 1244 00:42:22,480 --> 00:42:24,240 ALL PARTICIPANTS ARE DOING STUDY 1245 00:42:24,240 --> 00:42:27,080 RECEIVED BASE LINE ASSESSMENT. 1246 00:42:27,080 --> 00:42:29,360 AND THEN THEIR RANDOMIZED GUIDED 1247 00:42:29,360 --> 00:42:31,680 RELUXURIATION, THE CONTROL GROUP 1248 00:42:31,680 --> 00:42:33,080 OR ACCUPUNCTURE, THEY RECEIVE 1249 00:42:33,080 --> 00:42:34,760 5-6 WEEKS OF THE INTERVENTION 1250 00:42:34,760 --> 00:42:37,640 ANDEN THIS THEA 6 WEEKS A GET A 1251 00:42:37,640 --> 00:42:39,000 MIDPOINT ASSESSMENT WHERE THEY 1252 00:42:39,000 --> 00:42:40,760 REPEAT THE SURVEYS IF THE 1253 00:42:40,760 --> 00:42:41,680 PARTICIPANTS RESPONDED TO THE 1254 00:42:41,680 --> 00:42:44,320 INTERVENTION, THEY WILL GO ON TO 1255 00:42:44,320 --> 00:42:47,840 CONTINUE DATA COLLECTION AT 12 1256 00:42:47,840 --> 00:42:49,840 AND 24 WEEKS, IF THEY DO NOT 1257 00:42:49,840 --> 00:42:51,840 RESPOND TO THE INTERVENTION, 1258 00:42:51,840 --> 00:42:53,240 THEY ARE RERANDOMMIZED TO EITHER 1259 00:42:53,240 --> 00:42:57,080 IN THIS CASE, GUIDED RELAXATION 1260 00:42:57,080 --> 00:42:58,560 TO CONTINUE EMBEDDED RELAXATION 1261 00:42:58,560 --> 00:43:00,800 OR SECOND WORLD WAR ITCH TO THE 1262 00:43:00,800 --> 00:43:01,720 ACCUPUNCTURE INTERVENTION AND 1263 00:43:01,720 --> 00:43:04,560 THEN MEASURES ARE COLLECTED AT 1264 00:43:04,560 --> 00:43:06,640 12 AND 24 WEEKS FOR THE 1265 00:43:06,640 --> 00:43:08,280 ACCUPUNCTURE WEEK, THE SAME 1266 00:43:08,280 --> 00:43:10,040 THING, IF THEY GET A RESPONSE WE 1267 00:43:10,040 --> 00:43:11,760 WILL CONTINUE DATA COLLECTION 1268 00:43:11,760 --> 00:43:14,320 AND COLLECT MEASURES AT 12 AND 1269 00:43:14,320 --> 00:43:14,840 24 WEEKS. 1270 00:43:14,840 --> 00:43:17,240 IF THERE'S NO RESPONSE, THEN, 1271 00:43:17,240 --> 00:43:19,000 THEY'LL EITHER CONTINUE IN THE 1272 00:43:19,000 --> 00:43:21,400 ACCUPUNCTURE GRUP OR SWITCH TO 1273 00:43:21,400 --> 00:43:23,400 GUIDED RELAXATION FOR ANOTHER 1274 00:43:23,400 --> 00:43:25,200 5-6 WEEKS WHERE THEY'LL THEN GO 1275 00:43:25,200 --> 00:43:29,480 ON A 12 AND 24 WEEKS TO COLLECT 1276 00:43:29,480 --> 00:43:30,080 MEASURES. 1277 00:43:30,080 --> 00:43:30,680 NEXT, PLEASE. 1278 00:43:30,680 --> 00:43:36,600 OUR INTERVENTIONS ARE GUIDED 1279 00:43:36,600 --> 00:43:39,440 RELAXATION IT IS A MIND-BASED 1280 00:43:39,440 --> 00:43:41,000 RELAKSZATION WITH COGNITIVE 1281 00:43:41,000 --> 00:43:41,240 BENEFITS. 1282 00:43:41,240 --> 00:43:42,800 IT'S DELIVERED THROUGH DAILY 1283 00:43:42,800 --> 00:43:45,840 VIDEOS VIA THE WEB, THERE'S A 12 1284 00:43:45,840 --> 00:43:47,600 MINUTE BASE LINE VIDEO, THEN 1285 00:43:47,600 --> 00:43:49,480 PARTICIPANTS CAN CHOOSE FROM 6 1286 00:43:49,480 --> 00:43:57,360 ADDITIONAL VIDEO CLIPS, RANGING 1287 00:43:57,360 --> 00:43:58,360 FROM 2-20 MINUTES. 1288 00:43:58,360 --> 00:43:58,840 WITH BENEFITS. 1289 00:43:58,840 --> 00:44:04,560 WE'RE USING A STANDARDIZED 1290 00:44:04,560 --> 00:44:06,320 ACCUPUNCTURE PROTOCOL OF 12--2 1291 00:44:06,320 --> 00:44:07,600 TREATMENTS PER WEEK FOR WEEK 1292 00:44:07,600 --> 00:44:12,480 WEEKS FOR A TOTEERAL OF 10 1293 00:44:12,480 --> 00:44:15,920 TREATMENTS. 1294 00:44:15,920 --> 00:44:16,560 NEXT, PLEASE. 1295 00:44:16,560 --> 00:44:19,400 OUR OUTCOMES IN TERMS OF 1296 00:44:19,400 --> 00:44:20,040 EFFECTIVENESS, THE PRIMARY 1297 00:44:20,040 --> 00:44:22,280 OUTCOME IS PAIN MEASURED BY THE 1298 00:44:22,280 --> 00:44:24,440 PAIN IMPACT SCORE WHICH IS A 1299 00:44:24,440 --> 00:44:27,240 COMPOSITE OF MEASURE OF PAIN 1300 00:44:27,240 --> 00:44:30,640 INTENSITY, PAIN INTERFERENCE AND 1301 00:44:30,640 --> 00:44:31,720 FUNCTION. 1302 00:44:31,720 --> 00:44:32,480 NEXT, PLEASE. 1303 00:44:32,480 --> 00:44:34,480 IN TERMS OF IMPLEMENTATION 1304 00:44:34,480 --> 00:44:37,440 CHALLENGES, THERE IS UNEQUAL 1305 00:44:37,440 --> 00:44:39,440 ACCESS TO ACCUPUNCTURE AT OUR 3 1306 00:44:39,440 --> 00:44:39,920 SIGHTS. 1307 00:44:39,920 --> 00:44:43,000 OUR 3 HEALTHCARE SYSTEMS SERVE 1308 00:44:43,000 --> 00:44:45,480 URBAN, SUBURBAN ASK RURAL 1309 00:44:45,480 --> 00:44:45,800 COMMUNITIES. 1310 00:44:45,800 --> 00:44:46,920 ACCUPUNCTURE 1 OF OUR CHALLENGE 1311 00:44:46,920 --> 00:44:48,800 SYSTEM THAT SOME OF THE PATIENTS 1312 00:44:48,800 --> 00:44:50,000 ARE NEEDLE AVERS, IN EMERGING 1313 00:44:50,000 --> 00:44:52,680 ITS OF GUIDED RELAXATION, CELL 1314 00:44:52,680 --> 00:44:54,520 PHONE DATA PLANS ARE DRAINED 1315 00:44:54,520 --> 00:45:00,040 BEFORE THE INTERVENTION PHASE IS 1316 00:45:00,040 --> 00:45:02,200 COMPLETED. 1317 00:45:02,200 --> 00:45:02,840 NEXT, PLEASE. 1318 00:45:02,840 --> 00:45:05,640 IN TERMS OF SOLUTIONS, WE'RE 1319 00:45:05,640 --> 00:45:08,440 PROVIDING CARE, AT DUKE WE OFFER 1320 00:45:08,440 --> 00:45:09,440 ACCUPUNCTURE THROUGH DUKE 1321 00:45:09,440 --> 00:45:12,440 INTEGRATIVE MEDICINE AND 1322 00:45:12,440 --> 00:45:13,320 COMMUNITY ACCUPUNCTURE OFFICES 1323 00:45:13,320 --> 00:45:16,440 AT UNIVERSITY OF FLORIDA, WE 1324 00:45:16,440 --> 00:45:17,920 OFFER ACCUPUNCTURE THROUGH THE 1325 00:45:17,920 --> 00:45:19,360 UNIVERSITY OF FLORIDA INTEGRATED 1326 00:45:19,360 --> 00:45:22,120 MEDICINE CLINIC AND AT UIC, WE 1327 00:45:22,120 --> 00:45:23,960 REIMBURSE FOR PARKING WHICH IS 1328 00:45:23,960 --> 00:45:26,440 THE BIGGEST ISSUE IN TERMS OF 1329 00:45:26,440 --> 00:45:28,040 AVERSION TO NEEDLES, RECRUITERS 1330 00:45:28,040 --> 00:45:29,840 SHOW THE ACUE PUNCTURE NEEDLES 1331 00:45:29,840 --> 00:45:30,960 TAPED TO A CARD EXPW THE 1332 00:45:30,960 --> 00:45:34,240 PATIENTS GET IT SEE THAT THE 1333 00:45:34,240 --> 00:45:35,800 NEEDLES ARE SOLID AND THEY'RE 1334 00:45:35,800 --> 00:45:37,640 MUCH THINNER, ABOUT THE SIZE OF 1335 00:45:37,640 --> 00:45:41,000 A HUMAN HAIR AS COMPARED TO A 1336 00:45:41,000 --> 00:45:43,040 HOLOCORE NEEDLE THAT'S USED TO 1337 00:45:43,040 --> 00:45:46,160 DRAW BLOOD OR START AN IV. 1338 00:45:46,160 --> 00:45:47,240 THE PATIENTS ARE GIVEN 1339 00:45:47,240 --> 00:45:49,240 REASSURANCE THAT THE NEEDLES 1340 00:45:49,240 --> 00:45:55,040 WON'T BE INSERTED INTO LEG 1341 00:45:55,040 --> 00:45:57,080 ULCERS OR SCARS AND WE ASSURE 1342 00:45:57,080 --> 00:46:00,720 THEM THAT THE DE QI SENSATION 1343 00:46:00,720 --> 00:46:02,520 THAT THE SENSATION FELT WHEN 1344 00:46:02,520 --> 00:46:04,320 NEEDLES ARE INSERTED IS NORMAL. 1345 00:46:04,320 --> 00:46:06,520 WE ALSO PROVIDE DATA PLANS FOR 1346 00:46:06,520 --> 00:46:08,960 CELL PHONE AND TABLET USE, IT 1347 00:46:08,960 --> 00:46:10,240 ALLOWS THE PARTIC PLAN TO 1348 00:46:10,240 --> 00:46:11,440 ANALYZE BY AGES TO KEEP FROM 1349 00:46:11,440 --> 00:46:13,280 RUNNING OUT OF DATA AND ENABLING 1350 00:46:13,280 --> 00:46:15,240 COMPLOOGZ OF OUR INTERVENTION. 1351 00:46:15,240 --> 00:46:17,040 NEXT PLEASE. 1352 00:46:17,040 --> 00:46:20,800 HERE'S OUR TEAM AND NEXT PLEASE. 1353 00:46:20,800 --> 00:46:23,320 AND WE WOULD LIKE TO THANK THE 1354 00:46:23,320 --> 00:46:24,480 SICKLE CELL DISEASE PATIENTS AND 1355 00:46:24,480 --> 00:46:38,600 COMMUNITIES FOR THEIR SUPPORT. 1356 00:46:38,600 --> 00:46:38,840 THANK YOU. 1357 00:46:38,840 --> 00:46:39,840 >> THANK YOU VERY MUCH FOR THE 1358 00:46:39,840 --> 00:46:41,240 EXCELLENT TALK. 1359 00:46:41,240 --> 00:46:44,920 VERY ENLIGHTENING FOR ME ABOUT 1360 00:46:44,920 --> 00:46:46,880 PHYSICAL MODALITIES AND THE 1361 00:46:46,880 --> 00:46:47,480 TREATMENTS FOR SICKLE CELL 1362 00:46:47,480 --> 00:46:48,680 DISEASE AND I LOOK FORWARD TO 1363 00:46:48,680 --> 00:46:49,560 ADDRESSING QUESTIONS THAT CAME 1364 00:46:49,560 --> 00:46:50,480 UP FOR OUR PANEL. 1365 00:46:50,480 --> 00:46:54,240 I WANTED TO INTRODUCE OUR NEXT 1366 00:46:54,240 --> 00:46:56,160 SPEAKER DR. LIZ PRINCE IS AN 1367 00:46:56,160 --> 00:46:57,840 ADIOF THE ANT PROFESSOR OF 1368 00:46:57,840 --> 00:46:59,440 PSYCHIATRIST TREE AT JOHNS 1369 00:46:59,440 --> 00:47:00,960 HOPKINS UNIVERSITY OF SCHOOL OF 1370 00:47:00,960 --> 00:47:03,040 MEDICINE AND I WANT TO SAY SHE'S 1371 00:47:03,040 --> 00:47:04,760 A UNICORN BUT I AT LEAST KNOW OF 1372 00:47:04,760 --> 00:47:07,440 2 PEOPLE LIKE HER BEING A 1373 00:47:07,440 --> 00:47:09,680 PSYCHIATRIST THAT FOCUSES ON THE 1374 00:47:09,680 --> 00:47:11,240 MANAGEMENT OF PAIN AND 1375 00:47:11,240 --> 00:47:12,400 PSYCHIATRIC ILLNESS IN PEOPLE 1376 00:47:12,400 --> 00:47:14,920 WITH SICKLE CELL DISEASE. 1377 00:47:14,920 --> 00:47:19,840 AND SHE IS GOING TO TELL US 1378 00:47:19,840 --> 00:47:24,520 TODAY ABOUT THE USE OF 1379 00:47:24,520 --> 00:47:26,640 ANTIDEPRESSANTS AND 1380 00:47:26,640 --> 00:47:28,160 ANTIEPILEPTIC DRUGS FOR PAIN AND 1381 00:47:28,160 --> 00:47:30,680 PEOPLE WITH SICKLE CELL DISEASE. 1382 00:47:30,680 --> 00:47:31,000 DR. PRINCE. 1383 00:47:31,000 --> 00:47:32,240 >> THANKS SO MUCH FOR HAVING ME, 1384 00:47:32,240 --> 00:47:33,800 IT WON'T LET ME START MY VIDEO, 1385 00:47:33,800 --> 00:47:51,960 I THINK I GOT DEACTIVATED. 1386 00:47:51,960 --> 00:47:52,320 EXCELLENT. 1387 00:47:52,320 --> 00:47:55,160 THANK YOU FOR HAVING ME AND FOR 1388 00:47:55,160 --> 00:47:55,920 THE KIND INTRODUCTION. 1389 00:47:55,920 --> 00:47:59,840 I'M EXCITED TO TALK TODAY ABOUT 1390 00:47:59,840 --> 00:48:02,200 ANTIDEPRESSANTS AND 1391 00:48:02,200 --> 00:48:03,280 ANTIEPILEPTIC OR ANTICONVULSANT 1392 00:48:03,280 --> 00:48:03,760 MEDICATION FOR PAIN. 1393 00:48:03,760 --> 00:48:05,120 SO CAN YOU GO TO THE NEXT SLIDE. 1394 00:48:05,120 --> 00:48:06,760 I DON'T HAVE ANY DISCLOSURES SO 1395 00:48:06,760 --> 00:48:08,840 WE WILL GO ON TO THE NEXT SLIDE 1396 00:48:08,840 --> 00:48:09,240 AS WELL. 1397 00:48:09,240 --> 00:48:11,760 FIRST I JUST WANT TO DESCRIBE 1398 00:48:11,760 --> 00:48:12,800 SOME CONNECTIONS BETWEEN 1399 00:48:12,800 --> 00:48:14,640 DEPRESSION AND CHRONIC PAIN, 1400 00:48:14,640 --> 00:48:15,480 DEPRESSION AND SICKLE CELL 1401 00:48:15,480 --> 00:48:16,640 DISEASE, THESE ARE SOME THINGS 1402 00:48:16,640 --> 00:48:18,720 THAT HAVE COME UP TODAY, GOING 1403 00:48:18,720 --> 00:48:21,000 TO GO OVER THE ASH GUIDELINES 1404 00:48:21,000 --> 00:48:21,880 FOR CHRONIC PAIN AND THE EVIDENT 1405 00:48:21,880 --> 00:48:24,800 BASE THAT WAS USED FOR THE 1406 00:48:24,800 --> 00:48:27,880 RECOMMENDATIONS AROUND THOSE 1407 00:48:27,880 --> 00:48:29,640 MEDICINES, IDENTIFY LIKELY 1408 00:48:29,640 --> 00:48:32,240 MECHIMISMS FOR HOW THESE 1409 00:48:32,240 --> 00:48:33,000 PARTICULAR MEDICATIONS EFFECT 1410 00:48:33,000 --> 00:48:34,480 PAIN AND GO OVER PRACTICAL TIPS 1411 00:48:34,480 --> 00:48:38,440 FOR HOW TO USE THESE MEDICATIONS 1412 00:48:38,440 --> 00:48:38,760 IN PATIENTS. 1413 00:48:38,760 --> 00:48:43,680 SO WE CAN GO TO THE NEXT SLIDE. 1414 00:48:43,680 --> 00:48:44,960 STARTING OUT, WE KNOW THAT 1415 00:48:44,960 --> 00:48:46,360 DEPRESSION AND CHRONIC PAIN ARE 1416 00:48:46,360 --> 00:48:47,880 CONNECTED SO JUST A FEW THINGS 1417 00:48:47,880 --> 00:48:49,760 TO HIGHLIGHT FIRST, WHEN YOU 1418 00:48:49,760 --> 00:48:52,040 LOOK AT PEOPLE WHO HAVE CHRONIC 1419 00:48:52,040 --> 00:48:53,440 PAIN COMPARED TO PEOPLE WHO 1420 00:48:53,440 --> 00:48:55,400 DON'T HAVE CHRONIC PAIN, THOSE 1421 00:48:55,400 --> 00:48:57,040 WITH CHRONIC PAIN ARE GOING TO 1422 00:48:57,040 --> 00:48:59,080 SCORE HIGHER ON DEPRESSION 1423 00:48:59,080 --> 00:49:00,600 SCREENING INSTRUMENTS LIKE THE 1424 00:49:00,600 --> 00:49:03,080 PH Q, THEY'RE MORE LIKE TOW TO 1425 00:49:03,080 --> 00:49:04,000 SCREEN POSITIVE FOR DEPRESSION, 1426 00:49:04,000 --> 00:49:06,680 THIS WILL BE A HIGHER PROPORTION 1427 00:49:06,680 --> 00:49:09,320 AND THEN ALSO ARE MORE LIKELY IN 1428 00:49:09,320 --> 00:49:10,840 CLINICAL POPULATIONS TO BE 1429 00:49:10,840 --> 00:49:12,600 DIAGNOSED WITH MAJOR DEPRESSIVE 1430 00:49:12,600 --> 00:49:16,040 DISORDER AND THEN PEOPLE WHO 1431 00:49:16,040 --> 00:49:20,280 HAVE CHRONIC PAIN AND A 1432 00:49:20,280 --> 00:49:21,200 PSYCHIATRIC ILLNESS, COMPARE TO 1433 00:49:21,200 --> 00:49:23,560 THOSE WITH ONLY PAIN WILL HAVE 1434 00:49:23,560 --> 00:49:24,840 HIGHER SCORES, MORE DISABILITY 1435 00:49:24,840 --> 00:49:27,080 FROM THE PAIN THAT HAVE BEEN 1436 00:49:27,080 --> 00:49:28,680 FOUND TO HAVE REDUCED QUALITY OF 1437 00:49:28,680 --> 00:49:28,880 LIFE. 1438 00:49:28,880 --> 00:49:33,040 GO ON TO THE NEXT SLIDE. 1439 00:49:33,040 --> 00:49:35,160 WHAT WE KNOW ABOUT THE 1440 00:49:35,160 --> 00:49:36,840 CONNECTIONS BETWEEN DEPRESSION 1441 00:49:36,840 --> 00:49:37,840 AND SCD, AGAIN CONTINUING A 1442 00:49:37,840 --> 00:49:39,600 THEME THAT WE HEARD ABOUT WHICH 1443 00:49:39,600 --> 00:49:41,240 IS THAT REALLY DON'T HAVE ENOUGH 1444 00:49:41,240 --> 00:49:42,480 EVIDENCE AND DATA BUT WHAT WE 1445 00:49:42,480 --> 00:49:46,400 KNOW IS THAT AT LEAST THERE'S 1 1446 00:49:46,400 --> 00:49:48,040 STUDY OR GREATER THAN 35% OF 1447 00:49:48,040 --> 00:49:51,200 ADULTS WITH SICKLE CELL DISEASE 1448 00:49:51,200 --> 00:49:52,400 HAD DEPRESSION IN THIS STUDY AND 1449 00:49:52,400 --> 00:49:54,280 THAT'S A MUCH HIGHER RATE, THAN 1450 00:49:54,280 --> 00:49:57,680 YOU WOULD SEE IN A GBL ADULT 1451 00:49:57,680 --> 00:49:58,080 POPULATION. 1452 00:49:58,080 --> 00:49:59,840 WHAT WE SUDDEN THAT IN CHILDREN, 1453 00:49:59,840 --> 00:50:02,680 WITH SICKLE CELL DISEASE, HAVING 1454 00:50:02,680 --> 00:50:04,240 CHRONIC OR RECURRENT PAIN 1455 00:50:04,240 --> 00:50:04,920 INCREASES THE LIKELIHOOD THAT 1456 00:50:04,920 --> 00:50:06,440 THEY WILL HAVE DEPRESSION. 1457 00:50:06,440 --> 00:50:08,400 AND REALLY ALL OF THIS 1458 00:50:08,400 --> 00:50:10,120 INFORMATION THAT I'M SHARING 1459 00:50:10,120 --> 00:50:11,880 WITH THE LAST 2 SLIDES IS TO 1460 00:50:11,880 --> 00:50:13,760 AFFIRM THIS IDEA THAT MENTAL 1461 00:50:13,760 --> 00:50:17,240 ILLNESS AND PAIN ARE CONNECTED 1462 00:50:17,240 --> 00:50:18,680 AND THERE'S MUTUALLY 1463 00:50:18,680 --> 00:50:19,200 REINFORCEMENT FACTORS. 1464 00:50:19,200 --> 00:50:24,840 ON TO THE NEXT SLIDE. 1465 00:50:24,840 --> 00:50:26,640 THIS IS AN IMAGE THAT I REALLY 1466 00:50:26,640 --> 00:50:28,680 LOVE THEY BORROW FRIDAY SOME 1467 00:50:28,680 --> 00:50:31,600 SLIDES THAT WERE MADE AS PART OF 1468 00:50:31,600 --> 00:50:32,800 THE ASH CLINICAL PRACTICE 1469 00:50:32,800 --> 00:50:33,800 GUIDELINES. 1470 00:50:33,800 --> 00:50:36,800 WHAT I LIKE ABOUT IS IT SHOWS 1471 00:50:36,800 --> 00:50:38,120 THESE DIFFERENT FACTORS THAT ARE 1472 00:50:38,120 --> 00:50:39,320 ALL INTERCONNECTED AND HOW THEY 1473 00:50:39,320 --> 00:50:40,680 RELATE TO ACUTE AND CHRONIC PAIN 1474 00:50:40,680 --> 00:50:42,000 IN PATIENTS WITH CIRCLE CELL 1475 00:50:42,000 --> 00:50:45,560 DISEASE AND I HIGHLIGHTED THIS 1476 00:50:45,560 --> 00:50:47,440 NERVOUS SYSTEM SENSITIZATION AND 1477 00:50:47,440 --> 00:50:48,920 THEN, PSYCHOLOGICAL FACTORS OF 1478 00:50:48,920 --> 00:50:49,600 DEPRESSION AND ANXIETY HERE 1479 00:50:49,600 --> 00:50:51,000 BECAUSE I THINK THAT THE 1480 00:50:51,000 --> 00:50:52,440 MEDICINE THAT I'M GOING TO BE 1481 00:50:52,440 --> 00:50:55,080 TALKING ABOUT ARE REALLY ACTING 1482 00:50:55,080 --> 00:50:57,480 ON THOSE ASPECTS OF FACTORS THAT 1483 00:50:57,480 --> 00:51:05,240 CONTRIBUTE TO PAIN, SO THE NEXT 1484 00:51:05,240 --> 00:51:05,720 SLIDE, PLEASE. 1485 00:51:05,720 --> 00:51:07,240 SO--I KNOW THERE'S LOT OF WORDS 1486 00:51:07,240 --> 00:51:08,320 HERE BUT WE WILL SPIN THROUGH 1487 00:51:08,320 --> 00:51:13,240 THIS QUICK, SO THE 1488 00:51:13,240 --> 00:51:14,640 RECOMMENDATIONS RELATED TO 1489 00:51:14,640 --> 00:51:15,920 AVASCULAR NECROSIS, IS THERE'S 1490 00:51:15,920 --> 00:51:18,840 NOT A LOT OF HUGE STUDIES WE CAN 1491 00:51:18,840 --> 00:51:19,880 MAKE SOLID RECOMMENDATIONS FROM, 1492 00:51:19,880 --> 00:51:22,000 SO A LOT OF THIS IS BORROWED 1493 00:51:22,000 --> 00:51:23,880 FROM THE MANAGEMENT OF PAIN AND 1494 00:51:23,880 --> 00:51:27,480 OFTIO ARTHRITIS SO THERE'S A 1495 00:51:27,480 --> 00:51:33,920 CONDITIONAL RECOMMENDATIONS FOR 1496 00:51:33,920 --> 00:51:36,400 NSNRIs, LIKE UPTAKE INHIBITORS 1497 00:51:36,400 --> 00:51:41,920 AND THERE'S ALSO 1 FOR NSAIDS 1498 00:51:41,920 --> 00:51:43,000 AND NONTERROIDAL INFLAMMATTORY 1499 00:51:43,000 --> 00:51:44,360 MEDICATIONS, THERE WAS NONE FOR 1500 00:51:44,360 --> 00:51:47,640 CHILDREN AND THEN WITH PAIN WITH 1501 00:51:47,640 --> 00:51:49,640 OTHER SORT OF RELATED TO ABM, 1502 00:51:49,640 --> 00:51:51,000 THIS IS THE DATA THAT THE 1503 00:51:51,000 --> 00:51:53,880 EVIDENCE BASED FOR THIS IS SORT 1504 00:51:53,880 --> 00:51:55,200 OF AMANAGEMENT OF FIBROMYALGIA 1505 00:51:55,200 --> 00:51:59,720 PAIN SO AGAIN, WE SEE SNRIs 1506 00:51:59,720 --> 00:52:00,760 BEING A CONDITIONAL 1507 00:52:00,760 --> 00:52:03,120 RECOMMENDATION, WE SEE TRICYC 1508 00:52:03,120 --> 00:52:05,040 LIKE ANTIDEPRESSANTS AND THEN WE 1509 00:52:05,040 --> 00:52:06,920 ALSO SEE CONDITIONAL 1510 00:52:06,920 --> 00:52:08,520 RECOMMENDATION FOR GABBA PENTINE 1511 00:52:08,520 --> 00:52:11,440 REGIMENINNOIDS WHICH ARE AN 1512 00:52:11,440 --> 00:52:12,000 ANTIEPILEPTIC MEDICATION. 1513 00:52:12,000 --> 00:52:13,560 SO THERE'S REALLY NOT ENOUGH 1514 00:52:13,560 --> 00:52:18,080 EVIDENCE TO MAKE RECOMMENDATIONS 1515 00:52:18,080 --> 00:52:19,440 ABOUT PAIN RELATED TO SO LET'S 1516 00:52:19,440 --> 00:52:27,000 GO TO THE NEXT SLIDE. 1517 00:52:27,000 --> 00:52:36,240 THERE'S A PICTURE THERE'S LAYOT 1518 00:52:36,240 --> 00:52:37,440 OF--WE HAVE THE RED AND BLUE 1519 00:52:37,440 --> 00:52:40,120 LINE WHICH ARE THE ASEBDING AND 1520 00:52:40,120 --> 00:52:41,640 DESCENDING PATHWAYS OF MESSAGES 1521 00:52:41,640 --> 00:52:44,520 THAT LEAD DOWN TO THE LOWER LEFT 1522 00:52:44,520 --> 00:52:46,360 HAND CORNER, A CROSS SECTION OF 1523 00:52:46,360 --> 00:52:48,440 THE SPINAL CORD WHICH YOU CAN 1524 00:52:48,440 --> 00:52:51,440 SEE, BLOWN UP IN THE UPPER RIGHT 1525 00:52:51,440 --> 00:52:54,480 HAND CORNER SHOWING THE NERVE 1526 00:52:54,480 --> 00:52:55,520 CONNECTION AND SYNAPSES AND THEN 1527 00:52:55,520 --> 00:52:57,000 IN THE LOWER RIGHT HAND CORNER 1528 00:52:57,000 --> 00:52:59,320 WE HAVE THE HER PERIPHERAL NERVE 1529 00:52:59,320 --> 00:53:00,440 ENDINGS AND WHAT THIS IS SHOWING 1530 00:53:00,440 --> 00:53:02,120 US IS ALL OF THE DIFFERENT 1531 00:53:02,120 --> 00:53:05,560 PLACES WHERE PINE MESSAGING IS 1532 00:53:05,560 --> 00:53:06,200 HAPPENING. 1533 00:53:06,200 --> 00:53:07,400 AND HIGHLIGHTED HERE, THE REASON 1534 00:53:07,400 --> 00:53:10,440 I LIKE THIS PICTURE IS THAT THEY 1535 00:53:10,440 --> 00:53:12,040 LIST SOME OF THE DIFFERENT KINDS 1536 00:53:12,040 --> 00:53:13,640 OF TREATMENTS, SOME ARE 1537 00:53:13,640 --> 00:53:16,200 MEDICATIONS BUT SOME ARE 1538 00:53:16,200 --> 00:53:17,280 INTERVENTIONS SOME OF WHICH WE 1539 00:53:17,280 --> 00:53:19,200 ALREADY HEARD ABOUT TODAY AND 1540 00:53:19,200 --> 00:53:21,400 WHERE THEY ACT, FOR EXAMPLE WITH 1541 00:53:21,400 --> 00:53:25,040 THE BIG LUMPY BRAIN, WE SEE CBT 1542 00:53:25,040 --> 00:53:28,480 BUT ALSO ANTIDEPRESSANTS AND 1543 00:53:28,480 --> 00:53:30,280 ANTICONSULS ANT OR ANTIEPILEPTIC 1544 00:53:30,280 --> 00:53:30,920 MEDICATIONS HAVING ACTION THERE 1545 00:53:30,920 --> 00:53:32,160 ASK WHAT I REALLY WANTED TO 1546 00:53:32,160 --> 00:53:36,880 HIGHLIGHT IS THAT THERE IS 1547 00:53:36,880 --> 00:53:38,400 SEVERAL PLACES IN WHICH THINGS 1548 00:53:38,400 --> 00:53:40,280 ARE REPEATED SO FOR 1549 00:53:40,280 --> 00:53:41,200 ANTIDEPRESSANTS WE SEE THEY'RE 1550 00:53:41,200 --> 00:53:42,480 MENTIONED AT THE LEVEL OF BRAIN 1551 00:53:42,480 --> 00:53:43,880 WHEN WE LOOK AT THIS CROSS 1552 00:53:43,880 --> 00:53:47,440 SECTION OF THE SPINAL CORD, WE 1553 00:53:47,440 --> 00:53:51,720 CAN LOOK AT TRICYC LICK 1554 00:53:51,720 --> 00:53:52,760 ANTIDEPRESSANTS AND SNRIs ARE 1555 00:53:52,760 --> 00:53:54,280 MENTIONED HERE AND THEN ALSO 1556 00:53:54,280 --> 00:53:58,720 DOWN AT THE PERIPHERAL LEVEL, WE 1557 00:53:58,720 --> 00:54:00,000 SEE ANTIDEPRESSANTS AND SEVERAL 1558 00:54:00,000 --> 00:54:02,960 OTHER MEDICINES THAT ARE ALL 1559 00:54:02,960 --> 00:54:05,640 ANTIEPT LEAPTIC MEDICATION, SO 1560 00:54:05,640 --> 00:54:07,200 THESE MEDICINES ARE ACTING AT 1561 00:54:07,200 --> 00:54:08,160 SEVERAL DIFFERENT PLACES ALONG 1562 00:54:08,160 --> 00:54:10,160 THE LINE OF WHERE PAIN MESSAGING 1563 00:54:10,160 --> 00:54:10,520 IS HAPPENING. 1564 00:54:10,520 --> 00:54:19,120 SO WE MOVE ON TO THE NEXT SLIDE. 1565 00:54:19,120 --> 00:54:21,440 THIS IS A ZOOMED IN SYNAPSE SO 1566 00:54:21,440 --> 00:54:23,000 WE CAN SEE THEAXON AND THE 1567 00:54:23,000 --> 00:54:24,840 DENDRITE AND ALL THESE DOTS 1568 00:54:24,840 --> 00:54:26,160 WHICH ARE THE NEUROTRANSMITTERS 1569 00:54:26,160 --> 00:54:27,840 THAT ARE GOING BETWEEN THEM. 1570 00:54:27,840 --> 00:54:33,000 THIS 1 HIGHLIGHTS SPECIFICALLY A 1571 00:54:33,000 --> 00:54:34,320 MEDICINE CALLED AMITRANSCRIPTY 1572 00:54:34,320 --> 00:54:36,120 LINE WHICH IS A ANTIDEPRESSANT 1573 00:54:36,120 --> 00:54:39,160 AND WE VIA THAT AMITRANSCRIPT 1574 00:54:39,160 --> 00:54:44,200 LINE IS ACTING AT THE SEROTONIN 1575 00:54:44,200 --> 00:54:47,440 AND THE NEUROEPIDRENNALLIST, 1576 00:54:47,440 --> 00:54:49,200 REUPTAKE TRANSPORTERS SO BY 1577 00:54:49,200 --> 00:54:50,280 VERMEN INFECTED PREVENTING THE 1578 00:54:50,280 --> 00:54:51,800 REUPTAKE OF THESE THINGS THERE'S 1579 00:54:51,800 --> 00:54:53,080 MORE OF THOSE CHEMICALS 1580 00:54:53,080 --> 00:54:55,720 AVAILABLE IN THE SYNAPSE AND 1581 00:54:55,720 --> 00:54:57,320 THAT'S 1 PLACE WHERE THESE 1582 00:54:57,320 --> 00:54:58,640 MEDICINES ARE HAVING ACTION, SO 1583 00:54:58,640 --> 00:55:07,600 WE WILL KEEP MOVING. 1584 00:55:07,600 --> 00:55:11,160 NEXT SLIDE. 1585 00:55:11,160 --> 00:55:13,880 GREAT. 1586 00:55:13,880 --> 00:55:15,640 SO, SNRIs, SEROTONIN 1587 00:55:15,640 --> 00:55:16,760 NOREPINEPHRINE, REUPTAKE INHIB 1588 00:55:16,760 --> 00:55:21,640 THORS IDENTITY ARES LIKE 1589 00:55:21,640 --> 00:55:24,040 VENLAFAXINE, AND THIS IS THE 1590 00:55:24,040 --> 00:55:25,800 PRESINAT INCREASE IN BODY 1591 00:55:25,800 --> 00:55:34,040 INHIBITION OF THE REUPTAKE OF 1592 00:55:34,040 --> 00:55:36,040 SEROTONIN AND NOREEPINEPHRINE IN 1593 00:55:36,040 --> 00:55:38,040 PAIN AND INHIBITORY PATHWAYS, 1594 00:55:38,040 --> 00:55:39,240 AND THEY DON'T HAVE A LOT OF 1595 00:55:39,240 --> 00:55:41,040 EFFECT ON THE RECEPTORS, SOME 1596 00:55:41,040 --> 00:55:42,520 GOOD THINGS ABOUT THESE 1597 00:55:42,520 --> 00:55:43,840 MEDICINE, GENERALLY PRETTY SAFE, 1598 00:55:43,840 --> 00:55:45,240 GENERALLY PRETTY WELL TOLERATED 1599 00:55:45,240 --> 00:55:48,680 SOME DOWN SIDES THEY HAVE A 1600 00:55:48,680 --> 00:55:49,440 PRETTY UNPLEASANT 1601 00:55:49,440 --> 00:55:50,640 DISCONTINUATION SYNDROME SO I DO 1602 00:55:50,640 --> 00:55:51,720 TALK TO PATIENTS THAT EVEN 1603 00:55:51,720 --> 00:55:53,240 MISSING A DAY OF THESE MEDICINES 1604 00:55:53,240 --> 00:55:55,040 CAN MAKE YOU FEEL PRETTY CRAPY 1605 00:55:55,040 --> 00:55:57,320 SO THAT'S SOMETHING TO CONSIDER 1606 00:55:57,320 --> 00:55:59,640 YOU KNOW, OUR GOAL WHEN WE GIVE 1607 00:55:59,640 --> 00:56:00,920 SOMEONE A MEDICATION IS THAT IT 1608 00:56:00,920 --> 00:56:02,680 HELPS THEM TO BE BETTER BUT IF 1609 00:56:02,680 --> 00:56:04,640 THEY CAN'T TAKE IT CONSISTENTLY, 1610 00:56:04,640 --> 00:56:06,280 IT WILL MAKE THEM FEEL WORSE 1611 00:56:06,280 --> 00:56:08,480 THEN MAYBE THAT'S NOT THE BEST 1612 00:56:08,480 --> 00:56:11,320 GAME PLAN. 1613 00:56:11,320 --> 00:56:11,720 NEXT SLIDE. 1614 00:56:11,720 --> 00:56:14,200 SO THIS IS DATED DATA FROM A 1615 00:56:14,200 --> 00:56:17,440 STUDY LOOKING AT PAIN FROM 1616 00:56:17,440 --> 00:56:18,400 DIABETIC PERIPHERAL NEUROPATHY 1617 00:56:18,400 --> 00:56:20,680 AND WHAT WE SEE ON THE Y-AXIS IS 1618 00:56:20,680 --> 00:56:22,680 A CHANGE IN PAIN AND ON THE 1619 00:56:22,680 --> 00:56:24,640 AX-AXIS IS TIME AND WEEKS, AND 1620 00:56:24,640 --> 00:56:26,960 THIS IS A STUDY OF DID YOU 1621 00:56:26,960 --> 00:56:28,840 LOCKSA TEEN SO THEY HAD A 1622 00:56:28,840 --> 00:56:32,280 PLACEBO AND 2 DIFFERENT DOSES OF 1623 00:56:32,280 --> 00:56:34,000 DULXOTEEN GIVEN TO PATIENTS AND 1624 00:56:34,000 --> 00:56:35,520 THE BIG THING TO LIE LIGHT HERE 1625 00:56:35,520 --> 00:56:37,840 IS YOU CAN SEE THAT THE PLACEBO 1626 00:56:37,840 --> 00:56:39,840 SEPARATES OUT FROM THE PEOPLE 1627 00:56:39,840 --> 00:56:44,920 WHO GOT THE DULOXETINE, BUT IT 1628 00:56:44,920 --> 00:56:46,920 DOES BECOME THE MOST REMAXABLE 1629 00:56:46,920 --> 00:56:52,560 SO IT LET'S MOVE ON TO THE NEXT 1630 00:56:52,560 --> 00:56:52,760 SLIDE. 1631 00:56:52,760 --> 00:56:54,360 WHICH IS GOING TO BE MORE 1632 00:56:54,360 --> 00:56:56,400 PATIENTS IN THE CLINIC UPPERS A 1633 00:56:56,400 --> 00:56:57,640 REALLY SIMILAR TYPE OF THING 1634 00:56:57,640 --> 00:56:59,320 WHERE ON THE Y-AXIS WE HAVE A 1635 00:56:59,320 --> 00:57:02,360 CHANGE IN PAIN AND THEN WEEKS OF 1636 00:57:02,360 --> 00:57:05,400 TREATMENTOT X-AXIS, THIS IS A 1637 00:57:05,400 --> 00:57:09,440 STUDY IN AFTIO ARTHRITIS AND 1638 00:57:09,440 --> 00:57:11,040 AGAIN OF DULOXEIT, INE, AND WE 1639 00:57:11,040 --> 00:57:14,280 SEE AGAIN THAT THE PLACEBO ON 1640 00:57:14,280 --> 00:57:16,360 THE TOP AND THE DULOXETINE 1641 00:57:16,360 --> 00:57:19,200 SEPARATE OUT, BUT THIS IS TAKING 1642 00:57:19,200 --> 00:57:19,680 AN INSTANTANEOUS EFFECT. 1643 00:57:19,680 --> 00:57:22,280 GOING ON TO THE NEXT SLIDE. 1644 00:57:22,280 --> 00:57:28,200 ONE MORE FOR YOU HERE, SO THIS 1645 00:57:28,200 --> 00:57:33,920 HAS BEEN THE VENLAFAXINE, AND 1646 00:57:33,920 --> 00:57:35,840 WITH SPINAL CORD INJURY AND ON 1647 00:57:35,840 --> 00:57:36,440 DEPRESSION, WE'RE LOOKING AT 1648 00:57:36,440 --> 00:57:37,400 TIME AND SEEING THAT THE PATIENT 1649 00:57:37,400 --> 00:57:41,840 WHO IS WERE GIVEN THE 1650 00:57:41,840 --> 00:57:42,960 VENLAFAXINE, DO SEPARATE OUT 1651 00:57:42,960 --> 00:57:46,480 FROM THE PLACEBO BUT TELL TAKE 1652 00:57:46,480 --> 00:57:48,560 SEVERAL WEEKS. 1653 00:57:48,560 --> 00:57:50,400 NEXT, SLIDE, PLEASE, GREAT, SO 1654 00:57:50,400 --> 00:57:53,080 NOW WE WILL SPIN THROUGH 1655 00:57:53,080 --> 00:57:54,000 TRICYCKIC ANTIDEPRESSANTS THESE 1656 00:57:54,000 --> 00:57:59,240 ARE THINGS LIKE NORA TRANSCRIPT 1657 00:57:59,240 --> 00:58:00,160 LINE OR AMITRIPTYLINE, THEY WILL 1658 00:58:00,160 --> 00:58:01,840 HAVE A SIMILAR MECHANISM WHICH 1659 00:58:01,840 --> 00:58:03,840 IS THE REUPTAKE, THEY DO ALSO 1660 00:58:03,840 --> 00:58:07,600 HAVE ACTION ON SOME OTHER KINDS 1661 00:58:07,600 --> 00:58:11,720 OF RECEPTORS SO THEY'RE ACTING 1662 00:58:11,720 --> 00:58:13,120 ON COLONERGIC, EFTHIMIOSA 1663 00:58:13,120 --> 00:58:14,520 MINERGIC RECEPTORS AS WELL, SO 1664 00:58:14,520 --> 00:58:16,600 THEY DO HAVE ADDITIONAL ACTIVITY 1665 00:58:16,600 --> 00:58:17,720 AT PERIPHERAL NERVES WHICH IS 1666 00:58:17,720 --> 00:58:20,600 GREAT, THE OTHER THING THAT'S 1667 00:58:20,600 --> 00:58:22,360 HELPFUL ABOUT THE PREFERENCES IS 1668 00:58:22,360 --> 00:58:24,440 YOU CAN DO A BLOOD LEVEL TESTING 1669 00:58:24,440 --> 00:58:27,240 SO YOU CAN DO A 12 HOUR BLOOD 1670 00:58:27,240 --> 00:58:29,240 LEVEL OF THESE MEDICATIONS AND 1671 00:58:29,240 --> 00:58:30,000 IT IS MEANINGFUL INFORMATION 1672 00:58:30,000 --> 00:58:32,040 THAT YOU CAN TITRATE INTO A 1673 00:58:32,040 --> 00:58:33,880 THERAPEUTIC RANGE TO HAVE 1674 00:58:33,880 --> 00:58:34,400 EFFECT. 1675 00:58:34,400 --> 00:58:38,760 WHEREAS MEDICINES LIKE AFEXER 1676 00:58:38,760 --> 00:58:41,440 AND SIM BALTA HAVE A 1677 00:58:41,440 --> 00:58:42,840 STANDARDIZED DOSE BUT WE'RE NOT 1678 00:58:42,840 --> 00:58:43,640 MEASURING THE LEVELS OF THOSE IN 1679 00:58:43,640 --> 00:58:45,080 OUR PATIENTS AND ADJUSTING THE 1680 00:58:45,080 --> 00:58:46,640 DOSE BASED ON THAT. 1681 00:58:46,640 --> 00:58:48,080 DOWNED ISS, AGAIN, I MENTION 1682 00:58:48,080 --> 00:58:50,160 WILL ALL THESE OTHER RECEPTORS 1683 00:58:50,160 --> 00:58:52,040 THAT THEY'RE ACTING ON, SO 1684 00:58:52,040 --> 00:58:53,040 THERE'S PROBLEM WITH 1685 00:58:53,040 --> 00:58:56,680 TOLERABILITY WITH THOSE AND 1686 00:58:56,680 --> 00:58:57,400 ANTICOLLINERGIC, CONSTIPATION 1687 00:58:57,400 --> 00:58:59,360 AND STUFF. 1688 00:58:59,360 --> 00:59:00,440 THERE'S CARDIAC CONDUCTION 1689 00:59:00,440 --> 00:59:03,160 POTENTIAL EFFECTS SO CAN YOU 1690 00:59:03,160 --> 00:59:07,440 MONITOR EKGs AND THEY HAVE 1691 00:59:07,440 --> 00:59:08,920 LOTS OF ACTION IN MANY WAYS BUT 1692 00:59:08,920 --> 00:59:10,760 IT ALSO MEANS THEY CAN CAUSE 1693 00:59:10,760 --> 00:59:13,240 SIDE EFFECTS IN MANY WAYINGS 1694 00:59:13,240 --> 00:59:14,840 WHICH NOT THE AGAIN WHEN WE'RE 1695 00:59:14,840 --> 00:59:15,640 STARTING MEDICINES. 1696 00:59:15,640 --> 00:59:17,160 NEXT SLIDE, PLEASE. 1697 00:59:17,160 --> 00:59:23,440 SO THIS IS A STUDY FROM POST 1698 00:59:23,440 --> 00:59:28,800 HERPETIC NEURALGIA, AND THEY 1699 00:59:28,800 --> 00:59:29,480 COMPARED NORTRIPTYLINE, VERSUS 1700 00:59:29,480 --> 00:59:31,120 MORIN AND PLACENTA SEEBY, 1701 00:59:31,120 --> 00:59:32,640 THERE'S MORE DROP OUT WITH THE 1702 00:59:32,640 --> 00:59:35,120 STUDY WITH THE PATIENTS ON 1703 00:59:35,120 --> 00:59:36,640 MORPHINE THAN OTHER PATIENTS BUT 1704 00:59:36,640 --> 00:59:38,280 FOR THOSE WHO STUCK WITH IT, 1705 00:59:38,280 --> 00:59:41,160 THERE WAS PAIN SCORE REDUCTION 1706 00:59:41,160 --> 00:59:44,840 FROM BOTH OPIOIDS AND TRICYCLE 1707 00:59:44,840 --> 00:59:45,520 ANTIDEPRESS ABTS, WE TALKED 1708 00:59:45,520 --> 00:59:48,680 ABOUT THE SIDE EFFECT PROFILES 1709 00:59:48,680 --> 00:59:53,400 OF THESE, AND THAIZ CAN BE 1710 00:59:53,400 --> 00:59:53,920 UNPLEASANT UNFORTUNATELY. 1711 00:59:53,920 --> 00:59:56,400 IT WAS AN OLDER POPULATION SO 1712 00:59:56,400 --> 00:59:57,320 MAYBE MORE VULNERABLE BRAINS 1713 00:59:57,320 --> 00:59:58,800 GOING ON AS WELL. 1714 00:59:58,800 --> 00:59:59,840 NEXT SLIDE. 1715 00:59:59,840 --> 01:00:06,240 SOY NOW WE WILL TALK ABOUT 1716 01:00:06,240 --> 01:00:20,240 ANTICONVULSANTS OR, AND ALSO 1717 01:00:20,240 --> 01:00:21,120 THINGS--THE OVERALL MEDICATIONS 1718 01:00:21,120 --> 01:00:23,200 ARE THE 1S THAT HAVE THE KNOWN 1719 01:00:23,200 --> 01:00:26,800 SAFETY AND EFFICACY, THEY HAVE A 1720 01:00:26,800 --> 01:00:28,520 CROSS SECTION OF SPINAL CORD BUT 1721 01:00:28,520 --> 01:00:30,200 ALSO IN OTHER PLACES. 1722 01:00:30,200 --> 01:00:34,560 NEXT SLIDE, PLEASE. 1723 01:00:34,560 --> 01:00:35,760 AS PROMISED PRACTICAL TIPS ABOUT 1724 01:00:35,760 --> 01:00:37,840 HOW TO USE THESE PATIENTS. 1725 01:00:37,840 --> 01:00:39,520 USE THESE MEDICATIONS FOR OUR 1726 01:00:39,520 --> 01:00:39,800 PATIENTS. 1727 01:00:39,800 --> 01:00:40,680 SO THE FIRST THING IS YOU WANT 1728 01:00:40,680 --> 01:00:46,040 TO GET TO A REAL DOSE, OF THE 1729 01:00:46,040 --> 01:00:47,120 MEDICATION, SO, THAT'S EITHER 1730 01:00:47,120 --> 01:00:49,200 FOR MEDICINES THAT HAVE A BLOOD 1731 01:00:49,200 --> 01:00:51,720 LEVEL, YOU KNOW GET INTO A 1732 01:00:51,720 --> 01:00:52,920 THERAPEUTIC BLOOD LEVEL BUT 1733 01:00:52,920 --> 01:00:54,160 OTHERWISE JUSTA TO A DOSE THAT 1734 01:00:54,160 --> 01:00:56,040 WAS SORT OF IN THE LITERATURE IS 1735 01:00:56,040 --> 01:00:58,040 SORT OF THE BOOK MAXIMUM IF YOU 1736 01:00:58,040 --> 01:00:58,280 WILL. 1737 01:00:58,280 --> 01:00:59,640 AND YOU WANT TO DO THAT FOR 1738 01:00:59,640 --> 01:01:01,640 SEVERAL WEEKS IF YOU RECALL ALL 1739 01:01:01,640 --> 01:01:04,040 THOSE PICTURES SHORT OF SHOWED 1740 01:01:04,040 --> 01:01:04,920 THAT SEPARATION IDENTITY FROM 1741 01:01:04,920 --> 01:01:06,880 PLACEBO WAS NOT AN INSTANTANEOUS 1742 01:01:06,880 --> 01:01:07,640 THING, THAT'S SOMETHING THAT 1743 01:01:07,640 --> 01:01:09,480 WILL TAKE WEEKS OF CONSISTENCY, 1744 01:01:09,480 --> 01:01:10,600 BECAUSE THESE ARE MEDICINE THAT 1745 01:01:10,600 --> 01:01:14,080 ARE SORT OF NOT SUPER FAST. 1746 01:01:14,080 --> 01:01:16,000 WHAT YOU WANT TO DO IS ENCOURAGE 1747 01:01:16,000 --> 01:01:18,840 YOUR PATIENT TO KEEP A PAIN LOG 1748 01:01:18,840 --> 01:01:20,160 WHEN YOU'RE TRIALS THESE 1749 01:01:20,160 --> 01:01:20,920 MEDICINE BECAUSE OTHERWISE IT'S 1750 01:01:20,920 --> 01:01:22,440 LIKE TRYING TO KEEP TRACK OF 1751 01:01:22,440 --> 01:01:24,440 YOUR OWN HAIR GROWING FROM 1 DAY 1752 01:01:24,440 --> 01:01:25,480 TO THE NEXT, YOU'RE NOT 1753 01:01:25,480 --> 01:01:29,120 NECESSARILY GOING TO NOTICE 1754 01:01:29,120 --> 01:01:29,920 THAT. 1755 01:01:29,920 --> 01:01:31,640 BUT, OVER TIME YOU DID GET A 1756 01:01:31,640 --> 01:01:33,560 BETTER SENSE OF THAT. 1757 01:01:33,560 --> 01:01:35,240 AND IF AT FIRST YOU DON'T 1758 01:01:35,240 --> 01:01:38,480 SUCCEED, SO YOU TRIED SIM BALTA 1759 01:01:38,480 --> 01:01:40,880 FIRST FOR EXAMPLE, AND IT'S NOT 1760 01:01:40,880 --> 01:01:42,400 EFFECTIVE, TRY ANOTHER, THESE 1761 01:01:42,400 --> 01:01:43,240 MEDICINES ARE ALL SLIGHTLY 1762 01:01:43,240 --> 01:01:46,080 DIFFERENT AND I WOULD SAY THE 1763 01:01:46,080 --> 01:01:48,040 TRICYC LICKS ARE WORTH THE TRY 1764 01:01:48,040 --> 01:01:51,000 BECAUSE THEY CAN BE VERY HELPFUL 1765 01:01:51,000 --> 01:01:53,040 SO THAT'S SORT OF--THOSE ARE MY 1766 01:01:53,040 --> 01:01:57,320 PRACTICAL EPIGENETIC ITS--TIPS I 1767 01:01:57,320 --> 01:01:58,640 THINK, IS 1 OTHER THING TO 1768 01:01:58,640 --> 01:02:00,000 HIGHLIGHT IS I TALKED ABOUT THE 1769 01:02:00,000 --> 01:02:01,080 CONNECTION BETWEEN PAIN AND 1770 01:02:01,080 --> 01:02:01,880 DEPRESSION AND THE MANY 1771 01:02:01,880 --> 01:02:03,480 DIFFERENT PLACES THAT THESE 1772 01:02:03,480 --> 01:02:05,280 MEDICATIONS ACT AND SO, I DON'T 1773 01:02:05,280 --> 01:02:07,720 THINK THAT THE WAY THAT WE TREAT 1774 01:02:07,720 --> 01:02:08,960 DEPRESSION WITH THESE 1775 01:02:08,960 --> 01:02:09,840 MEDICATIONS IS IT NOT 1776 01:02:09,840 --> 01:02:12,920 NECESSARILY GOING TO BE THE SAME 1777 01:02:12,920 --> 01:02:16,440 THAT WE TREAT PAIN WITH THESE 1778 01:02:16,440 --> 01:02:16,760 MEDICATIONS. 1779 01:02:16,760 --> 01:02:20,800 SO ON TO THE NEXT SLIDE, COME IS 1780 01:02:20,800 --> 01:02:22,440 MY LAST SLIDE, I FOUND THIS 1781 01:02:22,440 --> 01:02:27,440 SUPER EXCITING PICTURE OF A SIN 1782 01:02:27,440 --> 01:02:28,960 APTION ONLINE SO I HOPE YOU 1783 01:02:28,960 --> 01:02:30,400 ENJOY IT AS MUCH AS I DO, AND 1784 01:02:30,400 --> 01:02:31,960 THANK YOU SO MUCH FOR HAVING ME 1785 01:02:31,960 --> 01:02:33,240 AND THE CONFERENCE FOLKS FOR 1786 01:02:33,240 --> 01:02:43,200 KEEPING THE SLIDES GOING. 1787 01:02:43,200 --> 01:02:45,400 >> THANK YOU VERY MUCH, THAT WAS 1788 01:02:45,400 --> 01:02:47,240 FANTASTIC DR. PRINCE AND WE HOPE 1789 01:02:47,240 --> 01:02:48,840 TO FIND MORE UNICORNS LIKE YOU 1790 01:02:48,840 --> 01:02:50,040 TO WORK WITH OUR PATIENT 1791 01:02:50,040 --> 01:02:50,360 POPULATION. 1792 01:02:50,360 --> 01:02:53,920 WE KNOW THAT THERE IS SO MUCH 1793 01:02:53,920 --> 01:02:56,320 ABOUT SICKLE CELL DISEASE THAT 1794 01:02:56,320 --> 01:02:57,480 AFFECTS MENTAL HEALTH AND VICE 1795 01:02:57,480 --> 01:03:00,960 VERSA AND YOU KNOW THE MORE WE 1796 01:03:00,960 --> 01:03:02,160 CAN DESTIGMATIZE MENTAL HEALTH 1797 01:03:02,160 --> 01:03:03,720 IN TERMS OF IMPROVING OUTCOMES 1798 01:03:03,720 --> 01:03:04,920 AND SICKLE CELL SEIZE, THE 1799 01:03:04,920 --> 01:03:07,120 BETTER, I THINK THERE ARE SO 1800 01:03:07,120 --> 01:03:08,800 MANY ANECDOTES WE CAN COULD 1801 01:03:08,800 --> 01:03:09,840 SHARE THAT WOULD REALLY SPEAK TO 1802 01:03:09,840 --> 01:03:13,240 THAT AND JUST TO MOVE THINGS 1803 01:03:13,240 --> 01:03:14,720 ALONG, I AM REALLY PSYCHESSED TO 1804 01:03:14,720 --> 01:03:15,640 INTRODUCE OUR NEXT SPEAKER AS 1805 01:03:15,640 --> 01:03:17,640 WELL AND AGAIN THE KEEP THE 1806 01:03:17,640 --> 01:03:18,600 QUESTIONS COMING, PLEASE PUT 1807 01:03:18,600 --> 01:03:20,560 THEM IN THE Q&A, WE WILL GO 1808 01:03:20,560 --> 01:03:23,440 THROUGH THEM AT THE PANEL, OUR 1809 01:03:23,440 --> 01:03:25,080 OTHER UNICORN WE WOULD LIKE TOO 1810 01:03:25,080 --> 01:03:27,440 INTRODUCE T IS DR. CARROLL, HE 1811 01:03:27,440 --> 01:03:29,320 APPRECIATES I'M CALLING HIM A 1812 01:03:29,320 --> 01:03:30,880 UNICORN AS WELL. 1813 01:03:30,880 --> 01:03:32,000 HE'S AN INTERNATIONALLY 1814 01:03:32,000 --> 01:03:34,560 RECOGNIZED EXPERT IN PULTY 1815 01:03:34,560 --> 01:03:35,960 DISCIPLINARY MANAGEMENT OF 1816 01:03:35,960 --> 01:03:37,320 COMPLEX PAIN, HIGH UTILIZATION 1817 01:03:37,320 --> 01:03:39,560 IN INDIVIDUALS WITH SICKLE CELL 1818 01:03:39,560 --> 01:03:42,640 DISEASE, HE IS A PIONEER OF THE 1819 01:03:42,640 --> 01:03:44,040 INTEGRATION OF CHRONIC PAIN 1820 01:03:44,040 --> 01:03:45,440 MANAGEMENT AND PSYCHEIATIC CARE, 1821 01:03:45,440 --> 01:03:48,040 HE IS OUR GO-TO FOR INDIVIDUALS 1822 01:03:48,040 --> 01:03:51,040 WITH WHOM WE'VE RUN OUT OF OTHER 1823 01:03:51,040 --> 01:03:53,960 OPTIONS, HE IS JUST AN AMAZING 1824 01:03:53,960 --> 01:03:55,440 INDIVIDUAL, HE'S PROBABLY GOING 1825 01:03:55,440 --> 01:03:57,520 TO BE ANNOYED BY THIS 1826 01:03:57,520 --> 01:04:00,840 INTRODUCTION AND A MEMBER OF THE 1827 01:04:00,840 --> 01:04:02,600 JOHNS HOPKINS CENTER FOR ADULTS, 1828 01:04:02,600 --> 01:04:04,840 REALLY HELPING TO DIRECT THE 1829 01:04:04,840 --> 01:04:07,440 INTEGRATIVE CARE OF PATIENTS 1830 01:04:07,440 --> 01:04:09,400 THROUGH PARTICIPATION AND 1831 01:04:09,400 --> 01:04:11,320 MULTIDISPLNARY ROUNDS DIRECT 1832 01:04:11,320 --> 01:04:13,200 PATIENT SUPER VISION, WORKING ON 1833 01:04:13,200 --> 01:04:13,880 INTEGRATING BEHAVIORIAL AND 1834 01:04:13,880 --> 01:04:15,520 PSYCHIATRIC CARE FOR A LONG TIME 1835 01:04:15,520 --> 01:04:17,400 AND SICKLE CELL DISEASE AND 1836 01:04:17,400 --> 01:04:21,120 REALRE EXCITED TO HAVE HIM HERE 1837 01:04:21,120 --> 01:04:29,320 TODAY TO PRESENT ON BUPRENORPH 1838 01:04:29,320 --> 01:04:30,960 INE FOR CHRONIC PAIN AND WHERE 1839 01:04:30,960 --> 01:04:32,000 WE GO FROM THERE. 1840 01:04:32,000 --> 01:04:36,360 >> ALL YOU DR. CARROLL. 1841 01:04:36,360 --> 01:04:39,120 HEALTH OUTCOMES, EVERYBODY, I'M 1842 01:04:39,120 --> 01:04:40,560 NOT ANNOYED BUT, YEAH THAT WAS A 1843 01:04:40,560 --> 01:04:44,840 LITTLE MUCH, BUT THANKS 1844 01:04:44,840 --> 01:04:47,120 DR. KANTER, SO LET'S TALK ABOUT 1845 01:04:47,120 --> 01:04:53,440 A VERY STRANGE DRUG CALLED 1846 01:04:53,440 --> 01:04:55,400 BUPRENORPH INE, I HEAR A LOT OF 1847 01:04:55,400 --> 01:04:57,280 INTEREST IN IT RECENTLY AND IT'S 1848 01:04:57,280 --> 01:05:00,720 USEFUL PROPERTIES AND I THINK IT 1849 01:05:00,720 --> 01:05:02,360 CAN PROBABLY HELP A FAIR NUMBER 1850 01:05:02,360 --> 01:05:03,840 OF PEOPLE WHEN RPGHT THINGS 1851 01:05:03,840 --> 01:05:05,560 HAVEN'T WORKED BUT I'M ALSO 1852 01:05:05,560 --> 01:05:07,000 GOING TO POOR A LITTLE COLD 1853 01:05:07,000 --> 01:05:15,120 WATER, I THINK ON THE END. 1854 01:05:15,120 --> 01:05:16,280 BECAUSE I THINK WHENEVER 1855 01:05:16,280 --> 01:05:17,640 SOMETHING'S NEW, WE THINK IT'S 1856 01:05:17,640 --> 01:05:21,080 GOING TO BE A MIRACLE, AND THEN 1857 01:05:21,080 --> 01:05:23,880 AFTER 5 YEARS WE FIND OUT IT'S 1858 01:05:23,880 --> 01:05:25,520 BEING ABUSED AND ME BEING A 1859 01:05:25,520 --> 01:05:26,800 SKEPTIC, I HAVE TO THROW THAT 1860 01:05:26,800 --> 01:05:26,960 IN. 1861 01:05:26,960 --> 01:05:28,360 SO ON TO THE NEXT SLIDE ISSUE 1862 01:05:28,360 --> 01:05:30,080 PLEASE. 1863 01:05:30,080 --> 01:05:31,960 SO I THINK, LIKE 80ISH% OF 1864 01:05:31,960 --> 01:05:44,040 LAWEDDER DALE YOU NEED TO KNOW 1865 01:05:44,040 --> 01:05:46,400 ABOUT BUPRENOHPH INE, AND IT'S A 1866 01:05:46,400 --> 01:05:47,840 OPID IDENTITY, IT'S A PASHT 1867 01:05:47,840 --> 01:05:50,000 AGONIST ON THE RECEPTOR AND THE 1868 01:05:50,000 --> 01:05:52,680 NEWER THINGS ARE THE BRAIN, 1869 01:05:52,680 --> 01:05:54,520 SPINAL CORD AND COLON, THAT 1870 01:05:54,520 --> 01:05:55,960 REALLY MEDIATE WHAT WE USUALLY 1871 01:05:55,960 --> 01:05:59,080 THINK OF AS OPIOID EFFECTS LIKE 1872 01:05:59,080 --> 01:06:00,720 ANNAL GEEZIA, TOLERANCE, 1873 01:06:00,720 --> 01:06:01,560 WITHDRAWAL, POSITIVE 1874 01:06:01,560 --> 01:06:02,680 REINFORCEMENT OR REWARD WHICH IS 1875 01:06:02,680 --> 01:06:06,480 WHAT LEADS TO ADDICTION. 1876 01:06:06,480 --> 01:06:07,560 CONSTIPATION TO SOME EXTENT. 1877 01:06:07,560 --> 01:06:08,880 SO SOME OF THE STUFF YOU THINK 1878 01:06:08,880 --> 01:06:13,080 OF AS AN OPIOID EFFECT IS FROM 1879 01:06:13,080 --> 01:06:16,040 THE NEW OPIOID RECEPTOR AND SO 1880 01:06:16,040 --> 01:06:18,400 WHAT PARTIAL AGONIST DO UNLIKE 1881 01:06:18,400 --> 01:06:19,080 MORPHINE AND METHADONE AND ALL 1882 01:06:19,080 --> 01:06:20,640 THE OTHER STUFF YOU THINK OF, 1883 01:06:20,640 --> 01:06:22,600 WHERE THE FULL AG MIST, THE 1884 01:06:22,600 --> 01:06:25,640 HIGHER THE DOSE, THE HIGHER THE 1885 01:06:25,640 --> 01:06:28,640 RECEPTORS ARE ACTIVATED, WITH 1886 01:06:28,640 --> 01:06:30,240 OTHER PARTIAL AGONISTS, IT'S 1887 01:06:30,240 --> 01:06:31,600 ACTIVATED SORT OF STEADILY WITH 1888 01:06:31,600 --> 01:06:33,040 INCREASING DOSE UP TO A POINT 1889 01:06:33,040 --> 01:06:34,920 AND THEN IT FLATTENED OUT AND 1890 01:06:34,920 --> 01:06:36,240 YOU GET THIS CEILING EFFECT 1891 01:06:36,240 --> 01:06:37,840 WHERE AT A CERTAIN LEVEL OF 1892 01:06:37,840 --> 01:06:49,760 TOLERANCE OR STAY DAILY DOSE AND 1893 01:06:49,760 --> 01:06:53,320 TAKE MORE BIEWP NOEVERRINE IS 1894 01:06:53,320 --> 01:06:54,720 SAFER THAN OTHERS BECAUSE IT'S 1895 01:06:54,720 --> 01:07:01,400 HARD TO OVERDOSE ON IT. 1896 01:07:01,400 --> 01:07:05,840 SO THAT'S 1 THING THAT'S 1897 01:07:05,840 --> 01:07:06,640 DIFFERENT ABOUT BUPRENORPHINE, 1898 01:07:06,640 --> 01:07:08,800 IS THAT IT STICKS TO RECEPTORS 1899 01:07:08,800 --> 01:07:10,400 LIKE FLU, O THE RECEPTOR 1900 01:07:10,400 --> 01:07:12,960 AFFINITY WHICH A MEASURE OF WHAT 1901 01:07:12,960 --> 01:07:16,560 I JUST SAID IS SIGNIFICANTLY 1902 01:07:16,560 --> 01:07:19,360 HIGHER THAN FOR MULTIPLE OTHER 1903 01:07:19,360 --> 01:07:20,760 OPIOIDS MAINLY BECAUSE WHEN 1904 01:07:20,760 --> 01:07:23,000 BUPRENORPHINE GETS ON A RECEPTOR 1905 01:07:23,000 --> 01:07:24,720 IS LOCKS INTO IT AND TAKES A 1906 01:07:24,720 --> 01:07:27,040 LONG TIME TO COME BACK OFF. 1907 01:07:27,040 --> 01:07:33,120 SOA THIS BOILS DOWN TO IS IF YOU 1908 01:07:33,120 --> 01:07:36,960 ARE TAKING ANOTHER OPIOID, AND, 1909 01:07:36,960 --> 01:07:38,600 STANDARD OPIOID AND YOU TAKE 1910 01:07:38,600 --> 01:07:39,960 BUPRENORPHINE WITH IT, THEY WILL 1911 01:07:39,960 --> 01:07:41,440 KICK THE OTHERS OFF THE 1912 01:07:41,440 --> 01:07:42,120 RESUPPORTORS, GOING THE OTHER 1913 01:07:42,120 --> 01:07:46,240 WAY IF YOU ARE SORT OF STEADILY 1914 01:07:46,240 --> 01:07:48,080 TAKING BUPRENORPHINE AND YOU 1915 01:07:48,080 --> 01:07:49,400 TAKE ANOTHER OPIOID ON TOP OF 1916 01:07:49,400 --> 01:07:51,720 IT, THEN THOSE RECEPTORS WILL BE 1917 01:07:51,720 --> 01:07:52,880 MOSTLY OCCUPIED BY THE 1918 01:07:52,880 --> 01:07:53,680 BUPRENORPHINE AND SOME OF THE 1919 01:07:53,680 --> 01:07:55,800 EFFECT WILL BE BLOCKED. 1920 01:07:55,800 --> 01:07:58,000 SO THERE ARE OTHER THINGS ABOUT 1921 01:07:58,000 --> 01:07:59,160 BUPRENORPHINE THAT ARE FUNNY BUT 1922 01:07:59,160 --> 01:08:01,160 I THINK IF YOU KNOW THOSE 2 1923 01:08:01,160 --> 01:08:02,240 THINGS, YOU KNOW MOST OF WHAT 1924 01:08:02,240 --> 01:08:05,880 YOU NEED TO KNOW TO UNDERSTAND 1925 01:08:05,880 --> 01:08:07,640 WHERE IT'S USEFUL, WHY IT MIGHT 1926 01:08:07,640 --> 01:08:08,880 BE USEFUL BUT ALSO SOME OF THE 1927 01:08:08,880 --> 01:08:10,200 TRICKS THAT YOU HAVE TO DEAL 1928 01:08:10,200 --> 01:08:20,800 WITH TO MANAGE IT. 1929 01:08:20,800 --> 01:08:21,240 NEXT SLIDE. 1930 01:08:21,240 --> 01:08:22,920 I THINK I ALREADY SAID MOST OF 1931 01:08:22,920 --> 01:08:24,200 THIS, BUT THE MAIN THING IS 1932 01:08:24,200 --> 01:08:28,160 SAFETY, YOU GET HIGHER DOSES AND 1933 01:08:28,160 --> 01:08:42,960 1 OF THE REASONS IT'S USED TO 1934 01:08:42,960 --> 01:08:45,160 TREAT ADDICTIONS, AND SO THERE'S 1935 01:08:45,160 --> 01:08:48,040 A LOT OF BREAK THROUGH, AND 1936 01:08:48,040 --> 01:08:48,760 PARTICULARLY THE SUBLINGUAL 1937 01:08:48,760 --> 01:08:50,840 PREPARATIONS OR THE PREPARATIONS 1938 01:08:50,840 --> 01:08:53,000 THAT ARE USED FOR PAIN 1939 01:08:53,000 --> 01:08:54,240 BUPRENORPHINE LASTS A LONG TIME 1940 01:08:54,240 --> 01:08:56,000 SO YOU DON'T GET A LOT OF BREAK 1941 01:08:56,000 --> 01:08:58,640 THROUGH WITH WITHDRAWAL, THERE'S 1942 01:08:58,640 --> 01:09:02,600 LESS CRAVING, CAN YOU BACK UP, 1943 01:09:02,600 --> 01:09:02,880 PLEASE? 1944 01:09:02,880 --> 01:09:05,320 SO ALSO, IN WE TALK ABOUT 1945 01:09:05,320 --> 01:09:07,640 SUBSTANCE USE DISORDERS, IT 1946 01:09:07,640 --> 01:09:08,800 BLUNTS THE REINFORCEMENT AND SO 1947 01:09:08,800 --> 01:09:11,040 SOMEONE HAS A PROBLEM WITH 1948 01:09:11,040 --> 01:09:12,040 OPIOIDS, THEY TAKE THEIR 1949 01:09:12,040 --> 01:09:13,320 BUPRENORPHINE BUT THEY SLIP UP 1 1950 01:09:13,320 --> 01:09:14,760 DAY AND THEY TAKE SOMETHING 1951 01:09:14,760 --> 01:09:16,480 ELSE, THEN, THEY DON'T GET THE 1952 01:09:16,480 --> 01:09:19,040 SAME REWARD OUT OF THAT OTHER 1953 01:09:19,040 --> 01:09:20,800 THING AND IT HAS A WAY OF 1954 01:09:20,800 --> 01:09:22,760 HELPING THEM NOT GO INTO FULL 1955 01:09:22,760 --> 01:09:23,120 RELAPSE. 1956 01:09:23,120 --> 01:09:24,200 I MISSED A REFERENCE TO THIS 1957 01:09:24,200 --> 01:09:26,840 SLIDE, BY THE WAY, IT'S KNOWN 1958 01:09:26,840 --> 01:09:29,680 THAT BUPRENORPHINE HAS A MORE 1959 01:09:29,680 --> 01:09:31,200 MODEST WITHDRAWAL SYNDROME THAN 1960 01:09:31,200 --> 01:09:32,680 RPGHT OPIOIDS, THE FOLKS THAT 1961 01:09:32,680 --> 01:09:35,360 DID THAT WERE AT HOPKINS AND THE 1962 01:09:35,360 --> 01:09:44,440 FIRST AUTHOR WAS MY OLD 1963 01:09:44,440 --> 01:09:47,600 COLLEAGUE DR. ANDREW TOMPKINs, 1964 01:09:47,600 --> 01:09:48,840 IF YOU WANT TO KNOW MORE ABOUT 1965 01:09:48,840 --> 01:09:50,960 THAT, YOU CAN LOOK IT UP. 1966 01:09:50,960 --> 01:09:51,680 SO NEXT SLIDE. 1967 01:09:51,680 --> 01:09:53,440 IT'S LONG BEEN KNOWN THAT 1968 01:09:53,440 --> 01:09:54,240 BUPRENORPHINE WORKS WELL ON 1969 01:09:54,240 --> 01:09:55,920 PAIN, IN FACT THE FIRST 1 WAS 1970 01:09:55,920 --> 01:09:59,840 APPROVED FOR PAIN, IT WAS CALLED 1971 01:09:59,840 --> 01:10:01,840 BUPRINEX, IT'S AN IV OR IM 1972 01:10:01,840 --> 01:10:04,640 PREPARATION THAT WAS APPROVED 1973 01:10:04,640 --> 01:10:07,360 FOR ACUTE PAIN PROBABLY MID90S, 1974 01:10:07,360 --> 01:10:11,360 EARLY 2000S AT THE LATEST. 1975 01:10:11,360 --> 01:10:12,800 I REMEMBER USING AN OFFLABEL FOR 1976 01:10:12,800 --> 01:10:13,880 THE TREATMENT OF WITHDRAWAL AND 1977 01:10:13,880 --> 01:10:18,000 PAIN BACK IN THE EARLY 2000S. 1978 01:10:18,000 --> 01:10:20,040 BUT WITH RESPECT TO CHRONIC 1979 01:10:20,040 --> 01:10:21,000 PAIN, IT'S ALSO KNOWN THAT IT 1980 01:10:21,000 --> 01:10:22,880 CAN WORK FOR THAT, AND THERE ARE 1981 01:10:22,880 --> 01:10:24,320 PREPARATIONS OUT OF IT OR ARE 1982 01:10:24,320 --> 01:10:25,840 APPROVED FOR THAT USE, I THINK 1983 01:10:25,840 --> 01:10:27,480 WE SKIPPED A SLIDE, CAN YOU BACK 1984 01:10:27,480 --> 01:10:28,440 UP 1. 1985 01:10:28,440 --> 01:10:32,080 SO THIS IS A META-ANALYSIS OF 1986 01:10:32,080 --> 01:10:34,360 PEOPLE WHO ARE TREATED FOR 1987 01:10:34,360 --> 01:10:36,720 OPIOID USE DISORDER ALSO HAVE 1988 01:10:36,720 --> 01:10:39,440 CHRONIC PAIN AND BUPRENORPHINE 1989 01:10:39,440 --> 01:10:40,960 HAD A BIG EFFECT ON CHRONIC 1990 01:10:40,960 --> 01:10:41,160 PAIN. 1991 01:10:41,160 --> 01:10:45,360 ON NOW ON TO THE NEXT SLIDE. 1992 01:10:45,360 --> 01:10:46,280 AND THIS IS SYNTHESIS OF STUDIES 1993 01:10:46,280 --> 01:10:50,840 THAT WERE DONE WITH PEOPLE WHO 1994 01:10:50,840 --> 01:10:53,120 DID NOT HAVE AN OPIOID USE 1995 01:10:53,120 --> 01:10:55,280 DISORDER THAT WERE TREATED WITH 1996 01:10:55,280 --> 01:10:56,840 BUPRENORPHINE AND IT DID HAVE A 1997 01:10:56,840 --> 01:10:59,160 FAVORABLE EFFECT WHICH IS NOT 1998 01:10:59,160 --> 01:10:59,520 SURPRISING. 1999 01:10:59,520 --> 01:10:59,800 NEXT. 2000 01:10:59,800 --> 01:11:01,480 SO WHY SHOULD WE USE THIS THING? 2001 01:11:01,480 --> 01:11:05,360 WELL, I THINK THERE ARE 3 BASIC 2002 01:11:05,360 --> 01:11:06,400 REASONS. 2003 01:11:06,400 --> 01:11:07,680 ONE IS, IT'S SAFER, APPROXIMATE 2004 01:11:07,680 --> 01:11:08,640 I'VE ALREADY TALKED ABOUT THAT 2005 01:11:08,640 --> 01:11:12,440 AND I THINK, YOU KNOW, RELATIVE 2006 01:11:12,440 --> 01:11:14,640 TO LIKE HIGH DOSE CHRONIC OPIOID 2007 01:11:14,640 --> 01:11:16,040 THERAPY AND THERAPY IN 2008 01:11:16,040 --> 01:11:17,560 PARTICULAR, IT'S ALMOST 2009 01:11:17,560 --> 01:11:19,320 QUALITATIVELY SAFER THAN OTHER 2010 01:11:19,320 --> 01:11:19,560 OPIOIDS. 2011 01:11:19,560 --> 01:11:21,040 THE OTHER THING IS THAT IT'S 2012 01:11:21,040 --> 01:11:22,360 DIFFERENT, SO IF YOU HAVE 2013 01:11:22,360 --> 01:11:24,440 SOMEONE WHO HAS BEEN ON CHRONIC 2014 01:11:24,440 --> 01:11:26,400 THERAPY AT SOME REASONABLE DOSE 2015 01:11:26,400 --> 01:11:27,680 OR MORE THAN A REASONABLE DOSE 2016 01:11:27,680 --> 01:11:32,440 AND IT'S NOT WORKING, THEN, YOU 2017 01:11:32,440 --> 01:11:34,560 CAN USE BUPRENORPHINE TO ROTATE 2018 01:11:34,560 --> 01:11:36,080 TO AND STAY WITH A STRAIGHT 2019 01:11:36,080 --> 01:11:38,160 FACE, FIRST OF ALL, YOU KNOW 2020 01:11:38,160 --> 01:11:39,240 IT'S SAFER AND SECOND IT JUST 2021 01:11:39,240 --> 01:11:40,200 MIGHT ACTUALLY WORK IN A 2022 01:11:40,200 --> 01:11:41,640 DIFFERENT WAY THAT COULD HELP 2023 01:11:41,640 --> 01:11:43,160 THE PAIN. 2024 01:11:43,160 --> 01:11:44,120 AND WE'VE CERTAINLY SEEN THAT. 2025 01:11:44,120 --> 01:11:45,960 AND THE OTHER PART OF IT IS THAT 2026 01:11:45,960 --> 01:11:48,200 IT HAS A FAVORABLE PROFILE 2027 01:11:48,200 --> 01:11:49,520 BEHAVIORIAL EFFECT. 2028 01:11:49,520 --> 01:11:51,240 SO REDUCED POSITIVE 2029 01:11:51,240 --> 01:11:52,400 REINFORCEMENT, MODEST 2030 01:11:52,400 --> 01:11:54,160 WITHDRAWAL, LONG ACTING, YOU SEE 2031 01:11:54,160 --> 01:11:55,760 LESS BREAK THROUGH AND SO FORTH. 2032 01:11:55,760 --> 01:11:56,920 I'VE HAD SOME PEOPLE ALSO 2033 01:11:56,920 --> 01:11:58,560 SIGNIFY THAT IT JUST--THEY DON'T 2034 01:11:58,560 --> 01:12:00,000 HAVE TO THINK ABOUT IT AS MUCH, 2035 01:12:00,000 --> 01:12:01,280 YOU KNOW YOU DON'T HAVE TO SORT 2036 01:12:01,280 --> 01:12:04,240 OF LIKE STAY ON TOP OF TAKING A 2037 01:12:04,240 --> 01:12:07,360 MEDICINE 3 OR 4 TIMES A DAY. 2038 01:12:07,360 --> 01:12:09,640 SO MY SLIDES KEEP SKIPPING ON 2039 01:12:09,640 --> 01:12:14,960 THEIR OWN, NEXT SLIDE, SO HOW DO 2040 01:12:14,960 --> 01:12:17,720 YOU USE THE THING, I WILL TALK 2041 01:12:17,720 --> 01:12:21,600 ABOUT HOW YOU SWITCH PEOPLE FROM 2042 01:12:21,600 --> 01:12:23,720 ANOTHER OPIOID AGONIST ON TO 2043 01:12:23,720 --> 01:12:24,720 BUPRENORPHINE AND THAT REQUIRES 2044 01:12:24,720 --> 01:12:25,600 TECHNIQUE BECAUSE OF THE CEILING 2045 01:12:25,600 --> 01:12:27,000 EFFECT AND THE WAY IT WORKS ON 2046 01:12:27,000 --> 01:12:31,640 RECEPTORS AND I AM NOW GOING TO 2047 01:12:31,640 --> 01:12:32,840 USE HIGHLY ADVANCED WE WILL USE 2048 01:12:32,840 --> 01:12:46,680 THE GRAPHICS TO SHOW THIS WHOSE 2049 01:12:46,680 --> 01:12:49,640 TAKING A RELATIVELY HIGH AND THE 2050 01:12:49,640 --> 01:12:50,480 OPIOID GOES UNSUPPORTED, 2051 01:12:50,480 --> 01:12:53,240 METABOLIZED DOWN AND GOES UP AND 2052 01:12:53,240 --> 01:12:53,720 BACK DOWN. 2053 01:12:53,720 --> 01:12:55,480 IT'S ABOVE THEIR LEVEL OF 2054 01:12:55,480 --> 01:12:56,440 TOLERANCE, THEY'RE NOT GOING 2055 01:12:56,440 --> 01:12:57,240 INTO WITHDRAWAL OR SUCH THINGS 2056 01:12:57,240 --> 01:12:59,800 LIKE THAT BUT IF YOU GIVE 2057 01:12:59,800 --> 01:13:01,080 BUPRENORPH ALONG WITH THIS 2058 01:13:01,080 --> 01:13:03,040 RELATIVELY HIGH DOSE THAT 2059 01:13:03,040 --> 01:13:04,400 SOMEONE'S TOLERANT, TOO, THE 2060 01:13:04,400 --> 01:13:06,280 BUPRENORPH CAN OUTCOME PETE FOR 2061 01:13:06,280 --> 01:13:07,400 THE RECEPTORS, DISPLACE IT AND 2062 01:13:07,400 --> 01:13:09,560 IF THEY'RE TOLERANCE IS ABOVE 2063 01:13:09,560 --> 01:13:10,400 THAT BUPRENORPH CEILING EFFECT, 2064 01:13:10,400 --> 01:13:13,840 CAN YOU THINK I WILL RECIPITATE 2065 01:13:13,840 --> 01:13:14,240 WITHDRAWAL. 2066 01:13:14,240 --> 01:13:16,040 PEOPLE CAN GO INTO OPIOID 2067 01:13:16,040 --> 01:13:17,280 WITHDRAWAL WHICH IS MISERABLE, 2068 01:13:17,280 --> 01:13:19,640 NOW IT'S NOT AS BAD AS IF YOU 2069 01:13:19,640 --> 01:13:24,200 GAVE A FULL OPIOID AGANIST AND 2070 01:13:24,200 --> 01:13:27,360 THEN ALLOWED THEM TO GET DOWN TO 2071 01:13:27,360 --> 01:13:28,560 0, BUT UNLESANT AND THERE'S NOT 2072 01:13:28,560 --> 01:13:30,520 A LOT TO DO ABOUT IT BECAUSE YOU 2073 01:13:30,520 --> 01:13:33,280 HAVE TO WADE FOR THE 2074 01:13:33,280 --> 01:13:34,400 BUPRENORPHINE TO BE METABOLIZED 2075 01:13:34,400 --> 01:13:35,240 OUT AND GO AWAY. 2076 01:13:35,240 --> 01:13:42,360 SO THIS SHOULD BE BE,A VOIDED. 2077 01:13:42,360 --> 01:13:44,080 BUT ALTHOUGH BUPRENORPHINE CAN 2078 01:13:44,080 --> 01:13:44,920 PRECIPITATE WITHDRAWAL, IT CAN 2079 01:13:44,920 --> 01:13:46,040 ALSO TREAT PROJECTION NEURONS OR 2080 01:13:46,040 --> 01:13:46,600 PIONS SPAINIOUS WITHDRAWAL. 2081 01:13:46,600 --> 01:13:49,320 SO IF YOU HAVE SOMEONE WHO'S 2082 01:13:49,320 --> 01:13:51,040 TAKING AN OPIOID, THEIR 2083 01:13:51,040 --> 01:13:52,400 TOLERANCE ISN'T PARTICULARLY 2084 01:13:52,400 --> 01:13:53,200 HIGH, THEY COMPLETELY STOP AND 2085 01:13:53,200 --> 01:13:54,600 THEY GO INTO SOME LEVEL OF 2086 01:13:54,600 --> 01:13:58,240 WITHDRAWAL AND YOU GIVE THEM 2087 01:13:58,240 --> 01:13:59,880 BUPRENORPHINE AND THE CEILING 2088 01:13:59,880 --> 01:14:01,520 EFFECT IS ABOVE THAT LEVEL OF 2089 01:14:01,520 --> 01:14:03,440 TOLERANCE IT WILL ARREST THAT 2090 01:14:03,440 --> 01:14:04,680 SPONTANEOUS WITHDRAWAL. 2091 01:14:04,680 --> 01:14:05,720 SOY DEPENDING ON THE PERSON'S 2092 01:14:05,720 --> 01:14:07,520 LEVEL OF TOLERANCE AND WHAT'S 2093 01:14:07,520 --> 01:14:08,680 CIRCULULATING IN THE SYSTEM, YOU 2094 01:14:08,680 --> 01:14:10,840 CAN HAVE THE WITHDRAWAL OR 2095 01:14:10,840 --> 01:14:17,520 SPONTANEOUS WITHDRAWAL TREATED 2096 01:14:17,520 --> 01:14:18,400 NEXT SLIDE. 2097 01:14:18,400 --> 01:14:19,680 OR WEIRDLY ENOUGH, THE SAME 2098 01:14:19,680 --> 01:14:21,880 PERSON WHO HAS A RELATIVELY HIGH 2099 01:14:21,880 --> 01:14:24,080 TOLERANCE, IF THEY COMPLETELY 2100 01:14:24,080 --> 01:14:25,120 STOP THE OPIOID THEY'RE TAKING 2101 01:14:25,120 --> 01:14:27,440 AND WAIT LONG ENOUGH, YOU CAN GO 2102 01:14:27,440 --> 01:14:29,160 INTO REALLY SEVERE WITHDRAWAL, 2103 01:14:29,160 --> 01:14:30,560 BUT THEN, BUPRENORPH, IF THERE'S 2104 01:14:30,560 --> 01:14:33,000 NO OTHER AGONIST TO IN THIS 2105 01:14:33,000 --> 01:14:34,520 PLACE CAN MODERATE THAT, BECAUSE 2106 01:14:34,520 --> 01:14:37,600 AT LEAST IT HAS SOME OPIOID 2107 01:14:37,600 --> 01:14:39,240 EFFECT, PROBABLY UP TO 90 OR 2108 01:14:39,240 --> 01:14:41,880 MORE CLINICAL TODAY, SO IT CAN 2109 01:14:41,880 --> 01:14:42,480 ACTUALLY MODERATE SPONTANEOUS 2110 01:14:42,480 --> 01:14:43,400 WITHDRAWAL FOR ALMOST THE SAME 2111 01:14:43,400 --> 01:14:44,920 PERSON THAT WOULD HAVE 2112 01:14:44,920 --> 01:14:46,880 PRECIPITATED WITHDRAWAL IF THEY 2113 01:14:46,880 --> 01:14:48,440 HAD CIRCULATING AGONIST, SO THIS 2114 01:14:48,440 --> 01:14:52,080 GETS WEIRD TO THINK THROUGH. 2115 01:14:52,080 --> 01:14:58,080 SEE, NEXT SLIDE. 2116 01:14:58,080 --> 01:14:59,400 BI BUT THERE'S A WAY TO THINK 2117 01:14:59,400 --> 01:15:01,040 ABOUT IT THAT SIMPLIFYS IT AND 2118 01:15:01,040 --> 01:15:04,240 IT COMES DOWN TO IS THE LOWER 2119 01:15:04,240 --> 01:15:05,640 SPRN'S TOLERANCE IS BEFORE THEY 2120 01:15:05,640 --> 01:15:08,040 HAVE TO TRANSITION OVER TO 2121 01:15:08,040 --> 01:15:11,040 BUPRENORPHINE, THE LESS LIKELY 2122 01:15:11,040 --> 01:15:12,680 YOU'RE GOING TO GET ABOUT BAD 2123 01:15:12,680 --> 01:15:13,240 THING HAPPEN. 2124 01:15:13,240 --> 01:15:16,440 SO THE LESS LIKELY YOU WILL HAVE 2125 01:15:16,440 --> 01:15:18,080 SPONTANEOUS WITHDRAWAL OR SEVERE 2126 01:15:18,080 --> 01:15:19,320 SPONTANEOUS WITHDRAWAL AND IF 2127 01:15:19,320 --> 01:15:22,040 YOU DO THE BUPRENORPHINE WILL 2128 01:15:22,040 --> 01:15:23,720 PROBABLY HELP IT. 2129 01:15:23,720 --> 01:15:25,440 AT THE SAME TIME IF SOMEONE'S 2130 01:15:25,440 --> 01:15:27,320 TOLERANCE IS LOW, THE 2131 01:15:27,320 --> 01:15:28,920 BUPRENORPHINE IS UNLIKELY TO 2132 01:15:28,920 --> 01:15:30,640 PRECIPITATE MUCH WITH THE 2133 01:15:30,640 --> 01:15:31,240 WITHDRAWAL. 2134 01:15:31,240 --> 01:15:31,960 SO REALLY THE MAIN THING THAT 2135 01:15:31,960 --> 01:15:34,200 CAN HELP TO GET PEOPLE FROM 2136 01:15:34,200 --> 01:15:35,920 ANOTHER AGONIST ON TO 2137 01:15:35,920 --> 01:15:38,640 BUPRENORPHINE IS TO HAVE THEM 2138 01:15:38,640 --> 01:15:42,040 TAPERED DOWN TO A LEVEL OF 2139 01:15:42,040 --> 01:15:43,880 TOLERANCE THAT THE BUPRENORPH 2140 01:15:43,880 --> 01:15:45,160 ARE LIKELY TO CAUSE TROUBLE SO 2141 01:15:45,160 --> 01:15:47,480 FOR US WHEN WE TRANSITION 2142 01:15:47,480 --> 01:15:50,200 PEOPLE, WE TYPICALLY TARGET 2143 01:15:50,200 --> 01:15:53,280 AROUND 90 TO A HUNDRED QUOTES 2144 01:15:53,280 --> 01:15:55,040 PER DAY, WE TAPER PEOPLE OFF 2145 01:15:55,040 --> 01:15:56,600 WITH THE LONG ACTING MEDICINES 2146 01:15:56,600 --> 01:15:57,760 FIRST THEY SEEM TO HAVE AN 2147 01:15:57,760 --> 01:15:59,680 EASIER TIME WITH THAT. 2148 01:15:59,680 --> 01:16:02,240 THEN WE DO THE TRANSITION IN A 2149 01:16:02,240 --> 01:16:03,600 FAIRLY CLASS CALAWAY, WE STOP 2150 01:16:03,600 --> 01:16:05,320 THE AGONIST, WAIT UNTIL IT'S 2151 01:16:05,320 --> 01:16:07,720 CLEARED OUT UNTIL PEOPLE HAVE 2152 01:16:07,720 --> 01:16:12,120 SOME MILD WITHDRAWAL, THEN KNOW 2153 01:16:12,120 --> 01:16:14,320 THAT IT'S PRETTY MUCH NOT 2154 01:16:14,320 --> 01:16:17,040 BOTHERING THEM AND DISPLACE, AND 2155 01:16:17,040 --> 01:16:19,800 THEN START THE BUPRENORPHINE AND 2156 01:16:19,800 --> 01:16:22,320 AS THE BUPRENORPH'SINE IS ADDED, 2157 01:16:22,320 --> 01:16:25,480 YOU SEE AUTOGONE AWAY AND THEN 2158 01:16:25,480 --> 01:16:28,560 THERE'S A DONE. 2159 01:16:28,560 --> 01:16:29,520 SO THEN YOU START WITH THE 2160 01:16:29,520 --> 01:16:32,080 AGONIST BUT YOU HAVE TO DO IT 2161 01:16:32,080 --> 01:16:33,240 SLOWLY TO, VOID PRECIPITATE 2162 01:16:33,240 --> 01:16:34,080 WITHDRAWAL AND THEN YOU'RE LEFT 2163 01:16:34,080 --> 01:16:36,640 AT THE END WITH THE PERSONS ON 2 2164 01:16:36,640 --> 01:16:38,040 DRUGS INSTEAD OF 1 YOU HAVE TO 2165 01:16:38,040 --> 01:16:39,280 TAPER OFF THE OLD AGONIST BUT 2166 01:16:39,280 --> 01:16:40,600 THERE ARE WAYS OF DOING THAT BUT 2167 01:16:40,600 --> 01:16:42,240 I WILL NOT GO INTO THAT TOO 2168 01:16:42,240 --> 01:16:48,440 MUCH. 2169 01:16:48,440 --> 01:16:49,160 NEXT SLIDE, PLEASE. 2170 01:16:49,160 --> 01:16:51,240 SO HERE'S SOME OF OUR EXPERIENCE 2171 01:16:51,240 --> 01:16:53,240 WITH SWITCHING PEOPLE OVER. 2172 01:16:53,240 --> 01:16:54,760 FOLKS WHO WE TARGET GET 2173 01:16:54,760 --> 01:16:56,840 HAPPENING PEOPLE DOWN TO 90 TO A 2174 01:16:56,840 --> 01:16:58,800 HUNDRED MORPHIN A DAY BEFORE WE 2175 01:16:58,800 --> 01:17:00,440 SWITCH OVER AND THAT'S THE BLUE 2176 01:17:00,440 --> 01:17:02,040 LINE ON THIS PICTURE HERE, YOU 2177 01:17:02,040 --> 01:17:03,520 CAN SEE WE HAVE TRIED SOME 2178 01:17:03,520 --> 01:17:05,720 PEOPLE WHO ARE HIGHER DOSES, 2179 01:17:05,720 --> 01:17:07,960 SOMETIMES WE'VE DONE THAT IN THE 2180 01:17:07,960 --> 01:17:09,720 HOSPITAL, BUT WHAT REALLY 2181 01:17:09,720 --> 01:17:13,000 HAPPENS IS PEOPLE WIND UP TAKING 2182 01:17:13,000 --> 01:17:16,840 BETWEEN 8 AND 16-MILLIGRAMS OF 2183 01:17:16,840 --> 01:17:21,440 EQUIVALENTS AND I HAVEN'T SPOKE 2184 01:17:21,440 --> 01:17:23,120 ON SUBOXONE YET, I WILL IN A 2185 01:17:23,120 --> 01:17:25,400 MINUTE BUT THESE ARE FAIRLY MISS 2186 01:17:25,400 --> 01:17:27,160 OF THE ROAD DOSES SO PEOPLE CAN 2187 01:17:27,160 --> 01:17:31,120 COME ON TO RELATIVELY MODEST 2188 01:17:31,120 --> 01:17:45,000 DOSES. 2189 01:17:45,000 --> 01:17:46,120 NEXT SLIDE. 2190 01:17:46,120 --> 01:17:51,200 SO THIS IS USED FOR TREATMENT 2191 01:17:51,200 --> 01:17:52,880 DISORDERS, THIS IS THE EASY TO 2192 01:17:52,880 --> 01:17:55,000 DOSE AND CAN YOU HAVE RELATIVELY 2193 01:17:55,000 --> 01:17:56,120 FINE CONTROL OF THE DOSING, 1 2194 01:17:56,120 --> 01:17:57,480 THING TO POINT OUT IS THAT THEY 2195 01:17:57,480 --> 01:18:02,840 CONTAIN A MEDICINE CALLED 2196 01:18:02,840 --> 01:18:06,760 NALOXONE, WHICH IS A MEDICINAN 2197 01:18:06,760 --> 01:18:07,280 TAGANIST, SOMETIMES IT'S 2198 01:18:07,280 --> 01:18:11,560 MISUNDERSTOOD WHAT IT'S DOING IN 2199 01:18:11,560 --> 01:18:17,720 THERE,. 2200 01:18:17,720 --> 01:18:19,080 NALOXONE WOULD BE THERE TO 2201 01:18:19,080 --> 01:18:20,720 PREVENT AN EFFECT OR CAUSE 2202 01:18:20,720 --> 01:18:24,160 WITHDRAWAL AS A DETERRENT. 2203 01:18:24,160 --> 01:18:25,080 IT'S NOT ABSORBED SUBLINGUAL AND 2204 01:18:25,080 --> 01:18:27,200 NOT A PART OF THE THERAPY AND 2205 01:18:27,200 --> 01:18:29,080 IT'S JUST USED FOR PREPARATION, 2206 01:18:29,080 --> 01:18:30,840 AND SOMETIMES PEOPLE WONDER WHAT 2207 01:18:30,840 --> 01:18:32,360 THAT'S DOING IN THERE AND THAT'S 2208 01:18:32,360 --> 01:18:33,560 WHAT IT'S THERE FOR. 2209 01:18:33,560 --> 01:18:38,440 AS I SAID YOU CAN TAKE IT 2210 01:18:38,440 --> 01:18:40,200 SUBLINGUALLY, OFTEN 2-3 TIMES A 2211 01:18:40,200 --> 01:18:42,040 DAY WORKS JUST FINE AND YOU DO 2212 01:18:42,040 --> 01:18:45,960 HAVE TO GET A PRESCRIPTION FOR 2213 01:18:45,960 --> 01:18:46,560 IT. 2214 01:18:46,560 --> 01:18:48,680 --DEA WAIVER TO PRESCRIBE IT. 2215 01:18:48,680 --> 01:18:49,080 NEXT SLIDE. 2216 01:18:49,080 --> 01:18:50,960 AS I MENTIONED BEFORE, THE FIRST 2217 01:18:50,960 --> 01:18:52,840 THING THAT WAS BUPRENORPHINE WAS 2218 01:18:52,840 --> 01:18:57,440 APROWFED FOR WAS FOR ACUTE PAIN, 2219 01:18:57,440 --> 01:18:58,360 BUPRENEX IS STILL AVAILABLE AND 2220 01:18:58,360 --> 01:19:00,840 IT WORKS FINE IF YOU HAVE PAIN 2221 01:19:00,840 --> 01:19:03,200 AND LOW TOLERANCE, IT HAS A 2222 01:19:03,200 --> 01:19:04,640 REMARKABLY SHORTER DURATION OF 2223 01:19:04,640 --> 01:19:08,640 SO YOU HAVE TO GIVE IT Q6 OR 4 2224 01:19:08,640 --> 01:19:10,000 HOURS AND IT'S APPROVED FOR USE 2225 01:19:10,000 --> 01:19:13,440 IN CHILDREN. 2226 01:19:13,440 --> 01:19:16,400 IT'S A BELBUCA IS LIKE A BUCCAL 2227 01:19:16,400 --> 01:19:17,840 FILM BUT IT'S HARD TO GET 2228 01:19:17,840 --> 01:19:21,320 INSURANCE TO PAY FOR AND 2229 01:19:21,320 --> 01:19:23,880 BUTRANSIS A PATCH THAT CAN LAST 2230 01:19:23,880 --> 01:19:28,160 FOR SEVERAL DAYS AT AIM TIME. 2231 01:19:28,160 --> 01:19:29,000 NEXT SLIDE. 2232 01:19:29,000 --> 01:19:30,840 SUBLOCADE IS AN EXTREMELY LONG 2233 01:19:30,840 --> 01:19:33,720 ACTING DURATION FOR THE USE OF 2234 01:19:33,720 --> 01:19:34,840 SUBSTANCE DISORDERS, 1 INJECTION 2235 01:19:34,840 --> 01:19:36,000 IT LASTS FOR A MONTH. 2236 01:19:36,000 --> 01:19:39,520 THERE'S ANOTHER THING CALLED 2237 01:19:39,520 --> 01:19:42,120 PROBUPH INE, AND IMPLANTABLE 2238 01:19:42,120 --> 01:19:45,320 RODS AND IT'S BEEN MADE 2239 01:19:45,320 --> 01:19:51,360 OBLIGATIONS SOLEAT SO IT'S NOT 2240 01:19:51,360 --> 01:19:52,240 WORTH TALKING ABOUT. 2241 01:19:52,240 --> 01:19:55,000 WHAT WE'VE - LOOKED AT IN FOLKS 2242 01:19:55,000 --> 01:19:57,440 THAT WE TRANSITION OVER TO 2243 01:19:57,440 --> 01:19:59,440 BUPRENORPHINE HAS MAINLY BEEN 2244 01:19:59,440 --> 01:20:01,640 ABOUT ACUTE CARE USE, AND THESE 2245 01:20:01,640 --> 01:20:03,640 ARE THE FIRST 40 SOME-ODD FOLKS 2246 01:20:03,640 --> 01:20:05,720 THAT WERE TRANSITIONED OVER TO 2247 01:20:05,720 --> 01:20:07,840 BUPRENORPHINE, WE'RE UP TO 2248 01:20:07,840 --> 01:20:09,360 70-SOMETHING, I THINK WHO 2249 01:20:09,360 --> 01:20:10,880 SWITCHED OVER AT OUR CENTER. 2250 01:20:10,880 --> 01:20:15,200 THESE ARE 6 MONTHS PREAND POST 2251 01:20:15,200 --> 01:20:15,600 ACUTE CARE VISITS. 2252 01:20:15,600 --> 01:20:18,560 SO YOU KNOW YOU COULD SEE THAT 2253 01:20:18,560 --> 01:20:20,200 OVERALL ACUTE CARE USE REALLY 2254 01:20:20,200 --> 01:20:23,040 DROPS OFF A GOOD BIT ON AVERAGE 2255 01:20:23,040 --> 01:20:24,840 WHEN PEOPLE TRANSITION BEFORE 2256 01:20:24,840 --> 01:20:25,240 AND AFTER. 2257 01:20:25,240 --> 01:20:26,440 AND YOU CAN ALSO SEE, I DON'T 2258 01:20:26,440 --> 01:20:28,240 KNOW IF YOU CAN SEE MY POINTER 2259 01:20:28,240 --> 01:20:29,880 BUT YOU GET THE OCCASIONAL 2260 01:20:29,880 --> 01:20:32,240 MIRACLE, YOU KNOW WE HAVE A FEW 2261 01:20:32,240 --> 01:20:34,480 PATIENTS WHO WERE IN AS MUCH AS 2262 01:20:34,480 --> 01:20:38,800 WEEKLY OR MULTIPLE TIMES A MONTH 2263 01:20:38,800 --> 01:20:40,560 WHOSE ACUTE CARE REALLY, REALLY 2264 01:20:40,560 --> 01:20:40,920 DROPPED OFF. 2265 01:20:40,920 --> 01:20:43,440 WE ALSO HAD SOME PEOPLE WHO HAVE 2266 01:20:43,440 --> 01:20:44,840 SIGNIFICANT CHRONIC PAIN WHO 2267 01:20:44,840 --> 01:20:47,360 FELT WAY BETTER ON BUPRENORPHINE 2268 01:20:47,360 --> 01:20:49,560 THAN THEY DID ON OTHER OPIOIDS 2269 01:20:49,560 --> 01:20:52,000 EVEN IN HIGH DOSES BUT HERE'S 2270 01:20:52,000 --> 01:20:54,080 WHERE I START POURING COLD WATER 2271 01:20:54,080 --> 01:20:58,480 ON, IN CONTRAST,OT POST SIDE, 2272 01:20:58,480 --> 01:21:01,200 THAT IS A LOT LESS BUT IF YOU 2273 01:21:01,200 --> 01:21:04,080 LOOK AT ABSOLUTE NUMBERS, THAT 2274 01:21:04,080 --> 01:21:06,240 IS NOT A LOW FREQUENCY OF ACUTE 2275 01:21:06,240 --> 01:21:07,560 CARE VISITS FOR PEOPLE WITH 2276 01:21:07,560 --> 01:21:08,840 SICKLE CELL DISEASE. 2277 01:21:08,840 --> 01:21:10,440 THAT'S ACTUALLY A PRETTY HIGH 2278 01:21:10,440 --> 01:21:12,840 FREQUENCY OF ACUTE CARE. 2279 01:21:12,840 --> 01:21:14,360 SO, THIS CAN HELP PEOPLE TO STAY 2280 01:21:14,360 --> 01:21:16,360 OUT OF THE INFUSION CENTER, FOR 2281 01:21:16,360 --> 01:21:19,000 ED AND SO FORTH BUT IT DOES NOT 2282 01:21:19,000 --> 01:21:21,360 CONVERT A VERY ILL AND COMPLEX 2283 01:21:21,360 --> 01:21:22,280 POPULATION EVER FOLKS WITH 2284 01:21:22,280 --> 01:21:26,160 CHRONIC PAIN AND FREQUENT ACUTE 2285 01:21:26,160 --> 01:21:28,760 PAIN TO TO FOLKS WHO ARE CURED. 2286 01:21:28,760 --> 01:21:29,840 THERE AREN'T NECESSARILY ALL 2287 01:21:29,840 --> 01:21:31,080 THAT MANY MIRACLES TO BE HAD AND 2288 01:21:31,080 --> 01:21:32,520 EVEN THOUGH THIS CAN BE USEFUL, 2289 01:21:32,520 --> 01:21:35,440 IT DOESN'T MAKE ALL THE PROBLEMS 2290 01:21:35,440 --> 01:21:36,080 GO AWAY. 2291 01:21:36,080 --> 01:21:38,960 ON THE SAME NOTE, WHEN PEOPLE 2292 01:21:38,960 --> 01:21:39,880 TRANSITION TO BUPRENORPHINE AT 2293 01:21:39,880 --> 01:21:42,760 OUR CENTER, IT'S PART OF A 2294 01:21:42,760 --> 01:21:44,840 LONG-TERM PRETTY HIGH INTENSITY 2295 01:21:44,840 --> 01:21:45,680 INTEGRATED THOUGHT PROCESS 2296 01:21:45,680 --> 01:21:47,120 AROUND HOW TO MANAGE CHRONIC 2297 01:21:47,120 --> 01:21:49,320 PAIN SO THESE ARE FOLK WHO IS 2298 01:21:49,320 --> 01:21:51,000 ARE OFTEN SEEN WEEKLY BY PRETTY 2299 01:21:51,000 --> 01:21:53,320 MUCH THE SAME PROVIDER, THEY'RE 2300 01:21:53,320 --> 01:21:54,840 OFTEN VERY AGGRESSIVE DISEASE 2301 01:21:54,840 --> 01:21:56,240 MODIFYING, PARTICULARLY AS 2302 01:21:56,240 --> 01:21:58,880 OPIOID DOSES TAPER, THEY'VE BEEN 2303 01:21:58,880 --> 01:22:00,800 TALKING ABOUT ARE THE OPIOIDS 2304 01:22:00,800 --> 01:22:02,320 WORKING OR NOT, WHAT'S THE RISK. 2305 01:22:02,320 --> 01:22:04,240 DO YOU WANT TO STAY ON THESE 2306 01:22:04,240 --> 01:22:05,800 THINGS, WE HAVE THIS THING 2307 01:22:05,800 --> 01:22:06,960 CALLED BUPRENORPHINE DO YOU WANT 2308 01:22:06,960 --> 01:22:09,440 TO TRY IT FOR MONTHS AND YEARS 2309 01:22:09,440 --> 01:22:10,280 PROBABLY BEFORE THIS HAPPENS, 2310 01:22:10,280 --> 01:22:11,880 AND I DON'T THINK IT'S SIMPLE 2311 01:22:11,880 --> 01:22:14,080 AS, YOU KNOW YOU CAN FIND OF 2312 01:22:14,080 --> 01:22:16,840 LEAP ON SOMEONE WITH A VERY 2313 01:22:16,840 --> 01:22:18,440 COMPLEX PROBLEM, PUT THEM ON 2314 01:22:18,440 --> 01:22:20,800 BUPRENORPH AND YOU KNOW 2315 01:22:20,800 --> 01:22:21,840 CELLESTIAL LIGHT SHINES DOWN. 2316 01:22:21,840 --> 01:22:23,440 THE THERE'S A LOT THAT GOES INTO 2317 01:22:23,440 --> 01:22:34,280 THIS THAT'S NOT JUST THE PILL. 2318 01:22:34,280 --> 01:22:34,720 NEXT SLIDE. 2319 01:22:34,720 --> 01:22:37,200 AND I THINK I JUST SAID ALL OF 2320 01:22:37,200 --> 01:22:38,560 THAT, WILL POINT OUT THAT IF YOU 2321 01:22:38,560 --> 01:22:40,640 HAVE SOMEONE ON BUPRENORPHINE 2322 01:22:40,640 --> 01:22:41,480 FOR THE RECEPTOR PHARMACOLOGY 2323 01:22:41,480 --> 01:22:43,000 THAT YOU HAVE TO HAVE A PLAN FOR 2324 01:22:43,000 --> 01:22:45,480 WHAT THEY DO WHEN THEY HAVE 2325 01:22:45,480 --> 01:22:45,800 ACUTE PAIN. 2326 01:22:45,800 --> 01:22:48,040 VERY OFTEN WE WILL HAVE PEOPLE 2327 01:22:48,040 --> 01:22:51,240 WHO TREAT OVER WITH FULL 2328 01:22:51,240 --> 01:22:52,360 AGONISTS, ALSO THERE ARE A FEW 2329 01:22:52,360 --> 01:22:54,640 PEOPLE WE HAD TO STOP THE 2330 01:22:54,640 --> 01:22:55,600 BUPRENORPHINE, START FULL 2331 01:22:55,600 --> 01:22:58,560 AGONIST AND AS THEIR CRISIS 2332 01:22:58,560 --> 01:22:59,720 RESOLVED SWITCH TO REINDUCTION 2333 01:22:59,720 --> 01:22:59,920 OVER. 2334 01:22:59,920 --> 01:23:00,720 SO YOU HAVE TO HAVE A THOUGHT 2335 01:23:00,720 --> 01:23:01,800 ABOUT HOW YOU WILL DO NAAND YOU 2336 01:23:01,800 --> 01:23:03,040 HAVE TO TALK ABOUT IT WITH THE 2337 01:23:03,040 --> 01:23:05,240 PATIENTS BEFORE YOU START. 2338 01:23:05,240 --> 01:23:06,440 AND THE OTHER THING IS, I THINK 2339 01:23:06,440 --> 01:23:10,440 I KIND OF TOUCHED ON THIS, BUT 2340 01:23:10,440 --> 01:23:12,280 YOU KNOW BUPRENORPHINE DOESN'T 2341 01:23:12,280 --> 01:23:12,840 CHANGE OUR BEHAVIOR. 2342 01:23:12,840 --> 01:23:15,000 SO, IF YOU DON'T HAVE AN 2343 01:23:15,000 --> 01:23:16,520 INTEGRATED SYSTEM FOR MANAGING 2344 01:23:16,520 --> 01:23:17,480 ACUTE CHRONIC PAIN, IF YOU DON'T 2345 01:23:17,480 --> 01:23:20,160 HAVE A WAY TO TALK TO PEOPLE 2346 01:23:20,160 --> 01:23:22,440 ABOUT THIS CSR IF YOUR ED PEOPLE 2347 01:23:22,440 --> 01:23:23,440 AND YOUR HOSPITAL PEOPLE AND 2348 01:23:23,440 --> 01:23:25,480 YOUR PAIN PEOPLE AND YOUR SICKLE 2349 01:23:25,480 --> 01:23:27,120 CELL PEOPLE ALL HAVE DIFFERENT 2350 01:23:27,120 --> 01:23:28,200 APPROACHES TO PAIN AND DON'T 2351 01:23:28,200 --> 01:23:30,000 KNOW WHAT TO DO WITH BUPRENORPH, 2352 01:23:30,000 --> 01:23:31,080 IT'S PROBABLY NOT GOING TO WORK 2353 01:23:31,080 --> 01:23:35,360 SO THIS HAS TO BE PART, I THINK, 2354 01:23:35,360 --> 01:23:36,440 OF A COMPREHENSIVE TOOL OF THAT 2355 01:23:36,440 --> 01:23:37,840 CONTEXT AND I WOULDN'T WANT TO 2356 01:23:37,840 --> 01:23:40,720 SELL IT AS SOME MIRACLE PILL YOU 2357 01:23:40,720 --> 01:23:41,720 COULD THROW AT EVERYONE. 2358 01:23:41,720 --> 01:23:43,640 I THINK THAT'S ALL I HAD TO SAY. 2359 01:23:43,640 --> 01:23:49,680 NEXT SLIDE, LET ME BE SURE. 2360 01:23:49,680 --> 01:23:53,320 OH YEAH, THAT WAS IT. 2361 01:23:53,320 --> 01:23:55,640 >> THANK YOU VERY MUCH 2362 01:23:55,640 --> 01:23:57,200 DR. CARROLL, I KNOW THERE A LOT 2363 01:23:57,200 --> 01:23:58,280 OF QUESTIONS, I CAN SEE THEM 2364 01:23:58,280 --> 01:24:00,000 BOTH POPPING UP IN THE CHAT AND 2365 01:24:00,000 --> 01:24:03,240 THE Q&A, WE WILL INVITE ALL 4 OF 2366 01:24:03,240 --> 01:24:05,000 OUR SPEAKERS UP SO WE CAN HAVE A 2367 01:24:05,000 --> 01:24:08,240 PANEL DISCUSSION AND DR. ST 2368 01:24:08,240 --> 01:24:10,240 ROUSE AND I WILL BE MODERATING 2369 01:24:10,240 --> 01:24:10,440 THAT. 2370 01:24:10,440 --> 01:24:11,480 I THINK THERE IS SO MUCH TO 2371 01:24:11,480 --> 01:24:13,360 LEARN ABOUT WHAT YOU SAID AND WE 2372 01:24:13,360 --> 01:24:15,320 NEED TO COORDINATE AND STUDY, I 2373 01:24:15,320 --> 01:24:18,240 CAN'T ECHO ENOUGH WITH WHAT 2374 01:24:18,240 --> 01:24:19,080 DR. CARROLL ENDED WITH, THE 2375 01:24:19,080 --> 01:24:21,400 IMPORTANCE OF TREATING SICKLELE 2376 01:24:21,400 --> 01:24:22,200 DISEASE AND REMINDING EVERYONE 2377 01:24:22,200 --> 01:24:23,400 THAT ALL THESE METHODS WORK BUT 2378 01:24:23,400 --> 01:24:25,400 THEY DON'T LEAD TO SICKLE CELL 2379 01:24:25,400 --> 01:24:27,120 DISEASE SO WE HAVE TO MAKE SURE 2380 01:24:27,120 --> 01:24:28,240 WE'RE TREATING SICKLE CELL IN 2381 01:24:28,240 --> 01:24:29,600 ADDITION TO TREATING PAIN AND 2382 01:24:29,600 --> 01:24:30,920 SOMETIMES THEY'RE NOT THE SAME 2383 01:24:30,920 --> 01:24:31,240 THING. 2384 01:24:31,240 --> 01:24:33,400 SO, I THINK THE COORDINATED 2385 01:24:33,400 --> 01:24:36,640 EFFORTS THAT HE SPOKE ABOUT ARE 2386 01:24:36,640 --> 01:24:37,880 SUPER IMIMPORTANT. 2387 01:24:37,880 --> 01:24:39,280 I'M GOING AHEAD IF IT'S OKAY 2388 01:24:39,280 --> 01:24:42,040 WITH YOU, DR. STROUSE, AND ASK 2389 01:24:42,040 --> 01:24:44,440 THE FIRST QUESTION, I SEE SO 2390 01:24:44,440 --> 01:24:45,640 MANY OF THEM, IT'S SORT OF HARD 2391 01:24:45,640 --> 01:24:46,920 TO KNOW WHERE THEY START AND 2392 01:24:46,920 --> 01:24:48,240 LET'S START WITH THE BEGINNING 2393 01:24:48,240 --> 01:24:49,760 ON THIS 1, PEOPLE LIVING WITH 2394 01:24:49,760 --> 01:24:51,640 SICKLE CELL TEASE HAVE LONG 2395 01:24:51,640 --> 01:24:54,080 KNOWN THAT ALTERPATIVE 2396 01:24:54,080 --> 01:24:55,440 THERAPIES, AND BENEFICIAL FOR 2397 01:24:55,440 --> 01:24:57,160 PAIN TREATMENT BUT MEDICAID AND 2398 01:24:57,160 --> 01:24:58,240 MEDICAID MANAGE TD CARE OF 2399 01:24:58,240 --> 01:25:00,600 COURSE DO NOT PAY FOR THESE 2400 01:25:00,600 --> 01:25:01,360 ALTERNATIVE THERAPIES. 2401 01:25:01,360 --> 01:25:04,520 AND THAT HAS MADE ACCUPUNCTURE 2402 01:25:04,520 --> 01:25:05,360 VERY COST PROHIBITIVE. 2403 01:25:05,360 --> 01:25:06,440 THIS CAME FROM GINGER DAVIS AND 2404 01:25:06,440 --> 01:25:11,280 I HAD THE SAME QUESTION FOR I 2405 01:25:11,280 --> 01:25:14,320 THINK DR. SCHLAGER, HOW DO WE 2406 01:25:14,320 --> 01:25:15,440 WELCOMER WOSTATE HEALTH 2407 01:25:15,440 --> 01:25:17,320 INSURANCES TO GET ALTERNATIVE 2408 01:25:17,320 --> 01:25:19,240 MEDICINE AND PLANS TREATMENT 2409 01:25:19,240 --> 01:25:19,920 PAID FOR? 2410 01:25:19,920 --> 01:25:21,640 >> WELL, FIRST OF ALL, THANK YOU 2411 01:25:21,640 --> 01:25:23,120 FOR THE QUESTION, IT'S OF GREAT 2412 01:25:23,120 --> 01:25:24,800 IMPORTANCE FOR OUR WORK WITH 2413 01:25:24,800 --> 01:25:27,440 SICKLE CELL AND FOR OUR WORK 2414 01:25:27,440 --> 01:25:28,840 WITH ALL CHRONIC PAIN PATIENT 2415 01:25:28,840 --> 01:25:29,880 WHO IS NEED ACCUPUNCTURE. 2416 01:25:29,880 --> 01:25:31,120 RIGHT NOW TO TELL YOU WHERE THE 2417 01:25:31,120 --> 01:25:35,400 STATE OF THE SCIENCE IS AT, 2418 01:25:35,400 --> 01:25:36,640 MEDICARE DOES COVER ACCUPUNCTURE 2419 01:25:36,640 --> 01:25:41,560 BUT ONLY FOR LOWER BACK PAIN AND 2420 01:25:41,560 --> 01:25:44,440 MEDICAID COVERS ACUE PINKTURE IN 2421 01:25:44,440 --> 01:25:46,000 13 STATES. 2422 01:25:46,000 --> 01:25:50,560 I AM A CONSULTANT FOR ILLINOIS, 2423 01:25:50,560 --> 01:25:52,320 WE'RE ABOUT TO GET MEDICAID 2424 01:25:52,320 --> 01:25:54,120 COVERAGE IN IMPEDIMENTS 2425 01:25:54,120 --> 01:25:55,440 ELIMINATED; WE WILL BE THE 2426 01:25:55,440 --> 01:25:56,680 14th STATE AND WE'RE HARBING 2427 01:25:56,680 --> 01:25:59,360 OUT ALL THE PAIN CONDITIONS IT 2428 01:25:59,360 --> 01:25:59,720 WILL TREAT. 2429 01:25:59,720 --> 01:26:03,640 ONE THING IN TERMS OF HEALTH 2430 01:26:03,640 --> 01:26:08,840 EQUITY THIS, IS A VERY STRONG, 2431 01:26:08,840 --> 01:26:10,400 VERY IMPORTANT HEALTH EQUITY 2432 01:26:10,400 --> 01:26:12,600 ISSUE THAT ACCUPUNCTURE IS ONLY 2433 01:26:12,600 --> 01:26:13,840 AFFORDABLE MANY TIMES OUT OF 2434 01:26:13,840 --> 01:26:16,400 POCKET, PAYMENT WHO ARE UPPER 2435 01:26:16,400 --> 01:26:18,000 MIDDLE CLASS, AND ACCUPUNCTURE 2436 01:26:18,000 --> 01:26:19,800 CLINICS ARE OFTEN IN UPPER 2437 01:26:19,800 --> 01:26:21,640 MIDDLE CLASS, UPPER CLASS AREAS, 2438 01:26:21,640 --> 01:26:25,120 AND NOT ACCEPTABLE TO SICKLE 2439 01:26:25,120 --> 01:26:27,000 CELL PATIENTS WHO OFTEN LIVE IN 2440 01:26:27,000 --> 01:26:31,680 URBAN OR RURAL POPULATIONS. 2441 01:26:31,680 --> 01:26:34,880 NIH AND PARTICULARLY THE NIH 2442 01:26:34,880 --> 01:26:37,280 PRISM--THE PRISM PROGRAM AS WELL 2443 01:26:37,280 --> 01:26:40,520 AS THE NIH PRAGMATIC TRIALS 2444 01:26:40,520 --> 01:26:43,720 COLLABRATORY UNDER THE DRUKS OF 2445 01:26:43,720 --> 01:26:45,920 WENDY WEBER WHO'S THE BRANCH 2446 01:26:45,920 --> 01:26:47,920 MANAGER FOR NCCIH IS ACUTELY 2447 01:26:47,920 --> 01:26:50,520 AWARE OF THIS HEALTH INEQUITY 2448 01:26:50,520 --> 01:26:53,840 AND 1 THING ABOUT PRAGMATIC 2449 01:26:53,840 --> 01:26:55,280 TRIALS, PRAGMATIC TRIALS PRODUCE 2450 01:26:55,280 --> 01:26:56,600 RESULTS THAT CAN BE GENERALIZED 2451 01:26:56,600 --> 01:26:58,640 AND APPLIED IN ROUTINE CLINICAL 2452 01:26:58,640 --> 01:27:02,320 SETTINGS AND THE NIH PRAGMATIC 2453 01:27:02,320 --> 01:27:04,760 TRIALS COLLABRATORY, BECAUSE 2454 01:27:04,760 --> 01:27:06,240 THEY FUND EMBEDDED PRAGMATIC 2455 01:27:06,240 --> 01:27:08,240 TRIALS THAT ARE EMBEDDED INTO 2456 01:27:08,240 --> 01:27:10,080 THE HEALTHCARE SETTING, THEY ARE 2457 01:27:10,080 --> 01:27:14,120 SERIOUS AND COMMITTED TO 2458 01:27:14,120 --> 01:27:16,200 SHIFTING THE POLITICAL CLIMATE 2459 01:27:16,200 --> 01:27:17,800 AND THE FUNDING CLIMATE IN THE 2460 01:27:17,800 --> 01:27:22,360 UNITED STATES AND SO, WENDY 2461 01:27:22,360 --> 01:27:24,240 WEBER HAS ALREADY BEEN TO 2462 01:27:24,240 --> 01:27:25,640 CAPITOL HILL TO THINK OF THE 2463 01:27:25,640 --> 01:27:27,280 HEAD OF CMS ABOUT EXPANDING 2464 01:27:27,280 --> 01:27:29,080 ACCUPUNCTURE TO THE TREATMENT OF 2465 01:27:29,080 --> 01:27:31,160 SICKLE CELL DISEASE PAIN AND 2466 01:27:31,160 --> 01:27:35,320 IT'S THIS KIND OF COLLABORATION 2467 01:27:35,320 --> 01:27:37,920 BETWEEN NIH AND THE NIH HEAL 2468 01:27:37,920 --> 01:27:41,360 INITIATIVE AND THE PRAGMATIC 2469 01:27:41,360 --> 01:27:43,640 TRIALS COLLABRATORY, AND 2470 01:27:43,640 --> 01:27:47,240 MEDICARE THAT IS GOLDEN. 2471 01:27:47,240 --> 01:27:49,240 IF MEDICARE STARTS FUNDING 2472 01:27:49,240 --> 01:27:51,280 ACCUPUNCTURE FOR CHRONIC SICKLE 2473 01:27:51,280 --> 01:27:53,640 CELL DISEASE PAIN, MEDICAID WILL 2474 01:27:53,640 --> 01:27:54,960 CONTINUE TO HAVE THE DOMINO FALL 2475 01:27:54,960 --> 01:27:59,960 AND COVER IT IN MORE STATES. 2476 01:27:59,960 --> 01:28:00,920 AND SO, THERE'S BASICALLY 2 2477 01:28:00,920 --> 01:28:03,040 THINGS GOING ON, ALL THE 2478 01:28:03,040 --> 01:28:04,560 WONDERFUL WORK THAT NIH AND THE 2479 01:28:04,560 --> 01:28:05,920 HEAL INITIATIVE AND THE 2480 01:28:05,920 --> 01:28:06,760 PRAGMATIC TRIALS COLLAB RATOORY 2481 01:28:06,760 --> 01:28:08,440 IS DOING TO HELP PEOPLE WITH 2482 01:28:08,440 --> 01:28:11,440 CHRONIC PAIN, PARTICULARLY 2483 01:28:11,440 --> 01:28:12,560 SICKLE CELL DISEASE, THEN WE'RE 2484 01:28:12,560 --> 01:28:14,280 ALSO APPROACHING IT ON THE STATE 2485 01:28:14,280 --> 01:28:18,640 LEVEL, SO HOW DO YOU DO IT ON 2486 01:28:18,640 --> 01:28:20,720 THE STATE LEVEL, IT IS--YOU NEED 2487 01:28:20,720 --> 01:28:24,520 A CHAMPION AND TO APPROACH A 2488 01:28:24,520 --> 01:28:28,960 STATE LEGISLATURE, A 2489 01:28:28,960 --> 01:28:31,040 REPRESENTATIVE WHO IS VERY 2490 01:28:31,040 --> 01:28:32,360 PROACUE PUNCTURE AND IN THIS 2491 01:28:32,360 --> 01:28:36,120 CASE, WE HAVE REPRESENTATIVE 2492 01:28:36,120 --> 01:28:39,640 TERRIES MAH WHO IS OF CHINESE 2493 01:28:39,640 --> 01:28:41,040 AMERICAN HERITAGE WHO HAS 2494 01:28:41,040 --> 01:28:43,120 CHAMPIONED THE WHOLE CAUSE OF 2495 01:28:43,120 --> 01:28:46,240 GETTING ACCUPUNCTURE COVERED BY 2496 01:28:46,240 --> 01:28:46,680 MEDICAID. 2497 01:28:46,680 --> 01:28:49,600 HER CONSTITUENTS IN HER DISTRICT 2498 01:28:49,600 --> 01:28:54,320 ARE CHINESE AND THEY WANT TO 2499 01:28:54,320 --> 01:28:55,480 MEDICAID TO COVER ACCUPUNCTURE 2500 01:28:55,480 --> 01:28:57,040 SO THIS IS THE WAY YOU START SO 2501 01:28:57,040 --> 01:29:02,600 I WOULD SAY, PARTNER WITH NOT 2502 01:29:02,600 --> 01:29:04,400 ONLY A REPRESENTATIVE WHO HAS A 2503 01:29:04,400 --> 01:29:07,160 VESTED INTEREST IN MEDICAID 2504 01:29:07,160 --> 01:29:11,720 COVERING ACCUPUNCTURE FOR THEIR 2505 01:29:11,720 --> 01:29:14,280 DISTRICT, BUT ALSO CONTACT THE 2506 01:29:14,280 --> 01:29:15,440 ACCUPUNCTURE ORGANIZATION SO 2507 01:29:15,440 --> 01:29:19,000 THOSE 2 IN TANDEM WORK AND THEN 2508 01:29:19,000 --> 01:29:20,800 RESEARCH, RESEARCH, RESEARCH, 2509 01:29:20,800 --> 01:29:24,560 THE MEDICAID AS WELL AS MEDICARE 2510 01:29:24,560 --> 01:29:26,280 PEOPLE, THESE STAKEHOLDERS WANT 2511 01:29:26,280 --> 01:29:28,040 TO SEE RESEARCH, THE VICARS 2512 01:29:28,040 --> 01:29:32,400 META-ANALYSIS THAT I SHARED WITH 2513 01:29:32,400 --> 01:29:34,880 YOU, HAS BEEN CRUCIAL, AS BEEN 2514 01:29:34,880 --> 01:29:38,160 INTEGRAL IN TERMS OF HAVING 2515 01:29:38,160 --> 01:29:40,000 SCIENTIFIC, BEING SCIENTIFIC 2516 01:29:40,000 --> 01:29:41,840 JUSTIFICATION FOR DOCUMENTING 2517 01:29:41,840 --> 01:29:46,960 THE EFFECTIVENESS OF 2518 01:29:46,960 --> 01:29:47,840 ACCUPUNCTURE SO THEY'RE COMING 2519 01:29:47,840 --> 01:29:49,160 FORTH, I HAVE OTHER RESEARCH AND 2520 01:29:49,160 --> 01:29:50,680 CHRONIC PAIN THAT I'M FUNDED ON 2521 01:29:50,680 --> 01:29:52,320 AND I WILL MOVE THOSE FORWARD 2522 01:29:52,320 --> 01:29:54,480 INTO KNOCKING AT THE DOOR OF MED 2523 01:29:54,480 --> 01:29:55,800 XAIR AND MEDICAID, ANY 2524 01:29:55,800 --> 01:29:57,400 QUESTIONS, YOU'RE MORE THAN 2525 01:29:57,400 --> 01:29:59,040 HAPPY TO CONNECT WITH ME, BUT 2526 01:29:59,040 --> 01:30:03,720 NA'S BASICALLY THE PROCESS, AND 2527 01:30:03,720 --> 01:30:04,560 IN--BECAUSE HEALTH EQUITY IS 2528 01:30:04,560 --> 01:30:07,840 SUCH A HOT ISSUE RIGHT NOW, AND 2529 01:30:07,840 --> 01:30:11,680 THE IMPORTANCE OF HAVING HEALTH 2530 01:30:11,680 --> 01:30:13,640 EQUITY AND COVER MANY DISEASE 2531 01:30:13,640 --> 01:30:15,400 CONDITIONS FOR PEOPLE ON 2532 01:30:15,400 --> 01:30:20,440 MEDICARE AND MEDICAID, BUT 2533 01:30:20,440 --> 01:30:21,640 PARTICULARLY CHRONIC PAIN AND 2534 01:30:21,640 --> 01:30:22,600 CERTAINLY SICKLE CELL, THIS IS 2535 01:30:22,600 --> 01:30:24,360 AN ISSUE THAT THE LEGISLATURES, 2536 01:30:24,360 --> 01:30:26,920 AS WELL AS THE STAKEHOLDERS AT 2537 01:30:26,920 --> 01:30:35,680 MEDICARE AND MEDICAID ARE VERY 2538 01:30:35,680 --> 01:30:36,240 OPEN TO. 2539 01:30:36,240 --> 01:30:36,680 >> THANK YOU. 2540 01:30:36,680 --> 01:30:40,040 I WILL ASK THE NEXT QUESTION 2541 01:30:40,040 --> 01:30:45,600 WHICH ALSO ADDRESSES QUESTIONS 2542 01:30:45,600 --> 01:30:47,440 ABOUT ISSUES TO ACCESS, IF THE 2543 01:30:47,440 --> 01:30:49,760 FIRST WAS PEER TO PEER, WHAT CAN 2544 01:30:49,760 --> 01:30:50,960 WE DO INCREASE ACCESS TO THESE 2545 01:30:50,960 --> 01:30:52,120 AND SPREAD THEM TO DIFFERENT 2546 01:30:52,120 --> 01:30:54,760 AREAS AND THE SECOND IS THAT FOR 2547 01:30:54,760 --> 01:30:55,480 PEOPLE THAT TELEMEDICINE DOESN'T 2548 01:30:55,480 --> 01:30:57,240 SEEM TO WORK THAT WELL, WHAT 2549 01:30:57,240 --> 01:31:00,080 SORT OF INTERVENTIONS ARE THERE 2550 01:31:00,080 --> 01:31:01,680 TO IMPROVE TELEMEDICINE FOR 2551 01:31:01,680 --> 01:31:02,960 BEHAVIORIAL HEALTH SERVICES FOR 2552 01:31:02,960 --> 01:31:05,080 PEOPLE WITH SICKLE CELL DISEASE 2553 01:31:05,080 --> 01:31:09,640 WITH A FOCUS ON PAIN MANAGEMENT? 2554 01:31:09,640 --> 01:31:10,960 >> YEAH, WELL, I WILL GO FIRST, 2555 01:31:10,960 --> 01:31:13,520 JUST QUICK ON THE PEER TO PEER 2556 01:31:13,520 --> 01:31:15,800 INTERVENTIONS, I THINK THAT 2557 01:31:15,800 --> 01:31:17,680 THOSE--THE PEER TO PEER MODELS 2558 01:31:17,680 --> 01:31:19,120 CAN BE EXTREMELY SUCCESSFUL, I 2559 01:31:19,120 --> 01:31:21,440 THINK THERE'S 2 THINGS THAT ARE 2560 01:31:21,440 --> 01:31:24,400 MAJOR BARRIERS, I THINK 1 IS THE 2561 01:31:24,400 --> 01:31:26,520 SYSTEM, WE WOULD LOVE TO SEE 2562 01:31:26,520 --> 01:31:28,400 CBOs RUNNING THESE PEER TO 2563 01:31:28,400 --> 01:31:29,440 PEER INTERVENTIONS BUT VEHICLE A 2564 01:31:29,440 --> 01:31:32,200 SYSTEM THAT CAN HAVE INTAKE AND 2565 01:31:32,200 --> 01:31:34,240 THEN DISTRIBUTE THE DIFFERENT 2566 01:31:34,240 --> 01:31:36,000 PEERS TO INDIVIDUALS FOR THEIR 2567 01:31:36,000 --> 01:31:37,120 THERAPY OR COACHING, WHATEVER IT 2568 01:31:37,120 --> 01:31:39,480 IS, I THINK HAVING A SYSTEM 2569 01:31:39,480 --> 01:31:40,800 THAT'S ROBUST AND IS FUNCTIONAL, 2570 01:31:40,800 --> 01:31:42,400 I THINK THAT'S CRITICAL TO HAVE 2571 01:31:42,400 --> 01:31:42,600 THAT. 2572 01:31:42,600 --> 01:31:44,840 THE OTHER PART IS THE TRAINING, 2573 01:31:44,840 --> 01:31:46,120 AND WE GOT A QUESTION ABOUT THIS 2574 01:31:46,120 --> 01:31:47,640 IN THE CHAT WHICH IS VERY GOOD, 2575 01:31:47,640 --> 01:31:49,440 LIKE WHAT LEVEL OF TRAINING DO 2576 01:31:49,440 --> 01:31:50,720 THE HEALTH COACHES GO THROUGH. 2577 01:31:50,720 --> 01:31:53,720 WE ACTUALLY STARTED OUT FOR THE 2578 01:31:53,720 --> 01:31:55,840 CHARISMA STUDY, WE STARTED OUT 2579 01:31:55,840 --> 01:31:58,320 WITH AN INTENSIVE TRAINING 2580 01:31:58,320 --> 01:31:59,000 PROGRAM. 2581 01:31:59,000 --> 01:32:01,920 I KNOW THAT EV'S GROUP WHO HAS 2582 01:32:01,920 --> 01:32:04,000 ALSO A PC ORI, THEY'RE DOING 2583 01:32:04,000 --> 01:32:05,880 TRAINING AS WELL AND THEY HAVE A 2584 01:32:05,880 --> 01:32:06,720 REALLY INTENSE TRAINING PROGRAM 2585 01:32:06,720 --> 01:32:09,280 FOR THEIR PEERS BUT THERE'S MUCH 2586 01:32:09,280 --> 01:32:11,120 ATTRITION AND IT'S REALLY HARD 2587 01:32:11,120 --> 01:32:14,560 TO GET THESE--EVEN THOSE WHO ARE 2588 01:32:14,560 --> 01:32:15,720 EXCITED ABOUT BEING A HEALTH 2589 01:32:15,720 --> 01:32:17,520 COACH OR BEING A PEER MENTOR TO 2590 01:32:17,520 --> 01:32:19,640 GET THEM THROUGH THE AMOUNT OF 2591 01:32:19,640 --> 01:32:21,000 TRAINING THAT WE REQUIRE FOR 2592 01:32:21,000 --> 01:32:23,680 THEM TO BE EFFECTIVE, SO WE 2593 01:32:23,680 --> 01:32:24,760 TRIED SCALING BACK THE TRAINING 2594 01:32:24,760 --> 01:32:26,640 QUITE A BIT AND HAVING A BIT OF 2595 01:32:26,640 --> 01:32:28,400 ON THE JOB TRAIN ASKING THAT'S 2596 01:32:28,400 --> 01:32:32,480 BEEN A LOT MORE--A LOT MORE 2597 01:32:32,480 --> 01:32:33,960 PROMISING OR EFFECT FOR US IN 2598 01:32:33,960 --> 01:32:35,440 TERMS OF RETAINING PEOPLE SO I 2599 01:32:35,440 --> 01:32:36,520 THINK THE TRAINING PIECE WE HAD 2600 01:32:36,520 --> 01:32:39,200 TO KIND OF GET THE SWEET SPOT OF 2601 01:32:39,200 --> 01:32:41,400 GIVING THEM ENOUGH THEY'RE NOT 2602 01:32:41,400 --> 01:32:45,000 DANGEROUS BUT NOT TOO MUCH BUT 2603 01:32:45,000 --> 01:32:56,320 IT'S NOT TOO ARDUOUS TO GET 2604 01:32:56,320 --> 01:32:56,560 THROUGH. 2605 01:32:56,560 --> 01:33:00,000 >> AND THE SECOND PART WAS THE 2606 01:33:00,000 --> 01:33:00,600 TELEMEDICINE PER BEHAVIORIAL 2607 01:33:00,600 --> 01:33:02,920 THELGT FROM THE A STANDPOINT OF 2608 01:33:02,920 --> 01:33:06,640 LICENSED SOCIAL WORKERS, 2609 01:33:06,640 --> 01:33:07,640 PSYCHOLOGISTS AND PSYCHIATRISTS 2610 01:33:07,640 --> 01:33:13,800 MOW DO WE APPROVE THE UPTAKE OF 2611 01:33:13,800 --> 01:33:14,200 THOSE? 2612 01:33:14,200 --> 01:33:15,560 >> I'M SURE LIZ HAS OPINIONS ON 2613 01:33:15,560 --> 01:33:16,920 THIS CONSIDERING SHE'S TRYING TO 2614 01:33:16,920 --> 01:33:20,960 WORK ON THINGS IN AIR RURAL AREA 2615 01:33:20,960 --> 01:33:23,960 NEAR US. 2616 01:33:23,960 --> 01:33:26,400 >> YEAH, YOU KNOW I DON'T 2617 01:33:26,400 --> 01:33:27,080 THINK--UNFORTUNATELY I DON'T 2618 01:33:27,080 --> 01:33:33,480 THINK THERE'S SORT OF A MAREACLE 2619 01:33:33,480 --> 01:33:35,520 SOLUTION HERE EITHER, I THINK 2620 01:33:35,520 --> 01:33:37,080 ENGAGEMENT IN CARE IS SOMETHING 2621 01:33:37,080 --> 01:33:38,440 THAT IS CLEARLY A CHALLENGE WITH 2622 01:33:38,440 --> 01:33:40,200 HER TODAY ABOUT YOU KNOW WE HAVE 2623 01:33:40,200 --> 01:33:41,440 THESE INTERVENTIONS THAT HAVE 2624 01:33:41,440 --> 01:33:45,360 DATA TO SUPPORT THEM TO BE 2625 01:33:45,360 --> 01:33:46,440 HELPFUL BUT GETTING THOSE 2626 01:33:46,440 --> 01:33:47,600 DELIVERED IS A CHALLENGE AND I 2627 01:33:47,600 --> 01:33:49,000 THINK WE EVEN HEARD TODAY ABOUT 2628 01:33:49,000 --> 01:33:51,440 SOME OF THESE BARRIERS WHERE 2629 01:33:51,440 --> 01:33:52,240 THERE'S TRANSPORTATION OR DATA 2630 01:33:52,240 --> 01:33:59,240 PLANS ON CELL PHONES OR YOU KNOW 2631 01:33:59,240 --> 01:34:00,240 JUST THE ACCEPTABILITY OF 2632 01:34:00,240 --> 01:34:01,160 PATIENTS FEELING THAT THIS IS 2633 01:34:01,160 --> 01:34:02,920 SOMETHING THEY THINK IS WORTH 2634 01:34:02,920 --> 01:34:05,520 WHILE. 2635 01:34:05,520 --> 01:34:08,000 AND I THINK THAT THE 2636 01:34:08,000 --> 01:34:08,760 JUSTICE--THERE'S A REALLY GREAT 2637 01:34:08,760 --> 01:34:10,800 QUESTION IN THE CHAT ABOUT YOU 2638 01:34:10,800 --> 01:34:12,960 KNOW HOW DO WE--WHICH OF THESE 2639 01:34:12,960 --> 01:34:14,320 INTERVENTIONS DO WE PICK FOR OUR 2640 01:34:14,320 --> 01:34:14,720 PATIENTS? 2641 01:34:14,720 --> 01:34:17,440 WE HAVE SO MANY OPTIONS, HOW DO 2642 01:34:17,440 --> 01:34:19,000 WE DECIDE? 2643 01:34:19,000 --> 01:34:20,640 AND ULTIMATELY I THINK 1 OF THE 2644 01:34:20,640 --> 01:34:22,440 BIGGEST DECIDERS IN THE THING 2645 01:34:22,440 --> 01:34:23,640 THAT HELPS WITH THE ADDRESS OF 2646 01:34:23,640 --> 01:34:25,720 THIS ISSUE OF ENGAGEMENT IS WHAT 2647 01:34:25,720 --> 01:34:27,440 DOES THE PATIENT WANT. 2648 01:34:27,440 --> 01:34:29,680 IT SOUNDS SO BASIC, BUT WHAT ARE 2649 01:34:29,680 --> 01:34:31,040 THEY INTERESTED IN, WHAT DID 2650 01:34:31,040 --> 01:34:33,160 THEY BELIEVE WILL BE EFFECTIVE 2651 01:34:33,160 --> 01:34:35,000 FOR THEM. 2652 01:34:35,000 --> 01:34:38,080 AND THAT'S HOW YOU KNOW YOU ARE 2653 01:34:38,080 --> 01:34:39,320 OFTEN--THAT IS 1 OF THE MOST 2654 01:34:39,320 --> 01:34:40,960 HELPFUL THINGS I THINK IN 2655 01:34:40,960 --> 01:34:42,440 ADDRESSING THESE ISSUES OF 2656 01:34:42,440 --> 01:34:44,000 ENGAGEMENT AND HAVING THIS BE 2657 01:34:44,000 --> 01:34:45,680 SOMETHING THAT'S MEANINGFUL FOR 2658 01:34:45,680 --> 01:34:48,000 THE PATIENT AND SO SORT OF 2659 01:34:48,000 --> 01:34:50,240 SAYING EVERYONE GETS 2660 01:34:50,240 --> 01:34:53,800 ACCUPUNCTURE, EVERYONE GETS 2661 01:34:53,800 --> 01:34:54,760 SYMBALTA, EVERYONE GETS 2662 01:34:54,760 --> 01:34:57,240 BUPRENORPHINE, NONE OF THESE 2663 01:34:57,240 --> 01:34:58,640 THINGS ARE THE 1 ANSWER AND IT'S 2664 01:34:58,640 --> 01:35:01,040 REALLY SORT OF WORKING WITH OUR 2665 01:35:01,040 --> 01:35:02,240 PATIENTS AND FINDING OUT WHAT 2666 01:35:02,240 --> 01:35:05,440 THE ISSUES OF ENGAGEMENT ARE FOR 2667 01:35:05,440 --> 01:35:06,920 THEM AND THESE PEER 2668 01:35:06,920 --> 01:35:08,520 INTERVENTIONS COMMUNITY AND 2669 01:35:08,520 --> 01:35:09,360 HEALTH WORKER INTERVENTIONS, 2670 01:35:09,360 --> 01:35:10,440 THESE ALSO HELP US DRILL DOWN TO 2671 01:35:10,440 --> 01:35:12,040 WHAT ARE THE BARRIERS FOR 2672 01:35:12,040 --> 01:35:20,360 ENGAGEMENT OF OUR PATIENTS. 2673 01:35:20,360 --> 01:35:20,720 >> I'M--SORRY. 2674 01:35:20,720 --> 01:35:24,400 >> NO, NO, THAT WAS MY THING. 2675 01:35:24,400 --> 01:35:27,920 >> 1 THING I WANT TO SAY AND SAY 2676 01:35:27,920 --> 01:35:32,640 DIRECTLY IS Y'ALL NEED TO KNOW 2677 01:35:32,640 --> 01:35:33,080 SOME PSYCHIATRY. 2678 01:35:33,080 --> 01:35:34,240 ONE OF THE MOST DIFFICULT THINGS 2679 01:35:34,240 --> 01:35:38,800 THAT I HAD TO DEAL WITH WHEN I 2680 01:35:38,800 --> 01:35:40,040 FIRST STARTED WAS HAVING THE 2681 01:35:40,040 --> 01:35:41,760 PATIENT COME IN, SIT IN THE 2682 01:35:41,760 --> 01:35:44,200 CHAIR AND I SAY, WELL WHAT 2683 01:35:44,200 --> 01:35:47,200 BRINGS YOU BY AND THE PATIENTS 2684 01:35:47,200 --> 01:35:48,640 SAY, I DON'T KNOW THEY JUST SAID 2685 01:35:48,640 --> 01:35:50,960 I NEEDED TO COME TALK TO 2686 01:35:50,960 --> 01:35:51,520 SOMEBODY. 2687 01:35:51,520 --> 01:35:56,640 THIS IS NOT A SET UP FOR 2688 01:35:56,640 --> 01:35:57,400 SUCCESS, Y'ALL. 2689 01:35:57,400 --> 01:35:59,400 WE NEED SOME SOPHISTICATION. 2690 01:35:59,400 --> 01:36:01,000 WE'RE DEALING WITH PEOPLE WHO 2691 01:36:01,000 --> 01:36:02,280 ALMOST ALL HAVE CHRONIC PAIN OR 2692 01:36:02,280 --> 01:36:05,040 WILL HAVE CHRONIC PAIN, WE NEED 2693 01:36:05,040 --> 01:36:07,600 SOME SOPHISTICATION ABOUT HOW 2694 01:36:07,600 --> 01:36:09,080 THIS INTERACTS WITH PSYCHIATRIC 2695 01:36:09,080 --> 01:36:11,240 ILLNESS, YOU NEED TO BE ABLE TO 2696 01:36:11,240 --> 01:36:13,440 TALK INTELLIGENTLY ABOUT HOW 2697 01:36:13,440 --> 01:36:14,800 DEPRESSION INTERACTING WITH 2698 01:36:14,800 --> 01:36:17,200 CHRONIC PAIN AND THE CAUSATION 2699 01:36:17,200 --> 01:36:19,960 IS NOT JUST 1 DIRECTION, AND IT 2700 01:36:19,960 --> 01:36:21,360 IS AN ILLNESS AND YOUR PAIN CAN 2701 01:36:21,360 --> 01:36:26,480 GET BETTER IF YOU GET YOUR 2702 01:36:26,480 --> 01:36:27,400 DEPRESSION TREATED. 2703 01:36:27,400 --> 01:36:30,360 VERY FREQUENTLY WHEN I HEAR 2704 01:36:30,360 --> 01:36:31,840 SOMEONE SAYS, WELL YOU HAVE BAD 2705 01:36:31,840 --> 01:36:34,760 PAIN AND YOU SEEM TO FEEL BAD, 2706 01:36:34,760 --> 01:36:36,120 MAYBE YOU SHOULD TALK TO 2707 01:36:36,120 --> 01:36:38,560 SOMEONE, THE ANSWER IS I CAN 2708 01:36:38,560 --> 01:36:40,440 TALK TO MY PASTOR, MY WIFE, WHY 2709 01:36:40,440 --> 01:36:42,920 DO I NEED TO SEE SOME GRAY 2710 01:36:42,920 --> 01:36:46,000 HAIRED WHITE GUY IN A TIE FOR 2711 01:36:46,000 --> 01:36:48,480 AND YOU NEED TO ANSWER THIS 2712 01:36:48,480 --> 01:36:48,760 QUESTION? 2713 01:36:48,760 --> 01:36:50,400 >> I THINK ALONG THOSE SAME 2714 01:36:50,400 --> 01:36:52,520 LINES BECAUSE I THINK IT'S SO 2715 01:36:52,520 --> 01:36:54,000 IMPORTANT AND HIGHLIGHTS HOW 2716 01:36:54,000 --> 01:36:56,440 MUCH WE NEED MULTIDISCIPLINARY 2717 01:36:56,440 --> 01:36:58,600 CARE, WE NEED MORE PSYCHIATRIST 2718 01:36:58,600 --> 01:36:59,720 LIKE DR. CARROLL AND DR. PRINCE 2719 01:36:59,720 --> 01:37:01,720 TO BE PART OF OUR TEAM TO HELP 2720 01:37:01,720 --> 01:37:03,560 US HAVE THESE CONVERSATIONS AND 2721 01:37:03,560 --> 01:37:04,960 ENGAGE US AND INDIVIDUALS AND AS 2722 01:37:04,960 --> 01:37:08,720 MANY PEOPLE KNOW, THERE'S 2723 01:37:08,720 --> 01:37:11,120 CERTAINLY STIGMA AGAINST 2724 01:37:11,120 --> 01:37:12,400 PSYCHIATRY IN ADDITION TO SIGMA 2725 01:37:12,400 --> 01:37:13,560 THAT'S ASSOCIATE WIDE PAIN SO 2726 01:37:13,560 --> 01:37:14,640 HAVING ALL PEOPLE IN 1 PLACE, 2727 01:37:14,640 --> 01:37:16,240 THEY WILL CAN TOM OUR SICKLE 2728 01:37:16,240 --> 01:37:17,640 CELL CENTER AND SO WE WANT TO 2729 01:37:17,640 --> 01:37:19,440 MAKE SURE THAT WE'RE ABLE TO 2730 01:37:19,440 --> 01:37:20,920 ENGAGE THEM IN PSYCHIATRIC 2731 01:37:20,920 --> 01:37:23,440 ASSISTANCE WHEN THEY'RE ALREADY 2732 01:37:23,440 --> 01:37:25,440 THERE FOR OTHER PURPOSES. 2733 01:37:25,440 --> 01:37:26,960 ON THAT SAME NOTE, I WANTED TO 2734 01:37:26,960 --> 01:37:28,680 THROW OUT A QUESTION THEY FIND 2735 01:37:28,680 --> 01:37:30,960 PROBABLY THE MOST DIFFICULT IS 2736 01:37:30,960 --> 01:37:33,720 THAT OR A THOUGHT, I GUESS FOR 2737 01:37:33,720 --> 01:37:37,720 1, FOR A LONG TIME, TD IDEA OF 2738 01:37:37,720 --> 01:37:42,160 WHY SEE, WE BELIEVE YOUR PAIN 2739 01:37:42,160 --> 01:37:43,040 HAS BEEN ASSOCIATED WITH 2740 01:37:43,040 --> 01:37:45,360 THEREFORE WE USE OPIOIDS MPLET 2741 01:37:45,360 --> 01:37:47,320 AS OPPOSE TO SEE SEE AND WE 2742 01:37:47,320 --> 01:37:49,160 BELIEVE PAIN, WE KNOW DEEPLY HOW 2743 01:37:49,160 --> 01:37:51,040 MUCH PAIN IS A PART OF SICKLE 2744 01:37:51,040 --> 01:37:53,640 CELL DISEASE, BUT HOW DO WE 2745 01:37:53,640 --> 01:37:56,760 DISASSOCIATE THOSE 2 THINGS? 2746 01:37:56,760 --> 01:37:58,400 HOW DO WE HELP PEOPLE UNDERSTAND 2747 01:37:58,400 --> 01:37:59,880 THAT BY SEEING AND BELIEVING 2748 01:37:59,880 --> 01:38:02,320 YOUR PAIN IT DOESN'T JUST MEAN I 2749 01:38:02,320 --> 01:38:03,880 HAVE TO ESCALATE RAIN SHOWER 2750 01:38:03,880 --> 01:38:06,120 OPIOIDS TO SEE AND BELIEVE YOUR 2751 01:38:06,120 --> 01:38:08,680 PAIN AS OPPOSED TO ALSO USING 2752 01:38:08,680 --> 01:38:09,280 THESE OTHER OPTIONS. 2753 01:38:09,280 --> 01:38:10,880 I'LL THROW THAT OUT, MAYBE 2754 01:38:10,880 --> 01:38:13,160 CHARGZ, START WITH YOU AND GET 2755 01:38:13,160 --> 01:38:14,120 EVERYBODY ELSE'S THOUGHTS? 2756 01:38:14,120 --> 01:38:18,400 >> YEAH, YOU KNOW BECAUSE I 2757 01:38:18,400 --> 01:38:20,280 THINK THAT WHAT PAT WAS TALKING 2758 01:38:20,280 --> 01:38:21,600 ABOUT, I THINK LENDS TO IT, JUST 2759 01:38:21,600 --> 01:38:23,920 IN TERMS OF THE EDUCATION AT THE 2760 01:38:23,920 --> 01:38:25,240 OUTSET, YOU KNOW I HAD THE 2761 01:38:25,240 --> 01:38:26,000 EXPERIENCE, I WAS SMILING 2762 01:38:26,000 --> 01:38:27,720 BECAUSE I HAD THE EXPERIENCE 2763 01:38:27,720 --> 01:38:29,040 WHERE A PROVIDER SAID, HEY, YOU 2764 01:38:29,040 --> 01:38:30,840 KNOWY WOO WILL CUT YOUR OPIOIDS 2765 01:38:30,840 --> 01:38:32,320 IN HALF AND THEN THE PATIENT WAS 2766 01:38:32,320 --> 01:38:34,560 LIKE, OH WHAT AM I GOING TO DO, 2767 01:38:34,560 --> 01:38:36,320 AND THEY'RE LIKE OH, HERE'S 2768 01:38:36,320 --> 01:38:37,680 DR. CHARLES HE'S GOING TO WORK 2769 01:38:37,680 --> 01:38:39,440 WITH YOU ON DEEP BREATHING OR 2770 01:38:39,440 --> 01:38:41,360 SOMETHING LIKE THAT, RIGHT? 2771 01:38:41,360 --> 01:38:42,120 SO, YOU KNOW-- 2772 01:38:42,120 --> 01:38:43,400 >> HOW'S THAT SESSION GO. 2773 01:38:43,400 --> 01:38:45,000 >> YEAH THAT WAS FANTASTIC AND 2774 01:38:45,000 --> 01:38:47,040 THE THING I'M A BLACK 2775 01:38:47,040 --> 01:38:48,440 PSYCHOLOGIST, RIGHT I'M NOT EVEN 2776 01:38:48,440 --> 01:38:50,760 A GRAY HAIRED WHITE GUY BAH 2777 01:38:50,760 --> 01:38:51,840 STILL THAT THAT INTRODUCTION AND 2778 01:38:51,840 --> 01:38:53,440 THE EDUCATION ON WHAT WE'RE 2779 01:38:53,440 --> 01:38:55,560 GOING TO DO IN TERMS OF OUR 2780 01:38:55,560 --> 01:38:56,160 BEHAVIORIAL APPROACH IS NOT 2781 01:38:56,160 --> 01:38:58,000 THERE FROM THE VERY, VERY 2782 01:38:58,000 --> 01:39:00,240 BEGINNING AND OBVIOUSLY IT HAS 2783 01:39:00,240 --> 01:39:02,200 TO START AT PEDIATRICS 2784 01:39:02,200 --> 01:39:03,840 BECAUSE--AND WHETHER THAT 2785 01:39:03,840 --> 01:39:04,680 EDUCATION IS APPROPRIATE OR NOT 2786 01:39:04,680 --> 01:39:07,400 BECAUSE I KNOW A LOT OF PATIENTS 2787 01:39:07,400 --> 01:39:09,800 TRANSITION AND THEY'RE LIKE OH 2788 01:39:09,800 --> 01:39:11,520 THEY'VE BEEN SHOVING THAT 2789 01:39:11,520 --> 01:39:12,440 PSYCHOLOGY STUFF DOWN MY THROAT 2790 01:39:12,440 --> 01:39:13,880 AND THE DEEP BREATHING AND I I'M 2791 01:39:13,880 --> 01:39:16,040 TIRED I DON'T WANT TO HEAR IT 2792 01:39:16,040 --> 01:39:17,880 AND THE MINDFULNESS SO THEY'RE 2793 01:39:17,880 --> 01:39:19,320 SICK OF IT BY THEN, BUT THEY 2794 01:39:19,320 --> 01:39:20,480 NEED TO CHANGE IT IN A DIFFERENT 2795 01:39:20,480 --> 01:39:21,880 WAY BUT THE EDUCATION NEEDS TO 2796 01:39:21,880 --> 01:39:23,120 BE THERE AND THE EXPECTATION AND 2797 01:39:23,120 --> 01:39:24,440 PART OF THE CULTURE AND I THINK 2798 01:39:24,440 --> 01:39:27,560 THAT THE PEER MODEL IS PIECE OF 2799 01:39:27,560 --> 01:39:28,800 THAT, AND PATIENTS HAVE SAID TO 2800 01:39:28,800 --> 01:39:30,320 ME SPECIFICALLY LIKE HEY, 2801 01:39:30,320 --> 01:39:31,360 DR. CHARLES WE LOVE AND YOU 2802 01:39:31,360 --> 01:39:32,440 EVERYTHING, BUT IF WE'RE GOING 2803 01:39:32,440 --> 01:39:34,280 TO LEARN ABOUT HOW TO MANAGE MY 2804 01:39:34,280 --> 01:39:35,600 SICKLE SEAL PAIN, I DON'T WANT 2805 01:39:35,600 --> 01:39:36,840 TO HEAR IT FROM YOU. 2806 01:39:36,840 --> 01:39:39,200 I WOULD MUCH RATHER HEAR IT FROM 2807 01:39:39,200 --> 01:39:40,560 SOME BE WHO'S BEEN THROUGH THIS 2808 01:39:40,560 --> 01:39:40,840 BEFORE. 2809 01:39:40,840 --> 01:39:46,440 SO I DO THINK IT'S A COMBINATION 2810 01:39:46,440 --> 01:39:47,040 OF THINGS. 2811 01:39:47,040 --> 01:39:54,200 >> I HAVE THOUGHTS ON THIS 2812 01:39:54,200 --> 01:39:54,480 ISSUE. 2813 01:39:54,480 --> 01:40:07,840 SO I THINK 1 PART OF IT IS I 2814 01:40:07,840 --> 01:40:09,000 THINK BELIEVING SOMEONE HAS PAIN 2815 01:40:09,000 --> 01:40:10,680 IS MORE THAN 1 WAY TO MANAGE IT. 2816 01:40:10,680 --> 01:40:12,800 SO THERE'S A DIAGNOSIS 2817 01:40:12,800 --> 01:40:14,480 ASSESSMENT PROBLEM AND THERE'S A 2818 01:40:14,480 --> 01:40:15,240 MANAGEMENT PROBLEM AND YOU KNOW 2819 01:40:15,240 --> 01:40:19,240 1 OF THE THINGS I THINK WE KIND 2820 01:40:19,240 --> 01:40:21,520 OF GOT TO ACKNOWLEDGE IS OPIOIDS 2821 01:40:21,520 --> 01:40:22,000 CAN FAIL. 2822 01:40:22,000 --> 01:40:25,880 YOU KNOW IF YOU LOOK AT CLINICAL 2823 01:40:25,880 --> 01:40:29,440 TRIALS EVEN AT 6 WEEKS, YOU GET 2824 01:40:29,440 --> 01:40:30,480 LIKE 10-20% DROP OUT AND WITH 2825 01:40:30,480 --> 01:40:33,640 THE NUMBER NEEDED TO TREAT THE 2826 01:40:33,640 --> 01:40:35,720 BENEFITS IS LIKE 3 SO IT FAILS 2827 01:40:35,720 --> 01:40:37,440 2/3RDS OF TIME AND WE OFTEN ACT 2828 01:40:37,440 --> 01:40:39,440 LIKE THAT AIN'T TRUE, LIKE YOU 2829 01:40:39,440 --> 01:40:41,360 HAVE TO DO IS FIND THE RIGHT 2830 01:40:41,360 --> 01:40:43,120 OPIOID AND DOSE, AND THERE ARE 2831 01:40:43,120 --> 01:40:45,320 SOME PEOPLE GET WAY UP THE TREE 2832 01:40:45,320 --> 01:40:48,400 AND HAVING THAT ITERATE OVER 2833 01:40:48,400 --> 01:40:49,920 MANY YEARS AND SO THERE'S 1 PART 2834 01:40:49,920 --> 01:40:52,720 IS, YOU KNOW WE HAVE TO 2835 01:40:52,720 --> 01:40:54,560 ACKNOWLEDGE THAT CHRONIC PAIN IS 2836 01:40:54,560 --> 01:40:57,360 HARD TO TREAT, NOTHING'S 2837 01:40:57,360 --> 01:40:58,840 UNIVERSALLY EFFECTIVE INCLUDING 2838 01:40:58,840 --> 01:41:00,120 OPIOIDS, WHICH MEANS YOU HAVE TO 2839 01:41:00,120 --> 01:41:01,560 HAVE A PLAN FOR WHEN THEY DON'T 2840 01:41:01,560 --> 01:41:03,000 WORK AND A DEFINITION OF WHEN 2841 01:41:03,000 --> 01:41:05,560 THEY DON'T WORK WHICH WE NEED 2842 01:41:05,560 --> 01:41:09,720 AND THAT'S ANOTHER PROBLEM AND 2843 01:41:09,720 --> 01:41:11,600 ANOTHER IS, YOU KNOW CHRONIC 2844 01:41:11,600 --> 01:41:12,800 PAIN DOESN'T HAPPEN TO 14 2845 01:41:12,800 --> 01:41:16,720 YEAR-OLDS OR 10 YEAR-OLDS. 2846 01:41:16,720 --> 01:41:18,240 AND IF FOLKS NEVER KNOW WHAT'S 2847 01:41:18,240 --> 01:41:19,840 COMING TO THEM UNTIL IT'S 2848 01:41:19,840 --> 01:41:21,680 ALREADY THERE AND THEY'RE AT 22, 2849 01:41:21,680 --> 01:41:24,320 25 AND THE PANE DOESN'T GO AWAY, 2850 01:41:24,320 --> 01:41:25,880 AND FOR THE LAST 2 DECADES 2851 01:41:25,880 --> 01:41:27,480 THEY'VE BEEN TOLD THIS IS THE 2852 01:41:27,480 --> 01:41:31,000 WAY YOU MANAGE SICKLE PAIN, YOU 2853 01:41:31,000 --> 01:41:34,440 KNOW, THAT'S HARD TO UNDO. 2854 01:41:34,440 --> 01:41:36,000 SO I THINK PEOPLE NEED TO KNOW 2855 01:41:36,000 --> 01:41:37,080 WHAT'S COMING THEIR WAY BEFORE 2856 01:41:37,080 --> 01:41:38,680 IT HITS THEM AND THAT WOULD HELP 2857 01:41:38,680 --> 01:41:42,840 US TO HAVE A MORE REALISTIC 2858 01:41:42,840 --> 01:41:43,200 CONVERSATION. 2859 01:41:43,200 --> 01:41:45,600 >> I THINK THAT THAT'S SO SMART 2860 01:41:45,600 --> 01:41:48,160 DR. CAROL AND 1 THE THINGS THAT 2861 01:41:48,160 --> 01:41:49,680 THE ALLIANCE HAS UNDERTAKEN 2862 01:41:49,680 --> 01:41:51,240 LENIENT THAT I HOPE YOU ALL WILL 2863 01:41:51,240 --> 01:41:54,000 HEAR MORE ABOUT IN THE COMING 2864 01:41:54,000 --> 01:41:55,280 MONTHS AND THE IMPORTANCE EVER A 2865 01:41:55,280 --> 01:41:56,680 LIFE SPAN APPROACH TO PAIN AND 2866 01:41:56,680 --> 01:41:57,640 THAT WE HAVE STOCK EXCHANGE STOP 2867 01:41:57,640 --> 01:41:58,400 THINKING IN EMERGING ITS WHAT 2868 01:41:58,400 --> 01:42:00,000 HAVE WE DO IN PEDIATRICS AND HAD 2869 01:42:00,000 --> 01:42:02,960 WHAT WE DO IN ADULT CARE AS 2870 01:42:02,960 --> 01:42:04,400 SEPARATE ENTITIES AND SO THE 2871 01:42:04,400 --> 01:42:06,640 MORE WE START TO WORK ON THIS 2872 01:42:06,640 --> 01:42:07,800 LIFE SPAN APROETCH TO PAIN WE 2873 01:42:07,800 --> 01:42:09,800 CAN DO WHAT YOU SUGGEST, BOTH 2874 01:42:09,800 --> 01:42:13,440 BEGINNING EARLY IN PEDIATRICS, 2875 01:42:13,440 --> 01:42:15,440 WITH OTHER INTERVENTIONS BESIDES 2876 01:42:15,440 --> 01:42:16,480 OPIOIDS BUT ALSO WITH THE 2877 01:42:16,480 --> 01:42:17,640 RECOGNITION OF COURSE THAT 2878 01:42:17,640 --> 01:42:18,960 CHRONIC PAIN WILL HAPPEN TO 2879 01:42:18,960 --> 01:42:21,160 QUITE A LOT OF PEOPLE AND SO, 2880 01:42:21,160 --> 01:42:23,800 MAYBE IF WE TAKE THAT APPROACH 2881 01:42:23,800 --> 01:42:26,440 AND TAKE A REAL LIFE APPROACH WE 2882 01:42:26,440 --> 01:42:28,680 WILL BE ABLE TO HOPEFULLY 2883 01:42:28,680 --> 01:42:31,800 IMPROVE ON SOME OF THIS GOING 2884 01:42:31,800 --> 01:42:32,000 FORWARD. 2885 01:42:32,000 --> 01:42:40,080 DR. STROUSE, DO YOU WANT TO ASK 2886 01:42:40,080 --> 01:42:40,600 THE NEXT QUESTION? 2887 01:42:40,600 --> 01:42:42,480 YOU HAVE TO GET OFF MUTE FIRST. 2888 01:42:42,480 --> 01:42:43,760 >> I WANTED TO ASK A QUESTION 2889 01:42:43,760 --> 01:42:46,240 ABOUT WHAT'S THE RIGHT TIME TO 2890 01:42:46,240 --> 01:42:46,920 INITIATE BUPRENORPHINE, WE 2891 01:42:46,920 --> 01:42:48,080 RECEIVED A REQUESTY ABOUT 2892 01:42:48,080 --> 01:42:50,640 WHETHER EARLY ON AS PEOPLE ARE 2893 01:42:50,640 --> 01:42:52,920 DEVELOPING CHRONIC PAIN ARE 2894 01:42:52,920 --> 01:42:55,240 THERE POTENTIAL ROLES VERSUS 2895 01:42:55,240 --> 01:42:56,240 DESENSITIZATION AND YOU KNOW 2896 01:42:56,240 --> 01:42:59,720 WHO'S THE RIGHT PERSON TO START 2897 01:42:59,720 --> 01:43:01,000 BUPRENORPHINE AND IT SHOULD IT 2898 01:43:01,000 --> 01:43:02,840 BE PEOPLE THAT WE FEEL LIKE ARE 2899 01:43:02,840 --> 01:43:06,240 NOT RESPONDING WELL TO OPIATES 2900 01:43:06,240 --> 01:43:07,960 OR OR CHALLENGES WITH OPIATES OR 2901 01:43:07,960 --> 01:43:09,320 SHOULD IT BE A BROADER 2902 01:43:09,320 --> 01:43:09,640 POPULATION? 2903 01:43:09,640 --> 01:43:16,160 >> I GUESS I WILL TAKE THAT 1, 2904 01:43:16,160 --> 01:43:17,560 WE DON'T KNOW IS THE ACTUAL 2905 01:43:17,560 --> 01:43:19,560 ANSWER TO THE QUESTION, NOW I 2906 01:43:19,560 --> 01:43:21,240 WILL WAVE MY HANDS IF AREA I 2907 01:43:21,240 --> 01:43:22,240 MACHINEUTE OR 2. 2908 01:43:22,240 --> 01:43:28,320 YOU KNOW WHAT WE'VE USED IT FOR 2909 01:43:28,320 --> 01:43:33,320 IS WHEN WE FUNDAMENTALLY THINK 2910 01:43:33,320 --> 01:43:34,640 THAT OPIOIDS EITHER BECAUSE THE 2911 01:43:34,640 --> 01:43:36,400 RISK IS UNACCEPTABLE OR THE 2912 01:43:36,400 --> 01:43:38,320 PATIENT'S JUST IN BAD PAIN OR 2913 01:43:38,320 --> 01:43:41,480 YOU GOTTA TRY SOMETHING ELSE, 2914 01:43:41,480 --> 01:43:45,400 AND SO WHAT WE'VE USED IT FOR 2915 01:43:45,400 --> 01:43:47,680 HAS BEEN ESSENTIA WILY OPIOID 2916 01:43:47,680 --> 01:43:51,200 FAILURE AT LEAST A SAFER AND 2917 01:43:51,200 --> 01:43:52,640 MAYBE DIFFERENT ALTERNATIVE. 2918 01:43:52,640 --> 01:43:56,120 AND I ALWAYS THINK THIS SORT OF 2919 01:43:56,120 --> 01:43:57,200 SELECTION CRITERIA IS TRICKY 2920 01:43:57,200 --> 01:44:02,400 BECAUSE YOU'RE TRYING TO FIGURE 2921 01:44:02,400 --> 01:44:03,720 OUT WHO'S THE LEAST LEAST BAD 2922 01:44:03,720 --> 01:44:04,680 OFF PERSON THAT MIGHT BENEFIT 2923 01:44:04,680 --> 01:44:06,760 WHICH IS A TRICKY THING TO 2924 01:44:06,760 --> 01:44:09,160 FIGURE OUT AND WE TOOK THE OTHER 2925 01:44:09,160 --> 01:44:11,120 WAY WE TOOK THE FOLKS IN THE 2926 01:44:11,120 --> 01:44:12,200 WORST SHAPE AND REALLY UP THE 2927 01:44:12,200 --> 01:44:13,720 TREE AND TRY TO HELP THIS WAY, 2928 01:44:13,720 --> 01:44:17,760 SO I DON'T KNOW HOW FAR DOWN THE 2929 01:44:17,760 --> 01:44:23,640 LADDER IT REALLY GOES I DO, I AM 2930 01:44:23,640 --> 01:44:24,640 A CORROSIVE SKEPTIC AND THERE 2931 01:44:24,640 --> 01:44:28,800 ARE STUDIES ON THAT TO THE MDNA 2932 01:44:28,800 --> 01:44:29,960 AND THE ANTAGONIST AND THE OTHER 2933 01:44:29,960 --> 01:44:30,960 THING, YOU BE SHOW ME. 2934 01:44:30,960 --> 01:44:35,160 SHOW ME THIS THING IS REALLY A 2935 01:44:35,160 --> 01:44:36,760 DIFFERENT OPIOID BECAUSE HISTORY 2936 01:44:36,760 --> 01:44:38,240 IS NOT KIND TO PEOPLE WHO COME 2937 01:44:38,240 --> 01:44:40,400 UP WITH A NEW OPIOID AND SAY 2938 01:44:40,400 --> 01:44:43,000 HEY, THIS 1'S REALLY DIFFERENT. 2939 01:44:43,000 --> 01:44:48,400 SO THAT BEING SAID AS FAR AS 2940 01:44:48,400 --> 01:44:50,560 LIKE USING IT EARLY I THINK 2941 01:44:50,560 --> 01:44:54,440 LOWISH DOSES IS JUST ANOTHER 2942 01:44:54,440 --> 01:44:56,400 OPIOID, AT HIGHER DOSES IT'S 2943 01:44:56,400 --> 01:44:58,000 SAFER BUT THEN HAVE YOU THE 2944 01:44:58,000 --> 01:44:59,200 PROBLEM OF WHERE DO YOU GO WITH 2945 01:44:59,200 --> 01:45:02,280 A HIGH DOSE IF SOMEONE HAS ACUTE 2946 01:45:02,280 --> 01:45:03,760 PAIN, SO THE SHORT ANSWER IS I 2947 01:45:03,760 --> 01:45:05,120 DON'T KNOW BUT LIKE I SAID 2948 01:45:05,120 --> 01:45:07,280 HISTORY IS NOT KIND TO PEOPLE 2949 01:45:07,280 --> 01:45:08,960 WHO THROW SOME NEW SHINY OPIOID 2950 01:45:08,960 --> 01:45:11,000 AND SAY THIS IS REALLY, REALLY 2951 01:45:11,000 --> 01:45:13,720 DIFFERENT SO I'M INCLINED TO BE 2952 01:45:13,720 --> 01:45:15,000 CAREFUL I TEND TO THINK WE 2953 01:45:15,000 --> 01:45:16,880 SHOULD RESERVE IT FOR WHEN THING 2954 01:45:16,880 --> 01:45:28,080 VS GONE GONE BADLY AND AND THEN 2955 01:45:28,080 --> 01:45:29,440 WE CAN USE BUPRENORPH. 2956 01:45:29,440 --> 01:45:32,440 I THINK WHAT YOU'RE SAYING TOO 2957 01:45:32,440 --> 01:45:33,280 IS REARRANGE OUR THOUGHTS ON 2958 01:45:33,280 --> 01:45:36,440 CHRONIC PAIN TO GET PEOPLE UP 2959 01:45:36,440 --> 01:45:38,000 THE TREE YOU'RE TALKING ABOUT 2960 01:45:38,000 --> 01:45:39,120 AND THAT'S WHAT YOU'RE SAYING 2961 01:45:39,120 --> 01:45:41,120 AND THE LIFE SPAN APPROACH, 2962 01:45:41,120 --> 01:45:42,040 SUPER, SUPER IMPORTANT WE ARE 2963 01:45:42,040 --> 01:45:44,200 FORTUNATE TO BE IN A AGE WHERE 2964 01:45:44,200 --> 01:45:46,840 WE ARE FINALLY MOVING FORWARD IN 2965 01:45:46,840 --> 01:45:48,320 OUTCOMES ON SICKLE CELL DISEASE 2966 01:45:48,320 --> 01:45:51,240 SO WE HAVE PLAN FOR NOT ONLY A 2 2967 01:45:51,240 --> 01:45:53,240 WEEK COURSE OF PAIN BUT HOW DO 2968 01:45:53,240 --> 01:45:53,640 WE APPROACH THAT. 2969 01:45:53,640 --> 01:45:57,240 THERE IS A QUESTION IN THE Q&A 2970 01:45:57,240 --> 01:45:58,520 FROM LORI VIC ABOUT TIME 2971 01:45:58,520 --> 01:46:01,160 INVESTMENT SHE FOUND THAT IN HER 2972 01:46:01,160 --> 01:46:01,840 STUDY BUILDING A RELATIONSHIP 2973 01:46:01,840 --> 01:46:06,080 TOOK A LOT OF TIME WHICH ALL OF 2974 01:46:06,080 --> 01:46:07,720 US WOULD ABSOLUTELY AGREE ON AND 2975 01:46:07,720 --> 01:46:09,680 SHE SPENT YEARS TRYING WITH 2976 01:46:09,680 --> 01:46:11,840 PARTICIPANTS TO BUILD 2977 01:46:11,840 --> 01:46:12,880 RELATIONSHIPS AND I THINK 2978 01:46:12,880 --> 01:46:15,520 DOCTOR, THIS IS A QUESTION MORE 2979 01:46:15,520 --> 01:46:17,280 FOR YOU, HOW DID YOU FIND TIME 2980 01:46:17,280 --> 01:46:18,600 INVESTMENT IN GETTING PATIENTS 2981 01:46:18,600 --> 01:46:27,320 ERNE GAUGED IN THE CHARISMA 2982 01:46:27,320 --> 01:46:27,520 STUDY? 2983 01:46:27,520 --> 01:46:29,320 >> YEAH, SO I DON'T THINK THAT 2984 01:46:29,320 --> 01:46:31,400 WE AS PROVIDERS DO A VERY GOOD 2985 01:46:31,400 --> 01:46:32,920 JOB BECAUSE THERE IS SUCH A TIME 2986 01:46:32,920 --> 01:46:34,840 RESTRICTION ON EVERYTHING WE'RE 2987 01:46:34,840 --> 01:46:36,640 DOING SO EVEN AS A PSYCHOLOGIST 2988 01:46:36,640 --> 01:46:39,000 I DON'T HAVE THAT MUCH TIME AND 2989 01:46:39,000 --> 01:46:40,840 TO SPEND ENOUGH TIME WHERE OR 2990 01:46:40,840 --> 01:46:42,200 THE TIME THAT'S NECESSARY TO 2991 01:46:42,200 --> 01:46:43,680 STAY IN CONTACT WITH SOMEBODY 2992 01:46:43,680 --> 01:46:45,240 AND DEVELOP THAT LEVEL OF TRUST 2993 01:46:45,240 --> 01:46:46,000 THAT THEY KNOW THAT YOU'RE GOING 2994 01:46:46,000 --> 01:46:47,760 TO BE THERE AND YOU KNOW THEY'RE 2995 01:46:47,760 --> 01:46:49,040 GOING TO EXPLIVEN THAT YOU'RE 2996 01:46:49,040 --> 01:46:51,640 GOING TO ACTUALLY ACTOT THINGS 2997 01:46:51,640 --> 01:46:54,960 THEY FIND TO BE IMPORTANT 2998 01:46:54,960 --> 01:46:56,120 AUTODIFFICULT SO TD 1 THING WE 2999 01:46:56,120 --> 01:46:58,760 REALLY DID IS LEVERAGE THE 3000 01:46:58,760 --> 01:46:59,600 COMMUNITY, OFTEN TIMES THE 3001 01:46:59,600 --> 01:47:00,760 COMMUNITY IS ESTABLISHED A MUCH 3002 01:47:00,760 --> 01:47:02,880 BETTER RELATIONSHIP WITH THE 3003 01:47:02,880 --> 01:47:04,280 PATIENTS THAN WE HAVE SO IF WE 3004 01:47:04,280 --> 01:47:10,240 CAN USE THESE COMMUNITIES AS THE 3005 01:47:10,240 --> 01:47:11,880 BRIDGE FOR THAT RELATIONSHIP, I 3006 01:47:11,880 --> 01:47:13,960 THINK THAT WORKS REALLY WELL, IT 3007 01:47:13,960 --> 01:47:15,720 HAS FOR US. 3008 01:47:15,720 --> 01:47:18,200 NOW IT'S NOT A PANACEA, IT'S NOT 3009 01:47:18,200 --> 01:47:20,640 GOING TO FIX EVERYTHING, OFTEN 3010 01:47:20,640 --> 01:47:22,600 TIMES SOME OF OUR PATIENTS HAVE 3011 01:47:22,600 --> 01:47:24,120 HAD NEGATIVE EXPERIENCES WITH 3012 01:47:24,120 --> 01:47:25,280 COMMUNITY-BASED FOLKS AS WELL 3013 01:47:25,280 --> 01:47:27,000 BUT IT IS REALLY A LOT BETTER 3014 01:47:27,000 --> 01:47:34,720 THAN US JUST TRYING TO DO IT ON 3015 01:47:34,720 --> 01:47:36,000 OUR OWN. 3016 01:47:36,000 --> 01:47:37,000 >> FANTASTIC, THANK YOU VERY 3017 01:47:37,000 --> 01:47:37,680 MUCH. 3018 01:47:37,680 --> 01:47:39,240 I SAW DR. CARROLL VIGOROUSLY 3019 01:47:39,240 --> 01:47:41,240 NODDING AS WELL AND THAT'S JUST 3020 01:47:41,240 --> 01:47:41,560 IMPORTANT. 3021 01:47:41,560 --> 01:47:42,600 THE TIME COMMITMENT IS REAL IN 3022 01:47:42,600 --> 01:47:43,320 WHAT WE ALL DO. 3023 01:47:43,320 --> 01:47:47,000 THIS IS A DISEASE THAT'S NOT 3024 01:47:47,000 --> 01:47:48,280 GETTING THE ATTENTION IT NEEDED 3025 01:47:48,280 --> 01:47:50,600 AND REALLY HAS SO MUCH STIGMA 3026 01:47:50,600 --> 01:47:51,680 ASSOCIATED THAT IT ALL TAKES ME 3027 01:47:51,680 --> 01:47:53,640 A LOT OF TIME, I WALK INTO A 3028 01:47:53,640 --> 01:47:58,680 ROOM JUST TO TALK ABOUT BLOOD 3029 01:47:58,680 --> 01:48:00,240 TRANSFUSIONS OR HYDROXY URAIA 3030 01:48:00,240 --> 01:48:01,640 AND SOMETIME ITS TAKES MONTHS 3031 01:48:01,640 --> 01:48:02,960 FOR SOMEONE TO LISTEN AND 1 3032 01:48:02,960 --> 01:48:04,640 THING I HEARD PAT SAY AND OTHERS 3033 01:48:04,640 --> 01:48:05,800 SAY, RIGHT IS MEETING THAT 3034 01:48:05,800 --> 01:48:07,840 INDIVIDUAL WHERE THEY ARE, IS 3035 01:48:07,840 --> 01:48:09,880 SUPER IMPORTANT WHEN YOU FIRST 3036 01:48:09,880 --> 01:48:12,840 MEET THAT INDIVIDUAL PATIENT 3037 01:48:12,840 --> 01:48:13,760 WHETHER THEY'RE 3 OR 30 3038 01:48:13,760 --> 01:48:14,840 UNDERSTAND WHAG THEIR BIGGEST 3039 01:48:14,840 --> 01:48:16,800 CONCERN IS RIGHT NOW TO GET BUY 3040 01:48:16,800 --> 01:48:20,920 IN BEFORE YOU GET TO SOME OF THE 3041 01:48:20,920 --> 01:48:23,240 HARDER PARTS, I THINK IS KEY, 3042 01:48:23,240 --> 01:48:24,280 DR. CARROLL DID YOU WANT TO ADD 3043 01:48:24,280 --> 01:48:26,800 ANYTHING ELSE TO THE TIME 3044 01:48:26,800 --> 01:48:35,240 INVESTMENT DISCUSSION. 3045 01:48:35,240 --> 01:48:36,960 >> NO, I DO THINK 1 THING I SAID 3046 01:48:36,960 --> 01:48:38,840 ABOUT THE TIME INVESTMENT IS 3047 01:48:38,840 --> 01:48:47,240 BEFORE YOU SEE THE PATIENT, 1 OF 3048 01:48:47,240 --> 01:48:48,200 THE--NOTHING FEEDS STIGMA LIKE 3049 01:48:48,200 --> 01:48:52,440 LACK OF KNOWLEDGE, YOU KNOW? 3050 01:48:52,440 --> 01:48:54,640 SO IF YOU KNOW SOMETHING ABOUT 3051 01:48:54,640 --> 01:48:56,360 WHAT DEPRESSION IS AND HOW IT 3052 01:48:56,360 --> 01:48:57,720 INTERACTING WITH CHRONIC PAIN 3053 01:48:57,720 --> 01:49:00,240 AND WHAT TREATMENT ACTUALLY 3054 01:49:00,240 --> 01:49:02,200 MEANS, AND YOU CAN SPEAK IN GOOD 3055 01:49:02,200 --> 01:49:05,000 FAITH WITH BOTH CARE AND 3056 01:49:05,000 --> 01:49:07,640 KNOWLEDGE, THAT HELPS A LOT. 3057 01:49:07,640 --> 01:49:08,280 YOU KNOW? 3058 01:49:08,280 --> 01:49:09,720 THAT BEATS THE HECK OUT OF WELL 3059 01:49:09,720 --> 01:49:11,640 I THINK YOU NEED TO TALK TO 3060 01:49:11,640 --> 01:49:12,520 SOMEBODY BUT I DON'T KNOW WHAT 3061 01:49:12,520 --> 01:49:14,640 TO TELL YOU ABOUT IT. 3062 01:49:14,640 --> 01:49:14,920 >> RIGHT. 3063 01:49:14,920 --> 01:49:17,240 >> SO, THE MORE YOU KNOW, THE 3064 01:49:17,240 --> 01:49:21,920 MORE YOU CAN PREPARE PEOPLE WITH 3065 01:49:21,920 --> 01:49:22,200 THAT UPON. 3066 01:49:22,200 --> 01:49:25,400 >> I AND I FOUND IT HELPFUL TO 3067 01:49:25,400 --> 01:49:26,800 TALK ABOUT MULTIDISCIPLINARY 3068 01:49:26,800 --> 01:49:28,080 PAIN MANAGEMENT AS THE STANDARD 3069 01:49:28,080 --> 01:49:29,240 OF WHAT PEOPLE THAT HAVE 3070 01:49:29,240 --> 01:49:31,240 RESOURCES GET AND OUR JOB IS TO 3071 01:49:31,240 --> 01:49:32,320 TRY TO CREATE THAT SYSTEM FOR 3072 01:49:32,320 --> 01:49:33,760 PEOPLE THAT DON'T HAVE A LOT OF 3073 01:49:33,760 --> 01:49:34,120 MONEY. 3074 01:49:34,120 --> 01:49:36,400 SO YOU KNOW A WE HAVE NOT ENOUGH 3075 01:49:36,400 --> 01:49:38,080 PSYCHOLOGISTS BUT WE HAVE 2 3076 01:49:38,080 --> 01:49:40,240 PSYCHOLOGISTS FOR A HALF DAY A 3077 01:49:40,240 --> 01:49:41,200 WEEK, THAT DON'T BILL BECAUSE 3078 01:49:41,200 --> 01:49:45,000 WHEN THEY HAVE TO BILL THEY 3079 01:49:45,000 --> 01:49:46,440 CAN'T SEE PEOPLE WITHOUT 3080 01:49:46,440 --> 01:49:47,000 SURPRISE BILLING, RIGHT? 3081 01:49:47,000 --> 01:49:49,440 AND YOU KNOW YOU HAVE SOMEONE 3082 01:49:49,440 --> 01:49:51,600 WHO GETS THE $500 BILL FOR THEIR 3083 01:49:51,600 --> 01:49:53,400 PSYCHOLOGY VISIT THEY TELL THEM 3084 01:49:53,400 --> 01:49:55,400 IS AN ESSENTIAL PART OF THEIR 3085 01:49:55,400 --> 01:49:57,760 CARE BECAUSE THEY HAVE PRIVATE 3086 01:49:57,760 --> 01:49:59,360 INSURANCE THAT CARVES OUT DUKE 3087 01:49:59,360 --> 01:50:03,840 PSYCHOLOGY, THEY DON'T COME 3088 01:50:03,840 --> 01:50:04,520 BACK. 3089 01:50:04,520 --> 01:50:04,720 RIGHT? 3090 01:50:04,720 --> 01:50:08,000 SO WE BOTH FRAME IT AS PART OF 3091 01:50:08,000 --> 01:50:09,280 THEIRENTIOUS SENTIAL PAIN 3092 01:50:09,280 --> 01:50:10,160 MANAGEMENT THAT BEHAVIORIAL 3093 01:50:10,160 --> 01:50:12,000 INTERVENTIONS ARE AN ESSENTIAL 3094 01:50:12,000 --> 01:50:13,160 COMPONENT OF PAIN MANAGEMENT AND 3095 01:50:13,160 --> 01:50:15,240 THEN WE TRY TO OVERCOME SOME OF 3096 01:50:15,240 --> 01:50:17,720 THE BARRIERS, WE CAN'T DO THE 3097 01:50:17,720 --> 01:50:18,440 TREATMENT INTENSITY WE WOULD 3098 01:50:18,440 --> 01:50:20,360 LIKE FOR PEOPLE THAT ARE BEING 3099 01:50:20,360 --> 01:50:21,240 SUPPORTED BY OUR STATE GRANT 3100 01:50:21,240 --> 01:50:22,960 BECAUSE WE DON'T HAVE THAT MUCH 3101 01:50:22,960 --> 01:50:25,160 PSYCHOLOGY SUPPORT AND NOW WE 3102 01:50:25,160 --> 01:50:28,440 HAVE 2 PSYCHOLOGISTS THAT 3103 01:50:28,440 --> 01:50:30,160 RECOGNIZE THAT OUR VERY 3104 01:50:30,160 --> 01:50:31,640 INTELLECTUAL WHITE GUY WASN'T A 3105 01:50:31,640 --> 01:50:36,840 GOOD FIT FOR EVERYONE, SO WE TRY 3106 01:50:36,840 --> 01:50:39,120 TO HAVE SOME CHOICES ABOUT WHO 3107 01:50:39,120 --> 01:50:41,000 PEOPLE CAN SEE, WE CAN'T--YOU 3108 01:50:41,000 --> 01:50:43,040 KNOW WE CAN'T MEET ALL THE 3109 01:50:43,040 --> 01:50:43,880 DIFFERENT IDENTITIES THAT 3110 01:50:43,880 --> 01:50:45,200 SOMETIMES PEOPLE NEED BUT WE TRY 3111 01:50:45,200 --> 01:50:46,840 TO AT LEAST ACKNOWLEDGE THAT AND 3112 01:50:46,840 --> 01:50:48,240 HAVE CHOICES FOR THEM. 3113 01:50:48,240 --> 01:50:48,520 >> YEAH. 3114 01:50:48,520 --> 01:50:51,800 >> I WANTED TO MAKE SURE THAT 3115 01:50:51,800 --> 01:50:52,040 WE-- 3116 01:50:52,040 --> 01:50:53,240 >> SORRY, 2 QUICK COMMENTS, JUST 3117 01:50:53,240 --> 01:50:55,160 WANTED TO COMMENT ON WHAT JULIE 3118 01:50:55,160 --> 01:50:57,160 WAS SAYING IN TERMS OF OFTEN 3119 01:50:57,160 --> 01:50:59,800 TIMES ROLLING WITH RESISTANCE, 3120 01:50:59,800 --> 01:51:00,880 IT'S A MOTIVATIONAL 3121 01:51:00,880 --> 01:51:01,520 INTERVIEWINGEC ITNIQUE BUT THERE 3122 01:51:01,520 --> 01:51:03,440 ARE A LOT OF TIMES PATIENTS ARE 3123 01:51:03,440 --> 01:51:05,160 WILLING WHETHER IT'S RATIONAL OR 3124 01:51:05,160 --> 01:51:06,600 NOT TO DO WHAT WE THINK IS BEST 3125 01:51:06,600 --> 01:51:08,360 FOR THEIR CARE AND OFTEN TIMES 3126 01:51:08,360 --> 01:51:09,400 THAT MIGHTIC MONTHS BEFORE THEY 3127 01:51:09,400 --> 01:51:11,640 SAY YES BUT IF WE FORCE 3128 01:51:11,640 --> 01:51:13,640 SOMETHING ON THEM, THAT 3129 01:51:13,640 --> 01:51:14,280 RELATIONSHIP IS BROKEN ALMOST 3130 01:51:14,280 --> 01:51:15,400 FOREVER AND IT'S HARD TO COME 3131 01:51:15,400 --> 01:51:16,000 BACK FROM THAT. 3132 01:51:16,000 --> 01:51:17,240 THE OTHER THING I WAS GOING TO 3133 01:51:17,240 --> 01:51:19,640 SAY IS THAT IN DOING QUALITATIVE 3134 01:51:19,640 --> 01:51:20,400 INTERVIEWS OUR PATIENTS HAVE 3135 01:51:20,400 --> 01:51:21,640 SAID THAT THAT KNOWLEDGE IS 3136 01:51:21,640 --> 01:51:23,160 ALMOST BETTER THAN THE IDENTITY 3137 01:51:23,160 --> 01:51:24,960 OF THE PERSON DOING THE THERAPY 3138 01:51:24,960 --> 01:51:26,600 OR THE COACHING, SO, THEY WANT 3139 01:51:26,600 --> 01:51:28,440 SOMEBODY WHO KNOWS ABOUT SICKLE 3140 01:51:28,440 --> 01:51:30,000 CELL AND KNOWS ABOUT MENTAL 3141 01:51:30,000 --> 01:51:31,440 HEALTH MORE SO THAN SOMEBODY WHO 3142 01:51:31,440 --> 01:51:34,000 ACTUALLY LOOKS LIKE THEM. 3143 01:51:34,000 --> 01:51:36,200 SO, YOU KNOW JUST TO POINT THAT 3144 01:51:36,200 --> 01:51:36,360 OUT. 3145 01:51:36,360 --> 01:51:37,360 >> THANK YOU. 3146 01:51:37,360 --> 01:51:41,840 I WANT TO MAKE SURE THAT WE ASK 3147 01:51:41,840 --> 01:51:44,880 NANCY'S QUESTION, HAS ACUE 3148 01:51:44,880 --> 01:51:47,240 PRESSURE BEEN CONSIDERED STUDIED 3149 01:51:47,240 --> 01:51:48,120 INSTEAD OF ACCUPUNCTURE FOR 3150 01:51:48,120 --> 01:51:59,080 PEOPLE WITH SICKLE CELL DISEASE? 3151 01:51:59,080 --> 01:51:59,440 >> SO, NO. 3152 01:51:59,440 --> 01:52:01,680 AS FAR AS I KNOW IT HAS NOT, BUT 3153 01:52:01,680 --> 01:52:03,360 AS YOU KNOW PEOPLE WHO HAVE 3154 01:52:03,360 --> 01:52:05,000 SICKLE CELL DISEASE HAVE SUCH A 3155 01:52:05,000 --> 01:52:07,320 HIGH BURDEN OF PAIN THAT IN MY 3156 01:52:07,320 --> 01:52:10,240 OPINION AND MY Ph.D. IS IN 3157 01:52:10,240 --> 01:52:11,240 ACCUPUNCTURE SCIENCE AND DM MY 3158 01:52:11,240 --> 01:52:13,000 OPINION, I DON'T THINK IT'S 3159 01:52:13,000 --> 01:52:13,840 STRONG ENOUGH. 3160 01:52:13,840 --> 01:52:15,640 I I'M NOT SAYING THAT ACUE 3161 01:52:15,640 --> 01:52:19,680 PRESSURE CAN'T BE USED IF 3162 01:52:19,680 --> 01:52:21,120 PATIENTS HAVE MUSK LO SKELETAL 3163 01:52:21,120 --> 01:52:22,640 PAIN AND WE COULD TEACH THEM HOW 3164 01:52:22,640 --> 01:52:25,480 TO DO IT, THAT WOULD BE 3165 01:52:25,480 --> 01:52:26,640 BENEFICIAL FOR SUPERFICIAL PAIN 3166 01:52:26,640 --> 01:52:27,840 BUT FOR DEEPER PANE WE HAVE TO 3167 01:52:27,840 --> 01:52:29,600 ACCESS WHAT ARE CALLED THE 3168 01:52:29,600 --> 01:52:31,440 CHANNELS IN THE MERIDIANS WHICH 3169 01:52:31,440 --> 01:52:32,880 ARE ACCESSED ON THE SURFACE OF 3170 01:52:32,880 --> 01:52:34,400 THE SKIN BUT ARE DEEPER ON THE 3171 01:52:34,400 --> 01:52:37,600 BODY AND THAT'S DONE WITH 3172 01:52:37,600 --> 01:52:41,240 ACCUPUNCTURE NEEDLES. 3173 01:52:41,240 --> 01:52:41,760 >> 2-MINUTE WARNING. 3174 01:52:41,760 --> 01:52:43,160 >> SO THANK YOU ALL VERY MUCH. 3175 01:52:43,160 --> 01:52:44,720 WE HAVE A COUPLE CLOSING 3176 01:52:44,720 --> 01:52:46,240 COMMENTS I WANT TO MAKE, AGAIN, 3177 01:52:46,240 --> 01:52:48,120 I THINK WE COULD ALL TALK ABOUT 3178 01:52:48,120 --> 01:52:49,840 THIS, RIGHT, ALL DAY LONG ABOUT 3179 01:52:49,840 --> 01:52:51,240 HOW IMPORTANT IT IS TO ENHANCE 3180 01:52:51,240 --> 01:52:55,240 THE WAY WE MANAGE AND TREAT PAIN 3181 01:52:55,240 --> 01:52:56,960 IN SICKLE CELL DISEASE HOW WE 3182 01:52:56,960 --> 01:52:57,680 PREVENT AND MANAGE CHRONIC PAIN 3183 01:52:57,680 --> 01:52:59,600 AND SORT OF WHERE DO WE GO FROM 3184 01:52:59,600 --> 01:53:01,440 LEER? 3185 01:53:01,440 --> 01:53:03,600 AND SO, WITH THAT I WANT TO 3186 01:53:03,600 --> 01:53:05,320 SHARE SOME SLIDES AND MOVE US 3187 01:53:05,320 --> 01:53:06,600 FORWARD A LITTLE BIT. 3188 01:53:06,600 --> 01:53:08,800 AGAIN, THANK YOU TO ALL OF OUR 3189 01:53:08,800 --> 01:53:11,800 AMAZING SPEAKERS. 3190 01:53:11,800 --> 01:53:13,880 SO,IME GOING TO TALK OVER THE 3191 01:53:13,880 --> 01:53:15,480 PERSPECTIVE OF THE NATIONAL 3192 01:53:15,480 --> 01:53:16,600 ALLIANCE OF SICKLE CELL CENTERS 3193 01:53:16,600 --> 01:53:24,600 ONCE I GET TO THE RIGHT 3194 01:53:24,600 --> 01:53:25,120 PRESENTATION MODE. 3195 01:53:25,120 --> 01:53:28,240 WHICH WE ALL KNOW TAKES A 3196 01:53:28,240 --> 01:53:29,200 SECONDS MORE IMPORTANTLY I WANT 3197 01:53:29,200 --> 01:53:30,360 TO RECOGNIZE A GENTLEMAN WHO HAS 3198 01:53:30,360 --> 01:53:32,480 BEEN A FOUNDER IN BRINGING TO 3199 01:53:32,480 --> 01:53:36,840 LIGHT THE AMOUNT OF PAIN THAT 3200 01:53:36,840 --> 01:53:38,200 HAS REAL REALLY AFFECTED 3201 01:53:38,200 --> 01:53:39,760 INDIVIDUALS LIVING WITH SICKLE 3202 01:53:39,760 --> 01:53:42,880 CELL DISEASE AND DR. BALLAS IS 3203 01:53:42,880 --> 01:53:44,840 SUCH AN AMAZING FIXTURE IN OUR 3204 01:53:44,840 --> 01:53:47,440 WORLD, HE'S BOARD CERTIFIED IN 3205 01:53:47,440 --> 01:53:48,800 INTERNAL MEDICINE, BLOOD 3206 01:53:48,800 --> 01:53:50,320 BANKING, PAIN MEDICINE AND PAIN 3207 01:53:50,320 --> 01:53:51,920 MANAGEMENT, I DON'T THINK YOU 3208 01:53:51,920 --> 01:53:53,560 WILL FIND ANYBODY ELSE LIKE 3209 01:53:53,560 --> 01:53:57,000 THAT, HOO IS EMERITUS PROFESSOR 3210 01:53:57,000 --> 01:53:59,080 OF POODIATRICS AT THOMAS 3211 01:53:59,080 --> 01:54:04,920 JEFFERSON, FORMER DIRECTOR OF 3212 01:54:04,920 --> 01:54:06,720 THE COMPREHENSIVE SICKLE CELL 3213 01:54:06,720 --> 01:54:09,360 DISEASE CENTER THERE, HE IS AT 3214 01:54:09,360 --> 01:54:10,840 END STAGE CANCERS AND THEY ASKED 3215 01:54:10,840 --> 01:54:12,960 US TO NOTIFY THE SICKLE CELL 3216 01:54:12,960 --> 01:54:14,440 COMMUNITY AND REQUEST PRAYERS 3217 01:54:14,440 --> 01:54:16,800 FOR A PEACEFUL END OF LIFE 3218 01:54:16,800 --> 01:54:18,440 TRANSITION FOR DR. BALLAS, EVEN 3219 01:54:18,440 --> 01:54:20,640 AT THE END OF HIS LIFE, HE 3220 01:54:20,640 --> 01:54:22,480 EXPRESSED HIS DEEP LOVE AND 3221 01:54:22,480 --> 01:54:23,320 ENDURING COMMITMENT TO 3222 01:54:23,320 --> 01:54:24,240 INDIVIDUALS LIVING WITH SICKLE 3223 01:54:24,240 --> 01:54:25,960 CELL DISEASE AND THEIR FAMILIES 3224 01:54:25,960 --> 01:54:27,440 AND THOSE HE WORKED WITH DURING 3225 01:54:27,440 --> 01:54:28,960 THE TIME OF HIS PRACTICE AND I 3226 01:54:28,960 --> 01:54:30,520 JUST WANT TO TAKE, YOU KNOW A 3227 01:54:30,520 --> 01:54:32,960 COUPLE OF SECONDS TO JOIN IN 3228 01:54:32,960 --> 01:54:35,080 REFLECTION THAT RELATE TO 3229 01:54:35,080 --> 01:54:36,680 SUPPORT DR. BALLAS AND HIS 3230 01:54:36,680 --> 01:54:40,640 FAMILY DURING THE SAN FRANCISCO 3231 01:54:40,640 --> 01:54:43,520 KRET TIME ANDA A TRUE TIME OF 3232 01:54:43,520 --> 01:54:45,520 FOR A DOCTOR WHO WAS COMMITTED 3233 01:54:45,520 --> 01:54:56,160 AND CARED FOR THE ENTIRE SICKLE 3234 01:54:56,160 --> 01:54:56,880 CELL COMMUNITY. 3235 01:54:56,880 --> 01:54:57,680 THANK YOU. 3236 01:54:57,680 --> 01:54:58,760 I KNOW HIS FAMILY APPRECIATES 3237 01:54:58,760 --> 01:54:59,800 THE LOVE AND THOUGHTS THAT WE 3238 01:54:59,800 --> 01:55:01,360 WILL SEND BACK TO THEM TO LET 3239 01:55:01,360 --> 01:55:03,640 THEM KNOW HOW MUCH HE WAS LOVED 3240 01:55:03,640 --> 01:55:05,840 WITHIN OUR COMMUNITY. 3241 01:55:05,840 --> 01:55:09,240 SORRY THESE ARE MY DISCLOSURES. 3242 01:55:09,240 --> 01:55:10,840 SO WHEN WE'RE TALKING ABOUT THE 3243 01:55:10,840 --> 01:55:12,640 NATIONAL ALLIANCE, WE ALL KNOW 3244 01:55:12,640 --> 01:55:14,360 AS WE'VE DISCUSSED THAT SICKLE 3245 01:55:14,360 --> 01:55:17,360 CELL IS A RARE DISEASE, IT 3246 01:55:17,360 --> 01:55:19,240 LIMITS LIFE EXPECTANCY DUE TO 3247 01:55:19,240 --> 01:55:20,840 CHRONIC COMPLICATIONS AND MANY 3248 01:55:20,840 --> 01:55:23,520 INDIVIDUALS AS WE SPENT THE LAST 3249 01:55:23,520 --> 01:55:25,080 COUPLE HOURS, THESE ONLY GET 3250 01:55:25,080 --> 01:55:26,240 MORE COMPLICATED AS PEOPLE GROW 3251 01:55:26,240 --> 01:55:27,920 OLDER AND LIFE GETS MORE 3252 01:55:27,920 --> 01:55:28,240 COMPLICATED. 3253 01:55:28,240 --> 01:55:30,160 SO WE NEED MORE HEALTHCARE 3254 01:55:30,160 --> 01:55:32,640 PROVIDERS WITH DISEASE SPECIFIC 3255 01:55:32,640 --> 01:55:35,720 KNOWLEDGE, AND AS REALLY JUST 3256 01:55:35,720 --> 01:55:41,880 DISCUSSED NOT JUST 3257 01:55:41,880 --> 01:55:42,520 PSYCHOLOGISTS, PSYCHIATRIST, 3258 01:55:42,520 --> 01:55:45,520 PEOPLE WHO CAN BE INVOLVED AND 3259 01:55:45,520 --> 01:55:46,200 TREATING COMPLICATIONS 3260 01:55:46,200 --> 01:55:47,720 THROUGHOUT THE LIFE SPAN. 3261 01:55:47,720 --> 01:55:49,440 WE ALSO KNOW IT'S ABOUT WHERE 3262 01:55:49,440 --> 01:55:52,640 YOU LIVE ON AN INDIVIDUAL LEVEL 3263 01:55:52,640 --> 01:55:53,560 AND HEALTHCARE ISN'T ALWAYS 3264 01:55:53,560 --> 01:55:55,320 STATE BASED BUT SOMETIMES COUNTY 3265 01:55:55,320 --> 01:55:57,040 BASED, YOU CAN HAVE INSURANCE 3266 01:55:57,040 --> 01:55:58,880 BUT NOT BE DIRECTED TO A 3267 01:55:58,880 --> 01:56:00,000 KNOWLEDGEABLE SICKLE CELL CENTER 3268 01:56:00,000 --> 01:56:02,040 OR PROVIDER AND WE @ ALLIANCE 3269 01:56:02,040 --> 01:56:03,440 ARE WORKING TO SHIFT THAT 3270 01:56:03,440 --> 01:56:04,520 PROGRAMMATIC CAMPUS ON WOULD 3271 01:56:04,520 --> 01:56:06,840 ABOUTING A SYSTEM OF CARE TO 3272 01:56:06,840 --> 01:56:07,800 ENHANCE ACCESS AND COORDINATION 3273 01:56:07,800 --> 01:56:11,640 THROUGHOUT THE LIFE SPAN. 3274 01:56:11,640 --> 01:56:13,920 AND TRULY INSURING THAT ALL WHO 3275 01:56:13,920 --> 01:56:15,120 LIVE WITH SICKLE CELL DISEASE, 3276 01:56:15,120 --> 01:56:18,040 AND HAVE ACCESS TO A SPECIALIST 3277 01:56:18,040 --> 01:56:18,640 AND APPROPRIATE COMPREHENSIVE 3278 01:56:18,640 --> 01:56:19,440 CARE AND THIS MEANS WOO VERMEN 3279 01:56:19,440 --> 01:56:20,960 INFECTED TO CHANGE THE SYSTEM OF 3280 01:56:20,960 --> 01:56:22,480 CARE FOR MORE PEOPLE IN MORE 3281 01:56:22,480 --> 01:56:25,200 AREAS USING HUB AND SPOKE, USING 3282 01:56:25,200 --> 01:56:25,760 TELEMEDICINE. 3283 01:56:25,760 --> 01:56:28,480 SO THE ALLIANCE WAS FOUNDED IN 3284 01:56:28,480 --> 01:56:30,160 2020 TO REALLY COME TOGETHER AS 3285 01:56:30,160 --> 01:56:32,800 A COORDINATED NETWORK TO 3286 01:56:32,800 --> 01:56:34,520 STANDARDIZE PRACTICE TO SAY THAT 3287 01:56:34,520 --> 01:56:35,800 EVERY INDIVIDUAL SHOULD EXPECT 3288 01:56:35,800 --> 01:56:39,320 TO RECEIVE THE SAME EQUITABLE 3289 01:56:39,320 --> 01:56:40,920 TREATMENT RELESS OF WHERE THEY 3290 01:56:40,920 --> 01:56:47,120 LIVE, WE ARE USING GRNDAD FOR 3291 01:56:47,120 --> 01:56:49,040 GLOBIN RESEARCH NETWORK FOR DATA 3292 01:56:49,040 --> 01:56:51,080 AND DISCOVERY AND WE'RE USING 3293 01:56:51,080 --> 01:56:53,440 ASH TO PROVIDE NECESSARY EXPERT 3294 01:56:53,440 --> 01:56:56,200 CARE TO ALL AGES LIVING WITH 3295 01:56:56,200 --> 01:56:57,040 SICKLE CELL DISEASE. 3296 01:56:57,040 --> 01:56:58,800 WE ARE RECOGNIZING SICK CELL 3297 01:56:58,800 --> 01:56:59,400 CELL THAT OFFER 3298 01:56:59,400 --> 01:57:01,040 MULTIDISCIPLINEAR COMPETENT CARE 3299 01:57:01,040 --> 01:57:01,640 ANDEE SIGNIFICANTLY INCREASED 3300 01:57:01,640 --> 01:57:03,000 THE NUMBER OF THOSE CENTERS AND 3301 01:57:03,000 --> 01:57:05,680 WE NOW HAVE DEFINITIONS OF BOTH 3302 01:57:05,680 --> 01:57:09,120 PEDIATRIC AND ADULT SICKLE CELL 3303 01:57:09,120 --> 01:57:09,760 CENTER BECAUSE BEFORE 2020 WE 3304 01:57:09,760 --> 01:57:11,040 DIDN'T KNOW WHAT THE SICKLE CELL 3305 01:57:11,040 --> 01:57:12,240 WAS, WE SAID THIS IS WHAT WE 3306 01:57:12,240 --> 01:57:13,880 THINK IT IS SO NOW WE HAVE 3307 01:57:13,880 --> 01:57:15,200 DEFINITIONS, AND NOW WE'RE 3308 01:57:15,200 --> 01:57:18,840 WORKING ON REICHING CONSENSUS ON 3309 01:57:18,840 --> 01:57:20,240 RECOMMEND MENDATIONS FOR WHICH 3310 01:57:20,240 --> 01:57:22,080 THERE ISN'T TRUE DATA SO WE CAN 3311 01:57:22,080 --> 01:57:24,240 MAKE THAT TRUE DATA AND DO 3312 01:57:24,240 --> 01:57:24,720 QUALITY IMPROVEMENT. 3313 01:57:24,720 --> 01:57:27,400 THIS IS A MAP OF OUR CURRENTLY 3314 01:57:27,400 --> 01:57:28,240 RECOGNIZED SICKLE CELL CENTERS 3315 01:57:28,240 --> 01:57:29,800 AND THIS IS REALLY AMAZING TO 3316 01:57:29,800 --> 01:57:31,960 ME, JUST HOW MUCH WE'VE GROWN, 3317 01:57:31,960 --> 01:57:34,840 WE OBVIOUSLY STILL HAVE A LOT OF 3318 01:57:34,840 --> 01:57:36,480 WORK TO DO, AND THERE ARE 3319 01:57:36,480 --> 01:57:38,440 SEVERAL CENTERS WHO ARE STILL 3320 01:57:38,440 --> 01:57:42,160 BUILDING AND ENGAGING AND I 3321 01:57:42,160 --> 01:57:43,880 FOLLOW YOU SINCE THIS SLIDE WAS 3322 01:57:43,880 --> 01:57:46,560 MADE A WEEK AND HALF AGO, THERE 3323 01:57:46,560 --> 01:57:48,480 ARE MORE SHOULD HAVE IT HAVE 3324 01:57:48,480 --> 01:57:51,080 BEEN RECOGNIZED THEY'RE NOT ON 3325 01:57:51,080 --> 01:57:52,280 THE MAP YET THESE ARE ALSO 3326 01:57:52,280 --> 01:57:54,120 CENTERS THAT ARE DEVELOPING SOON 3327 01:57:54,120 --> 01:57:57,680 TO BECOME FULL CENTERS AND 3328 01:57:57,680 --> 01:57:58,680 THERE'S A LOT MORE INFORMATION 3329 01:57:58,680 --> 01:58:02,240 TO COME ABOUT THAT, THIS IS AN 3330 01:58:02,240 --> 01:58:03,960 OLD ARTICLE NOW THATTA BEEN 3331 01:58:03,960 --> 01:58:05,240 REFERENCED MANY TIMES ABOUT WHAT 3332 01:58:05,240 --> 01:58:07,120 IS AN ADULT SICKLE CELL HAVE RHA 3333 01:58:07,120 --> 01:58:08,240 IS REQUIRED AND WHAT IS OPTICAL 3334 01:58:08,240 --> 01:58:10,160 IMAGES ARE MALAND WHAT IS 3335 01:58:10,160 --> 01:58:10,400 ADJUNCT. 3336 01:58:10,400 --> 01:58:11,800 AND THE REASON WE HAVE THIS AND 3337 01:58:11,800 --> 01:58:13,840 THAT IT'S SO SPRNT THAT IF WE 3338 01:58:13,840 --> 01:58:14,640 DON'T START SAYING THE SAME 3339 01:58:14,640 --> 01:58:15,920 THING ABOUT WHAT WE HAVE TO 3340 01:58:15,920 --> 01:58:17,360 HAVE, WE WILL NEVER GET IT AND 3341 01:58:17,360 --> 01:58:18,760 WE NEED TO MAKE SURE THAT THE 3342 01:58:18,760 --> 01:58:20,600 PAYORS THAT WE LIVE IN 3343 01:58:20,600 --> 01:58:22,240 UNDERSTAND ALL OF OUR 3344 01:58:22,240 --> 01:58:23,880 INDIVIDUALS LIVING WITHIC ISLE 3345 01:58:23,880 --> 01:58:26,200 CELL DISEASE DESERVE THIS AS AN 3346 01:58:26,200 --> 01:58:26,560 ADULT. 3347 01:58:26,560 --> 01:58:28,640 I ALWAYS SAY THAT YOU KNOW IF 3348 01:58:28,640 --> 01:58:30,240 YOU HAVE A BREAST CANCER PATIENT 3349 01:58:30,240 --> 01:58:32,040 LIVING IN RURAL ALABAMA YOU 3350 01:58:32,040 --> 01:58:33,640 DON'T ASK THEIR PRIMARY CARE 3351 01:58:33,640 --> 01:58:35,160 DOCTOR TO DREET THEIR BREAST 3352 01:58:35,160 --> 01:58:37,320 CANCER WE SHOULDN'T ASK THEIR 3353 01:58:37,320 --> 01:58:38,480 PRIMARY CARE DOCTOR TO TREAT 3354 01:58:38,480 --> 01:58:39,440 THEIR SICKLE CELL AS WELL, WE 3355 01:58:39,440 --> 01:58:40,760 SHOULD WORK WITH THE PRIMARY 3356 01:58:40,760 --> 01:58:42,160 CARE DOCTOR TO MAKE SURE THEY 3357 01:58:42,160 --> 01:58:44,720 GET EVERYTHING THEY NEED IN A 3358 01:58:44,720 --> 01:58:45,840 COMPREHENSIVE SETTING AND IT HAS 3359 01:58:45,840 --> 01:58:48,120 TO BE A THOUGHTFUL TEAM BASED 3360 01:58:48,120 --> 01:58:50,000 APPROACH, IT HAS TO BE CONSIST 3361 01:58:50,000 --> 01:58:51,360 AND THEN THE COORDINATED 3362 01:58:51,360 --> 01:58:53,120 THROUGHOUT THE MEDICAL 3363 01:58:53,120 --> 01:58:59,240 ENVIRONMENT AND IT HAS TO HAVE 3364 01:58:59,240 --> 01:59:00,640 POSITIVE OUTCOMES FOR PEOPLE 3365 01:59:00,640 --> 01:59:04,960 WITH SICKLE CELL DISEASE. 3366 01:59:04,960 --> 01:59:07,480 WE NOW HAVE ELMETROPOLITANS THAT 3367 01:59:07,480 --> 01:59:09,080 DEFINE A PEDIATRIC SICKLE CELL 3368 01:59:09,080 --> 01:59:10,680 CENTER AS WELL THORS FIND THE 3369 01:59:10,680 --> 01:59:12,480 SAME THINGS THAT WE'VE DONE IN 3370 01:59:12,480 --> 01:59:14,440 THE ADULTS SICKLE CELL CENTER, 3371 01:59:14,440 --> 01:59:15,600 WE'VE DONE AN IDENTIFY PROCESS 3372 01:59:15,600 --> 01:59:16,760 WITH THE COLLEAGUES ACROSS THE 3373 01:59:16,760 --> 01:59:17,640 COUNTRY AND ELSEWHERE, I DON'T 3374 01:59:17,640 --> 01:59:22,160 HAVE TIME TO TELL YOU ALL ABOUT 3375 01:59:22,160 --> 01:59:25,120 THAT DE PH I PROIEDURE TODAY BUT 3376 01:59:25,120 --> 01:59:26,240 THESE WERE THE ELEMENTS THAT 3377 01:59:26,240 --> 01:59:28,440 WERE REQUIRED TO BE A CENTER FOR 3378 01:59:28,440 --> 01:59:29,840 CHILDREN LIVING WITHIC ISLE CELL 3379 01:59:29,840 --> 01:59:31,160 DISEASE, THIS PAPER WILL BE 3380 01:59:31,160 --> 01:59:34,040 PUBLISHED VERY SOON AND HAS ALL 3381 01:59:34,040 --> 01:59:35,560 THE ADDITIONAL INFORMATION, IT'S 3382 01:59:35,560 --> 01:59:37,440 BEEN SUBMITTED AND IS IN PRESS 3383 01:59:37,440 --> 01:59:39,240 FOR PUBLICATION BUT AGAIN 3384 01:59:39,240 --> 01:59:40,240 RECOGNIZING WE'VE KNOWN ABOUT 3385 01:59:40,240 --> 01:59:42,440 THE TREATMENT OF SICKLE CELL AND 3386 01:59:42,440 --> 01:59:44,000 PEDIATRICS FOR A LONGER TIME SO 3387 01:59:44,000 --> 01:59:44,840 THERE'S MORE ELEMENTS THAT ARE 3388 01:59:44,840 --> 01:59:47,240 REQUIRED TO BE A PEDIATRIC 3389 01:59:47,240 --> 01:59:48,440 SICKLE CELL CENTER, OVERALL 3390 01:59:48,440 --> 01:59:50,040 WHETHER YOU'RE A CHILD OR ADULT, 3391 01:59:50,040 --> 01:59:52,400 YOU HAVE TO HAVE ACCESS TO 3392 01:59:52,400 --> 01:59:52,960 DISEASE MODIFYING THERAPY. 3393 01:59:52,960 --> 01:59:54,440 YOU HAVE TO HAVE DISEASE FOR 3394 01:59:54,440 --> 01:59:55,320 SICKLE CELL PRACTICE RESEARCH 3395 01:59:55,320 --> 01:59:57,800 NIEHS YOUR CENTER, THAT ENCLOUDS 3396 01:59:57,800 --> 02:00:00,040 IRON OVERLOAD TREATMENT AS WELL 3397 02:00:00,040 --> 02:00:02,720 AS APPROPRIATE BLOOD TRANSFUSION 3398 02:00:02,720 --> 02:00:03,720 MANAGEMENT, PAIN MANAGEMENT, 3399 02:00:03,720 --> 02:00:05,640 PLANNING AND NOT NEGLECTING THE 3400 02:00:05,640 --> 02:00:06,680 MENTAL HEALTH PLANNING AS WE 3401 02:00:06,680 --> 02:00:07,920 TALKED ABOUT TODAY, THE 3402 02:00:07,920 --> 02:00:09,120 IMPORTANCE OF MENTAL EXPHELGT 3403 02:00:09,120 --> 02:00:10,160 SICKLE CELL DISEASE CANNOT BE 3404 02:00:10,160 --> 02:00:12,240 SAID ENOUGH AND WE NEED TO KNOW 3405 02:00:12,240 --> 02:00:13,480 SAYING THAT OUTLOUD AND SHOUTING 3406 02:00:13,480 --> 02:00:15,840 IT FROM THE ROOF TOPPINGS, 3407 02:00:15,840 --> 02:00:17,120 INDIVIDUALS NEED BOTH 3408 02:00:17,120 --> 02:00:17,880 METROPOLITANNAL HEALTH AND 3409 02:00:17,880 --> 02:00:19,440 PHYSICAL HEALTH AND MENTAL 3410 02:00:19,440 --> 02:00:23,200 HEALTH IS PHYSICAL HEALTH. 3411 02:00:23,200 --> 02:00:24,640 SEE WHAT ABOUT CENTERS THAT 3412 02:00:24,640 --> 02:00:27,040 DON'T MEDE THESE DEFINITIONS, 3413 02:00:27,040 --> 02:00:28,040 WELL THERE'S ASSOCIATE CENTERS 3414 02:00:28,040 --> 02:00:29,080 WHICH I MENTIONED HAVE 3415 02:00:29,080 --> 02:00:31,360 COMPONENTS OF A SICKLE CELL 3416 02:00:31,360 --> 02:00:33,840 CENTER, THEY'RE IN DEVELOPMENT. 3417 02:00:33,840 --> 02:00:35,680 DATA COLLECTION CAN BE ONGOING, 3418 02:00:35,680 --> 02:00:43,880 AND THEY THEY HA GROW AS GROWTH 3419 02:00:43,880 --> 02:00:45,000 AS LOWS. 3420 02:00:45,000 --> 02:00:47,280 THESE ARE HUB AND SPOKE MODELS, 3421 02:00:47,280 --> 02:00:49,080 SO THEY CAN PROVIDE CARE AS AN 3422 02:00:49,080 --> 02:00:50,160 AFFILIATE CENTER, THEY CAN 3423 02:00:50,160 --> 02:00:51,920 RELYOT CENTER FOR SOME OF THE 3424 02:00:51,920 --> 02:00:53,320 COMPONENTS FOR EXAMPLE, A LOT OF 3425 02:00:53,320 --> 02:00:54,640 PLACES IN RURAL ALABAMA DON'T 3426 02:00:54,640 --> 02:00:56,280 HAVE THE CAPACITY TO DO AN MRI 3427 02:00:56,280 --> 02:00:58,560 OF THE LIVER TO ASSESS FOR IRON 3428 02:00:58,560 --> 02:00:59,520 OVERLOAD BUT THEY CAN CERTAINLY 3429 02:00:59,520 --> 02:01:01,360 GET A LOT OF THEIR TREATMENT IN 3430 02:01:01,360 --> 02:01:03,440 THEIR AFFILIATE CENTER AND THEN 3431 02:01:03,440 --> 02:01:05,720 COME ANNUALLY OR COME EVERY YEAR 3432 02:01:05,720 --> 02:01:07,800 AS NEEDED AND CAN WE WORK WITH 3433 02:01:07,800 --> 02:01:09,240 OUR COMMUNITY ON ONCOLOGY 3434 02:01:09,240 --> 02:01:11,200 PROGRAMS AT CENTERS AND HOW DO 3435 02:01:11,200 --> 02:01:12,720 WE GET BUY-IN FROM THEM BECAUSE 3436 02:01:12,720 --> 02:01:14,880 THAT WOULD INCREASE ACCESS TO 3437 02:01:14,880 --> 02:01:16,640 IRB, TOO, SO THE BOTTOM LINE IS 3438 02:01:16,640 --> 02:01:19,040 WE AT SICKLE CELL DISEASE 3439 02:01:19,040 --> 02:01:20,880 CENTERS MUST PROVIDE 3440 02:01:20,880 --> 02:01:22,120 COMPASSIONATE COMPREHENSIVE 3441 02:01:22,120 --> 02:01:23,920 CARE, TO BE COORDINATED HAVE TO 3442 02:01:23,920 --> 02:01:24,840 INSURE CONTINUOUS AND 3443 02:01:24,840 --> 02:01:26,400 PERSONALIZED CARE TO THAT 3444 02:01:26,400 --> 02:01:27,840 ATTENDS TO BOTH THE PHYSICAL AND 3445 02:01:27,840 --> 02:01:29,120 EMOTIONAL WELL BEING OF THE 3446 02:01:29,120 --> 02:01:29,440 INDIVIDUAL. 3447 02:01:29,440 --> 02:01:32,640 IT HAS TO BE EQUITABLE, THE TIME 3448 02:01:32,640 --> 02:01:33,640 FOR SAYING THAT INDIVIDUALS LIVE 3449 02:01:33,640 --> 02:01:34,920 IN THE SICKLE CELL DISEASE DO 3450 02:01:34,920 --> 02:01:36,440 NOT DESERVE A SICKLE CELL 3451 02:01:36,440 --> 02:01:37,640 SPECIALIST IS GONE, WE HAVE TO 3452 02:01:37,640 --> 02:01:38,680 ALL WORK TOGETHER TO SAY, WE 3453 02:01:38,680 --> 02:01:41,040 HAVE TO CREATE MORE SICKLE CELL 3454 02:01:41,040 --> 02:01:42,320 SPECIALISTS AND IT DOESN'T JUST 3455 02:01:42,320 --> 02:01:45,320 HAVE TO BE MDs, IT CAN BE OUR 3456 02:01:45,320 --> 02:01:46,800 APPs WHO ARE AMAZING TEAM 3457 02:01:46,800 --> 02:01:49,400 MEMBERS AS WELL AS PSYCHOLOGISTS 3458 02:01:49,400 --> 02:01:50,920 AND PSYCHIATRIST TRYSTS AND 3459 02:01:50,920 --> 02:01:51,840 COMMUNITY HEALTH WORKERS, 3460 02:01:51,840 --> 02:01:53,120 THERE'S A LOT OF WAYS TO 3461 02:01:53,120 --> 02:01:54,040 INCREASE ACCESS TO CARE, THIS 3462 02:01:54,040 --> 02:01:56,440 HAS TO BE A MORE COST EFFECTIVE 3463 02:01:56,440 --> 02:01:59,840 WAY TO CARE FOR THIS VULNERABLE 3464 02:01:59,840 --> 02:02:00,240 PATIENT POPULATION. 3465 02:02:00,240 --> 02:02:01,440 SO, I DIDN'T HAVE ANYTHING ELSE 3466 02:02:01,440 --> 02:02:04,200 TO SAY, I JUST WANT TO THANK THE 3467 02:02:04,200 --> 02:02:06,880 SPEAKERS AGAIN FOR SHARING ALL 3468 02:02:06,880 --> 02:02:08,560 OF THIS,A MAZING DATA TODAY, FOR 3469 02:02:08,560 --> 02:02:09,800 THOSE WHO ARE INTERESTED IN 3470 02:02:09,800 --> 02:02:11,040 LEARNING MORE ABOUT THE 3471 02:02:11,040 --> 02:02:14,800 ALLIANCE, GO TO SICKLE CELL 3472 02:02:14,800 --> 02:02:16,200 CENTERS, WWW .SICKLE CELL 3473 02:02:16,200 --> 02:02:17,680 CENTERS.ORGAND WE ARE GOING TO 3474 02:02:17,680 --> 02:02:19,240 MAKE THIS A REALITY FOR PEOPLE 3475 02:02:19,240 --> 02:02:20,480 LIVING WITH SICKLE CELL DISEASE 3476 02:02:20,480 --> 02:02:22,400 IN THE UNITED STATES EVERYWHERE. 3477 02:02:22,400 --> 02:02:24,000 SO WITH THAT, AGAIN, ON BEHALF 3478 02:02:24,000 --> 02:02:26,320 OF MYSELF, FROM THE NATIONAL 3479 02:02:26,320 --> 02:02:28,840 ALLIANCE OF SICKLE CELL CENTERS 3480 02:02:28,840 --> 02:02:32,160 AND SCAFIN OUR OUR SICKLE CELL 3481 02:02:32,160 --> 02:02:33,720 PROVIDER NETWORK, ALL OF OUR 3482 02:02:33,720 --> 02:02:34,760 SPEAKERS TODAY, THANK YOU SO 3483 02:02:34,760 --> 02:02:36,040 MUCH FOR YOUR ATTENDANCE AND WE 3484 02:02:36,040 --> 02:02:39,520 WILL TURN IT BACK OVER TO THE 3485 02:02:39,520 --> 02:02:39,800 NHLBI. 3486 02:02:39,800 --> 02:02:42,680 >> THANK YOU SO MUCH, WOW. 3487 02:02:42,680 --> 02:02:46,840 WHAT A SESSION. 3488 02:02:46,840 --> 02:02:47,400 EXCELLENT. 3489 02:02:47,400 --> 02:02:49,400 THANKS JULIE AND JJ AND 3490 02:02:49,400 --> 02:02:50,800 EVERYBODY ELSE ON THE PANEL. 3491 02:02:50,800 --> 02:02:54,920 SO I THINK I UNDERSTAND 3492 02:02:54,920 --> 02:02:56,000 DR. STROUSE, IS THAT HE WILL 3493 02:02:56,000 --> 02:03:00,640 INTRODUCE THE NEXT 4 PEEKERS, 3494 02:03:00,640 --> 02:03:02,080 ALSO, SO, IF HE'S STILL UP FOR 3495 02:03:02,080 --> 02:03:19,480 IT, PLEASE LET ME KNOW. 3496 02:03:19,480 --> 02:03:21,000 >> I AM, I AM NOT ALLOWED TO 3497 02:03:21,000 --> 02:03:22,080 PULL UP MY SLIDES? 3498 02:03:22,080 --> 02:03:25,080 I CAN DO IT IF--OH, I GUESS HAVE 3499 02:03:25,080 --> 02:03:39,200 YOU IT THERE. 3500 02:03:39,200 --> 02:03:39,520 GREAT. 3501 02:03:39,520 --> 02:03:40,720 >> IT IMIFS ME GREAT PLEASURE TO 3502 02:03:40,720 --> 02:03:50,520 INTRODUCE OUR NEXT SPEAKER, 3503 02:03:50,520 --> 02:03:51,320 DR. MODUPE IDOWU, DISCUSSING 3504 02:03:51,320 --> 02:03:54,120 MODIFYING SICKLE CELL THERAPIES 3505 02:03:54,120 --> 02:03:54,840 BASED ON SYMPTOMATOLOGY. 3506 02:03:54,840 --> 02:03:56,680 WITH THAT, LET'S HAVE YOU START 3507 02:03:56,680 --> 02:03:57,880 SO WE STAY ON TIME. 3508 02:03:57,880 --> 02:03:59,920 >> THANK YOU VERY MUCH FOR THE 3509 02:03:59,920 --> 02:04:02,440 INTRODUCTION, I WOULD LIKE TO 3510 02:04:02,440 --> 02:04:02,960 SHARE MY SLIDE. 3511 02:04:02,960 --> 02:04:09,400 IS SOMEONE GOING TO HELP SHARE 3512 02:04:09,400 --> 02:04:10,120 MY SLIDE. 3513 02:04:10,120 --> 02:04:11,640 >> I REALLY THANK THE ORGANIZER 3514 02:04:11,640 --> 02:04:14,280 OF THIS CONFERENCE FOR THE 3515 02:04:14,280 --> 02:04:15,240 INVITATION TO PRESENT TODAY. 3516 02:04:15,240 --> 02:04:23,280 YOU CAN GO ON TO THE NEXT SLIDE. 3517 02:04:23,280 --> 02:04:33,640 THESE ARE MY DISCLOSURES. 3518 02:04:33,640 --> 02:04:37,440 HEMOGLOBIN S IS IN THE SIXTH 3519 02:04:37,440 --> 02:04:41,320 QUADRANT OF THE BETA DPLOABIN 3520 02:04:41,320 --> 02:04:43,960 GENE REPLACES [INDISCERNIBLE] 3521 02:04:43,960 --> 02:04:46,880 RESIDUE BY UNVEILING RESIDUE, 3522 02:04:46,880 --> 02:04:50,520 FOR DEOX GENERATEDDATION, 3523 02:04:50,520 --> 02:04:51,600 [INDISCERNIBLE] FORM CAUSING 3524 02:04:51,600 --> 02:04:52,960 CELL PSYCHE LINING AND DAMAGE TO 3525 02:04:52,960 --> 02:04:54,640 THE MEMBRANE. 3526 02:04:54,640 --> 02:04:55,800 SOME CELLS [INDISCERNIBLE] 3527 02:04:55,800 --> 02:04:57,440 LEADING TO OCLOWGZ, THE 3528 02:04:57,440 --> 02:04:59,040 PATHOPHYSIOLOGY OF SICKLE CELL 3529 02:04:59,040 --> 02:05:02,800 DISEASE ASK COMPLEX AND IT 3530 02:05:02,800 --> 02:05:05,400 INVOLVES EREGHTROCYTE PSYCHE 3531 02:05:05,400 --> 02:05:13,440 LINE, [INDISCERNIBLE] EVENTS 3532 02:05:13,440 --> 02:05:17,760 EVENTS 3533 02:05:17,760 --> 02:05:20,880 HEMOLSIS, AND YOU CAN GO TO THE 3534 02:05:20,880 --> 02:05:22,440 NEXT SLIDE. 3535 02:05:22,440 --> 02:05:23,840 IT'S MANY COMPLIKAIGHTZS OF 3536 02:05:23,840 --> 02:05:25,240 SICKLE CELL DISEASE CAN BE 3537 02:05:25,240 --> 02:05:27,240 DIVIDE INTO 2 OVERLAPPING 3538 02:05:27,240 --> 02:05:33,640 SUBTYPES, EACH DRIVEN BY 3539 02:05:33,640 --> 02:05:37,960 DISTINCT MECHANISMS, LEG 3540 02:05:37,960 --> 02:05:39,440 ULCERATION, SUDDEN DEATH, STROKE 3541 02:05:39,440 --> 02:05:41,960 ARE ASSOCIATED WITH LOW STEADY 3542 02:05:41,960 --> 02:05:43,720 STATE HEMOGLOBIN LEVELS AND AN 3543 02:05:43,720 --> 02:05:50,520 INCREASED RATE OF INTRA RASCULAR 3544 02:05:50,520 --> 02:05:53,240 HEMOLYSIS, THAT'S SHOWN ON THE 3545 02:05:53,240 --> 02:05:57,640 LEFT HERE. 3546 02:05:57,640 --> 02:05:59,440 THIS VASE O-O'CLUESIVE RESULT 3547 02:05:59,440 --> 02:06:00,920 FROM [INDISCERNIBLE]. 3548 02:06:00,920 --> 02:06:02,640 THIS IS MEDICATED BY NITRIC 3549 02:06:02,640 --> 02:06:05,320 OXIDE AS CAN YOU SEE IN THE 3550 02:06:05,320 --> 02:06:11,040 FIGURE THERE, BY FREE PLASMA 3551 02:06:11,040 --> 02:06:13,680 HEMOGLOBIN AND REACTIVE SPECIES 3552 02:06:13,680 --> 02:06:17,960 AS WELL LOS ANGELES METABOLISM 3553 02:06:17,960 --> 02:06:33,120 BY PLASMA AGENICS, THIS PROCESS 3554 02:06:33,120 --> 02:06:36,240 OF HEME OLSIS, THE,A CUTE 3555 02:06:36,240 --> 02:06:39,640 SYNDROME, IF VASCULAR NECKROSIS 3556 02:06:39,640 --> 02:06:40,520 OF BONES AND VASCULAR RETINAL 3557 02:06:40,520 --> 02:06:42,800 LOCATION TIN OPEN MEETINGATHY, 3558 02:06:42,800 --> 02:06:50,960 AND STEADY STATE LEUKOCYTE AND 3559 02:06:50,960 --> 02:06:53,040 HIGH HEMOGLOB LYNN RESULTS. 3560 02:06:53,040 --> 02:06:54,920 THIS IS POST CAPILLARY VENUES BY 3561 02:06:54,920 --> 02:07:02,200 EREGHT 3562 02:07:02,200 --> 02:07:06,440 EREEGHT ROUGH ATOM VIETS AS 3563 02:07:06,440 --> 02:07:08,080 SHOWN HERE AND YOU CAN GO ON TO 3564 02:07:08,080 --> 02:07:10,160 THE NEXT SLIDE. 3565 02:07:10,160 --> 02:07:12,160 YOU CAN SEE ON THIS SLIDE, THE 3566 02:07:12,160 --> 02:07:15,160 ACUTE AND CHRONIC COMPLICATIONS 3567 02:07:15,160 --> 02:07:16,840 OF SICKLE CELL. 3568 02:07:16,840 --> 02:07:17,720 THE ACUTE COMPLICATIONS ARE 3569 02:07:17,720 --> 02:07:20,040 THOSE THAT WOULD BRING AN 3570 02:07:20,040 --> 02:07:23,040 INDIVIDUAL TO IMMEDIATE MEDICAL 3571 02:07:23,040 --> 02:07:24,880 ATTENTION AND I WILL TALK ABOUT 3572 02:07:24,880 --> 02:07:27,680 UP TO HOW WE CAN USE THE NEW 3573 02:07:27,680 --> 02:07:29,000 THERAPEUTICS WITH THE OLDER 1S 3574 02:07:29,000 --> 02:07:32,080 TO MANAGE SOME OF THIS 3575 02:07:32,080 --> 02:07:33,400 COMPLICATIONS AS OUTLINES HERE. 3576 02:07:33,400 --> 02:07:37,800 YOU CAN GO ON TO THE NEXT. 3577 02:07:37,800 --> 02:07:40,960 ON THIS PICTURE HERE, YOU CAN 3578 02:07:40,960 --> 02:07:42,680 SEE THE AGE DISTRIBUTION OF 3579 02:07:42,680 --> 02:07:45,920 CHRONIC SICKLE CELL DISEASES 3580 02:07:45,920 --> 02:07:47,440 COMPLICATIONS, THOSE THAT ARE 3581 02:07:47,440 --> 02:07:50,400 YOUNGER THAN AGE 6, YOU CAN SEE 3582 02:07:50,400 --> 02:07:54,800 THAT THEY'RE MOSTLY AFFECTED BY 3583 02:07:54,800 --> 02:07:57,120 ACUTE SYNDROME AND THE OLDER 3584 02:07:57,120 --> 02:08:00,440 THEY GET, SUCH COMPLICATIONS AS 3585 02:08:00,440 --> 02:08:03,440 KIDNEY DISEASE, AVASCULAR 3586 02:08:03,440 --> 02:08:03,880 NECROSIS, INCREASE. 3587 02:08:03,880 --> 02:08:15,360 GO ON TO THE NEXT, PLEASE. 3588 02:08:15,360 --> 02:08:18,440 THESE ARE THE MULTIPLE BIOLOGIC 3589 02:08:18,440 --> 02:08:19,440 TARGETS IN SICKLE CELL DISEASE 3590 02:08:19,440 --> 02:08:20,760 AND YOU CAN SEE THAT THE 1S THAT 3591 02:08:20,760 --> 02:08:23,640 ARE AIMED AT THE FETAL STEM 3592 02:08:23,640 --> 02:08:24,520 CELLS AND GENE THERAPY. 3593 02:08:24,520 --> 02:08:27,480 AND AS YOU GO ON, YOU CAN SEE 3594 02:08:27,480 --> 02:08:28,600 THOSE THAT I HIGHLIGHTED IN 3595 02:08:28,600 --> 02:08:32,560 BLUE, THOSE ARE THE 1S THAT HAVE 3596 02:08:32,560 --> 02:08:34,640 BEEN APPROVED, OWEVER, THERE ARE 3597 02:08:34,640 --> 02:08:36,720 SEVERAL THERAPEUTICS THAT ARE 3598 02:08:36,720 --> 02:08:37,920 QUITE PROMISING THAT ARE IN 3599 02:08:37,920 --> 02:08:39,240 CLINICAL TRIALS AND I WILL 3600 02:08:39,240 --> 02:08:40,480 MENTION A COUPLE OF THEM. 3601 02:08:40,480 --> 02:08:47,640 YOU CAN GO ON TO THE NEXT SLIDE. 3602 02:08:47,640 --> 02:08:49,360 STEM CELL TRANSPLANT AND CHRONIC 3603 02:08:49,360 --> 02:08:52,600 TRANSFUSION HAVE BEEN USED FOR 3604 02:08:52,600 --> 02:08:52,960 YEARS. 3605 02:08:52,960 --> 02:08:54,840 IN PEDIATRIC POPULATION FOR 3606 02:08:54,840 --> 02:08:57,160 EXAMPLE, STEM CELL TRANSPLANTS 3607 02:08:57,160 --> 02:09:00,040 HAS BEEN USED AND NOW, IN ADULT 3608 02:09:00,040 --> 02:09:04,000 POPULATION, WE THAN WE'RE USING 3609 02:09:04,000 --> 02:09:04,840 IT MORE. 3610 02:09:04,840 --> 02:09:08,520 I WILL NOT DISCUSS THIS MUCH 3611 02:09:08,520 --> 02:09:09,400 FURTHER. 3612 02:09:09,400 --> 02:09:11,120 FOR CHRONIC RED CELL 3613 02:09:11,120 --> 02:09:14,840 TRANSFUSION, WE DO USE THIS IN 3614 02:09:14,840 --> 02:09:16,720 MOST OF THE MOST SEVERE 3615 02:09:16,720 --> 02:09:18,840 COMPLICATIONS OF SICKLE CELL 3616 02:09:18,840 --> 02:09:23,480 SUCH AS THOSE AFFECTED WITH 3617 02:09:23,480 --> 02:09:27,360 ACUTE CHEST SYNDROME, MULTIORGAN 3618 02:09:27,360 --> 02:09:28,880 FAILURE, PULMONARY HYPERTENSION, 3619 02:09:28,880 --> 02:09:29,920 CHRONIC HYPOXIA, THOSE AFFECTED 3620 02:09:29,920 --> 02:09:32,240 WITH STROKE AND OTHER SEVERE 3621 02:09:32,240 --> 02:09:38,480 COMPLICATIONS OF SICKLE. 3622 02:09:38,480 --> 02:09:42,080 >> NEXT, PLEASE. 3623 02:09:42,080 --> 02:09:44,400 AND WITH HYDROXY URIA, THAT WAS 3624 02:09:44,400 --> 02:09:45,960 APPROVED IN 1988 AND IT'S STILL 3625 02:09:45,960 --> 02:09:49,160 THE STANDARD THERAPY FOR SICKLE 3626 02:09:49,160 --> 02:09:52,000 CELL ANEMIA, FOR THOSE THAT ARE 3627 02:09:52,000 --> 02:09:55,440 9 MONTHS OR AS DR. WARE 3628 02:09:55,440 --> 02:09:56,720 MENTIONED EARLIER FOR EVEN AS 3629 02:09:56,720 --> 02:10:03,040 YOUNG AS 6 MONTHS OLD CHILDREN. 3630 02:10:03,040 --> 02:10:05,960 AND ARE DIFFERENT WAYS THAT IT 3631 02:10:05,960 --> 02:10:11,440 HAS EFFECT, YOU KNOW IT DOES 3632 02:10:11,440 --> 02:10:15,160 INCREASE NITRIC OXIDE, DECREASE 3633 02:10:15,160 --> 02:10:16,600 MARKERS OF ADHESION, EBD O 3634 02:10:16,600 --> 02:10:19,240 THELLIAL ACTIVATION AND WE KNOW 3635 02:10:19,240 --> 02:10:20,440 IT DEFINITELY IMPROVED MOTILITY 3636 02:10:20,440 --> 02:10:25,600 AND MODEL CITIZEN BIDDITY IN THE 3637 02:10:25,600 --> 02:10:25,920 PATIENTS. 3638 02:10:25,920 --> 02:10:26,680 AND IT IS SAFE. 3639 02:10:26,680 --> 02:10:29,080 WE DO NOT HAVE CLINICAL EVIDENT 3640 02:10:29,080 --> 02:10:30,960 FOR CANCER OR MULTIDEN GIS WITH 3641 02:10:30,960 --> 02:10:35,240 THE USE OF HYDROXY UREA. 3642 02:10:35,240 --> 02:10:40,560 GO ON TO THE NEXT 1 PLEASE. 3643 02:10:40,560 --> 02:10:42,040 AND THIS DIAGRAM JUST BASICALLY 3644 02:10:42,040 --> 02:10:43,160 MENTIONED, YOU KNOW THE 3645 02:10:43,160 --> 02:10:45,840 MECHANISMS OF ACTION OF HYDROXY 3646 02:10:45,840 --> 02:10:51,240 UREA, THE NEXT SLIDE, PLEASE. 3647 02:10:51,240 --> 02:10:53,840 SO I WILL GO THROUGH JUST FEW 3648 02:10:53,840 --> 02:10:58,120 CASES TO TALK ABOUT THE USE OF 3649 02:10:58,120 --> 02:11:02,520 OTHER THERAPEUTICS. 3650 02:11:02,520 --> 02:11:04,800 CASE 1 THIS IS A PATIENT WITH 3651 02:11:04,800 --> 02:11:07,360 SICKLE SEAL DISEASE WITH 2-3 3652 02:11:07,360 --> 02:11:09,840 HOSPITALIZED FOR VOC PER YEAR, 3653 02:11:09,840 --> 02:11:12,280 AND ACUTE CHEST SYNDROME WHO IS 3654 02:11:12,280 --> 02:11:15,360 INTO NATURAL PRODUCTS, NOT 3655 02:11:15,360 --> 02:11:20,280 WANTING TO DRY HYDROXY UREA AND 3656 02:11:20,280 --> 02:11:21,280 RPGHT DISEASE MODIFYING 3657 02:11:21,280 --> 02:11:22,720 THERAPIES JUST BY THE FACT OF 3658 02:11:22,720 --> 02:11:23,880 TELLING THEM PATIENT ABOUT THE 3659 02:11:23,880 --> 02:11:28,440 EFFECTIVENESS OF THESE 3660 02:11:28,440 --> 02:11:29,640 THERAPEUTICS, WELL, I WOULD 3661 02:11:29,640 --> 02:11:31,240 NORMALLY, PATIENTS LIKE THIS, I 3662 02:11:31,240 --> 02:11:34,240 WILL LET THEM KNOW, STILL ABOUT 3663 02:11:34,240 --> 02:11:35,360 ALL THESE THERAPEUTICS BUT IN 3664 02:11:35,360 --> 02:11:38,640 ADDITION TO THAT, I WILL TELL 3665 02:11:38,640 --> 02:11:45,080 THEM ABOUT THE NEXT SLIDE. 3666 02:11:45,080 --> 02:11:47,600 L-GLUTEA MINE WHICH IS MORE OF 3667 02:11:47,600 --> 02:11:48,040 AN NATURAL PRODUCT. 3668 02:11:48,040 --> 02:11:50,440 IT IS AN ORAL PREDUSKERROR FOR 3669 02:11:50,440 --> 02:11:54,800 NADH THAT REDUCED FORNL OF NICK 3670 02:11:54,800 --> 02:11:58,160 O TINA MID ADENINE DINUCLEOTIDE 3671 02:11:58,160 --> 02:12:01,840 AND IT RESULTS IN 3672 02:12:01,840 --> 02:12:03,160 DECREASEDOXIDATIVE STRESS WITHIN 3673 02:12:03,160 --> 02:12:06,760 THE SICKLE REBLOOD CELLS 3674 02:12:06,760 --> 02:12:08,400 APPROVED IN 2017 AND YOU CAN 3675 02:12:08,400 --> 02:12:12,280 SEE, ON THIS SLIDE, YOU KNOW 3676 02:12:12,280 --> 02:12:13,960 JUST THE DIAGRAM OF HOW IT 3677 02:12:13,960 --> 02:12:14,160 WORKS. 3678 02:12:14,160 --> 02:12:23,160 YOU CAN GO TO THE NEXT SLIDE. 3679 02:12:23,160 --> 02:12:25,960 SO L-GLUTEA MINE SHOWED 25% 3680 02:12:25,960 --> 02:12:27,920 REDUCTION IN THE PAIN CRISIS, 3681 02:12:27,920 --> 02:12:29,480 30% LOWER HOSPITAL EYATION RATE 3682 02:12:29,480 --> 02:12:31,320 AND REDUCED NUMBER OF EPISODES 3683 02:12:31,320 --> 02:12:32,520 OF ACUTE CHEST SYNDROME. 3684 02:12:32,520 --> 02:12:34,640 SO FOR A PATIENT LIKE THAT, WITH 3685 02:12:34,640 --> 02:12:39,800 HISTORY OF ACUTE CHEST SYNDROME, 3686 02:12:39,800 --> 02:12:40,840 INCREASED VOCs, VERY RESERVED 3687 02:12:40,840 --> 02:12:45,040 IN TERMS OF THERAPEUTICS BUT 3688 02:12:45,040 --> 02:12:46,840 MORE INTO NATURAL PROD UBTS THIS 3689 02:12:46,840 --> 02:12:50,480 IS A VERY GOOD THERAPY THAT 1 3690 02:12:50,480 --> 02:12:57,040 CAN INTRODUCE TO SUCH PATIENTS. 3691 02:12:57,040 --> 02:12:58,640 NEXT, PLEASE. 3692 02:12:58,640 --> 02:13:03,360 CASE 2, MR. S IS A 25 YEAR-OLD 3693 02:13:03,360 --> 02:13:04,000 HBSS WITH MAJOR DEPRESSIVE 3694 02:13:04,000 --> 02:13:09,200 DISORDER WHO HAS BEEN ON MTB FOR 3695 02:13:09,200 --> 02:13:11,280 HYDROXY UREA FOR 7 YEARS; 3696 02:13:11,280 --> 02:13:13,000 HOWEVER IT IS BETTER CONTROL OF 3697 02:13:13,000 --> 02:13:15,280 SICK CELL CELL IS IMMUNE GLOBINS 3698 02:13:15,280 --> 02:13:19,040 IS A CLEAR RANGE OF 7-8, 3699 02:13:19,040 --> 02:13:20,160 INDIRECT BILI, TYPICALLY QUITE 3700 02:13:20,160 --> 02:13:29,480 HIGH AT 5 AND LDH OF 450 WITH A 3701 02:13:29,480 --> 02:13:33,840 NORMAL LEVEL OF 195. 3702 02:13:33,840 --> 02:13:36,280 KRE TINS ATINE IS .5, HE MENTION 3703 02:13:36,280 --> 02:13:38,640 THAD HE IS EMBARRASSED ABOUT THE 3704 02:13:38,640 --> 02:13:39,680 YELLOWISH DISCOLORATION OF HIS 3705 02:13:39,680 --> 02:13:43,000 EYES AND IS EVEN MORE DEPRESSED 3706 02:13:43,000 --> 02:13:45,240 BECAUSE HE'S TRYING TO FIT IN, 3707 02:13:45,240 --> 02:13:48,240 INTO HIS PEER GROUP BECAUSE, YOU 3708 02:13:48,240 --> 02:13:52,840 KNOW OF HIS YELLOWISH EYES, 3709 02:13:52,840 --> 02:13:53,640 DISCOLORATION, THAT'S 3710 02:13:53,640 --> 02:13:54,640 CONTRIBUTING TO HIS EMOTIONAL 3711 02:13:54,640 --> 02:13:55,080 STATE. 3712 02:13:55,080 --> 02:13:57,920 NEXT SLIDE, PLEASE. 3713 02:13:57,920 --> 02:14:00,360 SO FOR THIS PATIENT, YOU KNOW, I 3714 02:14:00,360 --> 02:14:05,040 WOULD TYPICALLY TALK ABOUT, YOU 3715 02:14:05,040 --> 02:14:17,680 KNOW HOW HEME HEMOLYSS CAN HELP, BUT 3716 02:14:17,680 --> 02:14:19,800 PATIENT IS TILL PRONE TO 3717 02:14:19,800 --> 02:14:22,840 MULTIORGAN DISEASE AND 3718 02:14:22,840 --> 02:14:25,200 DYSFUNCTION AND FAILURE BECAUSE 3719 02:14:25,200 --> 02:14:29,240 IT'S STILL CONSIDERED A HIGH 3720 02:14:29,240 --> 02:14:33,320 HEMOALIZER AT STEADY STATE SO AN 3721 02:14:33,320 --> 02:14:35,280 VOXELOTOR WOULD BE A GOOD DRUG 3722 02:14:35,280 --> 02:14:38,840 FOR THIS PATIENT, IT BINDS TO 3723 02:14:38,840 --> 02:14:41,920 THE GLOBIN CHANGE OF HEMOGLOBIN 3724 02:14:41,920 --> 02:14:44,480 RESULT NOTHING AN ALOESTERRIC 3725 02:14:44,480 --> 02:14:48,240 MODIFICATION OF WHICH INCREASES 3726 02:14:48,240 --> 02:14:51,080 THE HEMOGLOBIN, AND DECREASES 3727 02:14:51,080 --> 02:14:53,840 POLYMERIZATION OF TEND ENSEL OF 3728 02:14:53,840 --> 02:14:55,240 THE DEOXY-HBS, AND IMPROVING 3729 02:14:55,240 --> 02:14:57,640 SICKLE CELL RED CELL SURVIVAL, 3730 02:14:57,640 --> 02:15:04,360 INCREASE WITH HB AND DECREASE 3731 02:15:04,360 --> 02:15:05,240 RETICULOCYTE, AND TYPICALLY 3732 02:15:05,240 --> 02:15:06,880 THERE'S A DECREASE IN BILIRUBIN. 3733 02:15:06,880 --> 02:15:09,360 YOU CAN GO TO THE NEXT. 3734 02:15:09,360 --> 02:15:12,800 AND THEN HOPE, WHICH MANY OF YOU 3735 02:15:12,800 --> 02:15:17,840 ARE FAMILIAR WITH, YOU CAN SEE 3736 02:15:17,840 --> 02:15:20,920 274 PARTICIPANTS RANDOMIZED TO 3737 02:15:20,920 --> 02:15:23,720 900-MILLIGRAM AND 1500-MILLIGRAM 3738 02:15:23,720 --> 02:15:25,000 OF VOXELOTOR DOSE, AND 3739 02:15:25,000 --> 02:15:28,720 APPROXIMATELY 2/3RDS OF 3740 02:15:28,720 --> 02:15:32,640 RECEIVING HYDROXY UREA AND 3741 02:15:32,640 --> 02:15:33,320 VOXELOTOR SIGNIFICANTLY 3742 02:15:33,320 --> 02:15:35,680 INCREASED HEMODPLOABIN LEVELS 3743 02:15:35,680 --> 02:15:38,400 AND REDUCED HEMOLOGY SIS. 3744 02:15:38,400 --> 02:15:41,280 NEXT, THIS IS A REAL PERSON'S 3745 02:15:41,280 --> 02:15:44,480 SMEAR ON DAY 1 AND DAY 20. 3746 02:15:44,480 --> 02:15:47,520 YOU CAN APPRECIATE THAT THIS DAY 3747 02:15:47,520 --> 02:15:52,800 1 SLIDE BEFORE THE FIRST DOSE OF 3748 02:15:52,800 --> 02:15:55,600 VOXOLETOR, HAD MANY SICKLE RED 3749 02:15:55,600 --> 02:15:58,040 CELLS, HOWEVER, DAY 21, REALLY 3750 02:15:58,040 --> 02:16:02,560 YOU COULD SEE VERY FEW RED CELLS 3751 02:16:02,560 --> 02:16:04,680 AND THE PATIENT WAS LESS ANEMIC 3752 02:16:04,680 --> 02:16:08,440 ON DAY 21. 3753 02:16:08,440 --> 02:16:10,240 NEXT. 3754 02:16:10,240 --> 02:16:14,400 AND SAME PERSON'S LABS, ON DAY 3755 02:16:14,400 --> 02:16:16,280 1, HEMODPLOABIN FINE .4, DAY 3756 02:16:16,280 --> 02:16:16,520 2112.1. 3757 02:16:16,520 --> 02:16:21,440 ARE YOU COULD SEE THE TOTAL 3758 02:16:21,440 --> 02:16:23,240 BILIRUBIN GOING FROM 4.7 TO 3759 02:16:23,240 --> 02:16:26,640 NORMAL RANGE, 0.9, LDH FROM 300 3760 02:16:26,640 --> 02:16:28,360 TO 132. 3761 02:16:28,360 --> 02:16:30,080 AND THIS PATIENT FELT MUCH 3762 02:16:30,080 --> 02:16:37,680 BETTER, DOING BETTER IN TERMS OF 3763 02:16:37,680 --> 02:16:39,160 JUST HIMSELF OVERALL, EMOTIONAL 3764 02:16:39,160 --> 02:16:42,920 AND EVERYTHING ELSE. 3765 02:16:42,920 --> 02:16:46,000 AND THIS JUST SHOWED US THAT 3766 02:16:46,000 --> 02:16:50,040 MANY OF THESE PATIENTS STILL 3767 02:16:50,040 --> 02:16:50,840 SUSTAINED THEIR HEMOGLOBIN 3768 02:16:50,840 --> 02:16:54,960 RESPONSE EVEN FOR 72 WEEKS. 3769 02:16:54,960 --> 02:16:57,640 1 GRAM INCREASE WAS SUSTAINED BY 3770 02:16:57,640 --> 02:17:00,440 88.9% OF THE PATIENT COMPARED TO 3771 02:17:00,440 --> 02:17:06,400 25% OF THE PLACEBO GROUP. 3772 02:17:06,400 --> 02:17:08,840 AND 58.9% OF THE PATIENTS 3773 02:17:08,840 --> 02:17:10,880 SUSTAINED DECREASE OF THE GRAM, 3774 02:17:10,880 --> 02:17:13,120 COMPARED TO 3.3% OF THE PLACEBO 3775 02:17:13,120 --> 02:17:19,480 GROUP AND 20% OF THOSE PATIENT 3776 02:17:19,480 --> 02:17:22,360 ON BOTH VOXOLOTOR OBTAINED A 3777 02:17:22,360 --> 02:17:24,280 HEMOGLOBIN OF 3-GRAM HIGHER 3778 02:17:24,280 --> 02:17:28,320 COMPARED TO NONE OF THOSE ON 3779 02:17:28,320 --> 02:17:31,080 PLACEBO. 3780 02:17:31,080 --> 02:17:32,600 NEXT, PLEASE. 3781 02:17:32,600 --> 02:17:34,440 AND INCIDENTS OF VOIRKS Cs WAS 3782 02:17:34,440 --> 02:17:37,440 ALSO NOTED TO THE LOWEST IN 3783 02:17:37,440 --> 02:17:39,640 PATIENTS WITH HIGHEST HEMOGLOBIN 3784 02:17:39,640 --> 02:17:44,840 LEVELS FOR THOSE ON VOXOLOTER, 3785 02:17:44,840 --> 02:17:52,040 NEXT, PLEASE, BACK TO CASE 2, 3786 02:17:52,040 --> 02:17:55,840 MR. S, THE 25 YEAR-OLD THAT HAD 3787 02:17:55,840 --> 02:17:57,560 MAJOR DEPRESSIVE DISORDER WHO 3788 02:17:57,560 --> 02:18:01,280 WAS ON MTD FOR 7 YEARS, AND HE 3789 02:18:01,280 --> 02:18:02,960 IMPRIEWED TO 10, HEME OLDER 3790 02:18:02,960 --> 02:18:05,360 PEOPLE SIS PANEL IMPROVED 3791 02:18:05,360 --> 02:18:06,280 SIGNIFICANTLY AND EMOTIONAL 3792 02:18:06,280 --> 02:18:09,200 STATUS ALSO IMPROVED AND HE ALSO 3793 02:18:09,200 --> 02:18:10,440 NOTED IMPROVEMENT IN THE NATURE 3794 02:18:10,440 --> 02:18:14,640 AND DURATION OF HIS PAIN 3795 02:18:14,640 --> 02:18:14,880 EPISODES. 3796 02:18:14,880 --> 02:18:16,480 WE PUBLISHED IN THE NEW ENGLAND 3797 02:18:16,480 --> 02:18:19,080 JOURNAL LARN LAND JOURNAL OF 3798 02:18:19,080 --> 02:18:22,840 MEDICINE, PATIENTS OF VOXELOTOR 3799 02:18:22,840 --> 02:18:23,920 BENEFIT, FEWER PATIENTS REPORTED 3800 02:18:23,920 --> 02:18:25,760 THAT THEINATE IRB AND DURATION 3801 02:18:25,760 --> 02:18:30,080 OF THEIR PAIN IMPROVED WITH THE 3802 02:18:30,080 --> 02:18:32,840 VOXELOTOR THERAPY. 3803 02:18:32,840 --> 02:18:34,000 NEXT, PLEASE. 3804 02:18:34,000 --> 02:18:39,040 GBT601 IS A NEXT GENERATION HBS 3805 02:18:39,040 --> 02:18:40,840 POLYMERIZATION INHIBITOR THAT IS 3806 02:18:40,840 --> 02:18:46,640 IN CLINICAL TRIALS CURRENTLY. 3807 02:18:46,640 --> 02:18:48,960 NEXT. 3808 02:18:48,960 --> 02:18:49,360 PLEASE. 3809 02:18:49,360 --> 02:18:53,800 CASE 3, MS. K, PLS K, THAT'S A 3810 02:18:53,800 --> 02:18:57,040 TYPEY, IS A 24 YEAR-OLD MAN WITH 3811 02:18:57,040 --> 02:18:59,640 HBSS, WHO HAS 3-4 3812 02:18:59,640 --> 02:19:02,840 HOSPITALIZATIONS ARE VOC, HE HAS 3813 02:19:02,840 --> 02:19:05,000 CHRONIC BONE PRAIN, FREQUENT 3814 02:19:05,000 --> 02:19:06,840 PRIMATESSA PIMP, AND THAT IS 3815 02:19:06,840 --> 02:19:08,080 UNRESPONSIVE TO UROLOGY AND 3816 02:19:08,080 --> 02:19:11,920 OTHER INTERVENTIONS HE IS ON THE 3817 02:19:11,920 --> 02:19:13,000 HYDROXYEUREA AT MDD AND HE IS 3818 02:19:13,000 --> 02:19:14,760 INTERESTED IN ANY OTHER SICKLE 3819 02:19:14,760 --> 02:19:16,600 CELL THERAPY THAT WILL HELP HIM 3820 02:19:16,600 --> 02:19:19,600 AND ALSO BYE-BYE VO C, INDIRECT 3821 02:19:19,600 --> 02:19:28,440 BILLY OF 2, KID NEUROECTODERMAL 3822 02:19:28,440 --> 02:19:28,840 FUNCTION NORMAL. 3823 02:19:28,840 --> 02:19:29,040 NEXT. 3824 02:19:29,040 --> 02:19:30,320 SO FOR THIS PATIENT, I WOULD 3825 02:19:30,320 --> 02:19:34,920 CONSIDER THE ANING IT NASTI THE 3826 02:19:34,920 --> 02:19:35,760 UPREGULATION EVER P-SELECTIN AND 3827 02:19:35,760 --> 02:19:38,040 EBD O THELLIAL CELLS AND PLATE 3828 02:19:38,040 --> 02:19:39,360 THES CONTRIBUTES TO THE 3829 02:19:39,360 --> 02:19:41,040 CELL-CELL ISHT ACTIONS THAT ARE 3830 02:19:41,040 --> 02:19:43,440 INVOLVED IN THE PATHOGENESIS OF 3831 02:19:43,440 --> 02:19:44,920 THIS OCCLUSION AND THIS PAIN 3832 02:19:44,920 --> 02:19:47,680 CRISIS AND THE INTERFERANCE WITH 3833 02:19:47,680 --> 02:19:53,920 SELECTIN SEEMED TO BE A POWERFUL 3834 02:19:53,920 --> 02:19:56,560 OPTION FOR THE DISEASE, THE 3835 02:19:56,560 --> 02:19:57,520 SELECTIVITY HAVE BEEN ELEVATE 3836 02:19:57,520 --> 02:21:21,720 INDEED PATIENTS WITH SICKLE CELL 3837 02:21:21,720 --> 02:21:23,240 DISEASE, NEXT, PLEASE--AND IN 3838 02:21:23,240 --> 02:21:26,040 THE LOW DOSE 44%. 3839 02:21:26,040 --> 02:21:28,840 COMPARED TO PLACEBO. 3840 02:21:28,840 --> 02:21:29,680 NEXT. 3841 02:21:29,680 --> 02:21:29,920 PLEASE? 3842 02:21:29,920 --> 02:21:38,920 SO BACK TO CASE 3, MR. K GOT 3843 02:21:38,920 --> 02:21:41,240 STARTED ON PRES MEAS LAB, AFTER 3844 02:21:41,240 --> 02:21:52,120 2 MONTHS ON THERAPY HE NOTICED 3845 02:21:52,120 --> 02:21:55,040 IN HIS PRIAPISM, AND HE ALSO 3846 02:21:55,040 --> 02:21:58,280 IMPROVED TO 1-2 TIMES PER YEAR, 3847 02:21:58,280 --> 02:21:58,880 FOR HOSPITALIZATION, THIS 3848 02:21:58,880 --> 02:22:02,040 HIGHLIGHTED THAT IF THEY'RE 3849 02:22:02,040 --> 02:22:06,280 READY ON ON HYDROXY UREA, THERE 3850 02:22:06,280 --> 02:22:07,920 ARE OTHER THERAPIES, THERE'S 3851 02:22:07,920 --> 02:22:09,600 MORE THERAPIES THAT WILL HELP 3852 02:22:09,600 --> 02:22:14,680 AND WITH VOC BECAUSE OF THE 3853 02:22:14,680 --> 02:22:22,280 SELECTING INHIBITION, THERE, 3854 02:22:22,280 --> 02:22:23,000 NEXT. 3855 02:22:23,000 --> 02:22:25,480 INCLACUMAB, IS A AN INHIBITOR IN 3856 02:22:25,480 --> 02:22:30,080 THE PHASE 3 CLINICAL TRIAL TO 3857 02:22:30,080 --> 02:22:32,160 EVALUATE AND IS ADMINISTERED 3858 02:22:32,160 --> 02:22:33,320 EVERY 12 WEEKS. 3859 02:22:33,320 --> 02:22:36,200 AND ALSO THERE'S ANTIE-SELECTIN 3860 02:22:36,200 --> 02:22:38,280 THAT IS ALSO IN CLINICAL TRIAL 3861 02:22:38,280 --> 02:22:41,560 AND THIS IS GIVEN AS SUBCUE 3862 02:22:41,560 --> 02:22:44,840 INJECTION AND IT DEMONSTRATES 3863 02:22:44,840 --> 02:22:48,360 LONGER HALF LIFE, THAN 3864 02:22:48,360 --> 02:22:58,800 PREZULAMAB AND MAYBE EVEN REDUCE 3865 02:22:58,800 --> 02:23:02,840 NUTRIFILL ADDITION AND, THERE 3866 02:23:02,840 --> 02:23:08,880 ARE ALSO AND ACTIVATORS, THIS 3867 02:23:08,880 --> 02:23:12,200 WAS PRESENTED IN LAST--DURING 3868 02:23:12,200 --> 02:23:14,640 LAST KD--SALLY WAAND WITH VERY 3869 02:23:14,640 --> 02:23:18,040 GOOD EFFECT AND IMPROVEMENT IN 3870 02:23:18,040 --> 02:23:20,480 HEMEAT O LOGIC AND HEMOLYTIC 3871 02:23:20,480 --> 02:23:22,680 PARAMETERS AS YOU CAN SEE ON 3872 02:23:22,680 --> 02:23:25,600 THIS SLIGHT, AND YOU THE SITES 3873 02:23:25,600 --> 02:23:28,080 DECREASED AND LDH AND BILIRUBIN 3874 02:23:28,080 --> 02:23:34,320 ARE DECREASED IN MAJORITY OF THE 3875 02:23:34,320 --> 02:23:34,600 PATIENTS. 3876 02:23:34,600 --> 02:23:34,920 NEXT, PLEASE. 3877 02:23:34,920 --> 02:23:39,840 AND THEY ALSO HAD SIMILAR 3878 02:23:39,840 --> 02:23:42,160 EFFECTS ON HEME OLDER PEOPLE SIS 3879 02:23:42,160 --> 02:23:45,560 AND PARAMETER AS SEEN ON THIS 3880 02:23:45,560 --> 02:23:46,040 SLIDE. 3881 02:23:46,040 --> 02:23:47,280 NEXT SLIDE. 3882 02:23:47,280 --> 02:23:49,040 PLEASE. 3883 02:23:49,040 --> 02:23:54,880 SO, I WILL--I TREAT PATIENTS 3884 02:23:54,880 --> 02:23:57,160 WITH DIFFERENT SYMPTOMS, ALL 3885 02:23:57,160 --> 02:23:59,960 CONDITION I WOULD OFFER 3886 02:23:59,960 --> 02:24:00,680 HYDROXYEUREA AS STANDARD THERAPY 3887 02:24:00,680 --> 02:24:02,360 AND IN ADDITION TO THAT, THESE 3888 02:24:02,360 --> 02:24:07,080 PATIENTS IF THEY HAVE CHRONIC 3889 02:24:07,080 --> 02:24:11,440 SYMPTOMS HERE, LEG ULCER, 3890 02:24:11,440 --> 02:24:13,120 EXTENSIVE RBC IMMUNIZATION OR 3891 02:24:13,120 --> 02:24:15,280 THEY HAVE A STEADY STATE IN THE 3892 02:24:15,280 --> 02:24:22,280 BILL BILIRUBIN OR THEY HAVE HIGH 3893 02:24:22,280 --> 02:24:24,360 HEME OLYSIS AND I WILL 3894 02:24:24,360 --> 02:24:27,240 ACCELERATE PER FELPS AS APPROVED 3895 02:24:27,240 --> 02:24:29,240 THERAPY IN ADDITION TO THEIR 3896 02:24:29,240 --> 02:24:32,480 HYDROXY UREA, AND ALSO IF THEY 3897 02:24:32,480 --> 02:24:34,880 HAVE HIGH HEME OLSYS, AT THE 3898 02:24:34,880 --> 02:24:36,760 ESTATE STATE, IF THEY HAVE 3899 02:24:36,760 --> 02:24:38,640 FATIGUE OR SEVERE ANEMIA AND AT 3900 02:24:38,640 --> 02:24:42,240 A WILL ALSO CONSIDER OTHER 3901 02:24:42,240 --> 02:24:45,480 AFFINITY MEDICATIONS, IF THEY'RE 3902 02:24:45,480 --> 02:24:46,920 NOT IMPROVED, [INDISCERNIBLE] OR 3903 02:24:46,920 --> 02:24:48,920 ANOTHER OR THEY'RE 3904 02:24:48,920 --> 02:24:50,280 [INDISCERNIBLE] INTOLERANT, I 3905 02:24:50,280 --> 02:24:53,720 WILL ACTUALLY CONSIDER OFFERING 3906 02:24:53,720 --> 02:24:55,920 THEM AND TELLING THEM ABOUT 3907 02:24:55,920 --> 02:24:58,040 CLINICAL TRIAL DRUGS BECAUSE IN 3908 02:24:58,040 --> 02:25:01,440 MY OWN EXPERIENCE WITH PATIENTS 3909 02:25:01,440 --> 02:25:03,880 ARE HAVE BEEN TOLD OR INSTRUCTED 3910 02:25:03,880 --> 02:25:04,920 ABOUT THIS CLINICAL TRIAL 3911 02:25:04,920 --> 02:25:06,640 MEDICATIONS AND THEY'RE ABLE TO 3912 02:25:06,640 --> 02:25:11,400 TRY THIS EARLY, SOMETIMES THEY 3913 02:25:11,400 --> 02:25:13,760 GAIN BENEFIT EARLIER AND THEY'RE 3914 02:25:13,760 --> 02:25:16,160 ABLE TO EVEN REQUEST THAT AS 3915 02:25:16,160 --> 02:25:17,680 SOON AS THIS THERAPY GETS 3916 02:25:17,680 --> 02:25:19,640 APPROVED, THEY WANT TO BE ON 3917 02:25:19,640 --> 02:25:20,880 THESE THERAPIES. 3918 02:25:20,880 --> 02:25:24,320 SO I WILL HELP OUT SUCH 3919 02:25:24,320 --> 02:25:28,280 PATIENTS, PK ACTIVATORS SUCH AS 3920 02:25:28,280 --> 02:25:28,720 [INDISCERNIBLE], 3921 02:25:28,720 --> 02:25:29,160 META[INDISCERNIBLE]. 3922 02:25:29,160 --> 02:25:32,680 AND EVEN, YOU KNOW THE SECOND 3923 02:25:32,680 --> 02:25:36,000 GENERATION, YOU KNOW DRUGs 3924 02:25:36,000 --> 02:25:40,640 SUCH AS GBT 601. 3925 02:25:40,640 --> 02:25:43,000 SO CHRONIC SYNDROME PATIENTS OR 3926 02:25:43,000 --> 02:25:46,640 ANY PATIENT THAT IS NOT 3927 02:25:46,640 --> 02:25:49,840 RESPONSIVE TO UROLOGIC 3928 02:25:49,840 --> 02:25:50,560 INTERVENTIONS, I WILL RECOMMEND 3929 02:25:50,560 --> 02:25:55,640 TO THAT PATIENT TO CONSIDER 3930 02:25:55,640 --> 02:25:57,280 CRIZANLIZUMAB AND IF THEY ALSO 3931 02:25:57,280 --> 02:26:00,440 HAVE, IF A PATIENT HAS PROTEIN 3932 02:26:00,440 --> 02:26:04,640 UREA MAY ALSO CONSIDER CRISWR, 3933 02:26:04,640 --> 02:26:09,000 ANLIZUMAB, FOR PATIENTS WITH THE 3934 02:26:09,000 --> 02:26:10,280 SYNDROME, L-GLUTEA MINE IS ALSO 3935 02:26:10,280 --> 02:26:13,080 AN OPTION FOR THE PATIENT SO I 3936 02:26:13,080 --> 02:26:17,000 WILL TELL THEM ABOUT THIS 3937 02:26:17,000 --> 02:26:18,000 OPTION, FREQUENT VOC INTOLERANT 3938 02:26:18,000 --> 02:26:22,640 TO OR NOT INTERESTED IN 3939 02:26:22,640 --> 02:26:24,720 CRIZANLIZUMAB WILL CONSIDER 3940 02:26:24,720 --> 02:26:27,240 OTHER CLINICAL TRIAL THERAPY, 3941 02:26:27,240 --> 02:26:27,920 P-SELECTIN AND E-SELECTIN 3942 02:26:27,920 --> 02:26:30,000 IBT--INTEGRATE HIB THORS 3943 02:26:30,000 --> 02:26:32,560 IDENTITY ARES, AND OTHER YOU 3944 02:26:32,560 --> 02:26:41,920 KNOW E-SELECTIN DRUGS I JUST 3945 02:26:41,920 --> 02:26:45,240 TALKED ABOUT. 3946 02:26:45,240 --> 02:26:47,560 SO IN CONCLUSION, SICKLE CELL 3947 02:26:47,560 --> 02:26:49,440 DISEASE AND A DISABLES CONDITION 3948 02:26:49,440 --> 02:26:51,520 THAT AFFECTS MULTIPLE ORGAN 3949 02:26:51,520 --> 02:26:52,200 SYSTEMS. 3950 02:26:52,200 --> 02:26:54,560 SCD IS A SINGLE GENE DISORDER 3951 02:26:54,560 --> 02:26:56,440 WITH A COMPLEX PHENOTYPIC 3952 02:26:56,440 --> 02:26:56,720 EXPRESSION. 3953 02:26:56,720 --> 02:26:59,680 TREATMENT FOR SCD PATIENTS 3954 02:26:59,680 --> 02:27:01,440 SHOULD BE INDIVIDUALIZED. 3955 02:27:01,440 --> 02:27:02,600 NOVEL SCD MODIFYING THERAPIES 3956 02:27:02,600 --> 02:27:05,080 ARE NOW APPROVED FOR USE IN SCD 3957 02:27:05,080 --> 02:27:06,200 POPULATION AND SOME ARE 3958 02:27:06,200 --> 02:27:07,840 CURRENTLY IN CLINICAL TRIALS 3959 02:27:07,840 --> 02:27:08,400 WITH ENCOURAGING RESULTS. 3960 02:27:08,400 --> 02:27:10,840 EACH OF THE FDA APPROVED 3961 02:27:10,840 --> 02:27:11,640 PHARMACEUTICAL THERAPIES FOR 3962 02:27:11,640 --> 02:27:13,600 SICKLE SEAL DISEASE CAN BE 3963 02:27:13,600 --> 02:27:16,560 DESCRIBED AS COMBINATION THERAPY 3964 02:27:16,560 --> 02:27:18,760 WITH HYDROXY UREA AND OTHER 3965 02:27:18,760 --> 02:27:20,560 THERAPIES WHILE A SINGLE AGENT 3966 02:27:20,560 --> 02:27:29,800 IF THE PATIENT IS NOT TOLERANT 3967 02:27:29,800 --> 02:27:30,160 TO HYDROXEUREA. 3968 02:27:30,160 --> 02:27:31,040 THANK YOU VERY MUCH FOR YOUR 3969 02:27:31,040 --> 02:27:31,560 ATTENTION. 3970 02:27:31,560 --> 02:27:36,600 >> THANK YOU FOR YOUR EXCELLENT 3971 02:27:36,600 --> 02:27:37,160 PRESENTATION. 3972 02:27:37,160 --> 02:27:47,560 I THINK THE NEXT TALK IS 3973 02:27:47,560 --> 02:27:47,880 DR. COSTA. 3974 02:27:47,880 --> 02:27:48,480 >> HELLO. 3975 02:27:48,480 --> 02:27:50,080 >> I WILL SHARE MY SCREEN. 3976 02:27:50,080 --> 02:27:55,400 >> YES, IN THE MEAN TIME, YES, 3977 02:27:55,400 --> 02:27:57,120 THERE ARE SOME COMMENTS IN THE 3978 02:27:57,120 --> 02:27:58,440 CHAT FOR THE PREVIOUS TALK SO 3979 02:27:58,440 --> 02:28:01,320 PLEASE TRY TO RESPOND TO THOSE. 3980 02:28:01,320 --> 02:28:09,440 SORRY DR. COSTA PLEASE GO AHEAD. 3981 02:28:09,440 --> 02:28:11,440 SPEAKING ABOUT HEMATOPOIETIC 3982 02:28:11,440 --> 02:28:12,360 STEM CELL TRANSPLANTATION 3983 02:28:12,360 --> 02:28:13,600 REVERSES WHITE MATTER INJURY IN 3984 02:28:13,600 --> 02:28:15,280 SICKLE DISEASE DISEASE PATIENTS. 3985 02:28:15,280 --> 02:28:18,120 >> HELLO, I WOULD LIKE TO THANK 3986 02:28:18,120 --> 02:28:19,640 THE ORGANIZING COMMITTEE FOR 3987 02:28:19,640 --> 02:28:20,840 CUED COORDINATING THE EERVET AND 3988 02:28:20,840 --> 02:28:27,400 THE INVITATION, I AM A IN THE 3989 02:28:27,400 --> 02:28:33,000 BONE MARROW TRANSPLANT UNIT AT 3990 02:28:33,000 --> 02:28:34,600 THE RIBEIRAO PRETO MEDICAL 3991 02:28:34,600 --> 02:28:38,400 SCHOOL UNIVERSITY OF SAO P A 3992 02:28:38,400 --> 02:28:38,680 ULO, BRAZIL. 3993 02:28:38,680 --> 02:28:42,000 I HAVE NO CONFLICTS OF INTEREST. 3994 02:28:42,000 --> 02:28:47,160 OUR SERVICE HAS 53 LEE IDENTIFY 3995 02:28:47,160 --> 02:28:51,800 SIBLINGS IN THE STEM CELL 3996 02:28:51,800 --> 02:28:59,040 TRANSPLANT FOR DISEASE TRUSTEES 3997 02:28:59,040 --> 02:29:01,360 2000LY-2021, SURVIVAL WAS AROUND 3998 02:29:01,360 --> 02:29:04,080 5%, IT CONSISTED OF REGIMEN IN 3999 02:29:04,080 --> 02:29:06,240 ALL PATIENTS ACCEPT THOSE THAT 4000 02:29:06,240 --> 02:29:07,880 REDUCED IT IN CONDITIONING 4001 02:29:07,880 --> 02:29:12,120 REGIMEN IS FR USE OF HGT WAS THE 4002 02:29:12,120 --> 02:29:16,000 MOST USED REGIMEN IN DOSE AND 4003 02:29:16,000 --> 02:29:16,440 CHILDREN. 4004 02:29:16,440 --> 02:29:18,040 DURING MY PRESENTATION, I WILL 4005 02:29:18,040 --> 02:29:20,840 SHOW A DECISION IMAGING TO 4006 02:29:20,840 --> 02:29:21,600 [INDISCERNIBLE] INVOLVING 28 4007 02:29:21,600 --> 02:29:28,120 PATIENTS AND A CASE REPORT. 4008 02:29:28,120 --> 02:29:30,160 BRAIN INJURY SICKLE CELL DISEASE 4009 02:29:30,160 --> 02:29:33,240 COMPRICES OF A WIDE SPECTRUM OF 4010 02:29:33,240 --> 02:29:35,400 NEUROLOGICAL DAMAGE. 4011 02:29:35,400 --> 02:29:38,360 ALLO HSCT IS THE ONLY BROADLY 4012 02:29:38,360 --> 02:29:40,560 AVAILABLE CURATIVE TREATMENT FOR 4013 02:29:40,560 --> 02:29:45,240 SCD, WITH A 5 YEAR SURVIVAL FOR 4014 02:29:45,240 --> 02:29:46,240 TRANSPLANTATION. 4015 02:29:46,240 --> 02:29:49,800 TRANSPLANT CAN REDUCE 4016 02:29:49,800 --> 02:29:52,400 VELOCITIES, STOP PROGRESSION OF 4017 02:29:52,400 --> 02:29:56,080 VASCUE LOPATHY AND HELP WITH 4018 02:29:56,080 --> 02:29:56,440 STROKES. 4019 02:29:56,440 --> 02:30:00,520 DTI IS A MAGNETIC IMAGING 4020 02:30:00,520 --> 02:30:01,480 RESMANS NECKNIQUE OF WATER 4021 02:30:01,480 --> 02:30:03,200 MOLECULES IN THE CELL VALID AND 4022 02:30:03,200 --> 02:30:03,920 RELIABLE ENVIRONMENT, THIS 4023 02:30:03,920 --> 02:30:06,320 MOTION IS A RANDOM MOTION OF 4024 02:30:06,320 --> 02:30:07,840 PARTICLES CESS PEND IN A FLOAT 4025 02:30:07,840 --> 02:30:09,400 RESULTING FROM THEIR COLLISION. 4026 02:30:09,400 --> 02:30:12,800 WE CAN SEE IN THE FIGURE ON THE 4027 02:30:12,800 --> 02:30:15,240 LEFT, A FREE WATER WITH 4028 02:30:15,240 --> 02:30:16,360 ISOTROPIC, OUR OWN RESTRICTED 4029 02:30:16,360 --> 02:30:19,600 AFFUSION AND ON THE RIGHT, A 4030 02:30:19,600 --> 02:30:24,440 BUNDLE WITH THE TROPIC 4031 02:30:24,440 --> 02:30:25,320 RESTRICTED DIFFUSION. 4032 02:30:25,320 --> 02:30:28,280 DEPISHT IMAGING IS USED IN 4033 02:30:28,280 --> 02:30:31,560 DIFFERENT SITUATIONS SUCH AS TO 4034 02:30:31,560 --> 02:30:39,840 THE FACT ACUTE CEREBRAL 4035 02:30:39,840 --> 02:30:42,800 ISCHEMIA, AND VASE O GENIC AND 4036 02:30:42,800 --> 02:30:43,320 WHITE MATTER CONNECTIVITY. 4037 02:30:43,320 --> 02:30:46,080 IT IS A RAPID NONINVASIVE AND 4038 02:30:46,080 --> 02:30:48,520 NONCONTRAST METHOD THAT ENABLING 4039 02:30:48,520 --> 02:30:49,800 DETECTION OF WHITE MATTER 4040 02:30:49,800 --> 02:30:52,560 LESIONS NOT DETECT BIDE 4041 02:30:52,560 --> 02:30:54,840 CONVENTIONAL MAGNETIC RESONANCE 4042 02:30:54,840 --> 02:30:55,480 IMAGING. 4043 02:30:55,480 --> 02:30:56,840 MRI. 4044 02:30:56,840 --> 02:30:57,920 PREVIOUS STUDIES USING DTI 4045 02:30:57,920 --> 02:30:59,720 METHOD HAVE DETECTED WHITE 4046 02:30:59,720 --> 02:31:02,080 MATTER DAMAGE IN SCD PATIENTS 4047 02:31:02,080 --> 02:31:03,080 WITHOUT NEUROLOGICAL 4048 02:31:03,080 --> 02:31:04,080 MANIFESTATIONS OR ABNORMAL 4049 02:31:04,080 --> 02:31:10,640 IMAGING WHEN COMPARED TO 4050 02:31:10,640 --> 02:31:10,880 CONTROLS. 4051 02:31:10,880 --> 02:31:13,160 >> WE EVALUATED 28 PATIENT WHO 4052 02:31:13,160 --> 02:31:18,640 IS RECEIVED AN ALLO 4053 02:31:18,640 --> 02:31:19,360 TRANSPLANTATION, HL-IDENTICAL 4054 02:31:19,360 --> 02:31:22,440 TRANSPLANT, OVERT STROKE IN 11 4055 02:31:22,440 --> 02:31:25,320 PATIENTS, ABNORMAL TCD, VELOCITY 4056 02:31:25,320 --> 02:31:28,120 IN 7 PATIENTS AND OTHERS IN 10 4057 02:31:28,120 --> 02:31:28,440 PATIENTS. 4058 02:31:28,440 --> 02:31:30,080 DTI ACQUISITION WAS PERFORMED 4059 02:31:30,080 --> 02:31:31,840 BEFORE AND AFTER TRANSPLANT. 4060 02:31:31,840 --> 02:31:34,880 AND COMPARED TO THE DATA WITH 26 4061 02:31:34,880 --> 02:31:39,480 HEALTHY CONTROLS, MATCHED BY AGE 4062 02:31:39,480 --> 02:31:43,200 AND GENDER. 4063 02:31:43,200 --> 02:31:45,400 FRACTIONAL ANISOTROPY FA IS MOST 4064 02:31:45,400 --> 02:31:47,640 WIDELY USED DTI METRIC AND 4065 02:31:47,640 --> 02:31:48,560 REFLECTS HOW DIRECTIONAL 4066 02:31:48,560 --> 02:31:50,800 RESTRICTION OF WATER DIFFUSION 4067 02:31:50,800 --> 02:31:51,560 OCCURS ALONG AXONS. 4068 02:31:51,560 --> 02:31:53,840 WE CAN OBSERVE IN THE FIGURE, 4069 02:31:53,840 --> 02:31:56,960 THE EVALUATION OF DIFFUSION 4070 02:31:56,960 --> 02:31:58,440 SCALES ON TD LEFT IS THE 4071 02:31:58,440 --> 02:32:00,040 FRACTION ON THE MAP, IN THE 4072 02:32:00,040 --> 02:32:02,520 MIDDLE WAS IN THE MIDDLE BRAIN 4073 02:32:02,520 --> 02:32:03,760 MASSES WERE GENERATED AND EACH 4074 02:32:03,760 --> 02:32:08,760 COLOR REP AREY SENTS A CORTICALE 4075 02:32:08,760 --> 02:32:09,160 AREA. 4076 02:32:09,160 --> 02:32:10,840 AND ON THE WHITE ISSUES THE 4077 02:32:10,840 --> 02:32:14,440 WHITE MATTER MASK WAS ADAPT 4078 02:32:14,440 --> 02:32:15,480 OFFICE OF DIVERSITY THE 4079 02:32:15,480 --> 02:32:16,640 [INDISCERNIBLE] MAP. 4080 02:32:16,640 --> 02:32:21,000 THERE ARE OTHER DTI METRICS LIKE 4081 02:32:21,000 --> 02:32:22,280 MEAN DIFFUSIVITY THAT CAPTURES 4082 02:32:22,280 --> 02:32:26,640 THE AVERAGE DIFFUSION RATE IN 4083 02:32:26,640 --> 02:32:28,640 ALL DIRECTIONS. 4084 02:32:28,640 --> 02:32:31,000 ACKIAL DIFFUSIVITY WHICH 4085 02:32:31,000 --> 02:32:32,840 ENCOMPALSZS INFORMATION ON THE 4086 02:32:32,840 --> 02:32:34,120 PARALLEL MOVEMENT OF ACONNAL 4087 02:32:34,120 --> 02:32:36,960 FIBERS AND IS ASSOCIATED WITH 4088 02:32:36,960 --> 02:32:39,760 AXONAL INJURY. 4089 02:32:39,760 --> 02:32:40,680 RADIAL DIFFUSIVITY REFLECTING 4090 02:32:40,680 --> 02:32:43,200 PERP END DICKULAR DIFFUSION AND 4091 02:32:43,200 --> 02:32:44,480 IS ASSOCIATED WITH 4092 02:32:44,480 --> 02:32:45,840 DEMILENNATION, AND WHEN WE HAVE 4093 02:32:45,840 --> 02:32:48,880 WHITED MATTER LESIONS LIKE 4094 02:32:48,880 --> 02:32:49,600 EDEMA, DISCIPLINARY MILEINATION, 4095 02:32:49,600 --> 02:32:51,880 GLUE MARIOUSOSEIS AND THERE IS A 4096 02:32:51,880 --> 02:32:58,840 REDUCTION IN THIS AND INCREASED 4097 02:32:58,840 --> 02:32:59,280 [INDISCERNIBLE]. 4098 02:32:59,280 --> 02:33:04,280 DTI ALSO DEMONSTRATES BRAIN 4099 02:33:04,280 --> 02:33:06,280 CONNECTION THROUGH GRAPH 4100 02:33:06,280 --> 02:33:07,600 THEORIES, GLOBALENTIOUS 4101 02:33:07,600 --> 02:33:09,640 FICIENCYS CLUSTERING CO 4102 02:33:09,640 --> 02:33:12,040 EFFICIENTS AND PATH LENGTH 4103 02:33:12,040 --> 02:33:14,240 MEASURE THE NETWORK'S ABILITY TO 4104 02:33:14,240 --> 02:33:14,880 EXCHANGE PARALLEL INFORMATION 4105 02:33:14,880 --> 02:33:17,280 WITH ALL BRAIN AREAS, CONNECT 4106 02:33:17,280 --> 02:33:18,040 IVITY INTEGRATION AROUND 4107 02:33:18,040 --> 02:33:18,840 INDIVIDUAL NODES. 4108 02:33:18,840 --> 02:33:20,840 HIGHER VALUES OF GE REFLECT 4109 02:33:20,840 --> 02:33:26,760 BETTER INFORMATION TRANSITS AND 4110 02:33:26,760 --> 02:33:33,760 BRAIN FUNCTION. 4111 02:33:33,760 --> 02:33:40,640 WE USE IT FOR RESULTS. 4112 02:33:40,640 --> 02:33:43,440 BONE MARROW WAS USED AS A SOURCE 4113 02:33:43,440 --> 02:33:48,000 OF HSC, IN 27 PATIENTS AND 4114 02:33:48,000 --> 02:33:49,160 PERIPHERAL BLOOD IN 1 PATIENT, 4115 02:33:49,160 --> 02:33:52,440 ALL FACIENTS WE CEIVED MILE 4116 02:33:52,440 --> 02:33:53,160 ABRAITIVE CONDITIONING REGIMEN 4117 02:33:53,160 --> 02:33:58,200 AND ALL PATIENTS FULLY GRAFTED 4118 02:33:58,200 --> 02:34:00,240 AFTER TRANSPLANT. 4119 02:34:00,240 --> 02:34:01,640 THIRTEEN PATIENTS HAD HEMOGLOBIN 4120 02:34:01,640 --> 02:34:04,400 S LEVELS LOWER THAN 30% BEFORE 4121 02:34:04,400 --> 02:34:07,160 STARTING THE CONDITIONING 4122 02:34:07,160 --> 02:34:08,920 REGIMEN. 4123 02:34:08,920 --> 02:34:10,800 ALL PATIENTS LOWER THAN 50% AT 4124 02:34:10,800 --> 02:34:14,240 TIME OF POST TRANSPLANTED DTI 4125 02:34:14,240 --> 02:34:16,240 EVALUATION, ACCEPT FOR 1 PATIENT 4126 02:34:16,240 --> 02:34:20,280 THAT DEVELOPED SECONDARY GRAPHED 4127 02:34:20,280 --> 02:34:20,880 FAILURE. 4128 02:34:20,880 --> 02:34:24,240 THREE PATIENTS HAD NEUROLOGICAL 4129 02:34:24,240 --> 02:34:25,240 TOXICITY ASSOCIATED WITH 4130 02:34:25,240 --> 02:34:30,440 CYCLOSPORIN WHICH WAS COMPLETELY 4131 02:34:30,440 --> 02:34:31,760 REVERSED AFTER THIS 4132 02:34:31,760 --> 02:34:33,160 CONCONTINUATION OF THE 4133 02:34:33,160 --> 02:34:34,360 TRANSPLANTATION, AT THE MOMENT 4134 02:34:34,360 --> 02:34:37,360 OF FOLLOW UP, 15 PATIENTS WERE 4135 02:34:37,360 --> 02:34:38,480 UNDERIMMUNOSUPPRESSION AND MEAN 4136 02:34:38,480 --> 02:34:40,800 LEVELS OF HB WERE HIGHER THAN 4137 02:34:40,800 --> 02:34:42,920 BEFORE TRANSPLANT. 4138 02:34:42,920 --> 02:34:44,440 ROBBER DTI EVALUATION WAS 4139 02:34:44,440 --> 02:34:46,440 PERFORMED BEFORE AND AT THE 4140 02:34:46,440 --> 02:34:50,080 MEETING OF 17 MONTHS AFTER 4141 02:34:50,080 --> 02:34:51,680 TRANSPLANT, MOST TRANSPLANTED 4142 02:34:51,680 --> 02:34:54,000 DTI OCCURRED AT LEAST 6 MONTHS 4143 02:34:54,000 --> 02:34:55,400 AFTER THE LESS BLOOD TRANSFUSION 4144 02:34:55,400 --> 02:34:57,600 IN ALL PATIENTS AND NONE OF THE 4145 02:34:57,600 --> 02:35:00,080 PATIENT PRESENT THE NEW STROKES 4146 02:35:00,080 --> 02:35:05,600 AFTER TRANSPLANT BUT ARE SILENT 4147 02:35:05,600 --> 02:35:06,280 ARE OVER. 4148 02:35:06,280 --> 02:35:08,360 FRACTIONAL AND THE RESULT OF 4149 02:35:08,360 --> 02:35:11,000 INCREASE, THE MEAN RATIO IS 4150 02:35:11,000 --> 02:35:13,520 MAXIMUM REDUCE IT AND GLOBAL 4151 02:35:13,520 --> 02:35:14,800 EFFICIENCY IMPROVED. 4152 02:35:14,800 --> 02:35:16,720 THE REVERSIBLE OF CHANGE AFTER 4153 02:35:16,720 --> 02:35:18,440 TRANSPLANT SUGGESTS AN 4154 02:35:18,440 --> 02:35:20,760 INCOMPLETE TISSUE IPT GREATER 4155 02:35:20,760 --> 02:35:21,040 PAIRMENT. 4156 02:35:21,040 --> 02:35:21,640 IMPROVED MEASUREMENTS REFLECT 4157 02:35:21,640 --> 02:35:27,240 SOME DEGREE OF MILEIN REPAIR, 4158 02:35:27,240 --> 02:35:27,920 [INDISCERNIBLE]. 4159 02:35:27,920 --> 02:35:31,440 SICKLE CELL PATIENT HAD A LOWER 4160 02:35:31,440 --> 02:35:35,640 [INDISCERNIBLE] BEFORE 4161 02:35:35,640 --> 02:35:37,360 TRANSPLANT COMPARED TO HEALTH 4162 02:35:37,360 --> 02:35:38,640 CONTROLS, AFTER TRANSPLANT IT 4163 02:35:38,640 --> 02:35:40,680 WAS INCREASE AND WAS NOT 4164 02:35:40,680 --> 02:35:51,840 DIFFERENT FROM HEALTH CONTROLS. 4165 02:35:51,840 --> 02:35:53,040 GLOBAL EFFICIENCY INCREASED 4166 02:35:53,040 --> 02:35:54,400 AFTER THE PROCEDURE, 4167 02:35:54,400 --> 02:35:55,480 DEMONSTRATING A POTENTIAL 4168 02:35:55,480 --> 02:35:57,120 IMPROVEMENT OF BRAIN 4169 02:35:57,120 --> 02:36:00,640 STRUBLGHTURE CONNECTIVITY, WHICH 4170 02:36:00,640 --> 02:36:06,320 CAN BE ASSOCIATED WITH BETTER 4171 02:36:06,320 --> 02:36:06,640 NEUROLOGICAL 4172 02:36:06,640 --> 02:36:07,280 OUTCOMES--NEUROPSYCHOLOGICAL 4173 02:36:07,280 --> 02:36:07,840 OUTCOMES. 4174 02:36:07,840 --> 02:36:10,760 WE WILL INCORPORATE THIS IN 4175 02:36:10,760 --> 02:36:12,000 FUTURE STUDIES. 4176 02:36:12,000 --> 02:36:15,240 WE CONCLUDE THAD WE CAN REVERSE 4177 02:36:15,240 --> 02:36:17,000 STRUCTURAL BRAIN TISSUE DAMAGE 4178 02:36:17,000 --> 02:36:19,840 IN SCD PATIENTS BUT SPECIFIC 4179 02:36:19,840 --> 02:36:21,280 MECHANISMS OF IMPROVEMENT AND 4180 02:36:21,280 --> 02:36:22,640 CONTRIBUTING FACTORS SHOULD BE 4181 02:36:22,640 --> 02:36:26,360 BETTER INVESTIGATED BY FUTURE 4182 02:36:26,360 --> 02:36:27,160 STUDIES. 4183 02:36:27,160 --> 02:36:29,400 LIKE INCREASE HBS, AND REDUCED 4184 02:36:29,400 --> 02:36:31,720 HBS LEVELS AND ATTENUATE 4185 02:36:31,720 --> 02:36:32,640 ENDOTHELIAL DAMAGE. 4186 02:36:32,640 --> 02:36:35,160 NOW, I'M GOING TO PRESENT THE 4187 02:36:35,160 --> 02:36:37,120 CLINICAL CASE OF A PATIENT WHO 4188 02:36:37,120 --> 02:36:40,920 WAS NOT INCLUDED IN THE PREVIOUS 4189 02:36:40,920 --> 02:36:43,200 STUDY DUE TO EXTENSIVE 4190 02:36:43,200 --> 02:36:44,920 INVOLVEMENT OF CENTRAL NERVOUS 4191 02:36:44,920 --> 02:36:46,000 SYSTEM BEFORE TRANSPLANT. 4192 02:36:46,000 --> 02:36:48,560 IT IS AN 11 YEAR-OLD BOY, WITH 4193 02:36:48,560 --> 02:36:52,960 SICKLE CELL ANEMIA, HE HAD 3 4194 02:36:52,960 --> 02:36:55,280 ESCHEMIC STROKES WITH LEVEL 4195 02:36:55,280 --> 02:36:56,600 HEMIPARISSIES BEFORE THE 4196 02:36:56,600 --> 02:36:57,120 TRANSPLANT. 4197 02:36:57,120 --> 02:37:00,440 HE RECEIVED AN HLI IDENTICAL 4198 02:37:00,440 --> 02:37:03,040 SIBLING TRANSPLANT, THE DONOR 4199 02:37:03,040 --> 02:37:05,440 WAS A 12 YEAR-OLD BY WITH SICKLE 4200 02:37:05,440 --> 02:37:06,640 CELL TRAIT. 4201 02:37:06,640 --> 02:37:09,040 THE CO CONDITIONING RENAL CANCER 4202 02:37:09,040 --> 02:37:13,640 MEN CONSISTED OF FLUBU, AND ATG, 4203 02:37:13,640 --> 02:37:15,760 THE SOURCE OF THE STEM CELL WAS 4204 02:37:15,760 --> 02:37:18,640 BONE MARROW. 4205 02:37:18,640 --> 02:37:22,200 THE GVHD CONSISTED OF 4206 02:37:22,200 --> 02:37:25,320 METHOTREKSATE, CYCLOSPORIN AND 4207 02:37:25,320 --> 02:37:27,400 SEBS QUENT SIROLIMUS, AND AFTER 4208 02:37:27,400 --> 02:37:29,960 TRANSPLANT HE HAD MIXED CHIMERA 4209 02:37:29,960 --> 02:37:31,440 AND SICKLE CELL TRAIT. 4210 02:37:31,440 --> 02:37:35,080 HERE IS THE PRETRANSPLANT, MRI 4211 02:37:35,080 --> 02:37:37,040 WITH EXTENSE IEVER LESIONS 4212 02:37:37,040 --> 02:37:43,640 MAINLY IN THE RIGHT HEMEIS FEAR. 4213 02:37:43,640 --> 02:37:47,000 HE HAD MARKED STENOSIS OF THE 4214 02:37:47,000 --> 02:37:50,840 ARTERY WITH COLLATERAL 4215 02:37:50,840 --> 02:37:51,880 CIRCULATION WITH [INDISCERNIBLE] 4216 02:37:51,880 --> 02:37:52,560 PATTERN. 4217 02:37:52,560 --> 02:37:54,120 ONE YEAR AFTER TRANSPLANTATION, 4218 02:37:54,120 --> 02:37:58,200 HE HAD A MARKED REDUCTION OF 4219 02:37:58,200 --> 02:38:02,840 STENOSIS AND COLLATERAL THROUGH 4220 02:38:02,840 --> 02:38:03,480 COLLECTION. 4221 02:38:03,480 --> 02:38:05,800 WE PERFORMED DTI ASSESSMENT AND 4222 02:38:05,800 --> 02:38:07,200 IDENTIFY AN INCREASE IN 4223 02:38:07,200 --> 02:38:08,880 FRACTIONAL [INDISCERNIBLE] IN 4224 02:38:08,880 --> 02:38:10,640 THE LEFT HEMEIS FEAR AND NO 4225 02:38:10,640 --> 02:38:13,000 DIFFERENCE IN THE RIGHT HEMEIS 4226 02:38:13,000 --> 02:38:14,360 SPHERE, PROBABLY BECAUSE THERE 4227 02:38:14,360 --> 02:38:16,320 WAS NO VIABLE BRAIN TISSUE IN 4228 02:38:16,320 --> 02:38:23,040 THAT, IN THE RIGHT HEMISPHERE. 4229 02:38:23,040 --> 02:38:23,840 EIGHTEEN MONTHS AFTER 4230 02:38:23,840 --> 02:38:26,720 TRANSPLANT, THE PATIENT WAS NOT 4231 02:38:26,720 --> 02:38:29,160 USING IMMUNOSUPPRESSION AND HAD 4232 02:38:29,160 --> 02:38:29,520 NO GVHD. 4233 02:38:29,520 --> 02:38:31,680 TWO YEARS AFTER THE PROCEDURE, 4234 02:38:31,680 --> 02:38:34,440 THERE WAS NO EVIDENCE OF SICKLE 4235 02:38:34,440 --> 02:38:36,160 CELL ANEMIA, THE PATIENT HAD 4236 02:38:36,160 --> 02:38:38,880 IMPROVEMENT OF STRENGTH AND 4237 02:38:38,880 --> 02:38:44,000 MOTOR COORDINATION AND WAS 4238 02:38:44,000 --> 02:38:45,680 ATTENDING REGULAR SCHOOL. 4239 02:38:45,680 --> 02:38:47,440 IN CONCLUSION, IMPROVEMENTS IN 4240 02:38:47,440 --> 02:38:52,320 DTI MEASURES OF BRAIN TISSUE AND 4241 02:38:52,320 --> 02:38:54,120 IN VASCUE LOPATHY PATIENTS 4242 02:38:54,120 --> 02:38:54,840 DEMONSTRATE THAT ENTERTAIN 4243 02:38:54,840 --> 02:38:57,240 INJURY MAY BE REVERSIBLE AFTER 4244 02:38:57,240 --> 02:38:59,440 TRANSPLANTATION, IN THIS WAY, 4245 02:38:59,440 --> 02:39:01,480 EFFORTS ARE WARRANTED TO REFER 4246 02:39:01,480 --> 02:39:06,520 PATIENTS TO HSCT EARLY IN 4247 02:39:06,520 --> 02:39:31,040 DISEASE COURSE. 4248 02:39:31,040 --> 02:39:31,600 I WOULD-- 4249 02:39:31,600 --> 02:39:32,840 >> THANK YOU SO MUCH, THERE ARE 4250 02:39:32,840 --> 02:39:38,040 A COUPLE OF QUESTIONS FOR THE 4251 02:39:38,040 --> 02:39:45,680 CHAT, I WOULD LOOK AT THOSE AND 4252 02:39:45,680 --> 02:39:45,920 RESPOND. 4253 02:39:45,920 --> 02:39:47,240 STEPHANIE WHAT'S THE EXPERIENCE 4254 02:39:47,240 --> 02:39:49,640 OF DTI IN OTHER HOGGER ANS SUCH 4255 02:39:49,640 --> 02:39:51,200 AS BONE MARROW? 4256 02:39:51,200 --> 02:39:55,880 >> WE DIDN'T PERFORM THIS UNTIL 4257 02:39:55,880 --> 02:39:57,080 NOW BUT IT'S POSSIBLE TO DISCUSS 4258 02:39:57,080 --> 02:40:01,160 IT FOR THE FUTURE. 4259 02:40:01,160 --> 02:40:02,600 ROOK, I DON'T SEE ANY OTHER 4260 02:40:02,600 --> 02:40:04,080 QUESTIONS AT THE MOMENT SO THANK 4261 02:40:04,080 --> 02:40:05,480 YOU AGAIN FOR YOUR PRESENTATION 4262 02:40:05,480 --> 02:40:09,240 AND IF THERE ARE ANY COMMENTS IN 4263 02:40:09,240 --> 02:40:10,840 THE CHAT, PLEASE RESPOND TO 4264 02:40:10,840 --> 02:40:12,480 THEM. 4265 02:40:12,480 --> 02:40:13,120 THANK YOU. 4266 02:40:13,120 --> 02:40:19,480 >> OKAY, SO WE MOVE NEXT TO CURE 4267 02:40:19,480 --> 02:40:23,160 SICKLE SET 4268 02:40:23,160 --> 02:40:26,120 METADALLASCOWBOYS.COMA CATALOG 4269 02:40:26,120 --> 02:40:30,000 AND DR. JERREN STRATFORD, WILL 4270 02:40:30,000 --> 02:40:32,320 BE PRESENTING INSTEADY OF 4271 02:40:32,320 --> 02:40:36,440 DR. HELEN PAN. 4272 02:40:36,440 --> 02:40:36,840 DR. STRATFORD? 4273 02:40:36,840 --> 02:40:39,880 >> HELLO, CAN YOU SEE MY SLIDES? 4274 02:40:39,880 --> 02:40:41,760 >> YES WE CAN,. 4275 02:40:41,760 --> 02:40:43,360 >> YES, UNFORTALATELY DR. PAN IS 4276 02:40:43,360 --> 02:40:44,640 UNDER THE WEATHER AND WAS NOT 4277 02:40:44,640 --> 02:40:46,960 ABLE TO PRESENT SO I AM GOING TO 4278 02:40:46,960 --> 02:40:48,120 TAKE HER PLACE AND TALK ABOUT 4279 02:40:48,120 --> 02:40:50,240 SOME OF THE WORK THAT WE'VE 4280 02:40:50,240 --> 02:40:53,800 ABOUT KNOW DOING WITH THE CURE 4281 02:40:53,800 --> 02:41:03,760 SICKLE CELL METADATA CATALOG. 4282 02:41:03,760 --> 02:41:08,400 SO THE CATALOG IS A TOOL TO MAKE 4283 02:41:08,400 --> 02:41:11,880 DETAILSA FAIR, SO IT'S IT STANDS 4284 02:41:11,880 --> 02:41:13,360 FOR ACCESSIBLE, INTEROPERABLE 4285 02:41:13,360 --> 02:41:15,560 AND MAKING IT MORE, AND WE'RE 4286 02:41:15,560 --> 02:41:17,680 FOCUSING ON MAKING THE DATA MORE 4287 02:41:17,680 --> 02:41:17,960 FINDABLE. 4288 02:41:17,960 --> 02:41:19,840 SO SICKLE CELL RESEARCH HAS BEEN 4289 02:41:19,840 --> 02:41:22,440 ONGOING FOR SOMETIME AND SOME OF 4290 02:41:22,440 --> 02:41:23,840 THESE STUDIES HAVE IMMENSE 4291 02:41:23,840 --> 02:41:25,360 RESOURCES THAT WERE INVESTED 4292 02:41:25,360 --> 02:41:29,520 INTO THEM AND CONTINUE TO ADD 4293 02:41:29,520 --> 02:41:30,480 VALUE TO RESEARCH COMMUNITY AND 4294 02:41:30,480 --> 02:41:34,880 SO BEING ABLE TO IDENTIFY THE 4295 02:41:34,880 --> 02:41:36,320 STUDIES THAT ARE THAT CONTAIN 4296 02:41:36,320 --> 02:41:37,600 INFORMATION THAT MAY BE 4297 02:41:37,600 --> 02:41:39,280 APPLICABLE TO YOUR SCIENTIFIC 4298 02:41:39,280 --> 02:41:43,000 QUESTION, IS A GREAT WAY FOR US 4299 02:41:43,000 --> 02:41:44,240 TO REUSE SOME OF THE INVESTMENT 4300 02:41:44,240 --> 02:41:45,440 THAT HAS GONE INTO THESE STUDIES 4301 02:41:45,440 --> 02:41:49,000 IN THE PAST AS WELL AS COMBINE 4302 02:41:49,000 --> 02:41:50,840 THEM WITH SOME OF THE OTHER 4303 02:41:50,840 --> 02:41:54,160 STUDIES TO ASK ADDITIONAL 4304 02:41:54,160 --> 02:41:55,040 SCIENTIFIC QUESTIONS. 4305 02:41:55,040 --> 02:41:58,240 AND SO TO DO THIS, WE CREATEDDA 4306 02:41:58,240 --> 02:42:00,120 I PUBLIC TOOL WHICH IS A PEB 4307 02:42:00,120 --> 02:42:02,440 PORTAL WHERE USERS CAN COME, AND 4308 02:42:02,440 --> 02:42:04,480 IDENTIFY DATA SETS THAT MAY BE 4309 02:42:04,480 --> 02:42:06,800 APPLICABLE TO THEIR SCIENTIFIC 4310 02:42:06,800 --> 02:42:07,240 QUESTIONS. 4311 02:42:07,240 --> 02:42:09,840 SO TO DATE, WE'VE ALREADY 4312 02:42:09,840 --> 02:42:12,680 INCLUDED 20 STUDIES INTO THE 4313 02:42:12,680 --> 02:42:13,840 METADATA CATALOG, A NUMBER OF 4314 02:42:13,840 --> 02:42:16,520 THESE HAVE COME FROM EITHER 4315 02:42:16,520 --> 02:42:17,960 BIOLINK OR BIODATA CATALYST, WE 4316 02:42:17,960 --> 02:42:19,280 HAVE STUDIES FROM TOP MED AS 4317 02:42:19,280 --> 02:42:20,880 WELL AS 8 OTHER STUDIES, WHICH 4318 02:42:20,880 --> 02:42:23,040 WE WILL TALK ABOUT IN A MINUTE. 4319 02:42:23,040 --> 02:42:25,160 AND THE METHOD THAT WE HAVE GONE 4320 02:42:25,160 --> 02:42:27,800 THROUGH, TO MAKE THESE DATA MORE 4321 02:42:27,800 --> 02:42:30,640 FINDABLE IS BY CURATING THE 4322 02:42:30,640 --> 02:42:32,520 STUDIES INTO A SET OF DATA 4323 02:42:32,520 --> 02:42:34,320 ELEMENTS, SO WE HAVE LOOKED AT 4324 02:42:34,320 --> 02:42:37,160 THE VARIABLES THAT WERE 4325 02:42:37,160 --> 02:42:39,880 COLLECTED, AND ORGANIZED THEM IN 4326 02:42:39,880 --> 02:42:42,840 A WAY THAT THERE IS AN OVERLYING 4327 02:42:42,840 --> 02:42:45,480 CONCEPT, SUBCONCEPT AND THE DATA 4328 02:42:45,480 --> 02:42:47,040 ELEMENT THEMSELVES, AND HAVE 4329 02:42:47,040 --> 02:42:48,440 CURATED THE VARIABLES ACROSS 4330 02:42:48,440 --> 02:42:50,720 THESE STUDIES INTO THERE 4331 02:42:50,720 --> 02:42:51,280 HIERARCHY. 4332 02:42:51,280 --> 02:42:52,920 IN ADDITION WE'VE IDENTIFIED 4333 02:42:52,920 --> 02:42:56,960 STUDIES THAT USED PATIENT 4334 02:42:56,960 --> 02:42:58,560 REPORTED OUTCOMES, AND 4335 02:42:58,560 --> 02:43:02,200 IDENTIFIED WHICH 1S DID THIS AS 4336 02:43:02,200 --> 02:43:03,720 THAT IS A STANDARDIZED METRIC 4337 02:43:03,720 --> 02:43:05,840 AND EACH OF THESE STUDIES VALID 4338 02:43:05,840 --> 02:43:09,600 USED THE SAME RUBRIC AS THEY 4339 02:43:09,600 --> 02:43:11,520 COLLECTED THIS INFORMATION. 4340 02:43:11,520 --> 02:43:13,960 AND SO, BY HAVING THIS, YOU KNOW 4341 02:43:13,960 --> 02:43:16,160 KIND OF FRAMEWORK, WE'RE ABLE TO 4342 02:43:16,160 --> 02:43:17,760 BROWSE THESE STUDIES WITHOUT 4343 02:43:17,760 --> 02:43:18,840 ACTUALLY NEEDING TO KNOW MUCH 4344 02:43:18,840 --> 02:43:22,040 ABOUT WHAT THE ORIGINAL STUDY 4345 02:43:22,040 --> 02:43:23,640 INTENT WAS IN ORDER TO DETERMINE 4346 02:43:23,640 --> 02:43:26,760 WHETHER THAT DATA IS VALUABLE 4347 02:43:26,760 --> 02:43:29,960 FOR YOUR PARTICULAR QUESTION. 4348 02:43:29,960 --> 02:43:36,760 SO THE METADATA CATALOG IS 4349 02:43:36,760 --> 02:43:38,480 INDEXED SO THE WAY WE CAN GO 4350 02:43:38,480 --> 02:43:43,040 ABOUT THIS IS BY BROWSING THIS 4351 02:43:43,040 --> 02:43:44,280 CURATION AT BOTH THE STUDY LEVEL 4352 02:43:44,280 --> 02:43:47,640 AND AT THE VARIABLE LEVEL, AND 4353 02:43:47,640 --> 02:43:49,880 WE CAN THEN START TO COMBINE 4354 02:43:49,880 --> 02:43:51,440 INFORMATION ACROSS THE VARIOUS 4355 02:43:51,440 --> 02:43:53,200 ELEMENTS IN ORDER TO IDENTIFY 4356 02:43:53,200 --> 02:43:54,560 THE STUDIES AND THE VARIABLES 4357 02:43:54,560 --> 02:43:57,360 THAT ARE APPLICABLE TO OUR 4358 02:43:57,360 --> 02:43:57,640 QUESTIONS. 4359 02:43:57,640 --> 02:43:59,800 WE CAN BROWSE THEM IN A 4360 02:43:59,800 --> 02:44:02,320 HIERARCHY, WE CAN ALSO DO KEY 4361 02:44:02,320 --> 02:44:03,880 WORD SEARCHES OR IN COMBINATION 4362 02:44:03,880 --> 02:44:04,760 SEARCHES WHICH I WILL SHOW 4363 02:44:04,760 --> 02:44:07,760 NUCLEOTIDES THE NEXT FEW SLIDES. 4364 02:44:07,760 --> 02:44:12,720 SO THIS IS A SCREEN SHOT OF THE 4365 02:44:12,720 --> 02:44:13,640 WEB PORTAL. 4366 02:44:13,640 --> 02:44:15,800 AND THIS IS KIND OF THE LANDING 4367 02:44:15,800 --> 02:44:16,040 PAGE. 4368 02:44:16,040 --> 02:44:17,600 SO THERE'S A NUMBER OF DIFFERENT 4369 02:44:17,600 --> 02:44:19,240 RESOURCES AND DIRECTIONS CAN YOU 4370 02:44:19,240 --> 02:44:19,560 GO. 4371 02:44:19,560 --> 02:44:21,240 ONE OF THE FIRST THINGS THAT 4372 02:44:21,240 --> 02:44:23,920 PEEP - 4373 02:44:23,920 --> 02:44:24,920 -PEOPLE MAY WANT TO 4374 02:44:24,920 --> 02:44:26,040 UNDERSTAND IS THAT THE STUDIES 4375 02:44:26,040 --> 02:44:29,840 THAT HAVE BEEN INGESTED SO IF 4376 02:44:29,840 --> 02:44:31,480 YOU CLICK ON OUR BROWSE STUDIES 4377 02:44:31,480 --> 02:44:33,880 IT WILL TAKE YOU TO A PAGE THAT 4378 02:44:33,880 --> 02:44:37,440 LOOKS LIKE THIS. 4379 02:44:37,440 --> 02:44:38,680 FROM THISPARAGE, YOU CAN--FROM 4380 02:44:38,680 --> 02:44:40,440 THIS PAGE, YOU CAN IDENTIFY THE 4381 02:44:40,440 --> 02:44:40,840 STUDIES. 4382 02:44:40,840 --> 02:44:42,000 AS WELL AS VICTORIES THAT ARE 4383 02:44:42,000 --> 02:44:43,160 INVOLVE WIDE CREATING IT AND MAY 4384 02:44:43,160 --> 02:44:44,240 HAVE INFORMATION FOR YOU AS WELL 4385 02:44:44,240 --> 02:44:45,280 AS THE DATA LOCATIONS. 4386 02:44:45,280 --> 02:44:47,040 SO THERE ARE A NUMBER OF STUDIES 4387 02:44:47,040 --> 02:44:52,720 WHICH ARE AVAILABLE IN PUBLIC 4388 02:44:52,720 --> 02:44:53,000 LOCATIONS. 4389 02:44:53,000 --> 02:44:55,280 AND REPOSITORIES THAT YOU CAN 4390 02:44:55,280 --> 02:44:56,120 PULL, HOWEVER THERE ARE SOME 4391 02:44:56,120 --> 02:44:57,440 STUDIES THAT ARE ONGOING AND MAY 4392 02:44:57,440 --> 02:44:59,000 RESIDE WITH THE INVESTIGATORS OR 4393 02:44:59,000 --> 02:44:59,640 THEIR INTUITY. 4394 02:44:59,640 --> 02:45:01,760 SO BEING ABLE TO IDENTIFY WHERE 4395 02:45:01,760 --> 02:45:03,000 THOSE STUDIES ARE AND HOW YOU 4396 02:45:03,000 --> 02:45:06,200 CAN GET ACCESS TO THAT DATA IS 4397 02:45:06,200 --> 02:45:07,240 ALSO HIGHLY VALUABLE. 4398 02:45:07,240 --> 02:45:10,600 IN ADDITION, WE ALSO CURATE THE 4399 02:45:10,600 --> 02:45:11,400 NUMBER OF PARTICIPANTS WHICH 4400 02:45:11,400 --> 02:45:14,440 WERE IN THE STUDIES SO CAN YOU 4401 02:45:14,440 --> 02:45:15,240 UNDERSTAND THE SCOPE AND THE 4402 02:45:15,240 --> 02:45:18,120 SIZE OF THE STUDY, NOW FOR 4403 02:45:18,120 --> 02:45:25,160 INSTANCE WITH THIS PLACE HERE, 4404 02:45:25,160 --> 02:45:28,640 THIS DISPLACE WAS INFORMATION WE 4405 02:45:28,640 --> 02:45:30,880 PULLED FROM CLINICAL TRIALS .GOV 4406 02:45:30,880 --> 02:45:32,080 VERY EARLY IN THE PROCESS AND WE 4407 02:45:32,080 --> 02:45:33,840 KNOW THERE ARE MORE THAN 16 4408 02:45:33,840 --> 02:45:34,760 SUBJECTS SO WE'RE CONSTANTLY 4409 02:45:34,760 --> 02:45:35,880 LOOKING TO GET ADDITIONAL 4410 02:45:35,880 --> 02:45:39,040 RESOURCES TO BE ABLE TO UPDATE 4411 02:45:39,040 --> 02:45:41,400 THIS INFORMATION AND MAKE IT THE 4412 02:45:41,400 --> 02:45:43,040 MOST UP TO DATE INFORMATION SO 4413 02:45:43,040 --> 02:45:44,000 THAT PEOPLE CAN UNDERSTAND THE 4414 02:45:44,000 --> 02:45:46,440 SIZE OF THE STUDY AND HOW MANY 4415 02:45:46,440 --> 02:45:48,360 PARTICIPANTS, POTENTIALLY HAVE 4416 02:45:48,360 --> 02:45:49,640 THAT INFORMATION AND SO WE'RE 4417 02:45:49,640 --> 02:45:51,760 ALWAYS LOOKING FOR COLLABORATORS 4418 02:45:51,760 --> 02:45:54,320 WHO MAY BE ABLE TO PROVIDE US 4419 02:45:54,320 --> 02:45:56,080 WITH ADDITIONAL INFORMATION 4420 02:45:56,080 --> 02:45:58,280 WHICH WAS BEYOND THE KIND OF 4421 02:45:58,280 --> 02:46:01,960 PUBLIC DATA THAT WE ORIGINALLY 4422 02:46:01,960 --> 02:46:06,880 WERE ABLE TO GATHER. 4423 02:46:06,880 --> 02:46:09,400 SO WHEN WE LOOK AT THE STUDIES 4424 02:46:09,400 --> 02:46:11,120 WE CAN CLICK ON AN INDIVIDUAL 4425 02:46:11,120 --> 02:46:12,400 STUDY AND WE CAN GAIN MORE 4426 02:46:12,400 --> 02:46:15,400 INFORMATION ABOUT IT SO THIS IS 4427 02:46:15,400 --> 02:46:17,840 INFORMATION AT THE STUDY LEVEL. 4428 02:46:17,840 --> 02:46:18,520 THE METADATA FROM THE STUDY 4429 02:46:18,520 --> 02:46:21,680 LEVEL THAT WE HAVE CURATED INTO 4430 02:46:21,680 --> 02:46:22,760 A STANDARDIZED FORMAT SO WE CAN 4431 02:46:22,760 --> 02:46:24,360 GET INFORMATION ABOUT THE STUDY, 4432 02:46:24,360 --> 02:46:25,800 WHEN IT WAS CONDUCTED, WHAT TYPE 4433 02:46:25,800 --> 02:46:29,240 OF STUDY IT WAS, LINKS TO ANY 4434 02:46:29,240 --> 02:46:32,560 SORT OF OTHER DATABASES OR 4435 02:46:32,560 --> 02:46:33,240 WEBSITES THAT CONTAIN 4436 02:46:33,240 --> 02:46:36,080 INFORMATION ABOUT IT, AS WELL AS 4437 02:46:36,080 --> 02:46:37,320 BEING ABLE TO SEE THE RESEARCH 4438 02:46:37,320 --> 02:46:40,480 THAT HAS COME FROM IT AND 4439 02:46:40,480 --> 02:46:42,240 PUBLICATIONS, INFORMATION ABOUT 4440 02:46:42,240 --> 02:46:43,800 THE STUDY POPULATION, ALL 4441 02:46:43,800 --> 02:46:45,520 SUBJECT, OR SORRY, STUDY LEVEL 4442 02:46:45,520 --> 02:46:47,040 METADATA THAT WE WERE ABLE TO 4443 02:46:47,040 --> 02:46:49,360 GATHER ABOUT THE STUDY. 4444 02:46:49,360 --> 02:46:56,800 BUT IN ADDITION, THERE'S ALSO 4445 02:46:56,800 --> 02:46:58,000 VARIABLE LEVEL METADAT AND 4446 02:46:58,000 --> 02:46:59,280 THAT'S CONTAINED HERE IN THE 4447 02:46:59,280 --> 02:47:00,720 LAST 2 TABS HERE IN YELLOW AND 4448 02:47:00,720 --> 02:47:04,680 THE DAILY BASIS AT ELEMENTS AND 4449 02:47:04,680 --> 02:47:05,400 THE PRO MEASURES. 4450 02:47:05,400 --> 02:47:07,960 SO FOR INSTANCE IF YOU CLICK ON 4451 02:47:07,960 --> 02:47:08,840 THE DATA ELEMENTS TAB, CAN YOU 4452 02:47:08,840 --> 02:47:10,640 SEE A NUMBER OF THE CONCEPTS 4453 02:47:10,640 --> 02:47:12,920 WHICH ARE KIND OF THE HIGH LEVEL 4454 02:47:12,920 --> 02:47:16,120 OF OUR HIERARCHY AND THE NUMBER 4455 02:47:16,120 --> 02:47:20,080 OF VARIABLES THAT WERE COLLECTED 4456 02:47:20,080 --> 02:47:22,400 WITHIN THAT CONCEPT AND IF YOU 4457 02:47:22,400 --> 02:47:25,120 WERE TO CLIEK ON THIS BAR, IT 4458 02:47:25,120 --> 02:47:26,280 WOULD EXPAND AND YOU WOULD BE 4459 02:47:26,280 --> 02:47:27,960 ABLE TO SEE ALL OF THE 4460 02:47:27,960 --> 02:47:29,120 SUBCONCEPTS AND YOU CAN CLICK ON 4461 02:47:29,120 --> 02:47:31,360 THOSE FURTHER TO GET THE 4462 02:47:31,360 --> 02:47:32,720 ELEMENTS THAT RESIDE IF THERE SO 4463 02:47:32,720 --> 02:47:34,360 CAN YOU REALLY DIG DOWN INTO A 4464 02:47:34,360 --> 02:47:36,000 PARTICULAR STUDY AND SEE WHAT 4465 02:47:36,000 --> 02:47:39,040 TYPE OF DATA WAS COLLECTED. 4466 02:47:39,040 --> 02:47:41,440 NOW SIMILAR, CAN YOU ALSO DO 4467 02:47:41,440 --> 02:47:43,040 THAT FOR SOME OF THE PATIENT 4468 02:47:43,040 --> 02:47:45,160 REPORTED OUTCOMES SO THAT OUR 4469 02:47:45,160 --> 02:47:46,120 PRO MEASURES, SO IN THIS CASE, 4470 02:47:46,120 --> 02:47:48,840 THERE WAS A NUMBER OF PRO 4471 02:47:48,840 --> 02:47:50,120 MEASURE VARIABLES THAT DEALT 4472 02:47:50,120 --> 02:47:53,080 WITH MENTAL HEALTH AND 4473 02:47:53,080 --> 02:47:53,920 NEURODEVELOPMENT AND SO IF THIS 4474 02:47:53,920 --> 02:47:55,240 IS SOMETHING THAT IS INTEREST TO 4475 02:47:55,240 --> 02:47:58,440 YOUR STUDY, THAT MIGHT BE 1 WAY 4476 02:47:58,440 --> 02:48:00,960 CAN YOU GO ABOUT IT IS TO COME 4477 02:48:00,960 --> 02:48:03,200 TO THE STUDY PAGE AND LOOK AT 4478 02:48:03,200 --> 02:48:07,080 THE PARTICULAR PRO MEASURES. 4479 02:48:07,080 --> 02:48:08,280 NOW, HOWEVER, THERE ARE 20 4480 02:48:08,280 --> 02:48:09,840 STUDIES AND BEING ABLE TO LOOK 4481 02:48:09,840 --> 02:48:11,440 IN EACH 1 INDIVIDUALLY, HAS 4482 02:48:11,440 --> 02:48:12,720 VALUE BUT IF YOU WANTED TO LOOK 4483 02:48:12,720 --> 02:48:16,640 AT ALL OF THEM, THAT MIGHT TAKE 4484 02:48:16,640 --> 02:48:19,240 A LITTLE BIT OF TIME AND SO 4485 02:48:19,240 --> 02:48:21,440 THERE ARE OTHER BROWSING 4486 02:48:21,440 --> 02:48:22,400 FEATURES IN THE CATALOG THAT 4487 02:48:22,400 --> 02:48:24,320 MAKE IT EASY TO LOOK ACROSS ALL 4488 02:48:24,320 --> 02:48:27,680 OF THE STUDIES. 4489 02:48:27,680 --> 02:48:30,280 SO FOR INSTANCE, WHEN WE LOOK 4490 02:48:30,280 --> 02:48:32,280 HERE AT THE BROWSE BY DATA 4491 02:48:32,280 --> 02:48:36,240 ELEMENT, WE CAN SEE THAT THE 4492 02:48:36,240 --> 02:48:37,920 HIGH LEVEL CONCEPTS WITHIN OUR 4493 02:48:37,920 --> 02:48:39,640 HIERARCHY OVER HERE ON THE 4494 02:48:39,640 --> 02:48:40,640 LEFT-HAND SIDE OF THE SCREEN AND 4495 02:48:40,640 --> 02:48:42,880 WE CAN CLICK ON THOSE AND EXPAND 4496 02:48:42,880 --> 02:48:46,080 THOSE MENUS AND WE CAN APPLY 4497 02:48:46,080 --> 02:48:48,560 FILTERS, SO WITHOUT APPLYING ANY 4498 02:48:48,560 --> 02:48:50,040 FULTERS TO THE DATA WE HAVE 20 4499 02:48:50,040 --> 02:48:53,280 STUDIES AND WE CAN SEE ALL OF 4500 02:48:53,280 --> 02:48:55,040 THOSE 20 STUDIES, BUT LET'S SAY 4501 02:48:55,040 --> 02:48:56,760 THAT WE'RE PARTICULARLY 4502 02:48:56,760 --> 02:48:58,160 INTERESTED IN SKELETAL AND JOINT 4503 02:48:58,160 --> 02:49:05,560 PAIN, SO IF WE WERE TO COME TO 4504 02:49:05,560 --> 02:49:06,640 OUR HIERARCHY ON EVERY HERE WE 4505 02:49:06,640 --> 02:49:08,720 CAN LOOK AT THE CLINICAL STATUS 4506 02:49:08,720 --> 02:49:11,600 CONCEPT, WE CAN COME DOWN TO THE 4507 02:49:11,600 --> 02:49:15,600 PAIN SUBCONCEPT AND WE COULD SEE 4508 02:49:15,600 --> 02:49:16,640 SKELETAL AND JOINT PAIN RIGHT 4509 02:49:16,640 --> 02:49:18,240 HERE AND WHEN WE APPLY THAT 4510 02:49:18,240 --> 02:49:20,000 FILTER WE NOW HAVE ONLY 8 4511 02:49:20,000 --> 02:49:23,360 STUDIES THAT WERE ABLE TO 4512 02:49:23,360 --> 02:49:25,280 COLLECT INFORMATION ON THE 4513 02:49:25,280 --> 02:49:28,120 SKELETAL AND JOINT PAIN. 4514 02:49:28,120 --> 02:49:30,200 AND SO WE NOW KNOW THE STUDIES 4515 02:49:30,200 --> 02:49:33,080 BUT WE ALSO MAY WANT TO DIG IN A 4516 02:49:33,080 --> 02:49:34,480 BIT DEEPER SO OVER HERE ON THE 4517 02:49:34,480 --> 02:49:35,680 RIGHT HAND SIDE OF THE SCREEN, 4518 02:49:35,680 --> 02:49:37,440 WE HAVE THE SHOW VARIABLES, SO 4519 02:49:37,440 --> 02:49:39,480 WHEN WE COMPLIK ON SHOW 4520 02:49:39,480 --> 02:49:42,040 VARIABLES, WE CAN HAVE A POP UP 4521 02:49:42,040 --> 02:49:46,000 THAT SHOWS US THE STUDY THAT 4522 02:49:46,000 --> 02:49:46,600 COLLECTED THE INFORMATION. 4523 02:49:46,600 --> 02:49:50,720 THE VARIABLE NAME FROM THE 4524 02:49:50,720 --> 02:49:52,840 STUDY, AND A DISKRIPGZ OF THE 4525 02:49:52,840 --> 02:49:53,920 VARIABLE THAT THEY CAPTURED. 4526 02:49:53,920 --> 02:49:57,440 SO HAVING THIS CURATED STRUCTURE 4527 02:49:57,440 --> 02:49:58,840 IS VERY VALUABLE, BECAUSE, IF I 4528 02:49:58,840 --> 02:50:01,880 WERE TO COME IN HERE AND JUST DO 4529 02:50:01,880 --> 02:50:04,440 A SEARCH FOR PAIN, I WOULD 4530 02:50:04,440 --> 02:50:07,600 PROBABLY GET PAIN ACROSS ALL 4531 02:50:07,600 --> 02:50:11,600 DIFFERENT TYPES OF DOMAINS SO I 4532 02:50:11,600 --> 02:50:13,080 CAN HAVE ABDOMINAL PAIN, 4533 02:50:13,080 --> 02:50:15,400 HEADACHES BUT I'M INTERESTED 4534 02:50:15,400 --> 02:50:16,440 PARTICULARLY IN SKELETAL PAIN. 4535 02:50:16,440 --> 02:50:18,040 ALSO FIELD FUNCTIONS WERE TO 4536 02:50:18,040 --> 02:50:19,320 SEARCH FOR JUST FOR SKELETAL 4537 02:50:19,320 --> 02:50:21,080 PAIN I WOULD MISS A LOT OF THESE 4538 02:50:21,080 --> 02:50:22,640 VARIABLES BECAUSE I DON'T HAVE 4539 02:50:22,640 --> 02:50:33,960 THESE KEY WORDS AND SOMETIMES WE 4540 02:50:33,960 --> 02:50:35,560 HAVE INFORMATION ABOUT PAIN AND 4541 02:50:35,560 --> 02:50:36,840 SO BY HAVING THESE CLUSTERED 4542 02:50:36,840 --> 02:50:38,600 TOGETHER WE CAN CURATE THESE 4543 02:50:38,600 --> 02:50:40,240 ACROSS MULTILE STUDIES WHICH 4544 02:50:40,240 --> 02:50:41,440 COLLECTED SIMILAR DATA AND THIS 4545 02:50:41,440 --> 02:50:43,080 HELPS US TO REALLY DIG DOWN AND 4546 02:50:43,080 --> 02:50:44,680 FIGURE OUT WHICH DATA IS 4547 02:50:44,680 --> 02:50:47,000 AVAILABLE FOR US IN ORDER TO 4548 02:50:47,000 --> 02:50:51,520 ANSWER SOME OF OUR SCIENCE 4549 02:50:51,520 --> 02:50:51,800 QUESTIONS. 4550 02:50:51,800 --> 02:50:54,720 SO THIS TABLE RIGHT HERE KIND OF 4551 02:50:54,720 --> 02:50:56,400 GRIEBS, WE HAVE THE STUDIES OVER 4552 02:50:56,400 --> 02:50:59,760 HERE ON THE LEFT-HAND SIDE, AND 4553 02:50:59,760 --> 02:51:01,440 WE HAVE THE--YOU KNOW OUR HIGH 4554 02:51:01,440 --> 02:51:04,960 LEVEL CONCEPTS IN OUR HIERARCHY 4555 02:51:04,960 --> 02:51:05,920 KRSES THE COLUMNS SO WHAT YOU 4556 02:51:05,920 --> 02:51:08,440 CAN SEE IS THAT WE DO HAVE VERY 4557 02:51:08,440 --> 02:51:10,440 GOOD COVERAGE ACROSS THE 4558 02:51:10,440 --> 02:51:12,160 CLENICAL STATUS OF PATIENTS AND 4559 02:51:12,160 --> 02:51:13,920 PARTICIPANTS IN THE STUDIES, 4560 02:51:13,920 --> 02:51:16,600 MOST OF THE STUDIES COLLECTED 4561 02:51:16,600 --> 02:51:19,440 IT, WE HAVE A LOT OF VARIABLES 4562 02:51:19,440 --> 02:51:21,640 ACROSS A LOT OF THESE DIFFERENT 4563 02:51:21,640 --> 02:51:22,840 DOMAINS HOWEVER WE DO NOTICE 4564 02:51:22,840 --> 02:51:26,160 THAT WE'RE KIND OF HAVE LOW 4565 02:51:26,160 --> 02:51:27,960 COVERAGE ON INFORMATION ABOUT 4566 02:51:27,960 --> 02:51:29,240 STUDIES THAT COLLECTED 4567 02:51:29,240 --> 02:51:31,080 INFORMATION ON ENVIRONMENTAL 4568 02:51:31,080 --> 02:51:31,440 EXPOSURES. 4569 02:51:31,440 --> 02:51:33,960 SO WE'RE CONSTANTLY LOOKING FOR 4570 02:51:33,960 --> 02:51:35,440 NEW STUDIES WHICH CAN COME IN 4571 02:51:35,440 --> 02:51:38,720 AND BE CURATED INTO THE METADATA 4572 02:51:38,720 --> 02:51:40,360 CATALOG THAT CAN HELP US BOLSTER 4573 02:51:40,360 --> 02:51:43,040 SOME OF THESE STUDIES AND MAKE 4574 02:51:43,040 --> 02:51:45,360 MORE DATA AVAILABLE ACROSS SOME 4575 02:51:45,360 --> 02:51:46,960 OF THESE CONCEPTS WHICH WE MAY 4576 02:51:46,960 --> 02:51:48,240 NOT HAVE HAD AS MUCH INFORMATION 4577 02:51:48,240 --> 02:51:49,840 ON FOR THE STUDIES THAT HAVE 4578 02:51:49,840 --> 02:51:55,400 ALREADY BEEN ADJUSTED TO THE 4579 02:51:55,400 --> 02:51:55,920 CATALOG. 4580 02:51:55,920 --> 02:51:58,040 SO THIS IS ALSO A VISUAL VIEW OF 4581 02:51:58,040 --> 02:52:00,600 THAT SO IF WE LOOK AT ALL OF THE 4582 02:52:00,600 --> 02:52:02,040 VARIABLES WE HAVE ACROSS ALL 20 4583 02:52:02,040 --> 02:52:03,720 OF OUR STUDIES WE CAN SEE THAT 4584 02:52:03,720 --> 02:52:04,920 THE VAST MAJORITY OF THEM ARE 4585 02:52:04,920 --> 02:52:05,720 COVERING INFORMATION ABOUT THE 4586 02:52:05,720 --> 02:52:07,960 CLINICAL IS IT THEUS AND 4587 02:52:07,960 --> 02:52:08,360 LABORATORY TESTS. 4588 02:52:08,360 --> 02:52:12,200 BUT WE ALSO DO HAVE A NUMBER OF 4589 02:52:12,200 --> 02:52:15,240 STUDIES WHICH ARE HELPING US 4590 02:52:15,240 --> 02:52:16,480 UNDERSTAND EXPOSURE, UTILIZATION 4591 02:52:16,480 --> 02:52:19,280 AND QUALITY OF HEALTHCARE 4592 02:52:19,280 --> 02:52:20,520 INFORMATION ABOUT THE OTHER 4593 02:52:20,520 --> 02:52:22,240 PEOPLE THAT ARE CARING AND 4594 02:52:22,240 --> 02:52:28,280 FAMILY MEMBERS THAT ARE 4595 02:52:28,280 --> 02:52:29,000 SUPPORTING AND BUILDING THIS OUT 4596 02:52:29,000 --> 02:52:31,080 AND BEING ABLE TO IDENTIFY NEW 4597 02:52:31,080 --> 02:52:34,440 AREAS OF RESEARCH WHICH MAY BE 4598 02:52:34,440 --> 02:52:35,720 VERY RELEVANT, THIS IS THE BREAK 4599 02:52:35,720 --> 02:52:38,120 DOWN OF HOW THE CURATION HAS 4600 02:52:38,120 --> 02:52:39,680 GONE FOR DATA ELEMENTS TO GIVE 4601 02:52:39,680 --> 02:52:41,120 YOU A BETTER IDEA ABOUT WHAT 4602 02:52:41,120 --> 02:52:50,240 TYPE OF VARIABLES ARE IN THE 4603 02:52:50,240 --> 02:52:52,200 STUDY SO FAR: SO IN ADDITION TO 4604 02:52:52,200 --> 02:52:54,960 VARIABLES ABOUT THE STANDARDIZED 4605 02:52:54,960 --> 02:52:57,640 METRICS AND RUBRICS FOR PATIENT 4606 02:52:57,640 --> 02:52:58,640 REPORTED OUTCOMES SO SIMILAR TO 4607 02:52:58,640 --> 02:53:01,080 THE WAY THE DATA ELEMENTS WERE, 4608 02:53:01,080 --> 02:53:04,360 WE HAVE 16 STUDIES THAT 4609 02:53:04,360 --> 02:53:06,240 COLLECTED INFORMATION ON PATIENT 4610 02:53:06,240 --> 02:53:06,640 REPORTED OUTCOMES. 4611 02:53:06,640 --> 02:53:08,680 HERE IS A LIST OF ALL 16 OF 4612 02:53:08,680 --> 02:53:10,920 THOSE STUDIES AND THE NUMBER OF 4613 02:53:10,920 --> 02:53:13,640 SUBJECTS THAT WERE INVOLVED IN 4614 02:53:13,640 --> 02:53:13,920 THOSE. 4615 02:53:13,920 --> 02:53:16,040 SIMILAR TO THE DATA ELEMENTS WE 4616 02:53:16,040 --> 02:53:17,560 HAVE OUR HIERARCHY OVER HERE ON 4617 02:53:17,560 --> 02:53:20,440 THE LEFT-HAND SIDE OF THE SCREEN 4618 02:53:20,440 --> 02:53:23,200 THAT LISTS, THE PATIENT REPORTED 4619 02:53:23,200 --> 02:53:23,440 OUTCOMES. 4620 02:53:23,440 --> 02:53:25,440 SO YOU'LL NOTICE THAT A LOT OF 4621 02:53:25,440 --> 02:53:27,400 THESE PATIENT REPORTED OUTCOMES 4622 02:53:27,400 --> 02:53:31,600 WERE ONLY USED BY 1 OF THE 4623 02:53:31,600 --> 02:53:34,040 STUDIES AND THAT IS--A LOT OF 4624 02:53:34,040 --> 02:53:35,560 STUDIES WE SRO BEEN GOING ON AND 4625 02:53:35,560 --> 02:53:36,960 HAVE A HISTORY AND SO BEING ABLE 4626 02:53:36,960 --> 02:53:40,160 TO HAVE THESE PATIENT REPORTED 4627 02:53:40,160 --> 02:53:43,760 OUTCOMES BECOME MORE PREVALENT 4628 02:53:43,760 --> 02:53:47,640 IS AS WE INJECT NEW STUDIES INTO 4629 02:53:47,640 --> 02:53:49,240 THE METADATA CATALOG, WE GET 4630 02:53:49,240 --> 02:53:51,480 ADDITIONAL STUDY SAYS WE'RE 4631 02:53:51,480 --> 02:53:52,520 USING SIMILAR INSTRUMENTS. 4632 02:53:52,520 --> 02:53:54,400 SO OUR PROMEASURES ARE A BIT 4633 02:53:54,400 --> 02:53:55,920 MORE IMMATURE, BUT AS WE INGEST 4634 02:53:55,920 --> 02:53:58,080 MORE AND MORE STUDIES WE'RE 4635 02:53:58,080 --> 02:53:59,160 FINDING THERE ARE MORE AND MORE 4636 02:53:59,160 --> 02:54:01,720 STUDIES THAT USE THEM AND WILL 4637 02:54:01,720 --> 02:54:02,920 HAVE DIRECTLY COMPARABLE DATA 4638 02:54:02,920 --> 02:54:06,680 ACROSS THE 2 DIFFERENT STUDY 4639 02:54:06,680 --> 02:54:06,880 TYPES. 4640 02:54:06,880 --> 02:54:15,040 SO SIMILAR TO WE DID WITH 4641 02:54:15,040 --> 02:54:17,520 DATA--[SO SIMILAR TO THE DATA 4642 02:54:17,520 --> 02:54:18,880 ELEMENTS, YOU KNOW THIS IS THE 4643 02:54:18,880 --> 02:54:20,640 LIST OF THE 16 STUDIES THAT WE 4644 02:54:20,640 --> 02:54:26,440 HAVE AS WELL AS THE HIGH 4645 02:54:26,440 --> 02:54:31,240 LEVEL,IRE ARCHY FOR FOR THE 4646 02:54:31,240 --> 02:54:32,480 PROMEASURES, SO THE PRO MEASURES 4647 02:54:32,480 --> 02:54:33,400 THAT WERE COLLECTED ACROSS THE 4648 02:54:33,400 --> 02:54:35,640 DIFFERENT IS IT THES ACROSS 4649 02:54:35,640 --> 02:54:36,840 VARIOUS DIFFERENT TYPES AND IF 4650 02:54:36,840 --> 02:54:38,280 WE CAN BUILD THIS OUT WITH 4651 02:54:38,280 --> 02:54:40,360 ADDITIONAL STUDIES THIS WILL BE 4652 02:54:40,360 --> 02:54:41,440 A USEFUL RESOURCE FOR THE 4653 02:54:41,440 --> 02:54:47,080 COMMUNITY IN THE FUTURE. 4654 02:54:47,080 --> 02:54:49,440 ONE OF THE THINGS WE HAVE AS 4655 02:54:49,440 --> 02:54:52,200 WELL IS A SEARCH FEATURE, AND 4656 02:54:52,200 --> 02:54:57,000 THE TOP OF MY SLIDE MIGHTING 4657 02:54:57,000 --> 02:54:58,120 MISSING OKAY, HERE IT IS. 4658 02:54:58,120 --> 02:55:04,240 SO WHAT WE HAVE HERE IS THE 4659 02:55:04,240 --> 02:55:09,120 ABILITY TO BY KEY WORD ACROSS 4660 02:55:09,120 --> 02:55:11,200 BOTH THE SUBJECTS LEVEL METADATA 4661 02:55:11,200 --> 02:55:13,320 AS WELL AS STUDY LEVEL METADAILY 4662 02:55:13,320 --> 02:55:16,920 BASIS THEA SO IN THIS CASE IF WE 4663 02:55:16,920 --> 02:55:21,200 WANT TO COLLECT STUDIES WITH 4664 02:55:21,200 --> 02:55:23,880 PATIENTS TAKING HYDROXY UREA, WE 4665 02:55:23,880 --> 02:55:24,640 IESHES DENTIFIED 20 OF THE 4666 02:55:24,640 --> 02:55:27,200 STUDIES THAT COLLECTED THAT 4667 02:55:27,200 --> 02:55:27,480 INFORMATION. 4668 02:55:27,480 --> 02:55:34,240 BUT LET'S SAY WE'RE INTERESTED 4669 02:55:34,240 --> 02:55:38,440 IN AND THAT ALSO HAVE BRAIN, MRI 4670 02:55:38,440 --> 02:55:42,520 OR MRA IMAGING SO WE CAN COMBINE 4671 02:55:42,520 --> 02:55:47,840 INFORMATION AND STUDIES THAT 4672 02:55:47,840 --> 02:55:49,800 STUDY HYDROXY UREA FOR 4673 02:55:49,800 --> 02:55:50,920 INFORMATION THAT WE CAN BROWSE 4674 02:55:50,920 --> 02:55:52,640 DOWN AND SELECT THIS BOX HERE 4675 02:55:52,640 --> 02:55:54,080 FOR COLLECTING OF BRAIN MRIs 4676 02:55:54,080 --> 02:55:57,320 AND WE CAN SEE NOW THAT WE HAVE 4677 02:55:57,320 --> 02:55:59,720 7 STUDIES THAT ARE, THAT 4678 02:55:59,720 --> 02:56:00,680 COLLECTED BOTH AND HAD 4679 02:56:00,680 --> 02:56:03,840 INFORMATION ABOUT THESE BRAIN 4680 02:56:03,840 --> 02:56:05,600 IMAGING AS WELL AS INFORMATION 4681 02:56:05,600 --> 02:56:07,320 ABOUT PATIENTS TAKING HYDROXY 4682 02:56:07,320 --> 02:56:09,840 UREA, AND THERE'S A NUMBER OF 4683 02:56:09,840 --> 02:56:12,760 DIFFERENT DATA ELEMENTS THAT WE 4684 02:56:12,760 --> 02:56:15,120 CAN USE TO KIND OF DO THIS 4685 02:56:15,120 --> 02:56:16,800 FILTERING STRATEGY BOTH ACROSS 4686 02:56:16,800 --> 02:56:18,720 THE DATA ELEMENT DOMAINS AS WELL 4687 02:56:18,720 --> 02:56:20,440 AS PATIENT REPORTED OUTCOMES. 4688 02:56:20,440 --> 02:56:25,640 AND SO, WE CAN BUILD OUT THESE 4689 02:56:25,640 --> 02:56:27,800 KIND OF QUERIES BY ADDING NEW 4690 02:56:27,800 --> 02:56:29,080 LAYERS TO OUR SEARCH FEATURE. 4691 02:56:29,080 --> 02:56:31,440 SO IN THIS CASE, WE ADDED THE 4692 02:56:31,440 --> 02:56:33,640 DATA ELEMENT HERE FOR IMAGING, 4693 02:56:33,640 --> 02:56:35,400 WE CAN FURTHER EXPAND THAT OUT 4694 02:56:35,400 --> 02:56:37,040 TO SAY WELL, WE ALSO WANT TO 4695 02:56:37,040 --> 02:56:39,200 KNOW WHETHER THE STUDIES 4696 02:56:39,200 --> 02:56:40,240 COLLECTED BIOSPECIMENS FOR URINE 4697 02:56:40,240 --> 02:56:41,800 AND HAVE ACCESS TO THOSE STUDIES 4698 02:56:41,800 --> 02:56:44,480 TO QUERY FOR ADDITIONAL OR THOSE 4699 02:56:44,480 --> 02:56:46,360 SAMPLES TO QUERY FOR ADDITIONAL 4700 02:56:46,360 --> 02:56:48,240 MARKERS OR THINGS, AND IN THAT 4701 02:56:48,240 --> 02:56:51,520 CASE, NOW, WE'VE IDENTIFIED 2 4702 02:56:51,520 --> 02:56:54,240 STUDIES WHICH HAVE MET ALL THE 4703 02:56:54,240 --> 02:56:57,240 CRITERIA FOR HAVING HYDROXY UREA 4704 02:56:57,240 --> 02:56:59,240 FOR BRAIN IMAGING FOR MRI OR MRI 4705 02:56:59,240 --> 02:57:02,120 AS WELL AS DIRECTION OF 4706 02:57:02,120 --> 02:57:03,720 BIOSPECIMENS, SO IN THIS WAY, WE 4707 02:57:03,720 --> 02:57:05,240 CAN FILTER DOWN AND IDENTIFY THE 4708 02:57:05,240 --> 02:57:07,120 STUDIES WHICH MAY BE MOST 4709 02:57:07,120 --> 02:57:08,840 APPLICABLE SO WE CAN REUSE SOME 4710 02:57:08,840 --> 02:57:11,280 OF THE STUDIES WE HAVE ALREADY 4711 02:57:11,280 --> 02:57:16,240 COLLECTED AND INVESTED IN IN THE 4712 02:57:16,240 --> 02:57:16,640 PAST. 4713 02:57:16,640 --> 02:57:17,960 ONE OF THE NEW FEATURES THAT 4714 02:57:17,960 --> 02:57:21,400 WE'RE WORKING ON IN THE METADATA 4715 02:57:21,400 --> 02:57:22,280 CATALOG IS OUR SUBJECT FREQUENCY 4716 02:57:22,280 --> 02:57:22,800 TOOL. 4717 02:57:22,800 --> 02:57:24,920 SO FOR INSTANCE IF WE'RE LOOKING 4718 02:57:24,920 --> 02:57:28,760 TO BUILD A COHORT, AND 4719 02:57:28,760 --> 02:57:30,160 UNDERSTAND A NEW SCIENTIFIC 4720 02:57:30,160 --> 02:57:31,920 QUESTION, WE MAY BE INTERESTED 4721 02:57:31,920 --> 02:57:35,520 IN ONLY RECRUITING A SPECIFIC 4722 02:57:35,520 --> 02:57:37,040 NUMBER OF PATIENTS OR 4723 02:57:37,040 --> 02:57:38,120 AGGREGATING OR PATIENTS WITH A 4724 02:57:38,120 --> 02:57:40,080 SPECIFIC SET OF CRITERIA. 4725 02:57:40,080 --> 02:57:41,920 SO IN THIS CASE, YOU KNOW THIS 4726 02:57:41,920 --> 02:57:45,720 IS A NEW FEATURE THAT WE'VE 4727 02:57:45,720 --> 02:57:46,200 ADDED. 4728 02:57:46,200 --> 02:57:48,520 WE ONLY HAVE 2 STUDIES IN WHICH 4729 02:57:48,520 --> 02:57:51,640 ARE BROUGHT INTO THIS TOOL BOTH 4730 02:57:51,640 --> 02:57:54,760 SC DATA AND SCDIC, WE HAVE 6000 4731 02:57:54,760 --> 02:57:56,680 PATIENTS ACROSS THESE 2 STUDIES 4732 02:57:56,680 --> 02:58:00,120 AND IF WE'RE INTERESTED IN 4733 02:58:00,120 --> 02:58:01,720 FINDING INFORMATION ABOUT ONLY 4734 02:58:01,720 --> 02:58:05,240 PATIENTS WHICH HAVE AN SS-GENO 4735 02:58:05,240 --> 02:58:06,440 TYPE, WE CAN AND ONLY PATIENTS 4736 02:58:06,440 --> 02:58:10,080 THAT ARE AT LEAST 18 YEARS OF 4737 02:58:10,080 --> 02:58:11,640 AGE, WE CAN CLICK ON THESE 4738 02:58:11,640 --> 02:58:14,160 BOXES, AND WE CAN IDENTIFY THAT 4739 02:58:14,160 --> 02:58:18,360 THERE ARE 808 SUBJECTS IN THE 4740 02:58:18,360 --> 02:58:21,000 C-DATA AND 1500--ABOUT 1500 IN 4741 02:58:21,000 --> 02:58:23,800 THE SCDID DATA SET WHICH MEET 4742 02:58:23,800 --> 02:58:25,400 THAT CRITERIA, SO THESE MIGHT BE 4743 02:58:25,400 --> 02:58:26,680 AN OPPORTUNITY WHERE WE CAN PULL 4744 02:58:26,680 --> 02:58:27,880 THE INFORMATION FROM THESE 4745 02:58:27,880 --> 02:58:32,520 PATIENTS ACROSS THE 2 STUDIES 4746 02:58:32,520 --> 02:58:37,640 TOGETHER TO BUILD OUT OUR 4747 02:58:37,640 --> 02:58:37,880 COHORT. 4748 02:58:37,880 --> 02:58:40,120 SAME WAY WE WERE ABLE TO HAVE 4749 02:58:40,120 --> 02:58:41,840 ADDITIONAL LAYERS IN OUR SEARCH 4750 02:58:41,840 --> 02:58:43,040 FUNCTION, WE BUILT THAT IN HERE, 4751 02:58:43,040 --> 02:58:45,920 SO IN THIS CASE, IF WE WANTED TO 4752 02:58:45,920 --> 02:58:48,160 ONLY HAVE FEMALES WHICH HAVE A 4753 02:58:48,160 --> 02:58:50,360 HISTORY OF TAKING HYDROXY UREA, 4754 02:58:50,360 --> 02:58:52,280 WE CAN ADD THOSE BOXES AS WELL, 4755 02:58:52,280 --> 02:58:55,160 TO OUR FILTERS AND THAT NOROS 4756 02:58:55,160 --> 02:58:58,200 OUR COHORT DOWN TO ABOUT 462 4757 02:58:58,200 --> 02:58:59,960 SUBJECTS, ABOUT HALF OF THEM 4758 02:58:59,960 --> 02:59:03,360 COMING FROM C-DATA AND A LITTLE 4759 02:59:03,360 --> 02:59:04,440 MORE FROM SCIDID, SO THIS IS A 4760 02:59:04,440 --> 02:59:06,400 WAY WE CAN BUILD OUT THOSE 4761 02:59:06,400 --> 02:59:07,920 COHORTS HOE THAT WE CAN 4762 02:59:07,920 --> 02:59:09,520 INTERROGATE SOME OF THOSE 4763 02:59:09,520 --> 02:59:16,560 QUESTIONS THAT ARE APPLICABLE TO 4764 02:59:16,560 --> 02:59:16,880 OUR QUESTIONS. 4765 02:59:16,880 --> 02:59:18,080 ONE OF THE FEATURES WE'RE 4766 02:59:18,080 --> 02:59:19,880 LOOKING TO BUILD OUT FURTHER IS 4767 02:59:19,880 --> 02:59:21,400 BEING ABLE TO IDENTIFY THE 4768 02:59:21,400 --> 02:59:23,880 NUMBER OF SUBJECTS THAT MAY HAVE 4769 02:59:23,880 --> 02:59:28,520 ANY OF THE CURATED DATA 4770 02:59:28,520 --> 02:59:29,640 ELEMENTS, SO IN THIS PARTICULAR 4771 02:59:29,640 --> 02:59:31,640 CASE WE'RE NOTED ACTUALLY 4772 02:59:31,640 --> 02:59:33,120 LOOKING AT SOME OF THE RESPONSE 4773 02:59:33,120 --> 02:59:36,760 OPTIONS LIKE WE MAY NOT HAVE 4774 02:59:36,760 --> 02:59:38,360 INFORMATION ABOUT THE PARTICULAR 4775 02:59:38,360 --> 02:59:42,560 RESULTS OF A BRAIN SCAN, WE WILL 4776 02:59:42,560 --> 02:59:47,240 KNOW IT IS NUMBER OF 4777 02:59:47,240 --> 02:59:48,800 PARTICIPANTS THAT HAD THAT DATA 4778 02:59:48,800 --> 02:59:50,240 COLLECTED SO WE MAY NOT KNOW 4779 02:59:50,240 --> 02:59:51,400 WHAT THE RESULTS WERE AND THE 4780 02:59:51,400 --> 02:59:54,480 COHORT MAY NOT BE AS CLOSED, 4781 02:59:54,480 --> 02:59:56,240 HOWEVER, WE DO KNOW THAT THERE 4782 02:59:56,240 --> 02:59:57,600 WERE A CERTAIN NUMBER OF 4783 02:59:57,600 --> 02:59:58,840 PATIENTS THAT HAD THIS 4784 02:59:58,840 --> 03:00:00,040 INFORMATION COLLECTED AND SO WE 4785 03:00:00,040 --> 03:00:03,880 CAN BUILD OUT ADDITIONAL 4786 03:00:03,880 --> 03:00:05,640 INFORMATION CONSTRAINTS ON OUR 4787 03:00:05,640 --> 03:00:07,600 COHORTS, BY SAYING YOU HAVE TO 4788 03:00:07,600 --> 03:00:09,320 HAVE THIS INFORMATION COLLECTED, 4789 03:00:09,320 --> 03:00:11,760 SO THIS IS A NEW FEATURE, THAT 4790 03:00:11,760 --> 03:00:13,280 WE'RE IN THE PROCESS OF 4791 03:00:13,280 --> 03:00:15,240 DEVELOPING AND HOPEFULLY WILL BE 4792 03:00:15,240 --> 03:00:16,840 AVAILABLE, SOON IN ORDER TO HELP 4793 03:00:16,840 --> 03:00:18,920 PEOPLE TO BUILD OUT THESE 4794 03:00:18,920 --> 03:00:27,200 COHORTS AND INVESTIGATE NEW 4795 03:00:27,200 --> 03:00:27,880 QUESTIONS. 4796 03:00:27,880 --> 03:00:29,960 SO WITH THE METADATA CATALOG, WE 4797 03:00:29,960 --> 03:00:31,000 ARE LOOKING FOR OPPORTUNITIES TO 4798 03:00:31,000 --> 03:00:32,320 COLLABORATE WITH THE SICKLE CELL 4799 03:00:32,320 --> 03:00:33,720 COMMUNITY AND WE WOULD ENCOURAGE 4800 03:00:33,720 --> 03:00:38,000 YOU ALL TO GO TO THE METADATA 4801 03:00:38,000 --> 03:00:39,640 CATALOG AND TAKE A LOOK. 4802 03:00:39,640 --> 03:00:41,040 OUR CONTACT INFORMATION CAN BE 4803 03:00:41,040 --> 03:00:42,800 FOUND ON THE CATALOG, AND IF YOU 4804 03:00:42,800 --> 03:00:45,520 HAVE A STUDY THAT YOU WOULD LIKE 4805 03:00:45,520 --> 03:00:48,760 TO HAVE BROUGHT INTO THE 4806 03:00:48,760 --> 03:00:50,280 METADATA CATALOG AND IF YOU HAVE 4807 03:00:50,280 --> 03:00:53,320 ADDITIONAL INFORMATION THAT IS 4808 03:00:53,320 --> 03:00:55,720 AVAILABLE ABOUT SOME OF THE 4809 03:00:55,720 --> 03:00:57,240 STUDIES THAT WE'VE ALREADY 4810 03:00:57,240 --> 03:00:59,000 INGESTED THAT MAY NOT BE 4811 03:00:59,000 --> 03:01:00,560 PUBLICLY AVAILABLE, WE ARE VERY 4812 03:01:00,560 --> 03:01:07,440 INTERESTED IN COLLABORATING WITH 4813 03:01:07,440 --> 03:01:07,640 YOU. 4814 03:01:07,640 --> 03:01:09,360 TYPICALLY WE'VE BEEN DOING A 4815 03:01:09,360 --> 03:01:11,520 DATA CURATION TO DO OUR LIBRARY 4816 03:01:11,520 --> 03:01:14,480 SO IF YOU HAVE ANNOTATIONS OR 4817 03:01:14,480 --> 03:01:16,000 ADDITIONS TO THE DICTIONARYS 4818 03:01:16,000 --> 03:01:18,440 THAT WOULD BE HELPFUL AND WE'RE 4819 03:01:18,440 --> 03:01:19,840 WILLING TO KIND OF WORK WITH 4820 03:01:19,840 --> 03:01:21,800 INVESTIGATORS TO HELP BRING THE 4821 03:01:21,800 --> 03:01:24,200 MOST VALUABLE FROM THIS TOOL TO 4822 03:01:24,200 --> 03:01:26,160 THE INVESTIGATORS. 4823 03:01:26,160 --> 03:01:27,760 IN ADDITION, THE SUBJECT 4824 03:01:27,760 --> 03:01:30,160 FREQUENCY TOOL, WE'VE COLLECTED 4825 03:01:30,160 --> 03:01:31,000 INFORMATION AND RESPONSES FOR 10 4826 03:01:31,000 --> 03:01:33,360 OF THE KEY VARIABLES. 4827 03:01:33,360 --> 03:01:34,960 SO THESE ARE THINGS LIKE THE 4828 03:01:34,960 --> 03:01:36,680 GENO TYPES AND THE DEMOGRAPHICS 4829 03:01:36,680 --> 03:01:38,600 THAT WE WOULD USE TO BUILD 4830 03:01:38,600 --> 03:01:40,200 COHORTINGS BUT WE'RE ALWAYS 4831 03:01:40,200 --> 03:01:41,600 INTERESTED IN UNDERSTANDING THE 4832 03:01:41,600 --> 03:01:43,120 NEEDS OF THE COMMUNITY, SO IF 4833 03:01:43,120 --> 03:01:44,040 THERE ARE SPECIFIC THINGS THAT 4834 03:01:44,040 --> 03:01:46,640 YOU WOULD USE IN ORDER TO BUILD 4835 03:01:46,640 --> 03:01:49,240 YOUR COHORTS, WE WOULD LOVE TO 4836 03:01:49,240 --> 03:01:51,000 UNDERSTAND WHAT THOSE ARE AND 4837 03:01:51,000 --> 03:01:51,680 POTENTIALLY WE COULD THEN BUILD 4838 03:01:51,680 --> 03:01:53,200 THAT INTO THE SUBJECT FREQUENCY 4839 03:01:53,200 --> 03:01:55,240 TOOL AND MAKE THAT PUBLICLY 4840 03:01:55,240 --> 03:01:58,560 AVAILABLE TO OTHER RESEARCHERS 4841 03:01:58,560 --> 03:01:59,200 AS WELL. 4842 03:01:59,200 --> 03:02:00,320 SO IF YOU'RE INTERESTED IN 4843 03:02:00,320 --> 03:02:01,800 COLLABORATING WITH US, YEAH, 4844 03:02:01,800 --> 03:02:04,640 EVERYONE PLEASE GO CHECK OUT THE 4845 03:02:04,640 --> 03:02:05,400 METADATA CATALOG, ANY FEEDBACK 4846 03:02:05,400 --> 03:02:07,160 YOU HAVE OR IDEAS ABOUT HOW TO 4847 03:02:07,160 --> 03:02:09,680 BUILD IT OUT AND ADD ADDITIONAL 4848 03:02:09,680 --> 03:02:13,320 VALUE WOULD BE WONDERFUL. 4849 03:02:13,320 --> 03:02:14,840 AND WITH THAT, WE WOULD LIKE TO 4850 03:02:14,840 --> 03:02:17,640 ACKNOWLEDGE A NUMBER OF OUR 4851 03:02:17,640 --> 03:02:18,400 COLLABORATORS AND CONSULTANTS 4852 03:02:18,400 --> 03:02:22,080 WHO HAVE HELPED US TO BUILD OUT 4853 03:02:22,080 --> 03:02:23,440 THIS METADATA CATALOG, SO OUR 4854 03:02:23,440 --> 03:02:26,240 TEAM HERE AT RTI HAS BEEN 4855 03:02:26,240 --> 03:02:27,280 EXTENSIVE AND CONTRIBUTING FOR 4856 03:02:27,280 --> 03:02:31,040 ALL THE CURATION EFFORTS, AS 4857 03:02:31,040 --> 03:02:33,600 WELL AS MARTIA TREAD WELL WHO 4858 03:02:33,600 --> 03:02:36,040 HELPED CAN CONSULLING, THE 4859 03:02:36,040 --> 03:02:38,280 SICKLE CELL CONSORTIUM AND ALL 4860 03:02:38,280 --> 03:02:40,720 THE RESEARCHERS WHO HAVE OFFERED 4861 03:02:40,720 --> 03:02:43,720 UP ADVICE AND DATA DICTIONARIES 4862 03:02:43,720 --> 03:02:44,840 AND DATA SETS TO MAKE THIS 4863 03:02:44,840 --> 03:02:46,040 POSSIBLE AS WELL AS FUNDING. 4864 03:02:46,040 --> 03:02:48,120 AND THAT IS WHAT WE I'VE GOT TO 4865 03:02:48,120 --> 03:02:49,840 SHARE TODAY AND I GUESS, I CAN 4866 03:02:49,840 --> 03:02:51,920 TAKE A LOOK TO SEE IF THERE'S 4867 03:02:51,920 --> 03:03:01,880 ANY QUESTIONS IN THE CHAT. 4868 03:03:01,880 --> 03:03:04,320 >> THANK YOU DR. STRATFORD, VERY 4869 03:03:04,320 --> 03:03:05,400 NICE PRESENTATION, I THINK THERE 4870 03:03:05,400 --> 03:03:09,360 ARE A FEW COMMENTS IN THE CHAT, 4871 03:03:09,360 --> 03:03:11,960 I DON'T SEE ANY PARTICULAR 4872 03:03:11,960 --> 03:03:12,840 QUESTIONS. 4873 03:03:12,840 --> 03:03:13,080 >> YEAH. 4874 03:03:13,080 --> 03:03:17,040 NO, THANK YOU LUIS FOR POINTING 4875 03:03:17,040 --> 03:03:19,680 OUT THE OVERLAP BETWEEN SOME OF 4876 03:03:19,680 --> 03:03:21,000 THE ENROLLMENT, WE WILL HAVE TO 4877 03:03:21,000 --> 03:03:23,640 LOOK INTO THIS A BIT MORE ABOUT 4878 03:03:23,640 --> 03:03:27,480 HOW TO IDENTIFY IF THERE ARE ANY 4879 03:03:27,480 --> 03:03:28,320 PARTICULAR PATIENTS WHICH ARE 4880 03:03:28,320 --> 03:03:29,720 FOUND IN BOTH DATA SETS BECAUSE 4881 03:03:29,720 --> 03:03:31,440 THAT WOULD ALSO BE INKRED 4882 03:03:31,440 --> 03:03:32,520 BELIEVELY USEFUL ESPECIALLY IF 4883 03:03:32,520 --> 03:03:33,960 THERE IS A TIME DIFFERENCE 4884 03:03:33,960 --> 03:03:34,680 BETWEEN THE ENROLLMENT FROM 1 4885 03:03:34,680 --> 03:03:41,200 STUDY TO THE NEXT. 4886 03:03:41,200 --> 03:03:42,640 SO THANK YOU FOR POINTING THAT 4887 03:03:42,640 --> 03:03:46,680 OUT. 4888 03:03:46,680 --> 03:03:49,920 >> ANY OTHER QUESTIONS FOR 4889 03:03:49,920 --> 03:03:56,480 DR. STRATFORD AT THIS POINT. 4890 03:03:56,480 --> 03:03:58,840 SEEING NONE AT THE MEMORY CLONE 4891 03:03:58,840 --> 03:04:02,840 ENTD OUR NEXT SPEAKER IS 4892 03:04:02,840 --> 03:04:04,520 DR. CLAUDIA MORRIS ON? 4893 03:04:04,520 --> 03:04:20,280 DRRN DR. MORRIS? 4894 03:04:20,280 --> 03:04:25,480 I DON'T SEE DR. MORRIS ON AT THE 4895 03:04:25,480 --> 03:04:25,840 MOMENT. 4896 03:04:25,840 --> 03:04:27,600 SHE'S SUPPOSED TO GIVE THE NEXT 4897 03:04:27,600 --> 03:04:31,240 TALK, WHAT'S NEW WITH 4898 03:04:31,240 --> 03:04:33,520 ARGININE THERAPY IN SICKLE CELL 4899 03:04:33,520 --> 03:04:34,240 DISEASE? 4900 03:04:34,240 --> 03:04:35,520 >> SHE'S NOT ON THE CALL. 4901 03:04:35,520 --> 03:04:37,760 >> SHE'S NOT ON THE CALL, WELL, 4902 03:04:37,760 --> 03:04:41,960 IN THAT CASE, GIVEN THAT THIS 4903 03:04:41,960 --> 03:04:43,840 WAS GOING TO BE THE FINAL TALK 4904 03:04:43,840 --> 03:04:51,000 BEFORE WE BREAK FOR LUNCH, I 4905 03:04:51,000 --> 03:04:56,040 THINK IT MIGHT BE BETTER IF WE 4906 03:04:56,040 --> 03:04:58,400 BREAK FOR LUNCH NOW, INSTEADY 4907 03:04:58,400 --> 03:05:01,720 BECAUSE WE DON'T HAVE THE 4908 03:05:01,720 --> 03:05:05,400 SPEAKER AVAILABLE AT THE MOMENT. 4909 03:05:05,400 --> 03:05:09,320 UNFORTUNATELY SO WE WILL HAVE TO 4910 03:05:09,320 --> 03:05:13,640 SKIP THIS PART OF THE TALK IN 4911 03:05:13,640 --> 03:05:17,000 THE AGENDA AT THE MOMENT AND WE 4912 03:05:17,000 --> 03:05:20,080 WILL GET AN EXTRA 30 MINUTES. 4913 03:05:20,080 --> 03:05:23,440 WHY DON'T WE TRY TO COME BACK A 4914 03:05:23,440 --> 03:05:25,440 LITTLE EARLY INSTEADY OF COMING 4915 03:05:25,440 --> 03:05:28,280 BACK AT 1:15, WHY DON'T WE COME 4916 03:05:28,280 --> 03:05:32,480 BACK AT 1:00 O'CLOCK IF THAT IS 4917 03:05:32,480 --> 03:05:37,240 OKAY WITH THE NEXT SESSION 4918 03:05:37,240 --> 03:05:37,680 CHAIRS? 4919 03:05:37,680 --> 03:05:39,480 >> THIS IS NANCY, I KNOW SHE WAS 4920 03:05:39,480 --> 03:05:41,680 PLANNING TO SPEAK AND IT'S A 4921 03:05:41,680 --> 03:05:42,880 LITTLE BIT AHEAD OF SCHEDULE SO 4922 03:05:42,880 --> 03:05:47,280 MAYBE SHE WILL BE ABLE TO JOIN 4923 03:05:47,280 --> 03:05:52,520 WHILE WE'RE AT LUNCH? 4924 03:05:52,520 --> 03:05:53,240 >> OKAY. 4925 03:05:53,240 --> 03:05:53,840 WELL, I MEAN-- 4926 03:05:53,840 --> 03:05:56,640 >> ARE YOU LOOKING FOR ME. 4927 03:05:56,640 --> 03:05:59,000 >> YEAH, HERE'S CLAUDIA NOW. 4928 03:05:59,000 --> 03:06:00,040 >> HEY, SORRY. 4929 03:06:00,040 --> 03:06:05,800 >> SHE'S HERE, OH, OKAY, GREAT. 4930 03:06:05,800 --> 03:06:07,600 >> ARE WE STARTING EARLY? 4931 03:06:07,600 --> 03:06:08,640 >> WE WERE PREEMPTING YOU OUT 4932 03:06:08,640 --> 03:06:10,040 BUT I GUESS NOT. 4933 03:06:10,040 --> 03:06:14,160 SO THANK YOU FOR JOINING, 4934 03:06:14,160 --> 03:06:21,520 DR. CLAUDIA MORRIS IS GOING TO 4935 03:06:21,520 --> 03:06:24,360 TALK ABOUT THE ARGININE THERAPY 4936 03:06:24,360 --> 03:06:25,800 IN SICKLE CELL DISEASE AND 4937 03:06:25,800 --> 03:06:27,520 RESULTS OF PHASE 2 RANDOMIZED 4938 03:06:27,520 --> 03:06:31,000 CONTROLLED TRIALS IN THE U.S. 4939 03:06:31,000 --> 03:06:31,840 AND NIGERIA. 4940 03:06:31,840 --> 03:06:32,640 >> THANK YOU SO MUCH. 4941 03:06:32,640 --> 03:06:34,400 CAN YOU HEAR ME OKAY. 4942 03:06:34,400 --> 03:06:35,560 >> WE WE CAN HEAR YOU FINE? 4943 03:06:35,560 --> 03:06:37,640 , CAN YOU SEE MY SLIDES. 4944 03:06:37,640 --> 03:06:38,920 >> YES, WE CAN. 4945 03:06:38,920 --> 03:06:39,240 >> PERFECT. 4946 03:06:39,240 --> 03:06:39,640 >> THANK YOU. 4947 03:06:39,640 --> 03:06:41,240 WELL I APPRECIATE THE 4948 03:06:41,240 --> 03:06:42,880 INTRODUCTION AND THE INVITATION 4949 03:06:42,880 --> 03:06:44,840 TO TALK TODAY ON 4950 03:06:44,840 --> 03:06:45,560 ARE--ADMINISTRATIVE 4951 03:06:45,560 --> 03:06:46,040 GENERATEDDINE THERAPY. 4952 03:06:46,040 --> 03:06:47,480 SO I HAVE NO RELEVANT 4953 03:06:47,480 --> 03:06:50,520 DISCLOSURES BUT I WILL BE 4954 03:06:50,520 --> 03:06:55,760 SPEAKING ABOUT OFFLABEL USE 4955 03:06:55,760 --> 03:06:57,520 ABOUT L-ARGININE, UNDER AN 4956 03:06:57,520 --> 03:07:00,000 ACTIVE IND, THERE ARE PEOPLE IN 4957 03:07:00,000 --> 03:07:02,400 THE AUDIENCE WONDERING OH MY 4958 03:07:02,400 --> 03:07:06,920 GOSH IS SHE STILL TALKING ABOUT 4959 03:07:06,920 --> 03:07:09,040 THE ARGINE THERAPY, AND THATY 4960 03:07:09,040 --> 03:07:12,040 TRUE, WE STARTED TALKING ABOUT 4961 03:07:12,040 --> 03:07:13,600 ARGININE, THERAPY WITH MY K23 4962 03:07:13,600 --> 03:07:15,480 AWARD THAT WAS GRANTED FROM 4963 03:07:15,480 --> 03:07:18,360 NHLBI AND THIS IS JUST TO GIVE 4964 03:07:18,360 --> 03:07:19,840 THE YOUNG INVESTIGATORS IN THE 4965 03:07:19,840 --> 03:07:21,320 ODD EN--STRATEGIES AN IDEA OF 4966 03:07:21,320 --> 03:07:24,240 HOW IMPORTANT THE PERSISTENCE IS 4967 03:07:24,240 --> 03:07:26,800 ALONG THE JOURNEY BECAUSE IT HAS 4968 03:07:26,800 --> 03:07:28,520 BEEN AN INCREDIBLE JOURNEY TO 4969 03:07:28,520 --> 03:07:30,320 GET US TO 2020 WHEN WE WERE 4970 03:07:30,320 --> 03:07:33,480 FUNDED AGAIN BY NHLBI TO DO OUR 4971 03:07:33,480 --> 03:07:34,440 DEFINITIVE PHASE 3 TRIAL. 4972 03:07:34,440 --> 03:07:36,040 BUT I WANTED TO POINT OUT THAT 4973 03:07:36,040 --> 03:07:38,040 ALONG THE WAY, THERE WERE 4974 03:07:38,040 --> 03:07:40,880 MULTIPLE SCORES THAT DID NOT GET 4975 03:07:40,880 --> 03:07:43,320 FUNDED AND REVISIONS AND 4976 03:07:43,320 --> 03:07:45,640 ULTIMATE AWARDS THAT IF YOU'RE 4977 03:07:45,640 --> 03:07:49,040 NOT SUCCESSFUL INITIALLY, TRY, 4978 03:07:49,040 --> 03:07:52,120 TRY, AGAIN. 4979 03:07:52,120 --> 03:07:54,000 SO FOR THOSE UNFAMILIAR WITH 4980 03:07:54,000 --> 03:07:56,040 ARGININE, IT'S AN AMINO OOH SID 4981 03:07:56,040 --> 03:07:57,120 IN DIETARY PROTEIN AND 4982 03:07:57,120 --> 03:07:58,840 SINGICIZED TO THE INTESTINAL 4983 03:07:58,840 --> 03:08:02,040 ACCESS AND IT BECOMES ESSENTIAL 4984 03:08:02,040 --> 03:08:04,560 UNDER CONDIPGZS OF STRESS, 4985 03:08:04,560 --> 03:08:07,040 CATAGOLLIC STATE AND 4986 03:08:07,040 --> 03:08:07,760 PARTICULARLY FROM HOMOLYSIS, 4987 03:08:07,760 --> 03:08:11,120 IT'S NATURALLY FOUND IN THE DIET 4988 03:08:11,120 --> 03:08:15,240 AND INMEAT, DAIRY, SEAFOOD, NUTS 4989 03:08:15,240 --> 03:08:18,640 AND WATERMELON, AND NORMAL 4990 03:08:18,640 --> 03:08:20,640 BETWEEN 7-GRAMS A DAY AND IT IS 4991 03:08:20,640 --> 03:08:23,000 A NUTRITIONAL SUPPLEMENT WITH 4992 03:08:23,000 --> 03:08:25,800 THE LOW TOXICITY, AND ULTIMATELY 4993 03:08:25,800 --> 03:08:28,800 IT'S THE SUBSTRATE FOR POTENT 4994 03:08:28,800 --> 03:08:31,040 VASE O DILATORS, AND AND IT'S 4995 03:08:31,040 --> 03:08:33,800 BEEN RECENTLY MARKETED IN A 4996 03:08:33,800 --> 03:08:35,320 NATURAL ALTERNATIVE TO VIAGRA, 4997 03:08:35,320 --> 03:08:40,960 YOU WILL NEVER LOOK AT THE SAME 4998 03:08:40,960 --> 03:08:54,400 WAY AGAIN. 4999 03:08:54,400 --> 03:08:56,840 --THERE--THIS SLIDE SHOWS THE 5000 03:08:56,840 --> 03:08:58,240 SOURCE OF ARGININE, AND I WON'T 5001 03:08:58,240 --> 03:09:00,120 GO OVER THIS IN TOO MUCH DETAIL 5002 03:09:00,120 --> 03:09:02,240 BUT WE ALSO TALK ABOUT ARGININE 5003 03:09:02,240 --> 03:09:04,680 AS THE PRECURSOR TO NITRIC OXIDE 5004 03:09:04,680 --> 03:09:06,680 BUT YOU CAN SEE THAT THERE ARE A 5005 03:09:06,680 --> 03:09:08,680 NUMBER OF ENZYMES THAT ARE 5006 03:09:08,680 --> 03:09:11,840 INVOLVED, AND A NUMBER OF 5007 03:09:11,840 --> 03:09:12,720 BIOLOGICAL PATHWAYS THAT 5008 03:09:12,720 --> 03:09:14,240 ARGININE IS PLAYING A ROLE, 5009 03:09:14,240 --> 03:09:15,240 AGAIN HIGHLIGHTING FOR THOSE IN 5010 03:09:15,240 --> 03:09:16,880 THE AUDIENCE WHO ARE WONDERING 5011 03:09:16,880 --> 03:09:20,040 HOW THEY CAN COME UP WITH THE 5012 03:09:20,040 --> 03:09:22,520 NOVEL IDEA, ARGININE IS ALSO THE 5013 03:09:22,520 --> 03:09:24,440 PRECURSOR TO CREA TIN WHICH IS 5014 03:09:24,440 --> 03:09:26,760 REALLY IMPORTANT IN THE 5015 03:09:26,760 --> 03:09:27,360 METHYLATION PATHWAY AND 5016 03:09:27,360 --> 03:09:30,400 DETOXIFICATION AND THERE IS VERY 5017 03:09:30,400 --> 03:09:31,240 LITTLE INFORMATION ON ARGININE 5018 03:09:31,240 --> 03:09:32,960 THE PATHWAY ON SICKLE CELL 5019 03:09:32,960 --> 03:09:36,080 DISEASE, SO AGAIN, A GAP IN OUR 5020 03:09:36,080 --> 03:09:36,480 KNOWLEDGE. 5021 03:09:36,480 --> 03:09:40,840 IN THE PRESENCE OF NITRIC OXIDE, 5022 03:09:40,840 --> 03:09:43,240 IT GETS CONVERTED TO NITRIC 5023 03:09:43,240 --> 03:09:46,760 OXIDE AND WE HAVE THIS 5024 03:09:46,760 --> 03:09:49,640 PARADOXICAL DECREASE IN NITRIC 5025 03:09:49,640 --> 03:09:51,240 OXIDE PRODUCTION DESPITE NITRIC 5026 03:09:51,240 --> 03:09:53,640 OXIDE APPEARS TO BE ELEVATED IN 5027 03:09:53,640 --> 03:09:55,440 OTHER SICKLE CELL DISEASE AND 5028 03:09:55,440 --> 03:09:56,480 OTHER INFLAMMAR TOY CONDITIONS 5029 03:09:56,480 --> 03:09:58,040 BUT WORK HAS SHOWN THAT IN THE 5030 03:09:58,040 --> 03:10:04,360 SICKLE CELL MOUSE MODEL, THE 5031 03:10:04,360 --> 03:10:06,640 NITRIC OXIDE SYNTHASE IS 5032 03:10:06,640 --> 03:10:13,240 FUNCTIONAL AND IT WILL REOXIDIZE 5033 03:10:13,240 --> 03:10:14,360 WITH HEMOGLOBIN AND IT'S PRESENT 5034 03:10:14,360 --> 03:10:16,800 IN THE RED BLOOD CELLS AND IT'S 5035 03:10:16,800 --> 03:10:18,280 INCREASED FROM LIVER AND LIVER 5036 03:10:18,280 --> 03:10:19,480 DAMAGE AND DECREASED TRAUMA AND 5037 03:10:19,480 --> 03:10:21,680 THEREY A NUMBER OF ETIOLOGIES, 5038 03:10:21,680 --> 03:10:23,120 BUT THE BODY DOESN'T CARE WHERE 5039 03:10:23,120 --> 03:10:25,440 IT'S COMING FROM, ONCE IT'S IN 5040 03:10:25,440 --> 03:10:30,080 CIRCULATION, IT CONVERTS IT TO 5041 03:10:30,080 --> 03:10:31,880 ARGININE, AND THEN YOU HAVE 5042 03:10:31,880 --> 03:10:33,240 PROLIF RATESTIFY PATHWAYS THAT 5043 03:10:33,240 --> 03:10:35,800 LEAD TO THINGS LIKE VASCULAR 5044 03:10:35,800 --> 03:10:40,120 SMOOTH MUSCLE PROLIFERATION, 5045 03:10:40,120 --> 03:10:40,840 REMODELING, COLLAGEN 5046 03:10:40,840 --> 03:10:41,480 COMPOSITION, LUNG FIBROSIS WHEN 5047 03:10:41,480 --> 03:10:44,040 YOU THINK ABOUT THE LUNG BUT 5048 03:10:44,040 --> 03:10:46,920 THIS IS PROBABLY IMPORTANT IN 5049 03:10:46,920 --> 03:10:50,760 EVERY ORGAN WHERE IT'S IN 5050 03:10:50,760 --> 03:10:52,600 EXCESS, SO IT'S ARGININE IS JUST 5051 03:10:52,600 --> 03:10:54,760 IMPORTANT IT SHOULD NEVER BE 5052 03:10:54,760 --> 03:10:55,920 DEFICIENT PARTICULARLY SINCE WE 5053 03:10:55,920 --> 03:10:57,040 HAVE THE ABILITY TO SYNTHESIZE 5054 03:10:57,040 --> 03:10:59,040 IT, AND SO TAKEN UP IN THE FORM 5055 03:10:59,040 --> 03:11:00,560 OF DPLIEWTA MINE, CONVERTED IN 5056 03:11:00,560 --> 03:11:02,640 FROM THE DIET, TO SIT ROW LEAN 5057 03:11:02,640 --> 03:11:04,720 IN THE SMALL INTESTINE AND SIT 5058 03:11:04,720 --> 03:11:09,840 ROUGH ATOM LINE GETS CONVERT 5059 03:11:09,840 --> 03:11:10,640 INDEED THE KIDNEY. 5060 03:11:10,640 --> 03:11:13,760 ALTHOUGH THE MECHANISM IS LIKELY 5061 03:11:13,760 --> 03:11:16,560 MULTIFACTORIAL, WE RECENTLY 5062 03:11:16,560 --> 03:11:17,440 PUBLISHED OUR PHARMACOKINETIC 5063 03:11:17,440 --> 03:11:20,240 DATA TO SHOW THAT OUR DPLIEWTA 5064 03:11:20,240 --> 03:11:22,960 MINE LOAD DOES INFACT INCREASE 5065 03:11:22,960 --> 03:11:24,880 VIAABILITY AND THIS IS LIKELY 5066 03:11:24,880 --> 03:11:26,080 THAT THIS PATHWAY IS PLAYING A 5067 03:11:26,080 --> 03:11:26,640 ROLE AS WELL. 5068 03:11:26,640 --> 03:11:28,240 BUT IF HAVE YOU KIDNEY 5069 03:11:28,240 --> 03:11:29,600 DYSFUNCTION, WERE YOU AWARE NOT 5070 03:11:29,600 --> 03:11:31,080 ABLE TO CONVERT FROM SIT ROUGH 5071 03:11:31,080 --> 03:11:32,120 ATOM LEAN TO ARE--ADMINISTRATIVE 5072 03:11:32,120 --> 03:11:32,720 GENERATEDDINE AND APPROXIMATE 5073 03:11:32,720 --> 03:11:35,440 WITH THE WORK WE DID WITH MARK 5074 03:11:35,440 --> 03:11:39,720 AND COLLEAGUES WE FOUND IN OUR 5075 03:11:39,720 --> 03:11:41,040 DATABASE RISING LEVELS STRONGLY 5076 03:11:41,040 --> 03:11:42,320 CORRELATED TO KRE TINSA TIEN 5077 03:11:42,320 --> 03:11:44,520 LEVELS IN OUR PATIENTS WITH SICK 5078 03:11:44,520 --> 03:11:47,040 CELL CELL DISEASE AND THEY HAD 5079 03:11:47,040 --> 03:11:59,240 LOW ARGININE LEVELS SO THERE WAS 5080 03:11:59,240 --> 03:12:00,000 A--VERY VULNERABLE TOOXIDATIVE 5081 03:12:00,000 --> 03:12:01,640 STRESS AND CAN GET KNOCKED OUT 5082 03:12:01,640 --> 03:12:02,360 PRETTY QUICKLY. 5083 03:12:02,360 --> 03:12:03,440 SO AGAIN ANOTHER GAP IN OUR 5084 03:12:03,440 --> 03:12:04,960 KNOWLEDGE AND OUR AREA WHERE WE 5085 03:12:04,960 --> 03:12:06,000 NEED MORE STUDY. 5086 03:12:06,000 --> 03:12:07,640 BUT BECAUSE OF THIS, WE COINED 5087 03:12:07,640 --> 03:12:09,920 THE TERM GLOBAL ARCHINGLY 5088 03:12:09,920 --> 03:12:10,600 BIOAVAILABILITY RATIO BECAUSE IT 5089 03:12:10,600 --> 03:12:12,840 IS MORE THAN JUST THE ARGININE 5090 03:12:12,840 --> 03:12:14,200 IN YOUR PLASMA MAKES A 5091 03:12:14,200 --> 03:12:15,960 DIFFERENCE, IN THE PLACE OF 5092 03:12:15,960 --> 03:12:16,640 ARE--ADMINISTRATIVE GENERATED 5093 03:12:16,640 --> 03:12:19,080 ACE, IT GETS CONVERTED SO THIS 5094 03:12:19,080 --> 03:12:23,480 RATIO IS PLUS SIT ROUGH ATOM 5095 03:12:23,480 --> 03:12:26,280 LEAN, SO AS YOU'RE 5096 03:12:26,280 --> 03:12:27,840 ORNITHINCEREBELLUMSY, USE THE 5097 03:12:27,840 --> 03:12:29,240 SAME TRANSPORTER SO THE ARGININE 5098 03:12:29,240 --> 03:12:30,440 NEEDS TO GET FROM THE PLASMA 5099 03:12:30,440 --> 03:12:32,240 INTO THE CELLS SO NOW HAVE YOU 5100 03:12:32,240 --> 03:12:33,240 TRANSPORT DIFFICULTIES AND THEN 5101 03:12:33,240 --> 03:12:35,120 IF YOU THROW IN KIDNEY 5102 03:12:35,120 --> 03:12:36,400 DYSFUNCTION YOU, YOU WILL 5103 03:12:36,400 --> 03:12:37,560 NOTABLA TO SUPPORT THIS FROM SIT 5104 03:12:37,560 --> 03:12:39,520 ROUGH ATOM LEAN, AND I WANT YOU 5105 03:12:39,520 --> 03:12:42,400 TO KEEP IT IN MIND AS WEAUK 5106 03:12:42,400 --> 03:12:43,360 ABOUT OUR CLINICAL TRIALS. 5107 03:12:43,360 --> 03:12:45,360 SO A LOT OF DITS CUSHION ABOUT 5108 03:12:45,360 --> 03:12:47,400 AMINO ACIDS BUT A DROP IN ANY 5109 03:12:47,400 --> 03:12:50,240 SPECIFIC AMINO ACID DOES NOT 5110 03:12:50,240 --> 03:12:51,560 TRANSLATE TO--DOES NOT ALWAYS 5111 03:12:51,560 --> 03:12:53,440 TRANALATE TO A CLINICAL 5112 03:12:53,440 --> 03:12:54,040 SIGNIFICANT DEFICIENCY, SO 5113 03:12:54,040 --> 03:12:55,800 INERED ONER TO FOR A 5114 03:12:55,800 --> 03:12:56,440 NUCLEOTIDESITRATIONAL DEFICIENCY 5115 03:12:56,440 --> 03:12:57,600 HAS TO BE PRESENT, YOU HAVE TO 5116 03:12:57,600 --> 03:13:01,760 HAVE THESE 3 PRIMATES SESESS, A 5117 03:13:01,760 --> 03:13:03,120 BIOLOGICAL PROCESS DEPENDENTOT 5118 03:13:03,120 --> 03:13:05,080 NUTRIENT, THAT COMPROMISE LEADS 5119 03:13:05,080 --> 03:13:06,840 TO AN ABNORMAL PHYSIOLOGIC 5120 03:13:06,840 --> 03:13:09,160 RESPONSE THAT'S POSITIVE FOR 5121 03:13:09,160 --> 03:13:10,920 OUTCOMES AND THOSE POUR 5122 03:13:10,920 --> 03:13:12,440 OUTOUTCOMES ARE REPLACED FOR 5123 03:13:12,440 --> 03:13:13,800 AMINO ACIDS FOR REPLACEMENT SO 5124 03:13:13,800 --> 03:13:16,000 KEEP IN THIS MIND AS WE TALK 5125 03:13:16,000 --> 03:13:16,800 ABOUT CLINICAL TRIALS BUZZ I 5126 03:13:16,800 --> 03:13:18,440 WILL MAKE THE ARGUMENT THE END 5127 03:13:18,440 --> 03:13:20,560 THAT WE'RE REALLY TREATING A 5128 03:13:20,560 --> 03:13:23,240 NUTRITIONAL DEFICIENCY. 5129 03:13:23,240 --> 03:13:23,560 >> CLAUDIA,. 5130 03:13:23,560 --> 03:13:25,040 >> CLAUDIA, SORRY TO INTERRUPT 5131 03:13:25,040 --> 03:13:27,400 YOU BUT I THINK YOUR--ARE YOU 5132 03:13:27,400 --> 03:13:28,840 SEEING YOUR SLIDES, ARE SLIDES 5133 03:13:28,840 --> 03:13:31,640 THE RIGHT SLIDE BEING PROJECTED? 5134 03:13:31,640 --> 03:13:33,000 >> IT SAYS AMINE'S ACID 5135 03:13:33,000 --> 03:13:34,520 DEFICIENCIES ARE YOU NOT SEEING 5136 03:13:34,520 --> 03:13:35,040 MY SLIDES? 5137 03:13:35,040 --> 03:13:39,120 WE ARE SEEING SLIDES NHLBI IS 5138 03:13:39,120 --> 03:13:42,920 FORWARDING THEM SO MAKE YOU SAY 5139 03:13:42,920 --> 03:13:43,280 NEXT SLIDE. 5140 03:13:43,280 --> 03:13:51,920 NO, NO, I WAS MOVING THEM 5141 03:13:51,920 --> 03:13:52,280 MYSELF. 5142 03:13:52,280 --> 03:13:55,640 >> WE'RE LOOKING AT THE SLIDE 5143 03:13:55,640 --> 03:14:07,880 FOR DPLIEWTA MINE--DPLIEWTA MINE 5144 03:14:07,880 --> 03:14:08,400 AND CITRULLINE. 5145 03:14:08,400 --> 03:14:10,640 >> DO YOU WANT TO CONTINUE? 5146 03:14:10,640 --> 03:14:10,920 >> YES. 5147 03:14:10,920 --> 03:14:20,240 >> SO, HERE LET ME SEE. 5148 03:14:20,240 --> 03:14:21,040 SORRY ABOUT THAT. 5149 03:14:21,040 --> 03:14:22,440 YEAH, I REALIZED YOU WERE BEHIND 5150 03:14:22,440 --> 03:14:26,280 THE SLIDES. 5151 03:14:26,280 --> 03:14:28,360 SORRY, I THOUGHT--OKAY, HERE WE 5152 03:14:28,360 --> 03:14:30,760 GO, CAN YOU SEE THAT? 5153 03:14:30,760 --> 03:14:31,040 >> YES. 5154 03:14:31,040 --> 03:14:33,200 >> SO THIS WAS THE SLIDE THAT WE 5155 03:14:33,200 --> 03:14:38,280 HAD SPOKEEB SO TELL ME SOME I 5156 03:14:38,280 --> 03:14:38,960 START FROM HERE. 5157 03:14:38,960 --> 03:14:40,640 SO NANCY I HEARD YOU ASK 5158 03:14:40,640 --> 03:14:41,480 SOMETHING ABOUT THE PATHWAY, 5159 03:14:41,480 --> 03:14:42,360 WHAT WAS YOUR QUESTION. 5160 03:14:42,360 --> 03:14:44,640 , NO THIS WAS THE SLIDE WE'RE 5161 03:14:44,640 --> 03:14:47,040 LOOKING AT AND CLAUDIA YOU'RE 5162 03:14:47,040 --> 03:14:48,640 NOT IN FULL SCREEN VIEW RIGHT 5163 03:14:48,640 --> 03:14:50,640 NOW, I'M NOT SURE IF YOU CAN 5164 03:14:50,640 --> 03:14:53,520 CHANGE THAT, WE'RE LOOKING AT 2 5165 03:14:53,520 --> 03:14:53,760 SLIDES. 5166 03:14:53,760 --> 03:14:54,400 >> OH GEEZ. 5167 03:14:54,400 --> 03:14:55,520 OKAY. 5168 03:14:55,520 --> 03:14:56,360 SORRY ABOUT THAT. 5169 03:14:56,360 --> 03:14:58,440 >> THE IT PEOPLE KNOW HOW TO DO 5170 03:14:58,440 --> 03:14:58,800 THIS STUFF. 5171 03:14:58,800 --> 03:15:09,680 >> YOU CAN GO TO PRESENTER MODE. 5172 03:15:09,680 --> 03:15:09,960 >> IS-- 5173 03:15:09,960 --> 03:15:11,880 >> I THINK THE PROBLEM IS, I 5174 03:15:11,880 --> 03:15:12,560 STOPPED SHARING. 5175 03:15:12,560 --> 03:15:23,960 >> YOU DID. 5176 03:15:23,960 --> 03:15:24,280 >> OKAY. 5177 03:15:24,280 --> 03:15:44,320 CAN YOU SEE MY SLIDES NOW? 5178 03:15:44,320 --> 03:15:44,600 >> NO. 5179 03:15:44,600 --> 03:15:46,920 >> I AM SO SORRY. 5180 03:15:46,920 --> 03:15:47,200 >> YES. 5181 03:15:47,200 --> 03:15:48,240 >> YES, OKAY. 5182 03:15:48,240 --> 03:15:49,440 >> SORRY FOR INTERRUPTING. 5183 03:15:49,440 --> 03:15:50,240 >> NO WORRIES, THANK YOU FOR 5184 03:15:50,240 --> 03:15:50,920 TELLING ME. 5185 03:15:50,920 --> 03:15:52,840 SO WE JUST WENT THROUGH THE KIND 5186 03:15:52,840 --> 03:15:54,040 OF THE BIOLOGY SLIDE ANDIME 5187 03:15:54,040 --> 03:15:56,160 HAPPY TO SHARE THESE SLIDES WITH 5188 03:15:56,160 --> 03:16:00,520 ANYONE WHO WANTS TO SEE THEM IN 5189 03:16:00,520 --> 03:16:01,040 MORE DETAIL. 5190 03:16:01,040 --> 03:16:03,440 BUT AS WE TALKED ABOUT, IN ORDER 5191 03:16:03,440 --> 03:16:04,480 TO HAVE AMINO DEFICIENCY, YOU 5192 03:16:04,480 --> 03:16:08,440 HAVE TO HAVE THESE 3, ESTATES 5193 03:16:08,440 --> 03:16:12,000 PRESENT, THE BIOLOGICAL PROCESS 5194 03:16:12,000 --> 03:16:12,920 DEPENDENTOT NUTRIENT 5195 03:16:12,920 --> 03:16:14,080 COMPROMISED, THE COMPROMISE 5196 03:16:14,080 --> 03:16:15,720 LEADING TO POSITIVE AND POOR 5197 03:16:15,720 --> 03:16:17,360 OUTCOMES AND THOSE POOR OUTCOMES 5198 03:16:17,360 --> 03:16:22,520 NEED TO BE REVERSED BY AMINO 5199 03:16:22,520 --> 03:16:23,880 ACID PLACEMENT. 5200 03:16:23,880 --> 03:16:25,920 SO ULTIMATELY SICKLE CELL 5201 03:16:25,920 --> 03:16:28,080 DISEASE IS A MODEL FOR OTHER 5202 03:16:28,080 --> 03:16:29,760 DISEASE BUT HAS IMPLICATION FOR 5203 03:16:29,760 --> 03:16:30,920 SO MANY OTHER DISEASES SO WHEN 5204 03:16:30,920 --> 03:16:33,840 WE THINK ABOUT MECHANISMS OF 5205 03:16:33,840 --> 03:16:35,520 VASCUE LOPATHY, YOU ARE SIGHING 5206 03:16:35,520 --> 03:16:36,960 MY SLIDE, NO IN THE CENTER, YOU 5207 03:16:36,960 --> 03:16:38,400 CAN SEE MY POINTER. 5208 03:16:38,400 --> 03:16:41,040 >> PERFECT, OKAY, SO WHEN YOU 5209 03:16:41,040 --> 03:16:42,520 HAVE ENDONEALIAL DYSFUNCTION NO 5210 03:16:42,520 --> 03:16:44,160 DOES TAKE CENTRAL STAGE AND WE 5211 03:16:44,160 --> 03:16:45,760 TALKED BEFORE ABOUT THE 5212 03:16:45,760 --> 03:16:46,440 CONTRIBUTION OF HEME OLDER 5213 03:16:46,440 --> 03:16:49,240 PEOPLE SIS, SO YOU NORMALLY HAVE 5214 03:16:49,240 --> 03:16:50,400 SAFELY INCAPSULATED IN THE RED 5215 03:16:50,400 --> 03:16:53,240 BLOOD CELL ALL THE CONTENTS 5216 03:16:53,240 --> 03:16:56,040 WHICH INCLUDES SELF-HEMOGLOBIN 5217 03:16:56,040 --> 03:16:58,320 WHICH WILL CONSUME NITRIC OXIDE, 5218 03:16:58,320 --> 03:17:01,400 AND WE HAVE ARITHROCYTE THAT'S 5219 03:17:01,400 --> 03:17:04,840 RELEASED DURING HOMOLYSIS, AND 5220 03:17:04,840 --> 03:17:11,720 THEN RAPIDLY, AND CONSUMES THE 5221 03:17:11,720 --> 03:17:12,880 SUBSTRATE FOR NITRIC OXIDE 5222 03:17:12,880 --> 03:17:13,160 UPTAKE. 5223 03:17:13,160 --> 03:17:14,760 SO NOW YOU HIT THIS LEVEL, THE 5224 03:17:14,760 --> 03:17:24,120 ENZYME THAT CONEXPOSURE CONVERTS ARGININE , 5225 03:17:24,120 --> 03:17:25,480 IS PRODUCING SUPEROXIDE AND 5226 03:17:25,480 --> 03:17:27,160 WHICH FURTHER CONFIRMS AND ADDS 5227 03:17:27,160 --> 03:17:28,800 TO THE MILIEU OFOXIDATIVE STRESS 5228 03:17:28,800 --> 03:17:30,320 AND THIS IS AN IMPORTANT 5229 03:17:30,320 --> 03:17:33,040 PARADIGM NOT JUST FOR SICKLE 5230 03:17:33,040 --> 03:17:36,640 CELL DISEASE BUT FOR THALSEMIA, 5231 03:17:36,640 --> 03:17:38,800 MALARIA, RED BLEED CELL STORAGE 5232 03:17:38,800 --> 03:17:40,280 LESION, ANY TIME HAVE YOU HEME 5233 03:17:40,280 --> 03:17:41,880 OLDER PEOPLE SIS, YOU HAVE 5234 03:17:41,880 --> 03:17:42,920 IMPACT ON THIS IMPORTANT 5235 03:17:42,920 --> 03:17:46,280 PATHWAY, AND THERE ARE CLINICAL 5236 03:17:46,280 --> 03:17:47,080 CONSEQUENCES OF THIS, HEME 5237 03:17:47,080 --> 03:17:49,640 OLYMPIC SIS AND THIS HAS BEEN 5238 03:17:49,640 --> 03:17:53,520 KNOWN AS THE HEMOLYTIC 5239 03:17:53,520 --> 03:17:56,840 SUBPHENOTYPE, SICKLE CELL 5240 03:17:56,840 --> 03:17:59,760 DISEASE BY COLLEAGUES, THAT 5241 03:17:59,760 --> 03:18:07,640 INVOLVES EMPLOY LUG ULCERS, 5242 03:18:07,640 --> 03:18:11,440 PRIAPISM, AND WE'VE SEWN THAT 5243 03:18:11,440 --> 03:18:17,120 THERE'S ARGININE INSUFFICIENCY 5244 03:18:17,120 --> 03:18:18,200 AND ELEVATED ARGININE ACE IN 5245 03:18:18,200 --> 03:18:19,360 SICKLE CELL DISEASE, SO IF YOU 5246 03:18:19,360 --> 03:18:21,440 ARE HEGHTY YOU SHOULD NOT HAVE 5247 03:18:21,440 --> 03:18:23,240 ARGININE FLOATING AROUND IN OUR 5248 03:18:23,240 --> 03:18:25,120 PLASMA, IT'S AN INTRACELLULAR 5249 03:18:25,120 --> 03:18:26,920 ENZYME THAT'S RELEASED UPON CELL 5250 03:18:26,920 --> 03:18:30,120 DAMAGE OR CELL DEATH AND HAD IS 5251 03:18:30,120 --> 03:18:30,960 A REALLY IMPORTANT OBSERVATION 5252 03:18:30,960 --> 03:18:33,600 AS FAR AS UNDERSTANDING THE 5253 03:18:33,600 --> 03:18:35,080 MECHANISM OF THIS ACUTE ARGININE 5254 03:18:35,080 --> 03:18:35,840 DEFICIENCY. 5255 03:18:35,840 --> 03:18:37,240 WE ALSO LEARNED THAT ARGININE 5256 03:18:37,240 --> 03:18:39,680 LEVELS GET DROPPED TO LOWEST 5257 03:18:39,680 --> 03:18:41,440 LEVELS DURING ACUTE EPISODES OF 5258 03:18:41,440 --> 03:18:43,400 PAIN AND DIN DROAMS AND SO FROM 5259 03:18:43,400 --> 03:18:47,560 THE LAST BIOLOGY SLIDE THOUGH WE 5260 03:18:47,560 --> 03:18:50,160 TALKED ABOUT ARGININE AND 5261 03:18:50,160 --> 03:18:52,240 CONVERTS IT TO ORNITHINE, AND 5262 03:18:52,240 --> 03:18:54,680 IT'S LOW IN SICKLE CELL DISEASE 5263 03:18:54,680 --> 03:18:56,080 COMPARED TO NORMAL CONTROLS BUT 5264 03:18:56,080 --> 03:18:59,120 PROBABLY 1 OF MY MOST IMPORTANT 5265 03:18:59,120 --> 03:19:01,160 EARLY OBSERVATIONS WAS THAT THE 5266 03:19:01,160 --> 03:19:02,560 LOWEST LEVELS WERE FOUND IN 5267 03:19:02,560 --> 03:19:05,080 PATIENTS THAT ARE DIAGNOSED 5268 03:19:05,080 --> 03:19:05,640 CLINICALLY WITH PULMONARY 5269 03:19:05,640 --> 03:19:07,640 HYPERTENSION AND THIS IS BUYER 5270 03:19:07,640 --> 03:19:10,200 WE WERE DOING PULMONARY 5271 03:19:10,200 --> 03:19:11,080 HYPERTENSION SCREENING, AND 5272 03:19:11,080 --> 03:19:13,880 THESE WERE PATIENTS IN KNOWN TO 5273 03:19:13,880 --> 03:19:14,560 HAVE PULMONARY HYPERTENSION. 5274 03:19:14,560 --> 03:19:16,160 SO IF IT'S LOW GIVE IT BACK 5275 03:19:16,160 --> 03:19:17,200 THINKING THIS ISENT POSITIONAL 5276 03:19:17,200 --> 03:19:18,440 CLONING TENTIALLY A NUTRITIONAL 5277 03:19:18,440 --> 03:19:20,640 DEFICIENCY, THIS IS A FIRST 5278 03:19:20,640 --> 03:19:21,560 INTERVENTION STUDY, I DID THIS 5279 03:19:21,560 --> 03:19:27,600 WORK WHILE I WAS STILL AT K23, 5280 03:19:27,600 --> 03:19:30,400 AWARDEE AND WE GAVE A HUNDRED 5281 03:19:30,400 --> 03:19:33,640 MILLIGRAMS PER KILOORAL ARGININE 5282 03:19:33,640 --> 03:19:38,800 TO PATIENTS WHO HAD PULMONARY OR 5283 03:19:38,800 --> 03:19:40,240 SYSTOLIC DOPPLER ECEE AND WE 5284 03:19:40,240 --> 03:19:41,560 FOUND A SIGNIFICANT IMPROVEMENT 5285 03:19:41,560 --> 03:19:44,400 IN OVER 15% OF THE PULMONARY 5286 03:19:44,400 --> 03:19:47,920 PRESSURES BY 5 DAYS IN THESE 5287 03:19:47,920 --> 03:19:48,800 PATIENTS WITH PULMONARY 5288 03:19:48,800 --> 03:19:50,720 HYPERTENSION RISK AND THIS IS 5289 03:19:50,720 --> 03:19:53,280 SIMILAR TO THE CHANGES YOU SEE 5290 03:19:53,280 --> 03:19:55,280 WITH OTHER PULMONARY 5291 03:19:55,280 --> 03:19:58,440 HYPERTENSION DRUGS SUCH AS 5292 03:19:58,440 --> 03:19:59,520 SULDENAPH IL, AND THERE WERE 5293 03:19:59,520 --> 03:20:02,200 PATIENTS IN IN GROUP WHO HAD 5294 03:20:02,200 --> 03:20:03,880 SIGNIFICANT CHRONIC LEG ULCERS 5295 03:20:03,880 --> 03:20:06,400 AND THEIR LEG ULCERS RESOLVED 5296 03:20:06,400 --> 03:20:08,880 WHILE THEY WERE ON ARGININE 5297 03:20:08,880 --> 03:20:09,120 THERAPY. 5298 03:20:09,120 --> 03:20:11,200 SO ALSO IMPORTANT TO NOTE THAT 5299 03:20:11,200 --> 03:20:12,360 LOW VIABILITY HAS BEEN ASSOCIATE 5300 03:20:12,360 --> 03:20:15,920 WIDE INCREASED RISK OF DEATH BY 5301 03:20:15,920 --> 03:20:17,600 ARGININE-TO ORN, AND AS I 5302 03:20:17,600 --> 03:20:19,640 MENTIONED BEFORE THE RATIO SO WE 5303 03:20:19,640 --> 03:20:20,960 OBLIGATIONS STAINED A BLOOD TEST 5304 03:20:20,960 --> 03:20:23,240 ON AT A 0 AND FOLLOWED THESE 5305 03:20:23,240 --> 03:20:24,440 PATIENTS OUT OVER 4 + YEARS AND 5306 03:20:24,440 --> 03:20:26,160 NO DEATHS IN THE PATIENT WHO IS 5307 03:20:26,160 --> 03:20:31,040 HAD THE HIGHEST ARGININE VIA 5308 03:20:31,040 --> 03:20:33,640 BILITY AND WITH A RISK RATIO OF 5309 03:20:33,640 --> 03:20:33,880 3.6. 5310 03:20:33,880 --> 03:20:35,640 THIS HAS BEEN LOOKEDDA THE IN 5311 03:20:35,640 --> 03:20:36,720 PATIENTS WITHOUT SICKLE CELL 5312 03:20:36,720 --> 03:20:38,440 DISEASE, AT RISK FOR 5313 03:20:38,440 --> 03:20:39,440 CARDIOVASCULAR DISEASE AND IT IS 5314 03:20:39,440 --> 03:20:42,560 A MORE SENSITIVE PREDICTER OF 5315 03:20:42,560 --> 03:20:44,480 ADVERSE OUTCOMES THAN 5316 03:20:44,480 --> 03:20:45,560 CHOLESTEROL. 5317 03:20:45,560 --> 03:20:47,040 SO SUGGESTS THAT ARGININE PLAYS 5318 03:20:47,040 --> 03:20:49,440 A REALLY IMPORTANT ROLE IN 5319 03:20:49,440 --> 03:20:50,240 ENDOTHELIAL DYSFUNCTION THAT 5320 03:20:50,240 --> 03:20:51,480 GOES BEYOND SICKLE CELL DISEASE. 5321 03:20:51,480 --> 03:20:55,480 SO GOING BACK TO THE RESULTS OF 5322 03:20:55,480 --> 03:21:00,720 MY K23 STUDY, THIS WAS OUR 5323 03:21:00,720 --> 03:21:01,640 BLINDED RANDOMIZED PLACEBO PHASE 5324 03:21:01,640 --> 03:21:04,360 2 TRIAL, WHERE WE GIVE THE 5325 03:21:04,360 --> 03:21:07,880 ARGININE A HUNDRED MILLIGRAMS 5326 03:21:07,880 --> 03:21:11,200 FOR KILOFOR 53 TIMES A DAY FOR 5 5327 03:21:11,200 --> 03:21:12,760 DAYS, WE STARTED OUT RAPID 5328 03:21:12,760 --> 03:21:13,720 LOAMACYY, AND SWITCHED TO IV 5329 03:21:13,720 --> 03:21:16,160 BECAUSE WE HAD A HECK OF A TIME 5330 03:21:16,160 --> 03:21:18,120 GETTING PATIENTS TO COMPLY AND 5331 03:21:18,120 --> 03:21:20,360 ACTUALLY DRINK THE COCKTAIL WHEN 5332 03:21:20,360 --> 03:21:22,040 THEY'RE NOT FEELING WELL BUT NO 5333 03:21:22,040 --> 03:21:23,760 ISSUES WITH COMPLIANCE WITH 5334 03:21:23,760 --> 03:21:26,240 DELIVERING BY IV, SO 56 PATES 5335 03:21:26,240 --> 03:21:28,280 OVER AGE 3 ADMITTED FOR PAIN, 5336 03:21:28,280 --> 03:21:30,240 SIGNIFICANT DECREASE IN THE 5337 03:21:30,240 --> 03:21:34,840 OPIOID USE IN IV MORPHIN 5338 03:21:34,840 --> 03:21:36,040 EQUIVALENTS MILLIGRAM PERKILOIN 5339 03:21:36,040 --> 03:21:37,600 THE ARGININE ARM COMPARED TO 5340 03:21:37,600 --> 03:21:39,360 PLACEBO AND THIS REMAINED DEEP 5341 03:21:39,360 --> 03:21:41,680 EVEN WHEN WE EXCLUDED THESE 2 5342 03:21:41,680 --> 03:21:43,000 OUTLIERS, ALSO FOUND DECREASE IN 5343 03:21:43,000 --> 03:21:46,720 PAIN SCORES AND WE FOUND A 5344 03:21:46,720 --> 03:21:47,640 NONSTATTISTICALLY SIGNIFICANT 5345 03:21:47,640 --> 03:21:48,440 BUT CLINICALLY RELEVANT DEE 5346 03:21:48,440 --> 03:21:50,400 CREASE OF LENGTH IN HOSPITAL 5347 03:21:50,400 --> 03:21:54,800 STAY BY 17 HOURS. 5348 03:21:54,800 --> 03:21:57,280 THIS YOUNG INVESTIGATOR STUDY 5349 03:21:57,280 --> 03:21:59,120 WAS NOT A DECREASED LECT IN 5350 03:21:59,120 --> 03:22:01,200 HOSPITAL STAY BUT THE GOAL WAS 5351 03:22:01,200 --> 03:22:02,600 TO GENERATE DATA FOR OUR HOPE 5352 03:22:02,600 --> 03:22:04,200 FOR A PHASE THRIE TRIAL BUT WE 5353 03:22:04,200 --> 03:22:06,280 DID FIND A STRONG CORRELATION 5354 03:22:06,280 --> 03:22:08,560 BETWEEN TOTAL OPIOID USE AND THE 5355 03:22:08,560 --> 03:22:10,680 LINK TO HOSPITAL STAY AND OPIOID 5356 03:22:10,680 --> 03:22:12,440 USE IS A NICE SURROGATE FOR THIS 5357 03:22:12,440 --> 03:22:14,040 OTHER OUTCOME THAT WOULD 5358 03:22:14,040 --> 03:22:15,640 ACTUALLY REQUIRE HUNDREDS OF 5359 03:22:15,640 --> 03:22:18,360 PATIENTS TO ENROLL. 5360 03:22:18,360 --> 03:22:21,640 UNBEIMOWNST TO ME DURING THIS 5361 03:22:21,640 --> 03:22:24,200 TIME, DR. RICHARD ONALO WAS 5362 03:22:24,200 --> 03:22:25,080 FOLLOWING OUR WO, AND SCHEMING 5363 03:22:25,080 --> 03:22:27,480 ON HOW THIS COULD BE HELPFUL FOR 5364 03:22:27,480 --> 03:22:29,040 HIS PATIENTS IN NIGERIA WITH 5365 03:22:29,040 --> 03:22:30,040 SICKLE CELL DISEASE. 5366 03:22:30,040 --> 03:22:31,920 SOPHISTICATEDY HE REACHED OUT TO 5367 03:22:31,920 --> 03:22:35,360 ME AND HE VERY QUICKLY BECAME 1 5368 03:22:35,360 --> 03:22:37,360 OF MY STAR K24 MENTEES AND HE 5369 03:22:37,360 --> 03:22:38,520 WAS RECENTLY AWARDED HIS Ph.D. 5370 03:22:38,520 --> 03:22:40,560 FOR THE WORK HE DID IN ARGININE. 5371 03:22:40,560 --> 03:22:45,480 SO HIS GOAL WAS TO DETERMINE THE 5372 03:22:45,480 --> 03:22:47,000 ROLE OF OVERALL ARGININE IN 5373 03:22:47,000 --> 03:22:49,360 CHILDREN ADMITTED FOR PAIN IN 5374 03:22:49,360 --> 03:22:52,440 NIGERIA, WE PERFORMED A BLINDED 5375 03:22:52,440 --> 03:22:54,480 PHASE 2 RANDOMIZED CONTROL TRIAL 5376 03:22:54,480 --> 03:22:56,600 IN 2 HOSPITALS HE USED ORAL 5377 03:22:56,600 --> 03:22:58,760 ARGININE, AND MIXED IT WITH 5378 03:22:58,760 --> 03:23:00,160 GRAPE JUICE AND USED THE DOSE WE 5379 03:23:00,160 --> 03:23:07,040 HAD OUT OF THE OAKLAND STUDY, 5380 03:23:07,040 --> 03:23:10,240 THE 1 MG, DOSE EVERY 8 HOURS FOR 5381 03:23:10,240 --> 03:23:11,400 5 DAYS. 5382 03:23:11,400 --> 03:23:12,440 EVERYBODY WANTED THE GRAPE JUICE 5383 03:23:12,440 --> 03:23:14,640 AND WAS ASKING FOR IT WHEN IT 5384 03:23:14,640 --> 03:23:16,800 WASN'T TIME FOR THEIR STUDY 5385 03:23:16,800 --> 03:23:18,680 DRUG, SO A VERY DIFFERENT 5386 03:23:18,680 --> 03:23:19,400 POPULATION AND THINGS TO 5387 03:23:19,400 --> 03:23:20,720 CONSIDER WHEN WE'RE DOING 5388 03:23:20,720 --> 03:23:21,960 CLINICAL TRIAL DESIGN IN THE 5389 03:23:21,960 --> 03:23:23,800 UNITED STATES COMPARED TO LOW 5390 03:23:23,800 --> 03:23:30,200 RESOURCE ENVIRONMENT IN NIGERIA. 5391 03:23:30,200 --> 03:23:32,520 HE OBTAINED DRUG SAMPLES AT DAY 5392 03:23:32,520 --> 03:23:34,640 5 AND DISCHARGE AND HIS PRIMARY 5393 03:23:34,640 --> 03:23:37,760 OUTCOME MEASURE WAS THE MEASURE 5394 03:23:37,760 --> 03:23:42,360 QUANTIFICATION SCALE, MQS TOOL 5395 03:23:42,360 --> 03:23:44,840 THAT WAS VALIDATED IN 2007 AND 5396 03:23:44,840 --> 03:23:46,760 THIS PAISKLY ASSESSED ALL ANNAL 5397 03:23:46,760 --> 03:23:48,280 GEEZIA USE AND AGAIN WE HAD TO 5398 03:23:48,280 --> 03:23:51,080 THINK HARD ON WHAT WAS THE BEST 5399 03:23:51,080 --> 03:23:52,040 OUTCOME MEASURE FOR NIGERIA 5400 03:23:52,040 --> 03:23:55,040 BECAUSE I WAS USED TO USING IV 5401 03:23:55,040 --> 03:23:57,240 OPIOIDS AS OUR OUTCOME BUT THEY 5402 03:23:57,240 --> 03:23:58,640 JUST DON'T USE PARENT OPIOIDS 5403 03:23:58,640 --> 03:24:00,520 LIKE WE DO IN THE UNITED STATES. 5404 03:24:00,520 --> 03:24:03,320 PATIENTS MAY GET 1 DOSE OF AN IV 5405 03:24:03,320 --> 03:24:04,960 OPIOID WHEN THEY HIT THE 5406 03:24:04,960 --> 03:24:06,640 ENGINEER DEPARTMENT BUT THEN 5407 03:24:06,640 --> 03:24:07,720 THEY QUICKLY CHAIMPLE THEM OVER 5408 03:24:07,720 --> 03:24:09,720 TO ORALS SO THERE'S NOTHING WE 5409 03:24:09,720 --> 03:24:11,120 DO IN AN INTERVENTION STUDY THAT 5410 03:24:11,120 --> 03:24:18,240 WOULD AN IMPACT ON IV OPIOIDS. 5411 03:24:18,240 --> 03:24:20,480 INCLUSION KRIST TIER REVIEWIA 5412 03:24:20,480 --> 03:24:22,760 WAS AGE 5-17 YEARS WITH SICKLE 5413 03:24:22,760 --> 03:24:25,040 CELL DISEASE WITH A PAIN SCORE 5414 03:24:25,040 --> 03:24:26,960 OF 7 OR HIGHER AND THIS WAS A 5415 03:24:26,960 --> 03:24:28,640 NUMBER OF CLINICAL OUTCOMES HE 5416 03:24:28,640 --> 03:24:30,840 LOOKED AT BESIDES THE MQS SCORES 5417 03:24:30,840 --> 03:24:34,840 HE LOOKEDDA THE PAIN SCORES, 5418 03:24:34,840 --> 03:24:37,320 CARDIO PULMONARY OUTCOMES, DID 5419 03:24:37,320 --> 03:24:38,240 ECHOCARDIOGRAPHY ON DAY 0 AND 5420 03:24:38,240 --> 03:24:40,360 THEN AT DAY 5 FOR THE PATIENTS 5421 03:24:40,360 --> 03:24:42,240 WERE STILL ADMITTED AND TIME TO 5422 03:24:42,240 --> 03:24:43,800 CRISIS RESLIEWGZ AND TOTAL 5423 03:24:43,800 --> 03:24:47,480 LENGTH OF HOSPITAL STAY. 5424 03:24:47,480 --> 03:24:52,240 SO 68 PATIENTS WERE RECRUITED 5425 03:24:52,240 --> 03:24:56,040 AND THERE WERE NO RANDOMIZED 5426 03:24:56,040 --> 03:25:00,240 STUDIES, 50% OF THEM WERE MAIP, 5427 03:25:00,240 --> 03:25:02,320 PRETTY LOW HU USE ABOUT THAT'S 5428 03:25:02,320 --> 03:25:05,000 REFLECTIVE WHAT HAVE'S GOING ON 5429 03:25:05,000 --> 03:25:07,640 IN NIGERIA AND THEN WE FOUND 5430 03:25:07,640 --> 03:25:09,640 ARGININE AND GLOBAL ARGININE VIA 5431 03:25:09,640 --> 03:25:11,440 BILITY COMPARED TO CLA SEEB O IS 5432 03:25:11,440 --> 03:25:12,440 NOT UNEXPECTED BUT YOU CAN SEE 5433 03:25:12,440 --> 03:25:16,320 THAT EVEN IF YOU DO NOTHING, 5434 03:25:16,320 --> 03:25:17,320 YOUR LOW ARGININE DOES INCREASE 5435 03:25:17,320 --> 03:25:21,360 OVER TIME AT THE TIME OF 5436 03:25:21,360 --> 03:25:22,440 DISCHARGE BUT ARGININE 5437 03:25:22,440 --> 03:25:23,240 SUPPLEMENTATION INCREASED THAT 5438 03:25:23,240 --> 03:25:24,600 AMOUNT AND MYOCARDITIS SEEB O 5439 03:25:24,600 --> 03:25:26,080 THERE'S NO GLOBAL DIFFERENCE IN 5440 03:25:26,080 --> 03:25:28,320 VIABILITY, WHERE WE NOTED AN 5441 03:25:28,320 --> 03:25:29,600 IMPROVEMENT IN THE ARGININE ARM. 5442 03:25:29,600 --> 03:25:31,240 SO WE ALSO SAW A SIGNIFICANT 5443 03:25:31,240 --> 03:25:33,400 DISCIPLINARY CREASE IN THE MQS 5444 03:25:33,400 --> 03:25:35,040 SCORE IN THE ARM COMPARED TO 5445 03:25:35,040 --> 03:25:36,640 PLACEBO, THIS IS THE PRIMARY 5446 03:25:36,640 --> 03:25:39,040 OUTCOME MEASURE, SO HERE YOU 5447 03:25:39,040 --> 03:25:39,800 HAVE ARGININE VERSUS PLACEBO AND 5448 03:25:39,800 --> 03:25:43,080 IF YOU LOOK AT THE MEAN 5449 03:25:43,080 --> 03:25:45,000 CUMULATIVE MQS SCORE BEGAN TO 5450 03:25:45,000 --> 03:25:47,440 DIVERSE AFTER 24 HOIRS OF 5451 03:25:47,440 --> 03:25:47,680 THERAPY. 5452 03:25:47,680 --> 03:25:49,640 ALSO FOUND THAT THE MEAN DAILY 5453 03:25:49,640 --> 03:25:51,440 RATE OF DECLINE IN PAIN SCORES 5454 03:25:51,440 --> 03:25:54,520 WAS FASTER THAN IN PLACEBO AND 5455 03:25:54,520 --> 03:25:56,040 LOOKEDDA THE LOWEST PAIN SCORE 5456 03:25:56,040 --> 03:25:57,720 REPORTED FOR EACH DAY AND THE 5457 03:25:57,720 --> 03:25:59,200 HIGHEST PAIN SCORE REPORTED FOR 5458 03:25:59,200 --> 03:26:01,280 EACH DAY AND SO THE RED LINE IS 5459 03:26:01,280 --> 03:26:03,560 PLACEBO AND THE BLUE LINE IS 5460 03:26:03,560 --> 03:26:05,200 ARGININE SO DIFFERENT IN PAIN 5461 03:26:05,200 --> 03:26:08,200 SCORES DAILY, AGAIN STARTED TO 5462 03:26:08,200 --> 03:26:09,680 DIVERGE BY DAY 2. 5463 03:26:09,680 --> 03:26:10,520 HE ALSO LOOKED AT BLOOD 5464 03:26:10,520 --> 03:26:12,160 PRESSURE, SO WE KNOW AS 5465 03:26:12,160 --> 03:26:13,360 CLINICIANS KIDS WILL COME IN 5466 03:26:13,360 --> 03:26:14,720 WITH HIGH BLOOD PRESSURE WHEN 5467 03:26:14,720 --> 03:26:16,240 THEY'RE IN ACUTE PAIN AND HE 5468 03:26:16,240 --> 03:26:19,560 FOUND THAT THE DAILY PERCENT OF 5469 03:26:19,560 --> 03:26:21,640 DECLINE IN SYSTOLIC AND 5470 03:26:21,640 --> 03:26:23,800 DIASTOLIC WAS STEEPER IN THE 5471 03:26:23,800 --> 03:26:25,560 ARGININE ARM COMPARED TO PLACEBO 5472 03:26:25,560 --> 03:26:26,800 AND THIS WAS ALSO RECENTLY 5473 03:26:26,800 --> 03:26:29,440 PUBLISHED AND THEN LOOKINGA THE 5474 03:26:29,440 --> 03:26:30,640 CARDIO PULMONARY EFFECTS AND I 5475 03:26:30,640 --> 03:26:32,040 ENCOURAGE EVERYONE TO TAKE A 5476 03:26:32,040 --> 03:26:34,000 LOOK AT THIS PAPER BECAUSE IT'S 5477 03:26:34,000 --> 03:26:35,040 REALLYKS SIGHTING RESULTS BUT 5478 03:26:35,040 --> 03:26:36,440 IESM FOCUSING JUST NOW, BECAUSE 5479 03:26:36,440 --> 03:26:37,640 WE DON'T HAVE ENOUGH TIME TO GO 5480 03:26:37,640 --> 03:26:41,400 THROUGH IT ALL ON THE TR JET, 5481 03:26:41,400 --> 03:26:43,320 HERE YOU HAVE THE ARGININE 5482 03:26:43,320 --> 03:26:47,640 VERSUS PLACEBO, BLUE IS THE 5483 03:26:47,640 --> 03:26:49,240 PRESUPPLEMENT, TRJET, PINK IS 5484 03:26:49,240 --> 03:26:52,640 THE POST SUPPLEMENT TRJET, AND 5485 03:26:52,640 --> 03:26:54,840 QUH WE LOOK AT IT ALTASD 5486 03:26:54,840 --> 03:26:56,360 TOGETHER, THERE WAS A 22% 5487 03:26:56,360 --> 03:26:59,840 DECREASE IN THE JETS COMPARED TO 5488 03:26:59,840 --> 03:27:02,440 3.8% IN THE PLACEBO ARM. 5489 03:27:02,440 --> 03:27:05,200 NOW SOME OF THESE PATIENTS HAD A 5490 03:27:05,200 --> 03:27:07,240 NORMAL TRJET, BUT ON 60% OF 5491 03:27:07,240 --> 03:27:10,840 THESE PATIENTS HAD AN ELEVATED 5492 03:27:10,840 --> 03:27:12,840 TRJET AS AND THIS HAS BEEN 5493 03:27:12,840 --> 03:27:14,440 REPORTED BY DR. MATCHAD O AND 5494 03:27:14,440 --> 03:27:16,040 COLLEAGUES, SO WHEN WE BEING LAT 5495 03:27:16,040 --> 03:27:18,840 PATIENT BHOS HAD HAD AN 5496 03:27:18,840 --> 03:27:20,760 ABNORMALITIES NORNLAL TRJET, AND 5497 03:27:20,760 --> 03:27:23,640 THEY THERE WERE AN 82% REDUCTION 5498 03:27:23,640 --> 03:27:24,960 IN THE TRJET, SO WHAT'S 5499 03:27:24,960 --> 03:27:26,120 INTERESTING ABOUT IN IS THAT 5500 03:27:26,120 --> 03:27:31,120 THIS IS ACTUALLY POSSIBLY, A YET 5501 03:27:31,120 --> 03:27:32,320 UNRECOGNIZED BENEFIT OF ARGININE 5502 03:27:32,320 --> 03:27:34,040 THERAPY BECAUSE WE KNOW THESE 5503 03:27:34,040 --> 03:27:35,800 PATIENTS HAVE THE TRANSIENT 5504 03:27:35,800 --> 03:27:37,640 ELEVATIONS IN TRJET BUT IF 5505 03:27:37,640 --> 03:27:38,680 THERE'S ANY OXYGEN COMPROMISE 5506 03:27:38,680 --> 03:27:41,840 FRIDAY THAT, THAT WILL ACTUALLY 5507 03:27:41,840 --> 03:27:43,840 LEAD TO HIPOXEMIA AND INCREASED 5508 03:27:43,840 --> 03:27:45,440 SICKLING SO IT APPEARS THAT 5509 03:27:45,440 --> 03:27:49,240 ARGININE IN THE ACUTE PHASE LIKE 5510 03:27:49,240 --> 03:27:50,560 OUR PROPHYLACTIC STUDY HAS AN 5511 03:27:50,560 --> 03:27:54,680 INL PACT ON TRI KUS PUD AND 5512 03:27:54,680 --> 03:27:59,440 DOPPLER ECHO. 5513 03:27:59,440 --> 03:28:01,240 DR. ONOLAO'S GROUP ARE AND 5514 03:28:01,240 --> 03:28:02,640 SPECIFICALLY AND TRIP OWNINS, 5515 03:28:02,640 --> 03:28:04,680 NOW THESE ARE THE SORT OF 5516 03:28:04,680 --> 03:28:07,240 BIOMARKERS I GET IF A 60 5517 03:28:07,240 --> 03:28:09,200 YEAR-OLD PRESENTS TO MY 5518 03:28:09,200 --> 03:28:09,840 EMERGENCY DEPARTMENT WITH CHEST 5519 03:28:09,840 --> 03:28:13,640 PAIN YOU DON'T WANT TO GO INTO 5520 03:28:13,640 --> 03:28:14,880 MY PEDIATRIC EMERGENCY 5521 03:28:14,880 --> 03:28:16,440 DEPARTMENT BECAUSE THEN I'M 5522 03:28:16,440 --> 03:28:18,440 GETTING A TRIP OWNIN AND THEN 5523 03:28:18,440 --> 03:28:20,320 I'M CALLING 911, THEY BUT WITH 5524 03:28:20,320 --> 03:28:23,840 KIDS THEY COME IN WITH OOH CUTE 5525 03:28:23,840 --> 03:28:25,920 CHEOF THE PAIN AND TRIP OWNIN 5526 03:28:25,920 --> 03:28:27,840 AND THIS GIVES ME PAUSE AS TO 5527 03:28:27,840 --> 03:28:28,240 WHAT'S GOING ON. 5528 03:28:28,240 --> 03:28:31,960 SO HERE YOU HAVE THE TROPONIN 5529 03:28:31,960 --> 03:28:35,240 LEVELS AND THE BNP, IF WE LOOK 5530 03:28:35,240 --> 03:28:37,080 AT ALL PATIENTS THEY'RE ELEVATED 5531 03:28:37,080 --> 03:28:38,520 BUT REALLY THE DIFFERENCE IS IN 5532 03:28:38,520 --> 03:28:40,120 PATIENTS WITH AND WITHOUT ACUTE 5533 03:28:40,120 --> 03:28:41,520 CHEST SYNDROME SO VERY HIGH 5534 03:28:41,520 --> 03:28:43,120 LEVELS AND PATIENTS WITH ACUTE 5535 03:28:43,120 --> 03:28:46,200 CHEST SYNDROME AND HIGH TROPONIN 5536 03:28:46,200 --> 03:28:48,760 LEVELS AND YOU KNOW BARELY--THEY 5537 03:28:48,760 --> 03:28:50,160 WERE NORMAL IN PATIENTS WITH 5538 03:28:50,160 --> 03:28:52,360 SICKLE CELL PAIN WITHOUT CHEST 5539 03:28:52,360 --> 03:28:52,560 PAIN. 5540 03:28:52,560 --> 03:28:55,600 SO THEN, THERE WAS NO--THERE WAS 5541 03:28:55,600 --> 03:28:58,240 NO CORRELATION BETWEEN THESE 5542 03:28:58,240 --> 03:28:59,840 BIOMARKERS AND [INDISCERNIBLE] 5543 03:28:59,840 --> 03:29:04,040 VELOCITY, WHEN WE LOOK AT PREAND 5544 03:29:04,040 --> 03:29:06,080 POST SUPPLEMENTATION, ALTHOUGH 5545 03:29:06,080 --> 03:29:08,720 THE BMP AND TROPONINs TREND 5546 03:29:08,720 --> 03:29:09,840 INDEED THE RIGHT DIRECTION AT 5547 03:29:09,840 --> 03:29:11,240 THE TIME OF DISCHARGE SO SHOWING 5548 03:29:11,240 --> 03:29:13,440 THE PARENTS WERE IMPROVING THERE 5549 03:29:13,440 --> 03:29:15,240 WAS A STATISTICALLY SIGNIFICANT 5550 03:29:15,240 --> 03:29:17,440 PRIMARY REVIEWER UFMENT IN BNP 5551 03:29:17,440 --> 03:29:18,360 THAT WAS SIGNIFICANT IN THE 5552 03:29:18,360 --> 03:29:19,840 ARGININE ARM AND THEN FINALLY 5553 03:29:19,840 --> 03:29:22,440 THE MOST IMPORTANT CLINICAL 5554 03:29:22,440 --> 03:29:24,160 OUTCOMES, WERE THE TIME TO 5555 03:29:24,160 --> 03:29:25,760 CRISIS RESOLUTION AND LENGTH OF 5556 03:29:25,760 --> 03:29:27,440 HOSPITAL STAY, NOW, TIME TO 5557 03:29:27,440 --> 03:29:29,040 CRISIS RESOLUTION WAS DEFINED IN 5558 03:29:29,040 --> 03:29:31,600 THIS STUDY AS A PAIN SCORER OF 5559 03:29:31,600 --> 03:29:31,920 LESS THAN 4. 5560 03:29:31,920 --> 03:29:33,560 AND WE KNOW THAT THAT'S 5561 03:29:33,560 --> 03:29:34,680 PROBLEMATIC BECAUSE WE ALL KNOW 5562 03:29:34,680 --> 03:29:38,360 MANY PATIENT WHO IS NEVER LEAVE 5563 03:29:38,360 --> 03:29:39,960 THE HOSPITAL WITH A PAIN SCORE 5564 03:29:39,960 --> 03:29:40,600 THAT'S LESS THAN 4. 5565 03:29:40,600 --> 03:29:41,400 SO THERE WERE A NUMBER OF 5566 03:29:41,400 --> 03:29:42,840 PATIENT WHO IS HAD TO BE 5567 03:29:42,840 --> 03:29:44,000 SENSORRED FROM THIS BUT EVEN 5568 03:29:44,000 --> 03:29:45,080 STILL LOOKING AT THESE PATIENTS 5569 03:29:45,080 --> 03:29:46,440 THERE WAS A SIGNIFICANT DECREASE 5570 03:29:46,440 --> 03:29:48,760 IN TIME TO CRISIS RESLIEWGZ IN 5571 03:29:48,760 --> 03:29:50,040 THE ARGININE ARM COMPARED TO 5572 03:29:50,040 --> 03:29:52,440 PLACEBO AND THEN LOOKING AT BY 5573 03:29:52,440 --> 03:29:54,400 DAY 5, 54% OF THE CHILDREN ON 5574 03:29:54,400 --> 03:29:56,120 ARGININE HAD ALREADY BEEN 5575 03:29:56,120 --> 03:29:57,960 DISCHARGED COMPARED TO ONLY 24% 5576 03:29:57,960 --> 03:30:00,640 IN THE LA SEEB O ARM SO AGAIN 5577 03:30:00,640 --> 03:30:02,120 STATISTICALLY SIGNATURES 95 5578 03:30:02,120 --> 03:30:03,320 SCANT AND CLINICALLY RELEVANT 5579 03:30:03,320 --> 03:30:04,640 OBSERVATION AND HERE WE HAVE 5580 03:30:04,640 --> 03:30:06,320 LENGTH OF HOSPITAL STAY, WE HAD 5581 03:30:06,320 --> 03:30:07,240 THAT OUTCOME ON EVERY SINGLE 5582 03:30:07,240 --> 03:30:08,800 PATIENT AND THERE WAS A 5583 03:30:08,800 --> 03:30:13,840 SIGNIFICANT DECREASE IN LECT OF 5584 03:30:13,840 --> 03:30:16,240 HOSPITAL STAY BY NEARLY 2 DAYS 5585 03:30:16,240 --> 03:30:17,080 COMPARE TO PLACEBO. 5586 03:30:17,080 --> 03:30:20,480 SO MANY PATIENTS WERE SICK, THE 5587 03:30:20,480 --> 03:30:22,360 AVERAGE HOSPITAL STAY WAS 10 5588 03:30:22,360 --> 03:30:23,640 DAYS WHICH WAS VERY DIFFERENT 5589 03:30:23,640 --> 03:30:24,360 THAN THE MEAN HOSPITAL STAY IN 5590 03:30:24,360 --> 03:30:26,200 THE UNITED STATES WHEN WE TALK 5591 03:30:26,200 --> 03:30:27,240 ABOUT A LITTLE BIT MORE WHEN WE 5592 03:30:27,240 --> 03:30:31,040 LOOK AT SOME OF OUR OTHER STTDS 5593 03:30:31,040 --> 03:30:33,080 SO AS FAR AS SERIOUS ADVERSE 5594 03:30:33,080 --> 03:30:37,240 EVENTS THERE WERE NO AEs IN 5595 03:30:37,240 --> 03:30:39,320 THE ARM, THEY WERE MILD, SIMILAR 5596 03:30:39,320 --> 03:30:41,040 IN BOTH GROUPS, THERE WAS A 5597 03:30:41,040 --> 03:30:42,680 TREND TOWARDS INCREASED VOMITING 5598 03:30:42,680 --> 03:30:44,920 AND IT WASN'T SIGNIFICANT BUT I 5599 03:30:44,920 --> 03:30:46,680 THINK THIS IS CLINICALLY REVANT. 5600 03:30:46,680 --> 03:30:48,640 TWENTY% OF THESE PATIENTS HAD 5601 03:30:48,640 --> 03:30:51,160 NAUSEA AND VOMITING WE KNOW THAT 5602 03:30:51,160 --> 03:30:52,440 ORAL ARGININE WILL CAUSE STOMACH 5603 03:30:52,440 --> 03:30:55,560 UPSET SO WE MAY WANT TO BE MORE 5604 03:30:55,560 --> 03:30:58,400 LIBERAL WITH USING ZOFRAN IN 5605 03:30:58,400 --> 03:30:59,720 THESE PATIENTS TO TREAT THIS 5606 03:30:59,720 --> 03:31:01,360 SIDE EFFECT. 5607 03:31:01,360 --> 03:31:02,960 SO NOW SWITCHING GEARS TO THE 5608 03:31:02,960 --> 03:31:04,360 RESULTS OF OUR ATLANTA STUDY SO 5609 03:31:04,360 --> 03:31:06,320 WE ARE FOR THE FIRST TIME 5610 03:31:06,320 --> 03:31:08,920 REPORTING PHASE 2 RCT OF IV 5611 03:31:08,920 --> 03:31:10,320 ARGININE IN CHILDREN WITH SICKLE 5612 03:31:10,320 --> 03:31:12,080 CELL DISEASE AND PAIN SUPPORTED 5613 03:31:12,080 --> 03:31:14,840 BY THE FDA ORPHANED PRODUCTS 5614 03:31:14,840 --> 03:31:16,640 GRANT PROGRAM WHEN I GOT TO 5615 03:31:16,640 --> 03:31:16,840 EMORY. 5616 03:31:16,840 --> 03:31:18,840 SO OUR GOAL WAS TO DETERMINE 5617 03:31:18,840 --> 03:31:20,680 EFFICACY AND SAFETY OF CHILDREN 5618 03:31:20,680 --> 03:31:21,040 WITH SCD. 5619 03:31:21,040 --> 03:31:23,720 AND THE STUDY WAS DONE AT EMORY 5620 03:31:23,720 --> 03:31:26,840 CHILDREN'S HEALTHCARE ATLANTA. 5621 03:31:26,840 --> 03:31:27,720 ANOTHER BLINDED RANDOMIZED MA 5622 03:31:27,720 --> 03:31:30,040 SEEB O CONTROL PHASE, UTELIZING 5623 03:31:30,040 --> 03:31:33,200 2 OF OUR CHILDREN'S HOSPITALS, 5624 03:31:33,200 --> 03:31:35,480 WE USED IV ARGININE COMPARED TO 5625 03:31:35,480 --> 03:31:36,640 PLACENTA SEEBY, IV, 8 HOURS 5626 03:31:36,640 --> 03:31:38,840 DISCHARGE FOR A MAXIMUM OF 7 5627 03:31:38,840 --> 03:31:40,160 DAYS SUBJECTS WERE RANDOMIZED TO 5628 03:31:40,160 --> 03:31:44,560 1 OF 3 ARMS, THEY WERE 5629 03:31:44,560 --> 03:31:45,160 STRAIGHTIFIED FOR HYDROXUREEA 5630 03:31:45,160 --> 03:31:47,320 USE BECAUSE WE HAD PUBLISHED IN 5631 03:31:47,320 --> 03:31:49,480 BACK IN 20,032 THERE WAS A 5632 03:31:49,480 --> 03:31:50,760 SINNER GESTIC IMPACT ON NITRIC 5633 03:31:50,760 --> 03:31:53,200 OXIDE ROUGH ATOM DUKS WHEN 5634 03:31:53,200 --> 03:31:55,040 ARGININE AND HYDROXY UREA WERE 5635 03:31:55,040 --> 03:31:56,440 GIVEN TOGETHER SO WE USED OUR 5636 03:31:56,440 --> 03:31:57,640 STABBED ARD DOSE THAT WAS 5637 03:31:57,640 --> 03:32:00,440 SIMILAR TO THE DOSE WE USED IN 5638 03:32:00,440 --> 03:32:02,360 OAK LAND, A HUNDRED MILLIGRAMS 5639 03:32:02,360 --> 03:32:03,800 PER KILOGRAM FOR DOSE, 3 TOO 5640 03:32:03,800 --> 03:32:06,600 MANYS A DAY, AND THERE WAS A AN 5641 03:32:06,600 --> 03:32:08,000 ARM THAT RELIEVED A LOADING 5642 03:32:08,000 --> 03:32:11,760 DOSE, FOLLOW BIDE STANDARD DOATS 5643 03:32:11,760 --> 03:32:13,400 AND PLACEBO. 5644 03:32:13,400 --> 03:32:14,400 BLOOD SAMPLES WERE ABNORMALITIES 5645 03:32:14,400 --> 03:32:15,760 TAINED PRIOR TO ADMINISTRATION 5646 03:32:15,760 --> 03:32:18,960 AND DISCHARGED AGAIN PUTTING 5647 03:32:18,960 --> 03:32:22,640 TOGETHER A SCD PAIN REPOSITORY 5648 03:32:22,640 --> 03:32:25,960 AND O GROWING THIS A RESOURCE 5649 03:32:25,960 --> 03:32:30,360 AND OPEN TO COLLABORATORS. 5650 03:32:30,360 --> 03:32:32,280 ANY GENO TYPE REQUIRING OV 5651 03:32:32,280 --> 03:32:40,280 OPIOIDS HOSPITALIZED FOR PAIN. 5652 03:32:40,280 --> 03:32:43,160 AND PRIMARY OUTCOME AND TOTAL 5653 03:32:43,160 --> 03:32:46,480 OPIOID USE, TIME TO CRISIS 5654 03:32:46,480 --> 03:32:48,320 RESOLUTION, PATIENT REPORTED OUT 5655 03:32:48,320 --> 03:32:49,760 COMES, WE WOULD NEED OVER 300 5656 03:32:49,760 --> 03:32:51,840 PATIENTS BUT THAT WAS A 5657 03:32:51,840 --> 03:32:52,560 SECONDARY OUTCOME MEASURE, 5658 03:32:52,560 --> 03:32:54,720 LOOKING AT THE TIME OF STUDY 5659 03:32:54,720 --> 03:32:57,000 DRUG DELIVERY TO LAST IV OPIOID 5660 03:32:57,000 --> 03:32:58,040 SORT OF BORROWING THIS 5661 03:32:58,040 --> 03:33:00,040 DEFINITION FROM SOME OF THE 5662 03:33:00,040 --> 03:33:00,880 BIOFACAS REMEMBERRA STUDIES, 5663 03:33:00,880 --> 03:33:02,520 LOOKED AT PAIN SCORES AND 5664 03:33:02,520 --> 03:33:05,040 PATIENT REPORTED OUTCOMES, WE 5665 03:33:05,040 --> 03:33:06,640 OBTAINED BIOMARKERS OFOXIDATIVE 5666 03:33:06,640 --> 03:33:07,440 STRESS AND MITOCHONDRIAL 5667 03:33:07,440 --> 03:33:09,040 FUNCTION AND THAT UTILIZED A 5668 03:33:09,040 --> 03:33:11,240 FACT OF IND AND REGISTERED WITH 5669 03:33:11,240 --> 03:33:11,840 CLINICAL TRIALS .GOV. 5670 03:33:11,840 --> 03:33:14,200 SO IF OUR ENROLLMENT, WE KREENED 5671 03:33:14,200 --> 03:33:16,440 OVER 1500 PATIENTS AT OUR SINGLE 5672 03:33:16,440 --> 03:33:20,000 SITE TO HOSPITAL AREA. 5673 03:33:20,000 --> 03:33:21,520 AND WE ENDED UP RANDOMIZING A 5674 03:33:21,520 --> 03:33:23,800 HUNDRED OF THEM, AND CONSENTED 5675 03:33:23,800 --> 03:33:25,640 TO 114, AND THE PATIENTS WHO 5676 03:33:25,640 --> 03:33:27,360 WERE SCREEN FAILS WERE BASICALLY 5677 03:33:27,360 --> 03:33:29,040 PATIENTS WHO WE RANDOMIZED TRIAL 5678 03:33:29,040 --> 03:33:30,800 OHMIZED BEFORE THE PHARMACY, 5679 03:33:30,800 --> 03:33:33,680 ENROLLED BEFORE THE PHARMACY 5680 03:33:33,680 --> 03:33:34,800 WOULD LEAD BUT THEN GOT 5681 03:33:34,800 --> 03:33:36,440 DISCHARGED FROM THE HOSPITAL AND 5682 03:33:36,440 --> 03:33:38,720 MET A EXCLUES CRITERIA 5683 03:33:38,720 --> 03:33:40,040 CONSIDERED AN EXCLUSION CRITERIA 5684 03:33:40,040 --> 03:33:41,160 FAILURE SO THIS STRATEGY IS 5685 03:33:41,160 --> 03:33:44,280 REALLY PART OF THE SECRET TO OUR 5686 03:33:44,280 --> 03:33:45,920 SUCCESS BECAUSE WE ACTIVELY 5687 03:33:45,920 --> 03:33:47,320 RECRUIT PATIENTS IN THE 5688 03:33:47,320 --> 03:33:48,240 EMERGENCY ROOM DEPARTMENT, 74% 5689 03:33:48,240 --> 03:33:49,600 OF OUR PATIENTS WERE CONSENTED 5690 03:33:49,600 --> 03:33:51,040 IN THE ED, WE WERE APPROACHING 5691 03:33:51,040 --> 03:33:53,240 PATIENTS ON THE FLOOR AS WELL IF 5692 03:33:53,240 --> 03:33:54,280 THEY WERE ADMITTED OVER NIGHT 5693 03:33:54,280 --> 03:33:55,640 BUT MOST OF THE TIME THE PARENTS 5694 03:33:55,640 --> 03:33:59,600 WERE NOT THERE TO CONSENT SO WE 5695 03:33:59,600 --> 03:34:00,520 NOT ABLE TO ENROLL THOSE 5696 03:34:00,520 --> 03:34:01,680 PATIENTS OR THE PATIENTS AND 5697 03:34:01,680 --> 03:34:03,440 PARENTINGS WERE SO TIRED THEY 5698 03:34:03,440 --> 03:34:05,640 COULDN'T BE PROPERLY CONSENTED. 5699 03:34:05,640 --> 03:34:06,880 SO HERE'S OUR 108 PATIENTS. 5700 03:34:06,880 --> 03:34:08,400 WE HAVE 36 PATIENTS IN EACH ARM. 5701 03:34:08,400 --> 03:34:10,800 THIS IS THE STANDARD DOSE, THIS 5702 03:34:10,800 --> 03:34:12,680 IS THE ARGININE LOADING DOSE AND 5703 03:34:12,680 --> 03:34:15,000 THIS IS PLACEBO, NO DIFFERENCES 5704 03:34:15,000 --> 03:34:18,280 ACROSS OUR ARMS, THE AGE OF 5705 03:34:18,280 --> 03:34:19,480 PATIENTS WERE ABOUT 12, THERE 5706 03:34:19,480 --> 03:34:21,680 WAS A LITTLE BIT OF A TREND OF 5707 03:34:21,680 --> 03:34:23,320 OLDER KIDDINGS IN THE ARGININE 5708 03:34:23,320 --> 03:34:25,760 GROUPS COMPARED TO PLACEBO BUT 5709 03:34:25,760 --> 03:34:26,960 IT WASN'T STRATEGIC 5710 03:34:26,960 --> 03:34:28,320 PLANNISTICALLY SIGNIFICANT, 50% 5711 03:34:28,320 --> 03:34:32,240 MAIL, OVER 67% WERE ON HYDROXY 5712 03:34:32,240 --> 03:34:33,800 UREA WHICH IS PRETTY GOD AND 5713 03:34:33,800 --> 03:34:41,240 THEN ABOUT 70% OF THE PATIENTS 5714 03:34:41,240 --> 03:34:45,880 WERE SINGLE SS OR SINGLE S-0. 5715 03:34:45,880 --> 03:34:49,040 SO WE HERE WE HAVE CLINICAL OUTS 5716 03:34:49,040 --> 03:34:52,560 SO AS IRB MENTIONED WE LOOK THE 5717 03:34:52,560 --> 03:34:53,440 AT TOTEDDAL EQUIVALENTS AND 5718 03:34:53,440 --> 03:34:55,600 LOOKED AT TIME TO CRISIS 5719 03:34:55,600 --> 03:34:55,880 RESOLUTION. 5720 03:34:55,880 --> 03:34:57,720 WE ALSO DID A SUBANALYSIS TO 5721 03:34:57,720 --> 03:35:00,320 LOOK AT YUNGER KIDS 5722 03:35:00,320 --> 03:35:01,400 BECAUSE--YOUNGER KIDS BECAUSE WE 5723 03:35:01,400 --> 03:35:02,680 DID ADENTIFY A LOT OF KID 5724 03:35:02,680 --> 03:35:03,960 NEGLIGENCE THE OLDER GROUP, AND 5725 03:35:03,960 --> 03:35:06,240 SOME OF THE CHRONIC PATIENTS 5726 03:35:06,240 --> 03:35:07,440 WHICH WERE HOPE HOPING TO A 5727 03:35:07,440 --> 03:35:08,840 DEEPER DIVE WITH OUR ANALYSIS, 5728 03:35:08,840 --> 03:35:11,480 WE WILL GET YOU A BOX SHEET, SO 5729 03:35:11,480 --> 03:35:13,720 OUR TYPE WE HAD, WE WERE 5730 03:35:13,720 --> 03:35:14,920 PRESENTING THE UNADJUSTED VALUES 5731 03:35:14,920 --> 03:35:17,520 AND THE ADJUSTED VALUES, AND THE 5732 03:35:17,520 --> 03:35:20,920 AGGRESSION WAS JUSTIFIED FOR 5733 03:35:20,920 --> 03:35:22,760 HYDROXY UREA USE, AND WHICH 5734 03:35:22,760 --> 03:35:24,800 WE'RE ALL ITEMS THAT POTENTIALLY 5735 03:35:24,800 --> 03:35:25,720 IMPACT OUR OUTCOME MEASURES SO 5736 03:35:25,720 --> 03:35:29,080 IF YOU LOOK AT OUR P-VALUES, 5737 03:35:29,080 --> 03:35:29,880 NOTHING WAS STATISTICALLY 5738 03:35:29,880 --> 03:35:31,200 SIGNIFICANT BUT THERE WAS A 5739 03:35:31,200 --> 03:35:32,840 RELEVANT TREND ACROSS THE BOARD, 5740 03:35:32,840 --> 03:35:37,680 SO, LOOK BEING AT TOTAL IV 5741 03:35:37,680 --> 03:35:42,600 OPIOID USE, AND AND REQUIRED 45% 5742 03:35:42,600 --> 03:35:46,760 MORE IV OPIOIDS, IN THE ARMS, 5743 03:35:46,760 --> 03:35:48,280 AND OBSERVATION FRIDAY, IF WE 5744 03:35:48,280 --> 03:35:49,720 LOOKED JUST AT THE KIDS UNDER 5745 03:35:49,720 --> 03:35:53,640 17, THAT WAS MORE THAN 80% 5746 03:35:53,640 --> 03:35:55,640 INCREASED TOTAL OPIOID USE IN 5747 03:35:55,640 --> 03:35:57,320 THE PLACEBO ARM COMPARED TO 5748 03:35:57,320 --> 03:35:58,280 ARGININE, AND THEN LOOKING AT 5749 03:35:58,280 --> 03:36:00,360 OUR TIME TO CRISIS RESOLUTION, 5750 03:36:00,360 --> 03:36:03,760 SO IT WAS OVER 15 HOUR, 5751 03:36:03,760 --> 03:36:05,240 DIFFERENCE, LONGER TIME TO 5752 03:36:05,240 --> 03:36:07,440 CRISIS RESOLUTION IN THE 5753 03:36:07,440 --> 03:36:10,680 ARGININE COMPARED TO PLACEBO, 5754 03:36:10,680 --> 03:36:12,280 BUT, AND IF YOU LOOK AT THIS, 5755 03:36:12,280 --> 03:36:14,280 THOUGH, MOST OF OUR TIME TO 5756 03:36:14,280 --> 03:36:15,680 CRISIS RESOLUTION WAS LESS THAN 5757 03:36:15,680 --> 03:36:17,080 72 HOURS, SO I JUST WANTED TO 5758 03:36:17,080 --> 03:36:19,320 POINT OUT THAT THIS MAY NOT 5759 03:36:19,320 --> 03:36:20,520 ACTUALLY BE AN IDEAL OUTCOME 5760 03:36:20,520 --> 03:36:22,000 MEASURE, AND WE THINK ABOUT THE 5761 03:36:22,000 --> 03:36:23,520 STUDY WHERE PATIENTS WERE 5762 03:36:23,520 --> 03:36:25,200 HOSPITALIZED FOR DEN A DAYS WHEN 5763 03:36:25,200 --> 03:36:26,720 I LOOKEDDA THE MEAN OVER ALL 5764 03:36:26,720 --> 03:36:28,160 HOSPITAL STAY FOR THESE PATIENTS 5765 03:36:28,160 --> 03:36:30,920 IS ABOUT 2 AND HALF DAYS, SO 5766 03:36:30,920 --> 03:36:32,360 WE'VE REALLY DECREASED FROM 2000 5767 03:36:32,360 --> 03:36:34,640 WHEN I STARTED MY K23 PHASE 2 5768 03:36:34,640 --> 03:36:36,000 TRIAL, THE LENGTH OF HOSPITAL 5769 03:36:36,000 --> 03:36:37,720 STAY WAS 6 DAYS, THE BY THE TIME 5770 03:36:37,720 --> 03:36:40,080 I ENDED IT WAS DOWN TO 4 DAYS, 5771 03:36:40,080 --> 03:36:41,640 NOW WE'RE PUSHING IT BETWEEN 2 5772 03:36:41,640 --> 03:36:43,840 AND HALF AND 3 DAYS SO I THINK 5773 03:36:43,840 --> 03:36:47,320 AS A COMMUNITY OF CLINICAL 5774 03:36:47,320 --> 03:36:48,440 TRIALISTS, PAINS WE REALLY NEED 5775 03:36:48,440 --> 03:36:49,440 TO THINK ABOUT WHERE OR NOT 5776 03:36:49,440 --> 03:36:52,760 WE'LL BE ABLE TO PUSH THAT 5777 03:36:52,760 --> 03:36:54,440 NEEDLE ANY FURTHER BEYOND 24 5778 03:36:54,440 --> 03:36:56,680 HOURS WHEN THESE PATIENTS ARE 5779 03:36:56,680 --> 03:36:58,320 ONLY ADMITTED FOR 2 AND HALF FOR 5780 03:36:58,320 --> 03:36:59,800 3 DAYS, SO THE CHANGE HERE WAS 5781 03:36:59,800 --> 03:37:01,600 ABOUT 16 HOURS AND THE ADJUSTED 5782 03:37:01,600 --> 03:37:02,920 ANALYSIS, WHEN WE LOOKEDDALET 5783 03:37:02,920 --> 03:37:06,600 JUST THE YOUNGER KIDS JUST A BIT 5784 03:37:06,600 --> 03:37:08,240 BETTER CLOSE TO 21 HOURS AND 5785 03:37:08,240 --> 03:37:10,680 AGAIN, WE WOULD NEED A LARGER 5786 03:37:10,680 --> 03:37:13,680 SAMPLE SIZE FOR STATISTICAL 5787 03:37:13,680 --> 03:37:15,040 SIGNIFICANCE, FORTUNATELY WE 5788 03:37:15,040 --> 03:37:16,880 HAVE INTERESTING BIOLOGICAL 5789 03:37:16,880 --> 03:37:18,640 OBSERVATIONS, MORE INTERESTING 5790 03:37:18,640 --> 03:37:21,320 EVEN AFTER ANGELLA RIVERS 5791 03:37:21,320 --> 03:37:22,560 PRESENTATION YESTERDAY ABOUT THE 5792 03:37:22,560 --> 03:37:24,440 RED BLOOD CELLS, NOW WE HAVE 5793 03:37:24,440 --> 03:37:25,600 PUBLISHED IN BLOOD, THE LAST 5794 03:37:25,600 --> 03:37:28,520 YEAR, THAT THERE WAS A DOSE 5795 03:37:28,520 --> 03:37:29,520 DEPENDENT IMPROVE NMENT 5796 03:37:29,520 --> 03:37:33,360 MITOCHONDRIAL FUNCTION AND 5797 03:37:33,360 --> 03:37:35,760 OXIDATIVE STRESS, AND CONTROL 5798 03:37:35,760 --> 03:37:38,320 STUDY, AND DATA, FROM 5799 03:37:38,320 --> 03:37:40,040 PHARMACOKINETICS DATA THAT WAS 5800 03:37:40,040 --> 03:37:42,640 UTILIZE FRIDAY OUR R34 CLINICAL 5801 03:37:42,640 --> 03:37:43,840 TRIALS PLANNING GRANT TO PLAN 5802 03:37:43,840 --> 03:37:45,560 OUR PHASE 3 TRIAL SO WHAT WE 5803 03:37:45,560 --> 03:37:47,840 FOUND FROM THE PHASE 2 TRIAL 5804 03:37:47,840 --> 03:37:48,480 SUPPORTED THOSE ORIGINAL 5805 03:37:48,480 --> 03:37:50,000 OBSERVATIONS BUT NOW WE HAVE 5806 03:37:50,000 --> 03:37:52,320 PLACEBO GROUP, SO WHAT WE HAVE 5807 03:37:52,320 --> 03:37:54,520 IS SIGNIFICANT INCREASE, DOSE 5808 03:37:54,520 --> 03:37:58,080 DEPENDENT INCREASE AND COMPLEX 5 5809 03:37:58,080 --> 03:37:59,600 ACTIVITY AND COMPLEX 4 ACTIVITY 5810 03:37:59,600 --> 03:38:02,120 AFTER ARGININE SO THE FILLED 5811 03:38:02,120 --> 03:38:03,840 CIRCLES ARE ED PRESENTATION, AND 5812 03:38:03,840 --> 03:38:07,240 THE OPEN CIRCLES ARE ED 5813 03:38:07,240 --> 03:38:10,480 DISCHARGE, THE RED CIRCLES ARE 5814 03:38:10,480 --> 03:38:12,000 NOT ON HYDROXY UREA, AND 5815 03:38:12,000 --> 03:38:14,360 VISUALLY YOU CAN SEE THE 5816 03:38:14,360 --> 03:38:15,960 DIFFERENCE IN MITOCHONDRIAL 5817 03:38:15,960 --> 03:38:16,600 FUNCTION ANDOXIDATIVE STRESS ON 5818 03:38:16,600 --> 03:38:19,360 PATIENT WHO IS ARE NOT ON 5819 03:38:19,360 --> 03:38:22,440 HYDROXY UREA AND THIS IS 5820 03:38:22,440 --> 03:38:25,000 SIGNIFICANT SO PATIENTS WHO DO 5821 03:38:25,000 --> 03:38:27,200 NOT USE HYDROXY UREA HAVE WORSE 5822 03:38:27,200 --> 03:38:28,480 MIGHT O CHOBD RIA FUNCTION AND 5823 03:38:28,480 --> 03:38:29,800 HIGHER STRESS THAN THOSE 5824 03:38:29,800 --> 03:38:31,920 PATIENTS WHO ARE ON HYDROXY UREA 5825 03:38:31,920 --> 03:38:34,360 AND THAT'S NEVER BEEN REPORTED 5826 03:38:34,360 --> 03:38:34,600 BEFORE. 5827 03:38:34,600 --> 03:38:38,160 SO AGAIN, NO DIFFERENCE IN 5828 03:38:38,160 --> 03:38:38,760 CHANGES IN MITOCHONDRIAL 5829 03:38:38,760 --> 03:38:40,240 ACTIVITY AND PATIENTS IN THE 5830 03:38:40,240 --> 03:38:46,960 PROSEEB O ARMS AND THIS IS 5831 03:38:46,960 --> 03:38:49,200 CARBONYL ACTIVITY, THIS IS 5832 03:38:49,200 --> 03:38:51,360 PATIENTS IN RECEIVED ANY FORM OF 5833 03:38:51,360 --> 03:38:52,760 ARGININE, WHAT'S INTERESTING IS 5834 03:38:52,760 --> 03:38:54,520 THERE WAS ARN INCREASE IN THE 5835 03:38:54,520 --> 03:38:56,160 PLACEBO ARM SO ALTHOUGH THEY'RE 5836 03:38:56,160 --> 03:38:56,840 GETTING BETTER CLINICALLY 5837 03:38:56,840 --> 03:38:58,760 THERE'S STILL A LOT GOING ON 5838 03:38:58,760 --> 03:39:00,800 THAT'S MEN FASTING AN 5839 03:39:00,800 --> 03:39:01,640 INCREASEDOXIDATIVE STRESS AT THE 5840 03:39:01,640 --> 03:39:02,640 TIME OF DISCHARGE FROM THE 5841 03:39:02,640 --> 03:39:03,080 HOSPITAL. 5842 03:39:03,080 --> 03:39:07,560 SO AS FAR AS SAFETY, SAEs AND 5843 03:39:07,560 --> 03:39:08,400 AEs WERE SIMILAR ACROSS THE 5844 03:39:08,400 --> 03:39:10,160 STUDY ARMS AND THE SAFETY DATA 5845 03:39:10,160 --> 03:39:19,680 HAS BEEN ACTUALLY REPORTED BY 5846 03:39:19,680 --> 03:39:21,560 LORA RAY ESTIMATE THAD, WE ARE 5847 03:39:21,560 --> 03:39:23,480 TRYING TO BRING HER IN BECAUSE 5848 03:39:23,480 --> 03:39:25,440 WE NEED TORE NEPHROLOGISTS 5849 03:39:25,440 --> 03:39:27,440 THINKING ABOUT THESE PATIENTS. 5850 03:39:27,440 --> 03:39:31,280 SO WE HAD NO UNEXPECTED AEs 5851 03:39:31,280 --> 03:39:33,840 ARE SAEs BUT THERE WERE A LOT 5852 03:39:33,840 --> 03:39:35,680 OF--A LOT OF AEs SO ANYONE 5853 03:39:35,680 --> 03:39:37,560 DOING AN ACUTE PAIN STUDY NEEDS 5854 03:39:37,560 --> 03:39:40,280 TO BE PREPARED TO FILL OUT A LOT 5855 03:39:40,280 --> 03:39:42,360 OF FORMS, 360 AEs THEY WERE 5856 03:39:42,360 --> 03:39:45,240 ALL RELATIVELY MILD AND THE MOST 5857 03:39:45,240 --> 03:39:46,040 COMMON WERE GI COMPLAINT ASKS 5858 03:39:46,040 --> 03:39:47,800 THERE WERE NO DRVESS WITH ACROSS 5859 03:39:47,800 --> 03:39:49,360 THE STUDY ARMS AND I THINK THAT 5860 03:39:49,360 --> 03:39:50,320 THE TAKE AWAY MESSAGE FROM THIS 5861 03:39:50,320 --> 03:39:52,240 IS THAT A LOT OF OUR PATIENTS 5862 03:39:52,240 --> 03:39:55,120 ARE VOMITING IN THE EMERGENCY 5863 03:39:55,120 --> 03:39:57,080 DEPARTMENT AND WE'RE NOT ALWAYS 5864 03:39:57,080 --> 03:40:01,560 TREATING THEM WITH ZOFRAN, 5865 03:40:01,560 --> 03:40:02,360 INDEPENDENT OF THAT, SOMETHING 5866 03:40:02,360 --> 03:40:03,880 WE TBHEED TO PAY ATTENTION TO 5867 03:40:03,880 --> 03:40:06,880 BECAUSE THESE ARE ALSO SIDE 5868 03:40:06,880 --> 03:40:07,800 EFFECTS OF OPIOIDS. 5869 03:40:07,800 --> 03:40:11,800 AS FAR AS OUR SAEs, THERE WERE 5870 03:40:11,800 --> 03:40:15,040 27 IN THIS 18 PATIENTS ALL 5871 03:40:15,040 --> 03:40:16,000 INVOLVED HOSPITAL EYATION WITHIN 5872 03:40:16,000 --> 03:40:17,840 30 DAYS OF PROLONGED ADMISSION 5873 03:40:17,840 --> 03:40:20,440 BUT LOOKING AT THE 72 HOUR 5874 03:40:20,440 --> 03:40:21,760 REHOSPITALIZATION RATE WAS 6% 5875 03:40:21,760 --> 03:40:23,200 WHICH WAS MUCH LESS WHICH HAS 5876 03:40:23,200 --> 03:40:24,760 BEEN PREPORTED IN LITERATURE AT 5877 03:40:24,760 --> 03:40:24,920 20%. 5878 03:40:24,920 --> 03:40:31,200 SO 1 OF THE QUESTIONS THAT OFTEN 5879 03:40:31,200 --> 03:40:32,720 COMES UP, IS IMPACT ON LIVER AND 5880 03:40:32,720 --> 03:40:34,880 RENAL FUNCTION SO WE DID HAVE 5881 03:40:34,880 --> 03:40:36,200 SAFETY LA LABS IN THE STUDY AND 5882 03:40:36,200 --> 03:40:37,200 1 THING THAT WAS INTERESTING TO 5883 03:40:37,200 --> 03:40:38,920 OBSERVE IS THAT THERE WAS A 5884 03:40:38,920 --> 03:40:41,680 SUBGROUP OF PATIENT WHO IS 5885 03:40:41,680 --> 03:40:44,760 PRESENTED WITH ELEVATED LFTs 5886 03:40:44,760 --> 03:40:45,600 AND ABNORMAL LIVER FUNCTION THAT 5887 03:40:45,600 --> 03:40:48,360 WE WOULD NEVER KNOW BECAUSE I 5888 03:40:48,360 --> 03:40:49,600 USUALLY DON'T GET CMPs IN 5889 03:40:49,600 --> 03:40:50,960 THESE PATES, IT WAS INCREASED AT 5890 03:40:50,960 --> 03:40:53,240 THE TIME OF RANDOMIZATION BUT 5891 03:40:53,240 --> 03:40:55,040 OVER THE COURSE OF THEIR 5892 03:40:55,040 --> 03:40:56,800 ADMISSION, THE BILIRUBIN AND AST 5893 03:40:56,800 --> 03:40:57,760 EITHER REMAIN STABLE OR 5894 03:40:57,760 --> 03:40:59,480 DECREASED AT THE TIME OF 5895 03:40:59,480 --> 03:41:03,080 DISCHARGE, WHAT'S INTERESTING IS 5896 03:41:03,080 --> 03:41:04,720 THAT ALT CONTINUED TO INCREASE 5897 03:41:04,720 --> 03:41:05,840 ACROSS ALL STUDY ARMS SO THERE 5898 03:41:05,840 --> 03:41:08,440 WAS NO DIFFERENCE IN THOSE WHO 5899 03:41:08,440 --> 03:41:09,920 RECEIVED ARGININE VERSUS PLACEBO 5900 03:41:09,920 --> 03:41:12,960 BUT I YOU DID SEE THIS ONGOING 5901 03:41:12,960 --> 03:41:14,240 INCREASE, THIS MAY REPRESENT THE 5902 03:41:14,240 --> 03:41:15,720 COURSE OF LIVER DYSFUNCTION 5903 03:41:15,720 --> 03:41:17,080 DURING ACUTE PAIN WHICH IS 5904 03:41:17,080 --> 03:41:18,920 SOMETHING I HAD PREVIOUS THOUGHT 5905 03:41:18,920 --> 03:41:20,360 ABOUT EITHER, BUT IT DOES GIVE 5906 03:41:20,360 --> 03:41:22,800 ME PAUSE CONSIDERING ALL THE 5907 03:41:22,800 --> 03:41:23,880 TYLENOL WE TEND TO GIVE THESE 5908 03:41:23,880 --> 03:41:25,960 PATIENT WHEN IS THEY'RE ADMITTED 5909 03:41:25,960 --> 03:41:28,920 TO THE HOSPITAL. 5910 03:41:28,920 --> 03:41:30,280 KRE TINSA TIENINE WAS STABLE 5911 03:41:30,280 --> 03:41:30,680 ACROSS STUDY ARMS. 5912 03:41:30,680 --> 03:41:33,240 THERE WAS A MILD TO INCREASE IN 5913 03:41:33,240 --> 03:41:35,840 THE UN BETWEEN ANDROGEN ORDER OF 5914 03:41:35,840 --> 03:41:37,040 MICRONSIZATION AND TIME OF 5915 03:41:37,040 --> 03:41:38,200 DISCHARGE IN ARGININE GROUPS 5916 03:41:38,200 --> 03:41:40,120 ONLY WHICH MAKES SENSE BECAUSE 5917 03:41:40,120 --> 03:41:42,440 IT IS A NITROGEN LOAD BUT THIS 5918 03:41:42,440 --> 03:41:43,840 WAS NOT CLINICALLY RELEVANT AND 5919 03:41:43,840 --> 03:41:46,280 YOU CAN SEE IT WAS A INCREASE IN 5920 03:41:46,280 --> 03:41:48,760 BUN WITHIN THE RANGE OF NORMAL. 5921 03:41:48,760 --> 03:41:51,160 SERUM BI CARB REDECKED SLIGHTLY 5922 03:41:51,160 --> 03:41:53,240 IN THE ARGININE LOAD ARM BUT 5923 03:41:53,240 --> 03:41:55,080 AGAIN, IT WAS WITHIN THE RANGE 5924 03:41:55,080 --> 03:41:57,080 OF NORMAL AND NOT CLINICALLY 5925 03:41:57,080 --> 03:41:59,440 RELEVANT, AND THEN FINALLY, 5926 03:41:59,440 --> 03:42:00,160 POTASSIUM, INCREASED SLIGHTLY 5927 03:42:00,160 --> 03:42:02,040 FROM THE TIME OF RANDOMIZATION 5928 03:42:02,040 --> 03:42:04,600 IN THE STANDARD DOSE OF ARGININE 5929 03:42:04,600 --> 03:42:07,160 BUT AGAIN NO 1 BECAME HYPER 5930 03:42:07,160 --> 03:42:08,880 K-LEEMIC AND IT WAS WITHIN THE 5931 03:42:08,880 --> 03:42:11,040 RANGE OF NORMAL AND NONE OF THIS 5932 03:42:11,040 --> 03:42:11,640 WAS CLINICALLY RELEVANT. 5933 03:42:11,640 --> 03:42:13,440 SO THE REASON WE LOOK AT THESE 5934 03:42:13,440 --> 03:42:15,760 SPECIFICALLY IS BECAUSE ARGININE 5935 03:42:15,760 --> 03:42:18,560 IS DELIVERED AS L-ARGININE HYDRO 5936 03:42:18,560 --> 03:42:27,440 CHLORIDE WHICH IS ACIDIC BUT THE 5937 03:42:27,440 --> 03:42:29,000 SALINE, SO MAYBE WE WOULD HAVE A 5938 03:42:29,000 --> 03:42:31,800 DIFFERENT POINT THAT WOULD BE 5939 03:42:31,800 --> 03:42:32,160 NONACIDIC. 5940 03:42:32,160 --> 03:42:34,280 SO IT'S BEEN VERY SAFE, THERE'S 5941 03:42:34,280 --> 03:42:36,280 BEEN EXTENSIVE ANIMAL AND MUSEUM 5942 03:42:36,280 --> 03:42:38,280 MAN STUDIES, THE 921972 IT WAS 5943 03:42:38,280 --> 03:42:39,320 APPROVED USING HIGHER DOSES THAN 5944 03:42:39,320 --> 03:42:41,560 WE USE IN OUR STUDY AND IN FACT 5945 03:42:41,560 --> 03:42:44,640 THERE'S BEEN CONSIDER THAT I 5946 03:42:44,640 --> 03:42:46,120 HEARD FROM HEMEATOLOGY 5947 03:42:46,120 --> 03:42:48,120 COLLEAGUES ABOUT ITS POTENTIAL 5948 03:42:48,120 --> 03:42:49,440 FOR IMPACT ON THE LIVER, BUT 5949 03:42:49,440 --> 03:42:54,240 MORE AND MORE DATA IS USE COMING 5950 03:42:54,240 --> 03:42:58,320 OUT THAT IT'S USED FOR LIVER AND 5951 03:42:58,320 --> 03:43:10,120 IT'S USED FOR ACUTE HYPER 5952 03:43:10,120 --> 03:43:10,480 PNEUMONIA. 5953 03:43:10,480 --> 03:43:12,440 HYPER KALEMIA, RISKS IN PATIENTS 5954 03:43:12,440 --> 03:43:14,640 WITH ADVANCED RENAL HEPATICIN 5955 03:43:14,640 --> 03:43:18,000 SUFFICIENCY, SIDE EFFECTS ARE 5956 03:43:18,000 --> 03:43:19,400 NAUSEA AND VOMITING AND IF YOU 5957 03:43:19,400 --> 03:43:20,960 SLOW THE INFUSIONS IT MAY HELP, 5958 03:43:20,960 --> 03:43:22,640 BUT PFIZER HAS REPORTED THESE 5959 03:43:22,640 --> 03:43:23,800 SYMPTOMS IN ABOUT 3% OF PATIENTS 5960 03:43:23,800 --> 03:43:25,880 AND WE NOW HAVE GROWING 5961 03:43:25,880 --> 03:43:27,040 EXPERIENCE WITH SICKLE CELL DEC 5962 03:43:27,040 --> 03:43:28,640 WITH OUR STUDIES OVER THE 20 5963 03:43:28,640 --> 03:43:31,120 YEAR JOURNEY OF OVER 270 5964 03:43:31,120 --> 03:43:32,200 PATIENTS BEING RANDOMIZED INTO 1 5965 03:43:32,200 --> 03:43:35,040 STUDY OR ANOTHER OF IV ARGININE 5966 03:43:35,040 --> 03:43:35,800 OR PLACEBO. 5967 03:43:35,800 --> 03:43:37,040 AND ULTIMATELY ACROSS ALL THOO 5968 03:43:37,040 --> 03:43:40,560 TIME THERE'S BEEN NO UNEXPECTED 5969 03:43:40,560 --> 03:43:41,760 AEsOR SAEs RELATED TO STUDY 5970 03:43:41,760 --> 03:43:42,640 TO DATE. 5971 03:43:42,640 --> 03:43:45,400 SO IN CONCLUSION WE KNOW THAT 5972 03:43:45,400 --> 03:43:46,800 THE DEFICIENCY DOES PLAY A ROLE 5973 03:43:46,800 --> 03:43:51,320 IN SICKLE CELL DISEASE AND PAIN 5974 03:43:51,320 --> 03:43:54,640 AND ORAL ARGININE IS HELPFUL IN 5975 03:43:54,640 --> 03:43:56,480 ENVIRONMENTS, ORAL ARGININE HAS 5976 03:43:56,480 --> 03:44:03,320 BEEN PEN FICIAL, GENERALLY SAFE, 5977 03:44:03,320 --> 03:44:04,800 INIMPROVES CARDIO PULMONARY 5978 03:44:04,800 --> 03:44:08,600 INJECTION AND KUDOS TO DR. ONALO 5979 03:44:08,600 --> 03:44:09,800 FOR BEING MY STAR MENTEE IN THE 5980 03:44:09,800 --> 03:44:12,040 WORK HE WAS ABLE TO DO WITH VERY 5981 03:44:12,040 --> 03:44:12,440 LITTLE RESOURCES. 5982 03:44:12,440 --> 03:44:16,040 AND THEN AS FAR AS IV ARGININE, 5983 03:44:16,040 --> 03:44:18,240 SAFE, NUTRITIONAL SUPPLEMENT, 5984 03:44:18,240 --> 03:44:19,360 IMPROVES MITOCHONDRIAL FUNCTION. 5985 03:44:19,360 --> 03:44:21,160 >> ONE MINUTE WARNING. 5986 03:44:21,160 --> 03:44:22,320 >> OKAY, DECREASED OXIDATIVE 5987 03:44:22,320 --> 03:44:23,960 STRESS, BUT THERE'S A TREND IN 5988 03:44:23,960 --> 03:44:25,800 OPIOID USE AND A TREND TOWARDS 5989 03:44:25,800 --> 03:44:27,400 SHORTER TIME TO CRISIS 5990 03:44:27,400 --> 03:44:28,640 RESOLUTION, OUR LIMITATION IS 5991 03:44:28,640 --> 03:44:29,960 THAT THIS IS SINGLE CENTER, 5992 03:44:29,960 --> 03:44:31,680 SMALL SAMPLE SIZE AND WHAT WE 5993 03:44:31,680 --> 03:44:35,040 REALLY NEED IS THE PHASE 3 5994 03:44:35,040 --> 03:44:35,600 MULTICENTER TRIAL, IT'S 5995 03:44:35,600 --> 03:44:37,920 WARRANTIED AND I WANT TO THANK 5996 03:44:37,920 --> 03:44:38,960 NHLBI FOR SPONSORING START WHICH 5997 03:44:38,960 --> 03:44:40,680 IS A SICKLE CELL DISEASE 5998 03:44:40,680 --> 03:44:43,120 TREATMENT WITH ARGININE THERAPY 5999 03:44:43,120 --> 03:44:44,360 WHICH IS A 10 SITE STUDY RUN 6000 03:44:44,360 --> 03:44:46,320 OVER 6 YEARS THAT WILL HOPEFULLY 6001 03:44:46,320 --> 03:44:47,600 BE THE DEFINITIVE STUDY TO 6002 03:44:47,600 --> 03:44:49,200 ANSWER THIS QUESTION, SOMETIME 6003 03:44:49,200 --> 03:44:51,960 BEFORE I RETIRE, IT IS ENDORSED 6004 03:44:51,960 --> 03:44:54,040 BY PC ARN, WHICH IS THE APPLIED 6005 03:44:54,040 --> 03:44:55,200 RESEARCH NETWORK, SOME OF YOU 6006 03:44:55,200 --> 03:44:57,280 MAY REMEMBER THIS, WORK BY DAVID 6007 03:44:57,280 --> 03:45:00,040 AND COLLEAGUES, THE MAGIC STUDY, 6008 03:45:00,040 --> 03:45:01,480 FOR MING NEEZIUM STUDY CRISIS, 6009 03:45:01,480 --> 03:45:03,440 HE MADE HISTORY WHENEE ENROLLED 6010 03:45:03,440 --> 03:45:05,080 OVER 200 PATIENTS IN LESS THAN 3 6011 03:45:05,080 --> 03:45:06,280 YEARS KNOWING THE CHALLENGES 6012 03:45:06,280 --> 03:45:10,040 EVER ENROLLING IN SICKLE SEAL 6013 03:45:10,040 --> 03:45:11,200 CLINICAL TRIALS, VOV REMAINS BUT 6014 03:45:11,200 --> 03:45:12,640 KIDS WITH SICKLE CELL DISEASE 6015 03:45:12,640 --> 03:45:15,720 APPEAR, WELL THE MAGIC IS REALLY 6016 03:45:15,720 --> 03:45:18,040 PKARN AND USING THE NETWORK FOR 6017 03:45:18,040 --> 03:45:19,040 SUCCESSFUL TRIALS. 6018 03:45:19,040 --> 03:45:20,640 SO FOR OUR START TRIAL IS 360 6019 03:45:20,640 --> 03:45:22,720 WITH A LOFTY GOAL WITH JUST 10 6020 03:45:22,720 --> 03:45:23,640 CENTERS, I HAD TO CHANGE THE 6021 03:45:23,640 --> 03:45:26,280 NUMBER BECAUSE WE HAD ANOTHER 6022 03:45:26,280 --> 03:45:27,920 PATIENT RANDOMIZED WE ARE WELL 6023 03:45:27,920 --> 03:45:28,760 ABOVE OUR MILESTONES AND AGAIN 6024 03:45:28,760 --> 03:45:32,040 THAT'S THE POWER AND MAGIC OF PC 6025 03:45:32,040 --> 03:45:33,960 ARN AND ALL THE EMERGENCY 6026 03:45:33,960 --> 03:45:34,880 DEPARTMENT LEADERS WORKING WITH 6027 03:45:34,880 --> 03:45:36,200 TOGETHER WITH THE 6028 03:45:36,200 --> 03:45:37,280 HEMEATOLOGYISTS TO ACTUALLY 6029 03:45:37,280 --> 03:45:39,600 SUCCESSFULLY ENROLL IN STUDIES. 6030 03:45:39,600 --> 03:45:42,560 SO, KEY POINTS ARGININE IS 6031 03:45:42,560 --> 03:45:43,960 CONDITIONALLY EMINNOW ACID, 6032 03:45:43,960 --> 03:45:44,840 BECOMES ESSENTIAL UNDER 6033 03:45:44,840 --> 03:45:46,800 CONDITIONS OF STAT AND CATABOLIC 6034 03:45:46,800 --> 03:45:48,640 STATE AND CAPACITY OF THE 6035 03:45:48,640 --> 03:45:50,880 AMINE'S ACID SENTH SIS IS 6036 03:45:50,880 --> 03:45:52,040 EXCEEDED. 6037 03:45:52,040 --> 03:45:53,560 SICKLELE DISEASE REPRESENTS 6038 03:45:53,560 --> 03:45:54,800 ARGININE SYNDROME, DISTINCT 6039 03:45:54,800 --> 03:45:56,640 NUTRITIONAL REQUIREMENT, IT MAY 6040 03:45:56,640 --> 03:45:58,840 BENEFIT FROM ARGININE 6041 03:45:58,840 --> 03:45:59,640 REPLACEMENT THERAPY OR ART, IF 6042 03:45:59,640 --> 03:46:00,880 YOU REMEMBER WHAT I TOLD YOU IN 6043 03:46:00,880 --> 03:46:02,640 THE BEGINNING ABOUT WHEN A 6044 03:46:02,640 --> 03:46:03,640 NUTRITIONAL DEFICIENCY TO BE 6045 03:46:03,640 --> 03:46:06,800 PRESENT, YOU HAVE TO HAVE THE 6046 03:46:06,800 --> 03:46:08,240 BIOLOGICAL PROCESS, AND IT'S 6047 03:46:08,240 --> 03:46:10,320 COMPROMISED AND THINK ABOUT 6048 03:46:10,320 --> 03:46:12,400 PULMONARY RETENTION AND PAIN, 6049 03:46:12,400 --> 03:46:14,360 THAT LEADS TO PHYSIOLOGIC 6050 03:46:14,360 --> 03:46:15,800 RESPONSES AND POOR OUTCOMES THAT 6051 03:46:15,800 --> 03:46:17,800 ARE REVERSED BY AMINEEE ACID 6052 03:46:17,800 --> 03:46:19,800 REPOLICEMENT AND THE MECHANISM 6053 03:46:19,800 --> 03:46:22,920 OF ACTION IS MULTIFACTORRIA AND 6054 03:46:22,920 --> 03:46:24,640 MITOCHONDRIAL FUNCTION MAY 6055 03:46:24,640 --> 03:46:25,920 REPRESENT A NOVEL BIOLOGICAL 6056 03:46:25,920 --> 03:46:28,400 OUTCOME WE CAN USE IN THESE 6057 03:46:28,400 --> 03:46:29,360 TRIALS, MANY THANKS TO EVERYBODY 6058 03:46:29,360 --> 03:46:34,000 ALONG THE WAY AND MY METRICS OF 6059 03:46:34,000 --> 03:46:36,600 FOR K23, FOR HER EXCELLENT 6060 03:46:36,600 --> 03:46:37,480 MITOCHONDRIAL WORK, THE TEEM I 6061 03:46:37,480 --> 03:46:39,040 TEAM I HAVE THAT'S ENROLLING 6062 03:46:39,040 --> 03:46:41,040 EVENT TODAY IN THE START TRIAL, 6063 03:46:41,040 --> 03:46:42,280 IS THEN OF COURSE MY FAMILY BHO 6064 03:46:42,280 --> 03:46:44,120 PUT UP WITH ALL MY WORK ON THIS 6065 03:46:44,120 --> 03:46:47,800 FOR THE LAST 20 YEARS, THANK 6066 03:46:47,800 --> 03:46:47,960 YOU. 6067 03:46:47,960 --> 03:46:49,200 >> THANK YOU VERY MUCH 6068 03:46:49,200 --> 03:46:50,920 CONGRATULATIONS AND GREAT DATA 6069 03:46:50,920 --> 03:46:52,880 AND GREAT PRESENTATION. 6070 03:46:52,880 --> 03:46:56,520 MY APOLARIZEDS I ALMOST BOTCHED 6071 03:46:56,520 --> 03:46:57,440 YOUR PRESENTATION. 6072 03:46:57,440 --> 03:46:58,960 WE WERE RUNNING A LITTLE AHEAD 6073 03:46:58,960 --> 03:47:00,360 OF TIME WHICH USUALLY DOESN'T 6074 03:47:00,360 --> 03:47:02,000 HAPPEN BUT THANK YOU SO MUCH 6075 03:47:02,000 --> 03:47:02,240 AGAIN. 6076 03:47:02,240 --> 03:47:05,040 YOU HAVE QUITE A FEW COMMENTS 6077 03:47:05,040 --> 03:47:09,040 AND QUESTIONS IN THE Q&A, SO 6078 03:47:09,040 --> 03:47:11,000 WHICH YOU CAN RESPOND TO. 6079 03:47:11,000 --> 03:47:15,960 LET ME JUST READ 1 COMMENT, OR 6080 03:47:15,960 --> 03:47:17,640 QUESTION FROM A COLLEAGUE: CAN 6081 03:47:17,640 --> 03:47:19,680 YOU ELABORATE MORE ON 6082 03:47:19,680 --> 03:47:23,800 RELATIONSHIP BETWEEN ARGININE 6083 03:47:23,800 --> 03:47:25,880 DEFICIENCY OR CONVERSION AND CKD 6084 03:47:25,880 --> 03:47:26,440 IN SICKLE CELL? 6085 03:47:26,440 --> 03:47:28,160 >> SO I THINK THAT THAT'S AGAIN 6086 03:47:28,160 --> 03:47:32,760 A GAP IN OUR KNOWLEDGE AND WITH 6087 03:47:32,760 --> 03:47:34,800 LORETTA REYES IS 1 OUR MENTEES, 6088 03:47:34,800 --> 03:47:36,640 I AM ENCOURAGING HER TO WORK IN 6089 03:47:36,640 --> 03:47:39,200 THIS SPACE FYOU HAVE CKD, CAN 6090 03:47:39,200 --> 03:47:41,640 DEPENDS ON OW BAD YOUR KIDNEY 6091 03:47:41,640 --> 03:47:44,160 DYSFUNCTION IS, BUT TO THAT 6092 03:47:44,160 --> 03:47:45,240 ENZYME, IT CAN GET KNOCKED OUT 6093 03:47:45,240 --> 03:47:47,840 AND THEN YOU WOULD LOSE YOUR 6094 03:47:47,840 --> 03:47:49,360 ABILITY TO CONVERT SIT ROUGH 6095 03:47:49,360 --> 03:47:52,200 ATOM LEAN TO ARGININE AND THEN 6096 03:47:52,200 --> 03:47:55,240 YOU WILL HAVE A CONTRIBUTION TO 6097 03:47:55,240 --> 03:47:56,440 ARGININE DISREGULATION JUST BY 6098 03:47:56,440 --> 03:47:57,840 WAY OF KIDNEY DYSFUNCTION, AND 6099 03:47:57,840 --> 03:47:59,720 WE'VE SEEN IN THIS IN OUR ADULT 6100 03:47:59,720 --> 03:48:02,320 PATIENTS THAT THE PATIENT WHO IS 6101 03:48:02,320 --> 03:48:03,520 HAD PULT PULMONARY HYPERTENSION 6102 03:48:03,520 --> 03:48:05,240 WERE THERE'S A STRONG 6103 03:48:05,240 --> 03:48:08,720 CORRELATION BETWEEN TRJET AND 6104 03:48:08,720 --> 03:48:09,440 YOUR GLOBAL ARGININE 6105 03:48:09,440 --> 03:48:11,640 BIOAVAILABILITY RATIO AND THOSE 6106 03:48:11,640 --> 03:48:12,360 PATIENTS TENDED TO BE THE 6107 03:48:12,360 --> 03:48:13,640 PATIENT WHO IS HAD RENAL 6108 03:48:13,640 --> 03:48:15,640 DYSFUNCTION SO I THINK THERE'S A 6109 03:48:15,640 --> 03:48:18,600 COMBINATION OF EFFECTS THAT COME 6110 03:48:18,600 --> 03:48:19,880 TOGETHER THAT LIMIT YOUR 6111 03:48:19,880 --> 03:48:21,160 ARGININE VIA BILITY AND THE 6112 03:48:21,160 --> 03:48:22,360 KIDNEY IS IMPORTANT BECAUSE IT 6113 03:48:22,360 --> 03:48:24,520 SHOULD BE ABLE TO SYNTHESIZE 6114 03:48:24,520 --> 03:48:26,040 ARGININE WHEN IT COMES LOW AND 6115 03:48:26,040 --> 03:48:27,920 IT'S A PROBLEM WITH OUR PATIENTS 6116 03:48:27,920 --> 03:48:29,920 WITH SICKLE CELL AND CKD. 6117 03:48:29,920 --> 03:48:30,480 >> THANK YOU. 6118 03:48:30,480 --> 03:48:33,240 APPROXIMATE WITH THAT I THINK WE 6119 03:48:33,240 --> 03:48:35,840 WILL--THIS WAS THE LAST TALK 6120 03:48:35,840 --> 03:48:38,400 BEFORE WE BREAK FOR LUNCH. 6121 03:48:38,400 --> 03:48:40,760 WE HAVE ANOTHER EXCELLENT 6122 03:48:40,760 --> 03:48:42,240 SYMPOSIUM AGAIN TALKING ABOUT 6123 03:48:42,240 --> 03:48:46,800 PAIN AND SICKLE CELL THAT WILL 6124 03:48:46,800 --> 03:48:51,880 START EXACTLY AT 1:15 SO, PLEASE 6125 03:48:51,880 --> 03:48:54,840 MUTE YOUR MICROPHONES AND YOUR 6126 03:48:54,840 --> 03:48:57,640 CAMERAS AND WE WILL TUNE BACK AT 6127 03:48:57,640 --> 03:48:59,040 1:15. 6128 03:48:59,040 --> 03:49:03,800 SEE YOU THEN. 6129 03:49:03,800 --> 03:49:06,640 WE ARE GOING TO GET START WITH 6130 03:49:06,640 --> 03:49:09,040 LAST COMPONENT OF THIS THREE DAY 6131 03:49:09,040 --> 03:49:10,280 TALK. REALLY EXCITING TALKS AND 6132 03:49:10,280 --> 03:49:13,360 WE HAVE SAVED THE BEST FOR THE 6133 03:49:13,360 --> 03:49:14,840 LAST. SYMPOSIUM 6. THIS IS GOING 6134 03:49:14,840 --> 03:49:17,640 TO BE TALKING ABOUT REFINING THE 6135 03:49:17,640 --> 03:49:21,000 RESEARCH AGENDA FOR PAIN AND 6136 03:49:21,000 --> 03:49:25,080 SICKLE CELL DISEASE AND DR. 6137 03:49:25,080 --> 03:49:31,120 SMITH WALLY CHERYL STUDY AND 6138 03:49:31,120 --> 03:49:32,640 KALPNA GUPTA ARE THE CHAIRS FOR 6139 03:49:32,640 --> 03:49:34,600 THIS SESSION. TAKE IT AWAY. 6140 03:49:34,600 --> 03:49:36,640 >> THANK YOU. I WILL SHARE MY 6141 03:49:36,640 --> 03:49:42,640 SCREEN. 6142 03:49:42,640 --> 03:49:49,560 LET ME KNOW IF YOU CAN SEE IT. 6143 03:49:49,560 --> 03:49:52,000 >> YOU MAY WANT TO PUT IT IN 6144 03:49:52,000 --> 03:49:52,560 PRESENTATION MODE. 6145 03:49:52,560 --> 03:49:54,320 >> GOOD. 6146 03:49:54,320 --> 03:49:57,240 >> OKAY. SO AS STATED, WE ARE 6147 03:49:57,240 --> 03:50:01,640 GOING TO BE TALKING ABOUT 6148 03:50:01,640 --> 03:50:03,040 MECHANISTIC AND BASIC 6149 03:50:03,040 --> 03:50:04,880 TRANSLATIONAL APPROACHES TO 6150 03:50:04,880 --> 03:50:08,000 SICKLE CELL DISEASE AND PAIN. IT 6151 03:50:08,000 --> 03:50:09,440 MIGHT HAVE BEEN BETTER IF WE DID 6152 03:50:09,440 --> 03:50:11,800 THIS THIS MORNING AND THEN THIS 6153 03:50:11,800 --> 03:50:13,800 MORNING SESSION THEN THIS 6154 03:50:13,800 --> 03:50:16,640 AFTERNOON BECAUSE THOSE WERE 6155 03:50:16,640 --> 03:50:19,560 MORE APPLIED TREATMENT BASED 6156 03:50:19,560 --> 03:50:20,800 RECOMMENDATIONS BASED OFF WHAT 6157 03:50:20,800 --> 03:50:22,360 SOME OF THE THINGS WE ARE ARE 6158 03:50:22,360 --> 03:50:26,200 GOING TO TALK ABOUT THIS 6159 03:50:26,200 --> 03:50:27,480 AFTERNOON THOUGH KALPNA WILL 6160 03:50:27,480 --> 03:50:28,600 BRING YOU INTO THE TREATMENT 6161 03:50:28,600 --> 03:50:31,800 REALM. WHAT I WOULD LIKE TO DO 6162 03:50:31,800 --> 03:50:34,200 IS START BY TELLING YOU WHO IS 6163 03:50:34,200 --> 03:50:37,800 GOING TO SPEAK. AND THEN NOT 6164 03:50:37,800 --> 03:50:39,920 INTERRUPTING YOU ANY FURTHER. SO 6165 03:50:39,920 --> 03:50:42,560 WE WILL HAVE CHERYL STUDY, AND 6166 03:50:42,560 --> 03:50:45,040 AMANDA BRANDOW TALKING ABOUT 6167 03:50:45,040 --> 03:50:46,800 BRIDGING FROM BASIC TO 6168 03:50:46,800 --> 03:50:51,320 TRANSLATIONAL RESEARCH AND PAIN. 6169 03:50:51,320 --> 03:50:54,400 WE'LL HAVE NITYA BAKSHI TALK 6170 03:50:54,400 --> 03:50:56,240 ABOUT PHENOTYPIC EXPRESSIONS AND 6171 03:50:56,240 --> 03:51:00,000 OTHER WAYS OF EXPRESSING PAIN. 6172 03:51:00,000 --> 03:51:02,080 WE WILL HAVE PAT -- I THINK PAT 6173 03:51:02,080 --> 03:51:03,520 MIGHT GET THE PRIZE FOR SPEAKING 6174 03:51:03,520 --> 03:51:07,480 THE MOST AT THIS SERIES OF 6175 03:51:07,480 --> 03:51:12,080 MEETINGS. PAT CARROLL TALKING 6176 03:51:12,080 --> 03:51:13,800 ABOUT GUIDELINES AND TALKING 6177 03:51:13,800 --> 03:51:17,360 ABOUT APPROACHES TO CLINICAL 6178 03:51:17,360 --> 03:51:19,440 MANAGEMENT. THEY WILL GO WITHOUT 6179 03:51:19,440 --> 03:51:20,800 INTERRUPTION. WHAT I'M GOING TO 6180 03:51:20,800 --> 03:51:23,680 DO IS JUST SHOW YOU THAT IT DOES 6181 03:51:23,680 --> 03:51:26,080 TAKE A WHOLE DAY TO TALK ABOUT 6182 03:51:26,080 --> 03:51:28,680 PAIN. AND THAT THE NUMBER OF 6183 03:51:28,680 --> 03:51:30,680 ARTICLES PUBLISHED ON THIS TOPIC 6184 03:51:30,680 --> 03:51:34,320 IN SICKLE CELL DISEASE HAS 6185 03:51:34,320 --> 03:51:35,440 SKYROCKETED SINCE THE 1960s, 6186 03:51:35,440 --> 03:51:39,760 IT IS THE MOST COMMON SYMPTOM. 6187 03:51:39,760 --> 03:51:44,040 AND YET THE LEAST AMOUNT OF 6188 03:51:44,040 --> 03:51:46,680 CLEAR GUIDANCE ABOUT WHAT TO DO 6189 03:51:46,680 --> 03:51:49,160 FOR PAIN AND A LOT LESS 6190 03:51:49,160 --> 03:51:49,920 UNDERSTANDING ABOUT PAIN AND 6191 03:51:49,920 --> 03:51:50,720 SICKLE CELL DISEASE THAN WE 6192 03:51:50,720 --> 03:51:53,880 WOULD HAVE LIKED. THAT STEMS IN 6193 03:51:53,880 --> 03:51:55,800 PART FROM OUR LACK OF 6194 03:51:55,800 --> 03:51:58,960 UNDERSTANDING ABOUT PAIN IN 6195 03:51:58,960 --> 03:52:02,520 GENERAL. IT WAS ORIGINALLY KNOWN 6196 03:52:02,520 --> 03:52:03,520 PATIENTS WITH SICKLE CELL 6197 03:52:03,520 --> 03:52:05,640 DISEASE HAD PAIN BY TRIBAL 6198 03:52:05,640 --> 03:52:11,440 ELDERS IN AFRICA WHO USED 6199 03:52:11,440 --> 03:52:13,680 ONOMOTOPEA, THINGS LIKE CHEW WII 6200 03:52:13,680 --> 03:52:14,880 CHEW WII TO DESCRIBE SYMPTOMS OF 6201 03:52:14,880 --> 03:52:17,000 PATIENTS WITH SICKLE CELL 6202 03:52:17,000 --> 03:52:19,520 DISEASE AND THE NOTED TRIBAL 6203 03:52:19,520 --> 03:52:22,960 PREVALENCE AND NOTED FACT THAT 6204 03:52:22,960 --> 03:52:25,160 PATIENTS DIED SOON RATHER THAN 6205 03:52:25,160 --> 03:52:27,920 LATER. IN BIOLOGY OF SICKLE CELL 6206 03:52:27,920 --> 03:52:29,640 WAS CLEARLY WHAT HAPPENED IN THE 6207 03:52:29,640 --> 03:52:33,440 CENTURY OF THE 1900s AND WE 6208 03:52:33,440 --> 03:52:36,120 HAVE THE DISCOVERY OF THE 6209 03:52:36,120 --> 03:52:39,880 ABNORMAL CELLS IN 1910 IN 6210 03:52:39,880 --> 03:52:42,480 CHICAGO AT RUSH AND THEN THE 6211 03:52:42,480 --> 03:52:46,360 RELATIONSHIP OF PAIN RATE TO 6212 03:52:46,360 --> 03:52:47,320 MORTALITY BY PLATT AND OTHERS IN 6213 03:52:47,320 --> 03:52:50,160 THE COOPERATIVE STUDY, IN 1991 6214 03:52:50,160 --> 03:52:53,560 WITH A RELATIONSHIP OF 6215 03:52:53,560 --> 03:52:57,720 HEMOGLOBIN AS ONE BIOMARKER TO 6216 03:52:57,720 --> 03:52:59,920 MORTALITY. THEN WE BEGAN TO 6217 03:52:59,920 --> 03:53:02,800 EXPAND OUR UNDERSTANDING OF PAIN 6218 03:53:02,800 --> 03:53:04,040 AND SICKLE CELL DISEASE AS WE 6219 03:53:04,040 --> 03:53:05,920 DID PAIN IN OTHER DISEASES TO 6220 03:53:05,920 --> 03:53:09,440 SAY THAT IT IS A BIOPSYCHOSOCIAL 6221 03:53:09,440 --> 03:53:11,840 PHENOMENON, FIRST THAT PAIN 6222 03:53:11,840 --> 03:53:16,640 COMES WITH DAILY PREVAILING 6223 03:53:16,640 --> 03:53:19,040 WINDS, CHRONIC PAIN INTERCEPTED 6224 03:53:19,040 --> 03:53:23,840 BY HURRICANES AND TORNADOES OF 6225 03:53:23,840 --> 03:53:24,680 BASAL OKAY COLLUSIVE CRISES WE 6226 03:53:24,680 --> 03:53:27,640 CANNOT PREDICT. MANY WHICH ARE 6227 03:53:27,640 --> 03:53:30,680 MANAGED AT HOME. BUT THE 6228 03:53:30,680 --> 03:53:31,920 ACCOMPANYING PROBLEMS WITH THE 6229 03:53:31,920 --> 03:53:35,120 DAILY PREVAILING WINDS AND THESE 6230 03:53:35,120 --> 03:53:36,600 TORNADOES AND HURRICANES 6231 03:53:36,600 --> 03:53:38,760 ACCOMPANYING PROBLEMS ARE LEE 6232 03:53:38,760 --> 03:53:42,640 GENERAL AND NOT BIOLOGICAL BUT 6233 03:53:42,640 --> 03:53:44,920 BIOPSYCHOSOCIAL DEPRESSION 6234 03:53:44,920 --> 03:53:46,680 ANXIETY AND EVEN A BONE MARROW 6235 03:53:46,680 --> 03:53:48,800 TRANSPLANT DOESN'T GET RID OF 6236 03:53:48,800 --> 03:53:51,120 PAIN IN SICKLE CELL DISEASE, SO 6237 03:53:51,120 --> 03:53:55,160 THE PAIN MUST NOT BE BASAL OKAY 6238 03:53:55,160 --> 03:53:58,000 COLLUSIVE. OUR UNDERSTANDING OF 6239 03:53:58,000 --> 03:54:00,360 PAIN WAS VERY CAUSE EFFECT 6240 03:54:00,360 --> 03:54:01,800 RELATIONSHIP EARLY ON, WE 6241 03:54:01,800 --> 03:54:03,040 THOUGHT THE PAIN STIMULUS WAS 6242 03:54:03,040 --> 03:54:05,840 THE ONLY THING THAT COULD CAUSE 6243 03:54:05,840 --> 03:54:07,440 THE PAIN. WE NOW KNOW THAT IS 6244 03:54:07,440 --> 03:54:10,400 NOT TRUE. IT IS A 6245 03:54:10,400 --> 03:54:11,400 BIOPSYCHOSOCIAL PHENOMENON. THE 6246 03:54:11,400 --> 03:54:17,000 AMOUNT OF PAIN INPUT FOR EXAMPLE 6247 03:54:17,000 --> 03:54:24,560 VASVASOVASOOKAY COLLUSIVE BIOLOGY DOES 6248 03:54:24,560 --> 03:54:28,640 NOT DICTATE PAIN EXPRESSION. 6249 03:54:28,640 --> 03:54:30,560 THERE IS A COMMON NEUROMETRICS 6250 03:54:30,560 --> 03:54:36,240 WE ADAPTED IN OUR REVIEW 6251 03:54:36,240 --> 03:54:37,480 MULTI-MODAL ANALGESIC REGIMENS 6252 03:54:37,480 --> 03:54:39,360 THIS MORNING, WE REVIEWED THAT 6253 03:54:39,360 --> 03:54:40,640 RECENTLY AND IN THAT REVIEW 6254 03:54:40,640 --> 03:54:42,760 TRIED TO PUT THIS UNDERLYING 6255 03:54:42,760 --> 03:54:45,720 MODEL TO EXPLAIN WHY THOSE 6256 03:54:45,720 --> 03:54:46,480 ANALGESIC REGIMENS MIGHT BE 6257 03:54:46,480 --> 03:54:50,200 APPROPRIATE. SO ON THE LEFT-HAND 6258 03:54:50,200 --> 03:54:54,160 SIDE YOU HAVE COGNITIVE THAT IS 6259 03:54:54,160 --> 03:54:56,160 KNOWLEDGE OF PAIN, EITHER MEMORY 6260 03:54:56,160 --> 03:55:01,120 OF PAIN WHICH CAUSE 6261 03:55:01,120 --> 03:55:02,440 CATASTROPHIZING OR YOU MIGHT 6262 03:55:02,440 --> 03:55:05,560 THINK OF BIOLOGICAL MEMORY IN 6263 03:55:05,560 --> 03:55:10,800 THE FORM OF NEURAL PLASTICITY, 6264 03:55:10,800 --> 03:55:15,120 NEURAL PLASTICITY. YOU HAVE 6265 03:55:15,120 --> 03:55:23,800 SENSORY CHANGES VISCERAL CHANGES 6266 03:55:23,800 --> 03:55:25,640 MUSCULOSKELETAL CHANGES. THIS 6267 03:55:25,640 --> 03:55:30,040 TERM HAS COME INTO PLAY AND 6268 03:55:30,040 --> 03:55:30,640 DEFINITELY AFFECTS SICKLE CELL 6269 03:55:30,640 --> 03:55:32,040 DISEASE. THEN PEOPLE REACT TO 6270 03:55:32,040 --> 03:55:34,600 THEIR PAIN, DEPRESSION, ANXIETY, 6271 03:55:34,600 --> 03:55:36,800 THE WAY THEY FEEL ABOUT THEIR 6272 03:55:36,800 --> 03:55:38,680 PAIN MAY CHANGE BIOLOGY, 6273 03:55:38,680 --> 03:55:41,840 VASOCONSTRICTION ASSOCIATED WITH 6274 03:55:41,840 --> 03:55:43,360 NEURAL CHEMICAL RELEASE RELATED 6275 03:55:43,360 --> 03:55:48,040 TO ANXIETY. VERY COMPLEX SET OF 6276 03:55:48,040 --> 03:55:50,520 INPUTS. THE OUTPUTS ARE NOT 6277 03:55:50,520 --> 03:55:56,000 JUST PAIN BUT ALSO KENESIA 6278 03:55:56,000 --> 03:56:01,240 PHOBIA, INVOLUNTARY LACK OF 6279 03:56:01,240 --> 03:56:03,960 MOTION AND BEING STILL AND NOT 6280 03:56:03,960 --> 03:56:06,440 PARTICIPATING IN DAILY 6281 03:56:06,440 --> 03:56:07,920 ACTIVITIES. THEN THE STRESS 6282 03:56:07,920 --> 03:56:09,600 ASSOCIATED WITH IT. AGAIN IN THE 6283 03:56:09,600 --> 03:56:13,360 FORM OF CORTISOL WHICH IS A VASO 6284 03:56:13,360 --> 03:56:14,360 VASOACTIVE SUBSTANCE. THERE'S 6285 03:56:14,360 --> 03:56:18,200 MORE THAN WHAT IS ON THIS PAGE. 6286 03:56:18,200 --> 03:56:19,520 THIS IS A START TO TRY TO 6287 03:56:19,520 --> 03:56:22,600 EXPLAIN WHAT THE PAIN EXPERIENCE 6288 03:56:22,600 --> 03:56:24,280 IS AND IT IS BASIS FOR SOME OF 6289 03:56:24,280 --> 03:56:25,880 THE TARGETED THERAPIES THAT YOU 6290 03:56:25,880 --> 03:56:29,120 HEARD ABOUT THIS MORNING. SO NOT 6291 03:56:29,120 --> 03:56:31,000 ONLY ANALGESICS, NOT ONLY 6292 03:56:31,000 --> 03:56:36,080 DISEASE MODIFIERS, BUT ALSO 6293 03:56:36,080 --> 03:56:38,040 ACCEPTANCE COMMITMENT THERAPY, 6294 03:56:38,040 --> 03:56:40,360 COGNITIVE BEHAVIORAL THERAPY, 6295 03:56:40,360 --> 03:56:43,640 MIND BODY THERAPIES TO EXPOSE 6296 03:56:43,640 --> 03:56:45,000 THE PATIENT TO A DIFFERENT WAY 6297 03:56:45,000 --> 03:56:46,560 OF COPING WITH YOUR PAIN IN A 6298 03:56:46,560 --> 03:56:48,360 DIFFERENT WAY OF REACTING TO 6299 03:56:48,360 --> 03:56:52,000 THEIR PAIN HYPNOSIS, ET CETERA. 6300 03:56:52,000 --> 03:56:55,040 ACUTE PAIN HAS BEEN DEFINED FOR 6301 03:56:55,040 --> 03:56:59,040 SICKLE CELL DISEASE THAT'S HOW 6302 03:56:59,040 --> 03:57:01,000 FAR BEHIND WE ARE, TOOK UNTIL 6303 03:57:01,000 --> 03:57:02,800 018 TO SAY WHAT ACUTE PAIN IN 6304 03:57:02,800 --> 03:57:04,480 SICKLE CELL DISEASE WAS OTHER 6305 03:57:04,480 --> 03:57:06,920 THAN HOSPITAL UTILIZATION. THIS 6306 03:57:06,920 --> 03:57:12,320 IS A AGREED UPON DEFINITION 6307 03:57:12,320 --> 03:57:18,880 PUBLISHED ON THE ACCOUNT OF THE 6308 03:57:18,880 --> 03:57:20,800 AAAPT GROUP. SIMILARLY CHRONIC 6309 03:57:20,800 --> 03:57:24,120 PAIN IS DEFINED WE SAY PERSISTS 6310 03:57:24,120 --> 03:57:26,880 PAST NORMAL TIME OF HEALING, AND 6311 03:57:26,880 --> 03:57:28,640 CHRONIC NON-CANCER PAIN, IT IS 6312 03:57:28,640 --> 03:57:30,240 EITHER EVERY SIX MONTHS, EVERY 6313 03:57:30,240 --> 03:57:34,440 THREE MONTHS DEPENDING WHO YOU 6314 03:57:34,440 --> 03:57:37,200 READ AND SICKLE CELL DISEASE WE 6315 03:57:37,200 --> 03:57:38,920 PICKED SIX MONTHS AND SAID PAIN 6316 03:57:38,920 --> 03:57:41,040 ON MOST DAYS ARE MAJORITY OF 6317 03:57:41,040 --> 03:57:44,040 DAYS. OVER THE PAST SIX MONTHS. 6318 03:57:44,040 --> 03:57:47,440 WITH DIAGNOSTIC MODIFICATIO MODIFICATIONS 6319 03:57:47,440 --> 03:57:51,240 THAT TRY TO GIVE YOU AN IDEA 6320 03:57:51,240 --> 03:57:53,280 WHETHER NOSEY PLASTIC PAIN IS 6321 03:57:53,280 --> 03:57:55,480 ALSO PRESENT OR MOST COMMONLY A 6322 03:57:55,480 --> 03:58:01,920 MIXED PAIN PHENOTYPE. WITHIN 6323 03:58:01,920 --> 03:58:03,480 THAT PATIENTS CAN HAVE 6324 03:58:03,480 --> 03:58:04,800 EXACERBATION OF THEIR CHRONIC 6325 03:58:04,800 --> 03:58:08,760 PAIN THAT ARE NOT CALLED 6326 03:58:08,760 --> 03:58:10,000 VASOOCCLUSIVE CRISES. HERE YOU 6327 03:58:10,000 --> 03:58:11,880 CAN SEE THE NUMBER OF EPISODES 6328 03:58:11,880 --> 03:58:13,800 OF PATIENTS WHO HAD 6329 03:58:13,800 --> 03:58:15,920 EXACERBATIONS THAT DID NOT CALL 6330 03:58:15,920 --> 03:58:19,320 THEM VASOOCCLUSIVE CRISIS WAS 6331 03:58:19,320 --> 03:58:24,440 NOT ZERO. SO YOU HAVE A 6332 03:58:24,440 --> 03:58:26,880 WANDERING DAILY WINDS, 6333 03:58:26,880 --> 03:58:28,000 PREVAILING WINDS WANDERING UP 6334 03:58:28,000 --> 03:58:30,520 AND DOWN IN TERM OF INTENSITY, 6335 03:58:30,520 --> 03:58:35,120 AND THEN YOU HAVE PUNCTUATED HER 6336 03:58:35,120 --> 03:58:41,080 CANES AND TORNADOES. SOMEWHERE 6337 03:58:41,080 --> 03:58:44,160 ALONG THE WAY PAIN IN SICKLE 6338 03:58:44,160 --> 03:58:46,480 CELL DISEASE TRANSFORMS IN SOME 6339 03:58:46,480 --> 03:58:51,560 PATIENTS, IT TRANSFORMS FOR FROM 6340 03:58:51,560 --> 03:58:54,640 ACUTE CHRONIC VASOOCCLUSIVE 6341 03:58:54,640 --> 03:58:55,960 PHENOMENON, INFLAMMATORY 6342 03:58:55,960 --> 03:58:58,960 PHENOMENON TOP THE BEGINNING OF 6343 03:58:58,960 --> 03:59:00,400 CENTRAL AND PERIPHERAL 6344 03:59:00,400 --> 03:59:02,920 NEUROPATHIC PAIN OR NOCI PLASTIC 6345 03:59:02,920 --> 03:59:04,920 PAIN AND THAT TRANSFORMATION IS 6346 03:59:04,920 --> 03:59:09,120 STILL BEING STUDIED. WHY DOES IT 6347 03:59:09,120 --> 03:59:11,320 OCCUR IN SOME AND NOT IN OTHERS? 6348 03:59:11,320 --> 03:59:13,760 IS THAT GENES, HOW MUCH DOES IT 6349 03:59:13,760 --> 03:59:16,200 TAKE FOR IT TO OCCUR, IS THERE A 6350 03:59:16,200 --> 03:59:18,520 THRESHOLD AFFECT, IS IT GRADUAL 6351 03:59:18,520 --> 03:59:21,400 IN EVERY ONE? IT SEEMS TO HAPPEN 6352 03:59:21,400 --> 03:59:24,040 IN THE TEEN YEARS, MAYBE SICKLE 6353 03:59:24,040 --> 03:59:26,480 CELL DISEASE SHARES THIS WITH 6354 03:59:26,480 --> 03:59:30,280 OTHER SYNDROMES SO THE SAME 6355 03:59:30,280 --> 03:59:33,240 THERAPIES THAT YOU HEARD ABOUT 6356 03:59:33,240 --> 03:59:34,880 THIS MORNING THAT COULD BE USED 6357 03:59:34,880 --> 03:59:36,040 FOR SICKLE CELL DISEASE ARE 6358 03:59:36,040 --> 03:59:38,160 USEFUL IN OTHER SYNDROMES, 6359 03:59:38,160 --> 03:59:42,160 WORKING IN THE SAME MECHANISM. 6360 03:59:42,160 --> 03:59:44,720 WE JUST DON'T YET KNOW HOW ALL 6361 03:59:44,720 --> 03:59:46,280 OF IT WORKS. SOME OF WHAT YOU 6362 03:59:46,280 --> 03:59:47,960 ARE GOING TO HEAR TODAY IS 6363 03:59:47,960 --> 03:59:51,320 EXPLORING THAT. YOU HAVE ALREADY 6364 03:59:51,320 --> 03:59:55,360 HEARD ABOUT ALL THOSE DIFFERENT 6365 03:59:55,360 --> 03:59:55,880 COMPLIMENTARY INTEGRATIVE 6366 03:59:55,880 --> 03:59:57,040 APPROACHES TO CARE THIS MORNING 6367 03:59:57,040 --> 03:59:58,400 BUT GUESS WHAT, MOST PATIENTS 6368 03:59:58,400 --> 04:00:02,520 CAN'T GET THEIR HANDS ON THEM. 6369 04:00:02,520 --> 04:00:05,840 INSURANCE WILL NOT PAY FOR THEM. 6370 04:00:05,840 --> 04:00:08,400 CMS ACKNOWLEDGED THIS IN A VERY 6371 04:00:08,400 --> 04:00:10,080 DETAILED DIAGRAM PUBLISHED ABOUT 6372 04:00:10,080 --> 04:00:11,600 A MONTH AGO SHOWING THE 6373 04:00:11,600 --> 04:00:13,680 FINANCIAL BURDENS, THE MENTAL 6374 04:00:13,680 --> 04:00:17,440 HEALTH BURDENS, THE STIGMA FROM 6375 04:00:17,440 --> 04:00:18,960 FAMILY FRIENDS AND PHYSICIANS, 6376 04:00:18,960 --> 04:00:21,600 AND THE DYSFUNCTION ASSOCIATED 6377 04:00:21,600 --> 04:00:26,040 WITH CHRONIC PAIN. OF ALL KINDS. 6378 04:00:26,040 --> 04:00:27,440 INCLUDING SICKLE CELL DISEASE. 6379 04:00:27,440 --> 04:00:30,040 THE LACK OF INSURANCE COVERAGE 6380 04:00:30,040 --> 04:00:31,920 AND THE PROBLEMS THAT PEOPLE GO 6381 04:00:31,920 --> 04:00:34,640 THROUGH TRYING TO GET TREATMENTS 6382 04:00:34,640 --> 04:00:35,840 LIKE YOU HEARD THIS MORNING AND 6383 04:00:35,840 --> 04:00:36,960 WE WILL HEAR SOME THIS 6384 04:00:36,960 --> 04:00:41,040 AFTERNOON. AMANDA ALLOWED ME TO 6385 04:00:41,040 --> 04:00:43,040 USE THIS SLIDE, THIS IS WHAT YOU 6386 04:00:43,040 --> 04:00:45,000 SHOULD DO WHEN SOMEBODY COMES IN 6387 04:00:45,000 --> 04:00:46,240 WITH SICKLE CELL PAIN. DON'T 6388 04:00:46,240 --> 04:00:49,520 JUST ASSUME IT IS ALL A SIMPLE 6389 04:00:49,520 --> 04:00:51,160 STIMULUS RESPONSE PHENOMENON. 6390 04:00:51,160 --> 04:00:56,240 TRY AND ASSOCIATE SOME OF THOSE 6391 04:00:56,240 --> 04:00:59,280 PHENOTYPE DESCRIPTORS I TALKED 6392 04:00:59,280 --> 04:01:00,840 ABOUT WITH THERE SYMPTOMS AND 6393 04:01:00,840 --> 04:01:03,600 WITH THEIR DESCRIPTIONS AND TRY 6394 04:01:03,600 --> 04:01:06,360 TO COME UP WITH A PERSONALIZED 6395 04:01:06,360 --> 04:01:08,440 TARGETED TREATMENT STRATEGY, 6396 04:01:08,440 --> 04:01:10,560 INDIVIDUALIZED FOR THAT PERSON. 6397 04:01:10,560 --> 04:01:14,160 LIKELY MULTI-MODAL AND GET AS 6398 04:01:14,160 --> 04:01:16,640 MUCH PAID FOR AS YOU CAN. SO 6399 04:01:16,640 --> 04:01:20,320 RATHER THAN GO THROUGH ALL THESE 6400 04:01:20,320 --> 04:01:22,080 INDIVIDUALIZED DETAILS, I'M 6401 04:01:22,080 --> 04:01:25,840 GOING TO KEEP GOING AND HAND OFF 6402 04:01:25,840 --> 04:01:38,520 TO DR. STUFFCKY STUCKY. CLAUDIA CAMPBELL 6403 04:01:38,520 --> 04:01:46,040 WON'T BE PRESENTING. SO DR. 6404 04:01:46,040 --> 04:01:49,320 STUCKY, BRANDOW AND BAKSHI WILL 6405 04:01:49,320 --> 04:01:50,440 PRESENT. CHERYL. 6406 04:01:50,440 --> 04:01:53,040 >> THANK YOU VERY MUCH. AMANDA, 6407 04:01:53,040 --> 04:01:55,080 WE -- AMANDA AND I APPRECIATE 6408 04:01:55,080 --> 04:01:56,920 THIS OPPORTUNITY TO SPEAK TO 6409 04:01:56,920 --> 04:01:58,800 YOU. WE DECIDED THAT AMANDA 6410 04:01:58,800 --> 04:02:03,320 WOULD LEAD US OFF WITH HER 6411 04:02:03,320 --> 04:02:04,800 DESCRIPTION OF HER CLINICAL 6412 04:02:04,800 --> 04:02:06,280 STUDIES WITH PATIENTS WITH 6413 04:02:06,280 --> 04:02:09,440 SICKLE CELL DISEASE. SO I WILL 6414 04:02:09,440 --> 04:02:10,280 TURN THIS OVER TO AMANDA FIRST. 6415 04:02:10,280 --> 04:02:12,840 >>THANK YOU, DR. 6416 04:02:12,840 --> 04:02:14,760 SMITH AND EVERYONE AT THE NHLBI 6417 04:02:14,760 --> 04:02:17,360 FOR THE OPPORTUNITY TO TALK 6418 04:02:17,360 --> 04:02:19,720 TODAYTODAY. DR. STUCKY AND I WILL 6419 04:02:19,720 --> 04:02:22,120 GIVE COMBINED ENTITLED 6420 04:02:22,120 --> 04:02:22,680 INVESTIGATING SICKLE CELL 6421 04:02:22,680 --> 04:02:24,600 DISEASE PAIN FROM HUMAN TO MOUSE 6422 04:02:24,600 --> 04:02:27,560 AND IN BETWEEN. AND I WILL START 6423 04:02:27,560 --> 04:02:31,240 US OFF AS CHERYL SAID. SO 6424 04:02:31,240 --> 04:02:32,600 OVERVIEW TODAY I WILL IDENTIFY 6425 04:02:32,600 --> 04:02:35,560 GAPS IN PAIN RESEARCH THAT OUR 6426 04:02:35,560 --> 04:02:39,360 WORK IS ATTEMPTING TO FILL I 6427 04:02:39,360 --> 04:02:41,000 WILL DISCUSS CLINICAL 6428 04:02:41,000 --> 04:02:41,800 TRANSLATIONAL RESEARCH. DR. 6429 04:02:41,800 --> 04:02:44,000 STUCKY WILL DISCUSS BASIC PAIN 6430 04:02:44,000 --> 04:02:47,520 RESEARCH THEN CONCLUDE. SO THIS 6431 04:02:47,520 --> 04:02:50,440 SLIDE CAME FROM THE 2021 6432 04:02:50,440 --> 04:02:52,760 WORKSHOP THAT NIH SPONSORED 6433 04:02:52,760 --> 04:02:53,840 LOOKING AT SICKLE CELL DISEASE 6434 04:02:53,840 --> 04:02:58,240 PAIN LAST SUMMER. THIS SLIDE 6435 04:02:58,240 --> 04:02:59,920 DESCRIBES SOME OF THE GAPS THAT 6436 04:02:59,920 --> 04:03:01,800 NEED TO BE FILLED AND THE ONES 6437 04:03:01,800 --> 04:03:03,920 HIGHLIGHTED IN YELLOW ARE THE 6438 04:03:03,920 --> 04:03:05,440 ONES THAT OUR TOP WILL ADDRESS 6439 04:03:05,440 --> 04:03:07,560 TODAY INCLUDING OUR ACUTE PAIN 6440 04:03:07,560 --> 04:03:09,560 MECHANISM SIMILAR OR DIFFERENT 6441 04:03:09,560 --> 04:03:11,160 ACROSS PATIENTS, WHAT MECHANISMS 6442 04:03:11,160 --> 04:03:12,920 UNDERLIE THE ACUTE ON TOP OF 6443 04:03:12,920 --> 04:03:14,360 CHRONIC PAIN AND EITHER 6444 04:03:14,360 --> 04:03:15,560 INDIVIDUAL DIFFERENCES IN 6445 04:03:15,560 --> 04:03:19,000 BIOLOGY THAT UNDERLINE PAIN 6446 04:03:19,000 --> 04:03:20,840 SEVERITY. SO I WILL START 6447 04:03:20,840 --> 04:03:21,560 PRESENTING SOME OF THE WORK WE 6448 04:03:21,560 --> 04:03:24,040 ARE DOING IN MY LAB ON BEHALF OF 6449 04:03:24,040 --> 04:03:25,680 THE CO-AUTHORS ON THE SLIDE. 6450 04:03:25,680 --> 04:03:28,200 THIS IS ENTITLED IDENTIFICATION 6451 04:03:28,200 --> 04:03:30,840 OF BIOLOGICAL PROCESSES 6452 04:03:30,840 --> 04:03:31,600 ASSOCIATED WITH PAIN IN 6453 04:03:31,600 --> 04:03:32,240 INDIVIDUALS WITH SICKLE CELL 6454 04:03:32,240 --> 04:03:37,680 DISEASE. SO AS MOST KNOW DESPITE 6455 04:03:37,680 --> 04:03:39,640 THE SAME MUTATION THAT CAUSES 6456 04:03:39,640 --> 04:03:40,880 SICKLE CELL DISEASE THERE IS 6457 04:03:40,880 --> 04:03:42,520 SIGNIFICANT VARIABILITY IN PAIN 6458 04:03:42,520 --> 04:03:44,200 EXPRESSION BETWEEN INDIVIDUALS 6459 04:03:44,200 --> 04:03:46,640 AS DR. SMITH OPENED UP AND 6460 04:03:46,640 --> 04:03:48,800 TALKED ABOUT. MANY PATIENTS 6461 04:03:48,800 --> 04:03:50,320 EXPERIENCE FREQUENT AND 6462 04:03:50,320 --> 04:03:51,800 RECURRENT PAIN AND CHRONIC PAIN 6463 04:03:51,800 --> 04:03:54,880 WHILE OTHERS EXPERIENCE 6464 04:03:54,880 --> 04:03:56,200 FORTUNATELY ONLY OCCASIONAL 6465 04:03:56,200 --> 04:03:56,920 PAIN. HOWEVER THE KNOWLEDGE OF 6466 04:03:56,920 --> 04:03:59,000 THE BIOLOGY THAT DISTINGUISHES 6467 04:03:59,000 --> 04:04:00,120 THIS ENTERINDIVIDUAL PAIN 6468 04:04:00,120 --> 04:04:00,680 VARIABILITY IS NOT WELL 6469 04:04:00,680 --> 04:04:03,840 UNDERSTOOD. WORK IN OTHER PAIN 6470 04:04:03,840 --> 04:04:06,040 MODELS SHOWS THAT A VARIETY OF 6471 04:04:06,040 --> 04:04:07,800 NEURAL AND IMMUNE INTERACTIONS 6472 04:04:07,800 --> 04:04:09,680 DRIVE ACUTE AND CHRONIC PAIN. 6473 04:04:09,680 --> 04:04:11,320 THIS IS RELEVANT IN SICKLE CELL 6474 04:04:11,320 --> 04:04:12,440 DISEASE BECAUSE IT IS A KNOWN 6475 04:04:12,440 --> 04:04:14,880 CHRONIC INFLAMMATORY DISORDER. 6476 04:04:14,880 --> 04:04:16,720 WHICH CHRONIC IMMUNE ACTIVATION. 6477 04:04:16,720 --> 04:04:18,360 SO IF WE CAN IDENTIFY SOME OF 6478 04:04:18,360 --> 04:04:20,600 THESE BIOLOGICAL PATHWAYS 6479 04:04:20,600 --> 04:04:21,960 THROUGH GENE EXPRESSION ANALYSES 6480 04:04:21,960 --> 04:04:24,080 THAT CONTRIBUTE TO THIS 6481 04:04:24,080 --> 04:04:25,000 HETEROGENEITY, WE MIGHT BE ABLE 6482 04:04:25,000 --> 04:04:27,680 TO OVERCOME BARRIERS IN SICKLE 6483 04:04:27,680 --> 04:04:30,360 CELL SPACE HOW TO PROGNOSTIC 6484 04:04:30,360 --> 04:04:31,480 PAIN OUTCOMES FOR OUR PATIENTS. 6485 04:04:31,480 --> 04:04:33,640 THAT IS SOMETHING WE GET ASKED 6486 04:04:33,640 --> 04:04:37,600 AS PEDIATRIC PROVIDERS. WE ALSO 6487 04:04:37,600 --> 04:04:39,200 COULD HELP US IDENTIFY NOVEL 6488 04:04:39,200 --> 04:04:40,640 TARGETS THAT COULD BE LEVERAGED 6489 04:04:40,640 --> 04:04:44,000 FOR PAIN THERAPEUTICS. SO OUR 6490 04:04:44,000 --> 04:04:45,520 STUDY ADDRESSED TWO WAYS FIRST 6491 04:04:45,520 --> 04:04:47,160 TO IDENTIFY GROUPS OF GENES OR 6492 04:04:47,160 --> 04:04:49,000 MODULES THAT SIGNIFICANTLY 6493 04:04:49,000 --> 04:04:50,480 CORRELATE WITH HEALTHCARE 6494 04:04:50,480 --> 04:04:52,040 UTILIZATION FOR PAIN. AND 6495 04:04:52,040 --> 04:04:54,000 IDENTIFY GROUPS OF GENES THAT 6496 04:04:54,000 --> 04:04:55,360 SIGNIFICANTLY CORRELATE WITH 6497 04:04:55,360 --> 04:04:57,120 PAIN -- PATIENT RELATED -- PAIN 6498 04:04:57,120 --> 04:04:57,920 RELATED PATIENT REPORTED 6499 04:04:57,920 --> 04:05:01,080 OUTCOMES. WE HYPOTHESIZED THAT 6500 04:05:01,080 --> 04:05:03,640 GENE MODULES RELATED TO THE 6501 04:05:03,640 --> 04:05:05,040 IMMUNE SYSTEM WILL CORRELATE 6502 04:05:05,040 --> 04:05:06,600 WITH INCREASE CLINICAL 6503 04:05:06,600 --> 04:05:07,640 EXPRESSION OF PAIN IN 6504 04:05:07,640 --> 04:05:09,880 INDIVIDUALS WITH SICKLE CELL 6505 04:05:09,880 --> 04:05:12,760 DISEASE. WE STUDIED 27 6506 04:05:12,760 --> 04:05:14,880 INDIVIDUALS LESS THAN EQUAL TO 6507 04:05:14,880 --> 04:05:16,960 18 YEARS OF AGE, WE OBTAINED 6508 04:05:16,960 --> 04:05:18,320 PAIR SAMPLE DURING BASELINE 6509 04:05:18,320 --> 04:05:20,520 STATE OF HEALTH AND DURING ACUTE 6510 04:05:20,520 --> 04:05:23,200 PAIN EPISODE. WE COMPARED THESE 6511 04:05:23,200 --> 04:05:27,320 TO 45 HEALTHY BLACK CONTROLS. 6512 04:05:27,320 --> 04:05:29,360 WE CONDUCT PLASMA INDUCED 6513 04:05:29,360 --> 04:05:30,680 TRANSDUCTION ANALYSES AND FOR 6514 04:05:30,680 --> 04:05:34,080 THESE ANALYSES WE OBTAINED A 6515 04:05:34,080 --> 04:05:35,440 PERIPHERAL BLOOD NON-NUCLEAR 6516 04:05:35,440 --> 04:05:37,640 CELL FROM WELL CHARACTERIZED 6517 04:05:37,640 --> 04:05:41,040 DONOR. WE INCUBATED THE PBMCs 6518 04:05:41,040 --> 04:05:42,440 WITH PLASMA MA FROM INDIVIDUALS 6519 04:05:42,440 --> 04:05:43,800 WITH SICKLE CELL DISEASE DURING 6520 04:05:43,800 --> 04:05:45,440 BASELINE STATE AND ACUTE PAIN 6521 04:05:45,440 --> 04:05:48,480 AND HEALTHY BLACK CONTROLS. THIS 6522 04:05:48,480 --> 04:05:50,560 PBMC ACTED AS A SENSOR FOR 6523 04:05:50,560 --> 04:05:53,400 FACTORS THAT EXISTED IN THE 6524 04:05:53,400 --> 04:05:55,600 PATIENT AND CONTROL PLASMA. WE 6525 04:05:55,600 --> 04:05:57,600 PURIFIED THE RNA FROM THESE 6526 04:05:57,600 --> 04:06:00,040 PBMCs, LABELED AND HYBRIDIZED 6527 04:06:00,040 --> 04:06:03,360 IT TO AFFYMETRICS ARRAY TO LOOK 6528 04:06:03,360 --> 04:06:05,080 AT TRANSCRIPTION CHANGES. THEY 6529 04:06:05,080 --> 04:06:06,320 ALSO HAD CLINICAL PAIN 6530 04:06:06,320 --> 04:06:07,440 ASSESSMENTS THROUGH PAIN RELATED 6531 04:06:07,440 --> 04:06:09,560 PATIENT REPORTED OUTCOMES WHERE 6532 04:06:09,560 --> 04:06:12,840 WE USE THE PEDSQL SICKLE CELL 6533 04:06:12,840 --> 04:06:15,080 DISEASE MODULE SUB SCALES PAIN 6534 04:06:15,080 --> 04:06:16,600 AND HURT AND IMPACT. THESE ARE 6535 04:06:16,600 --> 04:06:18,040 SCORED ON DEVELOPER GUIDELINES 6536 04:06:18,040 --> 04:06:20,120 RANGING FROM 0 TO 100, HIGHER 6537 04:06:20,120 --> 04:06:20,800 SCORES REFLECT BETTER 6538 04:06:20,800 --> 04:06:23,040 FUNCTIONING. AND WE ALSO LOOK AT 6539 04:06:23,040 --> 04:06:25,800 THE NUMBER OF ACUTE CARE 6540 04:06:25,800 --> 04:06:28,720 ENCOUNTERS FOR PAIN THE PRIOR 6541 04:06:28,720 --> 04:06:31,160 THREE YEARS. DATA ANALYSIS 6542 04:06:31,160 --> 04:06:32,520 INCLUDED WEIGHTED GENE 6543 04:06:32,520 --> 04:06:34,000 CO-EXPRESSION NETWORK ANALYSIS, 6544 04:06:34,000 --> 04:06:36,720 OR WGCNA. WHICH IS A DATA 6545 04:06:36,720 --> 04:06:39,160 REDUCTION TECHNIQUE FOR VARIETY 6546 04:06:39,160 --> 04:06:42,600 OF GENETIC DECEMBER WHICH GROUPS 6547 04:06:42,600 --> 04:06:43,800 GENES WITH SIMILAR EXPRESSION 6548 04:06:43,800 --> 04:06:45,280 PATTERN VARIATION INTO SOMETHING 6549 04:06:45,280 --> 04:06:48,720 CALLED A MODULE. THESE MODULES 6550 04:06:48,720 --> 04:06:50,360 THEN REPRESENT CLUSTERS OF 6551 04:06:50,360 --> 04:06:52,280 HIGHLY INTERCONNECTED GENES. 6552 04:06:52,280 --> 04:06:59,000 EACH MODULE HAS A MODULE 6553 04:06:59,000 --> 04:07:00,000 EIGENGENE, REPRESENTATIVE OF THE 6554 04:07:00,000 --> 04:07:02,360 GENE EXPRESSION PROFILES IN THAT 6555 04:07:02,360 --> 04:07:05,360 MODULE. THIS MODULE GENE IS 6556 04:07:05,360 --> 04:07:06,640 CORRELATED WITH PHENOTYPIC 6557 04:07:06,640 --> 04:07:08,040 TRAITS AND IN OUR STUDY WE LOOK 6558 04:07:08,040 --> 04:07:10,000 AT PAIN RELATED PROS AND PAIN 6559 04:07:10,000 --> 04:07:13,360 HISTORY OF INDIVIDUAL. THE 6560 04:07:13,360 --> 04:07:17,560 MODULE EIGEN GENE OF 0.3 OR 6561 04:07:17,560 --> 04:07:19,320 HIGHER BETWEEN ONE PHENOTYPIC 6562 04:07:19,320 --> 04:07:20,520 SICKLE CELL DISEASE TRAIT WAS 6563 04:07:20,520 --> 04:07:23,760 RETAINED. THIS IS CALLED THE 6564 04:07:23,760 --> 04:07:25,800 EEGEN GENE SIGNIFICANCE. WE THEN 6565 04:07:25,800 --> 04:07:27,200 LOOKED AT THE BIOLOGICAL 6566 04:07:27,200 --> 04:07:29,600 PATHWAYS ASSOCIATED WITH THOSE 6567 04:07:29,600 --> 04:07:31,360 MODULES THROUGH ON TO LOGICAL 6568 04:07:31,360 --> 04:07:36,200 ANALYSES USING DATA. THIS IS 6569 04:07:36,200 --> 04:07:38,880 DEMOGRAPHICS OF OUR POPULATION. 6570 04:07:38,880 --> 04:07:41,360 OUR MEAN AGE OF OUR PATIENTS WAS 6571 04:07:41,360 --> 04:07:44,680 10.9 YEARS AND CONTROLS WAS 6572 04:07:44,680 --> 04:07:47,600 13.3. SIMILAR SEX IN BOTH GROUPS 6573 04:07:47,600 --> 04:07:50,480 OUR PATIENTS HAD APPROXIMATELY 6574 04:07:50,480 --> 04:07:54,400 FOUR PAIN EVENTS IN THEIR PAIN 6575 04:07:54,400 --> 04:07:55,640 HISTORY THAN THE PRIOR THREE 6576 04:07:55,640 --> 04:07:56,680 YEARS AND DIFFERENCES IN PATIENT 6577 04:07:56,680 --> 04:07:58,680 REPORTED OUTCOMES BETWEEN 6578 04:07:58,680 --> 04:08:00,080 BASELINE HEALTH AND ACUTE PAIN 6579 04:08:00,080 --> 04:08:05,440 ARE ON THE SLIDE. THESE 6580 04:08:05,440 --> 04:08:07,200 REPRESENT OUR HEAT MAPS FOR OUR 6581 04:08:07,200 --> 04:08:08,760 GENE EXPRESSION DATA AND I WILL 6582 04:08:08,760 --> 04:08:12,240 WALK YOU THROUGH THIS. AS 6583 04:08:12,240 --> 04:08:13,800 REMINDER RED REPRESENTS 6584 04:08:13,800 --> 04:08:15,920 UPREGULATION OF GENE OR 6585 04:08:15,920 --> 04:08:17,760 INCREASED EXPRESSION. THE PANEL 6586 04:08:17,760 --> 04:08:19,360 ON THE LEFT REPRESENTS THE MEAN 6587 04:08:19,360 --> 04:08:21,600 GENE EXPRESSION OF GROUPS AS A 6588 04:08:21,600 --> 04:08:24,240 WHOLE. THE PANEL HERE REPRESENTS 6589 04:08:24,240 --> 04:08:26,360 INDIVIDUAL EXPRESSIONS OF OUR 6590 04:08:26,360 --> 04:08:28,680 CONTROLS AND AS REMINDER A 6591 04:08:28,680 --> 04:08:29,840 COLUMN REPRESENTS AN INDIVIDUAL 6592 04:08:29,840 --> 04:08:31,520 AND A ROW REPRESENTS A DIFFERENT 6593 04:08:31,520 --> 04:08:32,960 GENE THAT CAN BE MAINTAINED 6594 04:08:32,960 --> 04:08:33,920 THROUGHOUT ALL THREE OF THESE 6595 04:08:33,920 --> 04:08:36,720 PANELS. THE TWO PANELS ON THE 6596 04:08:36,720 --> 04:08:38,600 RIGHT REPRESENT PATIENTS WITH 6597 04:08:38,600 --> 04:08:39,840 INDIVIDUAL SICKLE CELL DISEASE 6598 04:08:39,840 --> 04:08:40,960 DURING BASELINE STATE OF HEALTH 6599 04:08:40,960 --> 04:08:42,960 AND ACUTE PAIN AND AS A REMINDER 6600 04:08:42,960 --> 04:08:45,040 THESE ARE PAIRED SAMPLES FROM 6601 04:08:45,040 --> 04:08:46,040 THE SAME INDIVIDUALS AT 6602 04:08:46,040 --> 04:08:48,560 DIFFERENT STATES OF DISEASE. 6603 04:08:48,560 --> 04:08:50,360 GOING BACK TO THIS MEAN 6604 04:08:50,360 --> 04:08:52,240 EXPRESSION DATA, CONTROL IS ON 6605 04:08:52,240 --> 04:08:54,000 THE LEFT COLUMN AND THE PAIRED 6606 04:08:54,000 --> 04:08:57,560 SAMPLES ARE ON THE RIGHT. WE 6607 04:08:57,560 --> 04:08:59,680 ALSO ANALYZE AN UNPAIRED SAMPLE 6608 04:08:59,680 --> 04:09:01,240 DURING BASELINE STATE OF HEALTH 6609 04:09:01,240 --> 04:09:02,720 AND I WON'T TALK ABOUT THAT 6610 04:09:02,720 --> 04:09:03,960 DETAIL BUT REASON I RETAIN THIS 6611 04:09:03,960 --> 04:09:06,480 ON THE SLIDE IS TO JUST POINT 6612 04:09:06,480 --> 04:09:08,200 OUT THE IMPORTANCE OF ANALYZING 6613 04:09:08,200 --> 04:09:09,760 PAIRED SAMPLES. AS YOU CAN SEE 6614 04:09:09,760 --> 04:09:12,080 IF YOU FIRST LOOK AT THE 6615 04:09:12,080 --> 04:09:13,520 UNPAIRED DATA, THAT BASELINE 6616 04:09:13,520 --> 04:09:14,880 HEALTH AND COMPARE TO THE ACUTE 6617 04:09:14,880 --> 04:09:16,440 PAIN WHICH IS THE COLUMN ON THE 6618 04:09:16,440 --> 04:09:18,080 RIGHT YOU SEE THERE APPEARS TO 6619 04:09:18,080 --> 04:09:19,040 BE DIFFERENCES. HOWEVER, WHAT 6620 04:09:19,040 --> 04:09:21,960 YOU CAN SEE IS WHEN YOU LOOK AT 6621 04:09:21,960 --> 04:09:22,920 THE SAME PATIENT THOSE 6622 04:09:22,920 --> 04:09:24,600 DIFFERENCES AREN'T AS PRONOUNCED 6623 04:09:24,600 --> 04:09:25,240 BETWEEN THE TWO STATES OF 6624 04:09:25,240 --> 04:09:29,520 HEALTH. SO IT ALSO SUGGESTS THAT 6625 04:09:29,520 --> 04:09:30,760 INTERPATIENT INTERPATIENT 6626 04:09:30,760 --> 04:09:32,720 VARIABILITY THAT WE ARE SEEING 6627 04:09:32,720 --> 04:09:33,920 AND THAT WERE FURTHER TRYING TO 6628 04:09:33,920 --> 04:09:37,240 UNDERSTAND. SO OVERALL YOU CAN 6629 04:09:37,240 --> 04:09:38,200 SEE THAT PATIENTS WITH SICKLE 6630 04:09:38,200 --> 04:09:39,720 CELL DISEASE DO APPEAR DIFFERENT 6631 04:09:39,720 --> 04:09:41,680 FROM HEALTHY CONTROLS AND THEIR 6632 04:09:41,680 --> 04:09:43,400 GENE EXPRESSION. ALSO WHAT WE 6633 04:09:43,400 --> 04:09:46,200 WERE SURPRISE IS HOW SIMILAR IN 6634 04:09:46,200 --> 04:09:47,920 GENERAL THE PATIENTS LOOKED 6635 04:09:47,920 --> 04:09:49,800 BETWEEN THE TWO STATES OF 6636 04:09:49,800 --> 04:09:51,360 HEALTH, HOWEVER, IF YOU REALLY 6637 04:09:51,360 --> 04:09:52,920 LOOK AT AN INDIVIDUAL AND FOLLOW 6638 04:09:52,920 --> 04:09:55,760 WHAT COLUMN COMPARED TO ANOTHER 6639 04:09:55,760 --> 04:09:56,760 COLUMN ON THE DIFFERENT PAIN 6640 04:09:56,760 --> 04:09:57,960 STATES OR DIFFERENT DISEASE 6641 04:09:57,960 --> 04:09:59,440 STATES YOU CAN SEE THERE ARE 6642 04:09:59,440 --> 04:10:01,440 DIFFERENCES IN INTERINDIVIDUAL 6643 04:10:01,440 --> 04:10:02,720 VARIABILITY WHICH WE ARE TRYING 6644 04:10:02,720 --> 04:10:04,600 TO FULLY UNDERSTAND IF THAT IS 6645 04:10:04,600 --> 04:10:08,640 BIOLOGICALLY MEANINGFUL. THIS 6646 04:10:08,640 --> 04:10:12,000 SLIDE SHOWS OUR WGCNA ANALYSIS. 6647 04:10:12,000 --> 04:10:13,120 I WILL WALK YOU THROUGH THE 6648 04:10:13,120 --> 04:10:15,440 SLIDE NOW. WHAT YOU ARE SEEING 6649 04:10:15,440 --> 04:10:18,320 HERE IS THIS COLUMN HERE, OF THE 6650 04:10:18,320 --> 04:10:19,600 INDIVIDUAL COLORS REPRESENTS THE 6651 04:10:19,600 --> 04:10:21,320 MODULES THAT THESE GENES ARE 6652 04:10:21,320 --> 04:10:22,640 CLUSTERED INTO. THE NUMBER 6653 04:10:22,640 --> 04:10:26,600 REPRESENTS THE NUMBER OF GENES 6654 04:10:26,600 --> 04:10:31,360 WITHIN EACH MODULE. THE ROWS OR 6655 04:10:31,360 --> 04:10:32,760 COLUMNS REPRESENT DIFFERENT 6656 04:10:32,760 --> 04:10:33,960 PHENOTYPIC TRAITS WE WERE 6657 04:10:33,960 --> 04:10:35,760 INTERESTED IN BOTH PROS AND PAIN 6658 04:10:35,760 --> 04:10:38,040 HISTORY. TO THE LEFT OF THE 6659 04:10:38,040 --> 04:10:39,520 BLACK LINE ARE THOSE REPRESENTED 6660 04:10:39,520 --> 04:10:40,960 DURING ACUTE PAIN TO THE RIGHT 6661 04:10:40,960 --> 04:10:42,000 ARE THOSE REPRESENTED DURING 6662 04:10:42,000 --> 04:10:45,360 BASELINE STATE OF HEALTH. THE 6663 04:10:45,360 --> 04:10:47,800 NUMBERS CONTAINED WITHIN THESE 6664 04:10:47,800 --> 04:10:52,800 BOXES IS THE MODULE EEGENE GENE 6665 04:10:52,800 --> 04:10:54,320 CORRELATION TO PHENOTYPIC TRAIT 6666 04:10:54,320 --> 04:10:56,120 OF INTEREST ON THE BOTTOM BOTTOM 6667 04:10:56,120 --> 04:10:58,800 AND THE P VALUE IS IN 6668 04:10:58,800 --> 04:11:01,920 PARENTHESES. ON THE LEFT YOU SEE 6669 04:11:01,920 --> 04:11:04,280 THE GENE ONTOLOGY TERMS THAT ARE 6670 04:11:04,280 --> 04:11:05,920 RESULT OF OUR DATA ANALYSIS TO 6671 04:11:05,920 --> 04:11:07,600 HELP UNDERSTAND WHAT THESE 6672 04:11:07,600 --> 04:11:09,040 MODULES POTENTIALLY REPRESENT 6673 04:11:09,040 --> 04:11:12,000 FROM BIOLOGICAL PERSPECTIVE OR 6674 04:11:12,000 --> 04:11:14,160 CLUSTERS OF GENES. FOR THE SAKE 6675 04:11:14,160 --> 04:11:15,160 OF THIS TALK I WOULD LIKE TO 6676 04:11:15,160 --> 04:11:16,920 DRILL DOWN ON TWO OF THESE 6677 04:11:16,920 --> 04:11:18,360 MODULES THAT WE ARE SIGNIFICANT 6678 04:11:18,360 --> 04:11:20,240 AND RETAIN IN OUR ANALYSIS BOTH 6679 04:11:20,240 --> 04:11:22,120 THE GREEN MODULE AND THE BLUE 6680 04:11:22,120 --> 04:11:25,120 MODULE. THE REASON FOR THIS IS 6681 04:11:25,120 --> 04:11:26,560 THEIR BIOLOGICAL PATHWAYS 6682 04:11:26,560 --> 04:11:28,240 REPRESENT A LOT OF IMMUNE OR 6683 04:11:28,240 --> 04:11:32,200 INFLAMMATORY PATHWAYS. THESE 6684 04:11:32,200 --> 04:11:36,280 BOTH MODULES HAS MODULE 6685 04:11:36,280 --> 04:11:38,280 EEGENGENES ASSOCIATED WITH THE 6686 04:11:38,280 --> 04:11:40,080 PHENOTYPIC PAIN RELATED THAT WE 6687 04:11:40,080 --> 04:11:41,600 ARE INTERESTED IN. WHEN WE 6688 04:11:41,600 --> 04:11:43,160 FURTHER DRILL DOWN ON WHAT THESE 6689 04:11:43,160 --> 04:11:44,400 PATHWAYS REPRESENT, AS YOU CAN 6690 04:11:44,400 --> 04:11:46,800 SEE IN THE GREEN AND BLUE BOXES 6691 04:11:46,800 --> 04:11:48,200 ON THE LEFT THERE IS A VARIETY 6692 04:11:48,200 --> 04:11:52,160 OF IMMUNE MEDIATED PATHWAYS THAT 6693 04:11:52,160 --> 04:11:54,280 APPEAR TO BE CLOSELY ASSOCIATED 6694 04:11:54,280 --> 04:11:57,160 WITH PAIN PHENOTYPIC TRAITS THAT 6695 04:11:57,160 --> 04:11:58,960 DESERVES FURTHER EXPLORATION AND 6696 04:11:58,960 --> 04:12:01,680 WHETHER PATHWAYS MODULATE 6697 04:12:01,680 --> 04:12:03,640 BIOLOGICALLY AS NOVEL PAIN 6698 04:12:03,640 --> 04:12:05,920 THERAPEUTICS. FINALLY WE DRILL 6699 04:12:05,920 --> 04:12:07,360 DOWN FURTHER ON SOME OF THE 6700 04:12:07,360 --> 04:12:08,280 INDIVIDUAL CANDIDATE GENES 6701 04:12:08,280 --> 04:12:09,400 WITHIN THE MODULES AND THIS 6702 04:12:09,400 --> 04:12:11,080 REPRESENT -- THIS TABLE 6703 04:12:11,080 --> 04:12:14,600 REPRESENTS CANDIDATE GENES FROM 6704 04:12:14,600 --> 04:12:17,000 THE GREEN MODULE. AND WHAT WE 6705 04:12:17,000 --> 04:12:19,440 DID IS WE LOOK AT ASSOCIATION OF 6706 04:12:19,440 --> 04:12:20,360 THESE INDIVIDUAL GENES WITH SOME 6707 04:12:20,360 --> 04:12:22,520 OF O OUR PHENOTYPIC TRAITS AND 6708 04:12:22,520 --> 04:12:24,360 NUMBERS IN THE TABLE REPRESENT P 6709 04:12:24,360 --> 04:12:27,760 VALUES FOR THESE ASSOCIATIONS. 6710 04:12:27,760 --> 04:12:29,400 WE SELECTED SOME OF THESE GENES 6711 04:12:29,400 --> 04:12:30,880 TO ILLUSTRATE DISEASE GENES HAVE 6712 04:12:30,880 --> 04:12:32,120 BEEN SHOWN IN THE LITERATURE TO 6713 04:12:32,120 --> 04:12:36,280 BE ASSOCIATED WITH PAIN. OR PLAY 6714 04:12:36,280 --> 04:12:39,200 A ROLE IN PAIN. SO OF COURSE 6715 04:12:39,200 --> 04:12:40,680 WITH ANY SCIENTIFIC RESEARCH WE 6716 04:12:40,680 --> 04:12:41,880 ARE LEFT WITH MORE QUESTIONS 6717 04:12:41,880 --> 04:12:43,760 THAN ANSWERS AND ONE OF THE KEY 6718 04:12:43,760 --> 04:12:45,200 QUESTIONS, ARE THESE PATHWAYS 6719 04:12:45,200 --> 04:12:46,920 POTENTIAL TARGETS FOR 6720 04:12:46,920 --> 04:12:48,040 BIOLOGICALLY BASED NOVEL PAIN 6721 04:12:48,040 --> 04:12:49,600 TREATMENT. WE NEED TO REALLY 6722 04:12:49,600 --> 04:12:52,680 DEFINE THE PAIN BIOLOGY, AND 6723 04:12:52,680 --> 04:12:54,160 UNDERSTAND WHAT IS GOING ON 6724 04:12:54,160 --> 04:12:55,800 WITHIN THESE PATHWAYS AND NEED 6725 04:12:55,800 --> 04:12:59,400 TO TEST THESE TARGETS FOR PAIN 6726 04:12:59,400 --> 04:13:01,120 EFFICACY AND CLINICAL STUDIES. 6727 04:13:01,120 --> 04:13:03,320 WHAT I SHOWED YOU AS WE STARTED 6728 04:13:03,320 --> 04:13:05,640 WITHOUT WITH CLINICAL RESEARCH 6729 04:13:05,640 --> 04:13:07,200 FINDINGS WITH REALLY COLLECTING 6730 04:13:07,200 --> 04:13:09,000 PAIN DATA USING PATIENT REPORTED 6731 04:13:09,000 --> 04:13:10,800 OUTCOMES AND HEALTHCARE 6732 04:13:10,800 --> 04:13:12,640 UTILIZATION. WE LEVERAGED 6733 04:13:12,640 --> 04:13:15,080 TRANSLATIONAL RESEARCH AS A 6734 04:13:15,080 --> 04:13:18,800 BRIDGE IN USING PLASMA BASED 6735 04:13:18,800 --> 04:13:21,080 TRANSCRIPTION AND WGCNA ANALYSES 6736 04:13:21,080 --> 04:13:23,360 TO BRIDGE US TO OUR BASIC PAIN 6737 04:13:23,360 --> 04:13:25,600 RESEARCH WHERE WE CAN DRILL DOWN 6738 04:13:25,600 --> 04:13:27,280 FURTHER LEVERAGING THE ANIMAL 6739 04:13:27,280 --> 04:13:30,040 AND OTHER BASIC PAIN MODELS TO 6740 04:13:30,040 --> 04:13:32,960 GET AT PAIN MECHANISM TO TRY TO 6741 04:13:32,960 --> 04:13:34,200 DELIVER NOVEL THERAPIES SO NOW 6742 04:13:34,200 --> 04:13:37,480 TURN IT TO DR. STUCKY TO TALK 6743 04:13:37,480 --> 04:13:40,800 BASIC RESEARCH SHE IS DOING IN 6744 04:13:40,800 --> 04:13:41,560 HER LAB. 6745 04:13:41,560 --> 04:13:44,800 >> THANK YOU, AMANDA. SO NEXT WE 6746 04:13:44,800 --> 04:13:47,600 WANTED TO IDENTIFY NOVEL 6747 04:13:47,600 --> 04:13:51,360 CANDIDATE FACTORS IN SICKLE CELL 6748 04:13:51,360 --> 04:13:54,880 PATIENT PLASMA THAT IS ELEVATED 6749 04:13:54,880 --> 04:13:57,440 DURING ACUTE PAIN THAT MAY 6750 04:13:57,440 --> 04:14:00,640 SENSITIZE SENSORY NEURONS AND 6751 04:14:00,640 --> 04:14:02,080 NOCICEPTORS, THESE PAIN SENSING 6752 04:14:02,080 --> 04:14:04,000 NEURONS. SO OUR HYPOTHESIS IS 6753 04:14:04,000 --> 04:14:06,000 THAT FACTORS THAT ARE 6754 04:14:06,000 --> 04:14:08,720 CIRCULATING IN PATIENT PLASMA 6755 04:14:08,720 --> 04:14:10,200 MAY SENSITIZE THESE SENSORY 6756 04:14:10,200 --> 04:14:13,360 NEURONS AND PAIN SENSING 6757 04:14:13,360 --> 04:14:15,680 NOCICEPTORS IN ORDER TO DRIVE 6758 04:14:15,680 --> 04:14:18,040 EXCITABILITY AND THEN THE 6759 04:14:18,040 --> 04:14:19,200 SENSITIZATION OF THESE ASCENDING 6760 04:14:19,200 --> 04:14:21,520 PAIN PATHWAYS IN SICKLE CELL 6761 04:14:21,520 --> 04:14:29,360 DISEASE THAT G GO TO THE BRAIN. 6762 04:14:29,360 --> 04:14:33,400 THE RATIONALE FOR THIS IS THAT 6763 04:14:33,400 --> 04:14:39,200 THE DORSAL ROOT GANGLIA WHICH 6764 04:14:39,200 --> 04:14:40,840 LIE OUTSIDE THE SPINAL CORD ON 6765 04:14:40,840 --> 04:14:42,000 BOTH SIDES OF THE SPINAL CORD 6766 04:14:42,000 --> 04:14:44,720 FROM THE NEXT ON DOWN TO THE 6767 04:14:44,720 --> 04:14:46,600 SACRUM IN YOUR BODY, CONTAIN ALL 6768 04:14:46,600 --> 04:14:49,440 THE CELL BODIES OF ALL 6769 04:14:49,440 --> 04:14:50,880 PERIPHERAL SENSORY NEURONS AND 6770 04:14:50,880 --> 04:14:53,720 PAIN SENSING NEURONS THAT INNER 6771 04:14:53,720 --> 04:14:59,000 INVESTIGATINNERVATE TARGET THE SKIN MUSCLE 6772 04:14:59,000 --> 04:15:03,160 BONE TENDONS, AND JOINTS. SO 6773 04:15:03,160 --> 04:15:07,640 THIS IMAGE, THIS IMAGE SHOWS THE 6774 04:15:07,640 --> 04:15:09,320 VERTICAL COLUMN AND THESE 6775 04:15:09,320 --> 04:15:10,520 NOCICEPTORS AND IF I CAN HAVE 6776 04:15:10,520 --> 04:15:13,880 THE NEXT SLIDE. THIS IMAGE SHOWS 6777 04:15:13,880 --> 04:15:16,640 ON THE LEFT HERE THE HUMAN 6778 04:15:16,640 --> 04:15:20,280 SPINAL COLUMN WITH THE SPINAL 6779 04:15:20,280 --> 04:15:22,160 CORD AND THEN DORSAL ROOT 6780 04:15:22,160 --> 04:15:24,000 GANGLIA IF YOU CAN SEE ON THIS 6781 04:15:24,000 --> 04:15:27,400 INSET THE DORSAL ROOT GANGLIA 6782 04:15:27,400 --> 04:15:31,720 LIE BETWEEN THE PED CAN BELIEVESICLES OF T HE 6783 04:15:31,720 --> 04:15:35,040 BONE AND THE DORSAL ROOT GANGLIA 6784 04:15:35,040 --> 04:15:37,800 LIE ON EITHER SIDE OF SPINAL 6785 04:15:37,800 --> 04:15:39,760 COLUMN AND CONTAIN CELL BODIES 6786 04:15:39,760 --> 04:15:41,600 OF SENSORY NEURONS. SO 6787 04:15:41,600 --> 04:15:42,400 INTERESTINGLY IT IS FLOWN SINCE 6788 04:15:42,400 --> 04:15:45,920 THE 1970s THAT THE DORSAL ROOT 6789 04:15:45,920 --> 04:15:47,600 GANGLIA AND NERVES THAT LIE 6790 04:15:47,600 --> 04:15:50,160 AROUND THE DORSAL ROOT GANGLIA 6791 04:15:50,160 --> 04:15:52,680 LACK A BLOOD NERVE BARRIER. THIS 6792 04:15:52,680 --> 04:15:55,120 IS A CONCEPT THAT MANY PEOPLE 6793 04:15:55,120 --> 04:15:58,640 DON'T REALIZE AND HAVE OFTEN NOT 6794 04:15:58,640 --> 04:16:00,640 REALIZED OR THEY DON'T THINK 6795 04:16:00,640 --> 04:16:02,640 ABOUT OFTEN BUT THE IDEAS THAT 6796 04:16:02,640 --> 04:16:06,040 SUBSTANCES THAT ARE DELIVERED OR 6797 04:16:06,040 --> 04:16:08,360 OCCUR ARE ELEVATED IN THE 6798 04:16:08,360 --> 04:16:10,120 BLOODSTREAM CAN PROFUSE FROM THE 6799 04:16:10,120 --> 04:16:12,200 BLOOD TO GANGLIA IN ORDER TO 6800 04:16:12,200 --> 04:16:13,560 CIRCULATE AROUND THE CELL BODIES 6801 04:16:13,560 --> 04:16:16,080 OF THE SENSORY NEURON. THIS 6802 04:16:16,080 --> 04:16:20,320 STUDY IS FROM THE MID 1970s 6803 04:16:20,320 --> 04:16:22,640 WHERE A DYE HORSERADISH 6804 04:16:22,640 --> 04:16:24,720 PEROXIDASE WAS INJECTED IV INTO 6805 04:16:24,720 --> 04:16:26,600 A PATIENT AND WITHIN MINUTES 6806 04:16:26,600 --> 04:16:29,360 THAT HRP DYE IS SHOWN INTER 6807 04:16:29,360 --> 04:16:32,880 COLLATING INTO THE DORSAL ROOT 6808 04:16:32,880 --> 04:16:34,200 GANGLIA AND SURROUNDING 6809 04:16:34,200 --> 04:16:35,840 OUTLINING THE SINGLE CELL BODIES 6810 04:16:35,840 --> 04:16:37,480 OF SENSORY NEURONS AND 6811 04:16:37,480 --> 04:16:40,800 NOCICEPTORS. SO IF I CAN HAVE 6812 04:16:40,800 --> 04:16:43,360 THE NEXT SLIDE. OUR HYPOTHESIS 6813 04:16:43,360 --> 04:16:46,520 IS THEN THAT THESE FACTORS THAT 6814 04:16:46,520 --> 04:16:49,560 ARE ELEVATED IN PATIENT PLASMA 6815 04:16:49,560 --> 04:16:50,880 IN SICKLE CELL DISEASE 6816 04:16:50,880 --> 04:16:53,080 INDIVIDUALS MAY ACTUALLY INTER 6817 04:16:53,080 --> 04:16:55,520 COLLATE INTO THE DORSAL ROOT 6818 04:16:55,520 --> 04:16:57,320 GANGLIA AND SENSORY NEURONS, 6819 04:16:57,320 --> 04:16:59,200 SENSITIZE THOSE NEURONS AND 6820 04:16:59,200 --> 04:17:00,880 THERE BY DRIVE THE EXCITABILITY 6821 04:17:00,880 --> 04:17:02,640 AND THE SENSITIZATION OF THESE 6822 04:17:02,640 --> 04:17:05,480 PAIN PATHWAYS IN SICKLE CELL 6823 04:17:05,480 --> 04:17:07,200 DISEASE THAT GO O THE BRAIN. 6824 04:17:07,200 --> 04:17:11,800 NEXT SLIDE. FOR THIS STUDY WE 6825 04:17:11,800 --> 04:17:13,360 IDENTIFY GENES THAT WERE 6826 04:17:13,360 --> 04:17:16,480 DIFFERENTIALLY EXPRESSED IN 6827 04:17:16,480 --> 04:17:18,880 PATIENTS WITH SICKLE CELL 6828 04:17:18,880 --> 04:17:19,520 DISEASE VERSUS HEALTHY CONTROLS. 6829 04:17:19,520 --> 04:17:23,000 THIS IS FROM AMANDA'S DATA SET. 6830 04:17:23,000 --> 04:17:26,880 WE ASK DO THESE GENES DIRECTLY 6831 04:17:26,880 --> 04:17:28,200 INTERACT WITH HUMIDOR SAL ROOT 6832 04:17:28,200 --> 04:17:31,360 GANGLIA. AND CAN WE THERE BY 6833 04:17:31,360 --> 04:17:33,040 DETECT INTERACTIONS BETWEEN 6834 04:17:33,040 --> 04:17:35,360 LIGANDS IN THE PLASMA OF SICKLE 6835 04:17:35,360 --> 04:17:38,640 CELL DISEASE PATIENTS, RECEPTORS 6836 04:17:38,640 --> 04:17:41,520 ON HUMAN DRG NEURONS. NEXT 6837 04:17:41,520 --> 04:17:45,960 SLIDE. WE DID THIS IN 6838 04:17:45,960 --> 04:17:47,520 COLLABORATION WITH DR. TED PRICE 6839 04:17:47,520 --> 04:17:49,520 WHO IS AT UNIVERSITY OF TEXAS 6840 04:17:49,520 --> 04:17:52,960 DALLAS AND TED IS A WORLD EXPERT 6841 04:17:52,960 --> 04:17:56,040 IN EXAMINING HUMIDOR SAL ROOT 6842 04:17:56,040 --> 04:17:57,680 GANGLIA, THE GENES THE 6843 04:17:57,680 --> 04:18:00,480 TRANSCRIPTS IN HUMAN DRGs BOTH 6844 04:18:00,480 --> 04:18:02,240 UNDER NORMAL CONDITIONS AND NOW 6845 04:18:02,240 --> 04:18:04,120 IN PATIENTS WITH A VARIETY OF 6846 04:18:04,120 --> 04:18:07,200 DIFFERENT TYPES OF PAIN. SO WE 6847 04:18:07,200 --> 04:18:09,160 COLLABORATED WITH TED, TO USE 6848 04:18:09,160 --> 04:18:12,600 WHAT HE HAS DESIGNED AS A HUMAN 6849 04:18:12,600 --> 04:18:15,600 SENSORY NEURON INTERACTOME. THIS 6850 04:18:15,600 --> 04:18:18,000 IS AN INTERACTOME IN WHICH ONE 6851 04:18:18,000 --> 04:18:19,520 CAN LOOK AT DIFFERENT LIGANDS 6852 04:18:19,520 --> 04:18:22,360 AND RECEPTORS ON HUMAN DRG 6853 04:18:22,360 --> 04:18:25,560 NEURONS. IN DOING THIS WE FOUND 6854 04:18:25,560 --> 04:18:27,760 IN SICKLE CELL PATIENT PLASMA, 6855 04:18:27,760 --> 04:18:30,000 THERE WERE 29 UNIQUE 6856 04:18:30,000 --> 04:18:31,560 INTERACTIONS BETWEEN 11 LIGANDS 6857 04:18:31,560 --> 04:18:34,560 IN THE PLASMA AND 21 RECEPTORS 6858 04:18:34,560 --> 04:18:38,000 ON THE HUMAN DRG NEURONS. MOST 6859 04:18:38,000 --> 04:18:40,200 OF THESE ARE CYTOKINES OR 6860 04:18:40,200 --> 04:18:44,280 CHEMOKINE RECEPTORS. NEXT SLIDE. 6861 04:18:44,280 --> 04:18:46,040 THESE ARE SOME OF OUR TOP 6862 04:18:46,040 --> 04:18:47,920 CANDIDATES. IF YOU LOOK AT THE 6863 04:18:47,920 --> 04:18:50,080 TOP THOSE IN YELLOW, WHAT THESE 6864 04:18:50,080 --> 04:18:52,440 CANDIDATES ARE DEFINED BY IS THE 6865 04:18:52,440 --> 04:18:55,080 NUMBER OF INTERACTIONS OF THE 6866 04:18:55,080 --> 04:18:57,600 LIGAND WITH SENSORY NEURONS IN 6867 04:18:57,600 --> 04:18:59,520 THESE HUMAN NEURONS. SO THE MORE 6868 04:18:59,520 --> 04:19:01,200 NUMBER OF INTERACTIONS THE 6869 04:19:01,200 --> 04:19:04,120 HIGHER LIKELIHOOD THAT THERE IS 6870 04:19:04,120 --> 04:19:04,920 INTERACTION IN SICKLE CELL 6871 04:19:04,920 --> 04:19:08,320 DISEASE PLASMA WITH HUMAN 6872 04:19:08,320 --> 04:19:12,160 SENSORY NEURONS. SO NEXT SLIDE. 6873 04:19:12,160 --> 04:19:14,960 I WANT TO HIGHLIGHT A COUPLE OF 6874 04:19:14,960 --> 04:19:16,520 THESE THAT WE ALREADY FIGURED 6875 04:19:16,520 --> 04:19:19,000 OUT ARE ELEVATED AND INVOLVED IN 6876 04:19:19,000 --> 04:19:20,320 SICKLE CELL DISEASE, THEY WOULD 6877 04:19:20,320 --> 04:19:23,880 BE IN THE RED BOX HERE, 6878 04:19:23,880 --> 04:19:25,440 ENDOTHELIN 1 AND CHEMOKINE 6879 04:19:25,440 --> 04:19:31,160 LIGAND 7. SO FIRST FOR CHEMOKINE 6880 04:19:31,160 --> 04:19:33,160 LIGAND 7 CCL 7 HAS BEEN SHOWN TO 6881 04:19:33,160 --> 04:19:36,400 BE INVOLVED IN CHRONIC AND 6882 04:19:36,400 --> 04:19:37,800 INFLAMMATORY AND NEUROPATHIC 6883 04:19:37,800 --> 04:19:39,600 PAIN AND OTHER TYPES OF PAIN 6884 04:19:39,600 --> 04:19:41,360 DISORDERS OTHER THAN SICKLE CELL 6885 04:19:41,360 --> 04:19:44,000 DISEASE. AND ONE OF THE 6886 04:19:44,000 --> 04:19:47,120 CANNINGNATE RECEPTORS FOR CCL 7 6887 04:19:47,120 --> 04:19:54,320 IS THE CCR 2, CCR RECEPTOR 2, A 6888 04:19:54,320 --> 04:19:58,040 COGNATE GCL COUPLE RECEPTOR FOR 6889 04:19:58,040 --> 04:20:01,600 CCL 7. SO WHAT WE DID IS TO 6890 04:20:01,600 --> 04:20:04,360 INVESTIGATE THE ROLL OF CCR 2 6891 04:20:04,360 --> 04:20:05,800 RECEPTOR IN SICKLE CELL DISEASE, 6892 04:20:05,800 --> 04:20:08,200 WE KNOW PATIENTS WITH SICKLE 6893 04:20:08,200 --> 04:20:10,440 CELL DISEASE HAD 6894 04:20:10,440 --> 04:20:11,680 HYPERSENSITIVITY TO TOUCH AND 6895 04:20:11,680 --> 04:20:13,000 PAIN FROM THE MECHANICAL 6896 04:20:13,000 --> 04:20:17,640 STIMULI. SO WE USE OUR MOUSE 6897 04:20:17,640 --> 04:20:19,360 MODELS OF SICKLE CELL DISEASE, 6898 04:20:19,360 --> 04:20:22,120 THE BERKELEY MODEL AND THE TOWNS 6899 04:20:22,120 --> 04:20:25,200 MODEL AND WE DETEST BEHAVIORAL 6900 04:20:25,200 --> 04:20:27,760 TESTS WHERE WE CAN TEST 6901 04:20:27,760 --> 04:20:29,680 MECHANICAL SENSITIVITY OF MICE 6902 04:20:29,680 --> 04:20:31,440 BY TOUCHING THE BOTTOM OF PAW 6903 04:20:31,440 --> 04:20:33,600 WITH A VON CALIBRATED FILAMENT 6904 04:20:33,600 --> 04:20:35,680 AND MEASURE THE THRESHOLD WHICH 6905 04:20:35,680 --> 04:20:38,120 THE ANIMAL PULLS THE PAW AWAY 6906 04:20:38,120 --> 04:20:40,280 FROM THE STIMULUS. FOR THIS 6907 04:20:40,280 --> 04:20:42,880 STUDY WE INJECTED INHIBITOR OF 6908 04:20:42,880 --> 04:20:46,360 LOCKER TO THE CCR 2 RECEPTOR TO 6909 04:20:46,360 --> 04:20:49,520 DELIVER IP INTERPERITONEALLY OR 6910 04:20:49,520 --> 04:20:50,760 INTERPLANT OR DIRECTLY INTO THE 6911 04:20:50,760 --> 04:20:53,360 PAW. WHAT WE SEE AS FIRST OF ALL 6912 04:20:53,360 --> 04:20:55,360 COMPARED TO THE CONTROLS WHICH 6913 04:20:55,360 --> 04:20:57,200 ARE IN WHITE, THE BERKELEY 6914 04:20:57,200 --> 04:21:00,600 SICKLE CELL ANIMALS ALL IN PINK 6915 04:21:00,600 --> 04:21:02,680 ARE VERY, VERY SENSITIVE TO 6916 04:21:02,680 --> 04:21:04,360 MECHANICAL STIMULI COMPARED TO 6917 04:21:04,360 --> 04:21:06,400 THE CONTROLS. AND WHEN WE INJECT 6918 04:21:06,400 --> 04:21:09,360 THE CRR 2 INHIBITOR INTO THE 6919 04:21:09,360 --> 04:21:12,440 PAW, THIS DOSE DEPENDENTLY 6920 04:21:12,440 --> 04:21:17,400 REVERSES THE MECHANICAL 6921 04:21:17,400 --> 04:21:20,200 HYPERSENSITIVITY. WE ALSO KNOW 6922 04:21:20,200 --> 04:21:21,000 PATIENTS WITH SICKLE CELL 6923 04:21:21,000 --> 04:21:22,800 DISEASE HAVE EXTREME HIGH 6924 04:21:22,800 --> 04:21:24,600 SENSITIVITY TO COLD AND THAT 6925 04:21:24,600 --> 04:21:28,880 COLD STIMULI CAN EXACERBATE 6926 04:21:28,880 --> 04:21:32,040 PAINFUL EPISODES. SO WE ASKED 6927 04:21:32,040 --> 04:21:35,040 WHETHER OUR SICKLE CELL MICE 6928 04:21:35,040 --> 04:21:36,240 WOULD EXHIBIT COLD 6929 04:21:36,240 --> 04:21:37,880 HYPERSENSITIVITY AND WHETHER THE 6930 04:21:37,880 --> 04:21:40,120 CCR 2 BLOCKER WOULD AFFECT THAT. 6931 04:21:40,120 --> 04:21:42,120 SO FOR THIS WE PLACED ANIMALS ON 6932 04:21:42,120 --> 04:21:46,160 THE GLASS TABLE TOP AND WE PUT A 6933 04:21:46,160 --> 04:21:47,720 STICK OF DRY ICE AT BOTTOM OF 6934 04:21:47,720 --> 04:21:52,120 THE PAW AND THEN MEASURED THE 6935 04:21:52,120 --> 04:21:54,320 SPEED WHICH THE ANIMAL PULLED 6936 04:21:54,320 --> 04:21:58,320 ITS PAW AWAY FROM THE ICE. WHAT 6937 04:21:58,320 --> 04:22:01,320 YOU CAN SEE IS THE ANIMALS CAN 6938 04:22:01,320 --> 04:22:02,960 SICKLE CELL DISEASE WHETHER THEY 6939 04:22:02,960 --> 04:22:03,800 BE TOWNS OR BERKELEY SHOWN IN 6940 04:22:03,800 --> 04:22:06,000 THE WHITE BARS, ARE VERY 6941 04:22:06,000 --> 04:22:07,360 SENSITIVE TO COLD STIMULI 6942 04:22:07,360 --> 04:22:09,160 COMPARED TO CONTROLS. BUT WHEN 6943 04:22:09,160 --> 04:22:11,440 WE INJECT THE CCR 2 INHIBITOR 6944 04:22:11,440 --> 04:22:14,440 INTO THE PAW, WE CAN BLOCK OR 6945 04:22:14,440 --> 04:22:15,600 REVERSE THAT COLD 6946 04:22:15,600 --> 04:22:17,440 HYPERSENSITIVITY. SO THAT IS 6947 04:22:17,440 --> 04:22:19,640 QUITE EXCITING. NEXT SLIDE 6948 04:22:19,640 --> 04:22:22,440 PLEASE. THEN THE OTHER MOLECULE 6949 04:22:22,440 --> 04:22:25,200 THAT IS UP IN OUR INTERACTOME 6950 04:22:25,200 --> 04:22:27,400 WITH HUMAN NEURONS WAS 6951 04:22:27,400 --> 04:22:30,120 ENDOTHELIN 1. ENDOTHELIN 1 IS A 6952 04:22:30,120 --> 04:22:31,800 MOLECULE SHOWN TO BE INVOLVED IN 6953 04:22:31,800 --> 04:22:34,360 CHRONIC INFLAMMATORY AND 6954 04:22:34,360 --> 04:22:36,000 NEUROPATHIC PAIN IN OTHER 6955 04:22:36,000 --> 04:22:37,480 DISORDERS BESIDES SICKLE CELL 6956 04:22:37,480 --> 04:22:39,520 DISEASE. WE FOUND THAT IN THE 6957 04:22:39,520 --> 04:22:42,200 DORSAL ROOT GANGLIA OF SICKLE 6958 04:22:42,200 --> 04:22:44,960 CELL ANIMALS, ENDOTHELIN 11 6959 04:22:44,960 --> 04:22:46,720 ELEVATED IN THE DORSAL ROOT 6960 04:22:46,720 --> 04:22:49,840 GANGLIA SHOWN BY THIS RED ARROW 6961 04:22:49,840 --> 04:22:57,280 HERE. ANOTHER GROUP BRIANNA LUTZ 6962 04:22:57,280 --> 04:23:00,400 AND TAU SHOWED WHEN THEY LOOK AT 6963 04:23:00,400 --> 04:23:03,480 MECHANICAL SENSITIVITY IN SICKLE 6964 04:23:03,480 --> 04:23:06,280 MICE, WHAT THEY DID HERE IS 6965 04:23:06,280 --> 04:23:07,640 LOOKING AT VON BRIAN THRESHOLD 6966 04:23:07,640 --> 04:23:09,240 THEY LOOK AT FREQUENCY OF 6967 04:23:09,240 --> 04:23:11,040 RESPONSES TO A GIVEN SUPER 6968 04:23:11,040 --> 04:23:13,600 THRESHOLD FORCE TO THE PAW. AND 6969 04:23:13,600 --> 04:23:15,920 WHEN THEY INJECTED THE 6970 04:23:15,920 --> 04:23:18,280 ENDOTHELIN RECEPTOR INHIBITOR 6971 04:23:18,280 --> 04:23:20,640 INTO THE PAW, UNDER NORMAL 6972 04:23:20,640 --> 04:23:23,000 BASELINE SICKLE CONDITIONS, THEY 6973 04:23:23,000 --> 04:23:26,240 FOUND THAT REVERSED THE PAW 6974 04:23:26,240 --> 04:23:28,200 HYPERSENSITIVITY THAT'S THE ABT 6975 04:23:28,200 --> 04:23:29,960 COMPOUND IS THE ENDOTHELIN 6976 04:23:29,960 --> 04:23:31,520 RECEPTOR BLOCKER AND THAT 6977 04:23:31,520 --> 04:23:33,520 COMPLETELY REVERSED THE 6978 04:23:33,520 --> 04:23:36,840 MECHANICAL HYPERSENSITIVITY AT 6979 04:23:36,840 --> 04:23:38,480 BASELINE CHRONIC SICKLE CELL 6980 04:23:38,480 --> 04:23:42,000 CONDITIONS BUT ALSO WHEN THEY 6981 04:23:42,000 --> 04:23:44,120 INDUCED RED CELLS SICKLING ON AN 6982 04:23:44,120 --> 04:23:45,680 ACUTE LEVEL WITH HYPOXIA 6983 04:23:45,680 --> 04:23:47,600 TREATMENT SO DURING ACUTE PAIN 6984 04:23:47,600 --> 04:23:50,080 EVENT, IT REVERSES THE 6985 04:23:50,080 --> 04:23:51,680 HYPERSENSITIVITY TO MECHANICAL 6986 04:23:51,680 --> 04:23:55,120 TOUCH. NEXT SLIDE PLEASE.MENT 6987 04:23:55,120 --> 04:23:58,960 THEN THEY TESTED COLD 6988 04:23:58,960 --> 04:24:00,800 SENSITIVITY USING A COLD PLATE, 6989 04:24:00,800 --> 04:24:02,280 THEY PUT THE MICE ON A COLD 6990 04:24:02,280 --> 04:24:04,120 PLATE AND MEASURE HOW QUICKLY 6991 04:24:04,120 --> 04:24:05,600 ANIMALS PICK UP THEIR PAW IN 6992 04:24:05,600 --> 04:24:08,600 RESPONSE TO COLD STIMULUS. WHAT 6993 04:24:08,600 --> 04:24:14,000 THEY FOUND IS WHEN THEY INJECT 6994 04:24:14,000 --> 04:24:15,400 ENDOTHELIN RECEPTOR BLOCKER INTO 6995 04:24:15,400 --> 04:24:18,520 THE PAW, THAT REVERSED IN THE 6996 04:24:18,520 --> 04:24:21,720 ABT COMPOUND REVERSE THAT COLD 6997 04:24:21,720 --> 04:24:22,840 HYPERSENSITIVITY OF BASELINE 6998 04:24:22,840 --> 04:24:25,120 CHRONIC HYPERSENSITIVITY 6999 04:24:25,120 --> 04:24:27,040 CONDITIONS AND ALSO WHEN THEY 7000 04:24:27,040 --> 04:24:28,960 INDUCE ACUTE RED CELL SICKLING 7001 04:24:28,960 --> 04:24:35,080 WITH HYPOXIA TREATMENT. BUT WAIT 7002 04:24:35,080 --> 04:24:37,280 THERE IS MORE. BECAUSE YOU MIGHT 7003 04:24:37,280 --> 04:24:39,720 HAVE NOTICED IN IN OUR SENSORY 7004 04:24:39,720 --> 04:24:42,200 NEURON INTERACTOME THERE'S 7005 04:24:42,200 --> 04:24:43,120 SEVERAL CANDIDATES THAT HAVE 7006 04:24:43,120 --> 04:24:45,400 MORE INTERACTIONS BETWEEN THE 7007 04:24:45,400 --> 04:24:47,520 PLASMA LIGANDS AND DORSAL ROOT 7008 04:24:47,520 --> 04:24:50,280 GANGLIA, THE HUMAN GANGLIA. SOME 7009 04:24:50,280 --> 04:24:51,880 HAVE UP TO FIVE DIFFERENT 7010 04:24:51,880 --> 04:24:54,320 INTERACTIONS THESE ARE NOVEL 7011 04:24:54,320 --> 04:24:58,600 CANDIDATES NOT INVESTIGATED YET, 7012 04:24:58,600 --> 04:25:01,080 IL 16, CHEMOKINE LIGAND 5 AND 7013 04:25:01,080 --> 04:25:03,440 THEN COLONY STIMULATING FACTOR. 7014 04:25:03,440 --> 04:25:05,800 AND WE THINK THAT MAKES GOOD 7015 04:25:05,800 --> 04:25:07,440 SENSE BECAUSE THERE IS ALREADY 7016 04:25:07,440 --> 04:25:10,640 EVIDENCE IN THE LITERATURE IN 7017 04:25:10,640 --> 04:25:13,120 OTHER WAYS WHERE THERE IS A 7018 04:25:13,120 --> 04:25:16,000 LITTLE BIT OF EVIDENCE IN THE 7019 04:25:16,000 --> 04:25:17,480 LITERATURE THESE CANDIDATES 7020 04:25:17,480 --> 04:25:19,760 MAYBE INVOLVED IN SICKLE PAIN. 7021 04:25:19,760 --> 04:25:25,640 FIRST IL 16, POLYMORPHISMS IN IL 7022 04:25:25,640 --> 04:25:28,840 16 ARE SHOWN TO BE INVOLVED IN 7023 04:25:28,840 --> 04:25:30,800 PAINFUL ENDOMETRIOSIS. ENDOMETRIOSIS. 7024 04:25:30,800 --> 04:25:32,400 POLYMORPHISMS IN THE IL 16 ARE 7025 04:25:32,400 --> 04:25:36,280 SHOWN TO INCREASE THE RISK FOR 7026 04:25:36,280 --> 04:25:39,680 ISCHEMIC STROKE. SECOND CCL 5 IS 7027 04:25:39,680 --> 04:25:42,240 SHOWN TO DEHYDRATE RED BLOOD 7028 04:25:42,240 --> 04:25:47,800 CELLS AND THERE BY AGGRAVATE 7029 04:25:47,800 --> 04:25:48,400 VASOOCCLUSIVE CRISES IN SICKLE 7030 04:25:48,400 --> 04:25:50,200 CELL DISEASE AND CCL 5 IS SHOWN 7031 04:25:50,200 --> 04:25:52,400 INVOLVED IN MULTIPLE TYPES OF 7032 04:25:52,400 --> 04:25:55,520 CHRONIC PAIN. AND FINALLY COLONY 7033 04:25:55,520 --> 04:25:57,240 STIMULATING FACTOR 2 HAS BEEN 7034 04:25:57,240 --> 04:25:59,760 SHOWN TO MEDIATE INFLAMMATORY 7035 04:25:59,760 --> 04:26:02,720 AND ARTHRITIC PAIN IN NON-SICKLE 7036 04:26:02,720 --> 04:26:06,240 PAIN MODELS. SO WE THINK THAT 7037 04:26:06,240 --> 04:26:09,920 POTENTIALLY THESE NEW CANDIDATES 7038 04:26:09,920 --> 04:26:11,160 FOR SICKLE CELL DISEASE MIGHT BE 7039 04:26:11,160 --> 04:26:12,720 INVOLVED IN DRIVING THE PAIN 7040 04:26:12,720 --> 04:26:15,280 FROM THE PERIPHERY TO THE 7041 04:26:15,280 --> 04:26:18,400 ASCENDING PATHWAYS, IN SICKLE 7042 04:26:18,400 --> 04:26:22,200 CELL DISEASE. SO FINALLY, WE 7043 04:26:22,200 --> 04:26:24,520 THINK THAT A STRONG 7044 04:26:24,520 --> 04:26:26,400 TRANSLATIONAL APPROACH IS TO 7045 04:26:26,400 --> 04:26:30,400 FIRST IDENTIFY FACTORS IN 7046 04:26:30,400 --> 04:26:32,560 PATIENT PLASMA IN PATIENT PLASMA 7047 04:26:32,560 --> 04:26:34,640 AND THEN TEST INTERACTION WITH 7048 04:26:34,640 --> 04:26:36,920 HUMAN SENSORY NEURONS USING THIS 7049 04:26:36,920 --> 04:26:39,360 INTERACTOME AND THEN TAKE THESE 7050 04:26:39,360 --> 04:26:42,320 BACK INTO THE ANIMAL MODELS TO 7051 04:26:42,320 --> 04:26:44,600 TEST FOR EFFICACY IN PAIN 7052 04:26:44,600 --> 04:26:46,200 INHIBITION IN THE ANIMAL MODELS 7053 04:26:46,200 --> 04:26:47,760 AND LOOK FOR THE UNDERLYING 7054 04:26:47,760 --> 04:26:48,880 MECHANISMS THAT DRIVE THE PAIN 7055 04:26:48,880 --> 04:26:51,160 IN THESE ANIMAL MODELS OF SICKLE 7056 04:26:51,160 --> 04:26:53,000 CELL DISEASE, AND THEN 7057 04:26:53,000 --> 04:26:54,440 POTENTIALLY TAKE THESE 7058 04:26:54,440 --> 04:26:57,760 CANDIDATES BACK INTO PATIENTS 7059 04:26:57,760 --> 04:27:00,800 AND DO HUMAN TRIALS, SENSORY 7060 04:27:00,800 --> 04:27:02,160 NEURONS, TEST IN HUMAN TISSUE 7061 04:27:02,160 --> 04:27:04,200 AND POTENTIALLY TEST IN HUMAN 7062 04:27:04,200 --> 04:27:06,200 TRIALS AND POTENTIALLY PATIENTS 7063 04:27:06,200 --> 04:27:08,200 WITH SICKLE CELL DISEASE. SO WE 7064 04:27:08,200 --> 04:27:10,200 ARE VERY EXCITED ABOUT THIS, 7065 04:27:10,200 --> 04:27:11,960 BACK AND FORTH TRANSLATIONAL 7066 04:27:11,960 --> 04:27:14,160 MODEL THAT AMANDA AND I ARE -- 7067 04:27:14,160 --> 04:27:16,240 HAVE BEEN USING AND WE THINK 7068 04:27:16,240 --> 04:27:19,840 THAT IT IS HOPEFULLY A WAY TO 7069 04:27:19,840 --> 04:27:21,800 IDENTIFY VIABLE CANDIDATES FOR 7070 04:27:21,800 --> 04:27:23,200 NOVEL TREATMENT FOR SICKLE CELL 7071 04:27:23,200 --> 04:27:27,600 DISEASE IN PATIENTS. FINALLY 7072 04:27:27,600 --> 04:27:29,160 AMANDA AND I WOULD LIKE TO THANK 7073 04:27:29,160 --> 04:27:31,480 ALL OF OUR MANY COLLABORATORS AT 7074 04:27:31,480 --> 04:27:35,600 MEDICAL COLLEGE OF WISCONSIN, WE 7075 04:27:35,600 --> 04:27:38,520 ARE SO GRATEFUL FOR THESE 7076 04:27:38,520 --> 04:27:39,840 EXCELLENT COLLABORATORS AND 7077 04:27:39,840 --> 04:27:41,840 ESPECIALLY PATIENTS AND FAMILIES 7078 04:27:41,840 --> 04:27:44,200 THAT HAVE GIVEN THEIR TIME AND 7079 04:27:44,200 --> 04:27:46,200 WE HOPE TO HELP. THANK YOU FOR 7080 04:27:46,200 --> 04:27:47,400 OUR FUNDING. WITH THAT, THANK 7081 04:27:47,400 --> 04:27:50,120 YOU, VERY MUCH. ON BEHALF OF 7082 04:27:50,120 --> 04:28:07,120 AMANDA AND MYSELF. 7083 04:28:07,120 --> 04:28:08,600 >> NITYA. 7084 04:28:08,600 --> 04:28:09,600 >> GOOD AFTERNOON, THANK YOU FOR 7085 04:28:09,600 --> 04:28:11,240 INVITING ME TO PRESENT TODAY. I 7086 04:28:11,240 --> 04:28:12,400 JUST WANT TO BE SURE YOU CAN 7087 04:28:12,400 --> 04:28:19,640 HEAR ME CLEARLY. TODAY I'M GOING 7088 04:28:19,640 --> 04:28:24,320 TO TALK TO YOU ABOUT PAIN 7089 04:28:24,320 --> 04:28:25,320 PHENOTYPE AND SICKLE CELL 7090 04:28:25,320 --> 04:28:28,400 DISEASE, INSIGHTS FROM THE PAIN 7091 04:28:28,400 --> 04:28:29,840 AND SICKLE CELL DISEASE 7092 04:28:29,840 --> 04:28:36,160 EPIDEMIOLOGY STUDY OR PISCES. 7093 04:28:36,160 --> 04:28:38,560 I'LL PRESENTING ON BEHALF OF 7094 04:28:38,560 --> 04:28:39,680 (INAUDIBLE) FROM TABLE RECENTLY 7095 04:28:39,680 --> 04:28:41,000 PUBLISHED IN PAIN. NEXT SLIDE 7096 04:28:41,000 --> 04:28:47,520 PLEASE. AS WE KNOW 7097 04:28:47,520 --> 04:28:48,800 EPIDEMIOLOGICAL STUDY OF PAIN IN 7098 04:28:48,800 --> 04:28:54,320 SICKLE CELL DISEASE AND STUDY IN 7099 04:28:54,320 --> 04:28:55,000 ANALYZED 232 INDIVIDUAL WITH 7100 04:28:55,000 --> 04:28:57,920 SICKLE CELL DISEASE. AND IT 7101 04:28:57,920 --> 04:29:03,600 SHOWED US THAT ONLY MINORITY OF 7102 04:29:03,600 --> 04:29:08,120 DAYS PAIN WERE ASSOCIATED WITH 7103 04:29:08,120 --> 04:29:10,120 (INAUDIBLE) AND MOST PATIENTS 7104 04:29:10,120 --> 04:29:13,000 HAD PAIN ON MORE THAN HALF THE 7105 04:29:13,000 --> 04:29:17,400 DAYS AND SUBSTANTIAL ONE-THIRD 7106 04:29:17,400 --> 04:29:20,960 OF THEM NEARLY EVERY DAY OR 7107 04:29:20,960 --> 04:29:29,520 EVERY SINGLE DAY. NEXT SLIDE. T 7108 04:29:29,520 --> 04:29:36,160 IN PISCES AS IN MOST STUDIES, 7109 04:29:36,160 --> 04:29:38,200 PAIN EVENTS REPORTED OUTCOME OF 7110 04:29:38,200 --> 04:29:41,720 THE STUDY. WITHIN THE STUDY YOU 7111 04:29:41,720 --> 04:29:45,680 CAN SEE HERE THAT (INAUDIBLE) 7112 04:29:45,680 --> 04:29:47,880 INCREASED AS THE FREQUENCY OR 7113 04:29:47,880 --> 04:29:51,320 PROPORTION OF INSULIN INCREASED. 7114 04:29:51,320 --> 04:29:53,800 PAIN INTENSITY WAS INDEPENDENTLY 7115 04:29:53,800 --> 04:29:56,280 ASSOCIATED WITH HEALTH RELATED 7116 04:29:56,280 --> 04:30:02,000 QUALITY OF LIFE. AT A -- LEVEL 7117 04:30:02,000 --> 04:30:05,520 MAINTAIN INTENSITY PATIENT 7118 04:30:05,520 --> 04:30:08,040 OUTCOMES. HOWEVER, THERE ARE 7119 04:30:08,040 --> 04:30:09,800 SOME MANIPULATIONS PARTICULARLY 7120 04:30:09,800 --> 04:30:11,160 AT THE INDIVIDUAL LEVEL. MENTION 7121 04:30:11,160 --> 04:30:19,240 SLIDE PLEASE. AT THE INDIVIDUAL 7122 04:30:19,240 --> 04:30:20,240 LEVEL (INAUDIBLE) PAIN 7123 04:30:20,240 --> 04:30:25,760 PHENOTYPE. WE CAN SEE HERE THESE 7124 04:30:25,760 --> 04:30:28,920 DATA FROM ONE INITIAL STUDIES 7125 04:30:28,920 --> 04:30:35,480 WERE PAIN INTENSITY WAS STUDIED 7126 04:30:35,480 --> 04:30:41,080 USING ON BOTH INDIVIDUALS 7127 04:30:41,080 --> 04:30:42,800 INTENSITY IS IDENTICAL. HOWEVER 7128 04:30:42,800 --> 04:30:45,600 JUST LOOKING AT THESE GAPS YOU 7129 04:30:45,600 --> 04:30:49,640 KNOW PAIN PHENOTYPES ARE NOT 7130 04:30:49,640 --> 04:30:56,800 IDENTICAL AS ONE 50% AND AT 7131 04:30:56,800 --> 04:30:58,000 INDIVIDUAL LEVEL PAIN DELIVERY 7132 04:30:58,000 --> 04:31:07,520 IS NOT IDENTICAL. PROPOSED TO 7133 04:31:07,520 --> 04:31:09,480 INVESTIGATE INDIVIDUAL IN SICKLE 7134 04:31:09,480 --> 04:31:14,960 CELL DISEASE FOLLOWING FREQUENCY 7135 04:31:14,960 --> 04:31:17,640 (INAUDIBLE) DETERMINE 7136 04:31:17,640 --> 04:31:19,080 DEVELOPMENTS OF INTERINDIVIDUAL 7137 04:31:19,080 --> 04:31:22,600 TO PATIENT REPORTED OUTCOMES 7138 04:31:22,600 --> 04:31:24,880 OTHERS WITH SICKLE CELL DISEASE 7139 04:31:24,880 --> 04:31:30,120 WITH TWO SPECIFIC SUBTYPES IS IN 7140 04:31:30,120 --> 04:31:31,040 ASSOCIATED WITH PSYCHOLOGICAL 7141 04:31:31,040 --> 04:31:33,920 CHARACTERISTICS IN SICKLE CELL. 7142 04:31:33,920 --> 04:31:36,120 AND COULD BE USED TO IDENTIFY 7143 04:31:36,120 --> 04:31:37,600 SUB GROUPS OF PAIN PHENOTYPES ON 7144 04:31:37,600 --> 04:31:43,440 SICKLE CELL. NEXT SLIDE PLEASE. 7145 04:31:43,440 --> 04:31:50,200 SO IN ORDER TO STUDY VARIABILITY 7146 04:31:50,200 --> 04:31:52,320 MEASURABLE WE NEED WE DECIDED TO 7147 04:31:52,320 --> 04:31:55,720 STUDY THREE DIFFERENT ASPECTS OF 7148 04:31:55,720 --> 04:31:58,920 INTERINDIVIDUAL VARIABILITY ONE 7149 04:31:58,920 --> 04:32:02,160 IS THE (INAUDIBLE) STANDARD 7150 04:32:02,160 --> 04:32:03,640 DEVIATION. YOU CAN SEE IN THE 7151 04:32:03,640 --> 04:32:10,600 TWO GRAPHS THE INEQUITY THAT YOU 7152 04:32:10,600 --> 04:32:13,680 CAN SOMEWHAT MEASURE EXTENT 7153 04:32:13,680 --> 04:32:17,080 FLUCTUATION AT THE STANDARD 7154 04:32:17,080 --> 04:32:20,520 DEVIATION. THE OTHER ASPECT OF 7155 04:32:20,520 --> 04:32:22,600 INTERINDIVIDUAL IS TEMPORAL 7156 04:32:22,600 --> 04:32:26,640 INSTABILITY OF -- SO THE MEAN 7157 04:32:26,640 --> 04:32:30,600 SQUARE OF SUCCESS LOOKS AT THE 7158 04:32:30,600 --> 04:32:32,080 BOTH THE AMPLITUDE OF 7159 04:32:32,080 --> 04:32:35,800 FLUCTUATION AS WELL AS THE 7160 04:32:35,800 --> 04:32:38,800 TEMPORALTY FLUCTUATIONS SO IT 7161 04:32:38,800 --> 04:32:41,640 CAN MEASURE COME AT THE 7162 04:32:41,640 --> 04:32:43,280 BEGINNING OR END FOR EXAMPLE. 7163 04:32:43,280 --> 04:32:46,360 THE PROBABILITY OF ACUTE CHANGE 7164 04:32:46,360 --> 04:32:47,240 IS FREQUENCY OF THE 7165 04:32:47,240 --> 04:32:55,400 FLUCTUATIONS. YOU CAN SEE THESE 7166 04:32:55,400 --> 04:32:58,280 MEASURES CAN DISTINGUISH BETWEEN 7167 04:32:58,280 --> 04:32:59,840 PAIN INTENSITY COLLECTED OVER 7168 04:32:59,840 --> 04:33:06,120 TIME. THE LAST ONE IS TEMPORAL 7169 04:33:06,120 --> 04:33:07,600 DEPENDENCY OR FIRST QUARTER 7170 04:33:07,600 --> 04:33:10,200 AUTOCORRELATION WHICH 7171 04:33:10,200 --> 04:33:12,920 ESSENTIALLY TRIES TO MEASURE HOW 7172 04:33:12,920 --> 04:33:16,400 DOES PAIN FROM ONE DECOR LATE 7173 04:33:16,400 --> 04:33:20,880 WITH TO THE NEXT DAY. OR 7174 04:33:20,880 --> 04:33:25,360 YESTERDAY PAIN TODAY AND HERSIS 7175 04:33:25,360 --> 04:33:29,720 TENSE OF -- OR THAT ONCE PAIN 7176 04:33:29,720 --> 04:33:32,880 FLUCTUATES HOW LONG DOES IT STAY 7177 04:33:32,880 --> 04:33:33,440 ABOVE (INAUDIBLE) PAIN 7178 04:33:33,440 --> 04:33:43,160 INTENSITY. WE CALCULATED THESE 7179 04:33:43,160 --> 04:33:49,280 IN 139 INDIVIDUALS FROM THE 232 7180 04:33:49,280 --> 04:33:53,920 LESS THAN -- IN THE FIRST 7181 04:33:53,920 --> 04:33:56,120 (INAUDIBLE) SMALL NUMBER OF PAIN 7182 04:33:56,120 --> 04:34:01,280 SCORES, NO MORE THAN (INAUDIBLE) 7183 04:34:01,280 --> 04:34:04,160 AND REPRESENTS LESS THAN 2% OF 7184 04:34:04,160 --> 04:34:06,600 THE DATA. CALCULATED METHODS OF 7185 04:34:06,600 --> 04:34:11,240 PAIN INTENSITY VARIABILITY FOR 7186 04:34:11,240 --> 04:34:15,160 EACH INDIVIDUAL. NEXT SLIDE. 7187 04:34:15,160 --> 04:34:20,000 MEDIAN AGE WAS 33 YEARS WITH 7188 04:34:20,000 --> 04:34:25,120 MORE THAN HALF FEMALE. THE VAST 7189 04:34:25,120 --> 04:34:27,760 MAJORITY, 79% HAVE SICKLE CELL 7190 04:34:27,760 --> 04:34:28,720 (INAUDIBLE) PHENOTYPE. NEXT 7191 04:34:28,720 --> 04:34:34,240 SLIDE PLEASE. WHEN WE LOOKED AT 7192 04:34:34,240 --> 04:34:38,560 THESE ARE MEDIANS OF ONE OF THEM 7193 04:34:38,560 --> 04:34:41,520 AT A INDIVIDUAL LEVEL. YOU CAN 7194 04:34:41,520 --> 04:34:45,960 SEE THE MEAN -- 2.3 AND 7195 04:34:45,960 --> 04:34:49,800 PROPORTION OF IS ABOUT 70%. 7196 04:34:49,800 --> 04:34:53,200 WHICH THE OTHER MEASURES 7197 04:34:53,200 --> 04:34:54,160 (INAUDIBLE) PRESENTED HERE. NEXT 7198 04:34:54,160 --> 04:34:59,720 SLIDE PLEASE. WE THEN LOOK TO 7199 04:34:59,720 --> 04:35:01,800 SEE WHETHER THERE WAS A 7200 04:35:01,800 --> 04:35:03,560 CORRELATION BETWEEN 7201 04:35:03,560 --> 04:35:04,800 INTERINDIVIDUAL PAIN VARIABILITY 7202 04:35:04,800 --> 04:35:07,080 AND THE PAIN INTENSITY. SO FROM 7203 04:35:07,080 --> 04:35:10,200 THE SUBGROUP THAT'S THE FIRST 7204 04:35:10,200 --> 04:35:11,280 COLUMN TO THE NEXT THAT 7205 04:35:11,280 --> 04:35:14,600 REPRESENTS ALL PATIENTS YOU CAN 7206 04:35:14,600 --> 04:35:16,320 SEE THAT THERE ARE CORRELATIONS 7207 04:35:16,320 --> 04:35:18,280 BETWEEN METHODS OF PAIN 7208 04:35:18,280 --> 04:35:20,160 VARIABILITY SUCH AS STANDARD 7209 04:35:20,160 --> 04:35:21,960 DEVIATION, PROBABILITY OF KEY 7210 04:35:21,960 --> 04:35:25,840 CHANGE, AND SSD ON 7211 04:35:25,840 --> 04:35:27,080 AUTOCORRELATION WITH MEAN PAIN 7212 04:35:27,080 --> 04:35:30,360 INTENSITY. HOWEVER, THE PICTURE 7213 04:35:30,360 --> 04:35:33,640 IS A LITTLE MORE NUANCED WHEN 7214 04:35:33,640 --> 04:35:35,880 YOU EVALUATE THIS RELATIONSHIP 7215 04:35:35,880 --> 04:35:38,880 ON THE BASIS OF PAIN FREQUENCY. 7216 04:35:38,880 --> 04:35:42,320 SO AMONG THOSE WITH LESS THAN 7217 04:35:42,320 --> 04:35:47,040 50% -- WE FIND THE PAIN 7218 04:35:47,040 --> 04:35:49,800 INTENSITY VERY STRONGLY 7219 04:35:49,800 --> 04:35:53,280 CORRELATED. MORE THAN HALF BUT 7220 04:35:53,280 --> 04:36:00,800 LESS THAN 95%, CORRELATIONS ARE 7221 04:36:00,800 --> 04:36:10,960 STILL BUT THE CORRELATION, THOSE 7222 04:36:10,960 --> 04:36:12,680 WHO EXPERIENCE NEAR (INAUDIBLE) 7223 04:36:12,680 --> 04:36:16,200 CORRELATION BETWEEN PAIN 7224 04:36:16,200 --> 04:36:17,360 INTENSITY AND VARIABILITY 7225 04:36:17,360 --> 04:36:21,960 METHODS. THIS SUGGESTS THAT 7226 04:36:21,960 --> 04:36:24,920 THERE MAYBE -- PAIN VARIABILITY 7227 04:36:24,920 --> 04:36:30,600 PARTICULARLY IN EXPERIENCES ON 7228 04:36:30,600 --> 04:36:32,280 ALL THINGS ALMOST EVERY DAY. 7229 04:36:32,280 --> 04:36:44,080 NEXT SLIDE PLEASE. SO WHEN WE 7230 04:36:44,080 --> 04:36:50,360 LOOK AT THE RELATIONSHIP, 7231 04:36:50,360 --> 04:36:53,280 PSYCHOLOGICAL AND CLINICAL 7232 04:36:53,280 --> 04:36:56,680 CHARACTERISTICS, THIS COHORT WE 7233 04:36:56,680 --> 04:37:01,680 SEE PAIN VARIABILITY METHODS IN 7234 04:37:01,680 --> 04:37:04,000 GENERAL AS PAIN INTENSITY ARE 7235 04:37:04,000 --> 04:37:06,200 NEGATIVELY CORRELATED WITH 7236 04:37:06,200 --> 04:37:10,240 QUALITY OF LIFE. POSITIVELY 7237 04:37:10,240 --> 04:37:15,080 CORRELATED PSYCHOLOGICAL 7238 04:37:15,080 --> 04:37:17,840 DIAGNOSTICS WHICH ARE SUBMITTED 7239 04:37:17,840 --> 04:37:20,200 IN THE SYSTEM (INAUDIBLE) 7240 04:37:20,200 --> 04:37:23,200 OUTCOMES SUCH AS ANXIETY 7241 04:37:23,200 --> 04:37:25,840 DEPRESSION, COPING 7242 04:37:25,840 --> 04:37:28,200 CATASTROPHIZING AND STRESS. WE 7243 04:37:28,200 --> 04:37:34,640 ALSO SEE THAT PAIN (INAUDIBLE) 7244 04:37:34,640 --> 04:37:36,840 PROPORTION OF PAIN WITH 7245 04:37:36,840 --> 04:37:40,000 UTILIZATION. NEXT LIED PLEASE. 7246 04:37:40,000 --> 04:37:42,400 HOWEVER ONCE YOU START AGAIN 7247 04:37:42,400 --> 04:37:43,840 EVALUATING THIS IN THE CONTEXT 7248 04:37:43,840 --> 04:37:47,600 OF PAIN FREQUENCY, YOU SEE THE 7249 04:37:47,600 --> 04:37:49,680 RELATIONSHIPS ARE A LITTLE MORE 7250 04:37:49,680 --> 04:37:53,800 NUANCED IN THOSE WITH LESS THAN 7251 04:37:53,800 --> 04:37:59,840 50% PAIN DAYS YOU CAN SEE PAIN 7252 04:37:59,840 --> 04:38:05,120 VARIABILITY ACTUALLY CORRELATES 7253 04:38:05,120 --> 04:38:08,000 WITH PHYSICAL HEALTH. WHEREAS 7254 04:38:08,000 --> 04:38:13,680 ONCE YOU -- THOSE WITH THE ONLY 7255 04:38:13,680 --> 04:38:19,040 OUTCOME THAT ACTUALLY CORRELATES 7256 04:38:19,040 --> 04:38:27,040 IS (INAUDIBLE) AUTOCORRELATION. 7257 04:38:27,040 --> 04:38:29,040 SO THEREFORE WE NOW -- 7258 04:38:29,040 --> 04:38:31,200 INDIVIDUAL VARIABILITY IS 7259 04:38:31,200 --> 04:38:33,320 ASSOCIATED WITH PATIENT OUTCOMES 7260 04:38:33,320 --> 04:38:35,840 AND PSYCHOLOGICAL -- IN SICKLE 7261 04:38:35,840 --> 04:38:42,200 CELL DISEASE AND WE LOOK TO 7262 04:38:42,200 --> 04:38:44,480 QUESTION WHETHER INTRAINDIVIDUAL 7263 04:38:44,480 --> 04:38:46,600 COMPARABILITY COULD BE USED TO 7264 04:38:46,600 --> 04:38:48,000 SUBGROUPS OF PHENOTYPES WITH 7265 04:38:48,000 --> 04:38:51,240 SICKLE CELL DISEASE. NEXT SLIDE 7266 04:38:51,240 --> 04:38:55,400 PLEASE. TO DO SO WE ACTUALLY 7267 04:38:55,400 --> 04:38:57,880 USED UNSUPERVISED LEARNING 7268 04:38:57,880 --> 04:38:59,040 METHODS WHICH HAVE THE ADVANTAGE 7269 04:38:59,040 --> 04:39:02,880 WE DON'T RELY ON THE (INAUDIBLE) 7270 04:39:02,880 --> 04:39:06,000 AND IDENTIFY PREVIOUSLY UNDECKED 7271 04:39:06,000 --> 04:39:09,400 PATTERNS OF GROUPINGS IN DATA, 7272 04:39:09,400 --> 04:39:12,040 FOR THIS PARTICULAR STUDY WE 7273 04:39:12,040 --> 04:39:14,800 USED A K MEANS CLUSTER ANALYSIS 7274 04:39:14,800 --> 04:39:17,000 APPROACH. THIS IS A PARTITIONING 7275 04:39:17,000 --> 04:39:21,200 ALGORITHM THAT PARTITIONS INTO A 7276 04:39:21,200 --> 04:39:23,000 SPECIFIED NUMBER OF 7277 04:39:23,000 --> 04:39:24,840 NON-OVERLAPPING CLUSTERS. BASED 7278 04:39:24,840 --> 04:39:25,840 ON STRUCTURAL RELATIONSHIPS 7279 04:39:25,840 --> 04:39:29,480 AMONG THE VARIABLES. AND THE 7280 04:39:29,480 --> 04:39:31,200 GOAL IS TO MINIMIZE WITHIN 7281 04:39:31,200 --> 04:39:33,760 CLUSTER VARIATION SO 7282 04:39:33,760 --> 04:39:37,480 OBSERVATIONS IN THE CLUSTER ARE 7283 04:39:37,480 --> 04:39:38,720 SIMILAR TO EACH OTHER AND 7284 04:39:38,720 --> 04:39:40,200 DISTINCT FROM OBSERVATIONS IN 7285 04:39:40,200 --> 04:39:42,720 OTHER CLUSTERS OR SUB GROUPS. 7286 04:39:42,720 --> 04:39:46,920 NEXT SLIDE PLEASE. WE CHOSE 7287 04:39:46,920 --> 04:39:50,440 SINCE WE SPECIFIED CLUSTERS WE 7288 04:39:50,440 --> 04:39:53,840 -- BASED ON MULTIPLE TESTS THAT 7289 04:39:53,840 --> 04:39:59,520 WE HAD DONE THAT INDICATED THAT 7290 04:39:59,520 --> 04:40:03,400 -- CLUSTERS. NEXT SLIDE PLEASE. 7291 04:40:03,400 --> 04:40:09,400 THIS IS A HIGH LEVEL RESULT OF 7292 04:40:09,400 --> 04:40:12,600 OUR CLUSTER ANALYSIS. YOU CAN 7293 04:40:12,600 --> 04:40:14,000 SEE THREE DISTINCT 7294 04:40:14,000 --> 04:40:16,840 NON-OVERLAPPING CLUSTERS, 7295 04:40:16,840 --> 04:40:26,280 CLUSTER 1 HAD A -- MEDIAN 7296 04:40:26,280 --> 04:40:30,320 (INAUDIBLE) WITH 20% OF PAIN 7297 04:40:30,320 --> 04:40:33,000 DAYS AND -- PHYSICAL FUNCTION 7298 04:40:33,000 --> 04:40:37,480 SCORE. IT WAS ALSO THE CLUSTER 7299 04:40:37,480 --> 04:40:42,920 WITHIN -- EACH PATIENT CLUSTER 7300 04:40:42,920 --> 04:40:51,480 TWO AND THREE HAD SIMILAR 7301 04:40:51,480 --> 04:40:58,400 (INAUDIBLE) BUT CLUSTER 2 HIGH 7302 04:40:58,400 --> 04:41:07,560 -- HAVE PATIENTS THE HIGHEST -- 7303 04:41:07,560 --> 04:41:10,720 (INAUDIBLE) AND THE LOWEST 7304 04:41:10,720 --> 04:41:14,400 PHYSICAL FUNCTION SCORE. CLUSTER 7305 04:41:14,400 --> 04:41:17,160 3 HAD HIGH INSTABILITY SO HIGH 7306 04:41:17,160 --> 04:41:22,880 FLUCTUATIONS AND LOWER CLUSTER 2 7307 04:41:22,880 --> 04:41:30,000 BUT WITH CLOSE TO DAILY PAIN, 7308 04:41:30,000 --> 04:41:31,800 OPIOID USE PHYSICAL FUNCTION 7309 04:41:31,800 --> 04:41:35,400 SCORE ENDOCRINE CLUSTERS 1 AND 7310 04:41:35,400 --> 04:41:39,760 3. NEXT SLIDE. SO OUR -- 7311 04:41:39,760 --> 04:41:41,000 INTERINDIVIDUAL VARIABILITY IS 7312 04:41:41,000 --> 04:41:44,240 ASSOCIATED WITH PATIENT OUTCOMES 7313 04:41:44,240 --> 04:41:47,000 AND CHARACTERISTICS IN SICKLE 7314 04:41:47,000 --> 04:41:49,560 CELL DISEASE AND PAIN INTENSITY 7315 04:41:49,560 --> 04:41:55,600 WITHIN INDIVIDUAL VARIABILITY 7316 04:41:55,600 --> 04:41:56,160 PHENOTYPES IN SICKLE CELL 7317 04:41:56,160 --> 04:42:06,960 DISEASE. WE THINK THE NEXT STEPS 7318 04:42:06,960 --> 04:42:11,840 HERE (INAUDIBLE) CO-OPS. THEN 7319 04:42:11,840 --> 04:42:14,520 FROM HERE ONCE WE HAVE A GOOD 7320 04:42:14,520 --> 04:42:20,760 WAIVER CLINICALLY PHENOTYPE TO 7321 04:42:20,760 --> 04:42:25,520 THEN USE EXPERIMENT WITH CORTICO 7322 04:42:25,520 --> 04:42:28,800 SENSORY TESTING SEE DEFENSES 7323 04:42:28,800 --> 04:42:30,200 EXPERIMENTAL AMONG THESE 7324 04:42:30,200 --> 04:42:34,160 CLINICAL RELATED SUB GROUPS. I 7325 04:42:34,160 --> 04:42:36,440 WANT TO THANK EVERYBODY FOR THIS 7326 04:42:36,440 --> 04:42:46,400 PAPER AS WELL AS THE -- THANK 7327 04:42:46,400 --> 04:42:46,680 YOU. 7328 04:42:46,680 --> 04:42:48,400 >> THANK YOU. WE WILL MOVE 7329 04:42:48,400 --> 04:42:50,440 STRAIGHT AHEAD TO PAT AND THEN 7330 04:42:50,440 --> 04:42:52,040 HAVE A GOOD AMOUNT OF TIME FOR 7331 04:42:52,040 --> 04:43:04,320 DISCUSSION. 7332 04:43:04,320 --> 04:43:13,280 >> I'M NOT SEEING ME OR MY 7333 04:43:13,280 --> 04:43:15,000 SLIDES I SEE START VIDEO. THERE 7334 04:43:15,000 --> 04:43:29,040 I AM. SO I THINK I HAD A SLIDE 7335 04:43:29,040 --> 04:43:31,840 THE LAST TIME SO HOPEFULLY WON'T 7336 04:43:31,840 --> 04:43:35,640 AUTOADVANCE ON ME AGAIN. WE CAN 7337 04:43:35,640 --> 04:43:38,400 ACTUALLY MOVE TO THE FIRST 7338 04:43:38,400 --> 04:43:40,640 SLIDE. AS IS OFTEN THE CASE I 7339 04:43:40,640 --> 04:43:42,560 THINK MY ROLE HERE IS TO BE THE 7340 04:43:42,560 --> 04:43:47,840 DUMB GUY IN THE ROOM. I -- MY 7341 04:43:47,840 --> 04:43:51,000 TALK IS GOING TO BE FAR MORE 7342 04:43:51,000 --> 04:43:57,400 DATA FREE THAN THOSE OF MY 7343 04:43:57,400 --> 04:43:59,200 COLLEAGUES HERE. AS PARTS OF MY 7344 04:43:59,200 --> 04:44:00,520 ROLE BEING THE DUMB GUY IN THE 7345 04:44:00,520 --> 04:44:02,400 ROOM I HAVE TO CONFESS VERY 7346 04:44:02,400 --> 04:44:05,320 OFTEN I DON'T KNOW WHAT I'M 7347 04:44:05,320 --> 04:44:07,000 DOING. I TEND TAKE CARE OF 7348 04:44:07,000 --> 04:44:09,600 PATIENTS WHO HAVE VERY COMPLEX 7349 04:44:09,600 --> 04:44:14,120 CHRONIC PAIN, PSYCHIATRIC 7350 04:44:14,120 --> 04:44:16,680 CO-MORBIDITIES WITH SEVERE 7351 04:44:16,680 --> 04:44:18,240 SICKLE CELL DISEASE. I DON'T 7352 04:44:18,240 --> 04:44:19,360 THINK WE KNOW ENOUGH ABOUT WHAT 7353 04:44:19,360 --> 04:44:21,640 TO DO ABOUT CHRONIC PAIN. I WILL 7354 04:44:21,640 --> 04:44:25,600 LOOK AT -- SHOCKING STATEMENT. 7355 04:44:25,600 --> 04:44:29,200 BUT WHAT I WOULD LIKE TO DO IS 7356 04:44:29,200 --> 04:44:31,400 SAY WHAT I THINK WE NEED OR WHAT 7357 04:44:31,400 --> 04:44:35,800 PEOPLE LIKE ME MIGHT NEED TO DO 7358 04:44:35,800 --> 04:44:38,240 BETTER NOW WHILE HOPEFULLY DR. 7359 04:44:38,240 --> 04:44:41,520 BRANDOW AND DR. STUCKY AND 7360 04:44:41,520 --> 04:44:43,040 BAKSHI FIGURE WHAT WE CAN DO 7361 04:44:43,040 --> 04:44:44,600 WITH THE FUTURE. SO I WILL START 7362 04:44:44,600 --> 04:44:49,160 OUT TALKING ABOUT THE ASH 7363 04:44:49,160 --> 04:44:50,440 GUIDELINES. YOU CAN SEE THIS IS 7364 04:44:50,440 --> 04:44:51,880 TALKED ABOUT A FEW TIMES 7365 04:44:51,880 --> 04:44:53,320 ALREADY, I DON'T WANT TO BORE 7366 04:44:53,320 --> 04:44:54,840 YOU BUT THE POINT AND DR. 7367 04:44:54,840 --> 04:44:57,000 BRANDOW IS LEADER OF OUR PIRATE 7368 04:44:57,000 --> 04:45:01,240 DAN SO YOU CAN LOOK UP TO 7369 04:45:01,240 --> 04:45:03,000 MANUSCRIPT FROM A COUPLE OF 7370 04:45:03,000 --> 04:45:05,240 YEARS AGO TO SEE MORE DETAILS 7371 04:45:05,240 --> 04:45:07,880 AND THIS IS MY TAKE ON THINGS SO 7372 04:45:07,880 --> 04:45:12,440 MANY THINGS LEFT OUT. I ALSO 7373 04:45:12,440 --> 04:45:14,560 WILL HAVE A FEW THOUGHTS ABOUT 7374 04:45:14,560 --> 04:45:17,520 WHERE THEY FALL SHORT. THOSE 7375 04:45:17,520 --> 04:45:18,800 CRITIQUES HAVE NOTHING TO DO 7376 04:45:18,800 --> 04:45:21,080 WHATSOEVER WITH THE PEOPLE WHO 7377 04:45:21,080 --> 04:45:23,000 DEVELOP THEM, WHO WERE SOME OF 7378 04:45:23,000 --> 04:45:24,760 THE FINEST PEOPLE HAD THE HONOR 7379 04:45:24,760 --> 04:45:26,960 OF SITTING IN THE ROOM. IN 7380 04:45:26,960 --> 04:45:30,520 ESSENCE, WE ARE THE GUIDELINES 7381 04:45:30,520 --> 04:45:33,600 STOOD WAS WITH YEWS THE AAPT 7382 04:45:33,600 --> 04:45:34,720 CRITERIA, DR. SMITH MENTIONED 7383 04:45:34,720 --> 04:45:38,480 AND LOOK AT THE SPECIFIC CAUSES 7384 04:45:38,480 --> 04:45:40,920 OF AVASCULAR NECROSIS AND LEG 7385 04:45:40,920 --> 04:45:44,840 ULCERS AS WELL AS UNSPECIFIED 7386 04:45:44,840 --> 04:45:46,480 SICKLE CELL DISEASE PAIN. 7387 04:45:46,480 --> 04:45:47,800 BECAUSE THERE WAS SO LITTLE 7388 04:45:47,800 --> 04:45:48,840 DIRECT EVIDENCE TO PULL ON FOR 7389 04:45:48,840 --> 04:45:49,960 ANY OF THESE THINGS WE HAD TO 7390 04:45:49,960 --> 04:45:52,040 LOOK FOR ANALOGOUS CONDITIONS 7391 04:45:52,040 --> 04:45:54,160 AND AVASCULAR NECROSIS WE LOOK 7392 04:45:54,160 --> 04:45:56,480 AT OSTEOARTHRITIS AND FOR SICKLE 7393 04:45:56,480 --> 04:45:57,800 CELL DISEASE ITSELF WITH NO 7394 04:45:57,800 --> 04:45:59,800 OTHER ASSOCIATED OR IDENTIFIABLE 7395 04:45:59,800 --> 04:46:04,440 ASSOCIATED CAUSE WE LOOK FROM 7396 04:46:04,440 --> 04:46:06,560 FIBROMYALGIA, MOST INCOMPLETE 7397 04:46:06,560 --> 04:46:10,760 ANALOGIES OBVIOUSLY. BASED ON 7398 04:46:10,760 --> 04:46:13,960 THOSE ANALOGIES WE SUGGESTED 7399 04:46:13,960 --> 04:46:19,240 THAT THE INTERVENTIONS THAT DR. 7400 04:46:19,240 --> 04:46:25,320 -- MENTIONED EARLIER, SNRE 7401 04:46:25,320 --> 04:46:32,560 TRICYCLIC ANTI-DEPRESS SENTS AND 7402 04:46:32,560 --> 04:46:33,160 GABBAPENTINOIDS WITH OTHER 7403 04:46:33,160 --> 04:46:35,560 GENERAL MEDICINES. WE PUT IN A 7404 04:46:35,560 --> 04:46:37,520 JUSTIFIED THOUGHT THAT N SAIDS 7405 04:46:37,520 --> 04:46:38,880 MIGHT RECUR PARTICULAR THOUGHT 7406 04:46:38,880 --> 04:46:40,400 IN FOLKS WITH SICKLE CELL 7407 04:46:40,400 --> 04:46:41,920 DISEASE AND CHRONIC USE BECAUSE 7408 04:46:41,920 --> 04:46:44,160 OF RISK OF RENAL INJURY, THE 7409 04:46:44,160 --> 04:46:45,920 RISK OF ANTI-COAGULATION, 7410 04:46:45,920 --> 04:46:48,440 BLEEDING CLOTTING AND SO ON. SO 7411 04:46:48,440 --> 04:46:50,000 WHILE I THINK THEY ARE 7412 04:46:50,000 --> 04:46:52,640 FREQUENTLY USED, WE ALSO DON'T 7413 04:46:52,640 --> 04:46:53,640 KNOW THEIR RISK VERY WELL AND 7414 04:46:53,640 --> 04:46:54,600 THAT IS A BIG GAP THAT WE HAVE 7415 04:46:54,600 --> 04:47:02,080 GOT. AS NON-PHARMACOLOGIC 7416 04:47:02,080 --> 04:47:02,720 INTERVENTIONS, THEY WERE MANY OF 7417 04:47:02,720 --> 04:47:03,960 THE THINGS ALSO COVERED MANY THE 7418 04:47:03,960 --> 04:47:05,720 MORNING SESSION. WE HAD THE BEST 7419 04:47:05,720 --> 04:47:07,960 EVIDENCE FOR COGNITIVE 7420 04:47:07,960 --> 04:47:08,920 BEHAVIORAL PAIN MANAGEMENT 7421 04:47:08,920 --> 04:47:13,200 STRATEGIES AND THOSE THINGS THAT 7422 04:47:13,200 --> 04:47:16,280 DR. JOHN DISCUSSED THIS MORNING. 7423 04:47:16,280 --> 04:47:18,320 WE DIVIDED OTHER 7424 04:47:18,320 --> 04:47:19,880 NON-PHARMACOLOGIC TREATMENTS, 7425 04:47:19,880 --> 04:47:21,000 AND THOSE THINGS SOMEONE HAS TO 7426 04:47:21,000 --> 04:47:23,760 DO FOR YOU, ACUPUNCTURE AND 7427 04:47:23,760 --> 04:47:25,600 MASSAGE THERAPY AND PEOPLE 7428 04:47:25,600 --> 04:47:26,960 SELF-MANAGE PHYSICAL ACTIVITY OR 7429 04:47:26,960 --> 04:47:32,120 EXERCISE OR THINGS LIKE YOGA OR 7430 04:47:32,120 --> 04:47:34,560 COMBINED MOVEMENT PROGRAMS. WE 7431 04:47:34,560 --> 04:47:36,080 HAVE EVIDENCE FOR MASSAGE 7432 04:47:36,080 --> 04:47:38,040 THERAPY AND ACUPUNCTURE WHICH 7433 04:47:38,040 --> 04:47:39,800 WAS COVERED THIS MORNING AND 7434 04:47:39,800 --> 04:47:42,320 THOSE WERE SUGGEST WITH U WE 7435 04:47:42,320 --> 04:47:43,200 DIDN'T HAVE EVIDENCE TO SAY 7436 04:47:43,200 --> 04:47:45,880 ANYTHING ABOUT THE OTHER 7437 04:47:45,880 --> 04:47:50,160 INTERVENTIONS. MENTION SLIDE 7438 04:47:50,160 --> 04:47:51,800 PLEASE. SORRY PRESSING BUTTONS 7439 04:47:51,800 --> 04:47:55,440 ON MY OWN. AS TO OPIOIDS, WHAT 7440 04:47:55,440 --> 04:47:57,040 WE SAID WAS RELATIVELY SIMILAR 7441 04:47:57,040 --> 04:47:58,960 TO WHAT OTHER GUIDELINES HAVE 7442 04:47:58,960 --> 04:48:01,200 SAID WHICH IS TO SAY THAT PEOPLE 7443 04:48:01,200 --> 04:48:03,760 ARE EARLY IN THE COURSE CHRONIC 7444 04:48:03,760 --> 04:48:05,320 PAIN JUST DEVELOPING IT WE 7445 04:48:05,320 --> 04:48:07,320 SUGGESTED AGAIN STARTING CHRONIC 7446 04:48:07,320 --> 04:48:09,080 OPIOID THERAPY AND LESS PAIN 7447 04:48:09,080 --> 04:48:10,320 REFRACTORY TO OTHER THINGS. AND 7448 04:48:10,320 --> 04:48:13,680 IF PEOPLE ARE ALREADY ON CHRONIC 7449 04:48:13,680 --> 04:48:16,000 OPIOID THERAPY FOR CHRONIC PAIN 7450 04:48:16,000 --> 04:48:17,800 THEY ARE DOING WELL AND 7451 04:48:17,800 --> 04:48:18,800 PERCEIVED BENEFIT IN ESSENCE 7452 04:48:18,800 --> 04:48:20,560 THERE IS ONGOING DISCUSSION 7453 04:48:20,560 --> 04:48:24,280 ABOUT WHETHER THE RISKS ARE 7454 04:48:24,280 --> 04:48:25,800 WORTH THE CONTINUED BENEFIT AND 7455 04:48:25,800 --> 04:48:27,440 WHAT CAN BE DONE TO MODERATE 7456 04:48:27,440 --> 04:48:28,680 THEM WHILE MAINTAINING THAT 7457 04:48:28,680 --> 04:48:30,120 BENEFIT. BUT IF PEOPLE ARE DOING 7458 04:48:30,120 --> 04:48:33,360 POORLY OR AT RISK OF DOING 7459 04:48:33,360 --> 04:48:36,320 POORLY, THEN SHOULD TALK ABOUT 7460 04:48:36,320 --> 04:48:40,040 STOPPING IT THAT BEING DONE 7461 04:48:40,040 --> 04:48:43,800 CAREFULLY. NEXT SLIDE PLEASE. 7462 04:48:43,800 --> 04:48:47,200 THESE ARE SMALL SAMPLE OF OTHER 7463 04:48:47,200 --> 04:48:48,560 GUIDANCE THAT WERE SUGGESTED. 7464 04:48:48,560 --> 04:48:50,000 FIRST THAT I THINK IS ALWAYS 7465 04:48:50,000 --> 04:48:51,640 IMPORTANT TO SAY IS YOU CAN'T 7466 04:48:51,640 --> 04:48:52,560 TREAT SICKLE CELL DISEASE JUST 7467 04:48:52,560 --> 04:48:54,640 BY TREATING CHRONIC PAIN, THINK 7468 04:48:54,640 --> 04:49:00,640 IT IS IMPORTANT. SO OPTIMIZING 7469 04:49:00,640 --> 04:49:03,520 SICKLE CELL DISEASE MODIFYING 7470 04:49:03,520 --> 04:49:06,200 SICKLE CELL DISEASE PRIORITY AND 7471 04:49:06,200 --> 04:49:09,960 SHOULD BE TREAT WITH A PAIN 7472 04:49:09,960 --> 04:49:11,240 STRATEGY MORE POINTS MADE IN THE 7473 04:49:11,240 --> 04:49:12,160 MORNING. WHEN POSSIBLE 7474 04:49:12,160 --> 04:49:13,200 COLLABORATE WITH A PAIN 7475 04:49:13,200 --> 04:49:14,640 SPECIALIST AND SCREEN FOR 7476 04:49:14,640 --> 04:49:16,920 DEPRESSION AND TREAT IT. WITH 7477 04:49:16,920 --> 04:49:20,680 RESPECT TO OPIOID, PROBABLY 7478 04:49:20,680 --> 04:49:22,200 WEANING PEOPLE OFF OPIOID OR 7479 04:49:22,200 --> 04:49:24,240 DOWN OPIOID WITH SICKLE CELL 7480 04:49:24,240 --> 04:49:25,680 DISEASE MAYBE HIGHER RISK 7481 04:49:25,680 --> 04:49:27,680 PROPOSITION THAN OTHER 7482 04:49:27,680 --> 04:49:29,560 POPULATIONS BECAUSE OF THE ROLE 7483 04:49:29,560 --> 04:49:31,560 OF STRESS. IN ACUTE PAIN OR 7484 04:49:31,560 --> 04:49:34,960 DISEASE EXACERBATIONS. ALSO IF 7485 04:49:34,960 --> 04:49:36,280 OPIOID HAVEN'T WORKED FOR 7486 04:49:36,280 --> 04:49:38,080 CHRONIC PAIN FOR SOMEONE THAT 7487 04:49:38,080 --> 04:49:39,600 DOESN'T WANT TO WORK WITH ACUTE 7488 04:49:39,600 --> 04:49:42,720 PAIN SO ONE DOESN'T OBVIATE THE 7489 04:49:42,720 --> 04:49:43,600 USE FOR THE OTHER. NEXT SLIDE 7490 04:49:43,600 --> 04:49:48,320 PLEASE. HERE IS WHERE I THINK 7491 04:49:48,320 --> 04:49:52,280 THE WARTS WERE. ALL THESE THINGS 7492 04:49:52,280 --> 04:49:54,200 WERE BASED ON LOW CERTAINTY 7493 04:49:54,200 --> 04:49:55,400 EVIDENCE MOSTLY INDIRECT 7494 04:49:55,400 --> 04:49:56,520 EVIDENCE THOUGH WE HAD A LITTLE 7495 04:49:56,520 --> 04:49:57,640 BIT OF DIRECT EVIDENCE FOR SOME 7496 04:49:57,640 --> 04:50:00,880 OF THE COGNITIVE INTERVENTIONS. 7497 04:50:00,880 --> 04:50:02,320 BECAUSE WE HAD INDIRECT EVIDENCE 7498 04:50:02,320 --> 04:50:05,720 AND HAD TO PICK A PARTICULAR 7499 04:50:05,720 --> 04:50:08,400 ANALOGOUS CONDITION THERE ARE 7500 04:50:08,400 --> 04:50:11,440 LIMITS TO WHAT YOU CAN SAY FROM 7501 04:50:11,440 --> 04:50:14,120 THIS. PRAGMATICALLY SPEAKING, I 7502 04:50:14,120 --> 04:50:15,600 THINK IT IS LESS A PROBLEM THAN 7503 04:50:15,600 --> 04:50:18,400 IT MIGHT OTHERWISE BE. BECAUSE 7504 04:50:18,400 --> 04:50:19,720 OVERALL THESE RECOMMENDATIONS 7505 04:50:19,720 --> 04:50:20,920 KIND OF HARMONIZE WHAT WE KNOW 7506 04:50:20,920 --> 04:50:21,840 WORKS FOR CHRONIC PAIN IN 7507 04:50:21,840 --> 04:50:24,560 GENERAL. THE MEDICINES WE 7508 04:50:24,560 --> 04:50:27,120 SUGGESTED AS WELL AS THE OTHER 7509 04:50:27,120 --> 04:50:28,120 INTERVENTIONS WE SUGGEST ARE 7510 04:50:28,120 --> 04:50:30,600 THINGS BROADLY SPEAKING HAD BEEN 7511 04:50:30,600 --> 04:50:32,520 KNOWN TO WORK FOR CHRONIC PAIN 7512 04:50:32,520 --> 04:50:35,240 FOR QUITE A LONG TIME TIME. BIGGER 7513 04:50:35,240 --> 04:50:36,480 PICTURE QUESTIONS WE COULDN'T 7514 04:50:36,480 --> 04:50:39,240 ADDRESS WITH GUIDELINES 7515 04:50:39,240 --> 04:50:40,360 PARTICULARLY THE ISSUE OF 7516 04:50:40,360 --> 04:50:41,600 PREVENTION, WHAT CAN WE DO TO 7517 04:50:41,600 --> 04:50:43,920 KEEP PEOPLE FROM DEVELOPING 7518 04:50:43,920 --> 04:50:46,760 CHRONIC PAIN. NEXT SLIDE PLEASE 7519 04:50:46,760 --> 04:50:50,280 I THINK WE HAVE A BIGGER PROBLEM 7520 04:50:50,280 --> 04:50:54,000 THAN SIMPLY GUIDELINES BECAUSE I 7521 04:50:54,000 --> 04:50:57,160 THINK ONE OF THE -- WHERE I FIND 7522 04:50:57,160 --> 04:50:58,960 MYSELF STUCK IS I THINK WE HAVE 7523 04:50:58,960 --> 04:51:02,280 A SET OF TOOLS THAT WE HAVE GOOD 7524 04:51:02,280 --> 04:51:03,200 REASON TO BELIEVE WORK WHICH IS 7525 04:51:03,200 --> 04:51:05,720 TO SAY THEY SEPARATE FROM 7526 04:51:05,720 --> 04:51:07,400 PLACEBO, OR FOR COMPARATORS FOR 7527 04:51:07,400 --> 04:51:08,600 MULTIPLE OTHER PAINFUL 7528 04:51:08,600 --> 04:51:10,880 CONDITIONS OR EVEN SOMETIMES 7529 04:51:10,880 --> 04:51:12,880 SOME DATA IN SICKLE CELL DISEASE 7530 04:51:12,880 --> 04:51:15,400 BUT WHAT I HAVE TO FIGURE OUT 7531 04:51:15,400 --> 04:51:16,760 WHEN SOMEONE SITS DOWN IN FRONT 7532 04:51:16,760 --> 04:51:20,600 OF ME IS WHAT DO WE TRY FIRST 7533 04:51:20,600 --> 04:51:22,800 FOR HOW LONG AT WHAT DOSE OR 7534 04:51:22,800 --> 04:51:24,800 INTENSITY HOW DO I KNOW IF IT IS 7535 04:51:24,800 --> 04:51:26,600 WORKING OR NOT OR IF THERE IS A 7536 04:51:26,600 --> 04:51:27,800 PARTIAL RESPONSE DEPENDING ON 7537 04:51:27,800 --> 04:51:29,520 THE CLINICAL OUTCOME, WHAT IS 7538 04:51:29,520 --> 04:51:32,480 THE NEXT STEP? THAT IS CLINICAL 7539 04:51:32,480 --> 04:51:37,000 STRATEGY. OUR GUIDELINES AND 7540 04:51:37,000 --> 04:51:39,440 EVIDENCE BASE IS HEAVY ON 7541 04:51:39,440 --> 04:51:41,760 TACTICS AND TOOLS AND RELATIVELY 7542 04:51:41,760 --> 04:51:45,360 SHORT ON CLINICAL STRATEGY. AND 7543 04:51:45,360 --> 04:51:46,880 THEN ON THE SAME NOTE FOR 7544 04:51:46,880 --> 04:51:49,200 OPIOID, WHAT WE DID SAY AS FAR 7545 04:51:49,200 --> 04:51:52,560 AS IT WENT EACH OF THOSE TERMS I 7546 04:51:52,560 --> 04:51:57,400 WILL SHOW MY COMPULSIVE SIDE, I 7547 04:51:57,400 --> 04:51:58,760 THINK IS REALLY QUITE VAGUE. 7548 04:51:58,760 --> 04:52:02,280 WHAT IS MULTIPLE OTHER TREATMENT 7549 04:52:02,280 --> 04:52:04,720 MODALITIES MEAN SPECIFICALLY? 7550 04:52:04,720 --> 04:52:06,240 WHICH AND FOR HOW LONG? DO WE 7551 04:52:06,240 --> 04:52:08,120 KNOW WHAT FAILURE MEANS? THIS IS 7552 04:52:08,120 --> 04:52:09,480 ANOTHER DIFFICULTY THAT WE HAVE 7553 04:52:09,480 --> 04:52:13,400 IN CHRONIC PAIN IN GENERAL MANY 7554 04:52:13,400 --> 04:52:14,800 OUTCOMES OF CLINICAL TRIAL ARE 7555 04:52:14,800 --> 04:52:16,720 THINGS LIKE CHANGE FROM BASELINE 7556 04:52:16,720 --> 04:52:20,040 AT SIX WEEKS. THIS CAN BE FINE 7557 04:52:20,040 --> 04:52:21,200 AT SIX WEEKS BUT IF YOU HAVE 7558 04:52:21,200 --> 04:52:22,680 BOTH CHRONICALLY PAINFUL 7559 04:52:22,680 --> 04:52:25,000 CONDITION JUST TO SAY LIFE LONG 7560 04:52:25,000 --> 04:52:26,640 PLUS A SOLID CHANCE THAT IT IS 7561 04:52:26,640 --> 04:52:28,960 PROGRESSIVE WHICH IS TO SAY 7562 04:52:28,960 --> 04:52:30,120 DISEASE COURSE ITSELF MIGHT 7563 04:52:30,120 --> 04:52:31,200 WORSEN, HOW DO YOU TRANSLATE 7564 04:52:31,200 --> 04:52:33,800 THAT INTO A DEFINITION OF 7565 04:52:33,800 --> 04:52:35,240 SUCCESS OR FAILURE FIVE YEARS 7566 04:52:35,240 --> 04:52:37,880 LATER? SO MAYBE SOMEONE GETS 7567 04:52:37,880 --> 04:52:39,640 BETTER BY SAYING ONE OR TWO 7568 04:52:39,640 --> 04:52:41,000 POINTS ON THE NUMERIC RATING 7569 04:52:41,000 --> 04:52:43,360 SCALE IN SIX WEEKS BUT IF PAIN 7570 04:52:43,360 --> 04:52:46,320 IS 6 OUT OF 10 OR 7 OUT OF 10 ON 7571 04:52:46,320 --> 04:52:48,200 AVERAGE THREE YEARS, IS IT STILL 7572 04:52:48,200 --> 04:52:50,120 WORKING OR IS IT NOT WORKING AND 7573 04:52:50,120 --> 04:52:52,360 WHAT SHOULD WE DO ABOUT IT? ALSO 7574 04:52:52,360 --> 04:52:55,720 I HAVE TO GO ON RECORD BEING A 7575 04:52:55,720 --> 04:52:57,920 BIT OF A SKEPTIC ON THE PROBLEM 7576 04:52:57,920 --> 04:53:01,640 OF USING FUNCTION AS A OUTCOME. 7577 04:53:01,640 --> 04:53:07,200 ON THE ONE HAND I THINK IT IS 7578 04:53:07,200 --> 04:53:08,280 HIGHLY CLINICALLY RELEVANT. 7579 04:53:08,280 --> 04:53:10,240 HOWEVER I THINK TRYING TO 7580 04:53:10,240 --> 04:53:12,720 MEASURE IT IN A WAY IS BOTH 7581 04:53:12,720 --> 04:53:15,800 GENERAL AND VALID IS RICKY 7582 04:53:15,800 --> 04:53:16,680 BECAUSE BECAUSE SO MUCH A 7583 04:53:16,680 --> 04:53:19,400 FUNCTION IS ROLE DEPENDENT, WHAT 7584 04:53:19,400 --> 04:53:20,760 FUNCTION MEANS FOR A PARENT IS 7585 04:53:20,760 --> 04:53:22,080 DIFFERENT THAN WHAT IT MEANS 7586 04:53:22,080 --> 04:53:25,680 FROM A NURSE OR A BRICKLAYER. SO 7587 04:53:25,680 --> 04:53:28,800 I THINK THAT ITSELF ADDS LEVEL 7588 04:53:28,800 --> 04:53:31,320 OF VARIABILITY VERY TRICKY TO 7589 04:53:31,320 --> 04:53:33,000 MANAGEMENT WITH RESPECT TO 7590 04:53:33,000 --> 04:53:35,200 BALANCING RISK AND BENEFIT ONE 7591 04:53:35,200 --> 04:53:36,600 DIFFICULTIES IS THE RISKS AND 7592 04:53:36,600 --> 04:53:39,400 THE BENEFITS ARE QUALITATIVELY 7593 04:53:39,400 --> 04:53:41,840 DIFFERENT TYPES. SO THE BENEFITS 7594 04:53:41,840 --> 04:53:43,200 ARE OFTEN RELATIVELY STRAIGHT 7595 04:53:43,200 --> 04:53:44,600 FORWARD WHICH IS DOES IT IMPROVE 7596 04:53:44,600 --> 04:53:46,080 PAIN. OR AT LEAST PAIN 7597 04:53:46,080 --> 04:53:48,720 INTENSITY. WHEREAS THE RISKS 7598 04:53:48,720 --> 04:53:51,160 CAN VARY FROM STUFF THAT IS 7599 04:53:51,160 --> 04:53:51,960 REASONABLY IMMEDIATE AND 7600 04:53:51,960 --> 04:53:56,040 RELATIVELY EASY TO MEASURE LIKE 7601 04:53:56,040 --> 04:53:58,880 CONSTIPATION ALL THE WAY TO 7602 04:53:58,880 --> 04:54:02,280 RELATIVELY -- VERY LOW 7603 04:54:02,280 --> 04:54:03,400 PROBABILITY OF CATASTROPHIC 7604 04:54:03,400 --> 04:54:04,640 OUTCOME HAPPENING WITHIN THE 7605 04:54:04,640 --> 04:54:07,080 NEXT FIVE YEARS, BUT THAT 7606 04:54:07,080 --> 04:54:09,080 OUTCOME BEING CATASTROPHIC. SO 7607 04:54:09,080 --> 04:54:10,960 HOW IT IS SORT OF LIKE TRYING TO 7608 04:54:10,960 --> 04:54:13,800 COMPARE APPLES TO ROCKS. SO I 7609 04:54:13,800 --> 04:54:15,120 THINK BALANCING THOSE ON THE 7610 04:54:15,120 --> 04:54:17,880 SAME SCALE IS ALSO QUITE 7611 04:54:17,880 --> 04:54:23,640 DIFFICULT. NEXT SLIDE PLEASE. 7612 04:54:23,640 --> 04:54:25,200 HERE IS WHERE I SEE CLINICAL 7613 04:54:25,200 --> 04:54:26,920 STRATEGY AT RIGHT NOW. AND 7614 04:54:26,920 --> 04:54:33,040 GRANTED THIS IS A BIT OF A 7615 04:54:33,040 --> 04:54:34,160 CARICATURE. THERE IS TRUTH TO 7616 04:54:34,160 --> 04:54:35,680 IT. WE HAVE A BUCKET OF THINGS 7617 04:54:35,680 --> 04:54:40,800 WE ARE PRETTY SURE WORK. AND 7618 04:54:40,800 --> 04:54:42,280 ANOTHER BUCKET OF THINGS REASON 7619 04:54:42,280 --> 04:54:43,400 TO BELIEVE WORK BUT NOT 7620 04:54:43,400 --> 04:54:45,000 SUPPORTED QUITE AS MUCH BY 7621 04:54:45,000 --> 04:54:46,880 EVIDENCE AS WE WOULD LIKE. WE 7622 04:54:46,880 --> 04:54:48,520 MAINLY MINE FROM THE THINGS WE 7623 04:54:48,520 --> 04:54:55,320 ARE PRETTY SURE WORK. HOWEVER, 7624 04:54:55,320 --> 04:54:59,520 WE DON'T HAVE GREAT GUIDANCE OF 7625 04:54:59,520 --> 04:55:01,000 WHICH ONE WE SHOULD TRY FIRST OR 7626 04:55:01,000 --> 04:55:02,840 IN WHAT COMBINATIONS THAT GIVE 7627 04:55:02,840 --> 04:55:07,200 US THE BEST SHOT. WE ARE LEFT TO 7628 04:55:07,200 --> 04:55:08,720 DEVELOP IDIOSYNCRATIC IDEAS 7629 04:55:08,720 --> 04:55:10,160 ABOUT WHAT TO DO, HOW MANY TIMES 7630 04:55:10,160 --> 04:55:11,800 TO GO THROUGH THE CYCLE WHEN TO 7631 04:55:11,800 --> 04:55:14,720 DECLARE FAILURE. AT WHICH POINT 7632 04:55:14,720 --> 04:55:17,200 WE OFTEN WIND UP GOING TO 7633 04:55:17,200 --> 04:55:21,320 OPIOID. WITH OPIOID ROTATION CAN 7634 04:55:21,320 --> 04:55:24,520 WORK, DOSE ACCELERATIONS CAN 7635 04:55:24,520 --> 04:55:25,800 WORK, DOSE ACCELERATIONS 7636 04:55:25,800 --> 04:55:27,800 INCREASE RISK AND WE THEN HAVE 7637 04:55:27,800 --> 04:55:28,840 THIS QUESTION OF HOW MANY TIMES 7638 04:55:28,840 --> 04:55:31,160 WE GO THROUGH THOSE CYCLES, 7639 04:55:31,160 --> 04:55:33,600 UNTIL WE CALL IT A DAY. WHEN 7640 04:55:33,600 --> 04:55:36,480 BEDO CALL IT DAY, WHAT DO WE DO? 7641 04:55:36,480 --> 04:55:37,800 WE OFTEN HAVE CHRONIC OPIOID 7642 04:55:37,800 --> 04:55:39,080 THERAPY SOMETIMES AT HIGH DOSES 7643 04:55:39,080 --> 04:55:41,960 AND WE DON'T KNOW WHETHER TO 7644 04:55:41,960 --> 04:55:44,600 DECLARE FAILURE OR LEAVE WELL 7645 04:55:44,600 --> 04:55:46,720 ENOUGH ALONE OR PUT SOMEONE 7646 04:55:46,720 --> 04:55:50,760 THROUGH THE TROUBLE OF COMING 7647 04:55:50,760 --> 04:55:54,960 OFF OPIOID WHICH IS A TASK. SO 7648 04:55:54,960 --> 04:55:55,880 THE STRATEGIC PROBLEMS THAT I 7649 04:55:55,880 --> 04:55:57,960 WOULD LIKE US TO TRY TO SOLVE IS 7650 04:55:57,960 --> 04:56:00,840 FIRST OF ALL WHO IS IT THAT WE 7651 04:56:00,840 --> 04:56:03,200 SHOULD DO SOMETHING FOR AT ALL? 7652 04:56:03,200 --> 04:56:04,560 I KNOW I HAVE MOSTLY TALKED 7653 04:56:04,560 --> 04:56:06,880 ABOUT MEDICINE SO FAR, BUT WHEN 7654 04:56:06,880 --> 04:56:08,800 SHOULD WE OFFER COGNITIVE 7655 04:56:08,800 --> 04:56:13,160 THERAPIES SO FORTH FORTH. THERE IS 7656 04:56:13,160 --> 04:56:15,400 ALWAYS A LEVEL OF PAIN INTENSITY 7657 04:56:15,400 --> 04:56:18,760 OR OTHER BAD THING THAT IS LOW 7658 04:56:18,760 --> 04:56:20,720 ENOUGH THAT EXPOSING SOMEONE TO 7659 04:56:20,720 --> 04:56:22,280 ANY RISK IS NOT PROBABLY WORTH 7660 04:56:22,280 --> 04:56:24,240 ANY CHANCE OF BENEFIT BECAUSE 7661 04:56:24,240 --> 04:56:26,040 THEY ARE NOT ENOUGH TROUBLE TO 7662 04:56:26,040 --> 04:56:27,640 POSE BENEFIT BUT WE NEED TO HAVE 7663 04:56:27,640 --> 04:56:29,600 SOME IDEA WHAT THAT THRESHOLD 7664 04:56:29,600 --> 04:56:31,800 IS. THEN WHAT IS THE FIRST THING 7665 04:56:31,800 --> 04:56:33,400 WE SHOULD TRY? PROBABLY THIS IS 7666 04:56:33,400 --> 04:56:34,600 NOT NECESSARILY ONE THING, IT 7667 04:56:34,600 --> 04:56:37,360 MIGHT BE A SET OF TWO OR LEE 7668 04:56:37,360 --> 04:56:40,840 THINGS POSSIBLY COMBINATION. BUT 7669 04:56:40,840 --> 04:56:42,520 IT WOULD BE NICE TO HAVE SOME 7670 04:56:42,520 --> 04:56:44,000 AGREEMENT ON THIS SO WE CAN TEST 7671 04:56:44,000 --> 04:56:45,320 IT AND PROVE OURSELVES WRONG AND 7672 04:56:45,320 --> 04:56:46,640 DECIDE MAYBE IT SHOULDN'T BE 7673 04:56:46,640 --> 04:56:48,120 THESE THREE THINGS, ONLY THESE 7674 04:56:48,120 --> 04:56:50,360 TWO OR MAYBE THIS ONE. THIS IS A 7675 04:56:50,360 --> 04:56:52,440 THING THAT I THINK IS VITALLY 7676 04:56:52,440 --> 04:56:53,880 IMPORTANT AND I IMPORT THIS FROM 7677 04:56:53,880 --> 04:56:56,520 MY EXPERIENCE IN PSYCHIATRY, 7678 04:56:56,520 --> 04:56:58,880 REALLY, HOW DO YOU TELL IF IT IS 7679 04:56:58,880 --> 04:57:01,320 WORKING? IN PSYCHIATRY TALKING 7680 04:57:01,320 --> 04:57:02,320 TREATMENT FOR DEPRESSION, I 7681 04:57:02,320 --> 04:57:04,760 THINK WE ARE PRETTY GOOD AT 7682 04:57:04,760 --> 04:57:06,800 THIS. WE HAVE LEVELS OF OUTCOMES 7683 04:57:06,800 --> 04:57:08,720 FOR DEPRESSION. THERE IS 7684 04:57:08,720 --> 04:57:11,160 REMISSION. WHICH IS SUCCESS. 7685 04:57:11,160 --> 04:57:12,800 THERE IS RESPONSE WHICH IS 7686 04:57:12,800 --> 04:57:14,200 BASICALLY PARTIAL SUCCESS BUT 7687 04:57:14,200 --> 04:57:16,120 PEOPLE ARE STILL HIGH RISK OF 7688 04:57:16,120 --> 04:57:17,360 RELAPSE IF YOU ONLY LEAVE IT 7689 04:57:17,360 --> 04:57:18,400 THERE SO YOU HAVE TO KEEP IT 7690 04:57:18,400 --> 04:57:23,000 GOING. AND THERE IS NEITHER OF 7691 04:57:23,000 --> 04:57:25,320 THOSE. THEN THE BASED ON THOSE 7692 04:57:25,320 --> 04:57:27,280 DIFFERENT LEVELS OF RESPONSE, WE 7693 04:57:27,280 --> 04:57:29,080 HAVE REASONABLE EVIDENCE BASE 7694 04:57:29,080 --> 04:57:30,640 BEHIND WHAT TO DO. SO FOR 7695 04:57:30,640 --> 04:57:33,520 EXAMPLE, IF SOMEONE HAS 7696 04:57:33,520 --> 04:57:35,720 RESPONDED NOT OFTEN AUGMENT THE 7697 04:57:35,720 --> 04:57:38,240 THERAPY, IF THE PERSON HAS NOT 7698 04:57:38,240 --> 04:57:40,240 RESPONDED AT ALL WITHIN SIX 7699 04:57:40,240 --> 04:57:41,800 WEEKS MAXIMALLY TOLERATED DOSE 7700 04:57:41,800 --> 04:57:44,800 YOU DECLARE FAILURE AN SWITCH. 7701 04:57:44,800 --> 04:57:50,120 SO NEXT SLIDE PLEASE. HERE IS 7702 04:57:50,120 --> 04:57:52,560 WHAT I WOULD DO LOVE FOR US TO 7703 04:57:52,560 --> 04:57:55,200 HAVE. DEARLY LOVE FOR US TO HAVE 7704 04:57:55,200 --> 04:57:57,800 AN IDEA OF FOR WHOM WE SHOULD 7705 04:57:57,800 --> 04:58:00,080 START OFFERING THERAPY. AND MENU 7706 04:58:00,080 --> 04:58:02,800 OF THE FIRST FEW THINGS TO TRY. 7707 04:58:02,800 --> 04:58:04,680 WITH AN IDEA OF WHAT CONSTITUTES 7708 04:58:04,680 --> 04:58:07,400 AN ADEQUATE TRIAL FOR EACH ONE 7709 04:58:07,400 --> 04:58:11,840 OF THOSE THINGS. SOME IDEA ABOUT 7710 04:58:11,840 --> 04:58:14,080 WHAT THE IMPORTANT RESPONSES AND 7711 04:58:14,080 --> 04:58:15,760 LEVELS OF RESPONSES THAT TRIGGER 7712 04:58:15,760 --> 04:58:17,760 CLINICAL DECISIONS. SO FOR 7713 04:58:17,760 --> 04:58:21,280 EXAMPLE, IF WE ARE DOING 7714 04:58:21,280 --> 04:58:23,600 DELOXATINE, TRY UP TO 90 7715 04:58:23,600 --> 04:58:25,160 MILLIGRAMS TO 120 MILLIGRAMS PER 7716 04:58:25,160 --> 04:58:26,720 DAY FOR FOUR TO SIX WEEKS. IF 7717 04:58:26,720 --> 04:58:28,480 THAT DOESN'T WORK MEANING THERE 7718 04:58:28,480 --> 04:58:32,000 IS NO CHANGE IN PAIN INTENSITY, 7719 04:58:32,000 --> 04:58:36,400 SWITCH TOKING WITH ELSE.SWITCH TO SOMETHIN G ELSE OR IF 7720 04:58:36,400 --> 04:58:38,360 THERE IS PARTIAL RESPONSE ADD TO 7721 04:58:38,360 --> 04:58:39,480 SOMETHING ELSE THAT MIGHT HAVE A 7722 04:58:39,480 --> 04:58:42,040 CHANCE OF WORKING. IF THERE ARE 7723 04:58:42,040 --> 04:58:45,800 SUCH TRIALS, DR. SWEGER 7724 04:58:45,800 --> 04:58:46,520 DISCUSSED ONE FOR HER 7725 04:58:46,520 --> 04:58:47,840 INTERVENTIONS EARLIER THIS 7726 04:58:47,840 --> 04:58:49,520 MORNING AND ALSO AGAIN DRAWING 7727 04:58:49,520 --> 04:58:51,400 FROM EXPERIENCE IN PSYCHIATRY, 7728 04:58:51,400 --> 04:58:54,960 THE STAR AND D TRIAL, SIMILARLY 7729 04:58:54,960 --> 04:58:56,560 DESIGNED. SO THIS IS DOABLE AND 7730 04:58:56,560 --> 04:58:58,200 WE HAVE PARADIGMS AND I WOULD 7731 04:58:58,200 --> 04:58:59,440 LIKE TO SEE US TAKE SOMETHING 7732 04:58:59,440 --> 04:59:02,360 LIKE THIS ON. SO I THINK THAT IS 7733 04:59:02,360 --> 04:59:09,200 WHAT I HAD TO SAY. ONE OTHER 7734 04:59:09,200 --> 04:59:11,400 THING. WITH RESPECT OPIOID ONCE 7735 04:59:11,400 --> 04:59:13,200 PEOPLE DO ARE ON CHRONIC OPIOID 7736 04:59:13,200 --> 04:59:15,440 THERAPY I THINK THIS QUESTION OF 7737 04:59:15,440 --> 04:59:16,800 HOW MANY TIMES DO YOU ROTATE AND 7738 04:59:16,800 --> 04:59:20,600 WHAT DOSES DO YOU USE, IS 7739 04:59:20,600 --> 04:59:23,440 ANSWERABLE SO NICE IF WE HAD 7740 04:59:23,440 --> 04:59:25,520 SOME IDEA OF THAT, PROBABLY 7741 04:59:25,520 --> 04:59:27,160 CLINICAL OUTCOME FUNDAMENTALLY 7742 04:59:27,160 --> 04:59:29,200 DIVIDES INTO THREE AGAIN, THIS 7743 04:59:29,200 --> 04:59:30,800 IS ME BEING THE DUMB GUY, THREE 7744 04:59:30,800 --> 04:59:34,800 BUCKETS. ONE SET OF PEOPLE FOR 7745 04:59:34,800 --> 04:59:37,800 WHOM OPIOIDS FUNDAMENTALLY DON'T 7746 04:59:37,800 --> 04:59:40,000 WORK TO JUSTIFY MUCH RISK IN 7747 04:59:40,000 --> 04:59:40,880 WHICH CASE WE SHOULD TRY 7748 04:59:40,880 --> 04:59:42,400 SOMETHING ELSE. OTHER PEOPLE 7749 04:59:42,400 --> 04:59:44,880 FROM WHOM OPIOIDS WORK AND 7750 04:59:44,880 --> 04:59:46,680 SIMPLY WHAT WE ARE TRYING TO DO 7751 04:59:46,680 --> 04:59:50,400 IS MANAGE RISK, REDUCE IT IF 7752 04:59:50,400 --> 04:59:51,840 POSSIBLE, A THIRD GROUP OF 7753 04:59:51,840 --> 04:59:53,080 PEOPLE WHOM THERE ARE OPIOIDS 7754 04:59:53,080 --> 04:59:54,960 THE RISK IS LOW AND JUST LEAVE 7755 04:59:54,960 --> 04:59:57,200 WELL ENOUGH ALONE. AGAIN, I 7756 04:59:57,200 --> 05:00:00,680 THINK THESE QUESTIONS ARE 7757 05:00:00,680 --> 05:00:04,000 FUNDAMENTALLY ANSWERABLE. REALLY 7758 05:00:04,000 --> 05:00:05,920 HOPE WE COULD MAKE ESTABLISH 7759 05:00:05,920 --> 05:00:09,760 THEM. NEXT SLIDE. SEE I IF I HAD 7760 05:00:09,760 --> 05:00:11,400 ANYTHING ELSE. THAT IS ALL I 7761 05:00:11,400 --> 05:00:16,200 HAVE TO SAY. THANKS. 7762 05:00:16,200 --> 05:00:19,400 >> WE HAVE UNTIL 2:50 TO 7763 05:00:19,400 --> 05:00:23,640 ENTERTAIN QUESTIONS, TALK TO ONE 7764 05:00:23,640 --> 05:00:25,240 ANOTHER, AND I WILL TAKE THE 7765 05:00:25,240 --> 05:00:27,760 PREROGATIVE OF ASKING THE FIRST 7766 05:00:27,760 --> 05:00:32,000 QUESTION. WHICH WILL GO TO MY 7767 05:00:32,000 --> 05:00:39,800 FRIEND PAT. PAT, WE ARE 7768 05:00:39,800 --> 05:00:44,400 CRITICIZED OFTEN FOR WHAT WE DO 7769 05:00:44,400 --> 05:00:53,200 IN MANAGING PAIN AS 7770 05:00:53,200 --> 05:00:57,280 PSEUDOSCIENTIFIC AND THEN 7771 05:00:57,280 --> 05:00:59,280 CRITICIZED FOR NOT LIVING UP TO 7772 05:00:59,280 --> 05:01:05,520 THAT PSEUDOSCIENCE. CAN YOU GIVE 7773 05:01:05,520 --> 05:01:08,800 US DEFENSES AND I'M SPEAKING 7774 05:01:08,800 --> 05:01:15,120 ABOUT THE DEA PHARMACEUTICAL 7775 05:01:15,120 --> 05:01:18,080 DISPENSARIES, THE DRUGSTORES 7776 05:01:18,080 --> 05:01:20,400 THAT GIVE THE DRUGS OUT, 7777 05:01:20,400 --> 05:01:22,760 INSURANCE COMPANIES, 7778 05:01:22,760 --> 05:01:24,600 FORMULARIES, I'M REFERRING BACK 7779 05:01:24,600 --> 05:01:26,920 TO THAT VIDEO, TO THAT GRAPHIC 7780 05:01:26,920 --> 05:01:32,360 THAT I SHOWED CMS PUBLISHED 7781 05:01:32,360 --> 05:01:36,160 WHERE IN A GREAT ENVIRONMENT 7782 05:01:36,160 --> 05:01:37,680 LIKE SWEDEN WE CAN DO ANYTHING 7783 05:01:37,680 --> 05:01:40,960 WE WANT TO GET PAID FOR BUT NOT 7784 05:01:40,960 --> 05:01:42,200 SO IN THE UNITED STATES. 7785 05:01:42,200 --> 05:01:43,800 EVERYTHING YOU JUST SAID IS 7786 05:01:43,800 --> 05:01:46,200 SUBJECT TO THOSE RESTRICTIONS 7787 05:01:46,200 --> 05:01:49,440 AND CAN YOU GIVE US -- GIVE THE 7788 05:01:49,440 --> 05:01:53,200 AUDIENCE A LITTLE BIT OF HOW YOU 7789 05:01:53,200 --> 05:01:54,200 DEFEND GETTING SOME OF THOSE 7790 05:01:54,200 --> 05:01:56,280 THINGS DONE THAT YOU WOULD LIKE 7791 05:01:56,280 --> 05:01:57,720 TO DO AND YOU ARE TRYING TO DO 7792 05:01:57,720 --> 05:02:02,240 FOR YOUR PATIENTS. 7793 05:02:02,240 --> 05:02:04,120 >> SO I GET HIRED TO BE THE DUMB 7794 05:02:04,120 --> 05:02:05,800 GUY AND ALSO TO GET IN TROUBLE 7795 05:02:05,800 --> 05:02:07,240 SO I GUESS I'M ABOUT TO GET 7796 05:02:07,240 --> 05:02:10,840 MYSELF IN TROUBLE. I MEAN, I 7797 05:02:10,840 --> 05:02:19,000 DON'T KNOW, WALLY. THE BEGINNING 7798 05:02:19,000 --> 05:02:23,960 OF THE ANSWER, AIN'T NOBODY 7799 05:02:23,960 --> 05:02:28,360 BETTER OFF, CHRONIC PAIN IS HARD 7800 05:02:28,360 --> 05:02:30,720 TO TREAT, EVERYTHING WE USE HAS 7801 05:02:30,720 --> 05:02:31,600 RELATIVELY SMALL EFFECTS THAT 7802 05:02:31,600 --> 05:02:37,080 ARE HARD TO DETECT. AND I THINK 7803 05:02:37,080 --> 05:02:39,000 EVERYTHING I SAID ABOUT LACK OF 7804 05:02:39,000 --> 05:02:40,440 CLINICAL STRATEGY CHRONIC PAIN 7805 05:02:40,440 --> 05:02:42,680 IN GENERAL, WE ARE ALL IN THE 7806 05:02:42,680 --> 05:02:46,080 SAME BOAT. SO I THINK THERE IS 7807 05:02:46,080 --> 05:02:50,800 THE FIRST THING, WE NEED TO BACK 7808 05:02:50,800 --> 05:02:54,640 IT UP WITH EVIDENCE. WHAT I 7809 05:02:54,640 --> 05:02:55,880 SUGGESTED ABOUT HOW WE START 7810 05:02:55,880 --> 05:02:58,320 DEFINING, WHAT IS THE FIRST 7811 05:02:58,320 --> 05:02:59,880 THING -- FIRST FEW THINGS TO 7812 05:02:59,880 --> 05:03:02,360 OFFER AND SEE WHAT ACTUALLY 7813 05:03:02,360 --> 05:03:10,240 HAPPENS IS THE BEGINNING. AS TO 7814 05:03:10,240 --> 05:03:12,160 REGULATORY BODIES SO FORTH, A 7815 05:03:12,160 --> 05:03:14,480 LOT OF TIMES THAT GOES TO 7816 05:03:14,480 --> 05:03:16,080 OPIOIDS. I THINK THERE IS TWO 7817 05:03:16,080 --> 05:03:19,800 PARTS TO THAT, ONE PART OF IT IS 7818 05:03:19,800 --> 05:03:21,320 EVERYBODY HAS GOT TO REALIZE 7819 05:03:21,320 --> 05:03:24,600 OPIOID ARE COMPLICATED, AND THEY 7820 05:03:24,600 --> 05:03:26,640 WORK. BUT THEY OFTEN ALSO FAIL. 7821 05:03:26,640 --> 05:03:28,800 WE HAVE TO KEEP THOSE TWO THINGS 7822 05:03:28,800 --> 05:03:32,400 IN OUR HEADS SIMULTANEOUSLY. AND 7823 05:03:32,400 --> 05:03:34,320 THEY HAVE SIGNIFICANT ADVERSE 7824 05:03:34,320 --> 05:03:37,160 EFFECTS AND RISKS. SO IT IS WAY 7825 05:03:37,160 --> 05:03:39,560 TOO EASY TO LOOK AT ONE, GRAB 7826 05:03:39,560 --> 05:03:42,080 ONE ELEPHANT AND THINK YOU GOT A 7827 05:03:42,080 --> 05:03:44,000 ROPE AND GRAB ONE OF THE 7828 05:03:44,000 --> 05:03:45,600 ELEPHANT AND THINK IT IS A SNAKE 7829 05:03:45,600 --> 05:03:47,520 AND BUT YOU KNOW IT IS AN 7830 05:03:47,520 --> 05:03:51,120 ELEPHANT. AS TO THAT PART WE DO 7831 05:03:51,120 --> 05:03:56,840 HAVE TO REALIZE THAT OPIOID 7832 05:03:56,840 --> 05:04:01,000 CANNOT WORK AND SAY OUTLOUD THAT 7833 05:04:01,000 --> 05:04:02,440 LOT OF TIMES WE DON'T WORK AND 7834 05:04:02,440 --> 05:04:04,400 WE HAVE TO DECLARE FAILURE. WE 7835 05:04:04,400 --> 05:04:06,480 CAN'T KEEP ACTING LIKE YOU GOT 7836 05:04:06,480 --> 05:04:08,120 TO RESPOND TO RIGHT DOSE RIGHT 7837 05:04:08,120 --> 05:04:09,800 DRUG. I DON'T THINK IT IS THAT 7838 05:04:09,800 --> 05:04:12,560 SIMPLE. BUT OTHERS MIGHT 7839 05:04:12,560 --> 05:04:14,000 DISAGREE. AT THE SAME TIME THEY 7840 05:04:14,000 --> 05:04:17,400 DO WORK FOR SOME PEOPLE AND HAVE 7841 05:04:17,400 --> 05:04:20,280 BENEFIT CAN WELL BE SUSTAINED. 7842 05:04:20,280 --> 05:04:22,800 SO WE HAVE TO I THINK 7843 05:04:22,800 --> 05:04:24,360 DEMONSTRATE THAT BENEFIT AND FOR 7844 05:04:24,360 --> 05:04:26,360 WHOM IT IS SUSTAINED, BUT AT THE 7845 05:04:26,360 --> 05:04:28,640 SAME TIME GOT TO BE HONEST WITH 7846 05:04:28,640 --> 05:04:30,000 EVERYBODY AND OUR PATIENTS AND 7847 05:04:30,000 --> 05:04:32,760 HAVE A DEFINITION OF WHEN IT 7848 05:04:32,760 --> 05:04:34,520 DOESN'T WORK TOO AND THAT WILL 7849 05:04:34,520 --> 05:04:37,680 IMPROVE CONFIDENCE ON ALL PARTS. 7850 05:04:37,680 --> 05:04:39,360 THE PATIENTS TALKING FROM PLACE 7851 05:04:39,360 --> 05:04:42,200 OF CONCERN AND KNOWLEDGE AND 7852 05:04:42,200 --> 05:04:43,920 REGULATORS BEING RESPONSIBLE. 7853 05:04:43,920 --> 05:04:48,400 >> IS IT THE PLACE OF RESEARCH 7854 05:04:48,400 --> 05:04:51,160 OF CLINICIANS OR OF BOTH? TO 7855 05:04:51,160 --> 05:04:54,600 DEFINE THAT TERM WORKS? FOR 7856 05:04:54,600 --> 05:04:56,240 INSURANCE THAT DEFINES IT FOR 7857 05:04:56,240 --> 05:04:59,800 US, THEY OFTEN WILL DEFINE IT 7858 05:04:59,800 --> 05:05:02,560 FOR US. HOW DO WE DEFEND 7859 05:05:02,560 --> 05:05:04,000 OURSELVES WHEN THEY DEFINE IT 7860 05:05:04,000 --> 05:05:06,520 FOR US AND WE GO I BEG TO 7861 05:05:06,520 --> 05:05:08,800 DISAGREE? I SPEND MY TIME ON THE 7862 05:05:08,800 --> 05:05:10,520 PHONE, IN FACT I HIRED SOMEBODY 7863 05:05:10,520 --> 05:05:13,400 JUST TO SPEND THEIR TIME ON THE 7864 05:05:13,400 --> 05:05:17,680 PHONE SAYING NO IT WORKS. PLEASE 7865 05:05:17,680 --> 05:05:20,560 DO THIS. PLEASE LET OUR PATIENT 7866 05:05:20,560 --> 05:05:21,200 HAVE THIS. 7867 05:05:21,200 --> 05:05:22,880 >> WE HAVE CERTAIN WILL I TALKED 7868 05:05:22,880 --> 05:05:26,200 ABOUT CASES WHERE THE INSURANCE 7869 05:05:26,200 --> 05:05:26,680 THOUGHT THEY WERE DOING 7870 05:05:26,680 --> 05:05:27,960 SOMETHING TO PROTECT THE 7871 05:05:27,960 --> 05:05:29,800 PATIENT, IN FACT DISRUPTING CARE 7872 05:05:29,800 --> 05:05:31,800 O THE POINT PATIENT CARE FLU 7873 05:05:31,800 --> 05:05:36,040 APART. I DON'T HAVE MIRACULOUS 7874 05:05:36,040 --> 05:05:39,440 ANSWER. I THINK ETHICALLY 7875 05:05:39,440 --> 05:05:42,400 SPEAKING. CLINICIANS WE HAVE TO 7876 05:05:42,400 --> 05:05:44,960 HAVE A DEFINITION OF WORK OR 7877 05:05:44,960 --> 05:05:47,040 NOT. THE PROBLEM IS WE ARE 7878 05:05:47,040 --> 05:05:49,960 OPERATING FROM INACT CAT 7879 05:05:49,960 --> 05:05:51,960 EVIDENCE BASE. IF YOU DON'T HAVE 7880 05:05:51,960 --> 05:05:55,240 ANY DEFINITION OF FAILURE YOU 7881 05:05:55,240 --> 05:05:56,680 ARE NOT GOING TO STOP ANYTHING 7882 05:05:56,680 --> 05:05:57,800 AND YOU ACT LIKE EVERYTHING 7883 05:05:57,800 --> 05:05:59,800 WORKS AND THAT CLEARLY IS NOT 7884 05:05:59,800 --> 05:06:03,280 TRUE SO YOU WILL BE WRONG A LOT. 7885 05:06:03,280 --> 05:06:05,080 YOU WON'T SEEK SUCCESS BECAUSE 7886 05:06:05,080 --> 05:06:06,800 YOU WILL KEEP DOING STUFF THAT 7887 05:06:06,800 --> 05:06:09,400 IS NOT WORKING INSTEAD OF STUFF 7888 05:06:09,400 --> 05:06:11,600 THAT DOES. YOU EXPOSE PEOPLE TO 7889 05:06:11,600 --> 05:06:13,120 RISK BECAUSE THEY DON'T NEED TO 7890 05:06:13,120 --> 05:06:14,720 BE EXPOSED TO BECAUSE IT AIN'T 7891 05:06:14,720 --> 05:06:16,880 WORKING. WE AS CLINICS HAVE TO 7892 05:06:16,880 --> 05:06:18,560 HAVE A DEFINITION OF SUCCESS AND 7893 05:06:18,560 --> 05:06:21,080 FAILURE. OUR FUNDAMENTAL PROBLEM 7894 05:06:21,080 --> 05:06:24,480 IS WE HAVE GOT SOME ROUGH GUIDE 7895 05:06:24,480 --> 05:06:27,400 POSTS BUT IT REQUIRES US BEING 7896 05:06:27,400 --> 05:06:29,280 ARBITRARY. WITHIN THOSE GUIDE 7897 05:06:29,280 --> 05:06:32,600 POSTS, THAT IS DEEPLY 7898 05:06:32,600 --> 05:06:37,400 UNCOMFORTABLE. I THINK WE HAVE 7899 05:06:37,400 --> 05:06:40,840 TO BE STRAIGHT WITH PEOPLE. WE 7900 05:06:40,840 --> 05:06:44,400 HAD SOME ROUGH GUIDE POSTS, I'M 7901 05:06:44,400 --> 05:06:45,600 TAKING A GUESS HERE, I DON'T 7902 05:06:45,600 --> 05:06:47,480 KNOW THE EXACT RIGHT THING. IF 7903 05:06:47,480 --> 05:06:49,720 WE GO UP ON THE DOSE YOUR RISK 7904 05:06:49,720 --> 05:06:51,800 INCREASES AND PROBABLY THE 7905 05:06:51,800 --> 05:06:54,600 BENEFIT DOESN'T MUCH PAST A 7906 05:06:54,600 --> 05:06:58,080 CERTAIN POINT AT SAME TIME I 7907 05:06:58,080 --> 05:06:59,600 CAN'T SQUARE TO YOU EITHER WAY 7908 05:06:59,600 --> 05:07:01,840 SO WE BOTH HAVE TO DO SOME 7909 05:07:01,840 --> 05:07:05,440 NAVIGATING HERE. 7910 05:07:05,440 --> 05:07:10,920 >> ONE QUESTION IN THE -- TWO 7911 05:07:10,920 --> 05:07:14,800 QUESTIONS ABOUT THIS POINT. ONE 7912 05:07:14,800 --> 05:07:17,000 PERSON WANTED TO KNOW, YOU SORT 7913 05:07:17,000 --> 05:07:19,240 OF SAID YOU DON'T KNOW, WHEN 7914 05:07:19,240 --> 05:07:24,120 PAIN IS REFRACT TRY TO OPIOID, 7915 05:07:24,120 --> 05:07:25,600 AND ANOTHER WANTED TO MOW IF THE 7916 05:07:25,600 --> 05:07:29,800 PERSON IS ON ELOQUIST FOR ATRIAL 7917 05:07:29,800 --> 05:07:30,800 FIBRILLATION DOES THAT MATTER, 7918 05:07:30,800 --> 05:07:31,600 DOES THAT CHANGE ANYTHING? 7919 05:07:31,600 --> 05:07:36,280 >> IF YOU TOLD ME N SAIDS THEN 7920 05:07:36,280 --> 05:07:41,080 YEAH. WHERE I -- THERE ARE 7921 05:07:41,080 --> 05:07:43,520 PEOPLE HERE WHO KNOW WAY MORE 7922 05:07:43,520 --> 05:07:45,200 ABOUT THIS THAN I DO. AND THEY 7923 05:07:45,200 --> 05:07:47,120 ARE LOOKING AT YOU BUT THE WAY I 7924 05:07:47,120 --> 05:07:49,200 READ THINGS OUR PATIENTS ARE AT 7925 05:07:49,200 --> 05:07:52,440 RISK FOR CLOTTING AND BLEEDING 7926 05:07:52,440 --> 05:07:54,560 AND IMPORTANT CLOTTING 7927 05:07:54,560 --> 05:07:58,360 COAGULATION. WE HAVE THIS 7928 05:07:58,360 --> 05:08:00,000 PROBLEM OF RENAL DISEASE AND 7929 05:08:00,000 --> 05:08:02,640 ALSO STROKE. ALL THESE THINGS 7930 05:08:02,640 --> 05:08:06,200 ARE THINGS THAT COULD BE RISK 7931 05:08:06,200 --> 05:08:08,440 FOR CHRONIC N SAID THERAPY AND I 7932 05:08:08,440 --> 05:08:10,760 WORRY A LOT ABOUT IT. IF YOU 7933 05:08:10,760 --> 05:08:12,200 LOOK AT THE SPACE TRIAL WHERE 7934 05:08:12,200 --> 05:08:14,680 PEOPLE SPENT THEIR TIME 7935 05:08:14,680 --> 05:08:17,600 RANDOMIZE TO ALL NON-OPIOIDS OR 7936 05:08:17,600 --> 05:08:18,920 OPIOIDS, WHERE PEOPLE SPEND 7937 05:08:18,920 --> 05:08:21,000 THEIR TIME NON-OPIOID ARM WAS ON 7938 05:08:21,000 --> 05:08:25,480 N SAIDS SO SEEMS TO BE AN 7939 05:08:25,480 --> 05:08:27,600 IMPORTANT TOOL YET WE OFTEN USE 7940 05:08:27,600 --> 05:08:29,560 IT BUT DO WE REALLY KNOW WHAT WE 7941 05:08:29,560 --> 05:08:31,920 ARE DOING TO PEOPLE FOR FIVE TEN 7942 05:08:31,920 --> 05:08:34,400 YEARS? DO WE KNOW WHAT THEY ARE 7943 05:08:34,400 --> 05:08:36,720 DOING AT HOME? A LOT OF PEOPLE 7944 05:08:36,720 --> 05:08:39,680 TAKE DOSES OF IBUPROFEN 7945 05:08:39,680 --> 05:08:40,200 SOMETIMES. 7946 05:08:40,200 --> 05:08:41,600 >> TOM ASKED THE QUESTION HAS 7947 05:08:41,600 --> 05:08:43,480 ANYBODY LOOKED AT PERCEPTION OF 7948 05:08:43,480 --> 05:08:47,320 THE CARING OF THE PROVIDER AND 7949 05:08:47,320 --> 05:08:49,840 WITH RESPECT TO PAIN TREATMENT 7950 05:08:49,840 --> 05:08:52,520 THERE HAVE BEEN A NUMEROUS 7951 05:08:52,520 --> 05:08:56,080 STUDIES OF ADDITIVES OF PAIN 7952 05:08:56,080 --> 05:09:00,200 PROVIDERS, PEOPLE ASSIGNED TO 7953 05:09:00,200 --> 05:09:03,080 RELIEF PAIN AND BASICALLY THEY 7954 05:09:03,080 --> 05:09:05,280 ARE NOT DOING THEIR JOB. I WOULD 7955 05:09:05,280 --> 05:09:09,680 PUT IT THAT WAY. THEY ARE 7956 05:09:09,680 --> 05:09:11,120 FEELING UNCOMFORTABLE LIKE PAT 7957 05:09:11,120 --> 05:09:12,200 SAID. THEY DON'T FEEL 7958 05:09:12,200 --> 05:09:14,400 COMFORTABLE. THAT IS THEY DON'T 7959 05:09:14,400 --> 05:09:16,200 KNOW WHAT THEY ARE DOING, THEY 7960 05:09:16,200 --> 05:09:17,200 KNOW THEY DON'T KNOW WHAT THEY 7961 05:09:17,200 --> 05:09:19,120 ARE DOING AND THAT MAKES THEM 7962 05:09:19,120 --> 05:09:20,680 UNCOMFORTABLE. AND THEY DON'T 7963 05:09:20,680 --> 05:09:24,480 LIKE HAVING TO DO IT. THAT IS 7964 05:09:24,480 --> 05:09:26,600 THE SUMMARY WOULD YOU ADD TO 7965 05:09:26,600 --> 05:09:27,680 THAT ANYBODY SUMMARY OF THE 7966 05:09:27,680 --> 05:09:34,280 LITERATURE ON THAT? I THINK THAT 7967 05:09:34,280 --> 05:09:37,800 IS THE SUMMARY. 7968 05:09:37,800 --> 05:09:41,560 >> I DO THINK SIGNIFICANT CHUNK 7969 05:09:41,560 --> 05:09:45,200 OF THIS IS ABOUT ADDICTION. THAT 7970 05:09:45,200 --> 05:09:47,040 IS ONE OF THE THINGS THAT 7971 05:09:47,040 --> 05:09:50,160 TERRIFIES PEOPLE. ONE OF THE 7972 05:09:50,160 --> 05:09:52,640 PROBLEMS WE GOT THERE IS THAT I 7973 05:09:52,640 --> 05:09:54,200 DON'T THINK YOU CAN GET 7974 05:09:54,200 --> 05:09:56,320 NECESSARILY DEFINE QUOTE UNQUOTE 7975 05:09:56,320 --> 05:09:59,320 ADDICTION IN THIS CONTEXT ALL 7976 05:09:59,320 --> 05:10:00,720 THAT WELL. JUST BECAUSE OF THE 7977 05:10:00,720 --> 05:10:03,920 WAY OPIOIDS WORK ON BEHAVIOR. SO 7978 05:10:03,920 --> 05:10:05,360 I THINK -- I HAVE A CERTAIN 7979 05:10:05,360 --> 05:10:08,320 AMOUNT OF SYMPATHY FOR THE 7980 05:10:08,320 --> 05:10:12,480 COGNITIVE DISSONANCE SOME HAVE. 7981 05:10:12,480 --> 05:10:13,920 THEY ARE HELD TO ACCOUNT TO 7982 05:10:13,920 --> 05:10:14,920 PREVENT SOMETHING THEY CAN'T 7983 05:10:14,920 --> 05:10:18,800 SEE, HIGH INDEX OF SUSPICION FOR 7984 05:10:18,800 --> 05:10:20,040 IT BUT THEY ARE GOING TO SUSPECT 7985 05:10:20,040 --> 05:10:21,800 PEOPLE WHO HAVE NO REASON OF 7986 05:10:21,800 --> 05:10:25,680 BEING SUSPECTED. SO I THINK WE 7987 05:10:25,680 --> 05:10:27,880 GET STUCK IN THIS SITUATION 7988 05:10:27,880 --> 05:10:29,440 WHERE ALL OUR PATIENTS GET 7989 05:10:29,440 --> 05:10:32,520 LOOKED AT WITH A STAKE EYE BUT 7990 05:10:32,520 --> 05:10:34,400 IT DOESN'T CHANGE THINGS. IT 7991 05:10:34,400 --> 05:10:37,560 DOESN'T PREVENT THE TROUBLE NOR 7992 05:10:37,560 --> 05:10:39,440 DOES IT DO ANYTHING TO GET PAIN 7993 05:10:39,440 --> 05:10:41,800 CARE BETTER, OFTEN MAKES IT 7994 05:10:41,800 --> 05:10:44,400 WORSE. SO I THINK IF WE CAN HELP 7995 05:10:44,400 --> 05:10:46,000 OUR COLLEAGUES WITH DIFFERENT 7996 05:10:46,000 --> 05:10:48,400 PARADIGM AROUND THAT, IT WOULD 7997 05:10:48,400 --> 05:10:52,240 PROBABLY HELP. 7998 05:10:52,240 --> 05:10:54,440 >> I DON'T SEE ANY OTHER 7999 05:10:54,440 --> 05:10:56,400 QUESTIONS IN THE CHAT SO I HAVE 8000 05:10:56,400 --> 05:10:58,440 NO PROBLEM ASKING OTHER SPEAKERS 8001 05:10:58,440 --> 05:11:01,840 QUESTIONS, I REALLY APPRECIATED 8002 05:11:01,840 --> 05:11:05,160 THE ANALOGY OF THE CYCLE OF 8003 05:11:05,160 --> 05:11:07,440 TRANSLATIONAL RESEARCH. I'M NOT 8004 05:11:07,440 --> 05:11:09,440 SURE I SAW THAT PICTURE BEFORE. 8005 05:11:09,440 --> 05:11:11,640 BACK AND FORTH BETWEEN MAN AND 8006 05:11:11,640 --> 05:11:18,960 MOUSE. AND I LIKE THAT CONCEPT 8007 05:11:18,960 --> 05:11:21,960 AND WONDERED IF, STARTING WITH 8008 05:11:21,960 --> 05:11:24,640 DR. STUCKY, WONDERED IF YOU FELT 8009 05:11:24,640 --> 05:11:26,520 LIKE I'M GOING TO USE THE HEEL 8010 05:11:26,520 --> 05:11:27,760 INITIATIVE BECAUSE I KNOW ABOUT 8011 05:11:27,760 --> 05:11:29,200 THE HEEL INITIATIVE. IF YOU FELT 8012 05:11:29,200 --> 05:11:31,520 LIKE THE HEEL INITIATIVE IS 8013 05:11:31,520 --> 05:11:36,240 AWARE OF THIS APPROACH, YOU GOT 8014 05:11:36,240 --> 05:11:38,640 A TARGET YOU HAVE POTENTIAL 8015 05:11:38,640 --> 05:11:39,920 PROBE INTO THAT TARGET THAT 8016 05:11:39,920 --> 05:11:43,080 COULD TURN INTO POTENTIAL DRUG 8017 05:11:43,080 --> 05:11:45,400 AND YOU TESTED AND YOU GO TO 8018 05:11:45,400 --> 05:11:46,400 ANIMAL STUDIES AND BACK TO 8019 05:11:46,400 --> 05:11:48,000 HUMAN. 8020 05:11:48,000 --> 05:11:51,360 >> THANKS, WALLY. I THINK THEY 8021 05:11:51,360 --> 05:11:53,440 ARE AWARE OF IT BUT I DON'T 8022 05:11:53,440 --> 05:11:57,080 THINK THEY ARE ENCOURAGING 8023 05:11:57,080 --> 05:12:00,160 ENOUGH STUDIES THAT COULD REALLY 8024 05:12:00,160 --> 05:12:02,480 DO THIS. PARALLEL BACK AND FORTH 8025 05:12:02,480 --> 05:12:06,800 WAY. I ALSO THINK THAT THERE IS 8026 05:12:06,800 --> 05:12:09,360 NOT ENOUGH ENCOURAGEMENT FOR 8027 05:12:09,360 --> 05:12:11,200 PIs WHO ARE WORKING ON SICKLE 8028 05:12:11,200 --> 05:12:13,800 CELL DISEASE WHETHER CLINICAL OR 8029 05:12:13,800 --> 05:12:16,000 BASIC RESEARCH TO SUBMIT FOR 8030 05:12:16,000 --> 05:12:17,800 THESE KINDS OF STUDIES. SO I 8031 05:12:17,800 --> 05:12:20,440 THINK THERE NEED TO BE MORE 8032 05:12:20,440 --> 05:12:21,800 CALLS FOR THIS TYPE OF WORK AND 8033 05:12:21,800 --> 05:12:24,600 I THINK THERE NEED TO BE MORE 8034 05:12:24,600 --> 05:12:26,120 ANSWERS IN SUB -- AND 8035 05:12:26,120 --> 05:12:27,280 SUBMISSIONS FOR THIS KIND OF -- 8036 05:12:27,280 --> 05:12:28,600 THESE KINDS OF BACK AND FORTH 8037 05:12:28,600 --> 05:12:37,280 STUDIES. I THINK ALSO THERE IS 8038 05:12:37,280 --> 05:12:40,000 NOT ENOUGH STUDIES ON SICKLE 8039 05:12:40,000 --> 05:12:41,920 CELL DISEASE PAIN THAT ARE 8040 05:12:41,920 --> 05:12:44,640 GETTING FUNDED. AS WELL. 8041 05:12:44,640 --> 05:12:47,080 >> YEAH. I THINK THE HEEL 8042 05:12:47,080 --> 05:12:49,760 INITIATIVE IS SENSITIVE TO THAT. 8043 05:12:49,760 --> 05:12:52,200 THEY ARE ALSO SENSITIVE TO THE 8044 05:12:52,200 --> 05:12:54,000 DUAL PROBLEM OF SUBSTANCE USE 8045 05:12:54,000 --> 05:12:55,880 WITHIN THE CONTEXT OF SOMEBODY 8046 05:12:55,880 --> 05:12:59,880 WITH CHRONIC PAIN. THAT IS A NEW 8047 05:12:59,880 --> 05:13:06,240 SENSITIVITY ON THEIR PART. THEY 8048 05:13:06,240 --> 05:13:07,680 ARE FOR THE FIRST TIME PUTTING 8049 05:13:07,680 --> 05:13:09,200 OUT RFAs ABOUT THAT. SO THAT 8050 05:13:09,200 --> 05:13:12,520 MADE ME EXCITED ABOUT IT. THERE 8051 05:13:12,520 --> 05:13:14,320 ARE FUNDING SICKLE CELL SPECIFIC 8052 05:13:14,320 --> 05:13:16,800 STUDIES. I KNOW THAT. Y'ALL 8053 05:13:16,800 --> 05:13:17,800 PROBABLY EVERYBODY KNOWS ABOUT 8054 05:13:17,800 --> 05:13:20,320 THE RFAs ON THE STREET. 8055 05:13:20,320 --> 05:13:22,720 RELATED TO SICKLE CELL DISEASE. 8056 05:13:22,720 --> 05:13:26,200 >> ABSOLUTELY. I THINK WE NEED 8057 05:13:26,200 --> 05:13:28,360 MORE INDIVIDUALS ANSWERING THOSE 8058 05:13:28,360 --> 05:13:30,120 CALLSES AND SUBMITTING STRONG 8059 05:13:30,120 --> 05:13:32,000 APPLICATIONS AND WE NEED TO HAVE 8060 05:13:32,000 --> 05:13:35,400 THOSE APPLICATIONS SCORE WELL. 8061 05:13:35,400 --> 05:13:36,000 AND GET FUNDED. 8062 05:13:36,000 --> 05:13:44,080 >> QUESTION FOR AMANDA. IS THE 8063 05:13:44,080 --> 05:13:50,520 GUT BRAIN CONNECTION WELL 8064 05:13:50,520 --> 05:13:51,400 EMPHASIZED ENOUGH IN OTHER 8065 05:13:51,400 --> 05:13:52,400 CONDITIONS THAT WE CAN COPY THE 8066 05:13:52,400 --> 05:13:53,840 METHODS THEY ARE USING AND SHOW 8067 05:13:53,840 --> 05:13:55,600 THAT THEY ARE TRUE FOR SICKLE 8068 05:13:55,600 --> 05:13:57,760 CELL DISEASE? OR ARE YOU BLAZING 8069 05:13:57,760 --> 05:14:04,800 THE TRAIL BY YOURSELF? 8070 05:14:04,800 --> 05:14:06,720 >> THANKS, WALLY, IT IS STARTING 8071 05:14:06,720 --> 05:14:08,600 TO BE UNCOVERED AND INVESTIGATED 8072 05:14:08,600 --> 05:14:13,000 A LOT MORE IN DEPTH AND OTHER 8073 05:14:13,000 --> 05:14:15,600 PAN CONDITIONS. THERE IS 8074 05:14:15,600 --> 05:14:18,360 PROPOSED HYPOTHESIS HOW THE 8075 05:14:18,360 --> 05:14:19,960 CONNECTION EXISTS IN CONTEXT OF 8076 05:14:19,960 --> 05:14:22,280 PAIN. THERE IS BETTER MECHANISMS 8077 05:14:22,280 --> 05:14:26,600 WORKED OUT IN OTHER PAIN 8078 05:14:26,600 --> 05:14:28,920 DISORDERS I THINK THERE IS A 8079 05:14:28,920 --> 05:14:33,960 POST DOC WHO IS WORKING IN DR. 8080 05:14:33,960 --> 05:14:36,600 STUCKY'S LAB NOW MOVING TO A 8081 05:14:36,600 --> 05:14:38,040 FACULTY POSITION DOING EXCITING 8082 05:14:38,040 --> 05:14:40,000 WORK IN THE MURINE MODEL. SHE 8083 05:14:40,000 --> 05:14:44,360 HAS A K99 ROO TO LOOK AT THIS TO 8084 05:14:44,360 --> 05:14:49,880 UNDERSTAND MECHANISMS OF THE GUT 8085 05:14:49,880 --> 05:14:55,560 BRAIN CONNECTION. MY RO1 IN 8086 05:14:55,560 --> 05:14:57,320 HUMANS IS LOOKING AT HUMAN 8087 05:14:57,320 --> 05:14:58,600 ASPECTS OF THE GUTS CONNECTION 8088 05:14:58,600 --> 05:15:01,160 TO POTENTIALLY PAIN THROUGH 8089 05:15:01,160 --> 05:15:05,600 IMMUNOLOGIC PATHWAYS. THERE IS 8090 05:15:05,600 --> 05:15:07,160 OTHER WAYS OTHER THAN THE IMMUNE 8091 05:15:07,160 --> 05:15:08,720 SYSTEM THE GUT BRAIN CONNECTION 8092 05:15:08,720 --> 05:15:15,040 ACTUALLY COULD IMPACT PAIN AND 8093 05:15:15,040 --> 05:15:17,040 CENTRAL PAIN MECHANISMS IN THE 8094 05:15:17,040 --> 05:15:18,680 BRAIN AND SPINAL CORD. WE ARE 8095 05:15:18,680 --> 05:15:22,600 DOING PARALLEL WORK BOTH MYSELF 8096 05:15:22,600 --> 05:15:24,760 AND DR. SADLER TO TRY TO 8097 05:15:24,760 --> 05:15:26,720 INVESTIGATE THIS AT THE 8098 05:15:26,720 --> 05:15:29,000 MECHANISTIC LEVEL. WHAT YOU 8099 05:15:29,000 --> 05:15:30,200 REFER TO ABOUT TRANSLATIONAL 8100 05:15:30,200 --> 05:15:33,280 APPROACH IS IMPORTANT BECAUSE AS 8101 05:15:33,280 --> 05:15:34,400 CLINICAL TRANSLATIONAL 8102 05:15:34,400 --> 05:15:35,400 RESEARCHER I CAN LOOK AT 8103 05:15:35,400 --> 05:15:37,240 ASSOCIATIONS AND A LOT OF 8104 05:15:37,240 --> 05:15:38,400 CLINICAL STUFF AND DERIVE 8105 05:15:38,400 --> 05:15:42,480 QUESTIONS. IF WE WANT TO DRILL 8106 05:15:42,480 --> 05:15:43,800 DOWN DEFINITIVE MECHANISM 8107 05:15:43,800 --> 05:15:45,240 COLLABORATING WITH BASIC 8108 05:15:45,240 --> 05:15:48,400 SCIENTISTS IS REALLY IMPORTANT. 8109 05:15:48,400 --> 05:15:49,920 TO BRING DOWN TO MECHANISM TO 8110 05:15:49,920 --> 05:15:53,960 LOOK AT PATHWAYS THAT CAN BE 8111 05:15:53,960 --> 05:15:58,000 TARGETED, BROUGHT BACK TO HUMAN. 8112 05:15:58,000 --> 05:15:59,000 GREAT COLLABORATIONS I HAVE WITH 8113 05:15:59,000 --> 05:16:03,280 BASIC SCIENTISTS HAS BEEN NOT 8114 05:16:03,280 --> 05:16:06,600 ONLY INCREDIBLY HELPFUL FOR ME 8115 05:16:06,600 --> 05:16:07,920 AS CLINICAL TRANSLATIONAL 8116 05:16:07,920 --> 05:16:08,800 RESEARCHER AS FAR AS LEARNING 8117 05:16:08,800 --> 05:16:09,520 BUT ALSO MOVES THE FIELD 8118 05:16:09,520 --> 05:16:13,840 FORWARD. SO ANYONE WITH THE 8119 05:16:13,840 --> 05:16:15,520 OPPORTUNITY TO WORK IN THAT 8120 05:16:15,520 --> 05:16:17,200 MODEL IS IMPORTANT. TO ANSWER 8121 05:16:17,200 --> 05:16:19,800 QUESTION ABOUT MICROBIOME, IT 8122 05:16:19,800 --> 05:16:21,040 NEEDS TO BE FURTHER STUDIED IN 8123 05:16:21,040 --> 05:16:23,600 SICKLE CELL DISEASE BECAUSE 8124 05:16:23,600 --> 05:16:25,240 THERE'S SOME THINGS EVEN IF 8125 05:16:25,240 --> 05:16:27,640 FOUND IN OTHER PAIN CONDITIONS, 8126 05:16:27,640 --> 05:16:30,920 SICKLE CELL DISEASE IS IN ITSELF 8127 05:16:30,920 --> 05:16:31,800 A DIFFERENT DISEASE IN MANY 8128 05:16:31,800 --> 05:16:33,880 ASPECTS. SO I THINK WILL IS A 8129 05:16:33,880 --> 05:16:37,680 UNIQUE THINGS RELATED TO SICKLE 8130 05:16:37,680 --> 05:16:41,200 CELL DISEASE WE MAY BE FINDING 8131 05:16:41,200 --> 05:16:43,200 IN OUR DATA THAT DESERVES 8132 05:16:43,200 --> 05:16:45,120 FURTHER EXPLORATION IN CONTEXT 8133 05:16:45,120 --> 05:16:47,800 OF THE DISEASE MODEL. NOT JUST 8134 05:16:47,800 --> 05:16:49,000 COPY PASTE FROM DIFFERENT 8135 05:16:49,000 --> 05:16:58,680 DISEASE. NITYA'S QUESTION. YOU 8136 05:16:58,680 --> 05:17:00,320 GOT THIS NEAT THING THAT CAN USE 8137 05:17:00,320 --> 05:17:05,760 TO PHENOTYPE PATIENTS. WHAT DO 8138 05:17:05,760 --> 05:17:11,080 YOU NIH FUND NEXT? HOW ABOUT 8139 05:17:11,080 --> 05:17:13,960 THAT FOR A SOFTBALL? 8140 05:17:13,960 --> 05:17:15,680 >> I THINK WITH RESPECT TO 8141 05:17:15,680 --> 05:17:17,880 IDENTIFYING PAIN PHENOTYPES, I 8142 05:17:17,880 --> 05:17:24,680 THINK WE SHOULD FOCUS ON 8143 05:17:24,680 --> 05:17:26,160 MULTI-MODAL PHENOTYPING OF PAIN. 8144 05:17:26,160 --> 05:17:28,520 NOT JUST USING HEALTHCARE 8145 05:17:28,520 --> 05:17:30,200 UTILIZATION USED LONGEST TIME 8146 05:17:30,200 --> 05:17:32,560 AND NOT JUST USING PAIN 8147 05:17:32,560 --> 05:17:34,120 INTENSITY BUT COLLABORATION OF 8148 05:17:34,120 --> 05:17:37,640 PATIENT REPORTED OUTCOMES, SOME 8149 05:17:37,640 --> 05:17:40,600 DEEP UNDERSTANDING OF CLINICAL 8150 05:17:40,600 --> 05:17:44,200 PAIN FEELS LIKE IN TERMS OF 8151 05:17:44,200 --> 05:17:45,800 DECRYPTERS AND -- DESCRIPTORS 8152 05:17:45,800 --> 05:17:49,560 AND NOT JUST AT THE CONCEPTUAL 8153 05:17:49,560 --> 05:17:51,280 LEVEL BUT ALSO LONGITUDINALLY, 8154 05:17:51,280 --> 05:17:53,320 WHETHER TO SEE WHETHER THE 8155 05:17:53,320 --> 05:17:53,720 PHENOTYPES ARE -- 8156 05:17:53,720 --> 05:17:56,040 >> SO THE PATIENTS COMPLAIN 8157 05:17:56,040 --> 05:17:57,360 BECAUSE YOU TAKE 20 MINUTES TO 8158 05:17:57,360 --> 05:17:58,800 ASK ABOUT -- I SAID WHAT IS YOUR 8159 05:17:58,800 --> 05:17:59,920 PAIN LIKE? WHAT IS YOUR PAIN 8160 05:17:59,920 --> 05:18:03,160 LIKE? JUST ASK THEM UP DOWN AND 8161 05:18:03,160 --> 05:18:05,560 SIDEWAYS AND NAY ARE LIKE ENOUGH 8162 05:18:05,560 --> 05:18:08,600 ALREADY. YOU TOLD ME THIS 8163 05:18:08,600 --> 05:18:10,240 YOURSELF, IN YOUR HARD TO GET 8164 05:18:10,240 --> 05:18:12,800 THEM TO TELL YOU EVERY DAY OR 8165 05:18:12,800 --> 05:18:16,200 TELL YOU FOR 20 MINUTES. WHAT -- 8166 05:18:16,200 --> 05:18:19,920 HOW DO WE BALANCE RESPONDENT 8167 05:18:19,920 --> 05:18:22,120 BURDEN WITH NEED TO KNOW TO HAVE 8168 05:18:22,120 --> 05:18:22,400 ADEQUATE -- 8169 05:18:22,400 --> 05:18:23,680 >> I THINK THAT IS A GREAT 8170 05:18:23,680 --> 05:18:30,800 QUESTION. IF WE INVEST IN 8171 05:18:30,800 --> 05:18:34,400 RESEARCH THAT CAN IDENTIFY THE 8172 05:18:34,400 --> 05:18:35,800 MOST HIGH YIELD ITEMS THAT 8173 05:18:35,800 --> 05:18:37,600 PREDICT OUTCOMES, THAT WOULD BE 8174 05:18:37,600 --> 05:18:40,280 THE WAY TO GO BUT TO START OFF 8175 05:18:40,280 --> 05:18:45,120 WE WOULD HAVE TO GET A GOOD DEEP 8176 05:18:45,120 --> 05:18:46,400 UNDERSTANDING AT THE SAME TIME 8177 05:18:46,400 --> 05:18:53,320 TO BE ABLE TO MOVE FORWARD I 8178 05:18:53,320 --> 05:18:55,440 THINK NOT DOING THIS DOESN'T 8179 05:18:55,440 --> 05:18:58,960 ALLOW US TO INTERFACE WITH 8180 05:18:58,960 --> 05:19:01,840 TRANSLATIONAL RESEARCHERS, 8181 05:19:01,840 --> 05:19:04,040 BECAUSE AT THE END OF THE DAY 8182 05:19:04,040 --> 05:19:06,000 WHAT WE NEED MEASURING IS 8183 05:19:06,000 --> 05:19:08,200 HEALTHCARE UTILIZATION WHICH WE 8184 05:19:08,200 --> 05:19:12,920 KNOW HAS GONE DOWN OVER TIME OR 8185 05:19:12,920 --> 05:19:14,800 ON AVERAGE ESPECIALLY HYDROXY 8186 05:19:14,800 --> 05:19:17,840 UREA AND DEPENDING ON MULTIPLE 8187 05:19:17,840 --> 05:19:19,960 OTHER VARIABLES THAT MAY NOT BE 8188 05:19:19,960 --> 05:19:23,600 RELATED TO PAIN FREQUENCY. IT 8189 05:19:23,600 --> 05:19:27,920 IS HARD TO ASSESS PAIN FREQUENCY 8190 05:19:27,920 --> 05:19:33,400 BY RESPECT OF THIS. I KNOW AAPT 8191 05:19:33,400 --> 05:19:34,960 DEFINITION, HOW MANY OF YOU HAD 8192 05:19:34,960 --> 05:19:37,480 PAIN THE LAST SIX MONTHS BUT 8193 05:19:37,480 --> 05:19:39,400 OPERATIONALIZING IT IN CLINIC IS 8194 05:19:39,400 --> 05:19:39,560 -- 8195 05:19:39,560 --> 05:19:41,200 >> TERRIBLE. 8196 05:19:41,200 --> 05:19:43,400 >> IT IS DIFFICULT. UNLESS PAIN 8197 05:19:43,400 --> 05:19:45,160 IS ON MOST DAYS THEN EASY, 8198 05:19:45,160 --> 05:19:49,320 OTHERWISE IT IS HARD TO TELL. 8199 05:19:49,320 --> 05:19:53,640 WHAT THEY WERE ACTUALLY GETTING 8200 05:19:53,640 --> 05:19:53,960 (INAUDIBLE) 8201 05:19:53,960 --> 05:19:55,640 >> WE ARE GOING TO DONATE OUR 8202 05:19:55,640 --> 05:19:57,600 THREE MINUTES TO THE NEXT 8203 05:19:57,600 --> 05:19:58,760 SESSION BUT I WOULD ENCOURAGE 8204 05:19:58,760 --> 05:20:02,040 OUR PANELISTS TO KEEP AN EYE OUT 8205 05:20:02,040 --> 05:20:05,800 ON THE CHAT. AND AS AT HAS BEEN 8206 05:20:05,800 --> 05:20:07,600 DOING PLEASE ANSWER QUESTIONS 8207 05:20:07,600 --> 05:20:09,320 THAT COME UP IN THE CHAT THAT 8208 05:20:09,320 --> 05:20:13,400 ARE SEEMINGLY DIRECTED TO YOU. 8209 05:20:13,400 --> 05:20:14,560 OR YOU HAVE KNOWLEDGE ABOUT. I 8210 05:20:14,560 --> 05:20:18,600 WANT TO THANK THESE PARTICULAR 8211 05:20:18,600 --> 05:20:24,040 PANELISTS, FOR DEEP EXPERTISE 8212 05:20:24,040 --> 05:20:25,240 CRISP PRESENTATIONS THAT 8213 05:20:25,240 --> 05:20:27,600 SUMMARIZED A WHOLE LOT OF DATA 8214 05:20:27,600 --> 05:20:30,200 AND LOT OF WORK IN SOME CASES 8215 05:20:30,200 --> 05:20:34,600 TEN MINUTES. AND I THANK YOU FOR 8216 05:20:34,600 --> 05:20:36,160 CONTRIBUTING TO THIS TALK. 8217 05:20:36,160 --> 05:20:38,440 THANKS FOR PAT FOR BEING THE 8218 05:20:38,440 --> 05:20:41,320 OWL, THE WISE OWL. I DIDN'T SAY 8219 05:20:41,320 --> 05:20:43,320 OLD. THE WISE OWL OF OUR 8220 05:20:43,320 --> 05:20:45,160 DISCUSSION. 8221 05:20:45,160 --> 05:20:48,680 >> OLD WOULD BE MORE ACCURATE. 8222 05:20:48,680 --> 05:20:50,600 >> SO I'M GOING TO HAND IT OVER 8223 05:20:50,600 --> 05:20:51,400 TO DR. GUPTA. 8224 05:20:51,400 --> 05:21:01,360 >> THANK YOU WALLY. 8225 05:21:01,360 --> 05:21:02,040 CAPNA, ALL YOURS. 8226 05:21:02,040 --> 05:21:03,520 >> CAN YOU HEAR ME ALREADY? 8227 05:21:03,520 --> 05:21:04,720 >> YES WE CAN WE CAN. 8228 05:21:04,720 --> 05:21:26,000 >> CAN I SHARE MY SLIDES PLEASE. 8229 05:21:26,000 --> 05:21:27,360 I STARTED MY VIDEO BUT I DON'T 8230 05:21:27,360 --> 05:21:28,800 KNOW WHY IT IS NOT SHOWING. I AM 8231 05:21:28,800 --> 05:21:35,040 SHOWING. THAT'S ALL RIGHT. OKAY. 8232 05:21:35,040 --> 05:21:38,400 SO AS YOU SAW EARLIER TODAY, 8233 05:21:38,400 --> 05:21:40,800 FROM JULIE'S PRESENTATION, SHE 8234 05:21:40,800 --> 05:21:47,160 HAS SPOKEN ABOUT DR. BELL'S -- 8235 05:21:47,160 --> 05:21:48,960 VERY HARD TIME FOR US AND I'M 8236 05:21:48,960 --> 05:21:50,240 DEEPLY SADDENED TO INFORM YOU 8237 05:21:50,240 --> 05:21:52,000 THOSE WHO WERE NOT HERE IN THE 8238 05:21:52,000 --> 05:21:57,280 MORNING THAT OUR DEAR DR. 8239 05:21:57,280 --> 05:21:59,960 BALLAS, COMPASSIONATE PHYSICIAN 8240 05:21:59,960 --> 05:22:01,200 LEADING IN SICKLE CELL PAIN, HE 8241 05:22:01,200 --> 05:22:04,280 IS A GREAT SPIRIT, A HEELER AND 8242 05:22:04,280 --> 05:22:05,000 SO KNOWLEDGEABLE AND GREAT 8243 05:22:05,000 --> 05:22:08,720 FRIEND TO ALL OF US. HE -- I 8244 05:22:08,720 --> 05:22:12,040 CAN SAY PERSONALLY HE WAS MY 8245 05:22:12,040 --> 05:22:13,000 INSPIRATION AND ENCOURAGED ME 8246 05:22:13,000 --> 05:22:15,840 FROM THE START BEFORE I STARTED 8247 05:22:15,840 --> 05:22:18,280 STUDYING PAIN. THEREFORE I 8248 05:22:18,280 --> 05:22:19,280 COULDN'T START WITHOUT 8249 05:22:19,280 --> 05:22:22,120 REMEMBERING HIM AT THIS TIME, 8250 05:22:22,120 --> 05:22:23,160 BECAUSE HE WAS ALWAYS PRESENT AT 8251 05:22:23,160 --> 05:22:28,400 ALL OF OUR MEETINGS. NEVER 8252 05:22:28,400 --> 05:22:30,080 MISSED ASH OR SICKLE CELL 8253 05:22:30,080 --> 05:22:34,560 CLINICAL MEETING. THEREFORE, I 8254 05:22:34,560 --> 05:22:36,280 AM SHOWING HIS PICTURE AGAIN 8255 05:22:36,280 --> 05:22:38,160 TODAY AND HIS FAMILY WANTS US TO 8256 05:22:38,160 --> 05:22:41,680 PRAY FOR HIM. AND WISH HIM A 8257 05:22:41,680 --> 05:22:44,720 SMOOTHER TRANSITION AS HE IS 8258 05:22:44,720 --> 05:22:48,400 STRUGGLING IN HOSPICE CARE 8259 05:22:48,400 --> 05:22:52,800 FOLLOWING DIAGNOSIS OF END STAGE 8260 05:22:52,800 --> 05:22:54,120 CANCER TWO MONTHS AGO. THIS IS 8261 05:22:54,120 --> 05:22:55,920 ALL I LEARNED FROM MISDAUGHTER. 8262 05:22:55,920 --> 05:22:58,800 AND I'M CONVEYING IT TO YOU. I 8263 05:22:58,800 --> 05:23:01,440 HOPE YOU WILL JOIN ME IN PRAYING 8264 05:23:01,440 --> 05:23:06,200 FOR HIM AND HIS FAMILY TO BE IN 8265 05:23:06,200 --> 05:23:07,400 PEACE AND HAVE A SMOOTH 8266 05:23:07,400 --> 05:23:08,640 TRANSITION. THANK YOU, VERY 8267 05:23:08,640 --> 05:23:17,360 MUCH. 8268 05:23:17,360 --> 05:23:22,200 >> I WOULD LIKE TO START THIS 8269 05:23:22,200 --> 05:23:23,880 SESSION 8270 05:23:23,880 --> 05:23:25,600 >> CAN YOU SPEAK UP? ON 8271 05:23:25,600 --> 05:23:27,960 INTEGRATED TECHNOLOGY ENHANCED 8272 05:23:27,960 --> 05:23:29,600 APPROACH TO TARGET SICKLE CELL 8273 05:23:29,600 --> 05:23:32,920 PAIN. I'M SURE BY NOW ALL OF YOU 8274 05:23:32,920 --> 05:23:40,160 ARE EXPERTS IN SICKLE CELL PAIN. 8275 05:23:40,160 --> 05:23:42,720 AFTER THIS TOWER D E FORCE, IT 8276 05:23:42,720 --> 05:23:44,760 IS TIME FOR DESERT. I WILL NOT 8277 05:23:44,760 --> 05:23:46,760 SAY IT IS THE LAST SESSION BUT 8278 05:23:46,760 --> 05:23:50,400 IT IS A SWEET SESSION. AND I 8279 05:23:50,400 --> 05:23:51,960 HOPE YOU CAN BEAR WITH ALL OF US 8280 05:23:51,960 --> 05:23:53,080 SITTING HERE SINCE THE MORNING 8281 05:23:53,080 --> 05:23:56,960 AND I THANK YOU FOR THAT. THIS 8282 05:23:56,960 --> 05:24:00,200 SESSION IS AIMED AT DISCOVERY 8283 05:24:00,200 --> 05:24:06,240 SCIENCE, SO YOU WILL HEAR 8284 05:24:06,240 --> 05:24:08,000 NASCENT RESEARCH WHICH NEED SOME 8285 05:24:08,000 --> 05:24:08,960 TRANSLATION. THAT IS WHY IT IS 8286 05:24:08,960 --> 05:24:09,960 VERY IMPORTANT TO BRING IT 8287 05:24:09,960 --> 05:24:14,120 FORTH. WHAT IS OUR GOAL HERE? 8288 05:24:14,120 --> 05:24:16,320 OUR GOAL IS TO DEVELOP IN 8289 05:24:16,320 --> 05:24:18,000 MECHANISM BASED APPROACH TO FILL 8290 05:24:18,000 --> 05:24:21,040 THE GAPS THAT WE HAVE HEARD 8291 05:24:21,040 --> 05:24:22,560 DURING THE LAST THREE DAYS IN 8292 05:24:22,560 --> 05:24:23,640 UNDERSTANDING AND TREATMENT OF 8293 05:24:23,640 --> 05:24:26,280 PAIN, AND WHAT WE ARE TARGETING 8294 05:24:26,280 --> 05:24:28,680 IS USING NON-PHARMACOLOGIC 8295 05:24:28,680 --> 05:24:32,200 INTERVENTIONS USING A 8296 05:24:32,200 --> 05:24:37,200 MULTI-DISCIPLINARY EXPERTISE, WE 8297 05:24:37,200 --> 05:24:39,840 HEARD ABOUT PERIPHERAL 8298 05:24:39,840 --> 05:24:43,040 MECHANISMS VERY ENLIGHTENING 8299 05:24:43,040 --> 05:24:46,440 TALKS BY AMANDA BRANDOW AND 8300 05:24:46,440 --> 05:24:47,920 CHERYL STUCKY AND COLLEAGUES IN 8301 05:24:47,920 --> 05:24:50,000 BASIC SCIENCE BUT THERE IS A 8302 05:24:50,000 --> 05:24:52,320 LACK IN UNDERSTANDING THIS 8303 05:24:52,320 --> 05:24:57,480 COMPLEX LITTLE ORGAN, THE BRAIN, 8304 05:24:57,480 --> 05:24:59,360 AND HOW THE NERVOUS SYSTEM USING 8305 05:24:59,360 --> 05:25:00,880 TOP DOWN NEUROMODULATION AND 8306 05:25:00,880 --> 05:25:05,240 PERCEPTION WHICH ACTUALLY VERY 8307 05:25:05,240 --> 05:25:07,200 ELEGANTLY PAT CARROLL TALKED 8308 05:25:07,200 --> 05:25:08,280 ABOUT, PERCEPTION, WHAT HAVE WE 8309 05:25:08,280 --> 05:25:12,000 DONE WITH IT? HOW CAN WE USE IT 8310 05:25:12,000 --> 05:25:14,200 OR DO WE KNOW IT? IT IS VERY 8311 05:25:14,200 --> 05:25:15,560 CONFUSING AS YOU SAID. SO WHAT 8312 05:25:15,560 --> 05:25:19,040 HE ARE TRYING TO DO IS DISSECT 8313 05:25:19,040 --> 05:25:20,760 OUT THIS WHOLE TOP DOWN 8314 05:25:20,760 --> 05:25:22,120 NEUROMODULATION, THE ROLE OF 8315 05:25:22,120 --> 05:25:25,800 BRAIN AND HOW DO WE TAME THE 8316 05:25:25,800 --> 05:25:27,240 BRAIN? WHAT IS THE ROLE OF 8317 05:25:27,240 --> 05:25:28,600 ENVIRONMENT IN THIS 8318 05:25:28,600 --> 05:25:30,960 NEUROMODULATION INCLUDING 8319 05:25:30,960 --> 05:25:32,160 NUTRITION, COMPANIONSHIP AND 8320 05:25:32,160 --> 05:25:36,120 SLEEP? AND EGG GANTLY CLAUDIA 8321 05:25:36,120 --> 05:25:38,680 MORRIS HAS -- ELEGANTLY HAS 8322 05:25:38,680 --> 05:25:40,440 SHOWN NUTRITION FROM ARGININE 8323 05:25:40,440 --> 05:25:42,600 PLAYS A MAJOR ROLE IN PAIN. WE 8324 05:25:42,600 --> 05:25:44,720 HAVE BEEN TALKING ABOUT CHRONIC 8325 05:25:44,720 --> 05:25:48,200 PAIN QUITE A LOT. BUT WE 8326 05:25:48,200 --> 05:25:52,840 PROBABLY NEED TO KNOW CAN WE 8327 05:25:52,840 --> 05:25:56,280 PREDICT VOC? THIS IS THE BIGGEST 8328 05:25:56,280 --> 05:25:57,200 IRONY OF THIS DISEASE 8329 05:25:57,200 --> 05:25:58,920 SPECIFICALLY THAT IS 8330 05:25:58,920 --> 05:26:02,320 UNPREDICTABLE. THIS IS WHERE WE 8331 05:26:02,320 --> 05:26:04,280 BROUGHT EXPERTISE TOGETHER FROM 8332 05:26:04,280 --> 05:26:05,920 LEADING EXPERTS IN ENGINEERING 8333 05:26:05,920 --> 05:26:11,000 AND PHARMACOLOGIC INTERVENTIONS, 8334 05:26:11,000 --> 05:26:12,240 AND LITTLE ME TO BRING TO YOU 8335 05:26:12,240 --> 05:26:13,800 OUR THOUGHTS AND WORK OF MANY 8336 05:26:13,800 --> 05:26:18,160 YEARS. TOM COATS HAS BEEN 8337 05:26:18,160 --> 05:26:20,400 SHOWING FOR FEW YEARS NOW THAT 8338 05:26:20,400 --> 05:26:23,080 HOW THE CENTRAL NERVOUS SYSTEM 8339 05:26:23,080 --> 05:26:26,520 OR SYMPATHETIC NERVOUS SYSTEM 8340 05:26:26,520 --> 05:26:29,000 MODULATE PERIPHERAL ACTIVITY BY 8341 05:26:29,000 --> 05:26:30,520 WHEN HE JUST TOLD THE PATIENTS 8342 05:26:30,520 --> 05:26:33,880 THAT YOU WILL FEEL PAIN THEY 8343 05:26:33,880 --> 05:26:36,400 STARTED FEELING PAIN BEFORE THEY 8344 05:26:36,400 --> 05:26:39,600 INDUCED PAIN. SO THIS TELLS US 8345 05:26:39,600 --> 05:26:44,160 PERCEPTION IS A BIG MODULATOR OF 8346 05:26:44,160 --> 05:26:50,720 PAIN AND PERHAPS AS PAT SAID IN 8347 05:26:50,720 --> 05:26:52,800 HIS COMMENTS, FROM THE NERVOUS 8348 05:26:52,800 --> 05:26:53,720 SYSTEM FROM THE CENTRAL ACTIVITY 8349 05:26:53,720 --> 05:26:55,360 TO THE PERIPHERAL AND FROM THE 8350 05:26:55,360 --> 05:26:57,360 PERIPHERAL TO THE CENTRAL, THIS 8351 05:26:57,360 --> 05:26:59,200 IS WHAT WE ARE GOING TO SHOW 8352 05:26:59,200 --> 05:27:02,520 TODAY. SO WITH THIS I WOULD HAND 8353 05:27:02,520 --> 05:27:08,440 OVER THE FLOOR TO DR. KIMBERLEI 8354 05:27:08,440 --> 05:27:10,600 RICHARDSON, THE WHOLE CHAIR OF 8355 05:27:10,600 --> 05:27:13,000 THE SESSION, BUT BEFORE THAT, I 8356 05:27:13,000 --> 05:27:17,200 WOULD ALSO LIKE TO INTRODUCE DR. 8357 05:27:17,200 --> 05:27:20,760 HE WHO WILL GIVE THE FIRST TALK. 8358 05:27:20,760 --> 05:27:22,920 DR. HE ARE YOU READY? 8359 05:27:22,920 --> 05:27:24,600 >> YES. 8360 05:27:24,600 --> 05:27:31,000 >> OKAY. I WILL STOP SHARING MY 8361 05:27:31,000 --> 05:27:32,760 SLIDES. DR. HE IS PROFESSOR OF 8362 05:27:32,760 --> 05:27:37,400 BIOMEDICAL ENGINEERING AND 8363 05:27:37,400 --> 05:27:39,320 NEUROSCIENCE AT CARNEGIE MELLON 8364 05:27:39,320 --> 05:27:41,320 UNIVERSITY IN PITTSBURGH. PRIOR 8365 05:27:41,320 --> 05:27:43,200 TO JOINING CARNEGIE MELLON HE 8366 05:27:43,200 --> 05:27:46,720 WAS THE DIRECTOR OF FOUNDING 8367 05:27:46,720 --> 05:27:50,320 DIRECTOR OF THE INSTITUTE FOR 8368 05:27:50,320 --> 05:27:51,680 ENGINEERING MEDICINE UNIVERSITY 8369 05:27:51,680 --> 05:27:53,680 OF MINNESOTA AND ORGANIZATION ON 8370 05:27:53,680 --> 05:27:56,640 STEROIDS FOR RESEARCH. HE HAS 8371 05:27:56,640 --> 05:27:59,640 RESEARCH EXPERTISE IN NEURAL AND 8372 05:27:59,640 --> 05:28:02,800 -- INCLUDE -- ENGINEERING 8373 05:28:02,800 --> 05:28:06,000 INCLUDING NON-MODULATION 8374 05:28:06,000 --> 05:28:08,440 ULTRASOUND NEUROMODULATION. AND 8375 05:28:08,440 --> 05:28:11,760 EEG. HE DEVELOPS NON-TECHNIQUES 8376 05:28:11,760 --> 05:28:14,080 TO QUANTIFY SICKLE CELL PAIN AND 8377 05:28:14,080 --> 05:28:15,200 INDUCE OR SUPPRESS SICKLE CELL 8378 05:28:15,200 --> 05:28:17,200 PAIN USING FOCUSED ULTRASOUND 8379 05:28:17,200 --> 05:28:22,760 NEUROMODULATION. AS MULTIPLE PI 8380 05:28:22,760 --> 05:28:26,360 ON NHLBI EXCELLENCE RESEARCH 8381 05:28:26,360 --> 05:28:27,600 HUMAN -- HIS LABORATORY 8382 05:28:27,600 --> 05:28:30,000 ESTABLISHED THE POTENTIAL OF 8383 05:28:30,000 --> 05:28:31,840 QUANTITATIVE EEG FOR 8384 05:28:31,840 --> 05:28:35,040 QUANTITATION OF PAIN IN SICKLE 8385 05:28:35,040 --> 05:28:37,600 CELL DISEASE. WOULD BE GLAD TO 8386 05:28:37,600 --> 05:28:39,600 HEAR IT IS CLINICALLY, IT IS 8387 05:28:39,600 --> 05:28:41,560 UNDER CLINICAL TRANSLATION BY 8388 05:28:41,560 --> 05:28:45,080 SOME INDUSTRIES NOT BY HIM. HE 8389 05:28:45,080 --> 05:28:48,480 IS ALSO A FUNDED INVESTIGATOR OF 8390 05:28:48,480 --> 05:28:49,800 THE HEEL INITIATIVE ON WHAT HE'S 8391 05:28:49,800 --> 05:28:52,680 GOING TO PRESENT TODAY. DR. HE, 8392 05:28:52,680 --> 05:28:54,000 THANK YOU VERY MUCH FOR AGREEING 8393 05:28:54,000 --> 05:28:55,640 TO ACCEPT OUR INVITATION TO 8394 05:28:55,640 --> 05:28:58,640 SPEAK. 8395 05:28:58,640 --> 05:29:01,400 >> THANK YOU, DR. GUPTA. THANK 8396 05:29:01,400 --> 05:29:05,680 YOU FOR THE ORGANIZER. IT IS A 8397 05:29:05,680 --> 05:29:07,680 PLEASURE TO HAVE THIS 8398 05:29:07,680 --> 05:29:11,200 OPPORTUNITY TO PRESENT THE WORK 8399 05:29:11,200 --> 05:29:15,280 THAT AS YOU CAN SEE FROM THIS 8400 05:29:15,280 --> 05:29:18,120 SLIDE PAGE. THE WORK THAT IS A 8401 05:29:18,120 --> 05:29:20,320 CLOSE COLLABORATION BETWEEN MY 8402 05:29:20,320 --> 05:29:24,280 LAB AND CARNEGIE MELLON 8403 05:29:24,280 --> 05:29:27,560 UNIVERSITY TO DEVELOP FOCUS 8404 05:29:27,560 --> 05:29:31,000 ULTRASOUND NEUROMODULATION IN 8405 05:29:31,000 --> 05:29:34,400 DR. GUPTA'S LAB IN CALIFORNIA 8406 05:29:34,400 --> 05:29:35,840 WHERE HUMAN SICKLE MICE MODEL 8407 05:29:35,840 --> 05:29:39,520 WAS DEVELOPED AND PRODUCED HAS 8408 05:29:39,520 --> 05:29:43,200 SHIFTED TO PITTSBURGH AND WE 8409 05:29:43,200 --> 05:29:47,600 TESTED OUR DEVICE AND THAT -- SO 8410 05:29:47,600 --> 05:29:50,560 MY PRESENTATION WILL INCLUDE TWO 8411 05:29:50,560 --> 05:29:54,400 PART, ONE IS SOME OF THE GENERAL 8412 05:29:54,400 --> 05:29:56,280 INTRODUCTION UNIQUE 8413 05:29:56,280 --> 05:29:57,200 NEUROMODULATION TECHNOLOGY, 8414 05:29:57,200 --> 05:29:59,720 USING FOLKS ULTRA -- FOCUSED 8415 05:29:59,720 --> 05:30:01,920 ULTRASOUND, THEN I WILL PRESENT 8416 05:30:01,920 --> 05:30:06,200 OUR LATEST UNPUBLISHED RESULTS, 8417 05:30:06,200 --> 05:30:10,720 TO SHOW FOLKS ARE ULTRASOUND 8418 05:30:10,720 --> 05:30:11,320 NON-INVASIVELY SUPPRESS SICKLE 8419 05:30:11,320 --> 05:30:15,720 CELL PAIN IN P HUMAN MICE AND 8420 05:30:15,720 --> 05:30:20,680 MICE MODEL. AS GENERAL INTRO, I 8421 05:30:20,680 --> 05:30:23,440 WANT TO REITERATE MANY THINGS P 8422 05:30:23,440 --> 05:30:25,800 BEING SAID, CHRONIC PAIN WHICH 8423 05:30:25,800 --> 05:30:29,000 ARE RELEVANT TO SICKLE PAIN AND 8424 05:30:29,000 --> 05:30:31,720 AFFECTS A SIGNIFICANT PORTION OF 8425 05:30:31,720 --> 05:30:33,440 GENERAL POPULATION. AS YOU CAN 8426 05:30:33,440 --> 05:30:38,080 SEE THIS SLIDE HERE, THE CURRENT 8427 05:30:38,080 --> 05:30:41,080 PAIN TREATMENT METHOD INCLUDES 8428 05:30:41,080 --> 05:30:44,400 PHARMACOLOGY APPROACH OR NEURAL 8429 05:30:44,400 --> 05:30:47,040 MODULATION APPROACH, 8430 05:30:47,040 --> 05:30:48,240 NEUROMODULATION APPROACH 8431 05:30:48,240 --> 05:30:49,480 NEUROINVASIVE APPROACH SUCH AS 8432 05:30:49,480 --> 05:30:53,440 DEEP BRAIN STIMULATION, AND THE 8433 05:30:53,440 --> 05:30:56,520 MOTOR CORTEX STIMULATION SPINAL 8434 05:30:56,520 --> 05:30:58,640 CORD STIMULATION ALSO. THERE IS 8435 05:30:58,640 --> 05:31:01,320 A CLASS OF NON-INVASIVE 8436 05:31:01,320 --> 05:31:03,400 NEUROMODULATION TECHNOLOGY, 8437 05:31:03,400 --> 05:31:07,680 INCLUDING THE TRANSCRANIAL 8438 05:31:07,680 --> 05:31:09,400 DIRECT STIMULATION MAGNETIC 8439 05:31:09,400 --> 05:31:11,840 STIMULATION AND RECENTLY 8440 05:31:11,840 --> 05:31:14,040 TRANSCRANIAL FOCUSED ULTRASOUND 8441 05:31:14,040 --> 05:31:17,520 STIMULATION ARE BEING DEVELOPED 8442 05:31:17,520 --> 05:31:21,720 FOR THIS PURPOSE. THIS IS SCD 8443 05:31:21,720 --> 05:31:26,680 MEETING AND WE KNOW THIS IS A 8444 05:31:26,680 --> 05:31:28,200 CHALLENGE ONE COMMON HERE IS 8445 05:31:28,200 --> 05:31:31,400 THAT THE SICKLE PAIN, IT IS A 8446 05:31:31,400 --> 05:31:34,200 VERY WIDESPREAD SOMETIMES 8447 05:31:34,200 --> 05:31:35,800 UNPREDICTABLE PERIPHERAL PAIN. 8448 05:31:35,800 --> 05:31:37,680 YOU DO NOT KNOW WHICH PART OF 8449 05:31:37,680 --> 05:31:41,720 THE PERIPHERAL SYSTEM IS GOING 8450 05:31:41,720 --> 05:31:44,040 TO EXHIBIT IN PAIN. SO 8451 05:31:44,040 --> 05:31:48,360 MODULATING CENTRAL NERVOUS 8452 05:31:48,360 --> 05:31:50,240 SYSTEM AND TO SUPPRESS THE PAIN 8453 05:31:50,240 --> 05:31:52,600 MANAGE THE PAIN, REPRESENT A 8454 05:31:52,600 --> 05:31:57,200 IMPORTANT APPROACH. AS DR. 8455 05:31:57,200 --> 05:32:01,400 GUPTA MENTIONED IN PREVIOUSLY 8456 05:32:01,400 --> 05:32:11,120 FUNDED NIH PROGRAM GRANT, WE USE 8457 05:32:11,120 --> 05:32:14,480 EEG AND FUNCTIONAL MRI TO 8458 05:32:14,480 --> 05:32:16,640 CONDUCT NEUROIMAGING IN CONTROL, 8459 05:32:16,640 --> 05:32:18,120 HEALTHY HUMAN SUBJECT AND SSCD 8460 05:32:18,120 --> 05:32:24,400 PATIENT. AFTER WE FOUND THERE 8461 05:32:24,400 --> 05:32:26,320 IS BRAIN ACTIVATION GENERATED 8462 05:32:26,320 --> 05:32:28,040 THAT COULD BE OBSERVED IN THE 8463 05:32:28,040 --> 05:32:33,640 ALPHA REGION AND BETA REGION, WE 8464 05:32:33,640 --> 05:32:35,400 LOOK AT CONTRAST BETWEEN SICKLE 8465 05:32:35,400 --> 05:32:37,000 PATIENT AND HEALTHY PATIENT WE 8466 05:32:37,000 --> 05:32:40,080 CAN IDENTIFY CERTAIN BRAIN 8467 05:32:40,080 --> 05:32:47,600 TARGET INCLUDING ACC INSULA AND 8468 05:32:47,600 --> 05:32:49,480 THALAMUS. FROM THIS IMAGING 8469 05:32:49,480 --> 05:32:52,600 RESEARCH PROVIDE INFORMATION TO 8470 05:32:52,600 --> 05:32:55,720 HELP US TO DETERMINE WHERE FOCUS 8471 05:32:55,720 --> 05:32:56,760 ULTRASOUND STIMULATION CAN BE 8472 05:32:56,760 --> 05:33:02,520 DIRECTED. A LITTLE BIT INTRO 8473 05:33:02,520 --> 05:33:04,200 ABOUT NEUROMODULATION THOUGH WE 8474 05:33:04,200 --> 05:33:07,360 ALL I ASSUME MOST OF US KNOW 8475 05:33:07,360 --> 05:33:11,560 ALREADY, THE NEUROMODULATION 8476 05:33:11,560 --> 05:33:12,640 ESSENTIALLY INVOLVE DELIVERING 8477 05:33:12,640 --> 05:33:16,400 IF AS ICAL OR CHEMICAL ENERGY 8478 05:33:16,400 --> 05:33:20,000 INTO NERVOUS SYSTEM. IN 8479 05:33:20,000 --> 05:33:21,280 PARTICULAR IN THIS PRESENTATION 8480 05:33:21,280 --> 05:33:22,920 WHERE WE ARE FOCUSING ON BRAIN 8481 05:33:22,920 --> 05:33:25,080 SO IT WOULD BE FOR EXAMPLE 8482 05:33:25,080 --> 05:33:27,480 INVASIVE APPROACH INCLUDING DEEP 8483 05:33:27,480 --> 05:33:30,480 BRAIN STIMULATION OR CORTICO 8484 05:33:30,480 --> 05:33:34,120 STIMULATION AT MOTOR CORTEX OR 8485 05:33:34,120 --> 05:33:37,600 HERE NON-INVASIVE APPROACH 8486 05:33:37,600 --> 05:33:39,960 INCLUDING RAINS CRANIAL DIRECTED 8487 05:33:39,960 --> 05:33:41,440 STIMULATION TRANSCRANIAL 8488 05:33:41,440 --> 05:33:44,280 MAGNETIC SIMULATION AND 8489 05:33:44,280 --> 05:33:45,840 TRANSCRANIAL FOCUS ULTRASOUND 8490 05:33:45,840 --> 05:33:48,720 STIMULATION. HERE IS A PICTURE 8491 05:33:48,720 --> 05:33:52,400 TAKEN FROM A REVIEW ARTICLE 8492 05:33:52,400 --> 05:33:54,320 ILLUSTRATING VARIOUS APPROACH 8493 05:33:54,320 --> 05:33:58,920 INCLUDING DRUG DELIVERY AND 8494 05:33:58,920 --> 05:34:02,240 CERTAINLY INVASIVE LIKE 8495 05:34:02,240 --> 05:34:02,880 OPTOGENETICS KY CANNOT BE 8496 05:34:02,880 --> 05:34:04,120 APPLIED TO HUMAN TRANSLATION BY 8497 05:34:04,120 --> 05:34:07,760 NOW. HERE ARE GREEN COLOR 8498 05:34:07,760 --> 05:34:10,280 ILLUSTRATING VARIOUS 8499 05:34:10,280 --> 05:34:12,800 NON-INVASIVE NEUROMODULATION, 8500 05:34:12,800 --> 05:34:15,240 BRAIN NEUROMODULATION APPROACH, 8501 05:34:15,240 --> 05:34:17,080 HERE IS SPATIAL RESERVATION, 8502 05:34:17,080 --> 05:34:19,080 TEMPORAL RESOLUTION AN FOCUS 8503 05:34:19,080 --> 05:34:21,840 ULTRASOUND NEUROMODULATION HAS 8504 05:34:21,840 --> 05:34:28,400 PARTICULAR UNIQUE AND PROMISE 8505 05:34:28,400 --> 05:34:30,160 WHICH OFFER HIGH SPATIAL HIGH 8506 05:34:30,160 --> 05:34:32,280 TEMPORAL RESOLUTION FOR 8507 05:34:32,280 --> 05:34:34,920 NEUROMODULATION. WHAT EXACTLY 8508 05:34:34,920 --> 05:34:38,680 IS THE FOCUS ULTRASOUND 8509 05:34:38,680 --> 05:34:39,800 NEUROMODULATION? PARTICULARLY 8510 05:34:39,800 --> 05:34:42,080 TALKING TRANSCRANIAL. HERE THIS 8511 05:34:42,080 --> 05:34:44,040 IS ILLUSTRATION YOU CAN SEE 8512 05:34:44,040 --> 05:34:48,400 THERE COULD BE A MULTIPLE 8513 05:34:48,400 --> 05:34:51,720 ULTRASOUND TRANSDUCER, THAT CAN 8514 05:34:51,720 --> 05:34:55,000 DELIVER PHYSICAL ACOUSTIC ENERGY 8515 05:34:55,000 --> 05:34:58,960 WHICH GENERATE ESSENTIALLY 8516 05:34:58,960 --> 05:35:00,200 MECHANIC ALIBI OPERATION WAVE 8517 05:35:00,200 --> 05:35:02,800 THAT CAN GO TO ANY SPOT INSIDE 8518 05:35:02,800 --> 05:35:06,000 THE BRAIN, MEANING IT HAS DEEP 8519 05:35:06,000 --> 05:35:08,800 BRAIN PENETRATION, IT HAS HIGH 8520 05:35:08,800 --> 05:35:09,720 SPATIAL RESOLUTION, AND ALSO 8521 05:35:09,720 --> 05:35:13,360 HIGH TEMPORAL RESOLUTION, FOR 8522 05:35:13,360 --> 05:35:16,320 VARIOUS PURPOSE. THIS PICTURE IS 8523 05:35:16,320 --> 05:35:18,920 TAKEN FROM REVIEW PAPER WE 8524 05:35:18,920 --> 05:35:20,960 PUBLISH ABOUT FOCUS ULTRASOUND 8525 05:35:20,960 --> 05:35:25,480 NEUROMODULATION TO TREAT THE 8526 05:35:25,480 --> 05:35:28,000 PAIN. WHAT I MENTION FROM 8527 05:35:28,000 --> 05:35:30,400 NEUROIMAGING STUDY WHICH KNOW 8528 05:35:30,400 --> 05:35:31,920 CERTAIN TARGET NEUROSIXTY 8529 05:35:31,920 --> 05:35:34,160 CIRCUIT ARE INVOLVED IN PAIN 8530 05:35:34,160 --> 05:35:38,200 PROCESSING SO THAT IS ONE OTHER 8531 05:35:38,200 --> 05:35:42,400 -- A TARGETING AND SPOT THAT WE 8532 05:35:42,400 --> 05:35:46,600 STARTED OUR INVESTIGATION. ONE 8533 05:35:46,600 --> 05:35:48,600 QUESTION, WHAT WOULD BE THE 8534 05:35:48,600 --> 05:35:51,560 MECHANISM, WHY FOCUS ULTRASOUND 8535 05:35:51,560 --> 05:35:52,680 NEUROMODULATION WOULD WORK? 8536 05:35:52,680 --> 05:35:55,280 MULTIPLE HYPOTHESIS ABOUT WHAT 8537 05:35:55,280 --> 05:35:58,200 WOULD BE POSSIBLE MECHANISM 8538 05:35:58,200 --> 05:36:03,160 INCLUDING MEME BRAIN CAPACITY 8539 05:36:03,160 --> 05:36:05,800 AND MECHANOSENSITIVE ION 8540 05:36:05,800 --> 05:36:11,520 CHANNEL, EFFECTS MULTIPLE. OUR 8541 05:36:11,520 --> 05:36:13,320 GROUP AND THE (INAUDIBLE) WE 8542 05:36:13,320 --> 05:36:17,320 DIDN'T PROPOSE IT BUT WE 8543 05:36:17,320 --> 05:36:20,400 HYPOTHESIZE ACOUSTIC RADIATION 8544 05:36:20,400 --> 05:36:22,000 FORCE ACTING ON THE 8545 05:36:22,000 --> 05:36:25,920 MECHANOSENSITIVE ION CHANNEL 8546 05:36:25,920 --> 05:36:27,560 WOULD BE IMPORTANT MECHANISM WHY 8547 05:36:27,560 --> 05:36:30,440 FOCUS ULTRASOUND WOULD WORK. SO 8548 05:36:30,440 --> 05:36:32,560 I KNOW THE EQUATION IS TOO 8549 05:36:32,560 --> 05:36:35,560 DETAIL, I WANT TO POINT OUT 8550 05:36:35,560 --> 05:36:38,120 ACOUSTIC RADIATION FORCE CAN BE 8551 05:36:38,120 --> 05:36:41,800 DERIVED AS PROPORTIONAL TO A 8552 05:36:41,800 --> 05:36:44,640 IMPORTANT ULTRASOUND PARAMETER 8553 05:36:44,640 --> 05:36:45,960 CALLED PULSE REPETITION 8554 05:36:45,960 --> 05:36:50,800 FREQUENCY. ILLUSTRATE IN THIS 8555 05:36:50,800 --> 05:36:51,880 CARTOON HERE. SO NOW WE HAVE 8556 05:36:51,880 --> 05:36:54,160 BEEN LOOKING INTO THIS WHETHER 8557 05:36:54,160 --> 05:36:57,680 WE CAN WOULD USE THIS ACOUSTIC 8558 05:36:57,680 --> 05:37:02,000 RADIATION FORCE MODULATION TO 8559 05:37:02,000 --> 05:37:02,960 REIT PAIN. IN PARTICULAR SICKLE 8560 05:37:02,960 --> 05:37:09,240 PAIN SO THAT IS THE FOCUS WE ARE 8561 05:37:09,240 --> 05:37:11,240 LOOK INK TO. WE CONDUCT BASIC 8562 05:37:11,240 --> 05:37:13,760 RESEARCH HERE ILLUSTRATING IN 8563 05:37:13,760 --> 05:37:16,600 THE RODENT MODEL AND WITH 8564 05:37:16,600 --> 05:37:18,000 MULTI-ELECTRIC ARRAY O TO RECORD 8565 05:37:18,000 --> 05:37:21,040 YOU CAN SEE THE MULTI-UNIT 8566 05:37:21,040 --> 05:37:22,720 ACTIVITY ONCE THESE FOCUS 8567 05:37:22,720 --> 05:37:26,000 ULTRASOUND STIMULATION AT THE 8568 05:37:26,000 --> 05:37:27,800 SOMATOSENSORY CORTEX. WITH ALL 8569 05:37:27,800 --> 05:37:30,400 THE VARIOUS SHAM CONTROL, WE DID 8570 05:37:30,400 --> 05:37:36,560 NOT OBSERVE THIS. ALSO WE SOUGHT 8571 05:37:36,560 --> 05:37:38,600 OUT NEURON BASED ON WAVE FORM 8572 05:37:38,600 --> 05:37:41,400 ACTION POTENTIAL TO DIVIDE INTO 8573 05:37:41,400 --> 05:37:48,960 REGULAR SPIKING AND THE FASTEST 8574 05:37:48,960 --> 05:37:52,400 SPIKING OUT, THERE IS CLEAR 8575 05:37:52,400 --> 05:37:54,400 CORRESPONDENCE AND ONCE FOLKS 8576 05:37:54,400 --> 05:37:56,480 ULTRA -- FOCUS ULTRASOUND 8577 05:37:56,480 --> 05:37:57,600 STIMULATION THE NEURAL SPIKE 8578 05:37:57,600 --> 05:38:01,600 INCREASE WITH THIS PRF PARAMETER 8579 05:38:01,600 --> 05:38:03,280 INCREASE AND YOU CAN SEE 8580 05:38:03,280 --> 05:38:06,200 NEUROSPIKE IN FIRST INCREASE. IN 8581 05:38:06,200 --> 05:38:09,120 THE FASTEST SPIKING UNIT WE DID 8582 05:38:09,120 --> 05:38:12,600 NOT OBSERVE THIS PHENOMENON. 8583 05:38:12,600 --> 05:38:16,160 AFTER SPOTTING A GROUP OF RATS, 8584 05:38:16,160 --> 05:38:21,200 WE FOUND THERE IS A VERY 8585 05:38:21,200 --> 05:38:23,880 INTERESTING THAT NEUROTYPE 8586 05:38:23,880 --> 05:38:26,280 SPECIFIC RESPONSE TO FOCUS 8587 05:38:26,280 --> 05:38:27,000 ULTRASOUND NEUROMODULATION. THIS 8588 05:38:27,000 --> 05:38:30,920 IS IF YOU CHANGE THE PULSE 8589 05:38:30,920 --> 05:38:32,600 REPETITION FREAK CITY NEURAL 8590 05:38:32,600 --> 05:38:35,400 SPIKE FIRING RATE WILL CHANGE 8591 05:38:35,400 --> 05:38:38,120 BUT IN INHIBITORY NEURONS YOU DO 8592 05:38:38,120 --> 05:38:41,840 NOT OBSERVE THIS PHENOMENON. WE 8593 05:38:41,840 --> 05:38:44,040 FURTHER USE OPTOGENETICS AND TO 8594 05:38:44,040 --> 05:38:47,040 STUDY THIS EFFECT IN TRANSGENIC 8595 05:38:47,040 --> 05:38:51,800 MICE AND SIMILARLY FOUND IN A PV 8596 05:38:51,800 --> 05:38:55,120 NEURON, CAM K 2 ALPHA NEURON, 8597 05:38:55,120 --> 05:38:57,200 THERE IS A NEURON TYPE SPECIFIC 8598 05:38:57,200 --> 05:39:00,560 EFFECT OF FOCUS ULTRASOUND. SO 8599 05:39:00,560 --> 05:39:01,920 NOW COME TO SICKLE CELL PAIN 8600 05:39:01,920 --> 05:39:08,360 MANAGEMENT. WE USE THIS 8601 05:39:08,360 --> 05:39:11,240 HUMANIZED SICKLE CELL MICE MODEL 8602 05:39:11,240 --> 05:39:14,000 DR. GUPTA DEVELOP BUT THIS IS -- 8603 05:39:14,000 --> 05:39:15,000 MICE MODELS IS VERY SMALL. IN 8604 05:39:15,000 --> 05:39:17,000 ORDER TO HAVE THE SPECIFICITY 8605 05:39:17,000 --> 05:39:20,840 AND THE RESOLUTION WE HAVE 8606 05:39:20,840 --> 05:39:23,200 DEVELOPED A NOVEL ULTRASOUND 8607 05:39:23,200 --> 05:39:28,120 DEVICE ILLUSTRATE HERE WHICH AS 8608 05:39:28,120 --> 05:39:29,880 SHOWN ON PANEL B YOU CAN SEE 8609 05:39:29,880 --> 05:39:31,200 FROM HERE TO HERE IS ONE 8610 05:39:31,200 --> 05:39:37,160 MILLIMETER. OUR DEVICE AS A SUB 8611 05:39:37,160 --> 05:39:39,400 MILLIMETER LATERAL SPATIAL 8612 05:39:39,400 --> 05:39:43,000 SPECIFICITY. WHICH TO OUR 8613 05:39:43,000 --> 05:39:46,200 KNOWLEDGE THIS BIT -- ALL THE 8614 05:39:46,200 --> 05:39:48,600 EXISTING NON-INVASIVE NEURAL 8615 05:39:48,600 --> 05:39:53,200 MODULATION TECHNOLOGY IN TERMS 8616 05:39:53,200 --> 05:39:55,120 OF SPATIAL SPECIFICITY. THAT'S 8617 05:39:55,120 --> 05:39:57,800 ONE OF THE MERIT OF THE FOCUS 8618 05:39:57,800 --> 05:40:00,600 ULTRASOUND. WE CONDUCTED 8619 05:40:00,600 --> 05:40:02,160 EXPERIMENTATION AND THERE IN A 8620 05:40:02,160 --> 05:40:05,280 NUMBER OF EXPERIMENTAL MICE, AND 8621 05:40:05,280 --> 05:40:07,800 WE DID TWO EXPERIMENT. BEHAVIOR 8622 05:40:07,800 --> 05:40:12,320 TEST, ONE IS HOT PLATE TEST, TO 8623 05:40:12,320 --> 05:40:14,680 SEE THAT WHAT PAIN SENSITIVITY, 8624 05:40:14,680 --> 05:40:17,840 IN THIS EXPERIMENTAL MICE, 8625 05:40:17,840 --> 05:40:19,160 ANOTHER IS ROUTE OF PASSAGE YOU 8626 05:40:19,160 --> 05:40:22,160 SEE INTO THE MOTOR COORDINATION 8627 05:40:22,160 --> 05:40:24,440 AND THEN BALANCE WOULD BE -- BY 8628 05:40:24,440 --> 05:40:27,920 FOCUS ULTRASOUND STIMULATION. SO 8629 05:40:27,920 --> 05:40:29,800 WE DID ACTIVE CONTROL WITH OTHER 8630 05:40:29,800 --> 05:40:31,480 FOLKS ULTRA SOWN, SHAM CONTROL, 8631 05:40:31,480 --> 05:40:34,240 THAT FOCUS ULTRASOUND 8632 05:40:34,240 --> 05:40:37,800 STIMULATING DIFFERENT SPOT AND 8633 05:40:37,800 --> 05:40:39,800 THE TFAS SIMULATION, ULTRASOUND 8634 05:40:39,800 --> 05:40:40,600 STIMULATION AT SOME OTHER -- 8635 05:40:40,600 --> 05:40:43,480 >> TWO MINUTE WARNING. 8636 05:40:43,480 --> 05:40:47,640 >> THANK YOU. HERE IS THE 8637 05:40:47,640 --> 05:40:52,200 RESULT. FIRST WE TESTED THE Y -- 8638 05:40:52,200 --> 05:40:54,480 WILD TYPE MICE, YOU CAN SEE HERE 8639 05:40:54,480 --> 05:40:56,840 COMPARE WITH BASELINE THE RED 8640 05:40:56,840 --> 05:41:00,200 COLOR ILLUSTRATING THIS DECREASE 8641 05:41:00,200 --> 05:41:02,680 PAIN SENSITIVITY AND AFTER THREE 8642 05:41:02,680 --> 05:41:06,800 MINUTE OR AGO MINUTE WILL IS 8643 05:41:06,800 --> 05:41:07,440 STATISTICALLY SIGNIFICANT 8644 05:41:07,440 --> 05:41:11,000 DECREASE IN PAIN SENSITIVITY IN 8645 05:41:11,000 --> 05:41:13,800 THIS EXPERIMENTAL MICE. NEXT WE 8646 05:41:13,800 --> 05:41:18,720 LOOK INTO SICKLE CELL MICE. 8647 05:41:18,720 --> 05:41:20,840 SIMILARLY, SIMILAR TO WILD TYPE 8648 05:41:20,840 --> 05:41:22,080 MICE, THREE MINUTE OR EIGHT 8649 05:41:22,080 --> 05:41:25,800 MINUTE AFTER STIMULATION BY 8650 05:41:25,800 --> 05:41:30,400 USING LOW PRF, IN A SENSE IS 8651 05:41:30,400 --> 05:41:34,120 WITH LOW PULSE REPETITION 8652 05:41:34,120 --> 05:41:35,560 FREQUENCY WE FOUND WE CAN 8653 05:41:35,560 --> 05:41:38,200 SUPPRESS PAIN SENSITIVITY IN 8654 05:41:38,200 --> 05:41:40,760 SICKLE MICE. VERY INTERESTINGLY 8655 05:41:40,760 --> 05:41:44,800 IF WE USE VERY HIGH PRF IN THE 8656 05:41:44,800 --> 05:41:46,560 SAME SICKLE CELL MICE, WE FOUND 8657 05:41:46,560 --> 05:41:50,560 THIS PAIN SENSITIVITY ACTUALLY 8658 05:41:50,560 --> 05:41:53,280 WAS INCREASE. WHICH SUGGEST A 8659 05:41:53,280 --> 05:41:55,600 BIDIRECTIONAL MODULATION OF PAIN 8660 05:41:55,600 --> 05:41:58,200 SENSITIVITY BY USING FOCUS 8661 05:41:58,200 --> 05:42:01,760 ULTRASOUND THROUGH MODULATING 8662 05:42:01,760 --> 05:42:02,880 PRF PARAMETER AND ALSO SUGGEST 8663 05:42:02,880 --> 05:42:06,280 WE NEED TO BE CAREFUL IN TERMS 8664 05:42:06,280 --> 05:42:09,600 OF ACTUALLY CONDUCT CLINIC 8665 05:42:09,600 --> 05:42:11,400 TRANSLATION IN PATIENT. WE LOOK 8666 05:42:11,400 --> 05:42:14,680 INTO INSULA STIMULATION, IN THIS 8667 05:42:14,680 --> 05:42:16,800 CASE WE NOT JUST STAY AT THREE 8668 05:42:16,800 --> 05:42:19,080 MINUTE 8 MINUTE BUT WE ALSO 8669 05:42:19,080 --> 05:42:20,720 EXTENDS TO 13 MINUTES AND 60 8670 05:42:20,720 --> 05:42:23,480 MINUTES POST STIMULATION. AND 8671 05:42:23,480 --> 05:42:27,400 WE FOUND THAT USING LOW PRF, 8672 05:42:27,400 --> 05:42:31,320 THERE IS SIGNIFICANT DECREASE OF 8673 05:42:31,320 --> 05:42:36,120 THE PAIN SENSITIVITY, UP TO 30 8674 05:42:36,120 --> 05:42:38,120 MINUTES, AFTER STIMULATION. I 8675 05:42:38,120 --> 05:42:40,760 KNOW MY TIME IS COMING UP SO TO 8676 05:42:40,760 --> 05:42:43,760 SUMMARIZE WHAT WE FOUND. A 8677 05:42:43,760 --> 05:42:45,760 SINGLE SESSION OF FOCUS 8678 05:42:45,760 --> 05:42:47,680 ULTRASOUND STIMULATION AT 8679 05:42:47,680 --> 05:42:50,920 SPECIFIC PAIN PROCESSING 8680 05:42:50,920 --> 05:42:53,200 CIRCUITS AND THE RESULT IN 8681 05:42:53,200 --> 05:42:55,080 SIGNIFICANT CHANGES IN PAIN 8682 05:42:55,080 --> 05:43:03,000 RELATED BEHAVIOR EVOKED BY -- 8683 05:43:03,000 --> 05:43:05,240 >> WE LOST THE VOICE. 8684 05:43:05,240 --> 05:43:11,000 >> SORRY. AND IN SICKLE MICE. 8685 05:43:11,000 --> 05:43:15,200 SHORT TERM ATTENUATION OF 8686 05:43:15,200 --> 05:43:18,960 HYPERALGESIA IN FEMALE SICKLE 8687 05:43:18,960 --> 05:43:22,680 MICE AND CAN INDUCE THROUGH 8688 05:43:22,680 --> 05:43:24,320 FOCUS ULTRASOUND STIMULATION AND 8689 05:43:24,320 --> 05:43:26,600 FURTHERMORE IN THE SOMATOSENSORY 8690 05:43:26,600 --> 05:43:29,720 CORTEX BIDIRECTIONAL MODULATION 8691 05:43:29,720 --> 05:43:32,840 WAS OBSERVED WITH CERTAIN FOCUS 8692 05:43:32,840 --> 05:43:35,960 ULTRASOUND AND PARAMETER. 8693 05:43:35,960 --> 05:43:38,720 ROBUST LONG LASTING ATTENUATION 8694 05:43:38,720 --> 05:43:41,400 OF THERMAL HYPERALGESIA CAN 8695 05:43:41,400 --> 05:43:44,240 INDUCE IN SINGLE CELL TFAS 8696 05:43:44,240 --> 05:43:46,600 STIMULATION AT INSULA IN SICKLE 8697 05:43:46,600 --> 05:43:48,480 MICE. WHILE I DO NOT HAVE TIME 8698 05:43:48,480 --> 05:43:51,000 TO SHOW SLIDE, WE DID NOT 8699 05:43:51,000 --> 05:43:52,640 OBSERVE SIGNIFICANT CHANGE IN 8700 05:43:52,640 --> 05:43:56,000 MOTOR COORDINATION AND BALANCE 8701 05:43:56,000 --> 05:43:58,400 AFTER THE FOCUS ULTRASOUND AND 8702 05:43:58,400 --> 05:44:00,400 THE TREATMENT IN THIS 8703 05:44:00,400 --> 05:44:04,520 EXPERIMENTAL MICE. SO HIGH LEVEL 8704 05:44:04,520 --> 05:44:06,200 SUMMARY IS WE HAVE DEVELOPED A 8705 05:44:06,200 --> 05:44:09,400 NOVEL FOCUS ULTRASOUND 8706 05:44:09,400 --> 05:44:12,040 NEUROMODULATION TECHNOLOGY WITH 8707 05:44:12,040 --> 05:44:15,160 SUB MILLIMETER LATERAL SPATIAL 8708 05:44:15,160 --> 05:44:17,640 SPECIFICITY. WE DEMONSTRATE 8709 05:44:17,640 --> 05:44:20,640 FOCUS ULTRASOUND MODULATION AT 8710 05:44:20,640 --> 05:44:23,240 PRIMARY SOMATOSENSORY CORTEX 8711 05:44:23,240 --> 05:44:25,840 INSULA SUPPRESS PAIN SENSITIVITY 8712 05:44:25,840 --> 05:44:30,240 IN HUMANIZED MICE. I WOULD LIKE 8713 05:44:30,240 --> 05:44:33,320 TO ACKNOWLEDGE FUNDING SUPPORT 8714 05:44:33,320 --> 05:44:36,720 AND ALSO FOR COLLABORATORS WHO 8715 05:44:36,720 --> 05:44:38,960 CONTRIBUTED TO CERTAIN SLIDES AS 8716 05:44:38,960 --> 05:44:40,720 PRESENTED TODAY WHO ARE NOT 8717 05:44:40,720 --> 05:44:42,640 INCLUDED IN THE CO-AUTHORSHIP. 8718 05:44:42,640 --> 05:44:47,280 THANK YOU VERY MUCH. 8719 05:44:47,280 --> 05:44:50,560 >> THANK YOU, DR. HE. VERY 8720 05:44:50,560 --> 05:44:51,560 DELIGHTFUL PRESENTATION. WITH 8721 05:44:51,560 --> 05:44:55,400 THIS I WILL TURN THE FLOOR TO 8722 05:44:55,400 --> 05:44:56,800 DR. RICHARDSON TO CO-CHAIR. WE 8723 05:44:56,800 --> 05:44:57,760 WILL TAKE THE QUESTIONS AN 8724 05:44:57,760 --> 05:44:59,600 ANSWERS AT THE END OF THE 8725 05:44:59,600 --> 05:45:03,560 OVERALL SESSION. 8726 05:45:03,560 --> 05:45:08,880 >> THANK YOU, KALPNA. WE WILL GO 8727 05:45:08,880 --> 05:45:10,080 FURTHER INTO THE PRESENTATIONS 8728 05:45:10,080 --> 05:45:12,920 FOR TODAY. AND OUR NEXT 8729 05:45:12,920 --> 05:45:14,840 PRESENTER WILL BE ACTUALLY THE 8730 05:45:14,840 --> 05:45:18,240 CHAIR. DR. KALPNA GUPTA. GOING 8731 05:45:18,240 --> 05:45:22,400 TO INTRODUCE HER, DR. GUPTA IS 8732 05:45:22,400 --> 05:45:23,400 PROFESSOR OF MEDICINE DIVISION 8733 05:45:23,400 --> 05:45:27,600 OF HEMATOLOGY ONCOLOGY AND SUSAN 8734 05:45:27,600 --> 05:45:30,000 SAM WELLA INTEGRATIVE HEALTH 8735 05:45:30,000 --> 05:45:32,760 INSTITUTE AT THE UNIVERSITY OF 8736 05:45:32,760 --> 05:45:36,280 CALIFORNIA YO IRVINE. HER GOALS ARE 8737 05:45:36,280 --> 05:45:38,280 TO IDENTIFY MECHANISM BASED 8738 05:45:38,280 --> 05:45:39,520 TREATABLE TARGETS AT THE 8739 05:45:39,520 --> 05:45:41,200 INTERSECTION OF THE SICKLE CELL 8740 05:45:41,200 --> 05:45:43,800 DISEASE PROCESS AND PAIN. SHE 8741 05:45:43,800 --> 05:45:46,440 ALSO SERVES AS A MEMBER OF THE 8742 05:45:46,440 --> 05:45:48,680 DIVERSITY AND EQUITY INITIATIVE 8743 05:45:48,680 --> 05:45:52,000 OF THE AMERICAN SOCIETY OF 8744 05:45:52,000 --> 05:45:53,520 HEMATOLOGY. SCIENTIFIC WORKING 8745 05:45:53,520 --> 05:45:55,600 GROUP OF THE NATIONAL HEMOPHILIA 8746 05:45:55,600 --> 05:45:58,920 FOUNDATION. JUST TO ADD A 8747 05:45:58,920 --> 05:46:01,880 PERSONAL NOTE, I WILL SAY KALPNA 8748 05:46:01,880 --> 05:46:03,440 WAS VERY INSTRUMENTAL IN 8749 05:46:03,440 --> 05:46:05,200 FOSTERING MY RESEARCH INTERESTS 8750 05:46:05,200 --> 05:46:07,320 IN SICKLE CELL RESEARCH. SO 8751 05:46:07,320 --> 05:46:09,400 KALPNA. LOOKING FORWARD TO YOUR 8752 05:46:09,400 --> 05:46:13,960 TALK. 8753 05:46:13,960 --> 05:46:15,800 >> I AM DELIGHTED TO BE SPEAKING 8754 05:46:15,800 --> 05:46:17,240 ABOUT MY PASSION FOR PAIN IN 8755 05:46:17,240 --> 05:46:22,920 SICKLE CELL DISEASE. CAN I 8756 05:46:22,920 --> 05:46:36,000 SHARE MY SLIDES PLEASE. OUR 8757 05:46:36,000 --> 05:46:38,800 GOAL IS TO WORK ON APPROACHABLE 8758 05:46:38,800 --> 05:46:40,400 MECHANISM BASED INTEGRATIVE 8759 05:46:40,400 --> 05:46:42,200 STRATEGIES TO AMELIORATE PAIN. 8760 05:46:42,200 --> 05:46:47,600 WHEN I SAY APPROACHABLE, IT 8761 05:46:47,600 --> 05:46:49,320 MEANS WHETHER CAN BE DONE, WHAT 8762 05:46:49,320 --> 05:46:51,320 CAN WE DO NOW? MANY TIMES WHEN 8763 05:46:51,320 --> 05:46:52,520 SPEAKING IN COMMUNITY OR 8764 05:46:52,520 --> 05:46:54,000 DISCUSSING WITH PEOPLE SINCE I 8765 05:46:54,000 --> 05:46:55,720 DON'T TREAT PATIENTS PEOPLE ASK, 8766 05:46:55,720 --> 05:46:57,040 YOU HAVE DONE ALL THIS RESEARCH 8767 05:46:57,040 --> 05:46:59,920 BUT WHEN ARE YOU GOING TO 8768 05:46:59,920 --> 05:47:02,600 TRANSLATE IT MOST TRANSLATIONAL 8769 05:47:02,600 --> 05:47:05,720 GRANTS WE SUBMITTED GOT SHOT 8770 05:47:05,720 --> 05:47:11,880 DOWN. SO WE ARE STILL TRYING BUT 8771 05:47:11,880 --> 05:47:13,400 THERE ARE THINGS THAT CAN BE 8772 05:47:13,400 --> 05:47:14,600 DONE BASED ON WHAT WE HAVE FOUND 8773 05:47:14,600 --> 05:47:17,480 IN TERMS OF THE MECHANISM. 8774 05:47:17,480 --> 05:47:19,240 BEFORE I SPEAK ON ANYTHING THESE 8775 05:47:19,240 --> 05:47:21,720 ARE MY DISCLOSURES. NOT 8776 05:47:21,720 --> 05:47:22,920 TARGETING PAIN IN SICKLE CELL 8777 05:47:22,920 --> 05:47:25,320 DISEASE IS VERY COMPLEX AS WE 8778 05:47:25,320 --> 05:47:29,480 HAVE ALREADY HER. DR. STUCKY 8779 05:47:29,480 --> 05:47:33,400 AND BRANDOW NICELY LAID OUT THE 8780 05:47:33,400 --> 05:47:35,880 PERIPHERAL MECHANISMS WHICH ARE 8781 05:47:35,880 --> 05:47:39,080 MEDIATED THROUGH THE DORSAL ROOT 8782 05:47:39,080 --> 05:47:41,000 GANGLIA AND WE HAVE KNOWN FOR 8783 05:47:41,000 --> 05:47:43,000 MANY YEARS NOW NOT TOO MANY BUT 8784 05:47:43,000 --> 05:47:46,960 AT LEAST A DECADE WHAT ARE 8785 05:47:46,960 --> 05:47:48,800 PERIPHERAL MECHANISMS AND THE 8786 05:47:48,800 --> 05:47:50,400 MEETING FROM THE SICKLE CELL 8787 05:47:50,400 --> 05:47:52,400 DISEASE PROCESS, INCLUDING 8788 05:47:52,400 --> 05:47:58,320 CRISES, HYPOXIA ISCHEMIA 8789 05:47:58,320 --> 05:47:59,400 HEMOLYSIS, ORGAN DAMAGE ALL 8790 05:47:59,400 --> 05:48:02,880 WHICH CAN EVOKE PAIN. HYPOXIA 8791 05:48:02,880 --> 05:48:05,040 ISCHEMIA REPERFUSION INJURY, ALL 8792 05:48:05,040 --> 05:48:06,720 THESE CHEMICAL AND 8793 05:48:06,720 --> 05:48:08,080 NEUROMODULATORS IN THE PERIPHERY 8794 05:48:08,080 --> 05:48:09,200 RA WORKED OUT AS PRESENTED IN 8795 05:48:09,200 --> 05:48:13,120 THE PREVIOUS SESSION PART 1. -- 8796 05:48:13,120 --> 05:48:16,360 >> SORRY TO INTERRUPTS. SORRY TO 8797 05:48:16,360 --> 05:48:17,360 INTERRUPT CAN YOU SPEAK UP A 8798 05:48:17,360 --> 05:48:19,440 LITTLE BIT OR COME CLOSER TO THE 8799 05:48:19,440 --> 05:48:20,600 MICROPHONE? HAVING HARD TIME 8800 05:48:20,600 --> 05:48:20,920 HEARING YOU. 8801 05:48:20,920 --> 05:48:26,280 >> SORRY ABOUT THAT. WHAT IS 8802 05:48:26,280 --> 05:48:29,360 HAPPENING IN THE CENTRAL NERVOUS 8803 05:48:29,360 --> 05:48:32,160 SYSTEM OR THE BRAIN. BRAIN IS 8804 05:48:32,160 --> 05:48:33,080 MASTER ORCHESTRA AN IT IS 8805 05:48:33,080 --> 05:48:36,840 INVOLVED IN PERCEPTION OF PAIN. 8806 05:48:36,840 --> 05:48:38,600 WE KNOW ONE WAY STREET THAT IS 8807 05:48:38,600 --> 05:48:40,480 FROM THE PERIPHERY TO THE BRAIN 8808 05:48:40,480 --> 05:48:46,400 WHERE THE PAIN IS PERCEIVED. HOW 8809 05:48:46,400 --> 05:48:48,280 BRAIN CAN CHANGE THIS, OR CAN 8810 05:48:48,280 --> 05:48:51,360 BRAIN BE INITIATOR OF PAIN, 8811 05:48:51,360 --> 05:48:52,680 WHICH BRINGS BACK TO PERCEPTION. 8812 05:48:52,680 --> 05:48:54,960 HOW DOES IT DO THAT? 8813 05:48:54,960 --> 05:48:56,200 UNDERSTANDING IS VERY CLEAR AND 8814 05:48:56,200 --> 05:48:59,400 EVEN POORER IN SICKLE CELL 8815 05:48:59,400 --> 05:49:02,280 DISEASE. DR. (INAUDIBLE) HAD 8816 05:49:02,280 --> 05:49:04,600 ELEGANTLY SHOWN HYPNOTIC NUCLEI 8817 05:49:04,600 --> 05:49:07,640 IN THE HIPPOCAMPAL REGION OF 8818 05:49:07,640 --> 05:49:08,720 SICKLE CELL MICE YEARS AGO BUT 8819 05:49:08,720 --> 05:49:10,240 THAT IS ALL WE KNEW FROM THE 8820 05:49:10,240 --> 05:49:12,320 MECHANISM POINT OF VIEW. SO WE 8821 05:49:12,320 --> 05:49:14,440 STARTED ASKING THESE QUESTIONS 8822 05:49:14,440 --> 05:49:16,280 HOW DOES IT DO THAT. WE KNOW 8823 05:49:16,280 --> 05:49:18,600 WHEN THE SIGNAL GO FROM 8824 05:49:18,600 --> 05:49:20,400 PERIPHERY TO BRAIN, FROM P THE 8825 05:49:20,400 --> 05:49:22,120 BRAIN THROUGH TO LIMB BIC OR 8826 05:49:22,120 --> 05:49:23,800 DESCENDING PATHWAY SHOWN IN THE 8827 05:49:23,800 --> 05:49:27,600 BLUE ARROW, THIS CAN GO BACK TO 8828 05:49:27,600 --> 05:49:28,800 THE SPINAL CORD WHERE THEY CAN 8829 05:49:28,800 --> 05:49:32,960 BE MODIFIED AND THEN THROUGH 8830 05:49:32,960 --> 05:49:34,880 ANATOMIC RELEASE THROUGH BLUE 8831 05:49:34,880 --> 05:49:39,040 ARROWS, GO BACK TO DRG AND GO TO 8832 05:49:39,040 --> 05:49:43,160 PERIPHERY. SO WHAT GOES UP COMES 8833 05:49:43,160 --> 05:49:45,360 BACK. THIS MEANS ONCE THE SYSTEM 8834 05:49:45,360 --> 05:49:46,800 IS ACTIVATE THROUGH SOME 8835 05:49:46,800 --> 05:49:50,080 PERIPHERAL INJURY, OR NOXIOUS 8836 05:49:50,080 --> 05:49:52,280 INSERT, ACTUALLY THE SYSTEM CAN 8837 05:49:52,280 --> 05:49:56,040 BE ON AUTOREGULATION. THESE 8838 05:49:56,040 --> 05:49:59,880 DIFFERENT SPECIES OF 8839 05:49:59,880 --> 05:50:01,200 NEUROMODULATORS ARE SICKLE CELL 8840 05:50:01,200 --> 05:50:03,000 INFLAMMATION INCREASE DUE TO 8841 05:50:03,000 --> 05:50:05,960 DISEASE CAN BE FURTHER AUGMENTED 8842 05:50:05,960 --> 05:50:10,080 BY THIS ANATOMIC ACTIVITY GUIDED 8843 05:50:10,080 --> 05:50:13,920 BY THE BRAIN. SO IN ORDER TO 8844 05:50:13,920 --> 05:50:15,480 EXAMINE THIS WE THOUGHT WHAT IS 8845 05:50:15,480 --> 05:50:18,920 IT THAT REALLY INDUCES THE 8846 05:50:18,920 --> 05:50:21,680 BRAIN. THE QUESTION WAS, IT IS 8847 05:50:21,680 --> 05:50:24,080 USUALLY THE ENVIRONMENT. WE HEAR 8848 05:50:24,080 --> 05:50:27,720 BAD NEWS PAIN CAN INCREASE. CAN 8849 05:50:27,720 --> 05:50:28,840 THEN ENVIRONMENT INFLUENCE PAIN? 8850 05:50:28,840 --> 05:50:30,480 THE FACTORS ARE IN THE 8851 05:50:30,480 --> 05:50:32,200 ENVIRONMENT ARE BOTH ENDOGENOUS 8852 05:50:32,200 --> 05:50:34,040 WHICH IS IN THE BODY AND WHICH 8853 05:50:34,040 --> 05:50:36,600 ARE OUTSIDE THE BODY LIKE 8854 05:50:36,600 --> 05:50:38,680 NUTRITION, COMPANIONSHIP, SOCIAL 8855 05:50:38,680 --> 05:50:40,160 ISOLATION, WE HEARD ABOUT ALL 8856 05:50:40,160 --> 05:50:42,800 THESE LONELINESS STIGMAS, SLEEP, 8857 05:50:42,800 --> 05:50:44,680 SOMETHING WHICH HAS NOT BEEN 8858 05:50:44,680 --> 05:50:45,680 ADDRESSED IN THIS THREE DAY 8859 05:50:45,680 --> 05:50:48,240 MEETING. PLEASURE TRAUMA, 8860 05:50:48,240 --> 05:50:52,280 DEPRESSION ANXIETY, FOOD 8861 05:50:52,280 --> 05:50:54,960 SUPPLEMENTS, CANDIES HAVE IMPACT 8862 05:50:54,960 --> 05:50:57,600 ON THE PAIN SINCE THESE CAN BE 8863 05:50:57,600 --> 05:50:58,520 AUTOREGULATED BY INDIVIDUALS 8864 05:50:58,520 --> 05:51:00,960 THEMSELVES. AND THE EVIDENCE 8865 05:51:00,960 --> 05:51:03,360 COMES FROM THESE THREE VERY NICE 8866 05:51:03,360 --> 05:51:04,400 STUDIES FROM THREE DIFFERENT 8867 05:51:04,400 --> 05:51:07,240 PARTS OF THE WORLD. ONE FROM 8868 05:51:07,240 --> 05:51:10,000 ATLANTA IN 2001 WHERE WE FOUND 8869 05:51:10,000 --> 05:51:13,720 THAT PAIN WAS SIGNIFICANTLY 8870 05:51:13,720 --> 05:51:16,720 REDUCED AS FREQUENCY OF PAIN 8871 05:51:16,720 --> 05:51:18,800 EVENTS WITH FISH OIL. THE NEXT 8872 05:51:18,800 --> 05:51:22,680 STUDY WAS WITH OMEGA 3 CAPSULES 8873 05:51:22,680 --> 05:51:25,480 DRG AND EPA SIGNIFICANTLY REDUCE 8874 05:51:25,480 --> 05:51:30,320 CLINICAL VASOOCCLUSIVE EVENTS 8875 05:51:30,320 --> 05:51:34,000 FROM SUDAN THEY FOUND CO-ENZYME 8876 05:51:34,000 --> 05:51:37,680 Q 10 REDUCE INFLAMMATION AND 8877 05:51:37,680 --> 05:51:39,400 LIPID PEROXIDATION. SO OXIDATIVE 8878 05:51:39,400 --> 05:51:40,640 STRESS AND INFLAMMATION, WE 8879 05:51:40,640 --> 05:51:42,000 SPOKE ABOUT INFLAMMATION IN THE 8880 05:51:42,000 --> 05:51:46,960 PRIOR SESSION. NOW, IT IS VERY 8881 05:51:46,960 --> 05:51:48,520 DIFFICULT, ALMOST IMPOSSIBLE TO 8882 05:51:48,520 --> 05:51:50,520 OPEN UP THE BRAIN AND SEE WHAT 8883 05:51:50,520 --> 05:51:51,960 WE ARE LOOKING FOR IN A HUMAN 8884 05:51:51,960 --> 05:51:55,200 BRAIN. THESE HUMANIZED BERKELEY 8885 05:51:55,200 --> 05:51:57,960 MICE IS WHAT WE USE, AND WE ARE 8886 05:51:57,960 --> 05:52:00,400 ALL FAMILIAR WITH THIS MODEL, 8887 05:52:00,400 --> 05:52:03,040 THEY EXPRESS MORE THAN 99% HUMAN 8888 05:52:03,040 --> 05:52:06,800 SICKLE HEMOGLOBIN, SHOW MANY 8889 05:52:06,800 --> 05:52:08,120 SALIENT FEATURES BOTH 8890 05:52:08,120 --> 05:52:10,120 PATHOLOGICAL AND PAIN WHICH WE 8891 05:52:10,120 --> 05:52:11,600 OBSERVE -- WHICH ARE OBSERVED IN 8892 05:52:11,600 --> 05:52:12,880 SICKLE CELL DISEASE. 8893 05:52:12,880 --> 05:52:15,000 SO WHAT WE DID THE FIRST THING 8894 05:52:15,000 --> 05:52:17,920 WAS DIETARY MANIPULATION. SO TO 8895 05:52:17,920 --> 05:52:19,600 GIVE THESE MICE TWO DIFFERENT 8896 05:52:19,600 --> 05:52:22,360 KINDS OF DIET, ONE WAS THE 8897 05:52:22,360 --> 05:52:24,160 RODENT REGULAR DIET BY LABS ALL 8898 05:52:24,160 --> 05:52:27,360 OVER. AND THE OTHER WAS 8899 05:52:27,360 --> 05:52:28,440 FORMULATED DIET WHICH WE CALL 8900 05:52:28,440 --> 05:52:31,640 SICKLE DIET OR ENRICHED DIET. 8901 05:52:31,640 --> 05:52:36,160 THE INCREASE MINERALS AMINO 8902 05:52:36,160 --> 05:52:39,440 ACIDS FATTY ACIDS OMEGA 3 FATTY 8903 05:52:39,440 --> 05:52:45,120 ACIDS TO ACTUALLY INCREASE THE 8904 05:52:45,120 --> 05:52:48,000 DIETARY REQUIREMENT FOR THE HIGH 8905 05:52:48,000 --> 05:52:50,880 METABOLIC NEED OF SICKLE CELL 8906 05:52:50,880 --> 05:52:53,640 DISEASE PATIENTS AS -- OF THESE 8907 05:52:53,640 --> 05:52:56,480 MICE. AND VERY TALENTED YOUNG 8908 05:52:56,480 --> 05:52:58,920 MAN CAME IN MY LAB FOR MANY 8909 05:52:58,920 --> 05:53:02,440 YEARS AND SAYS UNDERGRADUATION 8910 05:53:02,440 --> 05:53:04,120 ACTUALLY OBSERVE THAT SOME OF 8911 05:53:04,120 --> 05:53:06,320 THE MICE DID NOT SHOW THE 8912 05:53:06,320 --> 05:53:07,760 FEATURES OF PAIN THAT WE HAVE 8913 05:53:07,760 --> 05:53:10,080 BEEN OBSERVING. AND WHAT 8914 05:53:10,080 --> 05:53:13,720 HAPPENED WAS BY ACCIDENT THESE 8915 05:53:13,720 --> 05:53:17,320 MICE WERE GIVEN SICKLE DIET FOR 8916 05:53:17,320 --> 05:53:19,600 LONG TIME AND SO HE UNDERTOOK A 8917 05:53:19,600 --> 05:53:21,160 STUDY WITH SEVERAL GROUPS OF 8918 05:53:21,160 --> 05:53:26,120 MICE WHERE HE HAD MICE DEPRIVED 8919 05:53:26,120 --> 05:53:27,840 OF THE RICH DIET GIVEN REGULAR 8920 05:53:27,840 --> 05:53:33,000 DIET DENOTED AS RD HERE. AND 8921 05:53:33,000 --> 05:53:34,160 ISOLATED WITHOUT FEMALE IN A 8922 05:53:34,160 --> 05:53:36,800 CAGE OR MALE IN A CAGE SO THEY 8923 05:53:36,800 --> 05:53:38,560 LIVED -- MALE WAS PLACED IN A 8924 05:53:38,560 --> 05:53:39,600 CAGE AND WE CALLED IT THE 8925 05:53:39,600 --> 05:53:45,840 DEPRIVED GROUP. NETTED E HAD 8926 05:53:45,840 --> 05:53:48,000 GOOD DIET NOR ISOLATED. HAPPY 8927 05:53:48,000 --> 05:53:49,400 GROUP WHERE MALE WAS HOUSED WITH 8928 05:53:49,400 --> 05:53:52,600 FEMALE COMPANION AND GIVEN THE 8929 05:53:52,600 --> 05:53:57,400 RICH SD SICKLE DIET. THAT WAS 8930 05:53:57,400 --> 05:54:01,480 UNHAPPY GROUP TO SIMULATE TRAUMA 8931 05:54:01,480 --> 05:54:03,160 OR STRATEGY OR OTHER 8932 05:54:03,160 --> 05:54:05,240 PSYCHOSOCIAL EFFECTORS. WHERE 8933 05:54:05,240 --> 05:54:07,440 THE MICE -- THE MALE MOUSE WAS 8934 05:54:07,440 --> 05:54:09,440 LIVING HAPPILY AS WE DENOTED IN 8935 05:54:09,440 --> 05:54:14,880 THE RED SQUARE HERE, WITH FEMALE 8936 05:54:14,880 --> 05:54:17,000 AND GOOD DIET AND WE WITHDREW 8937 05:54:17,000 --> 05:54:20,000 BOTH AND LEFT THE MALE ALONE. 8938 05:54:20,000 --> 05:54:24,600 WHAT WE FOUND WAS IN THE 8939 05:54:24,600 --> 05:54:27,600 DEPRIVED GROUP THERE WAS HIGHER 8940 05:54:27,600 --> 05:54:30,960 THING, HIGHER NUMBER ON THE 8941 05:54:30,960 --> 05:54:33,480 DASHED LINE ACTUALLY SHOWS PAIN 8942 05:54:33,480 --> 05:54:39,480 AND THE SOLID BARS SHOW THE 8943 05:54:39,480 --> 05:54:42,320 LEVELS. WHAT HE SERVED WAS THE 8944 05:54:42,320 --> 05:54:43,560 LEVELS IN THE SPECIFIC REGIONS 8945 05:54:43,560 --> 05:54:46,000 OF THE BRAIN OF THESE MICE, WERE 8946 05:54:46,000 --> 05:54:50,960 VERY LOW. BUT IN THE GROUP MALE 8947 05:54:50,960 --> 05:54:53,920 MOUSE WAS HOUSED WITH FEMALE AND 8948 05:54:53,920 --> 05:54:57,960 RECEIVED AN ENRICHED SICKLE 8949 05:54:57,960 --> 05:54:59,920 DIET, PAIN WAS LESS AND THE 8950 05:54:59,920 --> 05:55:03,680 SEROTONIN LEVELS WERE HIGH. 8951 05:55:03,680 --> 05:55:05,200 WHEN THEY WITHDREW THE FEMALE 8952 05:55:05,200 --> 05:55:06,720 FROM THIS MOUSE AND ALSO GAVE 8953 05:55:06,720 --> 05:55:11,240 THE MOUSE A POOR DIET, THE PAIN 8954 05:55:11,240 --> 05:55:13,200 LEVELS WENT UP AND SEROTONIN 8955 05:55:13,200 --> 05:55:16,160 LEVELS IN THE BRAIN WENT DOWN. 8956 05:55:16,160 --> 05:55:17,600 HOW DOES THIS HAPPEN? HOW DO WE 8957 05:55:17,600 --> 05:55:22,720 EXPLAIN THIS? SO WHAT HAPPENS IS 8958 05:55:22,720 --> 05:55:26,400 I SPOKE ABOUT THE BRAIN TARGETED 8959 05:55:26,400 --> 05:55:27,760 MECHANISMS, OR TOP DOWN 8960 05:55:27,760 --> 05:55:28,600 MECHANISMS THESE ARE DIFFERENT 8961 05:55:28,600 --> 05:55:30,960 REGIONS OF THE BRAIN ON THE LEFT 8962 05:55:30,960 --> 05:55:33,400 SIDE. AND AT THE BOTTOM IS THE 8963 05:55:33,400 --> 05:55:35,800 SPINAL CORD SECTION. THESE 8964 05:55:35,800 --> 05:55:40,960 DIFFERENT REGIONS OF BRAIN 8965 05:55:40,960 --> 05:55:44,040 HOUSED WITH NON-EPINEPHRINE 8966 05:55:44,040 --> 05:55:46,360 EJECT NEURONS IN DIFFERENT PARTS 8967 05:55:46,360 --> 05:55:50,680 OF THE BRAIN IN THE GYRUS, IN 8968 05:55:50,680 --> 05:55:54,640 PAG AND IN THE RBM REGIONS. WHAT 8969 05:55:54,640 --> 05:55:57,800 WE ARE DOING IS UPON 8970 05:55:57,800 --> 05:55:59,280 STIMULATION, FROM THE PERCEPTION 8971 05:55:59,280 --> 05:56:01,040 OR THROUGH THE CHEMICAL 8972 05:56:01,040 --> 05:56:02,520 MEDIATORS THAT CAN ALSO HAPPEN 8973 05:56:02,520 --> 05:56:04,560 BUT IT IS IMPORTANT TO NOTE 8974 05:56:04,560 --> 05:56:06,920 HERE, THAT IT CAN HAPPEN WITH 8975 05:56:06,920 --> 05:56:10,480 PERCEPTION. LIKE WE SAW THAT 8976 05:56:10,480 --> 05:56:11,680 WITHDRAWING THE FEMALE WE FAST 8977 05:56:11,680 --> 05:56:13,560 FRAME, DECREASE SEROTONIN 8978 05:56:13,560 --> 05:56:16,520 LEVELS. THESE ARE STIMULATED AND 8979 05:56:16,520 --> 05:56:18,840 RELEASE THEIR CONTENTS INTO THE 8980 05:56:18,840 --> 05:56:22,080 DORSAL HORN OF THE SPINAL CORD. 8981 05:56:22,080 --> 05:56:23,400 THAT IS WHERE THE GATE WHICH 8982 05:56:23,400 --> 05:56:28,200 ACTUALLY PROCESSES THE PAIN 8983 05:56:28,200 --> 05:56:29,800 NOCICEPTIVE INPUTS. ON THE RIGHT 8984 05:56:29,800 --> 05:56:35,280 YOU WILL SEE THAT THERE ARE 8985 05:56:35,280 --> 05:56:36,840 SYNAPTOSOMES WHERE -- PRIMARY 8986 05:56:36,840 --> 05:56:39,120 AND SECONDARY NEURONS WHICH MEET 8987 05:56:39,120 --> 05:56:40,840 IN THIS REGION. WHEN THERE IS A 8988 05:56:40,840 --> 05:56:43,480 HIGHER CONCENTRATION OF 8989 05:56:43,480 --> 05:56:46,760 SEROTONIN THERE IS LESS PAIN OR 8990 05:56:46,760 --> 05:56:53,440 THERE WOULD BE ACTIVATION OF THE 8991 05:56:53,440 --> 05:56:54,040 SENERTINERGIC RECEPTORS. IN 8992 05:56:54,040 --> 05:56:57,400 ORDER TO INCREASE CERTAIN DRUGS 8993 05:56:57,400 --> 05:57:00,160 ARE DEVELOPED LIKE DULOXETINE 8994 05:57:00,160 --> 05:57:02,720 SNRI PRIMARILY DEVELOPED FOR 8995 05:57:02,720 --> 05:57:05,160 DEPRESSION ANDEAN SHYTY BUT ALSO 8996 05:57:05,160 --> 05:57:07,320 HAS PA PAIN -- AND ANXIETY BUT 8997 05:57:07,320 --> 05:57:09,560 ALSO HAS PAIN RELIEVING EFFECTS 8998 05:57:09,560 --> 05:57:11,760 AS WE HEARD ABOUT TODAY. WHAT 8999 05:57:11,760 --> 05:57:13,520 HAPPENS IS WE BELIEVE THAT THERE 9000 05:57:13,520 --> 05:57:16,000 WAS STIMULATION OF THESE HIGHER 9001 05:57:16,000 --> 05:57:18,880 BRAIN CENTERS WITH THE DIETARY 9002 05:57:18,880 --> 05:57:21,600 AND COMPANIONSHIP MANIPULATIONS 9003 05:57:21,600 --> 05:57:24,920 THAT WE DID WITH THESE MICE MICE. AND 9004 05:57:24,920 --> 05:57:28,120 SHOWING US WHAT HE FOUND WAS 9005 05:57:28,120 --> 05:57:30,560 THAT WITHDRAWING OF PLEASURE 9006 05:57:30,560 --> 05:57:32,000 DIMINISH HEARSAY SPINAL 9007 05:57:32,000 --> 05:57:34,320 NOCICEPTIVE MECHANISMS THAT I 9008 05:57:34,320 --> 05:57:36,880 JUST SPOKE ABOUT. IN MANY THE 9009 05:57:36,880 --> 05:57:40,320 RPM REGION OF THE BRAIN IN THE 9010 05:57:40,320 --> 05:57:41,640 HEAVY CIRCUMSTANCES MICE HAD A 9011 05:57:41,640 --> 05:57:44,640 SIGNIFICANTLY HIGHER LEVEL OF 9012 05:57:44,640 --> 05:57:47,800 SEROTONIN. IT WAS ALSO INCREASE 9013 05:57:47,800 --> 05:57:50,040 BECAUSE RELEASED FROM THE RDP TO 9014 05:57:50,040 --> 05:57:51,560 THE SPINAL CORD IN THE SPINAL 9015 05:57:51,560 --> 05:57:53,880 CORD. SIMILARLY DOPAMINE WHICH 9016 05:57:53,880 --> 05:57:56,360 IS ALSO CALLED A HAPPY MOLECULE 9017 05:57:56,360 --> 05:57:58,560 WAS ALSO INCREASE IN THE 9018 05:57:58,560 --> 05:58:00,960 SPECIFIC PAG BRAIN REGION OF 9019 05:58:00,960 --> 05:58:05,160 THESE MICE WHICH WERE HAPPY RED 9020 05:58:05,160 --> 05:58:08,920 BARSS. WHAT WAS VERY EXCITING TO 9021 05:58:08,920 --> 05:58:12,080 NOTE HERE, 7 WITHDRAWAL OF THE 9022 05:58:12,080 --> 05:58:15,040 PLEASURE MAKING THEM UNHAPPY 9023 05:58:15,040 --> 05:58:18,000 REALLY REDUCED THE CONTENT OF 9024 05:58:18,000 --> 05:58:20,400 BOTH SEROTONIN AND DOPAMINE IN 9025 05:58:20,400 --> 05:58:24,440 THESE MICE. THIS SUGGESTS THESE 9026 05:58:24,440 --> 05:58:28,320 TOP DOWN MECHANISMS PLAY A 9027 05:58:28,320 --> 05:58:31,320 CRITICAL ROLE IN THE PERCEPTION 9028 05:58:31,320 --> 05:58:33,640 OF PAIN. AND WHAT WE FOUND WAS 9029 05:58:33,640 --> 05:58:35,200 EVEN MORE INTERESTING THERE WERE 9030 05:58:35,200 --> 05:58:36,240 MANY DIFFERENT GROUPS AND I'M 9031 05:58:36,240 --> 05:58:38,920 NOT GOING TO GO INTO DETAILS, 9032 05:58:38,920 --> 05:58:40,120 THAT COMPANIONSHIP WAS VERY 9033 05:58:40,120 --> 05:58:42,840 IMPORTANT. IF YOU LOOK AT THE 9034 05:58:42,840 --> 05:58:46,000 RIGHT SIDE ON THE TWO BARS THE 9035 05:58:46,000 --> 05:58:48,800 BLACK AND GREEN, THE GREEN BAR 9036 05:58:48,800 --> 05:58:51,800 SHOWS THAT THE MICE WERE STILL 9037 05:58:51,800 --> 05:58:54,000 ON THE POOR DIET BUSHY HAD A 9038 05:58:54,000 --> 05:58:57,880 COMPANION. AND WHEN WE DID THIS, 9039 05:58:57,880 --> 05:59:01,200 THEY STILL HAD HIGHER SEROTONIN 9040 05:59:01,200 --> 05:59:03,160 LEVELS IN T BRAIN RVM REGION. 9041 05:59:03,160 --> 05:59:05,040 WHICH SHOWS BY JUST PERCEPTION, 9042 05:59:05,040 --> 05:59:07,520 THERE WAS NO CHEMICAL STIMULUS, 9043 05:59:07,520 --> 05:59:08,960 THERE WAS NOTHING GOING INTO THE 9044 05:59:08,960 --> 05:59:13,560 BODY BUT BY JUST HAVING THE -- 9045 05:59:13,560 --> 05:59:15,880 ANOTHER COMPANION THEY HAD 9046 05:59:15,880 --> 05:59:17,880 INCREASE IN THE SEROTONIN LEVELS 9047 05:59:17,880 --> 05:59:20,400 HENCE THE LOWER PAIN. WE CAN 9048 05:59:20,400 --> 05:59:23,720 ALSO SEE BETWEEN RED AND MAGENTA 9049 05:59:23,720 --> 05:59:25,400 BARS ON THE RIGHT WITHDRAWING 9050 05:59:25,400 --> 05:59:28,000 THE COMPANION AND LIVING THE 9051 05:59:28,000 --> 05:59:30,360 POOR DIET LED TO A SHARP 9052 05:59:30,360 --> 05:59:31,800 DECREASE IN THE SEROTONIN 9053 05:59:31,800 --> 05:59:36,200 LEVELS. THIS WAS MATCHED WITH 9054 05:59:36,200 --> 05:59:38,720 INCREASE IN THE SPINAL CORD AND 9055 05:59:38,720 --> 05:59:41,320 SHOWS THE RESULTS. BUT WHAT CAME 9056 05:59:41,320 --> 05:59:44,960 AS A BIGGER SURPRISE TO US WAS 9057 05:59:44,960 --> 05:59:46,400 THESE MICE WERE ABOUT EIGHT 9058 05:59:46,400 --> 05:59:48,720 MONTHS OLD SO THEY HAD VERY 9059 05:59:48,720 --> 05:59:51,160 CHRONIC ORGAN DAMAGE AND 9060 05:59:51,160 --> 05:59:53,160 EVERYTHING IN THE PATHOBIOLOGY 9061 05:59:53,160 --> 05:59:58,000 WAS REALLY VERY HIGH. BUT IN 9062 05:59:58,000 --> 06:00:00,000 SPITE OF THAT WHEN WE WITHDREW 9063 06:00:00,000 --> 06:00:02,920 -- IF YOU LOOK AT THE FIRST 9064 06:00:02,920 --> 06:00:04,640 GRAPH AND THE BLUE BAR ON THE 9065 06:00:04,640 --> 06:00:07,920 RIGHT, THE RIGHT MOST BAR, WHICH 9066 06:00:07,920 --> 06:00:12,600 WAS THE WITHDRAWAL OF THE FEMALE 9067 06:00:12,600 --> 06:00:16,760 FROM THE MALE MOUSE THAT WAS 9068 06:00:16,760 --> 06:00:18,200 BEING FED SICKLE DIET AND WAS 9069 06:00:18,200 --> 06:00:22,600 COMPANION LED TO A INCREASE IN 9070 06:00:22,600 --> 06:00:24,280 THE WHITE BLOOD CELL COUNT WHICH 9071 06:00:24,280 --> 06:00:25,440 MEANS THERE WAS INCREASE IN 9072 06:00:25,440 --> 06:00:27,960 INFLAMMATION. AND WHAT WAS EVEN 9073 06:00:27,960 --> 06:00:30,000 MORE SURPRISING WAS THAT THERE 9074 06:00:30,000 --> 06:00:33,400 WAS AN INCREASE IN THE SPLEEN 9075 06:00:33,400 --> 06:00:37,440 SIZE. AGAIN AS PAT COMMENTED 9076 06:00:37,440 --> 06:00:39,360 WHATEVER HAPPENS IN THIS CENTRAL 9077 06:00:39,360 --> 06:00:40,720 NERVOUS SYSTEM INFLUENCE IT IS 9078 06:00:40,720 --> 06:00:43,920 PERIPHERY. 9079 06:00:43,920 --> 06:00:45,200 >> I HAVE ALREADY SHOWN YOU THIS 9080 06:00:45,200 --> 06:00:48,600 CARTOON AND SUGGEST -- THIS 9081 06:00:48,600 --> 06:00:51,760 MECHANISM SUGGESTS THAT 9082 06:00:51,760 --> 06:00:55,360 DULOXATENE CAN HAVE AN 9083 06:00:55,360 --> 06:00:59,160 ANTI-NOCICEPTIVE EFFECT. THOUGH 9084 06:00:59,160 --> 06:01:00,800 THESE STUDIES ARE NOT DONE IN 9085 06:01:00,800 --> 06:01:02,000 SICKLE PATIENTS OR MICE. WE 9086 06:01:02,000 --> 06:01:04,400 TREATED THESE MALE AND FEMALE 9087 06:01:04,400 --> 06:01:06,640 SICKLE MICE, NOW WE COULD NOT DO 9088 06:01:06,640 --> 06:01:08,720 DIETARY MANIPULATIONS AND 9089 06:01:08,720 --> 06:01:10,040 COMPANION MANIPULATIONS IN 9090 06:01:10,040 --> 06:01:11,160 FEMALE MICE BECAUSE WHEN WE 9091 06:01:11,160 --> 06:01:12,840 HOUSE THEM WITH MALES THEY 9092 06:01:12,840 --> 06:01:18,200 BECAME PREGNANT. SO WE GAVE THEM 9093 06:01:18,200 --> 06:01:20,000 DULOXATINE TO USE IT AS AN 9094 06:01:20,000 --> 06:01:22,960 INTERVENTION OF THE MECHANISM. 9095 06:01:22,960 --> 06:01:26,400 LOOK AT THE LOWER PANEL WHERE 9096 06:01:26,400 --> 06:01:29,840 LOWER VALUES ARE LESS PAIN AND 9097 06:01:29,840 --> 06:01:34,200 HIGHER VALUES ARE MORE PAIN, 9098 06:01:34,200 --> 06:01:37,400 THIS IS A TEST FOR HYPERALGESIA, 9099 06:01:37,400 --> 06:01:39,840 WHERE MICE ARE ON A POOR 9100 06:01:39,840 --> 06:01:41,600 PLATFORM AND NUMBER OF TIMES 9101 06:01:41,600 --> 06:01:43,240 THEY WITHDREW PAW TO AVOID COLD 9102 06:01:43,240 --> 06:01:47,560 WAS COUNTED EVERY TWO MINUTES. 9103 06:01:47,560 --> 06:01:51,480 WE FIND DULOXATINE AMELIORATES 9104 06:01:51,480 --> 06:01:53,040 HYPERALGESIA IN THESE MICE AT 9105 06:01:53,040 --> 06:01:56,040 BOTH DOSES 3-MILLIGRAM PER 9106 06:01:56,040 --> 06:01:57,680 KILOGRAM AND TEN MILLIGRAM PER 9107 06:01:57,680 --> 06:02:01,200 KILOGRAM IN MALE AND FEMALE 9108 06:02:01,200 --> 06:02:04,480 MICE, AND IT WAS TIME DEPENDENT. 9109 06:02:04,480 --> 06:02:06,000 SO THIS WAS FURTHER FOUND TOP 9110 06:02:06,000 --> 06:02:09,840 DOWN MECHANISMS PLAY A ROLE IN 9111 06:02:09,840 --> 06:02:13,320 PERCEPTION OF PAIN IN SICKLE 9112 06:02:13,320 --> 06:02:15,520 CELL DISEASE. SOMETIMES WE 9113 06:02:15,520 --> 06:02:17,600 REALIZE FROM THE CLINICAL 9114 06:02:17,600 --> 06:02:20,280 LITERATURE PEOPLE DEVELOP COPING 9115 06:02:20,280 --> 06:02:22,200 MECHANISMS AND CAN OVER RIDE 9116 06:02:22,200 --> 06:02:24,080 THESE EFFECTS SO STACY IN OUR 9117 06:02:24,080 --> 06:02:26,440 LAB NOW AT GEORGETOWN UNIVERSITY 9118 06:02:26,440 --> 06:02:28,960 REALLY WAS CURIOUS TO KNOW WHAT 9119 06:02:28,960 --> 06:02:31,400 HAPPENS IN THE OLDER MICE, SHE 9120 06:02:31,400 --> 06:02:32,640 TOOK THE MICE WHO SURVIVE -- 9121 06:02:32,640 --> 06:02:37,080 >> TWO MINUTE WARNING. AND 18 9122 06:02:37,080 --> 06:02:39,160 MONTHS OF AGE FOUND THE MALE 9123 06:02:39,160 --> 06:02:40,880 MICE WHICH WERE WITH COMPANION 9124 06:02:40,880 --> 06:02:43,400 HAD LESS PAIN BUT WHAT WAS 9125 06:02:43,400 --> 06:02:45,720 SURPRISING WAS BODY WEIGHT ALSO 9126 06:02:45,720 --> 06:02:49,440 INCREASE THOUGH ALL THE MICE ARE 9127 06:02:49,440 --> 06:02:50,960 FED SIMILAR DIET. THEY WERE 9128 06:02:50,960 --> 06:02:53,560 HAPPIER AND EATING MORE THOUGH 9129 06:02:53,560 --> 06:02:55,600 THE DIET WAS REGULAR, NOT THE 9130 06:02:55,600 --> 06:02:57,720 ENRICHED DIET. WITH THIS I WOULD 9131 06:02:57,720 --> 06:03:01,720 LIKE TO CONCLUDE THAT WE HAVE TO 9132 06:03:01,720 --> 06:03:04,480 THINK ABOUT THE ENVIROSOME AS 9133 06:03:04,480 --> 06:03:06,200 REGULATOR OF PAIN PERCEPTION. 9134 06:03:06,200 --> 06:03:08,280 AND THIS INCLUDES ALL THAT WE 9135 06:03:08,280 --> 06:03:09,760 DISCUSSED IN THE MORNING 9136 06:03:09,760 --> 06:03:12,400 SESSION, PSYCHOSOCIAL FACTORS 9137 06:03:12,400 --> 06:03:17,040 ANXIETY, DEPRESSION, STIGMA, 9138 06:03:17,040 --> 06:03:18,600 ISOLATION, SLEEP, DIET 9139 06:03:18,600 --> 06:03:22,680 SURROUNDING. WE KNOW WE CANNOT 9140 06:03:22,680 --> 06:03:23,960 PREVENT WHAT HAS BEEN STARTED IF 9141 06:03:23,960 --> 06:03:26,840 YOU SEE IN THE BLUE AND THE PINK 9142 06:03:26,840 --> 06:03:28,880 BATCHES ON THE BOTTOM BY THE 9143 06:03:28,880 --> 06:03:30,120 SICKLE CELL DISEASE OR SICKLING 9144 06:03:30,120 --> 06:03:34,600 OF RED BLOOD CELLS. MY HOPE IS 9145 06:03:34,600 --> 06:03:36,600 THAT WITH THIS KNOWLEDGE WE MAY 9146 06:03:36,600 --> 06:03:40,800 TRY TO CONTROL OUR ENVIRONMENT 9147 06:03:40,800 --> 06:03:43,680 WHICH CAN PROBABLY IF NOT CREATE 9148 06:03:43,680 --> 06:03:46,520 THE PAIN, BRING DOWN THE PAIN OR 9149 06:03:46,520 --> 06:03:48,280 IMPROVE OPIOID REQUIREMENT AND 9150 06:03:48,280 --> 06:03:53,400 MANY STUDIES OUT OF HOPKINS AND 9151 06:03:53,400 --> 06:03:55,840 DR. CARO'S WORK HAS SHOWN 9152 06:03:55,840 --> 06:03:58,400 FLUCTUATION IN/DR. CARROLL'S 9153 06:03:58,400 --> 06:03:59,840 WORK HAS SHOWN RESPONSE TO 9154 06:03:59,840 --> 06:04:01,080 TREATMENT. IS THIS THE REASON 9155 06:04:01,080 --> 06:04:03,480 THE ENVIRONMENT IS CHANGING? 9156 06:04:03,480 --> 06:04:05,000 SUPPOSING STUDENT GOT A BAD 9157 06:04:05,000 --> 06:04:06,320 GRADE, MAYBE PAIN GOES UP EVEN 9158 06:04:06,320 --> 06:04:09,480 THOUGH THE AMOUNT OF MORPHINE IS 9159 06:04:09,480 --> 06:04:11,120 THE SAME. THERE IS SOME ILLNESS 9160 06:04:11,120 --> 06:04:15,080 IN THE FAMILY. THIS BRINGS TO 9161 06:04:15,080 --> 06:04:17,160 ATTENTION THAT WE NEED TO DO 9162 06:04:17,160 --> 06:04:20,240 SOME MODIFICATION IN IF HOUR 9163 06:04:20,240 --> 06:04:23,000 ENVIRONMENT WHICH CAN BE UNDER 9164 06:04:23,000 --> 06:04:24,800 OUR CONTROL. OFTEN I'M ASKED ARE 9165 06:04:24,800 --> 06:04:28,520 THESE MICE OR MEN? HERE THIS 9166 06:04:28,520 --> 06:04:32,240 FIGURE SHOWS WHAT MODIFICATIONS 9167 06:04:32,240 --> 06:04:33,840 HAVE BEEN DONE TO ACTUALLY AT 9168 06:04:33,840 --> 06:04:37,600 DIFFERENT LEVELS WHICH IN MICE 9169 06:04:37,600 --> 06:04:42,040 MICE AND HUMANS MICE LEFT SIDE 9170 06:04:42,040 --> 06:04:44,760 HUMANS RIGHT SIDE, WITH 9171 06:04:44,760 --> 06:04:45,840 CANNABINOID DONE IN BOTH IN 9172 06:04:45,840 --> 06:04:47,200 HUMANS MANY STUDIES PRESENTED 9173 06:04:47,200 --> 06:04:50,800 TODAY AND OTHERWISE HAVE USED 9174 06:04:50,800 --> 06:04:52,920 PSYCHOSOCIAL MODULATION TO 9175 06:04:52,920 --> 06:04:55,200 REDUCE PAIN WHICH IS CBT 9176 06:04:55,200 --> 06:04:58,240 HYPNOSIS VIRTUAL REALITY, 9177 06:04:58,240 --> 06:05:00,880 RELAXATION, GUIDED IMAGERY, 9178 06:05:00,880 --> 06:05:03,480 ANTI-DESAINTS. WITH THAT HOE 9179 06:05:03,480 --> 06:05:04,600 ANTIDEPRESSANTS. WITH THAT I 9180 06:05:04,600 --> 06:05:08,600 HEARD A LOT ABOUT SOCIAL 9181 06:05:08,600 --> 06:05:11,880 PSYCHOLOGICAL FACTORS, THEIR 9182 06:05:11,880 --> 06:05:14,120 CONTROL, BUT EXCEPT DR. MORRIS'S 9183 06:05:14,120 --> 06:05:16,320 ELEGANT TALK ABOUT THE 9184 06:05:16,320 --> 06:05:18,040 INTERVENTION OF DIETARY 9185 06:05:18,040 --> 06:05:20,680 SUPPLEMENT ARGININE WE NEED TO 9186 06:05:20,680 --> 06:05:23,720 FOCUS ON FOOD ALSO AND AS WELL 9187 06:05:23,720 --> 06:05:26,800 AS COMPANIONSHIP. SHARING THE 9188 06:05:26,800 --> 06:05:28,200 BURDEN WILL DEFINITELY REDUCE 9189 06:05:28,200 --> 06:05:31,000 THE BURDEN. AND IN A HEALTHY 9190 06:05:31,000 --> 06:05:32,600 BODY WILL KEEP A HEALTHY MIND 9191 06:05:32,600 --> 06:05:36,560 AND THE MIND IS THE MASTER 9192 06:05:36,560 --> 06:05:39,320 ORCHESTRA TO REALLY GUIDE THE 9193 06:05:39,320 --> 06:05:42,600 BODY TO FEEL OR NOT TO FEEL THE 9194 06:05:42,600 --> 06:05:45,600 PAIN. THIS ALSO TELLS US THAT 9195 06:05:45,600 --> 06:05:49,120 WHAT DR. HE SHOWED WITH HIS DFUS 9196 06:05:49,120 --> 06:05:52,360 CAN BE EVEN MORE EFFECTIVE. ANY 9197 06:05:52,360 --> 06:05:53,560 INTERVENTION CAN BE MORE 9198 06:05:53,560 --> 06:05:55,400 EFFECTIVE IF WE CAN TAKE CARE OF 9199 06:05:55,400 --> 06:05:57,280 THESE FACTORS WHICH CAN BE 9200 06:05:57,280 --> 06:05:58,400 CONTROLLED BY US. WITH THAT I 9201 06:05:58,400 --> 06:06:01,320 WOULD LIKE TO THANK MY TEAM. WHO 9202 06:06:01,320 --> 06:06:04,960 HAD BEEN WORKING DAY AND NIGHT 9203 06:06:04,960 --> 06:06:09,400 AND MY COLLABORATOR DR. BADGAYAN 9204 06:06:09,400 --> 06:06:11,000 WHO IS INSTRUMENTAL, BECAUSE I 9205 06:06:11,000 --> 06:06:12,760 AM NOT A BRAIN SCIENTIST. AND HE 9206 06:06:12,760 --> 06:06:18,040 IS AN EXPERT IN SEROTONIN ERGIC 9207 06:06:18,040 --> 06:06:19,720 MECHANISM, BECAUSE OF HIM IT WAS 9208 06:06:19,720 --> 06:06:20,880 POSSIBLE TO UNDERTAKE THE STUDY. 9209 06:06:20,880 --> 06:06:22,720 I WOULD LIKE TO THANK YOU AND 9210 06:06:22,720 --> 06:06:24,360 THE ORGANIZERS. THANK YOU, VERY 9211 06:06:24,360 --> 06:06:39,200 MUCH. I THINK OUR NEXT SPEAKER 9212 06:06:39,200 --> 06:06:43,280 IS DR. KI KIMBERLEI RICHARDSON, 9213 06:06:43,280 --> 06:06:45,480 ASSOCIATE PROFESSOR MANY THE 9214 06:06:45,480 --> 06:06:47,600 DEPARTMENT OF PHARMACOLOGY AT 9215 06:06:47,600 --> 06:06:48,480 HOWARD UNIVERSITY COLLEGE OF 9216 06:06:48,480 --> 06:06:52,000 MEDICINE. HER LABORATORY 9217 06:06:52,000 --> 06:06:54,120 UTILIZES NEUROCHEMICAL 9218 06:06:54,120 --> 06:06:56,000 PHARMACOLOGICAL AND BEHAVIORAL 9219 06:06:56,000 --> 06:06:59,400 STRATEGIES TO STUDY THE ROLE OF 9220 06:06:59,400 --> 06:07:01,800 NEUROPEPTIDE REGULATION ON 9221 06:07:01,800 --> 06:07:03,520 CONSUMMATORY BEHAVIORS INCLUDING 9222 06:07:03,520 --> 06:07:07,720 FEEDING FORAGING AND ADDICTION. 9223 06:07:07,720 --> 06:07:10,080 SHE IS EMBARKED UPON PAIN 9224 06:07:10,080 --> 06:07:12,200 PROCESSING. SHE WILL PRESENT 9225 06:07:12,200 --> 06:07:14,920 VERY NOVEL FINDINGS ON THE 9226 06:07:14,920 --> 06:07:18,600 INFLUENCE OF A NOVEL SYSTEM, 9227 06:07:18,600 --> 06:07:20,640 OREXIN SYSTEM IN MEDIATING 9228 06:07:20,640 --> 06:07:21,640 HYPERALGESIA IN SICKLE CELL 9229 06:07:21,640 --> 06:07:24,960 DISEASE. AND DISCUSS THIS SYSTEM 9230 06:07:24,960 --> 06:07:31,040 AS A TARGET FOR INTERVENTIONS. 9231 06:07:31,040 --> 06:07:32,680 THIS IS ALSO BRAIN FOCUSED. 9232 06:07:32,680 --> 06:07:34,760 PROET NOD TO THE PROMOTING 9233 06:07:34,760 --> 06:07:37,320 DIVERSITY EQUITY AND INCLUSION 9234 06:07:37,320 --> 06:07:38,960 INITIATIVES TO INCREASE NUMBER 9235 06:07:38,960 --> 06:07:40,480 OF UNDER-REPRESENTED MINORITIES 9236 06:07:40,480 --> 06:07:44,360 IN BIOMEDICAL RESEARCH. WELCOME 9237 06:07:44,360 --> 06:07:45,240 DR. RICHARDSON AND THANK YOU FOR 9238 06:07:45,240 --> 06:07:47,160 ACCEPTING THE INVITATION. 9239 06:07:47,160 --> 06:07:58,200 >> THANK YOU VERY MUCH. I WILL 9240 06:07:58,200 --> 06:07:59,400 START MY SLIDES NOW. HOPEFULLY 9241 06:07:59,400 --> 06:08:04,200 ABLE TO SEE THEM. ARE YOU ABLE 9242 06:08:04,200 --> 06:08:05,800 TO SEE THEM? I THINK I'M 9243 06:08:05,800 --> 06:08:06,320 SHARING. 9244 06:08:06,320 --> 06:08:20,840 >> NO. NO. 9245 06:08:20,840 --> 06:08:30,440 >> MAYBE TAKING A LITTLE WHILE. 9246 06:08:30,440 --> 06:08:31,880 >> WE CAN SHARE THE SLIDES IF 9247 06:08:31,880 --> 06:08:33,120 YOU LIKE. 9248 06:08:33,120 --> 06:08:35,040 >> I'M GOING TO TRY ONE MORE 9249 06:08:35,040 --> 06:08:55,760 TIME. TODAY I WILL TALK ABOUT 9250 06:08:55,760 --> 06:08:58,040 TARGETING THE OREXIN SYSTEM FOR 9251 06:08:58,040 --> 06:08:59,280 PAIN SENSITIVITY AND SLEEP 9252 06:08:59,280 --> 06:09:00,200 INTERVENTIONS IN MANY SICKLE 9253 06:09:00,200 --> 06:09:03,680 CELL DISEASE. I'M GOING TO BE 9254 06:09:03,680 --> 06:09:05,800 PRESENTING DATA FROM A PILOT 9255 06:09:05,800 --> 06:09:08,320 STUDY TO INTRODUCE NEUROPEPTIDE 9256 06:09:08,320 --> 06:09:10,640 SYSTEM TO THIS PARTICULAR 9257 06:09:10,640 --> 06:09:13,240 COMMUNITY. AS A POSSIBLE 9258 06:09:13,240 --> 06:09:14,080 PHARMACOLOGICAL TARGET TO 9259 06:09:14,080 --> 06:09:16,120 IMPROVE THE QUALITY OF LIFE FOR 9260 06:09:16,120 --> 06:09:19,160 THOSE LIVING WITH SICKLE CELL 9261 06:09:19,160 --> 06:09:21,520 DISEASE. SO JUST TO GIVE YOU A 9262 06:09:21,520 --> 06:09:24,000 FLOW IN TERMS OF HOW THE 9263 06:09:24,000 --> 06:09:25,360 PRESENTATION WILL BE SET UP. I'M 9264 06:09:25,360 --> 06:09:26,760 GOING TO GIVE A LITTLE 9265 06:09:26,760 --> 06:09:29,600 BACKGROUND ABOUT OREXINS AND 9266 06:09:29,600 --> 06:09:31,200 PAIN, THEN SHARE SOME OF THE 9267 06:09:31,200 --> 06:09:32,440 DATA IN TERMS OF ESTABLISHING 9268 06:09:32,440 --> 06:09:35,560 BASELINE MEASUREMENTS OF PAIN 9269 06:09:35,560 --> 06:09:36,800 RESPONSES AND FALSE EXPRESSION 9270 06:09:36,800 --> 06:09:39,440 IN OREXIN NEURONS IN BOTH 9271 06:09:39,440 --> 06:09:41,600 CONTROL AS WELL AS SICKLE MICE. 9272 06:09:41,600 --> 06:09:44,240 THEN GIVE SOME BACKGROUND ABOUT 9273 06:09:44,240 --> 06:09:47,440 OREXIN RECEPTORS AND PAIN AND 9274 06:09:47,440 --> 06:09:49,480 PRESENT SOME DATA ASSESSING THE 9275 06:09:49,480 --> 06:09:52,640 ROLE OF OREXIN RECEPTOR 9276 06:09:52,640 --> 06:09:54,200 ANTAGONISM THEN FOLLOW WITH A 9277 06:09:54,200 --> 06:09:55,920 BRIEF DISCUSSION ABOUT TESTIMONY 9278 06:09:55,920 --> 06:09:58,800 ROLE OF OREXIN SIGNALING IN 9279 06:09:58,800 --> 06:10:00,760 DISREGULATION OF SLEEP, PAIN 9280 06:10:00,760 --> 06:10:03,400 PROCESSING AND HOW THAT MAY BE 9281 06:10:03,400 --> 06:10:04,360 ACTUALLY IMPORTANT IN SICKLE 9282 06:10:04,360 --> 06:10:07,400 CELL DISEASE. I HAVE NO 9283 06:10:07,400 --> 06:10:10,720 FINANCIAL INTERESTS TO DISCLOSE. 9284 06:10:10,720 --> 06:10:12,640 SICKLE CELL DISEASE IS A 9285 06:10:12,640 --> 06:10:13,800 HEMOGLOBINOPATHY THAT CAUSES 9286 06:10:13,800 --> 06:10:15,720 SICKLING OF RED BLOOD CELLS 9287 06:10:15,720 --> 06:10:19,440 RESULTS IN VESSEL DAMAGE, STROKE 9288 06:10:19,440 --> 06:10:22,480 ANEMIA, INFLAMMATION AND EXTREME 9289 06:10:22,480 --> 06:10:24,000 PAIN. THE PAIN IN SICKLE CELL 9290 06:10:24,000 --> 06:10:25,880 DISEASE IS ASSOCIATED WITH 9291 06:10:25,880 --> 06:10:28,640 SIGNIFICANT MORBIDITY AND 9292 06:10:28,640 --> 06:10:30,320 INCREASE MORTALITY. BECAUSE 9293 06:10:30,320 --> 06:10:32,680 EFFECTIVE PAIN MANAGEMENT IS A 9294 06:10:32,680 --> 06:10:33,840 CHALLENGE IN THIS POPULATION, 9295 06:10:33,840 --> 06:10:35,920 THERE IS A GREAT NEED TO 9296 06:10:35,920 --> 06:10:38,600 IDENTIFY SOME ALTERNATIVE 9297 06:10:38,600 --> 06:10:41,360 ANALGESIC AGENTS. BECAUSE OF 9298 06:10:41,360 --> 06:10:42,920 THIS, MANY PEOPLE REPORTED THAT 9299 06:10:42,920 --> 06:10:46,560 THEIR PAIN IS NOT NECESSARILY 9300 06:10:46,560 --> 06:10:48,320 MANAGED EFFECTIVELY SO IT IS 9301 06:10:48,320 --> 06:10:50,000 NECESSARY TO TRY TO PURSUE NEW 9302 06:10:50,000 --> 06:10:52,200 OPTIONS FOR PAIN TREATMENT. I 9303 06:10:52,200 --> 06:10:54,720 BELIEVE THE OREXIN SYSTEM MAY 9304 06:10:54,720 --> 06:10:56,120 OFFER A NOVEL APPROACH TO 9305 06:10:56,120 --> 06:10:58,680 TREATING PAIN. SO THIS 9306 06:10:58,680 --> 06:11:00,360 PARTICULAR NEURAL PEPTIDE SYSTEM 9307 06:11:00,360 --> 06:11:03,640 ALSO KNOWN AS HYPERCREE TINS 9308 06:11:03,640 --> 06:11:05,160 THEY ARE SYNTHESIZE WITHIN THE 9309 06:11:05,160 --> 06:11:09,320 DORSAL MEDIAL HYPOTHALAMUS, THE 9310 06:11:09,320 --> 06:11:13,640 PERIFORNICAL AREA AND LATERAL 9311 06:11:13,640 --> 06:11:15,120 HYPOTHALAMUS. THERE ARE TWO PEP 9312 06:11:15,120 --> 06:11:18,720 SIDES OREXIN A AND B. THERE ARE 9313 06:11:18,720 --> 06:11:20,160 TWO RECEPTORS THAT ARE G 9314 06:11:20,160 --> 06:11:23,040 COUPLED. SO THE OREXIN RECEPTOR 9315 06:11:23,040 --> 06:11:26,000 1 IS SELECTED FOR THE OREXIN A 9316 06:11:26,000 --> 06:11:28,600 PEPTIDE WHILE THE OREXIN 9317 06:11:28,600 --> 06:11:30,000 RECEPTOR 2 IS NON-SELECTIVE FOR 9318 06:11:30,000 --> 06:11:35,600 BOTH PEPTIDES. THE OREXIN 9319 06:11:35,600 --> 06:11:40,600 NEURONS INNERVATE VARIOUSRY 9320 06:11:40,600 --> 06:11:42,440 GENERALS INCLUDING SOME IN THE 9321 06:11:42,440 --> 06:11:45,000 DORSAL HORN. THEY ARE INVOLVED 9322 06:11:45,000 --> 06:11:47,200 IN AROUSAL, FEEDING NARCOLEPSY, 9323 06:11:47,200 --> 06:11:48,640 ENERGY BALANCE AND REWARD 9324 06:11:48,640 --> 06:11:50,400 PROCESSING SO MY BACKGROUND IS 9325 06:11:50,400 --> 06:11:52,600 DEALING WITH THE INFLUENCE OF 9326 06:11:52,600 --> 06:11:53,960 THIS PARTICULAR SYSTEM AND 9327 06:11:53,960 --> 06:11:55,440 REWARD PROCESSING. BUT IT IS 9328 06:11:55,440 --> 06:11:57,560 ALSO BEEN SHOWN THAT IT IS 9329 06:11:57,560 --> 06:12:02,600 INVOLVED IN ANALGESIA. THESE 9330 06:12:02,600 --> 06:12:03,680 PROJECTIONS GO TO BRAIN REGIONS 9331 06:12:03,680 --> 06:12:05,880 THAT PLAY A ROLE IN DESCENDING 9332 06:12:05,880 --> 06:12:11,600 PAIN INHIBITION. GIVEN THAT 9333 06:12:11,600 --> 06:12:13,400 THERE WERE SEVERAL STUDIES THAT 9334 06:12:13,400 --> 06:12:15,600 HAVE FOCUSED ON THE OREXIN 9335 06:12:15,600 --> 06:12:18,040 SYSTEM AND REWARD PROCESSING SO 9336 06:12:18,040 --> 06:12:19,680 TODAY WE WILL MOVE BEYOND THAT 9337 06:12:19,680 --> 06:12:22,800 AND FOCUS MORE SO ON ITS 9338 06:12:22,800 --> 06:12:24,920 RELATIONSHIP WITH PAIN. SOME OF 9339 06:12:24,920 --> 06:12:28,200 THE STUDIES HAVE SHOWN THAT THE 9340 06:12:28,200 --> 06:12:30,520 OREXIN A PEPTIDE HAS ANALGESIC 9341 06:12:30,520 --> 06:12:33,360 EFFECT ON INFLAMMATORY PAIN. IT 9342 06:12:33,360 --> 06:12:35,040 MAY AFFECT MECHANISMS UNDERLYING 9343 06:12:35,040 --> 06:12:37,680 THE MAINTENANCE OF NEUROPATHIC 9344 06:12:37,680 --> 06:12:41,960 PAIN. IT HAD BEEN STATED IN 9345 06:12:41,960 --> 06:12:43,560 PRIOR STUDIES THAT THE 9346 06:12:43,560 --> 06:12:45,360 OCCURRENCE OF NEUROPATHIC PAIN 9347 06:12:45,360 --> 06:12:47,200 WITHIN THE SICKLE CELL 9348 06:12:47,200 --> 06:12:48,440 POPULATION, MAYBE IN FACT TWICE 9349 06:12:48,440 --> 06:12:49,880 AS MUCH AS WHAT IS FOUND IN 9350 06:12:49,880 --> 06:12:54,000 OTHER CHRONIC PAIN POPULATIONS. 9351 06:12:54,000 --> 06:12:55,440 AND THERE ARE DEFINING 9352 06:12:55,440 --> 06:12:57,680 CHARACTERISTICS OF NEUROPATHIC 9353 06:12:57,680 --> 06:13:00,200 PAIN, TODAY I'M GOING TO FOCUS 9354 06:13:00,200 --> 06:13:03,160 ON HYPERAJEEZIA WHICH IS THAT 9355 06:13:03,160 --> 06:13:06,200 INCREASE PAINFUL SENSATION TO 9356 06:13:06,200 --> 06:13:07,000 NOXIOUS STIMULUS. IT IS ONE OF 9357 06:13:07,000 --> 06:13:09,200 THE FACTORS THAT IS USED TO 9358 06:13:09,200 --> 06:13:11,840 CHARACTERIZE NEUROPATHIC PAIN. 9359 06:13:11,840 --> 06:13:13,320 BEFORE IT CAN BE DETERMINED HOW 9360 06:13:13,320 --> 06:13:18,160 THE OREXIN SYSTEM IS INVOLVED IN 9361 06:13:18,160 --> 06:13:19,160 MEDIATION OF PAIN, AND HOW THAT 9362 06:13:19,160 --> 06:13:20,960 IS APPLIED TO SICKLE CELL, WHAT 9363 06:13:20,960 --> 06:13:24,560 WE WANT TO DO IS FIRST DETERMINE 9364 06:13:24,560 --> 06:13:25,760 WHETHER THERE WERE CHANGES IN 9365 06:13:25,760 --> 06:13:28,120 VARIOUS SUB POPULATIONS OF 9366 06:13:28,120 --> 06:13:29,880 OREXIN NEURONS, NOTHING IN THE 9367 06:13:29,880 --> 06:13:32,400 LITERATURE AS FAR AS ASSOCIATION 9368 06:13:32,400 --> 06:13:35,160 BETWEEN THIS PARTICULAR PEPTIDE 9369 06:13:35,160 --> 06:13:36,320 SYSTEM AND SICKLE CELL. WE 9370 06:13:36,320 --> 06:13:38,200 WANTED TO DO THAT IN ORDER TO 9371 06:13:38,200 --> 06:13:41,920 REALLY START TO GET AT THE 9372 06:13:41,920 --> 06:13:42,800 ACTIVITY OF THE NEURONAL 9373 06:13:42,800 --> 06:13:43,840 CIRCUITRY AND ALL THAT BECAUSE 9374 06:13:43,840 --> 06:13:46,080 THAT ULTIMATELY WILL HELP TO 9375 06:13:46,080 --> 06:13:48,400 ALLOW US TO HAVE A BETTER 9376 06:13:48,400 --> 06:13:49,280 PERSPECTIVE IN TERMS OF 9377 06:13:49,280 --> 06:13:50,320 DIFFERENT PATTERNS OF ACTIVITY 9378 06:13:50,320 --> 06:13:54,480 OF THE SUBPOPULATIONS OF THESE 9379 06:13:54,480 --> 06:13:57,040 NEURONS. SO IN ORDER TO DO THIS 9380 06:13:57,040 --> 06:13:59,360 WE COLLABORATED MY LAB 9381 06:13:59,360 --> 06:14:01,000 COLLABORATED WITH DR. GUPTA'S 9382 06:14:01,000 --> 06:14:03,800 LAB AND WE UTILIZE TRANSGENIC 9383 06:14:03,800 --> 06:14:05,800 MOUSE MODEL THAT EXPRESSES THE 9384 06:14:05,800 --> 06:14:08,000 SICKLE HEMOGLOBIN, HUMAN 9385 06:14:08,000 --> 06:14:10,840 HEMOGLOBIN. THAT FIRST GOAL WAS 9386 06:14:10,840 --> 06:14:12,120 TO KIND OF ESTABLISH BASELINE 9387 06:14:12,120 --> 06:14:14,440 MEASUREMENTS OF PAIN RESPONSES, 9388 06:14:14,440 --> 06:14:17,760 IN ADDITION TO ASSESSING FALSE 9389 06:14:17,760 --> 06:14:20,720 EXPRESSION IN OREXIN NEURONS. WE 9390 06:14:20,720 --> 06:14:26,360 DID THIS IN FEMALE MICE. 9391 06:14:26,360 --> 06:14:28,000 VARIOUS BEHAVIORAL TESTS WERE 9392 06:14:28,000 --> 06:14:30,920 PERFORMED TO CHARACTERIZE THE 9393 06:14:30,920 --> 06:14:33,200 HYPERALGESIA IN THE SICKLE MICE, 9394 06:14:33,200 --> 06:14:35,600 TRANSGENIC HOMOZYGOUS MICE THAT 9395 06:14:35,600 --> 06:14:37,320 EXPRESSED HUMAN SICKLE 9396 06:14:37,320 --> 06:14:39,400 HEMOGLOBIN. OF COURSE THE 9397 06:14:39,400 --> 06:14:40,520 CONTROL MICE, THESE ARE MICE 9398 06:14:40,520 --> 06:14:43,840 THAT HAVE THE SAME GENETIC 9399 06:14:43,840 --> 06:14:47,240 BACKGROUNDS BUT EXPRESS NORMAL 9400 06:14:47,240 --> 06:14:49,320 HEMOGLOBIN EXCLUSIVELY SO THE 9401 06:14:49,320 --> 06:14:51,440 BRAIN REGIONS WERE 9402 06:14:51,440 --> 06:14:52,760 IMMUNOHISTOCHEMICALLY PROCESSED 9403 06:14:52,760 --> 06:14:54,720 FOR CFOS USE AS MARKER FOR 9404 06:14:54,720 --> 06:14:55,600 NEURONAL ACTIVITY AND SECTIONS 9405 06:14:55,600 --> 06:14:58,600 WILL PROCESSED FOR THE OREXIN A 9406 06:14:58,600 --> 06:15:00,480 PEPTIDE. FOLLOWED BY THOSE 9407 06:15:00,480 --> 06:15:05,640 SALES ACTUALLY BEING QUANTIFIED 9408 06:15:05,640 --> 06:15:08,960 TO DETERMINE CHANGES IN DORSAL 9409 06:15:08,960 --> 06:15:11,000 MEDIAL HYPOTHALAMUS, THE LATERAL 9410 06:15:11,000 --> 06:15:11,600 HYPERTHALAMUS AFTER THE 9411 06:15:11,600 --> 06:15:13,360 BEHAVIORAL TEST. FOR THE SAKE 9412 06:15:13,360 --> 06:15:15,920 OF TIME I WILL PRESENT THE DATA 9413 06:15:15,920 --> 06:15:18,240 RELATIVE TO MECHANICAL AND 9414 06:15:18,240 --> 06:15:22,640 THERMAL OR HEAT HYPERALGESIA. SO 9415 06:15:22,640 --> 06:15:25,240 TO ASSESS SENSITIVITY TO THE 9416 06:15:25,240 --> 06:15:27,880 MECHANICAL STIMULUS, THE MICE 9417 06:15:27,880 --> 06:15:30,960 WERE PLACED ON A WIRE MESH UNDER 9418 06:15:30,960 --> 06:15:32,280 GLASS CONTAINER AND THE FILAMENT 9419 06:15:32,280 --> 06:15:34,440 WAS APPLIED TO THE SURFACE OF 9420 06:15:34,440 --> 06:15:38,440 THE HIND PAW, THE MICE. THE 9421 06:15:38,440 --> 06:15:40,600 FREQUENCY IN WHICH MICE MOVED 9422 06:15:40,600 --> 06:15:42,640 THEIR HAND FROM THE MESH WAS 9423 06:15:42,640 --> 06:15:44,320 RECORDED SO WHAT THIS IS SHOWING 9424 06:15:44,320 --> 06:15:46,520 IS SICKLE MICE INDICATED BY THE 9425 06:15:46,520 --> 06:15:51,000 BLACK BAR DISPLAY SIGNIFICANTLY 9426 06:15:51,000 --> 06:15:52,800 MORE PAW WITHDRAWAL FREQUENCY 9427 06:15:52,800 --> 06:15:55,560 VERSUS OUR CONTROL MICE. IN 9428 06:15:55,560 --> 06:15:58,080 ADDITION TO THAT, TO TEST FOR 9429 06:15:58,080 --> 06:16:03,200 HEAT SENSITIVITY, PAW WITHDRAWAL 9430 06:16:03,200 --> 06:16:06,000 LATENCY WAS RECORDED WHEN THE 9431 06:16:06,000 --> 06:16:07,440 PLANTAR SURFACE OF THE HYPPED 9432 06:16:07,440 --> 06:16:08,640 PAW WAS WITHDRAWN FROM THE HEAT 9433 06:16:08,640 --> 06:16:14,600 SUSURFACE. SHORTER INTERVALS 9434 06:16:14,600 --> 06:16:18,200 INDICATE HEAT SENSITIVITY AS BY 9435 06:16:18,200 --> 06:16:19,640 PAW WITHDRAW LATENCY IN THE 9436 06:16:19,640 --> 06:16:20,800 CONTROL. OUR CONTROL MICE WERE 9437 06:16:20,800 --> 06:16:22,800 ABLE TO ENDURE THE HEAT STIMULUS 9438 06:16:22,800 --> 06:16:24,920 MUCH LONGER THAN THE SICKLE MICE 9439 06:16:24,920 --> 06:16:27,240 WERE AND INCREASE SENSITIVITY TO 9440 06:16:27,240 --> 06:16:32,200 COLD AND TO HEAT, IS POSSIBLY 9441 06:16:32,200 --> 06:16:33,600 CUTANEOUS HYPERALGESIA, 9442 06:16:33,600 --> 06:16:34,840 CONSISTENT WITH OBSERVATIONS 9443 06:16:34,840 --> 06:16:37,600 THAT PAINFUL CRISIS IN PATIENTS 9444 06:16:37,600 --> 06:16:39,600 WITH SICKLE CELL MAYBE RELATED 9445 06:16:39,600 --> 06:16:44,120 TO WEATHER EXTREMES. FOLLOWING 9446 06:16:44,120 --> 06:16:46,000 ALL OF THE BEHAVIORAL TESTS, 9447 06:16:46,000 --> 06:16:51,600 AGAIN I'M PRESENTING THE MEEKAL 9448 06:16:51,600 --> 06:16:53,840 AND THERMAL HYPERALGESIA TODAY 9449 06:16:53,840 --> 06:16:55,520 BUT FOLLOWING THE TEST THE MICE 9450 06:16:55,520 --> 06:16:57,800 WERE PROFUSED AND SECTIONS WERE 9451 06:16:57,800 --> 06:17:00,000 PROCESSED FOR DOUBLE LABEL 9452 06:17:00,000 --> 06:17:01,000 IMMUNOHISTOCHEMISTRY. THE 9453 06:17:01,000 --> 06:17:03,000 PICTURE ABOVE SHOWS VARIOUS CELL 9454 06:17:03,000 --> 06:17:06,720 TYPES THAT WE SAW. SO THE RED 9455 06:17:06,720 --> 06:17:11,200 ARROWS ARE INDICATIVE OF SINGLE 9456 06:17:11,200 --> 06:17:12,800 SALE, CELLS ACTIVATED AS A 9457 06:17:12,800 --> 06:17:14,680 RESULT OF BEHAVIORAL TESTING BUT 9458 06:17:14,680 --> 06:17:19,200 THEY ARE NOT NECESSARILY OREXIN 9459 06:17:19,200 --> 06:17:23,800 POSITIVE. WE SAW SINGLE CELL 9460 06:17:23,800 --> 06:17:25,920 OREXIN CELLS, THESE ARE 9461 06:17:25,920 --> 06:17:29,120 INDICATED -- INDICATIVE OF GREEN 9462 06:17:29,120 --> 06:17:31,200 OWLS AND THESE STAINING FOR 9463 06:17:31,200 --> 06:17:32,880 OREXIN A PEPTIDE. THESE CELLS 9464 06:17:32,880 --> 06:17:36,320 WERE NOT ACTIVATED AS A RESULT 9465 06:17:36,320 --> 06:17:37,040 OF BEHAVE I DON'T RECALL TEST. 9466 06:17:37,040 --> 06:17:40,600 THE MOST RELEVANT FOR THIS ARE 9467 06:17:40,600 --> 06:17:42,160 DOUBLE LABEL CELLS WHICH ARE 9468 06:17:42,160 --> 06:17:46,400 FALSE POSITIVE OREXIN CELLS 9469 06:17:46,400 --> 06:17:54,800 INDIANA KAYTIVE OF THE BLUE 9470 06:17:54,800 --> 06:17:57,080 INDICATIVE OF BLUE ARROWS. 9471 06:17:57,080 --> 06:17:59,280 WHETHER THE LATERAL HYPOTHALAMUS 9472 06:17:59,280 --> 06:18:01,480 OR THE PERIFOREIGNCAL AREA. JUST 9473 06:18:01,480 --> 06:18:03,880 AS ASIDE THE LATERAL 9474 06:18:03,880 --> 06:18:05,440 HYPOTHALAMUS HAS BEEN A 9475 06:18:05,440 --> 06:18:07,280 ASSOCIATED WITH REWARD 9476 06:18:07,280 --> 06:18:09,720 PROCESSING. WHEREAS THE DORSAL 9477 06:18:09,720 --> 06:18:12,960 MEDIAL HYPOTHALAMUS HAVE BEEN 9478 06:18:12,960 --> 06:18:17,480 MORE ASSOCIATED SAY WITH AROUSAL 9479 06:18:17,480 --> 06:18:20,960 AND STRESS. SO THE RESULTS FROM 9480 06:18:20,960 --> 06:18:22,600 THE QUANTIFICATION IN FACT SHOW 9481 06:18:22,600 --> 06:18:26,640 THAT THE PERCENTAGE OF OREXIN 9482 06:18:26,640 --> 06:18:28,760 POSITIVE NEURONS THAT ARE FALSE 9483 06:18:28,760 --> 06:18:31,240 POSITIVE WITHIN THE PERIFORNICAL 9484 06:18:31,240 --> 06:18:33,120 AREA, THIS REPRESENTING OUR 9485 06:18:33,120 --> 06:18:37,080 CONTROL ANIMALS. WITHIN THE 9486 06:18:37,080 --> 06:18:38,320 PERIFORNICAL AREA THEY WERE 9487 06:18:38,320 --> 06:18:39,640 HIGHER THAN WHAT WAS SEEN WITHIN 9488 06:18:39,640 --> 06:18:42,960 THE LATERAL HYPOTHALAMUS. WHICH 9489 06:18:42,960 --> 06:18:44,080 MAKES SENSE BECAUSE AGAIN 9490 06:18:44,080 --> 06:18:46,200 LATERAL HYPOTHALAMUS IS MORE 9491 06:18:46,200 --> 06:18:47,560 ASSOCIATED AT LEAST WITH MORE 9492 06:18:47,560 --> 06:18:50,760 REWARD PROCESSING. IN IN TERMS 9493 06:18:50,760 --> 06:18:55,600 OF PERCENTAGE OF OREXIN FOS 9494 06:18:55,600 --> 06:18:57,360 CELLS RELATED TO THE CIRCLE 9495 06:18:57,360 --> 06:19:00,000 ANIMALS, WE SEE WITHIN THE 9496 06:19:00,000 --> 06:19:03,160 PERIFORNICAL AREA, YOU HAVE 9497 06:19:03,160 --> 06:19:04,120 SIGNIFICANTLY HIGHER PERCENTAGE 9498 06:19:04,120 --> 06:19:05,640 VERSUS WHAT YOU HAVE IN THE LH 9499 06:19:05,640 --> 06:19:07,600 BUT WE ALSO SAW SIGNIFICANT 9500 06:19:07,600 --> 06:19:09,480 DIFFERENCE WITHIN THE DORSAL 9501 06:19:09,480 --> 06:19:14,320 MEDIAL HYPOTHALAMUS. SO THE 9502 06:19:14,320 --> 06:19:17,200 TOPOGRAPHICAL DATA INDICATE THE 9503 06:19:17,200 --> 06:19:18,520 PERIFORNICAL AREAS MAYBE A 9504 06:19:18,520 --> 06:19:19,760 GENERAL TARGET REGION FOR 9505 06:19:19,760 --> 06:19:21,880 STUDYING PAIN, GIVEN THE 9506 06:19:21,880 --> 06:19:23,960 INCREASE ACTIVATION THAT WE SEE 9507 06:19:23,960 --> 06:19:27,560 IN BOLD GROUPS OF ANIMALS AFTER 9508 06:19:27,560 --> 06:19:30,000 THE PAIN -- THE DORSAL MEDIAL 9509 06:19:30,000 --> 06:19:31,240 HYPOTHALAMUS MAY PLAY A GREATER 9510 06:19:31,240 --> 06:19:33,360 ROLE IN MEDIATING THE MECHANISMS 9511 06:19:33,360 --> 06:19:35,480 ASSOCIATED WITH HYPERALGESIA IN 9512 06:19:35,480 --> 06:19:37,560 OUR SICKLE ANIMALS VERSUS THE 9513 06:19:37,560 --> 06:19:40,120 CONTROL ANIMALS. SO WE BELIEVE 9514 06:19:40,120 --> 06:19:41,680 MAYBE MORE DIVERSE DISTRIBUTION 9515 06:19:41,680 --> 06:19:44,120 OF OREXIN NEURONS ARE REQUIRED 9516 06:19:44,120 --> 06:19:47,320 TO PRODUCE THE ANALGESIA AFTER 9517 06:19:47,320 --> 06:19:49,840 PAIN TESTING IN SICKLE ANIMALS. 9518 06:19:49,840 --> 06:19:51,720 SO PERHAPS WHAT IS GOING ON IS 9519 06:19:51,720 --> 06:19:56,440 THE DORSAL MEDIAL OREXIN NEURONS 9520 06:19:56,440 --> 06:19:57,200 ARE PREFERENTIALLY RECRUITED 9521 06:19:57,200 --> 06:20:02,000 DURING THE PAIN TESTING, AND A 9522 06:20:02,000 --> 06:20:03,320 MORE GREATER DISTRIBUTION IN 9523 06:20:03,320 --> 06:20:05,400 TERMS OF DIVERSITY OF OREXIN 9524 06:20:05,400 --> 06:20:06,640 NEURONS MIGHT BE REQUIRED TO 9525 06:20:06,640 --> 06:20:08,560 PRODUCE ANALGESIA IN CIRCLE 9526 06:20:08,560 --> 06:20:12,240 ANIMALS. ONE THING FOR SURE, 9527 06:20:12,240 --> 06:20:14,920 IDENTIFYING SPECIFIC OREXIN 9528 06:20:14,920 --> 06:20:16,880 NEURONAL POPULATIONS IS INTEGRAL 9529 06:20:16,880 --> 06:20:20,080 IN TERMS OF UNDERSTANDING PAIN 9530 06:20:20,080 --> 06:20:21,880 PROCESSING. AND OF COURSE 9531 06:20:21,880 --> 06:20:24,600 HOPEFULLY THAT WILL ALLOW US TO 9532 06:20:24,600 --> 06:20:25,840 ELUCIDATE MECHANISMS THAT CAN 9533 06:20:25,840 --> 06:20:27,400 PROVIDE A MORE SELECTIVE 9534 06:20:27,400 --> 06:20:29,920 TARGETED APPROACH IN TERMS OF 9535 06:20:29,920 --> 06:20:33,200 TREATING PAIN IN SICKLE CELL 9536 06:20:33,200 --> 06:20:33,440 DISEASE. 9537 06:20:33,440 --> 06:20:34,560 >> TWO MINUTE WARNING. 9538 06:20:34,560 --> 06:20:38,720 >> SO IN ADDITION TO THE 9539 06:20:38,720 --> 06:20:40,600 FOCUSING ON THE NEUROPEPTIDE WE 9540 06:20:40,600 --> 06:20:42,200 WERE INTERESTED IN TERMS OF THE 9541 06:20:42,200 --> 06:20:46,200 RECEPTORS. THERE'S BEEN SEVERAL 9542 06:20:46,200 --> 06:20:48,480 REPORTS IN TERMS OF HOW THE 9543 06:20:48,480 --> 06:20:51,960 OREXIN RECEPTORS AND PAIN ARE 9544 06:20:51,960 --> 06:20:54,080 ASSOCIATED. OUR FIRST 9545 06:20:54,080 --> 06:20:55,120 EXPERIMENTS REALLY FOCUSED ON 9546 06:20:55,120 --> 06:21:00,360 THE PEPTIDE IN PARTICULAR. THESE 9547 06:21:00,360 --> 06:21:01,600 SPECIFIC REPORTS BASICALLY 9548 06:21:01,600 --> 06:21:05,440 SHOWING THAT IT IS THE OREXIN 9549 06:21:05,440 --> 06:21:07,360 RECEPTOR 1 MAY IN FACT BE MORE 9550 06:21:07,360 --> 06:21:09,000 IMPORTANT IN TERMS OF MEDIATING 9551 06:21:09,000 --> 06:21:12,000 THE PAIN. ONE OF THE QUESTIONS 9552 06:21:12,000 --> 06:21:15,200 CAN HYPERALGESIA BE POTENTIATED 9553 06:21:15,200 --> 06:21:18,080 WHEN OREXIN EFFECT IS 9554 06:21:18,080 --> 06:21:21,000 ADMINISTERED. WE HAD ANIMALS, 9555 06:21:21,000 --> 06:21:23,760 SICKLE AND CONTROL THAT 9556 06:21:23,760 --> 06:21:25,840 UNDERSTOOD WENT PAIN TESTING, 9557 06:21:25,840 --> 06:21:28,280 THEY WERE GIVEN RECEPTOR 1 9558 06:21:28,280 --> 06:21:29,720 ANTAGONIST 30 MINUTES PRIOR TO 9559 06:21:29,720 --> 06:21:31,480 TESTING AND ANIMALS ARE TESTED 9560 06:21:31,480 --> 06:21:33,440 ONE HOUR AND 24 HOURS AFTER 9561 06:21:33,440 --> 06:21:36,200 ADMINISTRATION OF THE OREXIN 9562 06:21:36,200 --> 06:21:39,480 RECEPTOR 1 ANTAGONIST. WE USE SB 9563 06:21:39,480 --> 06:21:42,200 338467. FOR SAKE OF TIME I'M 9564 06:21:42,200 --> 06:21:43,520 ONLY GOING TO PRESENT THE FEMALE 9565 06:21:43,520 --> 06:21:45,840 DATA. JUST TO KIND OF SUMMARIZE 9566 06:21:45,840 --> 06:21:48,840 BASICALLY WHAT IT IS SHOWING IS 9567 06:21:48,840 --> 06:21:51,800 THAT YOU HAVE A REDUCTION IN PAW 9568 06:21:51,800 --> 06:21:54,200 WITHDRAWAL LATENCY WITH PRIOR TO 9569 06:21:54,200 --> 06:21:57,840 GIVING THE OREXIN ANTAGONIST BUT 9570 06:21:57,840 --> 06:22:00,600 FURTHER POTENTIATION IN TERMS OF 9571 06:22:00,600 --> 06:22:03,440 -- FURTHER REDUCTION IN LATENCY 9572 06:22:03,440 --> 06:22:06,200 ONE HOUR AFTER THE SB IN FEMALE 9573 06:22:06,200 --> 06:22:07,960 ANIMALS. AND I WILL JUST LIKE TO 9574 06:22:07,960 --> 06:22:10,120 SAY THAT THIS IS SPECIFICALLY 9575 06:22:10,120 --> 06:22:12,160 FOR SICKLE ANIMALS SO WE DON'T 9576 06:22:12,160 --> 06:22:14,520 SEE THIS REDUCTION IN LATENCY 9577 06:22:14,520 --> 06:22:18,600 AFTER THE OREXIN ANTAGONIST IN 9578 06:22:18,600 --> 06:22:20,160 NORMAL ANIMALS, ONLY THE SICKLE 9579 06:22:20,160 --> 06:22:23,000 ANIMALS. SO BASICALLY WHAT WE 9580 06:22:23,000 --> 06:22:25,520 KNOW IS THE FACT THAT ONE, THE 9581 06:22:25,520 --> 06:22:28,400 DORSAL MEDIAL HYPOTHALAMUS, THAT 9582 06:22:28,400 --> 06:22:29,800 PARTICULAR SUBPOPULATION OF 9583 06:22:29,800 --> 06:22:31,880 NEURONS MAY IN FACT BE MORE 9584 06:22:31,880 --> 06:22:34,160 HEAVILY RECRUITED IN SICKLE CELL 9585 06:22:34,160 --> 06:22:35,400 AFTER PAINFUL STIMULUS AND ALSO 9586 06:22:35,400 --> 06:22:40,400 THAT IN FACT, FOR SICKLE CELL 9587 06:22:40,400 --> 06:22:41,960 FEMALE ANIMALS WE SEE THIS 9588 06:22:41,960 --> 06:22:43,800 FURTHER REDUCTION IN TERMS OF 9589 06:22:43,800 --> 06:22:46,000 LATENCY TO HEAT. SUGGESTING THAT 9590 06:22:46,000 --> 06:22:48,360 THERE MAYBE SOME DIFFERENTIAL 9591 06:22:48,360 --> 06:22:50,640 RESPONSIVENESS TO OREXIN 9592 06:22:50,640 --> 06:22:55,240 RECEPTOR ANTAGONIST. SO JUST TO 9593 06:22:55,240 --> 06:22:58,120 FINISH UP, IN TERMS OF OREXIN 9594 06:22:58,120 --> 06:23:00,080 SYSTEM IT PROJECTS SEVERAL BRAIN 9595 06:23:00,080 --> 06:23:01,520 REGIONS THAT MEDIATE SLEEP AS 9596 06:23:01,520 --> 06:23:04,000 WELL AS AROUSAL. SO STUDIES 9597 06:23:04,000 --> 06:23:06,640 REALLY HAVE SHOWN A GREAT DEGREE 9598 06:23:06,640 --> 06:23:08,600 OF CO-MORBIDITY BETWEEN PAIN AND 9599 06:23:08,600 --> 06:23:10,200 SLEEP IMPAIRMENT. BECAUSE OF 9600 06:23:10,200 --> 06:23:12,280 THIS THE THOUGHT IS SLEEP LOSS 9601 06:23:12,280 --> 06:23:14,880 MAY RESULT IN DEVELOPMENT OF 9602 06:23:14,880 --> 06:23:16,200 HYPERALGESIA, SO A CRITICAL ROLE 9603 06:23:16,200 --> 06:23:18,240 FOR THE OREXIN SYSTEM IN TERMS 9604 06:23:18,240 --> 06:23:20,560 OF REGULATION OF SLEEP AND PAIN 9605 06:23:20,560 --> 06:23:22,200 RELATIONSHIP REALLY SHOULD BE 9606 06:23:22,200 --> 06:23:25,480 INVESTIGATED. ALSO THE PAIN AND 9607 06:23:25,480 --> 06:23:29,440 SLEEP IMPAIRMENTS ARE TWO MAJOR 9608 06:23:29,440 --> 06:23:30,640 IMPORTANT OBSERVATIONS THAT ARE 9609 06:23:30,640 --> 06:23:33,080 FOUND WITHIN THE SICKLE 9610 06:23:33,080 --> 06:23:35,400 POPULATION. SO THIS IS JUST TO 9611 06:23:35,400 --> 06:23:38,240 SHOW SOME OF THE LITERATURE THAT 9612 06:23:38,240 --> 06:23:40,200 SO FAR HAS BEEN PUBLISHED AS FAR 9613 06:23:40,200 --> 06:23:44,120 AS RELATIONSHIP BETWEEN SLEEP 9614 06:23:44,120 --> 06:23:46,240 DISORDERS AND HOW OREXIN SYSTEM 9615 06:23:46,240 --> 06:23:48,000 CAN BE IMPACTED. WITH SLEEP 9616 06:23:48,000 --> 06:23:49,560 PATIENTS OFTEN TIME THERE IS IS 9617 06:23:49,560 --> 06:23:51,000 DECREASED DURATION, THEY HAVE 9618 06:23:51,000 --> 06:23:53,000 LATE ONSET OF SLEEP, I WILL 9619 06:23:53,000 --> 06:23:55,520 SPEND MORE TIME AWAKE -- OR 9620 06:23:55,520 --> 06:23:57,480 SPEND OR TIME AWAKE DURING THE 9621 06:23:57,480 --> 06:23:58,400 NIGHT OR INCREASED 9622 06:23:58,400 --> 06:24:01,480 FRAGMENTATION. THERE'S TWO 9623 06:24:01,480 --> 06:24:03,440 OREXIN SPECIFIC DUAL OREXIN 9624 06:24:03,440 --> 06:24:05,000 RECEPTOR ANTAGONIST, THEY 9625 06:24:05,000 --> 06:24:07,000 INHIBIT RECEPTOR SIGNALING AND 9626 06:24:07,000 --> 06:24:09,880 PROMOTE SLEEP BY REDUCING 9627 06:24:09,880 --> 06:24:12,200 WAKEFULNESS AND LATENCY TO 9628 06:24:12,200 --> 06:24:13,560 PERSISTENT SLEEP. THERE HAVE 9629 06:24:13,560 --> 06:24:14,840 BEEN CLINICAL TREATMENTS OF 9630 06:24:14,840 --> 06:24:17,080 SLEEP DISORDERS BUT IT MAINLY IS 9631 06:24:17,080 --> 06:24:20,400 FOCUSED ON THE OREXIN RECEPTOR 9632 06:24:20,400 --> 06:24:23,760 2. IT SEEMS AS IF THAT 9633 06:24:23,760 --> 06:24:25,200 PARTICULAR RECEPTOR IS MORE 9634 06:24:25,200 --> 06:24:27,000 IMPORTANT IN TERMS OF AROUSAL 9635 06:24:27,000 --> 06:24:31,680 AND SLEEP. HOWEVER THERE ARE TWO 9636 06:24:31,680 --> 06:24:34,840 DUAL OREXIN RECEPTOR ANTAGONISTS 9637 06:24:34,840 --> 06:24:36,400 NOW BEING USED AS SLEEP AIDS. 9638 06:24:36,400 --> 06:24:38,600 THEY HAVE BEEN FDA APPROVED. 9639 06:24:38,600 --> 06:24:40,600 >> SO IN CLOSING, THE POINT IS 9640 06:24:40,600 --> 06:24:42,840 THAT THE OREXIN SYSTEM MAYBE A 9641 06:24:42,840 --> 06:24:44,760 GOOD TARGET FOR PHARMACOLOGICAL 9642 06:24:44,760 --> 06:24:47,520 TREATMENT. REALLY TO ADDRESS 9643 06:24:47,520 --> 06:24:48,920 HYPERALGESIA EXPRESSED IN THIS 9644 06:24:48,920 --> 06:24:52,680 CASE IN FEMALES THAT HAVE SICKLE 9645 06:24:52,680 --> 06:24:54,200 CELL DISEASE.MENT DRUGS THAT 9646 06:24:54,200 --> 06:24:58,080 TARGET OREXIN A PEPTIDE 9647 06:24:58,080 --> 06:25:00,880 EXPRESSION AND TORR SAL MEDIAL 9648 06:25:00,880 --> 06:25:01,760 POPULATION MAY PROVE TO BE 9649 06:25:01,760 --> 06:25:04,680 EFFECTIVE IN REDUCING PAIN. AS 9650 06:25:04,680 --> 06:25:07,760 FAR AS SLEEP WHAT WE KNOW IS 9651 06:25:07,760 --> 06:25:10,400 THAT THESE DUAL OREXIN 9652 06:25:10,400 --> 06:25:11,800 ANTAGONISTS MAYBE USED TO TREAT 9653 06:25:11,800 --> 06:25:13,200 SLEEP DISORDERS WITHIN THE 9654 06:25:13,200 --> 06:25:15,160 SICKLE CELL POPULATION. THE GOOD 9655 06:25:15,160 --> 06:25:17,440 THING IS THEY DO POSE A LOWER 9656 06:25:17,440 --> 06:25:19,000 ABUSE POTENTIAL VERSUS OTHER 9657 06:25:19,000 --> 06:25:21,640 SLEEP AIDS. AND THAT IS THE 9658 06:25:21,640 --> 06:25:23,600 CONCLUSION OF THE TALK. JUST 9659 06:25:23,600 --> 06:25:28,400 WANTED TO HIGHLIGHT SOME OF THE 9660 06:25:28,400 --> 06:25:30,600 RECENT STUDIES THAT HAVE BEEN 9661 06:25:30,600 --> 06:25:32,160 DONE AND ACKNOWLEDGE THE FACT 9662 06:25:32,160 --> 06:25:35,280 THAT THE OREXIN SYSTEM HOPEFULLY 9663 06:25:35,280 --> 06:25:38,480 MAYBE A TARGET SYSTEM THAT OTHER 9664 06:25:38,480 --> 06:25:41,440 RESEARCHERS WHO ARE ON THIS 9665 06:25:41,440 --> 06:25:43,120 PARTICULAR MEETING MAY BE 9666 06:25:43,120 --> 06:25:45,520 INTERESTED IN STARTING TO 9667 06:25:45,520 --> 06:25:47,640 INVESTIGATE. I WANT TO 9668 06:25:47,640 --> 06:25:50,920 ACKNOWLEDGE IN IT NHLBI FOR THE 9669 06:25:50,920 --> 06:25:53,560 INVITATION, DR. GUPTA AND MY LAB 9670 06:25:53,560 --> 06:26:04,120 MEMBERS. THANK YOU. 9671 06:26:04,120 --> 06:26:06,880 >> THANK YOU, DR. RICHARDSON, 9672 06:26:06,880 --> 06:26:14,600 NOW I WILL INTRODUCE DR. 9673 06:26:14,600 --> 06:26:18,040 (INAUDIBLE) -- OUR NEXT SPEAKER 9674 06:26:18,040 --> 06:26:28,440 IS DR. MICHAEL KHOO, HE IS 9675 06:26:28,440 --> 06:26:30,200 CURRENTLY INTERIM CO-CHAIR OF 9676 06:26:30,200 --> 06:26:32,000 THE DEPARTMENT OF BIOMEDICAL 9677 06:26:32,000 --> 06:26:34,080 ENGINEERING AND DIRECTOR OF THE 9678 06:26:34,080 --> 06:26:36,280 USC CENTER FOR SLEEP HEALTH 9679 06:26:36,280 --> 06:26:38,280 USING BIOENGINEERING. HIS 9680 06:26:38,280 --> 06:26:40,040 PRIMARY RESEARCH FOCUS HAS BEEN 9681 06:26:40,040 --> 06:26:42,880 THE APPLICATION OF PHYSIOLOGICAL 9682 06:26:42,880 --> 06:26:45,480 CONTROL AND SIGNAL ANALYTICS TO 9683 06:26:45,480 --> 06:26:47,760 BETTER UNDERSTAND THE MECHANISMS 9684 06:26:47,760 --> 06:26:49,200 UNDERLYING SLEEP RELATED 9685 06:26:49,200 --> 06:26:51,840 BREATHING DISORDERS AND OTHER 9686 06:26:51,840 --> 06:26:54,480 CONNECTIONS WITH CARDIOMETABOLIC 9687 06:26:54,480 --> 06:26:57,400 DISEASE. HE IS CONTRIBUTING HIS 9688 06:26:57,400 --> 06:26:59,040 LEADING EXPERTISE IN SLEEP 9689 06:26:59,040 --> 06:27:00,560 HEALTH TO IMPROVE THE 9690 06:27:00,560 --> 06:27:02,880 UNDERSTANDING AND THE THERAPY OF 9691 06:27:02,880 --> 06:27:04,520 SICKLE CELL PAIN. . 9692 06:27:04,520 --> 06:27:06,600 DR. KHOO. 9693 06:27:06,600 --> 06:27:10,160 >> THANK YOU, DR. RICHARDSON. 9694 06:27:10,160 --> 06:27:25,000 LET ME SHARE MY SLIDES. SEE MY 9695 06:27:25,000 --> 06:27:25,200 SLIDE? 9696 06:27:25,200 --> 06:27:30,160 >> YES. 9697 06:27:30,160 --> 06:27:33,040 >> THANKS DR.S SMITH AND STUCKY 9698 06:27:33,040 --> 06:27:38,240 FOR ORGANIZING THIS SYMPOSIUM. I 9699 06:27:38,240 --> 06:27:40,320 WILL GIVE YOU -- THANK YOU DR. 9700 06:27:40,320 --> 06:27:45,040 RICHARDSON FOR STOPPING BEFORE 9701 06:27:45,040 --> 06:27:46,280 SOUTH CAROLINA SOUTHERN 9702 06:27:46,280 --> 06:27:49,000 CALIFORNIA. THANK YOU FOR THAT. 9703 06:27:49,000 --> 06:27:55,000 I WAS -- I WAS FIRST INVITED BY 9704 06:27:55,000 --> 06:27:56,840 KALPNA SHE GAVE A LONG BROAD 9705 06:27:56,840 --> 06:27:58,440 TITLE THAT ENCOMPASSED 9706 06:27:58,440 --> 06:28:01,000 EVERYTHING UNDER THE SUN SO I 9707 06:28:01,000 --> 06:28:02,680 DECIDED I WOULD TRY TO FOCUS ON 9708 06:28:02,680 --> 06:28:05,560 SUBJECT THAT IS MORE COMPLEX 9709 06:28:05,560 --> 06:28:09,000 WHAT WE ARE TALKING ABOUT TODAY. 9710 06:28:09,000 --> 06:28:11,480 PARTICULARLY ON -- I'M SPEAKING 9711 06:28:11,480 --> 06:28:14,560 AFTER YOU DR. RICHARDSON ON 9712 06:28:14,560 --> 06:28:16,040 SLEEP, DISORDERED BREATHING AND 9713 06:28:16,040 --> 06:28:17,360 SICKLE CELL PAIN. BEFORE I START 9714 06:28:17,360 --> 06:28:19,920 I WANT TO ALSO ACKNOWLEDGE MY 9715 06:28:19,920 --> 06:28:26,960 PARTNERS IN CRIME, DR. SANG 9716 06:28:26,960 --> 06:28:31,120 CHALACHEVA POST-DOC AT CARNEGIE 9717 06:28:31,120 --> 06:28:34,720 MELLON, DR. COATS MY LONG TIME 9718 06:28:34,720 --> 06:28:38,080 COLLABORATOR CHLA H. I WILL 9719 06:28:38,080 --> 06:28:41,200 START BY TALKING A LITTLE BIT 9720 06:28:41,200 --> 06:28:43,320 ABOUT THE PATHOPHYSIOLOGY SLEEP 9721 06:28:43,320 --> 06:28:44,560 DISORDERED BREATHING WHICH I 9722 06:28:44,560 --> 06:28:46,480 STUDIED FOR MANY YEARS. FIRST 9723 06:28:46,480 --> 06:28:48,200 THE MOST COMMON FORM OF SLEEP 9724 06:28:48,200 --> 06:28:49,520 DISORDERED BREATHING IS 9725 06:28:49,520 --> 06:28:50,880 OBSTRUCTIVE SLEEP APNEA, WHICH 9726 06:28:50,880 --> 06:28:54,960 MOST OF YOU KNOW ABOUT. THERE IS 9727 06:28:54,960 --> 06:28:59,720 WHAT HAPPENS IS THAT THERE IS 9728 06:28:59,720 --> 06:29:01,640 EPISODIC COLLAPSE SO IF YOU LOOK 9729 06:29:01,640 --> 06:29:04,720 AT THE PHYSIOLOGICAL -- 9730 06:29:04,720 --> 06:29:06,480 (INAUDIBLE) SLEEP STUDY FOR 9731 06:29:06,480 --> 06:29:08,880 EXAMPLE, THE SECOND PANEL SHOWS 9732 06:29:08,880 --> 06:29:14,480 RESPIRATORY AIR FLOW SO THERE IS 9733 06:29:14,480 --> 06:29:17,480 NO AIR COMING OUT OF YOUR NOSE. 9734 06:29:17,480 --> 06:29:20,280 THAT IS WHAT IS HAPPENING WHEN 9735 06:29:20,280 --> 06:29:23,680 YOU HAVE UPPER AIRWAY COLLAPSE, 9736 06:29:23,680 --> 06:29:25,600 YOU HAVE OBSTRUCTIVE VENTILATION 9737 06:29:25,600 --> 06:29:29,000 BUT IF YOU RESCUE EFFORT PUT IN 9738 06:29:29,000 --> 06:29:31,520 ESOPHAGEAL CATHETER TO MEASURE 9739 06:29:31,520 --> 06:29:34,000 EFFORT YOU CAN SEE SUBJECT IS 9740 06:29:34,000 --> 06:29:37,880 TRYING TO BREATHE WHILE UPPER 9741 06:29:37,880 --> 06:29:39,120 AIRWAYS COLLAPSE. YOU CAN SEE 9742 06:29:39,120 --> 06:29:41,800 LARGER AND LARGER BECAUSE CO 2 9743 06:29:41,800 --> 06:29:44,080 IS LOADING UP HYPOXIA IS LOADING 9744 06:29:44,080 --> 06:29:46,760 UP YOU CAN SEE BLOOD CULTURE 9745 06:29:46,760 --> 06:29:50,680 SATURATION IS GOING DOWN LIKE 9746 06:29:50,680 --> 06:29:53,080 CRAZY,. SO YOU HAVE THIS HYPOXIA 9747 06:29:53,080 --> 06:29:56,200 GOING ON. SO HEART RATE ALSO 9748 06:29:56,200 --> 06:29:59,920 GOES UP DURING THIS APNEA UNTIL 9749 06:29:59,920 --> 06:30:03,480 YOU HAVE A UPPER AIRWAY BECOMES 9750 06:30:03,480 --> 06:30:05,600 OPEN WHICH IS WHEN YOU START 9751 06:30:05,600 --> 06:30:07,400 BREATHING AGAIN. THIS OPENING 9752 06:30:07,400 --> 06:30:09,720 REOPENING OF UPPER AIRWAY IS 9753 06:30:09,720 --> 06:30:12,680 MOST OF THE TIME DUE TO BRIEF 9754 06:30:12,680 --> 06:30:13,920 AROUSAL FROM SLEEP IF YOU LOOK 9755 06:30:13,920 --> 06:30:17,360 AT THE EEG A PERSON STILL ASLEEP 9756 06:30:17,360 --> 06:30:20,320 ALL IS WELL UNTIL THE EFFORTS 9757 06:30:20,320 --> 06:30:22,320 BREAK OUT THE UPPER AIRWAY AND 9758 06:30:22,320 --> 06:30:24,240 NOW SUBJECT TO BREATHE AGAIN SO 9759 06:30:24,240 --> 06:30:26,160 THIS BREATHE AROUSAL FROM SLEEP, 9760 06:30:26,160 --> 06:30:30,000 WHEN THIS HAPPENS MANY, MANY 9761 06:30:30,000 --> 06:30:33,480 TIMES A NIGHT LEAD TO SLEEP 9762 06:30:33,480 --> 06:30:35,200 FRAGMENTATION SO TWO MAJOR 9763 06:30:35,200 --> 06:30:37,000 EFFECTS OF SLEEP DISORDERED 9764 06:30:37,000 --> 06:30:41,560 BORROWING IS HYPOXIA AND AROUSAL 9765 06:30:41,560 --> 06:30:44,640 PRODUCE FRAGMENTATION. THE THING 9766 06:30:44,640 --> 06:30:47,840 THAT ALSO SLEEP DISORDERED 9767 06:30:47,840 --> 06:30:48,960 BORROWING IS COMMON IN SICKLE 9768 06:30:48,960 --> 06:30:51,240 CELL DISEASE ESPECIALLY UP TO 9769 06:30:51,240 --> 06:30:58,160 69% REPORTED IN CHILDREN. SICKLE 9770 06:30:58,160 --> 06:30:59,800 CELL DISEASE, CAN -- HYPOXIA 9771 06:30:59,800 --> 06:31:02,280 FROM SICKLE CELL DISEASE TRIGGER 9772 06:31:02,280 --> 06:31:06,880 LARGE SCALE VASOOCCLUSION IN 9773 06:31:06,880 --> 06:31:14,400 SICKLE CELL DISEASE SO SO TURNS 9774 06:31:14,400 --> 06:31:16,000 OUT THEN AFTER THIS FEW STUDIES 9775 06:31:16,000 --> 06:31:21,160 DONE AT LARGER STUDY DONE ON 9776 06:31:21,160 --> 06:31:23,040 SUBJECT, THERE WAS SOME YEARS 9777 06:31:23,040 --> 06:31:26,480 AGO, THIS WAS DONE ONCOSHORT OF 9778 06:31:26,480 --> 06:31:27,320 OVER 200 CHILDREN SICKLE CELL 9779 06:31:27,320 --> 06:31:31,800 DISEASE, THIS IS A SLEEP COHORT 9780 06:31:31,800 --> 06:31:34,400 OF CHILDREN AND STUDIED HE IS 9781 06:31:34,400 --> 06:31:37,920 SUBJECTS FOR OVER FIVE YEARS, 9782 06:31:37,920 --> 06:31:39,960 RECORDED SICKLE CELL SAD 9783 06:31:39,960 --> 06:31:43,800 ASSOCIATED PAIN EPISODES WHICH 9784 06:31:43,800 --> 06:31:44,960 REQUIRE HOSPITAL ADMISSION AND 9785 06:31:44,960 --> 06:31:46,400 TREATMENT WITH OPIOID. HE ALSO 9786 06:31:46,400 --> 06:31:47,800 LOOKED AT ASSOCIATION BETWEEN 9787 06:31:47,800 --> 06:31:49,720 SLEEP PARAMETERS AND VOC PAIN 9788 06:31:49,720 --> 06:31:55,600 FREQUENCY. SO THE LONG SHOT OF 9789 06:31:55,600 --> 06:31:58,960 IT WAS THAT THERE WAS LOW 9790 06:31:58,960 --> 06:32:05,600 NOCTURNAL SPO 2 HYPOXIA AND THE 9791 06:32:05,600 --> 06:32:09,000 APNEA HIGH POP KNEEIA INDEX 9792 06:32:09,000 --> 06:32:10,640 WHICH HOW MANY -- FOR HOUR, 9793 06:32:10,640 --> 06:32:17,200 THOSE INDICES DID NOT PREDICT 9794 06:32:17,200 --> 06:32:20,440 FREQUENCY, WHICH WAS SURPRISING 9795 06:32:20,440 --> 06:32:23,600 HYPOXEMIA DUE O -- CONTRIBUTE TO 9796 06:32:23,600 --> 06:32:28,240 MORE VOC. SO THEN NOW WE WANT TO 9797 06:32:28,240 --> 06:32:33,920 SHOW YOU ANOTHER THING THAT 9798 06:32:33,920 --> 06:32:35,160 RELATES TO THE SLEEP 9799 06:32:35,160 --> 06:32:37,240 FRAGMENTATION THAT ACTUALLY 9800 06:32:37,240 --> 06:32:38,520 PEOPLE HAVE FOUND VERY MUCH FOR 9801 06:32:38,520 --> 06:32:40,200 IN TERMS OF SICKLE CELL DISEASE 9802 06:32:40,200 --> 06:32:42,840 WHICH IS THE (INAUDIBLE) OF 9803 06:32:42,840 --> 06:32:46,480 SYSTEM. FOR EXAMPLE MEASURE 9804 06:32:46,480 --> 06:32:48,800 SYMPATHETIC NERVE ACTIVITY, 9805 06:32:48,800 --> 06:32:52,440 DURING WAKEFULNESS AND DURING 9806 06:32:52,440 --> 06:32:54,800 STAGE 4 SLEEP. STAGE 3 SLEEP YOU 9807 06:32:54,800 --> 06:32:57,200 CAN SEE THAT THE SYMPATHETIC 9808 06:32:57,200 --> 06:33:01,520 ACTIVITY DECREASE SLEEP AS WELL 9809 06:33:01,520 --> 06:33:02,720 SYMPATHETIC DECREASE SLEEP BUT 9810 06:33:02,720 --> 06:33:03,920 IN THIS SUBJECT FOR EXAMPLE THIS 9811 06:33:03,920 --> 06:33:11,320 IS STUDY FROM MORGAN AND SKATRUD 9812 06:33:11,320 --> 06:33:18,800 IN 1990s IF YOU AROUSE WITH 9813 06:33:18,800 --> 06:33:21,320 ACOUSTIC TONE YOU HAVE SURGE OF 9814 06:33:21,320 --> 06:33:22,840 SYMPATHETIC ACTIVITY, SURGE OF 9815 06:33:22,840 --> 06:33:27,000 ACTIVITY. WHICH THEN LEADS TO A 9816 06:33:27,000 --> 06:33:30,800 QUICKENING OF HEART RATE. SOME 9817 06:33:30,800 --> 06:33:34,800 MORE VENTILATION AND INCREASE IN 9818 06:33:34,800 --> 06:33:39,440 BLOOD PRESSURE THAT GOES UP. 9819 06:33:39,440 --> 06:33:40,880 LOOK AT WHAT HAPPENS, PERSON 9820 06:33:40,880 --> 06:33:44,840 WITH SLEEP DISORDERED BREATHING. 9821 06:33:44,840 --> 06:33:46,600 ON VOCATIVE SLEEP APNEA, WHAT 9822 06:33:46,600 --> 06:33:52,680 PES IS WITH THESE CYCLES OF THE 9823 06:33:52,680 --> 06:33:55,520 APNEAS, YOU CAN SEE THE 9824 06:33:55,520 --> 06:33:56,880 RESPIRATORY EFFORTS DURING THE 9825 06:33:56,880 --> 06:33:58,400 -- ARE VERY STRONG AND THAT THEN 9826 06:33:58,400 --> 06:34:00,080 IT GOES BACK TO SLEEP AGAIN, SO 9827 06:34:00,080 --> 06:34:04,720 ON. SO BLOOD PRESSURE FLUCTUATES 9828 06:34:04,720 --> 06:34:05,800 SICKICALLILY I CAUSES SLEEP 9829 06:34:05,800 --> 06:34:10,000 BECAUSE OF THE BUILD UP DRIVE SO 9830 06:34:10,000 --> 06:34:13,640 LOOK AT THE SYMPATHETIC ACTIVITY 9831 06:34:13,640 --> 06:34:15,800 WAXES AND WANES THROUGHOUT THE 9832 06:34:15,800 --> 06:34:18,920 WHOLE TIME. WITH THAT BACKDROP 9833 06:34:18,920 --> 06:34:21,400 WE ARE ASKING THE QUESTION THEN, 9834 06:34:21,400 --> 06:34:24,000 THESE CHANGES IN THE -- OF THE 9835 06:34:24,000 --> 06:34:26,840 SYSTEM DURING SLEEP CAN HAVE AN 9836 06:34:26,840 --> 06:34:29,280 EFFECT ON SICKLE CELL DISEASE, 9837 06:34:29,280 --> 06:34:32,280 CAN HAVE IMPLICATIONS IN TERMS 9838 06:34:32,280 --> 06:34:36,200 OF MAYBE PROMOTING MORE VOC SO 9839 06:34:36,200 --> 06:34:37,960 AGAIN MANY STUDIES HAVE SHOWN 9840 06:34:37,960 --> 06:34:41,640 SICKLE CELL DISEASE PATIENTS 9841 06:34:41,640 --> 06:34:45,160 HAVE ABNORMAL FUNCTION DR. 9842 06:34:45,160 --> 06:34:46,720 COLLINS AND COATS AND SO ON AND 9843 06:34:46,720 --> 06:34:49,200 FROM OUR GROUP TO PATIENT 9844 06:34:49,200 --> 06:34:50,600 STUDIES HAVE ALSO FOUND THAT 9845 06:34:50,600 --> 06:34:55,000 THERE IS VENTRAL STRESS EXPOSURE 9846 06:34:55,000 --> 06:34:57,640 AND PAIN CAN TRIGGER VOC FROM 9847 06:34:57,640 --> 06:35:00,720 PATIENT REPORTS AND OUR STUDIES 9848 06:35:00,720 --> 06:35:03,240 NOW HAVE SHOWN THAT FOR SEVERAL 9849 06:35:03,240 --> 06:35:05,200 REASONS SHOWN THAT PAIN 9850 06:35:05,200 --> 06:35:08,960 EXPERIMENTAL PAIN MENTAL STRESS, 9851 06:35:08,960 --> 06:35:11,400 COLD EXPOSURE, COLD FACE 9852 06:35:11,400 --> 06:35:15,640 EXPOSURE LEAD TO 9853 06:35:15,640 --> 06:35:17,000 VASOCONSTRICTION. ALSO SICKLE 9854 06:35:17,000 --> 06:35:21,480 CELL SUBJECTS ALSO TEND TO PRIOR 9855 06:35:21,480 --> 06:35:24,400 TO ONSET OF VOC, THAT IS SHOWN 9856 06:35:24,400 --> 06:35:28,440 STUDY BY CHLA. SO THAT THE 9857 06:35:28,440 --> 06:35:30,960 (INAUDIBLE) OVER ITS PLACE OVER 9858 06:35:30,960 --> 06:35:33,800 A TIME TO SELF-ADMINISTER -- 9859 06:35:33,800 --> 06:35:36,000 FAST COMPARED TO CHRONIC STEADY 9860 06:35:36,000 --> 06:35:42,400 STATE GOING ON IN BLOOD -- BLOOD 9861 06:35:42,400 --> 06:35:44,000 FLOW, IN THE DISCUSSION THE PAST 9862 06:35:44,000 --> 06:35:47,480 COUPLE OF DAY DAYS SO THE ANALYSIS 9863 06:35:47,480 --> 06:35:50,680 IS THAT THIS MEDIATED 9864 06:35:50,680 --> 06:35:52,000 VASOCONSTRICTION WOULD LEAD TO 9865 06:35:52,000 --> 06:35:56,080 DROP IN PERFUSION WHICH INCREASE 9866 06:35:56,080 --> 06:35:58,400 TRANSIT TIME OF RED BLOOD CELLS 9867 06:35:58,400 --> 06:36:02,920 WHICH ARE SICKLING THROUGH 9868 06:36:02,920 --> 06:36:06,600 CAPILLARIES. LEAD TO LOWER 9869 06:36:06,600 --> 06:36:09,600 REPROFUSION LEAD TO MORE 9870 06:36:09,600 --> 06:36:12,920 VASOOCCLUSION. ADHESION 9871 06:36:12,920 --> 06:36:13,880 (INAUDIBLE) BEING STUCK IN THE 9872 06:36:13,880 --> 06:36:19,440 CAPILLARIES. SO TO QUANTIFY VASO 9873 06:36:19,440 --> 06:36:21,360 VASOCONSTRICTION IN HUMAN 9874 06:36:21,360 --> 06:36:23,600 SUBJECTS, WE CAN'T GO MEASURE IN 9875 06:36:23,600 --> 06:36:26,480 SMALL CAPILLARIES SO ON SO WHAT 9876 06:36:26,480 --> 06:36:30,560 WE DO EXTERNALLY TO MEASURE 9877 06:36:30,560 --> 06:36:37,240 NON-INVASIVELY, IS TO USE PULSE 9878 06:36:37,240 --> 06:36:39,720 OXIMETER. WHERE THERE IS 9879 06:36:39,720 --> 06:36:42,680 VASOCONSTRICTION YOU FIND THE 9880 06:36:42,680 --> 06:36:47,000 PPG DECREASE AMPLITUDE, INCREASE 9881 06:36:47,000 --> 06:36:50,880 IN AMPLITUDE. WHAT QUALIFY AS 9882 06:36:50,880 --> 06:36:53,680 AMPLITUDE OF PPG SIGNAL BEAT BY 9883 06:36:53,680 --> 06:36:55,760 BEAT, THIS GOES DOWN AND THEN 9884 06:36:55,760 --> 06:36:57,880 GOES BACK UP AGAIN. SO WHEN YOU 9885 06:36:57,880 --> 06:37:02,000 LOOK AT THE PPG SIGNAL AND 9886 06:37:02,000 --> 06:37:04,160 QUANTIFY BIT BY BIT YOU SEE 9887 06:37:04,160 --> 06:37:06,320 DURING VASOCONSTRICTION THIS 9888 06:37:06,320 --> 06:37:09,600 GOES DOWN AND SO THAT WHOLE AREA 9889 06:37:09,600 --> 06:37:12,320 WE IDENTIFY VASE SEW 9890 06:37:12,320 --> 06:37:13,640 CONSTRICTION IS QUANTIFIED IN 9891 06:37:13,640 --> 06:37:14,800 TERMS OF AVERAGE MAGNITUDE AND 9892 06:37:14,800 --> 06:37:17,560 IF THAT MAGNITUDE IS NOW 9893 06:37:17,560 --> 06:37:20,160 NORMALIZED BY MEAN LEVEL OF THE 9894 06:37:20,160 --> 06:37:23,680 PPG AMPLITUDE, WE ESTABLISH 9895 06:37:23,680 --> 06:37:25,840 PARAMETER WHICH CALL ELEVATES 9896 06:37:25,840 --> 06:37:27,560 THE VASOCONSTRICTION SO THAT IS 9897 06:37:27,560 --> 06:37:34,000 ALL WE USE TO QUANTIFY EXTENT OF 9898 06:37:34,000 --> 06:37:35,080 VASOCONSTRICTION, IN THIS CASE 9899 06:37:35,080 --> 06:37:37,480 ESTABLISH PRECIPITATED BY 9900 06:37:37,480 --> 06:37:39,080 AROUSAL FROM SLEEP WHICH CAUSES 9901 06:37:39,080 --> 06:37:44,240 THE VASOCONSTRICTION. SO WE 9902 06:37:44,240 --> 06:37:47,600 CALCULATED THIS BASED FROM THAT 9903 06:37:47,600 --> 06:37:48,200 WHETHER OR NOT HE WILL BUNCH OF 9904 06:37:48,200 --> 06:37:51,080 PATIENTS THAT WERE STUDIED BY 9905 06:37:51,080 --> 06:37:53,200 (INAUDIBLE) OVER 200 PATIENTS. 9906 06:37:53,200 --> 06:37:56,480 AND WE USE THIS PARAMETER ALLOW 9907 06:37:56,480 --> 06:37:57,560 SOME OTHERS TO TEST WHETHER OR 9908 06:37:57,560 --> 06:38:00,400 NOT THIS PARAMETER WOULD BEAT US 9909 06:38:00,400 --> 06:38:04,000 TO PREDICT THE VOC PAIN RATE 9910 06:38:04,000 --> 06:38:05,480 THEY MEASURED IN THAT BUNCH OF 9911 06:38:05,480 --> 06:38:09,400 PATIENTS AND IT DID. WITH QUITE 9912 06:38:09,400 --> 06:38:11,800 STRONG SIGNIFICANCE. ALLOWING 9913 06:38:11,800 --> 06:38:14,520 AGE AN HEMOGLOBIN LEVEL, WITH 9914 06:38:14,520 --> 06:38:18,120 THIS NEGATIVE REGRESSION MODEL 9915 06:38:18,120 --> 06:38:20,200 PREDICTED TO -- IF WE LOOK AT 9916 06:38:20,200 --> 06:38:27,960 THE SLEEP INDICES, AROUSAL INDEX 9917 06:38:27,960 --> 06:38:31,200 MOVEMENT INDEX AROUSAL, THOSE 9918 06:38:31,200 --> 06:38:33,200 WHICH SHOW SLEEP PRACTITIONERS 9919 06:38:33,200 --> 06:38:38,320 MEASURE, THEY DID NOT PREDICT 9920 06:38:38,320 --> 06:38:40,680 VOC RATE. THOUGH THEY DID 9921 06:38:40,680 --> 06:38:43,200 PREDICT (INAUDIBLE). SO THE 9922 06:38:43,200 --> 06:38:44,200 QUESTION WAS WHY WAS THAT THE 9923 06:38:44,200 --> 06:38:48,680 CASE? BEFORE I MOVE ON, JUST TO 9924 06:38:48,680 --> 06:38:51,480 SHOW IF YOU DIVIDE PATIENTS INTO 9925 06:38:51,480 --> 06:38:53,600 HIGH PAIN AND LOW AND NO PAIN 9926 06:38:53,600 --> 06:38:56,080 HIGH PAIN BEING MORE THAN 9927 06:38:56,080 --> 06:38:58,000 ONE-HALF EVENTS PER YEAR AND 9928 06:38:58,000 --> 06:38:59,560 THIS IS OVER PERIOD OF FIVE 9929 06:38:59,560 --> 06:39:01,880 YEARS, MANY OF THESE PATIENTS, 9930 06:39:01,880 --> 06:39:05,080 YOU FIND THAT TO ELEVATE HIGH 9931 06:39:05,080 --> 06:39:06,400 PAIN PATIENTS ARE SICK CLICKLY 9932 06:39:06,400 --> 06:39:09,600 HIGHER COMPARED TO LOWER LOW 9933 06:39:09,600 --> 06:39:11,760 PAIN PATIENTS. SO TO BETTER 9934 06:39:11,760 --> 06:39:13,520 UNDERSTAND THAT WE LOOK MORE 9935 06:39:13,520 --> 06:39:17,320 CLOSELY AS TO WHAT IS HAPPENING 9936 06:39:17,320 --> 06:39:21,240 DURING THE NIGHT MEDIAN OVER 9937 06:39:21,240 --> 06:39:23,640 NIGHT FOR EACH PATIENTS, SO THIS 9938 06:39:23,640 --> 06:39:27,200 WAS ONE NUMBER TO LOOK AT HOW 9939 06:39:27,200 --> 06:39:30,320 ACTUALLY SLEEP MODULATES H MORE 9940 06:39:30,320 --> 06:39:33,600 CLOSELY TO SEE FOR EXAMPLE WHEN 9941 06:39:33,600 --> 06:39:37,080 VASOCONSTRICTIONS ARE HAPPENING, 9942 06:39:37,080 --> 06:39:41,120 DOING WAKEFULNESS STAGE 1 SLEEP, 9943 06:39:41,120 --> 06:39:43,560 STAGE 2, DEEP SLEEP AND REM 9944 06:39:43,560 --> 06:39:46,400 SLEEP YOU CAN SEE SLEEP STATE, 9945 06:39:46,400 --> 06:39:49,800 IT DOES MODULATE THIS 9946 06:39:49,800 --> 06:39:51,720 (INAUDIBLE) AS YOU GO DEEPER, 9947 06:39:51,720 --> 06:39:55,840 THE EXTENT OF RESTRICTIONS ARE 9948 06:39:55,840 --> 06:39:58,200 REDUCED. AND IF YOU GO TO REM 9949 06:39:58,200 --> 06:40:02,240 SLEEP INCREASES (INAUDIBLE) IN 9950 06:40:02,240 --> 06:40:07,560 THIS CASE. THEN ALSO IF YOU LOOK 9951 06:40:07,560 --> 06:40:09,440 AT ALL THESE VASOCONSTRICTIONS 9952 06:40:09,440 --> 06:40:12,000 AND YOU TRY TO ASSOCIATE THEM 9953 06:40:12,000 --> 06:40:13,640 WITH EVENTS THAT ARE HAPPENING 9954 06:40:13,640 --> 06:40:15,520 DURING THOSE VASOCONSTRICTIONS 9955 06:40:15,520 --> 06:40:18,800 YOU LOOK AT ALL 9956 06:40:18,800 --> 06:40:19,320 VASOCONSTRICTIONS THESE 9957 06:40:19,320 --> 06:40:25,800 MAGNITUDE WE SAW, IF YOU LOOK AT 9958 06:40:25,800 --> 06:40:27,160 THOSE VASOCONSTRICTIONS WITHOUT 9959 06:40:27,160 --> 06:40:29,360 ANY ASSOCIATED SLEEP EVENTS 9960 06:40:29,360 --> 06:40:32,040 HERE, YOU CAN SEE THAT IS CLOSE 9961 06:40:32,040 --> 06:40:36,200 TO WHAT ALL THE OTHER -- 9962 06:40:36,200 --> 06:40:38,280 ASSOCIATES WITH THOSE THAT HAVE 9963 06:40:38,280 --> 06:40:46,120 -- HAPPENING WITHIN 37 THAT KIND 9964 06:40:46,120 --> 06:40:49,200 OF GRANT YOU CAN SEE INCREASES 9965 06:40:49,200 --> 06:40:49,840 VASOCONSTRICTION MAGNITUDE. YOU 9966 06:40:49,840 --> 06:40:52,560 HAVE AROUSALS AS WELL AND THAT 9967 06:40:52,560 --> 06:40:54,960 INCREASE EVEN MORE. SO THE 9968 06:40:54,960 --> 06:40:57,440 AROUSALS OF SLEEP ALONG WITH THE 9969 06:40:57,440 --> 06:41:00,960 EVENTS INCREASES (INAUDIBLE). 9970 06:41:00,960 --> 06:41:03,920 BUT THEN SO NOW IF YOU LOOK AT 9971 06:41:03,920 --> 06:41:07,360 IT NOW MORE DETAIL HERE, FOR 9972 06:41:07,360 --> 06:41:10,240 EXAMPLE, THIS SHOWS AN EXAMPLE 9973 06:41:10,240 --> 06:41:13,520 OF THE PPG AMPLITUDE BEAT BY 9974 06:41:13,520 --> 06:41:16,360 BEAT DURING SLEEP AND PATIENT 9975 06:41:16,360 --> 06:41:18,920 WHO HAVE HIGH -- LOW PAIN RATE 9976 06:41:18,920 --> 06:41:21,200 SO ZERO PAIN RATE PER YEAR, 9977 06:41:21,200 --> 06:41:22,800 WHEREAS IN THE BOTTOM PANEL HERE 9978 06:41:22,800 --> 06:41:26,320 IT SHOWS THE SAME TRACING IN 9979 06:41:26,320 --> 06:41:28,520 ANOTHER SUBJECT WITH HIGH PAIN 9980 06:41:28,520 --> 06:41:31,400 RATE, 7.2 EVENTS PEREE. SO YOU 9981 06:41:31,400 --> 06:41:33,400 CAN SEE THE AVERAGE OFF THIS 9982 06:41:33,400 --> 06:41:36,000 PATIENT IS 13% AND THE AVERAGE 9983 06:41:36,000 --> 06:41:38,400 FOR THE HIGH PAYMENT WAS 27% 9984 06:41:38,400 --> 06:41:42,360 TWICE AS MUCH. YOU CAN SEE HERE 9985 06:41:42,360 --> 06:41:45,120 PPG SHOWS AROUSAL EXAMPLE, THERE 9986 06:41:45,120 --> 06:41:46,600 IS A VASOCONSTRICTION GOING ON 9987 06:41:46,600 --> 06:41:51,560 AT THIS POINT. THEN AT THE SAME 9988 06:41:51,560 --> 06:41:54,160 TIME THERE ARE OTHER WAYS OVA 9989 06:41:54,160 --> 06:42:00,720 CO-CONSTRICTIONS GOING O OTHER 9990 06:42:00,720 --> 06:42:01,800 VASOCONSTRICTIONS. WHICH ARE 9991 06:42:01,800 --> 06:42:03,040 HAPPENING WITHOUT SLEEP EVENTS 9992 06:42:03,040 --> 06:42:05,240 ASSOCIATED WITH THEM. FOR THE 9993 06:42:05,240 --> 06:42:07,720 PATIENT WITH HIGH PAIN RATE YOU 9994 06:42:07,720 --> 06:42:09,920 CAN SEE THE VASOCONSTRICTIONS 9995 06:42:09,920 --> 06:42:13,400 ARE LARGER, NOT JUST DURING THE 9996 06:42:13,400 --> 06:42:14,720 AROUSAL BUT OTHER 9997 06:42:14,720 --> 06:42:15,600 VASOCONSTRICTIONS HAPPENING 9998 06:42:15,600 --> 06:42:21,480 BOUGHT ANY AROUS AROUSALS. IF YOU LOOK 9999 06:42:21,480 --> 06:42:23,840 AT WHAT HAPPENS THE PATIENTS IS 10000 06:42:23,840 --> 06:42:27,600 WHEN YOU HAVE NO EVENTS NO SLEEP 10001 06:42:27,600 --> 06:42:30,200 EVENTS VASOIS SMALLER AND 10002 06:42:30,200 --> 06:42:32,720 AROUSAL SOMETHING GOING ON, 10003 06:42:32,720 --> 06:42:34,920 RESPIRATORY EVENTS GOING ON YOU 10004 06:42:34,920 --> 06:42:36,400 HAVE HIGHER WHICH CONSISTS OF 10005 06:42:36,400 --> 06:42:38,000 WHAT WE JUST SHOWED. BUT AT THE 10006 06:42:38,000 --> 06:42:40,280 SAME TIME IF YOU LOOK AT THE 10007 06:42:40,280 --> 06:42:41,520 NUMBER OF VASOCONSTRICTIONS 10008 06:42:41,520 --> 06:42:43,600 GOING ON WITH NO EVENTS YOU FIND 10009 06:42:43,600 --> 06:42:46,600 THAT ALMOST 80% OF THOSE ARE 10010 06:42:46,600 --> 06:42:48,800 HAPPENING WITHOUT ANY EVENTS, 10011 06:42:48,800 --> 06:42:50,440 WHEREAS THOSE THAT ARE HAVING 10012 06:42:50,440 --> 06:42:54,320 EVENTS GOING ON AROUSAL, ONLY 10013 06:42:54,320 --> 06:42:58,840 ACCOUNT FOR 15%. SO YOU CAN SEE 10014 06:42:58,840 --> 06:43:00,320 HERE THAT VASOCONSTRICTION GOING 10015 06:43:00,320 --> 06:43:05,720 ON, PRETTY MUCH ALL THE TIME 10016 06:43:05,720 --> 06:43:08,160 PEOPLE WITH HIGH PAIN RATE THE 10017 06:43:08,160 --> 06:43:11,000 VASOCONSTRICTIONS LEAD TO LARGER 10018 06:43:11,000 --> 06:43:11,720 VASOCONSTRICTIONS THAN PEOPLE 10019 06:43:11,720 --> 06:43:16,960 WITH LOWER PAIN RATE. NOW THIS 10020 06:43:16,960 --> 06:43:19,040 IS JUST ANOTHER FIGURE WHICH 10021 06:43:19,040 --> 06:43:20,600 SHOWS OVER LARGER SPAN OF TIME, 10022 06:43:20,600 --> 06:43:23,080 WHICH IS MORE THAN HOUR HERE, 10023 06:43:23,080 --> 06:43:27,200 AGAIN, SHOWING THE (INAUDIBLE) 10024 06:43:27,200 --> 06:43:28,600 >> TWO MINUTE WARNING. 10025 06:43:28,600 --> 06:43:31,040 >> TENDS TO SHOW DETAIL BUT LOOK 10026 06:43:31,040 --> 06:43:33,280 AT THE PPG AMPLITUDE HERE THE 10027 06:43:33,280 --> 06:43:36,360 RED LINES INDICATE ALL THE 10028 06:43:36,360 --> 06:43:37,800 VASOCONSTRICTIONS ARE HAPPENING 10029 06:43:37,800 --> 06:43:39,240 BUT THEN YOU CAN COMPARE WITH 10030 06:43:39,240 --> 06:43:44,200 THE AROUSAL EVENTS, THE -- EVANS 10031 06:43:44,200 --> 06:43:47,760 ARE MUCH LOWER IN FREQUENCY, 10032 06:43:47,760 --> 06:43:50,680 COMPARED TO THESE 10033 06:43:50,680 --> 06:43:51,800 VASOCONSTRICTION EVENTS. SO IF 10034 06:43:51,800 --> 06:43:56,680 YOU LOOK AT THE TABLE THEN ABOUT 10035 06:43:56,680 --> 06:43:57,600 36 SRI CO-CONSTRICTIONS 10036 06:43:57,600 --> 06:43:59,040 HAPPENING PER HOW IN LOW PAIN 10037 06:43:59,040 --> 06:44:01,160 AND HIGH PAIN GROUP THERE IS NO 10038 06:44:01,160 --> 06:44:02,600 DIFFERENCE BUT IN THE AROUSALS 10039 06:44:02,600 --> 06:44:04,480 AND RESPIRATORY EVENTS MUCH 10040 06:44:04,480 --> 06:44:09,320 LOWER FREQUENCY HERE. SO TO LOOK 10041 06:44:09,320 --> 06:44:14,800 AT IT BIT MORE DETAIL, WE LOOK 10042 06:44:14,800 --> 06:44:18,200 AT THE SPECTRUM, THE CONTENT OF 10043 06:44:18,200 --> 06:44:21,920 THIS RESPIRATORY EVENTS SO FAR 10044 06:44:21,920 --> 06:44:25,120 SO IN -- YOU HAVE LOW PAIN 10045 06:44:25,120 --> 06:44:27,400 PATIENT WITH LOW BRAIN LEVEL 10046 06:44:27,400 --> 06:44:29,840 SLEEP DISORDERED BRAT BREATHING. 10047 06:44:29,840 --> 06:44:34,400 LOW PAIN PATIENT WITH HIGH 10048 06:44:34,400 --> 06:44:36,400 READING AND HIGH PAIN PATIENT 10049 06:44:36,400 --> 06:44:38,440 WITH LOW READING. IN THE 10050 06:44:38,440 --> 06:44:43,240 RESPIRATORY FREQUENCY YOU SEE 10051 06:44:43,240 --> 06:44:44,800 HERE, 3 HERTZ BREATHING 10052 06:44:44,800 --> 06:44:46,280 FREQUENCY, THAT'S THE BREATHING 10053 06:44:46,280 --> 06:44:47,400 FREQUENCY BUT AT THE SAME TIME 10054 06:44:47,400 --> 06:44:49,560 YOU SEE THIS LUMP, BUMP HERE 10055 06:44:49,560 --> 06:44:50,600 WHICH SHOWS THE FREQUENCY 10056 06:44:50,600 --> 06:44:53,400 ASSOCIATED WITH THE SLEEP 10057 06:44:53,400 --> 06:44:54,600 DISORDERED BORROWING SO PERSON 10058 06:44:54,600 --> 06:44:57,800 WITH HIGH YOU CAN SEE MUCH 10059 06:44:57,800 --> 06:45:00,720 DENSER -- HERE. IF YOU LOOK AT 10060 06:45:00,720 --> 06:45:06,080 THE HEART RATE AND THE PPG 10061 06:45:06,080 --> 06:45:06,920 AMPLITUDES YOU HAVE THOSE WITH 10062 06:45:06,920 --> 06:45:09,000 THE RESPIRATORY FREQUENCIES BUT 10063 06:45:09,000 --> 06:45:12,840 DOWN HERE AT THE VERY LOW 10064 06:45:12,840 --> 06:45:14,080 FREQUENCIES HERE, THERE'S NO 10065 06:45:14,080 --> 06:45:15,440 RESPIRATION INVOLVED SO THESE 10066 06:45:15,440 --> 06:45:18,120 THINGS ARE NOT ASSOCIATED WITH 10067 06:45:18,120 --> 06:45:19,960 ANY OF THESE SLEEP DISORDERED 10068 06:45:19,960 --> 06:45:21,800 BREATHING EVENTS THESE ARE 10069 06:45:21,800 --> 06:45:24,600 THINGS HAPPENING AT THE 10070 06:45:24,600 --> 06:45:26,680 INTRINSIC LEVEL AND YOU CAN SEE 10071 06:45:26,680 --> 06:45:29,000 THAT WITH THE HIGH PAIN SUBJECT 10072 06:45:29,000 --> 06:45:32,000 EVEN WITH NO SLEEP DISORDERED 10073 06:45:32,000 --> 06:45:34,440 BORROWING, THESE OSCILLATIONS 10074 06:45:34,440 --> 06:45:36,000 ARE LARGE IN AMPLITUDE COMPARED 10075 06:45:36,000 --> 06:45:41,800 TO SOMEONE WITH LOW PAIN, MUCH 10076 06:45:41,800 --> 06:45:44,320 HIGHER AMPLITUDES IN THE PPG 10077 06:45:44,320 --> 06:45:46,120 AMPLITUDE AND ALSO IN TERMS OF 10078 06:45:46,120 --> 06:45:51,520 CHANGES IN HEART RATE. SO THAT 10079 06:45:51,520 --> 06:45:53,040 IS DELINEATES WHAT IS HAPPENING 10080 06:45:53,040 --> 06:45:54,320 WITH SLEEP DISORDERED BORROWING 10081 06:45:54,320 --> 06:45:57,000 FROM THE OSCILLATION SEEING IN 10082 06:45:57,000 --> 06:45:59,480 THE PATIENTS IN ALL THE SICKLE 10083 06:45:59,480 --> 06:46:03,280 CELL PATIENTS. IN SUMMARY, THE 10084 06:46:03,280 --> 06:46:04,480 MAGNITUDE OF SRI CO-CONSTRICTION 10085 06:46:04,480 --> 06:46:06,000 REFLECT IT IS COLLECTIVE EFFECT 10086 06:46:06,000 --> 06:46:08,400 OF ALL SYMPATHETIC INPUTS AND 10087 06:46:08,400 --> 06:46:10,880 REPRESENTS THE NET IMPACT ON 10088 06:46:10,880 --> 06:46:12,480 MICROVASCULAR BLOOD FLOW AND 10089 06:46:12,480 --> 06:46:13,920 CONSEQUENCE LIKELIHOOD FOR 10090 06:46:13,920 --> 06:46:16,720 TRIGGERING LARGE SCALE 10091 06:46:16,720 --> 06:46:19,000 VASO-OCCLUSION IN SCD. SO SLEEP 10092 06:46:19,000 --> 06:46:22,080 DEPTH AND SLEEP DISORDERED 10093 06:46:22,080 --> 06:46:24,800 BREATHING MODULATE -- AROUSAL 10094 06:46:24,800 --> 06:46:27,880 INDEX AND MOVEMENT INDEX ARE 10095 06:46:27,880 --> 06:46:29,560 FREQUENCY MEASURES, DO NOT 10096 06:46:29,560 --> 06:46:31,760 ADEQUATELY REFLECT THE TOTAL 10097 06:46:31,760 --> 06:46:35,520 SYMPATHETIC INPUT FROM SBD. SO 10098 06:46:35,520 --> 06:46:38,800 ALTHOUGH SLEEP AND SDB PLAY A 10099 06:46:38,800 --> 06:46:40,800 MODULATORY ROLE IN INFLUENCING, 10100 06:46:40,800 --> 06:46:42,920 THE EPISODIC VASOCONSTRICTIONS 10101 06:46:42,920 --> 06:46:47,200 THAT OCCUR AT BRAIN ALL 10102 06:46:47,200 --> 06:46:51,200 FREQUENCIES .01 HZ, ARE MOST 10103 06:46:51,200 --> 06:46:52,960 PREVALENT AND BEST PREDICT THE 10104 06:46:52,960 --> 06:46:54,560 VOC PAIN EVENTS. SO THESE 10105 06:46:54,560 --> 06:46:57,040 FINDINGS ARE CONSISTENT WITH 10106 06:46:57,040 --> 06:47:00,000 HYPOTHESIS THAT THESE NEURALLY 10107 06:47:00,000 --> 06:47:01,520 INDUCE SRI CO-CONSTRICTION DUE 10108 06:47:01,520 --> 06:47:04,400 TO STRESS EXPOSURE PAIN ITSELF 10109 06:47:04,400 --> 06:47:06,160 SYMPATHETIC SURGES IN SLEEP 10110 06:47:06,160 --> 06:47:08,160 COULD TRIGGER VOC. FINALLY JUST 10111 06:47:08,160 --> 06:47:10,800 TO MAKE THE POINT HERE, I THINK 10112 06:47:10,800 --> 06:47:15,320 WHAT PEOPLE HAVE SAID HERE, ANS 10113 06:47:15,320 --> 06:47:16,400 VASOCONSTRICTION AND PAIN IS A 10114 06:47:16,400 --> 06:47:20,960 CLOSED LOOP SYSTEMMEN SYSTEM SO WHEN YOU 10115 06:47:20,960 --> 06:47:25,400 HAVE SOME STIMULUS THAT TRIGGER 10116 06:47:25,400 --> 06:47:26,000 ANS DEEP BRAIN CONSTRICTION 10117 06:47:26,000 --> 06:47:28,200 WHICH LEADS TO VASOOCCLUSION AND 10118 06:47:28,200 --> 06:47:30,600 PAIN, AT THE SAME TIME THE PAIN 10119 06:47:30,600 --> 06:47:31,560 ITSELF CAN CAUSE SIMILAR -- 10120 06:47:31,560 --> 06:47:33,440 ACTIVATE THE SYMPATHETIC NERVOUS 10121 06:47:33,440 --> 06:47:36,640 SYSTEM WHICH LEADS TO FURTHER 10122 06:47:36,640 --> 06:47:37,440 VASE SEW CONSTRICTION SO THERE'S 10123 06:47:37,440 --> 06:47:40,000 A FEEDBACK CYCLE THAT GOES ON IN 10124 06:47:40,000 --> 06:47:45,080 CASES OF VOC THAT'S WHAT I 10125 06:47:45,080 --> 06:47:46,480 BELIEVE HAS (INAUDIBLE) VERY 10126 06:47:46,480 --> 06:47:48,600 QUICKLY ONGOING STUFF GOING ON 10127 06:47:48,600 --> 06:47:51,120 TRY NOT TRYING TO DEVELOP A 10128 06:47:51,120 --> 06:47:53,800 WEARABLE DEVICE WITH CELL PHONE 10129 06:47:53,800 --> 06:47:57,040 CONNECTIVITY. THAT WE CAN 10130 06:47:57,040 --> 06:47:57,960 MEASURE THE (INAUDIBLE) IN 10131 06:47:57,960 --> 06:48:02,240 PEOPLE OUT OF THE LAB THE SLEEP 10132 06:48:02,240 --> 06:48:05,000 LAB BY LOOKING NIGHT BY NIGHT, 10133 06:48:05,000 --> 06:48:09,720 THIS EXAMPLE OF PILOT STUDY DONE 10134 06:48:09,720 --> 06:48:12,120 HERE, WE FIND IN THIS CASE 10135 06:48:12,120 --> 06:48:13,800 INCREASE -- NEXT DAY THE PATIENT 10136 06:48:13,800 --> 06:48:19,920 REPORTED PAIN. SO INCREASE IN 10137 06:48:19,920 --> 06:48:24,200 VOC HERE, MAYBE POST -- FOLLOWED 10138 06:48:24,200 --> 06:48:26,080 BY PAIN THE FOLLOWING DAYS. 10139 06:48:26,080 --> 06:48:28,200 THAT'S SOME EXCITING RESULTS 10140 06:48:28,200 --> 06:48:29,440 THAT WE HAVE HAD SO FAR BUT 10141 06:48:29,440 --> 06:48:31,000 STILL DOING LOT OF STUDIES TO 10142 06:48:31,000 --> 06:48:35,960 TRY TO VERIFY THIS. THANKS TO MY 10143 06:48:35,960 --> 06:48:39,600 COLLEAGUES HERE, WE HAVE A BIG 10144 06:48:39,600 --> 06:48:42,640 GROUP THANKS TO NHLBI FOR YOUR 10145 06:48:42,640 --> 06:48:45,680 FUNDING FOR THAT. ALSO OF COURSE 10146 06:48:45,680 --> 06:48:50,600 MICHAEL DEBAUN AND CARROLL ROSEN 10147 06:48:50,600 --> 06:48:51,600 AND OTHER STUDENTS, THESE 10148 06:48:51,600 --> 06:48:52,960 INDIVIDUALS HERE WHO ARE NOW 10149 06:48:52,960 --> 06:49:02,800 CARRYING AN TH ON NEW STUDIES. THANKS 10150 06:49:02,800 --> 06:49:04,240 TO OUR SOURCES OF FUNDING 10151 06:49:04,240 --> 06:49:08,880 PREVIOUSLY. THANKS VERY MUCH. 10152 06:49:08,880 --> 06:49:12,400 I'M DONE HERE. 10153 06:49:12,400 --> 06:49:15,480 >> THANK YOU VERY MUCH, DR. 10154 06:49:15,480 --> 06:49:17,160 KHOO. VERY ENLIGHTENING 10155 06:49:17,160 --> 06:49:18,360 PRESENTATION. COMPLEX BUT NICELY 10156 06:49:18,360 --> 06:49:20,120 PRESENTED. WITH THAT I WOULD 10157 06:49:20,120 --> 06:49:23,800 LIKE TO INTRODUCE NEXT SPEAKER. 10158 06:49:23,800 --> 06:49:27,800 DR. SARAH MARTIN Ph.D. 10159 06:49:27,800 --> 06:49:28,960 CLINICAL PSYCHOLOGIST AND 10160 06:49:28,960 --> 06:49:30,280 ASSISTANT PROFESSOR DEPARTMENT 10161 06:49:30,280 --> 06:49:33,080 OF ANESTHESIOLOGY AND OPERATIVE 10162 06:49:33,080 --> 06:49:34,760 -- PERIOPERATIVE CARE, 10163 06:49:34,760 --> 06:49:36,280 UNIVERSITY OF CALIFORNIA IRVINE 10164 06:49:36,280 --> 06:49:38,640 AND STAFF AT DEPARTMENT OF 10165 06:49:38,640 --> 06:49:40,480 EMERGENCY MEDICINE AT CHILDREN'S 10166 06:49:40,480 --> 06:49:41,920 HOSPITAL ORANGE COUNTY. SHE IS 10167 06:49:41,920 --> 06:49:44,200 ONE OF THE PRINCIPLE 10168 06:49:44,200 --> 06:49:45,320 INVESTIGATORS IN THE UNIVERSITY 10169 06:49:45,320 --> 06:49:48,400 OF CALIFORNIA IRVINE CENTER ON 10170 06:49:48,400 --> 06:49:50,720 STRESS AND HEALTH. HER RESEARCH 10171 06:49:50,720 --> 06:49:52,400 UTILIZES A BIOPSYCHOSOCIAL 10172 06:49:52,400 --> 06:49:54,800 APPROACH TO STUDY PEDIATRIC PAIN 10173 06:49:54,800 --> 06:49:56,240 AND CLINICAL OUTCOMES 10174 06:49:56,240 --> 06:49:58,840 SURROUNDING MEDICAL PROCEDURES 10175 06:49:58,840 --> 06:50:00,880 SICKLE CELL DISEASE AND CHRONIC 10176 06:50:00,880 --> 06:50:02,240 PAIN WITH A PARTICULAR INTEREST 10177 06:50:02,240 --> 06:50:04,560 IN ADDRESSING HEALTHCARE 10178 06:50:04,560 --> 06:50:06,520 DISPARITIES. WELCOME SARAH. LOOK 10179 06:50:06,520 --> 06:50:07,480 FORWARD TO HEARING YOUR 10180 06:50:07,480 --> 06:50:08,280 WONDERFUL PRESENTATION. 10181 06:50:08,280 --> 06:50:24,200 >> THAW. I WILL SHARE MY SCREEN. 10182 06:50:24,200 --> 06:50:29,920 CAN YOU SEE EVERYTHING OKAY? 10183 06:50:29,920 --> 06:50:31,480 >> IT IS IN PRESENTER MODE? 10184 06:50:31,480 --> 06:50:33,080 >> IT IS, DO YOU WANT ME TO NOT 10185 06:50:33,080 --> 06:50:33,880 SHARE IT THAT WAY? 10186 06:50:33,880 --> 06:50:35,360 >> CURRENTLY SEE YOUR NOTES AS 10187 06:50:35,360 --> 06:50:39,720 WELL AS THE NEXT SLIDE. THERE 10188 06:50:39,720 --> 06:50:43,800 YOU GO. GOOD TO GO. 10189 06:50:43,800 --> 06:50:46,880 >> ALL RIGHT. SO THANK YOU SO 10190 06:50:46,880 --> 06:50:49,560 MUCH FOR INVITING ME TO BE PART 10191 06:50:49,560 --> 06:50:52,720 OF THIS SESSION, HONORED TO BE 10192 06:50:52,720 --> 06:50:53,800 HERE AND THANK YOU TO THE 10193 06:50:53,800 --> 06:50:56,440 AUDIENCE FOR STICKING WITH US 10194 06:50:56,440 --> 06:51:01,200 UNTIL THE END. SO QUICK OVERVIEW 10195 06:51:01,200 --> 06:51:05,720 OF MY TALK OUTLINE, I WILL 10196 06:51:05,720 --> 06:51:07,280 DISCUSS PAIN STRESS AND VASCULAR 10197 06:51:07,280 --> 06:51:08,600 FUNCTION IN SICKLE CELL DISEASE 10198 06:51:08,600 --> 06:51:11,200 AND TALK ABOUT PSYCHOLOGICAL 10199 06:51:11,200 --> 06:51:13,320 NEUROMODULATORY INTERVENTIONS 10200 06:51:13,320 --> 06:51:14,600 SPECIFICALLY HYPNOSIS AND 10201 06:51:14,600 --> 06:51:17,600 PRESENT RESULT A PILOT HYPNOSIS 10202 06:51:17,600 --> 06:51:20,920 INTERVENTION FOR PAIN AND SICKLE 10203 06:51:20,920 --> 06:51:23,760 CELL AND DISCUSS SOCIAL 10204 06:51:23,760 --> 06:51:24,600 ECOLOGICAL DISADVANTAGE IN 10205 06:51:24,600 --> 06:51:28,920 SICKLE CELL DISEASE AND PRESENT 10206 06:51:28,920 --> 06:51:30,600 SOME NEW FINDINGS FROM 10207 06:51:30,600 --> 06:51:35,520 EXAMINATION ASSOCIATION AMONG 10208 06:51:35,520 --> 06:51:38,640 SOCIO ECOLOGICAL PAIN RESPONSES 10209 06:51:38,640 --> 06:51:44,240 AND END WITH NEXT STEPS. BEFORE 10210 06:51:44,240 --> 06:51:46,240 I GET TO THAT, I WOULD LIKE TO 10211 06:51:46,240 --> 06:51:47,400 ACKNOWLEDGE MY FUNDERS AND 10212 06:51:47,400 --> 06:51:51,000 MENTORS. WITHOUT WHOM NONE OF 10213 06:51:51,000 --> 06:51:53,320 THIS RESEARCH WOULD BE POSSIBLE. 10214 06:51:53,320 --> 06:51:55,960 DATA I PRESENT TODAY CAME OUT OF 10215 06:51:55,960 --> 06:51:59,880 MY F 32 FELLOWSHIP FUNDED BY 10216 06:51:59,880 --> 06:52:03,400 NHLBI AND CONDUCTED UNDER THE 10217 06:52:03,400 --> 06:52:07,360 MENTORSHIP OF DR. COATS, DR. 10218 06:52:07,360 --> 06:52:09,200 LAURA PAIN AND HAD SOME 10219 06:52:09,200 --> 06:52:11,080 EXTREMELY VALUABLE COMMUNITY 10220 06:52:11,080 --> 06:52:13,160 CONSULTATION FROM DR. CAROLYN 10221 06:52:13,160 --> 06:52:16,800 RALLY. ALSO I WOULD LIKE TO 10222 06:52:16,800 --> 06:52:19,640 THANK THE PARTICIPANTS AND 10223 06:52:19,640 --> 06:52:22,080 INDIVIDUAL C SICKLE CELL WHO HAD 10224 06:52:22,080 --> 06:52:24,760 THE PRIVILEGE TO LEARN FROM AND 10225 06:52:24,760 --> 06:52:26,440 COLLABORATORS WHO ALLOW ME TO 10226 06:52:26,440 --> 06:52:28,760 CONTINUE THIS WORK. AS WE KNOW, 10227 06:52:28,760 --> 06:52:30,440 YOU HAVE A GREAT OVERVIEW TODAY 10228 06:52:30,440 --> 06:52:32,440 SO FAR, DISEASE COMPLICATIONS 10229 06:52:32,440 --> 06:52:36,960 FROM SICKLE CELL DISEASE, 10230 06:52:36,960 --> 06:52:38,400 SPECIFICALLY, PAIN IN 10231 06:52:38,400 --> 06:52:39,080 PSYCHOSOCIAL IMPAIRMENT AND 10232 06:52:39,080 --> 06:52:44,000 HEALTHCARE UTILIZATION. DR. KHOO 10233 06:52:44,000 --> 06:52:48,000 HAD PROVIDED GREAT OVERVIEW ON 10234 06:52:48,000 --> 06:52:50,720 THIS PHI BURR AND MODEL AND 10235 06:52:50,720 --> 06:52:54,400 DISCUSSION ON HOW AUTONOMEICALLY 10236 06:52:54,400 --> 06:52:57,840 MODULATED VASOCONSTRICTION AND 10237 06:52:57,840 --> 06:52:58,720 SUBSEQUENT REDUCE PERIPHERAL 10238 06:52:58,720 --> 06:53:00,040 BLOOD FLOW MAY PLAY IMPORTANT 10239 06:53:00,040 --> 06:53:01,600 ROLE IN SICKLE CELL DISEASE PAIN 10240 06:53:01,600 --> 06:53:07,000 AND VASCULAR OCCLUSIVE EPISODES. 10241 06:53:07,000 --> 06:53:08,840 PAIN STRESS AND ANXIETY ALL 10242 06:53:08,840 --> 06:53:12,760 EFFECT AUTONOMIC FUNCTION AND 10243 06:53:12,760 --> 06:53:13,960 SYMPATHETIC ACTIVATION 10244 06:53:13,960 --> 06:53:14,800 POTENTIALLY CAUSING DOWNSTREAM 10245 06:53:14,800 --> 06:53:18,520 EFFECTS ON VASCULAR RESPONSES. 10246 06:53:18,520 --> 06:53:19,680 THINKING INTRODUCTION -- 10247 06:53:19,680 --> 06:53:20,520 INTERVENTION FOR THIS POPULATION 10248 06:53:20,520 --> 06:53:23,760 WE WANT TO CONSIDER SOMETHING TO 10249 06:53:23,760 --> 06:53:28,080 MODULATE THESE EFFECTS. SO WE 10250 06:53:28,080 --> 06:53:30,960 GOT A GREAT OVERVIEW OF NON-CARL 10251 06:53:30,960 --> 06:53:33,360 COLLAGECAL APPROACHES THIS 10252 06:53:33,360 --> 06:53:36,720 MORNING. AND DR. ASSANT PROVIDED 10253 06:53:36,720 --> 06:53:39,800 A DETAILED REVIEW OF THE CURRENT 10254 06:53:39,800 --> 06:53:41,800 EVIDENCE FOR COGNITIVE 10255 06:53:41,800 --> 06:53:44,560 BEHAVIORAL TREATMENT FOR PAIN. I 10256 06:53:44,560 --> 06:53:46,840 WILL ECHO HIS MESSAGE AND WHAT 10257 06:53:46,840 --> 06:53:48,800 HE PRESENTED IN SAYING THERE IS 10258 06:53:48,800 --> 06:53:51,560 GROWING EVIDENCE FOR COGNITIVE 10259 06:53:51,560 --> 06:53:54,760 BEHAVIORAL NEUROMODULATORY 10260 06:53:54,760 --> 06:53:56,320 INTERVENTION FOR PAIN, LESS SO 10261 06:53:56,320 --> 06:53:57,800 FOR SICKLE CELL. WHEN I SAY 10262 06:53:57,800 --> 06:54:01,360 THAT, I REFER TO BROADLY 10263 06:54:01,360 --> 06:54:02,600 INTERVENTIONS THAT TARGET 10264 06:54:02,600 --> 06:54:04,760 MODULATION AT CORTICAL LEVEL AND 10265 06:54:04,760 --> 06:54:07,640 ONE SUCH INTERVENTION IS 10266 06:54:07,640 --> 06:54:11,120 HYPNOSIS. I WAS THRILLED TO SEE 10267 06:54:11,120 --> 06:54:15,960 HYPNOSIS DR. SMITH SLIDE EARLIER 10268 06:54:15,960 --> 06:54:19,480 TODAY. HYPNOSIS IS BRIEFLY A 10269 06:54:19,480 --> 06:54:23,080 STATE OF FOCUSED ATTENTION BUT 10270 06:54:23,080 --> 06:54:25,560 ENGAGES INDIVIDUAL IMAGINATION 10271 06:54:25,560 --> 06:54:29,840 AND MIND BODY CONNECTION TO HELP 10272 06:54:29,840 --> 06:54:30,920 INDIVIDUAL FA FACILITATE CHANGES 10273 06:54:30,920 --> 06:54:33,600 IN PERCEPTION AND EXPERIENCE. 10274 06:54:33,600 --> 06:54:35,800 BROADER PAIN LITERATURE HYPNOSIS 10275 06:54:35,800 --> 06:54:39,000 IS CONSIDERED EVIDENCE BASE 10276 06:54:39,000 --> 06:54:40,240 TREATMENT FOR PAIN AND SHOWN TO 10277 06:54:40,240 --> 06:54:43,560 ALTER CENTRAL PAIN PROCESSES, 10278 06:54:43,560 --> 06:54:45,320 EFFECT AUTONOMIC STRESS RESPONSE 10279 06:54:45,320 --> 06:54:47,520 AND REDUCE DISSTRESS IN 10280 06:54:47,520 --> 06:54:52,560 INDIVIDUALS WITH PAIN. WE WANTED 10281 06:54:52,560 --> 06:54:55,280 TO ASSESS THE EFFECTIVENESS 10282 06:54:55,280 --> 06:54:56,760 HYPNOSIS ON EXPERIMENTAL 10283 06:54:56,760 --> 06:54:57,640 RESPONSES IN YOUTH WITH SICKLE 10284 06:54:57,640 --> 06:54:59,400 CELL. AND THE SPECIFIC AIMS OF 10285 06:54:59,400 --> 06:55:01,440 THIS STUDY WERE TO EXAMINE 10286 06:55:01,440 --> 06:55:04,000 EFFECT OF A SINGLE SESSION OF 10287 06:55:04,000 --> 06:55:06,160 SIP KNOWSIS VERSUS ATTENTION 10288 06:55:06,160 --> 06:55:07,760 CONTROL. ON TWO OUTCOMES, PAIN 10289 06:55:07,760 --> 06:55:10,400 SENSE TVTY, AND BLOOD FLOW 10290 06:55:10,400 --> 06:55:11,760 RESPONSES DURING EXPERIMENTAL 10291 06:55:11,760 --> 06:55:18,200 PAIN TASKS. SO BRIEFLY I WILL 10292 06:55:18,200 --> 06:55:19,760 DESCRIBE MORE DETAILS OF THE 10293 06:55:19,760 --> 06:55:21,400 METHODS IN THE NEXT FEW SLIDES 10294 06:55:21,400 --> 06:55:22,960 BUT THIS IS A RANDOMIZE CONTROL 10295 06:55:22,960 --> 06:55:27,640 TRIAL THAT INCLUDED 25 ADDRESS 10296 06:55:27,640 --> 06:55:29,600 SENTS YOUNG ADULTS 12 TO 21 WITH 10297 06:55:29,600 --> 06:55:31,040 SICKLE CELL. WE HOPED TO INCLUDE 10298 06:55:31,040 --> 06:55:36,040 A LARGER SAMPLE, HOWEVER, COVID 10299 06:55:36,040 --> 06:55:37,400 INTERRUPTED THE RECRUITMENT 10300 06:55:37,400 --> 06:55:39,240 EFFORTS. TWO MAIN OUTCOMES WERE 10301 06:55:39,240 --> 06:55:42,200 EXPERIMENTAL PAIN RESPONSE, SO 10302 06:55:42,200 --> 06:55:44,200 PAIN THRESHOLD PAIN TOLERANCE 10303 06:55:44,200 --> 06:55:47,800 AND INTENSITY. AND THEN ALSO 10304 06:55:47,800 --> 06:55:49,920 LOOKING AT VASCULAR RESPONSE IN 10305 06:55:49,920 --> 06:55:51,440 CHANGE BLOOD FLOW AMPLITUDE 10306 06:55:51,440 --> 06:55:56,600 MEASURED BY PPG. THIS FIGURE 10307 06:55:56,600 --> 06:55:58,080 PROVIDES AN OVERVIEW OF OUR 10308 06:55:58,080 --> 06:55:59,800 STUDY PROCEDURES SO STARTING 10309 06:55:59,800 --> 06:56:04,440 HERE ON THE LEFT, PARTICIPANTS 10310 06:56:04,440 --> 06:56:05,800 WEPT THROUGH TWO BLOCKS OF PAIN 10311 06:56:05,800 --> 06:56:07,760 TESTS SO THE FIRST BLOCK WAS 10312 06:56:07,760 --> 06:56:09,000 BEFORE TREATMENT CONDITION, 10313 06:56:09,000 --> 06:56:15,040 SECOND BLOCK WAS AFTER 10314 06:56:15,040 --> 06:56:16,600 RANDOMIZED WITH HYPNOSIS OR 10315 06:56:16,600 --> 06:56:18,240 RANDOM CONTROL. WITHIN EACH PAIN 10316 06:56:18,240 --> 06:56:20,680 BLOCK EXPOSED TO THERMAL HEAT 10317 06:56:20,680 --> 06:56:21,920 STIMULI REPRESENTED BY THESE 10318 06:56:21,920 --> 06:56:29,320 BLUE LINES HERE. IS AND THEY 10319 06:56:29,320 --> 06:56:31,000 UNDERWENT TWO SETS OF PAIN 10320 06:56:31,000 --> 06:56:33,160 TASKS, THRESHOLD INTOLERANCE AND 10321 06:56:33,160 --> 06:56:34,200 SECOND ASSESS SELF-REPORTED PAIN 10322 06:56:34,200 --> 06:56:42,120 INTENSITY. WE ALSO, DR. KHOO 10323 06:56:42,120 --> 06:56:43,360 PROVIDED SOME INTRODUCTION TO 10324 06:56:43,360 --> 06:56:45,240 THIS IDEA AS WELL, WE WERE 10325 06:56:45,240 --> 06:56:47,240 INTERESTED IN EFFECT OF THE PAIN 10326 06:56:47,240 --> 06:56:49,240 WARNING. SO ABOUT A MINUTE 10327 06:56:49,240 --> 06:56:51,360 BEFORE WE STARTED THE PAIN 10328 06:56:51,360 --> 06:56:52,440 PULSE, WE WARNED THE 10329 06:56:52,440 --> 06:56:53,640 PARTICIPANTS AND ABOUT A MINUTE 10330 06:56:53,640 --> 06:56:59,920 YOU WILL START TO FEEL PAIN. AND 10331 06:56:59,920 --> 06:57:05,360 WHAT WHAT DR. COATS AND DR. KHOO 10332 06:57:05,360 --> 06:57:07,200 AND TEAM HAVE FOUND IN THE LOWER 10333 06:57:07,200 --> 06:57:09,200 CORNER, THIS CHANGE IN BLOOD 10334 06:57:09,200 --> 06:57:11,600 FLOW AFTER THAT PAIN WARNING, 10335 06:57:11,600 --> 06:57:13,920 EVEN BEFORE THEY GET THE PAIN 10336 06:57:13,920 --> 06:57:17,200 PULSES SO WE WERE LOOKING AT 10337 06:57:17,200 --> 06:57:18,920 EFFECT OF INTERVENTION ON THAT 10338 06:57:18,920 --> 06:57:26,400 SPECIFIC PERIOD FOR THIS STUDY. 10339 06:57:26,400 --> 06:57:29,360 A QUICK OVERVIEW FOR TREATMENT 10340 06:57:29,360 --> 06:57:30,480 CONDITIONS BOTH 20 MINUTE FOR 10341 06:57:30,480 --> 06:57:32,160 HYPNOSIS, WE INCLUDED STANDARD 10342 06:57:32,160 --> 06:57:34,800 PROCEDURES FOR HYPNOSIS OR SELF 10343 06:57:34,800 --> 06:57:38,040 HYPNOSIS. AND INCLUDED INDUCTION 10344 06:57:38,040 --> 06:57:41,200 PHASE, AND INTENSIFICATION WHICH 10345 06:57:41,200 --> 06:57:42,200 HELPED HIGHEN THE PARTICIPANTS 10346 06:57:42,200 --> 06:57:48,400 FOCUSED ATTENTION AND THEN 10347 06:57:48,400 --> 06:57:49,760 SUGGESTIONS TO INCREASE COMFORT 10348 06:57:49,760 --> 06:57:52,280 OR REDUCE DISCOMFORT AND 10349 06:57:52,280 --> 06:57:53,400 SPECIFICALLY SPENT TIME 10350 06:57:53,400 --> 06:57:55,680 INCORPORATING HYPNOTIC 10351 06:57:55,680 --> 06:57:58,480 ANALGESIA. THIS PROVIDES 10352 06:57:58,480 --> 06:57:59,280 SUGGESTIONS TO COACH 10353 06:57:59,280 --> 06:57:59,960 PARTICIPANTS THROUGH CREATING 10354 06:57:59,960 --> 06:58:03,280 WHAT WE CALLED THEIR OWN SPECIAL 10355 06:58:03,280 --> 06:58:05,280 COMFORT MEDICINE. AND PRACTICE 10356 06:58:05,280 --> 06:58:08,040 USING THAT TOOL TO CONTROL 10357 06:58:08,040 --> 06:58:09,200 PERCEPTION WITH SPECIFIC 10358 06:58:09,200 --> 06:58:12,320 ATTENTION TO ARM THAT WAS 10359 06:58:12,320 --> 06:58:13,760 RECEIVED THE PAIN PULLETSES FOR 10360 06:58:13,760 --> 06:58:14,760 ATTENTION CONTROL YOU LISTEN TO 10361 06:58:14,760 --> 06:58:15,920 A COLLECTION OF HISTORICAL 10362 06:58:15,920 --> 06:58:24,840 STORIES. FOR RESULTS WE LOOK AT 10363 06:58:24,840 --> 06:58:29,000 PAIN SENSITIVITY AND PERIPHERAL 10364 06:58:29,000 --> 06:58:31,160 VASCULAR RESPONSES -- VAS 10365 06:58:31,160 --> 06:58:34,960 CO-CONSTRICTION RESPONSES. 10366 06:58:34,960 --> 06:58:38,000 STARTING WITH PAGE SENSITIVITY. 10367 06:58:38,000 --> 06:58:43,280 THE DATA HERE REFLECT PERCENT 10368 06:58:43,280 --> 06:58:44,200 CHANGE FROM PRE-TREATMENT TASK 10369 06:58:44,200 --> 06:58:48,280 TO POST TREATMENT TASK. THE Y 10370 06:58:48,280 --> 06:58:49,520 AXIS INDICATES THAT PERCENT 10371 06:58:49,520 --> 06:58:52,000 CHANGE SO HIGHER NUMBERS 10372 06:58:52,000 --> 06:58:54,200 INDICATE LESS PAIN SENSITIVITY 10373 06:58:54,200 --> 06:58:57,000 FOLLOWING INTERVENTION. SO 10374 06:58:57,000 --> 06:58:58,520 IMPROVEMENT. FOR PAIN THRESHOLD 10375 06:58:58,520 --> 06:59:00,920 STARTING ON THE LEFT WE DID SEE 10376 06:59:00,920 --> 06:59:03,800 A SIGNIFICANT TREATMENT EFFECT. 10377 06:59:03,800 --> 06:59:05,800 SO SIGNIFICANT DIFFERENCES 10378 06:59:05,800 --> 06:59:10,440 ACROSS TREATMENT CONDITION. FROM 10379 06:59:10,440 --> 06:59:11,480 PRE- TO POST TREATMENT PERIOD 10380 06:59:11,480 --> 06:59:14,200 WERE THOSE IN THE HYPNOSIS GROUP 10381 06:59:14,200 --> 06:59:18,800 DEMONSTRATED INCREASE PAIN 10382 06:59:18,800 --> 06:59:21,880 THRESHOLD FOR PAIN TREATMENT. ON 10383 06:59:21,880 --> 06:59:23,480 THE RIGHT WE SAW A SIMILAR TREND 10384 06:59:23,480 --> 06:59:24,920 BUT NO SIGNIFICANT PAIN EFFECT 10385 06:59:24,920 --> 06:59:29,840 OR SIGNIFICANT EFFECTS. SAME 10386 06:59:29,840 --> 06:59:31,000 FOR PAIN INTENSITY. WHILE THERE 10387 06:59:31,000 --> 06:59:32,400 WAS A MODERATE EFFECT AS 10388 06:59:32,400 --> 06:59:37,360 INDICATED BY THIS PARTIAL 10389 06:59:37,360 --> 06:59:40,440 SQUARED HERE AND AVERAGE 25% 10390 06:59:40,440 --> 06:59:41,600 REDUCTION IN PAIN INTENSITY WE 10391 06:59:41,600 --> 06:59:44,840 DIDN'T SEE A SIGNIFICANT AFFECT 10392 06:59:44,840 --> 06:59:47,000 FOR TREATMENT. SO NOW MOVING TO 10393 06:59:47,000 --> 06:59:49,520 THE VASCULAR RESPONSES. JUST AS 10394 06:59:49,520 --> 06:59:52,240 A REMINDER, THIS FIGURE DEPICTS 10395 06:59:52,240 --> 06:59:55,360 OR PROCEDURES AND WE WERE 10396 06:59:55,360 --> 06:59:56,800 INTERESTED IN CHANGE IN BLOOD 10397 06:59:56,800 --> 07:00:00,440 FLOW FROM BASE LINE OR RECOVERY 10398 07:00:00,440 --> 07:00:03,200 TO AFTER THAT VERBAL WARNING. SO 10399 07:00:03,200 --> 07:00:04,880 THE DATA HERE REPRESENT CHANGE 10400 07:00:04,880 --> 07:00:07,760 IN BLOOD FLOW. WITH LOWER LEVELS 10401 07:00:07,760 --> 07:00:09,400 INDICATING DECREASE BLOOD FLOW 10402 07:00:09,400 --> 07:00:14,480 OR VASCULAR CONSTRICTION. SO 10403 07:00:14,480 --> 07:00:16,000 STARTING THE RIGHT WITH FIRST 10404 07:00:16,000 --> 07:00:19,320 PAIN TASK WE DIDN'T SEE 10405 07:00:19,320 --> 07:00:22,200 SIGNIFICANT EFFECT BUT FAIRLY 10406 07:00:22,200 --> 07:00:26,400 LARGE EFFECT IN EXPECTED 10407 07:00:26,400 --> 07:00:31,600 DIRECTIONS. SO THERE WAS A TREND 10408 07:00:31,600 --> 07:00:33,600 FROM PRE TO POST TREATMENT, 10409 07:00:33,600 --> 07:00:35,600 TENDED TO INCREASE FOLLOWING 10410 07:00:35,600 --> 07:00:38,560 VERBAL WARNENING THE HYPNOSIS 10411 07:00:38,560 --> 07:00:41,680 GROUP. FOR PAIN TASK TOO WE SAW 10412 07:00:41,680 --> 07:00:43,000 A SIMILAR PATTERN, THIS WAS IN 10413 07:00:43,000 --> 07:00:44,600 FACT SIGNIFICANT SO A POSITIVE 10414 07:00:44,600 --> 07:00:46,200 CHANGE IN THAT BLOOD FLOW 10415 07:00:46,200 --> 07:00:51,720 RESPONSE IN THE HYPNOSIS GROUP. 10416 07:00:51,720 --> 07:00:54,600 SO PULLING RESULTS TOGETHER THEY 10417 07:00:54,600 --> 07:00:55,800 SUGGEST THAT THIS SINGLE SESSION 10418 07:00:55,800 --> 07:01:01,480 OF HYPNOSIS, MAY INFLUENCE SOME 10419 07:01:01,480 --> 07:01:03,360 ASPECT OF PAIN SENSITIVITY, 10420 07:01:03,360 --> 07:01:05,800 THESE WERE NAIVE HYPNOSIS 10421 07:01:05,800 --> 07:01:06,680 PARTICIPANTS SO THRILLED TO SEE 10422 07:01:06,680 --> 07:01:08,440 THESE EFFECTS. THE EFFECT OF 10423 07:01:08,440 --> 07:01:12,600 HYPNOSIS ON THE BLOOD FLOW 10424 07:01:12,600 --> 07:01:14,200 RESPONSE SUGGESTS THAT MAY HELP 10425 07:01:14,200 --> 07:01:18,400 MODULATE OR ATTENUATE THE 10426 07:01:18,400 --> 07:01:19,600 VASOCONSTRICTION RELATED TO PAIN 10427 07:01:19,600 --> 07:01:21,920 ANTICIPATION. THIS IS A SMALL 10428 07:01:21,920 --> 07:01:23,400 SAMPLE SO DEFINITE LIMITATIONS 10429 07:01:23,400 --> 07:01:24,960 AN FUTURE WORK IS NEEDED TO 10430 07:01:24,960 --> 07:01:27,800 EXPAND THESE FINDINGS AND 10431 07:01:27,800 --> 07:01:31,880 EXAMINE LONG TERM EFFECTS. NOW 10432 07:01:31,880 --> 07:01:34,000 SHIFTING GEARS TO THINK ABOUT 10433 07:01:34,000 --> 07:01:35,360 SOCIAL ENVIRONMENTAL CONTEXT IN 10434 07:01:35,360 --> 07:01:38,000 SICKLE CELL DISEASE. I LOVE DR. 10435 07:01:38,000 --> 07:01:41,200 GUPTA'S ENVIROSOME TERM, THIS IS 10436 07:01:41,200 --> 07:01:46,000 FACTORING IN THAT ENVIROSOME. 10437 07:01:46,000 --> 07:01:49,600 FOR THIS WE WANTED TO LOOK AT 10438 07:01:49,600 --> 07:01:51,000 THE EFFECT OF SOCIO HE CAN 10439 07:01:51,000 --> 07:01:52,320 LOGICAL STRESSORS AND WE KNOW 10440 07:01:52,320 --> 07:01:54,120 FROM BROADER LITERATURE THAT 10441 07:01:54,120 --> 07:01:56,320 THESE TYPES OF STRESSORS HAVE 10442 07:01:56,320 --> 07:01:58,360 BEEN SHOWN TO BE ASSOCIATED WITH 10443 07:01:58,360 --> 07:02:01,680 A VARIETY OF HEALTH INDICATORS 10444 07:02:01,680 --> 07:02:03,720 INCLUDING IMPORTANT 10445 07:02:03,720 --> 07:02:06,920 CARDIOVASCULAR AND AUTONOMIC 10446 07:02:06,920 --> 07:02:08,960 HEALTH INDICATER TOES AND WE 10447 07:02:08,960 --> 07:02:11,400 WANT O LOOK A THE EFFECT OF 10448 07:02:11,400 --> 07:02:12,520 STRESS IN SICKLE CELL DISEASE. 10449 07:02:12,520 --> 07:02:14,600 SO USING THAT SAME SAMPLE 10450 07:02:14,600 --> 07:02:15,600 DESCRIBED BEFORE PULLING DATA 10451 07:02:15,600 --> 07:02:18,200 FROM THE PRE TREATMENT PERIOD, 10452 07:02:18,200 --> 07:02:20,520 ALSO INCLUDING A MEASURE OF 10453 07:02:20,520 --> 07:02:22,000 SOCIAL ECOLOGICAL DISADVANTAGE 10454 07:02:22,000 --> 07:02:24,240 AND WE USE THE AREA DEPRIVATION 10455 07:02:24,240 --> 07:02:25,400 INDEX WHICH INCLUDES A VARIETY 10456 07:02:25,400 --> 07:02:30,040 OF FACTORS REFLECTING EMPLOYMENT 10457 07:02:30,040 --> 07:02:30,840 HOUSING QUALITY NEIGHBORHOOD 10458 07:02:30,840 --> 07:02:33,200 INCOME EDUCATION. IT RANGES FROM 10459 07:02:33,200 --> 07:02:35,600 1 TO 10, HIGHER NUMBERS INDICATE 10460 07:02:35,600 --> 07:02:39,800 MORE DISADVANTAGE. FOR THIS 10461 07:02:39,800 --> 07:02:43,760 OUTCOME WE LOOK AT VASCULAR 10462 07:02:43,760 --> 07:02:48,000 REACTIVITY AND THIS METRIC AND 10463 07:02:48,000 --> 07:02:49,720 ANALYSES WERE DEVELOPED BY DR. 10464 07:02:49,720 --> 07:02:51,800 KHOO AND HIS LAB AND I WILL DO 10465 07:02:51,800 --> 07:02:54,080 MY BEST TO DESCRIBE WHAT IS 10466 07:02:54,080 --> 07:02:58,400 SHOWN HERE. SO THROUGH COST 10467 07:02:58,400 --> 07:03:00,160 RELATION THEY INVERTED THE PAIN 10468 07:03:00,160 --> 07:03:02,200 PULSES SO HERE THESE BLUE LINES 10469 07:03:02,200 --> 07:03:04,760 THAT WE SAW EARLIER, INVERTED 10470 07:03:04,760 --> 07:03:09,200 THOSE. PAIN PULSE STIMULI ON TO 10471 07:03:09,200 --> 07:03:10,360 RECORDINGS OF BLOOD FLOW. IN 10472 07:03:10,360 --> 07:03:13,680 THIS LOWER FIGURE THE BLOOD FLOW 10473 07:03:13,680 --> 07:03:17,360 IS BLUE LINES AND THE PAIN 10474 07:03:17,360 --> 07:03:20,640 TEMPERATURE STIMULI ARE THE RED. 10475 07:03:20,640 --> 07:03:23,920 THEY LINE THOSE UP AND CREATED A 10476 07:03:23,920 --> 07:03:26,600 CROSS CORRELATION. WHICH 10477 07:03:26,600 --> 07:03:28,120 INDICATED SLOPE OF THE THE 10478 07:03:28,120 --> 07:03:34,000 LINEAR REGRESSION OF BLOOD FLOW 10479 07:03:34,000 --> 07:03:35,920 SIGNAL ON THE PAIN SIGNAL. SO 10480 07:03:35,920 --> 07:03:40,360 THIS GAVE A SLOPE OF 10481 07:03:40,360 --> 07:03:41,720 VASOREACTIVITY. LOWER NUMBERS 10482 07:03:41,720 --> 07:03:43,360 INDICATE A STRONGER 10483 07:03:43,360 --> 07:03:44,520 VASORESTRICTION RESPONSE TO THAT 10484 07:03:44,520 --> 07:03:48,280 PAIN STIMULI. FOR THE RESULTS 10485 07:03:48,280 --> 07:03:50,880 HERE, ON THE LEFT WE FIRST LOOK 10486 07:03:50,880 --> 07:03:54,960 AT BASELINE BLOOD FLOW, WE SAW 10487 07:03:54,960 --> 07:03:57,800 SIGNIFICANT ASSOCIATION. SO 10488 07:03:57,800 --> 07:03:58,840 HIGHER STRESS WAS ASSOCIATED 10489 07:03:58,840 --> 07:04:00,720 WITH LOWER BASELINE BLOOD FLOW. 10490 07:04:00,720 --> 07:04:02,320 ON THE RIGHT YOU LOOK AT THAT 10491 07:04:02,320 --> 07:04:05,760 VASCULAR REACTIVITY TO THE PAIN 10492 07:04:05,760 --> 07:04:07,440 STIMULI AND SAW ANOTHER 10493 07:04:07,440 --> 07:04:10,040 SIGNIFICANT ASSOCIATION. SOCIAL 10494 07:04:10,040 --> 07:04:12,000 ECOLOGICAL STRESS WAS ASSOCIATED 10495 07:04:12,000 --> 07:04:14,800 WITH STRONGER VASCULAR 10496 07:04:14,800 --> 07:04:20,760 RESTRICTION RESPONSE TO PAIN. SO 10497 07:04:20,760 --> 07:04:22,280 THINKING OF PULLING THIS ALL 10498 07:04:22,280 --> 07:04:24,400 TOGETHER COLLECTIVELY THE 10499 07:04:24,400 --> 07:04:25,760 RESULTS SUGGEST COGNITIVE 10500 07:04:25,760 --> 07:04:27,600 BEHAVIORAL NEUROMODULATORY BASE 10501 07:04:27,600 --> 07:04:29,440 INTERVENTIONS SUCH AS HYPNOSIS, 10502 07:04:29,440 --> 07:04:34,440 MAY BE A PROMISING APPROACH TO 10503 07:04:34,440 --> 07:04:36,760 TARGET SOME IMPORTANT 10504 07:04:36,760 --> 07:04:38,680 PSYCHOPHYSIOLOGICAL RESPONSES IN 10505 07:04:38,680 --> 07:04:41,160 PAIN IN SICKLE CELL DISEASE. IT 10506 07:04:41,160 --> 07:04:43,400 IS IMPORTANT TO CONSIDER BROADER 10507 07:04:43,400 --> 07:04:46,960 SOCIAL STRESS AS THEY -- THESE 10508 07:04:46,960 --> 07:04:49,200 MAY BE FURTHER FACTORS THAT MAY 10509 07:04:49,200 --> 07:04:51,320 EXACERBATE THESE RESPONSES IN 10510 07:04:51,320 --> 07:04:53,320 PAIN SICKLE CELL. SO POTENTIAL 10511 07:04:53,320 --> 07:04:55,520 NEXT STEPS, DEFINITELY AS I 10512 07:04:55,520 --> 07:04:56,240 MENTION BEFORE FUTURE WORK 10513 07:04:56,240 --> 07:04:58,240 NEEDED TO CONFIRM THE RESULTS IN 10514 07:04:58,240 --> 07:05:00,400 LARGER SAMPLES, AND WE WOULD 10515 07:05:00,400 --> 07:05:03,160 LIKE TO BUILD ON THESE FINDINGS, 10516 07:05:03,160 --> 07:05:06,040 DEVELOP AND TEST COMMUNITY 10517 07:05:06,040 --> 07:05:08,040 INFORMED ACCESSIBLE 10518 07:05:08,040 --> 07:05:09,400 INTERVENTION, POTENTIALLY 10519 07:05:09,400 --> 07:05:11,400 CONSIDER DIGITAL REMOTE 10520 07:05:11,400 --> 07:05:13,040 TREATMENT DELIVERY AND WEARABLE 10521 07:05:13,040 --> 07:05:17,000 DEVICES TO MONITOR OUTCOMES. AND 10522 07:05:17,000 --> 07:05:18,600 IN CLOSING LEAVE YOU ARE WITH 10523 07:05:18,600 --> 07:05:20,600 THIS FRAMEWORK. SO THE -- IN 10524 07:05:20,600 --> 07:05:22,880 THINKING ABOUT NEXT STEPS, NIMHG 10525 07:05:22,880 --> 07:05:24,360 PUT TOGETHER A FRAMEWORK TO 10526 07:05:24,360 --> 07:05:27,640 GUIDE FUTURE RESEARCH THAT 10527 07:05:27,640 --> 07:05:29,560 ADDRESSES COMPLEX AND 10528 07:05:29,560 --> 07:05:31,240 MULTI-FACETED NATURE OF MINORITY 10529 07:05:31,240 --> 07:05:32,880 HEALTH AND HEALTH DISPARITIES 10530 07:05:32,880 --> 07:05:34,800 AND THEY PUT TOGETHER THIS 10531 07:05:34,800 --> 07:05:37,280 FRAMEWORK TO ENCOURAGE 10532 07:05:37,280 --> 07:05:38,200 RESEARCHERS TO CONSIDER 10533 07:05:38,200 --> 07:05:40,920 DIFFERENT DOMAINS, AND DIFFICULT 10534 07:05:40,920 --> 07:05:42,480 LEVELS OF INFLUENCE WHEN 10535 07:05:42,480 --> 07:05:45,240 DESIGNING RESEARCH AND 10536 07:05:45,240 --> 07:05:47,200 INTERPRETING RESULTS SO WE CAN'T 10537 07:05:47,200 --> 07:05:49,080 INCLUDE ALL THESE THINGS BUT 10538 07:05:49,080 --> 07:05:50,360 KNOWING THAT INDIVIDUALS WITH 10539 07:05:50,360 --> 07:05:52,160 SICKLE CELL DISEASE ARE AT RISK 10540 07:05:52,160 --> 07:05:54,600 FOR EXPERIENCING HEALTH 10541 07:05:54,600 --> 07:05:56,160 DISPARITIES AND DIFFICULTY 10542 07:05:56,160 --> 07:05:57,720 ACCESSING CARE WE WANT TO FACTOR 10543 07:05:57,720 --> 07:06:00,520 IN BROADER SOCIAL INFLUENCES OR 10544 07:06:00,520 --> 07:06:04,800 MECHANISMS. THANK YOU SO MUCH. 10545 07:06:04,800 --> 07:06:07,200 FOR YOUR ATTENTION. 10546 07:06:07,200 --> 07:06:08,320 >> THANK YOU VERY MUCH, SARAH. 10547 07:06:08,320 --> 07:06:11,240 THAT WAS A VERY NICE 10548 07:06:11,240 --> 07:06:12,880 PRESENTATION. IT IS OPEN FOR 10549 07:06:12,880 --> 07:06:14,560 DISCUSSION AND I WOULD START 10550 07:06:14,560 --> 07:06:18,200 WITH THE QUESTIONS I HOPE ALL 10551 07:06:18,200 --> 07:06:19,480 THE SPEAKERS ARE THERE AND THEY 10552 07:06:19,480 --> 07:06:22,200 WILL BE ABLE TO ANSWER THEM. DR. 10553 07:06:22,200 --> 07:06:28,440 STUCKY HAS A QUESTION FOR DR. 10554 07:06:28,440 --> 07:06:30,200 HE. DR. HE, ARE YOU THERE TO 10555 07:06:30,200 --> 07:06:33,480 ANSWER? YES. THANKS FOR YOUR 10556 07:06:33,480 --> 07:06:35,000 TALK, IT IS VERY INTERESTING, 10557 07:06:35,000 --> 07:06:38,120 CAN YOU SPEAK TO WHICH 10558 07:06:38,120 --> 07:06:38,960 MEEKICALLY SENSITIVE ION 10559 07:06:38,960 --> 07:06:42,200 CHANNELS ACTIVATED BY ULTRASOUND 10560 07:06:42,200 --> 07:06:45,520 -- MECHANICKICLY ACTIVATED BY 10561 07:06:45,520 --> 07:06:46,560 ULTRASOUND AND WHAT REGION OF 10562 07:06:46,560 --> 07:06:48,360 THE NERVOUS SYSTEM OR BRAIN? 10563 07:06:48,360 --> 07:06:50,360 >> THANK YOU VERY MUCH, GREAT 10564 07:06:50,360 --> 07:06:54,120 QUESTION. FIRST OF ALL I HAVE TO 10565 07:06:54,120 --> 07:06:56,400 SAY VERY LITTLE KNOWLEDGE IS 10566 07:06:56,400 --> 07:07:00,400 AVAILABLE AT THIS TIME. THERE 10567 07:07:00,400 --> 07:07:05,560 WAS A RECENT CAL TECH STUDY IN 10568 07:07:05,560 --> 07:07:09,200 VITRO NEURON THAT -- WE FOUND 10569 07:07:09,200 --> 07:07:12,680 CALCIUM VOLTAGE GATED ION 10570 07:07:12,680 --> 07:07:15,160 CHANNELS INVOLVED THE ULTRASOUND 10571 07:07:15,160 --> 07:07:16,160 ACTIVATED IN NEURONAL 10572 07:07:16,160 --> 07:07:19,640 EXCITATION. THAT'S ALL WE KNOW. 10573 07:07:19,640 --> 07:07:22,120 SO THERE IS VERY LITTLE 10574 07:07:22,120 --> 07:07:25,280 KNOWLEDGE, IT IS STILL JUST ONE 10575 07:07:25,280 --> 07:07:27,720 HYPOTHESIS. GAINING SOME SUPPORT 10576 07:07:27,720 --> 07:07:33,840 INCLUDING OUR IN VIVO BOTH 10577 07:07:33,840 --> 07:07:37,040 ANIMAL MODEL AND NOT IN SICKLE 10578 07:07:37,040 --> 07:07:38,800 PAIN PATIENT BUT TO SUPPORT THIS 10579 07:07:38,800 --> 07:07:42,800 HYPOTHESIS. 10580 07:07:42,800 --> 07:07:44,600 >> THANK YOU VERY MUCH, DR. HE. 10581 07:07:44,600 --> 07:07:46,680 NEXT QUESTION IS FROM DR. 10582 07:07:46,680 --> 07:07:49,320 MORRIS, WAS THE FEMALE MOUSE 10583 07:07:49,320 --> 07:07:50,880 REALLY HAPPY AND COMMENT THAT 10584 07:07:50,880 --> 07:07:52,440 HEALTHY FOOD AND COMPANIONSHIP 10585 07:07:52,440 --> 07:07:55,120 IS EQUAL TO HAVE BEEN -- I CAN'T 10586 07:07:55,120 --> 07:07:56,360 ANSWER THIS QUESTION BECAUSE 10587 07:07:56,360 --> 07:07:58,640 FEMALE MICE OFTEN BECAME 10588 07:07:58,640 --> 07:08:00,520 PREGNANT SO IT IS CHALLENGING TO 10589 07:08:00,520 --> 07:08:06,800 ANALYZE PAIN IN THEM. DR. 10590 07:08:06,800 --> 07:08:08,440 (INAUDIBLE) HAS NICE SUGGESTION. 10591 07:08:08,440 --> 07:08:10,200 THE BIOPSYCHOSOCIAL MODEL OF 10592 07:08:10,200 --> 07:08:13,280 WORK SIMILARLY IF YOU GIVE 10593 07:08:13,280 --> 07:08:14,280 MOUSE OXYCODONE THEY WON'T EAT 10594 07:08:14,280 --> 07:08:16,840 SLEEP OR HAVE SEX, JUST MORE 10595 07:08:16,840 --> 07:08:21,000 OXYCO-DONE. GREAT IDEA. MAYBE I 10596 07:08:21,000 --> 07:08:23,200 WONDER IF OXYCODONE RELIEVE PAIN 10597 07:08:23,200 --> 07:08:25,160 OR NOT, THAT REMAINS TO BE SEEN 10598 07:08:25,160 --> 07:08:29,000 IN THIS MODEL. DR. (INAUDIBLE) 10599 07:08:29,000 --> 07:08:30,360 HAS A NICE COMMENT. THIS 10600 07:08:30,360 --> 07:08:31,200 DEMONSTRATES AND PROVIDES 10601 07:08:31,200 --> 07:08:33,680 EVIDENCE THAT IT IS NOT SIMPLY 10602 07:08:33,680 --> 07:08:35,680 ABOUT PERCEPTION. THIS WILL GO 10603 07:08:35,680 --> 07:08:37,120 LONG WAY ADDRESSING THE STIGMA 10604 07:08:37,120 --> 07:08:38,560 THAT INDIVIDUALS WITH SICKLE 10605 07:08:38,560 --> 07:08:39,680 CELL DISEASE FACE FROM 10606 07:08:39,680 --> 07:08:41,200 HEALTHCARE PROVIDERS AND 10607 07:08:41,200 --> 07:08:44,720 SCIENTISTS. I HOPE WE CAN 10608 07:08:44,720 --> 07:08:48,000 RECTIFY THIS AND DR. GREEN HAS 10609 07:08:48,000 --> 07:08:50,680 QUESTIONS FOR DR. MCFEARSON. CAN 10610 07:08:50,680 --> 07:08:52,560 YOU -- RICHARDSON, CAN YOU 10611 07:08:52,560 --> 07:08:56,600 INFORM THE NAMES OF THE OREXIN 10612 07:08:56,600 --> 07:09:00,440 PHARMACEUTICALS AND SHE ADMIRES 10613 07:09:00,440 --> 07:09:00,840 YOUR PRESENTATION. 10614 07:09:00,840 --> 07:09:04,080 >> YES, ACTUALLY PUT IN THE CHAT 10615 07:09:04,080 --> 07:09:05,960 THERE WERE -- THERE ARE ACTUALLY 10616 07:09:05,960 --> 07:09:09,480 TWO SO FAR THAT ARE FDA 10617 07:09:09,480 --> 07:09:12,480 APPROVED, SUBAREXIN AND 10618 07:09:12,480 --> 07:09:14,920 (INAUDIBLE) ARE APPROVED AS 10619 07:09:14,920 --> 07:09:19,360 SLEEP AIDS. 10620 07:09:19,360 --> 07:09:21,600 >> DR. STEPHANIE HAS A QUESTION. 10621 07:09:21,600 --> 07:09:24,800 HAVE YOU SEEN ANY CORRELATION 10622 07:09:24,800 --> 07:09:27,240 BETWEEN ACUTE CARE UTILIZATION, 10623 07:09:27,240 --> 07:09:29,800 THIS IS FOR DR. KHOO. 10624 07:09:29,800 --> 07:09:32,680 >> I WOULD REPLIED IN THE CHAT 10625 07:09:32,680 --> 07:09:36,960 THIS THAT THE DATA WE ANALYZE 10626 07:09:36,960 --> 07:09:39,760 FROM (INAUDIBLE) COHORT STUDY 10627 07:09:39,760 --> 07:09:41,720 WERE BASED ON VOC FREQUENCY 10628 07:09:41,720 --> 07:09:45,880 SPACE OF HOSPITALIZATION. AND 10629 07:09:45,880 --> 07:09:48,560 PATIENTS SO I GUESS IN THAT 10630 07:09:48,560 --> 07:09:50,400 SENSE, HAS TO DO WITH ACUTE CARE 10631 07:09:50,400 --> 07:09:53,800 UTILIZATION. 10632 07:09:53,800 --> 07:09:55,000 >> ANOTHER QUESTION FROM DR. 10633 07:09:55,000 --> 07:09:56,960 GREEN FOR YOU, DR. KHOO, HOW 10634 07:09:56,960 --> 07:09:59,480 DIFFICULT IS IT TO GET A READING 10635 07:09:59,480 --> 07:10:00,800 OF THE FINGER DEVICE? THIS SEEMS 10636 07:10:00,800 --> 07:10:02,400 TO BE IMPORTANT AND MAYBE 10637 07:10:02,400 --> 07:10:04,720 ADAPTABLE FOR CLINICIANS TO HELP 10638 07:10:04,720 --> 07:10:06,920 PATIENTS READILY. 10639 07:10:06,920 --> 07:10:09,960 >> ALSO ACTUALLY -- IT IS ON 10640 07:10:09,960 --> 07:10:11,840 EVERY PATIENT WHO IS UNDERGOING 10641 07:10:11,840 --> 07:10:13,600 SLEEP STUDY OR IN THE HOSPITAL. 10642 07:10:13,600 --> 07:10:15,600 SO BECAUSE PEOPLE ONLY LOOK AT 10643 07:10:15,600 --> 07:10:19,000 THE ULTRA SATURATION. THEY DON'T 10644 07:10:19,000 --> 07:10:21,200 LOOK AT THE PULSE SIGNAL. AND WE 10645 07:10:21,200 --> 07:10:22,600 ARE THE ONLY ONES WHO LOOK AT 10646 07:10:22,600 --> 07:10:24,200 THE MAGNITUDE OF THE PULSE 10647 07:10:24,200 --> 07:10:25,800 SIGNAL, PEOPLE LOOK AT PULSE 10648 07:10:25,800 --> 07:10:27,360 RATE OF THAT. SO THAT'S ONE OF 10649 07:10:27,360 --> 07:10:29,800 THE THINGS WE DID THAT IT IS 10650 07:10:29,800 --> 07:10:36,720 FROM A SICKLE THAT IS USED 10651 07:10:36,720 --> 07:10:37,800 ANYWHERE. BUT NOW WHAT WE ARE 10652 07:10:37,800 --> 07:10:40,200 TRYING TO DO IS MEASURE IN T 10653 07:10:40,200 --> 07:10:41,560 HOME SO THAT IS WHY WE TRY TO DO 10654 07:10:41,560 --> 07:10:45,800 IT ON A RISK LIKE THE APPLE 10655 07:10:45,800 --> 07:10:46,400 WATCH -- WRISTBAND LIKE THE 10656 07:10:46,400 --> 07:10:48,440 APPLE WATCH. MEASURE THAT. 10657 07:10:48,440 --> 07:10:51,360 >> THANK YOU. A QUESTION FOR DR. 10658 07:10:51,360 --> 07:10:55,560 HE FROM BOTH DR. STUCKY AND 10659 07:10:55,560 --> 07:10:56,880 COATES THEY WONDER IF THE 10660 07:10:56,880 --> 07:11:00,520 CHANNELS ARE INVOLVED. 10661 07:11:00,520 --> 07:11:03,320 >> I REPLY IN THE CHAT, I THINK 10662 07:11:03,320 --> 07:11:05,520 THESE ARE GREAT QUESTIONS, 10663 07:11:05,520 --> 07:11:07,000 PARTICULARLY INTERESTED IN THIS 10664 07:11:07,000 --> 07:11:11,520 RELEVANCE TO SSCD. VERY 10665 07:11:11,520 --> 07:11:13,040 INTERESTING TO LOOK INTO THEM 10666 07:11:13,040 --> 07:11:15,720 BUT TO NOT TO MY KNOWLEDGE NOT 10667 07:11:15,720 --> 07:11:18,800 AWARE OF A DIRECT ANSWER TO THE 10668 07:11:18,800 --> 07:11:22,440 QUESTION AS THEY SPAN FROM THE 10669 07:11:22,440 --> 07:11:22,800 LITERATURE. 10670 07:11:22,800 --> 07:11:25,800 >> THANK YOU VERY MUCH. FOR 10671 07:11:25,800 --> 07:11:27,320 STICKING IT OUT THIS LONG. I 10672 07:11:27,320 --> 07:11:30,640 HOPE EVERYBODY CAN RELAX, EAT 10673 07:11:30,640 --> 07:11:32,160 WELL, ENJOY GOOD COMPANY 10674 07:11:32,160 --> 07:11:32,640 TONIGHT. 10675 07:11:32,640 --> 07:11:36,200 >> THANK YOU SO MUCH, KALPNA FOR 10676 07:11:36,200 --> 07:11:39,920 A GREAT SESSION. THIS WAS A 10677 07:11:39,920 --> 07:11:41,880 GREAT 3 WONDERFUL DAYS OF FULL 10678 07:11:41,880 --> 07:11:43,920 SESSIONS. I WOULD LIKE TO THANK 10679 07:11:43,920 --> 07:11:49,400 ALL THE PRESENTERS AND ALL THE 10680 07:11:49,400 --> 07:11:52,120 FOLKS WHO HAVE ATTENDED THE 10681 07:11:52,120 --> 07:11:53,800 MEETING. THANK YOU SO MUCH. I 10682 07:11:53,800 --> 07:11:56,120 THINK WE HAVE LEARNED A LOT IN 10683 07:11:56,120 --> 07:11:57,640 THE THE LAST THREE DAYS ABOUT 10684 07:11:57,640 --> 07:12:00,400 SICKLE CELL AND LOT MORE. WE 10685 07:12:00,400 --> 07:12:04,600 REACHED FROM BASIC SCIENCE TO 10686 07:12:04,600 --> 07:12:08,120 CLINIC AND TO QUALITY OF LIFE 10687 07:12:08,120 --> 07:12:10,120 CURATIVE THERAPY GENE THERAPY, 10688 07:12:10,120 --> 07:12:13,600 WE DID OMICS AND DATA SCIENCE 10689 07:12:13,600 --> 07:12:18,240 AND SICKLE TRAIT AND OF COURSE 10690 07:12:18,240 --> 07:12:23,280 PAIN. SO SPECIAL THANKS TO TWO 10691 07:12:23,280 --> 07:12:24,400 IMPORTANT PEOPLE WORKING IN THE 10692 07:12:24,400 --> 07:12:26,760 BACKGROUND ALL THIS TIME MAKING 10693 07:12:26,760 --> 07:12:28,040 YOUR PICTURES AND SLIDE 10694 07:12:28,040 --> 07:12:30,840 MAGICALLY APPEAR AN DISAPPEAR 10695 07:12:30,840 --> 07:12:39,400 MANY THANKS TO AMIR AND TO ALEX 10696 07:12:39,400 --> 07:12:40,800 (INAUDIBLE) I HOPE I PRONOUNCED 10697 07:12:40,800 --> 07:12:44,160 THE LAST NAME CORRECTLY AND TO 10698 07:12:44,160 --> 07:12:46,560 NAOMI AND DELL,A AND MY 10699 07:12:46,560 --> 07:12:49,960 COLLEAGUES DBDR AND THANK YOU 10700 07:12:49,960 --> 07:12:54,640 ALL. STAY SAFE. AND GOODBYE 10701 07:12:54,640 --> 07:12:55,000 UNTIL WE MEET NEXT TIME. THANK 10702 07:12:55,000 --> 00:00:00,000 YOU.