1 00:00:05,187 --> 00:00:12,128 WELCOME TO THE NIH 16th SICKLE 2 00:00:12,128 --> 00:00:12,928 CELL IN FOCUS CONFERENCE. 3 00:00:12,928 --> 00:00:15,464 IT'S SO NICE TO SEE SOME OF YOU 4 00:00:15,464 --> 00:00:17,199 IN PERSON AND I'M MINDFUL THERE 5 00:00:17,199 --> 00:00:19,869 WILL BE OTHERS JOINING USSON 6 00:00:19,869 --> 00:00:20,069 LINE. 7 00:00:20,069 --> 00:00:21,871 WE'RE RUNNING A LITTLE BIT LATE. 8 00:00:21,871 --> 00:00:23,839 I APOLOGIZE. 9 00:00:23,839 --> 00:00:25,141 ALSO THERE MAY BE SOME GLITCHES 10 00:00:25,141 --> 00:00:28,410 BECAUSE IT'S THE FIRST TIME 11 00:00:28,410 --> 00:00:30,913 WE'RE BACK AFTER COVID SO DO 12 00:00:30,913 --> 00:00:32,581 EXCUSE US AND TELL US HOW WE CAN 13 00:00:32,581 --> 00:00:33,783 DO BETTER. 14 00:00:33,783 --> 00:00:39,955 WE WILL BEGIN SHORTLY WITH 15 00:00:39,955 --> 00:00:41,924 REMARKS FROM DR. JULIE PANEPINTO 16 00:00:41,924 --> 00:00:47,263 THE DIRECTOR OF BLOOD DISEASES 17 00:00:47,263 --> 00:00:55,271 AT NHLBI AND FOLLOWED BY RICK 18 00:00:55,271 --> 00:00:57,106 CHARLES ACTING SCIENTIFIC 19 00:00:57,106 --> 00:00:57,807 DIRECTOR. 20 00:00:57,807 --> 00:01:00,309 ALL OF YOU SHOULD HAVE GOT A 21 00:01:00,309 --> 00:01:01,877 COPY OF THE OFFICIAL PROGRAM 22 00:01:01,877 --> 00:01:04,713 MAILED TO ATTENDEES AND FOUND IN 23 00:01:04,713 --> 00:01:09,618 THE CONFERENCE WEBSITE. 24 00:01:09,618 --> 00:01:12,755 IF YOU'RE JOINING US FROM THE 25 00:01:12,755 --> 00:01:16,992 ONLINE VIDEOCAST YOU CAN SUBMIT 26 00:01:16,992 --> 00:01:20,763 S LIKE USING THE CHAT BOX 27 00:01:20,763 --> 00:01:21,597 FOLLOWING EACH TALK. 28 00:01:21,597 --> 00:01:24,800 IF WE ARE UNABLE TO GET YOUR 29 00:01:24,800 --> 00:01:26,135 QUESTIONS, WE'LL E-MAIL THEM TO 30 00:01:26,135 --> 00:01:29,205 THE SPEAKER FOR RESPONSE LATER. 31 00:01:29,205 --> 00:01:30,840 ANOTHER THING SOME OF OUR 32 00:01:30,840 --> 00:01:32,241 SPEAKERS HAVE SENT IN 33 00:01:32,241 --> 00:01:33,676 PRE-RECORDED TALKS BUT MIGHT BE 34 00:01:33,676 --> 00:01:36,612 AVAILABLE FOR A FEW MINUTES TO 35 00:01:36,612 --> 00:01:38,113 ANSWER QUESTIONS LIVE VIRTUALLY. 36 00:01:38,113 --> 00:01:41,217 IS SO I'M REALLY EXCITED THAT 37 00:01:41,217 --> 00:01:43,586 WE'RE ABLE TO BRING THIS 38 00:01:43,586 --> 00:01:45,688 TOGETHER NOW ON SITE AND LOOK 39 00:01:45,688 --> 00:01:47,623 FORWARD TO A SUCCESSFUL 40 00:01:47,623 --> 00:01:49,692 CONFERENCE AND THANK YOU ALL FOR 41 00:01:49,692 --> 00:01:50,626 JOINING US. 42 00:01:50,626 --> 00:01:53,229 SO WITH THAT I'LL HAND IT OVER 43 00:01:53,229 --> 00:02:01,837 TO JULIE. 44 00:02:01,837 --> 00:02:02,338 >> GOOD MORNING. 45 00:02:02,338 --> 00:02:04,406 I ECHO THE SENTIMENT IT'S GOOD 46 00:02:04,406 --> 00:02:05,674 TO SEE SOME OF YOU IN PERSON 47 00:02:05,674 --> 00:02:08,477 AFTER PARTICIPATING IN THIS 48 00:02:08,477 --> 00:02:10,980 VIRTUALLY FOR A FEW YEARS. 49 00:02:10,980 --> 00:02:12,348 SO I'M HERE TO PROVIDE JUST A 50 00:02:12,348 --> 00:02:15,117 VERY BRIEF OVERVIEW OF SOME OF 51 00:02:15,117 --> 00:02:17,920 THE RESEARCH WE FUND THROUGH THE 52 00:02:17,920 --> 00:02:20,723 BLOOD DIVISION AT THE NHLBI IN 53 00:02:20,723 --> 00:02:23,993 SICKLE CELL DISEASE WE FUND 54 00:02:23,993 --> 00:02:25,928 EARLY BASIC TRANSITIONAL 55 00:02:25,928 --> 00:02:29,899 RESEARCH THROUGH THE SHRINE 56 00:02:29,899 --> 00:02:33,035 COLLABORATIVE WITH NIDDK THAT 57 00:02:33,035 --> 00:02:35,237 STIMULATES RESEARCH IN 58 00:02:35,237 --> 00:02:38,040 NON-MALIGNANT HEMATOLOGY AND WE 59 00:02:38,040 --> 00:02:44,947 ALSO FUND CLINICAL TRIALS AT ALL 60 00:02:44,947 --> 00:02:51,921 PHASES FROM REALLY PHASE 1 OF 61 00:02:51,921 --> 00:02:52,521 IMPLEMENTATION RESEARCH AND 62 00:02:52,521 --> 00:02:53,656 CHRONIC BLOOD TRANSFUSIONS AND 63 00:02:53,656 --> 00:02:57,059 THE IMPACT IT MAY HAVE ON ADULTS 64 00:02:57,059 --> 00:03:01,897 AND MORTALITY IN SICKLE CELL 65 00:03:01,897 --> 00:03:03,332 DISEASE. 66 00:03:03,332 --> 00:03:11,273 WE'RE LOOKING AT THE AFFECT OF 67 00:03:11,273 --> 00:03:13,475 ARGENINE AND LOOKING AT SYSTEMS 68 00:03:13,475 --> 00:03:17,246 OF CARE. 69 00:03:17,246 --> 00:03:20,616 CONNECTING ADULTS WITH SICKLE 70 00:03:20,616 --> 00:03:21,884 CELL DISEASE TO SICKLE CELL 71 00:03:21,884 --> 00:03:25,854 DISEASE SPECIALISTS AND 72 00:03:25,854 --> 00:03:27,790 IMPROVING TIMELINESS OF CARE FOR 73 00:03:27,790 --> 00:03:29,258 INDIVIDUALS PRESENTING WITH PAIN 74 00:03:29,258 --> 00:03:30,626 TO THE EMERGENCY DEPARTMENT. 75 00:03:30,626 --> 00:03:32,528 WE HAVE GLOBAL INITIATIVES. 76 00:03:32,528 --> 00:03:34,096 TO HIGHLIGHT TWO WE HAVE BLOOD 77 00:03:34,096 --> 00:03:36,131 SAFE OUT OF AFRICA THAT AIMS TO 78 00:03:36,131 --> 00:03:38,834 INCREASE BLOOD SAFETY IN 79 00:03:38,834 --> 00:03:40,869 ADDITION TO INCREASING BLOOD 80 00:03:40,869 --> 00:03:43,706 DONORS WHICH IS A BIG NEED AND 81 00:03:43,706 --> 00:03:45,541 ENHANCING DELIVERY OF BLOOD AND 82 00:03:45,541 --> 00:03:48,677 THAT WOULD BE A HUGE IMPACT ON 83 00:03:48,677 --> 00:03:49,611 OUR SICKLE CELL DISEASE 84 00:03:49,611 --> 00:03:50,512 INDIVIDUALS LIVING WITH SICKLE 85 00:03:50,512 --> 00:03:51,280 CELL DISEASE. 86 00:03:51,280 --> 00:03:53,849 WE ALSO FUND SICKLE IN AFRICA 87 00:03:53,849 --> 00:03:56,385 WHICH IN ITS RENEWAL PHASE IN 88 00:03:56,385 --> 00:03:57,886 THE FIRST FACE WE BUILT 89 00:03:57,886 --> 00:03:59,154 INFRASTRUCTURE IN A LARGE 90 00:03:59,154 --> 00:04:01,223 REGISTRY WHICH MY UNDERSTANDING 91 00:04:01,223 --> 00:04:04,226 IS PROBABLY OVER 15,000 92 00:04:04,226 --> 00:04:05,894 INDIVIDUALS LIVING WITH DEVELOPS 93 00:04:05,894 --> 00:04:07,963 IN THE AFRICAN COUNTRIES. 94 00:04:07,963 --> 00:04:09,898 THE RENEWAL PHASE BUILT ON THE 95 00:04:09,898 --> 00:04:11,900 INFRASTRUCTURE AND TO IMPLEMENT 96 00:04:11,900 --> 00:04:13,235 LOCAL STANDARDS OF CARE AND DO 97 00:04:13,235 --> 00:04:14,536 OTHER DISSEMINATION AND 98 00:04:14,536 --> 00:04:17,873 IMPLEMENTATION WORK. 99 00:04:17,873 --> 00:04:20,109 WE ALSO THEN FUND OUR CURES 100 00:04:20,109 --> 00:04:20,409 INITIATIVE. 101 00:04:20,409 --> 00:04:21,877 MANY OF YOU KNOW THIS 102 00:04:21,877 --> 00:04:22,177 INITIATIVE. 103 00:04:22,177 --> 00:04:24,546 WE'RE FUNDING CURRENTLY TWO GENE 104 00:04:24,546 --> 00:04:25,280 THERAPY TRIALS. 105 00:04:25,280 --> 00:04:29,251 ONE IS CALLED THE GRASS TRIAL 106 00:04:29,251 --> 00:04:33,889 WHICH IS A PHASE 2 CLINICAL GENE 107 00:04:33,889 --> 00:04:38,394 THERAPY TRAIL USING A VECTOR TO 108 00:04:38,394 --> 00:04:40,062 INCREASE FETAL HEMOGLOBIN 109 00:04:40,062 --> 00:04:41,864 EXPRESSION RECRUITING AND DOING 110 00:04:41,864 --> 00:04:45,034 WELL WITH RECRUITMENT. 111 00:04:45,034 --> 00:04:47,936 WE HOPE TO HAVE OPEN IN THE NEXT 112 00:04:47,936 --> 00:04:51,907 ACADEMIC OR CALENDAR YEAR 2024 113 00:04:51,907 --> 00:04:55,477 THE CRISPR TRIAL USING CRISPR 114 00:04:55,477 --> 00:04:57,880 KAS 9 NUCLEUS AND THAT'S A PHASE 115 00:04:57,880 --> 00:05:00,416 1 STUDY WE DO HOPE WILL BE OPEN 116 00:05:00,416 --> 00:05:01,350 THIS COMING SUMMER. 117 00:05:01,350 --> 00:05:02,751 THOSE ARE A FEW HIGHLIGHTS. 118 00:05:02,751 --> 00:05:04,920 WE FUND MANY THINGS AND A CAN'T 119 00:05:04,920 --> 00:05:05,921 MENTION ALL OF THAT. 120 00:05:05,921 --> 00:05:07,322 I ENCOURAGE ALL OF TO YOU PLEASE 121 00:05:07,322 --> 00:05:08,557 SEND US YOUR RESEARCH AND 122 00:05:08,557 --> 00:05:09,892 PROPOSAL. 123 00:05:09,892 --> 00:05:11,894 WE WOULD LIKE TO FUND SICKLE 124 00:05:11,894 --> 00:05:12,895 CELL DISEASE RESEARCH. 125 00:05:12,895 --> 00:05:15,464 PLEASE CONTACT MYSELF OR OUR 126 00:05:15,464 --> 00:05:17,800 STAFF TO GUIDE YOU THROUGH THE 127 00:05:17,800 --> 00:05:18,033 PROCESS. 128 00:05:18,033 --> 00:05:19,568 THAT'S WHAT WE'RE HERE FOR 129 00:05:19,568 --> 00:05:20,736 ESPECIALLY IF YOU'RE THINKING 130 00:05:20,736 --> 00:05:22,638 ABOUT ANY TYPE OF CLINICAL 131 00:05:22,638 --> 00:05:22,838 TRIAL. 132 00:05:22,838 --> 00:05:24,740 THANK YOU AND I'LL TURN THIS 133 00:05:24,740 --> 00:05:26,442 OVER TO MAYBE THE START OF THE 134 00:05:26,442 --> 00:05:29,244 NEXT SESSION IF I DON'T SEE 135 00:05:29,244 --> 00:05:39,521 DR. CHILDS HERE. 136 00:06:15,557 --> 00:06:18,627 I'D LIKE TO INTRODUCE DR. RICK 137 00:06:18,627 --> 00:06:21,029 CHARLES OUR CLINICAL DIRECTOR 138 00:06:21,029 --> 00:06:23,265 AND ACTING SCIENTIFIC DIRECTOR. 139 00:06:23,265 --> 00:06:29,071 RICK HAS ALWAYS SUPPORTED THE 140 00:06:29,071 --> 00:06:31,607 SICKLE CELL PROGRAM AND IT'S 141 00:06:31,607 --> 00:06:33,142 VERY NICE OF YOU TO MAKE TIME. 142 00:06:33,142 --> 00:06:34,243 THANK YOU. 143 00:06:34,243 --> 00:06:41,283 >> GOOD MORNING, EVERYONE. 144 00:06:41,283 --> 00:06:43,519 BESIDES INVESTIGATOR AND 145 00:06:43,519 --> 00:06:44,686 CLINICAL DIRECTOR I'M ACTING 146 00:06:44,686 --> 00:06:45,888 SCIENTIFIC DIRECTOR SO I 147 00:06:45,888 --> 00:06:46,989 APOLOGIZE FOR BEING LATE THIS 148 00:06:46,989 --> 00:06:47,222 MORNING. 149 00:06:47,222 --> 00:06:50,425 I WANT TO WELCOME EVERYONE HERE 150 00:06:50,425 --> 00:06:54,563 TO THE 16th ANNUAL SICKLE CELL 151 00:06:54,563 --> 00:06:55,230 IN FOCUS CONFERENCE. 152 00:06:55,230 --> 00:06:59,301 FINALLY AFTER MORE THAN THREE 153 00:06:59,301 --> 00:07:00,469 YEARS OF THE PUBLIC HEALTH 154 00:07:00,469 --> 00:07:02,037 EMERGENCY AND WEARING MASKS WE 155 00:07:02,037 --> 00:07:06,675 CAN ALL MEET WITH MASKS OFF OF 156 00:07:06,675 --> 00:07:08,343 OUR FACE AND AS MANY OF YOU 157 00:07:08,343 --> 00:07:10,812 HEARD THERE WAS SOME FEAR ABOUT 158 00:07:10,812 --> 00:07:12,147 A GOVERNMENT SHUT DOWN A COUPLE 159 00:07:12,147 --> 00:07:13,515 WEEKS AGO AND I WAS IN 160 00:07:13,515 --> 00:07:14,850 PARTICULAR THINKING ABOUT ALL 161 00:07:14,850 --> 00:07:16,151 THE THINGS THAT HAPPENED IN 162 00:07:16,151 --> 00:07:17,286 GOVERNMENT SHUTDOWN AND THINKING 163 00:07:17,286 --> 00:07:18,153 ABOUT THE MEETING AND HOW 164 00:07:18,153 --> 00:07:20,122 TERRIBLE IT WOULD BE IF WE HAD 165 00:07:20,122 --> 00:07:22,291 TO CANCEL THIS MEETING. 166 00:07:22,291 --> 00:07:24,293 THANKFULLY THE STARS ALIGNED, 167 00:07:24,293 --> 00:07:27,029 GOVERNMENT DIDN'T SHUT DOWN AND 168 00:07:27,029 --> 00:07:28,096 WE'RE ALL HERE TODAY. 169 00:07:28,096 --> 00:07:31,600 I WANT TO GIVE A QUICK 170 00:07:31,600 --> 00:07:33,068 BACKGROUND ON THE NIH FOR THOSE 171 00:07:33,068 --> 00:07:36,471 THAT ARE NOT FAMILIAR WITH THE 172 00:07:36,471 --> 00:07:36,638 NIH. 173 00:07:36,638 --> 00:07:40,609 WE WERE ESTABLISHED AS AN ENTITY 174 00:07:40,609 --> 00:07:43,579 IN 1887 WITH THE INTENTION FOR 175 00:07:43,579 --> 00:07:46,715 THE NIH FOR THE WORLD'S PREMIER 176 00:07:46,715 --> 00:07:49,551 BIOMEDICAL RESEARCH 177 00:07:49,551 --> 00:07:49,885 ORGANIZATION. 178 00:07:49,885 --> 00:07:51,653 WE'RE DIVIDED INTO INTRAMURAL 179 00:07:51,653 --> 00:07:53,255 AND EXTRAMURAL PROGRAMS. 180 00:07:53,255 --> 00:07:55,057 AT THE INTRAMURAL PROGRAM 181 00:07:55,057 --> 00:07:57,359 CLINICAL RESEARCH IS CONDUCTED 182 00:07:57,359 --> 00:07:59,394 IN THE NIH CLINICAL CENTER WHICH 183 00:07:59,394 --> 00:08:01,029 IS OUR RESEARCH HOSPITAL TO 184 00:08:01,029 --> 00:08:04,266 COMPLETELY DEVOTED TO CLINICAL 185 00:08:04,266 --> 00:08:05,267 RESEARCH. 186 00:08:05,267 --> 00:08:09,404 WE HAVE MORE THAN 1600 CLINICAL 187 00:08:09,404 --> 00:08:11,206 RESEARCH TRIALS AND ALL CARE 188 00:08:11,206 --> 00:08:12,674 DELIVERED AT THE CLINICAL CENTER 189 00:08:12,674 --> 00:08:15,877 IS FREE OF CHARGE. 190 00:08:15,877 --> 00:08:17,279 ONE OF THE MAJOR CLINICAL 191 00:08:17,279 --> 00:08:20,849 RESEARCH EMPHASIS IS TO STUDY 192 00:08:20,849 --> 00:08:23,285 THE PATHOPHYSIOLOGY OF DISEASES 193 00:08:23,285 --> 00:08:25,454 INCLUDING DISEASES LIKE SICKLE 194 00:08:25,454 --> 00:08:27,189 CELL ANEMIA AND DEVELOP NEW AND 195 00:08:27,189 --> 00:08:31,927 FIRST IN HUMAN THERAPEUTICS FOR 196 00:08:31,927 --> 00:08:32,794 THOSE DISEASES. 197 00:08:32,794 --> 00:08:34,963 WE AIM TO DO RESEARCH HERE THAT 198 00:08:34,963 --> 00:08:37,899 CANNOT EASILY BE DONE OUTSIDE OF 199 00:08:37,899 --> 00:08:39,034 THE NIH CAMPUS. 200 00:08:39,034 --> 00:08:41,536 IN PARTICULAR RESEARCH WHERE 201 00:08:41,536 --> 00:08:44,072 MAYBE THERE'S NOT ENOUGH 202 00:08:44,072 --> 00:08:45,674 IMMEDIATE EVIDENCE TO SUPPORT 203 00:08:45,674 --> 00:08:47,442 CLINICAL TRIALS FOR GRANT 204 00:08:47,442 --> 00:08:49,878 FUNDING BUT WHERE THERE'S ENOUGH 205 00:08:49,878 --> 00:08:50,679 BIOLOGICAL EVIDENCE TO TAKE 206 00:08:50,679 --> 00:08:52,147 SOMETIMES A LEAP OF FAITH TO DO 207 00:08:52,147 --> 00:08:57,653 SOME OF THESE FIRST IN HUMAN 208 00:08:57,653 --> 00:08:59,087 TRIALS IF SUCCESSFUL CAN BE 209 00:08:59,087 --> 00:09:00,656 POTENTIALLY PARADIGM SHIFTING 210 00:09:00,656 --> 00:09:02,257 AND LEAD TO THE EVIDENCE THAT 211 00:09:02,257 --> 00:09:04,026 WOULD SUPPORT GRANT-FUNDED 212 00:09:04,026 --> 00:09:05,294 TRIALS IN THE EXTRAMURAL 213 00:09:05,294 --> 00:09:08,830 COMMUNITY. 214 00:09:08,830 --> 00:09:10,065 THERE'S BEEN NUMEROUS ADVANCES 215 00:09:10,065 --> 00:09:12,167 IN MEDICINE THAT OCCURRED 216 00:09:12,167 --> 00:09:15,003 BECAUSE OF RESEARCH CONDUCTED AT 217 00:09:15,003 --> 00:09:15,871 THE NIH CLINICAL CENTER. 218 00:09:15,871 --> 00:09:17,639 SOME INCLUDE THINGS LIKE THE 219 00:09:17,639 --> 00:09:19,341 FIRST DEMONSTRATION OF 220 00:09:19,341 --> 00:09:22,311 CHEMOTHERAPY COULD BE EFFECTIVE 221 00:09:22,311 --> 00:09:24,079 FOR CANCER. 222 00:09:24,079 --> 00:09:26,214 THE FIRST CURE OF CANCER OF 223 00:09:26,214 --> 00:09:29,284 HODGKIN'S DISEASE AND USE OF 224 00:09:29,284 --> 00:09:34,323 BLOOD LIPID LEVELS AS A MARKER 225 00:09:34,323 --> 00:09:35,357 OF CARDIOVASCULAR DISEASE AND 226 00:09:35,357 --> 00:09:38,193 THE FIRST THERAPEUTIC FOR AZT. 227 00:09:38,193 --> 00:09:40,062 THE FIRST DEMONSTRATION 228 00:09:40,062 --> 00:09:41,997 IMMUNOSUPPRESSION CAN BE USED TO 229 00:09:41,997 --> 00:09:43,465 TREAT AUTOIMMUNE DISEASES AND 230 00:09:43,465 --> 00:09:45,200 THE FIRST DEMONSTRATION THAT 231 00:09:45,200 --> 00:09:47,169 IMMUNOTHERAPY COULD BE 232 00:09:47,169 --> 00:09:47,769 SUCCESSFUL TO TREAT PATIENTS 233 00:09:47,769 --> 00:09:55,177 WITH CANCER. 234 00:09:55,177 --> 00:09:57,879 NHLBI IS PROUD TO SUPPORT 235 00:09:57,879 --> 00:10:00,015 CUTTING-EDGE RESEARCH FOR SICKLE 236 00:10:00,015 --> 00:10:01,917 CELL DISEASE AND IN THE PROGRAM 237 00:10:01,917 --> 00:10:03,719 THAT SUPPORT INCLUDES BOTH 238 00:10:03,719 --> 00:10:05,887 NATURAL HISTORY STUDIES WHERE WE 239 00:10:05,887 --> 00:10:07,622 DO OMICS TYPE OF RESEARCH AND 240 00:10:07,622 --> 00:10:10,792 DEEP PHENOTYPING ON PATIENTS AS 241 00:10:10,792 --> 00:10:12,761 WELL INVESTIGATOR INITIATED 242 00:10:12,761 --> 00:10:16,565 BENCH TO BEDSIDE RESEARCH AIMED 243 00:10:16,565 --> 00:10:18,934 AT DEVELOPING NEW THERAPEUTICS 244 00:10:18,934 --> 00:10:19,434 FOR SICKLE CELL DISEASE. 245 00:10:19,434 --> 00:10:22,604 AT THE DIR WE HAVE TWO SEPARATE 246 00:10:22,604 --> 00:10:25,774 BRANCHES MADE OF 100 STAFF THAT 247 00:10:25,774 --> 00:10:29,244 FOCUS RESEARCH ON SICKLE CELL 248 00:10:29,244 --> 00:10:35,250 THE SICKLE CELL BRANCH LED BY 249 00:10:35,250 --> 00:10:37,986 DR. SWEE LAY THEIN AND 250 00:10:37,986 --> 00:10:41,323 DR. TISDALE. 251 00:10:41,323 --> 00:10:42,657 THEY'VE DONE PIONEERING RESEARCH 252 00:10:42,657 --> 00:10:44,426 THAT'S LED TO NEW THERAPEUTICS 253 00:10:44,426 --> 00:10:48,163 AND SOME OF THAT RESEARCH 254 00:10:48,163 --> 00:10:50,232 INCLUDES THINGS LIKE THE 255 00:10:50,232 --> 00:10:55,437 DEVELOPMENT OF AND INITIAL 256 00:10:55,437 --> 00:11:00,942 TESTING IN SICKLE CELL DISEASE 257 00:11:00,942 --> 00:11:03,712 PATIENTS AND PREVENT OCCLUSION 258 00:11:03,712 --> 00:11:06,548 AND A FINDING THAT LED TO AGAIN 259 00:11:06,548 --> 00:11:17,058 ET -- GENETIC REACTIVATION OF 260 00:11:21,963 --> 00:11:24,466 HEMOGLOBIN AND FINDING HIGH CURE 261 00:11:24,466 --> 00:11:25,901 RATES AND NO GRAPH VERSUS HOST 262 00:11:25,901 --> 00:11:27,369 DISEASE IN THE MAJORITY OF 263 00:11:27,369 --> 00:11:29,738 PATIENTS TREATED WITH THESE 264 00:11:29,738 --> 00:11:32,974 REGIMENTS AND RECENTLY DR. FITU 265 00:11:32,974 --> 00:11:35,811 EXTENDED THE APPROACH TO INCLUDE 266 00:11:35,811 --> 00:11:40,949 PATIENTS UNDERGOING HAPLODEMIGO 267 00:11:40,949 --> 00:11:42,584 TRANSPLANTATION USING THAT 268 00:11:42,584 --> 00:11:45,187 APPROACH AS WELL. 269 00:11:45,187 --> 00:11:47,722 MOST RECENTLY GENETICALLY 270 00:11:47,722 --> 00:11:54,296 CORRECT THE BETA GLOBULIN GENE 271 00:11:54,296 --> 00:11:57,432 RESULTING IN COMPLETE EVASION OF 272 00:11:57,432 --> 00:11:57,666 EVENTS. 273 00:11:57,666 --> 00:12:01,870 WE'RE PROUD OF ALL OF THESE 274 00:12:01,870 --> 00:12:03,338 INVESTIGATORS WITHIN THE NHLBI 275 00:12:03,338 --> 00:12:04,339 CONDUCTING THIS PENE EARRING 276 00:12:04,339 --> 00:12:07,576 WORK THAT IS DIRECTLY IMPROVED 277 00:12:07,576 --> 00:12:10,645 THE LIVES OF PATIENTS WITH 278 00:12:10,645 --> 00:12:12,280 SICKLE CELL IN SOME PATIENTS HAS 279 00:12:12,280 --> 00:12:13,815 CURED THESE PATIENTS. 280 00:12:13,815 --> 00:12:17,185 WE IS HAVE DONE MUCH AS THE 281 00:12:17,185 --> 00:12:20,088 FORMER DIRECTOR OF THE NHLBI WAS 282 00:12:20,088 --> 00:12:21,423 FAMOUS FOR SAYING WE'VE DONE 283 00:12:21,423 --> 00:12:23,325 MUCH, WE HAVE MUCH TO DO. 284 00:12:23,325 --> 00:12:27,062 IN THE COMING YEARS THE NHLBI 285 00:12:27,062 --> 00:12:29,531 WILL COMMIT ADDITIONAL MONEY AND 286 00:12:29,531 --> 00:12:30,232 RESOURCES TO CONTINUE RESEARCH 287 00:12:30,232 --> 00:12:31,900 IN SICKLE CELL AND PROUD TO 288 00:12:31,900 --> 00:12:34,135 ANNOUNCE A MAJOR FOCUS OF THAT 289 00:12:34,135 --> 00:12:38,039 RESEARCH WILL BE TO DEVELOPING 290 00:12:38,039 --> 00:12:40,175 NEW IN VIVO GENE THERAPIES FOR 291 00:12:40,175 --> 00:12:46,681 THIS DISEASE AIMS AT GENETICALLY 292 00:12:46,681 --> 00:12:50,151 CORRECTING THE HEMATOPOIETIC 293 00:12:50,151 --> 00:12:51,753 STEM CELLS AND THEY PLAN TO 294 00:12:51,753 --> 00:12:54,189 DEVELOP A GENE THAT THERAPY 295 00:12:54,189 --> 00:12:55,957 CORPS FACILITY AIMED AT CELLULAR 296 00:12:55,957 --> 00:12:57,859 ENGINEERING FOR A MAJOR AMOUNT 297 00:12:57,859 --> 00:13:01,263 OF THAT WORK WILL BE FOCUSSED ON 298 00:13:01,263 --> 00:13:01,696 SICKLE CELL ANEMIA. 299 00:13:01,696 --> 00:13:04,466 I'M ALSO HAPPY TO ANNOUNCE OUR 300 00:13:04,466 --> 00:13:11,840 PARTNERSHIP WITH AN ORGANIZATION 301 00:13:11,840 --> 00:13:14,709 IN JAMAICA IS MOVING ALONG TOO. 302 00:13:14,709 --> 00:13:17,345 OUR HOPE IS TO ESTABLISH A 303 00:13:17,345 --> 00:13:18,847 FORMAL PARTNERSHIP WITH OUR 304 00:13:18,847 --> 00:13:22,183 COLLEAGUES IN JAMAICA SO THE 305 00:13:22,183 --> 00:13:23,985 CUTTING-EDGE RESEARCH AND NEW 306 00:13:23,985 --> 00:13:25,587 THERAPEUTICS WE'RE TESTING HERE 307 00:13:25,587 --> 00:13:29,157 AT THE NIH WILL POTENTIALLY BE 308 00:13:29,157 --> 00:13:33,461 AVAILABLE TO OUR JAMAICAN 309 00:13:33,461 --> 00:13:34,796 COLLEAGUES THROUGH TWO CENTER 310 00:13:34,796 --> 00:13:35,030 TRIALS. 311 00:13:35,030 --> 00:13:36,064 ONCE AGAIN, THANK YOU ALL FOR 312 00:13:36,064 --> 00:13:37,032 ATTENDING THIS MEETING. 313 00:13:37,032 --> 00:13:38,500 I HOPE YOU HAVE A GREAT MEETING 314 00:13:38,500 --> 00:13:39,601 AND I WANT TO THANK ALL OF YOU 315 00:13:39,601 --> 00:13:43,505 FOR THE WORK THAT YOU DO EVERY 316 00:13:43,505 --> 00:13:45,407 DAY TO IMPROVE THE QUALITY OF 317 00:13:45,407 --> 00:13:47,208 LIFE AND LONGEVITY OF THOSE 318 00:13:47,208 --> 00:13:49,277 PATIENT WHO'S ARE DEBILITATED 319 00:13:49,277 --> 00:13:50,812 AND HAVE THEIR LIVES SHORTENED 320 00:13:50,812 --> 00:13:51,346 BY THIS TERRIBLE DISEASE. 321 00:13:51,346 --> 00:14:01,523 THANK YOU. 322 00:14:07,662 --> 00:14:13,501 >> NOW WE'LL START WITH THIS 323 00:14:13,501 --> 00:14:16,204 DAY'S PROGRAM. 324 00:14:16,204 --> 00:14:18,506 DR. JENNIFER KNIGHT-MADDEN TAKE 325 00:14:18,506 --> 00:14:18,907 OVER. 326 00:14:18,907 --> 00:14:21,810 >> GOOD AMONG, EVERYBODY. 327 00:14:21,810 --> 00:14:22,043 WELCOME. 328 00:14:22,043 --> 00:14:24,479 THANK YOU FOR GETTING HERE SO ON 329 00:14:24,479 --> 00:14:28,617 TIME AND EARLY BOTH HERE AND 330 00:14:28,617 --> 00:14:28,850 ONLINE. 331 00:14:28,850 --> 00:14:30,485 WE'RE INTO SESSION 1 WHERE WE'RE 332 00:14:30,485 --> 00:14:32,687 LOOKING AT A GLOBAL LOOK AT 333 00:14:32,687 --> 00:14:33,121 SICKLE CELL DISEASE. 334 00:14:33,121 --> 00:14:38,493 WE START WITH TWO IMMINENT 335 00:14:38,493 --> 00:14:49,037 SPEAKERS DR. CHARLES ABRAMS AND 336 00:14:50,472 --> 00:14:57,879 ALEXIS THOMAS. 337 00:14:57,879 --> 00:15:04,819 DR. ABRAMS IS FROM THE 338 00:15:04,819 --> 00:15:06,254 PENNSYLVANIA UNIVERSITY AND VICE 339 00:15:06,254 --> 00:15:08,056 CHAIR FOR RESEARCH AND 340 00:15:08,056 --> 00:15:09,190 SCIENTIFIC OFFICER OF THE 341 00:15:09,190 --> 00:15:11,426 DEPARTMENT OF MEDICINE AT PENN. 342 00:15:11,426 --> 00:15:13,161 OVER THE PAST FEW YEARS HE'S 343 00:15:13,161 --> 00:15:16,197 ALSO LED ANNEST BY THE ASH 344 00:15:16,197 --> 00:15:18,400 RESEARCH COLLABORATIVE TO 345 00:15:18,400 --> 00:15:20,835 DEVELOP A NATIONAL CLINICAL 346 00:15:20,835 --> 00:15:22,971 TRIALS NETWORK WHICH FACILITATES 347 00:15:22,971 --> 00:15:25,073 INTERVENTIONAL TRIALS THAT WILL 348 00:15:25,073 --> 00:15:28,243 LEAD TO MORE RAPID FDA APPROVAL 349 00:15:28,243 --> 00:15:30,211 OF DRUGS DESIGN TO IMPROVE THE 350 00:15:30,211 --> 00:15:32,113 QUALITY OF LIFE FOR SICKLE CELL 351 00:15:32,113 --> 00:15:33,682 PATIENTS AND TO INCREASE THE 352 00:15:33,682 --> 00:15:34,282 SURVIVAL OF INDIVIDUALS WITH 353 00:15:34,282 --> 00:15:37,419 THIS DISORDER. 354 00:15:37,419 --> 00:15:39,888 HIS CO-SPEAKER IS ALEXIS THOMAS 355 00:15:39,888 --> 00:15:43,992 A CHIEF OF THE DIVISION OF 356 00:15:43,992 --> 00:15:45,260 HEMATOLOGY AT CHOC. 357 00:15:45,260 --> 00:15:48,663 SHE HOLDS THE ELIAS SCHWARTS 358 00:15:48,663 --> 00:15:50,865 CHAIR FOR HEMATOLOGY AND SERVED 359 00:15:50,865 --> 00:15:53,902 AS THE PRESIDENT OF ASH IN 2018. 360 00:15:53,902 --> 00:15:58,673 SHE'S A MEMBER OF THE ASH 361 00:15:58,673 --> 00:16:01,476 STEERING COMMITTEE AND USES THE 362 00:16:01,476 --> 00:16:03,945 MEDICAL DEGREE FROM TULANE 363 00:16:03,945 --> 00:16:05,380 UNIVERSITY AND HAS PRACTICED 34 364 00:16:05,380 --> 00:16:08,550 YEARS AND SPECIALIZES IN 365 00:16:08,550 --> 00:16:09,150 PEDIATRIC ANEMIA AND RED CELL 366 00:16:09,150 --> 00:16:13,922 HEMATOLOGY. 367 00:16:13,922 --> 00:16:16,991 I WELCOME DR. ABRAMS AND 368 00:16:16,991 --> 00:16:23,198 THOMPSON TO GIVE THEIR TALK. 369 00:16:23,198 --> 00:16:23,998 >> THANKS, EVERYONE. 370 00:16:23,998 --> 00:16:34,509 CAN WE GET THE FIRST SLIDE ON. 371 00:17:01,970 --> 00:17:03,371 >> SO THANKS AGAIN. 372 00:17:03,371 --> 00:17:06,975 ON BEHALF OF ASH, THE ASH 373 00:17:06,975 --> 00:17:09,010 RESEARCH COLLABORATIVE, MY 374 00:17:09,010 --> 00:17:10,812 PARTNER ALEXIS AND I WOULD LIKE 375 00:17:10,812 --> 00:17:13,882 TO THANK THE ORGANIZERS FOR A 376 00:17:13,882 --> 00:17:14,449 CHANCE TO SHARE WHAT WE'RE 377 00:17:14,449 --> 00:17:15,917 DOING. 378 00:17:15,917 --> 00:17:18,753 SO ABOUT HALF A DOZEN YEARS AGO 379 00:17:18,753 --> 00:17:21,256 THE AMERICAN SOCIETY OF 380 00:17:21,256 --> 00:17:23,258 HEMATOLOGY MADE A COMMITMENT TO 381 00:17:23,258 --> 00:17:25,126 IMPROVE THE LIVES OF INDIVIDUALS 382 00:17:25,126 --> 00:17:26,461 WITH SICKLE CELL DISEASE. 383 00:17:26,461 --> 00:17:27,629 THIS INVOLVED A MULTI-PRONG 384 00:17:27,629 --> 00:17:27,862 PROCESS. 385 00:17:27,862 --> 00:17:30,465 THERE WAS A PORTION DEDICATED TO 386 00:17:30,465 --> 00:17:32,834 ACCESS TO CARE, THERE WAS 387 00:17:32,834 --> 00:17:35,403 PARTNERING WITH FEDERAL AGENCIES 388 00:17:35,403 --> 00:17:37,739 TO HELP EFFECTUATE POLICY 389 00:17:37,739 --> 00:17:37,972 CHANGE. 390 00:17:37,972 --> 00:17:40,275 THERE WAS A FOUNDATION OF THE 391 00:17:40,275 --> 00:17:41,609 SICKLE CELL DISEASE COALITION TO 392 00:17:41,609 --> 00:17:43,678 GIVE A VOICE TO THE COMMUNITY 393 00:17:43,678 --> 00:17:45,880 WITH THIS DISEASE AND THEN THERE 394 00:17:45,880 --> 00:17:48,349 WERE WERE TWO INITIATIVES. 395 00:17:48,349 --> 00:17:49,184 A RESEARCH AND GLOBAL INITIATIVE 396 00:17:49,184 --> 00:17:53,021 THAT ALEXIS AND I ARE GOING TO 397 00:17:53,021 --> 00:17:53,521 BE TALKING ABOUT TODAY. 398 00:17:53,521 --> 00:17:54,522 THE RESEARCH INITIATIVE INVOLVED 399 00:17:54,522 --> 00:17:57,659 THE FORMATION OF THE ASH 400 00:17:57,659 --> 00:17:59,227 RESEARCH COLLABORATIVE IN I 401 00:17:59,227 --> 00:18:01,896 THINK 2018. 402 00:18:01,896 --> 00:18:06,401 SO SUCCINCTLY THIS WAS DESIGN TO 403 00:18:06,401 --> 00:18:08,269 FOSTER LARGE-SCALE 404 00:18:08,269 --> 00:18:08,937 MULTI-INSTITUTIONAL COOPERATIVE 405 00:18:08,937 --> 00:18:10,939 STUDIES TO IMPROVE THE LIVES OF 406 00:18:10,939 --> 00:18:12,273 INDIVIDUALS WITH SICKLE CELL. 407 00:18:12,273 --> 00:18:13,908 AND IT HAS TWO MAIN COMPONENTS 408 00:18:13,908 --> 00:18:15,210 TO IT. 409 00:18:15,210 --> 00:18:16,811 IT HAS A CLINICAL TRIAL NETWORK 410 00:18:16,811 --> 00:18:19,214 I'M GOING TO BE SPENDING SOME 411 00:18:19,214 --> 00:18:21,115 TIME DESCRIBING HERE TODAY AND 412 00:18:21,115 --> 00:18:23,585 THEN ALEXIS IS GOING TO BE 413 00:18:23,585 --> 00:18:24,185 TALKING ABOUT A DATA REGISTRY 414 00:18:24,185 --> 00:18:26,888 PROGRAM. 415 00:18:26,888 --> 00:18:29,190 ALEXIS WILL ALSO BE SPENDING 416 00:18:29,190 --> 00:18:32,727 TIME TALKING ABOUT THE GLOBAL 417 00:18:32,727 --> 00:18:36,064 WORK SPECIFICALLY AN INITIATIVE. 418 00:18:36,064 --> 00:18:37,198 THE CLINICAL TRIAL NETWORK WAS 419 00:18:37,198 --> 00:18:41,202 DESIGN TO ACCELERATE RESEARCH IN 420 00:18:41,202 --> 00:18:41,636 SICKLE CELL DISEASE. 421 00:18:41,636 --> 00:18:42,904 IT'S BEEN DESIGNED TO IMPROVE 422 00:18:42,904 --> 00:18:44,172 THE LIVE OF INDIVIDUALS WITH 423 00:18:44,172 --> 00:18:46,741 THIS DISORDER. 424 00:18:46,741 --> 00:18:48,710 SO WHAT MAKES A CLINICAL TRIAL 425 00:18:48,710 --> 00:18:48,943 NETWORK? 426 00:18:48,943 --> 00:18:50,778 IN OUR MINDS YOU NEED FOUR 427 00:18:50,778 --> 00:18:51,012 THINGS. 428 00:18:51,012 --> 00:18:51,946 FIRST AND FOREMOST IS THE 429 00:18:51,946 --> 00:18:52,714 COMMUNITY. 430 00:18:52,714 --> 00:18:54,716 WE SAID FROM THE BEGINNING WE 431 00:18:54,716 --> 00:18:56,351 WERE BUILDING THIS WITH THE 432 00:18:56,351 --> 00:18:59,454 COMMUNITY NOT FOR THE COMMUNITY. 433 00:18:59,454 --> 00:19:01,656 THE COMMUNITY HAS BEEN 434 00:19:01,656 --> 00:19:02,690 INCREDIBLY INFORMATIVE AT EVERY 435 00:19:02,690 --> 00:19:04,092 STEP AND TALK ABOUT HOW THAT 436 00:19:04,092 --> 00:19:06,361 WORKS IN A BIT. 437 00:19:06,361 --> 00:19:08,997 WE NEED INVESTIGATORS. 438 00:19:08,997 --> 00:19:10,765 WE NEED A TEAM OF COLLEAGUES WHO 439 00:19:10,765 --> 00:19:13,501 HAVE A RICH CULTURE OF DOING 440 00:19:13,501 --> 00:19:14,936 COOPERATIVE RESEARCH AND I'LL BE 441 00:19:14,936 --> 00:19:15,536 SPENDING SOME TIME IN THAT AS 442 00:19:15,536 --> 00:19:17,605 WELL. 443 00:19:17,605 --> 00:19:20,475 WE NEED SPONSORS OF TRIALS AND 444 00:19:20,475 --> 00:19:22,343 WHETHER THAT BE EXTRAMURAL 445 00:19:22,343 --> 00:19:23,945 FUNDED WORK OR FROM THE PRIVATE 446 00:19:23,945 --> 00:19:25,213 SECTOR AND I'LL BE DESCRIBING 447 00:19:25,213 --> 00:19:29,984 WHAT WE CAN DO FOR BOTH OF THOSE 448 00:19:29,984 --> 00:19:32,186 SPONSORS IN A BIT. 449 00:19:32,186 --> 00:19:35,390 ALEXIS WILL TALK ABOUT OUR DATA 450 00:19:35,390 --> 00:19:37,025 REGISTRY OR DATA. 451 00:19:37,025 --> 00:19:37,892 OUR CLINICAL TRIAL NETWORK. 452 00:19:37,892 --> 00:19:41,396 THIS IS WHERE WE STAND TODAY. 453 00:19:41,396 --> 00:19:42,363 WE HAVE 20 DIFFERENT CLINICAL 454 00:19:42,363 --> 00:19:45,833 TRIAL UNITS SCATTERED AND ALIGNS 455 00:19:45,833 --> 00:19:47,435 GEOGRAPHICALLY WITH THE 456 00:19:47,435 --> 00:19:48,002 DISTRIBUTION OF PEOPLE WITH 457 00:19:48,002 --> 00:19:50,038 SICKLE CELL DISEASE. 458 00:19:50,038 --> 00:19:54,042 AND YOU'LL NOTICE THAT EACH OF 459 00:19:54,042 --> 00:19:56,144 THESE CLINICAL TRIAL UNITS IS 460 00:19:56,144 --> 00:19:59,414 COMPOSED OF NOT ONLY A CENTRAL 461 00:19:59,414 --> 00:20:01,382 SITE HUB BUT MULTIPLE OTHER 462 00:20:01,382 --> 00:20:01,616 SITES. 463 00:20:01,616 --> 00:20:04,385 IF YOU WERE TO TOTAL ALL THE 464 00:20:04,385 --> 00:20:10,825 DOTS, JOHN, YOU LOOK LIKE A GOOD 465 00:20:10,825 --> 00:20:13,061 COUNTER, IF I WERE TO ASK YOU 466 00:20:13,061 --> 00:20:15,630 JOHN WOULD SAY IT'S OVER 90. 467 00:20:15,630 --> 00:20:17,165 THERE'S OVER 90 SITES WITH SOME 468 00:20:17,165 --> 00:20:18,700 AFFILIATION WITH OUR NETWORK. 469 00:20:18,700 --> 00:20:22,136 OUR RELATIONSHIP IS DEEPEST WITH 470 00:20:22,136 --> 00:20:25,873 THE 20 SITES LISTED AND SPELLED 471 00:20:25,873 --> 00:20:27,976 OUT RIGHT HERE BUT WE'RE WORKING 472 00:20:27,976 --> 00:20:31,946 TO BRING IN ALL THESE OTHER 473 00:20:31,946 --> 00:20:32,313 SITES. 474 00:20:32,313 --> 00:20:33,881 IF YOU WERE TO TOTAL THEM THEY 475 00:20:33,881 --> 00:20:36,084 CARE FOR OVER 40,000 INDIVIDUALS 476 00:20:36,084 --> 00:20:36,651 WITH SICKLE CELL DISEASE. 477 00:20:36,651 --> 00:20:39,721 THE POTENTIAL OF THE NETWORK IS 478 00:20:39,721 --> 00:20:41,255 ENORMOUS IF YOU THINK MORE THAN 479 00:20:41,255 --> 00:20:46,094 ONE OF EVERY THREE DEVELOPS WITH 480 00:20:46,094 --> 00:20:46,661 SICKLE CELL DISEASE IN THE 481 00:20:46,661 --> 00:20:49,063 COUNTRY IS SOMEHOW TOUCHED WITH 482 00:20:49,063 --> 00:20:50,298 SOME AFFILIATION WITH THIS 483 00:20:50,298 --> 00:20:50,631 NETWORK. 484 00:20:50,631 --> 00:20:52,000 SOME ARE TIGHTER THAN OTHERS BUT 485 00:20:52,000 --> 00:21:02,543 THIS IS WHERE WE'RE MARCHING TO. 486 00:21:03,778 --> 00:21:05,880 SO WE THESE SPONSORS OF TRIALS. 487 00:21:05,880 --> 00:21:07,982 ONE OF THE TYPES OF SPONSORS WE 488 00:21:07,982 --> 00:21:10,251 COULD WORK WITH IS THE PRIVATE 489 00:21:10,251 --> 00:21:11,185 SECTOR OF INDUSTRY. 490 00:21:11,185 --> 00:21:13,921 WE'VE BEEN DOING SEVERAL THINGS 491 00:21:13,921 --> 00:21:15,356 FOR OUR INDUSTRY PARTNERS. 492 00:21:15,356 --> 00:21:18,292 SO ONE, WE'VE BEEN LEVERAGING 493 00:21:18,292 --> 00:21:19,961 THE EXPERTISE OF OUR 494 00:21:19,961 --> 00:21:21,696 INVESTIGATORS WHO ADVISE ON 495 00:21:21,696 --> 00:21:22,463 STUDY DESIGN. 496 00:21:22,463 --> 00:21:26,100 WE'VE ALSO BEEN LEVERAGING THE 497 00:21:26,100 --> 00:21:26,968 EXPERTISE OF OUR COMMUNITY 498 00:21:26,968 --> 00:21:29,103 ADVISORY BOARDS I'LL DESCRIBE IN 499 00:21:29,103 --> 00:21:29,904 A MINUTE. 500 00:21:29,904 --> 00:21:31,906 TO GIVE PERSPECTIVE OF WHETHER A 501 00:21:31,906 --> 00:21:33,574 PATIENT OR PATIENT'S FAMILY 502 00:21:33,574 --> 00:21:34,742 MEMBER MIGHT THINK ABOUT A 503 00:21:34,742 --> 00:21:37,912 PARTICULAR TRIAL AND WE CAN ALSO 504 00:21:37,912 --> 00:21:42,383 CONNECT INDUSTRY WITH THE RIGHT 505 00:21:42,383 --> 00:21:42,617 SITES. 506 00:21:42,617 --> 00:21:44,352 THE COMMUNITY PROGRAM. 507 00:21:44,352 --> 00:21:46,888 IT HAS BEEN AN ESSENTIAL PARTNER 508 00:21:46,888 --> 00:21:49,891 IN EVERY STEP ALONG THE WAY OF 509 00:21:49,891 --> 00:21:51,392 THIS AND SO WE EDUCATE THEM BUT 510 00:21:51,392 --> 00:21:53,761 I THINK THEY PROBABLY EDUCATE US 511 00:21:53,761 --> 00:21:54,796 EVEN MORE. 512 00:21:54,796 --> 00:21:58,633 WE HAVE THIS RELATIONSHIP WHERE 513 00:21:58,633 --> 00:22:01,803 WE INFORM EACH OTHER. 514 00:22:01,803 --> 00:22:03,471 EACH OF OUR CLINICAL TRIAL SITES 515 00:22:03,471 --> 00:22:04,772 HAS A COMMUNITY ADVISORY BOARD 516 00:22:04,772 --> 00:22:06,207 AND SEVERAL MEMBERS OF THOSE 517 00:22:06,207 --> 00:22:09,977 BOARDS HAVE BEEN ELECTED TO A 518 00:22:09,977 --> 00:22:11,112 NATIONAL ADVISORY BOARD THAT 519 00:22:11,112 --> 00:22:13,915 WORKS WITH US AND WITH US WE 520 00:22:13,915 --> 00:22:16,184 RENEWED INDUSTRY SPONSORED 521 00:22:16,184 --> 00:22:17,919 TRIALS AND FORMED FOCUS GROUPS 522 00:22:17,919 --> 00:22:19,353 TO HELP INFORM STUDY DESIGN. 523 00:22:19,353 --> 00:22:21,456 THEY'VE ALSO BEEN HELPFUL AS 524 00:22:21,456 --> 00:22:25,293 WE'VE TRIED TO SET OUR OWN 525 00:22:25,293 --> 00:22:27,829 RESEARCH AGENDA FOR INVESTIGATOR 526 00:22:27,829 --> 00:22:29,430 INITIATED RESEARCH. 527 00:22:29,430 --> 00:22:31,732 THEY'VE DONE A SURVEY OF 528 00:22:31,732 --> 00:22:32,567 EDUCATIONAL MATERIAL OF WHAT 529 00:22:32,567 --> 00:22:34,302 IT'S LIKE TO PARTICIPATE IN A 530 00:22:34,302 --> 00:22:35,436 CLINICAL TRIAL AND WHAT WILL 531 00:22:35,436 --> 00:22:37,638 THAT MEAN FOR ME. 532 00:22:37,638 --> 00:22:39,941 WE IDENTIFIED MATERIAL FOR THIS 533 00:22:39,941 --> 00:22:40,975 PATIENT POPULATION AND 534 00:22:40,975 --> 00:22:41,909 IDENTIFIED GAPS AND WE'RE 535 00:22:41,909 --> 00:22:45,880 WORKING ON FILLING IN THOSE GAPS 536 00:22:45,880 --> 00:22:47,615 BY CREATING NEW ADDITIONAL 537 00:22:47,615 --> 00:22:48,783 EDUCATIONAL MATERIALS. 538 00:22:48,783 --> 00:22:50,451 ANOTHER THING THAT WE'RE DOING 539 00:22:50,451 --> 00:22:52,386 TOGETHER IS TRYING TO HARNESS 540 00:22:52,386 --> 00:22:55,456 THE POWER OF THE NETWORK BY 541 00:22:55,456 --> 00:22:57,692 DESIGNING OUR OWN MULTI-CENTER 542 00:22:57,692 --> 00:22:58,626 INVESTIGATOR INITIATED RESEARCH. 543 00:22:58,626 --> 00:23:01,129 SO THIS IS A COLLABORATION AMONG 544 00:23:01,129 --> 00:23:02,530 OUR INVESTIGATORS. 545 00:23:02,530 --> 00:23:05,833 SO WE'RE WORKING TO DEVELOP 546 00:23:05,833 --> 00:23:08,269 PEER-CONCEIVED, PEER REVIEWED 547 00:23:08,269 --> 00:23:10,304 AND PEER-WRITTEN PARTICLES WE'RE 548 00:23:10,304 --> 00:23:12,073 IN THE PROCESS OF SUBMITTING FOR 549 00:23:12,073 --> 00:23:14,642 EXTRAMURAL FUNDING. 550 00:23:14,642 --> 00:23:16,177 ONE STUDY THAT I'D LIKE TO 551 00:23:16,177 --> 00:23:17,111 MENTION IS ONE WE'RE JUST 552 00:23:17,111 --> 00:23:22,984 WRAPPING UP NOW AND THAT'S THE 553 00:23:22,984 --> 00:23:24,385 COVID-19 VACCINATION TRIAL. 554 00:23:24,385 --> 00:23:26,587 THIS STUDY WAS DESIGN TO ANSWER 555 00:23:26,587 --> 00:23:28,789 TWO FUNDAMENTAL QUESTIONS. 556 00:23:28,789 --> 00:23:31,559 FIRST, IS THE IMMUNITY INDUCED 557 00:23:31,559 --> 00:23:33,227 BY THE COVID VACCINE IN 558 00:23:33,227 --> 00:23:35,363 INDIVIDUALS WITH SICKLE CELL 559 00:23:35,363 --> 00:23:39,333 DISEASE SIMILAR TO THE IMMUNITY 560 00:23:39,333 --> 00:23:41,169 GENERATED IN THE GENERAL 561 00:23:41,169 --> 00:23:41,469 POPULATION. 562 00:23:41,469 --> 00:23:43,604 THE OTHER QUESTION THAT WAS VERY 563 00:23:43,604 --> 00:23:45,907 KEY TO THIS COMMUNITY IS DOES 564 00:23:45,907 --> 00:23:49,977 THE UNIQUE NATURE OF AN mRNA 565 00:23:49,977 --> 00:23:51,245 VACCINE INDUCE TOXICITY. 566 00:23:51,245 --> 00:23:54,415 WILL THIS INDUCE A CRISIS IN ME? 567 00:23:54,415 --> 00:23:57,885 I'M NOT GOING TO GO INTO ALL THE 568 00:23:57,885 --> 00:24:00,054 DETAILS OF THE STUDY BUT I'LL 569 00:24:00,054 --> 00:24:03,991 JUST TELL YOU OUR BOTTOM LINES. 570 00:24:03,991 --> 00:24:05,726 ANTIBODY PRODUCTION LOOKS ROBUST 571 00:24:05,726 --> 00:24:06,994 AND SIMILAR IN THIS PARTICULAR 572 00:24:06,994 --> 00:24:08,362 GROUP OF PATIENTS. 573 00:24:08,362 --> 00:24:11,432 IMPORTANTLY, IT DOESN'T SEEM TO 574 00:24:11,432 --> 00:24:13,267 BE INDUCING EXCESS CRISIS. 575 00:24:13,267 --> 00:24:15,703 SO, TO OUR KNOWLEDGE THIS IS THE 576 00:24:15,703 --> 00:24:18,372 LARGEST mRNA VACCINE TRIAL DONE 577 00:24:18,372 --> 00:24:18,773 IN SECOND HALFED. 578 00:24:18,773 --> 00:24:21,976 THE REASON THIS IS SO IMPORTANT 579 00:24:21,976 --> 00:24:23,978 NOT ONLY FOR COVID BUT mRNA 580 00:24:23,978 --> 00:24:25,880 VACCINES ARE PROBABLY HERE TO 581 00:24:25,880 --> 00:24:29,217 STAY AND PROBABLY WILL BE MANY 582 00:24:29,217 --> 00:24:33,187 MORE mRNA VACCINES INCLUDING 583 00:24:33,187 --> 00:24:35,156 SOME mRNA TECHNOLOGY USED FOR 584 00:24:35,156 --> 00:24:36,090 SICKLE CELL DISEASE FOR 585 00:24:36,090 --> 00:24:39,794 CORRECTIVE THERAPY. 586 00:24:39,794 --> 00:24:42,597 IT'S REASSURING THIS DOESN'T 587 00:24:42,597 --> 00:24:44,532 INDUCE A UNIQUE TOXICITY IN THIS 588 00:24:44,532 --> 00:24:45,566 PATIENT POPULATION. 589 00:24:45,566 --> 00:24:47,501 THIS WAS THE FIRST SAFETY AND 590 00:24:47,501 --> 00:24:49,904 ANTIBODY RESPONSE VACCINE TRIAL 591 00:24:49,904 --> 00:24:50,471 IN VERY YOUNG CHILDREN WITH 592 00:24:50,471 --> 00:24:55,309 SICKLE CELL DISEASE. 593 00:24:55,309 --> 00:24:56,744 I TOLD YOU ABOUT OUR COMMUNITY 594 00:24:56,744 --> 00:24:57,878 WORK AND ABOUT THE INVESTIGATORS 595 00:24:57,878 --> 00:25:00,314 AND ABOUT THE SPONSORS AND NOW 596 00:25:00,314 --> 00:25:04,252 MY PARTNER, ALEXIS, WILL TALK TO 597 00:25:04,252 --> 00:25:09,156 YOU ABOUT OUR DATA REGISTRY. 598 00:25:09,156 --> 00:25:09,824 >> THANK YOU. 599 00:25:09,824 --> 00:25:11,225 I'LL COVER THE DATA HUB AND 600 00:25:11,225 --> 00:25:14,328 LEARNING COMMUNITY AND FINALLY 601 00:25:14,328 --> 00:25:17,198 OUR GLOBAL EFFORTS COULD CONDA. 602 00:25:17,198 --> 00:25:20,801 THE ASH RC DATA HUB IS INTENDED 603 00:25:20,801 --> 00:25:22,703 TO BE APPLIED BROADLY IN 604 00:25:22,703 --> 00:25:24,739 HEMATOLOGY AND BEGUN ITS EFFORTS 605 00:25:24,739 --> 00:25:29,310 IN ONE MALIGNANT AND ONE 606 00:25:29,310 --> 00:25:29,877 NON-MALIGNANT DISORDER. 607 00:25:29,877 --> 00:25:31,712 IT'S FUNDAMENTALLY MEANT TO BE A 608 00:25:31,712 --> 00:25:36,917 REAL WORLD DATA SOURCE TO 609 00:25:36,917 --> 00:25:39,754 ACTUALLY DRIVE RESEARCH AS WELL 610 00:25:39,754 --> 00:25:41,489 AS CLINICAL CARE. 611 00:25:41,489 --> 00:25:44,425 AND WE'VE HAD THE ELECTRONIC 612 00:25:44,425 --> 00:25:47,628 MEDICAL SYSTEM AND WE ANTICIPATE 613 00:25:47,628 --> 00:25:50,097 TO IT TO INGEST DATA FROM 614 00:25:50,097 --> 00:25:53,100 PATIENT REPORTED OUTCOMES AND 615 00:25:53,100 --> 00:25:55,069 PATIENT-GENERATED HEALTH DATA 616 00:25:55,069 --> 00:25:57,772 AND OTHER POPULATION DATA. 617 00:25:57,772 --> 00:26:00,574 WE INGEST THE DATA AND WE 618 00:26:00,574 --> 00:26:05,112 INTEND FOR IT TO BE USED BY 619 00:26:05,112 --> 00:26:06,247 MULTIPLE STAKEHOLDERS TO ENHANCE 620 00:26:06,247 --> 00:26:08,549 CLINICAL CARE. 621 00:26:08,549 --> 00:26:09,250 THE ELECTRONIC HEALTH RECORD 622 00:26:09,250 --> 00:26:11,285 SYSTEM IS INGESTED IN MORE THAN 623 00:26:11,285 --> 00:26:13,954 ONE PARTICULAR PATHWAY. 624 00:26:13,954 --> 00:26:16,424 THE MOST COMMON ONES ARE CALLED 625 00:26:16,424 --> 00:26:19,560 OMOP AND FIRE AND A THIRD CALLED 626 00:26:19,560 --> 00:26:19,727 API. 627 00:26:19,727 --> 00:26:21,896 ONCE DATA IS ENTERED IN THE 628 00:26:21,896 --> 00:26:25,566 INDIVIDUAL SITES SEE THEIR OWN 629 00:26:25,566 --> 00:26:27,401 DATA IN A SITE SPECIFIC HUB 630 00:26:27,401 --> 00:26:31,439 PORTAL AVAILABLE TO THOSE 631 00:26:31,439 --> 00:26:32,473 INVESTIGATORS AND ONE LINE THAT 632 00:26:32,473 --> 00:26:34,141 INCLUDES THEIR OWN DATA AND A 633 00:26:34,141 --> 00:26:35,376 SECOND LINE THE AGGREGATE FOR 634 00:26:35,376 --> 00:26:37,912 ALL THE INFORMATION ACCUMULATED 635 00:26:37,912 --> 00:26:41,148 FROM ALL THE OTHER SITES. 636 00:26:41,148 --> 00:26:44,719 TODAY THERE'S A TOTAL OF 51 SITE 637 00:26:44,719 --> 00:26:49,824 ENROLLED IN THE DATA HUB. 638 00:26:49,824 --> 00:27:00,267 THERE'S 15 IT MIRRORS THE 639 00:27:10,244 --> 00:27:11,212 DISTRIBUTION OF WHERE SICKLE 640 00:27:11,212 --> 00:27:13,547 CELL DISEASE S LIVE. 641 00:27:13,547 --> 00:27:15,483 WE'RE JUST GETTING STARTED. 642 00:27:15,483 --> 00:27:19,387 THIS IS AN EXAMPLE OF THE 643 00:27:19,387 --> 00:27:21,889 INFORMATION THE MAJORITY ARE IN 644 00:27:21,889 --> 00:27:26,727 URBAN CENTERS AND WE'RE PLEASED 645 00:27:26,727 --> 00:27:28,229 AND PEDIATRIC AND ADULT PATIENTS 646 00:27:28,229 --> 00:27:33,434 AND IN MANY INSTANCES SITES THAT 647 00:27:33,434 --> 00:27:36,670 HAVE A COMBINATION OF BOTH ADULT 648 00:27:36,670 --> 00:27:37,538 AND PEDIATRIC PATIENT. 649 00:27:37,538 --> 00:27:39,473 WE HAVE TAKEN ON A ROBUST EFFORT 650 00:27:39,473 --> 00:27:49,884 IN A SELECTED NUMBER OF SITES TO 651 00:27:49,884 --> 00:27:53,454 USE INVESTIGATOR VERIFIED 652 00:27:53,454 --> 00:27:54,355 DIAGNOSES AND THIS IS AN 653 00:27:54,355 --> 00:27:57,892 INITIATIVE UNDERTAKEN TO ASK 654 00:27:57,892 --> 00:28:00,494 SITES TO GO BACK AND VERIFY THE 655 00:28:00,494 --> 00:28:02,897 DIAGNOSIS FOR PATIENTS SEEN IN 656 00:28:02,897 --> 00:28:05,332 2022 AND DISTRIBUTION OF THE 657 00:28:05,332 --> 00:28:06,267 PATIENTS THAT ARE NOW ALL 658 00:28:06,267 --> 00:28:10,137 PATIENTS WHO HAVE A SINGLE 659 00:28:10,137 --> 00:28:11,138 DIAGNOSIS NOT MULTIPLE SICKLE 660 00:28:11,138 --> 00:28:12,706 CELL DISEASE DIAGNOSIS BUT THE 661 00:28:12,706 --> 00:28:14,275 MOST SPECIFIC WE CAN. 662 00:28:14,275 --> 00:28:17,144 TWO-THIRDS ARE SS AS MIGHT BE 663 00:28:17,144 --> 00:28:17,445 EXPECTED. 664 00:28:17,445 --> 00:28:20,347 ANOTHER QUARTER ARE SC AND 665 00:28:20,347 --> 00:28:21,282 SMATTERING OF THE OTHER SICKLE 666 00:28:21,282 --> 00:28:24,652 CELL VARIANTS. 667 00:28:24,652 --> 00:28:27,021 WE THINK BY HAVING MORE 668 00:28:27,021 --> 00:28:29,223 CERTAINTY WILL ALLOW US TO APPLY 669 00:28:29,223 --> 00:28:32,059 OUR MEASURES OR OUR METHODS TO 670 00:28:32,059 --> 00:28:35,429 ACTUALLY BEGIN TO COLLECT AND 671 00:28:35,429 --> 00:28:36,030 STUDY MORE DATA THAT'S BEING 672 00:28:36,030 --> 00:28:45,506 COLLECTED. 673 00:28:45,506 --> 00:28:46,474 WHY LEARNING AND SICKLE CELL 674 00:28:46,474 --> 00:28:47,141 DISEASE? 675 00:28:47,141 --> 00:28:49,443 WE BELIEVE THIS KIND OF EFFORT 676 00:28:49,443 --> 00:28:51,378 WILL IMPROVE PATIENT OUTCOMES ON 677 00:28:51,378 --> 00:28:55,649 A NATIONWIDE BASIS AND ALLOW US 678 00:28:55,649 --> 00:28:56,851 TO ADOPTION OF EVIDENCE-BASED 679 00:28:56,851 --> 00:28:57,885 PRACTICES AND HOPE TO ESTABLISH 680 00:28:57,885 --> 00:29:04,258 A NETWORK OF PROVIDERS TO 681 00:29:04,258 --> 00:29:06,727 STANDARDIZE CARE ACROSS SICKLE 682 00:29:06,727 --> 00:29:09,230 CELL CENTERS AND DEVELOP 683 00:29:09,230 --> 00:29:09,597 LEADERS. 684 00:29:09,597 --> 00:29:13,067 WE'VE ESTABLISHED A SET OF 685 00:29:13,067 --> 00:29:14,969 MULTI-STAKEHOLDER TEAMS AT 15 686 00:29:14,969 --> 00:29:15,903 PILOT SITES. 687 00:29:15,903 --> 00:29:17,638 WE'VE ESTABLISHED COMMON GOALS 688 00:29:17,638 --> 00:29:19,840 AND IMPROVEMENT AREAS AND FROM 689 00:29:19,840 --> 00:29:20,975 THOSE CREATED CHANGE PACKAGES 690 00:29:20,975 --> 00:29:22,710 AND WE'LL USE THE DATA FROM 691 00:29:22,710 --> 00:29:23,377 PATIENTS IN THE DATA HUB TO 692 00:29:23,377 --> 00:29:30,184 MEASURE CHANGE. 693 00:29:30,184 --> 00:29:32,486 ASH HAD A VISION AND PARTNERED 694 00:29:32,486 --> 00:29:34,388 TO GET US STARTED WITH THE FIRST 695 00:29:34,388 --> 00:29:39,593 FEW AREAS TO BEGIN ENROLLMENT OF 696 00:29:39,593 --> 00:29:44,365 THE SITES LOOK TO AT THE QI 697 00:29:44,365 --> 00:29:45,032 CHANGE PACKAGES. 698 00:29:45,032 --> 00:29:47,234 WE COMPLETE NED IMPLEMENTATION 699 00:29:47,234 --> 00:29:47,801 AND ARE MOVING TOWARD THE 700 00:29:47,801 --> 00:29:52,239 NATIONAL LAUNCH. 701 00:29:52,239 --> 00:29:53,674 WE'VE CREATED A GLOBAL AIM TO 702 00:29:53,674 --> 00:29:54,942 IMPROVE THE LIFE COURSE AND 703 00:29:54,942 --> 00:29:57,211 QUALITY OF LIFE OF INDIVIDUALS 704 00:29:57,211 --> 00:29:59,313 LIVING WITH SICKLE CELL DISEASE. 705 00:29:59,313 --> 00:30:02,116 WE'VE RELIED ON INPUT FROM THE 706 00:30:02,116 --> 00:30:02,983 COMMUNITY AS WELL AS OUR 707 00:30:02,983 --> 00:30:04,718 INVESTIGATORS TO RANK A NUMBER 708 00:30:04,718 --> 00:30:06,120 OF THEMES OR KEY DRIVERS AND 709 00:30:06,120 --> 00:30:08,155 WE'VE BEGUN WORK ON THE FIRST 710 00:30:08,155 --> 00:30:08,355 THREE. 711 00:30:08,355 --> 00:30:12,459 SO JUST AS AN EXAMPLE THE 712 00:30:12,459 --> 00:30:14,495 EFFECTIVE USE OF SAFE AND 713 00:30:14,495 --> 00:30:15,262 EVIDENCE-BASED INFORMED 714 00:30:15,262 --> 00:30:17,264 THERAPIES AND OUR FIRST AND MOST 715 00:30:17,264 --> 00:30:19,366 DEVELOPED HAS BEEN TO INCREASE 716 00:30:19,366 --> 00:30:22,169 THE RELIABLE USE OF DISEASE 717 00:30:22,169 --> 00:30:26,473 MODIFIED THERAPIES INCLUDING 718 00:30:26,473 --> 00:30:28,909 HYDROXY URIA AND INCREASE THE 719 00:30:28,909 --> 00:30:32,513 USE OF OR DEVELOPMENT OF 720 00:30:32,513 --> 00:30:33,480 CO-DEVELOPMENT OF PAIN 721 00:30:33,480 --> 00:30:34,281 MANAGEMENT PLANS BETWEEN 722 00:30:34,281 --> 00:30:37,084 PROVIDERS AND PATIENTS AND WE 723 00:30:37,084 --> 00:30:38,852 JUST RECEIVED FUNDING LAST YEAR 724 00:30:38,852 --> 00:30:42,790 TO BEGIN THE THIRD ONE WHICH IS 725 00:30:42,790 --> 00:30:43,457 TO IMPROVE THE TRANSITION FROM 726 00:30:43,457 --> 00:30:46,760 PEDIATRIC TO ADULT CARE. 727 00:30:46,760 --> 00:30:49,863 >> I WANT TO TALK ABOUT CONDA 728 00:30:49,863 --> 00:30:52,666 WHICH WE ARE SO EXCITED ABOUT 729 00:30:52,666 --> 00:30:54,001 THE CONSORTIUM FOR NEWBORN 730 00:30:54,001 --> 00:31:00,074 SCREENING IN AFRICA. 731 00:31:00,074 --> 00:31:05,012 THIS BEGAN IN 2019 AND IT'S TO 732 00:31:05,012 --> 00:31:06,747 DEMONSTRATE THE LAB-BASED 733 00:31:06,747 --> 00:31:09,350 NEWBORN SCREENING AND EARLY 734 00:31:09,350 --> 00:31:13,253 INTERVENTION IN SEVEN 735 00:31:13,253 --> 00:31:14,922 SUB-SAHARAN AFRICAN COUNTRIES 736 00:31:14,922 --> 00:31:18,492 SCREENING BETWEEN 10,000 AND 737 00:31:18,492 --> 00:31:21,929 16,000 BABIES EACH YEAR AND 738 00:31:21,929 --> 00:31:22,997 IDENTIFY BABIES WITH SICKLE CELL 739 00:31:22,997 --> 00:31:25,899 DISEASE YOU USING 740 00:31:25,899 --> 00:31:28,535 LABORATORY-BASED METHODOLOGY AND 741 00:31:28,535 --> 00:31:30,237 WE ALSO CHARGED EACH ONE OF OUR 742 00:31:30,237 --> 00:31:33,340 PARTNERS TO WORK TO IDENTIFY 743 00:31:33,340 --> 00:31:37,244 NATIONAL AND INTERNATIONAL 744 00:31:37,244 --> 00:31:41,482 PARTNERS TO LOOK TOWARDS 745 00:31:41,482 --> 00:31:43,917 SUSTAINABILITY OF THE PROGRAMS. 746 00:31:43,917 --> 00:31:49,623 THE NEWBORN SCREENING AND IN 747 00:31:49,623 --> 00:31:53,894 PARTNERSHIP WITH CLINICAL STAFF 748 00:31:53,894 --> 00:31:56,730 AND LABORATORY BASED STAFF, 749 00:31:56,730 --> 00:31:58,732 TRAINING NURSES AND THE NEWBORN 750 00:31:58,732 --> 00:32:01,301 TRAINING ACTIVITIES IN LABOR AND 751 00:32:01,301 --> 00:32:04,138 DELIVERY OTHER TIMES PRIMARY 752 00:32:04,138 --> 00:32:05,939 CARE SITES OR IMMUNIZATION 753 00:32:05,939 --> 00:32:09,176 CLINICS AND LOOKING AT THE 754 00:32:09,176 --> 00:32:11,478 MECHANISM FOR DELIVERY OF THE 755 00:32:11,478 --> 00:32:16,884 SAMPLES AND ENSURING QUALITY 756 00:32:16,884 --> 00:32:17,184 IMPROVEMENT. 757 00:32:17,184 --> 00:32:18,118 THE CARE IN SICKLE CELL CENTERS 758 00:32:18,118 --> 00:32:21,555 AND CAN BE DONE AT OTHER CARE 759 00:32:21,555 --> 00:32:25,192 SITES ENSURES PATIENTS HAVE 760 00:32:25,192 --> 00:32:25,959 ACCESS TO EVIDENCE-BASED 761 00:32:25,959 --> 00:32:29,296 MEASURES TO FOLIC ACID, AND 762 00:32:29,296 --> 00:32:31,398 MALARIA PREVENTION AND HAVE BEEN 763 00:32:31,398 --> 00:32:32,666 FOCUSSED ON OVER ALL HEALTH 764 00:32:32,666 --> 00:32:34,435 MONITORING AND FAMILY EDUCATION 765 00:32:34,435 --> 00:32:35,936 WITH ADDITIONAL FUNDING TO THE 766 00:32:35,936 --> 00:32:37,905 SITES TO HELP WITH THAT. 767 00:32:37,905 --> 00:32:40,340 AND LOOKING FOR THEM BEING SEEN 768 00:32:40,340 --> 00:32:42,776 ON A REGULAR BASIS FOR 769 00:32:42,776 --> 00:32:43,043 FOLLOW-UP. 770 00:32:43,043 --> 00:32:45,746 THESE ARE SOME OF OUR RESULTS 771 00:32:45,746 --> 00:32:45,946 TODAY. 772 00:32:45,946 --> 00:32:50,651 WE SCREENED OVER 90,000 BABIES 773 00:32:50,651 --> 00:32:52,286 IN SUB-SAHARAN AFRICA AND THE 774 00:32:52,286 --> 00:32:55,255 NUMBER OF CHILDREN IDENTIFIED 775 00:32:55,255 --> 00:32:57,324 WITH SICKLE CELL DISEASE AND 776 00:32:57,324 --> 00:32:58,192 TRAIT ARE CONSISTENT WITH WHAT 777 00:32:58,192 --> 00:33:02,229 WE BELIEVE TO BE THE GENETICS IN 778 00:33:02,229 --> 00:33:03,263 THOSE AREAS PLUS THE BIRTH RATES 779 00:33:03,263 --> 00:33:05,632 AND WE'VE BEEN ABLE TO GET THESE 780 00:33:05,632 --> 00:33:09,236 CHILDREN INTO CARE TO BE GIVEN 781 00:33:09,236 --> 00:33:11,505 PENICILLIN. 782 00:33:11,505 --> 00:33:13,907 THE MOST COMMON SOURCE FOR 783 00:33:13,907 --> 00:33:20,047 MALARIA IS FOLIC ACID AND 784 00:33:20,047 --> 00:33:22,116 PNEUMOCOCCAL VACCINES AND BED 785 00:33:22,116 --> 00:33:22,316 NETS. 786 00:33:22,316 --> 00:33:27,554 WE'VE PLEASED WITH OUR 787 00:33:27,554 --> 00:33:29,156 PARTNERSHIP WHO DONATED 788 00:33:29,156 --> 00:33:30,891 EQUIPMENT TO COUNTRIES WHO DID 789 00:33:30,891 --> 00:33:33,794 NOT OTHERWISE HAVE IT ON SITE. 790 00:33:33,794 --> 00:33:39,032 THEY HELPED WITH TRAINING AND 791 00:33:39,032 --> 00:33:39,333 RETRAINING. 792 00:33:39,333 --> 00:33:44,171 THERE WAS A WE HAD A MAJOR 793 00:33:44,171 --> 00:33:46,540 SUMMIT WHERE ALL THE INDIVIDUAL 794 00:33:46,540 --> 00:33:49,777 COUNTRIES WITHIN CONSA AND 795 00:33:49,777 --> 00:33:52,045 OTHERS CAME TOGETHER TO WORK IN 796 00:33:52,045 --> 00:33:55,482 GHANA ON TECHNIQUES FOR THEIR 797 00:33:55,482 --> 00:33:57,885 LABORATORIES AND TO CONNECT THEM 798 00:33:57,885 --> 00:33:59,853 AS A NETWORK. 799 00:33:59,853 --> 00:34:01,889 WE ALSO HAVE OPPORTUNITIES FOR 800 00:34:01,889 --> 00:34:03,724 VIRTUAL CONSULTATIONS WITH SOME 801 00:34:03,724 --> 00:34:05,759 OF THE MORE ADVANCED OR MORE 802 00:34:05,759 --> 00:34:06,326 EXPERIENCED LABORATORIES IN 803 00:34:06,326 --> 00:34:08,395 AFRICA. 804 00:34:08,395 --> 00:34:10,397 AND THEN AGAIN WE HAD A 805 00:34:10,397 --> 00:34:12,599 LABORATORY SUMMIT LAST MONTH 806 00:34:12,599 --> 00:34:14,635 WHERE FOLKS GATHERED TO ACTUALLY 807 00:34:14,635 --> 00:34:17,538 LEARN FOR THE FIRST TIME OR TO 808 00:34:17,538 --> 00:34:20,107 REFRESH THEIR SKILLS. 809 00:34:20,107 --> 00:34:22,843 WE RECEIVED A SECOND GRANT TO 810 00:34:22,843 --> 00:34:24,311 LOOK AT HEALTH WORKFORCE 811 00:34:24,311 --> 00:34:25,979 EDUCATION AND THIS IS ACTUALLY 812 00:34:25,979 --> 00:34:27,781 ASKING EACH COUNTRY TO DEFINE 813 00:34:27,781 --> 00:34:31,051 HOW THEY'D LIKE TO PROCEED WITH 814 00:34:31,051 --> 00:34:32,886 THAT AND WE'RE LOOKING TOWARDS 815 00:34:32,886 --> 00:34:33,887 EDUCATING HEALTH CARE PROVIDERS 816 00:34:33,887 --> 00:34:36,056 AT THE PRIMARY LEVEL WHERE EVEN 817 00:34:36,056 --> 00:34:37,825 THOUGH WE INITIALLY TARGETED 818 00:34:37,825 --> 00:34:41,395 BIRTH HOSPITALS IN LARGE CITIES, 819 00:34:41,395 --> 00:34:42,396 WE RECOGNIZE THERE'LL BE MANY 820 00:34:42,396 --> 00:34:44,531 SICKLE CELL CHILDREN DIAGNOSED 821 00:34:44,531 --> 00:34:45,899 AND TREATED AT PRIMARY SITES. 822 00:34:45,899 --> 00:34:47,501 THE GOAL WOULD BE TO DEVELOP THE 823 00:34:47,501 --> 00:34:49,736 NETWORK TO ENSURE CHILDREN AT 824 00:34:49,736 --> 00:34:51,004 ALL LEVELS HAVE OPPORTUNITIES 825 00:34:51,004 --> 00:34:53,574 FOR FOLLOW-UP CARE AND REFERRAL 826 00:34:53,574 --> 00:34:55,442 AS A NEED. 827 00:34:55,442 --> 00:34:56,777 ASH IS ALSO WORKING IN 828 00:34:56,777 --> 00:34:57,878 COLLABORATION WITH OTHER 829 00:34:57,878 --> 00:34:59,479 PARTNERS. 830 00:34:59,479 --> 00:35:02,583 ONE IN PARTICULAR IS THE 831 00:35:02,583 --> 00:35:05,219 INITIATIVE THROUGH THE NATIONAL 832 00:35:05,219 --> 00:35:08,055 NCDI POVERTY NETWORK SICKLE IN 833 00:35:08,055 --> 00:35:10,457 AFRICA PARTIAL FUND FROM THE NIH 834 00:35:10,457 --> 00:35:13,126 AND OTHERS TO LEVERAGE THE 835 00:35:13,126 --> 00:35:14,862 CAPACITY TO EXPAND SICKLE CELL 836 00:35:14,862 --> 00:35:15,429 EFFORTS ACROSS SUB-SAHARAN 837 00:35:15,429 --> 00:35:23,770 AFRICA. 838 00:35:23,770 --> 00:35:25,472 SUSTAINABILITY IS OUR BIGGEST 839 00:35:25,472 --> 00:35:26,807 CHALLENGE AND HAVING 840 00:35:26,807 --> 00:35:28,909 PARTNERSHIPS WITH THESE 841 00:35:28,909 --> 00:35:29,543 GOVERNMENTS IN THESE COUNTRIES 842 00:35:29,543 --> 00:35:30,611 WILL BE CRITICAL. 843 00:35:30,611 --> 00:35:32,479 SOME MOVED TOWARDS HAVING THEIR 844 00:35:32,479 --> 00:35:34,381 NATIONAL PLANS BEING 845 00:35:34,381 --> 00:35:36,183 INCORPORATED INTO THE PLANS FOR 846 00:35:36,183 --> 00:35:38,252 THEIR COUNTRIES AND KENYA AND 847 00:35:38,252 --> 00:35:39,720 UGANDA ARE PARTICULAR EXAMPLES 848 00:35:39,720 --> 00:35:40,687 OF THAT. 849 00:35:40,687 --> 00:35:43,624 WE'VE ALSO PARTNERED WITH PHARMA 850 00:35:43,624 --> 00:35:45,959 IN PARTICULAR NOVARTIS WHICH HAS 851 00:35:45,959 --> 00:35:49,529 BEEN HELPFUL IN LOOKING AT 852 00:35:49,529 --> 00:35:51,632 OPPORTUNITIES TO HAVE LOW-COST 853 00:35:51,632 --> 00:35:56,136 ACCESS TO HYDROXY UREA AND USING 854 00:35:56,136 --> 00:35:59,506 AN ONLINE MOBILE APP BASED 855 00:35:59,506 --> 00:35:59,773 PROGRAM. 856 00:35:59,773 --> 00:36:00,874 WE PARTNERED WITH CIVIL 857 00:36:00,874 --> 00:36:02,943 SOCIETIES AND MEDIA CAMPAIGNS 858 00:36:02,943 --> 00:36:04,878 AND OTHER ORGANIZATIONS IN 859 00:36:04,878 --> 00:36:05,112 COUNTRY. 860 00:36:05,112 --> 00:36:09,549 MANY ARE FAMILIES OF PATIENTS OR 861 00:36:09,549 --> 00:36:10,884 PATIENTS THEMSELVES PARTICULARLY 862 00:36:10,884 --> 00:36:11,919 HELPFUL WITH GIVING US FEEDBACK 863 00:36:11,919 --> 00:36:13,820 AND INCREASING AWARENESS. 864 00:36:13,820 --> 00:36:15,522 WE'VE ALSO BEEN VERY PLEASED TO 865 00:36:15,522 --> 00:36:18,258 BE ONE OF THE FOUNDING MEMBERS 866 00:36:18,258 --> 00:36:22,663 OF THE WORLD COALITION ON SICKLE 867 00:36:22,663 --> 00:36:25,766 CELL DISEASE LAUNCHED IN MAY AT 868 00:36:25,766 --> 00:36:27,434 THE WORLD HEALTH ORGANIZATION 869 00:36:27,434 --> 00:36:29,569 AND WE RECOGNIZE THE 870 00:36:29,569 --> 00:36:30,470 SUSTAINABILITY EFFORTS WILL 871 00:36:30,470 --> 00:36:31,505 REQUIRE FUNDING FROM DONOR 872 00:36:31,505 --> 00:36:34,841 COUNTRIES AND WE'RE COMMITTED TO 873 00:36:34,841 --> 00:36:36,843 WORKING WITH COUNTRIES AS WELL 874 00:36:36,843 --> 00:36:38,946 AS INDUSTRY PARTNERS AS WELL AS 875 00:36:38,946 --> 00:36:41,248 NONPROFITS TOWARDS A FOCUS ON 876 00:36:41,248 --> 00:36:44,451 LOW AND MIDDLE INCOME COUNTRIES. 877 00:36:44,451 --> 00:36:46,687 IN SUMMARY, I THINK THIS NURSE 878 00:36:46,687 --> 00:36:53,226 FROM NIGERIA SUMMED IT UP SHE'S 879 00:36:53,226 --> 00:36:53,894 EMPOWERED PARENTS WITH NOCK AND 880 00:36:53,894 --> 00:36:54,561 SEEING THEM WORK TO UNDERSTAND 881 00:36:54,561 --> 00:36:59,700 THE PLAN OF CARE AND DISEASE 882 00:36:59,700 --> 00:37:00,200 PROCESS. 883 00:37:00,200 --> 00:37:03,737 SO THIS IS AN EXAMPLE OF A 884 00:37:03,737 --> 00:37:05,906 POTENTIAL FOR PARTNERSHIP 885 00:37:05,906 --> 00:37:07,174 NATIONALLY AND GLOBALLY TO 886 00:37:07,174 --> 00:37:07,741 ADVANCE SICKLE CELL DISEASE. 887 00:37:07,741 --> 00:37:17,918 THANK YOU. 888 00:37:48,415 --> 00:37:49,549 >> OUR NEXT TWO SPEAKERS ARE 889 00:37:49,549 --> 00:37:51,118 GOING TO BE ONLINE. 890 00:37:51,118 --> 00:37:54,287 THEY HAVE SENT PREPARED 891 00:37:54,287 --> 00:37:55,255 PRESENTATIONS. 892 00:37:55,255 --> 00:38:00,160 THE FIRST IS ISAAC ODAME THE 893 00:38:00,160 --> 00:38:02,396 HEMATOLOGY SECTION HEAD DIVISION 894 00:38:02,396 --> 00:38:08,935 OF HEMO AT HOSPITAL OF SICK 895 00:38:08,935 --> 00:38:11,171 CHILDREN IN TORONTO AND DIRECTOR 896 00:38:11,171 --> 00:38:12,773 OF PEDIATRIC HEMATOLOGY IN THE 897 00:38:12,773 --> 00:38:18,178 DEPARTMENT OF MEDICINE AND PIED 898 00:38:18,178 --> 00:38:19,579 PEDIATRICS AT UNIVERSITY OF 899 00:38:19,579 --> 00:38:24,785 TORONTO. 900 00:38:24,785 --> 00:38:27,054 AND PERHAPS MORE GERMANE TO THIS 901 00:38:27,054 --> 00:38:32,359 TALK THE MEDICAL DIRECTOR OF THE 902 00:38:32,359 --> 00:38:32,926 GLOBAL SICKLE CELL DISEASE 903 00:38:32,926 --> 00:38:34,694 NETWORK FOR GLOBAL HEALTH AND 904 00:38:34,694 --> 00:38:38,298 THAT IS BUILDING ENDURING 905 00:38:38,298 --> 00:38:40,033 COLLABORATIONS BETWEEN CLINICIAN 906 00:38:40,033 --> 00:38:41,001 SCIENTISTS WORLDWIDE TO FURTHER 907 00:38:41,001 --> 00:38:43,603 RESEARCH AND ADVANCE CARE FOR 908 00:38:43,603 --> 00:38:46,673 OUR PATIENTS WITH SICKLE CELL 909 00:38:46,673 --> 00:38:46,907 DISEASE. 910 00:38:46,907 --> 00:38:49,676 PARTICULARLY IN LMICs 911 00:38:49,676 --> 00:38:53,547 SHOULDERING THE HEAVIEST BURDEN. 912 00:38:53,547 --> 00:38:54,781 HIS PRESENTATION IS PRE RECORDED 913 00:38:54,781 --> 00:38:56,616 SO WE WILL WATCH THAT NOW. 914 00:38:56,616 --> 00:39:06,793 THANK YOU. 915 00:39:32,486 --> 00:39:33,120 >> GOOD MORNING. 916 00:39:33,120 --> 00:39:36,423 I'D LIKE TO THANK THE ORGANIZERS 917 00:39:36,423 --> 00:39:37,624 OF THIS SICKLE CELL IN FOCUS 918 00:39:37,624 --> 00:39:38,625 CONFERENCE FOR GIVING ME THE 919 00:39:38,625 --> 00:39:41,228 OPPORTUNITY TO PARTICIPATE IN 920 00:39:41,228 --> 00:39:44,364 THIS SESSION ON GLOBAL 921 00:39:44,364 --> 00:39:45,232 INITIATIVES. 922 00:39:45,232 --> 00:39:46,433 I'LL SPEAK TO YOU ON THE WORLD 923 00:39:46,433 --> 00:39:46,967 COALITION ON SICKLE CELL 924 00:39:46,967 --> 00:39:50,203 DISEASE. 925 00:39:50,203 --> 00:39:55,175 EARLIER THIS YEAR IN LANCET 926 00:39:55,175 --> 00:40:05,318 HEMATOLOGY PUBLISHED A REPORT ON 927 00:40:05,318 --> 00:40:06,987 THE MORTALITY RATES AND THE 928 00:40:06,987 --> 00:40:09,890 MORTALITY RATES AND ON THE RIGHT 929 00:40:09,890 --> 00:40:11,291 ARE THE TOTAL SICKLE CELL 930 00:40:11,291 --> 00:40:12,125 DISEASE MORTALITY RATE. 931 00:40:12,125 --> 00:40:18,298 THE DIFFERENCE REFLECTS ICD 932 00:40:18,298 --> 00:40:20,800 CODING WHICH REQUIRES ONE 933 00:40:20,800 --> 00:40:21,868 ATTRIBUTED TO ONE DEATH THE 934 00:40:21,868 --> 00:40:25,071 CAUSE SPECIFIC MORTALITY RATE 935 00:40:25,071 --> 00:40:27,307 AND THIS UNDERRATES DEATHS TO 936 00:40:27,307 --> 00:40:29,176 WHICH SICKLE CELL DISEASE COULD 937 00:40:29,176 --> 00:40:29,843 BE ATTRIBUTED AS A CONTRIBUTING 938 00:40:29,843 --> 00:40:33,747 FACTOR. 939 00:40:33,747 --> 00:40:35,549 TAKING MORTALITY RATES INTO 940 00:40:35,549 --> 00:40:41,555 CONSIDERATION THE MAP SHOWS 941 00:40:41,555 --> 00:40:43,924 SUB-SAHARAN AFRICA AND INDIA 942 00:40:43,924 --> 00:40:45,358 SOUTH CONTINENT. 943 00:40:45,358 --> 00:40:46,793 THE TRENDS IN MORTALITY RATE 944 00:40:46,793 --> 00:40:50,197 FROM 2000 TO 2020 THOSE 945 00:40:50,197 --> 00:40:51,498 INTERESTING TRENDS. 946 00:40:51,498 --> 00:40:53,633 THE COLOR CODING HERE REPRESENTS 947 00:40:53,633 --> 00:40:55,669 REGIONS OF THE WORLD. 948 00:40:55,669 --> 00:41:00,273 AND ON THE LEFT IT'S SHOWING A 949 00:41:00,273 --> 00:41:01,675 PERCENTAGE OF SICKLE CELL 950 00:41:01,675 --> 00:41:03,310 DISEASE MORTALITY AS A PERCENT 951 00:41:03,310 --> 00:41:05,545 AND OF OTHER CAUSES OF 952 00:41:05,545 --> 00:41:06,146 MORTALITY. 953 00:41:06,146 --> 00:41:09,950 THIS IS CAUSE-SPECIFIC MORTALITY 954 00:41:09,950 --> 00:41:11,585 AND TOTAL MORTALITY. 955 00:41:11,585 --> 00:41:15,121 OVER THE YEARS YOU CAN SEE THE 956 00:41:15,121 --> 00:41:18,291 SUB-SAHARAN AFRICA EMERGES AS 957 00:41:18,291 --> 00:41:21,328 THE AREA WHERE MORTALITY FROM 958 00:41:21,328 --> 00:41:22,195 SICKLE CELL DISEASE HAS 959 00:41:22,195 --> 00:41:25,565 INCREASED NOT ONLY FOR THE UNDER 960 00:41:25,565 --> 00:41:27,767 5 AGE GROUP BUT ACTUALLY EVEN 961 00:41:27,767 --> 00:41:35,075 HIGHER FOR THOSE UNDER 20 AND 962 00:41:35,075 --> 00:41:38,278 CONTINUES TO 15 AND SAME IN 963 00:41:38,278 --> 00:41:42,716 TOTAL MORTALITY RATE AND AREAS 964 00:41:42,716 --> 00:41:46,386 LIKE INDIA EMERGE AS HAVING 965 00:41:46,386 --> 00:41:47,587 INCREASE IN TOTAL SICKLE CELL 966 00:41:47,587 --> 00:41:51,591 DISEASE MORTALITY. 967 00:41:51,591 --> 00:41:58,031 IN TERMS OF MORTALITY RATES IN 968 00:41:58,031 --> 00:42:04,104 POPULATION OVER TO 2020 969 00:42:04,104 --> 00:42:06,139 SUB-SAHARAN INFRASTRUCTURE IS 970 00:42:06,139 --> 00:42:07,774 SIGNIFICANT UNDER 5 MORTALITY 971 00:42:07,774 --> 00:42:09,609 THOUGH THERE'S A TREND DOWNWARDS 972 00:42:09,609 --> 00:42:12,846 OVER THE PERIOD IT STILL REMAINS 973 00:42:12,846 --> 00:42:14,347 SIGNIFICANTLY HIGH IN CONTRAST 974 00:42:14,347 --> 00:42:17,584 TO OTHER REGIONS OF THE WORLD. 975 00:42:17,584 --> 00:42:18,685 THEREFORE, SICKLE CELL DISEASE 976 00:42:18,685 --> 00:42:23,423 MORTALITY IS REALLY IMPACTING 977 00:42:23,423 --> 00:42:24,324 DEVELOPMENT GOALS. 978 00:42:24,324 --> 00:42:27,027 INCIDENT RATES REMAIN THE SAME 979 00:42:27,027 --> 00:42:31,064 OVER THE PERIOD BUT THE PAIRS OF 980 00:42:31,064 --> 00:42:33,033 SICKLE CELL DISEASE INCREASED 981 00:42:33,033 --> 00:42:34,768 14% TO GREATER THAN 500,000 PER 982 00:42:34,768 --> 00:42:37,904 YEAR AND THIS IS CONTRIBUTED 983 00:42:37,904 --> 00:42:41,041 MAINLY TO POPULATION GROWTH IN 984 00:42:41,041 --> 00:42:44,411 SUB-SAHARAN AFRICA AND IN THE 985 00:42:44,411 --> 00:42:44,678 CARIBBEAN. 986 00:42:44,678 --> 00:42:45,278 THEREFORE TOTAL SICKLE CELL 987 00:42:45,278 --> 00:42:48,615 DISEASE MORTALITY RATES ARE TEN 988 00:42:48,615 --> 00:42:50,250 TIMES HIGHER THAN CAUSE SPECIFIC 989 00:42:50,250 --> 00:42:50,483 DEATHS. 990 00:42:50,483 --> 00:42:55,622 IN TERMS OF UNDER 5 MORTALITY, 991 00:42:55,622 --> 00:42:57,490 SICKLE CELL DISEASE MORTALITY 992 00:42:57,490 --> 00:43:02,862 RUNS ACROSS ALL CAUSES AND WHEN 993 00:43:02,862 --> 00:43:05,298 YOU TAKE SUB-SAHARAN AFRICA INTO 994 00:43:05,298 --> 00:43:09,002 CONSIDERATION IT RANKS 11th 995 00:43:09,002 --> 00:43:13,807 AHEAD OF MEASLES AND 996 00:43:13,807 --> 00:43:14,140 MALNUTRITION. 997 00:43:14,140 --> 00:43:17,577 THIS REFLECTS MATERNAL MORTALITY 998 00:43:17,577 --> 00:43:21,648 AND 3.2 AND AIM TO PREVENTIBLE 999 00:43:21,648 --> 00:43:24,684 DEATHS UNDER 5 YEARS OF AGE AND 1000 00:43:24,684 --> 00:43:28,888 3.4 TO PREVENT PREMATURE DEATH 1001 00:43:28,888 --> 00:43:30,557 FROM LUNG COMMUNICABLE DISEASES 1002 00:43:30,557 --> 00:43:33,393 WILL NOT BE MET WITHOUT 1003 00:43:33,393 --> 00:43:34,494 COMPREHENSIVE STRATEGIES TO 1004 00:43:34,494 --> 00:43:38,098 ADDRESS SICKLE CELL DISEASE. 1005 00:43:38,098 --> 00:43:41,601 THEREFORE SICKLE CELL DISEASE 1006 00:43:41,601 --> 00:43:44,637 REMAINS AN IMPERATIVE. 1007 00:43:44,637 --> 00:43:49,743 WHY IS MORTALITY HIGH IN 1008 00:43:49,743 --> 00:43:51,578 LOW-MIDDLE INCOME COUNTRIES AND 1009 00:43:51,578 --> 00:43:53,880 LACK OF SCREENING AND LACK OF 1010 00:43:53,880 --> 00:43:57,717 INTERVENTIONS LIKE HYDROXY UREA 1011 00:43:57,717 --> 00:43:59,586 THERAPY AS AFFORDABLE, FEASIBLE. 1012 00:43:59,586 --> 00:44:01,921 THIS IS A THERAPY AND POOR 1013 00:44:01,921 --> 00:44:08,461 ACCESS TO BLOOD TRANSFUSION, 1014 00:44:08,461 --> 00:44:09,763 HEALTH CARE INFRASTRUCTURE SO 1015 00:44:09,763 --> 00:44:13,032 ACCESS TO CARE IS NOT EVENLY 1016 00:44:13,032 --> 00:44:15,201 DISTRIBUTED ACROSS THE COUNTRY. 1017 00:44:15,201 --> 00:44:17,537 THERE'S LACK OF UNIVERSAL HEALTH 1018 00:44:17,537 --> 00:44:18,872 COVERAGE WHICH MEANS MANY 1019 00:44:18,872 --> 00:44:20,740 FAMILIES CANNOT AFFORD THE COST 1020 00:44:20,740 --> 00:44:21,741 OF CARE, TRAINING OF HEALTH CARE 1021 00:44:21,741 --> 00:44:24,244 WORKERS IS LACKING SO THE 1022 00:44:24,244 --> 00:44:25,879 EXPERTISE IS NOT EVENLY 1023 00:44:25,879 --> 00:44:32,419 DISTRIBUTED ACROSS THE COUNTRY 1024 00:44:32,419 --> 00:44:36,289 AND THE CASES FOR SICKLE CELL 1025 00:44:36,289 --> 00:44:39,225 DISEASE IS WEAK AND ABOVE ALL 1026 00:44:39,225 --> 00:44:42,028 GOVERNMENTS IN THIS PART OF THE 1027 00:44:42,028 --> 00:44:42,695 WORLD LACK THE POLITICAL WILL TO 1028 00:44:42,695 --> 00:44:48,668 ACT. 1029 00:44:48,668 --> 00:44:53,606 THE HIGH BARRIERS ARE TWOFOLD 1030 00:44:53,606 --> 00:44:56,209 SUPPORTING ANY OF THE 1031 00:44:56,209 --> 00:45:00,547 INTERVENTION THAT WE KNOW AND 1032 00:45:00,547 --> 00:45:03,116 REDUCE AND WHERE IMPLEMENTATION 1033 00:45:03,116 --> 00:45:04,617 IS TAKING PLACE THERE'S 1034 00:45:04,617 --> 00:45:07,120 INADEQUATE FUNDING TO SUSTAIN 1035 00:45:07,120 --> 00:45:10,089 THE PROGRAMS AND THE SCALING OF 1036 00:45:10,089 --> 00:45:11,591 PROGRAMS FOR COUNTRY WIDE REACH 1037 00:45:11,591 --> 00:45:15,762 WHICH IS WHY WE NEED THE 1038 00:45:15,762 --> 00:45:17,597 COALITION ON SICKLE CELL 1039 00:45:17,597 --> 00:45:17,897 DISEASE. 1040 00:45:17,897 --> 00:45:20,800 WHAT IS IT? 1041 00:45:20,800 --> 00:45:23,503 AN NATIONAL PUBLIC-PRIVATE 1042 00:45:23,503 --> 00:45:26,573 PARTNERSHIP INVOLVING ACADEMIC 1043 00:45:26,573 --> 00:45:28,408 SOCIETIES, PATIENT ORGANIZATIONS 1044 00:45:28,408 --> 00:45:31,444 AND FINANCIAL INSTITUTIONS, 1045 00:45:31,444 --> 00:45:34,080 INDUSTRY, THE PRIVATE AND PUBLIC 1046 00:45:34,080 --> 00:45:37,517 SECTOR AND THE GLOBAL FOCAL 1047 00:45:37,517 --> 00:45:41,154 POINT TO ADDRESS SICKLE CELL 1048 00:45:41,154 --> 00:45:44,190 DISEASE IN LOW AND MIDDLE INCOME 1049 00:45:44,190 --> 00:45:44,457 COUNTRIES. 1050 00:45:44,457 --> 00:45:47,360 IT WAS WORLDED THE WORLD HEALTH 1051 00:45:47,360 --> 00:45:48,661 ORGANIZATION AND WORLD BANK AND 1052 00:45:48,661 --> 00:45:51,397 THE U.S. DEPARTMENT OF HEALTH IN 1053 00:45:51,397 --> 00:46:00,607 2020 AND AIMS TO ENHANCE 1054 00:46:00,607 --> 00:46:05,578 COORDINATION IN THE IMPAIRED 1055 00:46:05,578 --> 00:46:05,845 COUNTRIES. 1056 00:46:05,845 --> 00:46:08,515 THIS YEAR IN MAY THE WORLD 1057 00:46:08,515 --> 00:46:14,821 HEALTH ASSEMBLY IN GENEVA THE 1058 00:46:14,821 --> 00:46:17,056 COALITION WAS LAUNCHED AND HAS 1059 00:46:17,056 --> 00:46:23,096 BECOME THE PLATFORM TO ADDRESS 1060 00:46:23,096 --> 00:46:33,439 SICKLE CELL DISEASE. 1061 00:46:33,973 --> 00:46:35,542 THE MISSION IS TO BE THE LEADING 1062 00:46:35,542 --> 00:46:37,911 GLOBAL ORGANIZATION ACTING AS 1063 00:46:37,911 --> 00:46:39,879 THE TRUSTED VOICE FOR SICKLE 1064 00:46:39,879 --> 00:46:41,648 CELL DISEASE COMMUNITY TOGETHER 1065 00:46:41,648 --> 00:46:43,850 AND NOT IN ISOLATION BUT IN 1066 00:46:43,850 --> 00:46:46,252 COLLABORATION WITH PARTNERS. 1067 00:46:46,252 --> 00:46:49,522 THE COALITION WILL WORK TO 1068 00:46:49,522 --> 00:46:51,591 VASTLY REDUCE CHILDHOOD 1069 00:46:51,591 --> 00:46:52,825 MORTALITY ASSOCIATED WITH SICKLE 1070 00:46:52,825 --> 00:46:55,161 CELL DISEASE AND SIGNIFICANTLY 1071 00:46:55,161 --> 00:46:58,932 IMPROVE THE LIVES OF PEOPLE 1072 00:46:58,932 --> 00:46:59,532 LIVING WITH DISEASE IN LOW 1073 00:46:59,532 --> 00:47:00,600 MIDDLE INCOME COUNTRIES. 1074 00:47:00,600 --> 00:47:09,943 THE TIME LINE IS AS FOLLOWS. 1075 00:47:09,943 --> 00:47:15,481 THEY HAVE AREAS IN WASHINGTON, 1076 00:47:15,481 --> 00:47:20,520 D.C. AND AFTER THE PANDEMIC 1077 00:47:20,520 --> 00:47:22,822 STALLED THE PROGRESS BUT WAS 1078 00:47:22,822 --> 00:47:29,529 REACTIVATED IN PARIS IN JUNE 1079 00:47:29,529 --> 00:47:29,729 2022. 1080 00:47:29,729 --> 00:47:30,630 FOLLOWING THAT THERE'S BEEN 1081 00:47:30,630 --> 00:47:32,732 VIRTUAL MEETINGS ENGAGING 1082 00:47:32,732 --> 00:47:33,533 PARTNERS AND PROVIDING 1083 00:47:33,533 --> 00:47:36,669 INFORMATION ABOUT THE PROGRESS 1084 00:47:36,669 --> 00:47:40,206 OF THE COALITION IN SEPTEMBER 1085 00:47:40,206 --> 00:47:43,209 2022 AND IN MAY 2023 THE 1086 00:47:43,209 --> 00:47:48,414 COALITION WAS LAUNCHED IN GE 1087 00:47:48,414 --> 00:47:49,015 GENEVA. 1088 00:47:49,015 --> 00:47:54,153 IN TERMS OF REFERENCE HAVE BEEN 1089 00:47:54,153 --> 00:47:56,556 SET UP A COMMITTEE TRANSITIONING 1090 00:47:56,556 --> 00:47:58,257 INTO A BOARD. 1091 00:47:58,257 --> 00:47:59,726 PATIENT VOICE IS GOING TO BE 1092 00:47:59,726 --> 00:48:05,565 SYSTEMATICALLY ENGAGED TO REMAIN 1093 00:48:05,565 --> 00:48:08,067 AS CENTRAL AND IMPORTANT PART OF 1094 00:48:08,067 --> 00:48:09,369 THE COALITION AS THE COALITION 1095 00:48:09,369 --> 00:48:12,405 IS INTENDED TO ADDRESS THE NEEDS 1096 00:48:12,405 --> 00:48:14,240 OF PATIENTS AND THEREFORE THEIR 1097 00:48:14,240 --> 00:48:17,210 VOICE HAS TO BE CENTRAL. 1098 00:48:17,210 --> 00:48:21,547 STRATEGY BUILDING IS GOING TO BE 1099 00:48:21,547 --> 00:48:22,448 CONTINUE IN THIS FALL LEADING US 1100 00:48:22,448 --> 00:48:28,621 TO THE COMING YEAR AND BEYOND. 1101 00:48:28,621 --> 00:48:33,660 THE STEERING COMMITTEE CURRENTLY 1102 00:48:33,660 --> 00:48:36,496 IS MADE UP OF REPRESENTATION IN 1103 00:48:36,496 --> 00:48:37,063 THE AFRICA SICKLE CELL 1104 00:48:37,063 --> 00:48:39,399 ORGANIZATION BASED IN KENYA. 1105 00:48:39,399 --> 00:48:42,101 AMERICAN SOCIETY OF HEMATOLOGY. 1106 00:48:42,101 --> 00:48:43,670 THE GLOBAL SICKLE CELL DISEASE 1107 00:48:43,670 --> 00:48:48,007 NETWORK THE PFR FOUNDATION WHICH 1108 00:48:48,007 --> 00:48:52,245 HAS MADE A FOOTPRINT IN 1109 00:48:52,245 --> 00:48:53,646 INFRASTRUCTURE AND THE WORLD 1110 00:48:53,646 --> 00:48:55,448 HEALTH ORGANIZATION AND INDUSTRY 1111 00:48:55,448 --> 00:49:01,888 PARTNERS PFIZER AND NOVARTIS AND 1112 00:49:01,888 --> 00:49:02,121 OTHERS. 1113 00:49:02,121 --> 00:49:06,793 THE COALITION HAS IDENTIFIED 1114 00:49:06,793 --> 00:49:08,294 FIVE PRIORITIES FOR ACTION AND 1115 00:49:08,294 --> 00:49:10,963 TO ORGANIZE ITS WORK IN FIVE 1116 00:49:10,963 --> 00:49:13,900 PILLARS FROM THE PERIOD 2024 TO 1117 00:49:13,900 --> 00:49:14,100 2025. 1118 00:49:14,100 --> 00:49:16,502 FIRST, TO SCALE UP NEWBORN 1119 00:49:16,502 --> 00:49:19,605 SCREENING IN INFANTS' DIAGNOSIS 1120 00:49:19,605 --> 00:49:23,643 AND EARLY DIAGNOSIS IN THESE 1121 00:49:23,643 --> 00:49:23,876 REGIONS. 1122 00:49:23,876 --> 00:49:24,911 TO INTEGRATE SICKLE CELL DISEASE 1123 00:49:24,911 --> 00:49:26,813 MANAGEMENT INTO PRIMARY CARE AND 1124 00:49:26,813 --> 00:49:29,649 MAKE IT ACCESSIBLE AROUND ALL 1125 00:49:29,649 --> 00:49:34,787 HEALTH SYSTEMS. 1126 00:49:34,787 --> 00:49:37,890 EXPAND ACCESS TO CARE AND ACCESS 1127 00:49:37,890 --> 00:49:41,027 TO HYDROXY UREA THERAPY AN 1128 00:49:41,027 --> 00:49:43,029 EFFECTIVE DISEASE MODIFYING 1129 00:49:43,029 --> 00:49:45,898 THERAPY WHICH IS FEASIBLE AND 1130 00:49:45,898 --> 00:49:47,033 IMPLEMENTABLE AND MAKE SURE 1131 00:49:47,033 --> 00:49:49,435 ADEQUATE RESOURCES ARE PROVIDED 1132 00:49:49,435 --> 00:49:50,536 FOR SICKLE CELL DISEASE 1133 00:49:50,536 --> 00:49:52,572 PROGRAMMING AND TO SUPPORT 1134 00:49:52,572 --> 00:49:54,707 RESEARCH PARTICULARLY TO COLLECT 1135 00:49:54,707 --> 00:50:00,413 RELIABLE DATA THAT REFLECTS 1136 00:50:00,413 --> 00:50:01,981 TRAINING EVALUATION OF THE 1137 00:50:01,981 --> 00:50:12,525 PROGRAM AND IMPROVE QUALITY OF 1138 00:50:17,730 --> 00:50:25,271 LIFE. 1139 00:50:25,271 --> 00:50:26,105 FIRST IS POLICY. 1140 00:50:26,105 --> 00:50:29,308 SECOND IS STAKEHOLDER ENGAGEMENT 1141 00:50:29,308 --> 00:50:31,644 AND OPERATIONS. 1142 00:50:31,644 --> 00:50:34,213 AND POLICY ASK AND OUTLINE A 1143 00:50:34,213 --> 00:50:36,249 SHARED POLICY NARRATIVE TO 1144 00:50:36,249 --> 00:50:37,483 BECOME THE BASIS FOR ADVOCACY 1145 00:50:37,483 --> 00:50:43,823 BOTH NATIONALLY AND GLOBALLY. 1146 00:50:43,823 --> 00:50:47,293 PROMOTE THE ADOPTION AND UPDATE 1147 00:50:47,293 --> 00:50:49,428 OF PLANS SUBMITTED TO FINANCIAL 1148 00:50:49,428 --> 00:50:50,096 INSTITUTIONS LIKE THE WORLD BANK 1149 00:50:50,096 --> 00:51:00,540 FOR FINANCING AND SUPPORT. 1150 00:51:01,641 --> 00:51:05,511 LOOKING AT TO ADVOCATE FOR THE 1151 00:51:05,511 --> 00:51:07,313 NEEDS OF INDIVIDUALS WITH 1152 00:51:07,313 --> 00:51:09,115 DEVELOPED AND ADVOCACY WILL BE A 1153 00:51:09,115 --> 00:51:11,317 FOCUS BY LEVERAGING CONGRESSES 1154 00:51:11,317 --> 00:51:14,954 AND EVENTS AS MILESTONE MOMENTS 1155 00:51:14,954 --> 00:51:20,426 THROUGHOUT THE YEAR TO SUPPORT 1156 00:51:20,426 --> 00:51:22,528 EFFORTS AND MOBILIZATION WILL BE 1157 00:51:22,528 --> 00:51:25,064 THAT WILL PROACTIVE SEEK 1158 00:51:25,064 --> 00:51:28,868 OPPORTUNITIES TO DO AND SECURE 1159 00:51:28,868 --> 00:51:29,735 AND SUPPORT FOR THE COALITION 1160 00:51:29,735 --> 00:51:33,039 AND COMMITMENT FROM FUNDERS ON 1161 00:51:33,039 --> 00:51:36,309 OUR PROGRAMMATIC WORK AND ENSURE 1162 00:51:36,309 --> 00:51:37,577 ADEQUATE MANAGEMENT, PROJECT 1163 00:51:37,577 --> 00:51:41,681 PLANNING AND IMPLEMENTATION AND 1164 00:51:41,681 --> 00:51:47,386 ALSO AND CONTINUOUS IMPROVEMENT 1165 00:51:47,386 --> 00:51:52,391 OF THE COALITION MEMBERSHIP IS 1166 00:51:52,391 --> 00:51:53,693 GOING TO BE ORGANIZED IN A 1167 00:51:53,693 --> 00:52:04,403 TIERED STRUCTURE BEGIN. 1168 00:52:05,738 --> 00:52:08,541 THE FULL MEMBERS WILL HAVE EARLY 1169 00:52:08,541 --> 00:52:13,412 ACCESS TO EVENTS INVITATIONS AND 1170 00:52:13,412 --> 00:52:15,781 PARTICIPATING IN COALITION 1171 00:52:15,781 --> 00:52:18,451 MEETINGS AND SHAPING POLICY AND 1172 00:52:18,451 --> 00:52:20,953 BEING PART OF WORKING STREAMS 1173 00:52:20,953 --> 00:52:21,554 THAT DISCUSS STRATEGY FOR THE 1174 00:52:21,554 --> 00:52:23,923 COALITION. 1175 00:52:23,923 --> 00:52:25,858 PREMIUM MEMBERS ARE GOING TO BE 1176 00:52:25,858 --> 00:52:27,960 ABLE TO HAVE FULL MEMBERSHIP AND 1177 00:52:27,960 --> 00:52:30,596 DRAW ON THE PRIVILEGES OF FULL 1178 00:52:30,596 --> 00:52:33,599 MEMBERSHIP BUT IN ADDITION BE 1179 00:52:33,599 --> 00:52:35,334 ABLE TO SET AGENDA FOR EVENTS 1180 00:52:35,334 --> 00:52:38,638 AND BE ABLE TO BE PART OF 1181 00:52:38,638 --> 00:52:40,573 STRATEGY COMMITTEES THAT WILL BE 1182 00:52:40,573 --> 00:52:41,140 DEVELOPING STRATEGY FOR THE 1183 00:52:41,140 --> 00:52:44,243 COALITION. 1184 00:52:44,243 --> 00:52:46,746 AND THE ANNUAL FEEDS ARE SHOWN 1185 00:52:46,746 --> 00:52:49,882 THERE 25K FOR AFFILIATE MEMBERS, 1186 00:52:49,882 --> 00:52:52,852 50K FOR FULL MEMBERS AND 100K 1187 00:52:52,852 --> 00:52:55,454 FOR PREMIUM MEMBERS. 1188 00:52:55,454 --> 00:52:57,890 PLEASE JOIN US. 1189 00:52:57,890 --> 00:53:02,228 WE'RE LOOKING FOR PASSIONATE 1190 00:53:02,228 --> 00:53:03,596 STAKEHOLDERS AND PARTNERS AND 1191 00:53:03,596 --> 00:53:06,232 COLLABORATORS FROM ALL SECTORS 1192 00:53:06,232 --> 00:53:08,301 AND FINANCIAL INSTITUTIONS AND 1193 00:53:08,301 --> 00:53:11,671 ACADEMICS SOCIETIES AND 1194 00:53:11,671 --> 00:53:12,004 INSTITUTIONS. 1195 00:53:12,004 --> 00:53:19,979 PLEASE CONTACT ANDREW ZAPFEL AND 1196 00:53:19,979 --> 00:53:23,049 PETER VARNUM BASED IN GENEVA. 1197 00:53:23,049 --> 00:53:25,384 LET ME ALSO TAKE THIS 1198 00:53:25,384 --> 00:53:31,090 OPPORTUNITY TO INVITE YOU TO 1199 00:53:31,090 --> 00:53:34,794 BLOCK THE DAYS JUNE 3 TO THE 1200 00:53:34,794 --> 00:53:45,338 JUNE 5 FOR THE GLOBAL CONGRESS 1201 00:53:45,972 --> 00:53:47,606 ON SICKLE CELL DISEASE AND THIS 1202 00:53:47,606 --> 00:53:49,141 IS GOVERNMENTAL AND 1203 00:53:49,141 --> 00:53:49,775 NON-GOVERNMENTAL AND 1204 00:53:49,775 --> 00:53:52,878 INTERNATIONAL PARTNERS AND THE 1205 00:53:52,878 --> 00:53:56,716 GLOBAL SICKLE CELL DISEASE 1206 00:53:56,716 --> 00:54:01,387 NETWORK HELD IN ABUJA THE CAL 1207 00:54:01,387 --> 00:54:03,155 WITH THE HIGHEST BURDEN OF 1208 00:54:03,155 --> 00:54:03,656 SICKLE CELL DISEASE. 1209 00:54:03,656 --> 00:54:07,727 WE HOPE TO BE ABLE TO BRING YOU 1210 00:54:07,727 --> 00:54:09,829 PROGRESS THAT THIS COALITION HAS 1211 00:54:09,829 --> 00:54:12,498 MADE AS A COLLABORATION AND 1212 00:54:12,498 --> 00:54:16,369 PARTNERSHIP THAT IS AIMED AT 1213 00:54:16,369 --> 00:54:17,003 VASTLY REDUCING SICKLE CELL 1214 00:54:17,003 --> 00:54:19,205 DISEASE MORTALITY AND IMPROVING 1215 00:54:19,205 --> 00:54:21,474 THE QUALITY OF LIFE OF PEOPLE 1216 00:54:21,474 --> 00:54:22,575 LIVING WITH SICKLE CELL DISEASE 1217 00:54:22,575 --> 00:54:25,578 AND WITH THAT I WANT TO SAY 1218 00:54:25,578 --> 00:54:26,078 THANK YOU VERY MUCH FOR 1219 00:54:26,078 --> 00:54:35,888 LISTENING. 1220 00:54:35,888 --> 00:54:36,389 >> WONDERFUL. 1221 00:54:36,389 --> 00:54:41,594 WE'RE GOING TO MOVE ON TO THE 1222 00:54:41,594 --> 00:54:43,029 NEXT SPEAKER BECAUSE DR. ODAME 1223 00:54:43,029 --> 00:54:43,596 IS NOT AVAILABLE TO ANSWER 1224 00:54:43,596 --> 00:54:46,399 QUESTIONS. 1225 00:54:46,399 --> 00:54:49,035 THE NEXT TALK WILL BE BY 1226 00:54:49,035 --> 00:54:52,505 DR. MARIE DOMINIQUE 1227 00:54:52,505 --> 00:54:53,639 HARDY-DESSOURCES WHO WORKED AT 1228 00:54:53,639 --> 00:54:55,908 FRENCH NATIONAL INSTITUTE OF 1229 00:54:55,908 --> 00:54:57,743 HEALTH AND MEDICAL RESEARCH FOR 1230 00:54:57,743 --> 00:55:01,113 MORE THAN 30 YEARS. 1231 00:55:01,113 --> 00:55:02,181 SHE'S BEEN INTERESTED IN SICKLE 1232 00:55:02,181 --> 00:55:05,684 CELL DISEASE SINCE HER Ph.D. AND 1233 00:55:05,684 --> 00:55:08,754 HELPED CREATE THE FIRST FRENCH 1234 00:55:08,754 --> 00:55:10,423 SICKLE CELL CENTER. 1235 00:55:10,423 --> 00:55:11,957 MARIE-DOMINIQUE IS A FOUNDING 1236 00:55:11,957 --> 00:55:16,929 MEMBER OF THE CARIBBEAN NETWORK 1237 00:55:16,929 --> 00:55:17,563 FOR RESEARCH IN SICKLE CELL 1238 00:55:17,563 --> 00:55:21,901 DISEASE IN PARIS WHICH IS AN 1239 00:55:21,901 --> 00:55:24,770 UNUSUAL ENTITY. 1240 00:55:24,770 --> 00:55:25,471 IN THE CARIBBEAN IT'S THE ONLY 1241 00:55:25,471 --> 00:55:27,606 ONE I KNOW WHERE WE HAVE FRENCH, 1242 00:55:27,606 --> 00:55:28,974 SPANISH AND ENGLISH SPEAKING 1243 00:55:28,974 --> 00:55:30,042 MEMBERS WHO WORK TOGETHER. 1244 00:55:30,042 --> 00:55:31,143 SHE'S BEEN PRESIDENT OF THE 1245 00:55:31,143 --> 00:55:33,312 BOARD OF DIRECTORS OF THIS 1246 00:55:33,312 --> 00:55:35,681 NETWORK SINCE ITS INCEPTION IN 1247 00:55:35,681 --> 00:55:39,318 2012 AND AS I SAID, HER TALK IS 1248 00:55:39,318 --> 00:55:40,920 GOING TO BE VIRTUAL BUT AT THE 1249 00:55:40,920 --> 00:55:43,956 END IF THERE ARE ANY QUESTIONS 1250 00:55:43,956 --> 00:55:45,424 I'LL TAKE THEM BECAUSE I'M THE 1251 00:55:45,424 --> 00:55:55,701 VICE PRESIDENT. 1252 00:56:21,894 --> 00:56:23,729 >> GOOD MORNING. 1253 00:56:23,729 --> 00:56:28,601 I'M MARIE-DOMINIQUE 1254 00:56:28,601 --> 00:56:32,238 HARDY-DESSOURCES AND REPORTING 1255 00:56:32,238 --> 00:56:35,574 ON AN INITIATIVE NET TO IMPROVE 1256 00:56:35,574 --> 00:56:37,243 THE LIVES OF PEOPLE WITH SICKLE 1257 00:56:37,243 --> 00:56:37,843 CELL DISEASE IN OUR CARIBBEAN 1258 00:56:37,843 --> 00:56:42,648 NATION. 1259 00:56:42,648 --> 00:56:44,216 CAREST HAS 10 YEARS OF 1260 00:56:44,216 --> 00:56:48,154 EXPERIENCE AND WE CAN LOOK BACK 1261 00:56:48,154 --> 00:56:53,726 AT THE RESEARCH OVER 10 YEARS 1262 00:56:53,726 --> 00:56:57,263 AND ANALYZE THEIR IMPACT. 1263 00:56:57,263 --> 00:56:59,798 BUT LET ME REMIND YOU THAT THE 1264 00:56:59,798 --> 00:57:01,901 CARIBBEAN IS A GROUP OF STATES 1265 00:57:01,901 --> 00:57:04,036 AND TERRITORIES BOTH ISLANDS AND 1266 00:57:04,036 --> 00:57:05,704 CONTINENTS AS SHOWN IN THE 1267 00:57:05,704 --> 00:57:11,110 SLIDE. 1268 00:57:11,110 --> 00:57:13,479 THEY SHARE A COMMON HISTORY AND 1269 00:57:13,479 --> 00:57:15,381 CULTURE AND GEOGRAPHY BUT 1270 00:57:15,381 --> 00:57:17,183 DIVERSITY OF LANGUAGE AND 1271 00:57:17,183 --> 00:57:19,385 GOVERNMENTS AND ECONOMIES. 1272 00:57:19,385 --> 00:57:29,261 AND IN THIS CONTEXT, THE DISEASE 1273 00:57:29,261 --> 00:57:35,734 IS A BURDEN AND SHARE SICKLE 1274 00:57:35,734 --> 00:57:42,441 CELL DISEASE GENE. 1275 00:57:42,441 --> 00:57:44,109 THE LAST OBSERVATION LED TO THE 1276 00:57:44,109 --> 00:57:48,881 SETTING UP OF THE CAREST NETWORK 1277 00:57:48,881 --> 00:57:54,353 AS DEDICATED TO COOPERATION. 1278 00:57:54,353 --> 00:57:56,989 THUS IN FEBRUARY 2012, THE 1279 00:57:56,989 --> 00:57:59,725 CAREST NETWORK WAS FORMALLY 1280 00:57:59,725 --> 00:58:05,164 ESTABLISHED AS A NON-PROFIT 1281 00:58:05,164 --> 00:58:08,434 ORGANIZATION TO MEET A CLEAR 1282 00:58:08,434 --> 00:58:10,135 NEED FOR COLLABORATION AMONG 1283 00:58:10,135 --> 00:58:10,936 PRACTITIONERS TO WORK TOGETHER 1284 00:58:10,936 --> 00:58:20,813 TO IMPROVE THE LIVES OF PEOPLE 1285 00:58:20,813 --> 00:58:21,614 WITH SICKLE CELL DISEASE THROUGH 1286 00:58:21,614 --> 00:58:23,716 RESEARCH, EDUCATION AND CLINICAL 1287 00:58:23,716 --> 00:58:26,185 CARE TO PROMOTE EARLY DIAGNOSIS 1288 00:58:26,185 --> 00:58:28,120 FOR NEWBORN SCREENING, 1289 00:58:28,120 --> 00:58:30,823 COLLABORATION ON RESEARCH 1290 00:58:30,823 --> 00:58:36,462 PRIORITIES TO CONDUCT CAMPAIGNS 1291 00:58:36,462 --> 00:58:43,035 TO PROMOTE THE RECOGNITION AS 1292 00:58:43,035 --> 00:58:48,073 PUBLIC HEALTH PRIORITIES. 1293 00:58:48,073 --> 00:58:54,146 LET US LOOK AT THE AREAS AND 1294 00:58:54,146 --> 00:58:56,081 FIRST AT THE RESEARCH FOR ACCESS 1295 00:58:56,081 --> 00:59:06,458 TO NEWBORN SCREENING. 1296 00:59:12,631 --> 00:59:15,000 THE BLUE INDICATES COUNTRIES AND 1297 00:59:15,000 --> 00:59:17,603 TERRITORIES THAT HAVE ACCESS TO 1298 00:59:17,603 --> 00:59:22,207 SCREENING BEFORE CAREST. 1299 00:59:22,207 --> 00:59:24,743 JAMAICA, FRENCH GUYANA AND 1300 00:59:24,743 --> 00:59:29,715 MARTINIQUE AND CUBA. 1301 00:59:29,715 --> 00:59:32,885 THE GREEN COLUMN REPRESENT 1302 00:59:32,885 --> 00:59:34,353 COUNTRIES THAT HAVE GAINED 1303 00:59:34,353 --> 00:59:35,421 ACCESS TO NEWBORN SCREENING WITH 1304 00:59:35,421 --> 00:59:41,727 THE SUPPORT OF CAREST. 1305 00:59:41,727 --> 00:59:47,066 IN JAMAICA, THE GREEN COLOR IN 1306 00:59:47,066 --> 00:59:49,702 ADDITION TO THE BLUE INDICATES 1307 00:59:49,702 --> 00:59:52,571 THE NEWBORN SCREENING WAS IN 1308 00:59:52,571 --> 00:59:57,876 PLACE BUT HAS BEEN STRENGTHENED 1309 00:59:57,876 --> 01:00:00,145 WITH THE SUPPORT AND INCLUDING 1310 01:00:00,145 --> 01:00:01,947 THE SICKLE CELL DISEASE ANEMIA 1311 01:00:01,947 --> 01:00:08,821 ASSOCIATION OF JAMAICA AND THE 1312 01:00:08,821 --> 01:00:09,888 CARIBBEAN INITIATIVE. 1313 01:00:09,888 --> 01:00:11,890 AND SCREENING COVERAGE INCREASED 1314 01:00:11,890 --> 01:00:17,730 FROM 30% TO 100% FROM 2015 WITH 1315 01:00:17,730 --> 01:00:25,104 THIS COLLABORATIVE SUPPORT. 1316 01:00:25,104 --> 01:00:26,605 FINALLY, THE YELLOW COVERS 1317 01:00:26,605 --> 01:00:28,640 INDICATE THE SCREENING PROGRAMS 1318 01:00:28,640 --> 01:00:33,879 WITH THE SUPPORT OF PARTNERS 1319 01:00:33,879 --> 01:00:41,720 OTHER THAN CAREST OTHER 1320 01:00:41,720 --> 01:00:43,989 LOCATIONS. 1321 01:00:43,989 --> 01:00:46,091 THE GREEN COLOR FOR HAITI IN 1322 01:00:46,091 --> 01:00:52,064 ADDITION TO THE YELLOW ONE 1323 01:00:52,064 --> 01:00:58,937 INDICATES THAT CAREST HAS 1324 01:00:58,937 --> 01:00:59,571 CONTRIBUTED CLINICIANS IN THE 1325 01:00:59,571 --> 01:01:06,111 SCREENING TECHNIQUES. 1326 01:01:06,111 --> 01:01:13,118 WE HAVE COMPARED ALL THE DATA 1327 01:01:13,118 --> 01:01:19,224 INCLUDING IN COSTA RICA AND 1328 01:01:19,224 --> 01:01:21,894 COLOMBIA AND THE DATA IN 1329 01:01:21,894 --> 01:01:26,899 NEONATAL SCREENING IN 2019. 1330 01:01:26,899 --> 01:01:32,337 IN ORDER TO PROVIDE ACCESS TO 1331 01:01:32,337 --> 01:01:33,672 NEWBORN SCREENING FOR SICKLE 1332 01:01:33,672 --> 01:01:35,741 CELL DISEASE IN THE CARIBBEAN 1333 01:01:35,741 --> 01:01:37,910 AND UPDATE OF THE PREVALENCE OF 1334 01:01:37,910 --> 01:01:39,478 THE DISEASE. 1335 01:01:39,478 --> 01:01:43,415 THANKS TO THE SCREENING PROGRAM 1336 01:01:43,415 --> 01:01:46,752 YOU CAN SEE THE PREVALENCE OF 1337 01:01:46,752 --> 01:01:52,090 DISEASE VARIES ACROSS THE 1338 01:01:52,090 --> 01:02:01,366 CARIBBEAN WITH JAMAICA AND CUBA. 1339 01:02:01,366 --> 01:02:03,068 THANKS TO THE SCREENING PROGRAM 1340 01:02:03,068 --> 01:02:09,541 IT'S ALSO BEEN ABLE TO PUBLISH 1341 01:02:09,541 --> 01:02:13,846 ITS FIRST DATA IN THE JOURNAL OF 1342 01:02:13,846 --> 01:02:15,814 MEDICAL SCREENING SHOWING SICKLE 1343 01:02:15,814 --> 01:02:20,686 CELL DISEASE WAS DIAGNOSED FOR 1 1344 01:02:20,686 --> 01:02:29,895 IN 150 NEWBORNS AND RECENTLY 1345 01:02:29,895 --> 01:02:38,470 ANTIGUA WAS ABLE TO TO HAVE DATA 1346 01:02:38,470 --> 01:02:40,839 PUBLISHED THIS YEAR IN THE 1347 01:02:40,839 --> 01:02:45,511 INTERNATIONAL JOURNAL OF KNEW 1348 01:02:45,511 --> 01:02:51,316 KNEWO -- NEONATAL DISEASE IT'S 1349 01:02:51,316 --> 01:02:54,219 DIAGNOSED IN 1 IN 222 NEWBORNS. 1350 01:02:54,219 --> 01:02:57,923 LET US LOOK AT THE IMPACT OF 1351 01:02:57,923 --> 01:03:04,930 CAREST ON RESEARCH. 1352 01:03:04,930 --> 01:03:13,906 RESEARCH HAS BEEN CONDUCTED BY 1353 01:03:13,906 --> 01:03:17,809 USING THIS IN JAMAICA AND OTHER 1354 01:03:17,809 --> 01:03:22,915 LOCATIONS AND EXPLORING THE 1355 01:03:22,915 --> 01:03:27,753 SICKLE CELL DISEASE SEVERITY AND 1356 01:03:27,753 --> 01:03:31,290 TO INDICATE THE ON SET OF VASO 1357 01:03:31,290 --> 01:03:33,458 OCCLUSIVE CRISIS. 1358 01:03:33,458 --> 01:03:35,761 THE STUDIES HAVE SHOWN THAT VASE 1359 01:03:35,761 --> 01:03:37,362 YO OCCLUSIVE CRISIS ARE 1360 01:03:37,362 --> 01:03:39,731 ASSOCIATED WITH AN EXACERBATION 1361 01:03:39,731 --> 01:03:45,337 OF OXIDATIVE STRESS, REDUCE 1362 01:03:45,337 --> 01:03:46,939 LEVELS OF ANTIBODIES THAT MAY BE 1363 01:03:46,939 --> 01:03:57,449 RELATED TO THE OXIDATION OF 1364 01:04:05,824 --> 01:04:09,661 BLOOD CELLS. 1365 01:04:09,661 --> 01:04:11,363 THE STUDIES PROVIDED THE 1366 01:04:11,363 --> 01:04:16,501 OPPORTUNITY FOR TRAINING YOUNG 1367 01:04:16,501 --> 01:04:21,673 SCIENT 1368 01:04:21,673 --> 01:04:22,107 SCIENTISTS. 1369 01:04:22,107 --> 01:04:23,175 THEIR NAMES ARE SHOWN ON THE 1370 01:04:23,175 --> 01:04:29,815 SLIDE IN RED AND ONE OF THE 1371 01:04:29,815 --> 01:04:34,086 YOUNG SCIENTIST IS CURRENTLY 1372 01:04:34,086 --> 01:04:36,722 WORKING ON A PROJECT TO 1373 01:04:36,722 --> 01:04:42,361 FOLLOW-UP HIS WORK. 1374 01:04:42,361 --> 01:04:44,796 THE TITLE THE MICROPARTICLES OF 1375 01:04:44,796 --> 01:04:47,766 SICKLE CELL DURING CRISIS OR 1376 01:04:47,766 --> 01:04:52,571 TAKING HYDROXYUREA MODIFY 1377 01:04:52,571 --> 01:04:53,772 INFLAMMATORY PROPERTIES. 1378 01:04:53,772 --> 01:04:57,275 THE AIM OF THE NEW PROJECT IS TO 1379 01:04:57,275 --> 01:05:01,179 EVALUATE THE EFFECT OF 1380 01:05:01,179 --> 01:05:03,782 HYDROXYUREA ON MICROPARTICLES 1381 01:05:03,782 --> 01:05:09,621 AND RESISTANCE TO HYDROXYUREA IN 1382 01:05:09,621 --> 01:05:10,589 SICKLE CELL ANEMIA. 1383 01:05:10,589 --> 01:05:13,058 IT PROPOSES TO CARRY OUT THE 1384 01:05:13,058 --> 01:05:17,195 PROJECT AS PART OF THE 1385 01:05:17,195 --> 01:05:21,566 COLLABORATION INVOLVING, CUBA, 1386 01:05:21,566 --> 01:05:27,339 JA MACHA -- JAMAICA AND 1387 01:05:27,339 --> 01:05:28,940 MARTINIQUE AND IT'S A PART OF 1388 01:05:28,940 --> 01:05:33,879 THE PROGRAM TO SUPPORT THE 1389 01:05:33,879 --> 01:05:35,414 DISSEMINATION OF KNOWLEDGE ABOUT 1390 01:05:35,414 --> 01:05:41,486 SICKLE CELL DISEASE AND 1391 01:05:41,486 --> 01:05:44,856 THALASSEMIA ACHIEVED THROUGH 1392 01:05:44,856 --> 01:05:45,891 PROGRAMS. 1393 01:05:45,891 --> 01:05:54,332 THE PROGRAM FOR DOCTORS AND 1394 01:05:54,332 --> 01:05:57,869 NURSES AS WELL AS THE JAMAICAN 1395 01:05:57,869 --> 01:05:58,503 MEMBERS. 1396 01:05:58,503 --> 01:06:09,014 IN THIS WAY UPDATED CLINICAL 1397 01:06:09,581 --> 01:06:11,917 PROGRAMS AND WE HAVE ORGANIZED 1398 01:06:11,917 --> 01:06:15,153 REGULAR CONFIDENCES TO SHARE 1399 01:06:15,153 --> 01:06:18,390 ADVANCES UP CARE AND RESEARCH. 1400 01:06:18,390 --> 01:06:26,198 THE LAST ONE IN FRENCH GUYANA IN 1401 01:06:26,198 --> 01:06:26,398 2018. 1402 01:06:26,398 --> 01:06:30,869 WE PLAN TO RESUME THE CONFERENCE 1403 01:06:30,869 --> 01:06:33,905 CYCLE INTERRUPTED BY THE COVID 1404 01:06:33,905 --> 01:06:37,843 PANDEMIC. 1405 01:06:37,843 --> 01:06:39,711 SHARING EXPERTISE ON APPROPRIATE 1406 01:06:39,711 --> 01:06:41,580 TREATMENT TO MANAGE COMPLICATION 1407 01:06:41,580 --> 01:06:44,649 OF THE DISEASE IS A KEY 1408 01:06:44,649 --> 01:06:45,217 OBJECTIVE OF THIS KNOWLEDGE 1409 01:06:45,217 --> 01:06:53,792 TRANSFER. 1410 01:06:53,792 --> 01:06:59,431 HYDROXYUREA APPEARS TO BE THE 1411 01:06:59,431 --> 01:07:08,507 MOST COMMON INTERVENTION BUT 1412 01:07:08,507 --> 01:07:11,710 LAST YEAR WE FOUNDED A COMPANY 1413 01:07:11,710 --> 01:07:22,387 TO PROVIDE FREE HIYDROXYUREA TO 1414 01:07:22,754 --> 01:07:24,456 CHILDREN AND IT REMAINS 1415 01:07:24,456 --> 01:07:29,795 IMPRACTICAL IN MOST COUNTRIES 1416 01:07:29,795 --> 01:07:33,899 EXCEPT FOR THE FRENCH 1417 01:07:33,899 --> 01:07:39,437 TERRITORIES WHERE IT'S POSSIBLE. 1418 01:07:39,437 --> 01:07:45,911 BUYING LIMITS THE ACCESSIBILITY 1419 01:07:45,911 --> 01:07:48,313 OF HEMATOPOIETIC STEM CELL 1420 01:07:48,313 --> 01:07:50,482 TRANSFUSION EXCEPT FOR THOSE IN 1421 01:07:50,482 --> 01:07:55,654 THE FRENCH TERRITORIES. 1422 01:07:55,654 --> 01:08:01,893 PREVENTION IS ALSO IMPORTANT FOR 1423 01:08:01,893 --> 01:08:09,901 US INTRODUCED IN COUNTRIES WITH 1424 01:08:09,901 --> 01:08:12,804 A DEDICATED SICKLE CELL CENTER 1425 01:08:12,804 --> 01:08:17,142 AS WELL AS IN DOMINICAN REPUBLIC 1426 01:08:17,142 --> 01:08:25,750 AND COSTA RICA AND GIVEN THE 1427 01:08:25,750 --> 01:08:27,519 SUPPORT AND TRAINING IS PLANNED 1428 01:08:27,519 --> 01:08:32,657 FOR GRENADA WITH THE SUPPORT OF 1429 01:08:32,657 --> 01:08:42,634 THE UNIVERSITY OF HOSPITAL 1430 01:08:42,634 --> 01:08:49,908 GUADALUPE AND YOU CAN SEE ON THE 1431 01:08:49,908 --> 01:08:57,883 SLIDE AND WE HAVE LAUNCHED AN 1432 01:08:57,883 --> 01:09:01,887 ONLINE PLATFORM CALLED SCOPE AND 1433 01:09:01,887 --> 01:09:05,724 AS A DRIVING COURSE. 1434 01:09:05,724 --> 01:09:12,297 WE BELIEVE THIS PLATFORM CAN BE 1435 01:09:12,297 --> 01:09:14,633 USEFUL TOOL TO ARRANGE 1436 01:09:14,633 --> 01:09:17,669 STAKEHOLDER INCLUDING POLICY 1437 01:09:17,669 --> 01:09:21,873 MAKERS TO IDENTIFY BEST 1438 01:09:21,873 --> 01:09:26,878 PRACTICES TO IMPLEMENT AND 1439 01:09:26,878 --> 01:09:29,948 IDENTIFY AND ADVOCATE FOR 1440 01:09:29,948 --> 01:09:33,885 SIMILAR CARE FOR THEIR 1441 01:09:33,885 --> 01:09:34,953 COUNTRIES. 1442 01:09:34,953 --> 01:09:40,325 SO I HAVE TRIED TO BRIEFLY 1443 01:09:40,325 --> 01:09:46,064 PRESENT THE CAREST 10 YEARS OF 1444 01:09:46,064 --> 01:09:46,831 ACTIVITY AND SPIRIT IN WHICH 1445 01:09:46,831 --> 01:09:48,566 THEY HAVE BEEN CARRIED OUT. 1446 01:09:48,566 --> 01:09:53,538 IT'S IMPORTANT TO SAY THIS 1447 01:09:53,538 --> 01:09:59,811 ACTIVITY IS DRIVEN BY A BOARD OF 1448 01:09:59,811 --> 01:10:01,780 DIRECTORS MADE UP OF DIFFERENT 1449 01:10:01,780 --> 01:10:02,948 MEMBERS OF THE CARIBBEAN AS 1450 01:10:02,948 --> 01:10:04,516 INDICATED BY THE ICONS AND THE 1451 01:10:04,516 --> 01:10:11,790 SLIDE. 1452 01:10:11,790 --> 01:10:14,526 WE CAN SEE LOOKING BACK 10 YEARS 1453 01:10:14,526 --> 01:10:16,761 IN ORDER TO CONTRIBUTE TO BE 1454 01:10:16,761 --> 01:10:20,265 EFFECTIVE IN IMPROVING THE LIVES 1455 01:10:20,265 --> 01:10:21,866 OF PEOPLE WITH SICKLE CELL 1456 01:10:21,866 --> 01:10:28,073 DISEASE IN OUR REGION, IT IS 1457 01:10:28,073 --> 01:10:31,710 IMPORTANT TO HAVE AN ASSOCIATION 1458 01:10:31,710 --> 01:10:33,845 WHICH PLAY A KEY ROLE WHERE 1459 01:10:33,845 --> 01:10:44,389 THERE IS NOT YET A SICKLE CELL 1460 01:10:45,957 --> 01:10:47,726 CLINIC. 1461 01:10:47,726 --> 01:10:52,397 WE ALSO CALL ON THE YOUNGER 1462 01:10:52,397 --> 01:10:57,769 GENERATION TRAINED BY US TO PLAY 1463 01:10:57,769 --> 01:11:06,277 THEIR FULL PART IN CONTINUING. 1464 01:11:06,277 --> 01:11:07,078 SO I THANK YOU FOR YOUR KIND 1465 01:11:07,078 --> 01:11:16,821 ATTENTION. 1466 01:11:16,821 --> 01:11:17,389 >> THANK YOU. 1467 01:11:17,389 --> 01:11:18,957 SO WE'RE ACTUALLY RUNNING ON 1468 01:11:18,957 --> 01:11:19,257 TIME. 1469 01:11:19,257 --> 01:11:21,860 AGAIN, WE HAVE TIME FOR ONE 1470 01:11:21,860 --> 01:11:29,634 QUESTION IF SOMEBODY HAS ONE. 1471 01:11:29,634 --> 01:11:31,469 IF NOT I'M NOT SEEING ANYTHING 1472 01:11:31,469 --> 01:11:32,237 HERE EITHER. 1473 01:11:32,237 --> 01:11:33,304 THANK YOU FOR YOUR ATTENTION 1474 01:11:33,304 --> 01:11:35,807 DURING THIS SESSION AND I'M 1475 01:11:35,807 --> 01:11:42,747 GOING HANDLE IT TO DR 1476 01:11:42,747 --> 01:11:53,058 DR. WEST-MITCHELL. 1477 01:11:56,728 --> 01:11:58,696 >> GOOD MORNING, EVERYONE. 1478 01:11:58,696 --> 01:12:00,698 WE'LL START SESSION 2 FOCUSSED 1479 01:12:00,698 --> 01:12:04,903 ON BLOOD TRANSFUSION. 1480 01:12:04,903 --> 01:12:07,772 OUR FIRST SPEAKER IS DR. SEAN 1481 01:12:07,772 --> 01:12:09,941 STOWELL WHO'S TALK HAS BEEN 1482 01:12:09,941 --> 01:12:20,151 RECORDED. 1483 01:12:20,151 --> 01:12:21,920 I'LL INTRODUCE DR. STOWELL THE 1484 01:12:21,920 --> 01:12:24,322 DIRECTOR OF THE NATIONAL CENTER 1485 01:12:24,322 --> 01:12:34,732 OF FUNCTIONAL DICOMICS. 1486 01:12:35,200 --> 01:12:38,269 -- GLYCOMICS AT HARVARD MEDICAL 1487 01:12:38,269 --> 01:12:41,840 SCHOOL AND HE RUNS A RESEARCH 1488 01:12:41,840 --> 01:12:51,015 PROGRAM AT BRIGHAM AND WILLIAMS 1489 01:12:51,015 --> 01:12:53,351 AND GOT TRAINING IN LABORATORY 1490 01:12:53,351 --> 01:12:55,820 AND TRANSFUSION MEDICINE. 1491 01:12:55,820 --> 01:12:57,222 HIS PRESENTATION IS PRERECORDED 1492 01:12:57,222 --> 01:13:07,632 SO WE'RE ABOUT TO START. 1493 01:13:10,401 --> 01:13:14,906 >> I WANT TO THANK SWEE, JOHN, 1494 01:13:14,906 --> 01:13:19,043 JENNIFER AND MONIKA FOR 1495 01:13:19,043 --> 01:13:21,079 ORGANIZATION OF ORGANIZING AND 1496 01:13:21,079 --> 01:13:24,449 INVITING ME TO TALK ABOUT MY 1497 01:13:24,449 --> 01:13:28,253 WORK IN WORKING WITH PATIENTS 1498 01:13:28,253 --> 01:13:29,854 WITH SICKLE CELL DISEASE AND I 1499 01:13:29,854 --> 01:13:32,090 THOUGHT I'D EMPHASIZE SOME OF 1500 01:13:32,090 --> 01:13:35,160 THE SPECIFIC TRANSFUSION 1501 01:13:35,160 --> 01:13:35,827 COMPLICATIONS PATIENTS WITH 1502 01:13:35,827 --> 01:13:36,528 SICKLE CELL DISEASE AND SOME 1503 01:13:36,528 --> 01:13:38,062 CHALLENGES THE COMPLICATIONS CAN 1504 01:13:38,062 --> 01:13:41,132 RESULT IN IN SEEKING TO 1505 01:13:41,132 --> 01:13:42,767 TRANSFUSE OR NOT TRANSFUSE. 1506 01:13:42,767 --> 01:13:47,839 I APOLOGIZE I CAN'T BE THERE. 1507 01:13:47,839 --> 01:13:50,842 I AGREED TO SPEAK IN SENEGAL, 1508 01:13:50,842 --> 01:13:53,778 AFRICA OTHERWISE I'D LOVE TO BE 1509 01:13:53,778 --> 01:13:53,978 THERE. 1510 01:13:53,978 --> 01:13:55,847 I'M GOING TO START WITH A CASE I 1511 01:13:55,847 --> 01:13:59,517 EXPERIENCED AS A RESIDENT THAT 1512 01:13:59,517 --> 01:14:02,320 INFLUENCED BY DESIRE TO STUDY 1513 01:14:02,320 --> 01:14:02,921 TRANSFUSION IN PARTICULAR IN 1514 01:14:02,921 --> 01:14:05,190 SICKLE CELL DISEASE IN GENERAL. 1515 01:14:05,190 --> 01:14:10,094 AND THE COMPLICATION THAT 1516 01:14:10,094 --> 01:14:11,829 RESULTS. 1517 01:14:11,829 --> 01:14:17,535 THIS A GENTLEMAN WITH SICKLE 1518 01:14:17,535 --> 01:14:21,873 CELL DISEASE PRESENTING AND HE 1519 01:14:21,873 --> 01:14:25,610 HAD MANY ANTIBIOTICS AND AT TIME 1520 01:14:25,610 --> 01:14:28,479 OF PRESENTATION RECORDS 1521 01:14:28,479 --> 01:14:32,550 INDICATED AN ANTI-S. 1522 01:14:32,550 --> 01:14:34,852 HIS BASELINE HEMOGLOBIN WAS 5. 1523 01:14:34,852 --> 01:14:36,621 A QUESTION WE HAD WAS HOW MANY 1524 01:14:36,621 --> 01:14:39,691 UNITS SHOULD WE GIVE FOR THE 1525 01:14:39,691 --> 01:14:41,259 PARTICULAR TRANSFUSION WITH THE 1526 01:14:41,259 --> 01:14:42,393 COMPLICATED HISTORY. 1527 01:14:42,393 --> 01:14:45,029 IF YOU WERE PRESENTED WITH THE 1528 01:14:45,029 --> 01:14:47,232 PATIENT HOW MANY UNITS WOULD YOU 1529 01:14:47,232 --> 01:14:51,135 PROCURE PRIOR TO SURGERY? 1530 01:14:51,135 --> 01:14:55,740 4, 5, 14, 17, JUST WALK THROUGH 1531 01:14:55,740 --> 01:14:58,843 THE CASE WITH ME AS I PRESENT. 1532 01:14:58,843 --> 01:15:02,580 WE DECIDED TO GIVE 7 UNITS. 1533 01:15:02,580 --> 01:15:04,816 IT TOOK ABOUT 6 WEEKS AND 1534 01:15:04,816 --> 01:15:08,086 TRANSFUSED BY THOSE UNITS AND 1535 01:15:08,086 --> 01:15:13,491 FOUND TO HAVE A HEMOGLOBIN CLOSE 1536 01:15:13,491 --> 01:15:15,994 TO 10 AND HE WAS THOUGHT TO BE 1537 01:15:15,994 --> 01:15:19,597 READY TO UNDER GO SURGERY. 1538 01:15:19,597 --> 01:15:24,969 THE SURGERY WAS UNEVENT. 1539 01:15:24,969 --> 01:15:25,303 . 1540 01:15:25,303 --> 01:15:29,073 TO BLEEDING EVENT OR ADDITIONAL 1541 01:15:29,073 --> 01:15:33,578 TRANSFUSION REQUIRED BUT HE 1542 01:15:33,578 --> 01:15:35,446 BECAME UNSTABLE AND WHAT WOULD 1543 01:15:35,446 --> 01:15:40,752 YOU DO IN THE SITUATION? 1544 01:15:40,752 --> 01:15:43,721 YOU HAVE TO FIGURE OUT POTENTIAL 1545 01:15:43,721 --> 01:15:49,260 SOURCE OF BLEEDING. 1546 01:15:49,260 --> 01:15:53,831 TRANSFUSE ONE UNIT OR GIVE RED 1547 01:15:53,831 --> 01:15:54,299 CELL SUBSTITUTES? 1548 01:15:54,299 --> 01:15:55,967 THE PATIENT WAS IMMEDIATELY 1549 01:15:55,967 --> 01:15:59,504 TAKEN BACK TO THE O.R. AND GIVEN 1550 01:15:59,504 --> 01:16:03,274 TWO UNITS ON THE WAY BECAUSE OF 1551 01:16:03,274 --> 01:16:07,879 HIS INSTABILITY. 1552 01:16:07,879 --> 01:16:10,715 IT WAS FOUND HE HAD THE 1553 01:16:10,715 --> 01:16:17,755 HEMOGLOBIN DOWN TO 5.7. 1554 01:16:17,755 --> 01:16:20,458 HE WAS TRANSFERRED TO THE ICU 1555 01:16:20,458 --> 01:16:23,494 AND ADDITIONAL UNITS WERE ORDERS 1556 01:16:23,494 --> 01:16:26,898 BECAUSE WE EXHAUSTED OUR 1557 01:16:26,898 --> 01:16:28,566 NATIONAL SUPPLY AND THE NEXT 24 1558 01:16:28,566 --> 01:16:32,003 HOURS THE PATIENT ALSO HAD A 1559 01:16:32,003 --> 01:16:37,809 HISTORY OF SEVERAL TRANSFUSION 1560 01:16:37,809 --> 01:16:39,577 REACTIONS AND WE WERE NERVOUS TO 1561 01:16:39,577 --> 01:16:45,717 TRANSFUSE HIM ANYTHING LESS THAN 1562 01:16:45,717 --> 01:16:47,885 FULLY COMPATIBLE AFTER 24 HOURS 1563 01:16:47,885 --> 01:16:58,429 HIS ONE UNIT WAS S POSITIVE AND 1564 01:17:01,733 --> 01:17:05,870 ONE E POSITIVE AND THE PATIENT 1565 01:17:05,870 --> 01:17:11,843 WE DID A CROSS MATCH AND THE S 1566 01:17:11,843 --> 01:17:13,077 POS UNIT WAS COMPATIBLE 1567 01:17:13,077 --> 01:17:15,546 PRESUMING THE ANTI-S WAS NOT 1568 01:17:15,546 --> 01:17:17,014 SHOWING AT THE TIME. 1569 01:17:17,014 --> 01:17:19,050 SO WHAT WOULD DO YOU IN THE 1570 01:17:19,050 --> 01:17:19,317 SITUATION? 1571 01:17:19,317 --> 01:17:21,052 WOULD YOU WITHHOLD TRANSFUSION 1572 01:17:21,052 --> 01:17:23,154 AND HOPE TO TURN IT AROUND AND 1573 01:17:23,154 --> 01:17:25,256 GIVE THE V POSITIVE OR S 1574 01:17:25,256 --> 01:17:28,359 POSITIVE ONLY OR BOTH UNITS OR 1575 01:17:28,359 --> 01:17:35,833 USE A BLOOD SUBSTITUTE? 1576 01:17:35,833 --> 01:17:39,737 AND THERE WERE ACCUSE ADVERSE 1577 01:17:39,737 --> 01:17:39,971 EVENTS. 1578 01:17:39,971 --> 01:17:44,842 POST HEMOGLOBIN WAS 5.4 AND THE 1579 01:17:44,842 --> 01:17:47,745 PATIENTS LABORATORY VALUES AND 1580 01:17:47,745 --> 01:17:51,149 CLINICAL STATS BEGIN TO 1581 01:17:51,149 --> 01:17:51,416 STABILIZE. 1582 01:17:51,416 --> 01:17:57,021 HE WAS GIVEN STEROIDS DURING THE 1583 01:17:57,021 --> 01:17:57,588 COURSE. 1584 01:17:57,588 --> 01:17:59,657 TWO ADDITIONAL UNITS BECAME 1585 01:17:59,657 --> 01:18:02,393 VALUABLE POST-OP DAY FOUR AND 1586 01:18:02,393 --> 01:18:03,795 SEVEN DAYS FOLLOWING TRANSFUSION 1587 01:18:03,795 --> 01:18:05,897 OR SURGERY HE HAD STABILIZED AND 1588 01:18:05,897 --> 01:18:08,232 HAD A HEMOGLOBIN 7.1 AND 1589 01:18:08,232 --> 01:18:14,972 TRANSFERRED FROM THE ICU TO THE 1590 01:18:14,972 --> 01:18:17,675 FOR. 1591 01:18:17,675 --> 01:18:21,879 FOR POST-OP DAY NINE HE WAS 1592 01:18:21,879 --> 01:18:24,949 POSITIVE FOR IHG AND BILIRUBIN 1593 01:18:24,949 --> 01:18:25,483 BEGAN TO INCREASE. 1594 01:18:25,483 --> 01:18:29,153 SO WHAT WE THINK IS GOING ON IS 1595 01:18:29,153 --> 01:18:32,423 THIS AN ADDITIONAL SURGICAL 1596 01:18:32,423 --> 01:18:33,524 BLEED, POTENTIAL DEVELOPMENT OF 1597 01:18:33,524 --> 01:18:35,059 A SICKLE CELL COMPLICATION DUE 1598 01:18:35,059 --> 01:18:42,033 TO UNDERLYING DISEASE, A DELAYED 1599 01:18:42,033 --> 01:18:47,171 REACTION OR HYPERHEMOLYSIS AND 1600 01:18:47,171 --> 01:18:50,942 IN TERM OF ICG IT WAS IMPORTANT 1601 01:18:50,942 --> 01:18:54,545 AND IN CONJUNCTION HIS ANTI-S 1602 01:18:54,545 --> 01:19:00,651 WENT FROM A 0 TO 4+ AND THERE 1603 01:19:00,651 --> 01:19:04,889 WAS A TRANSFUSED REACTION AND BY 1604 01:19:04,889 --> 01:19:10,428 POST-ON DAY 13 HIS HEMOGLOBIN 1605 01:19:10,428 --> 01:19:14,832 2.9 AND WHY IS IT CONTINUING TO 1606 01:19:14,832 --> 01:19:16,267 DECLINE BEYOND? 1607 01:19:16,267 --> 01:19:19,337 WAS HE DEVELOPING A SURGICAL 1608 01:19:19,337 --> 01:19:21,038 BLEED? 1609 01:19:21,038 --> 01:19:25,877 HAVING AN SICKLE CELL 1610 01:19:25,877 --> 01:19:26,744 COMPLICATION? 1611 01:19:26,744 --> 01:19:29,881 DELAYED REACTION OR POSSIBLE 1612 01:19:29,881 --> 01:19:33,684 HYPERHEMOLYSIS. 1613 01:19:33,684 --> 01:19:37,188 THERE'S NO EVIDENCE OF BLEED ON 1614 01:19:37,188 --> 01:19:38,990 EXAM OR IMAGING AND WAS 1615 01:19:38,990 --> 01:19:43,995 TRANSFERRED BACK TO ICU, POST-OP 1616 01:19:43,995 --> 01:19:48,900 DAY 15, TWO UNITS WERE FINALLY 1617 01:19:48,900 --> 01:19:50,668 IDENTIFIED BUT BY THE TIME THEY 1618 01:19:50,668 --> 01:19:53,638 WERE READY TO TRANSFUSED HE 1619 01:19:53,638 --> 01:19:55,640 UNFORTUNATELY DEVELOPED SIGNS OF 1620 01:19:55,640 --> 01:19:57,475 MULTI-ORGAN INJURY AND 1621 01:19:57,475 --> 01:20:00,278 UNFORTUNATELY REGRESSED TO ORGAN 1622 01:20:00,278 --> 01:20:03,281 FAILURE AND SUCCUMB ON POST-OP 1623 01:20:03,281 --> 01:20:04,982 DAY 17. 1624 01:20:04,982 --> 01:20:07,818 THIS WAS A DEVASTATING OUTCOME 1625 01:20:07,818 --> 01:20:09,020 AS A RESULT OF TRANSFUSION 1626 01:20:09,020 --> 01:20:11,889 COMPLICATION IN THESE PATIENTS 1627 01:20:11,889 --> 01:20:17,328 AND THE ABILITY TO PROCESS THE 1628 01:20:17,328 --> 01:20:21,365 BLOOD IN A TIMELY FASHION. 1629 01:20:21,365 --> 01:20:23,734 ANTIBODIES CAN CAUSE THESE TYPES 1630 01:20:23,734 --> 01:20:24,969 OF TRANSFUSION REACTIONS. 1631 01:20:24,969 --> 01:20:29,373 AT EMORY WE WOULD SEE FIVE OR 1632 01:20:29,373 --> 01:20:32,410 SIX OF THESE TYPES OF CASES 1633 01:20:32,410 --> 01:20:36,380 EVERY YEAR FOR OUR ABILITY TO 1634 01:20:36,380 --> 01:20:38,649 TRANSFUSE OR COMPLICATIONS. 1635 01:20:38,649 --> 01:20:40,117 THIS WAS A SIGNIFICANT MOTIVATOR 1636 01:20:40,117 --> 01:20:42,653 FOR ME PERSONALLY TO TRY TO 1637 01:20:42,653 --> 01:20:43,688 UNDERSTAND NOT ONLY THE 1638 01:20:43,688 --> 01:20:45,022 DEVELOPMENT OF THE ANTIBODIES 1639 01:20:45,022 --> 01:20:46,490 BUT WITH THE CONSEQUENCE OF THE 1640 01:20:46,490 --> 01:20:48,025 ANTIBODIES ONCE DEVELOPED IN THE 1641 01:20:48,025 --> 01:20:49,894 TRANSFUSION SETTING FROM THE 1642 01:20:49,894 --> 01:20:50,494 PATIENTS JUST NEED A SIMPLE 1643 01:20:50,494 --> 01:20:54,432 TRANSFUSION. 1644 01:20:54,432 --> 01:20:57,468 WHAT REGULATES ADVERSE OUTCOMES 1645 01:20:57,468 --> 01:20:59,470 OF TRANSFUSION WITH ANTIBODIES? 1646 01:20:59,470 --> 01:21:01,872 WE THINK IT'S AN IMPORTANT THING 1647 01:21:01,872 --> 01:21:03,341 TO STUDY. 1648 01:21:03,341 --> 01:21:04,842 THERE'S BEEN WORK ON THE 1649 01:21:04,842 --> 01:21:05,843 DEVELOPMENT OF ANTIBODIES AND 1650 01:21:05,843 --> 01:21:11,582 WORK BY OUR OWN GROUP AND 30% TO 1651 01:21:11,582 --> 01:21:14,952 40% OF PATIENTS PREVENTIVE 1652 01:21:14,952 --> 01:21:21,859 STRATEGIES WON'T BE SUPER USEFUL 1653 01:21:21,859 --> 01:21:29,834 AND WE TRY TO PREVENT THESE 1654 01:21:29,834 --> 01:21:30,901 FORMATIONS AND THE BLOOD IS 1655 01:21:30,901 --> 01:21:32,436 STILL A SIGNIFICANT PROBLEM IN 1656 01:21:32,436 --> 01:21:33,037 THESE PATIENTS. 1657 01:21:33,037 --> 01:21:37,675 I THINK THIS MAY CONTRIBUTE TO 1658 01:21:37,675 --> 01:21:39,910 WHAT WAS PUBLISHED ABOUT EIGHT 1659 01:21:39,910 --> 01:21:43,881 YEARS AGO NOW DEMONSTRATING THAT 1660 01:21:43,881 --> 01:21:48,953 PATIENTS HAD A HIGHER MORTALITY 1661 01:21:48,953 --> 01:21:51,422 RATE THAN OTHERS THAT WERE NOT 1662 01:21:51,422 --> 01:21:57,595 AND THERE'S A HYPOTHESIS THAT 1663 01:21:57,595 --> 01:22:02,133 PEOPLE WHO ARE ALOE IMMUNIZED 1664 01:22:02,133 --> 01:22:04,802 AND CAN BE IMPACTED AND THE 1665 01:22:04,802 --> 01:22:13,911 CELLS MAY BE POESH AS WELL. 1666 01:22:13,911 --> 01:22:17,181 -- IMPORTANT AS WELL AND IT'S 1667 01:22:17,181 --> 01:22:20,484 UNCOMMON FOR PATIENTS TO GET THE 1668 01:22:20,484 --> 01:22:22,987 TRANSFUSION RESULTING IN AN 1669 01:22:22,987 --> 01:22:23,988 ACUTE REACTIONS BUT THE REASON 1670 01:22:23,988 --> 01:22:25,656 THEY'RE PROBLEMATIC IS AS 1671 01:22:25,656 --> 01:22:29,593 FOLLOWS WHEN THE PATIENT 1672 01:22:29,593 --> 01:22:32,530 DEVELOPED A PRIMARY RESPONSE 1673 01:22:32,530 --> 01:22:35,099 WITH THE FIRST EXPOSURE TO THE 1674 01:22:35,099 --> 01:22:39,603 ANTIGEN AND THE AMBULATORY 1675 01:22:39,603 --> 01:22:41,572 RESPONSE CAN ARE OFTEN NOT LONG 1676 01:22:41,572 --> 01:22:44,675 LIVED ABOUT 50% TO 60% IN SOME 1677 01:22:44,675 --> 01:22:47,878 STUDIES CAN GO TO LEVELS 1678 01:22:47,878 --> 01:22:48,546 UNDETECTABLE CLINICALLY EITHER 1679 01:22:48,546 --> 01:22:50,448 IT'S NOT EITHER DETECTED BY ANY 1680 01:22:50,448 --> 01:22:51,949 HEALTH CARE SYSTEM BECAUSE THEY 1681 01:22:51,949 --> 01:22:55,953 DON'T ROUTINELY EVALUATE OR WAS 1682 01:22:55,953 --> 01:22:57,655 DETECTED WHEN A PATIENT SEEKS A 1683 01:22:57,655 --> 01:22:59,757 DIFFERENT HEALTH CARE SYSTEM AND 1684 01:22:59,757 --> 01:23:01,759 BECAUSE THERE'S NO NATURALIZED 1685 01:23:01,759 --> 01:23:04,161 SYSTEM TO COUNT THE ANTIBODIES 1686 01:23:04,161 --> 01:23:08,099 THERE'S NO WAY TO LOOK IF THE 1687 01:23:08,099 --> 01:23:09,934 PATIENT MADE ANTIBODIES AGAINST 1688 01:23:09,934 --> 01:23:12,336 ANY PARTICULAR ANTIGEN. 1689 01:23:12,336 --> 01:23:15,439 THAT HAPPENS WHEN PATIENTS GET 1690 01:23:15,439 --> 01:23:18,008 REEXPOSED TO AN ANTIGEN THEY 1691 01:23:18,008 --> 01:23:23,914 PREVIOUSLY MADE AN RESPONSE TO 1692 01:23:23,914 --> 01:23:29,887 AND IT CAN TRANSFUSE THE 1693 01:23:29,887 --> 01:23:35,292 HEMOGLOBIN A AND SOME PATIENTS 1694 01:23:35,292 --> 01:23:41,899 NOT ONLY CAN EXPERIENCE THE H 1695 01:23:41,899 --> 01:23:47,738 HEMOLYSIS IN THEIR OWN RED CELLS 1696 01:23:47,738 --> 01:23:49,974 AND FIRST THE DELAYED REACTION 1697 01:23:49,974 --> 01:23:54,779 AND THIS CASE WAS RECORDED IN 1698 01:23:54,779 --> 01:23:58,115 1962 OUT OF WASH-U AND WAS AN 1699 01:23:58,115 --> 01:24:02,086 EXAMPLE OF HYPERHEMOLYSIS AND 1700 01:24:02,086 --> 01:24:03,921 OUTLINED A FEATURE I DIDN'T 1701 01:24:03,921 --> 01:24:04,722 APPRECIATE WHERE THEY CAN OCCUR 1702 01:24:04,722 --> 01:24:06,223 IN THE ABSENCE OF ANTIBIOTIC. 1703 01:24:06,223 --> 01:24:10,761 I JUST DESCRIBED THE ROLE OF 1704 01:24:10,761 --> 01:24:13,898 ANTIBODIES IN THESE BUT IT CAN 1705 01:24:13,898 --> 01:24:19,503 RESULT IN CLEARANCE TO THE UNIT 1706 01:24:19,503 --> 01:24:21,539 AND HYPERHEMOLYSIS AND THEY 1707 01:24:21,539 --> 01:24:24,008 DON'T HAVE AN ANTIGEN AND IT'S 1708 01:24:24,008 --> 01:24:28,879 USUALLY DETECTED USING A SEGMENT 1709 01:24:28,879 --> 01:24:34,718 OF THE RED CELL AND COULD BE 1710 01:24:34,718 --> 01:24:43,694 THERE'S A PROCESS AT PLAY. 1711 01:24:43,694 --> 01:24:45,863 THESE ARE THOUGHT TO BE RARE 1 1712 01:24:45,863 --> 01:24:47,932 IN 1,000 TRANSFUSION AND THERE 1713 01:24:47,932 --> 01:24:52,169 WAS A STUDY LOOKING AT REACTION 1714 01:24:52,169 --> 01:24:53,938 FAIL AND MANY WERE NOT DIAGNOSED 1715 01:24:53,938 --> 01:24:56,740 AT THE TIME OR DETECTED OR 1716 01:24:56,740 --> 01:24:58,209 RECOGNIZED LATER ON AND THAT MAY 1717 01:24:58,209 --> 01:25:00,277 BE DUE TO THE FACT THAT A LOT OF 1718 01:25:00,277 --> 01:25:01,612 TIMES THESE PATIENTS PRESENT ONE 1719 01:25:01,612 --> 01:25:05,416 OR TWO OR THREE WEEKS AFTER THE 1720 01:25:05,416 --> 01:25:07,985 EVENT AND ONCE AGAIN MAY PRESENT 1721 01:25:07,985 --> 01:25:08,819 TO A DIFFERENT HEALTH CARE 1722 01:25:08,819 --> 01:25:10,588 FACILITY OR IT'S NOT KNOWN TO 1723 01:25:10,588 --> 01:25:11,889 THAT PROVIDER AND WHEN THEY 1724 01:25:11,889 --> 01:25:13,424 PRESENT IT CAN LOOK LIKE 1725 01:25:13,424 --> 01:25:15,659 UNDERLYING COMPLICATIONS OF THE 1726 01:25:15,659 --> 01:25:25,870 PATIENTS LIKE VASO OCCLUSIVE 1727 01:25:25,870 --> 01:25:29,840 CRISIS AND UNDERSTANDABLE IN THE 1728 01:25:29,840 --> 01:25:32,843 BLOOD BANK AND EVEN IF THE WORK 1729 01:25:32,843 --> 01:25:33,777 UP IS DONE IT MAY NOT BE 1730 01:25:33,777 --> 01:25:41,886 DETECTED. 1731 01:25:41,886 --> 01:25:42,586 RECOGNIZING THIS POTENTIAL 1732 01:25:42,586 --> 01:25:44,788 PROBLEM WITH ASSESSING WHEN THE 1733 01:25:44,788 --> 01:25:46,924 REACTIONS THAT OCCUR AND A STUDY 1734 01:25:46,924 --> 01:25:49,860 FROM PARIS LOOKED AT HEMOGLOBIN 1735 01:25:49,860 --> 01:25:53,898 MEASUREMENTS POST TRANSFUSION 1736 01:25:53,898 --> 01:25:56,200 AND WHEN THE PATIENT 1737 01:25:56,200 --> 01:25:58,836 RE-PRESENTED IN WEEKS AND THE 4% 1738 01:25:58,836 --> 01:26:03,807 TO 3% OF ALL EPISODIC 1739 01:26:03,807 --> 01:26:07,144 TRANSFUSIONS RESULTED IN THE HGR 1740 01:26:07,144 --> 01:26:10,381 AND 11% SUCCUMBED. 1741 01:26:10,381 --> 01:26:12,883 THESE REACTIONS ARE MORE FROEKT 1742 01:26:12,883 --> 01:26:13,884 AND DIFFICULT IN RESULTING IN 1743 01:26:13,884 --> 01:26:15,386 MORTALITY. 1744 01:26:15,386 --> 01:26:17,454 WE THINK OF TRANSFUSION 1745 01:26:17,454 --> 01:26:19,790 REACTIONS IN GENERAL WHICH IS 1746 01:26:19,790 --> 01:26:20,491 NOT ANY DIFFERENT IN THE SICKLE 1747 01:26:20,491 --> 01:26:23,928 CELL POPULATION YOU THINK OF 1748 01:26:23,928 --> 01:26:27,932 LARGER REACTIONS IN TRANSFUSION 1749 01:26:27,932 --> 01:26:30,467 AND COMMON TRANSFUSION REACTIONS 1750 01:26:30,467 --> 01:26:33,437 AND THEY'RE MORE OF A NUISANCE 1751 01:26:33,437 --> 01:26:36,473 AND IN THE KNOWN TO CAUSE 1752 01:26:36,473 --> 01:26:37,875 LONG-TERM ISSUES AND WE RECORDED 1753 01:26:37,875 --> 01:26:40,844 THEM FOLLOWING A TRANSFUSION OR 1754 01:26:40,844 --> 01:26:42,513 DURING A TRANSFUSION AND ONCE 1755 01:26:42,513 --> 01:26:44,748 AGAIN NOT SUPER COMMON BUT IN 1756 01:26:44,748 --> 01:26:46,183 THE FRENCH COHORT THESE 1757 01:26:46,183 --> 01:26:48,052 REACTIONS WERE THE MOST COMMON 1758 01:26:48,052 --> 01:26:50,387 BY A LONG SHOT AND NOT ONLY THE 1759 01:26:50,387 --> 01:26:53,590 MOST COMMON BUT AGAIN DEADLY. 1760 01:26:53,590 --> 01:26:55,326 THESE RESULTS SUGGEST PERHAPS WE 1761 01:26:55,326 --> 01:26:56,660 NEED TO BE MORE AWARE OF THE 1762 01:26:56,660 --> 01:26:57,995 REACTION AT LEAST I FEEL LIKE I 1763 01:26:57,995 --> 01:27:00,731 NEED TO BE MORE AWARE OF THE 1764 01:27:00,731 --> 01:27:02,766 REACTIONS NOT ONLY IN TERMS OF 1765 01:27:02,766 --> 01:27:04,969 BEING ABLE TO DIAGNOSE THEM AND 1766 01:27:04,969 --> 01:27:06,637 RECOGNIZE THE FEATURES THAT MAY 1767 01:27:06,637 --> 01:27:13,110 CONTRIBUTE TO THE 1768 01:27:13,110 --> 01:27:14,611 PATHOPHYSIOLOGY AND TREAT THEM 1769 01:27:14,611 --> 01:27:17,915 WHEN THEY OCCUR. 1770 01:27:17,915 --> 01:27:23,687 HEMOLYSIS CAN ALTER THE PATHWAY 1771 01:27:23,687 --> 01:27:25,990 AND WE LOOKED AT THE ACTIVATION 1772 01:27:25,990 --> 01:27:31,996 AND DHTRs AND MANY PATIENTS 1773 01:27:31,996 --> 01:27:35,165 DISPLAYED ACTIVATION OF 1774 01:27:35,165 --> 01:27:36,000 COMPLIMENT SUGGESTING A 1775 01:27:36,000 --> 01:27:40,070 COMPLEMENT MAY BE INVOLVED AND 1776 01:27:40,070 --> 01:27:47,011 TO STUDY THIS IN SICKLE CELL 1777 01:27:47,011 --> 01:27:48,545 COMPILATION AND WE CONDUCTED A 1778 01:27:48,545 --> 01:27:53,884 STUDY IN PATIENTS LOOKING AT 1779 01:27:53,884 --> 01:27:56,687 PATIENTS WITH ACUTE CHEST AND 1780 01:27:56,687 --> 01:28:00,991 DEVELOPING ACUTE CHEST SYNDROME 1781 01:28:00,991 --> 01:28:04,128 AT BASELINE WEEKS LATER TO 1782 01:28:04,128 --> 01:28:04,795 DETERMINE THE INCREASE IN SICKLE 1783 01:28:04,795 --> 01:28:09,400 CELL COMPLICATION. 1784 01:28:09,400 --> 01:28:13,003 NOT ONLY WERE PATIENTS FOUND TO 1785 01:28:13,003 --> 01:28:16,440 HAVE LOWER HEMOGLOBIN LEVEL AND 1786 01:28:16,440 --> 01:28:18,242 PATIENTS NOT TRANSFUSED BUT 1787 01:28:18,242 --> 01:28:23,947 THERE WAS SIGNIFICANT ELEVATIONS 1788 01:28:23,947 --> 01:28:29,653 IN ACTIVATION SHOWN WITH 1789 01:28:29,653 --> 01:28:33,023 COMPLIMENTS AND IT'S ONCE AGAIN 1790 01:28:33,023 --> 01:28:35,492 THE PATHWAY BLEED AND NOT ONLY 1791 01:28:35,492 --> 01:28:39,596 WERE BV LEVELS ELEVATE AND C5A 1792 01:28:39,596 --> 01:28:43,133 LEVELS AND OTHER LEVELS 1793 01:28:43,133 --> 01:28:43,400 ELEVATED. 1794 01:28:43,400 --> 01:28:46,236 THESE RESULTS SUGGESTED THE 1795 01:28:46,236 --> 01:28:49,473 ACTIVATION MAY OCCUR DURING A 1796 01:28:49,473 --> 01:28:50,741 SEVERE COMPLICATION SICKLE CELL 1797 01:28:50,741 --> 01:28:56,980 DISEASE SUCH AS ACUTE CHEST. 1798 01:28:56,980 --> 01:28:57,881 THEY'RE CORRELATIVE IN NATURE 1799 01:28:57,881 --> 01:28:59,950 AND WHETHER THE SYSTEM MAY BE 1800 01:28:59,950 --> 01:29:03,087 INVOLVED IN THE PROCESS. 1801 01:29:03,087 --> 01:29:07,758 SO TO DO THIS WE TURNED IN A 1802 01:29:07,758 --> 01:29:15,132 CHEST MODEL AND WHEN WE INJECTED 1803 01:29:15,132 --> 01:29:20,504 THE MICE TO MIMIC HEMOLYSIS THE 1804 01:29:20,504 --> 01:29:23,140 WILD TYPE A MICE THERE WAS NO 1805 01:29:23,140 --> 01:29:32,249 APPRECIABLE DIFFERENCE IN 1806 01:29:32,249 --> 01:29:34,618 CONTRAST THERE WAS AN INCREASE 1807 01:29:34,618 --> 01:29:36,920 IN C5 AND A COMPLIMENT MAY BE 1808 01:29:36,920 --> 01:29:38,622 ACTIVATING THE MICE AND MAY 1809 01:29:38,622 --> 01:29:41,191 CONTRIBUTE TO THE PANELO 1810 01:29:41,191 --> 01:29:42,459 PHYSIOLOGY OF ACUTE CHEST 1811 01:29:42,459 --> 01:29:43,060 SYNDROME. 1812 01:29:43,060 --> 01:29:44,862 AND NOT ONLY DO WE SEE IT 1813 01:29:44,862 --> 01:29:46,597 ELEVATED IN THE PLASMA BUT WE 1814 01:29:46,597 --> 01:29:47,965 LOOKED AT THE LUNG AND FOUND 1815 01:29:47,965 --> 01:29:51,268 COMPLEMENT WAS INCREASED IN 1816 01:29:51,268 --> 01:29:57,174 TERMS OF DEPOSITION OF 1817 01:29:57,174 --> 01:29:58,008 ENDOTHELIAL CELLS BUT NOT IN THE 1818 01:29:58,008 --> 01:30:01,578 WILD TYPE A MICE. 1819 01:30:01,578 --> 01:30:05,215 NOT ONLY COMBINANT POSITION AND 1820 01:30:05,215 --> 01:30:08,519 SAW CHANGES IN O2 STATS AND 1821 01:30:08,519 --> 01:30:11,588 CONSISTENT WITH CARDIOVASCULAR 1822 01:30:11,588 --> 01:30:12,990 COMPLICATIONS ASSOCIATED WITH 1823 01:30:12,990 --> 01:30:15,025 INJECTION ULTIMATELY RESULTED IN 1824 01:30:15,025 --> 01:30:17,161 INCREASED MORTALITY SPECIFICALLY 1825 01:30:17,161 --> 01:30:18,262 IN THE MICE WITH SICKLE CELL 1826 01:30:18,262 --> 01:30:21,899 DISEASE AND NOT WITH THE WILD 1827 01:30:21,899 --> 01:30:23,367 TYPE CONTROL. 1828 01:30:23,367 --> 01:30:25,869 THESE RESULTS SHOW ACUTE 1829 01:30:25,869 --> 01:30:30,874 CHEST-LIKE FEATURES IN THE MICE 1830 01:30:30,874 --> 01:30:32,609 ASSOCIATED WITH ACTIVATION. 1831 01:30:32,609 --> 01:30:35,179 IT DIDN'T DEMONSTRATE THE 1832 01:30:35,179 --> 01:30:36,180 COMPLEMENT INVOLVED IN THE 1833 01:30:36,180 --> 01:30:38,315 PROCESS AND THE COMPLEMENT CAN 1834 01:30:38,315 --> 01:30:43,854 DRIVE THE SAME PATHOPHYSIOLOGY 1835 01:30:43,854 --> 01:30:44,488 SPECIFICALLY SICKLE CELL DISEASE 1836 01:30:44,488 --> 01:30:49,726 MICE AND WE BYPASSED AND WE 1837 01:30:49,726 --> 01:30:50,627 INJECTED WHAT'S BEEN USED FOR 1838 01:30:50,627 --> 01:30:53,931 ALMOST HALF A CENTURY MORE TO 1839 01:30:53,931 --> 01:30:55,465 ACTIVATE COMPLEMENT AND DEPLETE 1840 01:30:55,465 --> 01:30:58,869 IT IN DOING SO WE FOUND UNLIKE 1841 01:30:58,869 --> 01:31:02,039 WILD TYPE MICE WHICH HAD AN 1842 01:31:02,039 --> 01:31:05,976 INCREASE IN ACTIVATION WERE MORE 1843 01:31:05,976 --> 01:31:08,145 PRONOUNCED. 1844 01:31:08,145 --> 01:31:10,514 NOT ONLY DO WE SEE INCREASED 1845 01:31:10,514 --> 01:31:11,815 LEVEL OF COMPLEMENT ACTIVATION 1846 01:31:11,815 --> 01:31:15,652 BUT THERE WAS A SIGNIFICANT 1847 01:31:15,652 --> 01:31:21,391 DECREASE IN THE HEMATOCRIT AND 1848 01:31:21,391 --> 01:31:22,559 SUGGESTING HEMOLYSIS INDUCED IN 1849 01:31:22,559 --> 01:31:24,661 THE MICE FOLLOWING EXPOSURE TIE 1850 01:31:24,661 --> 01:31:25,862 FACTOR THAT CAN ACTIVATE 1851 01:31:25,862 --> 01:31:27,631 COMPLIMENT. 1852 01:31:27,631 --> 01:31:32,436 WE LOOKED AT MORTALITY WE SAW 1853 01:31:32,436 --> 01:31:37,241 THE INJECTION SPECIFICALLY 1854 01:31:37,241 --> 01:31:40,611 RESULTED IN FATALITY IN THE 1855 01:31:40,611 --> 01:31:47,951 SICKLE CELL AND NOT WILD TYPE 1856 01:31:47,951 --> 01:31:49,886 CONTROL AND MOST MICE AREN'T 1857 01:31:49,886 --> 01:31:53,523 EXPOSED DELIBERATELY OR PATIENTS 1858 01:31:53,523 --> 01:31:57,861 TO THIS BUT WITH HEMOLYSIS MAY 1859 01:31:57,861 --> 01:32:03,400 DRIVE ACUTE CHEST THROUGH AN 1860 01:32:03,400 --> 01:32:05,068 ACTIVATION PATHWAY WE CROSSED 1861 01:32:05,068 --> 01:32:07,104 THE MICE WITH THE KNOCKOUT AND 1862 01:32:07,104 --> 01:32:09,973 TOOK OVER TWO AND A HALF YEARS 1863 01:32:09,973 --> 01:32:20,517 TO GENERATE THE MICE AND WE ASK 1864 01:32:21,952 --> 01:32:25,756 THE QUESTION IS COMPLIMENT 1865 01:32:25,756 --> 01:32:31,461 REQUIRED OR INVOLVED IN 1866 01:32:31,461 --> 01:32:37,034 HEMOLYSIS AN WE INJECTED MICE 1867 01:32:37,034 --> 01:32:40,170 AND WILD TYPE INJECTED WERE 1868 01:32:40,170 --> 01:32:41,872 RESISTANT AND AT LEAST IN THE 1869 01:32:41,872 --> 01:32:44,374 MODEL WE EXPOSED THE SAME MICE 1870 01:32:44,374 --> 01:32:47,611 TO THIS AND THEY WERE RESISTANT 1871 01:32:47,611 --> 01:32:50,180 TO COMPLEMENT ACTIVATION INDUCED 1872 01:32:50,180 --> 01:32:52,916 ACUTE CHEST. 1873 01:32:52,916 --> 01:32:55,018 AND IN THE MODEL THAT COMPLEMENT 1874 01:32:55,018 --> 01:32:57,854 MAY BE INVOLVED AND GIVEN THE 1875 01:32:57,854 --> 01:32:58,555 COMPLEMENT ACTIVATION 1876 01:32:58,555 --> 01:32:59,990 CORRELATIVE DATA IN ACUTE CHEST 1877 01:32:59,990 --> 01:33:03,493 AND WHAT WE SEE DURING THE 1878 01:33:03,493 --> 01:33:05,662 TRANSFUSION REACTION WHICH CAN 1879 01:33:05,662 --> 01:33:09,266 BE ACCOMPANIED BY HEMOLYSIS AND 1880 01:33:09,266 --> 01:33:12,269 MAY CONTRIBUTE TO SOME OF THE 1881 01:33:12,269 --> 01:33:13,904 PATHOPHYSIOLOGY THAT CAN OCCUR 1882 01:33:13,904 --> 01:33:20,410 DURING THE COMPLICATIONS. 1883 01:33:20,410 --> 01:33:25,549 DURING THE TIME WE CONDUCTED THE 1884 01:33:25,549 --> 01:33:28,118 STUDIES EARLY ON A FEMALE WITH 1885 01:33:28,118 --> 01:33:28,752 SICKLE CELL DISEASE PRESENTED 1886 01:33:28,752 --> 01:33:30,787 WITH A CLASSIC TRANSFUSION 1887 01:33:30,787 --> 01:33:32,723 REACTION AND YOU CAN SEE IT 1888 01:33:32,723 --> 01:33:35,892 OCCURRED AND HEMOGLOBIN 1889 01:33:35,892 --> 01:33:42,499 INCREASES AND THEN THE DECLINE 1890 01:33:42,499 --> 01:33:46,837 IN HEMOGLOBIN AND CONTINUES TO 1891 01:33:46,837 --> 01:33:51,842 FALL WITHIN THE THRESHOLD 1892 01:33:51,842 --> 01:33:57,547 CONSISTENT WITH HYPER HEHYPERHE 1893 01:33:57,547 --> 01:34:01,551 AND THE PATIENT GOT EPO AND WE 1894 01:34:01,551 --> 01:34:12,295 GOT RETUXI MMAB AND THEY TRIED 1895 01:34:19,002 --> 01:34:24,508 USE ECCOLUMAB AND LOOKED AT THE 1896 01:34:24,508 --> 01:34:27,844 ACTIVATION AS OUTLINED WITH BV 1897 01:34:27,844 --> 01:34:29,880 AND FOUND THE ACTIVATION WAS 1898 01:34:29,880 --> 01:34:34,151 SHUT DOWN AS THE HEMOGLOBIN 1899 01:34:34,151 --> 01:34:36,820 BEGAN TO INCREASE AND SO THEY 1900 01:34:36,820 --> 01:34:38,822 RECEIVED A SECOND DOSE WHICH 1901 01:34:38,822 --> 01:34:40,957 SHUT DOWN THE ACTIVATION AND 1902 01:34:40,957 --> 01:34:42,325 RESULTING IN THE ACTIVATION OF 1903 01:34:42,325 --> 01:34:48,031 THE REMOVAL AND THE PATIENTS WE 1904 01:34:48,031 --> 01:34:57,541 NOW TREATED WITH ECULIZUMAB AND 1905 01:34:57,541 --> 01:35:02,746 THEY WOULD NOT MAKE IT TYPICALLY 1906 01:35:02,746 --> 01:35:09,886 IN THE SITUATION WHICH COULD 1907 01:35:09,886 --> 01:35:13,890 HAVE BEEN TREATED WELL. 1908 01:35:13,890 --> 01:35:16,660 CLASSICALLY WE THINK OF INDUCING 1909 01:35:16,660 --> 01:35:18,495 MEMORY B CELLS FOR RESPONSE TO 1910 01:35:18,495 --> 01:35:24,034 DRIVE FORMATION TO ENGAGE AND 1911 01:35:24,034 --> 01:35:27,204 CAUSE HEMOLYSIS AND CAN ACTIVATE 1912 01:35:27,204 --> 01:35:29,873 AND CAUSE HEMOLYSIS OF THE 1913 01:35:29,873 --> 01:35:33,577 PATIENT'S OWN CELLS AND 1914 01:35:33,577 --> 01:35:38,715 POTENTIALLY CONTRIBUTE TO HYPER 1915 01:35:38,715 --> 01:35:40,984 HEMOLYSIS AND IT'S OCCURRING TO 1916 01:35:40,984 --> 01:35:45,889 CAUSE HEMOLYSIS INDEPENDENT OF 1917 01:35:45,889 --> 01:35:47,424 ANTIBODIES. 1918 01:35:47,424 --> 01:35:48,825 THIS HAS BEEN A STRIFE IN 1919 01:35:48,825 --> 01:35:49,726 PREVIOUS STUDIES WHERE 30% OF 1920 01:35:49,726 --> 01:35:54,397 THE DCRs WERE PRESENT WITHOUT 1921 01:35:54,397 --> 01:35:57,901 ANY DETECTABLE ANTIBODY BUT 1922 01:35:57,901 --> 01:35:59,903 REGARDLESS NO ANTIBODY IS 1923 01:35:59,903 --> 01:36:05,876 DETECTED BUT WHETHER IT'S TRULY 1924 01:36:05,876 --> 01:36:08,545 NOT USED WITH ASSAYS NEEDS TO BE 1925 01:36:08,545 --> 01:36:11,781 DETERMINED AND HEME CAN ACTIVATE 1926 01:36:11,781 --> 01:36:14,618 FURTHER COMPLEMENT PATHWAYS TO 1927 01:36:14,618 --> 01:36:17,821 DRIVE POSSIBLY HEMOLYSIS OF THE 1928 01:36:17,821 --> 01:36:18,555 PATIENT'S CELLS. 1929 01:36:18,555 --> 01:36:19,923 THIS HOPEFULLY ILLUSTRATES THE 1930 01:36:19,923 --> 01:36:23,994 CHALLENGES THAT CAN RESULT FROM 1931 01:36:23,994 --> 01:36:29,165 TRANSFUSION PATIENTS WHO ARE 1932 01:36:29,165 --> 01:36:31,735 ALLO IMMUNIZED AND WE LOOKED AT 1933 01:36:31,735 --> 01:36:32,702 THIS DIRECTLY BUT HEME AND 1934 01:36:32,702 --> 01:36:35,071 COMPLEMENT MAY PLAY SOME ROLE IN 1935 01:36:35,071 --> 01:36:35,539 THIS PROCESS. 1936 01:36:35,539 --> 01:36:36,873 OF COURSE ADDITIONAL STUDIES ARE 1937 01:36:36,873 --> 01:36:39,543 NEEDED TO DETERMINE IF THIS IS A 1938 01:36:39,543 --> 01:36:45,215 CASE WHETHER IT MAY BE 1939 01:36:45,215 --> 01:36:46,116 POTENTIALLY A PREVENTATIVE 1940 01:36:46,116 --> 01:36:48,018 MEASURE TO DO STUDIES IN THE 1941 01:36:48,018 --> 01:36:48,251 FUTURE. 1942 01:36:48,251 --> 01:36:49,786 WITH THAT I'D LIKE TO THANK ALL 1943 01:36:49,786 --> 01:36:51,354 THE PEOPLE IN THE LAB THAT DO 1944 01:36:51,354 --> 01:36:54,591 THESE STUDIES ONCE AGAIN AND I 1945 01:36:54,591 --> 01:36:58,461 WANT TO HIGHLIGHT SATISHA KNOT A 1946 01:36:58,461 --> 01:36:59,329 WONDERFUL COLLEAGUE AND FRIEND 1947 01:36:59,329 --> 01:37:02,832 WHO DROVE ALL THE STUDIES I 1948 01:37:02,832 --> 01:37:06,536 SHOWED IN THE MOUSE MODELS AND S 1949 01:37:06,536 --> 01:37:15,211 AND HAS HIS OWN LAB AT EMORY AND 1950 01:37:15,211 --> 01:37:19,482 DOING WELL AND ANOTHER STUDY OF 1951 01:37:19,482 --> 01:37:23,153 FACTORS THAT DRIVE 1952 01:37:23,153 --> 01:37:25,455 ALLOIMMUNIZATION AND HAPPY TO 1953 01:37:25,455 --> 01:37:30,160 ANSWER QUESTIONS IF I CAN JO 1954 01:37:30,160 --> 01:37:33,730 JOINON -- JOIN ONLINE DURING THE 1955 01:37:33,730 --> 01:37:34,097 SESSION. 1956 01:37:34,097 --> 01:37:35,799 >> WE'RE SORRY HE WASN'T ABLE TO 1957 01:37:35,799 --> 01:37:36,466 JOIN IN PERSON. 1958 01:37:36,466 --> 01:37:37,200 I THINK OUR NEXT SPEAKER IS 1959 01:37:37,200 --> 01:37:47,310 LIVE. 1960 01:37:49,512 --> 01:37:53,483 FOR THOSE WHO AREN'T AWARE, IF 1961 01:37:53,483 --> 01:37:56,786 YOU WANT TO SUBMIT A QUESTION 1962 01:37:56,786 --> 01:37:59,055 ONLINE JUST PRESS THE BUTTON 1963 01:37:59,055 --> 01:38:01,224 THAT SAYS SEND LIVE FEEDBACK. 1964 01:38:01,224 --> 01:38:02,492 IF YOU QUESTIONS IN PERSON YOU 1965 01:38:02,492 --> 01:38:03,026 CAN COME TO ONE OF THE 1966 01:38:03,026 --> 01:38:13,236 MICROPHONES. 1967 01:38:15,639 --> 01:38:23,146 DR. STELLA CHOU WILL TALK TO US 1968 01:38:23,146 --> 01:38:26,983 ON MOLECULAR GENOTYPING THE WAY 1969 01:38:26,983 --> 01:38:32,222 FORWARD FOR FINDING COMPATIBLE 1970 01:38:32,222 --> 01:38:32,522 ANTIBODIES. 1971 01:38:32,522 --> 01:38:41,431 SHE PRACTICES PEDIATRIC 1972 01:38:41,431 --> 01:38:48,038 HEMATOLOGY AND FOUND PATIENTS 1973 01:38:48,038 --> 01:38:51,007 WITH SICKLE CELL DISEASE CAN 1974 01:38:51,007 --> 01:39:01,551 CONTRIBUTE TO ALLOIMMUNIZATION. 1975 01:39:07,057 --> 01:39:09,893 >> WE'LL SWITCH GEARS AND TALK 1976 01:39:09,893 --> 01:39:14,230 ABOUT PREVENTION OF 1977 01:39:14,230 --> 01:39:16,966 ALLOIMMUNIZATION AND TALK WITH 1978 01:39:16,966 --> 01:39:19,602 PHENOTYPING TO HELP WITH SOME OF 1979 01:39:19,602 --> 01:39:29,946 THE DIFFICULT CASES. 1980 01:39:37,721 --> 01:39:42,325 I HAVE NO CONFLICTS OF INTEREST 1981 01:39:42,325 --> 01:39:47,564 TO DISCLOSE AND DISCUSS 1982 01:39:47,564 --> 01:39:49,866 ALLOIMMUNIZATION AND USING 1983 01:39:49,866 --> 01:39:55,538 ANTIGEN GENOTYPES AND DISCUSS 1984 01:39:55,538 --> 01:40:01,878 THE RED CELL TRANSFUSION. 1985 01:40:01,878 --> 01:40:03,780 MANY STILL RECEIVE THERAPY FOR 1986 01:40:03,780 --> 01:40:08,551 STROKE PREVENTION AND IT'S OFTEN 1987 01:40:08,551 --> 01:40:18,995 A PREREQUISITE FOR TRIALS. 1988 01:40:21,965 --> 01:40:24,134 ALLOIMMUNIZATION REMAINS A 1989 01:40:24,134 --> 01:40:25,902 CHALLENGING COMPLICATION AND CAN 1990 01:40:25,902 --> 01:40:27,470 PRECLUDE SOME OF THESE PATIENTS 1991 01:40:27,470 --> 01:40:30,774 FROM CURATIVE THERAPY DUE TO THE 1992 01:40:30,774 --> 01:40:31,307 INABILITY TO PROVIDE SAFE 1993 01:40:31,307 --> 01:40:33,576 TRANSFUSION SUPPORT. 1994 01:40:33,576 --> 01:40:37,113 SO AS MANY OF YOU ARE AWARE, THE 1995 01:40:37,113 --> 01:40:39,349 AMERICAN SOCIETY OF HEMATOLOGY 1996 01:40:39,349 --> 01:40:41,084 PUT OUT CLINICAL PRACTICE 1997 01:40:41,084 --> 01:40:41,651 GUIDELINES FOR SICKLE CELL 1998 01:40:41,651 --> 01:40:43,319 DISEASE AND ONE WAS FOR 1999 01:40:43,319 --> 01:40:45,889 TRANSFUSION SUPPORT. 2000 01:40:45,889 --> 01:40:48,291 IN THE GUIDELINES WE WERE ABLE 2001 01:40:48,291 --> 01:40:51,127 TO RECOMMEND ANTIGEN MATCHING 2002 01:40:51,127 --> 01:40:53,930 FOR RH AND CAL ANTIGENS FOR ALL 2003 01:40:53,930 --> 01:40:54,497 PATIENTS WITH SICKLE CELL 2004 01:40:54,497 --> 01:40:56,099 DISEASE AND THIS BECAME A STRONG 2005 01:40:56,099 --> 01:40:57,367 RECOMMENDATION BECAUSE WE WERE 2006 01:40:57,367 --> 01:40:59,969 ABLE IT LOOK BACK AT THE DATA 2007 01:40:59,969 --> 01:41:01,871 AND HAD MODERATE LEVEL OF 2008 01:41:01,871 --> 01:41:02,138 EVIDENCE. 2009 01:41:02,138 --> 01:41:04,808 WE ALSO RECOMMENDED THAT AN 2010 01:41:04,808 --> 01:41:06,676 EXTENDED PHENOTYPE FOR ALL 2011 01:41:06,676 --> 01:41:07,243 PATIENTS WITH SICKLE CELL 2012 01:41:07,243 --> 01:41:08,711 DISEASE BE ATTAINED AT THE 2013 01:41:08,711 --> 01:41:11,114 EARLIEST OPPORTUNITY AND IT WAS 2014 01:41:11,114 --> 01:41:14,684 A RECOMMENDATION BUT THAT THE 2015 01:41:14,684 --> 01:41:19,622 GENOTYPE WOULD BE PREFERRED OVER 2016 01:41:19,622 --> 01:41:24,027 A SEROLOGIC PHENOTYPE. 2017 01:41:24,027 --> 01:41:25,862 DESPITE MATCHING FOR ALMOST 2018 01:41:25,862 --> 01:41:28,932 THREE DECADES ANTIBODIES REMAIN 2019 01:41:28,932 --> 01:41:31,467 THE MOST COMMON SPECIFICITY WITH 2020 01:41:31,467 --> 01:41:32,669 PATIENTS WITH SICKLE CELL 2021 01:41:32,669 --> 01:41:34,304 DISEASE AND PATIENTS TRULY 2022 01:41:34,304 --> 01:41:41,311 AREN'T RH MATCHED WHEN PROVIDING 2023 01:41:41,311 --> 01:41:44,180 MATCHING DIVERSITY IN THE 2024 01:41:44,180 --> 01:41:49,886 PATIENTS WITH DONORS WITH 2025 01:41:49,886 --> 01:41:57,193 AFRICAN AMERICAN DESCENT HAVE 2026 01:41:57,193 --> 01:42:07,403 DIFFERENCES. 2027 01:42:08,004 --> 01:42:09,405 YOU CAN SEE APPROXIMATELY 2028 01:42:09,405 --> 01:42:10,807 TWO-THIRDS OF ANTIBODIES ARE 2029 01:42:10,807 --> 01:42:12,709 AGAINST THE RH SYSTEM. 2030 01:42:12,709 --> 01:42:14,644 AND WHAT'S INTRIGUING HERE IS 2031 01:42:14,644 --> 01:42:16,412 THAT IN THE BLUE ARE PATIENTS 2032 01:42:16,412 --> 01:42:19,215 WHO ARE ANTIGEN POSITIVE YET 2033 01:42:19,215 --> 01:42:21,451 MADE THAT ANTIBODY SPECIFICITY. 2034 01:42:21,451 --> 01:42:23,987 AND THOSE WE THINK ARE DUE TO 2035 01:42:23,987 --> 01:42:25,688 TWO THINGS. 2036 01:42:25,688 --> 01:42:26,890 30% OF THOSE ARE ANTIBODIES THAT 2037 01:42:26,890 --> 01:42:31,060 ARE ATTRIBUTED TO THE PATIENT'S 2038 01:42:31,060 --> 01:42:32,528 OWN TYPES. 2039 01:42:32,528 --> 01:42:36,065 THE TYPE IS D POSITIVE 2040 01:42:36,065 --> 01:42:38,668 SEROLOGICALLY BUT IT SHOWS A 2041 01:42:38,668 --> 01:42:46,476 PARTIAL DE-ANTIGEN AND BECOME AL 2042 01:42:46,476 --> 01:42:48,278 ALLOIMMUNIZED TO THE EPITOPE AND 2043 01:42:48,278 --> 01:42:49,913 THERE'S SOME EVIDENCE FROM CASE 2044 01:42:49,913 --> 01:42:52,849 REPORTS THAT RH VARIANTS IN THE 2045 01:42:52,849 --> 01:42:57,787 DONOR RED CELLS ARE AN UNDER 2046 01:42:57,787 --> 01:43:01,157 APPRECIATED RISK FACTOR FOR 2047 01:43:01,157 --> 01:43:02,425 ALLOIMMUNIZATION. 2048 01:43:02,425 --> 01:43:06,696 THERE'S RHD AND RHCD AND THEIR 2049 01:43:06,696 --> 01:43:08,231 VARIOUS COMBINATIONS AN THERE'S 2050 01:43:08,231 --> 01:43:10,633 TWO VARIANTS, A PARTIAL D 2051 01:43:10,633 --> 01:43:13,002 ANTIGEN THAT RESULTS FROM TWO 2052 01:43:13,002 --> 01:43:16,839 AMINO ACID CHANGES FROM THE 2053 01:43:16,839 --> 01:43:20,143 CONVENTIONAL D ANTIGEN AND I 2054 01:43:20,143 --> 01:43:22,211 SHOW AN EXAMPLE OF A COMMON 2055 01:43:22,211 --> 01:43:24,580 VARIANT THAT NOT ONLY CAUSES A 2056 01:43:24,580 --> 01:43:29,052 PATIENT WHO HAS THE ANTIGEN TO 2057 01:43:29,052 --> 01:43:31,054 EXPRESS PARTIAL C AND TO EXPRESS 2058 01:43:31,054 --> 01:43:38,962 AN ADDITIONAL ANTIGEN THE S 2059 01:43:38,962 --> 01:43:42,999 WHICH IS AN ANTIGEN INDIVIDUALS 2060 01:43:42,999 --> 01:43:45,568 WILL LACK AND IF YOU ARE EXPOSED 2061 01:43:45,568 --> 01:43:48,371 TO A DONOR THAT IS VS POSITIVE 2062 01:43:48,371 --> 01:43:54,077 BUT YOU YOURSELF ARE VS NEGATIVE 2063 01:43:54,077 --> 01:43:57,113 THAT PUTS YOU AT RISK AND WE SEE 2064 01:43:57,113 --> 01:43:58,448 PATIENTS RECEIVE BLOOD FROM 2065 01:43:58,448 --> 01:44:00,049 BLACK DONORS AND THEN DEVELOPING 2066 01:44:00,049 --> 01:44:04,487 THESE ANTIBODIES THAT WE CALL 2067 01:44:04,487 --> 01:44:06,089 ANTIBODIES TO LOW PREVALENCE 2068 01:44:06,089 --> 01:44:06,356 ANTIGENS. 2069 01:44:06,356 --> 01:44:11,027 AND THEN THE OTHER THING TO 2070 01:44:11,027 --> 01:44:14,597 POINT OUT HERE IS THE LOSS OF I 2071 01:44:14,597 --> 01:44:17,066 COMMON ANTIGEN HRP AND TALK 2072 01:44:17,066 --> 01:44:17,834 ABOUT THAT LATER WITH A 2073 01:44:17,834 --> 01:44:19,635 PARTICULAR CASE AND THE PATIENTS 2074 01:44:19,635 --> 01:44:21,471 WITH VARIANTS LACK WHAT WE CALL 2075 01:44:21,471 --> 01:44:23,706 A HIGH PREVALENCE ANTIGEN 2076 01:44:23,706 --> 01:44:24,974 MEANING MOST OF THE POPULATION 2077 01:44:24,974 --> 01:44:27,443 WILL EXPRESS THAT ANTIGEN AND 2078 01:44:27,443 --> 01:44:29,445 THE PATIENT MAKES AN ANTIBODY TO 2079 01:44:29,445 --> 01:44:31,581 THAT IT BECOMES DIFFICULT TO 2080 01:44:31,581 --> 01:44:32,915 FIND THE BLOOD THAT'S LACKING 2081 01:44:32,915 --> 01:44:34,017 AND THAT'S WHERE WE OFTEN TIMES 2082 01:44:34,017 --> 01:44:37,453 GET IN TROUBLE. 2083 01:44:37,453 --> 01:44:39,222 SCO RH VARIANT ARE QUITE 2084 01:44:39,222 --> 01:44:40,790 PREVALENT IN PATIENTS WITH 2085 01:44:40,790 --> 01:44:41,791 SICKLE CELL DISEASE AND THE 2086 01:44:41,791 --> 01:44:43,593 BLACK DONORS NEEDED TO SUPPORT 2087 01:44:43,593 --> 01:44:46,462 CEK MATCHING PROGRAMS. 2088 01:44:46,462 --> 01:44:49,665 SO HOW DO WE USE COMPREHENSIVE 2089 01:44:49,665 --> 01:44:49,966 PHENOTYPING? 2090 01:44:49,966 --> 01:44:57,106 WE GET A COMPREHENSIVE RH ALLELE 2091 01:44:57,106 --> 01:44:58,474 AUTHENTICATION FOR ALL PATIENTS 2092 01:44:58,474 --> 01:45:00,043 PERFORMED AT THE FIRST VISIT 2093 01:45:00,043 --> 01:45:02,678 WITH THE GENOTYPE PROVIDING 2094 01:45:02,678 --> 01:45:07,950 ANTIGEN INFORMATION ON 30 TO 35 2095 01:45:07,950 --> 01:45:08,217 ANTIGENS. 2096 01:45:08,217 --> 01:45:14,490 IT ALSO INFORMS ANTIBODY TEST TO 2097 01:45:14,490 --> 01:45:16,225 DIRECT OUR ANTIBODY 2098 01:45:16,225 --> 01:45:18,061 IDENTIFICATION AND USED TO GUIDE 2099 01:45:18,061 --> 01:45:21,664 PROPHYLACTIC RH MATCH 2100 01:45:21,664 --> 01:45:21,998 TRANSFUSIONS. 2101 01:45:21,998 --> 01:45:24,667 WHAT WE DO IS THERE'S A SUBSET 2102 01:45:24,667 --> 01:45:27,003 WE CONSIDER HIGH RISK RH 2103 01:45:27,003 --> 01:45:29,272 VARIANTS AND GIVE THE PATIENTS 2104 01:45:29,272 --> 01:45:30,840 ANTIGEN NEGATIVE RED CELLS 2105 01:45:30,840 --> 01:45:33,109 CONSISTENT WITH PROVIDING CEK 2106 01:45:33,109 --> 01:45:34,710 MATCH RED CELLS. 2107 01:45:34,710 --> 01:45:36,846 PATIENTS WHO HAVE ALLELES AND 2108 01:45:36,846 --> 01:45:38,581 CODING PARTIAL C WHICH I SHOW AN 2109 01:45:38,581 --> 01:45:41,784 EXAMPLE HERE, THIS ALLELE CAUSES 2110 01:45:41,784 --> 01:45:43,953 A PATIENT TO NOT EXPRESS D FROM 2111 01:45:43,953 --> 01:45:45,855 THE D LOCUS BUT EXPRESS A 2112 01:45:45,855 --> 01:45:47,790 PARTIAL BIG C AND THE PATIENTS 2113 01:45:47,790 --> 01:45:49,725 WILL TYPE STRONGLY BIG C 2114 01:45:49,725 --> 01:45:52,495 POSITIVE OR SEROLOGIC TEST 2115 01:45:52,495 --> 01:45:54,630 BUDGET IF EXPOSED TO 2116 01:45:54,630 --> 01:45:55,865 CONVENTIONAL BIG C BLOOD WILL 2117 01:45:55,865 --> 01:46:01,737 FORM ANTI-BIG C AND THEY'RE PUT 2118 01:46:01,737 --> 01:46:03,339 ON BIG C NEGATIVE BLOOD AND 2119 01:46:03,339 --> 01:46:06,876 THOSE ENCODING PARTIAL D ARE PUT 2120 01:46:06,876 --> 01:46:10,213 ON D NEGATIVE BLOOD 2121 01:46:10,213 --> 01:46:11,214 PROPHYLACTICALLY AND IF YOU'RE 2122 01:46:11,214 --> 01:46:12,715 UNABLE TO OB TAPE PHENOTYPING 2123 01:46:12,715 --> 01:46:14,851 FIRE PATIENT WE RECOMMEND THOSE 2124 01:46:14,851 --> 01:46:21,290 WHO ARE RN IMMUNIZED ARE 2125 01:46:21,290 --> 01:46:22,959 ALLOIMMUNIZED HAVE THE TESTING 2126 01:46:22,959 --> 01:46:25,194 BECAUSE IT DEPENDS ON THE 2127 01:46:25,194 --> 01:46:25,561 INSURANCE. 2128 01:46:25,561 --> 01:46:30,733 THE FIRST IS A 12-YEAR-OLD WITH 2129 01:46:30,733 --> 01:46:37,006 AUTOIMMUNE HEPATITIS AND NO 2130 01:46:37,006 --> 01:46:38,875 PLATELET COUNT WAS 87,000 AND 2131 01:46:38,875 --> 01:46:43,813 NEEDED A HEMOGLOBIN OF 4.2. 2132 01:46:43,813 --> 01:46:45,748 THEY ORDERED BLOOD BUT SHE'S 2133 01:46:45,748 --> 01:46:49,719 DIFFICULT TO MATCH BECAUSE SHE 2134 01:46:49,719 --> 01:46:54,824 MADE PREVIOUS ANTIBIG-C AND 2135 01:46:54,824 --> 01:46:58,895 LITTLE HRB AND CLEARLY SHE WAS A 2136 01:46:58,895 --> 01:47:00,997 PATIENT WHO SOME WOULD CALL A 2137 01:47:00,997 --> 01:47:03,933 RESPONDER WITH THREE LIFE TIME 2138 01:47:03,933 --> 01:47:04,534 TRANSFUSIONS AND THREE UNITS 2139 01:47:04,534 --> 01:47:05,868 EXPOSURE. 2140 01:47:05,868 --> 01:47:10,206 I SHOW HER EXTENDED PHENOTYPE 2141 01:47:10,206 --> 01:47:13,209 HERE AND HER RH PHENOTYPE SHOWS 2142 01:47:13,209 --> 01:47:16,345 SHE ESSENTIALLY HAS A PARTIAL D 2143 01:47:16,345 --> 01:47:16,579 ANTIGEN. 2144 01:47:16,579 --> 01:47:18,814 THIS ALLELE INCLUDES MORE OF A 2145 01:47:18,814 --> 01:47:23,486 SNIP LIKE THAT WE THINK OF FOR 2146 01:47:23,486 --> 01:47:27,924 RHD BUT SHE IS HOMOZYGOUS FOR 2147 01:47:27,924 --> 01:47:30,726 THIS ALLELE WHICH MEANS SHE HAS 2148 01:47:30,726 --> 01:47:33,329 PARTIAL LITTLE C AND LITTLE E 2149 01:47:33,329 --> 01:47:38,601 AND IS NEGATIVE FOR THE HRP 2150 01:47:38,601 --> 01:47:44,473 ANTIGENS SHE BECAME IMMUNIZED 2151 01:47:44,473 --> 01:47:45,007 TO. 2152 01:47:45,007 --> 01:47:48,711 TO FIND THESE ANTIGENS EIGHT 2153 01:47:48,711 --> 01:47:49,879 POTENTIAL DONORS IN THE RARE 2154 01:47:49,879 --> 01:47:51,447 DONOR PROGRAM WERE IDENTIFIED AS 2155 01:47:51,447 --> 01:47:53,883 BEING A MATCH BUT THERE WERE NO 2156 01:47:53,883 --> 01:47:55,451 DONOR UNITS AVAILABLE AT THE 2157 01:47:55,451 --> 01:48:00,122 TIME SO SHE WAS NOT TRANSFUSED 2158 01:48:00,122 --> 01:48:07,330 AND GIVEN SUPPORTIVE CARE. 2159 01:48:07,330 --> 01:48:12,101 HOWEVER, HER HEMOGLOBIN WAS AT 4 2160 01:48:12,101 --> 01:48:14,904 AND SPLENECTOMY NEEDED AND 2161 01:48:14,904 --> 01:48:17,907 NEEDED TRANSFUSION TO GO TO THE 2162 01:48:17,907 --> 01:48:18,107 O.R. 2163 01:48:18,107 --> 01:48:21,510 AGAIN THE HOSPITAL IDENTIFIED NO 2164 01:48:21,510 --> 01:48:23,713 COMPATIBLE UNITES BUT WE 2165 01:48:23,713 --> 01:48:31,187 CONTACTED AN ALTERNATIVE BLOOD 2166 01:48:31,187 --> 01:48:34,090 SUPPLIER WITH A FROZEN UNIT AND 2167 01:48:34,090 --> 01:48:40,263 SHE NEEDED A HOMOZYGOUS DONOR 2168 01:48:40,263 --> 01:48:42,098 AND THAT'S WHAT WAS LOCATED FOR 2169 01:48:42,098 --> 01:48:42,531 HER. 2170 01:48:42,531 --> 01:48:45,468 HER SURGERY WAS DELAYED BECAUSE 2171 01:48:45,468 --> 01:48:47,003 SHE MADE SO MANY ANTIBODIES WITH 2172 01:48:47,003 --> 01:48:52,441 ONLY THREE TRANSFUSIONS AND 2173 01:48:52,441 --> 01:48:57,046 TREATED HER WITH RITUXIMAB AND 2174 01:48:57,046 --> 01:48:58,814 MEASURED HER B CELL RESPONSE AND 2175 01:48:58,814 --> 01:49:04,453 SHE GOT A PRE-OP TRANSFUSION 2176 01:49:04,453 --> 01:49:12,328 WITH THE UNIT AND LOOKED AT DATA 2177 01:49:12,328 --> 01:49:14,263 FROM FOUR YEARS OF TRANSFUSION 2178 01:49:14,263 --> 01:49:20,036 OF 200 PATIENTS WE CARED FOR AND 2179 01:49:20,036 --> 01:49:23,439 LOOKED AT THE FREQUENCY OF RH 2180 01:49:23,439 --> 01:49:24,907 VARIANTS IN THE BLACK AND WHITE 2181 01:49:24,907 --> 01:49:25,808 DONOR POPULATIONS. 2182 01:49:25,808 --> 01:49:29,879 WE FOUND IT WAS FEASIBLE WITH A 2183 01:49:29,879 --> 01:49:33,549 ROBUST BLACK DONOR POOL. 2184 01:49:33,549 --> 01:49:36,786 OF THE 200 PATIENT THE PERCENT 2185 01:49:36,786 --> 01:49:38,487 MATCHED WITH THE PHENOTYPE AND 2186 01:49:38,487 --> 01:49:40,456 THE DONOR UNITS. 2187 01:49:40,456 --> 01:49:41,791 IF YOU GENOTYPE THIS MANY DONORS 2188 01:49:41,791 --> 01:49:44,493 PER DAY AND YOU CAN SEE WITH THE 2189 01:49:44,493 --> 01:49:46,962 BLACK DONORS WE WOULD BE ABLE TO 2190 01:49:46,962 --> 01:49:50,800 FIND THE GENOTYPE MATCHED UNITS 2191 01:49:50,800 --> 01:49:53,002 MORE READILY THAN WHITE DONORS 2192 01:49:53,002 --> 01:49:56,972 BECAUSE THEY WILL OFTEN TIME 2193 01:49:56,972 --> 01:50:00,109 HAVE THE SAME ALLELES AND WE'RE 2194 01:50:00,109 --> 01:50:02,745 REACHING HIGH 90% IF WE'RE 2195 01:50:02,745 --> 01:50:04,447 PHENOTYPING MORE THAN 90 DONORS 2196 01:50:04,447 --> 01:50:05,748 A DAY FOR THE POPULATION AND 2197 01:50:05,748 --> 01:50:08,651 COMPARED TO SEROLOGIC MATCHING 2198 01:50:08,651 --> 01:50:10,686 WE FOUND WE'D NEED TO SCREEN 2199 01:50:10,686 --> 01:50:15,057 TWICE AS MANY BLACK DONORS AS 2200 01:50:15,057 --> 01:50:15,725 SEROLOGIC SCREENING. 2201 01:50:15,725 --> 01:50:19,829 WE OPENED UP A STUDY FOR 2202 01:50:19,829 --> 01:50:22,865 PATIENTS WITH CHRONIC 2203 01:50:22,865 --> 01:50:25,868 TRANSFUSIONS IN A COLLABORATION 2204 01:50:25,868 --> 01:50:27,670 AT THE NEW YORK BLOOD CENTER AND 2205 01:50:27,670 --> 01:50:31,607 RESEARCH COORDINATOR AND THEY 2206 01:50:31,607 --> 01:50:36,011 SCREENED BLACK AND HISPANIC 2207 01:50:36,011 --> 01:50:38,447 DONORS AND THOSE THAT PASSED FOR 2208 01:50:38,447 --> 01:50:40,249 THE GENOTYPE WERE 2209 01:50:40,249 --> 01:50:41,484 COMPREHENSIVELY GENOTYPED. 2210 01:50:41,484 --> 01:50:43,953 THIS IS OUR APPROACH FOR RH 2211 01:50:43,953 --> 01:50:44,754 GENOTYPE MATCHING. 2212 01:50:44,754 --> 01:50:46,655 THIS IS AN EXAMPLE OF A 2213 01:50:46,655 --> 01:50:48,090 PATIENT'S GENOTYPE. 2214 01:50:48,090 --> 01:50:51,794 WE CAN PROVIDE AN EXACT RH MATCH 2215 01:50:51,794 --> 01:50:55,498 WITH ALL FOUR ALLELES AND USE 2216 01:50:55,498 --> 01:50:59,201 WHAT WE CALL LESS RESTRICTIVE 2217 01:50:59,201 --> 01:50:59,902 MATCH. 2218 01:50:59,902 --> 01:51:03,105 WE THINK OF THE CE48C AS 2219 01:51:03,105 --> 01:51:03,973 EQUIVALENT TO THE CONVENTIONAL 2220 01:51:03,973 --> 01:51:07,276 ALLELES. 2221 01:51:07,276 --> 01:51:09,912 SO THIS IS A PILOT STUDY. 2222 01:51:09,912 --> 01:51:11,981 THE GOAL WAS TO REACH 10 2223 01:51:11,981 --> 01:51:14,950 PATIENTS SIMULTANEOUSLY BEING ON 2224 01:51:14,950 --> 01:51:16,519 STUDY TO DATE. 2225 01:51:16,519 --> 01:51:19,188 WE'VE ENROLLED 15 PATIENTS WHO 2226 01:51:19,188 --> 01:51:21,891 HAVE BEEN ALL PEDIATRIC PATIENTS 2227 01:51:21,891 --> 01:51:23,793 AND THUS FAR 250 TRANSFUSION 2228 01:51:23,793 --> 01:51:26,495 UNITS FOR THE PATIENT REQUIRE 2229 01:51:26,495 --> 01:51:29,298 SIMPLE OR STRAIGHT TRANSFUSION A 2230 01:51:29,298 --> 01:51:30,966 TOTAL 267 GENOTYPE UNITS HAVE 2231 01:51:30,966 --> 01:51:33,869 BEEN TRANSFUSED TO THIS COHORT. 2232 01:51:33,869 --> 01:51:35,971 THIS PIE CHART SHOWS THE LEVEL 2233 01:51:35,971 --> 01:51:37,606 OF RH GENOTYPE MATCHING WE WERE 2234 01:51:37,606 --> 01:51:38,541 ABLE TO PROVIDE. 2235 01:51:38,541 --> 01:51:41,043 SO 100% GOT RH GENOTYPE MATCHED 2236 01:51:41,043 --> 01:51:44,213 OF THE 100%, 13% WERE THE LESS 2237 01:51:44,213 --> 01:51:46,982 RESTRICTIVE MATCH WHERE WE 2238 01:51:46,982 --> 01:51:49,018 ALLOWED THE INTERCHANGE WITH 2239 01:51:49,018 --> 01:51:50,553 CD48C WITH CE. 2240 01:51:50,553 --> 01:51:53,656 WE HAD A FEW OFF STUDY 2241 01:51:53,656 --> 01:51:54,256 TRANSFUSIONS FOR INSTANCE A 2242 01:51:54,256 --> 01:51:57,326 PRIORITY OF A PATIENT CAME IN 2243 01:51:57,326 --> 01:51:59,728 FOR AN ACUTE TRANSMISSION THEY 2244 01:51:59,728 --> 01:52:00,329 WOULD LIKELY NOT GET GENOTYPE 2245 01:52:00,329 --> 01:52:03,265 MATCHED UNITS. 2246 01:52:03,265 --> 01:52:05,501 I JUST WANT TO SHOW BECAUSE I 2247 01:52:05,501 --> 01:52:07,069 THOUGHT IT WAS INTERESTING DATA 2248 01:52:07,069 --> 01:52:11,106 WE KEPT TRACK OF OUR BLOOD 2249 01:52:11,106 --> 01:52:12,007 SUPPLIER OUR COLLABORATORS IN 2250 01:52:12,007 --> 01:52:13,209 THE NEW YORK BLOOD CENTER AND 2251 01:52:13,209 --> 01:52:15,711 THIS IS PRECOVID THEY WERE 2252 01:52:15,711 --> 01:52:17,746 COLLECTING NEARLY 6,000 UNITS 2253 01:52:17,746 --> 01:52:21,350 FROM BLACK DONORS PER QUARTER. 2254 01:52:21,350 --> 01:52:24,119 AND THIS IS WHERE COVID STARTED. 2255 01:52:24,119 --> 01:52:25,688 THIS IS ACTUALLY WHEN WE OPENED 2256 01:52:25,688 --> 01:52:26,722 OUR STUDY. 2257 01:52:26,722 --> 01:52:29,925 YOU CAN SEE THEY WERE HAVING A 2258 01:52:29,925 --> 01:52:31,760 VERY DIFFICULT TIME NOT FOR OUR 2259 01:52:31,760 --> 01:52:35,030 STUDY IN PARTICULAR BUT JUST NOW 2260 01:52:35,030 --> 01:52:36,665 SEVERAL YEARS LATER APPROACHING 2261 01:52:36,665 --> 01:52:37,299 THOSE BASELINE LEVELS OF BLACK 2262 01:52:37,299 --> 01:52:43,005 DONATIONS. 2263 01:52:43,005 --> 01:52:48,143 IN TERMS OF THE OUTCOMES TO DATE 2264 01:52:48,143 --> 01:52:58,687 AS EXPECTED WE HAVE SEEN NO RX 2265 01:53:02,791 --> 01:53:03,692 ALLOIMMUNIZATION AND HAVE NOT 2266 01:53:03,692 --> 01:53:05,127 SEEN THE RH MATCHED UNITS FOR 2267 01:53:05,127 --> 01:53:07,496 THEM AND YOU CAN SEE HERE OUR 2268 01:53:07,496 --> 01:53:08,163 INSTITUTIONAL POLICY IS TO 2269 01:53:08,163 --> 01:53:10,933 PROVIDE UNITS THAT ARE LESS THAN 2270 01:53:10,933 --> 01:53:13,402 21 DAYS OLD FROM COLLECTION AND 2271 01:53:13,402 --> 01:53:15,571 IN EACH BAR FROM THE PATIENT IS 2272 01:53:15,571 --> 01:53:18,274 PRE STUDY AND ON STUDIO AND YOU 2273 01:53:18,274 --> 01:53:20,676 CAN SEE MOST HAVE RECEIVED ALL 2274 01:53:20,676 --> 01:53:23,245 UNITS LESS THAN 21 DAYS. 2275 01:53:23,245 --> 01:53:25,447 ONE STARRED AND THE ONE WE 2276 01:53:25,447 --> 01:53:26,715 SCHEDULED THE MOST. 2277 01:53:26,715 --> 01:53:29,385 AND THEN SHOWN HERE BELOW IS THE 2278 01:53:29,385 --> 01:53:34,590 HEMOGLOBIN S AND NO STATISTICAL 2279 01:53:34,590 --> 01:53:36,492 DIFFERENCE BUT THERE'S A TREND 2280 01:53:36,492 --> 01:53:38,694 FOR SOME PATIENTS OF IMPROVED 2281 01:53:38,694 --> 01:53:45,901 CONTROL OF THEIR HEMOGLOBIN S 2282 01:53:45,901 --> 01:53:47,303 MATCHED BLOOD. 2283 01:53:47,303 --> 01:53:52,341 WE THINK IT'S LIKELY FEASIBLE 2284 01:53:52,341 --> 01:53:58,647 AND CAN MINIMIZE 2285 01:53:58,647 --> 01:54:00,983 ALLOIMMUNIZATION AND REQUIRE A 2286 01:54:00,983 --> 01:54:03,152 ROBUST POOL AND CERTAINLY THERE 2287 01:54:03,152 --> 01:54:08,123 ARE ISSUES WITH EFFICIENCY ONCE 2288 01:54:08,123 --> 01:54:14,029 THERE'S MORE SCALE UP AND WE 2289 01:54:14,029 --> 01:54:17,900 THINK THIS CAN ALLOW PRECISE RED 2290 01:54:17,900 --> 01:54:22,471 CELL ANTIGEN MATCHING AND THE 2291 01:54:22,471 --> 01:54:24,940 RATE IS ONE ANTIBODY PER 250 2292 01:54:24,940 --> 01:54:26,909 UNITS TRANSFUSED AND WHILE WE'VE 2293 01:54:26,909 --> 01:54:31,747 NOT IDENTIFIED ANY RH ANTIBODIES 2294 01:54:31,747 --> 01:54:34,216 IF WE GET TO 4,000 UNITS WE'D 2295 01:54:34,216 --> 01:54:36,185 HAVE A SIGNIFICANT P VALUE IF 2296 01:54:36,185 --> 01:54:41,190 THERE WAS EVEN LESS THAN 5RH 2297 01:54:41,190 --> 01:54:41,690 ANTIBODIES MADE. 2298 01:54:41,690 --> 01:54:43,158 SO THE SECOND CASE IS THE 2299 01:54:43,158 --> 01:54:46,128 5-YEAR-OLD BOY WE TOOK CARE OF 2300 01:54:46,128 --> 01:54:48,897 NOW ALMOST 10 YEARS AGO WHO HAS 2301 01:54:48,897 --> 01:54:53,435 HEMOGLOBIN SS WHO PRESENTED TO 2302 01:54:53,435 --> 01:54:56,038 THE EMERGENCY ROOM AND THIS IS 2303 01:54:56,038 --> 01:54:57,039 HIS URINE ON PRESENTATION. 2304 01:54:57,039 --> 01:55:03,245 HE HAD BEEN TRANSFUSED ONE UNIT 2305 01:55:03,245 --> 01:55:09,652 OF O POS 10 DAYS PRIOR FOR A 2306 01:55:09,652 --> 01:55:17,860 HEMOGLOBIN OF 6.5 AND IT WAS 4.2 2307 01:55:17,860 --> 01:55:28,771 WITHIN 24 HOURS AND HEMOGLOBINI 2308 01:55:30,272 --> 01:55:37,880 WAS 7 AND 4.2 THE NEXT DAY AND 2309 01:55:37,880 --> 01:55:41,884 THE ANTIBODY EVALUATION FIRST 2310 01:55:41,884 --> 01:55:44,319 FOOLED OUR BLOOD BANK TECHNOLOGY 2311 01:55:44,319 --> 01:55:48,157 AND IT TURNED OUT THE ONE CELL 2312 01:55:48,157 --> 01:55:49,892 WAS A D NEGATIVE CELL BUT 2313 01:55:49,892 --> 01:55:52,161 BECAUSE HE WAS D POSITIVE THEY 2314 01:55:52,161 --> 01:55:55,264 DIDN'T THINK HE'D HAVE AN ANTI-D 2315 01:55:55,264 --> 01:55:56,565 BUT THAT'S WHAT HE HAD AND WHEN 2316 01:55:56,565 --> 01:56:01,470 WE PHENOTYPED WE SAW HE WAS HEMO 2317 01:56:01,470 --> 01:56:04,873 ZYGOUS FOR THE PARTIAL D ANTIGEN 2318 01:56:04,873 --> 01:56:07,109 AND HAD BECOME DE-IMMUNIZED 2319 01:56:07,109 --> 01:56:08,477 BECAUSE HE'S A PATIENT WITH 2320 01:56:08,477 --> 01:56:13,716 PARTIAL D. 2321 01:56:13,716 --> 01:56:15,317 ANTI-D DOES OCCUR AN IN PATIENTS 2322 01:56:15,317 --> 01:56:17,720 WITH PARTIAL D ANTIGENS AND CAN 2323 01:56:17,720 --> 01:56:22,858 ALSO OCCUR IN PATIENTS WITH 2324 01:56:22,858 --> 01:56:25,327 CONVENTIONAL RHD TRANSFUSED WITH 2325 01:56:25,327 --> 01:56:28,397 UNITS PRIMARILY FROM BLACK 2326 01:56:28,397 --> 01:56:28,630 DONORS. 2327 01:56:28,630 --> 01:56:31,467 AND WHAT BECOMES CHALLENGING IS 2328 01:56:31,467 --> 01:56:33,869 ONCE WE HONOR THE ANTI-D. 2329 01:56:33,869 --> 01:56:35,637 WE DON'T EXPOSE THEM TO D 2330 01:56:35,637 --> 01:56:38,207 POSITIVE BLOOD AND PROVIDING 2331 01:56:38,207 --> 01:56:40,042 D-NEGATIVE RED CELLS TO PATIENT 2332 01:56:40,042 --> 01:56:42,411 WITH ANTI-D HAS A SIGNIFICANT 2333 01:56:42,411 --> 01:56:45,147 IMPACT ON THE D-NEGATIVE RED 2334 01:56:45,147 --> 01:56:45,547 CELL INVENTORY. 2335 01:56:45,547 --> 01:56:51,420 SO ONE QUESTION WE HAD WAS WERE 2336 01:56:51,420 --> 01:56:52,621 ALL THE PATIENTS SIGNIFICANT AND 2337 01:56:52,621 --> 01:56:55,424 CAN THEY WESTBOUND EXPOSED TO D 2338 01:56:55,424 --> 01:56:56,592 POSITIVE BLOOD? 2339 01:56:56,592 --> 01:56:59,094 WE LOOKED RETROSPECTIVELY AT OUR 2340 01:56:59,094 --> 01:57:01,163 DATA. 2341 01:57:01,163 --> 01:57:02,698 WE CATEGORIZED D POSITIVE INTO 2342 01:57:02,698 --> 01:57:07,770 THREE CATEGORIES. 2343 01:57:07,770 --> 01:57:10,272 DECONVENTIONAL ONE CONVENTIONAL 2344 01:57:10,272 --> 01:57:12,908 ALLELE FROM A PARTIAL D AND THIS 2345 01:57:12,908 --> 01:57:15,677 WAS 7% OF THE PATIENTS. 2346 01:57:15,677 --> 01:57:18,781 38% OF WHOM WHO WERE ON CHRONIC 2347 01:57:18,781 --> 01:57:23,218 TRANSFUSION AND D-POSITIVE DOW 2348 01:57:23,218 --> 01:57:25,954 ZERO WE THINK OF AS SIMILAR TO 2349 01:57:25,954 --> 01:57:28,724 RHD CONVENTIONAL AND NO 2350 01:57:28,724 --> 01:57:31,660 CONVENTIONAL ALLELE AND THIS IS 2351 01:57:31,660 --> 01:57:34,997 13% OF THE PATIENTS OF WHICH 44% 2352 01:57:34,997 --> 01:57:37,933 OF THE CHRONIC TRANSFUSED WERE 2353 01:57:37,933 --> 01:57:41,637 IN THE COHORT AND LASTLY THE D 2354 01:57:41,637 --> 01:57:43,172 POSITIVE PARTIAL WHERE THEY 2355 01:57:43,172 --> 01:57:48,677 COULD BE HEMEZYGOUS OR COMPOUND 2356 01:57:48,677 --> 01:57:49,344 HETEROZYGOUS. 2357 01:57:49,344 --> 01:57:51,613 AND THOSE WERE THE LAST SET OF 2358 01:57:51,613 --> 01:57:51,880 PATIENTS. 2359 01:57:51,880 --> 01:57:55,184 IF WE LOOKED AT ALL THE ANTI-D 2360 01:57:55,184 --> 01:57:56,785 FORMED THERE WAS 48 ANTI-D 2361 01:57:56,785 --> 01:57:59,021 ALTOGETHER AND YOU CAN SEE HERE 2362 01:57:59,021 --> 01:58:00,689 IS THE PERCENTAGE OF THE 2363 01:58:00,689 --> 01:58:03,725 PATIENTS WHO HAD FORMED ANTI-D 2364 01:58:03,725 --> 01:58:06,228 AND THE PARTIAL D COHORT 20% HAD 2365 01:58:06,228 --> 01:58:08,397 FORMED ANTI-D WHERE IT WAS CLOSE 2366 01:58:08,397 --> 01:58:10,666 TO 5% FOR THE CONVENTIONAL IN 2367 01:58:10,666 --> 01:58:12,234 THE DOW ZERO. 2368 01:58:12,234 --> 01:58:16,738 IF YOU LOOK AT ANTI-D RATE YOU 2369 01:58:16,738 --> 01:58:19,808 CAN SEE IT WAS THREE TO FIVE 2370 01:58:19,808 --> 01:58:23,879 TIMES HIGHER FOR THE PATIENTS 2371 01:58:23,879 --> 01:58:25,948 WITH PARTIAL D COMPARED TO 2372 01:58:25,948 --> 01:58:27,316 CONVENTIONAL D GROUPS. 2373 01:58:27,316 --> 01:58:31,854 AMONG THESE 48 INDIVIDUALS, 13 2374 01:58:31,854 --> 01:58:33,622 HAD A DELETE TRANSFUSION 2375 01:58:33,622 --> 01:58:36,225 REACTION OR POORER TRANSFUSED 2376 01:58:36,225 --> 01:58:40,495 RED CELL SURVIVAL BY LOOKING AT 2377 01:58:40,495 --> 01:58:43,765 THEIR HEMOGLOBIN S THE PATIENTS 2378 01:58:43,765 --> 01:58:45,634 WHO MADE ANTI-D BECAUSE THEY 2379 01:58:45,634 --> 01:58:49,338 WERE EXPOSED TO DONOR BLOOD WITH 2380 01:58:49,338 --> 01:58:53,175 A VARIANT SOMETIMES ALSO HAD A 2381 01:58:53,175 --> 01:58:54,610 CLINICALLY SIGNIFICANT REACTION 2382 01:58:54,610 --> 01:58:55,644 TO THAT BLOOD. 2383 01:58:55,644 --> 01:58:57,646 WE LOOKED AT THE OTHER ASPECTS 2384 01:58:57,646 --> 01:59:00,048 OF THE ANTI-D AND THE PATIENTS 2385 01:59:00,048 --> 01:59:01,383 WHO HAD PARTIAL D TEND TO MAKE 2386 01:59:01,383 --> 01:59:06,355 THEIR ANTI-D AT LOWER D POSITIVE 2387 01:59:06,355 --> 01:59:09,925 UNIT EXPOSURES. 2388 01:59:09,925 --> 01:59:11,793 MANY PATIENTS ARE CHRONICALLY 2389 01:59:11,793 --> 01:59:13,095 TRANSFUSED AND THE PATIENTS WITH 2390 01:59:13,095 --> 01:59:15,697 PARTIAL D FREQUENTLY MADE THE 2391 01:59:15,697 --> 01:59:16,665 ANTIBODY EARLY ON IN THEIR 2392 01:59:16,665 --> 01:59:18,166 EXPOSURES AND IF WE LOOKED AT 2393 01:59:18,166 --> 01:59:21,904 HOW LONG WE COULD SEE THE ANTI-D 2394 01:59:21,904 --> 01:59:23,505 PERSIST IN THEIR PLASMA THEY'RE 2395 01:59:23,505 --> 01:59:25,874 CHRONICALLY TRANSFUSED THE 2396 01:59:25,874 --> 01:59:27,943 ANTI-D PERSISTED LONGER IN THE 2397 01:59:27,943 --> 01:59:32,414 PATIENT PLASMA COMPARED TO THE 2398 01:59:32,414 --> 01:59:33,415 DOW O. 2399 01:59:33,415 --> 01:59:37,152 THE RATE OF ANTI-D WAS HIGHER 2400 01:59:37,152 --> 01:59:39,454 WITH PATIENT WITH PARTIAL D AND 2401 01:59:39,454 --> 01:59:40,722 MADE IT WITH LOWER EXPOSURES AND 2402 01:59:40,722 --> 01:59:43,025 THE ANTI-D PERSISTED IN THE 2403 01:59:43,025 --> 01:59:47,696 PLASMA LONGER. 2404 01:59:47,696 --> 01:59:50,565 AND SO PATIENTS WITH POTENTIAL D 2405 01:59:50,565 --> 01:59:51,466 CAN BENEFIT FROM TRANSFUSION AND 2406 01:59:51,466 --> 01:59:55,771 THAT'S WHAT WE DO FOR OUR 2407 01:59:55,771 --> 01:59:57,806 PATIENT AT OUR INSTITUTION. 2408 01:59:57,806 --> 02:00:03,111 IT HAS A SIGNIFICANT INCREASE OF 2409 02:00:03,111 --> 02:00:04,813 IMPACT FOR THOSE WHO REQUIRE D 2410 02:00:04,813 --> 02:00:05,480 NEGATIVE BLOOD. 2411 02:00:05,480 --> 02:00:09,918 AMONG THE COHORT OF 48, 32 2412 02:00:09,918 --> 02:00:14,389 PATIENTS WERE ON CHRONIC 2413 02:00:14,389 --> 02:00:16,558 TRANSFUSION AND REQUIRING AN 2414 02:00:16,558 --> 02:00:20,395 AVERAGE OF 62D NEGATIVE UNITS 2415 02:00:20,395 --> 02:00:24,666 PER YEAR PER INDIVIDUAL AND CAN 2416 02:00:24,666 --> 02:00:29,604 PATIENTS RECEIVE D POSITIVE RED 2417 02:00:29,604 --> 02:00:29,805 CELLS? 2418 02:00:29,805 --> 02:00:33,608 WE HAVE A FEASIBILITY STUDY IN 2419 02:00:33,608 --> 02:00:37,245 PROVIDING RDH MATCHED BLOOD ON 2420 02:00:37,245 --> 02:00:37,913 CHRONIC BLOOD CELL EXCHANGE TO 2421 02:00:37,913 --> 02:00:43,352 BE ELIGIBLE THE ANTI-D CANNOT BE 2422 02:00:43,352 --> 02:00:45,187 IN THE PAST SIX MONTHS AND THE 2423 02:00:45,187 --> 02:00:47,222 PATIENTS ARE ALL ON CHRONIC RED 2424 02:00:47,222 --> 02:00:50,892 CELL EXCHANGE WITH THE IDEA 2425 02:00:50,892 --> 02:00:52,794 RE-EXPOSE A PATIENT WITH FIVE 2426 02:00:52,794 --> 02:00:58,533 UNITS WITH ONE D POSITIVE UNIT 2427 02:00:58,533 --> 02:01:01,870 BECAUSE IT WOULD NOT BE 2428 02:01:01,870 --> 02:01:02,504 LIFE-THREATENING AND WE HAVE 2429 02:01:02,504 --> 02:01:03,972 THEM SUBSEQUENTLY COME BACK FOR 2430 02:01:03,972 --> 02:01:06,241 LABS A WEEK AFTER THE 2431 02:01:06,241 --> 02:01:07,809 TRANSFUSION TO MAKE SURE THE 2432 02:01:07,809 --> 02:01:09,911 ANTI-D HAS NOT REAPPEARED AND 2433 02:01:09,911 --> 02:01:11,279 THEN PROGRESSIVELY INCREASED THE 2434 02:01:11,279 --> 02:01:13,115 NUMBER OF D POSITIVE UNITS THEY 2435 02:01:13,115 --> 02:01:13,515 GET. 2436 02:01:13,515 --> 02:01:16,485 WE HAVE FOUR PATIENTS WHO HAVE 2437 02:01:16,485 --> 02:01:17,085 COMPLETED THIS. 2438 02:01:17,085 --> 02:01:19,721 EACH OF THE PATIENTS FOR THE 2439 02:01:19,721 --> 02:01:21,423 FIRST TWO VISITS GETS ONE D 2440 02:01:21,423 --> 02:01:23,125 POSITIVE AND THEY'RE ALL 2441 02:01:23,125 --> 02:01:25,694 PATIENTS THAT HAVE AT LEAST ONE 2442 02:01:25,694 --> 02:01:28,330 CONVENTIONAL RHD ALLELE AND YOU 2443 02:01:28,330 --> 02:01:30,399 CAN SEE OFTEN TIMES THE PATIENTS 2444 02:01:30,399 --> 02:01:33,135 ARE IMMUNIZED MAKING IT HARDER 2445 02:01:33,135 --> 02:01:35,904 TO FIND THEIR BLOOD AND FOR ALL 2446 02:01:35,904 --> 02:01:38,040 THESE PATIENTS EXCEPT THE LAST 2447 02:01:38,040 --> 02:01:41,810 ONE GOT BLOOD WITH TWO 2448 02:01:41,810 --> 02:01:45,347 CONVENTIONAL RHD ALLELE AND ONE 2449 02:01:45,347 --> 02:01:48,216 PATIENT GOT ONE WITH DOW 0. 2450 02:01:48,216 --> 02:01:50,552 IT DID NOT REAPPEAR AND THERE 2451 02:01:50,552 --> 02:01:53,889 WAS NO DIFFERENCE IN THEIR 2452 02:01:53,889 --> 02:01:58,160 HEMOGLOBIN S YOU CAN SEE PRESTUT 2453 02:01:58,160 --> 02:01:59,961 STUDY ON THE LEFT AND NO 2454 02:01:59,961 --> 02:02:01,596 DIFFERENCE IN THE AGE OF THEIR 2455 02:02:01,596 --> 02:02:05,767 UNITS AT THE TIME OF 2456 02:02:05,767 --> 02:02:06,535 TRANSFUSION. 2457 02:02:06,535 --> 02:02:12,174 TO CLOSE OUT A COMPREHENSIVE 2458 02:02:12,174 --> 02:02:14,309 PHENOTYPING CAN GUIDE DONOR 2459 02:02:14,309 --> 02:02:15,844 CHOICE AND SELECT BLOOD CELLS 2460 02:02:15,844 --> 02:02:21,883 FOR LESS CHALLENGING CASES AND 2461 02:02:21,883 --> 02:02:24,219 RHD MATCHED RED CELLS IF THE 2462 02:02:24,219 --> 02:02:25,887 FUTURE WOULD REQUIRE A ROBUST 2463 02:02:25,887 --> 02:02:27,456 AFRICAN AMERICAN DONOR POOL AND 2464 02:02:27,456 --> 02:02:30,158 MORE COST-EFFECTIVE NGS ASSAYS 2465 02:02:30,158 --> 02:02:32,294 WHICH I THINK WILL BE COMING IN 2466 02:02:32,294 --> 02:02:35,230 THE NEXT FEW YEARS BEING REALLY 2467 02:02:35,230 --> 02:02:40,102 A PARADIGM FOR USING MOLECULAR 2468 02:02:40,102 --> 02:02:41,470 TYPING FOR ALL PATIENTS. 2469 02:02:41,470 --> 02:02:45,640 I WANT TO END BY THANKING OUR 2470 02:02:45,640 --> 02:02:47,375 TWO RESEARCH COORDINATORS AND 2471 02:02:47,375 --> 02:02:52,647 OUR BLOOD BANK AND NURSING AND 2472 02:02:52,647 --> 02:02:53,915 THE NEW YORK BLOOD CENTER. 2473 02:02:53,915 --> 02:03:02,224 THANK YOU. 2474 02:03:02,224 --> 02:03:03,492 >> THANK YOU FOR THE EXCELLENT 2475 02:03:03,492 --> 02:03:03,692 TALK. 2476 02:03:03,692 --> 02:03:05,894 DOES ANYBODY HAVE ANY QUESTIONS? 2477 02:03:05,894 --> 02:03:16,371 THERE ARE NONE IN THE CHAT. 2478 02:03:17,305 --> 02:03:20,442 >> THAT WAS WONDERFUL. 2479 02:03:20,442 --> 02:03:20,942 THANK YOU SO MUCH. 2480 02:03:20,942 --> 02:03:23,945 I HAVE A COUPLE QUESTIONS. 2481 02:03:23,945 --> 02:03:29,885 FIRST IS THE PARTIAL D HAVE THE 2482 02:03:29,885 --> 02:03:40,162 ANTIBODY LONGER? 2483 02:03:43,298 --> 02:03:44,933 >> IT'S A COMPLETE LACK OF 2484 02:03:44,933 --> 02:03:47,068 ANTIGEN AND THE FOLKS WITH 2485 02:03:47,068 --> 02:03:49,204 CONVENTIONAL D ARE SEEING A D 2486 02:03:49,204 --> 02:03:50,472 ANTIGEN THAT'S SLIGHTLY 2487 02:03:50,472 --> 02:03:52,274 DIFFERENT AND WE'RE NOT ALWAYS 2488 02:03:52,274 --> 02:03:55,143 IT'S A D ANTIGEN. 2489 02:03:55,143 --> 02:04:01,917 IT COULD BE THE CE ANTIGEN 2490 02:04:01,917 --> 02:04:02,817 DIFFERENT. 2491 02:04:02,817 --> 02:04:07,489 >> THE SECOND QUESTION YOU'RE 2492 02:04:07,489 --> 02:04:10,859 LOOKING TO DEVELOP A CHIP TO DO 2493 02:04:10,859 --> 02:04:14,229 DIRECT GENOTYPES OR A BROAD NEXT 2494 02:04:14,229 --> 02:04:16,798 GEN EVOLUTION SEQUENCING? 2495 02:04:16,798 --> 02:04:22,370 >> THINK SOME ARE LOOKING AT 2496 02:04:22,370 --> 02:04:22,771 CHIPS. 2497 02:04:22,771 --> 02:04:25,774 IT'S COMPLEX AND BECAUSE THE 2498 02:04:25,774 --> 02:04:28,176 VARIATION COMES FROM PIECES OF D 2499 02:04:28,176 --> 02:04:31,580 GOING TO CD YOU CAN'T USE 2500 02:04:31,580 --> 02:04:32,814 STANDARD NGS STANDARD. 2501 02:04:32,814 --> 02:04:34,716 WE'RE WORKING AT THE NEW YORK 2502 02:04:34,716 --> 02:04:36,885 BLOOD CENTER ON TRYING TO 2503 02:04:36,885 --> 02:04:40,088 DEVELOP A BIO INFORMATIC PATHWAY 2504 02:04:40,088 --> 02:04:43,625 FOR NGS-BASED PATHWAYS USING 2505 02:04:43,625 --> 02:04:48,697 MORE OF THE QPCR BASED TO LOOK 2506 02:04:48,697 --> 02:04:54,236 AT COPY NUMBER RATHER THAN 2507 02:04:54,236 --> 02:04:55,503 RELYING ON A COMPANY TO DEVELOP 2508 02:04:55,503 --> 02:05:05,947 CHIPS THAT ARE EXPENSIVE. 2509 02:05:07,148 --> 02:05:11,820 >> ARE THE MOLECULAR PHENOTYPING 2510 02:05:11,820 --> 02:05:13,922 ACCEPTED BY MOST BLOOD BANKS IN 2511 02:05:13,922 --> 02:05:15,557 THE UNITED STATES. 2512 02:05:15,557 --> 02:05:17,359 AND ADULTS OFTEN GET TRANSFUSED 2513 02:05:17,359 --> 02:05:20,495 AT PERIPHERAL SMALL COMMUNITY 2514 02:05:20,495 --> 02:05:20,762 HOSPITALS. 2515 02:05:20,762 --> 02:05:21,429 I'VE BEEN DOING SICKLE CELL FOR 2516 02:05:21,429 --> 02:05:25,467 A LONG TIME AND I DON'T SEE THIS 2517 02:05:25,467 --> 02:05:25,734 IMPROVING. 2518 02:05:25,734 --> 02:05:29,104 AND THE PERIPHERAL HOSPITALS AND 2519 02:05:29,104 --> 02:05:31,339 WHAT DO YOU SUGGEST WE CAN DO 2520 02:05:31,339 --> 02:05:33,608 THIS TO MAKE THIS MORE UNIFORM? 2521 02:05:33,608 --> 02:05:35,910 I REMEMBER PEOPLE DIDN'T WANT TO 2522 02:05:35,910 --> 02:05:36,778 DO DE BECAUSE IT WAS TOO 2523 02:05:36,778 --> 02:05:42,517 EXPENSIVE. 2524 02:05:42,517 --> 02:05:44,052 IT'S A PRACTICAL QUESTION. 2525 02:05:44,052 --> 02:05:45,487 >> IT'S A VERY GOOD QUESTION. 2526 02:05:45,487 --> 02:05:48,256 THERE'S A FEW COMMENTS I'LL 2527 02:05:48,256 --> 02:05:48,890 MAKE. 2528 02:05:48,890 --> 02:05:52,727 ONE IS I'M A HUGE ADVOCATE FOR 2529 02:05:52,727 --> 02:05:56,731 MOLECULAR TYPING BECAUSE WE'VE 2530 02:05:56,731 --> 02:05:58,566 SHOWN LESS ERROR BECAUSE IT'S 2531 02:05:58,566 --> 02:06:02,070 AUTOMATED VERSUS A TECHNOLOGIST 2532 02:06:02,070 --> 02:06:06,308 TYPING AND WRITING ON A PIECE OF 2533 02:06:06,308 --> 02:06:10,512 PAPER THAT THEN GETS TRANSCRIBED 2534 02:06:10,512 --> 02:06:11,446 IN A COMPUTER SYSTEM. 2535 02:06:11,446 --> 02:06:14,082 AND THE ONE-TIME TEST IS LESS 2536 02:06:14,082 --> 02:06:16,318 THAN ONE TRANSFUSION THAT'S 2537 02:06:16,318 --> 02:06:17,218 ADMINISTERED. 2538 02:06:17,218 --> 02:06:18,420 ACTUALLY A FRACTION OF THE 2539 02:06:18,420 --> 02:06:19,487 TRANSFUSION ADMINISTERED. 2540 02:06:19,487 --> 02:06:22,424 FOR A PATIENT LIFE TIME I THINK 2541 02:06:22,424 --> 02:06:26,695 WE CAN ALL JUSTIFY THAT COST. 2542 02:06:26,695 --> 02:06:29,764 WE DID A COST ANALYSIS OURSELVES 2543 02:06:29,764 --> 02:06:31,966 AND IN TERMS OF OUR BLOOD BANK 2544 02:06:31,966 --> 02:06:33,902 HAVING TO KEEP TECHNOLOGISTS 2545 02:06:33,902 --> 02:06:36,771 TRAINED ON THE SEROLOGIC TYPING 2546 02:06:36,771 --> 02:06:40,275 IT'S MORE COST EFFECTIVE TO DO 2547 02:06:40,275 --> 02:06:41,876 IT THROUGH OUR REFERRAL CENTER. 2548 02:06:41,876 --> 02:06:44,012 SO GENOTYPING IS REALLY DONE AT 2549 02:06:44,012 --> 02:06:46,147 REFERRAL CENTERS RIGHT NOW AND I 2550 02:06:46,147 --> 02:06:49,884 THINK YOU PROBABLY HAVE TO HAVE 2551 02:06:49,884 --> 02:06:51,720 MORE STANDARDIZED FORMATS 2552 02:06:51,720 --> 02:06:53,021 BECAUSE IF YOU SEND YOUR 2553 02:06:53,021 --> 02:06:54,522 GENOTYPING YOU'RE SAMPLE IN FOR 2554 02:06:54,522 --> 02:06:56,458 GENOTYPING AT ONE LABORATORY IT 2555 02:06:56,458 --> 02:06:57,759 CAN BE DIFFERENT FROM ANOTHER 2556 02:06:57,759 --> 02:06:58,059 LABORATORY. 2557 02:06:58,059 --> 02:07:01,863 I THINK THAT'S IMPORTANT. 2558 02:07:01,863 --> 02:07:03,031 LASTLY THE DEPARTMENT OF HEALTH 2559 02:07:03,031 --> 02:07:06,601 AND HUMAN SERVICES THERE'S A 2560 02:07:06,601 --> 02:07:11,606 COMMITTEE NOW THAT'S BEEN 2561 02:07:11,606 --> 02:07:15,477 ESTABLISHED TO MOVE FORWARD WITH 2562 02:07:15,477 --> 02:07:17,879 A NATIONAL REGISTRY FOR 2563 02:07:17,879 --> 02:07:19,814 ALLOANTIBODIES AND I ADVOCATE 2564 02:07:19,814 --> 02:07:21,516 FOR INCLUDING PHENOTYPES OR 2565 02:07:21,516 --> 02:07:23,685 GENOTYPES BECAUSE EXACTLY WHAT 2566 02:07:23,685 --> 02:07:28,289 YOU SAID, A PATIENT MAY GO TO 2567 02:07:28,289 --> 02:07:29,391 ANOTHER INSTITUTION EITHER 2568 02:07:29,391 --> 02:07:30,725 TRANSITION THERE OR BE 2569 02:07:30,725 --> 02:07:32,093 TRAVELLING OR CHOOSING TO GO TO 2570 02:07:32,093 --> 02:07:32,727 ANOTHER INSTITUTION AND WE 2571 02:07:32,727 --> 02:07:34,929 SHOULD BE ABLE TO SHARE THIS 2572 02:07:34,929 --> 02:07:35,930 INFORMATION READILY. 2573 02:07:35,930 --> 02:07:39,334 I THINK WE'RE LOOKING AT WAYS 2574 02:07:39,334 --> 02:07:41,870 FOR THE HOSPITAL LABORATORY 2575 02:07:41,870 --> 02:07:45,073 SYSTEMS TO DATA DUMP TO THE 2576 02:07:45,073 --> 02:07:45,907 CENTRAL COORDINATING CENTER 2577 02:07:45,907 --> 02:07:53,381 WHICH THEN WOULD BE AVAILABLE TO 2578 02:07:53,381 --> 02:07:53,915 ALL HOSPITALS INCLUDING 2579 02:07:53,915 --> 02:07:54,416 COMMUNITY HOSPITALS. 2580 02:07:54,416 --> 02:07:57,152 AT A MINIMUM I THINK IT WILL 2581 02:07:57,152 --> 02:07:58,353 MEAN IF YOU'RE THE INSTITUTION 2582 02:07:58,353 --> 02:08:00,255 PROVIDING THE TRANSFUSION YOU 2583 02:08:00,255 --> 02:08:01,923 CAN SEE WHERE A PATIENT HAS HAD 2584 02:08:01,923 --> 02:08:05,326 A HISTORY OR RECORD AND YOU CAN 2585 02:08:05,326 --> 02:08:06,294 CALL THAT INSTITUTION'S BLOOD 2586 02:08:06,294 --> 02:08:09,431 BANK AND MAKE SURE THE PATIENT 2587 02:08:09,431 --> 02:08:12,300 DOESN'T HAVE AN ANTIBODY NOT 2588 02:08:12,300 --> 02:08:14,869 CURRENTLY DEMONSTRATING AS WAS 2589 02:08:14,869 --> 02:08:15,069 SHOWN. 2590 02:08:15,069 --> 02:08:24,712 THANK YOU. 2591 02:08:24,712 --> 02:08:25,914 >> THANK YOU. 2592 02:08:25,914 --> 02:08:27,649 IS THIS AUDIO BETTER? 2593 02:08:27,649 --> 02:08:28,116 ALL RIGHT. 2594 02:08:28,116 --> 02:08:29,317 IT'S MY PLEASURE TO INTRODUCE 2595 02:08:29,317 --> 02:08:31,352 OUR THIRD SPEAKER IN THIS 2596 02:08:31,352 --> 02:08:35,757 SESSION, DR. NEIL HANCHARD WHO 2597 02:08:35,757 --> 02:08:38,426 RVSED HIS MEDICAL DEGREE FROM 2598 02:08:38,426 --> 02:08:41,162 THE UNIVERSITY OF KINGSTON 2599 02:08:41,162 --> 02:08:44,799 JAMAICA AND WAS A RHODE SCHOLAR. 2600 02:08:44,799 --> 02:08:51,606 HE COMPLETED HIS CLINICAL 2601 02:08:51,606 --> 02:08:56,478 TRAINING AS A PEDIATRIC TRAINING 2602 02:08:56,478 --> 02:08:57,912 AND HE'S A SENIOR INVESTIGATOR 2603 02:08:57,912 --> 02:08:59,747 IN THE CENTER FOR PRECISION 2604 02:08:59,747 --> 02:09:01,182 HEALTH WITHIN THE NATIONAL HUMAN 2605 02:09:01,182 --> 02:09:03,418 RESEARCH INSTITUTE WHERE HE 2606 02:09:03,418 --> 02:09:04,819 HEADS THE CHILDHOOD COMPLEX 2607 02:09:04,819 --> 02:09:08,823 DISEASE GENOMICS STUDIO. 2608 02:09:08,823 --> 02:09:19,067 DR. HANCHARD. 2609 02:10:11,786 --> 02:10:15,323 >> I LIKE TO CALL MYSELF A HUMAN 2610 02:10:15,323 --> 02:10:17,892 GENETICISTS. 2611 02:10:17,892 --> 02:10:25,066 I APOLOGIZE FOR THE SWITCH FROM 2612 02:10:25,066 --> 02:10:27,035 MAC TO WINDOWS AND UNDERSTAND 2613 02:10:27,035 --> 02:10:27,669 WHY THERE'S VARIATION IN DISEASE 2614 02:10:27,669 --> 02:10:36,544 RISK. 2615 02:10:36,544 --> 02:10:38,112 WE ASK SPECIFIC QUESTIONS AS WE 2616 02:10:38,112 --> 02:10:41,649 GO ALONG AND I'LL TALK ABOUT 2617 02:10:41,649 --> 02:10:44,018 WORK WITH THE QUESTION OF SOME 2618 02:10:44,018 --> 02:10:45,687 INDIVIDUALS MAKE ANTIBODIES AND 2619 02:10:45,687 --> 02:10:49,190 SOME DON'T AND WHAT UNDER LIES 2620 02:10:49,190 --> 02:10:50,425 ALL THE RESEARCH IS THE IDEA 2621 02:10:50,425 --> 02:10:53,595 MOST OF THESE DISORDERS ARE MUCH 2622 02:10:53,595 --> 02:10:57,865 MORE PREVALENT IN INDIVIDUALS OF 2623 02:10:57,865 --> 02:11:00,268 AFRICAN ANCESTRY. 2624 02:11:00,268 --> 02:11:02,236 AND WE THINK ABOUT THE 2625 02:11:02,236 --> 02:11:05,873 APPROACHES AND MODELS IN THESE 2626 02:11:05,873 --> 02:11:06,074 AREAS. 2627 02:11:06,074 --> 02:11:08,343 THIS IS PARTICULARLY IMPORTANT 2628 02:11:08,343 --> 02:11:09,410 BECAUSE INDIVIDUALS OF AFRICAN 2629 02:11:09,410 --> 02:11:12,280 AMERICAN ANCESTRY ARE UNDER 2630 02:11:12,280 --> 02:11:13,815 REPRESENTED IN GENETIC STUDIES 2631 02:11:13,815 --> 02:11:16,451 AND LOOKING AT GENOME WIDE 2632 02:11:16,451 --> 02:11:17,018 ASSOCIATION STUDIES WHERE 2633 02:11:17,018 --> 02:11:21,356 THERE'S TENS OF THOUSANDS AND 2634 02:11:21,356 --> 02:11:23,925 INDIVIDUALS OF AFRICAN AMERICAN 2635 02:11:23,925 --> 02:11:26,227 ANCESTRY COUNT FOR LESS THAN 1% 2636 02:11:26,227 --> 02:11:28,930 OF THE PARTICIPANTS HEALTH AND 2637 02:11:28,930 --> 02:11:33,868 YOU LOOK AT LARGE SEQUENCING 2638 02:11:33,868 --> 02:11:36,304 DATABASES STANDING AS THE 2639 02:11:36,304 --> 02:11:40,041 REFERENCE AND THE EUROPEAN BIO 2640 02:11:40,041 --> 02:11:41,442 BANK MUCH LESS AFRICAN AMERICAN 2641 02:11:41,442 --> 02:11:47,048 ANCESTRY AND AT ODDS OF WHAT WE 2642 02:11:47,048 --> 02:11:48,750 KNOW ABOUT AFRICAN ANCESTRY IN 2643 02:11:48,750 --> 02:11:52,754 GENERAL AND THE NUMBER OF 2644 02:11:52,754 --> 02:11:53,888 VARIANTS IN THE GENE VARY MORE. 2645 02:11:53,888 --> 02:11:57,058 THE BIG PICTURE VIEW IS THAT 2646 02:11:57,058 --> 02:12:00,128 THERE ARE FEWER STUDIES THAT 2647 02:12:00,128 --> 02:12:00,695 INVOLVED INDIVIDUALS WITH 2648 02:12:00,695 --> 02:12:02,797 AFRICAN ANCESTRY AND THERE'S 2649 02:12:02,797 --> 02:12:05,700 MORE VARIATION AND MORE 2650 02:12:05,700 --> 02:12:06,334 COMPLEXITY TO THAT VARIATION 2651 02:12:06,334 --> 02:12:11,506 WHICH ALSO COMES TO BEAR. 2652 02:12:11,506 --> 02:12:13,875 SO WE KNOW THIS FROM MANY OF THE 2653 02:12:13,875 --> 02:12:15,777 BLOOD ANTIGENS THEY'RE DIFFERENT 2654 02:12:15,777 --> 02:12:17,478 AS YOU LOOK AT DIFFERENT 2655 02:12:17,478 --> 02:12:17,912 ANCESTRAL GROUPS. 2656 02:12:17,912 --> 02:12:23,718 HERE AGAIN LOOKING AT THE BLOOD 2657 02:12:23,718 --> 02:12:25,853 GROUPS YOU CAN SEE FOR INSTANCE 2658 02:12:25,853 --> 02:12:29,757 IT'S EXTREMELY COMMON AMONG 2659 02:12:29,757 --> 02:12:31,859 INDIVIDUALS WITH AFRICAN 2660 02:12:31,859 --> 02:12:33,861 ANCESTRY AND WHAT WE DON'T KNOW 2661 02:12:33,861 --> 02:12:36,664 REALLY THE EXTENT OF THE 2662 02:12:36,664 --> 02:12:37,298 VARIATION ACROSS ALL THE BLOOD 2663 02:12:37,298 --> 02:12:40,134 GROUPS. 2664 02:12:40,134 --> 02:12:42,003 AND BY EXTENT HOW DOES THAT 2665 02:12:42,003 --> 02:12:46,140 RELATE TO THE SUBSEQUENT ANTIGEN 2666 02:12:46,140 --> 02:12:47,909 FORMATION AND THEN WHETHER OR 2667 02:12:47,909 --> 02:12:50,078 NOT WE COULD PERHAPS USE THAT 2668 02:12:50,078 --> 02:12:52,113 KIND OF INFORMATION TO INFORM 2669 02:12:52,113 --> 02:12:55,349 FOR A GIVEN POPULATION WHICH 2670 02:12:55,349 --> 02:12:56,651 ANTIGENS WILL BE OF PARTICULAR 2671 02:12:56,651 --> 02:13:02,990 IMPORTANCE TO THE PATIENT. 2672 02:13:02,990 --> 02:13:06,327 WE LOOKED AT GENETIC VARIATION 2673 02:13:06,327 --> 02:13:11,933 IN A POPULATION FROM BRAZIL. 2674 02:13:11,933 --> 02:13:15,269 SO THE SICKLE ALLELE 1 IN 400 2675 02:13:15,269 --> 02:13:20,441 VARIES ACROSS THE COUNTRY. 2676 02:13:20,441 --> 02:13:26,080 BUT THE ALLOUME IMMUNIZATION 2677 02:13:26,080 --> 02:13:32,587 RATE IS STILL HIGH AND WE LOOKED 2678 02:13:32,587 --> 02:13:33,554 AT HALF FROM SICKLE CELL 2679 02:13:33,554 --> 02:13:35,556 PATIENTS AND THE OTHER HALF NOT 2680 02:13:35,556 --> 02:13:36,924 AND WE'RE ABLE TO DO WHOLE 2681 02:13:36,924 --> 02:13:39,460 GENOME SEQUENCING FOCUSSING ON 2682 02:13:39,460 --> 02:13:41,896 THE 18 GROUPS YOU SEE 2683 02:13:41,896 --> 02:13:43,197 REPRESENTED IN THE TABLE HERE. 2684 02:13:43,197 --> 02:13:47,435 THIS IS ALL WORK DONE BY A 2685 02:13:47,435 --> 02:13:57,779 POSTDOC IN THE LAB. 2686 02:14:05,820 --> 02:14:08,756 THEY HAD BETWEEN 20 AND 30 2687 02:14:08,756 --> 02:14:09,023 VARIANTS. 2688 02:14:09,023 --> 02:14:10,391 SO PEOPLE ARE CARING A LOT OF 2689 02:14:10,391 --> 02:14:11,058 VARIANTS OVER THE 18 GENES THAT 2690 02:14:11,058 --> 02:14:16,831 ARE THERE. 2691 02:14:16,831 --> 02:14:17,899 ILLUSTRATED PREVIOUSLY. 2692 02:14:17,899 --> 02:14:22,003 WHEN YOU LOOK AT WHERE THE 2693 02:14:22,003 --> 02:14:24,372 VARIANTS ARE OCCURRING, WE CAN 2694 02:14:24,372 --> 02:14:25,907 SEE PERHAPS AS MAY BE EXPECTED 2695 02:14:25,907 --> 02:14:28,576 THE VAST MAJORITY OF THE 2696 02:14:28,576 --> 02:14:30,244 VARIANTS ARE OCCURRING IN THE 2697 02:14:30,244 --> 02:14:40,721 COMPLEMENT RECEPTOR 1 GENE. 2698 02:14:42,523 --> 02:14:45,526 MANY ARE HAVING AN EFFECT ON 2699 02:14:45,526 --> 02:14:47,328 PROTEIN BUT DON'T KNOW IF THE 2700 02:14:47,328 --> 02:14:48,863 AFFECT IS STRONG OR NOT BUT SEE 2701 02:14:48,863 --> 02:14:52,500 A NUMBER OF VARIANTS MUCH MORE 2702 02:14:52,500 --> 02:14:53,835 DELETERIOUS TO THE PROTEIN. 2703 02:14:53,835 --> 02:14:57,505 YOU CAN SEE THOSE REPRESENTED IN 2704 02:14:57,505 --> 02:15:00,575 DIFFERENT COLORS INCLUDING SOME 2705 02:15:00,575 --> 02:15:03,611 THAT ARE NOVEL HAVEN'T BEEN 2706 02:15:03,611 --> 02:15:05,613 RECORDED PREVIOUSLY AND IN MORE 2707 02:15:05,613 --> 02:15:08,416 THAN ONE OF THE GROUPS WE HAVE. 2708 02:15:08,416 --> 02:15:11,152 THERE'S A SUBSTANTIVE AMOUNT OF 2709 02:15:11,152 --> 02:15:11,752 VARIATION THAT OCCURS IN THE 2710 02:15:11,752 --> 02:15:12,820 GENES IN THE INDIVIDUALS AND WE 2711 02:15:12,820 --> 02:15:15,890 TRY TO RELATE THAT BACK TO THE 2712 02:15:15,890 --> 02:15:18,326 ANTIGEN ABOUT A THIRD ARE 2713 02:15:18,326 --> 02:15:23,097 WELL-KNOWN SORT OF VARIANTS THAT 2714 02:15:23,097 --> 02:15:23,364 INTERACT. 2715 02:15:23,364 --> 02:15:25,900 THERE'S A GROUP WHERE WE SEE A 2716 02:15:25,900 --> 02:15:27,635 VARIANT AND CHANGE AND DON'T 2717 02:15:27,635 --> 02:15:29,203 KNOW THE PARTICULAR IMPACT OF 2718 02:15:29,203 --> 02:15:31,706 THAT AND THERE'S A SUB GROUP 2719 02:15:31,706 --> 02:15:33,407 WHERE WE'VE NEVER SEEN THAT 2720 02:15:33,407 --> 02:15:35,276 VARIANT BEFORE AND DON'T KNOW 2721 02:15:35,276 --> 02:15:37,378 WHAT IT MEANS MOVING FORWARD. 2722 02:15:37,378 --> 02:15:41,082 THE BIG PICTURE TAKE HOME IS 2723 02:15:41,082 --> 02:15:41,983 THERE'S A LOT OF VARIATION WE'RE 2724 02:15:41,983 --> 02:15:42,550 TRYING TO CHARACTERIZE AND 2725 02:15:42,550 --> 02:15:52,760 UNDERSTAND. 2726 02:16:00,401 --> 02:16:02,703 THE BRAZILIAN POPULATION HAVE 2727 02:16:02,703 --> 02:16:04,472 EUROPEAN AND NATIVE AMERICAN 2728 02:16:04,472 --> 02:16:08,242 ASSENCESTRY AND THAT VARIES ACR 2729 02:16:08,242 --> 02:16:08,809 THE COUNTRY WHERE YOU FIND 2730 02:16:08,809 --> 02:16:12,747 PROPORTIONS. 2731 02:16:12,747 --> 02:16:14,048 THIS IS WHAT IT LOOKS LIKE ON A 2732 02:16:14,048 --> 02:16:14,715 POPULATION LEVEL. 2733 02:16:14,715 --> 02:16:16,817 WE CAN USE GENETICS TO 2734 02:16:16,817 --> 02:16:18,319 UNDERSTAND WHAT IT LOOKS LIKE ON 2735 02:16:18,319 --> 02:16:22,590 AN INDIVIDUAL LEVEL. 2736 02:16:22,590 --> 02:16:24,558 THIS IS A LINE GRAPH AND EACH 2737 02:16:24,558 --> 02:16:26,394 SAY DIFFERENT INDIVIDUAL. 2738 02:16:26,394 --> 02:16:30,331 EACH COLOR REPRESENTS THE 2739 02:16:30,331 --> 02:16:31,666 ANCESTRY. 2740 02:16:31,666 --> 02:16:34,101 THE GREEN IS AFRICAN AND THE 2741 02:16:34,101 --> 02:16:36,337 EUROPEAN IN BLUE. 2742 02:16:36,337 --> 02:16:37,071 INDIVIDUALS BOTH WITH SICKLE 2743 02:16:37,071 --> 02:16:39,407 CELL AND WHO DON'T HAVE SICKLE 2744 02:16:39,407 --> 02:16:41,876 CELL HAVE A COMBINATION IN 2745 02:16:41,876 --> 02:16:49,884 VARYING AMOUNTS OF THE PARTIALLY 2746 02:16:49,884 --> 02:16:55,489 AFRICAN ANCESTRY AND THERE'S 2747 02:16:55,489 --> 02:16:57,091 SLIGHTLY MORE GREEN HERE THAN 2748 02:16:57,091 --> 02:17:00,194 THE NON-SICKLE CELL INDIVIDUALS. 2749 02:17:00,194 --> 02:17:01,896 SO WHAT WE'RE INTERESTED IN IS 2750 02:17:01,896 --> 02:17:05,132 HOW DOES THIS ANCESTRY RELATE TO 2751 02:17:05,132 --> 02:17:07,268 THE GENETIC GENES THAT WE ARE 2752 02:17:07,268 --> 02:17:08,469 INTERESTED IN IN THE GENETIC 2753 02:17:08,469 --> 02:17:10,204 VARIATION UNDER LIES THAT. 2754 02:17:10,204 --> 02:17:12,473 IN TRUTH WHAT WE WANT IS MORE OF 2755 02:17:12,473 --> 02:17:14,475 THIS KIND OF APPROACH WHICH IS 2756 02:17:14,475 --> 02:17:17,878 SOMETHING WE CAN DO NOW TO PAINT 2757 02:17:17,878 --> 02:17:20,047 THE GENOME SO EACH CHROMOSOME 2758 02:17:20,047 --> 02:17:21,515 YOU CAN UNDERSTAND WHETHER 2759 02:17:21,515 --> 02:17:22,717 YOU'RE PROMINENTLY GOING TO BE 2760 02:17:22,717 --> 02:17:26,487 EUROPEAN AT THE SITE OR MOSTLY 2761 02:17:26,487 --> 02:17:27,755 AFRICAN AT THE SITE. 2762 02:17:27,755 --> 02:17:32,426 YOU CAN TELL INDIVIDUALS WHO 2763 02:17:32,426 --> 02:17:33,861 HAVE SICKLE CELL TEND TO HAVE 2764 02:17:33,861 --> 02:17:36,497 AFRICAN ANCESTRY OVER THE BETA 2765 02:17:36,497 --> 02:17:39,734 GLOBIN GENE AND THOSE WHO DON'T 2766 02:17:39,734 --> 02:17:39,967 DO NOT. 2767 02:17:39,967 --> 02:17:41,869 WE CAN TRY TO USE THAT 2768 02:17:41,869 --> 02:17:46,874 INFORMATION TO UNDERSTAND 2769 02:17:46,874 --> 02:17:47,875 WHETHER ANCESTRY INFLUENCES YOUR 2770 02:17:47,875 --> 02:17:48,342 RISK. 2771 02:17:48,342 --> 02:17:50,745 WE LOOK AT THE VARIOUS 18 GENES 2772 02:17:50,745 --> 02:17:55,182 YOU CAN SEE ON AVERAGE MOST OF 2773 02:17:55,182 --> 02:17:56,784 THEM HAVE AROUND 30% AFRICAN 2774 02:17:56,784 --> 02:17:57,918 ANCESTRY OVER THAT PARTICULAR 2775 02:17:57,918 --> 02:18:06,694 REGION OF THE GENOME. 2776 02:18:06,694 --> 02:18:11,032 AND YOU CAN SEE AS ALL OF YOU 2777 02:18:11,032 --> 02:18:13,934 KNOW THE ALLELE IS PARTICULARLY 2778 02:18:13,934 --> 02:18:15,369 COMMON AMONG INDIVIDUALS WITH 2779 02:18:15,369 --> 02:18:20,374 AFRICAN ANCESTRY AND HAVING AN 2780 02:18:20,374 --> 02:18:23,044 INCREASED ANCESTRY AT THIS LOCUS 2781 02:18:23,044 --> 02:18:23,944 MAY BE OF IMPORTANCE. 2782 02:18:23,944 --> 02:18:28,949 WHEN WE LOCK AT THE ANCESTRY IN 2783 02:18:28,949 --> 02:18:30,151 NON-SICKLE CELL INDIVIDUALS THEY 2784 02:18:30,151 --> 02:18:34,522 HAVE A HIGHER PROPORTION OF 2785 02:18:34,522 --> 02:18:36,657 AFRICAN ANCESTRY AND PERHAPS AS 2786 02:18:36,657 --> 02:18:40,594 A RESULT WE CAN SEE FOR INSTANCE 2787 02:18:40,594 --> 02:18:41,896 THEY HAVE A VARIANT EXPECTED TO 2788 02:18:41,896 --> 02:18:48,402 HAVE AN IMPACT UPON THE GENE BUT 2789 02:18:48,402 --> 02:18:57,211 THE VARIANCE IS SLIGHTLY HIGHER 2790 02:18:57,211 --> 02:18:57,912 WITH INDIVIDUALS WITH SICKLE 2791 02:18:57,912 --> 02:18:59,713 CELL DISEASE CONTRIBUTE TO THE 2792 02:18:59,713 --> 02:19:02,450 INCREASED RISK PARTLY BECAUSE SO 2793 02:19:02,450 --> 02:19:04,318 MANY RED CELL ANTIGENS ARE 2794 02:19:04,318 --> 02:19:05,886 IMPORTANT AND SECTORS ARE 2795 02:19:05,886 --> 02:19:09,924 IMPORTANT IN MALARIA AND MALARIA 2796 02:19:09,924 --> 02:19:13,360 PROTECTION. 2797 02:19:13,360 --> 02:19:18,265 WE ALSO KNOW THE RISK IS NOT 2798 02:19:18,265 --> 02:19:18,466 EVEN. 2799 02:19:18,466 --> 02:19:20,534 SO EVEN WITHIN INDIVIDUALS WITH 2800 02:19:20,534 --> 02:19:21,602 SICKLE CELL DISEASE THERE'S A 2801 02:19:21,602 --> 02:19:24,371 VARIATION IN TERMS OF 2802 02:19:24,371 --> 02:19:25,906 INDIVIDUALS WHO MIGHT DEVELOP 2803 02:19:25,906 --> 02:19:27,374 ANTIBODIES AND MIGHT NOT. 2804 02:19:27,374 --> 02:19:29,143 THIS IS NOT PURELY A FUNCTION OF 2805 02:19:29,143 --> 02:19:32,813 JUST WHETHER OR NOT HAVE YOU A 2806 02:19:32,813 --> 02:19:34,949 MISMATCH BUT IN FACT THE VAST 2807 02:19:34,949 --> 02:19:36,484 MAJORITY OF INDIVIDUALS 2808 02:19:36,484 --> 02:19:37,885 GENERALLY DON'T MAKE ANTIBODIES 2809 02:19:37,885 --> 02:19:40,054 BUT THERE'S A SUBSET OF 2810 02:19:40,054 --> 02:19:41,422 INDIVIDUALS WHO SEEM TO MAKE 2811 02:19:41,422 --> 02:19:43,124 ANTIBODIES ALMOST EVERY TIME 2812 02:19:43,124 --> 02:19:48,362 THEY GET A TRANSFUSION LEADING 2813 02:19:48,362 --> 02:19:50,965 TO THIS ALLOIMMUNIZATION 2814 02:19:50,965 --> 02:19:51,232 RESPONDER. 2815 02:19:51,232 --> 02:19:54,135 AND THE RESPONDER PHENOMENON IN 2816 02:19:54,135 --> 02:19:55,402 TURN IS A COMPLEX TRAIT. 2817 02:19:55,402 --> 02:19:56,604 THERE'S A NUMBER OF FACTORS THAT 2818 02:19:56,604 --> 02:19:58,372 CONTRIBUTE TO THIS. 2819 02:19:58,372 --> 02:20:00,808 THINGS LIKE AGE OF THE UNITS, 2820 02:20:00,808 --> 02:20:04,578 NUMBER OF TRANSFUSIONS ONE HAS 2821 02:20:04,578 --> 02:20:07,515 RECEIVED, THERE'S A GREAT DEAL 2822 02:20:07,515 --> 02:20:10,985 OF INTEREST IN THE IMMUNE 2823 02:20:10,985 --> 02:20:11,886 PRIMING OF SICKLE CELL DISEASE 2824 02:20:11,886 --> 02:20:13,287 AND HIGHLY INFLAMMATORY STATES 2825 02:20:13,287 --> 02:20:14,255 MAY CONTRIBUTE TO THIS AS WELL. 2826 02:20:14,255 --> 02:20:16,524 AND SO WE WANTED TO TAKE AN 2827 02:20:16,524 --> 02:20:17,892 APPROACH THAT WOULD ASK THE 2828 02:20:17,892 --> 02:20:20,528 QUESTION THAT'S OFTEN ASK OF 2829 02:20:20,528 --> 02:20:24,398 COMPLEX TRAITS WHICH IS THERE 2830 02:20:24,398 --> 02:20:29,170 SOMETHING ABOUT RECIPIENTS 2831 02:20:29,170 --> 02:20:30,304 GENOME OTHERWISE THAT MAY 2832 02:20:30,304 --> 02:20:31,305 INCREASE IN RESPONDING. 2833 02:20:31,305 --> 02:20:32,840 WE HAD ACCESS TO INDIVIDUALS WHO 2834 02:20:32,840 --> 02:20:37,878 HAD BEEN TRANSFUSED THROUGH THE 2835 02:20:37,878 --> 02:20:41,182 BLOOD BANKING IN SHREVEPORT, 2836 02:20:41,182 --> 02:20:44,051 LOUISIANA AND SERVE OKLAHOMA, 2837 02:20:44,051 --> 02:20:45,886 ARKANSAS, LOUISIANA AND 2838 02:20:45,886 --> 02:20:47,154 SOUTHEAST TEXAS. 2839 02:20:47,154 --> 02:20:49,690 AND THEY HAD INDIVIDUALS ABOUT 2840 02:20:49,690 --> 02:20:50,357 300 INDIVIDUALS ROUGHLY SPLIT 2841 02:20:50,357 --> 02:20:52,226 BETWEEN RESPONDERS AND 2842 02:20:52,226 --> 02:20:53,494 NON-RESPONDERS AND YOU CAN SEE 2843 02:20:53,494 --> 02:21:03,404 THE DEMOGRAPHICS OF THE CARE. 2844 02:21:03,404 --> 02:21:04,772 AND WE WERE ABLE TO GENOTYPE THE 2845 02:21:04,772 --> 02:21:06,106 INDIVIDUALS IN A STANDARD 2846 02:21:06,106 --> 02:21:08,709 GENOTYPING CHIP AND LOOK FOR 2847 02:21:08,709 --> 02:21:11,579 EVIDENCE OF ASSOCIATION. 2848 02:21:11,579 --> 02:21:13,681 YOU SEE IN THE PLOT THE HIGHER 2849 02:21:13,681 --> 02:21:15,983 THE DOT THE MORE SIGNIFICANT AND 2850 02:21:15,983 --> 02:21:22,089 YOU CAN SEE THESE TWO LOCI 2851 02:21:22,089 --> 02:21:28,629 CHROMOSOME 2 AND 5 WE FIND 2852 02:21:28,629 --> 02:21:30,030 ALMOST GENOME WIDE SIGNIFICANCE 2853 02:21:30,030 --> 02:21:31,999 AT THE PARTICULAR SNIP AND GIVEN 2854 02:21:31,999 --> 02:21:34,368 THE SAMPLE SIZE AND THE FACT 2855 02:21:34,368 --> 02:21:38,005 THAT WE'RE IN AFRICAN ASSENCEST 2856 02:21:38,005 --> 02:21:39,707 MAY NOT HAVE CAPTURED EVERYTHING 2857 02:21:39,707 --> 02:21:42,176 AND WE DECIDED TO SEE IF WE CAN 2858 02:21:42,176 --> 02:21:43,410 REPLICATE OUR ASSOCIATION. 2859 02:21:43,410 --> 02:21:46,714 WE HAD ACCESS TO ANOTHER COHORT 2860 02:21:46,714 --> 02:21:50,284 OF INDIVIDUALS FROM CHICAGO WHO 2861 02:21:50,284 --> 02:21:52,286 ALSO WERE DIVIDED INTO 2862 02:21:52,286 --> 02:21:54,088 RESPONDERS AND NON RESPONDERS 2863 02:21:54,088 --> 02:21:57,258 USING THE SAME CLINICAL CRITERIA 2864 02:21:57,258 --> 02:21:59,560 OF HAVING CLINICALLY SIGNIFICANT 2865 02:21:59,560 --> 02:22:01,862 ANTIBODIES AFTER MULTIPLE 2866 02:22:01,862 --> 02:22:03,964 TRANSFUSIONS AND YOU CAN SEE THE 2867 02:22:03,964 --> 02:22:05,833 DIFFERENCES AND THE REPLICATION 2868 02:22:05,833 --> 02:22:09,903 COHORT IS MUCH SMALLER THAN OUR 2869 02:22:09,903 --> 02:22:15,009 DISCOVERY SET. 2870 02:22:15,009 --> 02:22:16,210 WHEN WE LOOKED AT THIS WE FOUND 2871 02:22:16,210 --> 02:22:19,780 A SIMILAR ASSOCIATION WHICH IS 2872 02:22:19,780 --> 02:22:20,914 THE FREQUENCY OF THE VARIANT IN 2873 02:22:20,914 --> 02:22:23,350 OUR CASES IS MUCH HIGHER THAN IN 2874 02:22:23,350 --> 02:22:25,319 THE CONTROLS IN DISCOVERY AND 2875 02:22:25,319 --> 02:22:26,253 REPLICATION SET AND THAT'S 2876 02:22:26,253 --> 02:22:27,121 HIGHLY SIGNIFICANT WHEN YOU PUT 2877 02:22:27,121 --> 02:22:31,659 THE TWO OF THEM TOGETHER WITH 2878 02:22:31,659 --> 02:22:33,694 IMPARTING A FAIRLY ROBUST ODDS 2879 02:22:33,694 --> 02:22:36,397 OF BECOMING AN ALLOIMMUNIZATION 2880 02:22:36,397 --> 02:22:37,464 RESPONDER. 2881 02:22:37,464 --> 02:22:39,867 SECONDARILY, WE ALSO HAD THE 2882 02:22:39,867 --> 02:22:41,969 OPPORTUNITY TO LOOK AT 2883 02:22:41,969 --> 02:22:44,772 INDIVIDUALS WHO MADE MULTIPLE 2884 02:22:44,772 --> 02:22:48,075 ANTIBODIES MORE THAN THREE ALLO 2885 02:22:48,075 --> 02:22:49,910 ANTIBODIES LOOKING AT BEYOND 2886 02:22:49,910 --> 02:22:53,881 THAT AND WE CAN SEE WE FIND MOST 2887 02:22:53,881 --> 02:22:57,685 OF THE SIGNAL IS DRIVEN AND THE 2888 02:22:57,685 --> 02:23:00,387 COHORT HAS BEEN DRIVEN BY THE 2889 02:23:00,387 --> 02:23:04,158 ANTIBODY FORMERS. 2890 02:23:04,158 --> 02:23:05,893 AGAIN THE SAME FREQUENCY 2891 02:23:05,893 --> 02:23:07,494 DIFFERENCES AND STATISTICAL 2892 02:23:07,494 --> 02:23:08,329 SIGNIFICANCE. 2893 02:23:08,329 --> 02:23:13,100 SO INTERESTINGLY WHEN WE LOOK AT 2894 02:23:13,100 --> 02:23:15,469 THIS ON CHROMOSOME 5 YOU CAN SEE 2895 02:23:15,469 --> 02:23:17,604 THE FREQUENCY IN CASES AND 2896 02:23:17,604 --> 02:23:19,807 CONTROLS WHEN WE LOOK GLOBALLY 2897 02:23:19,807 --> 02:23:21,075 AND AVERAGE THE BIG DATABASES 2898 02:23:21,075 --> 02:23:23,043 IT'S ABOUT 2% WHICH IS KIND OF 2899 02:23:23,043 --> 02:23:25,279 WHAT YOU HAVE IN THE CONTROLS. 2900 02:23:25,279 --> 02:23:27,715 IF HOWEVER, YOU BREAK THAT DOWN 2901 02:23:27,715 --> 02:23:31,151 AND LOOK AT FREQUENCY IN THE 2902 02:23:31,151 --> 02:23:32,619 DATABASES AMONG WEST AFRICAN 2903 02:23:32,619 --> 02:23:33,887 INDIVIDUALS IT'S ALMOST 10% AND 2904 02:23:33,887 --> 02:23:35,155 COMPLETELY ABSENT FROM 2905 02:23:35,155 --> 02:23:35,656 INDIVIDUALS OF EUROPEAN 2906 02:23:35,656 --> 02:23:37,558 ANCESTRY. 2907 02:23:37,558 --> 02:23:38,992 SO IT WON'T BE A SURPRISE THAT 2908 02:23:38,992 --> 02:23:40,728 AT THIS POINT WE START TO THINK 2909 02:23:40,728 --> 02:23:42,963 ABOUT CAN WE INTRODUCE OUR SAME 2910 02:23:42,963 --> 02:23:45,566 SET OF MODELS OF THINKING ABOUT 2911 02:23:45,566 --> 02:23:50,170 ADD MIXTURE WHICH OCCURS IN THE 2912 02:23:50,170 --> 02:23:51,472 INDIVIDUALS WITH SICKLE CELL 2913 02:23:51,472 --> 02:23:53,774 DISEASE AND TRY TO UNDERSTAND 2914 02:23:53,774 --> 02:23:54,408 THE CONTRIBUTION OF THE VARIANT 2915 02:23:54,408 --> 02:23:58,679 TO DISEASE. 2916 02:23:58,679 --> 02:24:02,383 AND SO ON AVERAGE MOST OF 2917 02:24:02,383 --> 02:24:08,122 AFRICAN AMERICANS HAVE 20% TO 2918 02:24:08,122 --> 02:24:09,323 25% EUROPEAN ANCESTRY IN THE 2919 02:24:09,323 --> 02:24:10,858 COHORT IT'S SLIGHTLY LOWER 2920 02:24:10,858 --> 02:24:14,428 CONSISTENT WITH THE IDEA WE'RE 2921 02:24:14,428 --> 02:24:15,829 GENERALLY MORE AFRICAN ANCESTRY 2922 02:24:15,829 --> 02:24:17,765 IN THE INDIVIDUAL AND SEE WHAT 2923 02:24:17,765 --> 02:24:19,666 THAT LOOKS LIKE IN CHROMOSOME 11 2924 02:24:19,666 --> 02:24:20,434 OUR BENCH MARCH. 2925 02:24:20,434 --> 02:24:24,171 WE CAN SEE AT THE BETA GLOBIN 2926 02:24:24,171 --> 02:24:29,543 LOCUS BOTH CASES AND CONTROLS 2927 02:24:29,543 --> 02:24:31,678 THEY'RE ALMOST 100% AFRICAN 2928 02:24:31,678 --> 02:24:34,047 ANCESTRY AND SEE THE GENOME WIDE 2929 02:24:34,047 --> 02:24:34,281 AVERAGE. 2930 02:24:34,281 --> 02:24:36,283 WHEN WE LOOK AT CHROMOSOME 5 WE 2931 02:24:36,283 --> 02:24:38,652 CAN SEE THERE'S NOT A SYSTEMATIC 2932 02:24:38,652 --> 02:24:41,221 DIFFERENCE BETWEEN THE CASES AND 2933 02:24:41,221 --> 02:24:41,722 CONTROLS. 2934 02:24:41,722 --> 02:24:43,223 WHICH IS ACTUALLY GOOD BECAUSE 2935 02:24:43,223 --> 02:24:44,925 WHAT WE CAN DO THEN IS ADJUST 2936 02:24:44,925 --> 02:24:46,860 OUR ASSOCIATION BASED ON THE 2937 02:24:46,860 --> 02:24:48,262 PARTICULAR SNIPBACK GROUND THAT 2938 02:24:48,262 --> 02:24:48,796 WE HAVE. 2939 02:24:48,796 --> 02:24:51,365 AND WHEN WE DO THAT AGAIN YOU 2940 02:24:51,365 --> 02:24:54,435 CAN SEE AFRICAN ANCESTRY IS 2941 02:24:54,435 --> 02:24:58,038 CARRYING THE ASSOCIATION WHEREAS 2942 02:24:58,038 --> 02:25:00,441 INDIVIDUALS AND CONDITION ON 2943 02:25:00,441 --> 02:25:01,341 EUROPEAN ANCESTRY DON'T SEE THE 2944 02:25:01,341 --> 02:25:03,210 SIGNAL AND IT'S THE ONLY SIGNAL 2945 02:25:03,210 --> 02:25:05,712 WE CAN SEE ACROSS THE GENOME. 2946 02:25:05,712 --> 02:25:08,348 SO FAR WE'VE LOOKED AT MULTIPLE 2947 02:25:08,348 --> 02:25:11,985 POPULATIONS AND DATABASES AND 2948 02:25:11,985 --> 02:25:13,554 AGAIN THIS VARIANT VARIES 2949 02:25:13,554 --> 02:25:18,725 BETWEEN 5% AND 10% OF AFRICAN 2950 02:25:18,725 --> 02:25:19,927 ANCESTRY AND HAVEN'T SEEN IT 2951 02:25:19,927 --> 02:25:21,795 OUTSIDE THE GROUPS. 2952 02:25:21,795 --> 02:25:25,899 THE RECIPIENT GENETICS CAN BE A 2953 02:25:25,899 --> 02:25:29,570 CONTRIBUTOR TO WHY SOME 2954 02:25:29,570 --> 02:25:30,204 INDIVIDUALS ARE ALLOIMMUNIZATION 2955 02:25:30,204 --> 02:25:30,771 RESPONDERS WITH SICKLE CELL 2956 02:25:30,771 --> 02:25:33,106 DISEASE. 2957 02:25:33,106 --> 02:25:34,441 SO WE ARE TRYING TO TAKE THAT 2958 02:25:34,441 --> 02:25:36,410 FORWARD BY THINKING MORE WITH 2959 02:25:36,410 --> 02:25:37,110 THE INDIVIDUAL LOCUS AND THE 2960 02:25:37,110 --> 02:25:41,882 GENE THAT WE FIND THERE. 2961 02:25:41,882 --> 02:25:45,419 SO THIS PARTICULAR SNIP OCCURS 2962 02:25:45,419 --> 02:25:49,857 OVER AN ENHANCER AND BIND TO THE 2963 02:25:49,857 --> 02:25:52,426 REGULATORY ELEMENTS AND IT 2964 02:25:52,426 --> 02:25:53,894 OCCURS RIGHT IN THE LONG 2965 02:25:53,894 --> 02:25:55,195 NON-CODING GENE. 2966 02:25:55,195 --> 02:25:57,898 THIS IS THE LINK GENE NOT NOT A 2967 02:25:57,898 --> 02:25:59,733 LOT IS KNOWN ABOUT THE GENE 2968 02:25:59,733 --> 02:26:01,168 EXCEPT FOR THE IDEA IT'S 2969 02:26:01,168 --> 02:26:03,270 EXPRESSED IN BOTH THE LIVER AND 2970 02:26:03,270 --> 02:26:08,375 THE SPLEEN. 2971 02:26:08,375 --> 02:26:12,913 WHICH AGAIN ARE SITES OF 2972 02:26:12,913 --> 02:26:23,423 HEMATOPOYS -- HEMATOPOIESIS 2973 02:26:24,324 --> 02:26:26,126 BREAKDOWN AND THERE'S GENE ALSO 2974 02:26:26,126 --> 02:26:27,361 HAS EXPRESSION IN THE LIVER AND 2975 02:26:27,361 --> 02:26:29,696 WE HAD TO GO BACK TO THE 2976 02:26:29,696 --> 02:26:31,965 TEXTBOOKS AND THINK OF WHAT IT 2977 02:26:31,965 --> 02:26:33,233 LOOKS LIKE IN THIS CONTEXT. 2978 02:26:33,233 --> 02:26:37,838 WE'RE FORTUNATE TO BE ABLE TO DO 2979 02:26:37,838 --> 02:26:40,774 CHEMICAL STRAINING FOR THIS 2980 02:26:40,774 --> 02:26:42,142 RECEPTOR PROTEIN IN SUBSEQUENT 2981 02:26:42,142 --> 02:26:46,980 SAMPLES AND WE CAN SEE THE GOLD 2982 02:26:46,980 --> 02:26:49,416 COLOR HERE IN THE RED IS PICKING 2983 02:26:49,416 --> 02:26:52,052 UP THE ANTIBODIES AND ANTIBODY 2984 02:26:52,052 --> 02:26:52,853 POSITIVE WHEREAS THE WHITE YOU 2985 02:26:52,853 --> 02:26:55,389 DON'T SEE MUCH OF IT. 2986 02:26:55,389 --> 02:26:57,891 IN THE RED MOST THE PROTEIN 2987 02:26:57,891 --> 02:27:00,427 WE'RE PICKING UP IS WITHIN THE 2988 02:27:00,427 --> 02:27:02,396 LYMPHOCYTES THAT ARE THERE. 2989 02:27:02,396 --> 02:27:04,398 SO AS WE LOOKED CLOSER INTO THE 2990 02:27:04,398 --> 02:27:08,402 GENE IT TURNS OUT THAT IT 2991 02:27:08,402 --> 02:27:13,807 ENCODES THE ALPHA IS BETA 2992 02:27:13,807 --> 02:27:16,877 RECEPTOR AND THE ROLE IN THE 2993 02:27:16,877 --> 02:27:22,282 SPLEEN IS NOT CLEARLY DELINEATED 2994 02:27:22,282 --> 02:27:23,817 OR CELLS OR CIRCUMSTANCES BUT 2995 02:27:23,817 --> 02:27:25,118 THERE'S A GROWING BODY OF 2996 02:27:25,118 --> 02:27:27,521 EVIDENCE THEY CAN MODULATE THE 2997 02:27:27,521 --> 02:27:28,989 INNATE IMMUNITY. 2998 02:27:28,989 --> 02:27:31,625 SO IT'S A PRETTY DECENT 2999 02:27:31,625 --> 02:27:31,992 CANDIDATE. 3000 02:27:31,992 --> 02:27:34,294 HOWEVER IT TURNS OUT THERE'S A 3001 02:27:34,294 --> 02:27:35,529 BETTER CANDIDATE A LITTLE BIT 3002 02:27:35,529 --> 02:27:36,229 AWAY. 3003 02:27:36,229 --> 02:27:39,132 SO ABOUT 500K UPSTREAM THERE'S 3004 02:27:39,132 --> 02:27:46,540 AN IL12B GENE AND IL12B GENE IS 3005 02:27:46,540 --> 02:27:49,543 IN THE SAME TYPO GRAPHICAL 3006 02:27:49,543 --> 02:27:52,646 ASSOCIATED DOMAIN ON 4D 3007 02:27:52,646 --> 02:27:53,914 CONFIRMATION AND THE GENOME 3008 02:27:53,914 --> 02:27:56,617 FOLDS IN THE SAME POCKET AS THE 3009 02:27:56,617 --> 02:28:00,187 ENHANCER AND THE COLLABORATOR 3010 02:28:00,187 --> 02:28:03,824 WAS FORTUNATE TO LOOK AT THIS IN 3011 02:28:03,824 --> 02:28:05,926 PERIPHERAL B CELLS AND COULD 3012 02:28:05,926 --> 02:28:07,194 DEMONSTRATE A PHYSICAL INTERACT 3013 02:28:07,194 --> 02:28:09,096 BETWEEN THE ENHANCER AND 3014 02:28:09,096 --> 02:28:13,400 PROMOTER OF THE IL12B GENE. 3015 02:28:13,400 --> 02:28:17,437 SO THAT WAS A POSITIVE THING. 3016 02:28:17,437 --> 02:28:20,173 THEN WE WAS ABLE TO SHOW 3017 02:28:20,173 --> 02:28:21,908 PROMINENT EXPRESSION IS IN 3018 02:28:21,908 --> 02:28:25,212 MONOCYTES AND B CELLS AND LESS 3019 02:28:25,212 --> 02:28:27,581 SO IN T CELLS AND OTHER RELATED 3020 02:28:27,581 --> 02:28:28,115 CELLS. 3021 02:28:28,115 --> 02:28:30,450 THAT MADE IT LOOK LIKE A VIABLE 3022 02:28:30,450 --> 02:28:32,919 CANDIDATE ESPECIALLY WHEN YOU 3023 02:28:32,919 --> 02:28:34,254 CONSIDER IF YOU THINK ABOUT 3024 02:28:34,254 --> 02:28:40,093 WHERE ENHANCERS AND THIS IL12B 3025 02:28:40,093 --> 02:28:41,294 GENE IT'S KNOWN TO BE INVOLVED 3026 02:28:41,294 --> 02:28:45,399 IN INTRACELLULAR PATHOGEN 3027 02:28:45,399 --> 02:28:45,899 RESPONSES. 3028 02:28:45,899 --> 02:28:47,868 SO, STIMULATES THE IMMUNE 3029 02:28:47,868 --> 02:28:49,903 RESPONSE WITH THE PATHOGENS 3030 02:28:49,903 --> 02:28:53,340 INCLUDING MICROPLASMAS AND IN 3031 02:28:53,340 --> 02:28:55,475 FACT JUST UP STREAM THERE'S A 3032 02:28:55,475 --> 02:28:57,511 GENETIC VARIANT ASSOCIATED WITH 3033 02:28:57,511 --> 02:29:00,180 RESISTANCE TO TB IN POPULATIONS 3034 02:29:00,180 --> 02:29:05,619 FROM EAST AFRICA SO UGANDA AND 3035 02:29:05,619 --> 02:29:07,154 TANZANIA AND PERHAPS IT'S AT THE 3036 02:29:07,154 --> 02:29:11,692 CRUX YOU MAY BE PROTECTED FROM 3037 02:29:11,692 --> 02:29:13,894 HAVING TB BUT LIKELY TO HAVE 3038 02:29:13,894 --> 02:29:16,563 ANOTHER IMMUNIZATION RESPONSE IN 3039 02:29:16,563 --> 02:29:17,931 RED CELLS AND THAT'S ALSO 3040 02:29:17,931 --> 02:29:19,132 CONSISTENT PERHAPS WITH SOME OF 3041 02:29:19,132 --> 02:29:22,569 THE MORE RECENT FINDINGS ABOUT 3042 02:29:22,569 --> 02:29:23,670 PRIOR IMMUNIZATION OTHERS HAVE 3043 02:29:23,670 --> 02:29:27,274 CONTRIBUTED. 3044 02:29:27,274 --> 02:29:29,109 SO WE HAVE BEEN THEN THINKING 3045 02:29:29,109 --> 02:29:31,645 HOW WE CAN TAKE THIS FORWARD 3046 02:29:31,645 --> 02:29:33,613 MORE AND WE DEVELOPED THE 3047 02:29:33,613 --> 02:29:35,015 WORKING MODEL THAT IN THE FACE 3048 02:29:35,015 --> 02:29:36,717 OF THIS KIND OF TRANSFUSION YOU 3049 02:29:36,717 --> 02:29:39,619 GET THIS INTERACTION THAT LEADS 3050 02:29:39,619 --> 02:29:44,291 TO MORE OF P4 AS THE IL12 3051 02:29:44,291 --> 02:29:44,524 PROTEIN. 3052 02:29:44,524 --> 02:29:49,996 YOU GET MORE OF THE SECRETION. 3053 02:29:49,996 --> 02:29:51,498 THAT INFLUENCES THE ANTIBODIES 3054 02:29:51,498 --> 02:29:54,601 AND IN INDIVIDUALS NEGATIVE WE 3055 02:29:54,601 --> 02:29:56,403 WOULD HAVE THAT OCCURRING. 3056 02:29:56,403 --> 02:29:59,740 AND SO WE'VE BEEN TRYING TO 3057 02:29:59,740 --> 02:30:00,774 EVALUATE THIS IN TERMS OF AT 3058 02:30:00,774 --> 02:30:03,143 LEAST STARTING AND LOOKING AT 3059 02:30:03,143 --> 02:30:04,411 THE FUNCTIONAL RELATIONSHIP 3060 02:30:04,411 --> 02:30:07,414 BETWEEN THE VARIANT ITSELF, 3061 02:30:07,414 --> 02:30:10,417 ENHANCER AND THE GENE AND THE 3062 02:30:10,417 --> 02:30:16,223 KEY IS ASCERTAINING INDIVIDUALS 3063 02:30:16,223 --> 02:30:17,891 WITH THE VARIANT. 3064 02:30:17,891 --> 02:30:21,695 WE'VE BEEN COLLABORATING WITH 3065 02:30:21,695 --> 02:30:28,068 DR. MITCHELL AND DR. THEIN TO 3066 02:30:28,068 --> 02:30:32,239 IDENTIFY INDIVIDUALS WITH WHOLE 3067 02:30:32,239 --> 02:30:33,306 SEQUENCING AND LOOKING AT THOSE 3068 02:30:33,306 --> 02:30:34,741 WITH THE VARIANT AND THOSE WHO 3069 02:30:34,741 --> 02:30:36,476 DON'T TO LOOK AT THEIR 3070 02:30:36,476 --> 02:30:38,411 TRANSFUSION RECORDS AND IDENTIFY 3071 02:30:38,411 --> 02:30:39,179 INDIVIDUALS WHO ARE RESPONDERS 3072 02:30:39,179 --> 02:30:40,914 AND NON-RESPONDERS AND THEN 3073 02:30:40,914 --> 02:30:44,651 AFTER TAKING THEIR SAMPLES THEN 3074 02:30:44,651 --> 02:30:51,124 LOOK AT WHAT'S HAPPENING AT THE 3075 02:30:51,124 --> 02:30:54,394 LOCUS USING SINGLE CELL AND 3076 02:30:54,394 --> 02:30:56,863 SEEING WHAT'S HAPPENING IN TERMS 3077 02:30:56,863 --> 02:30:58,698 OF CHROMATIN ACCESSIBILITY AND 3078 02:30:58,698 --> 02:31:00,333 LOOKING AT THE EXPRESSION OF THE 3079 02:31:00,333 --> 02:31:01,868 GENE AND MEASURE THE PROTEIN 3080 02:31:01,868 --> 02:31:03,136 DOWN STREAM AS WELL. 3081 02:31:03,136 --> 02:31:04,404 THIS CONTEXT ALSO ALLOWS US TO 3082 02:31:04,404 --> 02:31:09,910 THINK ABOUT HOW WE CAN INTRODUCE 3083 02:31:09,910 --> 02:31:18,351 TB AS AN ACTOR IN THIS MODEL. 3084 02:31:18,351 --> 02:31:20,053 WE'VE BEEN WORKING THROUGH THE 3085 02:31:20,053 --> 02:31:21,888 PIPELINE FOR THIS MODEL AND SO 3086 02:31:21,888 --> 02:31:24,057 WE CAN AT LEAST GET THE SINGLE 3087 02:31:24,057 --> 02:31:26,326 CELLS AND WE HAVE A PIPELINE FOR 3088 02:31:26,326 --> 02:31:29,830 BEING TO LOOK AT PBMCs AND 3089 02:31:29,830 --> 02:31:32,699 IDENTIFY MONOCYTES FROM THE 3090 02:31:32,699 --> 02:31:35,202 SINGLE CELL SEQUENCING AND CAN 3091 02:31:35,202 --> 02:31:37,704 STIMULATE THE PBMCs TO SEE 3092 02:31:37,704 --> 02:31:41,174 SUFFICIENT ACTIVITY OF IL12 IN 3093 02:31:41,174 --> 02:31:42,709 MATERIALS OF EXPRESSION AT 8 3094 02:31:42,709 --> 02:31:45,745 HOURS SEEMS TO BE MOSTLY IN M 3095 02:31:45,745 --> 02:31:50,417 MONOCYTES AND THEN YOU CAN SEE 3096 02:31:50,417 --> 02:31:52,719 PROTEIN PRODUCTION CORRESPONDS 3097 02:31:52,719 --> 02:31:54,354 TO THAT AGAIN OCCURRING A LITTLE 3098 02:31:54,354 --> 02:31:57,891 BIT LATER THAN THE 3099 02:31:57,891 --> 02:31:59,626 TRANSCRIPTIONAL RESPONSE BUT SEE 3100 02:31:59,626 --> 02:32:02,362 ROBUST PROTEIN REPRESENTS IN 48 3101 02:32:02,362 --> 02:32:08,902 HOURS AT MONOKITE -- MONOCYTES 3102 02:32:08,902 --> 02:32:10,537 AND B CELLS AND DOWN THE LINE WE 3103 02:32:10,537 --> 02:32:11,872 MAY THINK OF BLOCKING THIS 3104 02:32:11,872 --> 02:32:15,909 RESPONSE IN A MORE GENERIC OR 3105 02:32:15,909 --> 02:32:16,877 GENERAL APPROACH TO THE 3106 02:32:16,877 --> 02:32:17,878 ALLOIMMUNIZATION RESPONSE. 3107 02:32:17,878 --> 02:32:20,413 SO WE HAVEN'T QUITE FORGOTTEN 3108 02:32:20,413 --> 02:32:22,616 ABOUT THE OTHER GENE IN THAT 3109 02:32:22,616 --> 02:32:24,217 REGION AND WE'VE ALSO ARE 3110 02:32:24,217 --> 02:32:26,720 BUILDING WAYS OF FIGURING OUT 3111 02:32:26,720 --> 02:32:29,489 THE GENE EXPRESSION FOR THAT 3112 02:32:29,489 --> 02:32:32,592 GENE AND DOING SINGLE CELL WORK 3113 02:32:32,592 --> 02:32:34,327 ON SPLEEN TO COMPLIMENT THE WORK 3114 02:32:34,327 --> 02:32:36,363 IN THE PBMCs. 3115 02:32:36,363 --> 02:32:38,999 SO I'M GOING TO STOP THERE AND 3116 02:32:38,999 --> 02:32:39,633 THEN I'M HAPPY TO TAKE ANY 3117 02:32:39,633 --> 02:32:49,809 QUESTIONS. 3118 02:32:53,914 --> 02:32:55,348 THANK YOU VERY MUCH. 3119 02:32:55,348 --> 02:32:56,483 JUST ONE MINUTE IN CASE FOR 3120 02:32:56,483 --> 02:32:57,150 ANYONE IN THE ROOM. 3121 02:32:57,150 --> 02:32:58,318 THERE'S NO QUESTIONS IN THE CHAT 3122 02:32:58,318 --> 02:33:00,921 BUT JUST A REMINDER IF ANYONE 3123 02:33:00,921 --> 02:33:05,225 WANTS TO POSE A QUESTION PRESS 3124 02:33:05,225 --> 02:33:05,358 LOVE 3125 02:33:08,395 --> 02:33:09,829 LIVE FEEDBACK AND IF NOT WE HAVE 3126 02:33:09,829 --> 02:33:11,831 A FIVE-MINUTE BREAK. 3127 02:33:11,831 --> 02:33:28,937 THANK YOU, FOR THE GREAT TALK. 3128 02:33:28,937 --> 02:33:30,405 WHILE BE CHAIRING THE SESSION 3129 02:33:30,405 --> 02:33:32,007 AND MOVING THINGS ALONG. 3130 02:33:32,007 --> 02:33:37,279 OUR FIRST SPEAKER IS GOING TO BE 3131 02:33:37,279 --> 02:33:39,114 DR. AMANDA BRANDOW. 3132 02:33:39,114 --> 02:33:42,717 A PROFESSOR OF PEDIATRICS IN 3133 02:33:42,717 --> 02:33:45,153 WISCONSIN IN THE SECTIONS OF 3134 02:33:45,153 --> 02:33:48,323 HEMATOLOGY, ONCOLOGY AND BONE 3135 02:33:48,323 --> 02:33:49,991 MARROW TRANSPLANTATION AND 3136 02:33:49,991 --> 02:33:52,260 DIRECT THE CLINICAL RESEARCH 3137 02:33:52,260 --> 02:33:53,895 PROGRAM THERE. 3138 02:33:53,895 --> 02:33:56,164 SHE'S A PHYSICIAN SCIENTIST. 3139 02:33:56,164 --> 02:34:03,305 SHE LOOKS AFTER CHILDREN WITH 3140 02:34:03,305 --> 02:34:08,343 SICKLE CELL DISEASE OTHER 3141 02:34:08,343 --> 02:34:09,444 HEMATOLOGIC CONDITIONS AND HER 3142 02:34:09,444 --> 02:34:14,082 LAB IS INVESTIGATING THE 3143 02:34:14,082 --> 02:34:15,951 UNDERLYING NEUROBIOLOGY OF 3144 02:34:15,951 --> 02:34:17,652 INFLAMMATION AND THE MICROBIOME 3145 02:34:17,652 --> 02:34:19,654 AND THE TRANSPLANTATION AND 3146 02:34:19,654 --> 02:34:22,023 SHE'LL BE WITH US WHEN WE GET TO 3147 02:34:22,023 --> 02:34:22,257 THE END. 3148 02:34:22,257 --> 02:34:32,467 WE'LL START. 3149 02:34:45,981 --> 02:34:47,949 >> TALK ABOUT THE COMPLEXITIES 3150 02:34:47,949 --> 02:34:48,583 AND MANAGEMENT OF PAIN IN SICKLE 3151 02:34:48,583 --> 02:34:52,687 CELL DISEASE. 3152 02:34:52,687 --> 02:34:55,490 MY OBJECTIVES TODAY WILL BE TO 3153 02:34:55,490 --> 02:34:58,193 FIRST DESCRIBE THE COMPLEXITY OF 3154 02:34:58,193 --> 02:34:59,027 SICKLE CELL DISEASE PAIN 3155 02:34:59,027 --> 02:35:01,896 INCLUDING THE TAXONOMY, BIOLOGY 3156 02:35:01,896 --> 02:35:04,432 AND THE COMPLEX OF THE 3157 02:35:04,432 --> 02:35:05,767 PSYCHOSOCIAL MODEL. 3158 02:35:05,767 --> 02:35:10,071 I'LL THEN DISCUSS EVIDENCE-BASED 3159 02:35:10,071 --> 02:35:11,406 GUIDELINES FOR TREATMENT OF 3160 02:35:11,406 --> 02:35:12,974 SICKLE CELL DISEASE PAIN AND 3161 02:35:12,974 --> 02:35:14,943 PHARMACOLOGIC AND 3162 02:35:14,943 --> 02:35:16,878 NON-PHARMACOLOGIC TREATMENTS. 3163 02:35:16,878 --> 02:35:19,347 I'D LIKE TO OPEN WITH THE 3164 02:35:19,347 --> 02:35:19,881 COMPLEXITY OF SICKLE CELL 3165 02:35:19,881 --> 02:35:26,021 DISEASE PAIN. 3166 02:35:26,021 --> 02:35:28,223 THE PAIN TRAJECTORY ACROSS THE 3167 02:35:28,223 --> 02:35:31,893 LIFE SPAN OF INDIVIDUALS WITH 3168 02:35:31,893 --> 02:35:33,161 SICKLE CELL DISEASE IS COMPLEX 3169 02:35:33,161 --> 02:35:34,896 AND EVOLVES WITH TIME AND THE 3170 02:35:34,896 --> 02:35:36,665 YOUNG TODDLER AGE GROUPS THERE'S 3171 02:35:36,665 --> 02:35:39,868 MINIMAL PAIN OR ACUTE PAINFUL 3172 02:35:39,868 --> 02:35:40,602 EVENTS PRESENT. 3173 02:35:40,602 --> 02:35:43,271 THERE'S ACUTE AND INTERMITTENT 3174 02:35:43,271 --> 02:35:45,840 PAINT RESULTING IN EMERGENCY 3175 02:35:45,840 --> 02:35:49,444 ROOM DEPARTMENT VISITS AND 3176 02:35:49,444 --> 02:35:50,145 HOSPITALIZATIONS AND ACUTE 3177 02:35:50,145 --> 02:35:52,847 PAINFUL EVENTS ARE MANAGED AT 3178 02:35:52,847 --> 02:35:53,048 HOME. 3179 02:35:53,048 --> 02:35:55,383 AS PEOPLE AGE INTO CHILDHOOD AND 3180 02:35:55,383 --> 02:35:59,387 ADOLESCENCE THE ACUTE 3181 02:35:59,387 --> 02:36:02,023 INTERMITTENT PAIN BECOME MORE 3182 02:36:02,023 --> 02:36:09,898 FREQUENT AND HOSPITAL VISITS 3183 02:36:09,898 --> 02:36:12,200 INCREASE AND IT'S REFRACTORY TO 3184 02:36:12,200 --> 02:36:12,467 TREATMENT. 3185 02:36:12,467 --> 02:36:14,936 THERE'S INCREASED OPIOID USE AT 3186 02:36:14,936 --> 02:36:18,239 HOME, ACUTE PAINFUL EVENTS ARE 3187 02:36:18,239 --> 02:36:20,108 SUPER IMPOSED ON THE CHRONIC 3188 02:36:20,108 --> 02:36:22,944 DAILY PAIN AND WE SEE AN 3189 02:36:22,944 --> 02:36:24,279 INCREASED PREVALENCE OF SICKLE 3190 02:36:24,279 --> 02:36:26,114 CELL DISEASE COMORBIDITIES 3191 02:36:26,114 --> 02:36:29,384 INCLUDING AVASCULAR NECROSIS AND 3192 02:36:29,384 --> 02:36:30,518 LEG ULCERS THAT CONTRIBUTE. 3193 02:36:30,518 --> 02:36:34,489 THIS TRANSITION INTEREST ACUTE 3194 02:36:34,489 --> 02:36:36,224 TO CHRONIC PAIN IS THE FOCUS OF 3195 02:36:36,224 --> 02:36:36,925 A SIGNIFICANT AMOUNT OF RESEARCH 3196 02:36:36,925 --> 02:36:42,697 OVER THE LAST DECADE. 3197 02:36:42,697 --> 02:36:45,633 THIS FIGURE DISPLAYS A 3198 02:36:45,633 --> 02:36:46,434 HYPOTHETICAL MODEL OF SICKLE 3199 02:36:46,434 --> 02:36:48,236 CELL DISEASE PAIN I'LL WALK YOU 3200 02:36:48,236 --> 02:36:49,170 THROUGH NOW. 3201 02:36:49,170 --> 02:36:51,339 THE X AXIS LOOKS AT TIME AS A 3202 02:36:51,339 --> 02:36:52,774 VARIABLE WITH EARLY CHILDHOOD ON 3203 02:36:52,774 --> 02:36:57,545 THE LEFT AND ADULTHOOD ON THE 3204 02:36:57,545 --> 02:36:58,179 RIGHT. 3205 02:36:58,179 --> 02:37:00,448 THE Y AXIS THE ORANGE LINE 3206 02:37:00,448 --> 02:37:02,117 CHRONIC BASELINE PAIN SENSITIVE 3207 02:37:02,117 --> 02:37:04,352 AND THE RED DASH LINE THE 3208 02:37:04,352 --> 02:37:07,122 SEVERITY OF ACUTE PAIN AND THE 3209 02:37:07,122 --> 02:37:08,323 BLUE LINE THE RELATIVE OPIOID 3210 02:37:08,323 --> 02:37:09,090 REQUIREMENT OF TIME. 3211 02:37:09,090 --> 02:37:13,361 AS YOU CAN SEE BY DEPICTED IN 3212 02:37:13,361 --> 02:37:17,198 THE ORANGE LINE, WE KNOW THAT 3213 02:37:17,198 --> 02:37:18,299 THE CHRONIC BASELINE PAIN 3214 02:37:18,299 --> 02:37:23,004 SEVERITY INCREASES WITH AGE. 3215 02:37:23,004 --> 02:37:26,107 AS YOU SEE THE LINE OVER THE 3216 02:37:26,107 --> 02:37:27,408 COURSE OF A LIFE SPAN GOES UP. 3217 02:37:27,408 --> 02:37:29,410 WHEN YOU LOOK AT THE RED AND 3218 02:37:29,410 --> 02:37:32,914 BLUE LINES TOGETHER THE RED DASH 3219 02:37:32,914 --> 02:37:34,415 LINE REPRESENT THE RELATIVE 3220 02:37:34,415 --> 02:37:36,384 SEVERITY OF ACUTE PAIN WE SEE 3221 02:37:36,384 --> 02:37:42,323 INCREASES OVER TIME AS ONE AGES. 3222 02:37:42,323 --> 02:37:43,291 IN THE RECOMBINANT OPIOID 3223 02:37:43,291 --> 02:37:44,292 REQUIREMENT THAT ALSO INCREASES 3224 02:37:44,292 --> 02:37:46,361 IN PARALLEL WITH THE INCREASE OF 3225 02:37:46,361 --> 02:37:47,996 THE RELATIVE SEVERITY OF ACUTE 3226 02:37:47,996 --> 02:37:52,567 PAIN AN ADDITION TO THE CHRONIC 3227 02:37:52,567 --> 02:37:53,434 BASELINE PAIN SEVERITY. 3228 02:37:53,434 --> 02:37:55,503 BECAUSE OF THIS TRANSITION FROM 3229 02:37:55,503 --> 02:37:57,338 ACUTE TO CHRONIC PAIN THERE'S 3230 02:37:57,338 --> 02:37:59,374 LIKELY A NEUROPATHIC COMPONENT 3231 02:37:59,374 --> 02:38:04,078 THAT DEVELOPS OVER TIME AS THE 3232 02:38:04,078 --> 02:38:05,980 NERVOUS SYSTEM BECOMES 3233 02:38:05,980 --> 02:38:07,849 DESENSITIZED AND CONSIDER 3234 02:38:07,849 --> 02:38:09,150 RE-EVALUATION FOR NEURO PATHIC 3235 02:38:09,150 --> 02:38:10,819 PAIN WHICH IS ONE OF THE PAIN 3236 02:38:10,819 --> 02:38:13,822 TYPES THAT MANIFESTS CLINICALLY 3237 02:38:13,822 --> 02:38:19,027 WITH CHRONIC SENSITIZATION OF 3238 02:38:19,027 --> 02:38:19,928 THE NERVOUS SYSTEM AND DETERMINE 3239 02:38:19,928 --> 02:38:23,331 WHETHER THEY NEED AN ALTERNATIVE 3240 02:38:23,331 --> 02:38:26,100 FORM OF TREATMENT. 3241 02:38:26,100 --> 02:38:29,237 I'LL NOW GOING TO DISCUSS THE 3242 02:38:29,237 --> 02:38:30,839 TAXONOMY OF SICKLE CELL DISEASE 3243 02:38:30,839 --> 02:38:31,039 PAIN. 3244 02:38:31,039 --> 02:38:32,173 IN THE PAST, SICKLE CELL DISEASE 3245 02:38:32,173 --> 02:38:34,609 PAIN WAS FELT TO BE PRIMARILY 3246 02:38:34,609 --> 02:38:37,812 ACUTE AND WITHIN A CUTE PAIN 3247 02:38:37,812 --> 02:38:38,813 SPACE THERE WAS NON-SICKLE CELL 3248 02:38:38,813 --> 02:38:41,616 DISEASE CAUSES OF ACUTE PAIN AND 3249 02:38:41,616 --> 02:38:43,318 VASO OCCLUSIVE CRISIS CAUSES OF 3250 02:38:43,318 --> 02:38:44,385 ACUTE PAIN. 3251 02:38:44,385 --> 02:38:46,621 HOWEVER, THIS MODEL IS QUITE 3252 02:38:46,621 --> 02:38:48,723 OUTDATED AND IS NOW BEEN 3253 02:38:48,723 --> 02:38:55,029 REPLACED BY THIS VERY COMPLEX 3254 02:38:55,029 --> 02:38:56,097 SICKLE CELL DISEASE PAIN MODEL 3255 02:38:56,097 --> 02:38:57,832 THAT INCLUDES COMPONENTS OF 3256 02:38:57,832 --> 02:38:59,901 ACUTE PAIN AND CHRONIC PAIN. 3257 02:38:59,901 --> 02:39:01,970 ACUTE PAIN WE CONTINUE TO HAVE 3258 02:39:01,970 --> 02:39:03,304 ACUTE NON-CRISIS PAIN. 3259 02:39:03,304 --> 02:39:05,240 WE CONTINUE TO HAVE VASO 3260 02:39:05,240 --> 02:39:07,909 OCCLUSIVE PAINFUL EVENTS IN THE 3261 02:39:07,909 --> 02:39:09,277 CLASSIC TEACHINGS FOR SICKLE 3262 02:39:09,277 --> 02:39:11,312 CELL DISEASE ACUTE PAIN AND HAVE 3263 02:39:11,312 --> 02:39:15,183 ACUTE EXACERBATIONS OF CHRONIC 3264 02:39:15,183 --> 02:39:17,886 PAIN AND THE CHRONIC PAIN SPAJ 3265 02:39:17,886 --> 02:39:20,021 WE HAVE IDENTIFIABLE CAUSES AND 3266 02:39:20,021 --> 02:39:20,655 NON-IDENTIFIABLE CAUSES WHICH 3267 02:39:20,655 --> 02:39:22,724 I'LL TALK ABOUT MORE DETAIL IN 3268 02:39:22,724 --> 02:39:24,592 SUBSEQUENT SLIDES. 3269 02:39:24,592 --> 02:39:26,327 AND NO IDENTIFIABLE CAUSE SPACE 3270 02:39:26,327 --> 02:39:30,131 WE HAVE COMPONENTS OF NEURO 3271 02:39:30,131 --> 02:39:31,432 PATHIC, CHRONIC INFLAMMATORY 3272 02:39:31,432 --> 02:39:33,935 PAIN AND CHRONIC NOCICEPTIVE 3273 02:39:33,935 --> 02:39:37,105 PAIN AND DRILLING DOWN IN 3274 02:39:37,105 --> 02:39:38,806 NEUROPATHIC PAIN CENTRAL 3275 02:39:38,806 --> 02:39:42,010 SENSITIZATION I'LL WALK MORE 3276 02:39:42,010 --> 02:39:42,543 ABOUT. 3277 02:39:42,543 --> 02:39:45,847 -- TALK MORE ABOUT. 3278 02:39:45,847 --> 02:39:47,482 THE COMPLEXITY OF THE PAIN 3279 02:39:47,482 --> 02:39:52,887 TAXONOMY IS LIKELY DIRECTLY 3280 02:39:52,887 --> 02:39:55,023 DIRECTLY RELATED TO HE PAIN 3281 02:39:55,023 --> 02:39:55,323 TREATMENT. 3282 02:39:55,323 --> 02:39:59,227 THERE'S PAIN PHENOMENON OR 3283 02:39:59,227 --> 02:40:00,428 PAIN-RELATED DISEASE HAVE AS 3284 02:40:00,428 --> 02:40:01,829 MUCH AS COMPLEXITY OF PAIN 3285 02:40:01,829 --> 02:40:03,965 TAXONOMY AS WE SEE IN SICKLE 3286 02:40:03,965 --> 02:40:05,333 CELL DISEASE AND THIS LIKELY 3287 02:40:05,333 --> 02:40:07,969 GIVES US A CLUE OF WHY IT'S SUCH 3288 02:40:07,969 --> 02:40:11,439 A CHALLENGE TO TREAT FOR OUR 3289 02:40:11,439 --> 02:40:13,474 PATIENTS. 3290 02:40:13,474 --> 02:40:16,811 I'D LIKE TO TALK BRIEFLY ABOUT 3291 02:40:16,811 --> 02:40:21,616 THE AAPT DIAGNOSTIC CRITERIA FOR 3292 02:40:21,616 --> 02:40:22,717 PAIN FOR SICKLE CELL DISEASE 3293 02:40:22,717 --> 02:40:25,053 PUBLISHED AND LIKE TO HONE IN ON 3294 02:40:25,053 --> 02:40:26,454 ONE COMPONENT THE DIAGNOSTIC 3295 02:40:26,454 --> 02:40:28,489 CORE CRITERIA OF REPORTS OF 3296 02:40:28,489 --> 02:40:29,457 ONGOING PAIN PRESENT ON MOST 3297 02:40:29,457 --> 02:40:33,394 DAYS OVER THE PAST SIX MONTHS 3298 02:40:33,394 --> 02:40:35,163 EITHER IN SINGLE OR MULTIPLE 3299 02:40:35,163 --> 02:40:35,563 LOCATION. 3300 02:40:35,563 --> 02:40:37,398 THIS IS A KEY COMPONENT OF THE 3301 02:40:37,398 --> 02:40:38,733 DEFINITION AND ADAPTED FROM THE 3302 02:40:38,733 --> 02:40:40,134 INTERNATIONAL ASSOCIATION FOR 3303 02:40:40,134 --> 02:40:42,270 THE STUDY OF PAINS DEFINITION OR 3304 02:40:42,270 --> 02:40:44,539 THE IASP DEFINITION OF CHRONIC 3305 02:40:44,539 --> 02:40:47,008 WHICH IS PAIN THAT PERSISTS FOR 3306 02:40:47,008 --> 02:40:51,746 THREE MONTHS BEYOND THE INCITING 3307 02:40:51,746 --> 02:40:56,417 EVENT AND THIS DEFINITION WAS 3308 02:40:56,417 --> 02:41:00,722 ADAPTED TO PAIN IN MOST DAYS TO 3309 02:41:00,722 --> 02:41:01,689 DEFINE CLINICAL CHRONIC PAIN 3310 02:41:01,689 --> 02:41:03,925 WITHIN SICKLE CELL DISEASE. 3311 02:41:03,925 --> 02:41:06,160 FURTHER DRILLING DOWN THERE'S 3312 02:41:06,160 --> 02:41:11,165 THREE DIAGNOSTIC MODIFIERS AND 3313 02:41:11,165 --> 02:41:12,700 ONE CHRONIC PAIN WITH 3314 02:41:12,700 --> 02:41:14,068 CONTRIBUTORY DISEASE 3315 02:41:14,068 --> 02:41:16,337 COMPLICATIONS AND MIXED TYPE OF 3316 02:41:16,337 --> 02:41:16,904 PAIN THAT ENCOMPASS TWO OF 3317 02:41:16,904 --> 02:41:22,944 THESE. 3318 02:41:22,944 --> 02:41:25,613 UNDERLYING THE COMPLEX TAXONOMY 3319 02:41:25,613 --> 02:41:26,981 OF SICKLE CELL DISEASE PAIN IS 3320 02:41:26,981 --> 02:41:27,615 FURTHER COMPLEX BIOLOGY THAT 3321 02:41:27,615 --> 02:41:28,816 DRIVES SICKLE CELL PAIN AND I 3322 02:41:28,816 --> 02:41:30,251 TOUCHED ON THIS BRIEFLY BUT I'D 3323 02:41:30,251 --> 02:41:31,386 LIKE TO DRILL DOWN A LITTLE BIT 3324 02:41:31,386 --> 02:41:34,288 MORE IN DEPTH NOW. 3325 02:41:34,288 --> 02:41:35,890 FIRST, THERE'S NOCICEPTIVE 3326 02:41:35,890 --> 02:41:38,159 COMPONENTS LIKELY DRIVEN FROM 3327 02:41:38,159 --> 02:41:41,596 THE CLASSIC SICKLE CELL VASO 3328 02:41:41,596 --> 02:41:44,432 OCCLUSION THAT CAUSES TISSUE 3329 02:41:44,432 --> 02:41:50,138 ISCHEMIA AND REPERFUSION INJURY 3330 02:41:50,138 --> 02:41:53,041 AND COMBINENT INFLAMMATION AND 3331 02:41:53,041 --> 02:41:56,110 ABNORMALITIES PERIPHERAL NERVES, 3332 02:41:56,110 --> 02:41:58,813 BRAIN OR SPINAL CORD THAT 3333 02:41:58,813 --> 02:42:02,116 INITIATE TRANSMIT AND SUSTAIN 3334 02:42:02,116 --> 02:42:06,554 PAIN SIGNALS AT THE LEVEL OF THE 3335 02:42:06,554 --> 02:42:09,457 CENTRAL NERVOUS SYSTEM OR 3336 02:42:09,457 --> 02:42:10,191 PERIPHERAL NERVOUS SYSTEM. 3337 02:42:10,191 --> 02:42:15,263 THERE'S STRESS MEDIATED 3338 02:42:15,263 --> 02:42:16,297 COMPONENTS AND CERTAINLY 3339 02:42:16,297 --> 02:42:17,198 PSYCHOSOCIAL CONTRIBUTIONS AND 3340 02:42:17,198 --> 02:42:18,933 MENTAL HEALTH ISSUES INCLUDING 3341 02:42:18,933 --> 02:42:21,235 DEPRESSION AND ANXIETY THAT CAN 3342 02:42:21,235 --> 02:42:23,337 CONTRIBUTE TO PAIN AND CAN BE 3343 02:42:23,337 --> 02:42:23,905 EXACERBATED BY LIVING WITH 3344 02:42:23,905 --> 02:42:26,441 CHRONIC PAIN. 3345 02:42:26,441 --> 02:42:29,177 THIS BIOLOGY IS REALLY IMPORTANT 3346 02:42:29,177 --> 02:42:31,946 TO UNDERSTAND IN ORDER TO DRIVE 3347 02:42:31,946 --> 02:42:32,547 TARGETED THERAPIES FOR SICKLE 3348 02:42:32,547 --> 02:42:35,249 CELL DISEASE PAIN. 3349 02:42:35,249 --> 02:42:38,119 AND I WOULD ARGUE THAT TREATING 3350 02:42:38,119 --> 02:42:39,220 ALL SICKLE CELL DISEASE PAIN THE 3351 02:42:39,220 --> 02:42:41,189 SAME IS LIKE TREATING ALL FORMS 3352 02:42:41,189 --> 02:42:43,624 OF ANEMIA WITH THE SAME 3353 02:42:43,624 --> 02:42:43,991 APPROACH. 3354 02:42:43,991 --> 02:42:46,828 WE REALLY NEED THE ABILITY TO 3355 02:42:46,828 --> 02:42:47,895 DIFFERENTIATE IS THE BIOLOGY OF 3356 02:42:47,895 --> 02:42:49,030 SICKLE CELL DISEASE PAIN AND 3357 02:42:49,030 --> 02:42:51,132 DIFFERENTIATING THIS BIOLOGY IS 3358 02:42:51,132 --> 02:42:52,100 LIKELY VERY THERAPEUTICALLY 3359 02:42:52,100 --> 02:42:53,468 IMPORTANT AND THE FOCUS OF A LOT 3360 02:42:53,468 --> 02:42:58,739 OF RESEARCH GOING ON RIGHT NOW. 3361 02:42:58,739 --> 02:43:01,109 IN ADDITION TO THE COMPLEX 3362 02:43:01,109 --> 02:43:02,743 TAXONOMY AND THE COMPLEX 3363 02:43:02,743 --> 02:43:04,312 BIOLOGY, SICKLE CELL DISEASE 3364 02:43:04,312 --> 02:43:06,380 PAIN NEEDS TO BE BOTH THOUGHT 3365 02:43:06,380 --> 02:43:08,549 OF, INTERPRETED AND TREATED IN 3366 02:43:08,549 --> 02:43:10,885 THE BIO PSYCHOSOCIAL MODEL. 3367 02:43:10,885 --> 02:43:13,454 THIS IS DEPICTED ON THE FIGURE 3368 02:43:13,454 --> 02:43:17,225 ON THIS SLIDE LOOKING AT THE 3369 02:43:17,225 --> 02:43:19,460 BIOLOGICAL FACTORS INCLUDING 3370 02:43:19,460 --> 02:43:20,761 HEMATOLOGIC FACTORS AND CHRONIC 3371 02:43:20,761 --> 02:43:24,332 ORGAN DAMAGE AND THINKING OF THE 3372 02:43:24,332 --> 02:43:26,167 PSYCHOLOGICAL FACTORS 3373 02:43:26,167 --> 02:43:28,035 DEPRESSION, ANXIETY AND 3374 02:43:28,035 --> 02:43:29,036 HELPLESSNESS AMONG OTHER THINGS 3375 02:43:29,036 --> 02:43:33,774 AND THE SOCIOLOGICAL ISSUES 3376 02:43:33,774 --> 02:43:35,710 INCLUDING SOCIAL DETERMINATES OF 3377 02:43:35,710 --> 02:43:38,546 HEALTH AND STIGMA, TRIGGERS AND 3378 02:43:38,546 --> 02:43:42,650 LIFE EVENTS AND DISPARITIES. 3379 02:43:42,650 --> 02:43:44,519 EACH CONTRIBUTE INDIVIDUALLY TO 3380 02:43:44,519 --> 02:43:45,753 ACUTE PAIN, CHRONIC PAIN AND THE 3381 02:43:45,753 --> 02:43:47,088 INTERSECTION BETWEEN THE TWO. 3382 02:43:47,088 --> 02:43:47,755 IT'S IMPORTANT TO ALWAYS THINK 3383 02:43:47,755 --> 02:43:49,357 OF THIS MODEL AND PUT THE WORK 3384 02:43:49,357 --> 02:43:50,591 WE DO IN THE CONTEXT OF THESE 3385 02:43:50,591 --> 02:43:55,096 COMPONENTS. 3386 02:43:55,096 --> 02:43:59,333 SO IN SUMMARY, SICKLE CELL 3387 02:43:59,333 --> 02:44:00,935 DISEASE IS VERY COMPLEX AND 3388 02:44:00,935 --> 02:44:03,838 SICKLE CELL DISEASE PAIN IS 3389 02:44:03,838 --> 02:44:07,308 COMPLEX AND I'LL SUMMARIZE IT 3390 02:44:07,308 --> 02:44:08,142 BRIEFLY. 3391 02:44:08,142 --> 02:44:10,811 WE KNOW THERE'S EXTENSIVE 3392 02:44:10,811 --> 02:44:12,046 DIVERSE AND COMPLEX CLINICAL 3393 02:44:12,046 --> 02:44:15,316 PAIN EXPRESSION IN ACUTE AND 3394 02:44:15,316 --> 02:44:17,451 CHRONIC PAIN WHICH I BRIEFLY 3395 02:44:17,451 --> 02:44:17,885 DISCUSSED. 3396 02:44:17,885 --> 02:44:19,253 THERE'S VERY COMPLEX BIOLOGY. 3397 02:44:19,253 --> 02:44:20,555 MANY OF WHICH WE DON'T YET 3398 02:44:20,555 --> 02:44:24,959 UNDERSTAND SOME OF WHICH WE DO, 3399 02:44:24,959 --> 02:44:25,760 ARE BEGINNING TO UNDERSTAND A 3400 02:44:25,760 --> 02:44:26,794 LITTLE BIT ABOUT BUT THERE'S SO 3401 02:44:26,794 --> 02:44:29,530 MUCH WORK THAT NEEDS TO BE DONE 3402 02:44:29,530 --> 02:44:31,899 IN UNDERSTANDING THE BIOLOGY AND 3403 02:44:31,899 --> 02:44:32,934 FINALLY THE BIO PSYCHOSOCIAL 3404 02:44:32,934 --> 02:44:37,405 MODEL IS KEY TO INTERPRETING ALL 3405 02:44:37,405 --> 02:44:38,973 THESE COFACTORS COLLECTIVELY TO 3406 02:44:38,973 --> 02:44:42,143 UNDERSTAND THE CONTEXT OF WHAT 3407 02:44:42,143 --> 02:44:47,848 CONTRIBUTES TO THE PAIN THAT OUR 3408 02:44:47,848 --> 02:44:49,550 PATIENTS EXPERIENCE. 3409 02:44:49,550 --> 02:44:52,587 IN 3, WHERE THEY INTERSECT IS 3410 02:44:52,587 --> 02:44:53,254 COMPLEX PAIN TREATMENT. 3411 02:44:53,254 --> 02:44:55,957 PROBABLY THE REASON WHY WE HAVE 3412 02:44:55,957 --> 02:44:57,692 OFTEN TIMES DIFFICULTY TREATING 3413 02:44:57,692 --> 02:45:01,495 PAIN AND EFFECTIVELY TREATING 3414 02:45:01,495 --> 02:45:03,364 PAIN AND THE COMPLEXITY OF PAIN 3415 02:45:03,364 --> 02:45:05,766 UNDER LIES THE TREATMENT THAT 3416 02:45:05,766 --> 02:45:07,335 ALSO NEEDS TO BE COMPLEX IN 3417 02:45:07,335 --> 02:45:09,370 ORDER TO EFFECTIVELY MANAGE PAIN 3418 02:45:09,370 --> 02:45:10,371 AND IMPROVE THE QUALITY OF LIFE 3419 02:45:10,371 --> 02:45:20,915 OF INDIVIDUALS WE TAKE CARE OF. 3420 02:45:24,218 --> 02:45:26,787 I DECIDED TO FOCUS ON THE 3421 02:45:26,787 --> 02:45:32,159 AMERICAN SOCIETY OF HEMATOLOGY 3422 02:45:32,159 --> 02:45:33,561 PUBLISHED FOR THE MANAGEMENT OF 3423 02:45:33,561 --> 02:45:35,930 ACUTE AND CHRONIC PAIN AND THIS 3424 02:45:35,930 --> 02:45:38,165 FORMS A LARGE MULTIDISCIPLINARY 3425 02:45:38,165 --> 02:45:41,435 EXPERT PANEL THAT UNDERWENT AN 3426 02:45:41,435 --> 02:45:43,004 EVIDENCE-BASED SYSTEMATIC REVIEW 3427 02:45:43,004 --> 02:45:45,373 TO ASSIMILATE AND PUBLISH THE 3428 02:45:45,373 --> 02:45:45,740 GUIDELINES. 3429 02:45:45,740 --> 02:45:47,108 THERE'S MORE RESEARCH BEING DONE 3430 02:45:47,108 --> 02:45:47,341 NOW. 3431 02:45:47,341 --> 02:45:49,410 MANY OF WHICH YOU'LL HEAR IN THE 3432 02:45:49,410 --> 02:45:51,445 SUBSEQUENT TALKS TO TRY TO 3433 02:45:51,445 --> 02:45:53,114 EXPAND THESE GUIDELINES. 3434 02:45:53,114 --> 02:45:55,316 BUT I THOUGHT I'D USE THESE AS A 3435 02:45:55,316 --> 02:45:56,484 STARTING POINT FOR DISCUSSION OF 3436 02:45:56,484 --> 02:45:59,353 THE TREATMENT SINCE I HAD LITTLE 3437 02:45:59,353 --> 02:46:04,925 TIME. 3438 02:46:04,925 --> 02:46:06,994 THE TREATMENT NEEDS TO BE 3439 02:46:06,994 --> 02:46:11,832 THOUGHT OF IN A 3440 02:46:11,832 --> 02:46:13,467 MULTIDISCIPLINARY MULTIMODAL 3441 02:46:13,467 --> 02:46:14,669 APPROACH AND PAIN COLLEAGUES AND 3442 02:46:14,669 --> 02:46:15,803 COLLABORATORS AND PSYCHOLOGISTS 3443 02:46:15,803 --> 02:46:19,040 AND PSYCHIATRISTS AND THEIR 3444 02:46:19,040 --> 02:46:20,041 CONTRIBUTIONS. 3445 02:46:20,041 --> 02:46:22,476 PHYSICAL MEDICINE AND 3446 02:46:22,476 --> 02:46:25,980 REHABILITATION AND SOCIAL WORK 3447 02:46:25,980 --> 02:46:29,083 AND INTEGRATIVE WORK AND ALL 3448 02:46:29,083 --> 02:46:32,219 THESE MULTI-MODAL APPROACHES 3449 02:46:32,219 --> 02:46:33,487 CONTRIBUTING TO THE IMPROVEMENT 3450 02:46:33,487 --> 02:46:34,855 OF PAIN OF INDIVIDUALS LIVING 3451 02:46:34,855 --> 02:46:35,690 WITH SICKLE CELL DISEASE AND THE 3452 02:46:35,690 --> 02:46:37,091 CONTEXT OF THEIR FAMILY AND 3453 02:46:37,091 --> 02:46:37,892 SOCIAL SUPPORTS. 3454 02:46:37,892 --> 02:46:41,262 WE TRIED TO FRAME OUR GUIDELINES 3455 02:46:41,262 --> 02:46:44,165 IN THE CONTEXT OF THIS 3456 02:46:44,165 --> 02:46:45,366 MULTI-DISCIPLINARY MULTI-MODAL 3457 02:46:45,366 --> 02:46:46,334 APPROACH TO PAIN TREATMENT. 3458 02:46:46,334 --> 02:46:47,301 THIS IS IT THE HIGH LEVEL 3459 02:46:47,301 --> 02:46:50,004 OVERVIEW OF OUR GUIDELINES WHERE 3460 02:46:50,004 --> 02:46:51,505 WE LOOKED AT SICKLE CELL DISEASE 3461 02:46:51,505 --> 02:46:53,407 PAIN IN THE ACUTE AND CHRONIC 3462 02:46:53,407 --> 02:46:54,408 PAIN SPACES. 3463 02:46:54,408 --> 02:46:58,412 UNDER ACUTE PAIN SPACE WE LOOKED 3464 02:46:58,412 --> 02:47:00,448 AT ANALGESIC DELIVERY IN 3465 02:47:00,448 --> 02:47:03,217 LOCATION AND PROTOCOL AND 3466 02:47:03,217 --> 02:47:04,885 PHARMACOLOGIC AND 3467 02:47:04,885 --> 02:47:06,287 NON-PHARMACOLOGIC THERAPY AND IN 3468 02:47:06,287 --> 02:47:08,656 THE CHRONIC PAIN WE LOOKED AT 3469 02:47:08,656 --> 02:47:11,325 BOTH NON-OPIOID PHARMACOLOGIC 3470 02:47:11,325 --> 02:47:13,994 AND NON-PHARMACOLOGIC THERAPY 3471 02:47:13,994 --> 02:47:15,596 AND CHRONIC OPIOID THERAPY AND 3472 02:47:15,596 --> 02:47:20,768 CHRONIC TRANSFUSION THERAPY. 3473 02:47:20,768 --> 02:47:22,503 WE USED TWO DATA SOURCES 3474 02:47:22,503 --> 02:47:25,172 PRIMARILY DIRECT AND INDIRECT 3475 02:47:25,172 --> 02:47:25,439 EVIDENCE. 3476 02:47:25,439 --> 02:47:27,141 FOR DIRECT EVIDENCE IN 3477 02:47:27,141 --> 02:47:28,909 INDIVIDUALS WITH SICKLE CELL 3478 02:47:28,909 --> 02:47:30,911 DISEASE WE HAD MINIMAL EVIDENCE 3479 02:47:30,911 --> 02:47:32,480 AVAILABLE AND DIPPED INTO THE 3480 02:47:32,480 --> 02:47:40,755 INTERDIRECT -- INDIRECT EVIDENCE 3481 02:47:40,755 --> 02:47:42,957 AND WE COLLABORATED WITH THE 3482 02:47:42,957 --> 02:47:43,624 PRACTICE RESEARCH CENTER WHERE 3483 02:47:43,624 --> 02:47:46,327 THEY HELPED US CONDUCT AND 3484 02:47:46,327 --> 02:47:47,762 ASSIMILATE THE EVIDENCE REVIEWS 3485 02:47:47,762 --> 02:47:50,164 WE USED AS THE BASIS FOR OUR 3486 02:47:50,164 --> 02:47:51,999 GUIDELINES. 3487 02:47:51,999 --> 02:47:53,501 AS FAR AS THE INDIRECT EVIDENCE 3488 02:47:53,501 --> 02:47:58,005 GOES WE REACHED CONSENSUS VIA 3489 02:47:58,005 --> 02:48:00,875 SURVEY AND ONLINE PANEL 3490 02:48:00,875 --> 02:48:03,310 DISCUSSION ABOUT THE INDIRECT 3491 02:48:03,310 --> 02:48:05,045 EVIDENCE AND THE PAIN CONDITIONS 3492 02:48:05,045 --> 02:48:08,616 THAT PARALLEL THE ACUTE EVIDENCE 3493 02:48:08,616 --> 02:48:10,985 AND LOOKED AT THE SIMILARITY TO 3494 02:48:10,985 --> 02:48:13,654 THE BIOLOGY OR THE EXPERIENCE OF 3495 02:48:13,654 --> 02:48:14,255 INDIVIDUALS WITH SICKLE CELL 3496 02:48:14,255 --> 02:48:15,322 DISEASE DISEASE. 3497 02:48:15,322 --> 02:48:17,291 WE UTILIZED ONLY SYSTEMATIC 3498 02:48:17,291 --> 02:48:18,392 REVIEWS OR META-ANALYSIS THAT 3499 02:48:18,392 --> 02:48:20,628 INCLUDED FIVE OR MORE STUDIES 3500 02:48:20,628 --> 02:48:22,263 WHERE SINGLE INDIVIDUAL RESEARCH 3501 02:48:22,263 --> 02:48:23,964 STUDIES WERE ACTUALLY NOT USED 3502 02:48:23,964 --> 02:48:26,400 AS EVIDENCE FOR THE GUIDELINES 3503 02:48:26,400 --> 02:48:29,837 AND WE DOWN GRADE THE INDIRECT 3504 02:48:29,837 --> 02:48:32,873 EVIDENCE AS PER THE GRADE 3505 02:48:32,873 --> 02:48:33,641 POPULATION FOR DIRECTNESS. 3506 02:48:33,641 --> 02:48:35,309 THE COMPOSITION OF OUR PANEL 3507 02:48:35,309 --> 02:48:39,313 INCLUDED PEDIATRIC AND ADULT 3508 02:48:39,313 --> 02:48:41,148 PROVIDERS AND NURSING 3509 02:48:41,148 --> 02:48:42,716 COLLEAGUES, PSYCHOLOGY AND 3510 02:48:42,716 --> 02:48:44,151 PSYCHIATRY, REPRESENTATION, 3511 02:48:44,151 --> 02:48:47,087 EMERGENCY MEDICINE, A PATIENT 3512 02:48:47,087 --> 02:48:50,691 AND PARENT OF A YOUNG CHILD WITH 3513 02:48:50,691 --> 02:48:54,161 SICKLE CELL DISEASE AND OUR 3514 02:48:54,161 --> 02:48:54,962 METHODOLO 3515 02:48:54,962 --> 02:48:55,296 METHODOLOGIST. 3516 02:48:55,296 --> 02:48:56,630 WE HAD MAJOR CHALLENGES IN OUR 3517 02:48:56,630 --> 02:48:57,198 PANEL. 3518 02:48:57,198 --> 02:48:59,366 ONE BEING THE LACK OF DIRECT 3519 02:48:59,366 --> 02:49:01,402 EVIDENCE WITH MINIMAL IF ANY 3520 02:49:01,402 --> 02:49:03,037 HIGH QUALITY EVIDENCE AND 3521 02:49:03,037 --> 02:49:04,238 SIGNIFICANT LACK OF RANDOMIZED 3522 02:49:04,238 --> 02:49:05,406 CONTROL TRIALS. 3523 02:49:05,406 --> 02:49:07,975 THERE'S CHALLENGES IN HARNESSING 3524 02:49:07,975 --> 02:49:08,943 THE INDIRECT DATA AND LEVERAGING 3525 02:49:08,943 --> 02:49:11,912 THIS TO IMPROVE OUR IN 3526 02:49:11,912 --> 02:49:14,148 GUIDELINES AND DIFFERENTIATING 3527 02:49:14,148 --> 02:49:16,150 ACUTE AND CHRONIC PAIN IN THE 3528 02:49:16,150 --> 02:49:17,117 LITERATURE IN SICKLE CELL 3529 02:49:17,117 --> 02:49:19,320 DISEASE AND THE PEDIATRIC AND 3530 02:49:19,320 --> 02:49:20,521 ADULT DATA WERE NOT ALWAYS 3531 02:49:20,521 --> 02:49:22,089 AVAILABLE IN PARALLEL IN WHICH 3532 02:49:22,089 --> 02:49:23,724 TO USE OUR GUIDELINES. 3533 02:49:23,724 --> 02:49:25,826 NOW I'M GOING TO TAKE YOU 3534 02:49:25,826 --> 02:49:28,195 THROUGH A FEW GUIDELINES AS AN 3535 02:49:28,195 --> 02:49:30,998 EXAMPLE OF PAIN TREATMENT AND 3536 02:49:30,998 --> 02:49:36,003 I'LL PRESENT THE QUESTION FIRST 3537 02:49:36,003 --> 02:49:38,873 THAT WE OUR EVIDENCE-BASED 3538 02:49:38,873 --> 02:49:43,344 SEARCHS ON AND SIMULATION OF THE 3539 02:49:43,344 --> 02:49:45,412 DATA AND WE ASKED THE QUESTION 3540 02:49:45,412 --> 02:49:47,348 WHETHER PHARMACOLOGIC THERAPIES 3541 02:49:47,348 --> 02:49:49,783 IN ADDITION TO OR INSTEAD OF 3542 02:49:49,783 --> 02:49:51,785 OPIOIDS OR OTHER USUAL CARE 3543 02:49:51,785 --> 02:49:52,453 INTERVENTIONS SHOULD BE USED FOR 3544 02:49:52,453 --> 02:49:55,689 THE TREATMENT OF ACUTE PAIN IN 3545 02:49:55,689 --> 02:49:59,360 PATIENTS AND ADULTS WITH SICKLE 3546 02:49:59,360 --> 02:50:00,094 CELL DISEASE. 3547 02:50:00,094 --> 02:50:02,062 ON MY SLIDE ARE TWO 3548 02:50:02,062 --> 02:50:02,997 RECOMMENDATIONS THAT WERE 3549 02:50:02,997 --> 02:50:04,164 DERIVED FROM THE QUESTION. 3550 02:50:04,164 --> 02:50:05,966 THERE'S MORE THERE INCLUDED IN 3551 02:50:05,966 --> 02:50:08,202 THE COMPLETE PUBLICATION BUT THE 3552 02:50:08,202 --> 02:50:11,505 ONE RECOMMENDATION IS THE USE OF 3553 02:50:11,505 --> 02:50:13,607 ANALGESIC DOSING OF KETAMINE AS 3554 02:50:13,607 --> 02:50:16,977 AN ADJUNCT TREATMENT FOR PAIN 3555 02:50:16,977 --> 02:50:20,581 REFRACTORY OR NOT EFFECTUALLY 3556 02:50:20,581 --> 02:50:23,183 TREATED WITH OPIOIDS ALONE AND 3557 02:50:23,183 --> 02:50:25,085 THERE'S NO PUBLISHED DATA FOR 3558 02:50:25,085 --> 02:50:28,322 REFRACTORY AND WE LEFT THIS OPEN 3559 02:50:28,322 --> 02:50:30,157 TO THE DETERMINATION OF THE 3560 02:50:30,157 --> 02:50:34,228 CLINICIAN AND PATIENT AND SHARED 3561 02:50:34,228 --> 02:50:35,229 DECISION MAKING. 3562 02:50:35,229 --> 02:50:36,797 THE RECOMMENDED DOSE IS LISTED 3563 02:50:36,797 --> 02:50:39,867 ON MY SLIDE AND THIS WAS BASED 3564 02:50:39,867 --> 02:50:41,402 ON LOW CERTAINTY IN THE 3565 02:50:41,402 --> 02:50:44,939 STATEMENT OF ARTIFACTS AND 3566 02:50:44,939 --> 02:50:46,307 YOU'LL SEE CONDITIONAL 3567 02:50:46,307 --> 02:50:46,974 RECOMMENDATION BASED ON LOW 3568 02:50:46,974 --> 02:50:48,275 CERTAINTY IN THE EVIDENCE IS A 3569 02:50:48,275 --> 02:50:52,646 VERY COMMON THEME. 3570 02:50:52,646 --> 02:50:55,349 THE NEXT RECOMMENDATION IN THE 3571 02:50:55,349 --> 02:50:58,452 SPACE IS REGIONAL ANESTHESIA FOR 3572 02:50:58,452 --> 02:51:00,588 LOCAL OF A PAIN FOR PAIN 3573 02:51:00,588 --> 02:51:01,822 REFRACTORY OR NOT EFFECTIVELY 3574 02:51:01,822 --> 02:51:04,992 TREATED WITH OPIOIDS ALONE. 3575 02:51:04,992 --> 02:51:08,362 DELIVERED VIA A PERIPHERAL NERVE 3576 02:51:08,362 --> 02:51:12,132 CATHETER AND COMMON PLACE FOR 3577 02:51:12,132 --> 02:51:14,201 ABDOMINAL OR HIP OR LEG PAIN. 3578 02:51:14,201 --> 02:51:16,303 THIS OBVIOUSLY HAS TO BE 3579 02:51:16,303 --> 02:51:18,072 TECHNICALLY FEASIBLE BASED ON 3580 02:51:18,072 --> 02:51:19,840 THE ANATOMIC LOCATION AND HAVE 3581 02:51:19,840 --> 02:51:21,675 THE EXPERTISE OF SOMEBODY IN 3582 02:51:21,675 --> 02:51:25,079 PAIN MEDICINE TO DELIVER THIS 3583 02:51:25,079 --> 02:51:25,312 THERAPY. 3584 02:51:25,312 --> 02:51:25,913 AGAIN, THIS IS A CONDITIONAL 3585 02:51:25,913 --> 02:51:28,182 RECOMMENDATION. 3586 02:51:28,182 --> 02:51:30,351 SHIFTING TO NON-PHARMACOLOGIC 3587 02:51:30,351 --> 02:51:32,186 THERAPY FOR ACUTE PAIN WE ASKED 3588 02:51:32,186 --> 02:51:35,923 THE QUESTION OF SHOULD 3589 02:51:35,923 --> 02:51:36,690 NON-PHARMACOLOGIC THERAPIES BE 3590 02:51:36,690 --> 02:51:38,325 USED FOR THE TREATMENT OF ACUTE 3591 02:51:38,325 --> 02:51:39,460 PAIN IN CHILDREN AND ADULTS WITH 3592 02:51:39,460 --> 02:51:49,069 SICKLE CELL DISEASE. 3593 02:51:49,069 --> 02:51:51,338 THERE WERE SEVERAL 3594 02:51:51,338 --> 02:51:52,106 NON-PHARMACOLOGIC MODALITIES WE 3595 02:51:52,106 --> 02:51:53,841 LOOKED AT EVIDENCE FOR AND 3596 02:51:53,841 --> 02:51:55,843 SETTLED ON A VARIETY OF THESE 3597 02:51:55,843 --> 02:52:00,547 INCLUDING IN ADDITION TO 3598 02:52:00,547 --> 02:52:01,782 PHARMACOLOGIC MANAGEMENT 3599 02:52:01,782 --> 02:52:05,886 CONSIDERED INTEGRATING MASSAGE, 3600 02:52:05,886 --> 02:52:08,055 YOGA, TENS, GUIDED AUDIO AND 3601 02:52:08,055 --> 02:52:10,557 VISUAL RELAXATION. 3602 02:52:10,557 --> 02:52:11,325 CONDITIONAL RECOMMENDATIONS 3603 02:52:11,325 --> 02:52:13,861 BASED ON LOW CERTAINTY. 3604 02:52:13,861 --> 02:52:15,896 MOST HAVE VERY LOW SIDE EFFECT 3605 02:52:15,896 --> 02:52:16,764 PROFILES SO WE FOUND IT 3606 02:52:16,764 --> 02:52:19,133 IMPORTANT TO PUT THEM FORWARD AS 3607 02:52:19,133 --> 02:52:20,200 POTENTIAL INTERVENTIONS FOR ONE 3608 02:52:20,200 --> 02:52:22,236 TO CONSIDER TO AUGMENT THE 3609 02:52:22,236 --> 02:52:24,104 PHARMACOLOGIC THERAPY PEOPLE 3610 02:52:24,104 --> 02:52:27,341 WILL GET OR RECEIVE WHEN THEY'RE 3611 02:52:27,341 --> 02:52:30,210 HOSPITALIZED. 3612 02:52:30,210 --> 02:52:31,545 SHIFTING NOW INTO THE CHRONIC 3613 02:52:31,545 --> 02:52:32,513 PAIN SPACE, WE WERE INTERESTED 3614 02:52:32,513 --> 02:52:36,383 IN LOOKING AT NON-OPIOID 3615 02:52:36,383 --> 02:52:37,217 PHARMACOLOGIC THERAPY FOR 3616 02:52:37,217 --> 02:52:37,718 CHRONIC PAIN. 3617 02:52:37,718 --> 02:52:41,021 AND WE ASKED THE QUESTION OF 3618 02:52:41,021 --> 02:52:42,690 SHOULD NON-OPIOID PHARMACOLOGIC 3619 02:52:42,690 --> 02:52:44,191 THERAPY IN ADDITION OR INSTEAD 3620 02:52:44,191 --> 02:52:46,226 OF OPIOIDS OR OTHER USUAL CARE 3621 02:52:46,226 --> 02:52:47,161 INTERVENTIONS BE USED FOR 3622 02:52:47,161 --> 02:52:49,196 CHILDREN AND ADULT WITH SICKLE 3623 02:52:49,196 --> 02:52:50,764 CELL DISEASE IN CHRONIC PAIN 3624 02:52:50,764 --> 02:52:52,232 WITH NO IDENTIFIABLE CAUSE 3625 02:52:52,232 --> 02:52:52,933 BEYOND SICKLE CELL DISEASE. 3626 02:52:52,933 --> 02:52:54,535 SO THIS IS BRINGING US BACK TO 3627 02:52:54,535 --> 02:53:00,340 THE AAPT DEFINITION OF CHRONIC 3628 02:53:00,340 --> 02:53:03,310 PAIN PUBLISHED AT THE TIME OF 3629 02:53:03,310 --> 02:53:04,078 GUIDELINES. 3630 02:53:04,078 --> 02:53:06,080 THE SLIDE DEPICTS SOME 3631 02:53:06,080 --> 02:53:07,881 INTERVENTIONS THAT CAME FORWARD 3632 02:53:07,881 --> 02:53:10,784 IN THIS EVIDENCE-BASED REVIEW 3633 02:53:10,784 --> 02:53:13,287 WHERE WE LOOKED AT CHRONIC PAIN 3634 02:53:13,287 --> 02:53:14,955 WITH NO IDENTIFIABLE CAUSE 3635 02:53:14,955 --> 02:53:17,357 BEYOND SICKLE CELL DISEASE AND 3636 02:53:17,357 --> 02:53:19,326 SOME OF THE CONSIDERATIONS CAN 3637 02:53:19,326 --> 02:53:25,232 BE SNRI SUCH AS THESE LISTED. 3638 02:53:25,232 --> 02:53:28,202 AND THIS RECOMMENDATION WAS 3639 02:53:28,202 --> 02:53:29,536 SPECIFICALLY FOR ADULTS. 3640 02:53:29,536 --> 02:53:32,206 THERE'S A LACK OF PEDIATRIC DATA 3641 02:53:32,206 --> 02:53:33,307 AND THE PANEL FELT THERE ARE 3642 02:53:33,307 --> 02:53:35,109 BASED ON THE LACK OF PEDIATRIC 3643 02:53:35,109 --> 02:53:36,443 DATA WE COULD NOT SUPPORT A 3644 02:53:36,443 --> 02:53:36,977 RECOMMENDATION OF THESE 3645 02:53:36,977 --> 02:53:42,015 INTERVENTIONS FOR CHILDREN. 3646 02:53:42,015 --> 02:53:43,517 AGAIN, THIS IS A CONDITIONAL 3647 02:53:43,517 --> 02:53:44,418 RECOMMENDATION AND THIS WAS 3648 02:53:44,418 --> 02:53:50,190 BASED ON INDICT EVIDENCE FROM 3649 02:53:50,190 --> 02:53:53,260 THE FIBROMYALGIA FOUNDATION AS 3650 02:53:53,260 --> 02:53:55,295 THERE WAS NO EVIDENCE THAT 3651 02:53:55,295 --> 02:53:55,963 EXISTED IN THE CONTEXT OF SICKLE 3652 02:53:55,963 --> 02:54:03,670 CELL DISEASE SPECIFICALLY. 3653 02:54:03,670 --> 02:54:06,740 FINALLY WE WERE INTERESTED IN 3654 02:54:06,740 --> 02:54:09,676 LOOKING AT CHRONIC OPIOID 3655 02:54:09,676 --> 02:54:11,178 THERAPY OR PERIODIC PERIODIC 3656 02:54:11,178 --> 02:54:14,181 THERAPY IN PATIENTS WITH SICKLE 3657 02:54:14,181 --> 02:54:17,317 CELL DISEASE WITH CHRONIC PAIN. 3658 02:54:17,317 --> 02:54:18,519 A FEW GENERAL COMMENTS ABOUT 3659 02:54:18,519 --> 02:54:19,553 CHRONIC PAIN OPIOID THERAPY. 3660 02:54:19,553 --> 02:54:23,290 IT WAS IMPORTANT TO THE PANEL TO 3661 02:54:23,290 --> 02:54:26,193 CONSIDER A VERY INDIVIDUALIZED 3662 02:54:26,193 --> 02:54:29,997 APPROACH TO INITIATING FOR 3663 02:54:29,997 --> 02:54:31,298 DISCONTINUING THERAPY AND THIS 3664 02:54:31,298 --> 02:54:33,400 WAS BASED ON A BALANCE BETWEEN 3665 02:54:33,400 --> 02:54:35,302 RISK AND HARMS AND BENEFITS AND 3666 02:54:35,302 --> 02:54:38,205 ALSO CONSIDERING FUNCTIONAL 3667 02:54:38,205 --> 02:54:40,474 OUTCOMES FOR THE INDIVIDUAL 3668 02:54:40,474 --> 02:54:41,175 THAT'S RECEIVING CHRONIC OPIOID 3669 02:54:41,175 --> 02:54:42,810 THERAPY AND THE BENEFIT OVER 3670 02:54:42,810 --> 02:54:43,143 TIME. 3671 02:54:43,143 --> 02:54:45,779 A RECOMMENDATION IN THIS SPACE 3672 02:54:45,779 --> 02:54:46,980 ARE DIVIDED BASED ON THREE 3673 02:54:46,980 --> 02:54:48,482 DISTINCT PATIENT POPULATIONS 3674 02:54:48,482 --> 02:54:50,584 THAT HAVE A CLEAR PRESENCE OF 3675 02:54:50,584 --> 02:54:51,351 CHRONIC, RATHER THAN EPISODIC 3676 02:54:51,351 --> 02:54:56,223 PAIN. 3677 02:54:56,223 --> 02:54:57,724 SO THE FIRST POPULATION IS 3678 02:54:57,724 --> 02:54:59,993 EMERGING AND/OR RECENTLY 3679 02:54:59,993 --> 02:55:01,228 DEVELOPED CHRONIC PAIN. 3680 02:55:01,228 --> 02:55:03,764 THE PANEL RECOMMENDED AGAINST 3681 02:55:03,764 --> 02:55:07,668 THE INITIATION OF CHRONIC OPIOID 3682 02:55:07,668 --> 02:55:10,637 THERAPY AND REFRACTORY TO OTHER 3683 02:55:10,637 --> 02:55:12,105 MODALITY. 3684 02:55:12,105 --> 02:55:13,574 IF SOMEBODY'S ALREADY CHRONIC 3685 02:55:13,574 --> 02:55:14,741 OPIOID THERAPY AND FUNCTIONING 3686 02:55:14,741 --> 02:55:16,009 WELL AND THOUGHT TO HAVE 3687 02:55:16,009 --> 02:55:20,113 PERCEIVED BENEFIT THE PANEL 3688 02:55:20,113 --> 02:55:21,248 RECOMMENDED CONTINUATION OF 3689 02:55:21,248 --> 02:55:23,317 CHRONIC OPIOID THERAPY. 3690 02:55:23,317 --> 02:55:27,221 IF AN INDIVIDUAL'S RECEIVING 3691 02:55:27,221 --> 02:55:28,655 CHRONIC OPIOID THERAPY AND 3692 02:55:28,655 --> 02:55:38,565 FUNCTIONI IING POORLY THEY 3693 02:55:38,565 --> 02:55:39,933 RECOMMENDED AGAINST AND THESE 3694 02:55:39,933 --> 02:55:42,836 ARE ALL CONDITION 3695 02:55:42,836 --> 02:55:43,203 RECOMMENDATIONS. 3696 02:55:43,203 --> 02:55:44,538 WE WERE INTERESTED IN NON 3697 02:55:44,538 --> 02:55:46,006 PHARMACOLOGIC THERAPY AND ASKED 3698 02:55:46,006 --> 02:55:47,941 WHETHER IT SHOULD BE USED IN 3699 02:55:47,941 --> 02:55:49,209 ADDITION TO PHARMACOLOGIC 3700 02:55:49,209 --> 02:55:49,810 THERAPY FOR THE TREATMENT OF 3701 02:55:49,810 --> 02:55:54,114 CHRONIC PAIN. 3702 02:55:54,114 --> 02:55:57,184 "WE SETTLED ON PRIMARILY 3703 02:55:57,184 --> 02:56:02,222 FOCUSSING ON COGNITIVE 3704 02:56:02,222 --> 02:56:04,858 BEHAVIORAL THERAPY OR CBT AS AN 3705 02:56:04,858 --> 02:56:06,093 ADDITION TO OTHER STRATEGIES 3706 02:56:06,093 --> 02:56:08,228 THAT WERE CONSIDERED BY THE 3707 02:56:08,228 --> 02:56:09,529 PANEL INCLUDING ACCEPTANCE AND 3708 02:56:09,529 --> 02:56:12,266 COMMITMENT THERAPY AND MINDFUL 3709 02:56:12,266 --> 02:56:12,866 BASED TREATMENT AND COPING 3710 02:56:12,866 --> 02:56:14,668 SKILLS AND THERAPY AND THE PANEL 3711 02:56:14,668 --> 02:56:16,670 FELT LIKE THESE SHOULD BE USED 3712 02:56:16,670 --> 02:56:18,405 IN THE CONTEXT OF COMPREHENSIVE 3713 02:56:18,405 --> 02:56:20,407 DISEASE AND PAIN MANAGEMENT PLAN 3714 02:56:20,407 --> 02:56:23,543 AND THIS WAS A CONDITIONAL 3715 02:56:23,543 --> 02:56:28,115 RECOMMENDATION BASED ON THE 3716 02:56:28,115 --> 02:56:30,317 FIBROMYALGIA LITERATURE. 3717 02:56:30,317 --> 02:56:33,487 WE HAD A STATEMENT ON SCREENING 3718 02:56:33,487 --> 02:56:35,322 FOR MENTAL HEALTH COMORBIDITIES 3719 02:56:35,322 --> 02:56:37,224 SPECIFICALLY STATING THAT 3720 02:56:37,224 --> 02:56:43,330 PATIENTS SHOULD ROUTINELY 3721 02:56:43,330 --> 02:56:45,198 SCREENED AND FOR OTHER 3722 02:56:45,198 --> 02:56:45,899 PSYCHOLOGICAL COMORBIDITY. 3723 02:56:45,899 --> 02:56:47,734 A GOOD PRACTICE STATEMENT IS NOT 3724 02:56:47,734 --> 02:56:49,569 BASED ON A SYSTEMIC REVIEW OF 3725 02:56:49,569 --> 02:56:50,971 AVAILABLE EVIDENCE BUT MEANT TO 3726 02:56:50,971 --> 02:56:52,406 ENDORSE INTERVENTION OR 3727 02:56:52,406 --> 02:56:55,342 PRACTICES THAT THE GUIDELINE 3728 02:56:55,342 --> 02:56:59,346 PANEL AGREED HAVE UNEQUIVOCAL 3729 02:56:59,346 --> 02:57:01,381 NET BENEFIT AND NOT RECOMMEND BE 3730 02:57:01,381 --> 02:57:03,784 USED AND THESE THEREFORE CAN BE 3731 02:57:03,784 --> 02:57:04,251 INTERPRETED AS STRONG 3732 02:57:04,251 --> 02:57:07,321 RECOMMENDATIONS. 3733 02:57:07,321 --> 02:57:10,057 THEN IN THE CONTEXT OF SICKLE 3734 02:57:10,057 --> 02:57:13,360 CELL DISEASE THERAPEUTIC OPTIONS 3735 02:57:13,360 --> 02:57:23,870 VERY BRIEFLY WE KNOW HIGH -- 3736 02:57:29,409 --> 02:57:33,847 HIHY 3737 02:57:33,847 --> 02:57:35,315 DR 3738 02:57:35,315 --> 02:57:44,157 DROXIA AND OTHERS ARE KNOWN AND 3739 02:57:44,157 --> 02:57:46,293 CURATIVE THERAPY WITH BONE 3740 02:57:46,293 --> 02:57:49,329 MARROW TRANSPLANTATION IS 3741 02:57:49,329 --> 02:57:52,666 EFFECTIVE AT DECREASING VASO 3742 02:57:52,666 --> 02:57:55,302 OCCLUSIVE PAINFUL EVENTS BUT 3743 02:57:55,302 --> 02:58:00,207 THEY'VE BEEN SHOWN TO HAVE 3744 02:58:00,207 --> 02:58:02,009 THERAPY EFFECTIVE FOR CHRONIC 3745 02:58:02,009 --> 02:58:04,177 PAIN IS CURRENTLY THERE'S NO 3746 02:58:04,177 --> 02:58:07,314 ANSWER CURRENTLY TO THAT 3747 02:58:07,314 --> 02:58:07,914 QUESTION. 3748 02:58:07,914 --> 02:58:10,050 SO IT'S REALLY IMPORTANT TO 3749 02:58:10,050 --> 02:58:13,854 CONTINUE TO THINK OF BOTH THE 3750 02:58:13,854 --> 02:58:15,355 ASSESSMENT AND TREATMENTS OF 3751 02:58:15,355 --> 02:58:18,425 SICKLE CELL DISEASE PAIN IN A 3752 02:58:18,425 --> 02:58:23,296 MULTIDISCIPLINARY AND MULTIMODAL 3753 02:58:23,296 --> 02:58:26,233 APPROACH OR MODEL WITH THESE 3754 02:58:26,233 --> 02:58:29,069 IMPORTANT FACTORS AND A VARIETY 3755 02:58:29,069 --> 02:58:31,304 OF INTERVENTIONS AND ASSESSMENT 3756 02:58:31,304 --> 02:58:34,574 MEASURES I LISTS INCLUDING 3757 02:58:34,574 --> 02:58:36,843 INTEGRATIVE HEALTH APPROACHES 3758 02:58:36,843 --> 02:58:37,611 AND UNDERSTANDING SOCIAL 3759 02:58:37,611 --> 02:58:38,845 DETERMINATES OF HEALTH AND 3760 02:58:38,845 --> 02:58:45,819 PHYSICAL THERAPY, CDT, REGIONAL 3761 02:58:45,819 --> 02:58:49,022 ANESTHESIA AND I'LL LEAVE YOU 3762 02:58:49,022 --> 02:58:53,126 WITH THIS SUMMARY SLIDE WHICH IS 3763 02:58:53,126 --> 02:58:54,728 IDEALLY WHERE WE SHOULD GO OR 3764 02:58:54,728 --> 02:58:55,328 STRIVE FOR IN THE CONTEXT OF 3765 02:58:55,328 --> 02:58:59,166 PAIN. 3766 02:58:59,166 --> 02:59:01,168 WE'VE SHOWN PAIN IS COMPLEX IN 3767 02:59:01,168 --> 02:59:02,903 THE ASSESSMENT AND TAXONOMY AND 3768 02:59:02,903 --> 02:59:03,136 BIOLOGY. 3769 02:59:03,136 --> 02:59:05,272 SO BEING ABLE TO QUANTIFY THE 3770 02:59:05,272 --> 02:59:06,807 IMPACT OF PAIN UNDERSTANDING THE 3771 02:59:06,807 --> 02:59:10,110 EXTENT OF PAIN ON PATIENT 3772 02:59:10,110 --> 02:59:13,213 FUNCTIONING AND BEING ABLE TO 3773 02:59:13,213 --> 02:59:14,281 CAREFULLY PHENOTYPE THE PAIN 3774 02:59:14,281 --> 02:59:15,949 UTILIZING THE TOOLS IN OUR 3775 02:59:15,949 --> 02:59:17,918 TOOLBOX AND BASED ON THIS 3776 02:59:17,918 --> 02:59:19,719 COMPLEXITY THINKING ABOUT 3777 02:59:19,719 --> 02:59:23,323 PHARMACOLOGIC THERAPY THAT CAN 3778 02:59:23,323 --> 02:59:32,432 AND SHOULD BE USED, NON 3779 02:59:32,432 --> 02:59:35,302 PHARMACOLOGIC THERAPIES AND IN 3780 02:59:35,302 --> 02:59:37,471 AN IDEAL WORLD TARGETING TO 3781 02:59:37,471 --> 02:59:41,842 IMPROVE THE QUALITY OF THE LIFE 3782 02:59:41,842 --> 02:59:43,076 OF INDIVIDUALS LIVING WITH 3783 02:59:43,076 --> 02:59:43,510 SICKLE CELL DISEASE. 3784 02:59:43,510 --> 02:59:51,485 THANK YOU FOR YOUR ATTENTION. 3785 02:59:51,485 --> 02:59:52,252 AND THANK YOU FOR ALLOWING ME 3786 02:59:52,252 --> 02:59:57,691 TO SHARE WITH YOU TODAY. 3787 02:59:57,691 --> 03:00:03,330 >> IS THAT YOU ONLINE? 3788 03:00:03,330 --> 03:00:05,665 WE'LL GET DR. BRANDOW. 3789 03:00:05,665 --> 03:00:15,876 >> HI, PAT. 3790 03:00:34,361 --> 03:00:41,334 >> WHAT I'D LIKE TO ASK YOU 3791 03:00:41,334 --> 03:00:44,171 MENTIONED ABOUT RESEARCH ON THE 3792 03:00:44,171 --> 03:00:48,375 COMPLEXITY OF PAIN MAYBE YOU CAN 3793 03:00:48,375 --> 03:00:51,344 GIVE US A REVIEW OF WHAT'S GOING 3794 03:00:51,344 --> 03:00:54,915 ON AND SECONDLY IN THE CLINICAL 3795 03:00:54,915 --> 03:00:56,116 TRIALS USING PAIN AS THE END 3796 03:00:56,116 --> 03:00:58,385 POINT AND I LIKE THE WAY YOU SET 3797 03:00:58,385 --> 03:00:59,486 THE COMPLEXITY. 3798 03:00:59,486 --> 03:01:05,559 THERE'S ALSO ACUTE PAIN WHICH IS 3799 03:01:05,559 --> 03:01:06,793 NON-SICKLE CELL IN ONE OF YOUR 3800 03:01:06,793 --> 03:01:06,993 BOXES. 3801 03:01:06,993 --> 03:01:10,897 IF YOU'RE LOOKING FOR EFFECTS 3802 03:01:10,897 --> 03:01:16,036 AND PRESUMABLY CAUSING VASO 3803 03:01:16,036 --> 03:01:18,271 OCCLUSION, SHOULD WE ADD MARK 3804 03:01:18,271 --> 03:01:20,473 THAT SUPPORT VASO OCCLUSION 3805 03:01:20,473 --> 03:01:28,815 RATHER THAN JUST SAY ACUTE PAIN? 3806 03:01:28,815 --> 03:01:29,916 >> GREAT QUESTION THANK YOU FOR 3807 03:01:29,916 --> 03:01:30,850 THE EXCELLENT QUESTIONS. 3808 03:01:30,850 --> 03:01:37,557 I'LL TAKE THE FIRST ONE ABOUT 3809 03:01:37,557 --> 03:01:45,065 THE COMPLEXITY OF PAIN. 3810 03:01:45,065 --> 03:01:47,300 AND NOT ONLY LOOKING AT THE RED 3811 03:01:47,300 --> 03:01:48,668 CELL ABNORMALITY THAT 3812 03:01:48,668 --> 03:01:49,302 INITIATIVES THE PAIN IN YOUNG 3813 03:01:49,302 --> 03:01:50,637 LIFE BUT LOOKING AT THE 3814 03:01:50,637 --> 03:01:53,807 COMPONENTS OF PAIN FROM THE 3815 03:01:53,807 --> 03:01:55,942 CENTRAL NERVOUS SYSTEM AND BRAIN 3816 03:01:55,942 --> 03:01:59,112 AND SPINAL CORT AND PERIPHERAL 3817 03:01:59,112 --> 03:02:01,181 SYSTEM AND VISCERAL PAIN I THINK 3818 03:02:01,181 --> 03:02:03,550 WE KNOW LITTLE ABOUT AND I THINK 3819 03:02:03,550 --> 03:02:05,819 THE NEURAL BIOLOGY OF PAIN IS 3820 03:02:05,819 --> 03:02:07,921 BASICALLY NEEDS TO BE LOOKED AT 3821 03:02:07,921 --> 03:02:14,261 THE ORGAN SYSTEM LEVEL TO TRULY 3822 03:02:14,261 --> 03:02:19,332 UNDERSTAND AND WHAT IS DRIVING 3823 03:02:19,332 --> 03:02:21,501 IT AMONGST EACH OTHER AND ACROSS 3824 03:02:21,501 --> 03:02:23,903 THE LIFE SPAN IS WHAT MAKES IT 3825 03:02:23,903 --> 03:02:26,339 SO HIGHLY COMPLEX. 3826 03:02:26,339 --> 03:02:28,074 I THINK THERE'S A LOT OF PAIN 3827 03:02:28,074 --> 03:02:29,576 BIOLOGISTS THAT STUDIO PAIN 3828 03:02:29,576 --> 03:02:34,114 OUTSIDE OF SICKLE CELL DISEASE 3829 03:02:34,114 --> 03:02:36,082 THAT NEED TO BE INTERESTED AND 3830 03:02:36,082 --> 03:02:37,450 LURE INTO THE STUDY OF SICKLE 3831 03:02:37,450 --> 03:02:38,985 CELL DISEASE BECAUSE I THINK 3832 03:02:38,985 --> 03:02:41,187 THEY COME AT IT FROM A DIFFERENT 3833 03:02:41,187 --> 03:02:42,889 LENS. 3834 03:02:42,889 --> 03:02:47,294 I'VE LEARNED IMMENSELY PERFECT 3835 03:02:47,294 --> 03:02:49,229 THE COLLEAGUES THAT LOOK AT 3836 03:02:49,229 --> 03:02:50,263 LABORATORY MODELS. 3837 03:02:50,263 --> 03:02:51,231 THINKING ABOUT PAIN AND SICKLE 3838 03:02:51,231 --> 03:02:54,467 CELL DISEASE NOT JUST AS A 3839 03:02:54,467 --> 03:02:56,269 HEMATOLOGIC PROBLEM BUT AS A 3840 03:02:56,269 --> 03:02:57,737 GLOBAL SYSTEMS BASED APPROACH 3841 03:02:57,737 --> 03:02:59,873 AND HONING IN ON EACH SYSTEM AND 3842 03:02:59,873 --> 03:03:01,908 THE CONTRIBUTION OF PAIN I THINK 3843 03:03:01,908 --> 03:03:04,811 IS WHERE WE ABSOLUTELY NEED TO 3844 03:03:04,811 --> 03:03:06,246 CONTINUE TO GO WITH THE WORK 3845 03:03:06,246 --> 03:03:07,247 WE'RE DOING. 3846 03:03:07,247 --> 03:03:09,516 TO ANSWER YOUR SECOND QUESTION 3847 03:03:09,516 --> 03:03:14,587 ABOUT END POINTS FOR CLINICAL 3848 03:03:14,587 --> 03:03:22,028 TRIALS, I THINK WE NEED TO LOOK 3849 03:03:22,028 --> 03:03:23,697 AT A PATIENT-REPORTED OUTCOME OF 3850 03:03:23,697 --> 03:03:23,897 PAIN. 3851 03:03:23,897 --> 03:03:26,166 THE REPORT OF PAIN IS THE GOLD 3852 03:03:26,166 --> 03:03:28,034 STANDARD IS ASKING THE PATIENT 3853 03:03:28,034 --> 03:03:31,037 NOT NECESSARILY A BIOLOGICAL 3854 03:03:31,037 --> 03:03:32,005 CORRELATE TO SAY THEY ARE IN 3855 03:03:32,005 --> 03:03:34,341 PAIN BUT I THINK THERE'S IMMENSE 3856 03:03:34,341 --> 03:03:35,408 VALUE IN LOOK AT THE TWO 3857 03:03:35,408 --> 03:03:37,310 TOGETHER AND AS A COMPOSITE END 3858 03:03:37,310 --> 03:03:44,417 POINT OF CAN WE VALIDATE 3859 03:03:44,417 --> 03:03:45,919 PLASMA-BASED BIOMARKER IN THE 3860 03:03:45,919 --> 03:03:48,888 COMPANIONSHIP WITH A 3861 03:03:48,888 --> 03:03:51,224 PATIENT-REPORTED OUTCOME SO WE 3862 03:03:51,224 --> 03:03:53,226 KNOW THEY GO TOGETHER WHEN X 3863 03:03:53,226 --> 03:03:59,199 GOES UP PAIN IS WORSE. 3864 03:03:59,199 --> 03:04:00,667 LOOKING AT THEM TOGETHER THINK 3865 03:04:00,667 --> 03:04:10,043 IS REALLY IMPORTANT. 3866 03:04:10,043 --> 03:04:13,847 >> THANK YOU, WE'LL MEDE -- 3867 03:04:13,847 --> 03:04:15,315 NEED TO MOVE ON TO THE NEXT. 3868 03:04:15,315 --> 03:04:18,151 >> I'LL BE QUICK. 3869 03:04:18,151 --> 03:04:19,052 EXCELLENT TALK. 3870 03:04:19,052 --> 03:04:20,620 I WANT TO TALK ABOUT LIDOCAINE. 3871 03:04:20,620 --> 03:04:24,090 I DID NOT SEE THAT IN THE 3872 03:04:24,090 --> 03:04:24,357 OUTLINES. 3873 03:04:24,357 --> 03:04:28,628 OUR HOSPITAL JUST GOT LIDOCAINE 3874 03:04:28,628 --> 03:04:31,297 AS AN ADJUVANT AND RECENT DATA 3875 03:04:31,297 --> 03:04:33,566 SUPPORTING IT AND I WANT YOUR 3876 03:04:33,566 --> 03:04:34,434 THOUGHTS ON THAT. 3877 03:04:34,434 --> 03:04:34,801 EXCELLENT TALK. 3878 03:04:34,801 --> 03:04:35,101 THANK YOU. 3879 03:04:35,101 --> 03:04:35,702 >> THANK YOU SO MUCH FOR THE 3880 03:04:35,702 --> 03:04:45,311 QUESTION. 3881 03:04:45,311 --> 03:04:48,548 WHEN WE WROTE THE GUIDELINES 3882 03:04:48,548 --> 03:04:51,317 THEY WERE PUBLISHED IN 2020 AND 3883 03:04:51,317 --> 03:04:57,090 THE LITERATURE REVIEW TOOK PLACE 3884 03:04:57,090 --> 03:04:58,224 LONG BEFORE THAT AND WE SHARED 3885 03:04:58,224 --> 03:04:59,826 THE CONCERN WE NEED TO UPDATE 3886 03:04:59,826 --> 03:05:00,994 THEM AS SOON AS POSSIBLE. 3887 03:05:00,994 --> 03:05:05,298 AT THE TIME WE RECOMMENDED FOR 3888 03:05:05,298 --> 03:05:06,766 OPIOID REFRACTORY THE INITIATE 3889 03:05:06,766 --> 03:05:09,536 OF KETAMINE AND DID NOT INCLUDE 3890 03:05:09,536 --> 03:05:10,470 LIDOCAINE BECAUSE THE LITERATURE 3891 03:05:10,470 --> 03:05:13,907 AT THE TIME DIDN'T POINT TO THAT 3892 03:05:13,907 --> 03:05:16,009 DIRECTION HOWEVER, WE'RE IN THE 3893 03:05:16,009 --> 03:05:16,543 PROCESS OF DOING ANOTHER 3894 03:05:16,543 --> 03:05:17,577 LITERATURE SEARCH AND UPDATING 3895 03:05:17,577 --> 03:05:20,914 THOSE GUIDELINES. 3896 03:05:20,914 --> 03:05:27,287 SO WE WOULD LOVE TO LOOK AT 3897 03:05:27,287 --> 03:05:28,621 LIDOCAINE AND IF YOU HAVE 3898 03:05:28,621 --> 03:05:29,722 EVIDENCE FROM YOUR OWN 3899 03:05:29,722 --> 03:05:30,657 INSTITUTION IT WOULD BE 3900 03:05:30,657 --> 03:05:32,559 FANTASTIC TO ASSIMILATE AND PUT 3901 03:05:32,559 --> 03:05:33,693 OUT IN THE LITERATURE TO LEARN 3902 03:05:33,693 --> 03:05:35,295 FROM YOUR EXPERIENCE BECAUSE IT 3903 03:05:35,295 --> 03:05:36,529 WORKS THROUGH A DIFFERENT 3904 03:05:36,529 --> 03:05:37,697 PATHWAY AND THERE'S REASONS TO 3905 03:05:37,697 --> 03:05:38,898 BELIEVE IT WOULD BE EFFICACIOUS 3906 03:05:38,898 --> 03:05:43,303 OR EFFECTIVE IN TREATING SICKLE 3907 03:05:43,303 --> 03:05:44,170 CELL PAIN FOR CERTAIN 3908 03:05:44,170 --> 03:05:54,380 INDIVIDUALS. 3909 03:05:58,952 --> 03:06:01,321 >> WE'LL MOVE ON TO OUR NEXT 3910 03:06:01,321 --> 03:06:09,829 SPEAKER, SUSANNA CURTIS ON 3911 03:06:09,829 --> 03:06:18,304 CANNABINOIDS AND OPIOIDS. 3912 03:06:18,304 --> 03:06:20,840 ALSO LOOKING AT THE ROLE OF 3913 03:06:20,840 --> 03:06:22,208 DYSFUNCTIONAL INFLAMMATION AND 3914 03:06:22,208 --> 03:06:26,312 ORGAN DAMAGE IN PEOPLE WITH 3915 03:06:26,312 --> 03:06:27,714 SICKLE CELL DISEASE AND 3916 03:06:27,714 --> 03:06:28,481 DEVELOPING CHRONIC PAIN AND 3917 03:06:28,481 --> 03:06:30,717 INTERESTED IN EXAMINING THE 3918 03:06:30,717 --> 03:06:32,285 UTILITY OF CANNABINOIDS FOR 3919 03:06:32,285 --> 03:06:33,786 TREATING CHRONIC PAIN AND THAT'S 3920 03:06:33,786 --> 03:06:44,264 WHAT WE'LL HEAR ABOUT TODAY. 3921 03:07:15,929 --> 03:07:17,397 >> THANK YOU TO THE ORGANIZERS 3922 03:07:17,397 --> 03:07:20,300 AND FOR THE INVITATION TO SPEAK. 3923 03:07:20,300 --> 03:07:23,069 I'LL SPEAK ABOUT CANNABINOIDS 3924 03:07:23,069 --> 03:07:24,704 VERSUS OPIOIDS. 3925 03:07:24,704 --> 03:07:26,072 IT'S HARD TO SAY THEY'RE VERSE. 3926 03:07:26,072 --> 03:07:35,315 WHEN WE TALK ABOUT TREATING PAIN 3927 03:07:35,315 --> 03:07:36,783 WE NEED TO LOOK AT THEM AND TALK 3928 03:07:36,783 --> 03:07:47,126 ABOUT A COMPARISON. 3929 03:07:54,601 --> 03:07:58,771 WE'LL TALK ABOUT THEM AS 3930 03:07:58,771 --> 03:07:59,739 MULTI-RECEPTORS AND THEIR USE IN 3931 03:07:59,739 --> 03:08:02,575 PAIN AND ADVERSE EFFECTS AND HOW 3932 03:08:02,575 --> 03:08:03,943 DO WE USE THEM AND EVIDENCE DO 3933 03:08:03,943 --> 03:08:04,611 WE HAVE OF THEIR USE IN SICKLE 3934 03:08:04,611 --> 03:08:10,416 CELL DISEASE. 3935 03:08:10,416 --> 03:08:13,953 SO BOTH THE OPIOID AND THE 3936 03:08:13,953 --> 03:08:18,591 CANNABINOID SYSTEM ARE 3937 03:08:18,591 --> 03:08:21,461 ENDOGENOUS CENTRAL TO OUR NEURAL 3938 03:08:21,461 --> 03:08:23,596 LOGICAL DEVELOPMENT AND USED 3939 03:08:23,596 --> 03:08:25,765 BOTH IN PAIN AND OTHER THINGS 3940 03:08:25,765 --> 03:08:27,600 LIKE APPETITE AND SLEEP AND 3941 03:08:27,600 --> 03:08:28,001 REWARD. 3942 03:08:28,001 --> 03:08:33,006 SO ON THE LEFT YOU CAN SEE THE 3943 03:08:33,006 --> 03:08:34,707 INDIGENOUS OPIOID SYSTEM IN THE 3944 03:08:34,707 --> 03:08:35,808 CENTRAL NERVOUS SYSTEM THOUGH IT 3945 03:08:35,808 --> 03:08:37,010 HAS OTHER LOCATIONS AS WELL. 3946 03:08:37,010 --> 03:08:42,482 THE PRIMARY RECEPTORS ARE THE 3947 03:08:42,482 --> 03:08:42,849 KAPPA RECEPTORS. 3948 03:08:42,849 --> 03:08:44,283 THOSE THE ONES WE KNOW MOST 3949 03:08:44,283 --> 03:08:47,320 ABOUT AND TEND TO TARGET DRUGS. 3950 03:08:47,320 --> 03:08:49,288 I'LL GIVE YOU ONE OF MY FAVORITE 3951 03:08:49,288 --> 03:08:51,424 FUN FACTS ABOUT THE SYSTEM YOU 3952 03:08:51,424 --> 03:08:54,961 CAN STIMULATE INDIGENOUS OPIOIDS 3953 03:08:54,961 --> 03:08:57,497 WITH THE PEDIATRICIANS THAT'S 3954 03:08:57,497 --> 03:09:01,701 WHY THEY GIVE SUGAR WATER TO 3955 03:09:01,701 --> 03:09:05,004 BABIES FOR CIRCUMCISIONS AND 3956 03:09:05,004 --> 03:09:08,307 WHEN WE ARE SORE YOU CAN 3957 03:09:08,307 --> 03:09:11,277 CONSIDER DESSERT AND THE 3958 03:09:11,277 --> 03:09:15,648 CANNABINOID SYSTEM IS PERIPHERAL 3959 03:09:15,648 --> 03:09:19,619 AND HAS CANNABINOID RECEPTOR 1 3960 03:09:19,619 --> 03:09:21,821 AND 2. 3961 03:09:21,821 --> 03:09:27,093 CANNABINOID RECEPTOR 1 3962 03:09:27,093 --> 03:09:28,361 NEUROLOGIC AND IN THE PERIPHERAL 3963 03:09:28,361 --> 03:09:31,297 SYSTEM AND THE RECEPTOR THAT 3964 03:09:31,297 --> 03:09:35,301 DOES WHAT WE THINK ABOUT LIKE 3965 03:09:35,301 --> 03:09:38,104 PAIN, APPETITE, ANXIETY AND 3966 03:09:38,104 --> 03:09:38,304 SLEEP. 3967 03:09:38,304 --> 03:09:41,708 CANNABINOID RECEPTOR 2, YOU CAN 3968 03:09:41,708 --> 03:09:47,113 SEE IT'S LOCATED IN CNS AND 3969 03:09:47,113 --> 03:09:48,281 LOCATED ON THE MICROGLIA THE 3970 03:09:48,281 --> 03:09:52,018 IMMUNE CELLS OF THE NERVOUS 3971 03:09:52,018 --> 03:09:54,520 SYSTEM AND HAS THE PRIMARY 3972 03:09:54,520 --> 03:09:55,321 LOCATIONS AND IMMUNOLOGIC 3973 03:09:55,321 --> 03:10:04,497 RECEPTORS. 3974 03:10:04,497 --> 03:10:06,532 SO WHERE ARE WE IN DRUG 3975 03:10:06,532 --> 03:10:06,833 DEVELOPMENT 3976 03:10:06,833 --> 03:10:08,801 >> WHEN IT COMES TO OPIOIDS WE 3977 03:10:08,801 --> 03:10:10,503 HAVE BEEN DOING A LOT OF DRUG 3978 03:10:10,503 --> 03:10:12,004 DEVELOPMENT FOR A LONG TIME 3979 03:10:12,004 --> 03:10:14,006 THAT'S LED TO WONDERFUL THINGS 3980 03:10:14,006 --> 03:10:14,607 AND SOME REALLY SAD THINGS AS 3981 03:10:14,607 --> 03:10:17,744 WELL. 3982 03:10:17,744 --> 03:10:19,912 BUT WE HAVE REALLY DONE A NICE 3983 03:10:19,912 --> 03:10:21,581 JOB UNDERSTANDING THESE THREE 3984 03:10:21,581 --> 03:10:23,349 PRIMARY RECEPTORS UNDERSTANDING 3985 03:10:23,349 --> 03:10:26,319 THEIR ROLE AND UNDERSTANDING HOW 3986 03:10:26,319 --> 03:10:26,686 TO TARGET THEM. 3987 03:10:26,686 --> 03:10:28,654 SO THIS IS A LIST ACTUALLY OF 3988 03:10:28,654 --> 03:10:29,989 OVER THE COUNTER OPIOIDS. 3989 03:10:29,989 --> 03:10:31,891 SO WE CAN SEE NOT ONLY CAN WE 3990 03:10:31,891 --> 03:10:35,328 USE OPIOID FOR THINGS LIKE PAIN 3991 03:10:35,328 --> 03:10:41,734 BUT USE CODING TO TARGET COUGH 3992 03:10:41,734 --> 03:10:42,935 AND AS ANYBODY WHO TREATS SICKLE 3993 03:10:42,935 --> 03:10:44,570 CELL DISEASE IN THE HOSPITAL 3994 03:10:44,570 --> 03:10:47,840 KNOWS WE HAVE MANY NARCOTICS TO 3995 03:10:47,840 --> 03:10:48,875 TARGET THESE RECEPTORS. 3996 03:10:48,875 --> 03:10:50,743 WHEN IT COMES TO DRUG 3997 03:10:50,743 --> 03:10:52,545 DEVELOPMENT IN OPIOIDS WE HAVE 3998 03:10:52,545 --> 03:10:53,913 REALLY COME A LONG WAY AND HAVE 3999 03:10:53,913 --> 03:10:55,314 A NICE UNDERSTANDING OF THE 4000 03:10:55,314 --> 03:10:56,649 SYSTEM AND HAVE A LOT OF 4001 03:10:56,649 --> 03:10:59,352 DIFFERENT PHARMACOLOGIC OPTIONS 4002 03:10:59,352 --> 03:11:00,720 TO TARGET IT. 4003 03:11:00,720 --> 03:11:05,324 THAT'S NOT SO WITH CANNABINOIDS. 4004 03:11:05,324 --> 03:11:07,794 WE HAVE A MUCH MORE SHALLOW 4005 03:11:07,794 --> 03:11:10,630 UNDERSTANDING HOW TO STIMULATE 4006 03:11:10,630 --> 03:11:12,598 THE RECEPTORS AND HAVE VERY FEW 4007 03:11:12,598 --> 03:11:14,467 FDA APPROVED DRUGS TO USE. 4008 03:11:14,467 --> 03:11:18,371 THIS IS THE ENTIRE LIST HERE. 4009 03:11:18,371 --> 03:11:21,307 WE HAVE TWO FORMS OF THC. 4010 03:11:21,307 --> 03:11:24,644 THC IS WHAT WE THINK OF AS THE 4011 03:11:24,644 --> 03:11:26,245 PRIMARY ACTIVE INGREDIENT IN 4012 03:11:26,245 --> 03:11:27,747 CANNABIS A CANNABINOID RECEPTOR 4013 03:11:27,747 --> 03:11:29,649 1 AND 2 PARTIAL AGONIST. 4014 03:11:29,649 --> 03:11:31,250 YOU GET STIMULATION OF BOTH 4015 03:11:31,250 --> 03:11:32,084 RECEPTORS THERE. 4016 03:11:32,084 --> 03:11:35,354 SO THIS IS PROVED FOR THE OF 4017 03:11:35,354 --> 03:11:36,656 NAUSEA AND WEIGHT GAIN. 4018 03:11:36,656 --> 03:11:43,563 AND WE HAVE ONE FORMULATION OF C 4019 03:11:45,198 --> 03:11:48,000 -- CBD WHAT YOU SEE IN ALL THE 4020 03:11:48,000 --> 03:11:52,305 BAKE STORES WALKING DOWN THE 4021 03:11:52,305 --> 03:11:54,707 VOTE AND TRY TO SUGGEST IT FOR 4022 03:11:54,707 --> 03:11:56,175 USE FOR EVERYTHING UNDER THE SUN 4023 03:11:56,175 --> 03:11:57,777 INCLUDING USE FOR YOUR PETS AND 4024 03:11:57,777 --> 03:12:00,246 WHAT DO WE KNOW ABOUT THIS? 4025 03:12:00,246 --> 03:12:08,287 IT'S A RECEPTOR 1 AND 2 AN -- 4026 03:12:08,287 --> 03:12:09,789 ANTAGONIST AND WE DON'T KNOW 4027 03:12:09,789 --> 03:12:11,090 WHAT RECEPTORS IT'S TARGETING 4028 03:12:11,090 --> 03:12:15,628 BUT WE DO KNOW IS IT'S QUITE 4029 03:12:15,628 --> 03:12:17,630 ANTI-INFLAMMATORY AND SEEMS TO 4030 03:12:17,630 --> 03:12:19,332 CALM DOWN THE INMATE IMMUNE 4031 03:12:19,332 --> 03:12:23,135 SYSTEM AND SO WE HAVE ONE FDA 4032 03:12:23,135 --> 03:12:28,307 APPROVED CBD FORM USED FOR RARE 4033 03:12:28,307 --> 03:12:29,775 SEIZURE DISORDERS. 4034 03:12:29,775 --> 03:12:32,979 AND THERE'S AN ORAL SPRAY THAT 4035 03:12:32,979 --> 03:12:36,115 CONTAINS CBD AND THC NOT 4036 03:12:36,115 --> 03:12:37,116 APPROVED IN THE UNITED STATES 4037 03:12:37,116 --> 03:12:40,987 BUT APPROVED IN EUROPE AND GIVEN 4038 03:12:40,987 --> 03:12:44,257 FOR THE TREATMENT NEUROPATHIC 4039 03:12:44,257 --> 03:12:47,326 PAIN IN MULTIPLE SCLEROSIS. 4040 03:12:47,326 --> 03:12:49,428 WE HAVE SOME CANNABINOIDS IN A 4041 03:12:49,428 --> 03:12:51,163 REGULATED FORM BUT WE'RE FAR 4042 03:12:51,163 --> 03:12:51,797 BEHIND WHERE WE HAVE COME WITH 4043 03:12:51,797 --> 03:12:56,936 OPIOIDS. 4044 03:12:56,936 --> 03:12:59,372 WHAT ABOUT USE IN DIFFERENT PAIN 4045 03:12:59,372 --> 03:12:59,672 TYPES? 4046 03:12:59,672 --> 03:13:01,941 AS DR. BRANDOW ILLUSTRATED WE 4047 03:13:01,941 --> 03:13:05,411 KNOW WHEN IT COMES TO PAIN 4048 03:13:05,411 --> 03:13:06,679 SICKLE CELL DISEASE THERE'S MANY 4049 03:13:06,679 --> 03:13:08,781 CAUSES AND THERE'S A VARIETY OF 4050 03:13:08,781 --> 03:13:09,749 BIOLOGIES BEHIND THOSE CAUSES. 4051 03:13:09,749 --> 03:13:11,550 WHAT WE MIGHT DO TO TREAT PAIN 4052 03:13:11,550 --> 03:13:13,953 IN ONE INDIVIDUAL MAY BE VERY 4053 03:13:13,953 --> 03:13:15,655 DIFFERENT THAN WHAT WE'D DO FOR 4054 03:13:15,655 --> 03:13:16,355 ANOTHER INDIVIDUAL. 4055 03:13:16,355 --> 03:13:20,326 SO WHEN IT COMES TO ACUTE PAIN 4056 03:13:20,326 --> 03:13:23,329 THAT IS OF COURSE OUR CLASSIC 4057 03:13:23,329 --> 03:13:24,063 SICKLE CELL DISEASE CRISIS BUT 4058 03:13:24,063 --> 03:13:25,498 COULD BE OTHER SUDDEN TISSUE 4059 03:13:25,498 --> 03:13:27,767 DAMAGE WE KNOW OPIOIDS ARE 4060 03:13:27,767 --> 03:13:28,901 INCREDIBLY EFFECTIVE FOR ACUTE 4061 03:13:28,901 --> 03:13:30,803 PAIN AND ARE OUR BEST TREATMENT 4062 03:13:30,803 --> 03:13:33,940 FOR WHEN SOMEONE COMES IN WITH 4063 03:13:33,940 --> 03:13:35,908 PAIN WITH TISSUE DAMAGE. 4064 03:13:35,908 --> 03:13:38,344 CANNABINOIDS IN TERMS OF ACUTE 4065 03:13:38,344 --> 03:13:40,813 PAIN THE STUDIES ARE MIXED SOME 4066 03:13:40,813 --> 03:13:42,615 SHOW BENEFIT AND SOME DON'T WE 4067 03:13:42,615 --> 03:13:44,283 CAN'T SAY IT'S SO EFFECTIVE 4068 03:13:44,283 --> 03:13:46,085 THERE JUST YET. 4069 03:13:46,085 --> 03:13:47,687 BUT WHEN IT COMES TO CHRONIC 4070 03:13:47,687 --> 03:13:49,021 PAIN I THINK WE HAVE A LITTLE 4071 03:13:49,021 --> 03:13:51,324 BIT OF THE OPPOSITE SITUATION. 4072 03:13:51,324 --> 03:13:52,558 STUDIES COMPARING OPIOIDS TO 4073 03:13:52,558 --> 03:13:56,329 PLACEBO HAVE SHOWN IT DOES HAVE 4074 03:13:56,329 --> 03:13:58,864 SOME BENEFIT IN CHRONIC PAIN BUT 4075 03:13:58,864 --> 03:14:03,202 COMPARED TO OTHER NON-OPIOID 4076 03:14:03,202 --> 03:14:06,772 MEDICATIONS LIKE GABA PENT NOIDS 4077 03:14:06,772 --> 03:14:08,808 THEY SHOW OPIOIDS REALLY AREN'T 4078 03:14:08,808 --> 03:14:10,076 MORE EFFECTIVE THAN THOSE 4079 03:14:10,076 --> 03:14:12,845 MEDICATIONS BUT IN THE MEANWHILE 4080 03:14:12,845 --> 03:14:15,314 THE ADVERSE EFFECTS ARE MUCH 4081 03:14:15,314 --> 03:14:19,652 MORE CONCERNING. 4082 03:14:19,652 --> 03:14:22,722 YOU'RE TREATING CHRONIC PAIN 4083 03:14:22,722 --> 03:14:26,325 MAYBE IT'S NOT YOUR GO-TO AND 4084 03:14:26,325 --> 03:14:28,427 STUDIES HAVE SHOWN THERE SEALS 4085 03:14:28,427 --> 03:14:30,930 TO BE A TRUE BENEFIT IN PEOPLE 4086 03:14:30,930 --> 03:14:31,497 WITH DAILY PAIN FOR USE IN 4087 03:14:31,497 --> 03:14:34,533 CANNABINOIDS. 4088 03:14:34,533 --> 03:14:36,802 SOME SPECIFIC PAIN TYPE UNDER 4089 03:14:36,802 --> 03:14:38,838 THAT FOR NEUROPATHIC PAIN, PAIN 4090 03:14:38,838 --> 03:14:40,606 FROM NERVE DAMAGE AND OPIOIDS 4091 03:14:40,606 --> 03:14:43,309 AGAIN AREN'T REALLY EFFECTIVE 4092 03:14:43,309 --> 03:14:45,311 FOR TREATING NEUROPATHIC PAIN 4093 03:14:45,311 --> 03:14:48,047 AND CANNABINOIDS HAVE SHOWN A 4094 03:14:48,047 --> 03:14:52,118 BENEFIT IN NEURO PATHIC PAIN AND 4095 03:14:52,118 --> 03:14:53,486 PATIENTS WITH SICKLE CELL 4096 03:14:53,486 --> 03:14:55,788 DISEASE IT CAN BE IMPORTANT. 4097 03:14:55,788 --> 03:14:56,689 INFLAMMATORY PAIN. 4098 03:14:56,689 --> 03:15:01,327 THOSE OF US WHO HAVE SORE ARM 4099 03:15:01,327 --> 03:15:03,162 AFTER OUR COVID SHOT KNOW 4100 03:15:03,162 --> 03:15:04,296 INFLAMMATION EVEN ABSENT OF 4101 03:15:04,296 --> 03:15:06,432 TISSUE OR NERVE DAMAGE CAN CAUSE 4102 03:15:06,432 --> 03:15:10,269 PAIN IN AND OF ITSELF AND SICKLE 4103 03:15:10,269 --> 03:15:11,837 CELL DISEASE A DISEASE OF 4104 03:15:11,837 --> 03:15:12,371 CHRONIC INFLAMMATION HAS 4105 03:15:12,371 --> 03:15:13,773 INFLAMMATION CONTRIBUTING TO 4106 03:15:13,773 --> 03:15:13,973 PAIN. 4107 03:15:13,973 --> 03:15:18,611 NOW OPIOIDS ARE ACTUALLY 4108 03:15:18,611 --> 03:15:19,011 PRO-INFLAMMATORY. 4109 03:15:19,011 --> 03:15:21,614 OPIOIDS LIKE MORPHINE WILL 4110 03:15:21,614 --> 03:15:28,487 TRIGGER THE MAIN ACTOR -- 4111 03:15:28,487 --> 03:15:34,860 ACTIVATORS AND WILL CAUSE 4112 03:15:34,860 --> 03:15:37,596 INFLAMMATION WHERE IS 4113 03:15:37,596 --> 03:15:43,335 CANNABINOIDS ARE AN 4114 03:15:43,335 --> 03:15:45,304 ANTIINFLAMM 4115 03:15:45,304 --> 03:15:46,138 ANTIINFLAMMATORY -- 4116 03:15:46,138 --> 03:15:48,307 ANTI-INFLAMMATORY AND WE DON'T 4117 03:15:48,307 --> 03:15:50,843 HAVE THE DATA YET. 4118 03:15:50,843 --> 03:15:52,678 AND PAIN SENSITIZATION IS 4119 03:15:52,678 --> 03:15:56,248 IMPORTANT IN SICKLE CELL DISEASE 4120 03:15:56,248 --> 03:15:58,951 WE KNOW OPIOID CAN CAUSE OPIOID 4121 03:15:58,951 --> 03:16:00,352 HYPER ALGESIA AND THEMSELVES CAN 4122 03:16:00,352 --> 03:16:02,855 BE A PAIN OF PAIN SENSITIZATION 4123 03:16:02,855 --> 03:16:05,357 AND CANNABINOIDS HAVE BEEN KNOWN 4124 03:16:05,357 --> 03:16:06,792 TO REDUCE THRESHOLDS FOR PAIN 4125 03:16:06,792 --> 03:16:10,529 AND INCREASE PAIN TOLERANCE AND 4126 03:16:10,529 --> 03:16:12,832 DECREASE PAIN UNPLEASANTNESS AND 4127 03:16:12,832 --> 03:16:14,366 THERE'S A ROLE BUT WE NEED MORE 4128 03:16:14,366 --> 03:16:16,368 RESEARCH TO BE DONE. 4129 03:16:16,368 --> 03:16:18,904 AND HOW ABOUT ADVERSE EFFECTS. 4130 03:16:18,904 --> 03:16:23,275 SO BOTH OPIOIDS AND CANNABINOIDS 4131 03:16:23,275 --> 03:16:26,645 CAN LEAD TO SLOWER REACTION TIME 4132 03:16:26,645 --> 03:16:29,815 AND THEY CAN BOTH CAUSE EUPHORIA 4133 03:16:29,815 --> 03:16:32,351 AND DROWSINESS AND OF COURSE 4134 03:16:32,351 --> 03:16:34,019 USING THEM IN COMBINATION COULD 4135 03:16:34,019 --> 03:16:36,288 INCREASE THE SIDE EFFECTS. 4136 03:16:36,288 --> 03:16:38,357 THEY CAN BOTH CAUSE 4137 03:16:38,357 --> 03:16:42,761 CARDIOVASCULAR AFFECTS, 4138 03:16:42,761 --> 03:16:43,329 HYPOTENSION AND TACHYCARDIA. 4139 03:16:43,329 --> 03:16:47,333 BOTH CAUSE SIDE EFFECTS. 4140 03:16:47,333 --> 03:16:49,969 OPIOIDS TEND TO REDUCE APPETITE 4141 03:16:49,969 --> 03:16:50,803 AND CANNABINOID INCREASE 4142 03:16:50,803 --> 03:16:55,341 MOTILITY SO THEY CAN CAUSE 4143 03:16:55,341 --> 03:17:00,246 DIARRHEA AND ARE APPETITE 4144 03:17:00,246 --> 03:17:00,746 STIMULATED. 4145 03:17:00,746 --> 03:17:03,349 THEY ACCURATE TOLL LIGHT 4146 03:17:03,349 --> 03:17:06,919 RECEPTOR 4 SO WHEN PATIENTS 4147 03:17:06,919 --> 03:17:08,854 COMPLAIN THEY'RE VERY ITCHY IT'S 4148 03:17:08,854 --> 03:17:16,095 BECAUSE ALL THE HISTO MINES AND 4149 03:17:16,095 --> 03:17:18,264 THEY CAN CAUSE HYPER GONADISM 4150 03:17:18,264 --> 03:17:20,599 USED OVER TIME. 4151 03:17:20,599 --> 03:17:24,370 IN TERMS OF RESPIRATORY EFFECTS 4152 03:17:24,370 --> 03:17:25,738 WE KNOW THEY CAN CAUSE 4153 03:17:25,738 --> 03:17:27,773 RESPIRATORY DEPRESSION. 4154 03:17:27,773 --> 03:17:32,144 CANNABINOID CAN CAUSED 4155 03:17:32,144 --> 03:17:37,316 RESPIRATORY EFFECTS IN INHALED 4156 03:17:37,316 --> 03:17:41,921 MANNER AND IT IN CAN BE 4157 03:17:41,921 --> 03:17:43,122 ASSOCIATED WITH COUGH AND THAT'S 4158 03:17:43,122 --> 03:17:43,989 SOMETHING WE DON'T WANT TO 4159 03:17:43,989 --> 03:17:47,326 SUPPORT AND TALK TO THEM ABOUT. 4160 03:17:47,326 --> 03:17:50,196 CANNABINOIDS HAVE A UNIQUE 4161 03:17:50,196 --> 03:17:52,731 PROPERTY AND SEEM TO INCREASE 4162 03:17:52,731 --> 03:17:56,302 RISK OF PSYCHOSIS AND RATE IS 1 4163 03:17:56,302 --> 03:17:59,171 OF 100 BUT IN CANNABIS USERS 4164 03:17:59,171 --> 03:18:01,373 IT'S 2 OUT OF 100 BUT SEEMS TO 4165 03:18:01,373 --> 03:18:09,815 BE HIGHER IN PEOPLE WITH 4166 03:18:09,815 --> 03:18:12,218 PREDISPOSITION AND OVERDOSE. 4167 03:18:12,218 --> 03:18:14,353 BOTH CAN CAUSE OVERDOSE AND 4168 03:18:14,353 --> 03:18:18,324 THOUGH WE KNOW PATIENTS WITH 4169 03:18:18,324 --> 03:18:20,459 SICKLE CELL DISEASE DO HAVE 4170 03:18:20,459 --> 03:18:22,795 LOWER OPIOID RATES IT'S NOT 4171 03:18:22,795 --> 03:18:28,834 SOMETHING WE CAN IGNORE. 4172 03:18:28,834 --> 03:18:30,970 CANNABINOID OVERDOSE CAN CAUSE 4173 03:18:30,970 --> 03:18:35,307 DELIRIUM BUT IS NON-FATAL AND 4174 03:18:35,307 --> 03:18:38,677 BOTH CAN CAUSE LEGAL TOXICITY 4175 03:18:38,677 --> 03:18:42,181 AND I'VE LOOKED AT VERSIONS AND 4176 03:18:42,181 --> 03:18:45,417 BUT BOTH EXIST IN UNREGULATED 4177 03:18:45,417 --> 03:18:47,319 FORMS AND PEOPLE CAN PURCHASE 4178 03:18:47,319 --> 03:18:50,889 THEM MORE LEGALLY NOW THAN 10 4179 03:18:50,889 --> 03:18:55,294 YEARS AGO BUT MAYBE MORE IN 10 4180 03:18:55,294 --> 03:19:02,368 YEARS FROM NOW AND ILLEGALA 4181 03:19:02,368 --> 03:19:07,239 ILLEGALALITY -- ILLEGALITY AND 4182 03:19:07,239 --> 03:19:08,007 MOST PEOPLE WITH SICKLE CELL 4183 03:19:08,007 --> 03:19:09,608 DISEASE ARE PEOPLE OF COLOR AND 4184 03:19:09,608 --> 03:19:10,943 THEY'RE FOUR TIMES MORE LIKELY 4185 03:19:10,943 --> 03:19:14,380 TO BE ARRESTED FOR CANNABIS USE 4186 03:19:14,380 --> 03:19:15,981 AND PROSECUTED MORE HARSHLY SO 4187 03:19:15,981 --> 03:19:17,349 IT'S A CONCERN FOR OUR PATIENTS. 4188 03:19:17,349 --> 03:19:20,352 AND FINALLY WHAT ABOUT FINANCIAL 4189 03:19:20,352 --> 03:19:20,619 TOXICITY? 4190 03:19:20,619 --> 03:19:22,154 AGAIN, WE'VE DONE A LOT MORE 4191 03:19:22,154 --> 03:19:24,790 DRUG DEVELOPMENT FOR OPIOIDS. 4192 03:19:24,790 --> 03:19:26,358 WE HAVE MORE OPTIONS AND THINGS 4193 03:19:26,358 --> 03:19:30,095 TO PRESCRIBE PATIENTS AND WHEN 4194 03:19:30,095 --> 03:19:35,301 WE PRESCRIBE THEM FOR THE PART 4195 03:19:35,301 --> 03:19:36,702 PATIENTS AREN'T PAYING A LOT OF 4196 03:19:36,702 --> 03:19:39,305 OUT OF POCKET AND CANNABINOIDS 4197 03:19:39,305 --> 03:19:41,640 ARE FEDERALLY ILLEGAL MEANING NO 4198 03:19:41,640 --> 03:19:42,841 INSURANCE COMPANY WILL COVER IT 4199 03:19:42,841 --> 03:19:48,147 SO EVEN IF YOU HAVE A PATIENT ON 4200 03:19:48,147 --> 03:19:49,381 MEDICAL CANNABIS IT WILL BE OUT 4201 03:19:49,381 --> 03:19:51,250 OF POCKET AND THAT CAN ADD UP 4202 03:19:51,250 --> 03:19:51,684 QUICKLY. 4203 03:19:51,684 --> 03:19:54,820 ON AVERAGE AN OUNCE OF CANNABIS 4204 03:19:54,820 --> 03:19:58,557 IS ABOUT $300 AND AN OUNCE OF 4205 03:19:58,557 --> 03:20:01,226 CANNABIS DEPENDING CAN MAKE 4206 03:20:01,226 --> 03:20:03,262 ROUGHLY ABOUT 60 CANNABIS 4207 03:20:03,262 --> 03:20:03,696 CIGARETTES. 4208 03:20:03,696 --> 03:20:06,999 AGAIN, WE DON'T WANT TO 4209 03:20:06,999 --> 03:20:09,001 ENCOURAGE SMOKING BUT TO GIVE 4210 03:20:09,001 --> 03:20:11,303 YOU AN IDEA SOMEONE CAN SPEND A 4211 03:20:11,303 --> 03:20:13,272 LOT OF MONEY FOR DAILY PAIN AND 4212 03:20:13,272 --> 03:20:14,039 THIS CAN BECOME A BIG PROBLEM 4213 03:20:14,039 --> 03:20:15,507 FOR PATIENTS. 4214 03:20:15,507 --> 03:20:17,976 SO WHAT DO WE KNOW ABOUT SICKLE 4215 03:20:17,976 --> 03:20:18,344 CELL DISEASE? 4216 03:20:18,344 --> 03:20:22,247 I WON'T GO INTO THIS IN TOO MUCH 4217 03:20:22,247 --> 03:20:24,550 DETAIL BECAUSE DR. BRANDOW DID A 4218 03:20:24,550 --> 03:20:25,984 LOVELY JOB GOING OVER THE 4219 03:20:25,984 --> 03:20:27,786 GUIDELINES BUT FOR ACUTE PAIN WE 4220 03:20:27,786 --> 03:20:29,621 KNOW OPIOID THERAPY SHOULD BE 4221 03:20:29,621 --> 03:20:32,024 GIVEN RAPIDLY IDEALLY WITHIN THE 4222 03:20:32,024 --> 03:20:33,092 FIRST HOUR. 4223 03:20:33,092 --> 03:20:36,095 THERAPY SHOULD BE TAILORED WE 4224 03:20:36,095 --> 03:20:38,263 WANT AN INDIVIDUAL PAIN PLAN IN 4225 03:20:38,263 --> 03:20:43,235 PARTNERSHIP WITH THAT PATIENT 4226 03:20:43,235 --> 03:20:48,307 AND OTHER THERAPIES AS WELL. 4227 03:20:48,307 --> 03:20:51,744 CHRONIC PAIN IS MORE 4228 03:20:51,744 --> 03:20:52,044 COMPLICATED. 4229 03:20:52,044 --> 03:20:55,013 AS DR. BRANDOW STATED, CERTAINLY 4230 03:20:55,013 --> 03:20:59,351 WE WANT TO START WITH OTHER 4231 03:20:59,351 --> 03:21:02,388 AGENTS, SSRIs, PHYSICAL THERAPY, 4232 03:21:02,388 --> 03:21:03,288 OTHER OPTIONS BUT IF THEY 4233 03:21:03,288 --> 03:21:05,491 HAVEN'T BEEN EFFECTIVE FOR A 4234 03:21:05,491 --> 03:21:08,861 PATIENT WE CAN CONSIDER STARTING 4235 03:21:08,861 --> 03:21:10,696 CHRONIC OPIOID THERAPY AND 4236 03:21:10,696 --> 03:21:11,830 THEY'RE ALREADY ON IT WE SHOULD 4237 03:21:11,830 --> 03:21:15,134 WORK WITH THE PATIENT TO SEE HOW 4238 03:21:15,134 --> 03:21:16,034 IT'S WORKING FOR THEM AND WHAT 4239 03:21:16,034 --> 03:21:18,370 TO DO ABOUT IT. 4240 03:21:18,370 --> 03:21:22,608 NOW, WHEN IT COMES TO 4241 03:21:22,608 --> 03:21:23,909 CANNABINOIDS WE HAVE LESS DRUGS 4242 03:21:23,909 --> 03:21:26,712 AND HAVE DONE LESS RESEARCH. 4243 03:21:26,712 --> 03:21:28,380 SO THE AMERICAN SOCIETY OF 4244 03:21:28,380 --> 03:21:31,016 HEMATOLOGY SAID IN THEIR 2020 4245 03:21:31,016 --> 03:21:31,817 GUIDELINES IT'S A RESEARCH 4246 03:21:31,817 --> 03:21:35,320 PRIORITY THE BENEFITS AND RISK 4247 03:21:35,320 --> 03:21:35,988 OF CANNABINOIDS IN SICKLE CELL 4248 03:21:35,988 --> 03:21:38,090 DISEASE BE EXAMINED. 4249 03:21:38,090 --> 03:21:41,693 WHAT DO WE KNOW? 4250 03:21:41,693 --> 03:21:42,995 WE KNOW FROM MOUSE MODELS 4251 03:21:42,995 --> 03:21:47,332 CANNABINOID RECEPTOR 1 AND 2 IN 4252 03:21:47,332 --> 03:21:50,769 MICE WILL REDUCE INFLAMMATION 4253 03:21:50,769 --> 03:21:56,041 WHICH WHEN IT COMES TO SICKLE 4254 03:21:56,041 --> 03:21:58,811 CELL DISEASE HAS IMPORTANT 4255 03:21:58,811 --> 03:22:09,288 INDICATIONS AND CANABIDIOLE 4256 03:22:10,322 --> 03:22:14,426 REDUCES INFLAMMATION. 4257 03:22:14,426 --> 03:22:16,495 AND CHRONIC PAIN IS REPORTED AND 4258 03:22:16,495 --> 03:22:17,329 THAT'S HIGH COMPARED TO THE 4259 03:22:17,329 --> 03:22:18,497 GENERAL POPULATION BUT NOT HIGH 4260 03:22:18,497 --> 03:22:19,631 FOR OTHER POPULATIONS OF CHRONIC 4261 03:22:19,631 --> 03:22:20,132 PAIN. 4262 03:22:20,132 --> 03:22:23,502 THIS IS PRETTY TYPICAL FOR ANY 4263 03:22:23,502 --> 03:22:33,846 CHRONIC PAIN POPULATION. 4264 03:22:33,846 --> 03:22:34,546 RECEIVING MEDICAL CANNABIS 4265 03:22:34,546 --> 03:22:36,815 COMPARED TO PATIENTS THAT ASKED 4266 03:22:36,815 --> 03:22:39,051 FOR CERTIFIED IS RELATED TO 4267 03:22:39,051 --> 03:22:40,752 SUBSEQUENT REDUCTION IN 4268 03:22:40,752 --> 03:22:44,423 ADMISSIONS THESE ARE 4269 03:22:44,423 --> 03:22:45,724 CROSS-SECTIONAL STUDIES NOT 4270 03:22:45,724 --> 03:22:46,058 PROSPECTIVE. 4271 03:22:46,058 --> 03:22:50,696 THERE WAS FIVE DAYS OF INHALED 4272 03:22:50,696 --> 03:22:53,165 THC, CBD COMPARED TO PLACEBO. 4273 03:22:53,165 --> 03:22:54,166 IT'S AMAZING THE RESEARCHERS 4274 03:22:54,166 --> 03:22:55,934 WERE ABLE TO COMPLETE THE STUDY 4275 03:22:55,934 --> 03:22:58,003 BECAUSE THERE'S A LOT OF 4276 03:22:58,003 --> 03:23:01,540 CHALLENGES TO DOING PROSPECTIVE 4277 03:23:01,540 --> 03:23:02,808 CANNABINOID STUDIES. 4278 03:23:02,808 --> 03:23:06,545 THE STUDY SHOWED AN IMPROVEMENT 4279 03:23:06,545 --> 03:23:09,848 UP MOOD FROM PATIENTS WHO 4280 03:23:09,848 --> 03:23:11,817 INHALED THE CANNABIS BUT WASN'T 4281 03:23:11,817 --> 03:23:13,385 STATISTICALLY SIGNIFICANT 4282 03:23:13,385 --> 03:23:14,686 TOWARDS IN IMPROVEMENT IN DAILY 4283 03:23:14,686 --> 03:23:17,656 PAIN BUT IT WAS ONLY A FIVE-DAY 4284 03:23:17,656 --> 03:23:17,856 STUDY. 4285 03:23:17,856 --> 03:23:19,858 WHEN IT COMES TO MODULATING 4286 03:23:19,858 --> 03:23:21,693 CHRONIC PAIN WE THINK OF 4287 03:23:21,693 --> 03:23:23,328 MEDICINES NEEDING MONTHS NOT 4288 03:23:23,328 --> 03:23:25,130 DAYS. 4289 03:23:25,130 --> 03:23:28,667 AND I WILL THANK THE NHLBI FOR 4290 03:23:28,667 --> 03:23:32,905 FUNDING MY CASE STUDY WHICH IS 4291 03:23:32,905 --> 03:23:36,875 EXAMINING ORAL THC THIS 4292 03:23:36,875 --> 03:23:43,282 MEDICATION FOR EIGHT WEEKS AND 4293 03:23:43,282 --> 03:23:44,416 EVALUATING THE EFFECT OF CHRONIC 4294 03:23:44,416 --> 03:23:47,819 PAIN AND OTHER MARKERS. 4295 03:23:47,819 --> 03:23:49,388 A LOT OF EVIDENCE WE NEED BUT I 4296 03:23:49,388 --> 03:23:51,323 THINK THERE ARE THINGS GOING ON. 4297 03:23:51,323 --> 03:23:52,791 SO MAYBE IN THE NEXT DECADE WE 4298 03:23:52,791 --> 03:23:55,327 CAN START TO CATCH UP WITH OUR 4299 03:23:55,327 --> 03:23:57,329 DRUG DEVELOPMENT AND 4300 03:23:57,329 --> 03:23:59,331 UNDERSTANDING OF CANNABINOIDS. 4301 03:23:59,331 --> 03:24:01,033 IN CONCLUSION, WHEN IT COMES TO 4302 03:24:01,033 --> 03:24:03,602 ACUTE PAIN IN SICKLE CELL 4303 03:24:03,602 --> 03:24:06,405 DISEASE I THINK OPIOIDS SHOULD 4304 03:24:06,405 --> 03:24:07,339 BE UTILIZED AND THEY'RE A GREAT 4305 03:24:07,339 --> 03:24:08,507 TREATMENT FOR THAT. 4306 03:24:08,507 --> 03:24:10,275 WHEN IT COMES TO CHRONIC PAIN 4307 03:24:10,275 --> 03:24:12,110 THEY SHOULD BE MORE SECONDARY. 4308 03:24:12,110 --> 03:24:13,679 THEY'RE ON THE LIST BUT WE NEED 4309 03:24:13,679 --> 03:24:16,181 TO THINK OF OTHER THINGS. 4310 03:24:16,181 --> 03:24:18,383 CANNABINOIDS MAY HAVE A ROLE IN 4311 03:24:18,383 --> 03:24:18,984 CHRONIC PAIN AND SICKLE CELL 4312 03:24:18,984 --> 03:24:21,019 DISEASE BUT WE NEED MORE WORK IN 4313 03:24:21,019 --> 03:24:23,055 DRUG INVESTMENT AND RANDOMIZED 4314 03:24:23,055 --> 03:24:25,123 STUDIES BEFORE WE UNDERSTAND THE 4315 03:24:25,123 --> 03:24:26,224 BENEFIT AND RISK OF THE USE. 4316 03:24:26,224 --> 03:24:29,361 AND ULTIMATELY ALL DECISIONS 4317 03:24:29,361 --> 03:24:32,598 NEED TO BE MADE IN PARTNERSHIP 4318 03:24:32,598 --> 03:24:34,366 WITH THE PATIENTS AND ALL 4319 03:24:34,366 --> 03:24:35,734 DECISIONS WITH CANNABINOID 4320 03:24:35,734 --> 03:24:36,702 SHOULD BE MADE WITH HARM 4321 03:24:36,702 --> 03:24:37,402 REDUCTION IN MIND. 4322 03:24:37,402 --> 03:24:41,573 WHEN IT COMES TO THE 4323 03:24:41,573 --> 03:24:42,841 CONVERSATIONS WITH THE PATIENT 4324 03:24:42,841 --> 03:24:43,875 USING CHRONIC OPIOID THERAPY AND 4325 03:24:43,875 --> 03:24:45,777 MAYBE THERE'S A CONCERN ABOUT 4326 03:24:45,777 --> 03:24:47,312 THEIR FUNCTION PLEASE REMEMBER 4327 03:24:47,312 --> 03:24:49,982 SUDDEN REDUCTION AND SUDDENLY 4328 03:24:49,982 --> 03:24:53,051 CUTTING OFF SOMEBODY'S OPIOID 4329 03:24:53,051 --> 03:24:54,953 SUPPLY WHEN THEY'RE USING IT 4330 03:24:54,953 --> 03:24:56,121 CHRONICALLY IS ASSOCIATED WITH 4331 03:24:56,121 --> 03:24:58,557 OVERDOSE AND WE NEED TO WORK IN 4332 03:24:58,557 --> 03:24:59,358 PARTNERSHIP WITH OUR PATIENTS. 4333 03:24:59,358 --> 03:25:01,526 ONLY THE OTHER SIDE FOR THE 4334 03:25:01,526 --> 03:25:03,996 PATIENTS REPORTING CANNABIS IS 4335 03:25:03,996 --> 03:25:06,665 HELPFUL FOR THEIR PAIN, IF WE 4336 03:25:06,665 --> 03:25:09,301 GIVE THEM ACCESS TO MEDICAL 4337 03:25:09,301 --> 03:25:13,105 CANNABIS, THOUGH IT'S NOT AS 4338 03:25:13,105 --> 03:25:14,406 REGULATED AS AN FDA APPROVED 4339 03:25:14,406 --> 03:25:16,942 PRODUCT IT CAN BE USED IN EDIBLE 4340 03:25:16,942 --> 03:25:18,910 FORM AND GIVING THEM ACCESS TO 4341 03:25:18,910 --> 03:25:20,245 SOMETHING THAT IS REGULATED SO 4342 03:25:20,245 --> 03:25:23,081 AT LEAST WON'T HAVE THE RISK OF 4343 03:25:23,081 --> 03:25:26,118 BEING LACED WITH DANGEROUS S OR 4344 03:25:26,118 --> 03:25:27,586 THE LEGAL RAISING OF OBTAINING 4345 03:25:27,586 --> 03:25:32,391 SOMETHING ILLEGAL. 4346 03:25:32,391 --> 03:25:34,026 SO THANK YOU FOR YOUR ATTENTION 4347 03:25:34,026 --> 03:25:44,569 AND HAPPY TO TAKE ANY QUESTIONS. 4348 03:26:14,499 --> 03:26:18,103 >> MY SUGGESTION WOULD BE TO 4349 03:26:18,103 --> 03:26:22,374 STUDY MORE IN DWEFT -- 4350 03:26:22,374 --> 03:26:23,975 INGESTIBLES OR TRANS DERMAL FOR 4351 03:26:23,975 --> 03:26:24,309 CHRONIC PAIN. 4352 03:26:24,309 --> 03:26:26,044 I FIND IT HELPFUL FOR ME AND 4353 03:26:26,044 --> 03:26:29,281 WOULD CERTAINLY LIKE TO SEE THE 4354 03:26:29,281 --> 03:26:31,316 RESEARCH DONE FOR INGESTIBLES OR 4355 03:26:31,316 --> 03:26:33,485 TRANS DERMALS. 4356 03:26:33,485 --> 03:26:35,320 >> ABSOLUTELY. 4357 03:26:35,320 --> 03:26:35,921 THANK YOU FOR THAT EXCELLENT 4358 03:26:35,921 --> 03:26:46,064 COMMENT. 4359 03:27:08,520 --> 03:27:10,021 AND SMOKE ONLY LASTS ABOUT AN 4360 03:27:10,021 --> 03:27:12,591 HOUR AND INGESTIBLES CAN LAST 4361 03:27:12,591 --> 03:27:13,792 FROM EIGHT TO 12 HOURS. 4362 03:27:13,792 --> 03:27:18,497 I THINK WHEN WE ARE THINK OF 4363 03:27:18,497 --> 03:27:20,232 TREATING CHRONIC PAIN AN 4364 03:27:20,232 --> 03:27:20,899 INGESTIBLE IS POTENTIALLY MORE 4365 03:27:20,899 --> 03:27:21,166 EFFECTIVE. 4366 03:27:21,166 --> 03:27:31,510 THANK YOU FOR THAT. 4367 03:27:37,649 --> 03:27:40,285 >> DR. CURTIS THANKS FOR YOUR 4368 03:27:40,285 --> 03:27:41,953 NICE TALK AND HARD WORK IN 4369 03:27:41,953 --> 03:27:43,321 SOLVING THE RIDDLE. 4370 03:27:43,321 --> 03:27:44,422 GOOD LUCK TO YOU. 4371 03:27:44,422 --> 03:27:46,658 I WONDER IF YOU CAN COMMENT ON 4372 03:27:46,658 --> 03:27:51,329 THE INCREASED RATES OF PSYCHOTIC 4373 03:27:51,329 --> 03:27:53,532 EPISODES IN PEOPLE EXPOSED TO 4374 03:27:53,532 --> 03:27:56,601 MARIJUANA AND THIS IS A CONCERN 4375 03:27:56,601 --> 03:27:58,670 AND HAVE MORE THAN ONE ANECDOTE 4376 03:27:58,670 --> 03:28:00,839 OF THIS TRANSPIRING IN OUR WORK 4377 03:28:00,839 --> 03:28:01,907 AT JOHNS HOPKINS. 4378 03:28:01,907 --> 03:28:03,742 >> YES, IT'S ABSOLUTELY A 4379 03:28:03,742 --> 03:28:04,176 CONCERN. 4380 03:28:04,176 --> 03:28:06,578 IT DOES SEEM THAT ONE OF THE 4381 03:28:06,578 --> 03:28:09,648 SIDE EFFECTS OF PARTICULARLY THC 4382 03:28:09,648 --> 03:28:14,219 IS THIS RARE ACUTE PSYCHOTIC 4383 03:28:14,219 --> 03:28:14,452 EPISODE. 4384 03:28:14,452 --> 03:28:16,755 IT DOES SEEM LIKE MANY OF THESE 4385 03:28:16,755 --> 03:28:18,156 EPISODES OR AT LEAST THERE'S 4386 03:28:18,156 --> 03:28:20,492 MORE LIKELY TO HAPPEN IN 4387 03:28:20,492 --> 03:28:23,328 PATIENTS THAT HAVE ALREADY HAD 4388 03:28:23,328 --> 03:28:25,063 PREVIOUS PSYCHOTIC EPISODES OR 4389 03:28:25,063 --> 03:28:26,464 LEADS TO THEIR FIRST PSYCHOTIC 4390 03:28:26,464 --> 03:28:29,167 BREAK. 4391 03:28:29,167 --> 03:28:32,270 SO WHAT I WOULD SAY IS IN ANY 4392 03:28:32,270 --> 03:28:35,540 PATIENT WHO HAD PREVIOUS HISTORY 4393 03:28:35,540 --> 03:28:39,611 OF PSYCHOSIS OR CONCERN WITH 4394 03:28:39,611 --> 03:28:41,880 PARANOIA OR PSYCHOSIS IN THE 4395 03:28:41,880 --> 03:28:43,315 PATIENT I'D RECOMMEND THEM TO 4396 03:28:43,315 --> 03:28:45,817 NOT USE THC PRODUCTS. 4397 03:28:45,817 --> 03:28:46,985 IN TERMS OF PATIENTS THAT DON'T 4398 03:28:46,985 --> 03:28:49,521 HAVE THAT HISTORY, I THINK 4399 03:28:49,521 --> 03:28:50,488 UNFORTUNATELY IT'S A RARE BUT 4400 03:28:50,488 --> 03:28:58,697 DEVASTATING SIDE EFFECT. 4401 03:28:58,697 --> 03:29:01,132 >> SPEAKING WITH MY PSYCHIATRIST 4402 03:29:01,132 --> 03:29:03,301 HAT ON FOR 10 SECONDS, THE 4403 03:29:03,301 --> 03:29:04,936 LONGER TERM WORRY ABOUT 4404 03:29:04,936 --> 03:29:05,837 MARIJUANA SEEMS TO BE THERE'S A 4405 03:29:05,837 --> 03:29:08,173 LOT OF DIFFERENT MEDICINES IN 4406 03:29:08,173 --> 03:29:10,609 DRUGS THAT CAN CAUSE PSYCHOSIS 4407 03:29:10,609 --> 03:29:13,712 BUT WHEN IT'S CAUSED BY 4408 03:29:13,712 --> 03:29:16,748 MARIJUANA IT SEEMS TO BE MORE 4409 03:29:16,748 --> 03:29:18,350 LOOKLY CHRONIC AND WHAT WE HAVE 4410 03:29:18,350 --> 03:29:20,919 TO BE MOST WORRIED ABOUT. 4411 03:29:20,919 --> 03:29:25,223 >> LET'S MOVE ON, SHALL WE. 4412 03:29:25,223 --> 03:29:28,627 NEXT UP, WE HAVE DR. ZENA 4413 03:29:28,627 --> 03:29:31,296 QUEZADO AND I MUST APOLOGIZE BUT 4414 03:29:31,296 --> 03:29:34,599 I'M GOING TO NEED HELP IN THE 4415 03:29:34,599 --> 03:29:35,634 PRONUNCIATION BECAUSE MY 4416 03:29:35,634 --> 03:29:40,505 PORTUGUESE IS NON-EXISTENT. 4417 03:29:40,505 --> 03:29:46,478 CHAIR OF ATHESIOLOGY IN THE 4418 03:29:46,478 --> 03:29:47,545 DEPARTMENT OF NATIONAL INSTITUTE 4419 03:29:47,545 --> 03:29:53,785 OF HEALTH CLINICAL CENTER AND 4420 03:29:53,785 --> 03:29:55,620 RECEIVED HER M.D. IN BRAZIL AND 4421 03:29:55,620 --> 03:29:59,324 TRAINED IN CRITICAL MEDICINE AND 4422 03:29:59,324 --> 03:30:07,866 INTERNAL MEDICINE AND ANESTHETIC 4423 03:30:07,866 --> 03:30:10,802 PEDIATRIC AND PAIN MANAGEMENT 4424 03:30:10,802 --> 03:30:14,105 AND DR. QUEZADO WILL TALK TO US 4425 03:30:14,105 --> 03:30:24,382 ABOUT KETAMINE. 4426 03:30:48,473 --> 03:30:49,407 >> THANK YOU. 4427 03:30:49,407 --> 03:30:51,142 FIRST I'D LIKE TO THANK THE 4428 03:30:51,142 --> 03:30:54,813 ORGANIZERS FOR THE OPPORTUNITY 4429 03:30:54,813 --> 03:30:57,749 TO SPEAK TO YOU TODAY IN THIS 4430 03:30:57,749 --> 03:30:59,985 GREAT CONFERENCE. 4431 03:30:59,985 --> 03:31:03,088 SO, I AS DR. CARROLL 4432 03:31:03,088 --> 03:31:06,057 MENTIONED -- BY THE WAY, YOU DID 4433 03:31:06,057 --> 03:31:07,659 A GREAT JOB WITH YOUR 4434 03:31:07,659 --> 03:31:09,260 PORTUGUESE, ABOUT THE RULE OF 4435 03:31:09,260 --> 03:31:11,963 KETAMINE IN SICKLE CELL DISEASE. 4436 03:31:11,963 --> 03:31:14,466 SO WE'RE GOING TO REVIEW THE 4437 03:31:14,466 --> 03:31:19,104 RATIONALE FOR THE USE OF 4438 03:31:19,104 --> 03:31:19,838 KETAMINE TO TREAT SICKLE CELL 4439 03:31:19,838 --> 03:31:20,939 DISEASE AND BRIEFLY LOOK AT THE 4440 03:31:20,939 --> 03:31:23,341 GUIDELINES AND REVIEW THE 4441 03:31:23,341 --> 03:31:29,180 EVIDENCE IN SUPPORT ITS USE. 4442 03:31:29,180 --> 03:31:31,216 A LITTLE BIT ABOUT THE DRUG IT 4443 03:31:31,216 --> 03:31:35,887 WAS GENERATED IN 1962 LOOKING 4444 03:31:35,887 --> 03:31:39,824 FOR AN ANALOG OF PCP WITH A BETA 4445 03:31:39,824 --> 03:31:40,892 SIDE EFFECT PROFILE. 4446 03:31:40,892 --> 03:31:42,761 HE DESIGN WHAT WE USE AS 4447 03:31:42,761 --> 03:31:46,564 KETAMINE WHICH IS BASICALLY A 4448 03:31:46,564 --> 03:31:49,567 MIXTURE OF S AND R KETAMINE AND 4449 03:31:49,567 --> 03:31:50,435 THAT'S WHAT WE USED CLINICALLY 4450 03:31:50,435 --> 03:31:53,538 THESE DAYS. 4451 03:31:53,538 --> 03:31:57,442 IN 1970 THE FDA APPROVED 4452 03:31:57,442 --> 03:32:00,478 KETAMINE AS AN ANESTHETIC AND 4453 03:32:00,478 --> 03:32:02,480 USED IN THE BATTLEFIELD THROUGH 4454 03:32:02,480 --> 03:32:03,148 THE VIETNAM WAR. 4455 03:32:03,148 --> 03:32:07,185 IN THE '80s WE STARTED TO LEARN 4456 03:32:07,185 --> 03:32:10,388 ABOUT ITS EFFECT ON THE 4457 03:32:10,388 --> 03:32:10,655 RECEPTOR. 4458 03:32:10,655 --> 03:32:13,358 IN 2000 THE INVESTIGATIONAL USE 4459 03:32:13,358 --> 03:32:20,965 OF THE DRUG AS AN ANTIDEPRESSANT 4460 03:32:20,965 --> 03:32:22,834 AND OTHER PSYCHIATRIC ILLNESSES 4461 03:32:22,834 --> 03:32:27,205 AND IN 2019 THE FDA APPROVED F 4462 03:32:27,205 --> 03:32:29,774 KETAMINE FOR THE TREATMENT OF 4463 03:32:29,774 --> 03:32:31,109 TREATMENT-RESISTANCE DEPRESSION. 4464 03:32:31,109 --> 03:32:33,311 SO WHAT IS THE RECEPTOR THAT 4465 03:32:33,311 --> 03:32:35,313 CAUSES SUCH A BIG PROBLEM? 4466 03:32:35,313 --> 03:32:45,824 IT'S A GLUTAMATE RECEPTOR AND 4467 03:32:49,127 --> 03:32:55,333 ONCE IT'S ACTIVATED BY GLUTAMATE 4468 03:32:55,333 --> 03:32:59,003 IT GOES TO POST SYNAPTIC NEURONS 4469 03:32:59,003 --> 03:33:01,506 AND LEADS TO DESENSITIZATION OF 4470 03:33:01,506 --> 03:33:03,141 NOCICEPTIVE NEURON AND HAS A 4471 03:33:03,141 --> 03:33:11,316 ROLE IN THE MAINTENANCE OF 4472 03:33:11,316 --> 03:33:13,952 OPIOID TOLERANCE AND APART FROM 4473 03:33:13,952 --> 03:33:24,395 THE GLUTAMATE SITE IT'S A 4474 03:33:24,762 --> 03:33:26,431 NON-COMPETITIVE ANTAGONIST AN 4475 03:33:26,431 --> 03:33:29,767 BECAUSE OF -- IN ADDITION TO AN 4476 03:33:29,767 --> 03:33:34,672 NDA RECEPTOR AFFECT IT HAS 4477 03:33:34,672 --> 03:33:38,776 AFFECT IN OTHER SYSTEMS LIKE 4478 03:33:38,776 --> 03:33:49,320 OTHER RECEPTORS AND DOPE MIN 4479 03:33:50,555 --> 03:33:56,494 MINNER -- DOPAMINEERGIC 4480 03:33:56,494 --> 03:34:06,671 RECEPTORS. 4481 03:34:11,910 --> 03:34:15,313 GIVEN THE ROLE IN ANALGESIA THE 4482 03:34:15,313 --> 03:34:19,317 CIRCUMSTANCES IN SOME PATIENTS 4483 03:34:19,317 --> 03:34:22,854 WITH SICKLE CELL DISEASE PAIN 4484 03:34:22,854 --> 03:34:27,592 SHOW THE DRUG MAKES SENSE TO USE 4485 03:34:27,592 --> 03:34:31,296 IT AND WHAT OCCURS IS HERE IS A 4486 03:34:31,296 --> 03:34:36,568 CARTOON ILLUSTRATING THE 4487 03:34:36,568 --> 03:34:40,038 NOCICEPTOR CENTRAL TERMINAL IN 4488 03:34:40,038 --> 03:34:45,810 THE SPINAL CORD AND YOU HAVE ALL 4489 03:34:45,810 --> 03:34:53,184 THE NEURO TRANSMIT ETERS YOU SE 4490 03:34:53,184 --> 03:34:56,487 THE RECEPTOR CLOSED HERE. 4491 03:34:56,487 --> 03:34:58,556 THIS IS ADDRESSED. 4492 03:34:58,556 --> 03:35:00,225 KNOW WHEN HAVE YOU THE 4493 03:35:00,225 --> 03:35:02,493 NOCICEPTIVE INPUTS YOU RELEASE 4494 03:35:02,493 --> 03:35:07,532 OF THE TRANSMITTER AND 4495 03:35:07,532 --> 03:35:13,938 ACTIVATION OF A SLEW OF 4496 03:35:13,938 --> 03:35:17,175 RECEPTORS AND GLUTAMATE RECEPTOR 4497 03:35:17,175 --> 03:35:23,314 AND WHAT YOU SEE IS ENTRY IN THE 4498 03:35:23,314 --> 03:35:27,552 POST SYNAPTIC NEURONS AND THE 4499 03:35:27,552 --> 03:35:31,289 PROTEIN KINASE AND A WIND UP OF 4500 03:35:31,289 --> 03:35:34,292 THIS PHENOMENAL LEADING TO 4501 03:35:34,292 --> 03:35:34,826 CENTRAL SENSITIZATION. 4502 03:35:34,826 --> 03:35:36,928 IT'S A SIMPLISTIC WAY OF SAYING 4503 03:35:36,928 --> 03:35:40,965 IT'S WHAT WE KNOW HAPPENS. 4504 03:35:40,965 --> 03:35:44,535 THE RECEPTOR ALSO HAS A ROLE IN 4505 03:35:44,535 --> 03:35:46,404 OPIOID TOLERANCE WITH CHRONIC 4506 03:35:46,404 --> 03:35:50,608 USE OF OPIOIDS OF MORPHINE WITH 4507 03:35:50,608 --> 03:35:54,545 THE OPIOID RECEPTORS IN THE 4508 03:35:54,545 --> 03:35:56,814 CONSTANT INPUT OF NOCICEPTIVE 4509 03:35:56,814 --> 03:36:02,287 INPUT INTO THE MDA RECEPTOR AND 4510 03:36:02,287 --> 03:36:04,455 YOU HAVE THE CROSS-TALK LEADING 4511 03:36:04,455 --> 03:36:06,157 TO SIGNIFICANT BIO CHANGES I 4512 03:36:06,157 --> 03:36:10,295 DON'T HAVE TIME TO GO INTO BUT 4513 03:36:10,295 --> 03:36:12,463 INCREASING TO ACTIVATION OF 4514 03:36:12,463 --> 03:36:17,969 MICROGLIA ALL BELIEVED TO PLAY A 4515 03:36:17,969 --> 03:36:20,171 ROLE IN OPIOID INTOLERANCE AND 4516 03:36:20,171 --> 03:36:24,309 REGARD TO HYPERALGESIA THE 4517 03:36:24,309 --> 03:36:26,344 OPIOID MOLECULE IN THE BROWN 4518 03:36:26,344 --> 03:36:28,346 CIRCLES IS KNOWN TO ACTIVATE 4519 03:36:28,346 --> 03:36:32,984 MICROGLIA AND WHEN IT DOES SO 4520 03:36:32,984 --> 03:36:34,485 WHAT HAPPENS IS AN INCREASE IN 4521 03:36:34,485 --> 03:36:37,322 TRANSCRIPTION FACTORS IN 4522 03:36:37,322 --> 03:36:45,496 MICROGLIA AND PROINFLAMMATORY 4523 03:36:45,496 --> 03:36:47,732 KINOKINES AND DECREASE IN GABA 4524 03:36:47,732 --> 03:36:48,399 RECEPTOR REGULATION AND WHAT YOU 4525 03:36:48,399 --> 03:36:52,070 HAVE AT THE END IS AN INCREASE 4526 03:36:52,070 --> 03:36:53,004 IN INFLAMMATION AND INCREASE IN 4527 03:36:53,004 --> 03:36:56,507 PAIN SENSITIVITY ALL FEATURES 4528 03:36:56,507 --> 03:37:01,813 THAT OCCUR WITH OPIOID INDUCED 4529 03:37:01,813 --> 03:37:02,146 HYPERALGESIA. 4530 03:37:02,146 --> 03:37:03,314 BECAUSE OF THE NOCICEPTION IN 4531 03:37:03,314 --> 03:37:04,916 PAIN THERE'S BEEN AN INCREASED 4532 03:37:04,916 --> 03:37:08,453 INTEREST IN INCREASING THE DRUG 4533 03:37:08,453 --> 03:37:11,322 AS ANY ANALGESIC TO TREAT PAIN 4534 03:37:11,322 --> 03:37:14,525 APART FROM THE USE AS AN 4535 03:37:14,525 --> 03:37:17,929 ANALGESIC AND THERE IS VERY 4536 03:37:17,929 --> 03:37:19,330 SIGNIFICANT VARIABILITY ON WHEN 4537 03:37:19,330 --> 03:37:23,801 TO USE IT AND WHAT INDICATION. 4538 03:37:23,801 --> 03:37:26,003 WHAT IT WILL BEST SERVE. 4539 03:37:26,003 --> 03:37:28,706 IT'S USED IN TREATING 4540 03:37:28,706 --> 03:37:33,211 INDIVIDUALS WITH ACUTE AND 4541 03:37:33,211 --> 03:37:34,212 CHRONIC PAIN AND OPIOID 4542 03:37:34,212 --> 03:37:35,313 INTOLERANT PATIENTS AND USED IN 4543 03:37:35,313 --> 03:37:37,882 MANY PLACES IN THE HOSPITAL AND 4544 03:37:37,882 --> 03:37:38,516 EMERGENCY DEPARTMENTS AND 4545 03:37:38,516 --> 03:37:41,586 OPERATING ROOMS AND WE USE IT 4546 03:37:41,586 --> 03:37:41,786 OFTEN. 4547 03:37:41,786 --> 03:37:45,189 ACUTE CARE AWARDS AND ICU OR 4548 03:37:45,189 --> 03:37:46,424 PATIENT FACILITIES. 4549 03:37:46,424 --> 03:37:49,160 BOTH WITH SINGLE DOSE AND 4550 03:37:49,160 --> 03:37:50,628 CONTINUED INFUSIONS AND DOSE 4551 03:37:50,628 --> 03:37:54,632 VARIES QUITE A BIT. 4552 03:37:54,632 --> 03:37:55,900 THE GUIDELINES BECAUSE OF THE 4553 03:37:55,900 --> 03:37:57,568 WIDE VARIABILITY ON THE USER OF 4554 03:37:57,568 --> 03:38:01,839 THE DRUG, THE AMERICAN SOCIETY 4555 03:38:01,839 --> 03:38:03,307 OF REGIONAL PAIN MEDICINE AND 4556 03:38:03,307 --> 03:38:07,311 THE ACADEMY OF PAIN MEDICINE AND 4557 03:38:07,311 --> 03:38:11,149 AMERICAN SOCIETY OF 4558 03:38:11,149 --> 03:38:12,150 ANESTHESIOLOGISTS CAME UP WITH 4559 03:38:12,150 --> 03:38:15,820 GUIDELINE FOR THE TREATMENT OF 4560 03:38:15,820 --> 03:38:16,521 ACUTE AND CHRONIC PAIN. 4561 03:38:16,521 --> 03:38:17,522 THE RECOMMENDATION AT THIS POINT 4562 03:38:17,522 --> 03:38:20,091 IS FOR PATIENTS UNDERGOING 4563 03:38:20,091 --> 03:38:23,327 PAINFUL SURGERY WHO ARE OPIOID 4564 03:38:23,327 --> 03:38:30,067 DEPENDENT OR TOLERANT AND 4565 03:38:30,067 --> 03:38:33,271 PATIENTS WITH SICKLE CELL PAIN 4566 03:38:33,271 --> 03:38:37,608 AND PEOPLE WITH SLEEP APNEA AND 4567 03:38:37,608 --> 03:38:45,249 THE DOSES RECOMMENDED HERE AND 4568 03:38:45,249 --> 03:38:49,353 THAT ACCEPTED DEFINITION IS LESS 4569 03:38:49,353 --> 03:38:52,290 THAN ONE MILLIGRAM PER KILO PER 4570 03:38:52,290 --> 03:38:56,027 HOUR AND ONE HAS TO TAKE INTO 4571 03:38:56,027 --> 03:38:58,229 ACCOUNT INDIVIDUAL RESPONSES AND 4572 03:38:58,229 --> 03:39:02,533 CAN BE USED AS A STAND ALONE 4573 03:39:02,533 --> 03:39:04,802 TREATMENT OR ADJUNCT OPIOID 4574 03:39:04,802 --> 03:39:07,305 BECAUSE OF IT'S SPARING 4575 03:39:07,305 --> 03:39:10,775 PROPERTIES. 4576 03:39:10,775 --> 03:39:12,510 THERE ARE CONTRAINDICATIONS FOR 4577 03:39:12,510 --> 03:39:14,512 THE USE OFF THE DRUG INCLUDING 4578 03:39:14,512 --> 03:39:19,317 CARDIOVASCULAR DISEASE AND 4579 03:39:19,317 --> 03:39:24,989 DYSFUNCTION AND PSYCHOSIS IN 4580 03:39:24,989 --> 03:39:25,957 PREGNANCY. 4581 03:39:25,957 --> 03:39:28,960 THERE'S WEAK EVIDENCE TO SUGGEST 4582 03:39:28,960 --> 03:39:34,732 ACUTE PAIN IN KETAMINE LESS SO. 4583 03:39:34,732 --> 03:39:35,800 NOW FOR CHRONIC PAIN AND THE 4584 03:39:35,800 --> 03:39:39,303 EVIDENCE IS WEEK FOR PATIENTS 4585 03:39:39,303 --> 03:39:43,307 WITH SPINAL CORD INJURY RELATED 4586 03:39:43,307 --> 03:39:50,915 PAIN. 4587 03:39:50,915 --> 03:39:54,285 AND WEAK EVIDENCE FOR SICKLE 4588 03:39:54,285 --> 03:39:55,253 CELL CHRONIC PAIN AND SEVERAL 4589 03:39:55,253 --> 03:39:56,487 NEURO PATHIC CONDITIONS. 4590 03:39:56,487 --> 03:39:58,389 THE EVIDENCE IS NOT CONVINCING. 4591 03:39:58,389 --> 03:40:02,527 TO THOSE RANGES FOR CHRONIC PAIN 4592 03:40:02,527 --> 03:40:04,996 ARE USUALLY HIGHER AND ONE 4593 03:40:04,996 --> 03:40:09,700 SHOULD TYPICALLY USE FOR LONGER 4594 03:40:09,700 --> 03:40:11,202 TIMES AND KEEP IN MIND 4595 03:40:11,202 --> 03:40:13,137 INDIVIDUAL RESPONSES THE 4596 03:40:13,137 --> 03:40:15,306 CONTRAINDICATIONS ARE SIMILAR. 4597 03:40:15,306 --> 03:40:19,176 THE NON-PARENTAL KETAMINE 4598 03:40:19,176 --> 03:40:23,147 FORMATIONS OR THE USE OF OTHER 4599 03:40:23,147 --> 03:40:26,517 MMDA RECEPTORS CAN BE USED FOR 4600 03:40:26,517 --> 03:40:29,520 FOLLOW-UP AND USE INTRANASAL FOR 4601 03:40:29,520 --> 03:40:29,720 PAIN. 4602 03:40:29,720 --> 03:40:36,594 IT SHOULD BE ADMINISTERED AS 4603 03:40:36,594 --> 03:40:39,964 RECOMMENDED AND IN PLACE WHERE'S 4604 03:40:39,964 --> 03:40:40,698 HEMODYNAMIC AND RESPIRATORY 4605 03:40:40,698 --> 03:40:42,967 MONITORING CAN TAKE PLACE 4606 03:40:42,967 --> 03:40:45,236 BECAUSE THE DRUG CAN HAVE 4607 03:40:45,236 --> 03:40:47,004 AFFECTS ON THOSE SYSTEMS. 4608 03:40:47,004 --> 03:40:50,508 AND DR. BRANDOW AND CURTIS 4609 03:40:50,508 --> 03:40:52,076 MENTIONED THE ASH GUIDELINES 4610 03:40:52,076 --> 03:40:52,510 FROM 2020. 4611 03:40:52,510 --> 03:40:57,882 I'M NOT GOING TO REPEAT THEM BUT 4612 03:40:57,882 --> 03:40:58,816 THEY ISSUED A RECOMMENDATION FOR 4613 03:40:58,816 --> 03:41:00,985 THE USE OF THE DRUG BECAUSE OF 4614 03:41:00,985 --> 03:41:04,055 THE LOW TO MODERATE CERTAINTY OF 4615 03:41:04,055 --> 03:41:05,323 THE EVIDENCE SUPPORTING ITS USE. 4616 03:41:05,323 --> 03:41:07,692 I'M GOING TO JUST GO THROUGH 4617 03:41:07,692 --> 03:41:10,494 THIS AND REMINDING THE DOSES 4618 03:41:10,494 --> 03:41:14,966 POINT TO THREE MILLIGRAMS TO 4619 03:41:14,966 --> 03:41:17,001 KILO NOT TO EXCEED THE DOSES AND 4620 03:41:17,001 --> 03:41:19,203 THE POTENTIAL HARMS I'LL TALK 4621 03:41:19,203 --> 03:41:22,340 ABOUT THIS LATER BUT THE 4622 03:41:22,340 --> 03:41:23,341 HALLUCINATIONS AND THERE'S A 4623 03:41:23,341 --> 03:41:27,211 RISK OF DIVERSION AND IT DOES 4624 03:41:27,211 --> 03:41:28,446 WARRANT PEOPLE WITH EXPERIENCE 4625 03:41:28,446 --> 03:41:31,882 WITH THE USE OF KETAMINE TO 4626 03:41:31,882 --> 03:41:33,784 ADMINISTER THE DRUG. 4627 03:41:33,784 --> 03:41:35,119 SO WHAT DOES THE EVIDENCE 4628 03:41:35,119 --> 03:41:39,323 SUPPORT IN THE USE OF KETAMINE 4629 03:41:39,323 --> 03:41:40,725 FOR SICKLE CELL PAIN? 4630 03:41:40,725 --> 03:41:41,192 IT'S SPARSE. 4631 03:41:41,192 --> 03:41:43,928 THERE'S TWO PUBLISHED RANDOMIZED 4632 03:41:43,928 --> 03:41:46,697 CLINICAL TRIALS AND MOST THE 4633 03:41:46,697 --> 03:41:47,798 EVIDENCE IS BASED ON BASE REPORT 4634 03:41:47,798 --> 03:41:50,134 AND COHORT STUDIES AND WE'LL GO 4635 03:41:50,134 --> 03:41:54,472 OVER A FEW OF THEM BUT THERE'S 4636 03:41:54,472 --> 03:41:55,272 SIGNIFICANT VARIABILITY WHICH 4637 03:41:55,272 --> 03:41:56,807 MAKES IT MORE CHALLENGING AND 4638 03:41:56,807 --> 03:41:59,243 USED IN EMERGENCY ROOMS AND ICUs 4639 03:41:59,243 --> 03:42:00,411 AND PATIENT WARDS. 4640 03:42:00,411 --> 03:42:01,846 FIRST THE RANDOMIZED CLINICAL 4641 03:42:01,846 --> 03:42:02,079 TRIALS. 4642 03:42:02,079 --> 03:42:04,048 TWO OF THEM ARE MENTIONED THAT 4643 03:42:04,048 --> 03:42:09,453 HAVE BEEN PUBLISHED. 4644 03:42:09,453 --> 03:42:12,089 THE FIRST IN CHILDREN TRYING TO 4645 03:42:12,089 --> 03:42:13,858 CONDUCT IN UGANDA. 4646 03:42:13,858 --> 03:42:15,559 HERE'S THE AGE GROUP ABOUT 12 4647 03:42:15,559 --> 03:42:18,496 YEARS OF AGE AND SO THE STUDY 4648 03:42:18,496 --> 03:42:20,765 WAS IN THE EMERGENCY ROOM 4649 03:42:20,765 --> 03:42:21,999 PATIENTS COME IN WITH SICKLE 4650 03:42:21,999 --> 03:42:24,802 CELL ACUTE PAIN AND THEY HAD TWO 4651 03:42:24,802 --> 03:42:26,904 COMPARISON GROUPS. 4652 03:42:26,904 --> 03:42:29,740 KETAMINE AND THOSE IN CHILDREN 4653 03:42:29,740 --> 03:42:35,746 RECEIVING 1 MILLIGRAM PER KILO 4654 03:42:35,746 --> 03:42:41,385 INTERVENIOUSLY AND THE COMPARE 4655 03:42:41,385 --> 03:42:42,286 TO ANOTHER GROUP AND THERE WERE 4656 03:42:42,286 --> 03:42:44,088 SIMILAR REDUCTIONS IN PAIN 4657 03:42:44,088 --> 03:42:47,091 SCORES BUT HOWEVER, THE TIME 4658 03:42:47,091 --> 03:42:50,327 BETWEEN ADMINISTRATION AND THE 4659 03:42:50,327 --> 03:42:52,063 MAXIMUM CHANGE IN PAIN SCORE 4660 03:42:52,063 --> 03:42:55,399 OCCURRED WHILE SHORTER IN 4661 03:42:55,399 --> 03:42:57,535 PATIENTS RECEIVING KETAMINE. 4662 03:42:57,535 --> 03:42:59,370 THEY DID SEEK QUITE A BIT OF 4663 03:42:59,370 --> 03:43:03,340 SIDE EFFECTS INCLUDING 15% OF 4664 03:43:03,340 --> 03:43:09,547 THE PATIENTS AND 11% HAD 4665 03:43:09,547 --> 03:43:20,091 DYSPHORIA AND SALIVIZATION AND 4666 03:43:20,391 --> 03:43:22,126 THE TREATMENT FAILURE WERE 4667 03:43:22,126 --> 03:43:26,597 HIGHER IN THE MORE TEEN -- 4668 03:43:26,597 --> 03:43:28,365 MORPHINE TREATED GROUP. 4669 03:43:28,365 --> 03:43:30,935 THE SECOND TRIAL CONDUCTED IN 4670 03:43:30,935 --> 03:43:35,039 SAUDI ARABIA IN ADULTS THEY USED 4671 03:43:35,039 --> 03:43:37,141 A SMALLER DOSE .3 MILLIGRAMS PER 4672 03:43:37,141 --> 03:43:41,245 KILO AND MORE TEEN .1 PER KILO 4673 03:43:41,245 --> 03:43:43,147 AND FINDINGS SHOWED A SIMILAR 4674 03:43:43,147 --> 03:43:45,015 REDUCTION IN PAIN SCORE. 4675 03:43:45,015 --> 03:43:48,352 THOUGH THERE WAS SUGGESTION OF 4676 03:43:48,352 --> 03:43:52,022 OPIOIDS EFFECT FOR KETAMINE. 4677 03:43:52,022 --> 03:43:58,262 THIS IS ED, 120 MINUTES OF 4678 03:43:58,262 --> 03:43:58,562 OBSERVATION. 4679 03:43:58,562 --> 03:44:00,664 BECAUSE THERE'S A SMALLER DOSE 4680 03:44:00,664 --> 03:44:05,002 LIST INCIDENTS OF SIDE EFFECTS. 4681 03:44:05,002 --> 03:44:09,507 THE LARGE COHORT STUDIES IS MOST 4682 03:44:09,507 --> 03:44:10,908 WITH THE INFORMATION THERE'S 4683 03:44:10,908 --> 03:44:12,376 COHORT STUDIES. 4684 03:44:12,376 --> 03:44:15,513 ONE WAS DONE BY OUR GROUP AT THE 4685 03:44:15,513 --> 03:44:16,614 CHILDREN'S HOSPITAL IN D.C. 4686 03:44:16,614 --> 03:44:20,551 A SINGLE CENTER AND FOR PATIENTS 4687 03:44:20,551 --> 03:44:22,953 WITH ACUTE SICKLE CELL PAIN OVER 4688 03:44:22,953 --> 03:44:25,489 AN EIGHT-YEAR PERIOD NOT 4689 03:44:25,489 --> 03:44:26,757 INCLUDING PATIENTS WITH ACUTE 4690 03:44:26,757 --> 03:44:29,660 CHEST SYNDROME AND EXCLUDING 4691 03:44:29,660 --> 03:44:32,530 ADMINISTRATION OF KETAMINE THAT 4692 03:44:32,530 --> 03:44:37,601 WAS NOT MADE BY THE ACUTE PAIN. 4693 03:44:37,601 --> 03:44:39,503 SO STANDARDIZED SOMEWHAT. 4694 03:44:39,503 --> 03:44:42,239 THE INDICATIONS FOR THE USE OF 4695 03:44:42,239 --> 03:44:44,575 KETAMINE IN THE STUDY WERE 4696 03:44:44,575 --> 03:44:48,879 INADEQUATE ANALGESIA AND 4697 03:44:48,879 --> 03:44:54,819 PRESENCE OF UNDESIRABLE SIDE 4698 03:44:54,819 --> 03:44:58,055 EFFECTS AND OPIOID CONDITION. 4699 03:44:58,055 --> 03:45:04,195 WE HAD 85 PATIENTS AND SIMILAR 4700 03:45:04,195 --> 03:45:07,698 DISTRIBUTE USE OF MALES AND 4701 03:45:07,698 --> 03:45:15,306 FEMALES, CONCERN AND ADOLESCENTS 4702 03:45:15,306 --> 03:45:20,578 AND MEAN AGE OF 15 AND WHEN YOU 4703 03:45:20,578 --> 03:45:24,915 LOOK AT THE AND 20% WERE 4704 03:45:24,915 --> 03:45:25,816 ADMINISTERED TO CHILDREN BETWEEN 4705 03:45:25,816 --> 03:45:30,221 THE AGES OF 2 AND 11 AND 60% 4706 03:45:30,221 --> 03:45:34,992 BETWEEN THE AGES OF 12 AND 18 4707 03:45:34,992 --> 03:45:38,562 AND 20% FOR YOUNG ADULTS 19 TO 4708 03:45:38,562 --> 03:45:41,265 21. 4709 03:45:41,265 --> 03:45:46,337 THE NUMBER OF INFUSIONS FOR 4710 03:45:46,337 --> 03:45:51,675 PATIENTS IN OVER HALF THE 4711 03:45:51,675 --> 03:45:54,979 PATIENTS IN ABOUT 30% OR 15% OF 4712 03:45:54,979 --> 03:45:56,580 THE PATIENTS HAD OVER FIVE 4713 03:45:56,580 --> 03:45:59,350 INFUSIONS AND UP TO 11 AT A 4714 03:45:59,350 --> 03:46:00,651 TIME. 4715 03:46:00,651 --> 03:46:02,586 THE DURATION WENT FROM ONE DAY 4716 03:46:02,586 --> 03:46:04,588 TO SIX OR MORE DAYS. 4717 03:46:04,588 --> 03:46:08,459 AND THE DOSES ARE LISTED HERE. 4718 03:46:08,459 --> 03:46:11,595 THESE ARE THE DOSE FOR THE 4719 03:46:11,595 --> 03:46:15,032 CONTINUOUS INFUSION AND AT TIME 4720 03:46:15,032 --> 03:46:19,169 THE BOLUS OF ADMINISTRATION AND 4721 03:46:19,169 --> 03:46:21,605 REFLECT PRETTY MUCH WHAT YOU SEE 4722 03:46:21,605 --> 03:46:23,841 WHEN WE ADMIT SICKLE CELL 4723 03:46:23,841 --> 03:46:24,108 PATIENTS. 4724 03:46:24,108 --> 03:46:25,943 WHAT WE FOUND WAS A COHORT 4725 03:46:25,943 --> 03:46:26,610 STUDY. 4726 03:46:26,610 --> 03:46:28,479 THERE'S NO CONTROL GROUPS HERE. 4727 03:46:28,479 --> 03:46:30,481 SO WE DID SEE WHEN YOU COMPARE 4728 03:46:30,481 --> 03:46:35,319 THE LEVELS OF PAIN SCORE FROM 4729 03:46:35,319 --> 03:46:39,323 BEFORE KETAMINE WAS INITIATED 4730 03:46:39,323 --> 03:46:43,327 AND THE MEAN IN 95% CONFIDENCE 4731 03:46:43,327 --> 03:46:43,827 INTERVAL OF THE CHANGE. 4732 03:46:43,827 --> 03:46:47,164 SO A DROP IN 3 ON THE PAIN SCORE 4733 03:46:47,164 --> 03:46:48,899 AND THE SCALE THAT IS AND THERE 4734 03:46:48,899 --> 03:46:52,937 WAS ALSO A DECREASE IN OPIOID 4735 03:46:52,937 --> 03:46:54,538 INTAKE SHOWN HERE. 4736 03:46:54,538 --> 03:46:58,375 THIS IS MORPHINE EQUIVALENT. 4737 03:46:58,375 --> 03:47:00,544 THIS IS WHEN YOU LOOK AT THE 4738 03:47:00,544 --> 03:47:01,445 FIRST INDEPENDENT INFUSION FOR 4739 03:47:01,445 --> 03:47:03,314 EACH PATIENT AND WHEN YOU LOOK 4740 03:47:03,314 --> 03:47:09,553 AT OTHER INFUSIONS THE AFFECT IS 4741 03:47:09,553 --> 03:47:11,855 THE SAME AND DECREASE IN PAIN 4742 03:47:11,855 --> 03:47:13,857 SCORE AND WE LOOKED AT THE 4743 03:47:13,857 --> 03:47:15,326 PREDICTORS OF THE CHANGES IN 4744 03:47:15,326 --> 03:47:18,595 PAIN SCORING AND WE FOUND THAT 4745 03:47:18,595 --> 03:47:20,597 THIS IS A MULTIVARIATE ANALYSIS 4746 03:47:20,597 --> 03:47:23,334 MANY PATIENTS APPEARED TO HAVE 4747 03:47:23,334 --> 03:47:26,603 GREATER REDUCTION IN PAIN SCORE. 4748 03:47:26,603 --> 03:47:29,573 AND YOUNGER PATIENTS SIMILARLY 4749 03:47:29,573 --> 03:47:31,175 HAD GREATER REDUCTION IN PAIN 4750 03:47:31,175 --> 03:47:32,376 SCORE COMPARED TO OTHER PATIENTS 4751 03:47:32,376 --> 03:47:33,677 YOU CAN SEE HERE. 4752 03:47:33,677 --> 03:47:36,146 SO MALE IN YOUNGER PATIENTS WILL 4753 03:47:36,146 --> 03:47:36,747 HAVE GREATER INCREASE IN PAIN 4754 03:47:36,747 --> 03:47:38,949 SCORE. 4755 03:47:38,949 --> 03:47:41,752 THE PAIN LOCATION APPEARED TO 4756 03:47:41,752 --> 03:47:44,588 HAVE AN EFFECT IN THAT ABDOMINAL 4757 03:47:44,588 --> 03:47:45,289 PAIN. 4758 03:47:45,289 --> 03:47:46,457 THOSE ARE ASSOCIATED WITH 4759 03:47:46,457 --> 03:47:47,958 GREATER DECREASE IN PAIN SCORE 4760 03:47:47,958 --> 03:47:50,461 WITH THE USE OF KETAMINE. 4761 03:47:50,461 --> 03:47:52,563 GENOTYPE WAS ANOTHER FACTOR IN 4762 03:47:52,563 --> 03:47:54,698 THE MODEL AND NO AFFECT THERE. 4763 03:47:54,698 --> 03:47:56,233 NOW THE CHANGES IN OPIOID INTAKE 4764 03:47:56,233 --> 03:48:01,171 THE PREDICTORS ARE AGAIN AGE, 4765 03:48:01,171 --> 03:48:04,008 YOUNGER KIDS WILL HAVE A GREATER 4766 03:48:04,008 --> 03:48:08,145 REDUCTION IN MORPHINE IN OPIOID 4767 03:48:08,145 --> 03:48:11,048 USE AND WE SAW NO EFFECT OF SEX 4768 03:48:11,048 --> 03:48:16,053 IN THE PREDICTION AND A TREND TO 4769 03:48:16,053 --> 03:48:17,855 SUGGEST PATIENTS WITH SC DISEASE 4770 03:48:17,855 --> 03:48:20,224 WOULD HAVE LESSER DECREASE IN 4771 03:48:20,224 --> 03:48:20,824 OPIOID AND NO EFFECT IN PAIN 4772 03:48:20,824 --> 03:48:24,361 LOCATION. 4773 03:48:24,361 --> 03:48:27,664 WE ALSO LOOK AT WHEN YOU LOOK AT 4774 03:48:27,664 --> 03:48:30,968 THE ABSOLUTE DECREASE IN PAIN 4775 03:48:30,968 --> 03:48:33,237 SCORE IT DOESN'T MEAN ANYTHING. 4776 03:48:33,237 --> 03:48:36,940 WE LOOKED AT WHAT YIELDED WHAT 4777 03:48:36,940 --> 03:48:39,309 GROUP HAD THE MOST MEANINGFUL 4778 03:48:39,309 --> 03:48:40,110 CLINICAL REDUCTION. 4779 03:48:40,110 --> 03:48:44,348 FOR THIS STUDY WE DEFINED 4780 03:48:44,348 --> 03:48:46,550 CLINICALLY REDUCTION TO BE 4781 03:48:46,550 --> 03:48:47,551 GREATER THAN 20%. 4782 03:48:47,551 --> 03:48:49,620 THAT'S GOING TO BE SHOWN IN BLUE 4783 03:48:49,620 --> 03:48:50,521 IN LESS THAN 20% IN THIS BROWN 4784 03:48:50,521 --> 03:48:52,923 AREA. 4785 03:48:52,923 --> 03:49:02,366 GRAY I GUESS. 4786 03:49:02,366 --> 03:49:07,204 MALE PATIENTS HAD A GREATER 4787 03:49:07,204 --> 03:49:08,605 PROPORTION THAT YIELDED A 4788 03:49:08,605 --> 03:49:12,276 CLINICAL REDUCTION IN PAIN. 4789 03:49:12,276 --> 03:49:14,645 60% ADMINISTERED TO MALES WERE 4790 03:49:14,645 --> 03:49:15,412 COUPLED WITH CLINICAL MEANINGFUL 4791 03:49:15,412 --> 03:49:18,048 REDUCTION IN PAIN. 4792 03:49:18,048 --> 03:49:21,351 THOSE ADMINISTERED TO YOUNG 4793 03:49:21,351 --> 03:49:24,121 CHILDREN ABOUT 80% REACHED 4794 03:49:24,121 --> 03:49:26,123 CLINICALLY MEANINGFUL REDUCTION 4795 03:49:26,123 --> 03:49:32,463 AND PAIN LOCATED IN THE BACK 4796 03:49:32,463 --> 03:49:35,299 ABDOA -- 4797 03:49:35,299 --> 03:49:42,439 BLACK MEN WITH MEANINGFUL PAIN 4798 03:49:42,439 --> 03:49:46,844 SCORED AND LESS RESPOND TO 4799 03:49:46,844 --> 03:49:49,379 KETAMINE AS RESPONDS TO OPIOID 4800 03:49:49,379 --> 03:49:50,581 INTAKE. 4801 03:49:50,581 --> 03:49:51,315 A GROUP IN 4802 03:49:51,315 --> 03:50:01,825 THE LOOKED AT THE EXPERIENCE 4803 03:50:11,034 --> 03:50:20,611 THEY LOOKED AT THIS AFTER OPIOID 4804 03:50:20,611 --> 03:50:25,182 DCA IN LOWER DOSES AND IN THREE 4805 03:50:25,182 --> 03:50:31,321 DAYS OF DURATION AND WHAT IS 4806 03:50:31,321 --> 03:50:33,857 REMARKABLE IS THEY DID SEE A 4807 03:50:33,857 --> 03:50:38,228 SIGNIFICANT INCIDENT OF SIDE 4808 03:50:38,228 --> 03:50:43,300 EFFECTS INCLUDING 22% TO SHORTEN 4809 03:50:43,300 --> 03:50:45,736 THE DURATION OR DISCONTINUATION 4810 03:50:45,736 --> 03:50:47,271 OF THE INFUSION OR REDUCTION OF 4811 03:50:47,271 --> 03:50:51,942 THE DOSE. 4812 03:50:51,942 --> 03:51:02,853 AND THEY FOUND DISASSOCIAAIIATE 4813 03:51:14,131 --> 03:51:19,369 FEELINGS AND AT DUKE THEY FOUND 4814 03:51:19,369 --> 03:51:29,913 AFTER THREE DAYS AND HERE IS THE 4815 03:51:35,986 --> 03:51:36,253 DISTRIBUTION. 4816 03:51:36,253 --> 03:51:46,797 AND 30 YEARS IS THE MEDIAN ABLE. 4817 03:51:49,366 --> 03:51:51,034 AND FOUND ONCE YOU START 4818 03:51:51,034 --> 03:51:52,603 INFUSION THERE'S A SIGNIFICANT 4819 03:51:52,603 --> 03:51:55,339 REDUCTION IN PAIN RATE FROM THE 4820 03:51:55,339 --> 03:51:59,142 BASELINE FROM THE STUDY SHOWING 4821 03:51:59,142 --> 03:52:01,078 ON THE Y AXIS YOU HAVE CHANGES 4822 03:52:01,078 --> 03:52:02,212 IN PAIN SCORES. 4823 03:52:02,212 --> 03:52:04,281 IN BLUE ARE THE DATA POINTS FOR 4824 03:52:04,281 --> 03:52:09,753 KETAMINE INFUSIONS THAT WERE 4825 03:52:09,753 --> 03:52:10,854 INITIATED EARLY IN THE 4826 03:52:10,854 --> 03:52:12,189 HOSPITALIZATION WITHIN THREE 4827 03:52:12,189 --> 03:52:16,760 DAYS AND IN THE YELLOW, THE 4828 03:52:16,760 --> 03:52:18,795 KETAMINE INFUSIONS STARTED THREE 4829 03:52:18,795 --> 03:52:22,933 DAYS AFTER INFUSION. 4830 03:52:22,933 --> 03:52:26,370 THOUGH THE PRIME POINTS YIELDED 4831 03:52:26,370 --> 03:52:28,305 NO DIFFERENCE WHEN YOU LOOK AT 4832 03:52:28,305 --> 03:52:31,375 REDUCTION IN PAIN SCORES IN DAY 4833 03:52:31,375 --> 03:52:36,413 ONE AND TWO AFTER OF INFUSION 4834 03:52:36,413 --> 03:52:37,547 YIELDED ABOUT SIGNIFICANT 4835 03:52:37,547 --> 03:52:38,649 REDUCTION IN PAIN SCORE ABOUT 4836 03:52:38,649 --> 03:52:43,787 25%. 4837 03:52:43,787 --> 03:52:45,722 VERSUS 2% WHEN STARTED EARLIER 4838 03:52:45,722 --> 03:52:50,560 AND 30% FROM DAY TWO BUT 4839 03:52:50,560 --> 03:52:51,628 INTERESTINGLY THE FINDINGS FROM 4840 03:52:51,628 --> 03:52:53,530 DAY THREE OF KETAMINE INFUSION 4841 03:52:53,530 --> 03:52:55,132 WERE NOT SUSTAINED. 4842 03:52:55,132 --> 03:52:56,633 THERE WAS NO CHANGE IN PAIN 4843 03:52:56,633 --> 03:52:57,901 SCORES. 4844 03:52:57,901 --> 03:53:02,639 AND UNLIKE OUR GROUP IN KIDS, IN 4845 03:53:02,639 --> 03:53:05,876 ADULTS THERE WERE NO ASSOCIATION 4846 03:53:05,876 --> 03:53:08,979 OF THE RESPONSE IN THE PATIENT 4847 03:53:08,979 --> 03:53:09,579 CHARACTERISTICS. 4848 03:53:09,579 --> 03:53:11,014 FOR PAIN IN SICKLE CELL THERE'S 4849 03:53:11,014 --> 03:53:13,583 LESS DATA, VERY LITTLE USED A 4850 03:53:13,583 --> 03:53:19,323 FEW TIMES WITHOUT ANY ANECDOTAL 4851 03:53:19,323 --> 03:53:21,658 CHANGES IN PAIN OR OPIOID INTAKE 4852 03:53:21,658 --> 03:53:27,164 AND KETAMINE IS AN ANALGESIC AND 4853 03:53:27,164 --> 03:53:34,638 USED WITH MORPHINE IN EMERGENCY 4854 03:53:34,638 --> 03:53:39,176 ROOM WITH SECOND HAICKLE CELL D 4855 03:53:39,176 --> 03:53:42,245 AND THERE MAY BE OPIOID SPARING 4856 03:53:42,245 --> 03:53:44,514 EFFECT HOWEVER, YOU DO SEE MORE 4857 03:53:44,514 --> 03:53:46,183 I'D EFFECTS WHEN KETAMINE IS 4858 03:53:46,183 --> 03:53:51,154 USED AND IT'S AN ADJUVANT TO 4859 03:53:51,154 --> 03:53:56,560 OPIOID WITHOUT RANDOMIZED TRIALS 4860 03:53:56,560 --> 03:53:58,528 THE DATA SUGGESTS THERE'S 4861 03:53:58,528 --> 03:54:00,030 SIGNIFICANT OPIOID INTAKE AND 4862 03:54:00,030 --> 03:54:04,534 THE EFFECT OF KETAMINE VARIES 4863 03:54:04,534 --> 03:54:08,271 ACCORDING TO SEX, AGE, PAIN 4864 03:54:08,271 --> 03:54:12,576 LOCATION, GENOTYPE. 4865 03:54:12,576 --> 03:54:19,316 THE TIMING IT APPEARS IT'S 4866 03:54:19,316 --> 03:54:29,359 KETAMINE WHEN STARTED EARLIER 4867 03:54:29,359 --> 03:54:35,298 AND WHEN HAVE YOU PAIN DECREASED 4868 03:54:35,298 --> 03:54:37,968 SIDE EFFECTS AND SUSPICION OF 4869 03:54:37,968 --> 03:54:41,138 OPIOID INDUCED HYPERALGESIA 4870 03:54:41,138 --> 03:54:43,206 THERE MAY BE A GOOD INDICATION 4871 03:54:43,206 --> 03:54:44,441 FOR ITS USE. 4872 03:54:44,441 --> 03:54:47,744 AND WHEN TO START SOME 4873 03:54:47,744 --> 03:54:49,179 SUGGESTIONS EARLY INITIATION MAY 4874 03:54:49,179 --> 03:54:50,680 BE BENEFICIAL. 4875 03:54:50,680 --> 03:54:53,884 THE DRUG IMPROVE PAIN CONTROL 4876 03:54:53,884 --> 03:54:59,322 AND HAS OPIOID AFFECTS BASED ON 4877 03:54:59,322 --> 03:55:02,692 THE EVIDENCE I CITED BUT 4878 03:55:02,692 --> 03:55:08,632 DEFINITIVE EVIDENCE IS LACKING 4879 03:55:08,632 --> 03:55:12,502 BUT AND CAN HAVE UNDESIRABLE 4880 03:55:12,502 --> 03:55:14,538 AFFECTS AND RISKS. 4881 03:55:14,538 --> 03:55:16,306 ONE THING THAT IS INTERESTING 4882 03:55:16,306 --> 03:55:19,176 AND I'LL ASK BEFORE CARROLL WHAT 4883 03:55:19,176 --> 03:55:23,313 HE THINK IT REMAINS UNKNOWN WHEN 4884 03:55:23,313 --> 03:55:29,886 THE ANTIDEPRESSANT EFFECT PLAYS 4885 03:55:29,886 --> 03:55:33,557 A ROLE AND WHERE IT CAN BE 4886 03:55:33,557 --> 03:55:34,858 ADMINISTERED SAFELY AND HAVE THE 4887 03:55:34,858 --> 03:55:37,461 BUILT TO MONITOR KETAMINE 4888 03:55:37,461 --> 03:55:39,296 APPEARS TO BE A REASONABLE AND 4889 03:55:39,296 --> 03:55:43,500 USEFUL OPTION TO TREAT PATIENTS 4890 03:55:43,500 --> 03:55:46,436 WITH SICKLE CELL DISEASE. 4891 03:55:46,436 --> 03:55:50,640 THIS IS MY GROUP. 4892 03:55:50,640 --> 03:55:51,741 THANK YOU AND MY COLLABORATORS 4893 03:55:51,741 --> 03:55:52,242 AND THANK YOU FOR YOUR 4894 03:55:52,242 --> 03:56:02,419 ATTENTION. 4895 03:56:18,902 --> 03:56:20,170 >> I WANTED TO SHARE OUR 4896 03:56:20,170 --> 03:56:20,470 EXPERIENCE. 4897 03:56:20,470 --> 03:56:23,340 I DON'T KNOW IF YOU KNOW 4898 03:56:23,340 --> 03:56:26,643 DR. CARULO ALSO INTERESTED IN 4899 03:56:26,643 --> 03:56:27,043 SICKLE CELL CARE. 4900 03:56:27,043 --> 03:56:28,645 WE WORKED TOGETHER A LONG TIME 4901 03:56:28,645 --> 03:56:30,714 AND PUT IN PLACE A CLINICAL 4902 03:56:30,714 --> 03:56:32,949 PRACTICE GUIDELINE WHERE WE USED 4903 03:56:32,949 --> 03:56:38,221 VERY LOW DOSES OF METHADONE 4904 03:56:38,221 --> 03:56:43,026 MAXING OUT AVERAGE BETWEEN 2.5 4905 03:56:43,026 --> 03:56:46,062 TO 7 MILLIGRAMS PER DAY FOR 4906 03:56:46,062 --> 03:56:48,999 THREE DAYS AND SHOWED A ROBUST 4907 03:56:48,999 --> 03:56:51,468 DECREASE IN OPIOID USE AND OTHER 4908 03:56:51,468 --> 03:56:54,571 ADVERSE EFFECTS OF OPIOID AND 4909 03:56:54,571 --> 03:56:56,673 THE RATIONALE WAS TO USE FOR 4910 03:56:56,673 --> 03:56:58,642 ACUTE PAIN MANAGEMENT AND DIDN'T 4911 03:56:58,642 --> 03:57:00,443 HAVE TO DEAL WITH USING AN IV 4912 03:57:00,443 --> 03:57:02,479 INFUSION AND WONDERED WHAT YOUR 4913 03:57:02,479 --> 03:57:04,981 THOUGHTS WERE ABOUT THAT AS AN 4914 03:57:04,981 --> 03:57:06,049 ALTERNATIVE TO KETAMINE. 4915 03:57:06,049 --> 03:57:09,586 >> I THINK IT'S A FANTASTIC 4916 03:57:09,586 --> 03:57:09,853 APPROACH. 4917 03:57:09,853 --> 03:57:11,621 WE USE IT A LOT IN THE OPERATING 4918 03:57:11,621 --> 03:57:17,694 ROOM AS AN ANALGESIC AND IN THE 4919 03:57:17,694 --> 03:57:19,329 SETTING I TALKED TO VERONICA 4920 03:57:19,329 --> 03:57:22,198 ABOUT THAT IT'S FANTASTIC. 4921 03:57:22,198 --> 03:57:24,734 I ENDORSE IT. 4922 03:57:24,734 --> 03:57:26,670 >> A RANDOMIZED TRIAL MAYBE IN 4923 03:57:26,670 --> 03:57:36,880 OUR FUTURE. 4924 03:57:37,380 --> 03:57:38,582 >> THANK YOU. 4925 03:57:38,582 --> 03:57:41,985 YOU MENTIONED A COUPLE 4926 03:57:41,985 --> 03:57:42,485 CONTRAINDICATIONS WITH 4927 03:57:42,485 --> 03:57:43,320 CARDIOVASCULAR DISEASE AND I 4928 03:57:43,320 --> 03:57:46,389 HOPE YOU CAN COMMENT ABOUT THOSE 4929 03:57:46,389 --> 03:57:48,592 IN OUR SICKLE CELL POPULATION 4930 03:57:48,592 --> 03:57:48,992 PARTICULARLY. 4931 03:57:48,992 --> 03:57:52,529 >> YOU CAN SEE HYPERTENSION, 4932 03:57:52,529 --> 03:57:53,630 TACHYCARDIA EVEN WORSE IN THE 4933 03:57:53,630 --> 03:57:56,666 SETTING OF ANEMIA THE PATIENTS 4934 03:57:56,666 --> 03:58:01,705 DON'T TOLERATE THAT. 4935 03:58:01,705 --> 03:58:05,775 AND A DRUG WITH A RELATIVE 4936 03:58:05,775 --> 03:58:08,778 INDICATION AND IF YOU HAVE A 4937 03:58:08,778 --> 03:58:10,413 PATIENT THAT'S HYPERTENSIVE AND 4938 03:58:10,413 --> 03:58:12,949 YOU HAVE IT TREATED IT'S NOT 4939 03:58:12,949 --> 03:58:19,990 OBSOLETE. 4940 03:58:19,990 --> 03:58:23,326 WHAT DO YOU THINK ABOUT AS AN 4941 03:58:23,326 --> 03:58:25,362 ANTIDEPRESSANT? 4942 03:58:25,362 --> 03:58:27,364 MY QUESTION ABOUT KETAMINE IS 4943 03:58:27,364 --> 03:58:31,334 USUALLY IS THIS A MAGIC SHOT OR 4944 03:58:31,334 --> 03:58:36,272 MAGIC RIFLE? 4945 03:58:36,272 --> 03:58:39,342 I'VE HAD MANY PEOPLE WITH 4946 03:58:39,342 --> 03:58:41,845 OPINIONS ABOUT METHADONE AND 4947 03:58:41,845 --> 03:58:47,917 SHOULD WE PUT EVERYONE ON DEXO 4948 03:58:47,917 --> 03:58:55,325 ME 4949 03:58:55,325 --> 03:59:02,866 METHOPHINE. 4950 03:59:02,866 --> 03:59:13,276 >> NOW I WILL INTRODUCE 4951 03:59:14,144 --> 03:59:16,546 DR. CARROLL AN INTERNATIONALLY 4952 03:59:16,546 --> 03:59:18,682 RECOGNIZED EXPERT IN THE 4953 03:59:18,682 --> 03:59:20,316 MULTI-DISCIPLINARY MANAGEMENT OF 4954 03:59:20,316 --> 03:59:24,320 COMPLEX AND HIGH-UTILIZING 4955 03:59:24,320 --> 03:59:25,021 PATIENTS WITH SICKLE CELL 4956 03:59:25,021 --> 03:59:26,523 DISEASE AND COMPLETED THE 4957 03:59:26,523 --> 03:59:32,128 GRADUATE MEDICAL TRAINING IN 4958 03:59:32,128 --> 03:59:32,495 ST. LOUIS. 4959 03:59:32,495 --> 03:59:42,872 HE COMPLETE D 4960 04:00:37,127 --> 04:00:40,296 >> SO I'M GOING TO TRY NOT TO 4961 04:00:40,296 --> 04:00:41,464 KEEP YOU FROM LUNCH. 4962 04:00:41,464 --> 04:00:47,303 I'M GOING TO TALK TO YOU ABOUT 4963 04:00:47,303 --> 04:00:57,847 HOW WE USE BUPRENORPHINE AND WE 4964 04:01:14,798 --> 04:01:16,900 USE IT AT HOPKINS FOR A COUPLE 4965 04:01:16,900 --> 04:01:18,168 THINGS THAT SOMETIMES OVERLAP 4966 04:01:18,168 --> 04:01:20,303 AND PROBABLY OVERLAP LESS THAN 4967 04:01:20,303 --> 04:01:23,273 YOU THINK WHICH IS PEOPLE WHO 4968 04:01:23,273 --> 04:01:24,407 ARE ON CHRONIC PAIN OPIOID 4969 04:01:24,407 --> 04:01:26,276 THERAPY OFTEN AT HIGH DOSES 4970 04:01:26,276 --> 04:01:33,616 AREN'T DOING VERY WELL WITH IT 4971 04:01:33,616 --> 04:01:33,917 A 4972 04:01:33,917 --> 04:01:36,352 AND PEOPLE IN THE HOSPITAL A LOT 4973 04:01:36,352 --> 04:01:38,721 OR HAVE ACUTE CHRONIC PAIN OR 4974 04:01:38,721 --> 04:01:42,926 HAVING TROUBLE STABILIZING THE 4975 04:01:42,926 --> 04:01:44,727 OPIOID DOSE IN CHRONIC 4976 04:01:44,727 --> 04:01:49,532 OUTPATIENT DACARE FOR UTILIZATI. 4977 04:01:49,532 --> 04:01:59,909 IT'S NOT MANY PEOPLE. 4978 04:02:00,243 --> 04:02:04,314 THIS IS LOOKING AT OUT PATIENT 4979 04:02:04,314 --> 04:02:05,782 FOR A YEAR AND OUR CLINICAL 4980 04:02:05,782 --> 04:02:12,522 LOOKING AT PRETTY MUCH THE SAME 4981 04:02:12,522 --> 04:02:23,066 THING WHICH IS TWO-THIRDS TAKE 4982 04:02:28,404 --> 04:02:30,540 LESS THAN A PILL A DAY BECAUSE 4983 04:02:30,540 --> 04:02:32,141 OF THE WAY THE SKEW WORKS BUT 4984 04:02:32,141 --> 04:02:33,877 SOME PEOPLE TAKE A GOOD AMOUNT 4985 04:02:33,877 --> 04:02:35,278 OF OPIOID AS AN OUT PATIENT. 4986 04:02:35,278 --> 04:02:36,746 IT'S ALL BEND HERE. 4987 04:02:36,746 --> 04:02:38,715 THIS IS WHAT IT LOOKS LIKE IN 4988 04:02:38,715 --> 04:02:39,682 OUR CLINIC. 4989 04:02:39,682 --> 04:02:44,387 THIS IS PROBABLY AN OVER 4990 04:02:44,387 --> 04:02:44,687 ESTIMATION. 4991 04:02:44,687 --> 04:02:45,989 BUT WE DO SEE THERE'S SOME 4992 04:02:45,989 --> 04:02:47,323 PEOPLE WHO TAKE HIGH DOSES OF 4993 04:02:47,323 --> 04:02:50,727 OPIOIDS. 4994 04:02:50,727 --> 04:02:54,430 THE OTHER THING IS I THINK THIS 4995 04:02:54,430 --> 04:02:55,899 THING ABOUT FREQUENCY 4996 04:02:55,899 --> 04:02:58,735 UTILIZATION AND ACUTE CARE AND 4997 04:02:58,735 --> 04:03:00,570 ACUTE PAIN AND OUT-PATIENT 4998 04:03:00,570 --> 04:03:02,272 OPIOID USE ARE PROBABLY LESS 4999 04:03:02,272 --> 04:03:04,641 RELATED THAN WE THINK THEY ARE. 5000 04:03:04,641 --> 04:03:06,910 THIS IS FROM A STUDY FROM A 5001 04:03:06,910 --> 04:03:08,411 COLLEGIATE HOPKINS LOOKING AT 5002 04:03:08,411 --> 04:03:10,313 THIS DATA ON ONE AXIS AND 5003 04:03:10,313 --> 04:03:12,048 FREQUENCY OF ACUTE CARE VISITS 5004 04:03:12,048 --> 04:03:12,849 ON THE OTHER AXIS. 5005 04:03:12,849 --> 04:03:14,984 IF YOU DO JUST A STRAIGHT 5006 04:03:14,984 --> 04:03:19,489 CORRELATION BETWEEN THE TWO IT'S 5007 04:03:19,489 --> 04:03:23,326 A WEAK TO POSITIVE BUT IF YOU 5008 04:03:23,326 --> 04:03:25,028 SPLINE IT AT ONE PILL A DAY OR 5009 04:03:25,028 --> 04:03:26,496 LESS YOU SEE ALL THE 5010 04:03:26,496 --> 04:03:27,897 RELATIONSHIP ON THE LOW END. 5011 04:03:27,897 --> 04:03:30,600 PEOPLE AVERAGING A PILL A DAY OF 5012 04:03:30,600 --> 04:03:32,201 OPIOIDS ROUGHLY THE RELATIONSHIP 5013 04:03:32,201 --> 04:03:33,503 BETWEEN HOW MUCH OPIOID THEY 5014 04:03:33,503 --> 04:03:34,771 TAKE AND HOW MUCH THEY'RE IN THE 5015 04:03:34,771 --> 04:03:36,673 HOSPITAL IN THE ED OR INFUSION 5016 04:03:36,673 --> 04:03:41,444 CENTER IS BASICALLY NIL. 5017 04:03:41,444 --> 04:03:43,279 THIS COULD BE TRUE OF THE WORLD 5018 04:03:43,279 --> 04:03:44,347 OR JUST US. 5019 04:03:44,347 --> 04:03:45,815 LIKE I SAID, WE PAY CLOSE 5020 04:03:45,815 --> 04:03:48,618 ATTENTION TO THIS THING ABOUT 5021 04:03:48,618 --> 04:03:49,752 PEOPLE IN THE HOSPITAL A LOT OR 5022 04:03:49,752 --> 04:03:53,623 ARE ON LOTS OF OPIOIDS AND 5023 04:03:53,623 --> 04:03:56,726 HAVING A LOT OF PAIN AND SOME 5024 04:03:56,726 --> 04:03:57,994 WIND UP ON BUPRENORPHINE AND THE 5025 04:03:57,994 --> 04:03:59,529 REASON THERE'S NOT MUCH OF A 5026 04:03:59,529 --> 04:04:02,065 CORRELATION IS BECAUSE THE UPPER 5027 04:04:02,065 --> 04:04:02,832 QUADRANT IS EMPTY. 5028 04:04:02,832 --> 04:04:08,171 PEOPLE EXCLUDE FROM THE STUDIO 5029 04:04:08,171 --> 04:04:10,306 -- STUDY MAYBE THEY AREN'T JUST 5030 04:04:10,306 --> 04:04:12,809 LOOKED AT AND I'D BE INTERESTED 5031 04:04:12,809 --> 04:04:15,311 IF THIS IS IN OUR WORLD OR BACK 5032 04:04:15,311 --> 04:04:15,678 YARD. 5033 04:04:15,678 --> 04:04:16,646 THIS IS ABOUT USING 5034 04:04:16,646 --> 04:04:17,280 BUPRENORPHINE FOR THESE GROUPS 5035 04:04:17,280 --> 04:04:22,585 OF PEOPLE FOR THAT REASON. 5036 04:04:22,585 --> 04:04:27,323 THAT BEING SAID, SO I AM PATH 5037 04:04:27,323 --> 04:04:28,658 LOGICALLY SIMPLE MINDED AS MANY 5038 04:04:28,658 --> 04:04:30,126 PEOPLE IN THE ROOM CAN ATTEST 5039 04:04:30,126 --> 04:04:30,293 TO. 5040 04:04:30,293 --> 04:04:34,130 I LIKE TO MAKE THINGS I CAN 5041 04:04:34,130 --> 04:04:34,430 UNDERSTAND. 5042 04:04:34,430 --> 04:04:36,032 I THINK BUPRENORPHINE ABOUT 80% 5043 04:04:36,032 --> 04:04:37,467 OF WHAT YOU NEED TO KNOW ABOUT 5044 04:04:37,467 --> 04:04:39,202 THE PHARMACOLOGY IS WHAT IT DOES 5045 04:04:39,202 --> 04:04:43,306 AT ONE RECEPTOR AND NEED TO KNOW 5046 04:04:43,306 --> 04:04:46,609 TWO THINGS ABOUT IT. 5047 04:04:46,609 --> 04:04:49,612 THE OPIOID RECEPTOR AND THE 5048 04:04:49,612 --> 04:04:50,346 RESPIRATORY SUPPRESSION AND 5049 04:04:50,346 --> 04:04:52,015 ANALGESIA AND ABOUT ALL OF IT. 5050 04:04:52,015 --> 04:04:53,816 TWO THINGS ARE FUNNY ABOUT IT. 5051 04:04:53,816 --> 04:04:56,319 ONE IS IT'S A PARTIAL AGONIST. 5052 04:04:56,319 --> 04:04:57,820 THAT MEANS THERE COMES A POINT 5053 04:04:57,820 --> 04:04:59,689 WHERE YOU GIVE MORE 5054 04:04:59,689 --> 04:05:01,591 BUPRENORPHINE AND YOU STEADILY 5055 04:05:01,591 --> 04:05:05,962 GIVE MORE AND IT CEILINGS OUT 5056 04:05:05,962 --> 04:05:10,433 AND IT KEEPS OCCUPYING THE 5057 04:05:10,433 --> 04:05:12,268 RECEPTOR AND THING 1. 5058 04:05:12,268 --> 04:05:14,437 THING 2 IS IT STICKS TO 5059 04:05:14,437 --> 04:05:14,804 RECEPTORS LIKE 5060 04:05:14,804 --> 04:05:18,875 >>YGLUE SO WHEN IT'S 5061 04:05:18,875 --> 04:05:23,112 ON THERE IT DOESN'T COME OFF 5062 04:05:23,112 --> 04:05:26,883 EASY AND SOME USEFUL AND SOME 5063 04:05:26,883 --> 04:05:28,217 COMPLICATING. 5064 04:05:28,217 --> 04:05:30,920 THE MAIN USEFUL THING ABOUT IT 5065 04:05:30,920 --> 04:05:32,155 IS THE CAUSE OF THE AFFECT IF 5066 04:05:32,155 --> 04:05:35,324 YOU'RE TOLERANT TO A SOLID DOSE 5067 04:05:35,324 --> 04:05:37,160 OF OPIOID OR BUPRENORPHINE AND 5068 04:05:37,160 --> 04:05:39,695 YOU TAKE MORE YOU WIND UP HAVING 5069 04:05:39,695 --> 04:05:41,297 EFFECT CEILING OUT BEFORE THE 5070 04:05:41,297 --> 04:05:42,098 RESPIRATORY SUPPRESSION KICKS IN 5071 04:05:42,098 --> 04:05:43,599 AND IT'S SAFER IN TERMS OF NOT 5072 04:05:43,599 --> 04:05:46,102 HAVING AN OVERDOSES. 5073 04:05:46,102 --> 04:05:47,303 IT'S ONE OF THE REASONS IT'S 5074 04:05:47,303 --> 04:05:54,110 USED IN ADDICTION TREATMENT. 5075 04:05:54,110 --> 04:05:58,948 THE OTHER THING THAT'S 5076 04:05:58,948 --> 04:06:00,783 COMPLICATED AND YOU HAVE AN 5077 04:06:00,783 --> 04:06:03,319 AGONIST AND SOMEONE WITH HIGH 5078 04:06:03,319 --> 04:06:07,190 TOLERANCE THE BUPRENORPHINE WILL 5079 04:06:07,190 --> 04:06:09,959 OUT COMPETE IT AND CAUSE 5080 04:06:09,959 --> 04:06:11,060 PRECIPITATED WITHDRAWAL NOT AS 5081 04:06:11,060 --> 04:06:15,231 BAD AS A FULL ANTAGONIST BUT 5082 04:06:15,231 --> 04:06:16,532 WHEN YOU TRANSITION PEOPLE FROM 5083 04:06:16,532 --> 04:06:18,134 AGONIST TO BUPRENORPHINE IT CAN 5084 04:06:18,134 --> 04:06:18,601 TAKE TECHNIQUE. 5085 04:06:18,601 --> 04:06:20,803 THERE'S A COUPLE WAYS TO DO IT. 5086 04:06:20,803 --> 04:06:23,673 WE DO IT BOTH WAYS AT HOPKINS. 5087 04:06:23,673 --> 04:06:26,008 I DON'T GOT 20 MINUTES AND WON'T 5088 04:06:26,008 --> 04:06:27,110 GO DETAILS BUT IF YOU WANT TO 5089 04:06:27,110 --> 04:06:30,346 TALK ABOUT IT LATER, I'LL BE 5090 04:06:30,346 --> 04:06:31,314 BACK THERE. 5091 04:06:31,314 --> 04:06:37,954 MY E-MAIL ADDRESS IS UP THERE. 5092 04:06:37,954 --> 04:06:40,323 SOME NICE THINGS ABOUT IT IS IT 5093 04:06:40,323 --> 04:06:42,492 HAS MODEST WITHDRAWAL AND IT 5094 04:06:42,492 --> 04:06:47,029 DOES ACT AS AN ANALGESIC AND HAS 5095 04:06:47,029 --> 04:06:48,364 INTRINSIC AGONIST ACTIVITY. 5096 04:06:48,364 --> 04:06:50,299 IT WAS FIRST APPROVED FOR THE 5097 04:06:50,299 --> 04:06:52,869 USE IN PAIN FOR THE PARENT 5098 04:06:52,869 --> 04:06:54,971 VERSION FIRST APPROVED FOR PAIN 5099 04:06:54,971 --> 04:07:00,376 PROBABLY LATE 80s, EARLY '90s 5100 04:07:00,376 --> 04:07:02,912 AND ADDICTION TREATMENT AND 5101 04:07:02,912 --> 04:07:05,581 OTHERS AND LOTS OF INJECTABLES 5102 04:07:05,581 --> 04:07:07,383 AND LONG ACTINGS AND HAD TWO OR 5103 04:07:07,383 --> 04:07:13,055 THREE COME ONLINE FOR 5104 04:07:13,055 --> 04:07:13,689 INDICATIONS FOR CHRONIC PAIN 5105 04:07:13,689 --> 04:07:16,025 WHICH IS PROBABLY OTHERS COMING 5106 04:07:16,025 --> 04:07:17,326 SOON. 5107 04:07:17,326 --> 04:07:20,163 AND IT'S A FUNNY OPIOID. 5108 04:07:20,163 --> 04:07:21,664 IT REQUIRES TECHNIQUE AND HAS 5109 04:07:21,664 --> 04:07:21,964 ADVANTAGES. 5110 04:07:21,964 --> 04:07:26,903 ONE THING I SHOULD POINT OUT 5111 04:07:26,903 --> 04:07:29,805 ABOUT THE WHOLE SAFETY THING AS 5112 04:07:29,805 --> 04:07:31,874 IT SAFER IN TERMS OF OVERDOSE IF 5113 04:07:31,874 --> 04:07:34,610 YOU'RE TOLERANT TO OPIOIDS. 5114 04:07:34,610 --> 04:07:35,778 IF YOU HAVE SOMEONE NOT TOLERANT 5115 04:07:35,778 --> 04:07:38,114 TO OPIOIDS AND GIVE THEM A BOAT 5116 04:07:38,114 --> 04:07:40,116 LOAD OF BUPRENORPHINE YOU CAN 5117 04:07:40,116 --> 04:07:42,818 OVERDOSE AND CAN DIE AND IT'S 5118 04:07:42,818 --> 04:07:45,688 PRETTY DANGEROUS BECAUSE THE 5119 04:07:45,688 --> 04:07:46,956 RECEPTOR IDENTITY MAKES IT HARD 5120 04:07:46,956 --> 04:07:49,458 TO REVERSE WITH AN ANTAGONIST. 5121 04:07:49,458 --> 04:07:52,461 IT'S NOT LIKE YOU CAN THROW IT 5122 04:07:52,461 --> 04:07:54,897 AT ANYBODY AND IT WILL BE SAFER. 5123 04:07:54,897 --> 04:07:56,532 YOU HAVE TO KNOW WHAT YOU'RE 5124 04:07:56,532 --> 04:07:56,799 DOING. 5125 04:07:56,799 --> 04:07:58,801 IT'S BEEN STUDIED IN SICKLE CELL 5126 04:07:58,801 --> 04:08:03,906 DISEASE AND THERE'S BEEN A FEW 5127 04:08:03,906 --> 04:08:14,417 CASE STUDIES AND BOTH MAINLY 5128 04:08:18,554 --> 04:08:20,790 LOOKED AT ACUTE CARE UTILIZATION 5129 04:08:20,790 --> 04:08:24,427 AS AN OUTCOME. 5130 04:08:24,427 --> 04:08:26,796 SO OUR STUDY SIMILAR 5131 04:08:26,796 --> 04:08:28,264 DEMOGRAPHICS TO OUR OVER ALL 5132 04:08:28,264 --> 04:08:30,533 POPULATION IN THE CLINIC EXCEPT 5133 04:08:30,533 --> 04:08:38,074 PROBABLY MORE PEOPLE WITH SS AND 5134 04:08:38,074 --> 04:08:39,475 GENOTYPES I THINK AND TRANSITION 5135 04:08:39,475 --> 04:08:43,346 PEOPLE ON AVERAGE TO 160 MO 5136 04:08:43,346 --> 04:08:49,352 MORPHINE EQUIV LEAPTS A DAY. 5137 04:08:49,352 --> 04:08:51,554 -- EQUIVALENTS A DAY AND TAKE 5138 04:08:51,554 --> 04:08:54,457 THEM TO SOMETHING UNDER 100 5139 04:08:54,457 --> 04:08:58,828 MORPHINE EQUIVALENTS AND SOME WE 5140 04:08:58,828 --> 04:09:02,365 SWITCH OVER BY MICRODOSES AND WE 5141 04:09:02,365 --> 04:09:02,965 PUT ALL THOSE TOGETHER IN THE 5142 04:09:02,965 --> 04:09:05,167 STUDY. 5143 04:09:05,167 --> 04:09:08,638 THIS HERE IS A SLIDE THAT SHOWS 5144 04:09:08,638 --> 04:09:10,206 THE AMOUNT OF BUPRENORPHINE 5145 04:09:10,206 --> 04:09:11,641 PEOPLE WOUND UP ON RELATIVE TO 5146 04:09:11,641 --> 04:09:13,242 THE AMOUNT OF OPIOID THEY WERE 5147 04:09:13,242 --> 04:09:14,810 TAKING BEFORE. 5148 04:09:14,810 --> 04:09:16,212 AND THERE'S TWO LINES. 5149 04:09:16,212 --> 04:09:24,820 THE MATH -- MAGENTA IS PRE 5150 04:09:24,820 --> 04:09:26,555 TAPERING DOWN AND THE BLUE LINE 5151 04:09:26,555 --> 04:09:28,524 IS THE DOSE PEOPLE WERE TAKING 5152 04:09:28,524 --> 04:09:30,960 AT THE TIME THEY SWITCHED OVER 5153 04:09:30,960 --> 04:09:34,563 TO BUPRENORPHINE AND THEN THE Y 5154 04:09:34,563 --> 04:09:40,803 AXIS IS SABOXONE SUB LINGUAL 5155 04:09:40,803 --> 04:09:41,637 VERSIONS. 5156 04:09:41,637 --> 04:09:43,306 I'LL TELL YOU PART OF WHY THAT 5157 04:09:43,306 --> 04:09:45,207 IS IN A SECOND. 5158 04:09:45,207 --> 04:09:47,043 WHAT YOU'LL SEE IS THAT PEOPLE 5159 04:09:47,043 --> 04:09:50,279 WOUND UP BETWEEN LIKE 8 AND 16. 5160 04:09:50,279 --> 04:09:53,883 THEY HAD A FEW OUTLIERS TAKING 5161 04:09:53,883 --> 04:09:55,651 24 MILLIGRAMS A DAY OF 5162 04:09:55,651 --> 04:09:58,287 BUPRENORPHINE EQUIVALENTS. 5163 04:09:58,287 --> 04:10:02,124 AND I ALSO SAY THAT WE HAD FEW 5164 04:10:02,124 --> 04:10:03,659 HAVING VERY MUCH WITHDRAWAL AND 5165 04:10:03,659 --> 04:10:04,927 MOST OF WHAT THE WITHDRAWAL 5166 04:10:04,927 --> 04:10:06,896 PEOPLE HAD TO THE EXTENT THEY 5167 04:10:06,896 --> 04:10:09,031 HAD ANY HAD TO DO WITH THE DOSE 5168 04:10:09,031 --> 04:10:11,133 THEY WERE TAPERING DOWN TO AND 5169 04:10:11,133 --> 04:10:12,902 THE LOWER PEOPLE'S TOLERANCES 5170 04:10:12,902 --> 04:10:15,571 THE EASIER AND I CAN TALK TO YOU 5171 04:10:15,571 --> 04:10:16,172 ABOUT THAT LATER. 5172 04:10:16,172 --> 04:10:21,377 YOU CAN E-MAIL ME. 5173 04:10:21,377 --> 04:10:23,279 THE LINES ON THE GRAPH ARE THE 5174 04:10:23,279 --> 04:10:25,748 TWO MORE RECENTLY APPROVED 5175 04:10:25,748 --> 04:10:27,149 CHRONIC PAIN PREPARATIONS OF 5176 04:10:27,149 --> 04:10:27,783 BUPRENORPHINE. 5177 04:10:27,783 --> 04:10:31,220 IF YOU READ THEIR PACKAGE 5178 04:10:31,220 --> 04:10:32,788 INSERTS THEY DON'T THINK MUCH 5179 04:10:32,788 --> 04:10:34,690 ABOUT TRANSITIONS PEOPLE OVER ON 5180 04:10:34,690 --> 04:10:38,794 HIGH DOSES OF OPIOIDS. 5181 04:10:38,794 --> 04:10:42,865 SO RIGHT HERE IS WHAT THE 5182 04:10:42,865 --> 04:10:46,969 PACKAGE INSERT IS IMPLIED THE 5183 04:10:46,969 --> 04:10:50,639 MAXIMUM DOSE TO SWITCH PEOPLE 5184 04:10:50,639 --> 04:10:50,840 OVER. 5185 04:10:50,840 --> 04:10:52,074 HERE IS THE OTHER. 5186 04:10:52,074 --> 04:10:54,744 THEY HAVE WAY LESS IN THEM. 5187 04:10:54,744 --> 04:11:05,287 SO 2 MILLIGRAMS OF SUBOXONE AND 5188 04:11:07,857 --> 04:11:13,496 THE LOWEST DOSE YOU CAN GET IS 5189 04:11:13,496 --> 04:11:14,797 SOMETHING LIKE 75 MICROGRAMS IV 5190 04:11:14,797 --> 04:11:19,869 ALL DAY. 5191 04:11:19,869 --> 04:11:21,604 SO AND A LOT OF OUR FOLKS WIND 5192 04:11:21,604 --> 04:11:29,779 UP ON 16 MILLIGRAMS OF SUBOXONE 5193 04:11:29,779 --> 04:11:31,113 AND THEY'RE NOT FIT 5194 04:11:31,113 --> 04:11:32,882 TRANSITIONING PEOPLE FROM HIGH 5195 04:11:32,882 --> 04:11:33,082 DOSES. 5196 04:11:33,082 --> 04:11:35,317 THE MAIN OUTCOME WAS ACUTE CARE 5197 04:11:35,317 --> 04:11:37,086 UTILIZATION AND YOU SEE IT 5198 04:11:37,086 --> 04:11:37,787 DROPPED. 5199 04:11:37,787 --> 04:11:38,888 ON AVERAGE IT DROPPED BY ABOUT 5200 04:11:38,888 --> 04:11:48,497 THREE-QUARTERS. 5201 04:11:48,497 --> 04:11:52,001 THE THING LESS IMPRESSIVE THAN 5202 04:11:52,001 --> 04:11:54,403 IT SOUNDS IS THE POST 5203 04:11:54,403 --> 04:11:56,839 DISTRIBUTION IS NOT LOW 5204 04:11:56,839 --> 04:11:59,341 UTILIZING PEOPLE SICKLE CELL 5205 04:11:59,341 --> 04:12:00,443 DISEASE. 5206 04:12:00,443 --> 04:12:02,812 YOU'LL SEE FIVISH ACUTE CARE 5207 04:12:02,812 --> 04:12:08,651 VISITS PER SIX MONTHS. 5208 04:12:08,651 --> 04:12:10,219 AND SO I SHOULD EMPHASIZE THESE 5209 04:12:10,219 --> 04:12:11,587 FOLKS ARE SICK. 5210 04:12:11,587 --> 04:12:14,023 THEY HAVE CHRONIC PAIN. 5211 04:12:14,023 --> 04:12:18,861 THEY OFTEN HAVE FREQUENT ACUTE 5212 04:12:18,861 --> 04:12:20,229 PAIN AND PSYCHIATRIC MORBIDITIES 5213 04:12:20,229 --> 04:12:22,898 AND ETCETERA, ETCETERA. 5214 04:12:22,898 --> 04:12:24,567 WHICH IS TO SAY THERE'S NO 5215 04:12:24,567 --> 04:12:26,569 MIRACLE TO BE HAD HERE. 5216 04:12:26,569 --> 04:12:30,172 IT'S A USEFUL TOOL BUT WON'T FIX 5217 04:12:30,172 --> 04:12:30,606 EVERY PROBLEM. 5218 04:12:30,606 --> 04:12:32,842 THE OTHER THING THAT GOES 5219 04:12:32,842 --> 04:12:34,543 AGAINST THAT IS THERE'S A FAIR 5220 04:12:34,543 --> 04:12:37,279 NUMBER OF PEOPLE TRANSITIONED 5221 04:12:37,279 --> 04:12:41,484 THAT WERE NOT PARTICULARLY 5222 04:12:41,484 --> 04:12:42,485 FREQUENT VISITORS BEFORE THEY 5223 04:12:42,485 --> 04:12:44,353 TRANSITIONED OVER AND PEOPLE 5224 04:12:44,353 --> 04:12:49,058 GOING TO HIGH DOSES AND MORE 5225 04:12:49,058 --> 04:12:50,860 TEEN EQUIVALENTS AND FOR SOME 5226 04:12:50,860 --> 04:12:51,861 FOLKS THERE WASN'T A LOT OF 5227 04:12:51,861 --> 04:12:53,462 UTILIZATION TO REDUCE AND TO THE 5228 04:12:53,462 --> 04:12:55,197 EXTENT THERE WERE PEOPLE WHO HAD 5229 04:12:55,197 --> 04:12:57,199 HIGH UTILIZATION AND DROPPED OFF 5230 04:12:57,199 --> 04:12:59,335 IT'S KIND OF IMPRESSIVE AT THE 5231 04:12:59,335 --> 04:13:02,571 SAME TIME THE OVER ALL 5232 04:13:02,571 --> 04:13:06,909 POPULATION ARE STILL SICK FOLKS. 5233 04:13:06,909 --> 04:13:08,277 THIS IS NOT PEER REVIEWED. 5234 04:13:08,277 --> 04:13:10,079 IT'S A COMPLETE PACK OF LIES. 5235 04:13:10,079 --> 04:13:14,383 DON'T BELIEVE A WORD I SAY BUT 5236 04:13:14,383 --> 04:13:18,153 I'LL TELL YOU ANY WAY. 5237 04:13:18,153 --> 04:13:19,321 IT'S DC. 5238 04:13:19,321 --> 04:13:20,556 I WANTED TO LOOK AT WHAT 5239 04:13:20,556 --> 04:13:21,857 HAPPENED TO THE PEOPLE WHO DID 5240 04:13:21,857 --> 04:13:23,626 COME IN TO THE INFUSION CENTER 5241 04:13:23,626 --> 04:13:26,428 IN THE ED IN THE HOSPITAL AND SO 5242 04:13:26,428 --> 04:13:27,329 ON BECAUSE BUPRENORPHINE 5243 04:13:27,329 --> 04:13:36,772 COMPLICATE D -- COMPLICATES WH 5244 04:13:36,772 --> 04:13:38,807 WE USUALLY USE AND WE GET FANCY 5245 04:13:38,807 --> 04:13:41,310 AND SOMETIMES REDUCE PEOPLE'S 5246 04:13:41,310 --> 04:13:41,977 STANDING BUPRENORPHINE DOSE WHEN 5247 04:13:41,977 --> 04:13:44,380 THEY COME IN FOR ACUTE CARE. 5248 04:13:44,380 --> 04:13:47,783 WE OFTEN USE KETAMINE AND RELY 5249 04:13:47,783 --> 04:13:51,620 ON NSAIDS AND THE QUESTION IS 5250 04:13:51,620 --> 04:13:53,389 HAVE YOU IMPROVED ONE THING AND 5251 04:13:53,389 --> 04:13:54,490 MADE SOMETHING ELSE WORSE? 5252 04:13:54,490 --> 04:13:58,761 THE BEST OF MY ABILITY TO TELL 5253 04:13:58,761 --> 04:14:01,130 YOU IT HASN'T CROSSED PEER 5254 04:14:01,130 --> 04:14:03,299 REVIEW BUT WE DIDN'T MAKE IT 5255 04:14:03,299 --> 04:14:07,036 WORSE. 5256 04:14:07,036 --> 04:14:13,208 THESE ARE CO-EFFICIENTS AND 5257 04:14:13,208 --> 04:14:14,843 PEOPLE THAT WENT TO IN PATIENT 5258 04:14:14,843 --> 04:14:16,879 THEY SHOWED UP WITH THE SAME 5259 04:14:16,879 --> 04:14:20,482 LEVEL AND THE OPIOID USE WENT 5260 04:14:20,482 --> 04:14:22,952 DOWN AND THAT'S AN ARTIFACT 5261 04:14:22,952 --> 04:14:24,920 BECAUSE A LOT OF THESE FOLKS 5262 04:14:24,920 --> 04:14:28,757 WERE IN BUPRENORPHINE AND THAT'S 5263 04:14:28,757 --> 04:14:30,693 NOT IN THERE AND MORE KETAMINE 5264 04:14:30,693 --> 04:14:33,596 USE AND WE USED IT AND THE 5265 04:14:33,596 --> 04:14:34,997 SUPPLY RAN OUT SO WE RAN OUT OF 5266 04:14:34,997 --> 04:14:37,199 OUR CHANCE TO TRY AND PEOPLE 5267 04:14:37,199 --> 04:14:38,133 DIDN'T STAY LONGER. 5268 04:14:38,133 --> 04:14:40,202 THE ED WAS WEIRDER. 5269 04:14:40,202 --> 04:14:42,237 SO REMEMBER ALL THE VISITS 5270 04:14:42,237 --> 04:14:43,939 DROPPED OFF SO THEY REALLY 5271 04:14:43,939 --> 04:14:46,275 DROPPED OFF IN THE E.D. 5272 04:14:46,275 --> 04:14:52,648 SO MUCH DISPROPORTIONATE TO THE 5273 04:14:52,648 --> 04:14:55,117 IN PATIENT SO WE HAD LESS PAIN 5274 04:14:55,117 --> 04:14:56,385 IMPROVEMENT AND PEOPLE SHOWED UP 5275 04:14:56,385 --> 04:14:58,253 WITH LESS ACTUAL PAIN TO BEGIN 5276 04:14:58,253 --> 04:15:00,222 WITH SO IF YOU DO SUBTRACTING 5277 04:15:00,222 --> 04:15:01,991 THEY SEEM TO WIND UP AT ABOUT 5278 04:15:01,991 --> 04:15:04,560 THE SAME PLACE WHEN THEY LEAVE 5279 04:15:04,560 --> 04:15:06,061 AS BEFORE BUT THERE LESS OFTEN 5280 04:15:06,061 --> 04:15:16,572 SO I THINK IT'S STILL A WASH. 5281 04:15:17,706 --> 04:15:25,147 AND THERE WAS A STUDY OF OUR 5282 04:15:25,147 --> 04:15:31,020 FOLKS WHO TRANSITIONED TO 5283 04:15:31,020 --> 04:15:35,324 BUPRENORPHINE AND I THINK YOU 5284 04:15:35,324 --> 04:15:37,326 SHOULD READ THIS PAPER. 5285 04:15:37,326 --> 04:15:39,728 SEVERAL THINGS EMERGED AND THEY 5286 04:15:39,728 --> 04:15:40,996 TRANSITIONED TO BUPRENORPHINE 5287 04:15:40,996 --> 04:15:50,773 AND SOME DIDN'T STAY ON IT. 5288 04:15:50,773 --> 04:15:52,441 SOME THINGS EMERGED AND WHAT THE 5289 04:15:52,441 --> 04:15:55,310 WHOLE THING WAS MOTIVATED BY 5290 04:15:55,310 --> 04:15:58,747 FROM THE PATIENT SIDE WAS THEY 5291 04:15:58,747 --> 04:16:00,516 WEREN'T HAPPY WHERE THEIR LIFE 5292 04:16:00,516 --> 04:16:02,051 WERE GOING AND DIDN'T LIKE 5293 04:16:02,051 --> 04:16:03,318 OPIOIDS VERY MUCH BUT THERE WAS 5294 04:16:03,318 --> 04:16:05,487 THIS BALANCE BETWEEN THE FEAR OF 5295 04:16:05,487 --> 04:16:06,755 CHANGE AND SOMETHING MAYBE 5296 04:16:06,755 --> 04:16:08,657 GETTING WORSE AND THE HOPE MAYBE 5297 04:16:08,657 --> 04:16:09,692 SOMETHING WOULD GET BETTER AND 5298 04:16:09,692 --> 04:16:11,326 THEY TALKED A LOT ABOUT THE 5299 04:16:11,326 --> 04:16:12,428 IMPORTANCE OF THERAPEUTIC 5300 04:16:12,428 --> 04:16:13,195 RELATIONSHIP WITH OUR STAFF IN 5301 04:16:13,195 --> 04:16:18,901 TERMS OF MAKING THAT DECISION. 5302 04:16:18,901 --> 04:16:20,836 I THINK IT'S REALLY IMPORTANT. 5303 04:16:20,836 --> 04:16:22,971 IN TERMS OF THE PERSPECTIVE ON 5304 04:16:22,971 --> 04:16:24,773 THINGS PRE AND POST. 5305 04:16:24,773 --> 04:16:26,475 THERE WAS SOME STUFF WELL THIS 5306 04:16:26,475 --> 04:16:28,577 SEEMS LIKE IT'S BETTER AND SOME 5307 04:16:28,577 --> 04:16:32,114 STUFF THAT WAS EH, SAME STUFF, 5308 04:16:32,114 --> 04:16:37,252 MAYBE A LITTLE BIT DITCH -- 5309 04:16:37,252 --> 04:16:37,519 DIFFERENT. 5310 04:16:37,519 --> 04:16:42,357 PEM PEOPLE TALKED ABOUT THE 5311 04:16:42,357 --> 04:16:44,860 ADVERSE EFFECTS OF THE MEDICINE 5312 04:16:44,860 --> 04:16:50,933 AND FELT MORE ENGAGED AND 5313 04:16:50,933 --> 04:16:52,901 PRESENT IN THE BUPRENORPHINE AND 5314 04:16:52,901 --> 04:16:53,769 LESS THING IN THEIR HEAD LIKE 5315 04:16:53,769 --> 04:16:59,341 YOU DIDN'T HAVE TO MAKE SURE IT 5316 04:16:59,341 --> 04:17:02,344 WAS IN THEIR PURSE AND ONE 5317 04:17:02,344 --> 04:17:03,846 COMMENT WAS IT'S LIKE A 5318 04:17:03,846 --> 04:17:06,615 BACKGROUND MEDICATION BUT THEY 5319 04:17:06,615 --> 04:17:08,016 POINTED OUT YOU STILL HAVE TO 5320 04:17:08,016 --> 04:17:09,985 TAKE SOMETHING EVERY DAY AND YOU 5321 04:17:09,985 --> 04:17:12,221 HAVE SIDE EFFECT AND THERE'S 5322 04:17:12,221 --> 04:17:13,856 STIGMA ASSOCIATED WITH OPIOID 5323 04:17:13,856 --> 04:17:17,793 USE AND BUPRENORPHINE AND PEOPLE 5324 04:17:17,793 --> 04:17:19,294 WHO SEE YOU'RE ON BUPRENORPHINE 5325 04:17:19,294 --> 04:17:21,130 THEY THINK THINGS ABOUT YOU 5326 04:17:21,130 --> 04:17:23,065 WHICH MAY MAY ALREADY THINK. 5327 04:17:23,065 --> 04:17:25,968 SOME OF OUR PATIENTS SAID 5328 04:17:25,968 --> 04:17:26,802 THERE'S STIGMA THERE BOTH WAYS 5329 04:17:26,802 --> 04:17:30,239 AND MAY KNOW WHAT TO DO TO TREAT 5330 04:17:30,239 --> 04:17:31,006 THE PAIN. 5331 04:17:31,006 --> 04:17:31,673 THE BUPRENORPHINE AND COMPLICATE 5332 04:17:31,673 --> 04:17:35,210 THE PAIN TREATMENT. 5333 04:17:35,210 --> 04:17:38,847 LIKE I SAID, I THINK THIS IS A 5334 04:17:38,847 --> 04:17:42,985 FASCINATING STUDY. 5335 04:17:42,985 --> 04:17:44,887 LIKE I SAID, I THINK 5336 04:17:44,887 --> 04:17:46,889 BUPRENORPHINE IS A USEFUL TOOL 5337 04:17:46,889 --> 04:17:51,727 BUT I WANT TO EMPHASIZE THE WAY 5338 04:17:51,727 --> 04:18:02,070 WE DO IT WE'VE MADE COMPLEX PAIN 5339 04:18:02,070 --> 04:18:05,274 MANAGEMENT A STUDY AND SO AS WE 5340 04:18:05,274 --> 04:18:10,679 STARTED USING IT DROPPED INTO AN 5341 04:18:10,679 --> 04:18:14,883 OVER ALL STRATEGY 5342 04:18:14,883 --> 04:18:16,385 SO I THINK IT'S A TOOL TO HELP 5343 04:18:16,385 --> 04:18:18,554 US KIND OF FINISH SOME JOBS, BUT 5344 04:18:18,554 --> 04:18:20,422 I DON'T THINK, FOR EXAMPLE, THAT 5345 04:18:20,422 --> 04:18:22,057 IF YOU HAVE SOMEONE WHO'S 5346 04:18:22,057 --> 04:18:22,958 EXTREMELY COMPLICATED IN THE 5347 04:18:22,958 --> 04:18:24,459 HOSPITAL A WHOLE LOT, YOU HAVE A 5348 04:18:24,459 --> 04:18:26,228 TERRIBLE THERAPEUTIC 5349 04:18:26,228 --> 04:18:27,329 RELATIONSHIP WITH AND YOUR 5350 04:18:27,329 --> 04:18:28,397 ENTIRE SYSTEM IS NOT GEARED TO 5351 04:18:28,397 --> 04:18:32,034 TREAT THEM, JUST PUTTING THEM ON 5352 04:18:32,034 --> 04:18:33,135 BUPRENORPHINE IS PROBABLY NOT 5353 04:18:33,135 --> 04:18:34,236 GOING TO HAVE ALL THAT 5354 04:18:34,236 --> 04:18:34,803 JUSTIFICATION ITSELF. 5355 04:18:34,803 --> 04:18:36,972 AND I'VE SEEN CASES WHERE THAT'S 5356 04:18:36,972 --> 04:18:38,407 GONE PRETTY BADLY. 5357 04:18:38,407 --> 04:18:40,676 SO JUST TO HAMMER IT HOME, IT'S 5358 04:18:40,676 --> 04:18:43,512 STILL AN OPIOID, A WEIRD OPIOID, 5359 04:18:43,512 --> 04:18:46,915 BUT IT'S AN OPIOID, NOT GOING TO 5360 04:18:46,915 --> 04:18:47,583 TREAT SICKLE CELL DISEASE IN AND 5361 04:18:47,583 --> 04:18:48,417 OF ITSELF. 5362 04:18:48,417 --> 04:18:50,085 CHRONIC PAIN IS HARD TO TREAT, 5363 04:18:50,085 --> 04:18:51,687 HARD TO TREAT FOR ANY KIND OF 5364 04:18:51,687 --> 04:18:53,589 MEDICINE, HARD TO TREAT WITH 5365 04:18:53,589 --> 04:18:54,356 BUPRENORPHINE, IT'S GOING TO 5366 04:18:54,356 --> 04:18:55,991 COMPLICATE YOUR MANAGEMENT OF 5367 04:18:55,991 --> 04:18:57,059 ACUTE PAIN SO YOU HAVE TO HAVE A 5368 04:18:57,059 --> 04:18:58,360 WAY OF DOING THAT AND YOU HAVE 5369 04:18:58,360 --> 04:18:59,595 TO HAVE THAT FIGURED OUT BEFORE 5370 04:18:59,595 --> 04:19:00,929 YOU TRANSITION THE PATIENT OVER, 5371 04:19:00,929 --> 04:19:02,531 AND IT DOESN'T CHANGE ANYTHING 5372 04:19:02,531 --> 04:19:03,198 ELSE, RIGHT? 5373 04:19:03,198 --> 04:19:04,399 YOU'RE STILL GOING TO HAVE THE 5374 04:19:04,399 --> 04:19:05,534 SAME THERAPEUTIC RELATIONSHIP 5375 04:19:05,534 --> 04:19:06,702 YOU HAVE WITH THE PATIENT, THE 5376 04:19:06,702 --> 04:19:07,803 PATIENT IS STILL GOING TO HAVE 5377 04:19:07,803 --> 04:19:10,105 THEIR IDEAS ABOUT HOW THEIR PAIN 5378 04:19:10,105 --> 04:19:11,506 SHOULD BE MANAGED AND HOW THE 5379 04:19:11,506 --> 04:19:13,442 SYSTEM SHOULD RESPOND TO THEM 5380 04:19:13,442 --> 04:19:15,244 AND SO FORTH. 5381 04:19:15,244 --> 04:19:16,578 NO MEDICINE IS GOING TO CHANGE 5382 04:19:16,578 --> 04:19:17,546 ANY OF THAT. 5383 04:19:17,546 --> 04:19:20,382 SO THAT'S MOSTLY WHAT I HAD TO 5384 04:19:20,382 --> 04:19:24,086 SAY, AND THAT'S ME. 5385 04:19:24,086 --> 04:19:26,188 THAT'S AN L AND THAT'S A 1, IF 5386 04:19:26,188 --> 04:19:28,023 YOU'RE HANDWRITING IT, BECAUSE 5387 04:19:28,023 --> 04:19:29,992 POOR CHRIS CARROLL IN ECONOMICS 5388 04:19:29,992 --> 04:19:31,426 AT HOPKINS IS GETTING MY MAIL, 5389 04:19:31,426 --> 04:19:32,861 IT'S DRIVING THE MAN CRAZY, SO 5390 04:19:32,861 --> 04:19:33,929 MAKE SURE YOU WRITE IT DOWN IF 5391 04:19:33,929 --> 04:19:35,030 YOU WANT TO TALK TO ME. 5392 04:19:35,030 --> 04:19:36,365 AND THAT'S WHAT I HAD TO SAY. 5393 04:19:36,365 --> 04:19:41,937 [APPLAUSE] 5394 04:19:41,937 --> 04:19:42,604 ANY QUESTIONS? 5395 04:19:42,604 --> 04:19:53,081 I DON'T SEE ANY IN THE CHAT. 5396 04:19:53,382 --> 04:19:55,584 LOOKS LIKE NO. 5397 04:19:55,584 --> 04:19:56,018 OKAY. 5398 04:19:56,018 --> 04:19:58,220 WELL, THEN I GUESS IT'S 5399 04:19:58,220 --> 04:19:58,487 LUNCHTIME. 5400 04:19:58,487 --> 04:19:58,754 >> IT IS. 5401 04:19:58,754 --> 04:20:02,257 SO WE'RE RUNNING A BIT LATE. 5402 04:20:02,257 --> 04:20:03,992 JUST A BIT OF HOUSEKEEPING, IS 5403 04:20:03,992 --> 04:20:04,760 THAT OKAY? 5404 04:20:04,760 --> 04:20:08,672 SO WE'LL TAKE ABOUT 45 MINUTES LUNCH BREAK 5405 04:20:08,672 --> 04:20:10,640 I'M MONICA FROM JAMAICA. 5406 04:20:10,640 --> 04:20:11,808 ANOTHER JAMAICAN. 5407 04:20:11,808 --> 04:20:13,710 S WAY REALLY PLEASED, JENNIFER, 5408 04:20:13,710 --> 04:20:15,479 TO SEE HOW MANY JAMAICANS ARE 5409 04:20:15,479 --> 04:20:16,580 HERE. 5410 04:20:16,580 --> 04:20:17,981 YOU REALIZE HOW MUCH JAMAICANS 5411 04:20:17,981 --> 04:20:19,483 ARE HERE? 5412 04:20:19,483 --> 04:20:30,360 NEIL IS JAY M JAMAICAN, ANDREW - 5413 04:20:31,294 --> 04:20:32,395 MOVING GEARS A LITTLE BIT, GOING 5414 04:20:32,395 --> 04:20:34,431 INTO AN AREA OF REPRODUCTIVE 5415 04:20:34,431 --> 04:20:36,099 HEALTH ISSUES IN SICKLE CELL 5416 04:20:36,099 --> 04:20:37,033 DISEASE. 5417 04:20:37,033 --> 04:20:38,769 OUR FIRST SPEAKER IS GOING TO BE 5418 04:20:38,769 --> 04:20:40,270 DR. LYDIA PECKER, WHO IS AN 5419 04:20:40,270 --> 04:20:42,272 ASSISTANT PROFESSOR OF MEDICINE 5420 04:20:42,272 --> 04:20:44,741 AT JOHNS HOPKINS UNIVERSITY. 5421 04:20:44,741 --> 04:20:47,711 SHE RECEIVED HER 5422 04:20:47,711 --> 04:20:48,712 UNDERGRADUATE DEGREE IN AFRICAN 5423 04:20:48,712 --> 04:20:49,980 STUDIES FROM BROWN AND HER M.D. 5424 04:20:49,980 --> 04:20:52,883 FROM THE UNIVERSITY OF 5425 04:20:52,883 --> 04:20:54,251 PENNSYLVANIA MEDICAL SCHOOL. 5426 04:20:54,251 --> 04:20:55,819 SHE ALSO HOLDS A MASTER'S IN 5427 04:20:55,819 --> 04:20:57,754 HEALTH SCIENCE FROM THE 5428 04:20:57,754 --> 04:20:58,288 BLOOMBERG SCHOOL OF PUBLIC 5429 04:20:58,288 --> 04:20:59,189 HEALTH. 5430 04:20:59,189 --> 04:21:00,524 DR. PECKER'S PRIMARY RESEARCH IS 5431 04:21:00,524 --> 04:21:02,392 FOCUSED ON REPRODUCTIVE HEALTH 5432 04:21:02,392 --> 04:21:04,427 IN GIRLS AND WOMEN WITH SICKLE 5433 04:21:04,427 --> 04:21:07,063 CELL DISEASE, WITH PARTICULAR 5434 04:21:07,063 --> 04:21:09,699 FOCUS ON INFERTILITY RISKS AND 5435 04:21:09,699 --> 04:21:10,667 PREGNANCY. 5436 04:21:10,667 --> 04:21:12,302 SHE'S A MEMBER OF THE AMERICAN 5437 04:21:12,302 --> 04:21:13,870 SOCIETY OF HEMATOLOGY MATERNAL 5438 04:21:13,870 --> 04:21:15,071 HEALTH COMMITTEE, FOUNDATION FOR 5439 04:21:15,071 --> 04:21:18,108 WOMEN AND GIRLS WITH DISORDERS 5440 04:21:18,108 --> 04:21:20,076 MEDICAL ADVISORY COMMITTEE AND A 5441 04:21:20,076 --> 04:21:21,745 CO-FOUNDER OF THE SICKLE CELL 5442 04:21:21,745 --> 04:21:22,279 REPRODUCTIVE EDUCATION 5443 04:21:22,279 --> 04:21:22,846 DIRECTIVE. 5444 04:21:22,846 --> 04:21:23,947 SO WELCOME, I'M LOOKING FORWARD 5445 04:21:23,947 --> 04:21:34,291 TO YOUR TALK, LYDIA. 5446 04:21:35,826 --> 04:21:37,060 > 5447 04:21:37,060 --> 04:21:38,595 >> IT'S KIND OF A TREAT TO BE UP 5448 04:21:38,595 --> 04:21:39,896 HERE BECAUSE I REMEMBER MY FIRST 5449 04:21:39,896 --> 04:21:42,132 MEETING, I GOT TO SIT WAY IN THE 5450 04:21:42,132 --> 04:21:43,166 BACK AT SICKLE CELL IN FOCUS. 5451 04:21:43,166 --> 04:21:44,601 I HAD NO IDEA WHAT WAS GOING ON 5452 04:21:44,601 --> 04:21:48,972 AND I SAT WITH ELLIOTT FACHINSKI 5453 04:21:48,972 --> 04:21:50,473 AND HE JUST MUTTERED TO ME ABOUT 5454 04:21:50,473 --> 04:21:52,042 THE WHOLE MEETING ABOUT 5455 04:21:52,042 --> 04:21:52,642 EVERYTHING THAT WAS WRONG. 5456 04:21:52,642 --> 04:21:53,977 WE MISS YOU, ELLIOTT. 5457 04:21:53,977 --> 04:21:55,312 AND IF YOU'RE NEW TO THIS 5458 04:21:55,312 --> 04:21:56,313 MEETING AND YOU'RE NOT SITTING 5459 04:21:56,313 --> 04:21:58,548 NEXT TO AN ORIGINAL GANGSTER OF 5460 04:21:58,548 --> 04:21:59,916 SICKLE CELL DISEASE, GO SIT NEXT 5461 04:21:59,916 --> 04:22:01,117 TO ONE SO THEY CAN MUTTER AT YOU 5462 04:22:01,117 --> 04:22:02,786 FOR THE REST OF THE MEETING. 5463 04:22:02,786 --> 04:22:04,721 IT'S A SPECIAL EXPERIENCE. 5464 04:22:04,721 --> 04:22:15,165 NONE OF THOSE ARE MY NAME. 5465 04:22:31,615 --> 04:22:32,749 WHO'S GOT A GOOD JOKE? 5466 04:22:32,749 --> 04:22:33,583 NO? 5467 04:22:33,583 --> 04:22:40,457 DR. CARROLL? 5468 04:22:40,457 --> 04:22:46,596 WHO HAS A QUESTION IN THE CHAT? 5469 04:22:46,596 --> 04:22:47,697 DR. QUINN, YOU KNOW ANY GOOD 5470 04:22:47,697 --> 04:22:53,370 JOKES? 5471 04:22:53,370 --> 04:23:03,580 DR. LEONARD? 5472 04:24:00,303 --> 04:24:01,638 WELL, I'M FROM THE JAMAICAN 5473 04:24:01,638 --> 04:24:03,106 COLONY OF BROOKLYN, SO IT'S 5474 04:24:03,106 --> 04:24:05,709 REALLY NICE TO BE TOGETHER WITH 5475 04:24:05,709 --> 04:24:07,277 OUR COLLEAGUES FROM JAMAICA AND 5476 04:24:07,277 --> 04:24:08,979 TO MEET ONE ANOTHER IN PERSON IN 5477 04:24:08,979 --> 04:24:10,380 BETHESDA. 5478 04:24:10,380 --> 04:24:11,514 AND I'M REALLY DELIGHTED TO TALK 5479 04:24:11,514 --> 04:24:13,350 TO YOU ABOUT REPRODUCTIVE 5480 04:24:13,350 --> 04:24:13,650 HEALTHCARE. 5481 04:24:13,650 --> 04:24:14,784 THESE ARE MY DISCLOSURES. 5482 04:24:14,784 --> 04:24:19,489 I DID SOME CONSULTING WORK FOR 5483 04:24:19,489 --> 04:24:21,691 GBT AND NOVA NORDISK. 5484 04:24:21,691 --> 04:24:23,093 BOYS AND MEN'S REPRODUCTIVE 5485 04:24:23,093 --> 04:24:24,294 HEALTH ISN'T REALLY MY AREA OF 5486 04:24:24,294 --> 04:24:25,829 EXPERTISE BUT I REALLY STRONGLY 5487 04:24:25,829 --> 04:24:28,031 BELIEVE THAT IT DESERVES EXPERTS 5488 04:24:28,031 --> 04:24:29,366 WHO ARE COMMITTED TO ENSURING 5489 04:24:29,366 --> 04:24:31,935 THAT BOYS AND MEN RECEIVE 5490 04:24:31,935 --> 04:24:33,570 INDIVIDUALIZED HIGH QUALITY AND 5491 04:24:33,570 --> 04:24:35,005 EVIDENCE-BASED SEXUAL AND 5492 04:24:35,005 --> 04:24:36,239 REPRODUCTIVE HEALTHCARE. 5493 04:24:36,239 --> 04:24:37,640 WHILE THAT'S NOT THE TOTAL FOCUS 5494 04:24:37,640 --> 04:24:38,742 OF THIS TALK, I JUST WANTED TO 5495 04:24:38,742 --> 04:24:40,010 MAKE THAT STATEMENT REALLY 5496 04:24:40,010 --> 04:24:40,210 CLEAR. 5497 04:24:40,210 --> 04:24:41,478 THE OTHER THING I WANTED TO DO 5498 04:24:41,478 --> 04:24:44,414 AND I START TODAY DO THIS BY 5499 04:24:44,414 --> 04:24:47,517 CONJUCONJURE -- REMEMBER WE STAN 5500 04:24:47,517 --> 04:24:49,219 THE SHOULDERS OF GIANTS WHEN WE 5501 04:24:49,219 --> 04:24:49,886 DO THIS WORK. 5502 04:24:49,886 --> 04:24:51,254 WHAT MAKES REPRODUCTIVE 5503 04:24:51,254 --> 04:24:52,689 HEALTHCARE A CONCERN IN THE 5504 04:24:52,689 --> 04:24:53,423 SICKLE CELL DISEASE CLINIC IS 5505 04:24:53,423 --> 04:24:54,057 EVERYTHING THAT'S COME BEFORE. 5506 04:24:54,057 --> 04:24:55,125 SO I JUST WANTED TO TAKE A 5507 04:24:55,125 --> 04:24:56,926 MINUTE, WE CAN ALL TAKE LIKE A 5508 04:24:56,926 --> 04:24:58,495 DEEP BREATH AND IT CAN BE HARD 5509 04:24:58,495 --> 04:24:59,529 BEING A SICKLE CELL DOCTOR, I 5510 04:24:59,529 --> 04:25:01,464 JUST WANTED TO REMARK UPON HOW 5511 04:25:01,464 --> 04:25:04,467 FAR WE'VE COME IN 40 YEARS. 5512 04:25:04,467 --> 04:25:05,869 AND YET IT INDICATE HOW FAR WE 5513 04:25:05,869 --> 04:25:07,270 HAVE TO GO, BUT I JUST WANTED TO 5514 04:25:07,270 --> 04:25:11,341 TAKE THAT DEAP BREATH TOGETHER. 5515 04:25:11,341 --> 04:25:13,309 ONE OF THE THINGS WE'VE ACHIEVED 5516 04:25:13,309 --> 04:25:14,811 UNIVERSAL SURVIVAL, DR. QUINN'S 5517 04:25:14,811 --> 04:25:16,946 PUBLICATION REALLY BENCHMARKED 5518 04:25:16,946 --> 04:25:20,517 BENCHMARKEDTHAT FOR US IN THE DS 5519 04:25:20,517 --> 04:25:20,950 COHORT. 5520 04:25:20,950 --> 04:25:22,152 OUR YOUNG PEOPLE ARE STARTING TO 5521 04:25:22,152 --> 04:25:23,620 MEET THEIR LIFE'S HOPES AND 5522 04:25:23,620 --> 04:25:25,121 GOALS, THEIR EDUCATIONAL GOALS, 5523 04:25:25,121 --> 04:25:26,556 THEIR PROFESSIONAL GOALS, THEIR 5524 04:25:26,556 --> 04:25:27,891 PERSONAL AND RELATIONAL GOALS, 5525 04:25:27,891 --> 04:25:29,259 AND WE ARE SEEING INCREASINGLY 5526 04:25:29,259 --> 04:25:31,161 THAT IF YOU HAVE ACCESS TO HIGH 5527 04:25:31,161 --> 04:25:33,663 QUALITY LIFESPAN SICKLE CELL 5528 04:25:33,663 --> 04:25:34,831 DISEASE CARE, FIRST THAT IT 5529 04:25:34,831 --> 04:25:35,832 ENABLES OTHER THINGS, LIKE 5530 04:25:35,832 --> 04:25:37,567 ACCESS TO SEXUAL AND 5531 04:25:37,567 --> 04:25:38,468 REPRODUCTIVE HEALTHCARE, BUT 5532 04:25:38,468 --> 04:25:39,536 ALSO THAT IT'S JUST THE FLOOR 5533 04:25:39,536 --> 04:25:40,804 FOR DOING EVERYTHING WE NEED TO 5534 04:25:40,804 --> 04:25:42,505 DO FOR PEOPLE WITH SICKLE CELL 5535 04:25:42,505 --> 04:25:42,972 DISEASE. 5536 04:25:42,972 --> 04:25:45,475 WE CONTINUE TO SEE EVIDENCE OF 5537 04:25:45,475 --> 04:25:46,309 HYDROXYUREA'S PROFOUND BENEFIT 5538 04:25:46,309 --> 04:25:48,912 ACROSS THE LIFESPAN, EVEN AS WE 5539 04:25:48,912 --> 04:25:51,181 KNOW THAT THIS TRANSFORMATIONAL 5540 04:25:51,181 --> 04:25:52,782 THERAPY INTRODUCES NEW CARE 5541 04:25:52,782 --> 04:25:54,317 COMPLEXITIES IN ADULTHOOD IN 5542 04:25:54,317 --> 04:25:54,617 PARTICULAR. 5543 04:25:54,617 --> 04:25:56,820 AND FINALLY, CURATIVE THERAPIES, 5544 04:25:56,820 --> 04:25:58,254 WHICH ARE UNIVERSAL INDICATION 5545 04:25:58,254 --> 04:25:59,789 FOR FERTILITY PRESERVATION AND 5546 04:25:59,789 --> 04:26:01,458 REALLY FORCE OUR HAND ON THE 5547 04:26:01,458 --> 04:26:03,259 DISCUSSIONS AROUND FERTILITY 5548 04:26:03,259 --> 04:26:04,461 PRESERVATION IN THE SICKLE CELL 5549 04:26:04,461 --> 04:26:05,495 CLINIC ARE INCREASINGLY 5550 04:26:05,495 --> 04:26:06,496 AVAILABLE TO OUR PATIENTS. 5551 04:26:06,496 --> 04:26:14,104 WHAT AN AMAZING THING. 5552 04:26:14,104 --> 04:26:16,606 THIS IS A REPRODUCTIVE LIFE 5553 04:26:16,606 --> 04:26:18,007 PLAN, AND I WANTED TO JUST POINT 5554 04:26:18,007 --> 04:26:20,343 OUT THAT REPRODUCTIVE LIFE 5555 04:26:20,343 --> 04:26:21,744 PLANNING SPANS THE PEDIATRIC AND 5556 04:26:21,744 --> 04:26:23,213 ADULT CARE CONTEXTS, SO A LOT OF 5557 04:26:23,213 --> 04:26:25,248 WHAT WE'RE GOING TO SAY IS NOT 5558 04:26:25,248 --> 04:26:26,149 EXACTLY WHOLLY THE 5559 04:26:26,149 --> 04:26:27,684 RESPONSIBILITY OF PEDIATRICIANS 5560 04:26:27,684 --> 04:26:30,854 NOR WHOLLY THE RESPONSIBILITY OF 5561 04:26:30,854 --> 04:26:33,223 ADULT CARE PROVIDERS, AND THAT 5562 04:26:33,223 --> 04:26:34,991 THIS MAKES THIS WORK PERHAPS 5563 04:26:34,991 --> 04:26:36,126 MORE COMPLEX IN SOME WAYS BUT 5564 04:26:36,126 --> 04:26:37,494 ALSO EXCITING BECAUSE IT 5565 04:26:37,494 --> 04:26:40,763 INTRODUCES DIVERSE PRER PERSPECS 5566 04:26:40,763 --> 04:26:41,431 ON POTENTIALLY THE SAME 5567 04:26:41,431 --> 04:26:41,798 PROBLEMS. 5568 04:26:41,798 --> 04:26:42,999 I'M GOING TO START WITH A CASE 5569 04:26:42,999 --> 04:26:45,135 OF A YOUNG MAN THAT I CARED FOR, 5570 04:26:45,135 --> 04:26:46,769 A 27-YEAR-OLD WITH HEMOGLOBIN SS 5571 04:26:46,769 --> 04:26:48,738 WHO RECENTLY MOVED FROM ATLANTA 5572 04:26:48,738 --> 04:26:50,406 TO BALTIMORE WITH HIS FIANCE AND 5573 04:26:50,406 --> 04:26:51,841 HE'S TAKEN HYDROXYUREA FOR 10 5574 04:26:51,841 --> 04:26:52,909 YEARS AND MERCIFULLY FOR HIM 5575 04:26:52,909 --> 04:26:55,645 DOES NOT ROOT FOR THE ORIOLES. 5576 04:26:55,645 --> 04:26:57,247 THEY ARE PLANNING TO START THEIR 5577 04:26:57,247 --> 04:26:59,382 FAMILY AND HE WANTS TO KNOW WHAT 5578 04:26:59,382 --> 04:27:00,483 ANTICIPATORY GUIDANCE HE NEEDS, 5579 04:27:00,483 --> 04:27:01,551 WHAT HE SHOULD BE THINKING 5580 04:27:01,551 --> 04:27:01,885 ABOUT. 5581 04:27:01,885 --> 04:27:04,621 AND WHEN I TALK ABOUT 5582 04:27:04,621 --> 04:27:05,922 REPRODUCTIVE LIFE PLANNING AND 5583 04:27:05,922 --> 04:27:06,656 LIFESPANS IN PEOPLE WITH SICKLE 5584 04:27:06,656 --> 04:27:09,125 CELL DISEASE, I TEND TO PRESENT 5585 04:27:09,125 --> 04:27:10,627 IT LIKE THIS AS YOU SEE HERE, 5586 04:27:10,627 --> 04:27:13,530 WITH THIS KIND OF MORBID GRAPH 5587 04:27:13,530 --> 04:27:19,969 FROM HASSEL ET A.L. AL, THE LIFE 5588 04:27:19,969 --> 04:27:21,771 EXPECTANCY, AND WE PROVIDE 5589 04:27:21,771 --> 04:27:22,906 REPRODUCTIVE LIFE CARE TO A 5590 04:27:22,906 --> 04:27:24,174 GROUP OF PEOPLE WHO ARE RUNNING 5591 04:27:24,174 --> 04:27:25,642 OUT OF TIME BY THE TIME THEY'RE 5592 04:27:25,642 --> 04:27:25,875 20. 5593 04:27:25,875 --> 04:27:27,210 SO THERE'S ALL KINDS OF 5594 04:27:27,210 --> 04:27:29,245 URGENCIES THAT THAT PRESENTS, 5595 04:27:29,245 --> 04:27:30,547 AND ALSO ALL KINDS OF 5596 04:27:30,547 --> 04:27:32,182 COMPLEXITIES WHEN YOU THINK 5597 04:27:32,182 --> 04:27:33,516 ABOUT PLANNING, AND SO WE HAVE 5598 04:27:33,516 --> 04:27:34,918 TO HOLD THAT AT THE SAME TIME 5599 04:27:34,918 --> 04:27:37,420 THE URGENCY OF TREATING THIS 5600 04:27:37,420 --> 04:27:38,521 DISEASE AT THE SAME TIME 5601 04:27:38,521 --> 04:27:39,622 HONORING PEOPLE'S HOPES AND 5602 04:27:39,622 --> 04:27:40,924 DREAMS ABOUT THEIR FUTURE. 5603 04:27:40,924 --> 04:27:42,158 SO THE EFFECTS OF SICKLE CELL 5604 04:27:42,158 --> 04:27:43,326 DISEASE, I STRUCTURED THIS MALE 5605 04:27:43,326 --> 04:27:44,460 PART OF THE TALK TO REALLY BE 5606 04:27:44,460 --> 04:27:46,296 LIKE IF I WAS GOING TO DO MALE 5607 04:27:46,296 --> 04:27:46,930 STUFF, THESE ARE SOME OF THE 5608 04:27:46,930 --> 04:27:48,364 THINGS I WOULD START LOOKING 5609 04:27:48,364 --> 04:27:49,632 INTO BECAUSE WE DON'T HAVE A LOT 5610 04:27:49,632 --> 04:27:50,867 OF DATA ON ANY OF THIS. 5611 04:27:50,867 --> 04:27:52,535 SO IF YOU'RE INTERESTED IN THESE 5612 04:27:52,535 --> 04:27:53,870 QUESTIONS, MAYBE THESE ARE SOME 5613 04:27:53,870 --> 04:27:54,704 THINGS THAT WOULD BE OF CONCERN 5614 04:27:54,704 --> 04:27:57,540 TO. 5615 04:27:57,540 --> 04:27:58,741 BUT FOR MEN WITH SICKLE CELL 5616 04:27:58,741 --> 04:27:59,976 DISEASE, WE KNOW THERE'S 5617 04:27:59,976 --> 04:28:01,611 TESTICULAR DAMAGE, IT'S REALLY A 5618 04:28:01,611 --> 04:28:03,246 UNIVERSAL FEATURE OF THIS TEASE, 5619 04:28:03,246 --> 04:28:05,114 THE TESTICLES ARE AN END ORGAN. 5620 04:28:05,114 --> 04:28:10,887 IT LEADS TO HYPOGONADISM AND 5621 04:28:10,887 --> 04:28:14,390 SEMEN ABNORMALS IN MANY. 5622 04:28:14,390 --> 04:28:20,897 IASOSPERMIA TENDS TO BE 5623 04:28:20,897 --> 04:28:22,098 REVERSIBLE IN SOME CASES, WE 5624 04:28:22,098 --> 04:28:24,534 LACK REALLY ROBUST SYSTEMATIC 5625 04:28:24,534 --> 04:28:27,303 DATA AT THIS POINT. 5626 04:28:27,303 --> 04:28:28,271 THE EVIDENCE THAT EXISTS FROM 5627 04:28:28,271 --> 04:28:33,876 THE FRENCH IS REASSURING THAT 5628 04:28:33,876 --> 04:28:35,078 THE SPERMATOGONIAL POOL IS 5629 04:28:35,078 --> 04:28:37,614 UNAFFECTED IN PREPUBESCENT BOYS. 5630 04:28:37,614 --> 04:28:40,750 CURATIVE THERAPIES, HAPPILY YOU 5631 04:28:40,750 --> 04:28:43,419 CAN SHIELD THE TESTICLES UNLIKE 5632 04:28:43,419 --> 04:28:45,455 THE OVARIES FOR RADIATION. 5633 04:28:45,455 --> 04:28:47,357 SO ONE THING RAISED BY THE 5634 04:28:47,357 --> 04:28:48,224 EXISTING DATA IS A QUESTION I 5635 04:28:48,224 --> 04:28:49,659 HAD IS ARE WE MISSING DATA, ARE 5636 04:28:49,659 --> 04:28:51,060 WE MISSING PREGNANCIES IN OUR 5637 04:28:51,060 --> 04:28:51,761 YOUNG MEN WITH SICKLE CELL 5638 04:28:51,761 --> 04:28:53,763 DISEASE OR ARE WE MISSING 5639 04:28:53,763 --> 04:28:54,731 INFERTILITY? 5640 04:28:54,731 --> 04:28:56,165 THE FRENCH PUBLISHED LONG TERM 5641 04:28:56,165 --> 04:28:58,034 FOLLOW-UP DATA FROM THE HU 5642 04:28:58,034 --> 04:28:59,469 ESCORT COHORT, WHICH IS A COHORT 5643 04:28:59,469 --> 04:29:00,970 OF ADULTS AND CHILDREN WITH 5644 04:29:00,970 --> 04:29:03,273 SICKLE CELL DISEASE EXPOSED TO 5645 04:29:03,273 --> 04:29:06,175 HYDROXYUREA, AND IN THIS 5646 04:29:06,175 --> 04:29:09,445 PUBLICATION, 411 PATIENTS WERE 5647 04:29:09,445 --> 04:29:10,513 OVER 18 IN THIS COHORT AND 5648 04:29:10,513 --> 04:29:12,882 THEY'VE BEEN FOLLOWED FOR 4,000 5649 04:29:12,882 --> 04:29:14,183 PATIENT YEARS. 5650 04:29:14,183 --> 04:29:15,985 AND AMONG THOSE 411 ADULT MEN, 5651 04:29:15,985 --> 04:29:18,755 THEY ONLY IDENTIFIED 12 5652 04:29:18,755 --> 04:29:20,290 PREGNANTS IN PARTNERS OF 5653 04:29:20,290 --> 04:29:20,923 HU-TREATED MEN. 5654 04:29:20,923 --> 04:29:23,159 NOW, AGAIN, IS THIS MISSING DATA 5655 04:29:23,159 --> 04:29:23,860 WHICH THEY THEMSELVES SAY THEY 5656 04:29:23,860 --> 04:29:25,295 DIDN'T DEAL WITH IN THEIR STUDY? 5657 04:29:25,295 --> 04:29:26,796 IS THIS MISSING PREGNANCIES AND 5658 04:29:26,796 --> 04:29:28,598 IS THIS MISSING INFERTILITY? 5659 04:29:28,598 --> 04:29:29,132 WE DON'T KNOW. 5660 04:29:29,132 --> 04:29:31,868 IN THE SCDIC, THERE WERE 5661 04:29:31,868 --> 04:29:33,169 884 MALE PARTICIPANTS IN A STUDY 5662 04:29:33,169 --> 04:29:35,171 FROM PEDIATRIC BLOOD AND CANCER 5663 04:29:35,171 --> 04:29:36,806 PUBLISHED NOT LONG AGO, AND 5664 04:29:36,806 --> 04:29:38,641 AMONG MEN, THERE WAS A 16.9% 5665 04:29:38,641 --> 04:29:40,877 REPORT OF INFERTILITY THAT'S 5666 04:29:40,877 --> 04:29:41,811 HIGHER THAN AVERAGE FOR 5667 04:29:41,811 --> 04:29:43,813 UNAFFECTED MEP. 5668 04:29:43,813 --> 04:29:44,447 MEN. 5669 04:29:44,447 --> 04:29:46,616 AMONG THE 149 WHO REPORTED 5670 04:29:46,616 --> 04:29:48,284 INFERTILITY, ONLY 37 HAD BEEN TO 5671 04:29:48,284 --> 04:29:51,854 AN INFERTILITY SPECIALIST, AND 5672 04:29:51,854 --> 04:29:53,990 HAD SPERM ANALYSES PERFORMED AND 5673 04:29:53,990 --> 04:29:56,459 ABOUT HALF OF THEM HAD SEMEN 5674 04:29:56,459 --> 04:29:57,093 ABNORMALITIES, CONSISTENT WITH 5675 04:29:57,093 --> 04:29:57,894 WHAT WE KNOW ABOUT THIS DISEASE. 5676 04:29:57,894 --> 04:29:59,395 NOW TO BE CLEAR, THE RISK 5677 04:29:59,395 --> 04:30:00,763 FACTORS FOR INFERTILITY IN THIS 5678 04:30:00,763 --> 04:30:02,699 PATIENT POPULATION ARE NOT JUST 5679 04:30:02,699 --> 04:30:04,000 SPERM QUALITY. 5680 04:30:04,000 --> 04:30:06,669 THERE'S ERECTILE DYSFUNCTION, 5681 04:30:06,669 --> 04:30:07,737 COMPLEX HOSPITALIZATIONS, ALL 5682 04:30:07,737 --> 04:30:09,372 KINDS OF SOCIAL CHALLENGES 5683 04:30:09,372 --> 04:30:10,506 ASSOCIATED WITH THIS DISEASE. 5684 04:30:10,506 --> 04:30:12,008 SO WE'RE NOT PINNING THIS ON 5685 04:30:12,008 --> 04:30:14,310 SPERM, BUT JUST TO SAY THERE'S 5686 04:30:14,310 --> 04:30:15,945 SEVERAL STUDIES NOW RAISING THE 5687 04:30:15,945 --> 04:30:16,913 POSSIBILITY THAT WE'RE SEEING 5688 04:30:16,913 --> 04:30:18,481 HIGHER RATES OF INFERTILITY IN 5689 04:30:18,481 --> 04:30:19,782 THIS POPULATION THAN HAVE BEEN 5690 04:30:19,782 --> 04:30:21,517 PREVIOUSLY DISCUSSED. 5691 04:30:21,517 --> 04:30:22,752 AND IN FRANCE, WHERE THEY HAVE 5692 04:30:22,752 --> 04:30:24,721 ALWAYS HAD A VERY CONSERVATIVE 5693 04:30:24,721 --> 04:30:27,090 APPROACH TO FERTILITY 5694 04:30:27,090 --> 04:30:27,990 PRESERVATION, THEIR APPROACH IS 5695 04:30:27,990 --> 04:30:30,259 TO OFFER ALL MEN TREATED WITH 5696 04:30:30,259 --> 04:30:31,928 HYDROXYUREA A HYDROXYUREA 5697 04:30:31,928 --> 04:30:33,896 HOLIDAY AND FERTILITY 5698 04:30:33,896 --> 04:30:36,065 PRESERVATION IN DEFERENCE TO THE 5699 04:30:36,065 --> 04:30:36,933 DRUG'S POTENTIAL SIDE EFFECTS. 5700 04:30:36,933 --> 04:30:38,101 IT WOULD BE GREAT TO HEAR MORE 5701 04:30:38,101 --> 04:30:39,435 FROM THE FRENCH ABOUT HOW THEY 5702 04:30:39,435 --> 04:30:41,738 NAVIGATE THESE PROTOCOLS. 5703 04:30:41,738 --> 04:30:42,839 NOW, I TRIED TO MAKE THIS 5704 04:30:42,839 --> 04:30:44,073 PICTURE OF WHAT IT'S LIKE TO SIT 5705 04:30:44,073 --> 04:30:46,109 WITH A YOUNG MAN IN CLINIC AND 5706 04:30:46,109 --> 04:30:47,877 TALK ABOUT HYDROXYUREA AND 5707 04:30:47,877 --> 04:30:49,512 PREGNANCY, LIKE A 27-YEAR-OLD 5708 04:30:49,512 --> 04:30:51,214 WHO'S COMING TO YOU PLANNING 5709 04:30:51,214 --> 04:30:52,148 PREGNANCY. 5710 04:30:52,148 --> 04:30:53,349 AND I GUESS THIS SORT OF STARTS 5711 04:30:53,349 --> 04:30:54,884 IN THE UPPER LEFT-HAND CORNER, 5712 04:30:54,884 --> 04:30:56,919 DO YOU HAVE A BASELINE SPERM 5713 04:30:56,919 --> 04:30:57,487 ANALYSIS AVAILABLE? 5714 04:30:57,487 --> 04:30:58,588 AND USUALLY THE ANSWER TO THAT 5715 04:30:58,588 --> 04:31:00,056 IS NO. 5716 04:31:00,056 --> 04:31:01,124 BECAUSE MOST PEOPLE HAVE NOT 5717 04:31:01,124 --> 04:31:03,159 BEEN SENT FOR A BASELINE SEMEN 5718 04:31:03,159 --> 04:31:04,394 ANALYSIS. 5719 04:31:04,394 --> 04:31:08,131 THEY'RE CUMBERSOME, THEY REQUIRE 5720 04:31:08,131 --> 04:31:09,198 MASTURBATING, THEY'RE 5721 04:31:09,198 --> 04:31:10,433 EMBARRASSING, FOR SOME PEOPLE 5722 04:31:10,433 --> 04:31:12,802 THEY HAVEN'T BEEN COMPLETELY 5723 04:31:12,802 --> 04:31:13,836 EXPLAINED, ET CETERA. 5724 04:31:13,836 --> 04:31:15,638 BUT EVEN IF THERE WAS, HOW DO WE 5725 04:31:15,638 --> 04:31:16,205 DEFINE THAT? 5726 04:31:16,205 --> 04:31:17,573 FOR A POPULATION OF PATIENTS WHO 5727 04:31:17,573 --> 04:31:19,275 ARE INCREASINGLY EXPOSED TO 5728 04:31:19,275 --> 04:31:21,277 HYDROXYUREA, STARTING AT BIRTH 5729 04:31:21,277 --> 04:31:23,079 INTO ADULTHOOD, WHAT IS THEIR 5730 04:31:23,079 --> 04:31:25,148 NORMAL OR BASELINE SEMEN 5731 04:31:25,148 --> 04:31:25,915 ANALYSIS? 5732 04:31:25,915 --> 04:31:26,716 OKAY, FINE, SO MAYBE I DON'T 5733 04:31:26,716 --> 04:31:27,950 HAVE A SEMEN ANALYSIS. 5734 04:31:27,950 --> 04:31:29,419 ARE YOU WILLING TO GET ONE FOR 5735 04:31:29,419 --> 04:31:29,585 ME? 5736 04:31:29,585 --> 04:31:30,953 WHEN IS THAT TEST INDICATED? 5737 04:31:30,953 --> 04:31:32,588 SHOULD WE BE GETTING IT AT 5738 04:31:32,588 --> 04:31:34,223 TRANSITION TO ADULT CARE AS PART 5739 04:31:34,223 --> 04:31:35,158 OF ROUTINE LABS? 5740 04:31:35,158 --> 04:31:36,859 SHOULD WE BE DOING IT ONCE 5741 04:31:36,859 --> 04:31:39,162 PATIENTS HAVE INFERTILITY OR 5742 04:31:39,162 --> 04:31:41,664 SHOULD WE BE DOING IT AT SOME 5743 04:31:41,664 --> 04:31:42,565 TIME POINT BEFORE THEN? 5744 04:31:42,565 --> 04:31:43,666 PATIENTS WHO ARE UNWILLING, 5745 04:31:43,666 --> 04:31:45,301 UNINTERESTED OR UNABLE TO GET 5746 04:31:45,301 --> 04:31:46,602 SEMEN ANALYSES, WHAT SHOULD WE 5747 04:31:46,602 --> 04:31:49,238 TELL THEM ABOUT PURSUING 5748 04:31:49,238 --> 04:31:50,540 CONCEPTION OR FERTILITY 5749 04:31:50,540 --> 04:31:51,841 PRESERVATION ON OR OFF 5750 04:31:51,841 --> 04:31:52,175 HYDROXYUREA? 5751 04:31:52,175 --> 04:31:53,609 SHOULD WE WAIT AND SEE WHAT 5752 04:31:53,609 --> 04:31:55,044 THEIR SEMEN ANALYSIS IS BEFORE 5753 04:31:55,044 --> 04:31:57,547 WE HOLD THE HYDROXYUREA? 5754 04:31:57,547 --> 04:31:59,048 I MEAN, IT'S LIKE -- IT'S 5755 04:31:59,048 --> 04:32:00,616 BAFFLING AND IT'S A LOT TO TALK 5756 04:32:00,616 --> 04:32:01,584 ABOUT, AND YOU KNOW, THIS IS 5757 04:32:01,584 --> 04:32:02,452 WHAT THIS CONVERSATION IS LIKE 5758 04:32:02,452 --> 04:32:05,388 IN MY CLINIC. 5759 04:32:05,388 --> 04:32:07,123 SO MOSTLY IT'S THREE, FOUR OR 5760 04:32:07,123 --> 04:32:08,291 FIVE CONVERSATIONS, NOT JUST 5761 04:32:08,291 --> 04:32:08,991 ONE. 5762 04:32:08,991 --> 04:32:10,560 BECAUSE MEN HAVE TO MAKE A 5763 04:32:10,560 --> 04:32:11,861 DECISION ABOUT A LOT OF 5764 04:32:11,861 --> 04:32:13,496 DIFFERENT TIME POINTS. 5765 04:32:13,496 --> 04:32:14,263 ANYWAY, THIS WOULD BE A PLACE 5766 04:32:14,263 --> 04:32:15,698 WHERE I WOULD START LOOKING IN 5767 04:32:15,698 --> 04:32:16,933 THE ADULT CLINIC IF I WAS 5768 04:32:16,933 --> 04:32:18,968 INTERESTED IN THIS PROBLEM OF 5769 04:32:18,968 --> 04:32:20,603 DEFINING WHAT NORMAL SEMEN 5770 04:32:20,603 --> 04:32:21,604 PARAMETERS ARE FOR THIS 5771 04:32:21,604 --> 04:32:23,439 POPULATION AND HOW WE SHOULD BE 5772 04:32:23,439 --> 04:32:24,540 PROVIDING THIS CLINICAL CARE. 5773 04:32:24,540 --> 04:32:26,676 I THINK IT'S A MUCH MORE 5774 04:32:26,676 --> 04:32:27,944 DIFFICULT CONVERSATION IN LATE 5775 04:32:27,944 --> 04:32:28,878 ADOLESCENCE AND IN PEDIATRIC 5776 04:32:28,878 --> 04:32:31,414 CARE. 5777 04:32:31,414 --> 04:32:32,748 DURING THIS ROUTINE REVIEW OF 5778 04:32:32,748 --> 04:32:34,717 SYSTEM WITH THIS NEW PATIENT, HE 5779 04:32:34,717 --> 04:32:39,755 REPORTS NO HISTORY OF PRIAPISM 5780 04:32:39,755 --> 04:32:41,157 BUT HE DOESN'T EVEN KNOW WHAT 5781 04:32:41,157 --> 04:32:42,892 THAT IS. 5782 04:32:42,892 --> 04:32:43,926 THIS HIGHLIGHTS THAT ON THE DATA 5783 04:32:43,926 --> 04:32:45,027 THAT EXISTS, THERE'S A HIGH 5784 04:32:45,027 --> 04:32:47,263 CONCERN THAT WE UNDERDETICKET IT 5785 04:32:47,263 --> 04:32:48,297 AND I THINK PART OF THAT MAY 5786 04:32:48,297 --> 04:32:49,632 JUST BE DUE TO LACK OF KNOWLEDGE 5787 04:32:49,632 --> 04:32:51,567 ABOUT WHAT THIS COMPLICATION IS. 5788 04:32:51,567 --> 04:32:53,536 IN ANY CASE, IT AFFECTS ABOUT 5789 04:32:53,536 --> 04:32:55,137 30% OF BOYS AND MEN WITH SICKLE 5790 04:32:55,137 --> 04:32:55,471 CELL DISEASE. 5791 04:32:55,471 --> 04:32:57,773 IT'S A RISK FACTOR FOR ERECTILE 5792 04:32:57,773 --> 04:32:58,941 DYSFUNCTION WHICH IS A RISK 5793 04:32:58,941 --> 04:32:59,976 FACTOR FOR INFERTILITY. 5794 04:32:59,976 --> 04:33:02,378 IT'S ALSO A RISK FACTOR FOR 5795 04:33:02,378 --> 04:33:04,046 TERRIBLE DEPRESSION, ANXIETY, 5796 04:33:04,046 --> 04:33:05,147 REALLY LOW QUALITY OF LIFE AND 5797 04:33:05,147 --> 04:33:06,415 WE DON'T TALK ABOUT IT THIS WAY 5798 04:33:06,415 --> 04:33:08,718 BUT I'VE BEEN REALLY IMPRESSED 5799 04:33:08,718 --> 04:33:09,952 OVER THE LAST FIVE YEARS TO 5800 04:33:09,952 --> 04:33:11,354 OBSERVE HOW DISRUPTED SLEEP IS 5801 04:33:11,354 --> 04:33:15,725 FOR THESE YOUNG MEN WHO HAVE 5802 04:33:15,725 --> 04:33:16,359 PRIAPISM. 5803 04:33:16,359 --> 04:33:17,793 THEY WAKE UP EVERY NIGHT, IT 5804 04:33:17,793 --> 04:33:22,031 WON'T GO AWAY, THEY GET UP, THEY 5805 04:33:22,031 --> 04:33:23,065 INSTIGATE A STEAL SYNDROME BY 5806 04:33:23,065 --> 04:33:24,267 GOING FOR A WALK AND THEY LEARN 5807 04:33:24,267 --> 04:33:26,002 ALL OF THESE TECHNIQUES TO 5808 04:33:26,002 --> 04:33:27,370 SELF-MANAGE BUT WHAT THEY CANNOT 5809 04:33:27,370 --> 04:33:28,437 MANAGE AWAY IS THE DISRUPTED 5810 04:33:28,437 --> 04:33:30,373 SLEEP AND OF COURSE THAT'S JUST 5811 04:33:30,373 --> 04:33:33,943 A CYCLE OF PAIN AND DEPRESSION 5812 04:33:33,943 --> 04:33:34,477 CONTRIBUTE FOR FOR SURE. 5813 04:33:34,477 --> 04:33:36,546 WE DON'T HAVE GREAT TREATMENTS 5814 04:33:36,546 --> 04:33:38,281 FOR THIS ALTHOUGH WE'RE ALL 5815 04:33:38,281 --> 04:33:40,917 HOLDING OUT HOPE FOR THE FACE 5816 04:33:40,917 --> 04:33:41,817 2 CRIZANLIZUMAB STUDY UNDERWAY 5817 04:33:41,817 --> 04:33:43,886 AND FOR WHICH HOPEFUL OUTCOMES 5818 04:33:43,886 --> 04:33:49,825 SO FAR HAVE BEEN REPORTED. 5819 04:33:49,825 --> 04:33:52,495 IT REQUIRES MULTIDISCIPLINARY -- 5820 04:33:52,495 --> 04:33:53,863 WE NEED TO TEACH FAMILIES IT'S 5821 04:33:53,863 --> 04:33:54,997 AN EMERGENCY, PEOPLE NEED TO BE 5822 04:33:54,997 --> 04:33:57,500 SEEN FOR CARE IF THEY HAVE 5823 04:33:57,500 --> 04:33:59,435 PRIAPISM THAT LASTS MORE THAN 5824 04:33:59,435 --> 04:33:59,902 FOUR HOURS. 5825 04:33:59,902 --> 04:34:01,671 IT'S SO BAD I LIKE TO SAY IT 5826 04:34:01,671 --> 04:34:03,172 THIS WAY, IT'S AN INDICATION FOR 5827 04:34:03,172 --> 04:34:03,573 CURATIVE THERAPY. 5828 04:34:03,573 --> 04:34:05,474 MANY OF THE CURATIVE THERAPY 5829 04:34:05,474 --> 04:34:09,378 TRIALS HAVE PRIAPISM AS AN 5830 04:34:09,378 --> 04:34:10,012 INCLUSION CRITERIA. 5831 04:34:10,012 --> 04:34:11,881 SO IT'S A MARKER OF DISEASE 5832 04:34:11,881 --> 04:34:12,848 SEVERITY AND WE HAVE TO TREAT IT 5833 04:34:12,848 --> 04:34:17,153 THAT WAY. 5834 04:34:17,153 --> 04:34:19,221 THE SUN DOES NOT SHINE ON THIS 5835 04:34:19,221 --> 04:34:20,523 27-YEAR-OLD BECAUSE I SEND HIS 5836 04:34:20,523 --> 04:34:21,724 PARTNER FOR PARTNER TESTING AND 5837 04:34:21,724 --> 04:34:23,059 WHEN WE GET THE RESULTS BACK, 5838 04:34:23,059 --> 04:34:24,860 SHE HAS C TRAIT AND HER PARENTS 5839 04:34:24,860 --> 04:34:31,467 MAKE HER CALL OFF THE WEDDING. 5840 04:34:31,467 --> 04:34:33,035 WHICH LEADS ME TO MY FINAL POINT 5841 04:34:33,035 --> 04:34:34,303 ABOUT YOUNG MEN IN THE SICKLE 5842 04:34:34,303 --> 04:34:35,071 CELL DISEASE CLINIC WHICH IS 5843 04:34:35,071 --> 04:34:36,272 THAT I BELIEVE WE ARE MISSING 5844 04:34:36,272 --> 04:34:37,273 THE MENTAL HEALTH CARE NEEDS FOR 5845 04:34:37,273 --> 04:34:39,709 THIS PATIENT POPULATION. 5846 04:34:39,709 --> 04:34:41,844 IN THE UNITED STATES, 62% OF MEN 5847 04:34:41,844 --> 04:34:44,013 WHO IDENTIFY AS BLACK HAVE 5848 04:34:44,013 --> 04:34:45,481 EXPERIENCED TRAUMA, AND 40% OF 5849 04:34:45,481 --> 04:34:46,782 PEOPLE WITH SICKLE CELL DISEASE 5850 04:34:46,782 --> 04:34:48,951 IN GENERAL REPORT MENTAL 5851 04:34:48,951 --> 04:34:49,285 ILLNESS. 5852 04:34:49,285 --> 04:34:51,187 AS WE SCREEN FOR TRAUMATIC 5853 04:34:51,187 --> 04:34:52,688 EVENTS IN BALTIMORE FOR SURE, 5854 04:34:52,688 --> 04:34:54,757 WHICH IS A PRETTY VIOLENT CITY, 5855 04:34:54,757 --> 04:34:56,726 IT'S REALLY IMPRESSIVE HOW MANY 5856 04:34:56,726 --> 04:34:59,228 PEOPLE ARE ONE DEGREE OF 5857 04:34:59,228 --> 04:35:00,329 SEPARATION FROM EXTRAORDINARY 5858 04:35:00,329 --> 04:35:01,564 BODILY HARM. 5859 04:35:01,564 --> 04:35:03,232 YOU LAYER THAT ON TOP OF THE 5860 04:35:03,232 --> 04:35:04,800 SOCIAL EXPERIENCES OF LIFE WITH 5861 04:35:04,800 --> 04:35:07,503 SICKLE CELL DISEASE, WHICH ARE 5862 04:35:07,503 --> 04:35:10,439 THEMSELVES -- AFFECT ALL OF YOUR 5863 04:35:10,439 --> 04:35:11,641 SOCIAL RELATIONSHIPS, SO THESE 5864 04:35:11,641 --> 04:35:13,042 ARE PATIENTS WHO HAVE DELAYED 5865 04:35:13,042 --> 04:35:14,143 SEXUAL MATURITY, THEY HAVE A 5866 04:35:14,143 --> 04:35:15,211 HARD TIME MAKING FRIENDS IN 5867 04:35:15,211 --> 04:35:16,812 MIDDLE SCHOOL, THEY'RE BED 5868 04:35:16,812 --> 04:35:17,947 WETTERS, THEY'RE KIDS WHO 5869 04:35:17,947 --> 04:35:19,548 COULDN'T GO ON SLEEPOVERS 5870 04:35:19,548 --> 04:35:21,250 BECAUSE THEY WET THEIR BED AND 5871 04:35:21,250 --> 04:35:23,085 NOBODY EXPLAINED TO THEM IT 5872 04:35:23,085 --> 04:35:24,120 WASN'T THEIR FAULT IT WAS THEIR 5873 04:35:24,120 --> 04:35:24,820 SICKLE CELL DISEASE, AND THEY 5874 04:35:24,820 --> 04:35:27,123 HAVE ANXIETY ALTHOUGH THE BOYS 5875 04:35:27,123 --> 04:35:28,124 DON'T ALWAYS GET AS GOOD 5876 04:35:28,124 --> 04:35:29,258 TRAINING ABOUT TALKING ABOUT 5877 04:35:29,258 --> 04:35:30,693 THEIR FEELINGS ABOUT PASSING 5878 04:35:30,693 --> 04:35:32,128 THIS DISEASE ON TO THEIR 5879 04:35:32,128 --> 04:35:33,162 CHILDREN AND A LOT OF 5880 04:35:33,162 --> 04:35:35,297 MISUNDERSTANDING ABOUT HOW 5881 04:35:35,297 --> 04:35:36,198 SICKLE CELL DISEASE IS 5882 04:35:36,198 --> 04:35:36,699 INHERITED. 5883 04:35:36,699 --> 04:35:38,067 SO THERE'S BROAD NEED FOR 5884 04:35:38,067 --> 04:35:39,669 ENGAGEMENT OF OUR YOUNG MEN WITH 5885 04:35:39,669 --> 04:35:41,037 SICKLE CELL DISEASE. 5886 04:35:41,037 --> 04:35:42,538 AND THAT'S MY APPEAL TO ALL OF 5887 04:35:42,538 --> 04:35:44,206 YOU OUT THERE, TO CARE ABOUT THE 5888 04:35:44,206 --> 04:35:45,508 BOYS AND MEN WHO ARE COMING TO 5889 04:35:45,508 --> 04:35:47,043 MY CLINIC AND YOURS, BECAUSE I 5890 04:35:47,043 --> 04:35:49,345 THINK THEY REALLY NEED OUR CARE. 5891 04:35:49,345 --> 04:35:50,980 AND WITH THAT, I'M GOING TO 5892 04:35:50,980 --> 04:35:54,050 TRANSITION TO MY COMFORT ZONE 5893 04:35:54,050 --> 04:35:55,651 AND TALK A LITTLE BIT ABOUT 5894 04:35:55,651 --> 04:35:56,886 WOMEN'S REPRODUCTIVE HEL. 5895 04:35:56,886 --> 04:35:58,154 SO WE KNOW GIRLS AND WOMEN WITH 5896 04:35:58,154 --> 04:35:59,522 SICKLE CELL DISEASE FACE ANY 5897 04:35:59,522 --> 04:36:00,856 NUMBER OF COMPLICATIONS. 5898 04:36:00,856 --> 04:36:02,558 I'M GOING TO WALK YOU THROUGH A 5899 04:36:02,558 --> 04:36:03,559 REPRODUCTIVE LIFESPAN OF A 5900 04:36:03,559 --> 04:36:05,394 28-YEAR-OLD WITH HEMOGLOBIN SS 5901 04:36:05,394 --> 04:36:07,263 WHO WAS DIAGNOSED IN THE EARLY 5902 04:36:07,263 --> 04:36:08,664 1990s ON NEWBORN SCREENING, 5903 04:36:08,664 --> 04:36:10,966 AND HER BROTHER WAS CURED BY A 5904 04:36:10,966 --> 04:36:12,968 MATCH SIBLING DONOR TRANSPLANT. 5905 04:36:12,968 --> 04:36:14,970 HER ADOLESCENCE WAS INTERRUPTED 5906 04:36:14,970 --> 04:36:19,075 BY ACUTE CHEST, PAINFUL CRISES, 5907 04:36:19,075 --> 04:36:19,842 MENSTRUATION ASSOCIATED SICKLE 5908 04:36:19,842 --> 04:36:21,410 CELL PAIN, DAILY BACK PAIN AND 5909 04:36:21,410 --> 04:36:21,577 AVN. 5910 04:36:21,577 --> 04:36:23,579 IT WAS IN THAT CONTEXT THAT SHE 5911 04:36:23,579 --> 04:36:25,381 INITIATED BOTH HYDROXYUREA AND 5912 04:36:25,381 --> 04:36:26,916 HORMONAL CONTRACEPTIVE. 5913 04:36:26,916 --> 04:36:28,718 LET'S TALK A LITTLE BIT ABOUT 5914 04:36:28,718 --> 04:36:29,485 MENSTRUATION IN SICKLE CELL 5915 04:36:29,485 --> 04:36:29,819 DISEASE. 5916 04:36:29,819 --> 04:36:31,687 SO MANY GIRLS WITH SICKLE CELL 5917 04:36:31,687 --> 04:36:32,755 DISEASE START TO MENSTRUATE IN 5918 04:36:32,755 --> 04:36:34,523 THEIR MID TO LATE TEENAGE YEARS. 5919 04:36:34,523 --> 04:36:36,058 IT'S POSSIBLE THAT GENOTYPE 5920 04:36:36,058 --> 04:36:37,359 CONTRIBUTES TO THIS AND POSSIBLE 5921 04:36:37,359 --> 04:36:39,528 THAT TREATMENTS CHANGE THE 5922 04:36:39,528 --> 04:36:41,731 ONSET, THOUGH THAT'S VERY POORLY 5923 04:36:41,731 --> 04:36:42,064 DEFINED. 5924 04:36:42,064 --> 04:36:43,699 THIS IS A CONSTITUTIONAL DELAY 5925 04:36:43,699 --> 04:36:45,901 IN PUBERTY ONSET, SO THINGS THAT 5926 04:36:45,901 --> 04:36:47,436 CHANGE METABOLIC RATE LIKE 5927 04:36:47,436 --> 04:36:48,771 HYDROXYUREA AND CHRONIC 5928 04:36:48,771 --> 04:36:49,705 TRANSFUSIONS, IT'S PLAUSIBLE AT 5929 04:36:49,705 --> 04:36:53,242 LEAST THAT THEY MIGHT CHANGE THE 5930 04:36:53,242 --> 04:36:55,945 AGE AT PUBERTY. 5931 04:36:55,945 --> 04:36:57,947 THE ABSENCE OF PERIODS IN LATE 5932 04:36:57,947 --> 04:36:58,881 ADOLESCENCE IS NOT WELL 5933 04:36:58,881 --> 04:36:59,515 EXPLAINED BY SICKLE CELL 5934 04:36:59,515 --> 04:36:59,749 DISEASE. 5935 04:36:59,749 --> 04:37:00,883 IT SHOULD BE WORKED UP. 5936 04:37:00,883 --> 04:37:02,518 WE SHOULDN'T JUST LET OUR 5937 04:37:02,518 --> 04:37:03,919 COLLEAGUES ATTRIBUTE DELAYED 5938 04:37:03,919 --> 04:37:05,688 PUBERTY INTO THE LATE TEEN YEARS 5939 04:37:05,688 --> 04:37:06,922 AND EARLY 20s TO SICKLE CELL 5940 04:37:06,922 --> 04:37:07,957 DISEASE. 5941 04:37:07,957 --> 04:37:09,859 WE EXPECT REGULAR MEN STRAL 5942 04:37:09,859 --> 04:37:11,894 CYCLES, AND WE NEED TO TALK TO 5943 04:37:11,894 --> 04:37:12,928 OUR PATIENTS ABOUT THE KINDS OF 5944 04:37:12,928 --> 04:37:14,430 PAIN THEY EXPERIENCE WITH THEIR 5945 04:37:14,430 --> 04:37:16,532 MENSTRUATION AND PROVIDE SOME 5946 04:37:16,532 --> 04:37:18,033 ANTICIPATORY GUIDANCE THAT PAIN 5947 04:37:18,033 --> 04:37:20,569 IS NOT A CONSTANT ACROSS ONE'S 5948 04:37:20,569 --> 04:37:22,104 REPRODUCTIVE LIFESPAN, AND THAT 5949 04:37:22,104 --> 04:37:23,038 MENSTRUAL PAIN CAN ACTUALLY 5950 04:37:23,038 --> 04:37:24,306 START AS YOU GET OLDER SO 5951 04:37:24,306 --> 04:37:25,608 PERIODS THAT WERE ONCE NOT 5952 04:37:25,608 --> 04:37:27,543 PAINFUL MAY BECOME PAINFUL. 5953 04:37:27,543 --> 04:37:29,545 THIS IS LEO THE LATE BLOOMER WHO 5954 04:37:29,545 --> 04:37:30,713 I ALWAYS THINK OF WHEN I THINK 5955 04:37:30,713 --> 04:37:31,847 OF CHILDREN WITH SICKLE CELL 5956 04:37:31,847 --> 04:37:33,015 DISEASE AND IF YOU DON'T KNOW 5957 04:37:33,015 --> 04:37:35,217 THAT CHILDREN'S BOOK, IT'S A 5958 04:37:35,217 --> 04:37:35,985 GOOD ONE. 5959 04:37:35,985 --> 04:37:37,386 SO SICKLE PAIN IS ASSOCIATED 5960 04:37:37,386 --> 04:37:39,021 WITH MENSTRUATION, AND THIS IS 5961 04:37:39,021 --> 04:37:40,422 REALLY NICE WORK FROM MY 5962 04:37:40,422 --> 04:37:45,094 COLLEAGUE AND FRIEND DR. DEEVA 5963 04:37:45,094 --> 04:37:45,661 SHARMA. 5964 04:37:45,661 --> 04:37:48,497 HI, DEEVA, WE MISS YOU. 5965 04:37:48,497 --> 04:37:50,399 SHE IDENTIFIED IN A COHORT OF 5966 04:37:50,399 --> 04:37:51,867 WOMEN DOWN IN TENNESSEE THAT 5967 04:37:51,867 --> 04:37:53,102 THEY EXPLAINED THEIR EXPERIENCE 5968 04:37:53,102 --> 04:37:56,005 OF PAIN WITH MENSTRUATION EITHER 5969 04:37:56,005 --> 04:37:59,809 AS EXPERIENCING PERIOD PAIN 5970 04:37:59,809 --> 04:38:03,479 ONLY, 14% VASO-OCCLUSIVE SICKLE 5971 04:38:03,479 --> 04:38:04,947 PAIN AND 30% EXPERIENCE NEITHER. 5972 04:38:04,947 --> 04:38:06,282 TALKING TO WOMEN ABOUT THEIR 5973 04:38:06,282 --> 04:38:07,449 MENSTRUATION PAIN VERSUS THEIR 5974 04:38:07,449 --> 04:38:08,584 SICKLE PAIN IS ONE. 5975 04:38:08,584 --> 04:38:09,485 MOST FASCINATING THINGS THAT YOU 5976 04:38:09,485 --> 04:38:10,419 CAN DO IN THE CLINIC BECAUSE 5977 04:38:10,419 --> 04:38:11,487 IT'S LIKE ONE OF THESE PLACES 5978 04:38:11,487 --> 04:38:13,088 WHERE YOU HAVE THIS INSIGHT 5979 04:38:13,088 --> 04:38:14,690 ABOUT HOW SICKLE PAIN IS LIKE 5980 04:38:14,690 --> 04:38:16,392 JUST THIS CLEARLY DISTINCT 5981 04:38:16,392 --> 04:38:18,460 ENTITY FROM OTHER KINDS OF PAIN. 5982 04:38:18,460 --> 04:38:22,498 IN ANY CASE, WE KNOW THAT 5983 04:38:22,498 --> 04:38:23,599 THROMBOSIS RISK IN SICKLE CELL 5984 04:38:23,599 --> 04:38:26,402 IS AKIN TO OTHER HIGH RISK 5985 04:38:26,402 --> 04:38:27,570 THROMBOPHILIAS, AND WE KNOW THAT 5986 04:38:27,570 --> 04:38:29,238 IT'S PLAUSIBLE THAT 5987 04:38:29,238 --> 04:38:31,774 CONTRACEPTION COULD BE USED TO 5988 04:38:31,774 --> 04:38:32,908 AFFECT PAIN WITH PERIODS. 5989 04:38:32,908 --> 04:38:34,910 SO I JUST WANTED TO STRESS THAT 5990 04:38:34,910 --> 04:38:36,545 PROGESTIN ONLY CONTRACEPTION IS 5991 04:38:36,545 --> 04:38:37,146 FIRST LINE FOR SICKLE CELL 5992 04:38:37,146 --> 04:38:38,180 DISEASE AND I'LL TALK ABOUT THAT 5993 04:38:38,180 --> 04:38:40,416 IN A MOMENT. 5994 04:38:40,416 --> 04:38:41,817 THE OTHER THING THAT ISN'T WELL 5995 04:38:41,817 --> 04:38:42,852 ADDRESSED BY THE LITERATURE BUT 5996 04:38:42,852 --> 04:38:44,353 WE START TO SEE HINTS OF IT THAT 5997 04:38:44,353 --> 04:38:45,754 IT MIGHT BE EFFECTIVE IS IT'S 5998 04:38:45,754 --> 04:38:47,723 NEVER BEEN STUDIED WHETHER 5999 04:38:47,723 --> 04:38:48,958 COMBINATION THERAPY WITH 6000 04:38:48,958 --> 04:38:50,793 HYDROXYUREA AND CONTRASEPTION 6001 04:38:50,793 --> 04:38:51,994 MIGHT BE AN EFFECTIVE WAY TO 6002 04:38:51,994 --> 04:38:53,562 ADDRESS WOMEN WHO ARE REALLY 6003 04:38:53,562 --> 04:38:56,098 PROFOUNDLY AFFECTED BY MENSTRUAL 6004 04:38:56,098 --> 04:38:56,999 PAIN AND SICKLE CELL PAIN, AND 6005 04:38:56,999 --> 04:38:59,134 I'D REALLY LIKE TO ANSWER THAT 6006 04:38:59,134 --> 04:39:04,039 QUESTION SOMETIME IN THE FUTURE. 6007 04:39:04,039 --> 04:39:05,741 SO SHOULD WE BE THINKING OF THIS 6008 04:39:05,741 --> 04:39:07,076 AND DESCRIBING IT AS COMBINATION 6009 04:39:07,076 --> 04:39:07,877 THERAPY FOR OUR PATIENTS. 6010 04:39:07,877 --> 04:39:09,478 I'M NOT TRYING TO MAKE YOU GO 6011 04:39:09,478 --> 04:39:11,113 BLIND HERE, BUT RECENTLY WE WERE 6012 04:39:11,113 --> 04:39:13,315 AT THE CDC TALKING ABOUT THE 6013 04:39:13,315 --> 04:39:14,884 MEDICAL ELIGIBILITY CRITERIA FOR 6014 04:39:14,884 --> 04:39:15,718 CONTRACEPTION AND I JUST WANTED 6015 04:39:15,718 --> 04:39:18,287 TO WALK YOU THROUGH SOME OF THE 6016 04:39:18,287 --> 04:39:19,822 EVOLVING THINKING ABOUT 6017 04:39:19,822 --> 04:39:21,123 CONTRACEPTIVE USE FOR GIRLS AND 6018 04:39:21,123 --> 04:39:21,991 WOMEN WITH SICKLE CELL DISEASE. 6019 04:39:21,991 --> 04:39:23,492 SO JUST TO WALK YOU THROUGH THE 6020 04:39:23,492 --> 04:39:25,594 MEDICAL ELIGIBILITY CRITERIA FOR 6021 04:39:25,594 --> 04:39:26,896 CONTRACEPTION WHICH ARE THE CDC 6022 04:39:26,896 --> 04:39:30,099 GUIDELINES THAT BROADLY INFORM 6023 04:39:30,099 --> 04:39:31,066 CONTRACEPTION PRESCRIBING ACROSS 6024 04:39:31,066 --> 04:39:32,601 THE UNITED STATES, YOU CAN SEE 6025 04:39:32,601 --> 04:39:33,669 THERE'S A CONDITION, 6026 04:39:33,669 --> 04:39:34,570 SUBCONDITION AND THEN A NUMBER 6027 04:39:34,570 --> 04:39:36,205 OF DIFFERENT CONTRACEPTIVE 6028 04:39:36,205 --> 04:39:39,008 METHODS, COPPER IUD, HORMONAL 6029 04:39:39,008 --> 04:39:41,277 IUD, IMPLANT, DEPO, 6030 04:39:41,277 --> 04:39:42,044 PROGESTIN-ONLY PILLS AND THEN 6031 04:39:42,044 --> 04:39:43,312 THE COMBINED HORMONAL 6032 04:39:43,312 --> 04:39:44,747 CONTRACEPTION WHICH ARE 6033 04:39:44,747 --> 04:39:46,482 ESTROGEN-CONTAINING PILLS. 6034 04:39:46,482 --> 04:39:47,716 AND THERE'S A NUMBER OF 6035 04:39:47,716 --> 04:39:49,018 DIFFERENT OBSERVATIONS TO MAKE 6036 04:39:49,018 --> 04:39:50,252 HERE, BUT LET'S JUST FIND SICKLE 6037 04:39:50,252 --> 04:39:50,452 CELL. 6038 04:39:50,452 --> 04:39:52,154 IT'S A LITTLE HARD TO DO, ISN'T 6039 04:39:52,154 --> 04:39:52,721 IT? 6040 04:39:52,721 --> 04:39:55,491 IN THESE 2016 GUIDELINES, ALL 6041 04:39:55,491 --> 04:39:57,860 THE FORMS OF CONTRACEPTION WERE 6042 04:39:57,860 --> 04:39:59,028 GREEN LIGHTED FOR SICKLE CELL 6043 04:39:59,028 --> 04:39:59,428 DISEASE. 6044 04:39:59,428 --> 04:40:01,463 AND YET, PEOPLE WITH KNOWN 6045 04:40:01,463 --> 04:40:03,432 THROMBOGENIC MUTATIONS, WHICH 6046 04:40:03,432 --> 04:40:04,867 PEOPLE WITH SICKLE CELL DISEASE 6047 04:40:04,867 --> 04:40:09,438 BY VIRTU VIRTUE OF THEIR THROMBS 6048 04:40:09,438 --> 04:40:13,475 RISK, IT'S EQUIVALENT TO HT3 FOR 6049 04:40:13,475 --> 04:40:13,709 EXAMPLE. 6050 04:40:13,709 --> 04:40:14,977 IT WAS SUGGESTED THEY NOT 6051 04:40:14,977 --> 04:40:16,245 RECEIVE COMBINED HORMONAL 6052 04:40:16,245 --> 04:40:16,812 CONTRACEPTION. 6053 04:40:16,812 --> 04:40:17,646 I THINK THIS GETS EVEN MORE 6054 04:40:17,646 --> 04:40:18,981 INTERESTING AS YOU LOOK AT SOME 6055 04:40:18,981 --> 04:40:22,451 OF THESE OTHER CONDITIONS WHERE 6056 04:40:22,451 --> 04:40:23,786 CONTRACEPTION USE WAS SOMEHOW 6057 04:40:23,786 --> 04:40:24,753 RESTRICTED AND IDENTIFY THAT 6058 04:40:24,753 --> 04:40:26,422 MANY OF THESE THINGS HAPPEN TO 6059 04:40:26,422 --> 04:40:27,256 PEOPLE WITH SICKLE CELL DISEASE 6060 04:40:27,256 --> 04:40:29,892 AND YET THE GUIDELINE DOES NOT 6061 04:40:29,892 --> 04:40:31,427 CAPTURE ANY OF THIS NUANCE FOR 6062 04:40:31,427 --> 04:40:33,829 OUR PATIENT POPULATION, SO FOR 6063 04:40:33,829 --> 04:40:37,900 EXAMPLE, GALLBLADDER DISEASE, 6064 04:40:37,900 --> 04:40:40,402 NEAR UNIVERSAL FACTOR CHANGES 6065 04:40:40,402 --> 04:40:45,240 WHETHER YOU SHOULD BE PRESCRIBED 6066 04:40:45,240 --> 04:40:47,876 HORMONAL CONTRACEPTION. 6067 04:40:47,876 --> 04:40:49,912 ALL OF THESE ALSO HAVE A 6068 04:40:49,912 --> 04:40:50,846 RELATIVE CONTRAINDICATION TO 6069 04:40:50,846 --> 04:40:53,015 COMBINED HORMONAL CONTRACEPTION. 6070 04:40:53,015 --> 04:40:55,517 AND SO I WORRY THAT THE EXISTING 6071 04:40:55,517 --> 04:40:58,687 GUIDELINE DOES NOT HELP US THINK 6072 04:40:58,687 --> 04:41:02,491 WELL AND ESPECIALLY HELP PEOPLE 6073 04:41:02,491 --> 04:41:03,325 WITH SICKLE CELL DISEASE THINK 6074 04:41:03,325 --> 04:41:03,926 WELL ABOUT ALL THE DIFFERENT 6075 04:41:03,926 --> 04:41:05,327 KINDS OF COMPLICATIONS THAT 6076 04:41:05,327 --> 04:41:06,662 AFFECT OUR PATIENTS WE NEED TO 6077 04:41:06,662 --> 04:41:07,863 SCREEN FOR BEFORE WE PRESCRIBE 6078 04:41:07,863 --> 04:41:10,232 THEM CONTRACEPTION. 6079 04:41:10,232 --> 04:41:11,166 THERE'S ONE OTHER POINT I WANTED 6080 04:41:11,166 --> 04:41:12,501 TO MAKE ABOUT THIS GUIDELINE, 6081 04:41:12,501 --> 04:41:13,335 BECAUSE I THINK IT'S IMPORTANT 6082 04:41:13,335 --> 04:41:15,838 TO LEARN HOW TO READ WHAT BIG 6083 04:41:15,838 --> 04:41:16,939 POWERFUL INSTITUTIONS ARE DOING 6084 04:41:16,939 --> 04:41:19,108 WITH AND FOR SICKLE CELL DISEASE 6085 04:41:19,108 --> 04:41:19,975 WITH A KEEN EYE. 6086 04:41:19,975 --> 04:41:21,210 ONE OF THE THINGS THAT THIS 6087 04:41:21,210 --> 04:41:23,379 GUIDELINE DID IS IT BAKED 6088 04:41:23,379 --> 04:41:24,747 STRUCTURAL INEQUALITY INTO THE 6089 04:41:24,747 --> 04:41:25,914 CARE OF OUR PATIENTS. 6090 04:41:25,914 --> 04:41:27,716 AND THIS IS WHY WE NEED A SEAT 6091 04:41:27,716 --> 04:41:29,518 AT THE TABLE WHEN THE CDC MAKES 6092 04:41:29,518 --> 04:41:30,285 GUIDELINES LIKE THIS. 6093 04:41:30,285 --> 04:41:32,721 SO I'LL JUST POINT OUT, OUR 6094 04:41:32,721 --> 04:41:34,990 FRIEND CYSTIC FIBROSIS SOMEHOW 6095 04:41:34,990 --> 04:41:36,825 GOT MARKED AS A CONDITION AS 6096 04:41:36,825 --> 04:41:38,160 OPPOSED TO A SUBCONDITION, AND 6097 04:41:38,160 --> 04:41:41,597 WHAT YOU CAN SEE ON THIS LIST IS 6098 04:41:41,597 --> 04:41:43,198 THAT EVERYTHING THAT WAS LISTED 6099 04:41:43,198 --> 04:41:45,167 AS A CONDITION GETS NUANCE, IT 6100 04:41:45,167 --> 04:41:46,368 GETS POTENTIAL SUBCONDITIONS. 6101 04:41:46,368 --> 04:41:47,136 BUT SICKLE CELL DISEASE WAS 6102 04:41:47,136 --> 04:41:48,537 LISTED AS A SUBCONDITION, SO 6103 04:41:48,537 --> 04:41:50,606 IT'S IMPOSSIBLE TO BAKE IN 6104 04:41:50,606 --> 04:41:52,174 NUANCE INTO HOW WE CARE FOR 6105 04:41:52,174 --> 04:41:53,609 THESE PATIENTS INTO THE WAY THIS 6106 04:41:53,609 --> 04:41:56,512 GUIDELINE WAS WRITTEN. 6107 04:41:56,512 --> 04:41:59,348 AND SO IS IT THE BE ALL END ALL 6108 04:41:59,348 --> 04:42:00,249 HERE? 6109 04:42:00,249 --> 04:42:02,084 MAYBE NOT, BUT I THINK IT'S AN 6110 04:42:02,084 --> 04:42:03,419 IMPORTANT THING TO THINK ABOUT, 6111 04:42:03,419 --> 04:42:05,187 WHERE IS SICKLE CELL, WHY IS IT 6112 04:42:05,187 --> 04:42:06,655 BEING PUT IN A SUBCONDITION WHEN 6113 04:42:06,655 --> 04:42:08,223 SOME OF THESE OTHER DISEASES ARE 6114 04:42:08,223 --> 04:42:09,058 BEING PUT IN CONDITIONS. 6115 04:42:09,058 --> 04:42:11,393 THIS WAS A CRITIQUE THAT THE CDC 6116 04:42:11,393 --> 04:42:13,128 WAS OPEN TO, TO THEIR CREDIT. 6117 04:42:13,128 --> 04:42:14,563 SO COMING IN THE SPRING OF 2024, 6118 04:42:14,563 --> 04:42:16,365 YOU CAN EXPECT UPDATED GUIDANCE 6119 04:42:16,365 --> 04:42:17,299 ON SICKLE CELL DISEASE AND 6120 04:42:17,299 --> 04:42:18,233 HORMONAL CONTRACEPTION, AND 6121 04:42:18,233 --> 04:42:19,701 BECAUSE OF THE RECOGNIZED 6122 04:42:19,701 --> 04:42:21,003 THROMBOSIS RISKS ASSOCIATED WITH 6123 04:42:21,003 --> 04:42:22,538 THIS DISEASE, YOU CAN EXPECT 6124 04:42:22,538 --> 04:42:24,206 THAT THERE WILL BE MORE 6125 04:42:24,206 --> 04:42:25,507 RESTRICTIVE RECOMMENDATIONS FOR 6126 04:42:25,507 --> 04:42:26,942 COMBINED HORMONAL CONTRACEPTION 6127 04:42:26,942 --> 04:42:29,044 FOR THIS PATIENT POPULATION. 6128 04:42:29,044 --> 04:42:30,579 I DO NOT KNOW HOW THEY ARE GOING 6129 04:42:30,579 --> 04:42:31,880 TO RULE ON DEPO. 6130 04:42:31,880 --> 04:42:33,248 I THINK THIS IS A REALLY 6131 04:42:33,248 --> 04:42:33,649 CHALLENGING POINT. 6132 04:42:33,649 --> 04:42:34,917 THEY ARE MOVING TOWARDS 6133 04:42:34,917 --> 04:42:36,952 RESTRICTING DEPO ACCESS FOR 6134 04:42:36,952 --> 04:42:39,455 OTHER GROUPS OF HIGH RISK 6135 04:42:39,455 --> 04:42:40,389 THROMBOPHILIAS, AND YOU KNOW, WE 6136 04:42:40,389 --> 04:42:43,425 HAVE THIS ANCIENT DATA THAT DEPO 6137 04:42:43,425 --> 04:42:44,960 REDUCES PAIN IN WOMEN WITH 6138 04:42:44,960 --> 04:42:46,728 SICKLE CELL DISEASE AND SO WE 6139 04:42:46,728 --> 04:42:48,330 REALLY LIKE DEPO FOR THAT 6140 04:42:48,330 --> 04:42:48,797 REASON. 6141 04:42:48,797 --> 04:42:51,100 BUT ACTUALLY THE DATA PREDATES 6142 04:42:51,100 --> 04:42:52,835 HYDROXYUREA USE, SO I THINK WE 6143 04:42:52,835 --> 04:42:54,603 SHOULD REALLY NOT BE THINKING -- 6144 04:42:54,603 --> 04:42:56,105 HANGING OUR HATS ON THAT DATA. 6145 04:42:56,105 --> 04:42:59,074 IN ANY CASE, PEOPLE LIKE ANDREA 6146 04:42:59,074 --> 04:43:05,247 ROWE AND ANDREA SPARKENBOUGH ARE 6147 04:43:05,247 --> 04:43:06,315 INTERESTED, SARAH O'BRIEN, AND 6148 04:43:06,315 --> 04:43:07,649 WE SHOULD REALLY BE WATCHING 6149 04:43:07,649 --> 04:43:09,384 THEM AND CHEERING THEM ON AS 6150 04:43:09,384 --> 04:43:10,385 THEY TRY TO HELP US FIGURE OUT 6151 04:43:10,385 --> 04:43:13,522 SOME OF THESE PUZZLES RELATED TO 6152 04:43:13,522 --> 04:43:15,424 CONTRACEPTION AND THROMBOSIS 6153 04:43:15,424 --> 04:43:18,127 BECAUSE WHILE IT'S NICE TO 6154 04:43:18,127 --> 04:43:19,461 STRATIFY FOR OTHER POPULATIONS 6155 04:43:19,461 --> 04:43:21,730 IDEALLY WE WOULD HAVE SPECIFIC 6156 04:43:21,730 --> 04:43:23,932 DATA FOR RISK AND HIGHLY 6157 04:43:23,932 --> 04:43:24,500 INDIVIDUALIZED CARE. 6158 04:43:24,500 --> 04:43:26,935 THIS IS A FANTASTIC STUDY FROM 6159 04:43:26,935 --> 04:43:28,170 NIGERIA THAT INVOLVED HUNDREDS 6160 04:43:28,170 --> 04:43:29,905 OF PEOPLE WITH SICKLE CELL 6161 04:43:29,905 --> 04:43:30,806 DISEASE, WOMEN WITH SICKLE CELL 6162 04:43:30,806 --> 04:43:32,508 DISEASE WHO ARE MARRIED AND A 6163 04:43:32,508 --> 04:43:34,443 COUPLE HUNDRED CONTROLS, AND IT 6164 04:43:34,443 --> 04:43:38,180 JUST HIGHLIGHTED WHAT THE GROUP 6165 04:43:38,180 --> 04:43:39,214 AT MOUNT SINAI IN NEW YORK HAD 6166 04:43:39,214 --> 04:43:40,115 ALREADY IDENTIFIED, WHICH IS 6167 04:43:40,115 --> 04:43:41,316 THAT WOMEN WITH SICKLE CELL 6168 04:43:41,316 --> 04:43:44,920 DISEASE ARE AT INCREASED RISK 6169 04:43:44,920 --> 04:43:49,758 FOR DISPARUNIA, ASSOCIATED WITH 6170 04:43:49,758 --> 04:43:50,492 CHRONIC PAIN. 6171 04:43:50,492 --> 04:43:53,862 IT'S NOT SOMETHING WE TALK ABOUT 6172 04:43:53,862 --> 04:43:55,097 BUT CERTAINLY A QUALITY OF LIFE 6173 04:43:55,097 --> 04:43:55,330 ISSUE. 6174 04:43:55,330 --> 04:43:58,534 AND I HOPE YOU CAN SEE IN THIS 6175 04:43:58,534 --> 04:44:01,436 GRAPH FROM NIGERIAN MARRIED 6176 04:44:01,436 --> 04:44:02,905 WOMEN THAT THE SEXUAL 6177 04:44:02,905 --> 04:44:03,805 SATISFACTION AND MARITAL 6178 04:44:03,805 --> 04:44:04,606 SATISFACTION SCORES ARE JUST 6179 04:44:04,606 --> 04:44:06,808 ABOUT HALF OF THOSE TO 6180 04:44:06,808 --> 04:44:07,442 UNAFFECTED WOMEN. 6181 04:44:07,442 --> 04:44:08,644 HOW DOES IT COMPARE TO PEOPLE 6182 04:44:08,644 --> 04:44:09,778 WITH OTHER COMPLEX CHRONIC 6183 04:44:09,778 --> 04:44:14,049 CONDITIONS? I DON'T KNOW. 6184 04:44:14,049 --> 04:44:15,751 BUT IT CAN BE INTRINSICALLY 6185 04:44:15,751 --> 04:44:16,785 VALUABLE TO US AS WE TAKE CARE 6186 04:44:16,785 --> 04:44:18,954 OF OUR PATIENTS. 6187 04:44:18,954 --> 04:44:19,922 OKAY. 6188 04:44:19,922 --> 04:44:22,124 SO SHE TOOK SOME HORMONAL 6189 04:44:22,124 --> 04:44:23,759 CONTRACEPTION, COMBINED HORMONAL 6190 04:44:23,759 --> 04:44:24,526 CONTRACEPTION WITHOUT EVENT. 6191 04:44:24,526 --> 04:44:27,996 SHE TOOK HER HYDROXYUREA REALLY 6192 04:44:27,996 --> 04:44:29,364 WELL. 6193 04:44:29,364 --> 04:44:31,033 SHE GOT MARRIED AND SHE ACTUALLY 6194 04:44:31,033 --> 04:44:33,635 DIDN'T HAVE MANY COMPLICATIONS 6195 04:44:33,635 --> 04:44:38,774 IN LATE ADD LE SEN LENS, SHE HAA 6196 04:44:38,774 --> 04:44:40,375 LITTLE BIT OF AVN FOR WHICH SHE 6197 04:44:40,375 --> 04:44:41,977 TAKES A LITTLE BIT OF TYLENOL 6198 04:44:41,977 --> 04:44:43,645 AND NSAIDS. 6199 04:44:43,645 --> 04:44:45,247 IN ANY CASE, SHE TOLD ME SHE 6200 04:44:45,247 --> 04:44:46,181 WANTS TO GET PREGNANT. 6201 04:44:46,181 --> 04:44:47,316 SO LET'S WALK THROUGH WHAT WE 6202 04:44:47,316 --> 04:44:48,317 THINKING ABOUT, THE WHEELS THAT 6203 04:44:48,317 --> 04:44:49,651 START TURNING WHEN YOU'RE 6204 04:44:49,651 --> 04:44:50,319 PROVIDING PRECONCEPTION CARE TO 6205 04:44:50,319 --> 04:44:55,457 WOMEN WITH SICKLE CELL DISEASE. 6206 04:44:55,457 --> 04:44:56,959 THERE'S A LOT OF PIECES, ONLY TO 6207 04:44:56,959 --> 04:44:58,227 SAY WE NEED TO THINK ABOUT 6208 04:44:58,227 --> 04:45:01,964 PARTNER TESTING, GENETIC 6209 04:45:01,964 --> 04:45:02,898 COUNSELING, WHAT DISEASE 6210 04:45:02,898 --> 04:45:04,132 MODIFYING THERAPIES WE'RE USING, 6211 04:45:04,132 --> 04:45:05,434 WHAT OTHER MEDICATIONS NEED TO 6212 04:45:05,434 --> 04:45:09,805 BE STARTED AND STOPPED. 6213 04:45:09,805 --> 04:45:11,073 INCREASINGLY I TALK TO WOMEN 6214 04:45:11,073 --> 04:45:13,108 ABOUT FERTILITY AND INFERTILITY 6215 04:45:13,108 --> 04:45:15,143 MOSTLY BECAUSE THEY'RE ALREADY 6216 04:45:15,143 --> 04:45:16,111 WORRIED ABOUT IT SO IF I DON'T 6217 04:45:16,111 --> 04:45:17,779 BRING IT UP THEY'RE ANXIOUS. 6218 04:45:17,779 --> 04:45:20,048 HOW DO WE KNOW IF YOU'RE FERTILE 6219 04:45:20,048 --> 04:45:21,717 OR INFERTILE? 6220 04:45:21,717 --> 04:45:23,986 WE KNOW YOUR INFERTILE FOR 6221 04:45:23,986 --> 04:45:25,954 TRYING FOR 6 OR 12 MONTHS, 6222 04:45:25,954 --> 04:45:26,622 DEPENDING ON HOW OLD YOU ARE. 6223 04:45:26,622 --> 04:45:28,223 SO WE START TO TALK ABOUT THESE 6224 04:45:28,223 --> 04:45:30,125 THINGS AS PEOPLE START TO PURSUE 6225 04:45:30,125 --> 04:45:31,593 PREGNANCY. 6226 04:45:31,593 --> 04:45:35,063 THIS PATIENT DIDN'T HAVE -- I 6227 04:45:35,063 --> 04:45:36,265 THINK IT'S IMPORTANT WE 6228 04:45:36,265 --> 04:45:37,032 ACKNOWLEDGE THE EXISTENCE OF 6229 04:45:37,032 --> 04:45:38,100 THIS 20-YEAR-OLD TECHNOLOGY AND 6230 04:45:38,100 --> 04:45:39,768 START TO THINK WITH WHAT DATA WE 6231 04:45:39,768 --> 04:45:41,903 HAVE TO INFORMITY USE. 6232 04:45:41,903 --> 04:45:43,572 WE KNOW THAT HAVING A CHILD WITH 6233 04:45:43,572 --> 04:45:45,340 SICKLE CELL DISEASE ALTERS THE 6234 04:45:45,340 --> 04:45:46,975 REPRODUCTIVE LIFE PLANS OF 6235 04:45:46,975 --> 04:45:48,644 PARENTS WHO HAVE THESE CHILDREN, 6236 04:45:48,644 --> 04:45:51,913 AND WE ALSO KNOW FROM STUDIES 6237 04:45:51,913 --> 04:45:53,982 FROM CHOP AND CHILDREN'S 6238 04:45:53,982 --> 04:45:55,117 NATIONAL AND HOPKINS THAT 6239 04:45:55,117 --> 04:45:56,585 PARENTS AND YOUNG ADULTS WITH 6240 04:45:56,585 --> 04:45:57,486 SICKLE CELL DISEASE ARE 6241 04:45:57,486 --> 04:45:58,353 INTERESTED IN LEARNING ABOUT 6242 04:45:58,353 --> 04:46:00,122 THIS TECHNOLOGY EVEN IF THEY 6243 04:46:00,122 --> 04:46:01,757 WOULD NOT CHOOSE IT FOR 6244 04:46:01,757 --> 04:46:03,759 THEMSELVES. 6245 04:46:03,759 --> 04:46:05,360 SO IT HIGHLIGHTS HOW COUNSELING 6246 04:46:05,360 --> 04:46:07,529 ABOUT TECHNOLOGIES, CURATIVE 6247 04:46:07,529 --> 04:46:08,297 THERAPIES, IN VITRO 6248 04:46:08,297 --> 04:46:09,197 FERTILIZATION, BECOMES A MARKER 6249 04:46:09,197 --> 04:46:11,266 OF QUALITY OF CARE AND ALSO 6250 04:46:11,266 --> 04:46:14,303 EQUAL QUALITY CARE. 6251 04:46:14,303 --> 04:46:16,471 IVF IS A HIGHLY SUCCESSFUL 6252 04:46:16,471 --> 04:46:19,474 TECHNOLOGY AND TH THE DATA FROME 6253 04:46:19,474 --> 04:46:21,576 UNITED KINGDOM IS IN 60 COUPLES, 6254 04:46:21,576 --> 04:46:23,278 I ALAS THIS IS THE BEST AMASSED 6255 04:46:23,278 --> 04:46:24,212 DATA WE HAVE ON THIS SUBJECT. 6256 04:46:24,212 --> 04:46:25,747 IT'S A TRICKY THING TO STUDY 6257 04:46:25,747 --> 04:46:27,282 BECAUSE THIS ISN'T A POPULATION 6258 04:46:27,282 --> 04:46:28,250 THAT HAS INFERTILITY. 6259 04:46:28,250 --> 04:46:29,251 THEY HAVE ANOTHER INDICATION FOR 6260 04:46:29,251 --> 04:46:32,120 THE USE OF IVF WITH THERAPIES. 6261 04:46:32,120 --> 04:46:33,422 IN ANY CASE, THE BRITISH WHO 6262 04:46:33,422 --> 04:46:35,490 PROVIDE COVERAGE OF IVF WITH PGT 6263 04:46:35,490 --> 04:46:39,027 WITH AN INDICATION TO AVOID 6264 04:46:39,027 --> 04:46:41,463 IMPLANTING AN EMBRYO AFFECTED BY 6265 04:46:41,463 --> 04:46:42,497 SICKLE CELL DISEASE REPORTED 6266 04:46:42,497 --> 04:46:43,999 OUTCOMES IN 60 COUPLES WITH 6267 04:46:43,999 --> 04:46:45,400 SICKLE TRAIT OR DISEASE 6268 04:46:45,400 --> 04:46:46,301 INCLUDING THREE WOMEN IN THEIR 6269 04:46:46,301 --> 04:46:47,669 EARLY 30s WITH SICKLE CELL 6270 04:46:47,669 --> 04:46:49,404 DISEASE WHO ALL CONCEIVED. 6271 04:46:49,404 --> 04:46:52,708 THEY REPORT A 63% TAKE-HOME BABY 6272 04:46:52,708 --> 04:46:53,241 RATE. 6273 04:46:53,241 --> 04:46:56,611 DOCTOR SAYING THAT IS LIKE THE 6274 04:46:56,611 --> 04:46:57,846 CUTEST BRITISH EUCH NISM I'VE 6275 04:46:57,846 --> 04:46:59,648 EVER HEARD, THE TAKE-HOME BABY 6276 04:46:59,648 --> 04:46:59,881 RATE. 6277 04:46:59,881 --> 04:47:03,585 IN ANY CASE THEY REPORT A 63% 6278 04:47:03,585 --> 04:47:04,353 TAKE-HOME BABY RATE. 6279 04:47:04,353 --> 04:47:06,221 I THINK WHAT'S SO INTRIGUING IS 6280 04:47:06,221 --> 04:47:08,523 IT'S NOT 63% BECAUSE THAT'S LIKE 6281 04:47:08,523 --> 04:47:09,991 THE BEST THEY COULD DO. 6282 04:47:09,991 --> 04:47:11,626 IT'S 63% BECAUSE PEOPLE DROPPED 6283 04:47:11,626 --> 04:47:12,361 OUT. 6284 04:47:12,361 --> 04:47:13,895 PEOPLE DROP OUT OF DOING IVF 6285 04:47:13,895 --> 04:47:15,630 BECAUSE IT'S UNBELIEVABLY 6286 04:47:15,630 --> 04:47:16,965 UNCERTAIN, IT'S UNBELIEVABLY 6287 04:47:16,965 --> 04:47:18,867 TAXING AND IT'S UNBELIEVABLY 6288 04:47:18,867 --> 04:47:20,235 STRESSFUL ON RELATIONSHIPS. 6289 04:47:20,235 --> 04:47:22,537 AND SO IF YOU HAVE FAMILIES OR 6290 04:47:22,537 --> 04:47:23,905 FRIENDS OR LOVED ONES WHO ARE 6291 04:47:23,905 --> 04:47:25,307 GOING THROUGH THIS EXPERIENCE, 6292 04:47:25,307 --> 04:47:27,242 YOU SHOULD KNOW THAT THE 6293 04:47:27,242 --> 04:47:28,777 UNCERTAINTY ASSOCIATED WITH THIS 6294 04:47:28,777 --> 04:47:30,846 PROCESS IS FANTASTIC, AND IT IS 6295 04:47:30,846 --> 04:47:32,047 REALLY HARD ON PEOPLE. 6296 04:47:32,047 --> 04:47:33,682 AND I THINK THAT THAT IS ALSO 6297 04:47:33,682 --> 04:47:34,750 RELEVANT WHEN WE START THINKING 6298 04:47:34,750 --> 04:47:36,118 ABOUT WHAT WE ARE DOING WITH 6299 04:47:36,118 --> 04:47:37,686 FERTILITY PRESERVATION FOR OUR 6300 04:47:37,686 --> 04:47:39,287 PATIENTS, AND SO THERE'S SOME 6301 04:47:39,287 --> 04:47:41,590 RUNNING TOGETHER OF THOSE IDEAS. 6302 04:47:41,590 --> 04:47:43,458 IN ANY CASE, THIS EXISTS. 6303 04:47:43,458 --> 04:47:44,593 AND WHAT WE LEARNED IS WE 6304 04:47:44,593 --> 04:47:46,161 STARTED TALKING ABOUT THIS AT 6305 04:47:46,161 --> 04:47:47,562 HOPKINS, WAS THAT THERE WAS NOT 6306 04:47:47,562 --> 04:47:49,498 ONE TOOL FOR PEOPLE AFFECTED BY 6307 04:47:49,498 --> 04:47:51,299 SICKLE CELL DISEASE OR TRAIT TO 6308 04:47:51,299 --> 04:47:53,769 DESCRIBE WHAT IVF WITH PGT WAS 6309 04:47:53,769 --> 04:47:55,670 THAT WAS DISEASE-SPECIFIC. 6310 04:47:55,670 --> 04:47:57,205 AND THAT EXISTING TOOLS WERE 6311 04:47:57,205 --> 04:47:58,607 WRITTEN AT THE 14TH TO 17TH 6312 04:47:58,607 --> 04:48:00,809 GRADE READING LEVEL. 6313 04:48:00,809 --> 04:48:02,377 NOTHING SAYS WHO A TECHNOLOGY IS 6314 04:48:02,377 --> 04:48:04,880 INTENDED FOR MORE THAN THAT, I 6315 04:48:04,880 --> 04:48:05,781 THINK. 6316 04:48:05,781 --> 04:48:07,215 IN ANY CASE, WE TRIED TO REPAIR 6317 04:48:07,215 --> 04:48:07,582 THAT PROBLEM. 6318 04:48:07,582 --> 04:48:08,683 THIS IS A FAMILY PLANNING 6319 04:48:08,683 --> 04:48:10,452 OPTIONS FOR PEOPLE WITH SICKLE 6320 04:48:10,452 --> 04:48:12,854 CELL TRAIT AND DISEASE DEVELOPED 6321 04:48:12,854 --> 04:48:14,923 AT HOPKINS AND IT MEETS U.S. 6322 04:48:14,923 --> 04:48:16,224 PATIENT EDUCATION HEALTH 6323 04:48:16,224 --> 04:48:17,959 LITERACY STANDARDS, AND IT WAS 6324 04:48:17,959 --> 04:48:19,928 DEEMED ACCEPTABLE, HOPEFUL AND 6325 04:48:19,928 --> 04:48:21,163 USEFUL BY OUR COMMUNITY PARTNERS 6326 04:48:21,163 --> 04:48:22,731 AND BY OUR PATIENTS AND IT'S 6327 04:48:22,731 --> 04:48:24,766 FREELY AVAILABLE ON THE SICKLE 6328 04:48:24,766 --> 04:48:25,567 CELL RED WEBSITE. 6329 04:48:25,567 --> 04:48:29,504 THE URL IS BELOW. 6330 04:48:29,504 --> 04:48:30,806 SO WE GIVE HER SOME INFORMATION 6331 04:48:30,806 --> 04:48:32,274 AND SHE SAYS WE MIGHT WANT TO 6332 04:48:32,274 --> 04:48:33,542 WAIT A COUPLE YEARS TO START OUR 6333 04:48:33,542 --> 04:48:34,109 FAMILY. 6334 04:48:34,109 --> 04:48:34,743 MAYBE NOT TODAY. 6335 04:48:34,743 --> 04:48:35,744 WHAT DO YOU THINK? 6336 04:48:35,744 --> 04:48:36,812 SHOULD I START TODAY? 6337 04:48:36,812 --> 04:48:38,580 I'M 28. 6338 04:48:38,580 --> 04:48:40,115 WELL, HERE'S WHAT IT'S LOOKING 6339 04:48:40,115 --> 04:48:40,916 LIKE. 6340 04:48:40,916 --> 04:48:42,184 SICKLE CELL DISEASE IS A DISEASE 6341 04:48:42,184 --> 04:48:43,485 OF ACCELERATED AGING. 6342 04:48:43,485 --> 04:48:44,219 IT MAKES SENSE THAT THIS WOULD 6343 04:48:44,219 --> 04:48:46,822 BE A DISEASE WITH A NARROW 6344 04:48:46,822 --> 04:48:47,222 FERTILE WINDOW. 6345 04:48:47,222 --> 04:48:48,890 YOU THINK ABOUT IT, MEN AR KEY 6346 04:48:48,890 --> 04:48:51,660 IS LATER AND WE SEE SOME EARLY 6347 04:48:51,660 --> 04:48:53,728 SIGNS THAT MENOPAUSE IS SOONER, 6348 04:48:53,728 --> 04:48:55,163 THAT SCRUNCHES IN YOUR 6349 04:48:55,163 --> 04:48:55,831 REPRODUCTIVE WINDOW. 6350 04:48:55,831 --> 04:48:58,433 JUST THAT ALONE BY LOGIC WOULD 6351 04:48:58,433 --> 04:49:01,937 DO IT. 6352 04:49:01,937 --> 04:49:03,638 SO THE CHALLENGE IS DO WE HAVE 6353 04:49:03,638 --> 04:49:04,473 GREAT CONTEMPORARY DATA? 6354 04:49:04,473 --> 04:49:05,240 WE DON'T. 6355 04:49:05,240 --> 04:49:07,909 BUT IN MENARCHE IN GIRLS WITH 6356 04:49:07,909 --> 04:49:08,844 SICKLE CELL DISEASE IT'S ABOUT 6357 04:49:08,844 --> 04:49:09,678 13, IN THE GENERAL POPULATION 6358 04:49:09,678 --> 04:49:12,047 IT'S CLOSER TO 11, AND 6359 04:49:12,047 --> 04:49:17,052 MENOPAUSE, THE LATE DR. SAMIR 6360 04:49:17,052 --> 04:49:18,286 BALLAS HELPED PUBLISH THE BEST 6361 04:49:18,286 --> 04:49:20,155 PAPER WE HAVE OF 15 BRAZILIAN 6362 04:49:20,155 --> 04:49:21,523 WOMEN WITH SS DISEASE AND THEIR 6363 04:49:21,523 --> 04:49:23,758 AGE AT MENOPAUSE, WHICH WAS 6364 04:49:23,758 --> 04:49:25,427 YOUNGER, 46 YEARS, AS OPPOSED TO 6365 04:49:25,427 --> 04:49:26,928 501 IN THE GENERAL BRAZILIAN 6366 04:49:26,928 --> 04:49:27,429 POPULATION. 6367 04:49:27,429 --> 04:49:29,231 IT'S IMPORTANT TO NOTE THAT THE 6368 04:49:29,231 --> 04:49:30,732 10 YEARS BEFORE MENOPAUSE ARE 6369 04:49:30,732 --> 04:49:32,634 ASSOCIATED WITH INFERTILITY 6370 04:49:32,634 --> 04:49:34,402 ONSET IN UNAFFECTED PEOPLE. 6371 04:49:34,402 --> 04:49:37,038 SO AGAIN, 46 YEARS, IF THAT'S 6372 04:49:37,038 --> 04:49:38,640 THE AGE AT ONSET OF MENOPAUSE, 6373 04:49:38,640 --> 04:49:40,308 YOU TAKE THAT BACK 10 YEARS AND 6374 04:49:40,308 --> 04:49:42,944 YOU'RE LOOKING AT AN AGE OF 6375 04:49:42,944 --> 04:49:43,812 INFERTILITY ONSET OF 35, 6376 04:49:43,812 --> 04:49:45,046 PROBABLY SOONER THAN THE GENERAL 6377 04:49:45,046 --> 04:49:46,348 POPULATION. 6378 04:49:46,348 --> 04:49:48,016 WE WERE INTERESTED IN THE 6379 04:49:48,016 --> 04:49:49,518 PROBLEM OF ANTIMA LAYERIAN 6380 04:49:49,518 --> 04:49:51,520 HORMONE, WHICH IS A MARKER OF 6381 04:49:51,520 --> 04:49:52,487 OVARIAN RESERVE THAT CAN BE 6382 04:49:52,487 --> 04:49:54,289 MEASURED ANY TIME IN THE 6383 04:49:54,289 --> 04:49:54,789 MENSTRUAL CYCLE. 6384 04:49:54,789 --> 04:49:55,891 WE WERE FORTUNATE TO RECEIVE 6385 04:49:55,891 --> 04:49:58,860 FUNDING FROM NHLBI TO HAVE A 6386 04:49:58,860 --> 04:50:01,396 LOOK AT THE SAMPLES FROM THE 6387 04:50:01,396 --> 04:50:02,564 CENTER OF HYDROXYUREA. 6388 04:50:02,564 --> 04:50:05,834 THIS INVOLVED ONLY WOMEN AND MEP 6389 04:50:05,834 --> 04:50:08,236 WITH SS DISEASE, NO BETA 6390 04:50:08,236 --> 04:50:09,237 THALASSEMIA IN THERE. 6391 04:50:09,237 --> 04:50:11,473 THERE WERE SAMPLES FROM 6392 04:50:11,473 --> 04:50:12,741 98 SUBJECTS FROM THAT STUDY. 6393 04:50:12,741 --> 04:50:13,975 UNFORTUNATELY THERE WERE ONLY 6394 04:50:13,975 --> 04:50:14,876 FOLLOW-UP SAMPLES AVAILABLE, SO 6395 04:50:14,876 --> 04:50:16,378 THERE WERE NO SAMPLES AVAILABLE 6396 04:50:16,378 --> 04:50:17,512 IN THE RANDOMIZED PART OF THE 6397 04:50:17,512 --> 04:50:18,914 STUDY TO START TO GET AT THIS 6398 04:50:18,914 --> 04:50:19,781 PROBLEM OF HYDROXYUREA IN THE 6399 04:50:19,781 --> 04:50:21,216 MOST ROBUST WAY. 6400 04:50:21,216 --> 04:50:23,251 BUT THIS IS WHAT WE FOUND, SO 6401 04:50:23,251 --> 04:50:26,121 AMH IS ON THE Y AXIS AND AH IS 6402 04:50:26,121 --> 04:50:26,922 ON THE X AXIS. 6403 04:50:26,922 --> 04:50:28,156 I HOPE THAT YOU CAN SEE THESE 6404 04:50:28,156 --> 04:50:30,525 BOXES WHICH ARE THE BOX PLOTS OF 6405 04:50:30,525 --> 04:50:32,527 THE AMHs FOR OUR STUDY 6406 04:50:32,527 --> 04:50:32,961 POPULATION. 6407 04:50:32,961 --> 04:50:36,097 THE BLACK BOXES ARE THE MH 6408 04:50:36,097 --> 04:50:37,232 LEVELS IN NORMATIVE CONTROL 6409 04:50:37,232 --> 04:50:38,099 DATA. 6410 04:50:38,099 --> 04:50:39,834 THE GREY BARS, I HOPE YOU AGREE, 6411 04:50:39,834 --> 04:50:41,903 ARE BELOW THE NORMATIVE BLACK 6412 04:50:41,903 --> 04:50:43,438 BARS, AND THEN YOU ALSO SEE THIS 6413 04:50:43,438 --> 04:50:44,973 DASHED LINE OF DIMINISHED 6414 04:50:44,973 --> 04:50:46,741 OVARIAN RESERVE, AND WOMEN WITH 6415 04:50:46,741 --> 04:50:47,342 SICKLE CELL DISEASE AT LEAST 6416 04:50:47,342 --> 04:50:49,177 SOME OF THEM ARE HAVING 6417 04:50:49,177 --> 04:50:50,445 DIMINISHED OVARIAN RESERVE AS 6418 04:50:50,445 --> 04:50:54,883 SOON AS AGE 20 OR 25. 6419 04:50:54,883 --> 04:50:56,651 AND SO WHAT ARE THE PLAUSIBLE 6420 04:50:56,651 --> 04:50:58,453 MECHANISMS OF OVARIAN INJURY IN 6421 04:50:58,453 --> 04:50:59,721 SICKLE CELL DISEASE? 6422 04:50:59,721 --> 04:51:01,256 DR. QUINN, THANK YOU FOR THIS 6423 04:51:01,256 --> 04:51:01,690 PICTURE. 6424 04:51:01,690 --> 04:51:04,192 THERE'S A COUPLE WAYS TO THINK 6425 04:51:04,192 --> 04:51:05,627 ABOUT OVARIAN INJURY IN SICKLE 6426 04:51:05,627 --> 04:51:06,628 CELL DISEASE, AND I'LL WALK YOU 6427 04:51:06,628 --> 04:51:07,395 THROUGH THIS. 6428 04:51:07,395 --> 04:51:08,496 SO SICKLE CELL DISEASE 6429 04:51:08,496 --> 04:51:10,565 PATHOPHYSIOLOGY BASICALLY 6430 04:51:10,565 --> 04:51:12,767 EVERYTHING THAT SICKLE CELL DOES 6431 04:51:12,767 --> 04:51:14,970 TO EVERY END ORGAN, OVARIES 6432 04:51:14,970 --> 04:51:16,838 DON'T LIKE THOSE THINGS EITHER, 6433 04:51:16,838 --> 04:51:18,707 SO THEY CAN BE CONCEPTUALIZED AS 6434 04:51:18,707 --> 04:51:19,641 AN END ORGAN IN SICKLE CELL 6435 04:51:19,641 --> 04:51:22,744 DISEASE AND THERE'S HEMOLYSIS, 6436 04:51:22,744 --> 04:51:27,482 ANEMIA, HYPOXIC ISCHEMIC INJURY, 6437 04:51:27,482 --> 04:51:28,450 ET CETERA. 6438 04:51:28,450 --> 04:51:29,651 WHETHER THAT LEADS TO 6439 04:51:29,651 --> 04:51:31,720 ACCELERATED DECLINE IN EGG 6440 04:51:31,720 --> 04:51:33,922 QUANTITY AND EGG QUALITY HAS NOT 6441 04:51:33,922 --> 04:51:35,557 BEEN ESTABLISHED, BUT THERE'S 6442 04:51:35,557 --> 04:51:36,424 QUESTIONS ABOUT HYDROXYUREA AND 6443 04:51:36,424 --> 04:51:37,759 CHRONIC TRANSFUSIONS. 6444 04:51:37,759 --> 04:51:39,661 THIS IS THE SUMMARY OF THE 6445 04:51:39,661 --> 04:51:42,263 EXISTING EPIDEMIOLOGY OF 6446 04:51:42,263 --> 04:51:46,301 HYDROXYUREA AND OVARIAN RESERVE, 6447 04:51:46,301 --> 04:51:47,268 POST PUBESCENT PEOPLE. 6448 04:51:47,268 --> 04:51:48,937 WE PUT TOGETHER DATA FROM 6449 04:51:48,937 --> 04:51:50,038 84 SUBJECT ACROSS THREE 6450 04:51:50,038 --> 04:51:51,072 SUBJECTS. 6451 04:51:51,072 --> 04:51:52,140 ALL HAD SICKLE CELL ANEMIA AND 6452 04:51:52,140 --> 04:51:53,541 WERE UNDER 30 YEARS OF AGE. 6453 04:51:53,541 --> 04:51:55,310 THERE WERE 27 SUBJECTS WITH 6454 04:51:55,310 --> 04:51:56,144 DIMINISHED OVARIAN RESERVE, 6455 04:51:56,144 --> 04:51:57,846 WHICH IS AN INDICATION FOR 6456 04:51:57,846 --> 04:51:59,147 FERTILITY PRESERVATION. 6457 04:51:59,147 --> 04:52:01,549 AND ONLY HYDROXYUREA-EXPOSED 6458 04:52:01,549 --> 04:52:03,018 SUBJECTS HAD DIMINISHED OVARIAN 6459 04:52:03,018 --> 04:52:04,519 RESERVE IN THIS SMALL COHORT. 6460 04:52:04,519 --> 04:52:07,422 THE NUMBER TO HARM IS 1.9 TO 6461 04:52:07,422 --> 04:52:07,722 4.8. 6462 04:52:07,722 --> 04:52:10,525 IN ONE OF OUR STUDIES THAT WE 6463 04:52:10,525 --> 04:52:13,895 DID AT HOPKINS, A HIGHER MCV WAS 6464 04:52:13,895 --> 04:52:15,497 ASSOCIATED WITH OVARIAN RESERVE. 6465 04:52:15,497 --> 04:52:16,564 IN FACT HYDROXYUREA TREATED 6466 04:52:16,564 --> 04:52:18,133 PATIENTS WHO DID NOT HAVE AN 6467 04:52:18,133 --> 04:52:20,301 ELEVATED MCV IS NOT HAVE 6468 04:52:20,301 --> 04:52:20,969 DIMINISHED OVARIAN RESERVE. 6469 04:52:20,969 --> 04:52:23,104 WE ALSO SEE SIGNS THAT MENOPAUSE 6470 04:52:23,104 --> 04:52:24,939 MAY OCCUR EARLIER IN PEOPLE 6471 04:52:24,939 --> 04:52:25,840 TREATED WITH HYDROXYUREA. 6472 04:52:25,840 --> 04:52:27,242 AGAIN VERY SMALL STUDY, AND AS 6473 04:52:27,242 --> 04:52:28,677 IS THE CASE IN ALL OF THESE 6474 04:52:28,677 --> 04:52:29,878 STUDIES, NOT YET POSSIBLE TO 6475 04:52:29,878 --> 04:52:31,212 TEASE OUT THE COMPLICATION OF 6476 04:52:31,212 --> 04:52:34,282 WHETHER THIS IS DISEASE SEVERITY 6477 04:52:34,282 --> 04:52:35,717 OR DRUG, ASSOCIATION NOT 6478 04:52:35,717 --> 04:52:38,987 CAUSATION STUDIES. 6479 04:52:38,987 --> 04:52:41,489 THANKS AGAIN, DR. QUINN. 6480 04:52:41,489 --> 04:52:43,058 SO WE ADOPTED DR. QUINN'S 6481 04:52:43,058 --> 04:52:48,263 EDITORIAL INTO A HASHTAG, AND 6482 04:52:48,263 --> 04:52:49,330 THE CENTRAL PREMISE ARGUMENT 6483 04:52:49,330 --> 04:52:51,299 THAT WE MADE USING OUR DATA WAS 6484 04:52:51,299 --> 04:52:52,901 THAT WE'RE SEEING DIMINISHED 6485 04:52:52,901 --> 04:52:54,769 OVARIAN RESERVE IN A FRACTION OF 6486 04:52:54,769 --> 04:52:56,571 YOUNG PEOPLE UNDER 30 YEARS OF 6487 04:52:56,571 --> 04:52:57,639 AGE WITH SICKLE CELL ANEMIA. 6488 04:52:57,639 --> 04:52:59,474 WE HAVE FERTILITY PRESERVATION 6489 04:52:59,474 --> 04:53:00,709 AS STANDARDS OF CARE FOR PEOPLE 6490 04:53:00,709 --> 04:53:02,143 WITH OVARIES IN THE FORM OF 6491 04:53:02,143 --> 04:53:04,746 OVARIAN TISSUE CRYOPRESERVATION 6492 04:53:04,746 --> 04:53:08,283 AND OOCYTE AND EMBRYO -- 6493 04:53:08,283 --> 04:53:08,616 PRESERVATION. 6494 04:53:08,616 --> 04:53:09,851 WHAT WE SEE IN THE DATA IS THE 6495 04:53:09,851 --> 04:53:11,252 PEOPLE WE SHOULD BE HAVING THIS 6496 04:53:11,252 --> 04:53:12,353 CONVERSATION WITH, ALTHOUGH THE 6497 04:53:12,353 --> 04:53:14,222 TIMING AND CONTENT IS TO BE 6498 04:53:14,222 --> 04:53:15,857 DETERMINED, IS THAT THOSE FOR 6499 04:53:15,857 --> 04:53:17,292 WHOM HYDROXYUREA IS INDICATED 6500 04:53:17,292 --> 04:53:19,194 SHOULD HAVE THIS DISCUSSED WITH 6501 04:53:19,194 --> 04:53:22,130 THEM. 6502 04:53:22,130 --> 04:53:24,099 IN ADDITION, WHO ELSE ARE WE 6503 04:53:24,099 --> 04:53:24,966 THINKING ABOUT THIS? 6504 04:53:24,966 --> 04:53:25,967 SO WE'RE THINKING ABOUT 6505 04:53:25,967 --> 04:53:26,835 HYDROXYUREA, PEOPLE WITH AN 6506 04:53:26,835 --> 04:53:28,203 INDICATION TO TAKE HYDROXYUREA, 6507 04:53:28,203 --> 04:53:30,138 SO DISEASE SEVERITY AND/OR 6508 04:53:30,138 --> 04:53:32,107 CHILDREN WITH SS DISEASE. 6509 04:53:32,107 --> 04:53:33,208 THE OTHER GROUP OF PEOPLE THAT 6510 04:53:33,208 --> 04:53:35,610 WE'RE STARTING TO THINK ABOUT 6511 04:53:35,610 --> 04:53:37,078 FERTILITY PRESERVATION FOR ARE 6512 04:53:37,078 --> 04:53:39,748 PEOPLE WHO ARE POSTPONING CHILD 6513 04:53:39,748 --> 04:53:41,783 BEARING OR OTHERWISE HAVING 6514 04:53:41,783 --> 04:53:44,285 CHALLENGES AROUND CONCEPTION. 6515 04:53:44,285 --> 04:53:46,221 THE OTHER THING ABOUT THIS IS 6516 04:53:46,221 --> 04:53:47,255 THAT WE KNOW THAT OUR PATIENTS 6517 04:53:47,255 --> 04:53:49,023 SEEM TO HAVE INCREASED RISK FOR 6518 04:53:49,023 --> 04:53:49,557 INFERTILITY. 6519 04:53:49,557 --> 04:53:50,859 THE INFERTILITY RISK FACTORS ARE 6520 04:53:50,859 --> 04:53:51,292 BROAD. 6521 04:53:51,292 --> 04:53:53,294 WE GENERALLY SAY THAT YOU SHOULD 6522 04:53:53,294 --> 04:53:55,597 GIVE PEOPLE 12 MONTHS TO 6523 04:53:55,597 --> 04:53:58,066 CONCEIVE IF THEY'RE UNDER AGE 35 6524 04:53:58,066 --> 04:53:59,300 AND 6 MONTHS TO CONCEIVE IF 6525 04:53:59,300 --> 04:54:01,069 THEY'RE OVER AGE 35, BUT WHETHER 6526 04:54:01,069 --> 04:54:02,437 THOSE VALUES HOLD FOR OUR 6527 04:54:02,437 --> 04:54:04,038 PATIENT POPULATION IS ENTIRELY 6528 04:54:04,038 --> 04:54:05,006 UNCLEAR. 6529 04:54:05,006 --> 04:54:06,107 AND I'VE GIVEN ALL OF THE 6530 04:54:06,107 --> 04:54:07,776 BARRIERS AND CONSTRAINTS OUR 6531 04:54:07,776 --> 04:54:09,544 PATIENTS FACE GETTING TO 6532 04:54:09,544 --> 04:54:10,211 INFERTILITY SPECIALISTS. 6533 04:54:10,211 --> 04:54:12,413 I THINK IT'S WORTH STARTING THE 6534 04:54:12,413 --> 04:54:13,715 REFERRAL PROCESS EARLY SO THAT 6535 04:54:13,715 --> 04:54:15,116 OKAY, IF YOU DON'T NEED THEM, 6536 04:54:15,116 --> 04:54:16,484 YOU DON'T NEED THEM. 6537 04:54:16,484 --> 04:54:18,553 IN ANY CASE, THIS IS SOME OF THE 6538 04:54:18,553 --> 04:54:19,621 WORK AND SOME OF THE CHALLENGES 6539 04:54:19,621 --> 04:54:21,489 WE'VE BEEN THINKING ABOUT, ABOUT 6540 04:54:21,489 --> 04:54:22,457 FERTILITY PRESERVATION. 6541 04:54:22,457 --> 04:54:24,692 IT'S EASY TO FEEL DOOM AND GLOOM 6542 04:54:24,692 --> 04:54:25,827 ABOUT THIS STUFF BUT SOME OF THE 6543 04:54:25,827 --> 04:54:27,695 DATA LOOKS PRETTY NEAT. 6544 04:54:27,695 --> 04:54:28,696 THIS IS CHILDREN WITH SICKLE 6545 04:54:28,696 --> 04:54:30,665 CELL DISEASE, AND IF THIS IS 6546 04:54:30,665 --> 04:54:31,766 FROM DENMARK, THESE CHILDREN 6547 04:54:31,766 --> 04:54:33,001 WERE HEADED FOR CURATIVE 6548 04:54:33,001 --> 04:54:35,203 THERAPIES AND IT'S A COMPA COMPN 6549 04:54:35,203 --> 04:54:37,806 OF CHILDREN WITHOUT SICKLE OR 6550 04:54:37,806 --> 04:54:39,808 THALASSEMIA, THE RED TRIANGLES 6551 04:54:39,808 --> 04:54:43,011 ARE THAL AND THE BLUE DIAMOND 6552 04:54:43,011 --> 04:54:44,312 ARE SICKLE CELL DISEASE. 6553 04:54:44,312 --> 04:54:45,513 WHAT THEY'VE SHOWN IN THIS DATA, 6554 04:54:45,513 --> 04:54:47,582 AND IT SEEMS TO BE TRUE IN OTHER 6555 04:54:47,582 --> 04:54:48,883 COHORTS, ASH DATA PRESENTED BY 6556 04:54:48,883 --> 04:54:50,151 THE FRENCH LAST YEAR SORT OF 6557 04:54:50,151 --> 04:54:52,120 AFFIRMED THIS, IS THAT THE EGG 6558 04:54:52,120 --> 04:54:53,888 SUPPLY IN CHILDHOOD LOOKS PRETTY 6559 04:54:53,888 --> 04:54:56,491 GOOD, SO IT MAKES US WONDER, 6560 04:54:56,491 --> 04:54:57,492 SHOULD WE BE TRYING TO 6561 04:54:57,492 --> 04:54:59,294 UNDERSTAND MORE ABOUT OVARIAN 6562 04:54:59,294 --> 04:54:59,961 TISSUE CRYOPRESERVATION IN 6563 04:54:59,961 --> 04:55:01,129 CHILDREN AND DOING THAT UP 6564 04:55:01,129 --> 04:55:01,696 FRONT? 6565 04:55:01,696 --> 04:55:03,031 A SURGEON FROM DARTMOUTH A 6566 04:55:03,031 --> 04:55:04,532 COUPLE WEEKS AGO ASKED ME WHEN 6567 04:55:04,532 --> 04:55:07,936 HE WAS DO COLEY CYST STECT MES 6568 04:55:07,936 --> 04:55:09,704 ON THE PATIENTS IS IF HE SHOULD 6569 04:55:09,704 --> 04:55:11,005 TAKE A LITTLE OVARIAN TISSUE. 6570 04:55:11,005 --> 04:55:12,006 I THOUGHT IT WAS A LITTLE TOO 6571 04:55:12,006 --> 04:55:13,241 FAR IN THE FUTURE BUT I THINK 6572 04:55:13,241 --> 04:55:16,644 IT'S A QUESTION WORTH ASKING. 6573 04:55:16,644 --> 04:55:18,379 DR. MANWANI, BY THE LOOK ON YOUR 6574 04:55:18,379 --> 04:55:19,581 FACE I KNOW YOU'RE GETTING READY 6575 04:55:19,581 --> 04:55:20,281 TO ANSWER IT, THANK YOU. 6576 04:55:20,281 --> 04:55:21,716 SO IN ANY CASE, THE PROBLEM IS 6577 04:55:21,716 --> 04:55:23,117 LIKE WHAT DO WE DO? 6578 04:55:23,117 --> 04:55:25,153 WE PRESERVE TISSUE, WE PRESERVE 6579 04:55:25,153 --> 04:55:26,221 EMBRYOS, WE PRESERVE EGGS AND 6580 04:55:26,221 --> 04:55:27,522 THEN WE DON'T KNOW WHAT THE 6581 04:55:27,522 --> 04:55:28,656 OUTCOMES ARE AND THAT'S REALLY 6582 04:55:28,656 --> 04:55:30,124 TRUE, I CAN'T TELL YOU WHAT THE 6583 04:55:30,124 --> 04:55:32,060 OUTCOMES ARE WITH THESE 6584 04:55:32,060 --> 04:55:32,560 CRYOPRESERVED MATERIALS. 6585 04:55:32,560 --> 04:55:33,628 WE JUST DON'T HAVE THE DATA YET 6586 04:55:33,628 --> 04:55:35,163 AND WE DON'T HAVE THE SYSTEMS TO 6587 04:55:35,163 --> 04:55:36,064 COLLECT THE DATA PARTICULARLY 6588 04:55:36,064 --> 04:55:36,331 WELL. 6589 04:55:36,331 --> 04:55:38,933 WE'RE WORKING ON THAT. 6590 04:55:38,933 --> 04:55:39,901 FERTILITY PRESERVATION FOR OUR 6591 04:55:39,901 --> 04:55:41,002 PATIENT POPULATION IS I THINK 6592 04:55:41,002 --> 04:55:45,206 ONLY GOING TO INCREASE UNTIL DRN 6593 04:55:45,206 --> 04:55:47,375 HELP US FIND LESS TOXIC PREPTIVE 6594 04:55:47,375 --> 04:55:48,743 REGIMENS TO BRING CURE TO OUR 6595 04:55:48,743 --> 04:55:50,445 PATIENTS. 6596 04:55:50,445 --> 04:55:51,045 DR. TISDALE REASSURES ME THAT 6597 04:55:51,045 --> 04:55:54,048 THIS IS COMING. 6598 04:55:54,048 --> 04:55:55,650 BUT UNTIL THEN, FERTILITY 6599 04:55:55,650 --> 04:55:56,851 PRESERVATION IS GOING TO BE, I 6600 04:55:56,851 --> 04:55:58,386 THINK, AN INCREASING PART OF OUR 6601 04:55:58,386 --> 04:55:59,487 LANDSCAPE, AND I WANTED TO 6602 04:55:59,487 --> 04:56:00,488 STRESS THAT WE HAVE TO BE ABLE 6603 04:56:00,488 --> 04:56:01,456 TO DO THIS SAFELY FOR OUR 6604 04:56:01,456 --> 04:56:02,156 PATIENTS. 6605 04:56:02,156 --> 04:56:04,692 THIS IS OUR PROTOCOL AT HOPKINS 6606 04:56:04,692 --> 04:56:06,027 THAT WE USE WHEN WE'RE SENDING 6607 04:56:06,027 --> 04:56:07,595 PEOPLE THROUGH EGG HARVEST. 6608 04:56:07,595 --> 04:56:09,597 AND IT'S A PROTOCOL THAT WE RUN 6609 04:56:09,597 --> 04:56:12,133 IN CLOSE COLLABORATION WITH OUR 6610 04:56:12,133 --> 04:56:13,568 REPRODUCTIVE ENDOCRINOLOGISTS, 6611 04:56:13,568 --> 04:56:15,336 AND IT HELPED US IDENTIFY SOME 6612 04:56:15,336 --> 04:56:16,638 PITFALLS AND RISKS THAT MIGHT BE 6613 04:56:16,638 --> 04:56:17,972 UNIQUE TO PEOPLE WITH SICKLE 6614 04:56:17,972 --> 04:56:18,506 CELL DISEASE. 6615 04:56:18,506 --> 04:56:22,410 PARTICULARLY THERE'S AN EXPECTED 6616 04:56:22,410 --> 04:56:23,177 HYPERESTROGENEMIC STATE WITH 6617 04:56:23,177 --> 04:56:24,579 THIS PROCEDURE, SO THROMBOSIS 6618 04:56:24,579 --> 04:56:26,481 RISK MAY BE HIGH. 6619 04:56:26,481 --> 04:56:29,784 ANESTHESIOLOGISTS LOVE TO 6620 04:56:29,784 --> 04:56:31,653 GIVE -- WE TELL THEM DON'T DO 6621 04:56:31,653 --> 04:56:33,621 THAT WITH OUR PATIENTS. 6622 04:56:33,621 --> 04:56:35,590 AND PATIENTS MAY OR MAY NOT BE 6623 04:56:35,590 --> 04:56:38,993 AT INCREASED RISK FOR OVARIAN 6624 04:56:38,993 --> 04:56:39,994 HYPERSTIMULATION. 6625 04:56:39,994 --> 04:56:41,429 WHILE THE RISK IS GOING DOWN ALL 6626 04:56:41,429 --> 04:56:43,531 THE TIME IT'S A CAPILLARY LEAK 6627 04:56:43,531 --> 04:56:44,832 SYNDROME THAT CAN AFFECT THE 6628 04:56:44,832 --> 04:56:47,135 WHOLE BODY, BUT PARTICULARLY THE 6629 04:56:47,135 --> 04:56:49,570 LUNGS AND THE KIDNEYS AND THE GI 6630 04:56:49,570 --> 04:56:51,039 TRACT, SO IT CAN CAUSE PAIN AND 6631 04:56:51,039 --> 04:56:51,539 OTHER THINGS. 6632 04:56:51,539 --> 04:56:53,441 NOTHING THAT OUR PATIENTS LIKE. 6633 04:56:53,441 --> 04:56:55,476 WHEN MY PATIENTS GO FOR OVARIAN 6634 04:56:55,476 --> 04:56:56,844 HYPERSTIM I TELL THEM TO DO 6635 04:56:56,844 --> 04:56:58,680 DAILY WEIGHTS ON THEMSELVES FOR 6636 04:56:58,680 --> 04:56:59,580 ABOUT 5 TO 10 DAYS AFTER 6637 04:56:59,580 --> 04:57:00,815 PROCEDURE, BECAUSE MY THEORY, 6638 04:57:00,815 --> 04:57:03,117 WHICH IS TOTALLY THEORY, IS THAT 6639 04:57:03,117 --> 04:57:05,086 IF THEY ARE HAVING OVARIAN 6640 04:57:05,086 --> 04:57:06,621 HYPERSTIM AND IT'S A CAPILLARY 6641 04:57:06,621 --> 04:57:08,623 LEAK, THE FIRST THING I'LL SEE 6642 04:57:08,623 --> 04:57:09,791 IS THEIR WEIGHT WILL START TO GO 6643 04:57:09,791 --> 04:57:12,093 UP SO IT HELPS ME ANTICIPATE ANY 6644 04:57:12,093 --> 04:57:12,994 OWE TENSION PROBLEMS. 6645 04:57:12,994 --> 04:57:13,962 THE OTHER THING HERE IS THAT FOR 6646 04:57:13,962 --> 04:57:17,932 ALL OF OUR PATIENTS WITH SS OR S 6647 04:57:17,932 --> 04:57:19,701 BETA -- THALASSEMIA, WE TRY TO 6648 04:57:19,701 --> 04:57:21,436 GIVE THEM A HYDROXYUREA HOLIDAY. 6649 04:57:21,436 --> 04:57:23,004 HOW LONG, WE DON'T KNOW. 6650 04:57:23,004 --> 04:57:24,706 MAYBE ONE TO THREE MONTHS IF YOU 6651 04:57:24,706 --> 04:57:27,041 CAN, AND WE PUT THEM ON EXCHANGE 6652 04:57:27,041 --> 04:57:27,909 TRANSFUSIONS AND ALWAYS IF 6653 04:57:27,909 --> 04:57:29,477 THEY'RE NOT ON HYDROXYUREA OR 6654 04:57:29,477 --> 04:57:31,579 CHANGES TO BEGIN WITH, GIVE THEM 6655 04:57:31,579 --> 04:57:35,016 A TRANSFUSION JUST AS A 6656 04:57:35,016 --> 04:57:35,817 PREOPERATIVE PREPARATION FOR THE 6657 04:57:35,817 --> 04:57:38,086 STIM. 6658 04:57:38,086 --> 04:57:39,253 SOME HOPEFULNESS FROM OUR 6659 04:57:39,253 --> 04:57:40,355 COMMUNITY, WE NOWAK SES TO 6660 04:57:40,355 --> 04:57:41,689 FERTILITY PRESERVATION IS A 6661 04:57:41,689 --> 04:57:43,891 MASSIVE PROBLEM, AND I JUST 6662 04:57:43,891 --> 04:57:46,427 WANTED TO SHARE WITH YOU THAT BE 6663 04:57:46,427 --> 04:57:48,596 THE MATCH HAS PARTNERED WITH THE 6664 04:57:48,596 --> 04:57:50,031 SICKLE CELL REPRODUCTIVE HEALTH 6665 04:57:50,031 --> 04:57:50,965 DIRECTIVE AND IN THE LAST YEAR 6666 04:57:50,965 --> 04:57:52,867 HAS PROVIDED 16 GRANTS TO 6667 04:57:52,867 --> 04:57:55,870 PRESERVE FERTILITY FOR YOUNG 6668 04:57:55,870 --> 04:57:57,505 PEOPLE SECURING THERAPY FOR 6669 04:57:57,505 --> 04:57:58,139 PEOPLE WITH SICKLE CELL DISEASE. 6670 04:57:58,139 --> 04:57:59,140 YOU GUYS ARE REALLY DEAD OUT 6671 04:57:59,140 --> 04:57:59,507 THERE. 6672 04:57:59,507 --> 04:58:00,575 I KNOW YOU JUST HAD LUNCH. 6673 04:58:00,575 --> 04:58:02,710 THIS IS GREAT, YOU GUYS! 6674 04:58:02,710 --> 04:58:03,611 COME ON! 6675 04:58:03,611 --> 04:58:05,546 SO LISTEN, THIS IS REALLY 6676 04:58:05,546 --> 04:58:07,115 EXCITING, BE THE MATCH DIDN'T 6677 04:58:07,115 --> 04:58:07,782 REALIZE THERE WAS SUCH A NEED 6678 04:58:07,782 --> 04:58:09,283 FOR THIS, BUT ONCE THEY 6679 04:58:09,283 --> 04:58:10,418 RECOGNIZED THE NEED, THEY AGREED 6680 04:58:10,418 --> 04:58:11,619 TO CONTINUE THE PROGRAM FOR 6681 04:58:11,619 --> 04:58:14,722 ANOTHER YEAR, SO AS LONG AS OUR 6682 04:58:14,722 --> 04:58:15,456 COMMUNITY CONTINUES TO PURSUE 6683 04:58:15,456 --> 04:58:16,891 THIS FUNDING AND THERE ISN'T 6684 04:58:16,891 --> 04:58:18,226 MUCH PRIVATE FUNDING LIKE THIS 6685 04:58:18,226 --> 04:58:19,460 FOR INDIVIDUALS WITH SICKLE CELL 6686 04:58:19,460 --> 04:58:20,528 DISEASE, HOPEFULLY THE PROGRAM 6687 04:58:20,528 --> 04:58:23,064 WILL STAY ALIVE. 6688 04:58:23,064 --> 04:58:24,799 OKAY, WELL, EEN THE PLANNERS 6689 04:58:24,799 --> 04:58:26,300 SOMETIMES JUST DECIDE TO GET 6690 04:58:26,300 --> 04:58:27,502 PREGNANT, AND THAT IS WHAT 6691 04:58:27,502 --> 04:58:28,636 HAPPENED TO THIS YOUNG WOMAN. 6692 04:58:28,636 --> 04:58:29,871 SHE GOT PREGNANT, STOPPED HER 6693 04:58:29,871 --> 04:58:31,072 HYDROXYUREA, SHE CALLED ME UP 6694 04:58:31,072 --> 04:58:33,808 AND SHE SAID I HAVEN'T BEEN OFF 6695 04:58:33,808 --> 04:58:35,343 HYDROXYUREA SINCE I WAS A KID 6696 04:58:35,343 --> 04:58:36,811 AND I'M GETTING PAIN LIKE I'VE 6697 04:58:36,811 --> 04:58:38,146 NEVER HAD BEFORE, I JUST GOT OUT 6698 04:58:38,146 --> 04:58:39,414 OF THE HOSPITAL, WHAT SHOULD WE 6699 04:58:39,414 --> 04:58:41,516 DO NEXT? 6700 04:58:41,516 --> 04:58:43,618 WE ARE LIVING THROUGH A TOTALLY 6701 04:58:43,618 --> 04:58:45,987 STAGNANT TIME FOR PREGNANCY FOR 6702 04:58:45,987 --> 04:58:47,055 WOMEN WITH SICKLE CELL DISEASE, 6703 04:58:47,055 --> 04:58:48,456 AND I REALLY HOPE THAT IN THE 6704 04:58:48,456 --> 04:58:50,191 NEXT DECADE, WE CAN START TO 6705 04:58:50,191 --> 04:58:51,325 TURN THIS YACHT AROUND. 6706 04:58:51,325 --> 04:58:52,994 THESE ARE THREE PAPERS PUBLISHED 6707 04:58:52,994 --> 04:58:55,430 IN THE LAST 12 MONTHS, 24 6708 04:58:55,430 --> 04:58:56,898 MONTHS, ABOUT MATERNAL MORBIDITY 6709 04:58:56,898 --> 04:58:58,800 AND MORTALITY IN JAMAICA AND IN 6710 04:58:58,800 --> 04:58:59,834 THE UNITED STATES AND THEY ALL 6711 04:58:59,834 --> 04:59:01,869 DREW THE SAME CONCLUSION FROM 6712 04:59:01,869 --> 04:59:03,237 INDEPENDENT DATASETS, WHICH IS 6713 04:59:03,237 --> 04:59:05,206 THAT MATERNAL MORTALITY AND 6714 04:59:05,206 --> 04:59:06,841 MORBIDITY FOR GIRLS -- FOR WOMEN 6715 04:59:06,841 --> 04:59:08,810 WITH SICKLE CELL DISEASE IS 6716 04:59:08,810 --> 04:59:12,313 STAGNANT. 6717 04:59:12,313 --> 04:59:13,514 AND STRUCTURAL RACISM IS ALWAYS 6718 04:59:13,514 --> 04:59:15,249 PART OF THE PROBLEM FOR SICKLE 6719 04:59:15,249 --> 04:59:15,583 CELL DISEASE. 6720 04:59:15,583 --> 04:59:18,586 IN OUR ANALYSIS, STRUCTURAL AND 6721 04:59:18,586 --> 04:59:19,487 INTERPERSONAL RACISM MAY BE 6722 04:59:19,487 --> 04:59:21,222 ACCOUNTED FOR ABOUT 30% OF 6723 04:59:21,222 --> 04:59:22,090 SICKLE CELL DISEASE ASSOCIATED 6724 04:59:22,090 --> 04:59:24,559 SEVERE MATERNAL MORTALITY AND 6725 04:59:24,559 --> 04:59:25,393 MORBIDITY, AND A LOVELY PAPER 6726 04:59:25,393 --> 04:59:27,829 FROM OUR COLLEAGUES IN VIRGINIA 6727 04:59:27,829 --> 04:59:30,064 AND SOUTH CAROLINA AND FIVE U.S. 6728 04:59:30,064 --> 04:59:31,766 STATES, SICKLE CELL DISEASE 6729 04:59:31,766 --> 04:59:35,403 ACCOUNTED FOR .37% OF ABOUT A 6730 04:59:35,403 --> 04:59:36,537 MILLION PREGNANCIES IN PEOPLE 6731 04:59:36,537 --> 04:59:38,940 WHO IDENTIFY AS BLACK, BUT 6732 04:59:38,940 --> 04:59:42,310 ACCOUNTED FOR 6.9% OF THE SEVERE 6733 04:59:42,310 --> 04:59:44,445 MATERNAL MORBIDITY AND 8.9% OF 6734 04:59:44,445 --> 04:59:48,116 THE BLACK-WHITE SMM DISPARITY. 6735 04:59:48,116 --> 04:59:50,618 AND SO WE HAVE USED THIS TO 6736 04:59:50,618 --> 04:59:51,986 ARGUE THAT YOU CAN'T ACTUALLY 6737 04:59:51,986 --> 04:59:54,856 SOLVE THE RIDDLE OF MATERNAL 6738 04:59:54,856 --> 04:59:56,023 HEALTH DISPARITIES IN THIS 6739 04:59:56,023 --> 04:59:57,258 COUNTRY WITHOUT TAKING ON SICKLE 6740 04:59:57,258 --> 04:59:57,592 CELL DISEASE. 6741 04:59:57,592 --> 04:59:59,560 WE HAVE TO DO THIS TOGETHER WITH 6742 04:59:59,560 --> 05:00:00,895 OUR COLLEAGUES IN OB. 6743 05:00:00,895 --> 05:00:01,963 WELL, HOW BAD IS IT? 6744 05:00:01,963 --> 05:00:03,564 THIS IS FROM A RECENT ANALYSIS 6745 05:00:03,564 --> 05:00:04,532 OF THE NATIONAL INPATIENT 6746 05:00:04,532 --> 05:00:04,966 SAMPLE. 6747 05:00:04,966 --> 05:00:06,934 THESE ARE SEVERE MATERNAL 6748 05:00:06,934 --> 05:00:10,605 MORBIDITY INDEX, AND THE ONE 6749 05:00:10,605 --> 05:00:13,674 LINE IS PEOPLE WHO IDENTIFY AS 6750 05:00:13,674 --> 05:00:15,143 WHITE WHO ARE UNAFFECTED BY 6751 05:00:15,143 --> 05:00:16,277 SICKLE CELL DISEASE. 6752 05:00:16,277 --> 05:00:18,012 THE BLUE/PURPLE IS PEOPLE WHO 6753 05:00:18,012 --> 05:00:19,847 IDENTIFY AS BLACK, AND THE 6754 05:00:19,847 --> 05:00:20,948 ORANGE/YELLOW IS PEOPLE WHO 6755 05:00:20,948 --> 05:00:21,616 IDENTIFY AS BLACK AND HAVE 6756 05:00:21,616 --> 05:00:24,218 SICKLE CELL DISEASE. 6757 05:00:24,218 --> 05:00:25,119 AND OF COURSE ALL THESE PEOPLE 6758 05:00:25,119 --> 05:00:25,620 WERE PREGNANT. 6759 05:00:25,620 --> 05:00:26,687 SO I HOPE WHAT YOU CAN SEE IS 6760 05:00:26,687 --> 05:00:28,322 THAT THERE ARE FANTASTIC 6761 05:00:28,322 --> 05:00:30,892 INCREASED RISKS OF STROKES, 6762 05:00:30,892 --> 05:00:33,127 EMBOLI, ACUTE RESPIRATORY 6763 05:00:33,127 --> 05:00:35,363 DISTRESS SYNDROME, PULMONARY 6764 05:00:35,363 --> 05:00:37,298 EDEMA, THE NEED FOR VENTILATION, 6765 05:00:37,298 --> 05:00:39,000 SEPSIS, KIDNEY FAILURE, ET 6766 05:00:39,000 --> 05:00:39,300 CETERA. 6767 05:00:39,300 --> 05:00:40,468 THERE ARE ALSO CONCERNING 6768 05:00:40,468 --> 05:00:42,570 OUTCOMES FOR THE BABIES. 6769 05:00:42,570 --> 05:00:44,005 IUGR IS COMMON, PROBABLY RELATED 6770 05:00:44,005 --> 05:00:45,973 TO PLACENTAL ABNORMALITIES. 6771 05:00:45,973 --> 05:00:47,975 THE PLACENTA IS ALSO AN ENDORGAN 6772 05:00:47,975 --> 05:00:50,077 IN THIS DISEASE, AND FETAL 6773 05:00:50,077 --> 05:00:51,145 DEMISE IS ALSO MORE COMMON THAN 6774 05:00:51,145 --> 05:00:52,780 WE WOULD LIKE, PRETERM DELIVERY 6775 05:00:52,780 --> 05:00:53,181 TOO. 6776 05:00:53,181 --> 05:00:55,650 SO I WANTED TO TALK A LIT LITTLE 6777 05:00:55,650 --> 05:00:58,386 BIT ABOUT WHAT WE KNOW ABOUT 6778 05:00:58,386 --> 05:01:00,121 TRANSFUSIONS FOR THIS CONDITION 6779 05:01:00,121 --> 05:01:01,222 BECAUSE AT THE MOMENT, IT'S THE 6780 05:01:01,222 --> 05:01:03,791 ONLY THERAPY THAT DOESN'T HOLD A 6781 05:01:03,791 --> 05:01:04,458 TRYOGENIC RISK. 6782 05:01:04,458 --> 05:01:05,760 WE'LL TALK A LITTLE ABOUT 6783 05:01:05,760 --> 05:01:06,527 HYDROXYUREA BUT BLOOD 6784 05:01:06,527 --> 05:01:07,929 TRANSFUSIONS ARE REALLY THE 6785 05:01:07,929 --> 05:01:10,097 SAFEST THERAPY WE HAVE TO OFFER 6786 05:01:10,097 --> 05:01:10,765 WOMEN WITH SICKLE CELL DISEASE 6787 05:01:10,765 --> 05:01:11,132 IN PREGNANCY. 6788 05:01:11,132 --> 05:01:12,900 I WANTED TO TALK ABOUT THIS IN 6789 05:01:12,900 --> 05:01:14,135 THE CONTEXT OF HOW WE THINK 6790 05:01:14,135 --> 05:01:15,369 ABOUT THE STRENGTHS OF DIFFERENT 6791 05:01:15,369 --> 05:01:16,904 KINDS OF DATA BECAUSE THERE'S A 6792 05:01:16,904 --> 05:01:22,910 PAPER BY DR. KING AND 6793 05:01:22,910 --> 05:01:23,945 MALINOWSKI, I JUST WANTED TO 6794 05:01:23,945 --> 05:01:24,912 WALK YOU THROUGH THE RESULTS OF 6795 05:01:24,912 --> 05:01:25,947 THAT STUDY. 6796 05:01:25,947 --> 05:01:29,550 AMONG 12 STUDIES WITH 1200 6797 05:01:29,550 --> 05:01:30,751 PATIENTS, PROPHYLACTIC 6798 05:01:30,751 --> 05:01:32,420 TRANSFUSIONS DECREASED MATERNAL 6799 05:01:32,420 --> 05:01:33,988 MORTALITY SIGNIFICANTLY. 6800 05:01:33,988 --> 05:01:36,390 PAINFUL EVENTS, PE, PERINATAL 6801 05:01:36,390 --> 05:01:37,959 MORTALITY, NEONATAL DEATH AND 6802 05:01:37,959 --> 05:01:40,428 PRETERM BIRTH. 6803 05:01:40,428 --> 05:01:41,662 AND ALTHOUGH THERE WERE LOW 6804 05:01:41,662 --> 05:01:42,763 EVENT RATES FOR SOME 6805 05:01:42,763 --> 05:01:44,632 COMPLICATIONS AND THE AUTHORS 6806 05:01:44,632 --> 05:01:47,168 CONCLUDED THIS NEEDED FURTHER 6807 05:01:47,168 --> 05:01:50,638 STUDY, NONETHELESS, IT'S DATA 6808 05:01:50,638 --> 05:01:52,006 WITH END POINTS WE REALLY CARE 6809 05:01:52,006 --> 05:01:52,473 ABOUT. 6810 05:01:52,473 --> 05:01:53,874 SOME PEOPLE SAY YEAH, BUT IT WAS 6811 05:01:53,874 --> 05:01:55,343 A NEGATIVE RANDOMIZED CONTROL 6812 05:01:55,343 --> 05:01:55,676 TRIAL. 6813 05:01:55,676 --> 05:01:57,311 FIRST TO REMIND US ABOUT THE 6814 05:01:57,311 --> 05:01:59,313 HIERARCHY OF DATA, META ANALYSES 6815 05:01:59,313 --> 05:02:01,849 HAVE MORE WEIGHT THAN RANDOMIZED 6816 05:02:01,849 --> 05:02:03,384 CONTROL TRIALS. 6817 05:02:03,384 --> 05:02:04,285 THE 1998 RANDOMIZED CONTROL 6818 05:02:04,285 --> 05:02:06,254 TRIAL FROM A LONG TIME AGO 6819 05:02:06,254 --> 05:02:08,122 IDENTIFIED THAT TRANSFUSIONS 6820 05:02:08,122 --> 05:02:09,323 INITIATED ONCE PEOPLE BECAME 6821 05:02:09,323 --> 05:02:12,526 PREGNANT DID NOT CHANGE FETAL 6822 05:02:12,526 --> 05:02:13,995 OUTCOMES, AND THAT HAS BEEN USED 6823 05:02:13,995 --> 05:02:15,296 TO INTERPRET THE DATA AS A 6824 05:02:15,296 --> 05:02:16,797 NEGATIVE STUDY, BUT ACTUALLY 6825 05:02:16,797 --> 05:02:17,832 CHRONIC TRANSFUSIONS REDUCE 6826 05:02:17,832 --> 05:02:19,267 PAINFUL CRISES AND OTHER SICKLE 6827 05:02:19,267 --> 05:02:20,368 CELL COMPLICATIONS. 6828 05:02:20,368 --> 05:02:21,636 SO I GUESS I WOULD POSE TO YOU 6829 05:02:21,636 --> 05:02:24,705 IN THE PRESENCE OF EQUIPOISE 6830 05:02:24,705 --> 05:02:26,407 WHAT'S YOUR THRESHOLD FOR 6831 05:02:26,407 --> 05:02:27,208 INTERVENTION? 6832 05:02:27,208 --> 05:02:27,975 PATIENTS WHO ARE PREVIOUSLY 6833 05:02:27,975 --> 05:02:28,843 STABLE ON HYDROXYUREA EITHER 6834 05:02:28,843 --> 05:02:31,445 STARTED IN CHILDHOOD OR DUE TO 6835 05:02:31,445 --> 05:02:32,480 COMPLICATIONS, SHOULD WE PUT ALL 6836 05:02:32,480 --> 05:02:33,581 OF THEM ON TRANSFUSIONS? 6837 05:02:33,581 --> 05:02:34,849 WHAT ABOUT THINKING ABOUT THE 6838 05:02:34,849 --> 05:02:35,950 DOWNSTREAM EFFECTS OF PAIN? 6839 05:02:35,950 --> 05:02:37,251 I WORRY THAT WE DON'T THINK 6840 05:02:37,251 --> 05:02:38,552 ABOUT THIS WHEN WE THINK ABOUT 6841 05:02:38,552 --> 05:02:39,420 PAIN IN PREGNANCY. 6842 05:02:39,420 --> 05:02:41,889 SO IF WE PREVENT PAIN, WE 6843 05:02:41,889 --> 05:02:43,557 PREVENT HOSPITALIZATION, 6844 05:02:43,557 --> 05:02:46,227 THROMBOSIS, ACUTE CHEST, 6845 05:02:46,227 --> 05:02:48,162 MATERNAL FETAL OPIOID EXPOSURE, 6846 05:02:48,162 --> 05:02:49,497 IMPROVED QUALITY OF LIFE IN 6847 05:02:49,497 --> 05:02:51,232 PREGNANCY PERHAPS AND ALSO 6848 05:02:51,232 --> 05:02:52,366 REDUCE TOXIC STRESS ASSOCIATED 6849 05:02:52,366 --> 05:02:53,501 WITH RACISM WHEN YOU HAVE TO GO 6850 05:02:53,501 --> 05:02:54,602 INTO HEALTHCARE SYSTEMS THAT 6851 05:02:54,602 --> 05:02:56,037 AREN'T DESIGNED TO SERVE YOU 6852 05:02:56,037 --> 05:02:56,904 NECESSARILY. 6853 05:02:56,904 --> 05:02:58,539 MATERNAL ANEMIA IS A RECOGNIZED 6854 05:02:58,539 --> 05:03:00,574 RISK FACTOR FOR ADVERSE 6855 05:03:00,574 --> 05:03:00,841 OUTCOMES. 6856 05:03:00,841 --> 05:03:02,877 ALL OF OUR PATIENTS HAVE 6857 05:03:02,877 --> 05:03:03,411 MATERNAL ANEMIA. 6858 05:03:03,411 --> 05:03:05,046 IN THE STRESSFUL POSTPARTUM 6859 05:03:05,046 --> 05:03:06,213 PERIOD WHERE NOBODY SLEEPS AND 6860 05:03:06,213 --> 05:03:07,315 THE IMPACT OF YOUR TEASE MIGHT 6861 05:03:07,315 --> 05:03:10,484 DISEASE MIGHTGO UP, WE HAVE THEY 6862 05:03:10,484 --> 05:03:11,319 TO HELP STABILIZE THINGS. 6863 05:03:11,319 --> 05:03:12,953 I THINK ONE OF OUR GREATEST 6864 05:03:12,953 --> 05:03:13,954 PREOCCUPATIONS WITH USING 6865 05:03:13,954 --> 05:03:15,389 TRANSFUSIONS IN HIGH RESOURCE 6866 05:03:15,389 --> 05:03:16,691 SETTINGS FOR PREGNANCY IS THE 6867 05:03:16,691 --> 05:03:18,993 RISK OF ALEUM NIGHIZATION AND MY 6868 05:03:18,993 --> 05:03:20,027 STUDENT CLAIRE WILL BE 6869 05:03:20,027 --> 05:03:20,861 PRESENTING AN ORAL ABSTRACT 6870 05:03:20,861 --> 05:03:21,729 ABOUT THAT AT ASH. 6871 05:03:21,729 --> 05:03:23,197 THESE ARE TWO TOOLS TO HELP YOU 6872 05:03:23,197 --> 05:03:24,765 THINK ABOUT WHO SHOULD BE GOING 6873 05:03:24,765 --> 05:03:27,201 ON TRANSFUSIONS IN PREGNANCY. 6874 05:03:27,201 --> 05:03:29,503 THE AMERICAN AMERICAN SOCIETY OF 6875 05:03:29,503 --> 05:03:32,239 HEMATOLOGY GUIDELINES AND THE 6876 05:03:32,239 --> 05:03:33,474 RISK PREDICTION TOOL WHICH YOU 6877 05:03:33,474 --> 05:03:34,909 CAN PLAY WITH ON THE INTERNET, 6878 05:03:34,909 --> 05:03:36,811 IT TURNS OUT THESE TWO TOOLS 6879 05:03:36,811 --> 05:03:38,245 WORK ABOUT THE SAME AND I'M 6880 05:03:38,245 --> 05:03:40,648 REALLY LOOKING FORWARD TO THEM 6881 05:03:40,648 --> 05:03:41,649 VALIDATING THEIR TOOLS SO WE CAN 6882 05:03:41,649 --> 05:03:43,184 SHARE IT WITH OUR OBs. 6883 05:03:43,184 --> 05:03:44,618 THIS IS OUR APPROACH TO 6884 05:03:44,618 --> 05:03:46,287 TRANSFUSION AT JOHNS HOPKINS. 6885 05:03:46,287 --> 05:03:48,155 WE TRANSFUSE EVERYONE WITH SS 6886 05:03:48,155 --> 05:03:50,491 AND S BETA NULL THALASSEMIA 6887 05:03:50,491 --> 05:03:52,026 BEFORE PREGNANCY IF THEY'RE 6888 05:03:52,026 --> 05:03:52,860 PLANNERS AND THEY TELL US 6889 05:03:52,860 --> 05:03:54,128 THEY'RE GETTING PREGNANT, AND 6890 05:03:54,128 --> 05:03:56,464 ONCE THEY ARE PREGNANT, IF THEY 6891 05:03:56,464 --> 05:03:58,666 ARE NOT PLANNERS. 6892 05:03:58,666 --> 05:04:00,401 SO THE TRANSFUSIONS ARE HELPING, 6893 05:04:00,401 --> 05:04:01,969 WHAT ELSE SHOULD I WORRY ABOUT? 6894 05:04:01,969 --> 05:04:03,604 I KNOW MY TIME IS UP, I'M GOING 6895 05:04:03,604 --> 05:04:04,705 TO KEEP GOING AND THEN I'M GOING 6896 05:04:04,705 --> 05:04:06,107 TO BE DONE. 6897 05:04:06,107 --> 05:04:06,707 2 MORE MINUTES. 6898 05:04:06,707 --> 05:04:08,175 SO WE SHOULD WORRY ABOUT ACUTE 6899 05:04:08,175 --> 05:04:08,709 CHEST SYNDROME. 6900 05:04:08,709 --> 05:04:10,378 CAN WE REMEDIATE THIS BY PUTTING 6901 05:04:10,378 --> 05:04:11,712 PEOPLE ON TRANSFUSIONS AND CAN 6902 05:04:11,712 --> 05:04:15,216 WE GET INCENTIVE SPIROMETRY TO 6903 05:04:15,216 --> 05:04:16,217 ALL OF THE LABOR AND DELIVERY 6904 05:04:16,217 --> 05:04:16,917 UNITS IN THE COUNTRY? 6905 05:04:16,917 --> 05:04:19,220 I LEARNED AT A BIG SOCIETY OF 6906 05:04:19,220 --> 05:04:20,121 MATERNAL FETAL MEDICINE MEETING 6907 05:04:20,121 --> 05:04:22,757 A COUPLE MONTHS AGO THAT AMONG 6908 05:04:22,757 --> 05:04:25,526 THE SIX HERE 70 HOSPITALS -- 6909 05:04:25,526 --> 05:04:28,262 NOBODY HAD A PROTOCOL AND SENT 6910 05:04:28,262 --> 05:04:29,397 FOR SPIROMETRY WHEN 6911 05:04:29,397 --> 05:04:29,997 HOSPITALIZED. 6912 05:04:29,997 --> 05:04:31,165 WE SHOULD BE THINKING ABOUT 6913 05:04:31,165 --> 05:04:33,000 BEING MORE AGGRESSIVE WITH 6914 05:04:33,000 --> 05:04:33,801 THROMBOPROPHYLAXIS IN THIS 6915 05:04:33,801 --> 05:04:34,869 POPULATION. 6916 05:04:34,869 --> 05:04:37,438 VTE RISK IS AS HIGH AS 11% IN 6917 05:04:37,438 --> 05:04:40,508 PREG Z THE ASH SICKLE CELL VTE 6918 05:04:40,508 --> 05:04:41,509 PREGNANCY GUIDELINES SAY THAT 6919 05:04:41,509 --> 05:04:43,944 THE THRESHOLD FOR INTERVENTION 6920 05:04:43,944 --> 05:04:45,846 WITH ANTI-COAGULATION 6921 05:04:45,846 --> 05:04:47,114 PROPHYLAXIS IS 1 TO 2%. 6922 05:04:47,114 --> 05:04:49,483 SO THESE GUYS ARE WAY OUTSIDE 6923 05:04:49,483 --> 05:04:50,284 THAT RISK. 6924 05:04:50,284 --> 05:04:53,788 THE THIRD TRY MOSTLY SUNNY TER 6925 05:04:53,788 --> 05:04:55,055 AND ANTENATAL RISK IS THE 6926 05:04:55,055 --> 05:04:57,525 HIGHEST TIME PERIOD AND BRITISH 6927 05:04:57,525 --> 05:04:58,659 GUIDELINES, CANADIAN GUIDELINES 6928 05:04:58,659 --> 05:05:00,928 AND NOW SOME U.S. CENTERS ARE 6929 05:05:00,928 --> 05:05:02,830 INITIATING PROAF LACKTIVE 6930 05:05:02,830 --> 05:05:03,564 ANTI-COAGULATION DURING THIS 6931 05:05:03,564 --> 05:05:04,365 TIME PERIOD. 6932 05:05:04,365 --> 05:05:06,000 FINALLY I JUST WANTED TO POINT 6933 05:05:06,000 --> 05:05:08,068 TO SOME DATA ABOUT GESTATIONAL 6934 05:05:08,068 --> 05:05:08,936 HYPERTENSIVE DISORDERS. 6935 05:05:08,936 --> 05:05:13,040 PLOOP IN OUR PABLOOD PRESSURE IS 6936 05:05:13,040 --> 05:05:15,176 IS LOW AND THE 140/90 THRESHOLD 6937 05:05:15,176 --> 05:05:19,146 CLEARLY DOESN'T APPLY TO THEM. 6938 05:05:19,146 --> 05:05:24,151 DRTHE DIASTOLIC BLOOD PRESSURESN 6939 05:05:24,151 --> 05:05:25,886 THIS COHORT WERE SO LOW THAT 6940 05:05:25,886 --> 05:05:27,421 THERE WAS NOT ONE MEASURE IN THE 6941 05:05:27,421 --> 05:05:29,423 WHOLE COHORT THAT EVER WAS A 6942 05:05:29,423 --> 05:05:30,758 DICE STOLG OF 90. 6943 05:05:30,758 --> 05:05:33,160 SO THAT DIASTOLIC BLOOD PRESSURE 6944 05:05:33,160 --> 05:05:34,762 OF 90 IS NEVER GOING TO DETECT 6945 05:05:34,762 --> 05:05:35,729 HYPERTENSION IN PREGNANT PEOPLE 6946 05:05:35,729 --> 05:05:38,232 WITH SICKLE CELL DISEASE. 6947 05:05:38,232 --> 05:05:39,433 WE ALSO DON'T TALK ABOUT WHAT'S 6948 05:05:39,433 --> 05:05:40,734 HAPPENING TO THE BABIES BORN TO 6949 05:05:40,734 --> 05:05:43,103 WOMEN WITH SICKLE CELL DISEASE. 6950 05:05:43,103 --> 05:05:46,841 IA PRELIMINARY STUDY, THEY LOOKD 6951 05:05:46,841 --> 05:05:49,510 AT THE BOSTON BIRTH COHORT AND 6952 05:05:49,510 --> 05:05:51,679 COMPARED IN A RIGOROUS MATCHED 6953 05:05:51,679 --> 05:05:53,547 WAY PHYSICAL AND COGNITIVE 6954 05:05:53,547 --> 05:05:54,715 DEVELOPMENTAL OUTCOMES OF BABIES 6955 05:05:54,715 --> 05:05:56,650 BORN TO WOMEN WITH SICKLE CELL 6956 05:05:56,650 --> 05:05:58,085 DISEASE COMPARED TO MATCHED 6957 05:05:58,085 --> 05:05:59,186 CONTROLS, AND YOU CAN SEE THERE 6958 05:05:59,186 --> 05:06:01,288 WERE DIFFERENCES IN WEIGHT, 6959 05:06:01,288 --> 05:06:02,756 OBESITY AND ADHD. 6960 05:06:02,756 --> 05:06:03,824 ARE WE BEING TAUING TO OUR 6961 05:06:03,824 --> 05:06:08,562 TALKING TO OUR PATIENTSABOUT TH? 6962 05:06:08,562 --> 05:06:09,129 THE LAST THING. 6963 05:06:09,129 --> 05:06:11,699 WE'RE MOVING TO ODESSA, TEXAS, 6964 05:06:11,699 --> 05:06:13,901 AND THAT'S NOT CLOSE ENOUGH TO 6965 05:06:13,901 --> 05:06:16,036 DR. ALISHA NURO, IS IT? 6966 05:06:16,036 --> 05:06:17,571 NO. 6967 05:06:17,571 --> 05:06:18,105 IT'S FIVE HOURS. 6968 05:06:18,105 --> 05:06:19,974 THIS IS MY FINAL POINT, WHICH IS 6969 05:06:19,974 --> 05:06:21,909 THAT WE CANNOT SOLVE THE RIDDLE 6970 05:06:21,909 --> 05:06:23,644 OF UNSAFE PREGNANCY FOR WOMEN 6971 05:06:23,644 --> 05:06:25,045 WITH SICKLE CELL DISEASE WITHOUT 6972 05:06:25,045 --> 05:06:25,946 COMPREHENSIVE SICKLE CELL 6973 05:06:25,946 --> 05:06:26,380 DISEASE CARE. 6974 05:06:26,380 --> 05:06:28,382 WHAT YOU CAN SEE ON THE LEFT IS 6975 05:06:28,382 --> 05:06:32,186 A MAP OF SICKLE CELL DISEASE 6976 05:06:32,186 --> 05:06:33,854 CENTERS, AND INDIVIDUALS WITH 6977 05:06:33,854 --> 05:06:34,855 SICKLE CELL DISEASE, AND ON THE 6978 05:06:34,855 --> 05:06:36,457 RIGHT, YOU CAN SEE MATERNITY 6979 05:06:36,457 --> 05:06:39,226 CARE DESERTS MAPPED OUT IN RED. 6980 05:06:39,226 --> 05:06:40,794 IT GIVES YOU A SENSE THAT 6981 05:06:40,794 --> 05:06:42,429 PARTICULARLY ODESSA, TEXAS, BUT 6982 05:06:42,429 --> 05:06:43,430 MUCH OF THE MIDDLE OF THE 6983 05:06:43,430 --> 05:06:45,366 COUNTRY AND MUCH OF THE SOUTH 6984 05:06:45,366 --> 05:06:47,501 ARE AT RISK FOR NOT BEING ABLE 6985 05:06:47,501 --> 05:06:49,503 TO PROVIDE HIGH QUALITY CARE IN 6986 05:06:49,503 --> 05:06:52,106 PREGNANT PEOPLE WITH SICKLE CELL 6987 05:06:52,106 --> 05:06:53,173 DISEASE SIMPLY BECAUSE THERE'S 6988 05:06:53,173 --> 05:06:54,608 NOT ANY MATERNITY CARE FOR 6989 05:06:54,608 --> 05:06:55,109 ANYONE. 6990 05:06:55,109 --> 05:06:56,410 THE CDC HAS RECENTLY PARTNERED 6991 05:06:56,410 --> 05:06:58,045 WITH US TO DEVELOP HANDOUTS FOR 6992 05:06:58,045 --> 05:06:58,579 OUR PATIENTS. 6993 05:06:58,579 --> 05:07:00,147 THIS IS A RESOURCE FOR YOU IN 6994 05:07:00,147 --> 05:07:00,748 YOUR CLINICS. 6995 05:07:00,748 --> 05:07:02,449 WE HAVE THREE GUIDELINES AND 6996 05:07:02,449 --> 05:07:04,685 THAT'S IT. 6997 05:07:04,685 --> 05:07:05,619 MULTIDISCIPLINARY CARE, WE CAN'T 6998 05:07:05,619 --> 05:07:07,321 DO IT WITHOUT OUR COLLEAGUES. 6999 05:07:07,321 --> 05:07:09,390 THIS PERSPECTIVE BLEW MY MIND. 7000 05:07:09,390 --> 05:07:10,524 DR. ANDY JAMES SAID TO ME, IT 7001 05:07:10,524 --> 05:07:11,959 NEVER EVEN OCCURRED TO ME THAT 7002 05:07:11,959 --> 05:07:15,296 THE PERSON IN THIS PICTURE WITH 7003 05:07:15,296 --> 05:07:16,130 SICKLE CELL DISEASE WAS THE 7004 05:07:16,130 --> 05:07:16,363 BABY. 7005 05:07:16,363 --> 05:07:18,198 WE SEE THE PROBLEMS A LITTLE BIT 7006 05:07:18,198 --> 05:07:18,566 DIFFERENTLY. 7007 05:07:18,566 --> 05:07:20,000 AND I THINK SEEING THE PROBLEMS 7008 05:07:20,000 --> 05:07:21,235 AND THE SOLUTIONS DIFFERENTLY IS 7009 05:07:21,235 --> 05:07:22,970 ONLY TO THE STRENGTHS OF OUR 7010 05:07:22,970 --> 05:07:24,171 PATIENTS AND TO THE BETTERMENT 7011 05:07:24,171 --> 05:07:25,472 OF OUR PATIENTS. 7012 05:07:25,472 --> 05:07:27,308 IN CONCLUSION, CONTEMPORARY 7013 05:07:27,308 --> 05:07:27,975 SICKLE CELL DISEASE CARE 7014 05:07:27,975 --> 05:07:29,810 REQUIRES US TO INCORPORATE 7015 05:07:29,810 --> 05:07:33,581 DIMENSIONS OF REPRODUCTIVE 7016 05:07:33,581 --> 05:07:35,115 HEALTHCARE, IT INVOLVES 7017 05:07:35,115 --> 05:07:36,116 TREATMENT DECISION LACED WITH 7018 05:07:36,116 --> 05:07:37,618 UNCERTAINTY AND THE INADEQUACY 7019 05:07:37,618 --> 05:07:39,587 OF FULLY FUNDED COMPREHENSIVE 7020 05:07:39,587 --> 05:07:41,188 SICKLE CELL CENTERS JEOPARDIZES 7021 05:07:41,188 --> 05:07:42,089 THE ABILITY TO PROVIDE THIS 7022 05:07:42,089 --> 05:07:42,923 CARE. 7023 05:07:42,923 --> 05:07:44,124 I THINK WE CAN HELP OUR YOUNG 7024 05:07:44,124 --> 05:07:45,759 PEOPLE MAKE REPRODUCTIVE LIFE 7025 05:07:45,759 --> 05:07:47,795 PLANS, IN PENCIL, AND PROVIDE 7026 05:07:47,795 --> 05:07:48,996 ITERATIVE COUNSELING TO THEM 7027 05:07:48,996 --> 05:07:52,433 ACROSS TIME, AND THIS CARRIES 7028 05:07:52,433 --> 05:07:53,167 INTERSECTIONAL, 7029 05:07:53,167 --> 05:07:53,867 MULTIDISCIPLINARY AND OFFERS 7030 05:07:53,867 --> 05:07:55,536 MANY JUK TOURS THAT REQUIRE 7031 05:07:55,536 --> 05:07:57,438 SHARED DECISION-MAKING. 7032 05:07:57,438 --> 05:07:57,871 THANK YOU. 7033 05:07:57,871 --> 05:07:59,473 [APPLAUSE] 7034 05:07:59,473 --> 05:08:01,375 THESE ARE SOME CLINICAL 7035 05:08:01,375 --> 05:08:02,476 RESOURCES, TAKE A SCREEN SHOT 7036 05:08:02,476 --> 05:08:03,911 AND WE'LL MOVE ON, BUT ALL OF 7037 05:08:03,911 --> 05:08:04,979 THESE THINGS HAVE TOOLS THAT YOU 7038 05:08:04,979 --> 05:08:05,980 COULD USE TO HELP YOUR PATIENTS. 7039 05:08:05,980 --> 05:08:07,414 AND YOU CAN READ -- YOU CAN 7040 05:08:07,414 --> 05:08:09,483 WATCH THAT WHOLE CONFERENCE ON 7041 05:08:09,483 --> 05:08:14,221 THE INTERNET. 7042 05:08:14,221 --> 05:08:15,122 >> THANK YOU SO MUCH. 7043 05:08:15,122 --> 05:08:17,725 THAT WAS SUCH A WONDERFULLY 7044 05:08:17,725 --> 05:08:19,927 DELIVERED AND VERY COMPREHENSIVE 7045 05:08:19,927 --> 05:08:22,162 TALK ON REPRODUCTIVE HEALTH 7046 05:08:22,162 --> 05:08:24,331 ISSUES IN BOYS AND GIRLS, MEN 7047 05:08:24,331 --> 05:08:25,032 AND WOMEN WITH SICKLE CELL 7048 05:08:25,032 --> 05:08:25,466 DISEASE. 7049 05:08:25,466 --> 05:08:28,102 I'M GLAD WE FOCUSED ON MEN AS 7050 05:08:28,102 --> 05:08:28,669 WELL. 7051 05:08:28,669 --> 05:08:30,371 AND JUST HIGHLIGHT THE FACT THAT 7052 05:08:30,371 --> 05:08:31,538 SO MUCH WORK IS NEEDED. 7053 05:08:31,538 --> 05:08:36,076 WE HAVE WOMEN IN JAMAICA WHO 7054 05:08:36,076 --> 05:08:36,644 REFUSE TO TAKE HYDROXYUREA 7055 05:08:36,644 --> 05:08:37,945 BECAUSE THEY WANT TO GET 7056 05:08:37,945 --> 05:08:39,146 PREGNANT. 7057 05:08:39,146 --> 05:08:40,147 CULTURALLY, SOCIALLY HAVING A 7058 05:08:40,147 --> 05:08:42,416 BABY IS VERY, VERY IMPORTANT TO 7059 05:08:42,416 --> 05:08:44,685 MANY, MANY WOMEN. 7060 05:08:44,685 --> 05:08:47,287 SO LOTS OF ISSUES. 7061 05:08:47,287 --> 05:08:48,956 WE DON'T HAVE ANY QUESTIONS 7062 05:08:48,956 --> 05:08:50,424 ONLINE AND JUST A REMINDER 7063 05:08:50,424 --> 05:08:54,161 ONLINE AUDIENCE TO CLICK ON 7064 05:08:54,161 --> 05:08:55,929 "SEND FEEDBACK" IF YOU HAVE ANY 7065 05:08:55,929 --> 05:08:57,164 QUESTIONS, RIGHT? 7066 05:08:57,164 --> 05:08:59,767 THAT'S THE -- RIGHT, NANCY, 7067 05:08:59,767 --> 05:09:00,768 RIGHT. 7068 05:09:00,768 --> 05:09:02,069 SO ANYBODY IN THE ONLINE 7069 05:09:02,069 --> 05:09:04,071 AUDIENCE WHO HAS A QUESTION OR A 7070 05:09:04,071 --> 05:09:09,176 COMMENT, SEND IT O ON THE SEND 7071 05:09:09,176 --> 05:09:10,244 FEEDBACK TAB ON YOUR ZOOM. 7072 05:09:10,244 --> 05:09:10,611 OKAY. 7073 05:09:10,611 --> 05:09:14,081 ANY QUESTIONS HERE OR COMMENTS 7074 05:09:14,081 --> 05:09:19,186 FOR LYDIA? 7075 05:09:19,186 --> 05:09:19,620 OKAY. 7076 05:09:19,620 --> 05:09:21,121 WE'LL HAVE GOOD CHATS OUTSIDE OF 7077 05:09:21,121 --> 05:09:21,622 THE SESSION, LYDIA. 7078 05:09:21,622 --> 05:09:23,190 I'M GOING TO INTRODUCE OUR NEXT 7079 05:09:23,190 --> 05:09:25,826 SPEAKER, WHO IS ALSO FROM 7080 05:09:25,826 --> 05:09:26,794 JAMAICA, JAMAICA IN THE 7081 05:09:26,794 --> 05:09:28,395 CARIBBEAN THIS TIME. 7082 05:09:28,395 --> 05:09:30,330 DR. BELINDA MORRISON, WHO IS A 7083 05:09:30,330 --> 05:09:31,732 CONSULTANT UROLOGIST AT THE 7084 05:09:31,732 --> 05:09:33,600 UNIVERSITY HOSPITAL OF THE WEST 7085 05:09:33,600 --> 05:09:35,436 INDIES, AND A SENIOR LECTURER 7086 05:09:35,436 --> 05:09:37,438 AND HEAD OF THE DIVISION OF 7087 05:09:37,438 --> 05:09:39,339 UROLOGY AT THE UNIVERSITY OF THE 7088 05:09:39,339 --> 05:09:39,807 WEST INDIES. 7089 05:09:39,807 --> 05:09:41,742 SHE COMPLETED HER UNDERGRADUATE 7090 05:09:41,742 --> 05:09:43,744 AND GRADUATE AND PO POSTGRADUATE 7091 05:09:43,744 --> 05:09:44,845 TRAINING AT THE UNIVERSITY OF 7092 05:09:44,845 --> 05:09:46,847 WEST INDIES MONA CAMPUS WITH A 7093 05:09:46,847 --> 05:09:49,383 ONE-YEAR RESIDENCY AT THE 7094 05:09:49,383 --> 05:09:52,086 UNIVERSITY OF TORONTO. 7095 05:09:52,086 --> 05:09:58,459 PROSTATE CANCER AND ANDROLOGY. 7096 05:09:58,459 --> 05:10:00,761 DR. MORRISON HAS MADE MANY LOCAL 7097 05:10:00,761 --> 05:10:02,229 REGIONAL AND INTERNATIONAL 7098 05:10:02,229 --> 05:10:03,664 PRESENTATIONS TO AUDIENCES IN 7099 05:10:03,664 --> 05:10:06,567 HER FIELD OF UROLOGY, INCLUDING 7100 05:10:06,567 --> 05:10:08,669 AT SCIFF IN PREVIOUS YEARS. 7101 05:10:08,669 --> 05:10:11,138 SHE'S EXTENSIVELY INVOLVED IN 7102 05:10:11,138 --> 05:10:12,339 RESEARCH, PARTICULARLY AS IT 7103 05:10:12,339 --> 05:10:14,274 RELATES TO ANDROLOGY AND SICKLE 7104 05:10:14,274 --> 05:10:14,942 CELL DISEASE. 7105 05:10:14,942 --> 05:10:16,143 DR. MORRISON COMPLETED A 7106 05:10:16,143 --> 05:10:18,145 TWO-YEAR RESEARCH FELLOWSHIP AT 7107 05:10:18,145 --> 05:10:20,280 THE SICKLE CELL UNIT IN JAMAICA, 7108 05:10:20,280 --> 05:10:24,451 AND CURRENTLY RUNS A MONTHLY 7109 05:10:24,451 --> 05:10:25,819 VOLUNTEER CLINIC AT HER UNIT. 7110 05:10:25,819 --> 05:10:28,689 SHE IS ALSO THE PAST PRESIDENT 7111 05:10:28,689 --> 05:10:31,391 OF JAMAICA UROLOGICAL SOCIETY, 7112 05:10:31,391 --> 05:10:36,864 IMMEDIATE PAST PRESIDENT OF TH 7113 05:10:36,864 --> 05:10:37,397 THE -- AMERICAN UROLOGICAL 7114 05:10:37,397 --> 05:10:38,665 ASSOCIATION AND SEXUAL MEDICINE 7115 05:10:38,665 --> 05:10:40,934 SOCIETY OF NORTH PLAIRK. 7116 05:10:40,934 --> 05:10:43,270 WELL SUITED TO SPEAK TO US ON 7117 05:10:43,270 --> 05:10:46,607 SPERM COUNTS AND MOTILITY. 7118 05:10:46,607 --> 05:10:48,809 DR. MORRISON, SHE WILL BE 7119 05:10:48,809 --> 05:10:49,376 PRESENTING VIRTUALLY. 7120 05:10:49,376 --> 05:10:59,553 THANK YOU. 7121 05:11:31,952 --> 05:11:32,786 -- AFFECTED PATIENTS WITH 7122 05:11:32,786 --> 05:11:33,253 SICKLE CELL DISEASE. 7123 05:11:33,253 --> 05:11:35,622 AS A UROLOGIST WORKING IN 7124 05:11:35,622 --> 05:11:37,524 JAMAICA, I'VE HAD QUITE A BIT OF 7125 05:11:37,524 --> 05:11:38,325 EXPOSURE TO PATIENTS WITH SICKLE 7126 05:11:38,325 --> 05:11:40,160 CELL DISEASE FOR AT LEAST THE 7127 05:11:40,160 --> 05:11:41,695 PAST 15 YEARS, AND SO TODAY, I'D 7128 05:11:41,695 --> 05:11:43,730 LIKE TO SHARE ON SOME OF THE 7129 05:11:43,730 --> 05:11:46,233 CHALLENGES THAT THESE PATIENTS 7130 05:11:46,233 --> 05:11:47,768 FACE, SPECIFICALLY AS IT RELATES 7131 05:11:47,768 --> 05:11:56,810 TO MALE FERTILITY, AND A PATIENT 7132 05:11:56,810 --> 05:11:57,911 I SAW SEVERAL YEARS AGO. 7133 05:11:57,911 --> 05:11:59,413 THERE ARE NO DISCLOSURES TO 7134 05:11:59,413 --> 05:12:01,682 DOCUMENT THIS MORNING. 7135 05:12:01,682 --> 05:12:04,284 SO I SPEAK ABOUT A 29-YEAR-OLD 7136 05:12:04,284 --> 05:12:05,552 MALE PATIENT WITH HOMOZYGOUS 7137 05:12:05,552 --> 05:12:06,053 SICKLE CELL DISEASE WHO 7138 05:12:06,053 --> 05:12:08,021 PRESENTED TO ME AT THE CLINIC AT 7139 05:12:08,021 --> 05:12:08,722 THE SICKLE CELL UNIT. 7140 05:12:08,722 --> 05:12:11,491 HE HAD A HISTORY OF PRACTICE 7141 05:12:11,491 --> 05:12:15,662 DURING HIS TEENAGE YEARS 7142 05:12:15,662 --> 05:12:17,030 MOSTLY -- EPISODES BUT NO 7143 05:12:17,030 --> 05:12:17,497 EPISODE RECENTLY. 7144 05:12:17,497 --> 05:12:21,902 HE HAD NEVER HAD ANY INVASIVE 7145 05:12:21,902 --> 05:12:24,705 TREATMENT FOR HIS PRIAPISM, AND 7146 05:12:24,705 --> 05:12:26,773 PRETTY MUCH MOST EPISODES HAD 7147 05:12:26,773 --> 05:12:27,808 RESOLVED SPONTANEOUSLY. 7148 05:12:27,808 --> 05:12:29,743 HE DENIED ANY HISTORY OF 7149 05:12:29,743 --> 05:12:30,978 ERECTILE DYSFUNCTION. 7150 05:12:30,978 --> 05:12:32,779 HE HAD OCCASIONAL PAINFUL CRISES 7151 05:12:32,779 --> 05:12:34,915 WHICH WERE PRETTY MUCH MANAGED 7152 05:12:34,915 --> 05:12:37,317 BY OUTPATIENT MANAGEMENT WL ORAL 7153 05:12:37,317 --> 05:12:38,518 ANALGESICS, AND HE CAME TO ME 7154 05:12:38,518 --> 05:12:39,720 EXPRESSING A DESIRE TO HAVE A 7155 05:12:39,720 --> 05:12:40,821 CHILD. 7156 05:12:40,821 --> 05:12:42,522 I TOOK A DETAILED HISTORY FROM 7157 05:12:42,522 --> 05:12:46,293 HIM AND WRECK RECOGNIZED WITH S 7158 05:12:46,293 --> 05:12:47,394 PARTNER HE HAD BEEN TRYING FOR 7159 05:12:47,394 --> 05:12:49,429 AT LEAST TWO YEARS AND HAD TRIED 7160 05:12:49,429 --> 05:12:52,032 WITH PREVIOUS PARTERS IN WITH NO 7161 05:12:52,032 --> 05:12:53,967 SUCCESS. 7162 05:12:53,967 --> 05:12:55,602 NO ALCOHOL USE, NO USE OF 7163 05:12:55,602 --> 05:12:58,305 ILLICIT DRUGS, HE HAD NO PRIOR 7164 05:12:58,305 --> 05:13:00,774 PELVIC OR INGUINAL SURGERY AS A 7165 05:13:00,774 --> 05:13:02,042 CHILD, NO EXPOSURE TO RADIATION 7166 05:13:02,042 --> 05:13:05,979 OR CHEMOTHERAPY, NO EXPOSURE -- 7167 05:13:05,979 --> 05:13:07,648 NO VARICOCELES ON EXAMINATION 7168 05:13:07,648 --> 05:13:08,982 AND HE HAD A NORMAL EXAMINATION 7169 05:13:08,982 --> 05:13:13,020 IN TERMS OF GENITOURINARY -- 7170 05:13:13,020 --> 05:13:13,921 GENITAL EXAMINATION. 7171 05:13:13,921 --> 05:13:15,422 NORMAL SIZED TESTES ON EXAM AND 7172 05:13:15,422 --> 05:13:17,824 IT WAS QUITE OBVIOUS THAT THIS 7173 05:13:17,824 --> 05:13:19,126 ISSUE WITH LACK OF HAVING A 7174 05:13:19,126 --> 05:13:20,627 CHILD WAS CAUSING GREAT DISTRESS 7175 05:13:20,627 --> 05:13:23,230 FOR HIM AND HIS PARTNER. 7176 05:13:23,230 --> 05:13:26,400 SO WHAT WE WENT FIRST FOR WAS A 7177 05:13:26,400 --> 05:13:27,467 SEMEN ANALYSIS, WHICH WE THINK 7178 05:13:27,467 --> 05:13:29,436 IS A BASELINE INVESTIGATION FOR 7179 05:13:29,436 --> 05:13:30,837 ANY PATIENT WHO IS HAVING ANY 7180 05:13:30,837 --> 05:13:34,808 ISSUE WITH FERTILITY. 7181 05:13:34,808 --> 05:13:40,580 THE FIRST DEMONSTRATED NO SPERM, 7182 05:13:40,580 --> 05:13:42,950 SO AZOSPERMIC. 7183 05:13:42,950 --> 05:13:46,019 WE DECIDED TO REPEAT AND THIS 7184 05:13:46,019 --> 05:13:49,923 CONFIRMED AZOOSP ERMIA. 7185 05:13:49,923 --> 05:13:51,491 THE PRESENCE OF SICKLE CELL 7186 05:13:51,491 --> 05:13:57,431 DISEASE MAY AFFECT HIS RISK FOR 7187 05:13:57,431 --> 05:13:57,864 FERTILITY. 7188 05:13:57,864 --> 05:14:01,601 I REFERRED BOTH HIM AND HIMSELF 7189 05:14:01,601 --> 05:14:03,470 FOR CONSULTATION ABOUT POTENTIAL 7190 05:14:03,470 --> 05:14:05,172 OPTIONS FOR ASSISTED 7191 05:14:05,172 --> 05:14:05,839 REPRODUCTIVE TECHNIQUES. 7192 05:14:05,839 --> 05:14:08,642 SO THIS IS WHAT WE'RE GOING TO 7193 05:14:08,642 --> 05:14:09,343 SPEAK ABOUT THIS MORNING. 7194 05:14:09,343 --> 05:14:11,411 WE'RE GOING TO BE SPEAKING ABOUT 7195 05:14:11,411 --> 05:14:14,214 MALE REPRODUCTIVE HEALTH AND 7196 05:14:14,214 --> 05:14:15,048 SEMEN ANALYSIS IN SICKLE CELL 7197 05:14:15,048 --> 05:14:16,183 DISEASE. 7198 05:14:16,183 --> 05:14:19,052 SO MALE REPRODUCTIVE HEALTH IN 7199 05:14:19,052 --> 05:14:20,153 SICKLE CELL DISEASE HAS BEEN 7200 05:14:20,153 --> 05:14:21,555 POORLY STUDIED. 7201 05:14:21,555 --> 05:14:22,522 ANY REVIEW OF THE LITERATURE 7202 05:14:22,522 --> 05:14:24,925 WILL SHOW VERY FEW STUDIES 7203 05:14:24,925 --> 05:14:27,961 LOOKING AT THE PRESENCE OF THESE 7204 05:14:27,961 --> 05:14:29,963 ABNORMALITIES AND ETIOLOGY AND 7205 05:14:29,963 --> 05:14:30,430 MANAGEMENT. 7206 05:14:30,430 --> 05:14:32,799 AND THIS MAY BE ONE OF THE 7207 05:14:32,799 --> 05:14:34,501 REASONS, BOTH PHYSICIANS AND 7208 05:14:34,501 --> 05:14:39,172 PATIENTS PRIORITY OVER THE 7209 05:14:39,172 --> 05:14:40,807 YEARS, POTENTIALLY 7210 05:14:40,807 --> 05:14:41,842 LIFE-THREATENING OR MON 7211 05:14:41,842 --> 05:14:42,376 COMMON -- OF SICKLE CELL 7212 05:14:42,376 --> 05:14:43,143 DISEASE, THIS COULD RANGE FROM 7213 05:14:43,143 --> 05:14:48,682 THE BOTHERSOME COMPLICATIONS O 7214 05:14:48,682 --> 05:14:50,784 OF -- WHICH WE SEE OFTEN FROM 7215 05:14:50,784 --> 05:14:53,387 PAIN FROM REPETITIVE PAINFUL 7216 05:14:53,387 --> 05:14:55,655 CRISES, FROM MAJOR CHRONIC 7217 05:14:55,655 --> 05:14:58,058 INFECTIONS, PULMONARY 7218 05:14:58,058 --> 05:15:00,127 COMPLICATIONS OR OTHERS, SO WHEN 7219 05:15:00,127 --> 05:15:02,162 PATIENTS ARE SICK AND THEY HAVE 7220 05:15:02,162 --> 05:15:05,332 THESE REPEATED ILLNESSES OR 7221 05:15:05,332 --> 05:15:09,302 ADMISSION TO HOSPITAL, CERTAINLY 7222 05:15:09,302 --> 05:15:11,638 THE -- WILL NOT BE ON FERTILITY. 7223 05:15:11,638 --> 05:15:14,007 NOW THE LACK OF A PARTNER DUE TO 7224 05:15:14,007 --> 05:15:15,008 THE COMPLICATION OF SICKLE CELL 7225 05:15:15,008 --> 05:15:16,209 DISEASE MAY ALSO BE ANOTHER 7226 05:15:16,209 --> 05:15:17,077 PARTNER. 7227 05:15:17,077 --> 05:15:18,678 SO THAT HAS NOT BEEN STUDIED 7228 05:15:18,678 --> 05:15:20,213 VERY GREATLY, HOW MANY OF THESE 7229 05:15:20,213 --> 05:15:21,882 PATIENTS HAVE PARTNERS OR HAVE 7230 05:15:21,882 --> 05:15:23,350 CHALLENGES FINDING PARTNERS. 7231 05:15:23,350 --> 05:15:25,919 AND THE CHALLENGES FINDING 7232 05:15:25,919 --> 05:15:27,354 PARTNERS MAY BE BECAUSE THEY 7233 05:15:27,354 --> 05:15:30,824 SPEND SO MUCH OF THEIR TIME IN 7234 05:15:30,824 --> 05:15:31,925 THE HOSPITAL, BUT THOSE WHO 7235 05:15:31,925 --> 05:15:35,562 DEVELOP LEG ULCERS ARE OFTEN 7236 05:15:35,562 --> 05:15:36,363 DEFORMITIES WE OFTEN SEE IN 7237 05:15:36,363 --> 05:15:37,164 SICKLE CELL DISEASE, THEY MAY 7238 05:15:37,164 --> 05:15:38,665 HAVE ISSUES CONCERNING THEIR 7239 05:15:38,665 --> 05:15:39,866 BODIES, THEIR COMFORT LEVELS 7240 05:15:39,866 --> 05:15:41,902 WITH THEIR BODIES, DEPRESSION 7241 05:15:41,902 --> 05:15:43,170 RELATED TO THEIR BODIES WHICH WE 7242 05:15:43,170 --> 05:15:45,439 KNOW IS A MAJOR ISSUE, SO THAT 7243 05:15:45,439 --> 05:15:46,506 MAY EVEN AFFECT THEIR INTEREST 7244 05:15:46,506 --> 05:15:48,341 OR THEIR ABILITY TO FIND ANOTHER 7245 05:15:48,341 --> 05:15:49,543 PARTNER, LET ALONE THINK ABOUT 7246 05:15:49,543 --> 05:15:52,379 FERTILITY. 7247 05:15:52,379 --> 05:15:54,314 THERE ARE ALSO LEGITIMATE 7248 05:15:54,314 --> 05:15:55,482 CONCERNS IN SOME OF THESE 7249 05:15:55,482 --> 05:15:57,284 PATIENTS REGARDING POTENTIAL 7250 05:15:57,284 --> 05:15:58,452 GENETIC TRANSMISSION OF THE 7251 05:15:58,452 --> 05:15:59,619 SICKLE CELL GENE TO THEIR 7252 05:15:59,619 --> 05:16:01,488 CHILDREN WHEN THEY SEE SOME OF 7253 05:16:01,488 --> 05:16:02,355 THE COMPLICATIONS THEY DEVELOP, 7254 05:16:02,355 --> 05:16:04,057 THEY MAY NOT BE COMFORTABLE IN 7255 05:16:04,057 --> 05:16:05,158 HAVING CHILDREN WHO MAY 7256 05:16:05,158 --> 05:16:06,693 POTENTIALLY HAVE THESE 7257 05:16:06,693 --> 05:16:07,994 COMPLICATIONS AS WELL. 7258 05:16:07,994 --> 05:16:09,729 NOW THE MEANS OF ASSESSMENT OF 7259 05:16:09,729 --> 05:16:11,231 MALE FERTILITY MAY NOT ALWAYS BE 7260 05:16:11,231 --> 05:16:12,165 SOCIALLY ACCEPTABLE. 7261 05:16:12,165 --> 05:16:15,735 AS WE SEE, THE PRIMARY TEST TO 7262 05:16:15,735 --> 05:16:17,771 DO IS A SEMEN ANALYSIS, AND MANY 7263 05:16:17,771 --> 05:16:19,573 MEN ARE NOT COMFORTABLE WITH THE 7264 05:16:19,573 --> 05:16:21,108 MEANS AT WHICH A SEMEN ANALYSIS 7265 05:16:21,108 --> 05:16:23,243 IS DONE. 7266 05:16:23,243 --> 05:16:24,344 THERE MAY BE EMBARRASSMENT IN 7267 05:16:24,344 --> 05:16:26,079 SOME OF THE MALES IN DISCUSSING 7268 05:16:26,079 --> 05:16:27,180 THE ISSUE WITH FERTILITY WITH 7269 05:16:27,180 --> 05:16:29,116 THEIR CAREGIVERS, AND THERE MAY 7270 05:16:29,116 --> 05:16:30,450 BE LACK OF KNOWLEDGE OF THE 7271 05:16:30,450 --> 05:16:32,886 PATIENTS AND THEIR CAREGIVERS ON 7272 05:16:32,886 --> 05:16:34,354 THE FERTILITY COMPLICATIONS THAT 7273 05:16:34,354 --> 05:16:35,822 THEY ARE SEEING IN SICKLE CELL 7274 05:16:35,822 --> 05:16:41,495 DISEASE. 7275 05:16:41,495 --> 05:16:45,532 SO, WE KNOW THAT WHO SAYS HEALTH 7276 05:16:45,532 --> 05:16:47,033 IS NOT SIMPLY A STATE OF 7277 05:16:47,033 --> 05:16:48,001 PHYSICAL WELL-BEING, IT'S A 7278 05:16:48,001 --> 05:16:49,703 STATE OF PHYSICAL, MENTAL AND 7279 05:16:49,703 --> 05:16:55,041 SOCIAL WELL-BEING, AND NOT 7280 05:16:55,041 --> 05:16:56,676 SIMPLY MERELY THE ABSENCE OF 7281 05:16:56,676 --> 05:16:58,211 DISEASE OR FERTILITY. 7282 05:16:58,211 --> 05:16:59,513 SO WE HAVE TO THINK NOT JUST 7283 05:16:59,513 --> 05:17:01,681 ABOUT THEIR PHYSICAL WELL-BEING 7284 05:17:01,681 --> 05:17:03,683 BUT WE MUST THINK ABOUT THEIR 7285 05:17:03,683 --> 05:17:06,520 MENTAL, PSYCHOLOGICAL, AND THEIR 7286 05:17:06,520 --> 05:17:07,687 REPRODUCTIVE CERTAINLY COMES 7287 05:17:07,687 --> 05:17:09,289 UNDER THE UMBRELLA OF COMPLETE 7288 05:17:09,289 --> 05:17:12,025 HEALTH. 7289 05:17:12,025 --> 05:17:13,160 AND AS PATIENTS WITH SICKLE CELL 7290 05:17:13,160 --> 05:17:14,561 DISEASE ARE LIVING LONGER, MUCH 7291 05:17:14,561 --> 05:17:17,197 BETTER AND HEAL HEALTHIER LIVES, 7292 05:17:17,197 --> 05:17:18,798 FERTILITY PRESERVATION MUST BE 7293 05:17:18,798 --> 05:17:23,703 ADDRESSED IN THESE PATIENTS. 7294 05:17:23,703 --> 05:17:26,540 SO FERTILITY IS DEFINED AS THE 7295 05:17:26,540 --> 05:17:28,208 ABILITY TO CONCEIVE CHILDREN. 7296 05:17:28,208 --> 05:17:29,843 INFERTILITY IS THE FAILURE TO 7297 05:17:29,843 --> 05:17:32,412 ESTABLISH A CLINICAL PREGNANCY 7298 05:17:32,412 --> 05:17:35,448 AFTER 12 MONTHS OF REGULAR AND 7299 05:17:35,448 --> 05:17:36,349 UNPROTECTED SEXUAL INTERCOURSE. 7300 05:17:36,349 --> 05:17:39,219 IN WOMEN WHO ARE WITH AGE OF 35 7301 05:17:39,219 --> 05:17:40,687 YEARS, THE TIME SPAN IS 7302 05:17:40,687 --> 05:17:41,254 SHORTENED TO SIX MONTHS. 7303 05:17:41,254 --> 05:17:42,322 SO ESSENTIALLY IF A PATIENT 7304 05:17:42,322 --> 05:17:43,390 COMES AND SAYS THEY'RE TRYING TO 7305 05:17:43,390 --> 05:17:44,891 HAVE A CHILD AND THEY'RE HAVING 7306 05:17:44,891 --> 05:17:46,693 A CHALLENGE, ONCE THAT PATIENT 7307 05:17:46,693 --> 05:17:50,263 IS LESS THAN 35 YEARS OF AGE, 7308 05:17:50,263 --> 05:17:52,666 YOU WOULD FIND OUT IF THEY HAVE 7309 05:17:52,666 --> 05:17:54,100 BEEN TRYING FOR 12 MONTHS OR 7310 05:17:54,100 --> 05:17:55,635 MORE AND IF THEY'VE BEEN TRYING 7311 05:17:55,635 --> 05:17:57,904 FOR OVER 12 MONTHS WITHOUT ANY 7312 05:17:57,904 --> 05:18:00,340 SUCCESS, THEN WE WOULD SAY THAT 7313 05:18:00,340 --> 05:18:02,209 THEY ARE LIKELY TO HAVE 7314 05:18:02,209 --> 05:18:03,910 INFERTILITY OR SUBFERTILITY. 7315 05:18:03,910 --> 05:18:08,215 IN THE GRAND SCHEME OF THINGS, 7316 05:18:08,215 --> 05:18:09,749 FERTILITY -- INFERTILITY AFFECTS 7317 05:18:09,749 --> 05:18:11,151 MAYBE ABOUT 10% OF COUPLES 7318 05:18:11,151 --> 05:18:13,954 WORLDWIDE, AND THE MALE FACTOR 7319 05:18:13,954 --> 05:18:16,823 IS FOUND -- A SOLE MALE FACTOR 7320 05:18:16,823 --> 05:18:19,292 IS FOUND IN ABOUT 20% OF CASES, 7321 05:18:19,292 --> 05:18:20,627 ANOTHER 20 TO 30% OF CASES IS 7322 05:18:20,627 --> 05:18:21,995 COMBINED MALE AND FEMALE. 7323 05:18:21,995 --> 05:18:23,797 SO OVERALL, A MALE FACTOR IS 7324 05:18:23,797 --> 05:18:25,699 PRESENT IN APPROXIMATELY 50% OF 7325 05:18:25,699 --> 05:18:28,902 CASES. 7326 05:18:28,902 --> 05:18:30,103 AND SICKLE CELL DISEASE, NOT A 7327 05:18:30,103 --> 05:18:33,940 LOT OF DATA ON THE PREVALENCE OF 7328 05:18:33,940 --> 05:18:35,108 INFERTILITY, BUT CERTAINLY FROM 7329 05:18:35,108 --> 05:18:37,544 ONE STUDY THAT WAS REPORTED BY 7330 05:18:37,544 --> 05:18:40,480 STEVENSON, WE SEE THAT 16.9% OF 7331 05:18:40,480 --> 05:18:43,717 MALES AND 23% OF FEMALES HAVE 7332 05:18:43,717 --> 05:18:44,784 SELF-REPORTED INFERTILITY, AND 7333 05:18:44,784 --> 05:18:47,487 CERTAINLY THIS MAY BE AN 7334 05:18:47,487 --> 05:18:48,788 UNDERESTIMATE AS MORE PATIENTS 7335 05:18:48,788 --> 05:18:50,624 ARE EVALUATED AND DIFFERENT 7336 05:18:50,624 --> 05:18:54,461 TYPES OF STUDIES ARE DONE, WE 7337 05:18:54,461 --> 05:18:55,862 MAY SEE THE RATES ARE MUCH 7338 05:18:55,862 --> 05:18:56,196 HIGHER. 7339 05:18:56,196 --> 05:18:58,098 SO DEFINITELY WE CAN SEE 7340 05:18:58,098 --> 05:18:59,366 STARTING WITH THESE RATES WHICH 7341 05:18:59,366 --> 05:19:02,002 I BELIEVE ARE UNDERREPORTED, 7342 05:19:02,002 --> 05:19:02,636 THEY'RE DEFINITELY MORE THAN 7343 05:19:02,636 --> 05:19:04,537 WHAT IS CONSIDERED IN THE NORMAL 7344 05:19:04,537 --> 05:19:05,639 POPULATION. 7345 05:19:05,639 --> 05:19:12,012 SO WHAT TYPE OF -- WE CAN LOOK 7346 05:19:12,012 --> 05:19:13,313 AT MEN IN FERTILITY AFFECTED 7347 05:19:13,313 --> 05:19:17,817 FROM A CENTRAL LEVEL, THE 7348 05:19:17,817 --> 05:19:18,818 HYPOTHALAMUS, PITUITARY LEVEL, 7349 05:19:18,818 --> 05:19:22,355 IN TERMS OF HORMONAL CAUSES. 7350 05:19:22,355 --> 05:19:26,126 WE MAY SEE IT BE DIRECTLY AT A 7351 05:19:26,126 --> 05:19:29,296 LEVEL OF THE GONADS, OR AT THE 7352 05:19:29,296 --> 05:19:33,967 LEVEL OF THE TUBES WHERE SPERM 7353 05:19:33,967 --> 05:19:34,334 IS RELEASED. 7354 05:19:34,334 --> 05:19:36,303 SO THE CENTRAL LEVEL HORMONAL 7355 05:19:36,303 --> 05:19:39,739 PROBLEMS MAY BE PITUITARY 7356 05:19:39,739 --> 05:19:44,444 PROBLEMS, THEY MAY BE DUE TO A 7357 05:19:44,444 --> 05:19:48,081 LACK OF FSH OR DUE TO ANABOLIC 7358 05:19:48,081 --> 05:19:49,783 STEROID USE. 7359 05:19:49,783 --> 05:19:51,418 AT THE LEVEL OF THE GONADS, 7360 05:19:51,418 --> 05:19:53,286 WHERE THERE MAY BE TOXICITY TO 7361 05:19:53,286 --> 05:19:55,488 THE DOUGH IN ADDITIONS, EITHER 7362 05:19:55,488 --> 05:19:59,526 FROM EXPOSURE TO CHEMOTHERAPY OR 7363 05:19:59,526 --> 05:20:00,727 RADIATION, EITHER FROM TRAUMA TO 7364 05:20:00,727 --> 05:20:04,831 THE TESTES, EITHER SEVERE 7365 05:20:04,831 --> 05:20:06,499 INFECTIONS, SEXUALLY TRANSMITTED 7366 05:20:06,499 --> 05:20:07,901 INFECTIONS, CONGENITAL REASONS, 7367 05:20:07,901 --> 05:20:11,871 MAYBE AN UNDESCENDED TESTES, 7368 05:20:11,871 --> 05:20:13,173 TORSION THAT IS NOT QUICKLY 7369 05:20:13,173 --> 05:20:15,809 TREATED RESULTING IN EITHER 7370 05:20:15,809 --> 05:20:18,845 ISCHEMIA TO THE TESTES OR AN 7371 05:20:18,845 --> 05:20:20,046 ORCHIECTOMY. 7372 05:20:20,046 --> 05:20:26,186 GENETIC OR HO -- MIGHT BE SEEN N 7373 05:20:26,186 --> 05:20:30,890 QUITE A FEW UNKNOWN CAUSES OF -- 7374 05:20:30,890 --> 05:20:35,795 THERE ARE ALSO CASES RELATED TO 7375 05:20:35,795 --> 05:20:37,864 VASECTOMY, WHICH IS A REQUEST A 7376 05:20:37,864 --> 05:20:40,800 PATIENT WOULD MAKE BUT 7377 05:20:40,800 --> 05:20:42,202 SOMETIMES -- PATIENTS MAY 7378 05:20:42,202 --> 05:20:45,839 DEVELOP ANTISTERM ANTIBODIES, IN 7379 05:20:45,839 --> 05:20:48,575 IN PERSONS WHO HAVE HAD 7380 05:20:48,575 --> 05:20:50,477 VASECTOMY OR INJURIES TO THE 7381 05:20:50,477 --> 05:20:53,179 TESTES, AND OF COURSE SEXUAL 7382 05:20:53,179 --> 05:20:56,116 PROBLEMS, ERECTILE DYSFUNCTION, 7383 05:20:56,116 --> 05:21:00,186 RETROGRADE OR ANEJACULATION, 7384 05:21:00,186 --> 05:21:02,322 INFREQUENT INTERCOURSE, 7385 05:21:02,322 --> 05:21:03,957 RETROGRADE EJACULATION, AND 7386 05:21:03,957 --> 05:21:08,128 NEUROLOGICAL PROBLEMS AS WE SEE 7387 05:21:08,128 --> 05:21:09,262 IN -- OR SOME MEDICATIONS. 7388 05:21:09,262 --> 05:21:12,632 THERE ARE A WHOLE HOST OF CAUSES 7389 05:21:12,632 --> 05:21:13,700 OF MALE INFERTILITY. 7390 05:21:13,700 --> 05:21:18,171 AS WE MENTIONED BEFORE, THE 7391 05:21:18,171 --> 05:21:20,306 BASIC -- IS A THOROUGH 7392 05:21:20,306 --> 05:21:21,908 REPRODUCTIVE HISTORY, BUT AT 7393 05:21:21,908 --> 05:21:22,876 LEAST ONE SEMEN ANALYSIS. 7394 05:21:22,876 --> 05:21:24,511 THIS IS USUALLY DONE AFTER A 7395 05:21:24,511 --> 05:21:26,446 PERIOD OF ABSTINENCE FOR TWO TO 7396 05:21:26,446 --> 05:21:30,383 THREE DAYS, AND THEN BY 7397 05:21:30,383 --> 05:21:32,585 MASTURBATION, PATIENT PRODUCES A 7398 05:21:32,585 --> 05:21:33,987 SAMPLE. 7399 05:21:33,987 --> 05:21:35,522 A LOT OF PATIENTS ARE NOT 7400 05:21:35,522 --> 05:21:36,756 COMFORTABLE WITH THIS, I WILL 7401 05:21:36,756 --> 05:21:38,491 SAY, IN MY EXPERIENCE, AND SOME 7402 05:21:38,491 --> 05:21:40,794 PATIENTS PREFER TO USE THE 7403 05:21:40,794 --> 05:21:42,662 ANTISPERM CIDAL CONDOMS, BUT 7404 05:21:42,662 --> 05:21:44,431 EVEN SO, SOMETIMES THAT'S NOT 7405 05:21:44,431 --> 05:21:47,934 CONVENIENT FOR THEM. 7406 05:21:47,934 --> 05:21:50,804 WHAT DOES WHO SAY THE REFERENCE 7407 05:21:50,804 --> 05:21:53,339 VALUES FOR NORMAL SEMEN ANALYSIS 7408 05:21:53,339 --> 05:21:53,673 ARE? 7409 05:21:53,673 --> 05:21:56,876 SO THERE HAVE BEEN A CHANGE OVER 7410 05:21:56,876 --> 05:22:00,480 THE YEARS IN TERMS OF WHAT ARE 7411 05:22:00,480 --> 05:22:01,047 CONSIDERED NORMAL REFERENCE 7412 05:22:01,047 --> 05:22:01,915 RANGES FOR ANALYSIS OF THE 7413 05:22:01,915 --> 05:22:02,382 SEMEN. 7414 05:22:02,382 --> 05:22:03,349 SO MOST PEOPLE WHEN THEY THINK 7415 05:22:03,349 --> 05:22:05,718 ABOUT A SEMEN ANALYSIS, THEY 7416 05:22:05,718 --> 05:22:07,020 SIMPLY THINK OF WHAT IS CALLED A 7417 05:22:07,020 --> 05:22:09,255 SPERM COUNT, BUT WE HAVE VARIOUS 7418 05:22:09,255 --> 05:22:10,190 THINGS WE LOOK AT. 7419 05:22:10,190 --> 05:22:11,758 THE VOLUME CAN GIVE US A PICTURE 7420 05:22:11,758 --> 05:22:13,893 AS TO WHETHER THERE IS AN 7421 05:22:13,893 --> 05:22:16,830 OBSTRUCTIVE CAUSE SUCH AS A 7422 05:22:16,830 --> 05:22:17,964 NON-OBSTRUCTIVE OR OR 7423 05:22:17,964 --> 05:22:21,868 OBSTRUCTIVE CAUSE, UNOBSTRUCTIVE 7424 05:22:21,868 --> 05:22:24,838 CAUSE, ONE MAY SEE SOMEONE WHO 7425 05:22:24,838 --> 05:22:28,441 HAS HAD PREVIOUS TESTICULAR OR 7426 05:22:28,441 --> 05:22:30,510 GONADAL -- INGUINAL SURGERY, 7427 05:22:30,510 --> 05:22:36,783 PERHAPS AS A CHILD AND THE 7428 05:22:36,783 --> 05:22:38,051 SPERMATIC CORD HAS BEEN LIGATED 7429 05:22:38,051 --> 05:22:39,919 OR TIED OFF. 7430 05:22:39,919 --> 05:22:41,221 OBSTRUCTIVE CAUSES MAY BE SEEN 7431 05:22:41,221 --> 05:22:49,095 IN PERSONS WHO'VE HAD 7432 05:22:49,095 --> 05:22:50,396 EPIDIDIMITIS IN THE PACE AND 7433 05:22:50,396 --> 05:22:52,398 OTHER CAUSES THAT CAN LEAD TO 7434 05:22:52,398 --> 05:22:52,799 LOW VOLUME. 7435 05:22:52,799 --> 05:22:54,434 SO WE LOOK AT THE VOLUME, THE 7436 05:22:54,434 --> 05:22:56,169 SPERM CONCENTRATION, WHAT 7437 05:22:56,169 --> 05:22:57,837 EVERYONE CALLS A COUNT. 7438 05:22:57,837 --> 05:23:05,078 AND IN 1990 M 1999, THIS SHIFTEN 7439 05:23:05,078 --> 05:23:06,679 IN 2010 TO 50 MILLION, AND THE 7440 05:23:06,679 --> 05:23:08,948 MOST RECENT UPDATED VERSION OF 7441 05:23:08,948 --> 05:23:11,384 THE WHO SUGGESTS 60 MILLION AS A 7442 05:23:11,384 --> 05:23:13,119 MINIMUM FOR THE CONCENTRATION. 7443 05:23:13,119 --> 05:23:16,656 FOR THE TOTAL AT LEAST GREATER 7444 05:23:16,656 --> 05:23:19,259 THAN 50% WERE CONSIDERED NORMAL, 7445 05:23:19,259 --> 05:23:20,326 THEN IT WAS SHIFTED DOWN TO 40, 7446 05:23:20,326 --> 05:23:25,231 THEN IT INCREASED TO 42. 7447 05:23:25,231 --> 05:23:32,438 AND FOR NORMOZOOSPERMIA, THERE 7448 05:23:32,438 --> 05:23:35,275 WAS MORE, BUT WE'LL FOCUS MAIN 7449 05:23:35,275 --> 05:23:43,349 LEA ON CON SIN TRAIT 16 TRAITIO- 7450 05:23:43,349 --> 05:23:45,652 STUDIES HAVE DOCUMENTED THAT 7451 05:23:45,652 --> 05:23:47,720 MALES AND FEMALES WITH SICKLE 7452 05:23:47,720 --> 05:23:50,390 CELL DISEASE HAVE DELAYED 7453 05:23:50,390 --> 05:23:54,093 PUBERTY. 7454 05:23:54,093 --> 05:23:55,395 AND PUBLISHED IN THE NEW ENGLAND 7455 05:23:55,395 --> 05:23:57,463 JOURNAL IN 1984 SUGGESTS THIS 7456 05:23:57,463 --> 05:23:59,132 MAY BE A CONSTITUTIONAL DELAY 7457 05:23:59,132 --> 05:24:01,601 SINCE YES THEY DO HAVE A DELAYED 7458 05:24:01,601 --> 05:24:04,237 PUBERTY, MAYBE BY TWO YEARS OR 7459 05:24:04,237 --> 05:24:07,307 MORE, THAN THE RISK OF THE 7460 05:24:07,307 --> 05:24:11,678 ADOLESCENT NONE SICKLE CELL 7461 05:24:11,678 --> 05:24:13,746 COHORTS, HOWEVER, THINGS SEEM TO 7462 05:24:13,746 --> 05:24:16,149 NORMALIZE AFTER. 7463 05:24:16,149 --> 05:24:17,917 OTHERS THOUGHT IT MAY BE DUE TO 7464 05:24:17,917 --> 05:24:19,752 THE CHRONIC ANEMIA, CHRONIC 7465 05:24:19,752 --> 05:24:20,653 DISEASE, AND OTHERS HAVE THOUGHT 7466 05:24:20,653 --> 05:24:24,490 IT MAY BE ENDOCRINE-RELATED 7467 05:24:24,490 --> 05:24:26,159 WHERE THEIR IS INCREASE IN 7468 05:24:26,159 --> 05:24:27,126 HORMONES AND THIS HAS BEEN 7469 05:24:27,126 --> 05:24:29,262 DOCUMENTED IN LOCAL STUDIES IN 7470 05:24:29,262 --> 05:24:32,332 JAMAICA THAT IN ADOLESCENTS, 7471 05:24:32,332 --> 05:24:39,272 THERE ARE HIGHER LEVELS THESE 7472 05:24:39,272 --> 05:24:40,607 GONADOTROPINS SUGGESTING AN 7473 05:24:40,607 --> 05:24:41,774 ENDOCRINE CAUSE BUT WHAT WE'RE 7474 05:24:41,774 --> 05:24:44,510 NOT SURE OF THE EXACT CAUSE OF 7475 05:24:44,510 --> 05:24:47,246 THE DELAY, AND IF IT CONTINUES 7476 05:24:47,246 --> 05:24:50,183 INTO ADULTHOOD AND HOW IT 7477 05:24:50,183 --> 05:24:51,384 AFFECTS THEM, PARTICULARLY THE 7478 05:24:51,384 --> 05:24:52,385 MEN. 7479 05:24:52,385 --> 05:24:54,487 SO LET'S LOOK AT SOME OF THE 7480 05:24:54,487 --> 05:24:56,356 STUDIES THAT HAVE BEEN 7481 05:24:56,356 --> 05:24:58,191 PUBLISHED. 7482 05:24:58,191 --> 05:25:00,026 IN AN EXTENSIVE SEARCH OF THE 7483 05:25:00,026 --> 05:25:01,995 LITERATURE, WHAT I FOUND WERE 7484 05:25:01,995 --> 05:25:02,895 SEVEN PUBLISHED PAPERS LOOKING 7485 05:25:02,895 --> 05:25:04,731 AT SEMEN ANALYSIS AND SICKLE 7486 05:25:04,731 --> 05:25:06,599 CELL DISEASE OVER THE YEARS. 7487 05:25:06,599 --> 05:25:09,769 FIRLS PUBLISHED PAPER WAS IN 7488 05:25:09,769 --> 05:25:12,005 1974 BY FRIEDMAN, AND HE STUDIED 7489 05:25:12,005 --> 05:25:15,475 EIGHT YOUNG BLACK MEN, AGE RANGE 7490 05:25:15,475 --> 05:25:17,777 WAS FROM 22 TO 34 YEARS, WHO HAD 7491 05:25:17,777 --> 05:25:19,879 SICKLE CELL DISEASE. 7492 05:25:19,879 --> 05:25:25,885 SEVEN HAD HOMOZYGOUS SICKLE CELL 7493 05:25:25,885 --> 05:25:29,055 DISEASE, ONE HAD S BETA THAL. 7494 05:25:29,055 --> 05:25:33,326 THEY TOOK A HISTORY ON DISEASE 7495 05:25:33,326 --> 05:25:35,828 SEVERITY, ONSET OF PUBERTY, 7496 05:25:35,828 --> 05:25:38,564 SEXUAL HISTORY AND PATERNITY. 7497 05:25:38,564 --> 05:25:44,904 THEY ALSO EXAMINED THEIR FSH, 7498 05:25:44,904 --> 05:25:50,576 THREE OF THESE FOUR PATIENTS HAD 7499 05:25:50,576 --> 05:25:52,145 OLIGOSPERMOUS, LESS THAN 7500 05:25:52,145 --> 05:25:53,446 20 MILLION PER ML. 7501 05:25:53,446 --> 05:25:54,781 SPERM CONCENTRATION, SORRY. 7502 05:25:54,781 --> 05:26:01,621 BUT THEY ALL HAD NORMAL 7503 05:26:01,621 --> 05:26:04,824 TESTOSTERONE FOR THEIR AGE. 7504 05:26:04,824 --> 05:26:07,593 LUTEINIZING HORMONE, FSH 7505 05:26:07,593 --> 05:26:08,861 REGULATOR HORMONE FOR SPERM 7506 05:26:08,861 --> 05:26:11,297 PRODUCTION IN A MALE. 7507 05:26:11,297 --> 05:26:18,271 FSH WAS NORMAL BUT LHIF WE LOOK 7508 05:26:18,271 --> 05:26:22,775 AT THE TABLE FROM THIS PAPER, WE 7509 05:26:22,775 --> 05:26:26,579 SEE PATIENTS NUMBER ONE, TWO, 7510 05:26:26,579 --> 05:26:29,782 THREE AND SIX HAD SEMEN ANALYSIS 7511 05:26:29,782 --> 05:26:31,284 DONE, AND HERE AT THE BOTTOM, 7512 05:26:31,284 --> 05:26:32,151 THEY'LL TELL YOU WHAT THE 7513 05:26:32,151 --> 05:26:33,586 REFERENCE RANGE IS AT THAT TIME. 7514 05:26:33,586 --> 05:26:35,121 NORMAL WOULD HAVE BEEN GREATER 7515 05:26:35,121 --> 05:26:36,355 THAN 20 MILLION AND WHAT WE SEE 7516 05:26:36,355 --> 05:26:38,991 IS PATIENT ONE HAD A COUNT OF 7517 05:26:38,991 --> 05:26:39,926 2 MILLION, PATIENT TWO HAD A 7518 05:26:39,926 --> 05:26:42,228 COUNT OF 14.2 MILLION, PATIENT 7519 05:26:42,228 --> 05:26:44,464 THREE HAD 8.8. 7520 05:26:44,464 --> 05:26:48,167 ONLY PATIENT SIX WHO HAD A 7521 05:26:48,167 --> 05:26:51,904 NORMAL SPERM CONCENTRATION AND 7522 05:26:51,904 --> 05:26:52,205 52 MILLION. 7523 05:26:52,205 --> 05:26:55,708 WE SEE THAT MOTILITY WAS -- IN 7524 05:26:55,708 --> 05:26:59,645 ONLY ONE PATIENT WAS 30 TO 50%. 7525 05:26:59,645 --> 05:27:00,980 VOLUME AT THAT TIME WAS 7526 05:27:00,980 --> 05:27:03,483 CONSIDERED NORMAL IF IT WAS 3 TO 7527 05:27:03,483 --> 05:27:05,918 5 MLs AND IT WAS LOWER IN 7528 05:27:05,918 --> 05:27:10,056 PATIENT ONE AND PATIENT SIX. 7529 05:27:10,056 --> 05:27:12,125 SO ESSENTIALLY WE SEE THERE ARE 7530 05:27:12,125 --> 05:27:13,226 ABNORMAL PARAMETERS IN THREE OF 7531 05:27:13,226 --> 05:27:15,528 THESE FOUR PATIENTS. 7532 05:27:15,528 --> 05:27:16,529 BUT OF COURSE THIS IS A SMALL 7533 05:27:16,529 --> 05:27:19,465 CASE SERIES, ONLY FOUR PATIENTS. 7534 05:27:19,465 --> 05:27:21,000 THOUGH THEY SUGGESTED THAT THEY 7535 05:27:21,000 --> 05:27:23,302 COLLECTED DATA ON THEIR HISTORY 7536 05:27:23,302 --> 05:27:29,208 AND SEXUAL HISTORY, THERE WAS NO 7537 05:27:29,208 --> 05:27:31,811 DOCUMENTATION OF OTHER POSSIBLE 7538 05:27:31,811 --> 05:27:34,680 CAUSES OF SUBFERTILITY AND 7539 05:27:34,680 --> 05:27:39,252 AUTHORS POSTULATED ISCHEMIA 7540 05:27:39,252 --> 05:27:41,888 SECONDARY TO SICKLING WAS A 7541 05:27:41,888 --> 05:27:42,421 CAUSE. 7542 05:27:42,421 --> 05:27:44,390 IF IT WAS A PRIMARY CAUSE, FSH 7543 05:27:44,390 --> 05:27:47,927 LEVEL WOS HAVE BEENS WOULD HAVED 7544 05:27:47,927 --> 05:27:49,762 THIS WAS NOT THE CASE. 7545 05:27:49,762 --> 05:27:51,164 THE SECOND PAPER PUBLISHED WAS 7546 05:27:51,164 --> 05:27:53,299 IN 1980, SMALL CASE SERIES AS 7547 05:27:53,299 --> 05:27:53,800 WELL. 7548 05:27:53,800 --> 05:27:54,367 PATIENTS WITH SICKLE CELL 7549 05:27:54,367 --> 05:27:56,435 DISEASE OR SEMEN ANALYSIS WERE 7550 05:27:56,435 --> 05:27:56,769 REPORTED. 7551 05:27:56,769 --> 05:27:58,504 WHAT THEY SAW WAS THERE WAS 7552 05:27:58,504 --> 05:28:00,506 REDUCED FORWARD PROGRESSION, SO 7553 05:28:00,506 --> 05:28:01,474 MOTILITY WAS AFFECTED AND 7554 05:28:01,474 --> 05:28:03,342 MORPHOLOGY HAD A STRESS PATTERN, 7555 05:28:03,342 --> 05:28:06,379 AND BASED ON THIS PATTERN, WHICH 7556 05:28:06,379 --> 05:28:07,914 THE AUTHOR SAID IT MIMICKED WHAT 7557 05:28:07,914 --> 05:28:10,983 WE SEE IN VARICOCELES, THEY 7558 05:28:10,983 --> 05:28:13,286 THOUGHT A TESTY CAL HYPOXIA WAS 7559 05:28:13,286 --> 05:28:15,788 A CAUSE, AGAIN SUGGESTING A 7560 05:28:15,788 --> 05:28:22,395 PRIMARY CAUSE WAS THE RESULT. 7561 05:28:22,395 --> 05:28:23,396 THIRD PAPER PUBLISHED IN THE 7562 05:28:23,396 --> 05:28:29,836 LANCET IN 1981, 40 -- MEAN AGE 7563 05:28:29,836 --> 05:28:31,137 OF 20 YEARS, AND THEY WERE SEEN 7564 05:28:31,137 --> 05:28:33,372 IN AN OUTPATIENT DEPARTMENT IN 7565 05:28:33,372 --> 05:28:33,906 NIGERIA. 7566 05:28:33,906 --> 05:28:36,075 ALL PATIENTS HE TIME WERE IN 7567 05:28:36,075 --> 05:28:37,176 STEADY STATE OF THE DISEASE, AND 7568 05:28:37,176 --> 05:28:39,212 THEY TOOK A HISTORY ON THEIR 7569 05:28:39,212 --> 05:28:40,546 AGE, MARITAL STATUS, SEXUAL 7570 05:28:40,546 --> 05:28:42,715 EXPERIENCE AND WHETHER THEY'D 7571 05:28:42,715 --> 05:28:44,417 FATHERED CHILDREN OR NOT, BUT 7572 05:28:44,417 --> 05:28:46,118 NONE OF THIS WAS EVER CONFIRMED 7573 05:28:46,118 --> 05:28:46,986 OR CORROBORATED. 7574 05:28:46,986 --> 05:28:49,722 TWO SEMEN ANALYSES WERE DONE IN 7575 05:28:49,722 --> 05:28:52,658 EACH PATIENT AFTER A PERIOD OF 7576 05:28:52,658 --> 05:28:52,959 ABSTINENCE. 7577 05:28:52,959 --> 05:28:54,160 HOWEVER OF THE 40 PATIENTS, ONLY 7578 05:28:54,160 --> 05:28:56,195 23 PROVIDED SAMPLES FOR SEMEN, 7579 05:28:56,195 --> 05:28:58,164 AND THERE WERE 25 MALE CONTROLS 7580 05:28:58,164 --> 05:29:00,867 AND THESE CONTROLS WERE PERSONS 7581 05:29:00,867 --> 05:29:03,436 WHO HAD WIVES OR PARTNERS 7582 05:29:03,436 --> 05:29:05,304 ATTENDING AN ANTENATAL CLINIC AT 7583 05:29:05,304 --> 05:29:06,906 THE TIME. 7584 05:29:06,906 --> 05:29:09,909 OF THE PATIENTS, FOUR WERE 7585 05:29:09,909 --> 05:29:11,744 MARRIED WITH NO CHILDREN IN 7586 05:29:11,744 --> 05:29:12,278 WEDLOCK, SO THESE WERE THE 7587 05:29:12,278 --> 05:29:14,046 PATIENTS WITH SICKLE CELL 7588 05:29:14,046 --> 05:29:14,313 DISEASE. 7589 05:29:14,313 --> 05:29:16,349 FOUR WERE MARRIED BUT NO 7590 05:29:16,349 --> 05:29:18,117 CHILDREN IN WEDLOCK. 7591 05:29:18,117 --> 05:29:19,418 BUT THREE OF THESE REPORTED THAT 7592 05:29:19,418 --> 05:29:20,720 THEY HAD CHILDREN OUTSIDE OF 7593 05:29:20,720 --> 05:29:25,124 WEDLOCK. 7594 05:29:25,124 --> 05:29:30,930 36 WERE UNMA UNMARRIED. 7595 05:29:30,930 --> 05:29:38,304 10 HAD HISTORY OF COITUS, AND 7596 05:29:38,304 --> 05:29:40,106 ONE CHILD OF THE 36 UNMARRIED. 7597 05:29:40,106 --> 05:29:41,173 NO PATIENT WITH SICKLE CELL 7598 05:29:41,173 --> 05:29:42,975 DISEASE HAD A SEMEN ANALYSIS 7599 05:29:42,975 --> 05:29:44,944 THAT WAS NORMAL FROM THIS STUDY. 7600 05:29:44,944 --> 05:29:46,145 SO THE ABNORMALITIES WERE EITHER 7601 05:29:46,145 --> 05:29:49,215 IN THE CONCENTRATION WHICH WAS 7602 05:29:49,215 --> 05:29:51,884 LOWER, THE TOTAL COUNT, THE 7603 05:29:51,884 --> 05:29:54,754 MOTILITY, AND THE MORPHOLOGY. 7604 05:29:54,754 --> 05:29:55,755 AND THE CAUSE AGAIN WAS 7605 05:29:55,755 --> 05:29:58,691 SUGGESTED TO BE POTENTIALLY 7606 05:29:58,691 --> 05:30:00,660 PRIMARY SIMPLY BECAUSE THIS SAME 7607 05:30:00,660 --> 05:30:02,628 GROUP HAD STUDIED SEVERAL OTHER 7608 05:30:02,628 --> 05:30:03,462 PATIENTS WITH SICKLE CELL 7609 05:30:03,462 --> 05:30:05,131 DISEASE AND THEY LOOKED AT 7610 05:30:05,131 --> 05:30:07,800 THINGS LIKE THE FSH, LH AND 7611 05:30:07,800 --> 05:30:08,534 TESTOSTERONE, AND WHAT THEY 7612 05:30:08,534 --> 05:30:10,403 FOUND IN THAT STUDY, WHICH WAS 7613 05:30:10,403 --> 05:30:13,372 PUBLISHED IN A MEDICAL JOURNAL 7614 05:30:13,372 --> 05:30:16,409 IN 1987, WAS THAT THEY HAD LOWER 7615 05:30:16,409 --> 05:30:19,812 TESTOSTERONE LEVELS AND ELEVATED 7616 05:30:19,812 --> 05:30:21,147 FSH LEVELS. 7617 05:30:21,147 --> 05:30:23,983 AND SO IT WAS THOUGHT THAT THE 7618 05:30:23,983 --> 05:30:25,952 CAUSE WAS PRIMARY. 7619 05:30:25,952 --> 05:30:27,620 SO THOUGH THE FSH LEVELS WERE 7620 05:30:27,620 --> 05:30:29,188 NOT DONE IN THIS PARTICULAR 7621 05:30:29,188 --> 05:30:32,191 STUDY GROUP, IN ANOTHER STUDY 7622 05:30:32,191 --> 05:30:35,261 FROM THE SAME AUTHORS, THEY SAW 7623 05:30:35,261 --> 05:30:37,129 THAT FSH LEVELS WERE ELEVATED. 7624 05:30:37,129 --> 05:30:40,099 SO THEY POSTULATED THIS MAY BE A 7625 05:30:40,099 --> 05:30:40,733 PRIMARY FAILURE. 7626 05:30:40,733 --> 05:30:43,402 WE HAD ANOTHER STUDY PUBLISHED 7627 05:30:43,402 --> 05:30:45,771 IN 1988, WHERE WE HAD 25 7628 05:30:45,771 --> 05:30:47,306 PATIENTS WITH SICKLE CELL ANEMIA 7629 05:30:47,306 --> 05:30:51,143 COMPARED TO 25 WITH HBAA, AND 7630 05:30:51,143 --> 05:30:53,746 ALL PATIENTS WITH SICKLE CELL 7631 05:30:53,746 --> 05:30:57,383 DISEASE HAD EITHER -- AN 7632 05:30:57,383 --> 05:30:59,118 ABNORMALITY IN EITHER EJACULATE 7633 05:30:59,118 --> 05:31:00,619 VOLUME, SPERM DENSITY OR SPERM 7634 05:31:00,619 --> 05:31:01,754 MORPHOLOGY. 7635 05:31:01,754 --> 05:31:02,321 AND IT WAS SIGNIFICANTLY 7636 05:31:02,321 --> 05:31:05,691 REDUCED. 7637 05:31:05,691 --> 05:31:06,792 AGAIN THEY POSTULATED THAT IT 7638 05:31:06,792 --> 05:31:11,931 MAY BE A PRIMARY DYSFUNCTION AS 7639 05:31:11,931 --> 05:31:14,367 WELL AS -- THEY FOUND VOLUME OF 7640 05:31:14,367 --> 05:31:16,102 SEMEN WAS LOWERED AND WE KNOW 7641 05:31:16,102 --> 05:31:18,204 THAT VOLUME COMES PRIMARILY FROM 7642 05:31:18,204 --> 05:31:20,840 PROSTATE AND SEMINAL VESICLES SO 7643 05:31:20,840 --> 05:31:23,709 THEY FIGURED THAT IT WAS A 7644 05:31:23,709 --> 05:31:30,616 GENERAL PRIMARY CAUSE. 7645 05:31:30,616 --> 05:31:33,119 IN 1995, PAPER LOOKING AT 7646 05:31:33,119 --> 05:31:33,886 22 PATIENTS WITH SICKLE CELL 7647 05:31:33,886 --> 05:31:35,621 DISEASE ALL STEADY STATE, 20 7648 05:31:35,621 --> 05:31:36,722 CONTROLS, THESE WERE YOUNG 7649 05:31:36,722 --> 05:31:38,457 PERSONS BETWEEN THE AGES OF 18 7650 05:31:38,457 --> 05:31:40,259 TO 40 YEARS AND EXCLUDED 7651 05:31:40,259 --> 05:31:41,427 ANYTHING THAT WOULD BE 7652 05:31:41,427 --> 05:31:42,762 CONSIDERED A CONFOUNDER OR 7653 05:31:42,762 --> 05:31:44,597 SOMETHING THAT COULD POTENTIALLY 7654 05:31:44,597 --> 05:31:46,132 ALSO CAUSE ABNORMAL FERTILITY IN 7655 05:31:46,132 --> 05:31:46,999 THESE PATIENTS. 7656 05:31:46,999 --> 05:31:48,868 THEY TOOK A HISTORY LOOKING AT 7657 05:31:48,868 --> 05:31:50,002 THEIR SEXUAL FUNCTION, MARITAL 7658 05:31:50,002 --> 05:31:51,704 STATUS AND PATERNITY. 7659 05:31:51,704 --> 05:31:53,606 PATIENTS WERE WEIGHED AND 7660 05:31:53,606 --> 05:31:56,776 MEASURED AND TESTOSTERONE, FSH, 7661 05:31:56,776 --> 05:31:59,412 LH AND PROLACTIN WERE MEASURED 7662 05:31:59,412 --> 05:32:00,846 AND TWO SEMEN ANALYSIS DONE 7663 05:32:00,846 --> 05:32:02,515 AFTER PERIOD OF ABSTINENCE. 7664 05:32:02,515 --> 05:32:04,083 WHAT DID THEY FIND? 7665 05:32:04,083 --> 05:32:04,884 WE LOOK AT THE SICKLE CELL 7666 05:32:04,884 --> 05:32:06,819 PATIENTS VERSUS CONTROL, YOU SEE 7667 05:32:06,819 --> 05:32:07,353 PATIENTS WITH SICKLE CELL 7668 05:32:07,353 --> 05:32:10,022 DISEASE HAD SIGNIFICANTLY LOWER 7669 05:32:10,022 --> 05:32:12,958 SPERM DENSITY, SO THIS WOULD BE 7670 05:32:12,958 --> 05:32:15,428 CONSIDERED CONCENTRATIONS -- 7671 05:32:15,428 --> 05:32:16,929 DIFFERENCE IN TERMINOLOGY AT THE 7672 05:32:16,929 --> 05:32:19,765 TIME, CONCENTRATION WAS 21.4, 7673 05:32:19,765 --> 05:32:21,867 COMPARED TO 69 IN THE CONTROLS. 7674 05:32:21,867 --> 05:32:23,469 OF COURSE WE SEE THE STANDARD 7675 05:32:23,469 --> 05:32:24,837 DEVIATION IS QUITE HIGH, SO WE 7676 05:32:24,837 --> 05:32:27,440 HAD A WIDE RANGE. 7677 05:32:27,440 --> 05:32:30,943 MOTILITY WAS LESS, 42% VERSUS 7678 05:32:30,943 --> 05:32:32,945 73% OF THE CONTROLS, AND 7679 05:32:32,945 --> 05:32:36,415 MORPHOLOGY WAS ALSO MUCH LOWER 7680 05:32:36,415 --> 05:32:39,418 AS WELL AS TESTICULAR VOLUME. 7681 05:32:39,418 --> 05:32:40,986 10 OF THE 20 PATIENTS IN THIS 7682 05:32:40,986 --> 05:32:42,688 STUDY EITHER HAD AN ISSUE WITH 7683 05:32:42,688 --> 05:32:47,226 EITHER LOW LIBIDO, ERECTILE 7684 05:32:47,226 --> 05:32:49,295 DYSFUNCTION OR PRIAPISM, ALL 7685 05:32:49,295 --> 05:32:50,596 THINGS WE KNOW CAN AFFECT 7686 05:32:50,596 --> 05:32:51,363 FERTILITY. 7687 05:32:51,363 --> 05:32:52,565 ONLY ONE CONTROL HAD AN ISSUE 7688 05:32:52,565 --> 05:32:59,405 WITH ERECTILE DYSFUNCTION. 7689 05:32:59,405 --> 05:33:00,639 ONLY ONE PATIENT WITH SICKLE 7690 05:33:00,639 --> 05:33:02,308 CELL DISEASE REPORTED HAVING 7691 05:33:02,308 --> 05:33:03,943 FATHERED A CHILD WHEREAS NINE 7692 05:33:03,943 --> 05:33:07,480 CONTROLS HAD. 7693 05:33:07,480 --> 05:33:08,914 SO YOU KNOW, WHEN THEY LOOKED AT 7694 05:33:08,914 --> 05:33:10,316 OTHER DETAILS LIKE THE 7695 05:33:10,316 --> 05:33:13,853 TESTOSTERONE LEVEL THE, FSH, LH, 7696 05:33:13,853 --> 05:33:15,888 PROLACTIN LEVELS, WE FIND 7697 05:33:15,888 --> 05:33:16,889 TESTOSTERONE LEVELS WERE 7698 05:33:16,889 --> 05:33:18,524 SIGNIFICANTLY LOWER IN PATIENTS 7699 05:33:18,524 --> 05:33:19,925 WITH SICKLE CELL ANEMIA, THIS 7700 05:33:19,925 --> 05:33:21,093 HAS BEEN KEEPING WITH SEVERAL 7701 05:33:21,093 --> 05:33:22,595 OTHER STUDIES THAT HAVE BEEN 7702 05:33:22,595 --> 05:33:23,963 PUBLISHED OVER THE YEARS. 7703 05:33:23,963 --> 05:33:25,931 FSH, HOWEVER, WAS NOT 7704 05:33:25,931 --> 05:33:28,100 SIGNIFICANTLY HIGHER. 7705 05:33:28,100 --> 05:33:29,568 THERE WAS A TREND TO IT BUT IT 7706 05:33:29,568 --> 05:33:31,070 WAS NOT OF STATISTICAL 7707 05:33:31,070 --> 05:33:31,504 SIGNIFICANCE. 7708 05:33:31,504 --> 05:33:34,340 AND LUTEINIZING HORMONES LEVELS 7709 05:33:34,340 --> 05:33:36,842 WERE HIGHER AS WELL. 7710 05:33:36,842 --> 05:33:39,645 THE AUTHORS FOUND THAT THERE WAS 7711 05:33:39,645 --> 05:33:42,648 A DIFFERENCE WITH THE LEVELS OF 7712 05:33:42,648 --> 05:33:44,783 THE TESTICULAR VOLUME, 7713 05:33:44,783 --> 05:33:45,818 TESTOSTERONE LEVELS AND SPERM 7714 05:33:45,818 --> 05:33:46,652 COUNT DEPENDING ON THE AGE OF 7715 05:33:46,652 --> 05:33:47,453 THE PATIENT. 7716 05:33:47,453 --> 05:33:49,355 SO IF WE LOOK AT THIS TABLE, 7717 05:33:49,355 --> 05:33:51,223 PATIENTS WITH SICKLE CELL ANEMIA 7718 05:33:51,223 --> 05:33:53,726 OVER 25 YEARS HAD A HIGHER LEVEL 7719 05:33:53,726 --> 05:33:57,463 OF TESTOSTERONE, OF TESTICULAR 7720 05:33:57,463 --> 05:34:00,966 VOLUME, OF EVEN BMI THAN THOSE 7721 05:34:00,966 --> 05:34:02,301 WHO WERE LESS THAN 25. 7722 05:34:02,301 --> 05:34:03,936 THERE WAS NOT A SIGNIFICANT 7723 05:34:03,936 --> 05:34:05,271 DIFFERENCE IN THEIR SPERM COUNT, 7724 05:34:05,271 --> 05:34:07,673 EVEN THOUGH THERE WAS A TREND TO 7725 05:34:07,673 --> 05:34:08,774 THAT. 7726 05:34:08,774 --> 05:34:11,510 SO WHAT THEY THOUGHT WAS THAT 7727 05:34:11,510 --> 05:34:13,512 WHATEVER CAUSED THE INSULT IN 7728 05:34:13,512 --> 05:34:15,581 THESE PATIENTS PROBABLY FROM 7729 05:34:15,581 --> 05:34:16,482 ADOLESCENCE IMPROVED WITH TIME 7730 05:34:16,482 --> 05:34:18,884 BUT IT CERTAINLY DID NOT 7731 05:34:18,884 --> 05:34:20,486 NORMALIZE. 7732 05:34:20,486 --> 05:34:23,222 THEY DID NOT ASSESS DISEASE 7733 05:34:23,222 --> 05:34:25,057 SEVERITY IN THEIR PATIENTS AND 7734 05:34:25,057 --> 05:34:26,025 THIS ALSO IS A CROSS-SECTIONAL 7735 05:34:26,025 --> 05:34:28,594 STUDY. 7736 05:34:28,594 --> 05:34:31,430 SO THE LARGER SERIES TO DATE 7737 05:34:31,430 --> 05:34:33,699 LOOKING AT SEMEN ANALYSIS IN 7738 05:34:33,699 --> 05:34:37,303 SICKLE CELL DISEASE IS THAT 7739 05:34:37,303 --> 05:34:40,105 PUBLISHED IN -- THIS WAS PUBL 7740 05:34:40,105 --> 05:34:45,244 PUBLISHED SOMETIME LATER, AND IN 7741 05:34:45,244 --> 05:34:49,381 2008, AND THEY HAD 108 SEMEN 7742 05:34:49,381 --> 05:34:58,023 ANALYSIS FROM 44 PATIENTS. 7743 05:34:58,023 --> 05:35:00,826 FROM 4 PATIENTS. 7744 05:35:00,826 --> 05:35:01,160 44 PATIENTS. 7745 05:35:01,160 --> 05:35:02,761 THE MAIN AIM OF THE PAPER WAS TO 7746 05:35:02,761 --> 05:35:03,696 LOOK AT THE INFERENCE OF SICKLE 7747 05:35:03,696 --> 05:35:05,364 CELL DISEASE AS WELL AS 7748 05:35:05,364 --> 05:35:06,599 TREATMENT WITH HYDROXYUREA AND 7749 05:35:06,599 --> 05:35:07,066 SPERM PARAMETERS. 7750 05:35:07,066 --> 05:35:08,834 WE KNOW THAT THERE ARE A FEW 7751 05:35:08,834 --> 05:35:10,236 STUDYS THAT HAVE BEEN DONE THAT 7752 05:35:10,236 --> 05:35:11,637 HAVE SUGGESTED THAT THERE IS NO 7753 05:35:11,637 --> 05:35:12,771 CHANGE AND SEVERAL OTHERS WHICH 7754 05:35:12,771 --> 05:35:15,207 HAVE SUGGESTED THAT HYDROXYUREA 7755 05:35:15,207 --> 05:35:17,042 DOES IMPACT SEMEN PARAMETERS IN 7756 05:35:17,042 --> 05:35:19,011 SICKLE CELL DISEASE. 7757 05:35:19,011 --> 05:35:21,547 FROM THIS STUDY, 91% OF PATIENTS 7758 05:35:21,547 --> 05:35:24,683 WITH PRE-TREATMENT SEMEN 7759 05:35:24,683 --> 05:35:26,285 ANALYSIS HAD AT LEAST ONE 7760 05:35:26,285 --> 05:35:29,154 ABNORMALITY, AND ALL SEMEN 7761 05:35:29,154 --> 05:35:30,055 PARAMETERS WERE WITHIN SIX 7762 05:35:30,055 --> 05:35:31,557 MONTHS OF TREATMENT BUT AFTER 7763 05:35:31,557 --> 05:35:33,092 STOPPING TREATMENT, THE 7764 05:35:33,092 --> 05:35:36,595 PARAMETERS SEEMED TO RECOVER, 7765 05:35:36,595 --> 05:35:37,863 BUT NOT -- AFTER STOPPING 7766 05:35:37,863 --> 05:35:39,965 TREATMENT, THE PARAMETERS DID 7767 05:35:39,965 --> 05:35:41,767 NOT SEEM TO RECOVER TO 7768 05:35:41,767 --> 05:35:43,068 PRE-TREATMENT LEVELS. 7769 05:35:43,068 --> 05:35:46,238 SO HERE WE HAVE A TABLE FROM 7770 05:35:46,238 --> 05:35:47,539 THAT SAID PAPER WHERE WE LOOK AT 7771 05:35:47,539 --> 05:35:52,911 THE VOLUME OF E EJACULATE, DIDNT 7772 05:35:52,911 --> 05:35:57,883 SEEM TO BE A SIGNIFICANT DROP, 7773 05:35:57,883 --> 05:36:01,420 3MLs VERSUS 2.68 TO 2.99, ALL 7774 05:36:01,420 --> 05:36:02,121 USING CURRENT REFERENCE 7775 05:36:02,121 --> 05:36:03,289 GUIDELINES WITHIN THE NORMAL 7776 05:36:03,289 --> 05:36:06,025 RANGE, BUT WHAT WE SEE IS THAT 7777 05:36:06,025 --> 05:36:08,694 THE SPERM CONCENTRATION WAS 38.5 7778 05:36:08,694 --> 05:36:13,232 PLUS OR MINUS 43, SO A WIDE 7779 05:36:13,232 --> 05:36:17,903 RANGE FROM .02 TO 2.80. 7780 05:36:17,903 --> 05:36:19,238 THIS IS PRE-TREATMENT. 7781 05:36:19,238 --> 05:36:20,673 WITHIN SIX MONTHS OF TREATMENT 7782 05:36:20,673 --> 05:36:24,310 CIRCLES CAN'T DROP TO 2.66, 7783 05:36:24,310 --> 05:36:26,145 AFTER TREATMENT INCREASED A BIT, 7784 05:36:26,145 --> 05:36:28,314 BUT STILL USING THE GUIDELINES 7785 05:36:28,314 --> 05:36:29,448 WHEN THIS STUDY WAS DONE WOULD 7786 05:36:29,448 --> 05:36:33,419 HAVE BEEN LOWER. 7787 05:36:33,419 --> 05:36:35,788 CERTAINLY A DROP IN YOUR SPERM 7788 05:36:35,788 --> 05:36:37,690 CONCENTRATION OVER THE PERIOD OF 7789 05:36:37,690 --> 05:36:38,524 TIME. 7790 05:36:38,524 --> 05:36:40,859 IF WE USE OUR CURRENT WORLD 7791 05:36:40,859 --> 05:36:41,493 HEALTH ORGANIZATION GUIDELINES 7792 05:36:41,493 --> 05:36:43,362 OR REFERENCE VALUES, 18.46 WOULD 7793 05:36:43,362 --> 05:36:44,763 BE CONSIDERED NORMAL. 7794 05:36:44,763 --> 05:36:47,132 BUT IF WE COMPARE TO THE 7795 05:36:47,132 --> 05:36:50,269 PRE-TREATMENT, 38.5 TO 18.46, 7796 05:36:50,269 --> 05:36:52,171 THERE'S A DEFINITE DROP. 7797 05:36:52,171 --> 05:36:54,373 TOTAL COUNT FOR THIS WOULD BE 7798 05:36:54,373 --> 05:36:56,041 THE CONCENTRATION DRK A MULTIPLE 7799 05:36:56,041 --> 05:36:59,111 OF A CONCENTRATION IN VOLUME, 7800 05:36:59,111 --> 05:37:01,780 114 WENT DOWN TO 7, WENT UP TO 7801 05:37:01,780 --> 05:37:03,082 61 AFTER TREATMENT, TWO YEARS 7802 05:37:03,082 --> 05:37:04,583 AFTER TREATMENT. 7803 05:37:04,583 --> 05:37:08,087 AND MOTILITY DID NOT APPEAR TO 7804 05:37:08,087 --> 05:37:11,790 BE SIGNIFICANTLY AFFECTED. 7805 05:37:11,790 --> 05:37:13,025 SO THIS IS JUST ONE INDIVIDUAL 7806 05:37:13,025 --> 05:37:14,760 PATIENT WHERE WE LOOK AT THE 7807 05:37:14,760 --> 05:37:16,195 PARAMETERS BEFORE TREATMENT, 7808 05:37:16,195 --> 05:37:17,896 THREE SAMPLES WERE TAKEN. 7809 05:37:17,896 --> 05:37:19,598 AFTER TREATMENT, AFTER FOUR 7810 05:37:19,598 --> 05:37:21,033 YEARS, AND AFTER FIVE YEARS. 7811 05:37:21,033 --> 05:37:24,670 AND WE SEE THAT THE SPERM 7812 05:37:24,670 --> 05:37:27,206 CONCENTRATION REDUCED FROM 7813 05:37:27,206 --> 05:37:29,375 37.2 TO 17.5, TO 31.6, EVEN 7814 05:37:29,375 --> 05:37:30,676 BEFORE TREATMENT, AND AFTER FOUR 7815 05:37:30,676 --> 05:37:33,879 YEARS OF TREATMENT, 3.3 TO 1.2. 7816 05:37:33,879 --> 05:37:36,281 SO THERE APPEAR TO BE SOME 7817 05:37:36,281 --> 05:37:37,416 IMPACTS ON THIS PATIENT WHICH 7818 05:37:37,416 --> 05:37:41,754 DID NOT NORMALIZE AFTER 7819 05:37:41,754 --> 05:37:42,721 TREATMENT WAS STOPPED. 7820 05:37:42,721 --> 05:37:48,127 SO WE KNOW HYDROXYUREA CAN -- 7821 05:37:48,127 --> 05:37:50,629 THERE APPEARS TO BE REVERSIBLE 7822 05:37:50,629 --> 05:37:52,164 DECREASE IN SPERM COUNT, NORMAL 7823 05:37:52,164 --> 05:37:54,066 SPERM MORPHOLOGY AND MOTILITY. 7824 05:37:54,066 --> 05:37:57,536 SO WE SEE HERE THAT THE IMPACT 7825 05:37:57,536 --> 05:38:00,272 OF TREATMENT ON THE SPERM 7826 05:38:00,272 --> 05:38:01,940 PARAMETERS IN A PATIENT WHO 7827 05:38:01,940 --> 05:38:04,777 ALREADY MAY HAVE SOME METABOLIC 7828 05:38:04,777 --> 05:38:05,844 CAUSE FOR THEIR IMPAIRED 7829 05:38:05,844 --> 05:38:11,350 PARAMETERS. 7830 05:38:11,350 --> 05:38:15,421 A GROUP IN INDIA DID AGE MATCHED 7831 05:38:15,421 --> 05:38:17,356 CASE CONTROL STUDY, YOUNG 7832 05:38:17,356 --> 05:38:19,658 PATIENTS, 18 TO 45 YEARS, ALL 7833 05:38:19,658 --> 05:38:21,627 PATIENTS WERE IN STEADY STATE, 7834 05:38:21,627 --> 05:38:23,529 AND THEY EXAMINED THE PATIENTS 7835 05:38:23,529 --> 05:38:25,731 AND THEY LOOKED AT SPERM COUNT, 7836 05:38:25,731 --> 05:38:29,968 AND THEY LOOK AT SEMEN ANALYSIS. 7837 05:38:29,968 --> 05:38:30,636 SURPRISINGLY THIS IS THE ONLY 7838 05:38:30,636 --> 05:38:32,037 PAPER IN LITERATURE THAT HAS 7839 05:38:32,037 --> 05:38:33,038 DOCUMENTED THAT PATIENTS WITH 7840 05:38:33,038 --> 05:38:34,273 SICKLE CELL DISEASE HAVE A 7841 05:38:34,273 --> 05:38:35,707 HIGHER COUNT THAN THOSE WITHOUT 7842 05:38:35,707 --> 05:38:36,175 SICKLE CELL DISEASE. 7843 05:38:36,175 --> 05:38:38,310 IF YOU LOOK AT THIS PAPER 7844 05:38:38,310 --> 05:38:39,378 PUBLISHED HERE, THE TABLE 7845 05:38:39,378 --> 05:38:42,381 SUGGESTS THAT THE TOTAL COUNT 7846 05:38:42,381 --> 05:38:43,816 WAS 57.6 IN THE SICKLE CELL 7847 05:38:43,816 --> 05:38:47,653 PATIENTS VERSUS 39.75 IN 7848 05:38:47,653 --> 05:38:48,554 NON-SICKLE CELL PATIENTS. 7849 05:38:48,554 --> 05:38:51,089 MOTILITY WAS HIGHER, AS WELL AS 7850 05:38:51,089 --> 05:38:53,258 MORPHOLOGY WAS NORMAL. 7851 05:38:53,258 --> 05:38:56,528 THE AUTHORS DID DOCUMENT THAT 7852 05:38:56,528 --> 05:38:59,264 INFERTILITY WAS QUITE COMMON IN 7853 05:38:59,264 --> 05:39:01,366 THIS REGION SAMPLE, NOT 7854 05:39:01,366 --> 05:39:03,569 WITHSTANDING, THEY DID FIND HIGH 7855 05:39:03,569 --> 05:39:06,672 LEVELS OF NORMAL SEMEN ANALYSIS 7856 05:39:06,672 --> 05:39:10,576 PATTERNS IN THESE PATIENTS. 7857 05:39:10,576 --> 05:39:12,811 SO WHAT'S ETIOLOGY OF NORMAL 7858 05:39:12,811 --> 05:39:13,946 SEMEN PARAMETERS IN SICKLE CELL 7859 05:39:13,946 --> 05:39:14,179 DISEASE? 7860 05:39:14,179 --> 05:39:16,181 IF WE LOOK AT THESE PAPERS, 7861 05:39:16,181 --> 05:39:19,451 WE'LL SEE THAT THERE ARE A 7862 05:39:19,451 --> 05:39:21,253 NUMBER OF -- ETIOLOGIES. 7863 05:39:21,253 --> 05:39:25,057 ONE ISCHEMIA DUE TO SICKLING, SO 7864 05:39:25,057 --> 05:39:26,291 ISCHEMIA -- TESTICLE ISCHEMIA, 7865 05:39:26,291 --> 05:39:27,493 THERE HAVE BEEN A FEW CASE 7866 05:39:27,493 --> 05:39:28,794 REPORTS WITH PATIENTS WHO HAVE 7867 05:39:28,794 --> 05:39:30,295 HAD ISCHEMIA LEADING TO EVEN 7868 05:39:30,295 --> 05:39:31,129 INFARCT IN SICKLE CELL DISEASE, 7869 05:39:31,129 --> 05:39:34,933 SO THAT'S ONE THEORY. 7870 05:39:34,933 --> 05:39:36,134 TESTICULAR HYPOXIA IS THOUGHT TO 7871 05:39:36,134 --> 05:39:36,468 BE ONE. 7872 05:39:36,468 --> 05:39:38,871 OTHERS THINK IT MAY BE DUE TO 7873 05:39:38,871 --> 05:39:40,239 DYSFUNCTION OF ACCESSORY GLANDS. 7874 05:39:40,239 --> 05:39:41,840 THERE MAY BE A SECONDARY 7875 05:39:41,840 --> 05:39:43,308 FAILURE, NOT NECESSARILY PRIMARY 7876 05:39:43,308 --> 05:39:47,112 FAILURES, IN PREVIOUS -- DUE TO 7877 05:39:47,112 --> 05:39:49,314 CENTRAL INFARCTS EITHER OF THE 7878 05:39:49,314 --> 05:39:51,717 HYPOTHALAMUS OR PITUITARY GLAND, 7879 05:39:51,717 --> 05:39:55,888 REDUCED LIBIDO WITH -- 7880 05:39:55,888 --> 05:39:56,955 HYPOGONADISM SO LACK OF INTEREST 7881 05:39:56,955 --> 05:40:00,192 IN SEX MAY MEAN LACK OF STRONG 7882 05:40:00,192 --> 05:40:04,563 ERECTIONS AND WITHOUT 7883 05:40:04,563 --> 05:40:05,764 COPULATIONS PATIENTS CAN'T GET 7884 05:40:05,764 --> 05:40:10,269 PREG NATE. 7885 05:40:10,269 --> 05:40:10,602 PREGNANT. 7886 05:40:10,602 --> 05:40:13,405 MAY BE IATROGENIC AS WE JUST SAW 7887 05:40:13,405 --> 05:40:16,108 DUE TO HYDROXYUREA OR CONDITION 7888 05:40:16,108 --> 05:40:17,276 BEFORE STEM CELL TRANSPLANTS FOR 7889 05:40:17,276 --> 05:40:17,976 THESE PATIENTS. 7890 05:40:17,976 --> 05:40:19,211 SO WHAT ARE OUR SUGGESTIONS, 7891 05:40:19,211 --> 05:40:21,146 WHAT ARE MY SUGGESTIONS? 7892 05:40:21,146 --> 05:40:23,115 I SUGGEST THAT WE EVALUATE ALL 7893 05:40:23,115 --> 05:40:23,882 ADULT MALES WITH SICKLE CELL 7894 05:40:23,882 --> 05:40:24,383 DISEASE. 7895 05:40:24,383 --> 05:40:25,651 WE MUST HAVE A DISCUSSION WITH 7896 05:40:25,651 --> 05:40:27,786 THEM ABOUT DESIRE FOR FERTILITY, 7897 05:40:27,786 --> 05:40:29,121 AND IF THEY'VE EVER BEEN TESTED 7898 05:40:29,121 --> 05:40:32,691 OR IF THEY DO HAVE CHILDREN. 7899 05:40:32,691 --> 05:40:34,426 I THINK IF INFERTILITY IS FOUND 7900 05:40:34,426 --> 05:40:36,261 AFTER DOING A SEMEN ANALYSIS, 7901 05:40:36,261 --> 05:40:39,097 ETIOLOGY MUST BE DETERMINED, AND 7902 05:40:39,097 --> 05:40:40,465 WE CONSIDER POSSIBLE 7903 05:40:40,465 --> 05:40:44,369 CRYOPRESERVATION IN ELIGIBLE 7904 05:40:44,369 --> 05:40:45,470 PATIENTS BEFORE BEGINNING 7905 05:40:45,470 --> 05:40:46,872 HYDROXYUREA OR BEFORE EVEN DOING 7906 05:40:46,872 --> 05:40:47,706 STEM CELL TRANSPLANTS. 7907 05:40:47,706 --> 05:40:49,107 IN THE FUTURE, I THINK PATIENT 7908 05:40:49,107 --> 05:40:50,108 EDUCATION IS VERY IMPORTANT. 7909 05:40:50,108 --> 05:40:52,945 A VERY LOVELY PAPER THAT WAS 7910 05:40:52,945 --> 05:40:55,480 PUBLISHED FROM THE CLINICAL 7911 05:40:55,480 --> 05:40:57,482 TRIALS GROUP LAST YEAR JUNE 7912 05:40:57,482 --> 05:41:03,488 LOOKED AT FERTILITY TESTING IN 7913 05:41:03,488 --> 05:41:04,089 MALES WITH SICKLE CELL DISEASE 7914 05:41:04,089 --> 05:41:04,990 AND THEIR CAREGIVERS. 7915 05:41:04,990 --> 05:41:06,558 WHAT WE SAW WAS THAT MAYBE 7916 05:41:06,558 --> 05:41:07,859 KNOWLEDGE LEVEL COST HAVE 7917 05:41:07,859 --> 05:41:08,961 IMPROVED BETWEEN THE CAREGIVERS 7918 05:41:08,961 --> 05:41:11,196 AND THE PATIENTS BUT THERE WAS 7919 05:41:11,196 --> 05:41:12,364 CERTAINLY A STRONG DESIRE 7920 05:41:12,364 --> 05:41:13,465 FOREKNOWLEDGE ABOUT FERTILITY IN 7921 05:41:13,465 --> 05:41:15,200 THESE PATIENTS, SO I THINK 7922 05:41:15,200 --> 05:41:16,868 EDUCATION IS VERY IMPORTANT, 7923 05:41:16,868 --> 05:41:18,737 EVEN FROM LEVEL OF ADOLESCENCE. 7924 05:41:18,737 --> 05:41:20,238 I THINK WE NEED TO DEFINITELY DO 7925 05:41:20,238 --> 05:41:22,140 FURTHER STUDIES ON ETIOLOGY. 7926 05:41:22,140 --> 05:41:24,142 THERE'S MUCH MORE THAN JUST 7927 05:41:24,142 --> 05:41:25,177 LOOKING AT THINKING THAT IT MAY 7928 05:41:25,177 --> 05:41:27,079 BE DUE TO INFARCTION OR 7929 05:41:27,079 --> 05:41:31,850 ISCHEMIA, BUT PERHAPS MANY OTHER 7930 05:41:31,850 --> 05:41:33,452 CAUSES ARE RESPONSIBLE. 7931 05:41:33,452 --> 05:41:35,954 CERTAINLY IN THE GRAND SCHEME OF 7932 05:41:35,954 --> 05:41:37,289 FERTILITY EVALUATION AND 7933 05:41:37,289 --> 05:41:38,824 FERTILITY ETIOLOGY, IN GENERAL, 7934 05:41:38,824 --> 05:41:42,594 IN THE GENERAL POPULATION, 7935 05:41:42,594 --> 05:41:45,631 OXIDATIVE STRESS IS A MAJOR 7936 05:41:45,631 --> 05:41:48,066 CAUSE, AN EMERGING MAJOR CAUSE. 7937 05:41:48,066 --> 05:41:50,902 KURNS EVIDENCE LINKS ACTIVE 7938 05:41:50,902 --> 05:41:52,804 STRESS TO MALE INFERTILITY, 7939 05:41:52,804 --> 05:41:56,508 SPERM DAMAGE, INCREASED RISK OF 7940 05:41:56,508 --> 05:41:58,076 RECURRENT ABORTIONS AND GENETIC 7941 05:41:58,076 --> 05:41:59,911 DISEASES. 7942 05:41:59,911 --> 05:42:02,180 IN PATIENTS OF PATIENTS WITH 7943 05:42:02,180 --> 05:42:03,649 HIGH LEVELS OF OXIDATIVE STRESS, 7944 05:42:03,649 --> 05:42:06,418 THEY SAY THIS PERHAPS COULD BE 7945 05:42:06,418 --> 05:42:07,953 ONE OF THE MAJOR CAUSES IN THEM. 7946 05:42:07,953 --> 05:42:09,054 WHAT HAS BEEN FOUND IN THOSE 7947 05:42:09,054 --> 05:42:11,256 PERSON WITH OXIDATIVE STRESS IN 7948 05:42:11,256 --> 05:42:12,924 THE GENERAL POPULATION AND 7949 05:42:12,924 --> 05:42:14,059 NON-SICKLE CELL POPULATION, 7950 05:42:14,059 --> 05:42:18,363 EARLY IDENTIFICATION POSSIBLY 7951 05:42:18,363 --> 05:42:20,332 EVEN TREATING THE OXIDATIVE 7952 05:42:20,332 --> 05:42:22,067 STRESS MAY REDUCE MALE 7953 05:42:22,067 --> 05:42:22,934 INFERTILITY. 7954 05:42:22,934 --> 05:42:25,737 SO IN SUMMARY, ABNORMALITIES OF 7955 05:42:25,737 --> 05:42:27,339 SEMEN PARAMETERS ARE COMMON IN 7956 05:42:27,339 --> 05:42:28,006 SICKLE CELL DISEASE. 7957 05:42:28,006 --> 05:42:30,542 EXACT ETIOLOGY REMAINS ELUSIVE. 7958 05:42:30,542 --> 05:42:31,710 PATIENT EDUCATION AND EVALUATION 7959 05:42:31,710 --> 05:42:33,945 IS IMPERATIVE. 7960 05:42:33,945 --> 05:42:34,713 AND SPERM CRYOPRESERVATION 7961 05:42:34,713 --> 05:42:36,615 SHOULD BE CONSIDERED PRIOR TO 7962 05:42:36,615 --> 05:42:38,383 USE OF NEWER TREATMENTS. 7963 05:42:38,383 --> 05:42:48,593 I THANK YOU. 7964 05:42:51,997 --> 05:42:56,168 >> KNEW THANK YOU SO MUCH, BEL, 7965 05:42:56,168 --> 05:42:58,070 FOR A GREAT LOOK AT SEMEN AND 7966 05:42:58,070 --> 05:42:59,838 ISSUES IN SICKLE CELL DISEASE 7967 05:42:59,838 --> 05:43:00,405 MALES. 7968 05:43:00,405 --> 05:43:01,606 SHE'S NOT AVAILABLE FOR 7969 05:43:01,606 --> 05:43:04,042 QUESTIONS BUT IF YOU DO HAVE, IF 7970 05:43:04,042 --> 05:43:05,377 THE AUDIENCE HAS ANY QUESTIONS 7971 05:43:05,377 --> 05:43:06,645 THAT WE WILL HAVE THEM ANSWERED 7972 05:43:06,645 --> 05:43:09,314 BY HER. 7973 05:43:09,314 --> 05:43:11,583 WE ARE RUNNING -- 2 MINUTES 7974 05:43:11,583 --> 05:43:12,984 BREAK, IS THAT OKAY WITH 7975 05:43:12,984 --> 05:43:14,853 EVERYONE? 7976 05:43:14,853 --> 05:43:16,988 AND COME RIGHT BACK BY 3:15 TO 7977 05:43:16,988 --> 05:43:18,290 START OUR LAST SESSION. 7978 05:43:18,290 --> 05:43:19,524 TAKE A STRETCH BREAK, PLEASE. 7979 05:43:19,524 --> 05:43:29,701 THANK YOU. 7980 05:45:17,085 --> 05:45:21,156 DURING THE PANDEMIC. 7981 05:45:21,156 --> 05:45:22,791 THE COVID-19 PANDEMIC CHANGED 7982 05:45:22,791 --> 05:45:23,458 ALL OUR NORMS. 7983 05:45:23,458 --> 05:45:26,861 WE WERE NOW LIVING IN A WORLD OF 7984 05:45:26,861 --> 05:45:29,731 LOCKDOWNS, SOCIAL DISTANCING, 7985 05:45:29,731 --> 05:45:32,367 MASKING AND HAND HYGIENE. 7986 05:45:32,367 --> 05:45:34,803 DELIVERY OF SAFE AND EFFECTIVE 7987 05:45:34,803 --> 05:45:36,638 HEALTHCARE BECAME A CHALLENGE, 7988 05:45:36,638 --> 05:45:39,374 ESPECIALLY FOR VULNERABLE 7989 05:45:39,374 --> 05:45:40,809 POPULATIONS, AND TELEHEALTH WAS 7990 05:45:40,809 --> 05:45:41,810 THE SOLUTION. 7991 05:45:41,810 --> 05:45:43,578 THERE WAS AN EXPLOSION OF 7992 05:45:43,578 --> 05:45:45,380 TELEHEALTH SERVICES WORLDWIDE, 7993 05:45:45,380 --> 05:45:47,182 AS IT ALLOWED HEALTHCARE 7994 05:45:47,182 --> 05:45:49,584 PROVIDERS TO CONTINUE TO CARE 7995 05:45:49,584 --> 05:45:52,687 AND MANAGE PATIENTS AT A SAFE 7996 05:45:52,687 --> 05:45:55,023 DISTANCE, DECREASING THEIR RISK 7997 05:45:55,023 --> 05:45:58,760 AND EXPOSURE TO INFECTION. 7998 05:45:58,760 --> 05:46:02,363 TELEHEALTH IS NOT A NEW CONCEPT. 7999 05:46:02,363 --> 05:46:04,699 IT'ITS HISTORY ACTUALLY DATES BK 8000 05:46:04,699 --> 05:46:07,101 TO THE 1960s, AND KEY ELEMENTS 8001 05:46:07,101 --> 05:46:08,436 OF ITS DEFINITION ARE, ONE, IT 8002 05:46:08,436 --> 05:46:10,605 IS A TOOL FOR THE DELIVERY OF 8003 05:46:10,605 --> 05:46:12,173 HEALTHCARE, IT IS NOT THE 8004 05:46:12,173 --> 05:46:14,909 HEALTHCARE SERVICE IN ITSELF. 8005 05:46:14,909 --> 05:46:17,545 TWO, IT PROVIDES HEALTHCARE AT A 8006 05:46:17,545 --> 05:46:21,516 DISTANCE, AND THREE, IT USES ICT 8007 05:46:21,516 --> 05:46:22,383 TECHNOLOGIES FOR INFORMATION 8008 05:46:22,383 --> 05:46:27,155 EXCHANGE. 8009 05:46:27,155 --> 05:46:31,593 IN ITS STRICTNESS SENSE, 8010 05:46:31,593 --> 05:46:34,829 TELEHEALTH REFERS TO INFORMATION 8011 05:46:34,829 --> 05:46:36,231 AND COMMUNICATION, ACCESS AND 8012 05:46:36,231 --> 05:46:38,333 INCREASING COSTS HAVE BEEN WELL 8013 05:46:38,333 --> 05:46:38,600 DESCRIBED. 8014 05:46:38,600 --> 05:46:40,034 SIMILARLY, ITS CHALLENGES AND 8015 05:46:40,034 --> 05:46:42,237 BARRIERS ARE ALSO WELL-KNOWN. 8016 05:46:42,237 --> 05:46:43,872 AND IMPORTANT FOR THE INCREASE 8017 05:46:43,872 --> 05:46:46,241 IN SERVICES DURING THE PANDEMIC 8018 05:46:46,241 --> 05:46:49,177 WAS THE REMOVAL OF REGULATORY 8019 05:46:49,177 --> 05:46:50,979 AND REIMBURSEMENT ISSUES 8020 05:46:50,979 --> 05:46:52,580 ALLOWING FOR CARE ACROSS STATE 8021 05:46:52,580 --> 05:46:55,216 LINES IN THE U.S. AND MORE 8022 05:46:55,216 --> 05:46:59,954 IMPORTANTLY, TO ALLOW FOR 8023 05:46:59,954 --> 05:47:01,389 AUDIO-ONLY VISITS. 8024 05:47:01,389 --> 05:47:03,224 THE TERMS TELEHEALTH AND 8025 05:47:03,224 --> 05:47:04,759 TELEMEDICINE ARE OFTEN USED 8026 05:47:04,759 --> 05:47:06,094 INTERCHANGEABLY, BUT FOR 8027 05:47:06,094 --> 05:47:07,996 CLARITY, TELEHEALTH IS A BROAD 8028 05:47:07,996 --> 05:47:10,265 TERM WHICH REFERS TO MORE 8029 05:47:10,265 --> 05:47:11,599 CLINICAL AS WELL AS NON-CLINICAL 8030 05:47:11,599 --> 05:47:13,935 SERVICES SUCH AS PROVIDER 8031 05:47:13,935 --> 05:47:14,469 TRAINING, ADMINISTRATIVE 8032 05:47:14,469 --> 05:47:17,605 MEETINGS AND CONTINUING MEDICAL 8033 05:47:17,605 --> 05:47:19,507 EDUCATION. 8034 05:47:19,507 --> 05:47:21,409 ON THE OTHER HAND, TELEMEDICINE 8035 05:47:21,409 --> 05:47:23,945 IS A SUBSET OF TELEHEALTH AND 8036 05:47:23,945 --> 05:47:25,079 REFERS SPECIFICALLY TO REMOTE 8037 05:47:25,079 --> 05:47:29,550 CLINICAL SERVICES. 8038 05:47:29,550 --> 05:47:33,087 BEFORE COVID, TELEHEALTH 8039 05:47:33,087 --> 05:47:35,924 UTILIZATION VARIED ACROSS 8040 05:47:35,924 --> 05:47:39,227 NATIONS AND COUNTRIES. 8041 05:47:39,227 --> 05:47:41,062 TECHNOLOGIES AND REGULATIONS 8042 05:47:41,062 --> 05:47:42,430 SURROUNDING TELEHEALTH 8043 05:47:42,430 --> 05:47:43,298 SIGNIFICANTLY INFLUENCED ITS 8044 05:47:43,298 --> 05:47:45,466 USAGE. 8045 05:47:45,466 --> 05:47:47,502 FOREIGNERS INCLUDED DEVELOPED 8046 05:47:47,502 --> 05:47:51,239 COUNTRIES LIKE THE U.S., YET 8047 05:47:51,239 --> 05:47:59,580 INTERINTERESTINGLY ONLY ABOUT -T 8048 05:47:59,580 --> 05:48:00,815 USED TELEHEALTH SERVICES IN 8049 05:48:00,815 --> 05:48:01,015 2016. 8050 05:48:01,015 --> 05:48:02,884 ON THE OTHER HAND, PRECOVID IN 8051 05:48:02,884 --> 05:48:05,420 LOW AND MIDDLE INCOME COUNTRIES, 8052 05:48:05,420 --> 05:48:07,422 TELEHEALTH WAS MOSTLY 8053 05:48:07,422 --> 05:48:11,893 NON-EXISTENT OR IN ITS INFANCY. 8054 05:48:11,893 --> 05:48:13,294 WITH THE ONSET OF COVID AS 8055 05:48:13,294 --> 05:48:15,129 MENTIONED BEFORE, THERE WAS AN 8056 05:48:15,129 --> 05:48:16,864 EXPLOSION OF TELEHEALTH 8057 05:48:16,864 --> 05:48:17,231 SERVICES. 8058 05:48:17,231 --> 05:48:22,470 IIN THE FIRST QUARTER OF 2020, T 8059 05:48:22,470 --> 05:48:23,938 SHOWED 154% INCREASE IN 8060 05:48:23,938 --> 05:48:26,174 TELEHEALTH VISITS. 8061 05:48:26,174 --> 05:48:28,176 NOW SAID TO HAVE STABILIZED 8062 05:48:28,176 --> 05:48:29,877 SOMEWHERE AROUND 38 TIMES HIGHER 8063 05:48:29,877 --> 05:48:33,881 THAN LEVELS IN 2019. 8064 05:48:33,881 --> 05:48:37,251 IN ONTARIO, CANADA, PRE-COVID 8065 05:48:37,251 --> 05:48:38,319 TELEMEDICINE VISITS WERE 8066 05:48:38,319 --> 05:48:41,055 REPORTED AT 11 VISITS PER 8067 05:48:41,055 --> 05:48:42,724 THOUSAND PATIENTS IN RURAL 8068 05:48:42,724 --> 05:48:44,726 AREAS, AND 7 VISITS PER THOUSAND 8069 05:48:44,726 --> 05:48:47,462 PATIENTS IN URBAN AREAS. 8070 05:48:47,462 --> 05:48:49,063 COMPARE THAT TO POST-COVID, 8071 05:48:49,063 --> 05:48:52,633 WHERE VISITS WERE NOW 8072 05:48:52,633 --> 05:48:54,168 147 PERCENT THOUSAND AMONG RURAL 8073 05:48:54,168 --> 05:48:57,205 PATIENTS, AND 220 VISITS PER 8074 05:48:57,205 --> 05:49:02,877 THOUSAND AMONG URBAN DWELLERS. 8075 05:49:02,877 --> 05:49:13,688 TELTELEHEALTH USE WA INCREASED % 8076 05:49:18,192 --> 05:49:20,395 IN A SURVEY CONDUCTED ACROSS 8077 05:49:20,395 --> 05:49:20,962 DIFFERENT COUNTRIES IN THE 8078 05:49:20,962 --> 05:49:22,230 MIDDLE EAST AND NORTH AFRICA 8079 05:49:22,230 --> 05:49:22,463 REGION. 8080 05:49:22,463 --> 05:49:23,998 IN A LITERATURE REVIEW OF 8081 05:49:23,998 --> 05:49:27,001 TELEHEALTH SERVICES, 66 WERE 8082 05:49:27,001 --> 05:49:28,269 NEWLY ADOPTED INITIATIVES DURING 8083 05:49:28,269 --> 05:49:28,936 THE PANDEMIC. 8084 05:49:28,936 --> 05:49:30,338 THERE WERE OTHER SUCH REPORTS 8085 05:49:30,338 --> 05:49:31,639 HIGHLIGHTING THE GROWTH OF 8086 05:49:31,639 --> 05:49:33,174 TELEHEALTH DURING THE PANDEMIC. 8087 05:49:33,174 --> 05:49:36,677 INDEED IF WE ACTUALLY LOOK AT A 8088 05:49:36,677 --> 05:49:38,913 SCOPE IN REVIEW DONE IN JANUARY 8089 05:49:38,913 --> 05:49:40,882 OF JUNE TO 2020, TELEHEALTH WAS 8090 05:49:40,882 --> 05:49:44,886 BEING USED WORLDWIDE BUT MOSTLY 8091 05:49:44,886 --> 05:49:50,525 IN THE AMERICAS AND IN EUROPE, 8092 05:49:50,525 --> 05:49:51,959 MOSTLY HIGH INCOME COUNTRIES, 8093 05:49:51,959 --> 05:49:54,929 AND MOST OF THE TELEHEALTH 8094 05:49:54,929 --> 05:49:56,597 VISITS WERE FOR CLINICAL CARE OR 8095 05:49:56,597 --> 05:50:01,869 FOR FOLLOW-UP. 8096 05:50:01,869 --> 05:50:05,073 SICKLE CELL DISEASE IS A CHRONIC 8097 05:50:05,073 --> 05:50:09,444 HEREDITARY HEMOGLOBINOPATHY. 8098 05:50:09,444 --> 05:50:11,512 LIFETIME MORBIDITY AND DECREASED 8099 05:50:11,512 --> 05:50:13,147 SURVIVAL, THEY WERE CONSIDERED A 8100 05:50:13,147 --> 05:50:13,981 VULNERABLE POPULATION IF THEY 8101 05:50:13,981 --> 05:50:16,951 WERE TO GET COVID INFECTION. 8102 05:50:16,951 --> 05:50:21,556 AS SUCH, THIS LED TO THE 8103 05:50:21,556 --> 05:50:24,025 IMPLEMENTATION OF THE SECURE 8104 05:50:24,025 --> 05:50:28,830 REGISTRY, GLOBAL REGISTRY VERY 8105 05:50:28,830 --> 05:50:30,965 EARLY IN THE PANDEMIC AND THIS 8106 05:50:30,965 --> 05:50:32,767 HAS SINCE REPORTED GREATER RISK 8107 05:50:32,767 --> 05:50:34,001 OF SERIOUS ILLNESS, 8108 05:50:34,001 --> 05:50:35,436 HOSPITALIZATION AND DEATH FROM 8109 05:50:35,436 --> 05:50:40,675 COVID IN PERSONS WITH DISEASE. 8110 05:50:40,675 --> 05:50:42,677 WITH REGARDS TO HEALTHCARE 8111 05:50:42,677 --> 05:50:44,011 UTILIZATION, GLOBALLY THERE WAS 8112 05:50:44,011 --> 05:50:47,815 A DECLINE IN HEALTHCARE 8113 05:50:47,815 --> 05:50:48,783 UTILIZATION DURING THE PANDEMIC, 8114 05:50:48,783 --> 05:50:49,917 AND THIS TREND WAS NOTED IN 8115 05:50:49,917 --> 05:50:54,755 PERSONS WITH DISEASE. 8116 05:50:54,755 --> 05:50:56,290 REPORT FROM A U.S.-BASED 8117 05:50:56,290 --> 05:50:57,258 COMMUNITY ORGANIZATION FROM 8118 05:50:57,258 --> 05:50:59,861 PEOPLE WITH DISEASE SHOWED THAT 8119 05:50:59,861 --> 05:51:03,531 ONLY 35% SOUGHT ER CARE AND 53% 8120 05:51:03,531 --> 05:51:05,933 REPORTED MANAGING THEIR PAIN 8121 05:51:05,933 --> 05:51:07,135 CRISIS AT HOME DURING THE 8122 05:51:07,135 --> 05:51:08,336 PANDEMIC. 8123 05:51:08,336 --> 05:51:10,371 A SPECIALTY CENTER IN THE UK 8124 05:51:10,371 --> 05:51:13,141 REPORTED APPROXIMATELY 49% 8125 05:51:13,141 --> 05:51:15,776 REDUCTION IN PATIENT ADMISSIONS 8126 05:51:15,776 --> 05:51:17,778 FOR VASO-OCCLUSIVE CRISES IN THE 8127 05:51:17,778 --> 05:51:18,513 FIRST THREE MONTHS OF THE 8128 05:51:18,513 --> 05:51:25,419 PANDEMIC. 8129 05:51:25,419 --> 05:51:30,291 THEN IF WE LOOK ON TCD SCREEN 8130 05:51:30,291 --> 05:51:33,561 SCREENING, THEY REPORTED A 67% 8131 05:51:33,561 --> 05:51:39,901 DECLINE IN TCD SCREENING. 8132 05:51:39,901 --> 05:51:44,405 WITH REGARD TO TELEMEDICINE, 8133 05:51:44,405 --> 05:51:47,475 BEFORE COINDIVIDUALS REPORTS OF 8134 05:51:47,475 --> 05:51:51,312 A TELEMEDICINE CLINIC FOR ADULT 8135 05:51:51,312 --> 05:51:52,513 PATIENTS INCREASED ACCESS TO 8136 05:51:52,513 --> 05:51:54,849 CARE AND SIMILARLY TELEMEDICINE 8137 05:51:54,849 --> 05:51:56,584 VISITS ALLOWED FOR CONTACT WITH 8138 05:51:56,584 --> 05:51:59,120 SICKLE CELL DISEASE CHILDREN WHO 8139 05:51:59,120 --> 05:52:01,589 HAD DEFAULTED FROM CARE IN A 8140 05:52:01,589 --> 05:52:02,790 RURAL MEDICALLY UNDERSERVED 8141 05:52:02,790 --> 05:52:04,959 AREA. 8142 05:52:04,959 --> 05:52:10,565 AFTER COVID, IN ONE REPORT IN 8143 05:52:10,565 --> 05:52:12,033 CHILDREN, OUTPATIENT TELEHEALTH 8144 05:52:12,033 --> 05:52:14,101 VISITS INCREASED FROM .4% 8145 05:52:14,101 --> 05:52:16,437 PREPANDEMIC TO 10.7% IN THE 8146 05:52:16,437 --> 05:52:19,040 PANDEMIC. 8147 05:52:19,040 --> 05:52:20,942 AND REPORTS OUT OF NIGERIA SHOW 8148 05:52:20,942 --> 05:52:23,444 THAT APRIL TO JULY 2020, THERE 8149 05:52:23,444 --> 05:52:26,280 WAS A GRADUAL INCREASE IN PHONE 8150 05:52:26,280 --> 05:52:29,584 COMMUNICATION WITH PHYSICIANS, 8151 05:52:29,584 --> 05:52:30,885 AND 60.8% OF THE PARTICIPANTS 8152 05:52:30,885 --> 05:52:34,956 OPTED TO CONTINUE MOBILE 8153 05:52:34,956 --> 05:52:42,063 TELEMEDICINE CARE AFTERWARDS. 8154 05:52:42,063 --> 05:52:43,698 THE SICKLE CELL UNIT IS A 8155 05:52:43,698 --> 05:52:46,200 COMPREHENSIVE CARE CENTER FOR 8156 05:52:46,200 --> 05:52:46,634 SICKLE CELL DISEASE. 8157 05:52:46,634 --> 05:52:48,703 WE HAVE OVER 10,000 PATIENTS IN 8158 05:52:48,703 --> 05:52:52,340 OUR DATABASE. 8159 05:52:52,340 --> 05:52:55,977 WE SEE ROUGHLY 2,500 PATIENTS 8160 05:52:55,977 --> 05:52:59,080 EACH YEAR FOR ABOUT 9,000 8161 05:52:59,080 --> 05:52:59,814 PATIENT VISITS. 8162 05:52:59,814 --> 05:53:01,415 OUR SERVICES INCLUDE HEALTH 8163 05:53:01,415 --> 05:53:05,786 MAINTENANCE VISITS AND A DAY 8164 05:53:05,786 --> 05:53:08,422 WARD TO TREAT ACUTE 8165 05:53:08,422 --> 05:53:08,756 COMPLICATIONS. 8166 05:53:08,756 --> 05:53:11,425 WE HAD TO DEVISE WAYS TO 8167 05:53:11,425 --> 05:53:12,126 SAFELILY VISIT WITH PATIENTS 8168 05:53:12,126 --> 05:53:13,361 DURING THE PANDEMIC, AND THIS 8169 05:53:13,361 --> 05:53:15,129 LED TO THE IMPLEMENTATION OF 8170 05:53:15,129 --> 05:53:16,864 TELEVISITS. 8171 05:53:16,864 --> 05:53:18,532 TELEVISITS WERE ESSENTIALLY 8172 05:53:18,532 --> 05:53:19,734 TELEPHONE CHECK-INS WITH 8173 05:53:19,734 --> 05:53:23,904 PATIENTS WHO WERE MOSTLY ROUTINE 8174 05:53:23,904 --> 05:53:25,006 APPOINTMENTS OR FOLLOW-UP VISITS 8175 05:53:25,006 --> 05:53:27,842 FOR LAB REVIEW. 8176 05:53:27,842 --> 05:53:30,778 AS SUCH, WE SOUGHT TO EXAMINE 8177 05:53:30,778 --> 05:53:33,848 THE USE OF TELEHEALTH AS AN 8178 05:53:33,848 --> 05:53:36,183 ALTERNATE TOOL FOR THE DELIVERY 8179 05:53:36,183 --> 05:53:37,285 OF PARTICULAR HEALTHCARE IN 8180 05:53:37,285 --> 05:53:37,952 PERSONS WITH SICKLE CELL DISEASE 8181 05:53:37,952 --> 05:53:40,121 A VULNERABLE POPULATION DURING 8182 05:53:40,121 --> 05:53:42,189 THE COVID-19 PANDEMIC. 8183 05:53:42,189 --> 05:53:44,492 SPECIFICALLY, WE WANTED TO 8184 05:53:44,492 --> 05:53:46,160 COMPARE IN TWO PANDEMIC YEARS TO 8185 05:53:46,160 --> 05:53:49,797 THE YEAR PRIOR, CLINIC 8186 05:53:49,797 --> 05:53:51,899 REGISTRATION NUMBERS, DAYCARE 8187 05:53:51,899 --> 05:53:53,601 ADMISSIONS AND IN-PERSON VERSUS 8188 05:53:53,601 --> 05:53:59,206 TELEVISITS. 8189 05:53:59,206 --> 05:54:00,308 JAMAICA'S FIRST COVID-19 PATIENT 8190 05:54:00,308 --> 05:54:02,610 PRESENTED ON MARCH 10, 2020. 8191 05:54:02,610 --> 05:54:05,579 AS SUCH, THIS WAS A 8192 05:54:05,579 --> 05:54:07,982 RETROSPECTIVE ANALYSIS OF 8193 05:54:07,982 --> 05:54:09,483 PATIENT ENCOUNTERS OVER A 8194 05:54:09,483 --> 05:54:10,651 THREE-YEAR PERIOD. 8195 05:54:10,651 --> 05:54:13,788 YEAR ZERO, PREPANDEMIC, YEAR ONE 8196 05:54:13,788 --> 05:54:14,922 AND YEAR TWO DURING THE 8197 05:54:14,922 --> 05:54:16,757 PANDEMIC. 8198 05:54:16,757 --> 05:54:19,060 THE PATIENT ENCOUNTERS THAT WE 8199 05:54:19,060 --> 05:54:21,195 EXAMINED INCLUDED REGISTRATION 8200 05:54:21,195 --> 05:54:22,897 NUMBERS, DEFINED AS CLINIC 8201 05:54:22,897 --> 05:54:26,067 WALK-INS FOR PHYSICIAN OR 8202 05:54:26,067 --> 05:54:27,768 TREATMENT-ONLY VISITS, AND STUDY 8203 05:54:27,768 --> 05:54:29,537 VISITS, WHICH WE DEFINED AS 8204 05:54:29,537 --> 05:54:31,939 PHYSICIAN TO PATIENT CONSULTS, 8205 05:54:31,939 --> 05:54:33,874 EITHER FACE-TO-FACE OR A 8206 05:54:33,874 --> 05:54:40,781 TELEVISIT. 8207 05:54:40,781 --> 05:54:43,617 ANALYSIS WAS PERFORMED AND 8208 05:54:43,617 --> 05:54:45,686 VERSION 16 WAS USED FOR 8209 05:54:45,686 --> 05:54:45,953 ANALYSIS. 8210 05:54:45,953 --> 05:54:48,589 ETHICS APPROVAL WAS OBTAINED FOR 8211 05:54:48,589 --> 05:54:51,225 THE MONA CAMPUS RESEARCH ETHICS 8212 05:54:51,225 --> 05:54:52,827 COMMITTEE. 8213 05:54:52,827 --> 05:54:53,427 AND OUR RESULTS. 8214 05:54:53,427 --> 05:54:57,298 THERE WAS A TOTAL REGISTRATION 8215 05:54:57,298 --> 05:55:02,837 NUMBER OF 17,295 PATIENTS. 8216 05:55:02,837 --> 05:55:05,439 COMPARED TO YEAR ZERO, NUMBERS 8217 05:55:05,439 --> 05:55:09,844 FELL IN YEAR ONE BY 43.8%, AND 8218 05:55:09,844 --> 05:55:17,251 IN YEAR TWO, BY 35%. 8219 05:55:17,251 --> 05:55:18,619 WHEN WE LOOKED AT MONTHLY 8220 05:55:18,619 --> 05:55:20,554 REGISTRATION NUMBERS, OUR LOWEST 8221 05:55:20,554 --> 05:55:21,856 REGISTRATION NUMBERS WERE IN 8222 05:55:21,856 --> 05:55:23,023 APRIL AND MAY 2020, BUT 8223 05:55:23,023 --> 05:55:25,226 REGISTRATION NUMBERS AGAIN FELL 8224 05:55:25,226 --> 05:55:29,463 IN SEPTEMBER 2020 AND OCTOB 8225 05:55:29,463 --> 05:55:30,598 OCTOBER 2021 DURING THE FIRST 8226 05:55:30,598 --> 05:55:32,500 AND THE THIRD WAVES OF THE 8227 05:55:32,500 --> 05:55:35,269 PANDEMIC. 8228 05:55:35,269 --> 05:55:38,105 WITH REGARDS TO DAY-CARE 8229 05:55:38,105 --> 05:55:39,440 ADMISSIONS, THERE WAS A STEADY 8230 05:55:39,440 --> 05:55:41,709 DOWNWARD TREND IN YEAR ONE AND 8231 05:55:41,709 --> 05:55:42,743 YEAR TWO. 8232 05:55:42,743 --> 05:55:44,945 THE TOTAL ADMISSIONS AS WELL AS 8233 05:55:44,945 --> 05:55:48,315 FOR BOTH ADULT AND CHILD 8234 05:55:48,315 --> 05:55:49,683 ADMISSIONS, HOWEVER, DECLINE WAS 8235 05:55:49,683 --> 05:55:51,786 MORE NOTICEABLE WITH CHILD 8236 05:55:51,786 --> 05:55:54,188 ADMISSIONS. 8237 05:55:54,188 --> 05:55:59,393 WITH REGARDS TO PATIENT NUMBERS, 8238 05:55:59,393 --> 05:56:03,697 3,429 PATIENTS HAD A STUDY VISIT 8239 05:56:03,697 --> 05:56:05,099 OVER THE THREE-YEAR PERIOD. 8240 05:56:05,099 --> 05:56:07,301 40% OF THE PATIENTS WITH STUDY 8241 05:56:07,301 --> 05:56:09,069 VISITS WERE SEEN AT LEAST ONCE 8242 05:56:09,069 --> 05:56:14,108 IN EACH YEAR, AND 33.5% WERE 8243 05:56:14,108 --> 05:56:17,344 SEEN IN ONLY ONE STUDY YEAR. 8244 05:56:17,344 --> 05:56:22,016 FOR STUDY VISITS, THERE WERE 8245 05:56:22,016 --> 05:56:25,319 21,905 STUDY VISITS RECORDED, 8246 05:56:25,319 --> 05:56:30,858 AND THESE OCCURRED IN 3,429 8247 05:56:30,858 --> 05:56:31,292 INDIVIDUALS. 8248 05:56:31,292 --> 05:56:36,497 MOST WERE ADULT, FEMALE, AND HAD 8249 05:56:36,497 --> 05:56:37,731 HBSS GENOTYPE. 8250 05:56:37,731 --> 05:56:40,100 STUDY VISITS INCREASED IN YEAR 8251 05:56:40,100 --> 05:56:45,306 ONE BY 4.9%, AND IN YEAR TWO BY 8252 05:56:45,306 --> 05:56:48,909 1.3% COMPARED TO YEAR ZERO. 8253 05:56:48,909 --> 05:56:52,246 MOST OF OUR STUDY VISITS WERE IN 8254 05:56:52,246 --> 05:56:52,813 PERSON. 8255 05:56:52,813 --> 05:56:54,548 HOWEVER, IN-PERSON VISITS FELL 8256 05:56:54,548 --> 05:57:00,354 IN YEAR ONE BY 24%, AND IN YEAR 8257 05:57:00,354 --> 05:57:03,791 TWO BY 34.5%. 8258 05:57:03,791 --> 05:57:06,694 DURING THE PANDEMIC YEARS, 8259 05:57:06,694 --> 05:57:11,999 TELEVISITS ACCOUNTED FOR 31.4%, 8260 05:57:11,999 --> 05:57:13,734 ALL STUDY VISITS, AND THERE WAS 8261 05:57:13,734 --> 05:57:17,104 AN INCREASE BY 23.1% IN 8262 05:57:17,104 --> 05:57:18,639 TELEVISITS BETWEEN YEAR ONE AND 8263 05:57:18,639 --> 05:57:21,942 YEAR TWO. 8264 05:57:21,942 --> 05:57:23,777 STUDY VISITS INCREASED IN ADULTS 8265 05:57:23,777 --> 05:57:28,315 IN THE PANDEMIC YEARS BY 30.1% 8266 05:57:28,315 --> 05:57:33,153 IN YEAR ONE, AND 8.2% IN YEAR 8267 05:57:33,153 --> 05:57:35,256 TWO. 8268 05:57:35,256 --> 05:57:36,991 HOWEVER, THEY FELL IN THE 8269 05:57:36,991 --> 05:57:40,261 CHILDREN IN THE PANDEMIC YEARS 8270 05:57:40,261 --> 05:57:45,032 BY 3.2% AND 6.2% IN YEAR ONE AND 8271 05:57:45,032 --> 05:57:47,668 YEAR TWO RESPECTIVELY. 8272 05:57:47,668 --> 05:57:49,470 BOTH TELEVISITS, HOWEVER, 8273 05:57:49,470 --> 05:57:52,506 INCREASED IN ADULTS AND CHILDREN 8274 05:57:52,506 --> 05:58:00,814 IN THE PANDEMIC YEARS. 8275 05:58:00,814 --> 05:58:02,116 ALL VISITS WERE NOT CODED AND 8276 05:58:02,116 --> 05:58:04,451 THIS REFERS TO THE FINAL 8277 05:58:04,451 --> 05:58:05,786 DIAGNOSIS GIVEN AT THE END OF 8278 05:58:05,786 --> 05:58:07,621 THE VISIT. 8279 05:58:07,621 --> 05:58:12,560 IN THE PANDEMIC YEARS, 96.7% OF 8280 05:58:12,560 --> 05:58:19,066 THE VISITS WERE CODED, 60.4% OF 8281 05:58:19,066 --> 05:58:20,601 THE TELEVISITS WERE CODED. 8282 05:58:20,601 --> 05:58:24,872 AND WHEN WE LOOK ON THE CODED 8283 05:58:24,872 --> 05:58:26,373 TELEVISITS, 78.3% WERE 8284 05:58:26,373 --> 05:58:29,543 ASSOCIATED WITH A WELL VISIT, 8285 05:58:29,543 --> 05:58:31,946 17.6% WITH THE HYDROXYUREA 8286 05:58:31,946 --> 05:58:35,382 VISIT, AND 2.8% WERE ASSOCIATED 8287 05:58:35,382 --> 05:58:41,221 WITH A PAIN VISIT. 8288 05:58:41,221 --> 05:58:43,157 SO LOOKING AT THIS, WE CAN SEE 8289 05:58:43,157 --> 05:58:44,291 THAT SICKLE CELL UNIT 8290 05:58:44,291 --> 05:58:45,826 REGISTRATION NUMBERS FELL IN THE 8291 05:58:45,826 --> 05:58:46,961 PANDEMIC YEARS, BUT THEY DID 8292 05:58:46,961 --> 05:58:48,062 SHOW AN INCREASE IN THE SECOND 8293 05:58:48,062 --> 05:58:49,663 YEAR OF THE PANDEMIC. 8294 05:58:49,663 --> 05:58:51,265 AND THIS IS ACTUALLY KEEPING 8295 05:58:51,265 --> 05:58:53,467 WITH OTHER STUDIES THAT HAVE 8296 05:58:53,467 --> 05:58:56,470 SHOWN A REBOUND IN HEALTHCARE 8297 05:58:56,470 --> 05:58:57,571 UTILIZATION AFTER THE EARLY 8298 05:58:57,571 --> 05:58:59,974 PANDEMIC PERIOD. 8299 05:58:59,974 --> 05:59:02,376 THE DECLINING NUMBERS FOR OUR 8300 05:59:02,376 --> 05:59:05,279 DAY WARD WAS CONSISTENT WITH ER 8301 05:59:05,279 --> 05:59:05,879 TRENDS. 8302 05:59:05,879 --> 05:59:07,615 OUR NUMBERS, HOWEVER, MAY HAVE 8303 05:59:07,615 --> 05:59:08,882 BEEN AMPLIFIED BY A DIRECT 8304 05:59:08,882 --> 05:59:12,553 REFERRAL TO HOSPITAL POLICY FOR 8305 05:59:12,553 --> 05:59:14,355 PATIENTS WHO AT TRIAGE HAVE A 8306 05:59:14,355 --> 05:59:17,725 HIGH RISK ASSESSMENT FOR COVID 8307 05:59:17,725 --> 05:59:20,527 AS OUR CLINIC ORIENTATION DID 8308 05:59:20,527 --> 05:59:29,203 NOT ALLOW US TO SEPARATE THESE 8309 05:59:29,203 --> 05:59:31,238 INDIVIDUALS FROM OTHER PATIENTS, 8310 05:59:31,238 --> 05:59:34,108 SO WE DID NOT WANT TO PUT OUR 8311 05:59:34,108 --> 05:59:40,914 OTHER PATIENTS AT RISK. 8312 05:59:40,914 --> 05:59:42,316 OUR STUDY ALSO SHOWED AN 8313 05:59:42,316 --> 05:59:44,618 INCREASE IN STUDY VISITS DURING 8314 05:59:44,618 --> 05:59:46,320 THE PANDEMIC YEARS, AND THIS WAS 8315 05:59:46,320 --> 05:59:49,289 MOSTLY DUE TO THE ADDITION OF 8316 05:59:49,289 --> 05:59:52,793 TELEVISITS, WHICH ARE CODED FOR 8317 05:59:52,793 --> 05:59:55,029 31.4% OF STUDY VISITS IN THE 8318 05:59:55,029 --> 05:59:56,664 PANDEMIC YEARS, AND BOTH 8319 05:59:56,664 --> 05:59:58,732 CAREGIVERS AND PATIENTS WITH 8320 05:59:58,732 --> 06:00:00,267 SICKLE CELL DISEASE IN A NUMBER 8321 06:00:00,267 --> 06:00:01,902 OF STUDIES HAVE SHOWN HIGH 8322 06:00:01,902 --> 06:00:03,804 SATISFACTION WITH USE OF 8323 06:00:03,804 --> 06:00:04,805 TELEHEALTH IN HEALTHCARE 8324 06:00:04,805 --> 06:00:08,609 DELIVERY. 8325 06:00:08,609 --> 06:00:10,110 DESPITE AN INCREASE IN STUDY 8326 06:00:10,110 --> 06:00:11,845 VISITS, THE NUMBER OF PERSONS 8327 06:00:11,845 --> 06:00:17,785 UTILIZING SERVICES FELL. 8328 06:00:17,785 --> 06:00:19,319 PATIENT BARRIERS, INCLUDING 8329 06:00:19,319 --> 06:00:20,688 TELECOMMUNICATION CHALLENGES, 8330 06:00:20,688 --> 06:00:22,322 LIMITED KNOWLEDGE ABOUT 8331 06:00:22,322 --> 06:00:24,591 TELEHEALTH, MAY HAVE AFFECTED 8332 06:00:24,591 --> 06:00:28,395 ACCESS AND USE. 8333 06:00:28,395 --> 06:00:29,797 ALMOST A THIRD OF ALL PATIENTS 8334 06:00:29,797 --> 06:00:31,665 WERE ONLY SEEN IN ONE STUDY 8335 06:00:31,665 --> 06:00:33,834 YEAR, AND THIS IS A LITTLE BIT 8336 06:00:33,834 --> 06:00:36,203 UNEXPECTED AS MOST OLDER 8337 06:00:36,203 --> 06:00:37,337 CHILDREN AND ADULTS WOULD BE 8338 06:00:37,337 --> 06:00:40,040 EXPECTED TO HAVE AT LEAST ONE TO 8339 06:00:40,040 --> 06:00:42,476 TWO ROUTINE HEALTH MAINTENANCE 8340 06:00:42,476 --> 06:00:46,146 CHECKS AND YOUNGER CHILDREN UP 8341 06:00:46,146 --> 06:00:47,414 TO FOUR ROUTINE HEALTH 8342 06:00:47,414 --> 06:00:52,252 MAINTENANCE CHECKS EACH YEAR. 8343 06:00:52,252 --> 06:00:53,854 WE LOST CONTACT WITH 17% OF 8344 06:00:53,854 --> 06:00:57,458 PATIENTS WHO WERE ONLY SEEN IN 8345 06:00:57,458 --> 06:00:59,093 THE PREPANDEMIC YEARS DESPITE 8346 06:00:59,093 --> 06:01:00,327 TELEVISITS. 8347 06:01:00,327 --> 06:01:02,429 ON THE OTHER HAND, ALMOST A 8348 06:01:02,429 --> 06:01:04,198 QUARTER OF OUR PATIENTS WERE 8349 06:01:04,198 --> 06:01:07,301 ONLY SEEN IN THE PANDEMIC YEARS, 8350 06:01:07,301 --> 06:01:08,802 AND SO IT IS PROBABLE THAT 8351 06:01:08,802 --> 06:01:10,170 TELEVISITS ALLOWED US TO REACH 8352 06:01:10,170 --> 06:01:13,006 OUT TO SOME PERSONS WHO HAD 8353 06:01:13,006 --> 06:01:16,210 DEFAULTED FROM CARE. 8354 06:01:16,210 --> 06:01:18,879 SO IF WE LOOK AHEAD, IT SEEMS 8355 06:01:18,879 --> 06:01:21,815 CLEAR THAT THERE IS A ROLE FOR 8356 06:01:21,815 --> 06:01:23,383 TELEMEDICINE IN SICKLE CELL 8357 06:01:23,383 --> 06:01:24,151 DISEASE HEALTHCARE. 8358 06:01:24,151 --> 06:01:26,253 IT HAS BEEN SHOWN TO BE FEASIBLE 8359 06:01:26,253 --> 06:01:28,388 AND ACCEPTABLE BY BOTH PATIENTS 8360 06:01:28,388 --> 06:01:30,657 AND HEALTHCARE PROVIDERS, 8361 06:01:30,657 --> 06:01:31,892 HOWEVER, AS PROVIDERS, WE WILL 8362 06:01:31,892 --> 06:01:34,795 NEED TO ASSESS OUR DELIVERY 8363 06:01:34,795 --> 06:01:37,231 SYSTEMS, LEGISLATION, INSURANCE, 8364 06:01:37,231 --> 06:01:38,132 ET CETERA, THAT'S GOING TO BE 8365 06:01:38,132 --> 06:01:42,302 NEEDED TO FACILITATE 8366 06:01:42,302 --> 06:01:43,403 TELEMEDICINE, AND DEFINITELY 8367 06:01:43,403 --> 06:01:44,838 FURTHER RESEARCH IS NEEDED ON 8368 06:01:44,838 --> 06:01:47,007 HEALTH OUTCOMES AND EXPERIENCES 8369 06:01:47,007 --> 06:01:48,842 WITH TELEMEDICINE. 8370 06:01:48,842 --> 06:01:59,253 THESE ARE MY REFERENCES. 8371 06:02:00,621 --> 06:02:02,022 THANK YOU, EVERYBODY, AND I HOPE 8372 06:02:02,022 --> 06:02:02,956 YOU ENJOY THE REST OF YOUR 8373 06:02:02,956 --> 06:02:07,094 CONFERENCE. 8374 06:02:07,094 --> 06:02:16,737 GOODBYE. 8375 06:02:16,737 --> 06:02:18,238 >> THANK YOU, DR. KING. 8376 06:02:18,238 --> 06:02:19,373 DR. KING IS ON ZOOM WITH US, SO 8377 06:02:19,373 --> 06:02:21,141 IF THERE ARE ANY QUESTIONS HERE 8378 06:02:21,141 --> 06:02:22,743 IN THE AUDIENCE, SHE WILL BE 8379 06:02:22,743 --> 06:02:32,319 ABLE TO TAKE THEM LIVE. 8380 06:02:32,319 --> 06:02:33,687 I DON'T SEE ANY QUESTIONS IN THE 8381 06:02:33,687 --> 06:02:33,921 CHAT. 8382 06:02:33,921 --> 06:02:35,789 FOR THOSE WHO ARE ON VIRTUALLY, 8383 06:02:35,789 --> 06:02:39,226 YOU HAVE TO RELEASE THEM TO LIVE 8384 06:02:39,226 --> 06:02:40,794 FEEDBACK, SO THEN WE CAN 8385 06:02:40,794 --> 06:02:42,129 TRANSFER THEM AND CHAT AND 8386 06:02:42,129 --> 06:02:43,130 PRESENT THEM TO DR. KING FOR 8387 06:02:43,130 --> 06:02:44,198 YOU. 8388 06:02:44,198 --> 06:02:49,002 DR. KING, I HAVE A QUESTION. 8389 06:02:49,002 --> 06:02:50,404 IS THERE ANY ABILITY TO LOOK AT 8390 06:02:50,404 --> 06:02:51,905 YOUR DATA TO SEE IF THERE ARE 8391 06:02:51,905 --> 06:02:54,575 ANY PREDICTORS FOR 8392 06:02:54,575 --> 06:02:56,376 CHARACTERISTICS IN YOUR PATIENT 8393 06:02:56,376 --> 06:02:59,012 POPULATION THAT WOULD IDENTIFY 8394 06:02:59,012 --> 06:03:01,048 THOSE WHO ARE A BETTER FIT FOR 8395 06:03:01,048 --> 06:03:03,483 TELEHEALTH, BECAUSE WE DID 8396 06:03:03,483 --> 06:03:04,952 SEE -- WE DID HAVE DIVERSE 8397 06:03:04,952 --> 06:03:07,154 EXPERIENCES AT OUR CENTER WHERE 8398 06:03:07,154 --> 06:03:10,657 SOME PATIENTS WERE POORLY 8399 06:03:10,657 --> 06:03:13,026 CONNECTED, THEN BECAME FURTHER 8400 06:03:13,026 --> 06:03:14,161 NON-ADHERENT AFTER TELEHEALTH 8401 06:03:14,161 --> 06:03:17,331 IMPLEMENTATION. 8402 06:03:17,331 --> 06:03:19,266 >> WE HAVEN'T ACTUALLY LOOKED AT 8403 06:03:19,266 --> 06:03:20,100 THAT. 8404 06:03:20,100 --> 06:03:24,938 WE DO KNOW THAT FOR MOBILE AND 8405 06:03:24,938 --> 06:03:26,874 CONNECTIVITY IS ALWAYS A PROBLEM 8406 06:03:26,874 --> 06:03:31,912 IN JAMAICA. 8407 06:03:31,912 --> 06:03:34,514 WE ALSO ARE CULTURALLY -- YOU 8408 06:03:34,514 --> 06:03:36,583 KNOW, A NUMBER OF OUR PATIENTS, 8409 06:03:36,583 --> 06:03:38,151 UNLESS THEY ACTUALLY COME TO THE 8410 06:03:38,151 --> 06:03:40,687 DOCTOR TO HAVE THEIR CHEST 8411 06:03:40,687 --> 06:03:41,788 SOUNDED, AS WE WOULD SAY, THEY 8412 06:03:41,788 --> 06:03:42,656 WOULDN'T FEEL THAT THEY WOULD 8413 06:03:42,656 --> 06:03:46,693 HAVE HAD AN ADEQUATE VISIT BY A 8414 06:03:46,693 --> 06:03:48,428 DOCTOR. 8415 06:03:48,428 --> 06:03:50,163 AND SO WE WOULD PROBABLY NEED TO 8416 06:03:50,163 --> 06:03:51,598 EXAMINE A LITTLE BIT MORE TO SEE 8417 06:03:51,598 --> 06:03:53,634 THE DIFFERENCES IN THE 8418 06:03:53,634 --> 06:03:55,435 CHARACTERISTICS OF THE PATIENTS 8419 06:03:55,435 --> 06:03:57,838 WHO WERE MORE COMPLIANT WITH THE 8420 06:03:57,838 --> 06:04:00,641 TELEHEALTH VISITS AND THOSE WHO 8421 06:04:00,641 --> 06:04:01,041 WEREN'T. 8422 06:04:01,041 --> 06:04:03,176 >> THANK YOU SO MUCH. 8423 06:04:03,176 --> 06:04:05,445 APPRECIATE T TH IT. 8424 06:04:05,445 --> 06:04:06,513 THAT WAS WONDERFUL. 8425 06:04:06,513 --> 06:04:07,814 ALL RIGHT, WE WILL MOVE ON TO 8426 06:04:07,814 --> 06:04:09,216 OUR NEXT TALK, WHICH IS CURRENT 8427 06:04:09,216 --> 06:04:11,518 AND EMERGING THERAPEUTIC AGENTS 8428 06:04:11,518 --> 06:04:14,054 IN SICKLE CELL DISEASE. 8429 06:04:14,054 --> 06:04:16,189 THIS TALK WILL BE PRESENTED BY 8430 06:04:16,189 --> 06:04:18,792 DR. CHARLES QUINN, WHO IS ALSO A 8431 06:04:18,792 --> 06:04:20,794 PEDIATRIC PROVIDER, PEDIATRIC 8432 06:04:20,794 --> 06:04:22,095 HEMATOLOGIST, PROFESSOR OF 8433 06:04:22,095 --> 06:04:23,897 PEDIATRICS AT CINCINNATI 8434 06:04:23,897 --> 06:04:24,898 CHILDREN'S HOSPITAL MEDICAL 8435 06:04:24,898 --> 06:04:25,565 CENTER. 8436 06:04:25,565 --> 06:04:27,768 HE'S THE MEDICAL DIRECTOR OF THE 8437 06:04:27,768 --> 06:04:28,735 PEDIATRIC SICKLE CELL PROGRAM 8438 06:04:28,735 --> 06:04:31,972 AND CO-DIRECTOR OF THE 8439 06:04:31,972 --> 06:04:33,040 ERYTHROCYTE DIAGNOSTIC 8440 06:04:33,040 --> 06:04:33,707 LABORATORY, AND WE LOOK FORWARD 8441 06:04:33,707 --> 06:04:36,310 TO HEARING FROM HIM ABOUT 8442 06:04:36,310 --> 06:04:40,180 CURRENT THERAPEUTICS. 8443 06:04:40,180 --> 06:04:48,956 >> THANK YOU FOR THE INVITATION. 8444 06:04:48,956 --> 06:04:52,826 EARLIER WE WERE REVIEWING OUR 8445 06:04:52,826 --> 06:04:54,428 JAMAICAN CONNECTION. 8446 06:04:54,428 --> 06:04:56,730 SADLY I'M NOT FROM JAMAICA BUT 8447 06:04:56,730 --> 06:04:59,099 THE LAST TIME I WAS IN JAMAICA, 8448 06:04:59,099 --> 06:04:59,766 I LOST A TOOTH. 8449 06:04:59,766 --> 06:05:03,270 MY DENTIST TELLS ME IT WAS A 8450 06:05:03,270 --> 06:05:05,672 CONGENITAL ABNORMALITY OF FUSION 8451 06:05:05,672 --> 06:05:06,506 OF THE ENAMEL. 8452 06:05:06,506 --> 06:05:07,808 I LIKE TO TELL PEOPLE I WAS IN A 8453 06:05:07,808 --> 06:05:08,375 BAR FIGHT. 8454 06:05:08,375 --> 06:05:09,476 IT'S MUCH MORE INTERESTING. 8455 06:05:09,476 --> 06:05:12,312 ALL RIGHT. 8456 06:05:12,312 --> 06:05:13,647 SO CURRENT -- I HOPE I DON'T 8457 06:05:13,647 --> 06:05:17,017 LOSE ANOTHER TOOTH AT THIS SCIF 8458 06:05:17,017 --> 06:05:17,784 CONFERENCE HERE. 8459 06:05:17,784 --> 06:05:19,319 CURRENT AND EMERGING THERAPEUTIC 8460 06:05:19,319 --> 06:05:20,320 AGENTS IN SICKLE CELL DISEASE. 8461 06:05:20,320 --> 06:05:22,856 I'M GOING TO FOCUS HERE ON THE 8462 06:05:22,856 --> 06:05:23,690 FDA-APPROVED THERAPIES FOR 8463 06:05:23,690 --> 06:05:25,258 SICKLE CELL DISEASE, AND RIGHT 8464 06:05:25,258 --> 06:05:27,027 AT THE BEGINNING, AT THE OUTSET, 8465 06:05:27,027 --> 06:05:31,932 THIS IS GOING TO BE A U.S. OR A 8466 06:05:31,932 --> 06:05:33,900 HIGH RESOURCE ENVIRONMENT 8467 06:05:33,900 --> 06:05:36,503 CENTRIC VIEW AND CENTRIC TALK. 8468 06:05:36,503 --> 06:05:38,038 THESE ARE THE -- SO YOU MIGHT 8469 06:05:38,038 --> 06:05:40,440 ASK, WELL, ARE THESE EMERGING 8470 06:05:40,440 --> 06:05:42,175 THERAPIES IN THE U.S.? 8471 06:05:42,175 --> 06:05:43,410 AND, WELL, THESE ARE THE CURRENT 8472 06:05:43,410 --> 06:05:44,945 AGENTS, BUT I THINK THEY'RE 8473 06:05:44,945 --> 06:05:48,281 RESPECTIVE AND THEIR ADDITIVE 8474 06:05:48,281 --> 06:05:49,716 ROLES ARE STILL EMERGING. 8475 06:05:49,716 --> 06:05:51,251 WHEREAS ANOTHER REG WILL TRI 8476 06:05:51,251 --> 06:05:55,989 RREGULATORYREGIONS OR COUNTRIESE 8477 06:05:55,989 --> 06:05:57,190 TRULY EMERGING AS THEY MAY 8478 06:05:57,190 --> 06:05:57,724 BECOME AVAILABLE SOON. 8479 06:05:57,724 --> 06:05:59,259 SO WE'LL TALK ABOUT THESE FOUR. 8480 06:05:59,259 --> 06:06:02,062 I HAVE RECEIVED RESEARCH FUNDING 8481 06:06:02,062 --> 06:06:07,234 FOR SOME PKPT WORK FOR 8482 06:06:07,234 --> 06:06:08,769 L-GLUTAMINE FROM THE 8483 06:06:08,769 --> 06:06:10,937 MANUFACTURER OF ENDARI. 8484 06:06:10,937 --> 06:06:13,673 ALL RIGHT. 8485 06:06:13,673 --> 06:06:15,075 SO EVERYTHING WITH SICKLE CELL 8486 06:06:15,075 --> 06:06:16,510 DISEASE AND SICKLE CELL ANEMIA 8487 06:06:16,510 --> 06:06:18,879 IN PARTICULAR START WITH SICKLE 8488 06:06:18,879 --> 06:06:20,680 HEMOGLOBIN, AND A MUTATION IS 8489 06:06:20,680 --> 06:06:22,849 HERE, AS YOU ALL KNOW IT, AND 8490 06:06:22,849 --> 06:06:25,452 WHAT THAT MUTATION LEADS TO IS 8491 06:06:25,452 --> 06:06:28,688 POLYMERIZATION OF HEMOGLOBIN IN 8492 06:06:28,688 --> 06:06:30,424 THE DEOOXYGENATED STATE. 8493 06:06:30,424 --> 06:06:31,858 YOU KNOW THE RED BLOOD CELL IS 8494 06:06:31,858 --> 06:06:33,126 PACKED FULL OF HEMOGLOBIN, AND 8495 06:06:33,126 --> 06:06:35,662 IT SHOULD BE, EVEN THOUGH THE 8496 06:06:35,662 --> 06:06:37,330 RED BLOOD CELLS TIGHTLY PACKED 8497 06:06:37,330 --> 06:06:38,665 WITH HEMOGLOBIN, IT SHOULD BE 8498 06:06:38,665 --> 06:06:39,900 FREELY SOLUBLE, BUT BECAUSE OF 8499 06:06:39,900 --> 06:06:44,071 THIS MUTATION, THEIR 8500 06:06:44,071 --> 06:06:45,338 INTERMOLECULAR CONTEXT UPON 8501 06:06:45,338 --> 06:06:46,306 DEOXYGENATION THAT LEAD TO A 8502 06:06:46,306 --> 06:06:47,407 CYCLIC AND REVERSIBLE PROCESS 8503 06:06:47,407 --> 06:06:49,776 THAT DAMAGES THE MEMBRANE HERE. 8504 06:06:49,776 --> 06:06:50,777 AND ONE THING TO POINT OUT HERE 8505 06:06:50,777 --> 06:06:53,814 IS THAT ALL PATHOPHYSIOLOGY IN 8506 06:06:53,814 --> 06:06:55,048 SICKLE CELL DISEASE IS 8507 06:06:55,048 --> 06:06:56,983 DOWNSTREAM FROM THE ABNORMAL 8508 06:06:56,983 --> 06:06:57,951 HEMOGLOBIN AND ITS 8509 06:06:57,951 --> 06:07:00,987 POLYMERIZATION, SO NIL THERAPY 8510 06:07:00,987 --> 06:07:03,190 THAT YOU DEVISE FOR SICKLE CELL, 8511 06:07:03,190 --> 06:07:07,494 THE CLOSER IT IS TO THIS CAUSE 8512 06:07:07,494 --> 06:07:08,895 OF POLYMERIZATION, THE BETTER 8513 06:07:08,895 --> 06:07:10,197 THE THERAPY IT WILL LIKELY TO 8514 06:07:10,197 --> 06:07:14,301 BE. 8515 06:07:14,301 --> 06:07:16,036 NOW WE'LL TALK ABOUT THE FOUR 8516 06:07:16,036 --> 06:07:18,538 AGENTS THAT ARE FDA-APPROVED. 8517 06:07:18,538 --> 06:07:19,106 THE FIRST IS HYDROXYUREA. 8518 06:07:19,106 --> 06:07:20,507 THIS IS THE ONE THAT'S BEEN 8519 06:07:20,507 --> 06:07:21,808 KNOWN ABOUT FOR THE LONGEST TIME 8520 06:07:21,808 --> 06:07:24,077 THAT WE'VE BEEN USING IT FOR 8521 06:07:24,077 --> 06:07:25,178 DECADES, REALLY. 8522 06:07:25,178 --> 06:07:26,947 PROOF OF PRINCIPLE STUDIES IN 8523 06:07:26,947 --> 06:07:29,416 SICKLE CELL IN THE 80s, IT WAS 8524 06:07:29,416 --> 06:07:31,418 FDA-APPROVED FOR ADULTS 18 AND 8525 06:07:31,418 --> 06:07:35,288 OLDER IN 1998, BUT ONLY UNTIL 8526 06:07:35,288 --> 06:07:37,824 2017 WAS IT FDA-APPROVED IN KIDS 8527 06:07:37,824 --> 06:07:40,460 GREATER THAN EQUAL TO 2 YEARS OF 8528 06:07:40,460 --> 06:07:40,627 AGE. 8529 06:07:40,627 --> 06:07:42,062 NOW, ITS MECHANISM OF ACTION, 8530 06:07:42,062 --> 06:07:44,164 YOU LOOK IT UP, YOU MAYBE 8531 06:07:44,164 --> 06:07:48,401 LEARNED IT AS A MEDICAL STUDENT, 8532 06:07:48,401 --> 06:07:50,704 IS A RIBONUCLEOTIDE REDUCTASE 8533 06:07:50,704 --> 06:07:51,204 INHIBITOR. 8534 06:07:51,204 --> 06:07:52,906 HOW EXACTLY THIS MECHANISM OF 8535 06:07:52,906 --> 06:07:55,242 ACTION LEADS TO THE LABORATORY 8536 06:07:55,242 --> 06:07:56,476 CLINICAL EFFECTS IS A BIT OF A 8537 06:07:56,476 --> 06:07:58,178 BLACK BOX AND THAT DESERVES A 8538 06:07:58,178 --> 06:07:59,513 LOT OF RESEARCH IN AND OF 8539 06:07:59,513 --> 06:08:00,747 ITSELF, BUT WHEN WE GIVE 8540 06:08:00,747 --> 06:08:02,549 HYDROXYUREA, WE INDUCE FETAL 8541 06:08:02,549 --> 06:08:05,652 HEMOGLOBIN, AND AS YOU REMEMBER, 8542 06:08:05,652 --> 06:08:07,420 DOWN HERE, HEMOGLOBIN F IS 8543 06:08:07,420 --> 06:08:10,323 INCORPORATED INTO THAT FIBER AS 8544 06:08:10,323 --> 06:08:12,392 IT'S GROWING AND INHIBITS 8545 06:08:12,392 --> 06:08:13,226 FURTHER POLYMERIZATION SO YOU 8546 06:08:13,226 --> 06:08:14,661 CAN THINK OF IT AS A CHAIN 8547 06:08:14,661 --> 06:08:15,095 TERMINATOR. 8548 06:08:15,095 --> 06:08:18,798 SO IT INDUCES FETAL HEMOGLOBIN, 8549 06:08:18,798 --> 06:08:20,433 AND THEN OTHER LABORATORY 8550 06:08:20,433 --> 06:08:24,137 EFFECTS INCREASED MCV, INCREASED 8551 06:08:24,137 --> 06:08:25,272 CELLULAR HYDRATION, DECREASED 8552 06:08:25,272 --> 06:08:26,973 WHITE COUNT, PLATELET COUNT, ALL 8553 06:08:26,973 --> 06:08:27,641 THESE OTHER THINGS. 8554 06:08:27,641 --> 06:08:29,376 AND THIS, AS YOU KNOW, IS A 8555 06:08:29,376 --> 06:08:30,677 MEDICINE THAT'S TAKEN ORALLY AND 8556 06:08:30,677 --> 06:08:31,645 ONCE A DAY. 8557 06:08:31,645 --> 06:08:34,848 SO IT DOES HAVE PLEIOTROPIC 8558 06:08:34,848 --> 06:08:37,217 EFFECTS BUT MOST OF THE EFFECTS, 8559 06:08:37,217 --> 06:08:38,151 THE PREDOMINANT EFFECTS RELATE 8560 06:08:38,151 --> 06:08:39,419 TO INDUCTION OF FETAL 8561 06:08:39,419 --> 06:08:39,753 HEMOGLOBIN. 8562 06:08:39,753 --> 06:08:41,521 AND I LIKE TO SHOW THIS SLIDE 8563 06:08:41,521 --> 06:08:44,124 BECAUSE THIS WAS IN THE STUDY 8564 06:08:44,124 --> 06:08:46,226 HALL IN ASH A COUPLE OF YEARS 8565 06:08:46,226 --> 06:08:46,593 AGO. 8566 06:08:46,593 --> 06:08:49,596 I WALKED BY GENE THERAPY BOOT 8567 06:08:49,596 --> 06:08:51,298 STUDY RATIONALE, FETAL 8568 06:08:51,298 --> 06:08:53,633 HEMOGLOBIN IS THE STRONGEST 8569 06:08:53,633 --> 06:08:54,834 PREDICTOR OF SICKLE CELL DISEASE 8570 06:08:54,834 --> 06:08:55,936 CLINICAL COURSE. 8571 06:08:55,936 --> 06:08:57,837 IT SAID HERE AVERAGE HEMOGLOBIN 8572 06:08:57,837 --> 06:08:59,339 F LEVELS AFTER TREATMENT, 9 TO 8573 06:08:59,339 --> 06:08:59,806 18%. 8574 06:08:59,806 --> 06:09:01,575 I SAID THAT'S INTERESTING. 8575 06:09:01,575 --> 06:09:04,277 AND DOWN HERE, IT SAYS THAT THE 8576 06:09:04,277 --> 06:09:05,145 CURATIVE OR FUNCTIONAL 8577 06:09:05,145 --> 06:09:06,346 LIQUEURTIVE NEW TREATMENTS AIM 8578 06:09:06,346 --> 06:09:07,948 FOR GREATER THAN 30%. 8579 06:09:07,948 --> 06:09:09,015 SO CLEARLY THAT'S NOT 8580 06:09:09,015 --> 06:09:09,583 HYDROXYUREA, RIGHT? 8581 06:09:09,583 --> 06:09:11,651 SO THIS IS AN OLD DRUG THAT 8582 06:09:11,651 --> 06:09:14,321 NEEDS REPLACEMENT, OR IS IT? 8583 06:09:14,321 --> 06:09:15,589 AND THE ANSWER IS YES IF YOU 8584 06:09:15,589 --> 06:09:23,530 STILL USE IT LIKE IT'S THE 19 TE 8585 06:09:23,530 --> 06:09:23,897 1990s. 8586 06:09:23,897 --> 06:09:27,234 SO IT'S AN OLD DRUG BUT WE CAN 8587 06:09:27,234 --> 06:09:32,505 USE NEW -- WE CAN ACHIEVE MUCH 8588 06:09:32,505 --> 06:09:34,107 GREATER HEMOGLOBIN F INDUCTION 8589 06:09:34,107 --> 06:09:35,575 IN CHILDREN AND MAINTAIN THIS 8590 06:09:35,575 --> 06:09:37,177 OVER MANY YEARS, UP TO CLOSE TO 8591 06:09:37,177 --> 06:09:38,578 A DECADE NOW FOR SOME OF THESE. 8592 06:09:38,578 --> 06:09:40,046 SO THE AVERAGE F THAT WE'RE 8593 06:09:40,046 --> 06:09:42,315 GETTING IS 20 TO 40%, SO REALLY 8594 06:09:42,315 --> 06:09:43,483 HAD TO EXTRAPOLATE OFF THIS 8595 06:09:43,483 --> 06:09:44,050 THING HERE. 8596 06:09:44,050 --> 06:09:45,252 AND HOW DO WE DO THAT? 8597 06:09:45,252 --> 06:09:47,621 WE HAVE TO START EARLY. 8598 06:09:47,621 --> 06:09:49,789 AND I'M TALKING 6 TO 9 MONTHS OF 8599 06:09:49,789 --> 06:09:52,659 AGE, PRESYMPTOMATIC OR PREMOST 8600 06:09:52,659 --> 06:09:53,326 SYMPTOMS, RIGHT, AND THEN WE 8601 06:09:53,326 --> 06:09:55,395 HAVE TO USE THE OPTIMAL DOSE, 8602 06:09:55,395 --> 06:09:58,898 AND WE AT LEAST DO IT BY 8603 06:09:58,898 --> 06:10:00,834 PK-GUIDED THERAPY, BECAUSE 8604 06:10:00,834 --> 06:10:03,270 EVERYBODY IS DIFFERENT. 8605 06:10:03,270 --> 06:10:04,904 EVERYBODY METABOLIZES, HANDLES 8606 06:10:04,904 --> 06:10:07,907 DRUG DIFFERENTLY, ANY DRUG, AND 8607 06:10:07,907 --> 06:10:08,775 STARTING EVERYBODY AT A STANDARD 8608 06:10:08,775 --> 06:10:15,582 PER KIE L KILO DOSE YOU'RE LIKET 8609 06:10:15,582 --> 06:10:17,117 OPTIMIZING THERAPY FOR ANYBODY. 8610 06:10:17,117 --> 06:10:20,053 WE DON'T SLOWLY WORK UP TO THE 8611 06:10:20,053 --> 06:10:22,055 M.T.V., BEGIN AT THE PREDICTED 8612 06:10:22,055 --> 06:10:23,523 M.T.V. AND MAINTAIN THAT OPTIMAL 8613 06:10:23,523 --> 06:10:24,557 DOSE OVER TIME. 8614 06:10:24,557 --> 06:10:26,059 AND THAT MAINTENANCE IS ACTUALLY 8615 06:10:26,059 --> 06:10:27,394 WHAT TAKES A LOT OF EFFORT. 8616 06:10:27,394 --> 06:10:28,862 FREQUENT DOSE ADJUSTMENTS IN 8617 06:10:28,862 --> 06:10:29,429 GROWING KIDS. 8618 06:10:29,429 --> 06:10:31,398 SO EVERY VISIT, EVERY OTHER 8619 06:10:31,398 --> 06:10:32,399 VISIT YOU'RE TWEAKING THE 8620 06:10:32,399 --> 06:10:32,799 HYDROXYUREA DOSE. 8621 06:10:32,799 --> 06:10:34,801 IF YOU DON'T DO THAT, THEY'LL 8622 06:10:34,801 --> 06:10:38,271 QUICKLY OUTGROW THEIR DOSE AND 8623 06:10:38,271 --> 06:10:39,272 DEVELOP PROBLEMS AS A 8624 06:10:39,272 --> 06:10:40,240 CONSEQUENCE OF THAT. 8625 06:10:40,240 --> 06:10:46,780 AND THAT REQUIRES A SYSTEM AND A 8626 06:10:46,780 --> 06:10:49,015 LOT OF RESOURCES ESPECIALLY 8627 06:10:49,015 --> 06:10:49,749 AROUND PATIENT ADHERENCE AND 8628 06:10:49,749 --> 06:10:51,518 SUPPORT TO MAKE THAT HAPPEN, AND 8629 06:10:51,518 --> 06:10:53,153 NOT ONLY DOES THAT REQUIRE A LOT 8630 06:10:53,153 --> 06:10:55,221 OF -- A BIG SYSTEM AND A LOT OF 8631 06:10:55,221 --> 06:10:56,089 RESOURCES. 8632 06:10:56,089 --> 06:10:59,225 THAT'S GOT TO BE MAINTAINED OVER 8633 06:10:59,225 --> 06:10:59,826 THE LIFE OF THE INDIVIDUAL IF 8634 06:10:59,826 --> 06:11:00,927 YOU'RE GOING TO CONTINUE USING 8635 06:11:00,927 --> 06:11:02,295 HYDROXYUREA IN AN OPTIMAL WAY. 8636 06:11:02,295 --> 06:11:05,832 AND SO WE CAN USE WITH PK-GUIDED 8637 06:11:05,832 --> 06:11:07,133 THERAPY AND STARTING EARLY, WE 8638 06:11:07,133 --> 06:11:09,269 CAN GET REALLY ROBUST INDUCTION 8639 06:11:09,269 --> 06:11:12,639 OF FETAL HEMOGLOBIN, YOU KNOW, 8640 06:11:12,639 --> 06:11:16,076 AVERAGE IS -- THIS IS AN EXAMPLE 8641 06:11:16,076 --> 06:11:17,644 PATIENT, WHEN YOU'RE BORN YOU 8642 06:11:17,644 --> 06:11:19,846 HAVE PREDOM NABTLY FETAL 8643 06:11:19,846 --> 06:11:20,480 HEMOGLOBIN, IT DECLINES. 8644 06:11:20,480 --> 06:11:21,881 THIS IS WHEN YOU START 8645 06:11:21,881 --> 06:11:22,749 HYDROXYUREA HERE. 8646 06:11:22,749 --> 06:11:23,983 MAYBE EVEN EARLIER. 8647 06:11:23,983 --> 06:11:25,418 YOU DON'T WANT TO JUST PREVENT 8648 06:11:25,418 --> 06:11:26,786 THE DECLINE, BUT YOU WANT TO 8649 06:11:26,786 --> 06:11:29,155 BRING IT RIGHT BACK UP, RIGHT? 8650 06:11:29,155 --> 06:11:31,591 AND IF WE DO THAT EARLY, AT THE 8651 06:11:31,591 --> 06:11:34,327 RIGHT DOSE, WE CAN ACHIEVE NEAR 8652 06:11:34,327 --> 06:11:37,430 PAN CELLULAR F CELL HEMOIMLOA 8653 06:11:37,430 --> 06:11:39,432 BIN F EXPRESSION, SO THIS IS AN 8654 06:11:39,432 --> 06:11:41,634 EXAMPLE PATIENT WITH 98% F 8655 06:11:41,634 --> 06:11:42,635 CELLS. 8656 06:11:42,635 --> 06:11:44,604 SO ESSENTIALLY PAN-CELLULAR. 8657 06:11:44,604 --> 06:11:46,639 OF COURSE NOT EVERYBODY IS 8658 06:11:46,639 --> 06:11:48,641 PAN-CELLULAR. 8659 06:11:48,641 --> 06:11:50,310 ABOUT 50% OF THIS COHORT THAT 8660 06:11:50,310 --> 06:11:52,345 WE'RE FOLLOWING HAS PAN CELLULAR 8661 06:11:52,345 --> 06:11:54,981 OR NEAR PAN CELLULAR FETAL 8662 06:11:54,981 --> 06:11:56,049 HEMOGLOBIN EXPRESSION. 8663 06:11:56,049 --> 06:11:57,884 OBVIOUSLY THERE'S SOME THAT HAVE 8664 06:11:57,884 --> 06:11:59,319 LESSER RESPONSES FOR VARIOUS 8665 06:11:59,319 --> 06:12:04,124 REASONS, AND THIS IS WHAT 8666 06:12:04,124 --> 06:12:05,558 TROUBLES ALL OF US IN THE FIELD, 8667 06:12:05,558 --> 06:12:06,292 RIGHT? 8668 06:12:06,292 --> 06:12:08,495 AND SO AGAIN, WHAT DO WE DO? 8669 06:12:08,495 --> 06:12:09,696 THIS IS WHAT WE HAVE. 8670 06:12:09,696 --> 06:12:11,631 YOU HAVE TO START EARLY AND YOU 8671 06:12:11,631 --> 06:12:12,966 HAVE TO OPTIMIZE THE DOSE AND 8672 06:12:12,966 --> 06:12:15,368 THEN YOU HAVE TO MAINTAIN THAT 8673 06:12:15,368 --> 06:12:16,336 OPTIMAL DOSE OVER TIME, RIGHT? 8674 06:12:16,336 --> 06:12:17,871 AND NOT ONLY DO YOU HAVE TO LOOK 8675 06:12:17,871 --> 06:12:19,706 AT IT IN THE INDIVIDUAL BUT YOU 8676 06:12:19,706 --> 06:12:23,543 HAVE TO HAVE A SYSTEM-WIDE OR A 8677 06:12:23,543 --> 06:12:24,177 POPULATION-BASED METHOD OF 8678 06:12:24,177 --> 06:12:24,644 TRACKING THIS. 8679 06:12:24,644 --> 06:12:27,881 SO HERE WE CAN SEE PERCENT FETAL 8680 06:12:27,881 --> 06:12:29,749 HEMOGLOBIN, 40% OVER EIGHT 8681 06:12:29,749 --> 06:12:33,920 YEARS, 40% OVER EIGHT YEARS, AND 8682 06:12:33,920 --> 06:12:35,321 SO THAT'S GREAT WHEN YOU HAVE 8683 06:12:35,321 --> 06:12:35,989 ONE OF THESE INDIVIDUAL PATIENTS 8684 06:12:35,989 --> 06:12:36,990 THAT DOES EXTREMELY WELL. 8685 06:12:36,990 --> 06:12:38,158 WHAT ABOUT FOR THE ENTIRE 8686 06:12:38,158 --> 06:12:38,691 POPULATION? 8687 06:12:38,691 --> 06:12:41,261 SO THIS IS -- WE'RE MEASURING 8688 06:12:41,261 --> 06:12:42,996 FETAL HEMOGLOBIN AS A QI END 8689 06:12:42,996 --> 06:12:47,033 POINT, RIGHT, FOR SICKLE CELL 8690 06:12:47,033 --> 06:12:48,201 PATIENTS, SICKLE CELL ANEMIA WHO 8691 06:12:48,201 --> 06:12:50,170 ARE ON HYDROXYUREA. 8692 06:12:50,170 --> 06:12:53,506 AND THESE ARE THE PROPORTION OF 8693 06:12:53,506 --> 06:12:56,109 PATIENTS IN BLACK HERE WHOSE 8694 06:12:56,109 --> 06:12:57,410 FETAL HEMOGLOBIN IS GREATER THAN 8695 06:12:57,410 --> 06:12:58,111 20%. 8696 06:12:58,111 --> 06:13:00,713 SO 70% OF THE ENTIRE POPULATION, 8697 06:13:00,713 --> 06:13:03,316 UP TO AGE 21, HAS A FETAL 8698 06:13:03,316 --> 06:13:04,217 HEMOGLOBIN GREATER THAN 20%. 8699 06:13:04,217 --> 06:13:06,019 THAT USED TO BE REALLY GOOD. 8700 06:13:06,019 --> 06:13:08,421 I DON'T THINK IT'S THAT GOOD 8701 06:13:08,421 --> 06:13:11,825 ANYMORE, SO WE REALLY NEED TO 8702 06:13:11,825 --> 06:13:13,626 IMPROVE THAT, SO ABOUT 40% OF 8703 06:13:13,626 --> 06:13:15,395 OUR POPULATION IS AT LEAST 30%. 8704 06:13:15,395 --> 06:13:17,363 ONCE WE GET THE F TO 30%, WE'RE 8705 06:13:17,363 --> 06:13:19,532 GETTING ABOUT 80% F CELLS, SO 8706 06:13:19,532 --> 06:13:22,302 WE'VE GOT LOTS MORE PROTECTION 8707 06:13:22,302 --> 06:13:23,603 OF ERYTHROCYTE FROM SICKLING. 8708 06:13:23,603 --> 06:13:25,238 SO START EARLY, OPTIMIZE THE 8709 06:13:25,238 --> 06:13:28,308 KODOSE AND MAINTAIN IT OVER TIM. 8710 06:13:28,308 --> 06:13:30,844 SO I THINK I'M PREACHING TO THE 8711 06:13:30,844 --> 06:13:35,215 CHOIR HERE IN THAT RESPECT. 8712 06:13:35,215 --> 06:13:36,416 BUT WHAT DO WE KNOW ABOUT 8713 06:13:36,416 --> 06:13:36,716 HYDROXYUREA? 8714 06:13:36,716 --> 06:13:40,320 IT TEE CREASES PAINFUL EPISODES, 8715 06:13:40,320 --> 06:13:41,654 DECREASES CHEST SYNDROME. 8716 06:13:41,654 --> 06:13:43,590 DECREASES STROKE, BOTH PRIMARY 8717 06:13:43,590 --> 06:13:47,560 AND SECONDARY, DECREASES THE 8718 06:13:47,560 --> 06:13:52,799 FREQUENCY OF PLA TRANSFUSIONS, 8719 06:13:52,799 --> 06:13:54,634 INCREASES HEMOGLOBIN, INCREASES 8720 06:13:54,634 --> 06:13:58,605 HEMOGLOBIN F, IMPROVES RHEOLOGY, 8721 06:13:58,605 --> 06:13:59,639 IMPROVES QUALITY OF LIFE, PRO 8722 06:13:59,639 --> 06:14:03,376 LONGS LIFE AND YEARLY COST OF 8723 06:14:03,376 --> 06:14:06,546 ABOUT $2,000 PER YEAR OF LIFE. 8724 06:14:06,546 --> 06:14:07,547 SO LET'S TALK ABOUT PATIENTS AND 8725 06:14:07,547 --> 06:14:08,848 HOW THEY FIT INTO THAT PARADIGM. 8726 06:14:08,848 --> 06:14:10,016 WHEN WE'RE THINKING ABOUT THAT, 8727 06:14:10,016 --> 06:14:12,218 GOING BACK TO THAT QUESTION 8728 06:14:12,218 --> 06:14:14,754 ABOUT HYDROXYUREA, IS IT THE OLD 8729 06:14:14,754 --> 06:14:16,256 DRUG THAT NEEDS REPLACEMENT OR 8730 06:14:16,256 --> 06:14:17,824 IS IT THE THING THAT'S CLOSEST 8731 06:14:17,824 --> 06:14:18,691 TO THE CURE CURRENTLY THAT 8732 06:14:18,691 --> 06:14:21,661 SHOULD BE MET OR EXCEEDED BY NEW 8733 06:14:21,661 --> 06:14:24,564 THERAPIES? 8734 06:14:24,564 --> 06:14:26,366 I THINK THE ANSWER IS YES, I 8735 06:14:26,366 --> 06:14:28,067 THINK IT DOES NEED REPLACEMENT 8736 06:14:28,067 --> 06:14:30,803 BY SOMETHING BETTER BUT BE SURE 8737 06:14:30,803 --> 06:14:31,571 THAT WE REPLACE IT WITH 8738 06:14:31,571 --> 06:14:32,805 SOMETHING BETTER. 8739 06:14:32,805 --> 06:14:34,974 SO L-GLUTAMINE, EARLY STUDIES 8740 06:14:34,974 --> 06:14:37,076 WERE DONE IN THE 1970s, BUT IT 8741 06:14:37,076 --> 06:14:40,313 WASN'T UNTIL 2017 THAT IT WAS 8742 06:14:40,313 --> 06:14:42,348 APPROVED FOR PEOPLE WITH SICKLE 8743 06:14:42,348 --> 06:14:46,019 CELL DISEASE AGE 5 AND UP. 8744 06:14:46,019 --> 06:14:47,453 AND THERE'S A LOT OF TEXT HERE, 8745 06:14:47,453 --> 06:14:48,555 BUT HOW IS GLUTAMINE IMPORTANT 8746 06:14:48,555 --> 06:14:49,522 TO THE BODY? 8747 06:14:49,522 --> 06:14:50,957 THAT'S SORT OF LIKE ASKING HOW 8748 06:14:50,957 --> 06:14:52,025 IS GLUCOSE IMPORTANT TO THE 8749 06:14:52,025 --> 06:14:53,726 BODY, OR HOW IS PHOSPHOROUS 8750 06:14:53,726 --> 06:14:54,527 IMPORTANT TO THE BODY? 8751 06:14:54,527 --> 06:14:57,363 THIS IS ONE OF THE MOST ABUNDANT 8752 06:14:57,363 --> 06:14:58,464 AMINO ACIDS IN THE BODY, AND SO 8753 06:14:58,464 --> 06:15:01,568 IT DOES A LOT OF THINGS. 8754 06:15:01,568 --> 06:15:04,938 BUT AS A HEMATOLOGIST, PROBABLY 8755 06:15:04,938 --> 06:15:06,906 TOO NARROW OF A VIEW THINKING 8756 06:15:06,906 --> 06:15:10,510 ABOUT HOW GLUTAMINE MIGHT WORK. 8757 06:15:10,510 --> 06:15:12,912 IT IS A PRECURSOR FOR THE 8758 06:15:12,912 --> 06:15:20,219 SYNTHESIS OF GLUTATHIONE, GSH, 8759 06:15:20,219 --> 06:15:23,423 ADENINE AND ARGININE. 8760 06:15:23,423 --> 06:15:25,792 BUT ITS MECHANISM OF ACTION IS 8761 06:15:25,792 --> 06:15:29,963 REALLY NOT WELL CHARACTERIZED. 8762 06:15:29,963 --> 06:15:32,799 IT'S THOUGHT TO BE MAINLY AROUND 8763 06:15:32,799 --> 06:15:33,466 REDUCED OXIDATIVE STRESS BECAUSE 8764 06:15:33,466 --> 06:15:33,900 OF THIS. 8765 06:15:33,900 --> 06:15:36,002 IT'S AN ORAL POWDER, YOU TAKE IT 8766 06:15:36,002 --> 06:15:36,502 TWICE DAILY. 8767 06:15:36,502 --> 06:15:38,237 SO HYDROXYUREA IS ONCE DAILY. 8768 06:15:38,237 --> 06:15:41,207 HERE A POWDER YOU HAVE TO MIX IN 8769 06:15:41,207 --> 06:15:42,609 SOMETHING OR SPREAD ON 8770 06:15:42,609 --> 06:15:45,278 SOMETHING, PEOPLE DON'T LIKE IT. 8771 06:15:45,278 --> 06:15:48,448 IT'S NOT ANYTHING THAT IS TWICE 8772 06:15:48,448 --> 06:15:50,316 A DAY IS NOT AS GOOD AS ONCE A 8773 06:15:50,316 --> 06:15:53,319 DAY IN TERMS OF PALATABILITY AND 8774 06:15:53,319 --> 06:15:53,653 ACCEPTABILITY. 8775 06:15:53,653 --> 06:15:56,689 AND WHAT DOES DO, AT LEAST IN 8776 06:15:56,689 --> 06:15:58,391 TWO OR THREE CLINICAL TRIALS, 8777 06:15:58,391 --> 06:16:00,627 SHOWED DECREASED FREQUENCY OF 8778 06:16:00,627 --> 06:16:04,430 PAINFUL EPISODES AND PAINFUL 8779 06:16:04,430 --> 06:16:07,367 SICKLE CELL-RELATED ACUTE 8780 06:16:07,367 --> 06:16:09,802 EVENTS. 8781 06:16:09,802 --> 06:16:11,337 BUT IT DIDN'T DO MUCH OF THE 8782 06:16:11,337 --> 06:16:12,405 OTHER THINGS THAT HYDROXYUREA 8783 06:16:12,405 --> 06:16:13,272 DOES HERE. 8784 06:16:13,272 --> 06:16:16,042 SO THIS IS JUST SOME HISTORY 8785 06:16:16,042 --> 06:16:18,311 HERE OF SS ERYTHROCYTES AND 8786 06:16:18,311 --> 06:16:19,612 GLUTAMINE, AND REALLY I 8787 06:16:19,612 --> 06:16:20,613 EXPLAINED THIS IN THE PREVIOUS 8788 06:16:20,613 --> 06:16:22,515 SLIDE, BUT THE THEORY IS THAT 8789 06:16:22,515 --> 06:16:25,852 THE INCREASED NAD TURNOVER DUE 8790 06:16:25,852 --> 06:16:31,424 TO ONGOING OXIDATIVE INJURY WITH 8791 06:16:31,424 --> 06:16:34,327 A COMPENSATORY INCREASE -- TO 8792 06:16:34,327 --> 06:16:36,696 SUPPORT NAD SYNTHESIS, AND THAT 8793 06:16:36,696 --> 06:16:40,833 FORMED THE BASIS FOR STUDIES, 8794 06:16:40,833 --> 06:16:42,201 HERE'S ANOTHER WAY OF THINKING 8795 06:16:42,201 --> 06:16:44,570 ABOUT IT HERE, ERYTHROCYTE, 8796 06:16:44,570 --> 06:16:45,972 OXIDATIVE STRESS FROM THE 8797 06:16:45,972 --> 06:16:48,541 ERYTHROCYTE DUE TO SICKLE 8798 06:16:48,541 --> 06:16:49,375 HEMOGLOBIN AND THE DOWNSTREAM 8799 06:16:49,375 --> 06:16:50,309 CONSEQUENCES OF POLYMERIZATION, 8800 06:16:50,309 --> 06:16:54,647 AND WHAT CAN QUENCH OXIDATIVE 8801 06:16:54,647 --> 06:16:59,352 STRESS NADPH GLUTE THIGH YOAN 8802 06:16:59,352 --> 06:17:01,254 AND A PRECURSOR IS L-GLUTAMINE. 8803 06:17:01,254 --> 06:17:03,956 SO THAT MAKES A NICE STORY FOR 8804 06:17:03,956 --> 06:17:04,957 THE HEMATOLOGIST BUT REALLY THE 8805 06:17:04,957 --> 06:17:06,392 MECHANISM OF ACTION IS UNCLEAR 8806 06:17:06,392 --> 06:17:07,894 SO WE'VE BEEN DOING SOME -- AND 8807 06:17:07,894 --> 06:17:09,028 I TOOK OUT SOME OF THE STUDIES 8808 06:17:09,028 --> 06:17:11,631 THAT WE'VE DONE FOR THIS 8809 06:17:11,631 --> 06:17:12,932 PARTICULAR TALK MAKING IT A BIT 8810 06:17:12,932 --> 06:17:16,936 MORE CLINICAL LOOKING AT THE 8811 06:17:16,936 --> 06:17:18,237 PK-PD ASSOCIATIONS WITH 8812 06:17:18,237 --> 06:17:20,440 GLUTAMINE, BUT WHAT WE FOUND, IF 8813 06:17:20,440 --> 06:17:22,041 WE NOT JUST -- WE DON'T JUST 8814 06:17:22,041 --> 06:17:25,211 LOOK AT HOW MUCH L-GLUTAMINE 8815 06:17:25,211 --> 06:17:29,582 YOUR DOSE IS, LIKE 30 MG, YOU 8816 06:17:29,582 --> 06:17:31,317 KNOW, WHAT -- IT'S LIKE HOW 8817 06:17:31,317 --> 06:17:32,852 MUCH -- WHAT WAS THE MAXIMUM 8818 06:17:32,852 --> 06:17:33,186 CONCENTRATION? 8819 06:17:33,186 --> 06:17:34,320 WHAT WAS THE AREA UNDER THE 8820 06:17:34,320 --> 06:17:36,589 CURVE THAT YOU ACHIEVED IN YOUR 8821 06:17:36,589 --> 06:17:38,157 BLOODSTREAM WHEN YOU GOT GLUED 8822 06:17:38,157 --> 06:17:41,094 GLEUT MEAN? 8823 06:17:41,094 --> 06:17:42,128 GLUTAMINE? 8824 06:17:42,128 --> 06:17:49,335 SO WE FOUND HIGHER C MAX OR 8825 06:17:49,335 --> 06:17:49,969 AUCs -- DECREASED POINT OF 8826 06:17:49,969 --> 06:17:53,773 SICKLING BY OXYGEN GRADIENT 8827 06:17:53,773 --> 06:17:55,341 CYTOMETRY, INCREASED ARGININE 8828 06:17:55,341 --> 06:17:57,110 BIOAVAILABILITY AND HAD SOME 8829 06:17:57,110 --> 06:17:58,644 OTHER EFFECTS BUT INTERESTINGLY 8830 06:17:58,644 --> 06:18:00,747 IT MADE BLOOD MORE VISCOUS AND 8831 06:18:00,747 --> 06:18:03,349 HAD SOME OTHER THINGS LIKE 8832 06:18:03,349 --> 06:18:03,983 HEMOGLOBIN, HEMATOCRIT WENT UP 8833 06:18:03,983 --> 06:18:05,785 BUT THAT COULD MAKE VISCOSITY 8834 06:18:05,785 --> 06:18:07,420 HIGHER UNLESS THERE'S AN 8835 06:18:07,420 --> 06:18:09,322 OTHERWISE BENEFICIAL IMPROVEMENT 8836 06:18:09,322 --> 06:18:10,723 IN RHEOLOGY. 8837 06:18:10,723 --> 06:18:12,291 SO I THINK THIS IS WHY THE 8838 06:18:12,291 --> 06:18:13,526 BENEFICIAL EFFECTS OF GLUTAMINE 8839 06:18:13,526 --> 06:18:15,027 ARE HARD TO TEASE OUT, 8840 06:18:15,027 --> 06:18:16,095 ESPECIALLY IN A CLINICAL TRIAL 8841 06:18:16,095 --> 06:18:19,098 THAT'S JUST FOCUSED ON 8842 06:18:19,098 --> 06:18:21,834 VASO-OCCLUSIVE CRISIS, ONE 8843 06:18:21,834 --> 06:18:22,835 THING, AND SICKLE CELL AFFECTS 8844 06:18:22,835 --> 06:18:24,036 SO MANY DIFFERENT THINGS, AND I 8845 06:18:24,036 --> 06:18:24,904 THINK DIFFERENT PEOPLE ARE 8846 06:18:24,904 --> 06:18:26,339 DIFFERENT, AND ARE GOING TO 8847 06:18:26,339 --> 06:18:27,874 RESPOND DIFFERENTLY TO THIS 8848 06:18:27,874 --> 06:18:29,976 MEDICATION. 8849 06:18:29,976 --> 06:18:32,044 SO WE DON'T KNOW MUCH ABOUT IT. 8850 06:18:32,044 --> 06:18:35,848 IT SEEMS TO DECREASE PAIN. 8851 06:18:35,848 --> 06:18:37,717 SO -- BUT NOT SO MUCH IN THE WAY 8852 06:18:37,717 --> 06:18:39,585 OF STRONG EVIDENCE FOR CHEST 8853 06:18:39,585 --> 06:18:40,820 SYNDROME WITH STROKE, IT DOESN'T 8854 06:18:40,820 --> 06:18:43,556 DO ANYTHING WITH TRANSFUSIONS, 8855 06:18:43,556 --> 06:18:46,592 HEMOGLOBIN, HEMOGLOBIN F. 8856 06:18:46,592 --> 06:18:49,262 POSSIBLY IT IMPROVES RHEOLOGY 8857 06:18:49,262 --> 06:18:50,797 BUT THAT'S SOME OF THE 8858 06:18:50,797 --> 06:18:51,697 PHARMACODYNAMIC STUDIES THAT 8859 06:18:51,697 --> 06:18:52,999 WE'RE DOING, AND IT'S MORE 8860 06:18:52,999 --> 06:18:53,533 EX-PIN SIEVE. 8861 06:18:53,533 --> 06:18:55,701 IT MAY IMPROVE QUALITY OF LIFE 8862 06:18:55,701 --> 06:18:56,903 BUT NOBODY HAS DONE THAT STUDY 8863 06:18:56,903 --> 06:18:58,204 AND PROVIDED DIRECT EVIDENCE FOR 8864 06:18:58,204 --> 06:18:58,404 THAT. 8865 06:18:58,404 --> 06:19:00,640 SAME THING WITH PROLONGATION OF 8866 06:19:00,640 --> 06:19:01,707 LIFE. 8867 06:19:01,707 --> 06:19:04,777 SO HYDROXYUREA AND L-GLUTAMINE. 8868 06:19:04,777 --> 06:19:08,447 NOW, WE'LL DO CRIZANLIZUMAB 8869 06:19:08,447 --> 06:19:08,815 NEXT. 8870 06:19:08,815 --> 06:19:10,249 I THINK IT WELL-KNOWN TO THIS 8871 06:19:10,249 --> 06:19:11,117 GROUP. 8872 06:19:11,117 --> 06:19:13,719 WE STARTED LEARNING ABOUT 8873 06:19:13,719 --> 06:19:16,789 ADHESIONS AND SELECTINS IN 8874 06:19:16,789 --> 06:19:17,723 SICKLE CELL DISEASE IN THE 8875 06:19:17,723 --> 06:19:17,924 1990s. 8876 06:19:17,924 --> 06:19:20,426 THIS WAS APPROVED IN 2019 FOR 16 8877 06:19:20,426 --> 06:19:24,730 AND UP, AND AS YOU KNOW, 8878 06:19:24,730 --> 06:19:27,533 HUMANIZED MONOCLONAL ANTIBODY 8879 06:19:27,533 --> 06:19:37,043 AGAINST P SELECTINS -- NOT ONLY 8880 06:19:37,043 --> 06:19:38,811 TO EACH OTHER BUT TO THE 8881 06:19:38,811 --> 06:19:40,813 ENDOTHELIAL SURFACE AS WELL, AND 8882 06:19:40,813 --> 06:19:44,317 SO THIS CAUSES STASIS AND THEN 8883 06:19:44,317 --> 06:19:46,919 SECONDARY TO THAT, BECAUSE OF 8884 06:19:46,919 --> 06:19:48,788 DEOXYGENATION, A VASOOCCLUSION, 8885 06:19:48,788 --> 06:19:51,490 AND THEN ISCHEMIA REPERFUSION 8886 06:19:51,490 --> 06:19:52,625 INJURY. 8887 06:19:52,625 --> 06:19:57,330 SO IF WE GIVE P-SELECTIN, IT CAN 8888 06:19:57,330 --> 06:19:58,631 INHIBIT SOME OF THOSE 8889 06:19:58,631 --> 06:20:01,801 INTERACTIONS AND DECREASE 8890 06:20:01,801 --> 06:20:03,536 VASOOCCLUSION. 8891 06:20:03,536 --> 06:20:05,504 AND SO LABORATORY EFFECTS, 8892 06:20:05,504 --> 06:20:06,939 THERE'S NOT MUCH THAT HAPPENS IN 8893 06:20:06,939 --> 06:20:08,474 THE BLOOD COUNTS THAT YOU CAN 8894 06:20:08,474 --> 06:20:12,311 MEASURE OR SEE, AND IT'S GIVEN 8895 06:20:12,311 --> 06:20:14,480 BY AN IV INFUSION MONTHLY. 8896 06:20:14,480 --> 06:20:17,116 SO AGAIN, LIKE L-GLUTAMINE, 8897 06:20:17,116 --> 06:20:17,984 DECREASES PAIN. 8898 06:20:17,984 --> 06:20:19,852 THIS ONE IS GIVEN IV, IT'S GIVEN 8899 06:20:19,852 --> 06:20:21,153 MONTHLY EXCEPT FOR THE FIRST 8900 06:20:21,153 --> 06:20:22,521 THREE DOSES, WHICH ARE TWO WEEKS 8901 06:20:22,521 --> 06:20:24,123 APART. 8902 06:20:24,123 --> 06:20:25,324 NOW THE PROBLEM IS, I DON'T KNOW 8903 06:20:25,324 --> 06:20:26,859 HOW MUCH LONGER WE'LL BE TALKING 8904 06:20:26,859 --> 06:20:28,728 ABOUT THIS. 8905 06:20:28,728 --> 06:20:30,162 HOPEFULLY -- WE DO HAVE PATIENT 8906 06:20:30,162 --> 06:20:31,664 ON ALL OF THESE THERAPIES THAT 8907 06:20:31,664 --> 06:20:40,006 I'M TALKING ABOUT WITH -- SO 8908 06:20:40,006 --> 06:20:42,441 JUST BECAUSE I DON'T POINT OUT 8909 06:20:42,441 --> 06:20:43,476 SOMETHING IT DOESN'T MEAN I 8910 06:20:43,476 --> 06:20:45,478 DON'T THINK IT'S WORTHWHILE. 8911 06:20:45,478 --> 06:20:48,114 NO STATISTICALLY SIGNIFICANT 8912 06:20:48,114 --> 06:20:51,550 DIFFERENCE BETWEEN CRIZ AND 8913 06:20:51,550 --> 06:20:53,619 PLACEBO, SO THIS REGULATORY FATE 8914 06:20:53,619 --> 06:20:56,956 IN THE U.S. AND THE E.U. IS 8915 06:20:56,956 --> 06:20:57,790 PROBABLY GOING TO BE DIFFERENT, 8916 06:20:57,790 --> 06:20:58,591 SO I DON'T KNOW WHERE THAT'S 8917 06:20:58,591 --> 06:20:59,926 GOING TO END UP. 8918 06:20:59,926 --> 06:21:01,594 BUT RIGHT NOW, WE HAVE IT, AND I 8919 06:21:01,594 --> 06:21:03,529 DO USE IT AND IT SEEMS TO BE 8920 06:21:03,529 --> 06:21:05,264 HELPFUL FOR A SMALL POPULATION 8921 06:21:05,264 --> 06:21:07,867 OF PATIENTS THAT GET THAT FAR. 8922 06:21:07,867 --> 06:21:09,268 SO WHAT DOES DO? 8923 06:21:09,268 --> 06:21:13,306 DECREASES PAINFUL EPISODES, YES. 8924 06:21:13,306 --> 06:21:14,674 LESS INFORMATION ABOUT CHEST 8925 06:21:14,674 --> 06:21:15,975 SYNDROME, STROKE, THAT SORT OF 8926 06:21:15,975 --> 06:21:16,509 THING. 8927 06:21:16,509 --> 06:21:18,678 NO EFFECTS ON YOUR BLOOD COUNTS. 8928 06:21:18,678 --> 06:21:20,446 AND IT'S A LOT MORE EXPENSIVE, 8929 06:21:20,446 --> 06:21:26,218 RIGHT, SO $100,000. 8930 06:21:26,218 --> 06:21:28,454 NOW LET'S ADD IN ANOTHER THING. 8931 06:21:28,454 --> 06:21:29,522 SO HERE, COMPARISON OF EFFECTS 8932 06:21:29,522 --> 06:21:32,491 OF THESE DIFFERENT AGENTS ON VOC 8933 06:21:32,491 --> 06:21:34,427 RATE, AND THIS WAS PUBLISHED IN 8934 06:21:34,427 --> 06:21:35,928 2021. 8935 06:21:35,928 --> 06:21:39,065 AND THE MSH TRIAL, L-GLUTAMINE 8936 06:21:39,065 --> 06:21:40,766 PHASE THREE STUDIES, THE SUSTAIN 8937 06:21:40,766 --> 06:21:40,967 TRIAL. 8938 06:21:40,967 --> 06:21:44,103 YOU CAN SEE EACH OF THESE 8939 06:21:44,103 --> 06:21:46,872 DECREASED ANNUALIZED CRISIS RATE 8940 06:21:46,872 --> 06:21:50,276 BY ABOUT 45%, PRETTY EQUIVALENT, 8941 06:21:50,276 --> 06:21:51,777 SO THESE SHOULD BE 8942 06:21:51,777 --> 06:21:52,144 INTERCHANGEABLE. 8943 06:21:52,144 --> 06:21:53,746 WELL, I THINK IF YOU'RE USING 8944 06:21:53,746 --> 06:21:56,749 HYDROXYUREA AS IT WAS IN 1995, 8945 06:21:56,749 --> 06:21:58,951 THAT THAT'S UND UNDERTREATMENT. 8946 06:21:58,951 --> 06:22:00,820 BECAUSE WE CAN SEE MUCH MORE 8947 06:22:00,820 --> 06:22:02,021 DRAMATIC EFFECTS NOW. 8948 06:22:02,021 --> 06:22:03,789 IF YOU OPTIMIZE THE DOSE FOR 8949 06:22:03,789 --> 06:22:04,824 EACH INDIVIDUAL AND MAINTAIN 8950 06:22:04,824 --> 06:22:06,959 THAT OVER TIME. 8951 06:22:06,959 --> 06:22:10,563 SO THIS IS COMPARING 90s DATA 8952 06:22:10,563 --> 06:22:13,499 TO 2015, 2020 DATA, AND WE USE 8953 06:22:13,499 --> 06:22:14,867 HYDROXYUREA DIFFERENTLY. 8954 06:22:14,867 --> 06:22:18,938 WE MAY USE CRIZ AND GLUTAMINE 8955 06:22:18,938 --> 06:22:21,974 AND VOX DIFFERENTLY IN 2040, AND 8956 06:22:21,974 --> 06:22:25,578 WE'LL HAVE TO M KOL BACK AND COD 8957 06:22:25,578 --> 06:22:26,479 REMIND OURSELVES ABOUT THAT AS 8958 06:22:26,479 --> 06:22:26,946 WELL. 8959 06:22:26,946 --> 06:22:29,181 SO EACH CAN DECREASE VOC RATE 8960 06:22:29,181 --> 06:22:31,484 AND SUPERFICIALLY IT SEEMS LIKE 8961 06:22:31,484 --> 06:22:32,151 THEY'RE RELATIVELY EQUIVALENT, 8962 06:22:32,151 --> 06:22:33,886 BUT REMEMBER THAT THE MSH TRIAL 8963 06:22:33,886 --> 06:22:35,254 WAS RELATIVE UNDER TREATMENT. 8964 06:22:35,254 --> 06:22:37,390 COMPARED TO HOW WE USE IT IN 8965 06:22:37,390 --> 06:22:38,724 HEALTHY CHILDREN WITH SICKLE 8966 06:22:38,724 --> 06:22:41,027 CELL ANEMIA STARTED EARLY TODAY. 8967 06:22:41,027 --> 06:22:42,294 ALL RIGHT. 8968 06:22:42,294 --> 06:22:51,404 SO VOX IS THE OTHER TREATMENT, 8969 06:22:51,404 --> 06:22:52,638 WE KNEW THERE WAS SOMETHING 8970 06:22:52,638 --> 06:22:54,073 DIFFERENT ABOUT HEMOGLOBIN 8971 06:22:54,073 --> 06:22:55,474 OXYGEN AFFINITY IN SICKLE CELL 8972 06:22:55,474 --> 06:22:57,243 DISEASE STARTING IN THE 1950s, 8973 06:22:57,243 --> 06:23:00,713 AND THIS WAS AN AGENT THAT WAS 8974 06:23:00,713 --> 06:23:02,548 APPROVED IN 2019 AND THEN 8975 06:23:02,548 --> 06:23:04,650 REDUCED AGE OF INDICATION IN 20 8976 06:23:04,650 --> 06:23:05,184 WEN ONE. 8977 06:23:05,184 --> 06:23:05,985 SO WHAT IS IT? 8978 06:23:05,985 --> 06:23:07,386 IF YOU READ THE PACKAGE INSERT, 8979 06:23:07,386 --> 06:23:09,855 IT SAYS THIS IS A FIRST IN CLASS 8980 06:23:09,855 --> 06:23:14,293 POLYMERIZATION INHIBITOR. 8981 06:23:14,293 --> 06:23:15,728 WELL, IT'S NOT REALLY, PER SE. 8982 06:23:15,728 --> 06:23:16,829 IT DECREASES THE FORMATION OF 8983 06:23:16,829 --> 06:23:19,031 THE THING THAT POLYMERIZES. 8984 06:23:19,031 --> 06:23:20,132 SO IT'S UPSTREAM OF THAT. 8985 06:23:20,132 --> 06:23:22,535 IT INCREASES HEMOGLOBIN OXYGEN 8986 06:23:22,535 --> 06:23:26,572 AFFINITY, SO IT STABILIZES THE 8987 06:23:26,572 --> 06:23:27,139 ALLOSTERIC R STATE. 8988 06:23:27,139 --> 06:23:28,541 WHAT DOES DO, LABORATORY 8989 06:23:28,541 --> 06:23:28,774 EFFECTS? 8990 06:23:28,774 --> 06:23:32,278 IT DOES INCREASE YOUR 8991 06:23:32,278 --> 06:23:35,147 HEMOGLOBIN, DECREASES RETICS AND 8992 06:23:35,147 --> 06:23:37,116 SURROGATE MARKERS OF HEMOLYSIS, 8993 06:23:37,116 --> 06:23:39,118 SO IT DOES SEEM TO HAVE SOME 8994 06:23:39,118 --> 06:23:40,719 EFFECT ON IMPROVING YOUR BLOOD 8995 06:23:40,719 --> 06:23:41,053 COUNTS. 8996 06:23:41,053 --> 06:23:42,555 THIS IS NICE, IT'S TAKEN ORALLY 8997 06:23:42,555 --> 06:23:44,457 AND ONCE DAILY, AND THEN THE 8998 06:23:44,457 --> 06:23:45,925 CLINICAL EFFECTS, DECREASED 8999 06:23:45,925 --> 06:23:46,425 ANEMIA. 9000 06:23:46,425 --> 06:23:48,294 SO HERE, THIS WAS DIFFERENT THAN 9001 06:23:48,294 --> 06:23:50,396 THE CRIZ AND THE ENDARI. 9002 06:23:50,396 --> 06:23:51,764 HERE WE HAVE SOMETHING TARGETING 9003 06:23:51,764 --> 06:23:52,631 THE ANEMIA. 9004 06:23:52,631 --> 06:23:57,670 AND AGAIN, REMEMBER, IT COVAL 9005 06:23:57,670 --> 06:24:00,806 COVALENTLY MINDS BIENDZ THE -- 9006 06:24:00,806 --> 06:24:02,908 IT'S NOT A RAPID ON/OFF SORT OF 9007 06:24:02,908 --> 06:24:03,109 THING. 9008 06:24:03,109 --> 06:24:04,543 I JUST WANTED TO BRING UP SOME 9009 06:24:04,543 --> 06:24:10,649 OLD STUDIES HERE. 9010 06:24:10,649 --> 06:24:12,251 EVERYBODY TALKS ABOUT THIS AS IF 9011 06:24:12,251 --> 06:24:17,890 THERE IS SOME INTRINSICALLY 9012 06:24:17,890 --> 06:24:19,325 ABNORMAL DECREASED OXYGEN 9013 06:24:19,325 --> 06:24:20,826 AFFINITY OF HEMOGLOBIN S. 9014 06:24:20,826 --> 06:24:21,494 THAT'S NOT TRUE. 9015 06:24:21,494 --> 06:24:23,028 THE OXYGEN AFFINITY OF S IS THE 9016 06:24:23,028 --> 06:24:24,463 SAME AT A, AND THAT COMES FROM 9017 06:24:24,463 --> 06:24:25,664 THE ORIGINAL REPORT. 9018 06:24:25,664 --> 06:24:28,000 IT'S JUST THAT THOSE HEMOGLOBIN 9019 06:24:28,000 --> 06:24:30,569 MOLECULES ARE IN A RED CELL THAT 9020 06:24:30,569 --> 06:24:35,808 HAS MORE 2, 3-DPG, SO THAT WILL 9021 06:24:35,808 --> 06:24:37,076 DECREASE OXYGEN AFFINITY, 9022 06:24:37,076 --> 06:24:39,979 INCREASE THE FRACTION OF 9023 06:24:39,979 --> 06:24:40,346 DEOXYHEMOGLOBIN. 9024 06:24:40,346 --> 06:24:43,249 SO YOU COULD EITHER DECREASE THE 9025 06:24:43,249 --> 06:24:47,553 PRODUCTION OF 2, 3-DPG OR YOU 9026 06:24:47,553 --> 06:24:49,822 COULD INTRINSICALLY MAKE 9027 06:24:49,822 --> 06:24:51,490 HEMOGLOBIN A OR S HAVE A HIGHER 9028 06:24:51,490 --> 06:24:53,759 AFFINITY FOR OXYGEN. 9029 06:24:53,759 --> 06:24:55,427 VOXELOTOR DOES THE LATTER. 9030 06:24:55,427 --> 06:24:57,763 OTHER EMERGING BUT NOT APPROVED 9031 06:24:57,763 --> 06:25:01,901 STUDIES, AGENTS LIKE PK 9032 06:25:01,901 --> 06:25:08,641 ACTIVATORS ACTUALLY DECREASE THE 9033 06:25:08,641 --> 06:25:12,178 PRODUCTION OF 2, 3-DPG AND MAY 9034 06:25:12,178 --> 06:25:13,179 ACHIEVE THE SAME EFFECT 9035 06:25:13,179 --> 06:25:13,512 DIFFERENTLY. 9036 06:25:13,512 --> 06:25:17,049 SO THIS IS JUST SHOWING YOU THE 9037 06:25:17,049 --> 06:25:18,684 EFFECT OF VOXELOTOR ON 9038 06:25:18,684 --> 06:25:20,186 HEMOGLOBIN OXYGEN AFFINITY. 9039 06:25:20,186 --> 06:25:21,620 HERE'S PO2, SO AS YOU DIAL UP 9040 06:25:21,620 --> 06:25:24,089 THE AMOUNT OF OXYGEN IN THE 9041 06:25:24,089 --> 06:25:27,626 SOLUTION, HEMOGLOBIN SHOULD BE 9042 06:25:27,626 --> 06:25:29,195 INCREASINGLY SATURATED, AND SO 9043 06:25:29,195 --> 06:25:32,598 ANYTHING THAT SHIFTS TO THE LEFT 9044 06:25:32,598 --> 06:25:33,566 INCREASES OXYGEN AFFINITY, 9045 06:25:33,566 --> 06:25:33,899 RIGHT? 9046 06:25:33,899 --> 06:25:36,101 SO IT ONLY TAKES A LITTLE BIT OF 9047 06:25:36,101 --> 06:25:38,571 OXYGEN TO GET HIGHER SATURATION. 9048 06:25:38,571 --> 06:25:42,308 AND SO THIS IS NICELY MOD LATES 9049 06:25:42,308 --> 06:25:43,108 HEMOGLOBIN OXYGEN AFFINITY. 9050 06:25:43,108 --> 06:25:45,444 IT DOES IT IN A DIFFERENT WAY 9051 06:25:45,444 --> 06:25:48,147 THAN 2, 3-DPG, WHICH AFFECT ALL 9052 06:25:48,147 --> 06:25:51,417 THE HEMOGLOBIN MOLECULES. 9053 06:25:51,417 --> 06:25:54,053 HERE VOXELOTOR MODIFIES ABOUT A 9054 06:25:54,053 --> 06:25:57,890 THIRD, 30% OR SO OF HEMOGLOBIN 9055 06:25:57,890 --> 06:25:58,991 MOLECULES, MAKES THEM VERY HIGH 9056 06:25:58,991 --> 06:26:00,292 OXYGEN AFFINITY, BUT THE REST 9057 06:26:00,292 --> 06:26:02,061 ARE UNMODIFIED. 9058 06:26:02,061 --> 06:26:03,495 SO IT'S DIFFERENT, AND I TOOK 9059 06:26:03,495 --> 06:26:05,464 OUT A SLIDE TO ILLUSTRATE THAT 9060 06:26:05,464 --> 06:26:08,200 FOR TIME, BUT AGAIN, VOXELOTOR, 9061 06:26:08,200 --> 06:26:11,370 IT'S COVALENT HEMOGLOBIN 9062 06:26:11,370 --> 06:26:13,105 MODIFICATION, ALLOSTERIC R STATE 9063 06:26:13,105 --> 06:26:13,772 STABILIZER. 9064 06:26:13,772 --> 06:26:14,807 SO WHAT DOES DO? 9065 06:26:14,807 --> 06:26:16,508 IT INCREASES OXYGEN AFFINITY. 9066 06:26:16,508 --> 06:26:18,644 SO IF YOU CAN'T DEOXYGENATE, 9067 06:26:18,644 --> 06:26:20,246 THEN YOU'LL HAVE DECREASED 9068 06:26:20,246 --> 06:26:20,512 SICKLING. 9069 06:26:20,512 --> 06:26:22,047 OF COURSE YOU ALSO NEED 9070 06:26:22,047 --> 06:26:23,015 DEOXYGENATION TO LIVE, RIGHT? 9071 06:26:23,015 --> 06:26:24,883 YOU NEED OXYGEN TO LIVE SO YOU 9072 06:26:24,883 --> 06:26:26,585 NEED TO DEOXYGENATE, SO IT'S 9073 06:26:26,585 --> 06:26:27,219 THAT BALANCE. 9074 06:26:27,219 --> 06:26:28,621 SO YOU DON'T WANT TO INCREASE 9075 06:26:28,621 --> 06:26:31,390 THE OXYGEN AFFINITY TOO FAR TO 9076 06:26:31,390 --> 06:26:33,359 DECREASE HEMOGLOBIN OXYGEN 9077 06:26:33,359 --> 06:26:35,327 UNLOADING, BUT YOU WOULD LIKE TO 9078 06:26:35,327 --> 06:26:37,529 DECREASE SICKLING, IMPROVE THE 9079 06:26:37,529 --> 06:26:39,265 HEMOGLOBIN OXYGEN DELIVERY, 9080 06:26:39,265 --> 06:26:41,800 IMPROVE RHEOLOGY AND WHERE DOES 9081 06:26:41,800 --> 06:26:43,335 THE BALANCE LIE IN THIS 9082 06:26:43,335 --> 06:26:45,037 PARTICULAR ILLUSTRATION, THIS 9083 06:26:45,037 --> 06:26:46,839 WAS FROM A STUDY ILLUSTRATING 9084 06:26:46,839 --> 06:26:49,074 THE EFFECTS OF WHAT WAS SEEN IN 9085 06:26:49,074 --> 06:26:50,476 THAT PARTICULAR STUDY, AND I'M 9086 06:26:50,476 --> 06:26:52,244 NOT SUGGESTING THAT VOXELOTOR 9087 06:26:52,244 --> 06:26:54,113 ALWAYS DECREASES OXYGEN DELIVERY 9088 06:26:54,113 --> 06:26:55,781 TO TISSUES, BUT THIS IS THE 9089 06:26:55,781 --> 06:26:56,548 BALANCE, AND IT'S PROBABLY 9090 06:26:56,548 --> 06:26:57,850 DIFFERENT IN DIFFERENT PEOPLE, 9091 06:26:57,850 --> 06:26:58,617 RIGHT? 9092 06:26:58,617 --> 06:27:01,987 AND LIKE HYDROXYUREA, YOU SHOULD 9093 06:27:01,987 --> 06:27:03,889 PROBABLY DO PK AND OPTIMIZATION 9094 06:27:03,889 --> 06:27:05,124 STUDIES AND FIGURE OUT WHAT IS 9095 06:27:05,124 --> 06:27:06,292 THE BEST DOSE, NOT EVERYBODY 9096 06:27:06,292 --> 06:27:07,493 SHOULD TAKE THE SAME DOSE. 9097 06:27:07,493 --> 06:27:08,594 AND THIS IS ANOTHER WAY OF 9098 06:27:08,594 --> 06:27:09,828 LOOKING AT IT. 9099 06:27:09,828 --> 06:27:15,100 SO PEOPLE IN VOXELOTOR STUDY HAD 9100 06:27:15,100 --> 06:27:17,703 AUGUAUGMENTATION IN THEIR 9101 06:27:17,703 --> 06:27:18,237 HEMOGLOBIN, SOME VERY 9102 06:27:18,237 --> 06:27:19,238 DRAMATICALLY. 9103 06:27:19,238 --> 06:27:21,040 SOME, HEMOGLOBIN DECREASED, AND 9104 06:27:21,040 --> 06:27:22,207 SOME ARE IN THE MIDDLE HERE, SO 9105 06:27:22,207 --> 06:27:23,776 THERE ARE PROBABLY SOME THAT DO 9106 06:27:23,776 --> 06:27:26,378 HAVE A NET GAIN IN OXYGEN 9107 06:27:26,378 --> 06:27:28,080 DELIVERY CAPACITY AND 9108 06:27:28,080 --> 06:27:29,315 IMPROVEMENT IN BLOOD FLOW, BUT 9109 06:27:29,315 --> 06:27:30,349 THERE ARE PROBABLY SOME THAT 9110 06:27:30,349 --> 06:27:33,419 HAVE A NET LOSS, AND DO THEY 9111 06:27:33,419 --> 06:27:34,420 HAVE AN IMPROVEMENT IN BLOOD 9112 06:27:34,420 --> 06:27:34,853 FLOW? 9113 06:27:34,853 --> 06:27:36,322 DON'T KNOW. 9114 06:27:36,322 --> 06:27:38,123 AND SO THIS IS AN AREA THAT 9115 06:27:38,123 --> 06:27:39,358 NEEDS TO BE STUDIED. 9116 06:27:39,358 --> 06:27:41,060 SO IF WE PUT THESE TOGETHER 9117 06:27:41,060 --> 06:27:43,429 HERE, WE CAN SEE THAT VOXELOTOR 9118 06:27:43,429 --> 06:27:44,763 DOESN'T DO MUCH OTHER THAN 9119 06:27:44,763 --> 06:27:46,432 INCREASE YOUR HEMOGLOBIN AS FAR 9120 06:27:46,432 --> 06:27:48,367 AS WE KNOW IT CURRENTLY. 9121 06:27:48,367 --> 06:27:49,935 THERE MAY BE MORE BUT IT HASN'T 9122 06:27:49,935 --> 06:27:53,505 BEEN SHOWN. 9123 06:27:53,505 --> 06:27:55,007 IN RANDOMIZED TRIALS 9124 06:27:55,007 --> 06:27:56,408 YET AND IT EXPENSIVE LIKE ANY OF 9125 06:27:56,408 --> 06:27:57,309 THE NEWER AGENTS. 9126 06:27:57,309 --> 06:27:58,811 SO WHEN WE THINK ABOUT THESE 9127 06:27:58,811 --> 06:28:00,479 EMERGING THERAPIES, SO TO SPEAK, 9128 06:28:00,479 --> 06:28:03,148 THE FACTORS TO CONSIDER IN MY 9129 06:28:03,148 --> 06:28:05,451 MIND, AT LEAST I'M LUCKY TO LIVE 9130 06:28:05,451 --> 06:28:06,752 AND PRACTICE IN A CENTER THAT 9131 06:28:06,752 --> 06:28:10,756 HAS THESE OPTIONS, WE CAN THINK 9132 06:28:10,756 --> 06:28:13,959 ABOUT ALL OF THESE -- THIS CAN 9133 06:28:13,959 --> 06:28:16,462 BE DONE FOR SICKLE CELL DISEASE 9134 06:28:16,462 --> 06:28:18,163 BROADLY, NOT JUST SICKLE CELL 9135 06:28:18,163 --> 06:28:19,598 ANEMIA, BUT MOST OF THE DATA ARE 9136 06:28:19,598 --> 06:28:20,933 FROM SICKLE CELL ANEMIA, SO WHEN 9137 06:28:20,933 --> 06:28:22,134 WE HAVE THESE AGENTS, WE CAN 9138 06:28:22,134 --> 06:28:23,235 THINK ABOUT HOW OLD THE PATIENT 9139 06:28:23,235 --> 06:28:25,537 IS, SO THE PATIENT'S AGE, 9140 06:28:25,537 --> 06:28:26,672 PATIENT PREFERENCE, DO THEY WANT 9141 06:28:26,672 --> 06:28:28,741 TO TAKE SOMETHING ORAL OR IV, IS 9142 06:28:28,741 --> 06:28:31,577 IT BURDENSOME TO TAKE SOMETHING 9143 06:28:31,577 --> 06:28:33,112 DAILY OR TWICE DAILY, AND THEN 9144 06:28:33,112 --> 06:28:34,980 WHAT ARE THE THERAPEUTIC 9145 06:28:34,980 --> 06:28:36,648 BENEFITS YOU'RE TRYING TO 9146 06:28:36,648 --> 06:28:39,852 ACHIEVE? 9147 06:28:39,852 --> 06:28:43,455 AND THAT MIGHT INFORM WHAT 9148 06:28:43,455 --> 06:28:44,590 THERAPY YOU'RE GOING TO ADD ON 9149 06:28:44,590 --> 06:28:46,558 TO THE BACKBONE OF THERAPY. 9150 06:28:46,558 --> 06:28:48,761 AND THEN COST, MONEY AND 9151 06:28:48,761 --> 06:28:49,862 INFRASTRUCTURE, YOU'LL NEED AN 9152 06:28:49,862 --> 06:28:51,530 INFUSION CENTER, FOR EXAMPLE. 9153 06:28:51,530 --> 06:28:54,633 SO ANOTHER WAY -- MY VIEW IS 9154 06:28:54,633 --> 06:28:55,768 THAT OPTIMIZED HYDROXYUREA 9155 06:28:55,768 --> 06:28:57,169 SHOULD BE THE BACKBONE OF 9156 06:28:57,169 --> 06:28:58,904 THERAPY TO WHICH OTHER PAIGHTS 9157 06:28:58,904 --> 06:29:01,874 ARE ADDED SO WE CAN PREVENT ALL 9158 06:29:01,874 --> 06:29:03,142 THOSE THINGS THAT WE'VE BEEN 9159 06:29:03,142 --> 06:29:05,110 TALKING ABOUT TODAY AS MUCH AS 9160 06:29:05,110 --> 06:29:06,278 POSSIBLE, RATHER THAN TREAT THEM 9161 06:29:06,278 --> 06:29:07,813 AFTER THEY HAPPEN. 9162 06:29:07,813 --> 06:29:12,851 AND THIS TAKES A SYSTEM, SO WE 9163 06:29:12,851 --> 06:29:17,356 START HYDROXYUREA EARLY, AND 9164 06:29:17,356 --> 06:29:18,323 THERE'S A PSYCHOSOCIAL GROUP 9165 06:29:18,323 --> 06:29:20,959 THAT HELPS US WITH HESITATION, 9166 06:29:20,959 --> 06:29:23,061 SHARED DECISION-MAKING, 9167 06:29:23,061 --> 06:29:27,666 ADHERENCE, AND TO THAT, 9168 06:29:27,666 --> 06:29:29,568 DEPENDING ON THE CLINICAL 9169 06:29:29,568 --> 06:29:30,302 CIRCUMSTANCES, IF THERE'S PAIN, 9170 06:29:30,302 --> 06:29:32,704 WE CAN TALK ABOUT DO YOU WANT TO 9171 06:29:32,704 --> 06:29:35,808 ADD CRIZ OR GLUTAMINE, WE HAD 9172 06:29:35,808 --> 06:29:38,010 VOXELOTOR OR SOME COMBINATION 9173 06:29:38,010 --> 06:29:39,878 OF -- WE HAVEN'T GOTTEN TO A 9174 06:29:39,878 --> 06:29:40,479 COMBINATION OF THREE YET, BUT 9175 06:29:40,479 --> 06:29:42,080 I'M SURE WE WILL, BUT THIS DOES 9176 06:29:42,080 --> 06:29:44,817 TAKE EFFORT AND TIME, AND SO IN 9177 06:29:44,817 --> 06:29:47,820 SUMMARY THEN, I THINK THAT MAYBE 9178 06:29:47,820 --> 06:29:50,222 I HAVEN'T SHOWED YOU ALL THE 9179 06:29:50,222 --> 06:29:54,426 DATA, BUT USING PK GUIDED 9180 06:29:54,426 --> 06:29:57,696 HYDROXYUREA INITIATED MTD IN 9181 06:29:57,696 --> 06:30:00,632 EARLY CHILDHOOD, WE CAN INDUCE 9182 06:30:00,632 --> 06:30:02,634 PAN-CELLULAR IN A LARGE VOLUME 9183 06:30:02,634 --> 06:30:04,169 OF PATIENTS WITH SICKLE CELL AND 9184 06:30:04,169 --> 06:30:05,037 WE'RE FOLLOWING THIS COHORT OVER 9185 06:30:05,037 --> 06:30:05,370 TIME. 9186 06:30:05,370 --> 06:30:08,240 WHAT WE DO IS WE ADD THOSE OTHER 9187 06:30:08,240 --> 06:30:12,444 THERAPIES THAT ARE AVAILABLE TO 9188 06:30:12,444 --> 06:30:14,513 OPTIMIZE THERAPY, IF THERE'S 9189 06:30:14,513 --> 06:30:16,114 PREDOMINENCE OF PAIN DESPITE 9190 06:30:16,114 --> 06:30:18,484 HYDROXYUREA, ADD ON CRIZ OR L 9191 06:30:18,484 --> 06:30:19,718 GLUED MEAN OR THE OTHER. 9192 06:30:19,718 --> 06:30:21,854 BUT YOU KNOW, IN THE AGE OF 9193 06:30:21,854 --> 06:30:23,188 GENETIC AND CURATIVE THERAPIES 9194 06:30:23,188 --> 06:30:26,091 THAT ARE HERE AND NOW, SO YOU 9195 06:30:26,091 --> 06:30:27,493 MIGHT THINK WHY ARE WE BOTHERING 9196 06:30:27,493 --> 06:30:30,229 WITH THIS? 9197 06:30:30,229 --> 06:30:31,597 WELL, PATIENT ARE ALIVE NOW AND 9198 06:30:31,597 --> 06:30:33,799 WE NEED TO IMPROVE AND MAINTAIN 9199 06:30:33,799 --> 06:30:35,968 THEIR CURRENT HEALTH AND WE WANT 9200 06:30:35,968 --> 06:30:38,403 TO KEEP THEM AS HEALTHY AS 9201 06:30:38,403 --> 06:30:40,072 POSSIBLE FOR THEIR CURRENT AND 9202 06:30:40,072 --> 06:30:41,907 FUTURE ITERATIONS OF GENETIC AND 9203 06:30:41,907 --> 06:30:42,341 CURATIVE THERAPY. 9204 06:30:42,341 --> 06:30:44,009 I'M TELLING PATIENTS PROBABLY IN 9205 06:30:44,009 --> 06:30:45,344 YOUR LIFETIME YOU'RE GOING TO 9206 06:30:45,344 --> 06:30:46,645 GET A GENETIC THERAPY BUT WITH 9207 06:30:46,645 --> 06:30:50,082 HWEHAVE TO KEEP YOU HEALTHY BECE 9208 06:30:50,082 --> 06:30:51,049 ANY ORGAN DAMAGE YOU SUSTAIN 9209 06:30:51,049 --> 06:30:52,251 UNTIL THEN, THAT'S NOT GOING TO 9210 06:30:52,251 --> 06:30:53,151 GET BETTER. 9211 06:30:53,151 --> 06:30:54,720 SO EVEN THOUGH GENETIC AND 9212 06:30:54,720 --> 06:30:56,588 CURATIVE THERAPIES, UNIVERSAL 9213 06:30:56,588 --> 06:30:58,757 THERAPIES ARE ON THE HORIZON, 9214 06:30:58,757 --> 06:31:00,292 YOU STILL HAVE TO KEEP THE 9215 06:31:00,292 --> 06:31:01,293 PATIENTS VERY HEALTHY, AS MUCH 9216 06:31:01,293 --> 06:31:02,060 AS POSSIBLE NOW. 9217 06:31:02,060 --> 06:31:04,029 AND I'LL STOP THERE. 9218 06:31:04,029 --> 06:31:04,296 THANKS. 9219 06:31:04,296 --> 06:31:14,473 [APPLAUSE] 9220 06:31:18,911 --> 06:31:20,746 >> THANK YOU SO MUCH. 9221 06:31:20,746 --> 06:31:23,448 I HAVE ONE QUESTION IN THE CHAT 9222 06:31:23,448 --> 06:31:24,583 THAT I'D LIKE TO BRING UP TO 9223 06:31:24,583 --> 06:31:24,850 YOU. 9224 06:31:24,850 --> 06:31:28,520 THIS IS FROM TIFFANY CHEN. 9225 06:31:28,520 --> 06:31:31,023 SHE SAYS, I ALSO SHARE YOUR 9226 06:31:31,023 --> 06:31:33,325 ENTHUSIASM FOR HYDROXYUREA AT 9227 06:31:33,325 --> 06:31:34,126 OPTIMALLY TITRATED DOSES. 9228 06:31:34,126 --> 06:31:36,828 DO YOU ANTICIPATE IN THE MODERN 9229 06:31:36,828 --> 06:31:40,465 ERA THAT PEDIATRICS SCD PATIENTS 9230 06:31:40,465 --> 06:31:42,568 STARTED AT A VERY YOUNG AGE ON 9231 06:31:42,568 --> 06:31:44,870 PK-GUIDED DOSING WILL BE ABLE TO 9232 06:31:44,870 --> 06:31:47,873 MAINTAIN OPTIMAL -- DOSES FOR 9233 06:31:47,873 --> 06:31:49,274 MAXIMAL F INDUCTION INTO 9234 06:31:49,274 --> 06:31:50,375 ADULTHOOD, AND IF NOT, WHAT DO 9235 06:31:50,375 --> 06:31:52,277 YOU THINK ARE THE SPECIFIC 9236 06:31:52,277 --> 06:31:53,412 BARRIERS? 9237 06:31:53,412 --> 06:31:56,081 >> YEAH, SO THE ANSWER TO THE 9238 06:31:56,081 --> 06:31:58,951 FIRST PART, IS I THINK IT CAN, 9239 06:31:58,951 --> 06:32:00,319 BUT WE'RE STILL FOLLOWING -- YOU 9240 06:32:00,319 --> 06:32:01,286 KNOW, WE'VE ONLY FOLLOWED 9241 06:32:01,286 --> 06:32:03,188 PATIENTS ABOUT 10 YEARS NOW, 9242 06:32:03,188 --> 06:32:04,356 SO -- AND FOR THOSE THAT 9243 06:32:04,356 --> 06:32:09,227 CONTINUE TO TAKE IT, AND FOR 9244 06:32:09,227 --> 06:32:10,963 THOSE IN WHOM WE'RE ABLE TO KEEP 9245 06:32:10,963 --> 06:32:16,301 UP WITH THE DOA IT S DOSE, IT SE 9246 06:32:16,301 --> 06:32:16,735 EFFECTIVE. 9247 06:32:16,735 --> 06:32:20,906 BUT THERE MAY BE SOME 9248 06:32:20,906 --> 06:32:21,940 DEVELOPMENTAL -- BUT AT LEAST 9249 06:32:21,940 --> 06:32:22,774 WE'RE KEEPING YOU HEALTHY UNTIL 9250 06:32:22,774 --> 06:32:24,076 YOU CAN GET YOUR CURATIVE 9251 06:32:24,076 --> 06:32:25,711 THERAPY HOPEFULLY IN YOUR 9252 06:32:25,711 --> 06:32:26,278 PATIENT'S LIFETIME. 9253 06:32:26,278 --> 06:32:28,146 I THINK THE BIGGEST BARRIER THAT 9254 06:32:28,146 --> 06:32:31,416 WE HAVE IS LIKE ANY CHRONIC 9255 06:32:31,416 --> 06:32:33,185 DISEASE IS ADHERENCE. 9256 06:32:33,185 --> 06:32:36,288 SO IF YOU HAVE A SICKLE CELL 9257 06:32:36,288 --> 06:32:37,623 TREATMENT CENTER, YOU HAVE TO DO 9258 06:32:37,623 --> 06:32:39,825 SOMETHING TO SUPPORT PATIENT 9259 06:32:39,825 --> 06:32:41,627 ADHERENCE, AND WE HAVE SOME 9260 06:32:41,627 --> 06:32:42,594 PSYCHOLOGISTS THAT ARE 9261 06:32:42,594 --> 06:32:44,763 INTEGRATED INTO OUR TEAM, AND 9262 06:32:44,763 --> 06:32:46,765 YES, THEY DO MENTAL HEALTH, BUT 9263 06:32:46,765 --> 06:32:48,400 ONE OF THE MAIN THINGS THEY DO 9264 06:32:48,400 --> 06:32:50,135 IS ADHERENCE SUPPORT. 9265 06:32:50,135 --> 06:32:51,603 SO I THINK THAT IS THE BIGGEST 9266 06:32:51,603 --> 06:33:01,747 BARRIER. 9267 06:33:02,481 --> 06:33:03,315 OH, THAT'S GOOD. 9268 06:33:03,315 --> 06:33:07,185 I DIDN'T WANT ANY QUESTIONS. 9269 06:33:07,185 --> 06:33:17,462 I CAN HEAR YOU. 9270 06:33:26,071 --> 06:33:29,174 >> -- SO EARLY AND ESPECIALLY 9271 06:33:29,174 --> 06:33:32,144 WITH WHAT LYDIA HAS JUST 9272 06:33:32,144 --> 06:33:34,312 PRESENTED ABOUT DIMINISHED 9273 06:33:34,312 --> 06:33:36,748 OVARIAN RESERVE. 9274 06:33:36,748 --> 06:33:40,385 -- USING THE NEUTROPENIA KIND 9275 06:33:40,385 --> 06:33:42,020 OF -- JUST USING THE MCV. 9276 06:33:42,020 --> 06:33:44,222 SO YOU START THE CHILDREN AS 9277 06:33:44,222 --> 06:33:46,425 YOUNG AS SIX MONTHS OR NINE 9278 06:33:46,425 --> 06:33:48,960 MONTHS, DO YOU NOT HAVE ANY 9279 06:33:48,960 --> 06:33:49,194 CONCERN? 9280 06:33:49,194 --> 06:33:50,762 >> WELL, WE DO HAVE CONCERNS, 9281 06:33:50,762 --> 06:33:53,365 AND WE'RE MONITORING THEM 9282 06:33:53,365 --> 06:33:55,333 CLOSELY PROSPECTIVELY AND IN 9283 06:33:55,333 --> 06:33:56,535 DETAILED ORGAN ASSESSMENTS, 9284 06:33:56,535 --> 06:33:57,836 EVERYTHING FROM MRIs OF THE 9285 06:33:57,836 --> 06:33:59,504 HEART AND BRAIN AND THAT SORT OF 9286 06:33:59,504 --> 06:34:05,510 THING, SO YES, BUT AS YOU 9287 06:34:05,510 --> 06:34:07,045 PROBABLY -- THESE KIDS ARE 9288 06:34:07,045 --> 06:34:07,646 HEALTHIER. 9289 06:34:07,646 --> 06:34:09,414 THEY DON'T HAVE GROWTH DELAY. 9290 06:34:09,414 --> 06:34:12,184 WE'RE NOT -- WE HAVE OBESITY, WE 9291 06:34:12,184 --> 06:34:16,021 HAVE THE PROBLEM OF PREGNANCY 9292 06:34:16,021 --> 06:34:21,460 AND PREVENTING PREGNANCIES, AN 9293 06:34:21,460 --> 06:34:22,160 AND -- WHAT WAS THE SECOND PART 9294 06:34:22,160 --> 06:34:25,997 OF YOUR QUESTION THERE? 9295 06:34:25,997 --> 06:34:27,365 >> HOW DO YOU SLEEP -- 9296 06:34:27,365 --> 06:34:30,068 >> OH, SO YOU TAKE A 9297 06:34:30,068 --> 06:34:31,036 CONSERVATIVE ENVIRONMENT, ONCE 9298 06:34:31,036 --> 06:34:32,370 YOU SEE AN EFFECT, THEN CAN YOU 9299 06:34:32,370 --> 06:34:34,306 GO AHEAD AND STOP, WELL, I MEAN, 9300 06:34:34,306 --> 06:34:37,109 LET'S JUST APPLY THAT TO ASTHMA. 9301 06:34:37,109 --> 06:34:38,977 SO IF YOU GIVE A BRONCHODILATOR, 9302 06:34:38,977 --> 06:34:40,545 YOU CAN KEEP SOMEBODY OUT OF THE 9303 06:34:40,545 --> 06:34:42,481 ICU AND GETTING THEM -- PREVENT 9304 06:34:42,481 --> 06:34:43,849 THEM FROM BEING INTUBATED, BUT 9305 06:34:43,849 --> 06:34:45,117 IS THAT THE MAIN GOAL, JUST TO 9306 06:34:45,117 --> 06:34:46,785 PREVENT THEM FROM BEING 9307 06:34:46,785 --> 06:34:48,086 INTUBATED, OR DO YOU REALLY WANT 9308 06:34:48,086 --> 06:34:49,488 TO IMPROVE THEIR PULMONARY 9309 06:34:49,488 --> 06:34:50,689 HEALTH BROADLY? 9310 06:34:50,689 --> 06:34:51,123 WHAT ABOUT DIABETES? 9311 06:34:51,123 --> 06:34:52,657 IF YOU GIVE THEM JUST ENOUGH 9312 06:34:52,657 --> 06:34:54,092 INSULIN TO PREVENT THEM FROM 9313 06:34:54,092 --> 06:34:56,595 HAVING DKA, SEU YOU'VE MADE AN 9314 06:34:56,595 --> 06:34:57,262 EFFECT BUT YOU WOULDN'T STOP 9315 06:34:57,262 --> 06:34:59,698 THERE, RIGHT, BECAUSE YOU KNOW 9316 06:34:59,698 --> 06:35:01,133 DIABETES IS A LIFELONG SEVERE 9317 06:35:01,133 --> 06:35:02,434 DISEASE THAT CAUSES ORGAN 9318 06:35:02,434 --> 06:35:03,535 DAMAGE, SO YOU WANT TO TITRATE 9319 06:35:03,535 --> 06:35:05,737 THAT TO GET MAXIMAL -- WE DON'T 9320 06:35:05,737 --> 06:35:07,973 WANT TO GO BEYOND MAXIMAL 9321 06:35:07,973 --> 06:35:09,741 CLINICAL BENEFIT, BUT WE WANT TO 9322 06:35:09,741 --> 06:35:12,210 TITRATE TO CLINICAL BENEFIT. 9323 06:35:12,210 --> 06:35:15,013 AND THE THINGS THAT WE MEASURE 9324 06:35:15,013 --> 06:35:16,014 ARE OVERT COMPLICATIONS. 9325 06:35:16,014 --> 06:35:17,315 >> THERE IS A CRUCIAL 9326 06:35:17,315 --> 06:35:18,116 DIFFERENCE. 9327 06:35:18,116 --> 06:35:19,284 DIABETES, YOU HAVE THE GLUCOSE 9328 06:35:19,284 --> 06:35:22,354 LEVELS TO HELP YOU. 9329 06:35:22,354 --> 06:35:25,557 BLOOD PRESSURE, YOU HAVE THE 9330 06:35:25,557 --> 06:35:27,959 NUMBERS TO INDICATE. 9331 06:35:27,959 --> 06:35:29,060 HYDROXYUREA, ALL OF THESE ARE 9332 06:35:29,060 --> 06:35:30,695 JUST NUMBERS. 9333 06:35:30,695 --> 06:35:32,063 YOU'RE TREATING THE PATIENT. 9334 06:35:32,063 --> 06:35:33,899 >> RIGHT, WE'RE TREATING THE 9335 06:35:33,899 --> 06:35:36,101 PATIENT, AND WE KNOW -- 9336 06:35:36,101 --> 06:35:38,470 >> AND ACTUALLY THE GREEK STUDY, 9337 06:35:38,470 --> 06:35:40,972 THEY DON'T USE MTD AND THEY ALSO 9338 06:35:40,972 --> 06:35:41,740 PROLONGED THE LIVES. 9339 06:35:41,740 --> 06:35:44,609 >> OH, YEAH, THEY'LL GO UP, BUT 9340 06:35:44,609 --> 06:35:46,645 NOT IN TO PAN-CELLULAR 9341 06:35:46,645 --> 06:35:47,445 INDUCTION. 9342 06:35:47,445 --> 06:35:49,681 I MEAN, WE DON'T -- WE'RE NOT 9343 06:35:49,681 --> 06:35:50,916 PUTTING KIDS ON CHRONIC 9344 06:35:50,916 --> 06:35:52,651 TRANSFUSIONS ANYMORE. 9345 06:35:52,651 --> 06:35:53,652 THE CHRONIC TRANSFUSION 9346 06:35:53,652 --> 06:35:54,753 POPULATION IS SHRINKING. 9347 06:35:54,753 --> 06:35:56,788 WE DON'T SEE -- WE DON'T EVEN 9348 06:35:56,788 --> 06:35:58,256 SEE ABNORMAL TCDs ANYMORE. 9349 06:35:58,256 --> 06:36:00,158 I MEAN, EVERYTHING -- AND THE 9350 06:36:00,158 --> 06:36:01,259 INPATIENT POPULATION IS 9351 06:36:01,259 --> 06:36:01,560 SHRINKING. 9352 06:36:01,560 --> 06:36:06,398 WE HAD A SEQUESTRATION EVENT THE 9353 06:36:06,398 --> 06:36:07,365 OTHER DAY AND EVERYBODY WAS 9354 06:36:07,365 --> 06:36:07,933 LIKE, WHAT IS THAT? 9355 06:36:07,933 --> 06:36:10,268 I WAS LIKE, WELL, THIS IS HOW IT 9356 06:36:10,268 --> 06:36:11,136 USED TO BE. 9357 06:36:11,136 --> 06:36:12,771 SO WE'RE JUST NOT SEEING WHAT WE 9358 06:36:12,771 --> 06:36:13,305 DID BEFORE. 9359 06:36:13,305 --> 06:36:18,610 SO I THINK THAT OVERALL, I MEAN, 9360 06:36:18,610 --> 06:36:20,045 WHAT WE'RE MEASURING AND WHAT 9361 06:36:20,045 --> 06:36:22,414 YOU SEE IS JUST THE TIP OF THE 9362 06:36:22,414 --> 06:36:23,215 ICEBERG. 9363 06:36:23,215 --> 06:36:24,115 BECAUSE THERE'S CHRONIC 9364 06:36:24,115 --> 06:36:25,851 INSIDIOUS CUMULATIVE 9365 06:36:25,851 --> 06:36:26,618 IRREVERSIBLE ORGAN DAMAGE 9366 06:36:26,618 --> 06:36:30,088 HAPPENING EVERY DAY, WE CAN'T 9367 06:36:30,088 --> 06:36:32,457 MEASURE THAT DIRECTLY, EASILY, 9368 06:36:32,457 --> 06:36:34,526 WE CAN WITH SOME MECHANISMS BUT 9369 06:36:34,526 --> 06:36:35,961 YOU CAN'T PUT SOMEBODY IN THE 9370 06:36:35,961 --> 06:36:37,195 SCANNER AND GIVE THEM GADOLINIUM 9371 06:36:37,195 --> 06:36:41,366 ALL THE TIME. 9372 06:36:41,366 --> 06:36:43,635 SO WE'RE HOPING FOR A HEALTHIER 9373 06:36:43,635 --> 06:36:47,839 POPULATION THAT AREN'T A 9374 06:36:47,839 --> 06:36:48,173 AZOOSPERMIC. 9375 06:36:48,173 --> 06:36:49,908 AND LYDIA, YOU WERE HOPING FOR 9376 06:36:49,908 --> 06:36:51,843 SOME ARGUMENTS AND SOME 9377 06:36:51,843 --> 06:36:52,277 PUNCHING. 9378 06:36:52,277 --> 06:36:53,345 >> NO, NO. 9379 06:36:53,345 --> 06:36:54,546 I THINK WHAT YOU'RE SAYING IS 9380 06:36:54,546 --> 06:36:55,747 VERY IMPORTANT BECAUSE I GET A 9381 06:36:55,747 --> 06:36:59,117 LOT OF QUESTIONS IN MY TALKS 9382 06:36:59,117 --> 06:37:00,518 ABOUT THE IMMENSE AMOUNT OF 9383 06:37:00,518 --> 06:37:03,021 ANXIETY THAT MY DATA PROVOKES, 9384 06:37:03,021 --> 06:37:04,990 PARTICULARLY FOR PEDIATRIC 9385 06:37:04,990 --> 06:37:06,892 PRACTITIONERS, AND I THINK THAT 9386 06:37:06,892 --> 06:37:08,560 PART OF THE ANSWER TO THAT 9387 06:37:08,560 --> 06:37:11,196 ANXIETY IS THAT WE HAVE TO HELP 9388 06:37:11,196 --> 06:37:13,231 PEOPLE IMAGINE HEALTHY CHILD 9389 06:37:13,231 --> 06:37:15,000 HOODS FROM CHILDREN WITH SICKLE 9390 06:37:15,000 --> 06:37:16,234 CELL DISEASE, AND I THINK THAT 9391 06:37:16,234 --> 06:37:17,669 YOUR DATA HELPS WITH THAT 9392 06:37:17,669 --> 06:37:18,403 FAILURE TO IMAGINE. 9393 06:37:18,403 --> 06:37:19,838 SO THAT WAS THE FIRST THING I 9394 06:37:19,838 --> 06:37:21,039 WANTED TO ACKNOWLEDGE. 9395 06:37:21,039 --> 06:37:22,874 YOU MENTIONED THAT YOU'RE 9396 06:37:22,874 --> 06:37:24,175 FOLLOWING END ORGAN ASSESSMENTS, 9397 06:37:24,175 --> 06:37:25,977 SO I WONDERED IF WERE YOU 9398 06:37:25,977 --> 06:37:28,413 INCLUDING IN POST PUBESCENT 9399 06:37:28,413 --> 06:37:34,920 GIRLS ANTIMA LAYE ANTIMA -- 9400 06:37:34,920 --> 06:37:37,822 >> YES, AND SEMEN ANALYSIS FOR 9401 06:37:37,822 --> 06:37:39,024 THOSE WHO WILL BE WILLING TO 9402 06:37:39,024 --> 06:37:40,125 HELP US WITH THAT INFORMATION. 9403 06:37:40,125 --> 06:37:41,793 >> I HAD ANOTHER QUESTION WHICH 9404 06:37:41,793 --> 06:37:43,128 WAS YOUR GROUP HAS PUBLISHED 9405 06:37:43,128 --> 06:37:46,698 THAT YOU INCORPORATE FERTILITY 9406 06:37:46,698 --> 06:37:48,667 RISK COUNSELING INTO YOUR 9407 06:37:48,667 --> 06:37:49,834 HYDROXYUREA PRESCRIBING PARADIGM 9408 06:37:49,834 --> 06:37:51,403 BUT YOU'VE NEVER DESCRIBED THE 9409 06:37:51,403 --> 06:37:52,470 COMPONENTS OF THAT COUNSELING. 9410 06:37:52,470 --> 06:37:53,505 COULD YOU TALK A LITTLE BIT 9411 06:37:53,505 --> 06:37:54,706 ABOUT -- COULD YOU MODEL THAT 9412 06:37:54,706 --> 06:37:55,774 CONVERSATION FOR US? 9413 06:37:55,774 --> 06:37:57,776 BECAUSE I THINK IT'S A SOURCE OF 9414 06:37:57,776 --> 06:37:59,010 IMMENSE ANXIETY FOR MANY OF THE 9415 06:37:59,010 --> 06:38:00,912 PEOPLE I MEET OUT HERE IN SICKLE 9416 06:38:00,912 --> 06:38:01,179 CELL LAND. 9417 06:38:01,179 --> 06:38:03,448 >> YEAH, I THINK IT AN EXCELLENT 9418 06:38:03,448 --> 06:38:10,655 AND IMPORTANT QUESTION. 9419 06:38:10,655 --> 06:38:14,626 I'M NOT SURE I CAN DO JUSTICE TO 9420 06:38:14,626 --> 06:38:19,531 IT, BUT THOSE CONVERSATIONS, 9421 06:38:19,531 --> 06:38:21,299 IT'S NOT A MONOLITHIC 9422 06:38:21,299 --> 06:38:21,833 CONVERSATION. 9423 06:38:21,833 --> 06:38:23,501 BUT SINCE I SEE PATIENTS FROM 9424 06:38:23,501 --> 06:38:25,337 BIRTH UNTIL 21, LITTLE BITS OF 9425 06:38:25,337 --> 06:38:27,272 IT HAPPEN OVER TIME. 9426 06:38:27,272 --> 06:38:29,474 AND WE ADD IN BITS OF THAT. 9427 06:38:29,474 --> 06:38:32,544 I THINK WE'RE STILL TRYING TO 9428 06:38:32,544 --> 06:38:36,047 BUILD IN AS WELL AS YOU HAVE, 9429 06:38:36,047 --> 06:38:36,848 THINGS LIKE FERTILITY 9430 06:38:36,848 --> 06:38:39,150 ASSESSMENTS AND OVARIAN RESERVE 9431 06:38:39,150 --> 06:38:42,320 ASSESSMENTS, I DON'T HAVE A 9432 06:38:42,320 --> 06:38:44,856 SYSTEMATIC WAY OF DOING THAT NOW 9433 06:38:44,856 --> 06:38:48,293 OTHER THAN JUST TALKING ABOUT IT 9434 06:38:48,293 --> 06:38:51,162 OVER TIME WITH PATIENTS. 9435 06:38:51,162 --> 06:38:54,699 AND AS AN ANECDOTE, YOU HAVE TO 9436 06:38:54,699 --> 06:38:55,767 BE VERY CAREFUL ABOUT THE WAY 9437 06:38:55,767 --> 06:38:58,970 YOU TALK ABOUT IT WITH PATIENTS, 9438 06:38:58,970 --> 06:39:03,775 BECAUSE WHEN WE HAVE -- ONE OF 9439 06:39:03,775 --> 06:39:04,776 THE NURSE PRACTITIONERS TOLD ME 9440 06:39:04,776 --> 06:39:05,977 SHE WAS TALKING TO HER TEEN 9441 06:39:05,977 --> 06:39:07,112 PATIENT AND SHE SAID, NOW YOU 9442 06:39:07,112 --> 06:39:08,380 KNOW WHEN YOU'RE ON HYDROXYUREA, 9443 06:39:08,380 --> 06:39:09,614 YOU CAN'T GET PREGNANT WHILE 9444 06:39:09,614 --> 06:39:11,950 YOU'RE ON HYDROXYUREA. 9445 06:39:11,950 --> 06:39:13,451 LIKE -- BUT WHEN SHE CAME BACK 9446 06:39:13,451 --> 06:39:14,986 PREGNANT, SHE'S LIKE, I THOUGHT 9447 06:39:14,986 --> 06:39:16,354 YOU SAID I COULDN'T GET 9448 06:39:16,354 --> 06:39:17,455 PREGNANT. 9449 06:39:17,455 --> 06:39:20,258 SO CAN'T, SHOULDN'T, WE DO HAVE 9450 06:39:20,258 --> 06:39:21,459 TO BE VERY CAREFUL. 9451 06:39:21,459 --> 06:39:23,962 SO I DON'T HAVE A GREAT ANSWER 9452 06:39:23,962 --> 06:39:25,030 TO YOUR QUESTION OTHER THAN IT 9453 06:39:25,030 --> 06:39:26,531 ORGANIC AND IT HAPPENS OVER THE 9454 06:39:26,531 --> 06:39:28,833 SPACE OF 21 YEARS AND I THINK WE 9455 06:39:28,833 --> 06:39:30,235 CAN LEARN FROM YOU AND WHAT 9456 06:39:30,235 --> 06:39:34,039 YOU'RE DOING TO IMPROVE OUR 9457 06:39:34,039 --> 06:39:38,443 PROCESSES. 9458 06:39:38,443 --> 06:39:40,245 BUT REMEMBER YOU DO HAVE TO GROW 9459 06:39:40,245 --> 06:39:42,013 UP TO BE ABLE TO HAVE A CHILD, 9460 06:39:42,013 --> 06:39:43,415 YOU HAVE TO BE HEALTHY ENOUGH TO 9461 06:39:43,415 --> 06:39:45,784 HAVE A CHILD, AND HOPEFULLY YOU 9462 06:39:45,784 --> 06:39:47,719 CAN BE HEALTHY ENOUGH THAT YOU 9463 06:39:47,719 --> 06:39:50,522 CAN HAVE A SAFE PREGNANCY. 9464 06:39:50,522 --> 06:39:51,389 >> THANK YOU. 9465 06:39:51,389 --> 06:39:52,590 >> CAN I HAVE A QUESTION, 9466 06:39:52,590 --> 06:39:53,691 PLEASE? 9467 06:39:53,691 --> 06:39:56,761 >> I THINK WE'LL HAVE TO ASK DR. 9468 06:39:56,761 --> 06:39:57,962 >> OKAY, OKAY. 9469 06:39:57,962 --> 06:39:58,563 >> THANK YOU, THOUGH. 9470 06:39:58,563 --> 06:40:00,632 AND I DO AGREE, THAT'S A VERY 9471 06:40:00,632 --> 06:40:04,602 DIFFICULT POSITION TO BE IN. 9472 06:40:04,602 --> 06:40:05,570 WE'LL MOVE ON. 9473 06:40:05,570 --> 06:40:06,337 ALL RIGHT. 9474 06:40:06,337 --> 06:40:08,239 I HAVE MANY THOUGHTS AS WELL BUT 9475 06:40:08,239 --> 06:40:09,207 WE'LL MOVE ON. 9476 06:40:09,207 --> 06:40:13,511 OUR NEXT SPEAKER WILL BE JOINING 9477 06:40:13,511 --> 06:40:14,646 US AS A PRERECORDED TALK. 9478 06:40:14,646 --> 06:40:17,348 WE HAVE DR. WALLY SMITH, WHO 9479 06:40:17,348 --> 06:40:19,417 WILL BE PRESENTING TO US REAL 9480 06:40:19,417 --> 06:40:21,486 WORLD USE OF CURRENT 9481 06:40:21,486 --> 06:40:22,120 THERAPEUTICS IN SICKLE CELL 9482 06:40:22,120 --> 06:40:22,353 DISEASE. 9483 06:40:22,353 --> 06:40:23,955 THIS WILL GIVE US A VERY 9484 06:40:23,955 --> 06:40:26,791 DIFFERENT PERSPECTIVE FROM 9485 06:40:26,791 --> 06:40:29,894 DR. QUINN'S, I IMAGINE. 9486 06:40:29,894 --> 06:40:32,430 DR. SMITH IS THE FLORENCE NEIL 9487 06:40:32,430 --> 06:40:33,998 COOPER SMITH PROFESSOR OF SICKLE 9488 06:40:33,998 --> 06:40:36,835 CELL DISEASE AT VIRGINIA 9489 06:40:36,835 --> 06:40:37,669 COMMONWEALTH UNIVERSITY. 9490 06:40:37,669 --> 06:40:39,671 HE HAS CARED FOR PATIENTS WITH 9491 06:40:39,671 --> 06:40:42,540 SICKLE CELL DISEASE FOR OVER 40 9492 06:40:42,540 --> 06:40:44,609 YEARS, IS BEST KNOWN FOR HIS 9493 06:40:44,609 --> 06:40:46,044 PISCES STUDY, AND I LOOK FORWARD 9494 06:40:46,044 --> 06:40:56,521 TO HEARING HIS PERSPECTIVE. 9495 06:41:22,580 --> 06:41:26,351 >> THANK YOU FOR THE OPPORTUNITY 9496 06:41:26,351 --> 06:41:28,186 TO TALK TODAY ABOUT REAL WORLD 9497 06:41:28,186 --> 06:41:29,587 USE OF CURRENT THERAPIES FOR 9498 06:41:29,587 --> 06:41:34,092 SICKLE CELL DISEASE. 9499 06:41:34,092 --> 06:41:38,730 THESE ARE MY CONFLICTS, AND -- 9500 06:41:38,730 --> 06:41:42,467 CONFLICTS OF INTEREST. 9501 06:41:42,467 --> 06:41:44,536 I'M GOING TO TRY TO ANSWER 9502 06:41:44,536 --> 06:41:46,237 SEVERAL COMMON QUESTIONS, 9503 06:41:46,237 --> 06:41:47,305 FREQUENTLY ASKED QUESTIONS 9504 06:41:47,305 --> 06:41:48,640 REGARDING REAL WORLD USE OF 9505 06:41:48,640 --> 06:41:50,375 THERAPIES FOR SICKLE CELL 9506 06:41:50,375 --> 06:41:50,875 DISEASE TODAY. 9507 06:41:50,875 --> 06:41:52,610 AND WARN YOU IN ADVANCE THAT WE 9508 06:41:52,610 --> 06:41:54,679 DON'T HAVE GOOD DATA TO ANSWER A 9509 06:41:54,679 --> 06:42:00,285 NUMBER OF THESE QUESTIONS. 9510 06:42:00,285 --> 06:42:01,986 THERE'S FEW PUBLISHED STUDIES 9511 06:42:01,986 --> 06:42:04,289 ABOUT MANY OF THESE QUESTIONS. 9512 06:42:04,289 --> 06:42:05,957 MANY OF THE DATABASES THAT WE 9513 06:42:05,957 --> 06:42:07,392 MIGHT WANT TO USE TO ANSWER 9514 06:42:07,392 --> 06:42:11,462 THESE QUESTIONS SUCH AS MARKET 9515 06:42:11,462 --> 06:42:14,065 SCAN AND THE PHARMA DATABASE ARE 9516 06:42:14,065 --> 06:42:15,700 PROPRIETARY AND THERE ARE FEW 9517 06:42:15,700 --> 06:42:17,202 PHASE FOUR STUDIES FOR 9518 06:42:17,202 --> 06:42:18,536 INDIVIDUAL AGENTS. 9519 06:42:18,536 --> 06:42:20,338 FURTHER, THERE'S VERY LITTLE 9520 06:42:20,338 --> 06:42:22,407 INFORMATION ABOUT ADHERENCE TO 9521 06:42:22,407 --> 06:42:27,245 ANYTHING EXCEPT HYDROXYUREA. 9522 06:42:27,245 --> 06:42:29,581 IN FACT, ONLY A THIRD OF AFRICAN 9523 06:42:29,581 --> 06:42:32,217 AMERICANS POLLED ARE AWARE THAT 9524 06:42:32,217 --> 06:42:33,551 SICKLE CELL DISEASE 9525 06:42:33,551 --> 06:42:34,419 DISPROPORTIONATELY AFFECTS 9526 06:42:34,419 --> 06:42:36,187 PEOPLE OF AFRICAN DESCENT. 9527 06:42:36,187 --> 06:42:39,757 EXOWB S SO THIS GOES ALONG WITH 9528 06:42:39,757 --> 06:42:40,959 THE LITTLE ATTENTION OFTEN BEING 9529 06:42:40,959 --> 06:42:42,927 PAID TO ISSUES RELATED TO REAL 9530 06:42:42,927 --> 06:42:44,362 WORLD USE OF THERAPEUTICS IN 9531 06:42:44,362 --> 06:42:47,332 SICKLE CELL DISEASE. 9532 06:42:47,332 --> 06:42:47,966 HERE'S THE FIRST QUESTION I'LL 9533 06:42:47,966 --> 06:42:50,768 TRY TO ANSWER. 9534 06:42:50,768 --> 06:42:54,005 HOW ARE YOU OR HOW ARE WE, AS 9535 06:42:54,005 --> 06:42:55,740 PEDIATRICIANS AND ADULT 9536 06:42:55,740 --> 06:42:57,675 PROVIDERS, DOING WITH ROUTINE 9537 06:42:57,675 --> 06:42:59,377 VACCINATIONS AND PROPHYLACTIC 9538 06:42:59,377 --> 06:43:01,246 PENICILLIN AND STROKE 9539 06:43:01,246 --> 06:43:01,813 PREVENTION? 9540 06:43:01,813 --> 06:43:03,982 WHICH EVERYBODY WOULD AGREE IS 9541 06:43:03,982 --> 06:43:04,949 COST-EFFECTIVE AND IMPORTANT 9542 06:43:04,949 --> 06:43:09,420 THERAPY. 9543 06:43:09,420 --> 06:43:11,155 ITS NET BENEFIT TO SOCIETY PER 9544 06:43:11,155 --> 06:43:12,690 THE U.S. PREVENTIVE HEALTH 9545 06:43:12,690 --> 06:43:14,859 SERVICES TASK FORCE, IT'S 9546 06:43:14,859 --> 06:43:19,330 MANDATED IN ALL 50 STATES. 9547 06:43:19,330 --> 06:43:21,266 AND IT'S RECOMMENDED WORLDWIDE 9548 06:43:21,266 --> 06:43:23,801 IN COUNTRIES SUCH AS THE UNITED 9549 06:43:23,801 --> 06:43:26,137 STATES, ENGLAND, FRANCE, SPAIN, 9550 06:43:26,137 --> 06:43:28,473 BELGIUM AND THE NETHERLANDS. 9551 06:43:28,473 --> 06:43:29,574 THE BRITISH NATIONAL HEALTH 9552 06:43:29,574 --> 06:43:31,542 SERVICE AND THE WORLD HEALTH 9553 06:43:31,542 --> 06:43:32,710 ORGANIZATION HAVE GUIDELINES 9554 06:43:32,710 --> 06:43:36,948 PUBLISHED ON THIS. 9555 06:43:36,948 --> 06:43:39,484 IN THE UNITED STATES, THE 9556 06:43:39,484 --> 06:43:43,254 MORTALITY DUE TO SICKLE CELL 9557 06:43:43,254 --> 06:43:44,889 DISEASE IS RAPIDLY DECLINING, 9558 06:43:44,889 --> 06:43:46,090 LARGELY ATTRIBUTED TO NEWBORN 9559 06:43:46,090 --> 06:43:47,292 SCREENING. 9560 06:43:47,292 --> 06:43:49,661 SIMILARLY IN A JAMAICAN COHORT, 9561 06:43:49,661 --> 06:43:51,996 THERE'S BEEN INCREASED SURVIVAL 9562 06:43:51,996 --> 06:43:54,499 OVER TIME, AGAIN, ATTRIBUTED TO 9563 06:43:54,499 --> 06:43:57,535 NEWBORN SCREENING. 9564 06:43:57,535 --> 06:44:02,106 AND DESPITE THIS, THERE IS NOT 9565 06:44:02,106 --> 06:44:06,577 THE USE OF THE FOLLOW-UP TESTS 9566 06:44:06,577 --> 06:44:08,846 SUCH AS PROPHYLACTIC PENICILLIN 9567 06:44:08,846 --> 06:44:11,683 OR, IN THIS CASE, TRANSCRANIAL 9568 06:44:11,683 --> 06:44:12,517 DOPPLER SCREENING. 9569 06:44:12,517 --> 06:44:16,921 FEWER THAN HALF OF THE CHILDREN 9570 06:44:16,921 --> 06:44:20,291 RECEIVED ANNUAL TRANSCRANIAL 9571 06:44:20,291 --> 06:44:22,193 DOPPLER SCREENING IN ONE MARKET 9572 06:44:22,193 --> 06:44:22,393 STUDY. 9573 06:44:22,393 --> 06:44:25,063 THOTHESE ARE PEOPLE WITH PRIVATE 9574 06:44:25,063 --> 06:44:26,130 INSURANCE SO PAYMENT SHOULD NOT 9575 06:44:26,130 --> 06:44:29,434 BE A PROBLEM. 9576 06:44:29,434 --> 06:44:31,736 SO PEOPLE ARE MISSING OUT ON 9577 06:44:31,736 --> 06:44:34,172 CHRONIC TRANSFUSION AND STROKE 9578 06:44:34,172 --> 06:44:36,174 PREVENTION IN A LARGE NUMBER OF 9579 06:44:36,174 --> 06:44:37,608 CASES WHEN IT'S VERY CLEAR THAT 9580 06:44:37,608 --> 06:44:38,910 THAT IS SOMETHING WE SHOULD BE 9581 06:44:38,910 --> 06:44:48,586 DOING. 9582 06:44:48,586 --> 06:44:51,789 THERE'S ALSO OVERALL 9583 06:44:51,789 --> 06:44:54,325 UNDERUTILIZATION OF NEEDED 9584 06:44:54,325 --> 06:44:54,959 THERAPIES AMONG PATIENTS WITH 9585 06:44:54,959 --> 06:44:55,426 SICKLE CELL DISEASE. 9586 06:44:55,426 --> 06:44:58,930 THIS IS A STUDY OF PATIENTS WITH 9587 06:44:58,930 --> 06:44:59,997 CEREBROVASCULAR DISEASE, BUT YOU 9588 06:44:59,997 --> 06:45:01,666 CAN IMAGINE SIMILAR STUDIES OF 9589 06:45:01,666 --> 06:45:02,967 PATIENTS WITHOUT SCREEN ROW 9590 06:45:02,967 --> 06:45:11,075 VASCULAR SCREEN CEREBROVASCULARW 9591 06:45:11,075 --> 06:45:12,276 UTILIZATION OF THINGS SUCH AS 9592 06:45:12,276 --> 06:45:13,945 BLOOD TRANSFUSION, TCD, 9593 06:45:13,945 --> 06:45:18,750 HYDROXYUREA, ET CETERA. 9594 06:45:18,750 --> 06:45:22,286 IT IS POSSIBLE TO IMPROVE 9595 06:45:22,286 --> 06:45:23,921 QUALITY IN PATIENTS WITH SICKLE 9596 06:45:23,921 --> 06:45:24,288 CELL DISEASE. 9597 06:45:24,288 --> 06:45:26,224 THIS IS THE QUALITY OF 9598 06:45:26,224 --> 06:45:27,859 TRANSITION SUPPORT, AND HERE 9599 06:45:27,859 --> 06:45:37,435 WE'RE SHOWING INCREASES IN THE 9600 06:45:37,435 --> 06:45:38,102 14ST3P-UP SITES. 9601 06:45:38,102 --> 06:45:39,771 THIS WAS A STUDY OF PEER 9602 06:45:39,771 --> 06:45:41,506 MENTORING TO IMPROVE THE 9603 06:45:41,506 --> 06:45:43,040 TRANSITION QUALITY IN 9604 06:45:43,040 --> 06:45:44,142 ADOLESCENTS AND YOUNG ADULTS. 9605 06:45:44,142 --> 06:45:48,679 AND YOU CAN SEE HERE DRASTIC 9606 06:45:48,679 --> 06:45:50,415 IMPROVEMENTS IN BOTH PEDIATRIC 9607 06:45:50,415 --> 06:45:51,516 AND ADULT QUALITY IMPROVEMENT 9608 06:45:51,516 --> 06:45:52,583 SCORES OVER THE COURSE OF THE 9609 06:45:52,583 --> 06:45:53,251 STUDY. 9610 06:45:53,251 --> 06:45:55,620 WITH OR WITHOUT PEER MENTORING. 9611 06:45:55,620 --> 06:45:57,355 SO IT IS POSSIBLE TO IMPROVE 9612 06:45:57,355 --> 06:46:00,758 THESE THINGS. 9613 06:46:00,758 --> 06:46:02,860 AND WE HAVE THE NATIONAL 9614 06:46:02,860 --> 06:46:06,230 ALLIANCE OF SICKLE CELL CENTERS, 9615 06:46:06,230 --> 06:46:07,932 WHOSE GOAL IS TO IMPROVE THE 9616 06:46:07,932 --> 06:46:10,635 QUALITY OF CARE FOR PATIENTS 9617 06:46:10,635 --> 06:46:11,969 WITH SICKLE CELL DISEASE TO SET 9618 06:46:11,969 --> 06:46:14,105 STANDARDS OF CARE, COME UP WITH 9619 06:46:14,105 --> 06:46:14,772 CONSENSUS RECOMMENDATIONS ON 9620 06:46:14,772 --> 06:46:18,242 WHAT IS HIGH QUALITY CARE, AND 9621 06:46:18,242 --> 06:46:19,510 QUALITY INDICATORS AND THEN 9622 06:46:19,510 --> 06:46:21,179 MEASURE OURSELVES AGAINST THOSE 9623 06:46:21,179 --> 06:46:22,046 QUALITY INDICATORS. 9624 06:46:22,046 --> 06:46:24,215 BUT WE ARE VERY, VERY EARLY IN 9625 06:46:24,215 --> 06:46:29,754 THAT PROCESS. 9626 06:46:29,754 --> 06:46:30,988 NEXT QUESTION, HOW DO YOU 9627 06:46:30,988 --> 06:46:31,889 PRESCRIBE HYDROXYUREA? 9628 06:46:31,889 --> 06:46:33,925 DO YOU USE THE MAXIMUM TOLERATED 9629 06:46:33,925 --> 06:46:36,394 APPROACH OR DO YOU USE A FIRM 9630 06:46:36,394 --> 06:46:38,029 FIXED DOSE? 9631 06:46:38,029 --> 06:46:40,431 AND DOES IT MATTER WHAT SETTING 9632 06:46:40,431 --> 06:46:42,066 IN WHICH YOU'RE ASKING THAT 9633 06:46:42,066 --> 06:46:43,067 QUESTION? 9634 06:46:43,067 --> 06:46:45,102 LOW RESOURCE SETTING OR A RURAL 9635 06:46:45,102 --> 06:46:46,604 PRACTICE SETTING VERSUS A HIGH 9636 06:46:46,604 --> 06:46:49,106 RESOURCE SETTING OR AN URBAN 9637 06:46:49,106 --> 06:46:52,043 SICKLE CELL CENTER WITH WELL 9638 06:46:52,043 --> 06:46:54,946 STAFFED AND HIGHLY RESOURCED 9639 06:46:54,946 --> 06:46:56,781 PROARS. 9640 06:46:56,781 --> 06:47:02,920 PROVIDPROVIDER. 9641 06:47:02,920 --> 06:47:04,155 THIS HAS BEEN HIGHLIGHTED IN A 9642 06:47:04,155 --> 06:47:05,556 RECENT ARTICLE BY CHARLES QUINN 9643 06:47:05,556 --> 06:47:09,460 IN BLOOD. 9644 06:47:09,460 --> 06:47:10,228 HERE'S THE DATA. 9645 06:47:10,228 --> 06:47:15,933 MOST OF YOU ARE AWARE THAT 9646 06:47:15,933 --> 06:47:19,837 RUSSELL -- HAS BEEN INTERESTED 9647 06:47:19,837 --> 06:47:21,439 IN MTD USE IN HYDROXYUREA EVEN 9648 06:47:21,439 --> 06:47:23,975 IN LOW RESOURCE SETTINGS, AND HE 9649 06:47:23,975 --> 06:47:25,343 STUDIED PATIENTS USING 15 TO 9650 06:47:25,343 --> 06:47:26,410 20 MILLIGRAMS PER KILOGRAM PER 9651 06:47:26,410 --> 06:47:28,646 DAY FOR SIX MONTHS AND THEN 9652 06:47:28,646 --> 06:47:29,647 ESCALATED THEM, FOUND THAT THIS 9653 06:47:29,647 --> 06:47:35,319 WAS FEASIBLE TO DO, FOUND VERY 9654 06:47:35,319 --> 06:47:37,355 LITTLE DOSE LIMITING TOXICITY 9655 06:47:37,355 --> 06:47:42,159 AND REDUCED DEATH AND THIS WAS 9656 06:47:42,159 --> 06:47:43,828 IMPORTANT ENOUGH TO BE PUBLISHED 9657 06:47:43,828 --> 06:47:47,398 IN THE NEW ENGLAND JOURNAL. 9658 06:47:47,398 --> 06:47:52,970 IN CONTRAST, HERE IS A STUDY BY 9659 06:47:52,970 --> 06:47:57,074 MIKE DEBAUD AND OTHERS IN ONE 9660 06:47:57,074 --> 06:47:57,742 SUB-SAHARAN AFRICAN COUNTRY 9661 06:47:57,742 --> 06:48:01,012 WHICH SHOWED THAT THERE WAS NO 9662 06:48:01,012 --> 06:48:03,648 DIFFERENCE IN MAIN OUTCOMES 9663 06:48:03,648 --> 06:48:05,483 BETWEEN 10 MILLIGRAMS AND 9664 06:48:05,483 --> 06:48:07,752 20 MILLIGRAMS PER KILO PER DAY 9665 06:48:07,752 --> 06:48:10,488 OF HYDROXYUREA IN A FIXED ORAL 9666 06:48:10,488 --> 06:48:12,890 DOSE. 9667 06:48:12,890 --> 06:48:13,958 THE CONCLUSION WAS THAT 9668 06:48:13,958 --> 06:48:15,393 10 MILLIGRAMS PER KILOGRAM PER 9669 06:48:15,393 --> 06:48:19,664 DAY OF HYDROXYUREA IS THE 9670 06:48:19,664 --> 06:48:21,899 MINIMUM KNOWN EFFICACIOUS DOSE 9671 06:48:21,899 --> 06:48:25,469 FOR STROKE PRESE PREVENTION IN S 9672 06:48:25,469 --> 06:48:26,037 PARTICULAR STUDY AND THEY 9673 06:48:26,037 --> 06:48:28,005 ACTUALLY STOPPED THE TRIAL. 9674 06:48:28,005 --> 06:48:30,841 LATELY, THERE'S BEEN A STUDY BY 9675 06:48:30,841 --> 06:48:34,445 AMBROSE AND OTHERS USING 9676 06:48:34,445 --> 06:48:39,417 HYDROXYUREA AT 20 MILLIGRAMS PER 9677 06:48:39,417 --> 06:48:41,385 DAY TO THE MAXIMUM TOLERATED 9678 06:48:41,385 --> 06:48:43,020 DOSE IN ORDER TO SEE WHAT THAT 9679 06:48:43,020 --> 06:48:46,624 DOES TO THE TRANSCRANIAL DOPPLER 9680 06:48:46,624 --> 06:48:47,892 VELOCITY. 9681 06:48:47,892 --> 06:48:50,995 AND THE FINDING WAS THAT IT 9682 06:48:50,995 --> 06:48:56,634 DECREASED, DECREASED FROM -- TO 9683 06:48:56,634 --> 06:48:59,470 149 AFTER BEGINNING THE STUDY, 9684 06:48:59,470 --> 06:49:02,940 VERSUS 182 AND BASELINE. 9685 06:49:02,940 --> 06:49:05,509 THEY'RE GIVING HYDROXYUREA AT 9686 06:49:05,509 --> 06:49:09,046 THE MAXIMUM TOLERATED DOSE IN 9687 06:49:09,046 --> 06:49:10,815 RESPONSE TO THE TRANSCRANIAL 9688 06:49:10,815 --> 06:49:13,284 DOPPLER READING. 9689 06:49:13,284 --> 06:49:14,752 SO YOU CAN KIND OF PAY YOUR 9690 06:49:14,752 --> 06:49:15,820 MONEY AND TAKE YOUR CHOICE ABOUT 9691 06:49:15,820 --> 06:49:16,988 WHAT YOU SHOULD DO. 9692 06:49:16,988 --> 06:49:18,723 CLEARLY A MINIMUM DOSE MIGHT BE 9693 06:49:18,723 --> 06:49:20,925 AN EFFECTIVE STRATEGY IN THE 9694 06:49:20,925 --> 06:49:22,994 APPROPRIATE SETTING. 9695 06:49:22,994 --> 06:49:26,464 BUT ESCALATION TO MAXIMUM POLL 9696 06:49:26,464 --> 06:49:29,634 TOLERATED DOSE IS NOT ASSOCIATED 9697 06:49:29,634 --> 06:49:31,736 WITH TOXICITIES AND MAY BE AS 9698 06:49:31,736 --> 06:49:36,073 EFFECTIVE OR MORE EFFECTIVE. 9699 06:49:36,073 --> 06:49:38,175 WHAT DO YOU DO TO MAKE PEOPLE 9700 06:49:38,175 --> 06:49:38,876 TAKE THEIR HYDROXYUREA? 9701 06:49:38,876 --> 06:49:40,411 AND THAT'S A BIG PROBLEM IN THE 9702 06:49:40,411 --> 06:49:41,746 UNITED STATES. 9703 06:49:41,746 --> 06:49:43,047 HOW DO YOU MONITOR THIS, HOW 9704 06:49:43,047 --> 06:49:45,883 OFTEN SHOULD YOU MONITOR THIS. 9705 06:49:45,883 --> 06:49:47,985 THERE'S MANY, MANY BARRIERS. 9706 06:49:47,985 --> 06:49:50,988 PHYSICIANS ARE NOT PRESCRIBING 9707 06:49:50,988 --> 06:49:51,989 HYDROXYUREA OFTEN THE WAY THAT 9708 06:49:51,989 --> 06:49:53,624 THEY SHOULD BE. 9709 06:49:53,624 --> 06:49:55,159 THERE ARE DOUBTS BOTH IN THE 9710 06:49:55,159 --> 06:49:56,527 PHYSICIAN'S MIND AND IN THE 9711 06:49:56,527 --> 06:50:00,131 PATIENT'S MINDS ABOUT 9712 06:50:00,131 --> 06:50:01,699 HYDROXYUREA EFFECTIVENESS. 9713 06:50:01,699 --> 06:50:02,566 PATIENTS DON'T FEEL ANYTHING 9714 06:50:02,566 --> 06:50:03,868 WHEN YOU GIVE THEM HYDROXYUREA 9715 06:50:03,868 --> 06:50:05,236 AT FIRST SO THEY DOUBT ITS 9716 06:50:05,236 --> 06:50:06,137 EFFECTIVENESS. 9717 06:50:06,137 --> 06:50:08,506 THE PATIENTS HAVE APPREHENSION 9718 06:50:08,506 --> 06:50:09,607 ON THE OTHER HAND ABOUT THE 9719 06:50:09,607 --> 06:50:10,741 BLACK BOX WARNINGS ON THE 9720 06:50:10,741 --> 06:50:12,343 LABELS. 9721 06:50:12,343 --> 06:50:14,078 ABOUT ADVERSE EFFECTS. 9722 06:50:14,078 --> 06:50:17,548 ABOUT CONCERNS FOR INFERTILITY 9723 06:50:17,548 --> 06:50:20,051 AND THE NEED TO USE 9724 06:50:20,051 --> 06:50:20,818 CONTRACEPTIVES IN ORDER TO NOT 9725 06:50:20,818 --> 06:50:22,153 GET PREGNANT, AND OF COURSE THEY 9726 06:50:22,153 --> 06:50:24,321 DON'T ADHERE FOR LONG PERIODS OF 9727 06:50:24,321 --> 06:50:28,659 TIME WHEN THEY DON'T SEE BIG 9728 06:50:28,659 --> 06:50:31,562 SUBJECTIVE CHANGES. 9729 06:50:31,562 --> 06:50:32,930 THE STATES ARE NOT INVESTING ANY 9730 06:50:32,930 --> 06:50:34,899 MONEY IN THIS THE WAY WE INVEST 9731 06:50:34,899 --> 06:50:36,734 IN PROPHYLACTIC PENICILLIN AND 9732 06:50:36,734 --> 06:50:38,803 NEWBORN SCREENING. 9733 06:50:38,803 --> 06:50:40,671 AND THE NUMBER OF PATIENTS WHO 9734 06:50:40,671 --> 06:50:43,240 ARE ADULTS IS NOT FOLLOWED BY 9735 06:50:43,240 --> 06:50:44,575 MOST STATES IN THE UNITED 9736 06:50:44,575 --> 06:50:47,078 STATES, SO WE DON'T EVEN KNOW 9737 06:50:47,078 --> 06:50:48,879 HOW MANY ADULTS HAVE SICKLE CELL 9738 06:50:48,879 --> 06:50:50,681 DISEASE IN MOST STATES, ALTHOUGH 9739 06:50:50,681 --> 06:50:52,416 WE ESTIMATE BASED ON THE CLAIMS 9740 06:50:52,416 --> 06:50:54,685 DATA THAT TWO THIRDS OF 9741 06:50:54,685 --> 06:50:56,153 AMERICANS WHO HAVE SICKLE CELL 9742 06:50:56,153 --> 06:51:02,660 DISEASE ARE ADULTS. 9743 06:51:02,660 --> 06:51:05,863 WHAT WE DO KNOW IS THAT IF YOU 9744 06:51:05,863 --> 06:51:08,733 TAKE HYDROXYUREA BETTER, YOU 9745 06:51:08,733 --> 06:51:09,233 FEEL BETTER. 9746 06:51:09,233 --> 06:51:11,302 YOU HAVE BETTER RELATED QUALITY 9747 06:51:11,302 --> 06:51:14,271 OF LIFE SCORES, MORE PAIN 9748 06:51:14,271 --> 06:51:16,340 IMPACT, LESS FATIGUE, AND THIS 9749 06:51:16,340 --> 06:51:18,008 WAS SHOWN AS EARLY AS THE 9750 06:51:18,008 --> 06:51:18,943 MULTICENTER STUDY FOR 9751 06:51:18,943 --> 06:51:20,911 HYDROXYUREA BUT THIS IS AN 9752 06:51:20,911 --> 06:51:25,950 ARTICLE PUBLISHED IN 2022. 9753 06:51:25,950 --> 06:51:28,219 IN INDIVIDUALS WITH SICKLE CELL 9754 06:51:28,219 --> 06:51:29,787 DISEASE FROM 12 DIFFERENT 9755 06:51:29,787 --> 06:51:32,356 STUDIES. 9756 06:51:32,356 --> 06:51:34,325 WE DON'T HAVE SIMILAR STUDIES TO 9757 06:51:34,325 --> 06:51:36,260 EVALUATE ADHERENCE WITH 9758 06:51:36,260 --> 06:51:38,295 L-GLUTAMINE, VOXELOTOR OR 9759 06:51:38,295 --> 06:51:39,296 CRIZANLIZUMAB TO MATCH UP WITH 9760 06:51:39,296 --> 06:51:44,001 THIS. 9761 06:51:44,001 --> 06:51:48,806 WE ALSO KNOW THAT IT IS 9762 06:51:48,806 --> 06:51:52,810 DIFFICULT TO FIND GOOD DATA ON 9763 06:51:52,810 --> 06:51:54,178 TECHNIQUES TO IMPROVE 9764 06:51:54,178 --> 06:51:58,182 HYDROXYUREA ADHERENCE. 9765 06:51:58,182 --> 06:52:00,050 BASICALLY THE RESULT OF THIS 9766 06:52:00,050 --> 06:52:01,452 SYSTEMATIC REVIEW WAS THAT MORE 9767 06:52:01,452 --> 06:52:02,453 STUDIES ON HYDROXYUREA ADHERENCE 9768 06:52:02,453 --> 06:52:03,654 ARE NEEDED. 9769 06:52:03,654 --> 06:52:08,592 AND THAT FEW STUDIES TESTED 9770 06:52:08,592 --> 06:52:09,660 ADHERENCE OTHER THAN BEHAVIORAL 9771 06:52:09,660 --> 06:52:15,766 CHANGE. 9772 06:52:15,766 --> 06:52:22,239 IF YOU LOOK AT THE FEW STUDIES 9773 06:52:22,239 --> 06:52:26,043 THAT ARE THERE TO TRY TO IMPROVE 9774 06:52:26,043 --> 06:52:27,444 ADHERENCE, YOU CAN SEE THAT 9775 06:52:27,444 --> 06:52:30,614 YOUNG ADULTS ACTUALLY HAVE 9776 06:52:30,614 --> 06:52:31,582 SIGNIFICANTLY HIGHER HYDROXYUREA 9777 06:52:31,582 --> 06:52:34,151 ADHERENCE COMPARED TO CHILDREN 9778 06:52:34,151 --> 06:52:37,788 IN ADOLESCENCE, KIND OF 9779 06:52:37,788 --> 06:52:38,622 CONTRA -- COUNTERINTUITIVE TO 9780 06:52:38,622 --> 06:52:40,191 WHAT I WOULD HAVE EXPECTED. 9781 06:52:40,191 --> 06:52:42,226 AND THEN PATIENTS WITH LOWER 9782 06:52:42,226 --> 06:52:44,628 HYDROXYUREA ADHERENCE AND 9783 06:52:44,628 --> 06:52:46,163 CHRONIC PAIN HAD INCREASED 9784 06:52:46,163 --> 06:52:48,933 HEALTHCARE UTILIZATION SIMILAR 9785 06:52:48,933 --> 06:52:51,068 TO WHAT WE WOULD HAVE EXPECTED. 9786 06:52:51,068 --> 06:52:54,438 NO ASSOCIATIONS WITH GENDER, 9787 06:52:54,438 --> 06:52:55,539 SOCIOECONOMIC STATUS, DISTANCE 9788 06:52:55,539 --> 06:52:58,509 FROM CARE, OR HYDROXYUREA 9789 06:52:58,509 --> 06:53:04,415 DURATION. 9790 06:53:04,415 --> 06:53:05,549 HERE IS A SCALE, IF YOU WANTED 9791 06:53:05,549 --> 06:53:09,420 TO TRY TO MEASURE ADHERENCE THAT 9792 06:53:09,420 --> 06:53:11,121 HAS RECENTLY BEEN PUBLISHED 9793 06:53:11,121 --> 06:53:12,756 SUGGESTING A WAY TO MORE EASILY 9794 06:53:12,756 --> 06:53:15,926 MEASURE ADHERENCE IS CALLED THE 9795 06:53:15,926 --> 06:53:16,827 HYDROXYUREA EVALUATION OF 9796 06:53:16,827 --> 06:53:18,262 ADHERENCE FOR LIFE SCALE, 9797 06:53:18,262 --> 06:53:19,296 ACTUALLY CAME UPON IT IN 9798 06:53:19,296 --> 06:53:20,865 PREPARATION TO GIVE THIS TALK. 9799 06:53:20,865 --> 06:53:22,900 WAS NOT AWARE THAT IT EXISTED. 9800 06:53:22,900 --> 06:53:27,471 AS YOU CAN SEE, THERE'S ABOUT 9801 06:53:27,471 --> 06:53:30,841 20-SOME ITEMS, THERE'S EIGHT 9802 06:53:30,841 --> 06:53:33,911 SUBSCALES WITH THREE ITEMS EACH, 9803 06:53:33,911 --> 06:53:35,679 DOSE, REMEMBER, PLAN, COST, 9804 06:53:35,679 --> 06:53:36,680 UNDERSTAND, EFFECTIVENESS, 9805 06:53:36,680 --> 06:53:39,416 LABORATORY AND PHARMACY THIS 9806 06:53:39,416 --> 06:53:41,652 DOES REQUIRE PERMISSION TO USE, 9807 06:53:41,652 --> 06:53:43,554 SO PLEASE CONTACT THE AUTHORS IF 9808 06:53:43,554 --> 06:53:46,657 YOU WOULD LIKE TO USE THIS. 9809 06:53:46,657 --> 06:53:50,494 THE FIRST AUTHOR'S NAME IS 9810 06:53:50,494 --> 06:53:54,198 JANSON. 9811 06:53:54,198 --> 06:53:57,234 IF YOU GET SOPHISTICATED, YOU 9812 06:53:57,234 --> 06:53:59,003 CAN USE VIDEO DIRECTLY OBSERVE 9813 06:53:59,003 --> 06:54:00,304 THERAPY, OR YOU CAN USE 9814 06:54:00,304 --> 06:54:04,875 ELECTRONIC PILL MONITORING, AND 9815 06:54:04,875 --> 06:54:05,409 MEDICATION ADMINISTRATION 9816 06:54:05,409 --> 06:54:08,579 RECORDS TO MEASURE ADHERENCE. 9817 06:54:08,579 --> 06:54:09,246 WITH HYDROXYUREA. 9818 06:54:09,246 --> 06:54:10,915 AND OF COURSE YOU CAN USE THE 9819 06:54:10,915 --> 06:54:13,684 INDIRECT METHODS, WE ALL ARE 9820 06:54:13,684 --> 06:54:17,554 AWARE. 9821 06:54:17,554 --> 06:54:19,623 -- VOLUME AND THE FETAL 9822 06:54:19,623 --> 06:54:22,126 HEMOGLOBIN, BUT THOSE ARE KIND 9823 06:54:22,126 --> 06:54:26,730 OF INDIRECT AS BEHAVIORALLY 9824 06:54:26,730 --> 06:54:27,364 ORIENTED MEASURES. 9825 06:54:27,364 --> 06:54:32,069 HERE IN THIS STUDY, HIGHER 9826 06:54:32,069 --> 06:54:34,438 HYDROXYUREA EXPOSURE WAS OF 9827 06:54:34,438 --> 06:54:37,274 COURSE ASSOCIATED WITH IMPROVED 9828 06:54:37,274 --> 06:54:38,275 HEMATOLOGIC PARAMETERS. 9829 06:54:38,275 --> 06:54:39,576 AND THE NOTE IS THE STUDY WAS 9830 06:54:39,576 --> 06:54:41,312 BEING DONE IN THE HIGH INCOME 9831 06:54:41,312 --> 06:54:42,880 SETTING, SUGGESTING THAT IN LOW 9832 06:54:42,880 --> 06:54:47,952 INCOME SETTINGS, THESE METHODS 9833 06:54:47,952 --> 06:54:58,495 MAY NOT BE AVAILABLE OR USEFUL. 9834 06:54:59,964 --> 06:55:01,732 WE CHOSE TO USE COMMUNITY HEALTH 9835 06:55:01,732 --> 06:55:03,033 WORKERS TO TRY TO IMPROVE 9836 06:55:03,033 --> 06:55:04,568 HYDROXYUREA ADHERENCE. 9837 06:55:04,568 --> 06:55:07,805 OUR CLINIC IS IN A RELATIVELY 9838 06:55:07,805 --> 06:55:13,310 LOW INCOME, URBAN MEDICAL CARE 9839 06:55:13,310 --> 06:55:16,013 SYSTEM, AND WE WERE AWARE THAT 9840 06:55:16,013 --> 06:55:19,350 COMMUNITY HEALTH WORKERS WORK 9841 06:55:19,350 --> 06:55:21,251 ONE-ON-ONE WITH INDIVIDUALS WITH 9842 06:55:21,251 --> 06:55:23,654 MANY DISEASES TO IMPROVE HEALTH 9843 06:55:23,654 --> 06:55:26,056 OUTCOMES, SUCH AS DIABETES AND 9844 06:55:26,056 --> 06:55:26,824 CONGESTIVE HEART FAILURE. 9845 06:55:26,824 --> 06:55:29,326 AND THERE ARE MANY, MANY 9846 06:55:29,326 --> 06:55:30,594 MILLIONS OF THESE PEOPLE AND YOU 9847 06:55:30,594 --> 06:55:31,695 CAN SEE SOME OF THEM HERE. 9848 06:55:31,695 --> 06:55:33,130 THEY MAY BE TRAINED AS NURSES 9849 06:55:33,130 --> 06:55:35,466 BUT WE WERE PARTICULARLY 9850 06:55:35,466 --> 06:55:38,902 INTERESTED IN PEER LATE HEALTH H 9851 06:55:38,902 --> 06:55:40,204 PROVIDERS SO WE WENT WITH 9852 06:55:40,204 --> 06:55:44,842 NON-TRAINED LAY PEOPLE. 9853 06:55:44,842 --> 06:55:48,178 WE STUDIED THIS UNDER THE GUISE 9854 06:55:48,178 --> 06:55:51,749 OF A RANDOMIZED CONTROL TRIAL, 9855 06:55:51,749 --> 06:55:52,750 CALLED ENHANCING USE OF 9856 06:55:52,750 --> 06:55:54,618 HYDROXYUREA IN SICKLE CELL 9857 06:55:54,618 --> 06:55:56,387 DISEASE USING PATIENT 9858 06:55:56,387 --> 06:55:57,554 NAVIGATORS. 9859 06:55:57,554 --> 06:56:05,963 WE RENAMED THE STUDY SHIP HU. 9860 06:56:05,963 --> 06:56:08,132 WE HAD TWO HYPOTHESES. 9861 06:56:08,132 --> 06:56:09,333 THE SECOND HAD TO DO WITH 9862 06:56:09,333 --> 06:56:10,534 GETTING PATIENTS INTO CLINIC, 9863 06:56:10,534 --> 06:56:13,570 BUT OUR SECOND HYPOTHESIS WAS 9864 06:56:13,570 --> 06:56:16,073 THAT HYDROXYUREA-ELIGIBLE 9865 06:56:16,073 --> 06:56:18,142 PATIENTS EXPOSED TO PATIENT 9866 06:56:18,142 --> 06:56:19,877 NAVIGATORS OR THESE COMMUNITY 9867 06:56:19,877 --> 06:56:29,253 HEALTH WORKERS, WOULD HAVE 9868 06:56:29,253 --> 06:56:33,757 IMPROVED AT HEE ADHERENCE AND ID 9869 06:56:33,757 --> 06:56:34,458 LABORATORY CHARACTERISTICS 9870 06:56:34,458 --> 06:56:35,392 REFLECTING ADHERENCE TO 9871 06:56:35,392 --> 06:56:35,692 HYDROXYUREA. 9872 06:56:35,692 --> 06:56:37,828 WE DID OUR STUDY IN SPECIALTY 9873 06:56:37,828 --> 06:56:38,362 CLINICS. 9874 06:56:38,362 --> 06:56:42,299 WE USED PRESCRIBING ALGORITHMS 9875 06:56:42,299 --> 06:56:43,767 IN BOTH THE CONTROL AND THE 9876 06:56:43,767 --> 06:56:47,004 EXPERIMENTAL ARMS. 9877 06:56:47,004 --> 06:56:50,941 WE RECOGNIZED THAT MERE VERBAL 9878 06:56:50,941 --> 06:56:51,909 ASCENT OF BEING ON HYDROXYUREA 9879 06:56:51,909 --> 06:56:54,878 IS NOT THE SAME AS ACTUALLY 9880 06:56:54,878 --> 06:56:57,581 TAKING HYDROXYUREA, SO WE TRIED 9881 06:56:57,581 --> 06:57:00,250 TO USE MORE SOPHISTICATED 9882 06:57:00,250 --> 06:57:02,953 METHODS WITH SOME SUCCESS TO 9883 06:57:02,953 --> 06:57:03,520 GAUGE WHETHER PATIENTS WERE 9884 06:57:03,520 --> 06:57:04,588 ACTUALLY TAKING THEIR 9885 06:57:04,588 --> 06:57:08,725 HYDROXYUREA. 9886 06:57:08,725 --> 06:57:10,160 MAYBE THE BIGGEST DOWN FALL OF 9887 06:57:10,160 --> 06:57:11,728 THIS STUDY WAS THAT THE 9888 06:57:11,728 --> 06:57:13,197 PHYSICIANS INVOLVED WERE BLINDED 9889 06:57:13,197 --> 06:57:15,866 TO WHETHER THEIR PATIENTS WERE 9890 06:57:15,866 --> 06:57:17,868 GETTING INTERVENTIONS BY 9891 06:57:17,868 --> 06:57:19,169 COMMUNITY HEALTH WORKERS. 9892 06:57:19,169 --> 06:57:20,070 SO IT WAS NOT A TEAM 9893 06:57:20,070 --> 06:57:21,638 INTERVENTION, AND THE WORK WITH 9894 06:57:21,638 --> 06:57:24,007 THE COMMUNITY HEALTH WORKER WAS 9895 06:57:24,007 --> 06:57:25,175 ISOLATED FROM THE WORK OF THE 9896 06:57:25,175 --> 06:57:28,145 FEZ AND WE PHYSICIAN AND WE WERE 9897 06:57:28,145 --> 06:57:29,813 TO TALK TO ONE ANOTHER ABOUT 9898 06:57:29,813 --> 06:57:30,647 WHETHER OUR PATIENTS WERE USING 9899 06:57:30,647 --> 06:57:40,858 HYDROXYUREA. 9900 06:57:43,594 --> 06:57:47,297 HAVING TROUBLE HERE. 9901 06:57:47,297 --> 06:57:49,066 THIS IS JUST OUR PROTOCOL FOR 9902 06:57:49,066 --> 06:57:50,501 HOW WE OFFERED HYDROXYUREA TO 9903 06:57:50,501 --> 06:57:53,137 THE PATIENT. 9904 06:57:53,137 --> 06:57:55,873 AGAIN, IT WAS BLINDED AND WE 9905 06:57:55,873 --> 06:57:59,042 USED A PRETTY MUCH STANDARD NIH 9906 06:57:59,042 --> 06:58:00,210 HYDROXYUREA ELIGIBILITY 9907 06:58:00,210 --> 06:58:00,711 CRITERIA. 9908 06:58:00,711 --> 06:58:04,481 WE HAD A SCRIPT AND WE 9909 06:58:04,481 --> 06:58:05,916 DOCUMENTED EVERY TIME WE OFFERED 9910 06:58:05,916 --> 06:58:07,184 THE MEDICATION TO PATIENTS, EVEN 9911 06:58:07,184 --> 06:58:09,052 IF THEY REFUSED AND WE CAME 9912 06:58:09,052 --> 06:58:14,858 BACK. 9913 06:58:14,858 --> 06:58:18,028 WE RECORDED ALL OF THIS AND OUR 9914 06:58:18,028 --> 06:58:19,663 ANALYSIS INCLUDED THE PERCENT OF 9915 06:58:19,663 --> 06:58:21,298 THE PEOPLE WHO WERE ELIGIBLE FOR 9916 06:58:21,298 --> 06:58:22,499 HYDROXYUREA WHO WERE ACTUALLY ON 9917 06:58:22,499 --> 06:58:23,300 IT. 9918 06:58:23,300 --> 06:58:24,468 AND WHETHER THAT CHANGED OVER 9919 06:58:24,468 --> 06:58:25,769 TIME. 9920 06:58:25,769 --> 06:58:27,938 WE ALSO LOOKED AT THE PERCENTAGE 9921 06:58:27,938 --> 06:58:30,407 OF ENROLLED PATIENTS ON 9922 06:58:30,407 --> 06:58:31,575 HYDROXYUREA, AND THEN THE 9923 06:58:31,575 --> 06:58:33,644 REASONS WHY PATIENTS WERE NOT ON 9924 06:58:33,644 --> 06:58:34,878 HYDROXYUREA, AND WE LOOKED AT, 9925 06:58:34,878 --> 06:58:39,049 OF COURSE, SELF-REPORT FOR USING 9926 06:58:39,049 --> 06:58:41,485 HYDROXYUREA. 9927 06:58:41,485 --> 06:58:43,220 THESE ARE OUR RESULTS. 9928 06:58:43,220 --> 06:58:44,621 A WHOLE LOT OF PEOPLE SAID THEY 9929 06:58:44,621 --> 06:58:48,492 WERE ON HYDROXYUREA. 9930 06:58:48,492 --> 06:58:50,761 AND THAT WAS KIND OF A SURPRISE 9931 06:58:50,761 --> 06:58:53,330 AND CERTAINLY HIGHER THAN WHAT 9932 06:58:53,330 --> 06:58:54,831 WE HAD ANTICIPATED AT THE 9933 06:58:54,831 --> 06:58:59,469 BEGINNING OF OUR STUDY. 9934 06:58:59,469 --> 06:59:01,038 WE DID NOT SEE ANY VARIATION IN 9935 06:59:01,038 --> 06:59:03,774 WHO WAS ON HYDROXYUREA BY 9936 06:59:03,774 --> 06:59:06,510 GENDER, OR BY PEDIATRIC VERSUS 9937 06:59:06,510 --> 06:59:08,245 ADULT CLINIC MEMBERSHIP. 9938 06:59:08,245 --> 06:59:10,247 WE DID NOT SEE ANY DIFFERENCE BY 9939 06:59:10,247 --> 06:59:11,815 GENOTYPE. 9940 06:59:11,815 --> 06:59:14,051 IT WAS A SLIGHT VARIATION BY S 9941 06:59:14,051 --> 06:59:18,722 BETA SURE ZERO VERSUS SS, OTHEN 9942 06:59:18,722 --> 06:59:26,029 THAT, NOT A LOT OF DIFFERENCE. 9943 06:59:26,029 --> 06:59:26,697 THE LABS. 9944 06:59:26,697 --> 06:59:29,766 THEY DIDN'T CHANGE THAT MUCH. 9945 06:59:29,766 --> 06:59:32,402 THE FETAL HEMOGLOBIN WENT UP BY 9946 06:59:32,402 --> 06:59:33,904 ABOUT 1 1/2 TO 2%. 9947 06:59:33,904 --> 06:59:36,106 THE WHITE COUNT WENT DOWN, 9948 06:59:36,106 --> 06:59:37,307 ABSOLUTE NEUTROPHIL COUNT WENT 9949 06:59:37,307 --> 06:59:40,010 DOWN, HEMOGLOBIN DIDN'T REALLY 9950 06:59:40,010 --> 06:59:41,545 CHANGE, THE RETIC COUNT DIDN'T 9951 06:59:41,545 --> 06:59:42,512 CHANGE THAT MUCH. 9952 06:59:42,512 --> 06:59:45,382 THIS IS FROM CONTROLS VERSUS 9953 06:59:45,382 --> 06:59:48,218 EXPERIMENTAL PATIENTS. 9954 06:59:48,218 --> 06:59:50,821 SIMILARLY, THOSE WHO GOT 9955 06:59:50,821 --> 06:59:53,357 NAVIGATORS IN THE EXPERIMENTAL 9956 06:59:53,357 --> 06:59:56,293 GROUP DID NOT HAVE NEW UPTAKE OF 9957 06:59:56,293 --> 06:59:57,594 HYDROXYUREA AND YOU CAN SEE THAT 9958 06:59:57,594 --> 06:59:59,162 THERE WAS NOT VERY MUCH ROOM FOR 9959 06:59:59,162 --> 07:00:01,231 IMPROVEMENT THERE. 9960 07:00:01,231 --> 07:00:03,767 THE DISCONTINUATION RATE WAS NOT 9961 07:00:03,767 --> 07:00:08,839 THAT GREAT. 9962 07:00:08,839 --> 07:00:09,406 OF A DIFFERENCE 9963 07:00:09,406 --> 07:00:10,407 BETWEEN GROUPS AS WELL. 9964 07:00:10,407 --> 07:00:12,643 THE ONE THING WE DID SEE IS THAT 9965 07:00:12,643 --> 07:00:13,543 PEOPLE WERE MORE CONSISTENT IN 9966 07:00:13,543 --> 07:00:17,247 THE EXPERIMENTAL GROUP AT 12 9967 07:00:17,247 --> 07:00:18,515 MONTHS IN TAKING THEIR 9968 07:00:18,515 --> 07:00:19,016 HYDROXYUREA. 9969 07:00:19,016 --> 07:00:21,585 SO THIS NUMBER IS A NUMBER OF 9970 07:00:21,585 --> 07:00:23,587 HOW MANY TIMES YOU MISSED 9971 07:00:23,587 --> 07:00:26,189 HYDROXYUREA IN THE LAST 30 DAYS 9972 07:00:26,189 --> 07:00:27,824 BY REPORT, SELF-REPORT. 9973 07:00:27,824 --> 07:00:30,527 AND THAT WAS A LOWER NUMBER IN 9974 07:00:30,527 --> 07:00:31,895 THE EXPERIMENTAL GROUP THAN IN 9975 07:00:31,895 --> 07:00:41,305 THE CONTROL GROUP. 9976 07:00:41,305 --> 07:00:43,473 AND THAT'S WHAT WE KNOW ABOUT 9977 07:00:43,473 --> 07:00:45,342 ADHERENCE TO HYDROXYUREA. 9978 07:00:45,342 --> 07:00:46,310 HERE'S ANOTHER QUESTION. 9979 07:00:46,310 --> 07:00:49,046 DO YOU PRESCRIBE OR OFFER 9980 07:00:49,046 --> 07:00:50,914 HYDROXYUREA IN EVERY PATIENT? 9981 07:00:50,914 --> 07:00:54,284 OR DO YOU TRY NEWER DISEASE 9982 07:00:54,284 --> 07:00:55,752 MODIFIERS FIRST? 9983 07:00:55,752 --> 07:00:57,688 AND IF YOU DO SO, WHICH ONES DO 9984 07:00:57,688 --> 07:00:59,323 YOU TRY? 9985 07:00:59,323 --> 07:01:01,825 AND DO YOU HAVE PATIENTS WHO END 9986 07:01:01,825 --> 07:01:03,794 UP ON COMBINATIONS OF NEWER 9987 07:01:03,794 --> 07:01:05,796 DISEASE MODIFIERS WITHOUT 9988 07:01:05,796 --> 07:01:07,631 HYDROXYUREA? 9989 07:01:07,631 --> 07:01:10,267 THIS IS A QUESTION A LOT OF 9990 07:01:10,267 --> 07:01:11,568 PEOPLE WANT TO KNOW, BECAUSE 9991 07:01:11,568 --> 07:01:13,070 THERE'S SO MUCH MONEY TIED UP IN 9992 07:01:13,070 --> 07:01:15,906 THESE MEDICATIONS AND EVERYBODY 9993 07:01:15,906 --> 07:01:18,842 WANTS TO GET EFFECTS THAT ARE 9994 07:01:18,842 --> 07:01:25,115 FAST AND DO IT CHEAPLY. 9995 07:01:25,115 --> 07:01:29,586 AND WHAT WE KNOW IS ISIR HAS 9996 07:01:29,586 --> 07:01:30,854 BEEN THE PUSHER OF THIS. 9997 07:01:30,854 --> 07:01:32,522 THIS IS AN OLD STUDY, THEY 9998 07:01:32,522 --> 07:01:34,891 RECENTLY RELEASED THEIR 9999 07:01:34,891 --> 07:01:37,127 INDIVIDUAL COST-EFFECTIVENESS 10000 07:01:37,127 --> 07:01:41,164 RATIOS FOR GENE THERAPY, THE TWO 10001 07:01:41,164 --> 07:01:45,068 GENE THERAPIES UP FOR APPROVAL 10002 07:01:45,068 --> 07:01:48,238 THIS DECEMBER. 10003 07:01:48,238 --> 07:01:49,673 BUT IN EITHER CASE, THIS 10004 07:01:49,673 --> 07:01:51,007 PUBLICATION HERE OR IN THE CASE 10005 07:01:51,007 --> 07:01:53,977 OF THE GENE THERAPY, THEY'RE 10006 07:01:53,977 --> 07:01:55,679 FINDING FOR A PAYOR PERSPECTIVE, 10007 07:01:55,679 --> 07:01:57,447 AND I WANT TO EMPHASIZE, THIS IS 10008 07:01:57,447 --> 07:02:01,151 NOT A SOCIETAL OR PATIENT 10009 07:02:01,151 --> 07:02:03,453 PERSPECTIVE BUT A PAYOR PORE 10010 07:02:03,453 --> 07:02:06,523 SPERTIVE, YOU'RE TALKING ABOUT 10011 07:02:06,523 --> 07:02:09,893 $88,000 A YEAR FOR THE 10012 07:02:09,893 --> 07:02:13,830 CRIZANLIZUMAB, 84,000 FOR 10013 07:02:13,830 --> 07:02:16,433 VOXELOTOR AND 24,000 FOR L GLUTE 10014 07:02:16,433 --> 07:02:18,301 MEAN, LEADING TO GREATER THAN A 10015 07:02:18,301 --> 07:02:19,936 MILLION DOLLARS PER QUALITY 10016 07:02:19,936 --> 07:02:22,906 ADJUSTED LIFE YEAR 10017 07:02:22,906 --> 07:02:25,242 COST-EFFECTIVENESS RATIOS, AND 10018 07:02:25,242 --> 07:02:27,944 FEW QUALITY ADJUSTED LIFE YEARS 10019 07:02:27,944 --> 07:02:31,982 GAINED FOR ANY OF THESE DRUGS. 10020 07:02:31,982 --> 07:02:33,717 WE CERTAINLY HAVE BEEN 10021 07:02:33,717 --> 07:02:35,886 PRESCRIBING THESE DRUGS DESPITE 10022 07:02:35,886 --> 07:02:38,021 THE ICER PUBLICATION. 10023 07:02:38,021 --> 07:02:40,157 AND PATIENTS HAVE CERTAINLY BEEN 10024 07:02:40,157 --> 07:02:43,660 DERIVING BENEFIT FROM THEM, 10025 07:02:43,660 --> 07:02:50,233 SUBJECTIVELY AND OBJECTIVELY. 10026 07:02:50,233 --> 07:02:51,535 SO WHAT DO WE DO? 10027 07:02:51,535 --> 07:02:56,139 WELL, WE TRY TO USE SHARED 10028 07:02:56,139 --> 07:02:56,640 DECISION-MAKING WITH THE 10029 07:02:56,640 --> 07:02:58,642 PATIENT. 10030 07:02:58,642 --> 07:03:04,614 AND WE HAVE A PAMPHLET THAT GOES 10031 07:03:04,614 --> 07:03:07,317 ACROSS THE SPECTRUM. 10032 07:03:07,317 --> 07:03:08,785 I'M NOT SHOWING YOU THE PAMPHLET 10033 07:03:08,785 --> 07:03:10,454 TODAY BUT BELIEVE ME, WE HAVE A 10034 07:03:10,454 --> 07:03:12,022 PAMPHLET JUST LIKE THIS, 10035 07:03:12,022 --> 07:03:13,423 NON-BRANDED, THAT WE HAND OUT TO 10036 07:03:13,423 --> 07:03:15,158 OUR PATIENTS IN ORDER TO EXPLAIN 10037 07:03:15,158 --> 07:03:18,228 TO THEM WHAT IT IS WE'RE 10038 07:03:18,228 --> 07:03:20,497 OFFERING AND WHAT THEY CAN DO IN 10039 07:03:20,497 --> 07:03:23,433 TERMS OF MAKING THEIR CHOICES, 10040 07:03:23,433 --> 07:03:26,436 AND IT HAS SIDE EFFECTS IN HOW 10041 07:03:26,436 --> 07:03:28,772 YOU TAKE IT, I HAVE TO TAKE IT 10042 07:03:28,772 --> 07:03:30,273 ALL MY LIFE, WHAT ARE THE 10043 07:03:30,273 --> 07:03:31,308 MONITORING PARAMETERS, ET 10044 07:03:31,308 --> 07:03:31,708 CETERA. 10045 07:03:31,708 --> 07:03:33,743 AND WE TRY TO LET THE PATIENTS 10046 07:03:33,743 --> 07:03:34,845 THINK THIS OVER AND MAKE THE 10047 07:03:34,845 --> 07:03:38,648 DECISION FOR THEMSELVES. 10048 07:03:38,648 --> 07:03:40,884 IF THEY ASK US WHERE YOU DO, WE 10049 07:03:40,884 --> 07:03:42,352 GIVE OUR OPINION, BUT WE TRY TO 10050 07:03:42,352 --> 07:03:43,687 HELP THE PATIENTS COME TO A 10051 07:03:43,687 --> 07:03:44,554 CONCLUSION BECAUSE IF THEY DON'T 10052 07:03:44,554 --> 07:03:46,389 HAVE THE BUY-IN, THEY'RE 10053 07:03:46,389 --> 07:03:47,324 CERTAINLY NOT GOING TO TAKE THE 10054 07:03:47,324 --> 07:03:49,526 DRUGS. 10055 07:03:49,526 --> 07:03:51,561 WHEN DO YOU HAVE THAT 10056 07:03:51,561 --> 07:03:53,530 CONVERSATION ABOUT CURATIVE 10057 07:03:53,530 --> 07:03:54,397 INTENT? 10058 07:03:54,397 --> 07:03:55,899 AND I WOULD SAY AT VARIOUS 10059 07:03:55,899 --> 07:03:57,467 POINTS. 10060 07:03:57,467 --> 07:03:59,569 ONE CERTAINLY INFLECTION POINT 10061 07:03:59,569 --> 07:04:01,304 IS AFTER A BIG EVENT. 10062 07:04:01,304 --> 07:04:03,206 PATIENTS WILL OFTEN SAY, I'M 10063 07:04:03,206 --> 07:04:04,274 SCARED, I THINK I'M GOING TO 10064 07:04:04,274 --> 07:04:05,809 DIE, WHAT CAN I DO? 10065 07:04:05,809 --> 07:04:08,245 AND THAT'S OFTEN A WINDOW TO 10066 07:04:08,245 --> 07:04:11,047 HAVE A CONVERSATION ABOUT 10067 07:04:11,047 --> 07:04:14,417 THERAPY WITH CURATIVE INTENT. 10068 07:04:14,417 --> 07:04:15,752 SOMETIMES NEW PATIENTS LIKE TO 10069 07:04:15,752 --> 07:04:16,853 HEAR THIS CONVERSATION, BUT I 10070 07:04:16,853 --> 07:04:18,655 WOULD SAY MOST NEW PATIENTS, 10071 07:04:18,655 --> 07:04:20,690 WHEN YOU'RE TRYING TO TALK TO 10072 07:04:20,690 --> 07:04:21,925 THEM ABOUT FOUR DIFFERENT 10073 07:04:21,925 --> 07:04:26,930 DISEASE MODIFIERS AND THREE 10074 07:04:26,930 --> 07:04:29,533 POSSIBLE DIFFERENT DISEASE -- 10075 07:04:29,533 --> 07:04:33,169 CURATIVE DISEASE INTENT 10076 07:04:33,169 --> 07:04:33,937 THERAPIES, IT'S A LONG 10077 07:04:33,937 --> 07:04:34,471 CONVERSATION. 10078 07:04:34,471 --> 07:04:37,073 IT TAKES TIME AND YOU HAVE TO DO 10079 07:04:37,073 --> 07:04:41,645 IT OVER SEVERAL CLINIC VISIT AND 10080 07:04:41,645 --> 07:04:43,079 THE FAMILY HAS TO BE INVOLVED 10081 07:04:43,079 --> 07:04:45,582 AND IT IS NOT A VERY QUICK 10082 07:04:45,582 --> 07:04:49,286 DECISION. 10083 07:04:49,286 --> 07:04:50,620 PATIENTS CHANGE THEIR MIND 10084 07:04:50,620 --> 07:04:51,922 SOMETIMES, SO WE ALLOW THAT AS 10085 07:04:51,922 --> 07:04:52,889 WELL. 10086 07:04:52,889 --> 07:04:56,760 WE TRY TO GET ALL OF THE 10087 07:04:56,760 --> 07:04:58,929 INFORMATION THAT PATIENTS ARE 10088 07:04:58,929 --> 07:05:00,797 ASKING FOR, REPEATEDLY 10089 07:05:00,797 --> 07:05:01,431 SOMETIMES. 10090 07:05:01,431 --> 07:05:03,833 SO THAT'S HOW WE DO IT AND IN 10091 07:05:03,833 --> 07:05:05,201 THE ADULT WORLD, IT'S A LITTLE 10092 07:05:05,201 --> 07:05:07,671 BIT DIFFERENT BECAUSE YOU DON'T 10093 07:05:07,671 --> 07:05:09,105 HAVE A PARENT MAKING THE 10094 07:05:09,105 --> 07:05:10,674 DECISION, YOU HAVE THE ADULT AND 10095 07:05:10,674 --> 07:05:15,245 THEIR SIGNIFICANT OTHER. 10096 07:05:15,245 --> 07:05:16,479 AND THEN LAST, WHAT ARE YOU 10097 07:05:16,479 --> 07:05:17,681 DOING WITH OPIOID USE FOR 10098 07:05:17,681 --> 07:05:18,081 CHRONIC PAIN? 10099 07:05:18,081 --> 07:05:19,816 YOU ARE MAINLY GOING UP? 10100 07:05:19,816 --> 07:05:21,551 ARE YOU MAINLY KEEPING PEOPLE 10101 07:05:21,551 --> 07:05:22,452 THE SAME? 10102 07:05:22,452 --> 07:05:24,421 OR ARE YOU MAINLY DECREASING? 10103 07:05:24,421 --> 07:05:25,922 AND BY NOW YOU'VE ALREADY HEARD 10104 07:05:25,922 --> 07:05:28,558 A GREAT DEAL ABOUT OPIOIDS, THE 10105 07:05:28,558 --> 07:05:31,194 PROBLEMS WITH OPIOIDS. 10106 07:05:31,194 --> 07:05:33,063 I WOULD SAY WE'RE MAINLY GOING 10107 07:05:33,063 --> 07:05:34,464 DOWN, BUT WHAT ARE WE 10108 07:05:34,464 --> 07:05:35,465 SUBSTITUTING FOR OPIOIDS? 10109 07:05:35,465 --> 07:05:36,533 AND THAT'S WHERE THE PROBLEM 10110 07:05:36,533 --> 07:05:38,501 LIES. 10111 07:05:38,501 --> 07:05:42,105 GETTING PAYMENT FOR INTEGRATIVE 10112 07:05:42,105 --> 07:05:48,311 CARE AND FOR ANY NON-OPIOID 10113 07:05:48,311 --> 07:05:51,181 THERAPIES THAT DON'T INVOLVE 10114 07:05:51,181 --> 07:05:52,048 PHARMACEUTICALS IS DIFFICULT. 10115 07:05:52,048 --> 07:05:54,985 AND THAT'S WHERE THE PROBLEM IS, 10116 07:05:54,985 --> 07:05:57,287 AND THIS IS A KNOWN PROBLEM. 10117 07:05:57,287 --> 07:05:58,755 PEOPLE ARE NOT ABLE TO GET THESE 10118 07:05:58,755 --> 07:06:00,890 THINGS PAID FOR. 10119 07:06:00,890 --> 07:06:04,327 SO IT'S A DIFFICULT AND ARDUOUS 10120 07:06:04,327 --> 07:06:06,896 TASK TO TRY TO TAPER SOMEBODY'S 10121 07:06:06,896 --> 07:06:07,230 OPIOIDS. 10122 07:06:07,230 --> 07:06:08,865 BUT WE ARE TRYING TO DO IT WHEN 10123 07:06:08,865 --> 07:06:10,767 IT'S APPROPRIATE. 10124 07:06:10,767 --> 07:06:13,937 THAT'S ABOUT WHAT I HAVE TO SAY 10125 07:06:13,937 --> 07:06:15,739 ON THE THERAPEUTIC JOURNEY IN 10126 07:06:15,739 --> 07:06:18,642 REAL LIFE FOR MANAGING PATIENTS 10127 07:06:18,642 --> 07:06:19,509 WITH SICKLE CELL DISEASE, AND 10128 07:06:19,509 --> 07:06:20,944 I'LL BE GLAD TO TAKE QUESTIONS 10129 07:06:20,944 --> 07:06:22,012 AT THE APPROPRIATE TIME. 10130 07:06:22,012 --> 07:06:24,280 THANK YOU VERY MUCH. 10131 07:06:24,280 --> 07:06:30,320 [APPLAUSE] 10132 07:06:30,320 --> 07:06:32,822 >> SO THAT WAS A PRE-RECORDED 10133 07:06:32,822 --> 07:06:34,257 SESSION AND THANK YOU TO 10134 07:06:34,257 --> 07:06:35,959 DR. WALLY SMITH FOR THAT VERY 10135 07:06:35,959 --> 07:06:37,093 RICH PERSPECTIVE. 10136 07:06:37,093 --> 07:06:38,828 HE'S NOT ABLE TO JOIN US, BUT IF 10137 07:06:38,828 --> 07:06:39,929 ANYONE HAS QUESTIONS, YOU CAN 10138 07:06:39,929 --> 07:06:41,264 SHARE WITH THE ORGANIZERS AND 10139 07:06:41,264 --> 07:06:42,632 THEY WILL MAKE SURE TO GET THE 10140 07:06:42,632 --> 07:06:44,634 QUESTIONS TO HIM. 10141 07:06:44,634 --> 07:06:46,603 AND FINALLY, OUR LAST SPEAKER 10142 07:06:46,603 --> 07:06:50,273 FOR THIS SESSION, LAST BUT NOT 10143 07:06:50,273 --> 07:06:52,909 LEAST, WE HAVE DR. KARINA 10144 07:06:52,909 --> 07:06:53,810 YAZDANBAKHSH. 10145 07:06:53,810 --> 07:06:55,178 SHE'S THE VASOPRESSIN AND 10146 07:06:55,178 --> 07:07:02,018 DVICE PRESIDENT AT THENEW YORK N 10147 07:07:02,018 --> 07:07:02,552 NEW YORK. 10148 07:07:02,552 --> 07:07:04,287 A LONG TIME FRIEND AND 10149 07:07:04,287 --> 07:07:05,188 COLLABORATOR, HER CURRENT 10150 07:07:05,188 --> 07:07:07,157 RESEARCH IS FOCUSED ON 10151 07:07:07,157 --> 07:07:09,526 UNDERSTANDING MECHANISMS OF 10152 07:07:09,526 --> 07:07:16,666 TRANSFUSION ASSOCIATED ALLO 10153 07:07:16,666 --> 07:07:18,435 IMMUNIZATION, SHE'S A RECIPIENT 10154 07:07:18,435 --> 07:07:20,303 OF MANY NIH GRANTS AND AWARDS, 10155 07:07:20,303 --> 07:07:21,571 AND SHE MADE ME PROMISE I 10156 07:07:21,571 --> 07:07:22,939 WOULDN'T GO THROUGH ALL OF THEM. 10157 07:07:22,939 --> 07:07:33,116 SO KARINA. 10158 07:07:43,293 --> 07:07:53,470 >> THANK YOU. 10159 07:08:14,891 --> 07:08:16,025 >> OKAY. 10160 07:08:16,025 --> 07:08:21,598 SO FIRST OF ALL, THANK YOU FOR 10161 07:08:21,598 --> 07:08:22,899 GIVING ME THE OPPORTUNITY TO 10162 07:08:22,899 --> 07:08:25,001 PRESENT SOME OF OUR WORK. 10163 07:08:25,001 --> 07:08:28,371 SO I HAVE NOTHING TO DECLARE. 10164 07:08:28,371 --> 07:08:30,640 SO WE KNOW WE HAVE ANEMIA IN 10165 07:08:30,640 --> 07:08:32,108 SICKLE CELL DISEASE, RED CELL 10166 07:08:32,108 --> 07:08:34,744 DESTRUCTION CAN OCCUR EXTRA 10167 07:08:34,744 --> 07:08:37,347 VASCULARLY OR INTRAVASCULARLY IN 10168 07:08:37,347 --> 07:08:40,216 SICKLE CELL DISEASE. 10169 07:08:40,216 --> 07:08:44,921 WE KNOW THERE'S INTRAVASCULAR 10170 07:08:44,921 --> 07:08:54,664 HEMOLYSIS, AND HO1 LEVELS WHICH 10171 07:08:54,664 --> 07:08:57,600 BREAKS DOWN HEME IS UPREGULATED. 10172 07:08:57,600 --> 07:09:00,003 WE KNOW THAT EXCESSIVE HEME CAN 10173 07:09:00,003 --> 07:09:02,438 ACTIVATE THE UNDERLYING 10174 07:09:02,438 --> 07:09:03,106 ENDOTHELIUM. 10175 07:09:03,106 --> 07:09:06,075 YOU GET INCREASED ACTIVATION OF 10176 07:09:06,075 --> 07:09:08,011 ENDOTHELIAL ADHESION MOLECULES, 10177 07:09:08,011 --> 07:09:10,413 APOP TOLL TICK MARKERS, AND 10178 07:09:10,413 --> 07:09:12,549 THESE LEAD TO ATTACHMENT OF 10179 07:09:12,549 --> 07:09:16,553 ACTIVATED LEUKOCYTES, RED 10180 07:09:16,553 --> 07:09:18,521 CELLS -- WITH LEADS TO 10181 07:09:18,521 --> 07:09:18,955 VASOOCCLUSION. 10182 07:09:18,955 --> 07:09:20,924 WE ALSO KNOW FROM ANIMAL MODELS 10183 07:09:20,924 --> 07:09:23,960 THAT YOU INJECT FREE HEME AND 10184 07:09:23,960 --> 07:09:27,397 THAT INDUCES VASCULAR STASIS AND 10185 07:09:27,397 --> 07:09:30,967 ACUTE CHEST SYNDROME. 10186 07:09:30,967 --> 07:09:34,370 JUST BRIEFLY ABOUT CIRCULATING 10187 07:09:34,370 --> 07:09:36,706 MONOCYTES, THAT'S ARE WHAT WE 10188 07:09:36,706 --> 07:09:38,608 REALLY KNOW AS PRECURSORS FOR 10189 07:09:38,608 --> 07:09:40,310 MACROPHAGES AND DENDRITIC CELLS. 10190 07:09:40,310 --> 07:09:41,744 BUT THERE'S INCREASING EVIDENCE 10191 07:09:41,744 --> 07:09:44,113 THAT THESE CIRCULATING 10192 07:09:44,113 --> 07:09:46,983 MONOCYTES, WHILE IN THE BLOOD, 10193 07:09:46,983 --> 07:09:48,952 THEY DISPLAY INDIVIDUAL 10194 07:09:48,952 --> 07:09:51,788 FUNCTIONAL ACTIVITIES. 10195 07:09:51,788 --> 07:09:55,825 SO WE KNOW THAT THEY'RE PRODUCED 10196 07:09:55,825 --> 07:09:57,727 BOTH IN MICE AND IN HUMAN IN THE 10197 07:09:57,727 --> 07:09:58,494 BONE MARROW. 10198 07:09:58,494 --> 07:09:59,863 THEY GET RELEASED INTO THE 10199 07:09:59,863 --> 07:10:01,865 CIRCULATION, AND THERE WE CAN 10200 07:10:01,865 --> 07:10:04,133 DISTINGUISH THEM BASED ON 10201 07:10:04,133 --> 07:10:07,237 VARIOUS SURFACE MARKERS. 10202 07:10:07,237 --> 07:10:10,506 THIS IS FOR MOUSE, THIS IS FOR 10203 07:10:10,506 --> 07:10:10,974 HUMAN. 10204 07:10:10,974 --> 07:10:14,444 IT'S NOW BELIEVED THAT THE 10205 07:10:14,444 --> 07:10:16,512 MAJORITY OF THE CIRCULATING 10206 07:10:16,512 --> 07:10:18,248 MONOCYTES IN HUMANS, AT LEAST, 10207 07:10:18,248 --> 07:10:21,117 WHICH ARE CLASSICAL MONOCYTES, 10208 07:10:21,117 --> 07:10:22,285 THEY DIFFERENTIATE FURTHER IN 10209 07:10:22,285 --> 07:10:23,319 THE CIRCULATION, GIVING RISE TO 10210 07:10:23,319 --> 07:10:26,256 THESE NON-CLASSICAL MONOCYTES, 10211 07:10:26,256 --> 07:10:30,493 WE CALL THEM NOW PATROLLING 10212 07:10:30,493 --> 07:10:32,061 MONOCYTES. 10213 07:10:32,061 --> 07:10:34,130 IN MOUSE WE HAVE -- THEY HAVE 10214 07:10:34,130 --> 07:10:35,131 IDENTIFIED THE TRANSCRIPTION 10215 07:10:35,131 --> 07:10:36,366 FACTOR THAT IS IMPORTANT FOR 10216 07:10:36,366 --> 07:10:37,300 THIS DIFFERENTIATION. 10217 07:10:37,300 --> 07:10:40,503 IN HUMANS, WE STILL DON'T KNOW, 10218 07:10:40,503 --> 07:10:42,071 THIS IS UNDER ACTIVE RESEARCH. 10219 07:10:42,071 --> 07:10:43,706 WHAT ARE THESE PATROLLING 10220 07:10:43,706 --> 07:10:45,141 MONOCYTES THAT OUR LAB BECAME 10221 07:10:45,141 --> 07:10:46,843 VERY OBSESSED WITH? 10222 07:10:46,843 --> 07:10:49,812 SO THESE AS I SAID, THESE ARE 10223 07:10:49,812 --> 07:10:53,516 THESE NON-CLASSICAL MONOCYTES, 10224 07:10:53,516 --> 07:10:55,618 AND IT WAS SHOWN A FEW YEARS 10225 07:10:55,618 --> 07:10:59,889 AGO, THEY CRAWLED ALONG THE 10226 07:10:59,889 --> 07:11:03,092 VASCULATURE AND PHAGOCYTE -- IN 10227 07:11:03,092 --> 07:11:05,662 MOUSE MODELS, THEY WERE SHOWN IN 10228 07:11:05,662 --> 07:11:08,197 AT LEAST ATHEROSCLEROSIS MODEL, 10229 07:11:08,197 --> 07:11:11,034 THEY CONTROL ENDOTHELIAL DAMAGE 10230 07:11:11,034 --> 07:11:12,568 AND ALZHEIMER'S DISEASE MODELS, 10231 07:11:12,568 --> 07:11:14,871 THEY CLEAR VASCULAR AMYLOID BAY 10232 07:11:14,871 --> 07:11:15,738 DA. 10233 07:11:15,738 --> 07:11:18,374 THEY CRAWL ALONG AS I SAID AND 10234 07:11:18,374 --> 07:11:20,977 THEY REMOVE PARTICLES AND 10235 07:11:20,977 --> 07:11:21,778 DEBRIS. 10236 07:11:21,778 --> 07:11:24,380 WHAT WE HAD SHOWN A FEW YEARS 10237 07:11:24,380 --> 07:11:26,616 AGO THAT THESE NON-CLASSICAL 10238 07:11:26,616 --> 07:11:29,752 ONES OR THESE PATROLLING 10239 07:11:29,752 --> 07:11:31,754 MONOCYTES EXPRESS HIGH LEVELS OF 10240 07:11:31,754 --> 07:11:33,389 H01, AND WHAT WE WERE MORE 10241 07:11:33,389 --> 07:11:34,891 INTERESTED IN WAS THEIR ABILITY 10242 07:11:34,891 --> 07:11:37,327 OF THESE PATROLLING MONOCYTES 10243 07:11:37,327 --> 07:11:40,930 EXPRESSING THESE HIGH LEVELS AND 10244 07:11:40,930 --> 07:11:42,131 CONTROLLING UNDER HEMOLYTIC 10245 07:11:42,131 --> 07:11:44,767 CONDITIONS T-CELL 10246 07:11:44,767 --> 07:11:45,501 ANTI-INFLAMMATORY PROFILE. 10247 07:11:45,501 --> 07:11:47,370 WE'VE NOW GONE ON TO SHOW THAT 10248 07:11:47,370 --> 07:11:52,508 THESE PETROLEUM MONOCYTES REMOVE 10249 07:11:52,508 --> 07:11:54,310 ENDOTHELIAL ATTACHED SICKLE RED 10250 07:11:54,310 --> 07:11:56,212 CELLS. 10251 07:11:56,212 --> 07:11:58,314 THIS WAS -- FOR US WAS A BIG 10252 07:11:58,314 --> 07:12:00,717 FINDING BECAUSE NOW WE CAN THINK 10253 07:12:00,717 --> 07:12:04,554 OF THAT THEY MAYBE ARE ALSO 10254 07:12:04,554 --> 07:12:07,757 INVOLVED IN CONTROLLING 10255 07:12:07,757 --> 07:12:09,125 VASOOCCLUSION, AND ACTUALLY WHAT 10256 07:12:09,125 --> 07:12:11,995 WE FOUND WAS THAT AT STEADY 10257 07:12:11,995 --> 07:12:14,297 STATE COMPARED TO HEALTHY 10258 07:12:14,297 --> 07:12:17,133 DONORS, PATIENTS HAD REDUCED 10259 07:12:17,133 --> 07:12:21,437 NUMBERS OF THESE PATROLLING 10260 07:12:21,437 --> 07:12:22,839 MONOCYTES, SPECIFICALLY 10261 07:12:22,839 --> 07:12:24,073 FREQUENCIES, AND THEIR NUMBERS 10262 07:12:24,073 --> 07:12:26,676 WAS EVEN FURTHER REDUCED WHEN 10263 07:12:26,676 --> 07:12:28,444 THE PATIENT WAS EXPERIENCING 10264 07:12:28,444 --> 07:12:30,179 ACUTE CRISIS. 10265 07:12:30,179 --> 07:12:33,583 SO WE SHOWED THAT PATROLLING 10266 07:12:33,583 --> 07:12:35,218 MONOCYTES ARE CORRELATED 10267 07:12:35,218 --> 07:12:37,620 NEGATIVELY WITH VASO-OCCLUSIVE 10268 07:12:37,620 --> 07:12:40,623 CRISIS IN SICKLE CELL, AND KIND 10269 07:12:40,623 --> 07:12:42,125 OF INDICATING MAYBE THEY ARE 10270 07:12:42,125 --> 07:12:44,193 REALLY INVOLVED IN PROTECTING 10271 07:12:44,193 --> 07:12:46,929 THE VASCULAR END TEAL YUM BY 10272 07:12:46,929 --> 07:12:49,999 THEIR ABILITY TO REMOVE THE 10273 07:12:49,999 --> 07:12:51,868 SICKLED ATTACHED CELLS. 10274 07:12:51,868 --> 07:12:53,736 IN FACT IF WE MANIPULATED THEIR 10275 07:12:53,736 --> 07:12:55,505 NUMBERS IN MOUSE MODELS, ALL THE 10276 07:12:55,505 --> 07:12:57,240 MOUSE MODELS NOW, WHAT WE FOUND 10277 07:12:57,240 --> 07:13:00,076 WAS WE COULD POTENTIALLY 10278 07:13:00,076 --> 07:13:02,378 DECREASE THE AMOUNT OF STASIS IF 10279 07:13:02,378 --> 07:13:04,247 WE INCREASE THEIR NUMBERS IN 10280 07:13:04,247 --> 07:13:08,618 THESE SICKLE MOUSE MODELS, THE 10281 07:13:08,618 --> 07:13:10,186 TOWNES MODEL, AND IF WE REMOVE 10282 07:13:10,186 --> 07:13:15,558 THEM, YOU REALLY EXASPERATED THE 10283 07:13:15,558 --> 07:13:17,760 INFARCTS THAT WE SAW IN THE 10284 07:13:17,760 --> 07:13:20,363 PATHOLOGY, AS WELL AS THE 10285 07:13:20,363 --> 07:13:22,899 ATTACHMENT, THE STASIS TO THE 10286 07:13:22,899 --> 07:13:24,067 VASCULAR WALL. 10287 07:13:24,067 --> 07:13:27,036 SO WHAT WE ASKED WAS MORE LIKE 10288 07:13:27,036 --> 07:13:29,772 WHY IS IT THAT THESE PATROLLING 10289 07:13:29,772 --> 07:13:31,507 MONOCYTE NUMBERS ARE LOW? 10290 07:13:31,507 --> 07:13:34,177 JUST THAT STEADY STATE, NOT 10291 07:13:34,177 --> 07:13:37,580 DURING VASO-OCCLUSIVE CRISIS, 10292 07:13:37,580 --> 07:13:38,314 JUST STEADY STATE. 10293 07:13:38,314 --> 07:13:41,851 AS I SAID, THERE'S INCREASING 10294 07:13:41,851 --> 07:13:43,386 EVIDENCE THAT PATROLLING 10295 07:13:43,386 --> 07:13:47,523 MONOCYTE ARE DERIVED FROM 10296 07:13:47,523 --> 07:13:50,693 CIRCULATING MONOCYTES SO OUR 10297 07:13:50,693 --> 07:13:53,329 FOCUS TURNED TO THESE CLASSIC 10298 07:13:53,329 --> 07:13:55,798 MON TYPES, AGAIN BASED ON 10299 07:13:55,798 --> 07:13:58,501 SURFACE MARKERS, THAT'S HOW WE 10300 07:13:58,501 --> 07:13:59,902 DISTINGUISH THEM. 10301 07:13:59,902 --> 07:14:02,738 BY SELF-SORTING THESE FROM 10302 07:14:02,738 --> 07:14:03,973 PATIENTS AND COMPARING THEM TO 10303 07:14:03,973 --> 07:14:08,678 CONTROLS, WE FOUND SICKLE 10304 07:14:08,678 --> 07:14:13,649 PATIENTS -- THE LEVELS OF GENES 10305 07:14:13,649 --> 07:14:16,085 THAT DEPICT THE INTERFERON ONE, 10306 07:14:16,085 --> 07:14:17,487 INTERFERON SIX SIGNATURE 10307 07:14:17,487 --> 07:14:19,122 RESPONSE GENE WAS ELEVATED. 10308 07:14:19,122 --> 07:14:21,124 AND WE ALSO WENT INTO THE 10309 07:14:21,124 --> 07:14:22,291 PLASMA, AND THIS WAS ACTUALLY 10310 07:14:22,291 --> 07:14:25,094 ALSO SHOWN FOR NEW TRIP FILLS AT 10311 07:14:25,094 --> 07:14:27,096 THE SAME TIME AND ALSO TOTAL MOM 10312 07:14:27,096 --> 07:14:33,069 KNOW SITE BYMONOCYTE BY LOOKINGR 10313 07:14:33,069 --> 07:14:36,105 GROUPS. 10314 07:14:36,105 --> 07:14:39,375 IN SICKLE MICE WE SAW THIS 10315 07:14:39,375 --> 07:14:40,143 INTERFERON CYTOKINE. 10316 07:14:40,143 --> 07:14:42,044 WE STARTED LOOKING AT A LOT OF 10317 07:14:42,044 --> 07:14:47,049 ASSOCIATION WITH VARIOUS 10318 07:14:47,049 --> 07:14:47,917 CHARACTERISTICS OF THESE 10319 07:14:47,917 --> 07:14:50,453 PATIENTS, AND WHAT WE FOUND WAS 10320 07:14:50,453 --> 07:14:53,389 A NICE CORRELATION BETWEEN TOTAL 10321 07:14:53,389 --> 07:14:56,359 HEME IN THE PLASMA OF PATIENTS 10322 07:14:56,359 --> 07:14:59,395 AND THEN THESE INTERFERON, TYPE 10323 07:14:59,395 --> 07:15:01,097 I INTERFERON ALPHA LEVELS. 10324 07:15:01,097 --> 07:15:03,699 SO THIS SUGGESTED THAT TO US 10325 07:15:03,699 --> 07:15:07,537 THAT MAYBE IT'S HEMOLYSIS, THE 10326 07:15:07,537 --> 07:15:13,109 HEME THAT IS INDUCING THE 10327 07:15:13,109 --> 07:15:17,613 INCREASE INTERFERON -- TYPE 10328 07:15:17,613 --> 07:15:18,080 1 INTERFERON. 10329 07:15:18,080 --> 07:15:19,949 SO WE WENT BACK TO OUR MODEL, 10330 07:15:19,949 --> 07:15:24,754 WILD TYPE MICE, AND WE INDUCED I 10331 07:15:24,754 --> 07:15:29,125 A CUTE HEMOLYSIS. 10332 07:15:29,125 --> 07:15:31,627 AND THEN LOOKED FOR THIS 10333 07:15:31,627 --> 07:15:33,930 INTERFERON IN THE BLOOD THE NEXT 10334 07:15:33,930 --> 07:15:38,401 DAY, AND WHAT WE FOUND THAT IN 10335 07:15:38,401 --> 07:15:40,636 FACT INTERFERON ALPHA LEVELS 10336 07:15:40,636 --> 07:15:41,304 INCREASED WITH ALL THESE 10337 07:15:41,304 --> 07:15:42,371 TREATMENTS. 10338 07:15:42,371 --> 07:15:43,806 I DON'T HAVE TIME TO GO INTO IT 10339 07:15:43,806 --> 07:15:45,775 BUT THIS IS ALL PUBLISHED. 10340 07:15:45,775 --> 07:15:51,981 WHAT WE FOUND WAS IT WAS THE -- 10341 07:15:51,981 --> 07:15:53,416 THEY WERE RELEASING THIS 10342 07:15:53,416 --> 07:15:57,386 INTERFERON INTO THE CIRCULATION, 10343 07:15:57,386 --> 07:15:58,854 AND WE LOOKED AT THE PATHWAY, 10344 07:15:58,854 --> 07:16:00,890 THE SIGNALING PATHWAY THAT WAS 10345 07:16:00,890 --> 07:16:05,161 IMPORTANT, IT WAS 10346 07:16:05,161 --> 07:16:05,795 TLR4 INDEPENDENT, BUT IT WAS 10347 07:16:05,795 --> 07:16:11,167 THROUGH THE SIGNALING PATHWAY, 10348 07:16:11,167 --> 07:16:13,803 TBK1, AND THEN THE I CAP PA B 10349 07:16:13,803 --> 07:16:15,037 KINASE EPSILON. 10350 07:16:15,037 --> 07:16:17,807 AND THIS WAS KIND OF INDUCING 10351 07:16:17,807 --> 07:16:19,475 THE INTERFERON TO BE PRODUCED 10352 07:16:19,475 --> 07:16:23,212 AND THEN THIS TYPE 1 INTERFERON 10353 07:16:23,212 --> 07:16:29,018 GOES AND INDUCES A DOWNSTREAM 10354 07:16:29,018 --> 07:16:30,486 SIGNAL, MULTIPLE GENES ARE 10355 07:16:30,486 --> 07:16:31,387 ACTIVATED AND THE ONE THAT 10356 07:16:31,387 --> 07:16:35,057 CAUGHT OUR ATTENTION WAS THIS 10357 07:16:35,057 --> 07:16:37,460 CHEMOKINE LIGAND 2CCL2. 10358 07:16:37,460 --> 07:16:42,832 WHAT THIS CHEMOKINE DOES IS IT 10359 07:16:42,832 --> 07:16:44,567 RECRUITS MONOCYTES TO INJURED 10360 07:16:44,567 --> 07:16:44,800 TISSUE. 10361 07:16:44,800 --> 07:16:46,702 WHAT WE FOUND WAS JUST LIKE IT 10362 07:16:46,702 --> 07:16:49,639 HAD ALREADY BEEN DESCRIBED IN 10363 07:16:49,639 --> 07:16:51,607 HUMANS THAT THEIR LEVELS WERE 10364 07:16:51,607 --> 07:16:52,375 INCREASED IN SICKLE PATIENTS AND 10365 07:16:52,375 --> 07:16:54,277 WHAT WE FOUND IN SICKLE MICE WAS 10366 07:16:54,277 --> 07:16:55,611 INCREASED AND THEN JUST TO 10367 07:16:55,611 --> 07:16:58,347 CONFIRM THAT THIS WAS THE CC 10368 07:16:58,347 --> 07:16:59,915 WILL 2 WAS DOWNSTREAM OF THIS 10369 07:16:59,915 --> 07:17:02,251 HEME INDUCED INTERFERON, WE USED 10370 07:17:02,251 --> 07:17:05,087 THIS INTERFERON RECEPTOR 10371 07:17:05,087 --> 07:17:06,989 KNOCKOUT MICE, INJECTED THEM 10372 07:17:06,989 --> 07:17:07,523 WITH HEME. 10373 07:17:07,523 --> 07:17:09,025 AS YOU SEE, THIS IS THE CONTROL, 10374 07:17:09,025 --> 07:17:11,627 YOU SEE UPREGULATION OF CCL2 BUT 10375 07:17:11,627 --> 07:17:13,763 IN THIS INTERFERON RECEPTOR 10376 07:17:13,763 --> 07:17:15,264 KNOCKOUT MICE NOW THE EFFECT OF 10377 07:17:15,264 --> 07:17:17,066 HEME YOU DON'T SEE THE CCL2 AS 10378 07:17:17,066 --> 07:17:20,269 MUCH BEING PRODUCED INDICATING 10379 07:17:20,269 --> 07:17:22,638 THAT IS DEFINITELY CCL2 IS 10380 07:17:22,638 --> 07:17:24,874 DOWNSTREAM OF THIS HEME INDUCED 10381 07:17:24,874 --> 07:17:29,045 INTERFERON RESPONSE. 10382 07:17:29,045 --> 07:17:31,414 SO THIS IS WHAT IT'S DOING, THE 10383 07:17:31,414 --> 07:17:32,748 CHEMOKINE, IT TELLS THE 10384 07:17:32,748 --> 07:17:34,183 CLASSICAL MONOCYTE COME INTO THE 10385 07:17:34,183 --> 07:17:35,484 TISSUE, INJURED TISSUE, AND 10386 07:17:35,484 --> 07:17:38,421 THERE IT JUST DIFFERENTIATES 10387 07:17:38,421 --> 07:17:41,390 DOWN THIS PATHWAY, AND WE CAN 10388 07:17:41,390 --> 07:17:44,160 DISTINGUISH THESE DIFFERENT CELL 10389 07:17:44,160 --> 07:17:46,595 TYPES, DIFFERENTIATION STEPS BY 10390 07:17:46,595 --> 07:17:50,499 USING VARIOUS MARKERS DEPICTED 10391 07:17:50,499 --> 07:17:52,335 HERE AND BASICALLY WHAT WE FOUND 10392 07:17:52,335 --> 07:17:54,103 IN THESE SICKLE MICE, WE SEE 10393 07:17:54,103 --> 07:17:55,971 MICE INCREASE IN CLASSICAL 10394 07:17:55,971 --> 07:17:57,173 MONOCYTES IN THE LIVER, MORE SO 10395 07:17:57,173 --> 07:18:02,978 THAN IN THE SPLEEN, AND 10396 07:18:02,978 --> 07:18:04,513 IMPORTANTLY THE NEXT STEP OF 10397 07:18:04,513 --> 07:18:05,214 DIFFERENTIATION, IN THE LIVER 10398 07:18:05,214 --> 07:18:07,483 YOU SEE A LOT OF THESE TRANSIENT 10399 07:18:07,483 --> 07:18:08,818 MONOCYTES WHICH ARE GOING DOWN 10400 07:18:08,818 --> 07:18:12,621 THAT PATHWAY, SIX FOLD INCREASE. 10401 07:18:12,621 --> 07:18:14,724 AND THE BEST ONE WAS THIS 10402 07:18:14,724 --> 07:18:17,059 MONOCYTE DERIVED MACROPHAGES 10403 07:18:17,059 --> 07:18:18,294 FURTHER DOWN AND WAS, AGAIN, IN 10404 07:18:18,294 --> 07:18:20,262 THE LIVER. 10405 07:18:20,262 --> 07:18:22,531 REALLY, THIS WAS 13 FOLD 10406 07:18:22,531 --> 07:18:24,934 EXPANSION OF THESE MONOCYTE 10407 07:18:24,934 --> 07:18:26,569 DERIVED MACROPHAGES. 10408 07:18:26,569 --> 07:18:27,903 AND THIS IS JUST SHOWING THAT IF 10409 07:18:27,903 --> 07:18:32,308 YOU INJECTED THE MICE WITH HEME, 10410 07:18:32,308 --> 07:18:34,944 YOU ALSO SAW EXPANSION OF THESE 10411 07:18:34,944 --> 07:18:36,445 MONOCYTE DERIVED MACROPHAGES AND 10412 07:18:36,445 --> 07:18:39,648 SIX FOLD HERE, AND THIS THIS WAS 10413 07:18:39,648 --> 07:18:41,650 CURTAILED IF YOU USED THE 10414 07:18:41,650 --> 07:18:42,718 INTERFERON RECEPTOR KNOCKOUT 10415 07:18:42,718 --> 07:18:44,120 MICE AGAIN FOLLOWING INJECTION 10416 07:18:44,120 --> 07:18:47,022 OF HEME, OR YOU USE THE RECEPTOR 10417 07:18:47,022 --> 07:18:50,793 THAT BINDS TO CCL2, THE KNOCKOUT 10418 07:18:50,793 --> 07:18:53,929 OF THAT, AND ALSO THAT ALSO DID 10419 07:18:53,929 --> 07:18:55,164 NOT RESPOND TO THE EFFECTS OF 10420 07:18:55,164 --> 07:18:57,633 HEME. 10421 07:18:57,633 --> 07:18:59,935 SO WHAT WE HAVE IS THAT -- SO 10422 07:18:59,935 --> 07:19:01,404 YOU HAVE YOUR RESIDENT 10423 07:19:01,404 --> 07:19:04,039 MACROPHAGE PRODUCING THE 10424 07:19:04,039 --> 07:19:06,342 INTERFERON, THAT INDUCES CCL2, 10425 07:19:06,342 --> 07:19:07,543 THIS CHEMOKINE THAT TELLS THE 10426 07:19:07,543 --> 07:19:10,279 BLOOD CLASSICAL MONOCYTE, COME 10427 07:19:10,279 --> 07:19:12,148 IN TO THE LIVER WHERE IT JUST 10428 07:19:12,148 --> 07:19:13,582 NOW DIFFERENTIATES AND 10429 07:19:13,582 --> 07:19:14,550 EVENTUALLY IS GOING TO GO INTO 10430 07:19:14,550 --> 07:19:19,288 THE MACROPHAGE POOL. 10431 07:19:19,288 --> 07:19:21,157 SO AS I SAID, THE CLASSICAL 10432 07:19:21,157 --> 07:19:22,391 MONOCYTE IS SUPPOSED TO GIVE 10433 07:19:22,391 --> 07:19:24,293 RISE TO THIS PATROLLING MONOCYTE 10434 07:19:24,293 --> 07:19:25,561 IN THE BLOOD, BUT IF IT'S GOING 10435 07:19:25,561 --> 07:19:26,929 ALL THE TIME INTO THE LIVER, 10436 07:19:26,929 --> 07:19:29,732 COULD IT BE THAT WE JUST ARE 10437 07:19:29,732 --> 07:19:33,569 KIND OF THE BALANCE IS NOW 10438 07:19:33,569 --> 07:19:34,170 PERTURBED IN SICKLE CELL AND 10439 07:19:34,170 --> 07:19:37,206 THAT IS WHY YOU HAVE THIS 10440 07:19:37,206 --> 07:19:39,742 DIFFERENTIATION NOT HAPPENING AS 10441 07:19:39,742 --> 07:19:43,879 EFFECTIVELY UNDER TH THESE 10442 07:19:43,879 --> 07:19:45,347 HEMOLYTIC CONDITIONS THAT I 10443 07:19:45,347 --> 07:19:45,714 DESCRIBED. 10444 07:19:45,714 --> 07:19:48,951 SO TO UNDERSTAND, TO KIND OF 10445 07:19:48,951 --> 07:19:52,521 EXPLORE THIS IDEA FURTHER, WE 10446 07:19:52,521 --> 07:19:54,457 LOOKED AT ADDITIONAL MONOCYTE 10447 07:19:54,457 --> 07:19:56,492 FACTORS, SO WE KNOW WITH HAVE 10448 07:19:56,492 --> 07:20:02,031 MONO CYTOSIS IN SICKLE CELL, AN, 10449 07:20:02,031 --> 07:20:03,833 BEING PRODUCED FROM THE BONE 10450 07:20:03,833 --> 07:20:08,904 PLAYER OWFROM THE BONEMARROW IN. 10451 07:20:08,904 --> 07:20:11,140 WE LOOKED AT ONE KEY FACTOR FOR 10452 07:20:11,140 --> 07:20:13,008 MONOCYTES WHICH IS CSF-1. 10453 07:20:13,008 --> 07:20:15,110 AND WE SAW THOSE LEVELS WERE 10454 07:20:15,110 --> 07:20:21,050 INRECREASINCREASED IN OUR SICKLS 10455 07:20:21,050 --> 07:20:22,718 AS WELL AS OUR MICE SO AGAIN WE 10456 07:20:22,718 --> 07:20:23,819 INJECTED HEME TO SEE IF THAT 10457 07:20:23,819 --> 07:20:25,087 LEVEL GOES UP AND OF COURSE, 10458 07:20:25,087 --> 07:20:27,623 AGAIN, WE SAW -- NOT OF COURSE. 10459 07:20:27,623 --> 07:20:31,160 WE SAW INDUCTION OF 10460 07:20:31,160 --> 07:20:32,027 CSF-1 DOSE-RESPONSE HERE JUST 10461 07:20:32,027 --> 07:20:36,832 SHOWING THE DOSE-RESPONSE TO THE 10462 07:20:36,832 --> 07:20:40,769 EFFECTS OF HEME AND THEN IF WE 10463 07:20:40,769 --> 07:20:43,739 PRE-TREATED MICE WITH HEMOPEXIN 10464 07:20:43,739 --> 07:20:46,075 YOU DIDN'T SEE THE UPREGULATION 10465 07:20:46,075 --> 07:20:48,010 OF CSF-1, REALLY INDICATING THAT 10466 07:20:48,010 --> 07:20:50,346 HEME IS THE ONE THAT IS INDUCING 10467 07:20:50,346 --> 07:20:53,115 THE CSF-1 IN OUR WILD TYPE MICE 10468 07:20:53,115 --> 07:20:56,151 HERE. 10469 07:20:56,151 --> 07:20:59,989 SO WHAT ABOUT NOW STARTING TO 10470 07:20:59,989 --> 07:21:03,826 MANIPULATE THE CSF-1 LEVELS TO 10471 07:21:03,826 --> 07:21:07,029 SEE IF WE'RE AFFECTING MONOCYTE 10472 07:21:07,029 --> 07:21:07,763 PATROLLING NUMBERS. 10473 07:21:07,763 --> 07:21:10,499 SO THAT'S WHAT WE DID, WE 10474 07:21:10,499 --> 07:21:16,639 INJECTED CSF-1 AND BOTH NUMBERS 10475 07:21:16,639 --> 07:21:17,673 INCREASED IN THE CIRCULATION, 10476 07:21:17,673 --> 07:21:22,778 BUT ACTUALLY IT WAS THE 10477 07:21:22,778 --> 07:21:25,214 PATROLLING MONOCYTE ONE IN RED 10478 07:21:25,214 --> 07:21:27,583 THAT JUST KEPT GOING ON. 10479 07:21:27,583 --> 07:21:28,584 REALLY SPECIFICALLY EXPANDING 10480 07:21:28,584 --> 07:21:30,052 THE PATROLLING MONOCYTE AS 10481 07:21:30,052 --> 07:21:33,222 OPPOSED TO THE CLASSICAL ONES, 10482 07:21:33,222 --> 07:21:33,956 AND AT THE SAME TIME THAT WE 10483 07:21:33,956 --> 07:21:36,425 WERE DOING THIS, PAPER CAME OUT 10484 07:21:36,425 --> 07:21:38,827 IN IMMUNITY SHOWING THAT 10485 07:21:38,827 --> 07:21:39,929 CSF-1 ACTUALLY DOES INDUCE 10486 07:21:39,929 --> 07:21:41,897 PATROLLING MONOCYTE NUMBERS TOO. 10487 07:21:41,897 --> 07:21:47,403 SO WHAT ABOUT IF WE PREVENTED -- 10488 07:21:47,403 --> 07:21:51,040 BLOCKED CSF-1 LEVELS WITH 10489 07:21:51,040 --> 07:21:51,807 ANTIBODIES, AND THAT'S WHAT WE 10490 07:21:51,807 --> 07:21:53,542 FOUND, IT REALLY EFFECTIVELY 10491 07:21:53,542 --> 07:21:55,177 TARGETED PATROLLING MONOCYTE 10492 07:21:55,177 --> 07:21:57,079 NUMBERS HERE, BUT NOT THE 10493 07:21:57,079 --> 07:21:59,248 CLASSICAL MONOCYTE. 10494 07:21:59,248 --> 07:22:02,151 SO HAVING ESTABLISHED CSF-1 IS 10495 07:22:02,151 --> 07:22:05,354 PLAYING A ROLE IN CONTROLLING 10496 07:22:05,354 --> 07:22:06,622 PATROLLING NUMBERS, NOW THE NEXT 10497 07:22:06,622 --> 07:22:08,490 QUESTION WAS, WE WERE JUST KIND 10498 07:22:08,490 --> 07:22:10,459 OF CURIOUS WHAT IS GOING ON. 10499 07:22:10,459 --> 07:22:16,398 SO HEMOLYSIS ON ONE HAND, RIGHT, 10500 07:22:16,398 --> 07:22:17,566 IS -- SO AGAIN, I DON'T HAVE 10501 07:22:17,566 --> 07:22:19,702 TIME TO SHOW THAT -- WE SHOWED 10502 07:22:19,702 --> 07:22:22,304 THAT HEMOLYSIS THROUGH 10503 07:22:22,304 --> 07:22:26,809 ENDOTHELIAL AND RF2 IS 10504 07:22:26,809 --> 07:22:28,844 RESPONSIBLE FOR INDUCTION OF CSF 10505 07:22:28,844 --> 07:22:30,813 ONE AND THIS IS IMPORTANT FOR 10506 07:22:30,813 --> 07:22:32,448 PATROLLING MONOCYTE 10507 07:22:32,448 --> 07:22:33,082 DIFFERENTIATION FROM THE 10508 07:22:33,082 --> 07:22:34,450 CLASSICAL MONOCYTE, BUT AT THE 10509 07:22:34,450 --> 07:22:38,253 SAME TIME, HEMOLYSIS AS I SAID 10510 07:22:38,253 --> 07:22:40,889 FROM TYPE I INTERFERON INDUCES 10511 07:22:40,889 --> 07:22:42,458 CCL2 TO BECOME MACROPHAGES. 10512 07:22:42,458 --> 07:22:44,860 SO BASICALLY IT'S REALLY -- IT'S 10513 07:22:44,860 --> 07:22:47,930 GOING TO BE A BATTLE BETWEEN CSF 10514 07:22:47,930 --> 07:22:49,498 1 AND CCL2 THAT'S GOING TO 10515 07:22:49,498 --> 07:22:50,799 CONTROL THESE PATROLLING 10516 07:22:50,799 --> 07:22:52,334 MONOCYTE NUMBERS, AT LEAST 10517 07:22:52,334 --> 07:22:56,105 THAT'S WHAT WE HYPOTHESIZED. 10518 07:22:56,105 --> 07:22:58,173 AND THAT'S ACTUALLY WHAT WE 10519 07:22:58,173 --> 07:23:02,911 FOUND, IF YOU JUST LOOK AT CSF-N 10520 07:23:02,911 --> 07:23:03,979 OF THE PATIENTS AND PATROLLING 10521 07:23:03,979 --> 07:23:07,249 MONOCYTE NUMBERS, THERE WAS 10522 07:23:07,249 --> 07:23:10,786 HARDLY NR CORRELATION. 10523 07:23:10,786 --> 07:23:11,887 CCL2, WE SAW IT WAS LIKE A TREND 10524 07:23:11,887 --> 07:23:13,956 TOWARDS THE LEVELS CORRELATED 10525 07:23:13,956 --> 07:23:15,391 WITH PATROLLING MONOCYTE 10526 07:23:15,391 --> 07:23:17,259 NUMBERS, BUT IT WAS REALLY THE 10527 07:23:17,259 --> 07:23:21,864 RATIO BETWEEN THE CSF-1 TO 10528 07:23:21,864 --> 07:23:22,831 CCL2 THAT WAS DETERMINING 10529 07:23:22,831 --> 07:23:24,633 PATROLLING MONOCYTE NUMBERS. 10530 07:23:24,633 --> 07:23:29,605 SO WHAT IS HAPPENING THE WAY 10531 07:23:29,605 --> 07:23:31,940 WE'RE THINKING ABOUT THIS, IN 10532 07:23:31,940 --> 07:23:33,409 THE VASCULATURE, YOU HAVE THE 10533 07:23:33,409 --> 07:23:34,777 CLASSICAL MONOCYTES, YOU HAVE 10534 07:23:34,777 --> 07:23:37,680 THE CSF-1 INDUCING PATROLLING 10535 07:23:37,680 --> 07:23:38,881 MONOCYTES TO BE PRODUCED, BUT AT 10536 07:23:38,881 --> 07:23:44,720 THE SAME TIME, CCL-2 IS TELLING 10537 07:23:44,720 --> 07:23:46,555 THE CLASSICAL MONOCYTE TO GO 10538 07:23:46,555 --> 07:23:49,458 INTO THE TISSUE. 10539 07:23:49,458 --> 07:23:50,159 AND DIFFERENTIATE THERE. 10540 07:23:50,159 --> 07:23:54,863 SO WE ASK, WHAT IF WE BLOCKED 10541 07:23:54,863 --> 07:23:56,732 THIS TRANS MIGRATION OF THIS 10542 07:23:56,732 --> 07:23:57,866 CLASSICAL MONOCYTES GOING INTO 10543 07:23:57,866 --> 07:23:59,001 THE TISSUE? 10544 07:23:59,001 --> 07:24:01,170 WOULD WE GET AN INCREASE IN 10545 07:24:01,170 --> 07:24:05,874 PATROLLING MONOCYTE NUMBERS? 10546 07:24:05,874 --> 07:24:08,077 AND WE SHOWED IN VITRO, AT 10547 07:24:08,077 --> 07:24:10,579 LEAST, AGAIN I DON'T HAVE TIME 10548 07:24:10,579 --> 07:24:14,349 BUT IT'S IN THE PAPER, THAT IT 10549 07:24:14,349 --> 07:24:15,350 PREVENTS THIS TRANS MIGRATION 10550 07:24:15,350 --> 07:24:18,253 AND IT'S KNOWN TO DO THAT. 10551 07:24:18,253 --> 07:24:23,425 SORE WHAT WE DID -- SO THIS IS 10552 07:24:23,425 --> 07:24:24,293 WHAT WE DID. 10553 07:24:24,293 --> 07:24:25,728 WE USE OUR SICKLE MICE, THIS IS 10554 07:24:25,728 --> 07:24:29,665 MY LAST DATA SLIDE, WE 10555 07:24:29,665 --> 07:24:33,602 PRE-TREATED MICE WITH EITHER 10556 07:24:33,602 --> 07:24:35,370 ANTIP SELECTIN OR ISOTYPE 10557 07:24:35,370 --> 07:24:39,541 CONTROL AND/OR PLUS CSF-1. 10558 07:24:39,541 --> 07:24:44,346 SO THE IDEA BEING THAT ANTIP 10559 07:24:44,346 --> 07:24:46,048 SELECTIN WILL PREVENT THE TRANS 10560 07:24:46,048 --> 07:24:47,683 MIGRATION, WE SHOULD GET MORE 10561 07:24:47,683 --> 07:24:50,085 PATROLLING MONOCYTES, 10562 07:24:50,085 --> 07:24:51,520 CSF-1 HELPING THE 10563 07:24:51,520 --> 07:24:53,021 DIFFERENTIATION OF PATROLLING 10564 07:24:53,021 --> 07:24:54,123 MONOCYTES, LET'S SEE. 10565 07:24:54,123 --> 07:24:56,458 SO CLASSICAL MONOCYTE IN THE 10566 07:24:56,458 --> 07:24:57,693 BLOOD, NOTHING HAPPENED, THERE 10567 07:24:57,693 --> 07:24:59,495 WAS NO DIFFERENCE. 10568 07:24:59,495 --> 07:25:03,332 HOWEVER, ONCE WE GAVE THE MICE 10569 07:25:03,332 --> 07:25:05,834 ANTIP SELECTIN, WE SAW INCREASE 10570 07:25:05,834 --> 07:25:08,637 IN PATROLLING MONOCYTE NUMBERS. 10571 07:25:08,637 --> 07:25:15,711 IF WE GAVE THEM ANTIP SELE 10572 07:25:15,711 --> 07:25:16,879 SELECTINCO -- CSF-1, THE NUMBERS 10573 07:25:16,879 --> 07:25:17,513 WENT UP MORE. 10574 07:25:17,513 --> 07:25:20,716 WHAT WAS MORE IMPORTANT, AGAIN, 10575 07:25:20,716 --> 07:25:22,818 WITH ANTIP SELECTIN ALONE, 10576 07:25:22,818 --> 07:25:25,788 STASIS WENT DOWN. 10577 07:25:25,788 --> 07:25:29,558 BUT COAB ADMINISTRATION -- WAS 10578 07:25:29,558 --> 07:25:31,894 MORE EFFECTIVE IN PREVENTING 10579 07:25:31,894 --> 07:25:33,462 STASIS. 10580 07:25:33,462 --> 07:25:35,964 CSF-1 WAS BETTER AT CONTROLLING 10581 07:25:35,964 --> 07:25:39,034 CELL DEATH WHEN GIVEN ACTUALLY 10582 07:25:39,034 --> 07:25:41,537 BY ITS OWN. 10583 07:25:41,537 --> 07:25:48,677 AGAIN, AS EXPECTED, ANTIP 10584 07:25:48,677 --> 07:25:51,146 SELECTINPREVENTED THIS CLASSICAL 10585 07:25:51,146 --> 07:25:53,582 MONOCYTES GOING INTO THE LIVER. 10586 07:25:53,582 --> 07:25:55,117 CSF-1 HAS NO EFFECT IN THIS 10587 07:25:55,117 --> 07:25:56,451 ASPECT. 10588 07:25:56,451 --> 07:25:58,821 IT JUST AFFECTS PATROLLING 10589 07:25:58,821 --> 07:26:02,558 MONOCYTE IN THE -- IN BLOOD. 10590 07:26:02,558 --> 07:26:04,560 ALSO WITH LIVER FURTHER DOWN 10591 07:26:04,560 --> 07:26:05,561 DIFFERENTIATION, WE DIDN'T SEE 10592 07:26:05,561 --> 07:26:11,133 AN EFFECT BUT HOWEVER CSF 10593 07:26:11,133 --> 07:26:13,035 CSF-1 AGAIN ANTIP 10594 07:26:13,035 --> 07:26:14,870 SELECTININHIBITED THE NUMBERS OF 10595 07:26:14,870 --> 07:26:17,139 THESE TRANSIENT MONOCYTES IN THE 10596 07:26:17,139 --> 07:26:17,739 LIVER. 10597 07:26:17,739 --> 07:26:21,810 SO IT'S PREVENTING THE CLASSICAL 10598 07:26:21,810 --> 07:26:24,079 MONOCYTES GOING INTO THE LIVER. 10599 07:26:24,079 --> 07:26:25,614 SO THIS IS OUR WORKING MODEL. 10600 07:26:25,614 --> 07:26:27,349 WE'RE SAYING THE CLASSICAL 10601 07:26:27,349 --> 07:26:29,852 MONOCYTES ON ONE SIDE CAN BECOME 10602 07:26:29,852 --> 07:26:33,322 MACROPHAGES ON THE OTHER, BECOME 10603 07:26:33,322 --> 07:26:34,656 PATROLLING MONOCYTES, 10604 07:26:34,656 --> 07:26:35,424 DIFFERENTIATE IN THE BLOOD OR GO 10605 07:26:35,424 --> 07:26:38,527 TO THE TISSUE. 10606 07:26:38,527 --> 07:26:41,363 WE'RE SAYING THAT TYPE I 10607 07:26:41,363 --> 07:26:44,566 INTERFERON THROUGH CCL2 UNDER 10608 07:26:44,566 --> 07:26:47,169 HEMOLYTIC CONDITIONS DRIVES THE 10609 07:26:47,169 --> 07:26:49,271 MACROPHAGE DIFFERENTIATION IN 10610 07:26:49,271 --> 07:26:50,772 HOWEVER IN THE CIRCULATION IS 10611 07:26:50,772 --> 07:26:57,646 THE RF2CS -- SO IT'S REALLY THE 10612 07:26:57,646 --> 07:26:59,381 RATIO OF THESE TWO THAT IS GOING 10613 07:26:59,381 --> 07:27:01,083 TO DECIDE HOW MUCH PATROLLING 10614 07:27:01,083 --> 07:27:02,384 MONOCYTE ARE GOING TO STAY IN 10615 07:27:02,384 --> 07:27:03,151 THE VASCULATURE. 10616 07:27:03,151 --> 07:27:05,821 IF THIS LEVEL IS HIGH RELATIVE 10617 07:27:05,821 --> 07:27:09,358 TO THIS LEVEL, TO CCL2, YOU SEE 10618 07:27:09,358 --> 07:27:11,526 AN EXPANSION OF THESE PATROLLING 10619 07:27:11,526 --> 07:27:12,227 MONOCYTES. 10620 07:27:12,227 --> 07:27:14,730 AND MAYBE THIS COULD BE A WAY TO 10621 07:27:14,730 --> 07:27:16,899 INCREASE THEIR NUMBERS AND AS A 10622 07:27:16,899 --> 07:27:18,567 RESULT, IF YOU HAVE HIGHER 10623 07:27:18,567 --> 07:27:20,269 PATROLLING NUMBERS, YOU'RE GOING 10624 07:27:20,269 --> 07:27:24,606 TO PREVENT VASO-OCCLUSIVE CRISIS 10625 07:27:24,606 --> 07:27:25,574 EVENT. 10626 07:27:25,574 --> 07:27:28,810 ANTIP SELECTINHIGH PRESSURE 10627 07:27:28,810 --> 07:27:34,883 ININ DIFFERENTIATESTHIS POSITIOT 10628 07:27:34,883 --> 07:27:36,285 BLOOD PATROLLING MONOCYTES 10629 07:27:36,285 --> 07:27:39,655 SHOULD GO UP WITH ANTIP SELECTIN 10630 07:27:39,655 --> 07:27:41,290 BUT THIS IS ONLY GOING TO HAVE 10631 07:27:41,290 --> 07:27:43,158 IF YOU HAVE THESE TWO RATIOS 10632 07:27:43,158 --> 07:27:43,425 THERE. 10633 07:27:43,425 --> 07:27:46,128 SO IT'S POSSIBLE THAT THE 10634 07:27:46,128 --> 07:27:50,365 STUDIES WITH CRIZ THAT HAVE NOT 10635 07:27:50,365 --> 07:27:52,100 WORK, IT COULD BE, WE'RE 10636 07:27:52,100 --> 07:27:53,335 POSTULATING, THAT REALLY WE HAVE 10637 07:27:53,335 --> 07:27:55,771 TO BE LOOKING AT THE RELATIVE 10638 07:27:55,771 --> 07:28:00,609 RATIOS OF THESE CCL-2 TO 10639 07:28:00,609 --> 07:28:01,777 CSF-1 AS WELL AS PATROLLING 10640 07:28:01,777 --> 07:28:03,345 MONOCYTE NUMBERS IN THOSE 10641 07:28:03,345 --> 07:28:03,679 PATIENTS. 10642 07:28:03,679 --> 07:28:06,114 HOWEVER, WE THINK IT IS THE 10643 07:28:06,114 --> 07:28:10,585 COMBO, THE ANTI-P SELECTIN PLUS 10644 07:28:10,585 --> 07:28:12,087 CSF-1 THAT REALLY IS GOING TO 10645 07:28:12,087 --> 07:28:13,388 IMPROVE BLOOD PATROLLING 10646 07:28:13,388 --> 07:28:14,389 MONOCYTE NUMBERS, AND THAT'S 10647 07:28:14,389 --> 07:28:17,793 GOING TO BE REALLY EFFECTIVE IN 10648 07:28:17,793 --> 07:28:21,964 PREVENTING -- WITH THAT I'D LIKE 10649 07:28:21,964 --> 07:28:25,434 TO THANK THE PEOPLE, JUST 10650 07:28:25,434 --> 07:28:26,802 BRILLIANT, WE'VE BEEN WORKING 10651 07:28:26,802 --> 07:28:28,036 TOGETHER FOR A WHILE, THIS IS MY 10652 07:28:28,036 --> 07:28:31,373 LAB, GRATEFUL TO THE NYBC SICKLE 10653 07:28:31,373 --> 07:28:34,743 CELL TRANSFUSION RESEARCH GROUP. 10654 07:28:34,743 --> 07:28:38,013 WE HAVE, OF COURSE, OUR CLINICAL 10655 07:28:38,013 --> 07:28:40,983 COLLABORATORS, AND OF COURSE 10656 07:28:40,983 --> 07:28:44,519 NONE OF THIS WORK WOULD HAPPEN 10657 07:28:44,519 --> 07:28:46,688 WITHOUT FUNDING SUPPORT FROM 10658 07:28:46,688 --> 07:28:47,055 NHLBI. 10659 07:28:47,055 --> 07:28:48,056 THANK YOU. 10660 07:28:48,056 --> 07:28:55,731 [APPLAUSE] 10661 07:28:55,731 --> 07:28:57,532 >> THANK YOU, KARINA. 10662 07:28:57,532 --> 07:28:59,968 THERE IS ONE QUESTION IN THE 10663 07:28:59,968 --> 07:29:02,371 CHAT. 10664 07:29:02,371 --> 07:29:04,339 IT'S FROM SHAINA ALLEN. 10665 07:29:04,339 --> 07:29:04,806 FANTASTIC TALK. 10666 07:29:04,806 --> 07:29:06,208 ARE YOU ABLE TO SEE A DIFFERENCE 10667 07:29:06,208 --> 07:29:07,809 IN MONOCYTE DIFFERENTIATION WITH 10668 07:29:07,809 --> 07:29:10,445 AGE AND YOU HAVE LOOKED AT THE 10669 07:29:10,445 --> 07:29:12,714 ROLE OF NOTCH SIGNALING IN THIS 10670 07:29:12,714 --> 07:29:14,349 PROCESS, GIVEN THAT IT HAS BEEN 10671 07:29:14,349 --> 07:29:17,052 SHOWN TO BE DISREGULATED IN 10672 07:29:17,052 --> 07:29:17,786 AGING? 10673 07:29:17,786 --> 07:29:18,987 CURIOUS IF PLAYING A ROLE IN 10674 07:29:18,987 --> 07:29:20,956 SICKLE CELL DISEASE AND RAPID 10675 07:29:20,956 --> 07:29:22,057 AGING PHENOTYPE. 10676 07:29:22,057 --> 07:29:22,758 >> THANKS. 10677 07:29:22,758 --> 07:29:23,892 THAT'S A GREAT QUESTION. 10678 07:29:23,892 --> 07:29:26,995 SO ALL I CAN TELL YOU, THE NOTCH 10679 07:29:26,995 --> 07:29:27,729 SIGNALING, WE'RE LOOKING AT THAT 10680 07:29:27,729 --> 07:29:29,631 FOR EXPANDING THESE PATROLLING 10681 07:29:29,631 --> 07:29:34,703 MONOCYTE IN VITRO, SO WITH 10682 07:29:34,703 --> 07:29:39,107 RESPECT TO AGING, IN PATIENTS, 10683 07:29:39,107 --> 07:29:41,843 NO WE HAVEN'T LOOKED AT IT. 10684 07:29:41,843 --> 07:29:46,948 IN MICE, WE'RE LOOKING AT IT. 10685 07:29:46,948 --> 07:29:48,884 >> THANKS, KARINA. 10686 07:29:48,884 --> 07:29:49,618 ALL RIGHT. 10687 07:29:49,618 --> 07:29:51,586 SO THAT BRINGS US TO THE END OF 10688 07:29:51,586 --> 07:29:52,054 OUR SESSION. 10689 07:29:52,054 --> 07:29:53,388 THANK YOU, EVERYBODY, FOR 10690 07:29:53,388 --> 07:29:54,656 STAYING AND THANK YOU VERY MUCH 10691 07:29:54,656 --> 07:29:56,792 TO ALL THE SPEAKERS. 10692 07:29:56,792 --> 07:29:57,259 APPRECIATE IT. 10693 07:29:57,259 --> 07:30:06,334 [APPLAUSE] 10694 07:30:06,334 --> 07:30:07,969 >> SO THANK YOU ALL FOR STAYING 10695 07:30:07,969 --> 07:30:08,904 TO THE VERY END. 10696 07:30:08,904 --> 07:30:12,808 AND WE LOOK FORWARD TO ANOTHER 10697 07:30:12,808 --> 07:30:13,642 DAY. 10698 07:30:13,642 --> 07:30:19,181 SO HOPEFULLY WE'LL BE MORE 10699 07:30:19,181 --> 07:30:20,182 KEEPING WITH THE TIME. 10700 07:30:20,182 --> 07:30:21,650 THANK YOU TO THE CHAIRS AND THE 10701 07:30:21,650 --> 07:30:22,484 SPEAKERS. 10702 07:30:22,484 --> 07:30:32,661 [APPLAUSE]