1 00:00:05,960 --> 00:00:09,760 >>WE INVITE YOU TO 2 00:00:09,760 --> 00:00:14,760 THE TACKLING BRAIN AND MUSCLE 3 00:00:14,760 --> 00:00:20,160 DISFUNCTION IN AXE RDS WORKSHOP. 4 00:00:20,160 --> 00:00:22,240 THIS SESSION IS BEING RECORDED 5 00:00:22,240 --> 00:00:24,560 AND PLEASE MAINTAIN RESEARCH 6 00:00:24,560 --> 00:00:25,800 INTEGRITY AND CONFIDENTIALITY 7 00:00:25,800 --> 00:00:27,880 AND WOULD LIKE FOR YOU TO USE 8 00:00:27,880 --> 00:00:30,080 THE CHAT FOR DISCUSSION AND 9 00:00:30,080 --> 00:00:31,920 ENCOURAGE YOU TO PUT QUESTIONS 10 00:00:31,920 --> 00:00:35,440 IN THE CHAT. MODERATORS WILL 11 00:00:35,440 --> 00:00:39,560 MODERATE THE CHAT BOX. KEEP 12 00:00:39,560 --> 00:00:41,720 YOUR CAMERAS OFF UNLESS YOU ARE 13 00:00:41,720 --> 00:00:43,480 SPEAKING. PLEASE ENJOY THE 14 00:00:43,480 --> 00:00:48,440 WORKSHOP. THANKS FOR JOINING US 15 00:00:48,440 --> 00:00:48,680 TODAY. 16 00:00:48,680 --> 00:00:52,520 >> GOOD MORNING, EVERYONE. I'M 17 00:00:52,520 --> 00:00:55,640 CHRISTIAN GOMEZ AND PROGRAM 18 00:00:55,640 --> 00:00:57,200 OFFICER IN DIVISION OF LAND 19 00:00:57,200 --> 00:00:58,800 DISEASES AND CHARGE TODAY TO 20 00:00:58,800 --> 00:01:00,800 KICK OFF ACTIVITIES FOR THE 21 00:01:00,800 --> 00:01:05,160 SECOND DAY OF EXCITING WORKSHOP 22 00:01:05,160 --> 00:01:08,760 TACKLING BRAIN AND MUSCLE 23 00:01:08,760 --> 00:01:11,560 DYSFUNCTIONS IN ARDS SURVIVORS 24 00:01:11,560 --> 00:01:15,280 AND RECAP OF YESTERDAY'S 25 00:01:15,280 --> 00:01:17,440 ACTIVITIES. SESSION 1 WE DID 26 00:01:17,440 --> 00:01:19,720 MUSCLE DYSFUNCTIONS AND CAN 27 00:01:19,720 --> 00:01:21,760 MEASURE AND HOW MANY MEASURE 28 00:01:21,760 --> 00:01:24,000 TRANSLATES TO BE VALUABLE FOR 29 00:01:24,000 --> 00:01:27,680 PATIENTS IS A CHALLENGE WE NEED 30 00:01:27,680 --> 00:01:28,480 TO MEET. 31 00:01:28,480 --> 00:01:32,160 NEXT ISSIN VIVO AT HOME AND 32 00:01:32,160 --> 00:01:34,600 SOCIAL MEDIA AND TEXT ANALYSIS 33 00:01:34,600 --> 00:01:36,800 CAN INCORPORATE REAL-WORLD TASKS 34 00:01:36,800 --> 00:01:39,320 INTO STANDARD MISSIONS AND 35 00:01:39,320 --> 00:01:40,480 [INDISCERNIBLE] WHEN CONSIDERING 36 00:01:40,480 --> 00:01:42,760 NEXT INNOVATION MEASUREMENTS 37 00:01:42,760 --> 00:01:48,160 INCLUDING INCORPORATING H AND 38 00:01:48,160 --> 00:01:50,880 [INDISCERNIBLE] ARND AND DIGITAL 39 00:01:50,880 --> 00:01:53,360 POVERTY AMONG OTHERS. WITH SUCH 40 00:01:53,360 --> 00:01:55,360 TOOLS, WE COULD BE ABLE TO 41 00:01:55,360 --> 00:01:57,640 ASSESS HOW PATIENTS ADAPT TO 42 00:01:57,640 --> 00:02:00,840 THEIR ENVIRONMENT FOLLOWING 43 00:02:00,840 --> 00:02:02,920 ACUTE DISEASES AND FOR 44 00:02:02,920 --> 00:02:04,040 IDENTIFICATION WE NEED TO 45 00:02:04,040 --> 00:02:07,080 DISCUSS IT AND WILL CONSIDER 46 00:02:07,080 --> 00:02:10,480 ADAPTATIONS AS THOSE RELATED TO 47 00:02:10,480 --> 00:02:13,800 STATUS AND ASSISTIVE DEVICES AND 48 00:02:13,800 --> 00:02:16,040 EQUITY AND EPRIORITIZATION OF 49 00:02:16,040 --> 00:02:18,360 PATIENT VALUES AND SUCH EFFORT 50 00:02:18,360 --> 00:02:21,960 MAY HELP TO OVERCOME BARRIERS 51 00:02:21,960 --> 00:02:29,840 FOR PATIENTS AND INFORM POLICY 52 00:02:29,840 --> 00:02:33,280 DEVELOPMENTS AND MEDICINE DURING 53 00:02:33,280 --> 00:02:35,960 COVID AND OVERCOMING CAREERS AND 54 00:02:35,960 --> 00:02:38,280 SOMETHING WE CAN MAKE AND 55 00:02:38,280 --> 00:02:39,880 ANOTHER CHALLENGE. 56 00:02:39,880 --> 00:02:41,200 PERTAINS TO PRIMARY CARE 57 00:02:41,200 --> 00:02:43,640 COMMUNITY AND RESOURCES TO REACH 58 00:02:43,640 --> 00:02:45,520 OUT TO UNDERSERVED COMMUNITIES 59 00:02:45,520 --> 00:02:49,000 TO THOSE AWAY FROM MAJOR URBAN 60 00:02:49,000 --> 00:02:50,760 AREAS AND TO SPECIAL POPULATIONS 61 00:02:50,760 --> 00:02:55,840 IS INTENSIVE SUPPORT AND 62 00:02:55,840 --> 00:02:57,800 RELATIONSHIP BETWEEN STAFF AND 63 00:02:57,800 --> 00:03:01,120 PATIENT MIGHT HELP TO OVERCOME 64 00:03:01,120 --> 00:03:03,320 CRITICALLY RELEVANT SOCIAL 65 00:03:03,320 --> 00:03:05,960 DETERMINANTS OF HEALTH SUCH AS 66 00:03:05,960 --> 00:03:06,320 CONNECTIVENESS. 67 00:03:06,320 --> 00:03:08,240 LET'S COME BACK TO TOPIC OF 68 00:03:08,240 --> 00:03:10,080 ADAPTATION AND IN CONTEXT OF 69 00:03:10,080 --> 00:03:12,520 DIVERSITY, EQUITY, INCLUSION, 70 00:03:12,520 --> 00:03:14,880 AND ACCESSIBILITY. 71 00:03:14,880 --> 00:03:20,440 HOW IS THAT'LL EFRNGS RESEARCH 72 00:03:20,440 --> 00:03:22,360 AGENDA AND INVESTIGATORS MIGHT 73 00:03:22,360 --> 00:03:26,400 START BY ADDRESSING POINTS IN 74 00:03:26,400 --> 00:03:29,160 CLARIFICATIONS AND SPECIFICALLY 75 00:03:29,160 --> 00:03:31,560 IN RESEARCH STRATEGY SECTIONS, 76 00:03:31,560 --> 00:03:32,600 SOMETHING WE ARE NOT 77 00:03:32,600 --> 00:03:34,040 APPRECIATIVE OF PROG IT GRAM 78 00:03:34,040 --> 00:03:35,720 SITE HERE. WE MIGHT ADDRESS 79 00:03:35,720 --> 00:03:37,800 SOME FORMAL ASPECT. HERE IS 80 00:03:37,800 --> 00:03:39,640 MAIN QUESTION. IF THIS IS A 81 00:03:39,640 --> 00:03:41,840 CASE FOR THE PATIENT, WOULD THEY 82 00:03:41,840 --> 00:03:44,480 BE COMFORTABLE WITH ADDED 83 00:03:44,480 --> 00:03:46,600 REFINEMENT OR MODIFY OR EFFECT 84 00:03:46,600 --> 00:03:48,600 BASIS ROAD TO RECOVERY AND 85 00:03:48,600 --> 00:03:50,480 IMPORTANTLY HAVING A MEANINGFUL 86 00:03:50,480 --> 00:03:52,720 LIFE IS SOMETHING FOR US TO 87 00:03:52,720 --> 00:03:52,960 THINK. 88 00:03:52,960 --> 00:03:55,040 IN SOME, WE PROBABLY MEASURE AND 89 00:03:55,040 --> 00:03:58,760 NEED TO GET BETTER AT 90 00:03:58,760 --> 00:03:59,480 INDIVIDUALIZED PATIENT LEVEL FOR 91 00:03:59,480 --> 00:04:03,080 THAT PURPOSE AND APPROACH TO 92 00:04:03,080 --> 00:04:04,600 DEVELOP ADAPTIVE OUTCOME 93 00:04:04,600 --> 00:04:07,200 MEASURES INCLUDING PATIENTS 94 00:04:07,200 --> 00:04:10,000 INDIVIDUALIZED THRESHOLD ON 95 00:04:10,000 --> 00:04:12,080 OUTCOME THAT BENEFIT COULD BE 96 00:04:12,080 --> 00:04:13,200 PROPOSED AND PARADIGM SHIFTS 97 00:04:13,200 --> 00:04:16,760 THEM AND PROPOSES ADAPTATION AND 98 00:04:16,760 --> 00:04:20,400 ACCOMMODATION. TOGETHER, 99 00:04:20,400 --> 00:04:23,200 PATIENTS ROAD TO HAVING A 100 00:04:23,200 --> 00:04:25,200 MEANINGFUL LIFE SHOULD BE 101 00:04:25,200 --> 00:04:25,520 CONSIDERED. 102 00:04:25,520 --> 00:04:28,280 SESSION 2, COMMONALITIES IN 103 00:04:28,280 --> 00:04:32,480 PATHOGENESIS AND NEUROCOGNITIVE 104 00:04:32,480 --> 00:04:35,160 DISFUNCTION AND SCENARIOS LIKE 105 00:04:35,160 --> 00:04:39,680 -- AND CLINICAL MANIFESTATIONS 106 00:04:39,680 --> 00:04:43,080 AND COVID FOLK SEEM TO BE 107 00:04:43,080 --> 00:04:45,640 EXPLAINED BY BIOLOGICAL 108 00:04:45,640 --> 00:04:47,720 MECHANISM IN CENTRAL SERVOUS 109 00:04:47,720 --> 00:04:49,920 SYSTEM AND REGULATION AND 110 00:04:49,920 --> 00:04:52,240 NEGATIVE IMPAIRMENT AND BASED ON 111 00:04:52,240 --> 00:04:56,560 COMMONALITIES BIOMARKERS OF 112 00:04:56,560 --> 00:04:58,160 MANIFESTATIONS OF IMPAIRMENT MAY 113 00:04:58,160 --> 00:05:05,040 BE REVEALED AND NOTED THAT 114 00:05:05,040 --> 00:05:06,240 PATHOLOGY. 115 00:05:06,240 --> 00:05:08,560 PROTEINO PATH ESIS OF THE LUNG 116 00:05:08,560 --> 00:05:12,400 LEAD TO INFERIOR PRODUCTION OF 117 00:05:12,400 --> 00:05:16,000 [INDISCERNIBLE] FOR EXAMPLE THAT 118 00:05:16,000 --> 00:05:17,240 CONTRIBUTES TO [INDISCERNIBLE] 119 00:05:17,240 --> 00:05:19,320 SUCH AS INFECTION AND DISCUSSED 120 00:05:19,320 --> 00:05:20,880 IN SESSION 1 WE NEED TO DEVELOP 121 00:05:20,880 --> 00:05:24,440 A TOOLKIT OF PRECLINICAL 122 00:05:24,440 --> 00:05:25,000 DISCOVERY SCIENCE THAT CAN 123 00:05:25,000 --> 00:05:29,040 REFLECT UNIQUE EXPERIENCES OF 124 00:05:29,040 --> 00:05:32,440 PATIENTS AND RELATIVE VALUE OF 125 00:05:32,440 --> 00:05:35,120 EXPERIMENTAL MODELS AND TOOLS 126 00:05:35,120 --> 00:05:38,760 INTRODUCING OUTCOMES RELATED TO 127 00:05:38,760 --> 00:05:40,720 SURVIVORS AND THOSE RELATED 128 00:05:40,720 --> 00:05:42,920 CORRELATIONS AND BEHAVIORS AND 129 00:05:42,920 --> 00:05:45,200 ANATOMY WAS DISCUSSED AND 130 00:05:45,200 --> 00:05:46,640 PARADIGM SHIFT TO DISCUSS WE 131 00:05:46,640 --> 00:05:47,600 SHOULD INCLUDE [INDISCERNIBLE] 132 00:05:47,600 --> 00:05:50,680 TO PATHOGEN AND SPECIFIC 133 00:05:50,680 --> 00:05:52,120 MECHANISMS TO DISCRIMINATE 134 00:05:52,120 --> 00:05:55,120 SICKNESS BEHAVIOR AND TO STUDY 135 00:05:55,120 --> 00:05:56,360 LEARNED AND DISEASED 136 00:05:56,360 --> 00:06:00,480 [INDISCERNIBLE] SUCH AS PSTD. 137 00:06:00,480 --> 00:06:05,080 OUR ASPIRATIONAL STATE IS STRONG 138 00:06:05,080 --> 00:06:08,360 FACE AND GOING TO BE USEFUL FOR 139 00:06:08,360 --> 00:06:10,680 HUMAN-BASED RESEARCH AND MODERN 140 00:06:10,680 --> 00:06:12,640 REAL-WORLD SCENARIOS AND FOR 141 00:06:12,640 --> 00:06:15,040 FORMER BASED ON SPECIFIC DATA 142 00:06:15,040 --> 00:06:17,800 LEADING TO MOLECULAR CLASSIFIER 143 00:06:17,800 --> 00:06:20,720 IS NEEDED AND LATTER EXPOSED 144 00:06:20,720 --> 00:06:24,240 ANIMALS ADDRESSING CHALLENGE OF 145 00:06:24,240 --> 00:06:25,960 HETEROGENOUS POPULATIONS TOWARDS 146 00:06:25,960 --> 00:06:28,840 ROUTE OF RECOVERY AND RESILIENCE 147 00:06:28,840 --> 00:06:31,520 WE HAVE TO DISTINGUISH BETWEEN 148 00:06:31,520 --> 00:06:33,160 THIS REGULATION SUCH WE THINK OR 149 00:06:33,160 --> 00:06:36,680 SEE NEUROPLASTICITY INFLAMMATION 150 00:06:36,680 --> 00:06:37,960 VERSUS DISTRACTION AND WE DON'T 151 00:06:37,960 --> 00:06:41,320 SEE AS MUCH IN PATIENTS AS WE 152 00:06:41,320 --> 00:06:43,880 SEE THIS REGULATION AND 153 00:06:43,880 --> 00:06:45,600 REVERSING PATHOLOGY BY 154 00:06:45,600 --> 00:06:48,160 MOLECULARLY COACHING CELLS SO 155 00:06:48,160 --> 00:06:50,280 THEY COME BACK TO HOMEOSTASIS 156 00:06:50,280 --> 00:06:52,400 WOULD BE A REASONABLE STRATEGY 157 00:06:52,400 --> 00:06:55,400 ANDALITY TERN TIFLY PROTECTING 158 00:06:55,400 --> 00:06:58,600 BRAIN DURING ACUTE FACE AND 159 00:06:58,600 --> 00:07:00,440 TACKLE COMPLICATIONS THAT HAVE 160 00:07:00,440 --> 00:07:01,800 [INDISCERNIBLE] WE MAY HAVE 161 00:07:01,800 --> 00:07:04,360 PATIENTS OF SEVERE COGNITIVE 162 00:07:04,360 --> 00:07:05,680 DISFUNCTION AND MAYBE WE WANT TO 163 00:07:05,680 --> 00:07:07,480 TEST THIS INTERESTING HYPOTHESIS 164 00:07:07,480 --> 00:07:10,360 WITH RELEVANCE TO RECOVERY AND 165 00:07:10,360 --> 00:07:13,720 RESILIENCE, ANIMAL MODELS TO BE 166 00:07:13,720 --> 00:07:16,720 SUITED FOR THE PURPOSE AND 167 00:07:16,720 --> 00:07:18,840 DISCUSSING PRECLINICAL DATA IS 168 00:07:18,840 --> 00:07:20,600 STILL NEEDED AND FOLLOWING THIS 169 00:07:20,600 --> 00:07:22,880 RECAP OF DAY 1, I WOULD LIKE TO 170 00:07:22,880 --> 00:07:24,480 TICK OFF DAY 2 AND CONTINUE WITH 171 00:07:24,480 --> 00:07:26,960 THE EXCITING PROGRAM. 172 00:07:26,960 --> 00:07:30,840 SESSION 3, PATHOGENESIS AND 173 00:07:30,840 --> 00:07:33,840 RECOVERY OF BASAL DISFUNCTION IN 174 00:07:33,840 --> 00:07:38,080 ARDS SURVIVORS IS BY 175 00:07:38,080 --> 00:07:40,360 [INDISCERNIBLE] AND IS AN 176 00:07:40,360 --> 00:07:43,280 ASSOCIATE PROFESSOR AND 177 00:07:43,280 --> 00:07:46,480 ASSISTANT CHIEF AT DEPARTMENT OF 178 00:07:46,480 --> 00:07:50,760 MEDICINE -- IMMUNOLOGICAL 179 00:07:50,760 --> 00:07:56,320 DISEA 180 00:07:56,320 --> 00:07:56,560 DISEASES. 181 00:07:56,560 --> 00:08:00,520 -- PARTICULARLY THOSE WITH ARDS 182 00:08:00,520 --> 00:08:03,280 AND [INDISCERNIBLE] SCIENTISTS 183 00:08:03,280 --> 00:08:05,200 AND HOSPITAL DURING HEALTH 184 00:08:05,200 --> 00:08:07,240 [INDISCERNIBLE] AND ASSOCIATE 185 00:08:07,240 --> 00:08:09,280 PROFESSOR OF MEDICINE AT 186 00:08:09,280 --> 00:08:11,400 UNIVERSITY OF TORONTO AND HAS 187 00:08:11,400 --> 00:08:14,320 PROGRAM OF BASIC AND 188 00:08:14,320 --> 00:08:16,280 TRANSLATIONAL RESEARCH FOCUSED 189 00:08:16,280 --> 00:08:20,200 ON PREVENTION AND CONTRACTED 190 00:08:20,200 --> 00:08:23,320 DISFUNCTION AND THE FLOOR IS 191 00:08:23,320 --> 00:08:31,600 YOU 192 00:08:31,600 --> 00:08:31,800 YOURS. 193 00:08:31,800 --> 00:08:34,320 >> THANK YOU, DR. GOMEZ AND 194 00:08:34,320 --> 00:08:35,280 SESSION CHAIRS. 195 00:08:35,280 --> 00:08:37,440 THANKS TO ALL OF YOU AND WELCOME 196 00:08:37,440 --> 00:08:42,440 TO SESSION 3 ON LBI WORKSHOP. 197 00:08:42,440 --> 00:08:47,320 WE ARE HONORED TO CHAIR THIS 198 00:08:47,320 --> 00:08:49,920 SESSION WITH THREE OUTSTANDING 199 00:08:49,920 --> 00:08:52,720 SPEAKERS RANGING FROM MECHANISMS 200 00:08:52,720 --> 00:08:55,040 UNDERLYING MUSCLE ATROPHY TO 201 00:08:55,040 --> 00:08:57,080 COMPLEX PRECLINICAL AND 202 00:08:57,080 --> 00:08:58,880 TRANSLATIONAL HUMAN STUDIES 203 00:08:58,880 --> 00:09:02,400 MODELING THE ICU ENVIRONMENT TO 204 00:09:02,400 --> 00:09:04,800 MUSCLE REGENERATION. 205 00:09:04,800 --> 00:09:06,520 SOME DISCUSSION WITH PROGRAM 206 00:09:06,520 --> 00:09:08,200 CO-CHAIRS IN THE LAST MONTHS 207 00:09:08,200 --> 00:09:10,000 ABOUT THIS SESSION FOCUSED ON 208 00:09:10,000 --> 00:09:12,880 TRYING TO COME UP WITH PRIORITY 209 00:09:12,880 --> 00:09:14,840 CONSENSUS WHERE TO FOCUS 210 00:09:14,840 --> 00:09:17,040 MECHANISTIC INVESTIGATION IN 211 00:09:17,040 --> 00:09:17,880 THIS FIELD. 212 00:09:17,880 --> 00:09:20,760 FOR INSTANCE, SHOULD WE FOCUS 213 00:09:20,760 --> 00:09:22,080 INVESTIGATION AND INTERVENTIONS 214 00:09:22,080 --> 00:09:26,680 ON MINIMIZING MUSCLE WASTING OR 215 00:09:26,680 --> 00:09:28,520 FOCUS ACCELERATING MUSCLE 216 00:09:28,520 --> 00:09:31,080 RECOVERY AND SPEAKERS WILL FOCUS 217 00:09:31,080 --> 00:09:34,840 ON KEY MECHANISMS UNDERLYING 218 00:09:34,840 --> 00:09:35,960 SKELETAL MUSCLE INJURY AND 219 00:09:35,960 --> 00:09:38,720 RECOVERY PLAYING A MAJOR ROLE IN 220 00:09:38,720 --> 00:09:41,200 SYNDROME OF PICS WE HEARD SO 221 00:09:41,200 --> 00:09:43,240 MUCH ABOUT YESTERDAY AND WILL 222 00:09:43,240 --> 00:09:44,640 OFFER INSIGHT INTO THESE 223 00:09:44,640 --> 00:09:44,960 QUESTIONS. 224 00:09:44,960 --> 00:09:46,960 WHILE WE MAY COME TO SOME 225 00:09:46,960 --> 00:09:48,360 CONSENSUS ABOUT WHICH AREA IS 226 00:09:48,360 --> 00:09:49,960 THE MOST IMPORTANT TO FOCUS ON 227 00:09:49,960 --> 00:09:52,360 OVER THE NEXT YEARS, IT IS MY 228 00:09:52,360 --> 00:09:53,520 HUMBLE OPINION THAT THE 229 00:09:53,520 --> 00:09:57,040 PROCESSES OF MUSCLE INJURY AND 230 00:09:57,040 --> 00:09:58,680 RECOVERY ARE SO INTERTWINED THAT 231 00:09:58,680 --> 00:10:00,920 IT IS HARD TO SAY WE SHOULD 232 00:10:00,920 --> 00:10:03,440 PRIORITIZE ONE OVER THE OTHER. 233 00:10:03,440 --> 00:10:13,160 FOR INSTANCE, MANY INTERVENTIONS 234 00:10:13,160 --> 00:10:15,600 TARGETING -- MIGHT HAVE EFFECT 235 00:10:15,600 --> 00:10:16,920 ON MUSCLE INJURY AND WE MIGHT 236 00:10:16,920 --> 00:10:19,440 NEED TO STUDY IT BETTER. 237 00:10:19,440 --> 00:10:21,200 LASTLY, IT IS IMPORTANT TO 238 00:10:21,200 --> 00:10:23,320 REMEMBER WHILE SKELETAL MUSCLE 239 00:10:23,320 --> 00:10:24,800 IS CLASSICALLY RECOGNIZED AS 240 00:10:24,800 --> 00:10:27,320 LARGEST ORGAN IN THE BODY 241 00:10:27,320 --> 00:10:28,480 COORDINATING LOCOMOTION AND 242 00:10:28,480 --> 00:10:31,800 PHYSICAL FUNCTION, IT IS ALSO 243 00:10:31,800 --> 00:10:32,400 INCREASINGLY RECOGNIZED AS 244 00:10:32,400 --> 00:10:35,720 ENDOCRINE IMMUNE ORGAN THAT IS 245 00:10:35,720 --> 00:10:38,960 INVOLVED IN CRITICAL 246 00:10:38,960 --> 00:10:40,320 ORGAN-TO-ORGAN CROSS-TALK, A 247 00:10:40,320 --> 00:10:42,040 PROCESS SO FUNDAMENTAL TO 248 00:10:42,040 --> 00:10:46,000 PATHOLOGY OF ARDS THAT WE ALL 249 00:10:46,000 --> 00:10:46,200 KNOW. 250 00:10:46,200 --> 00:10:48,440 AS WE CONSIDER TARGETING 251 00:10:48,440 --> 00:10:50,560 INVESTIGATION AND INTERVENTIONS 252 00:10:50,560 --> 00:10:53,840 ON SKELETAL MUSCLE SYSTEM IN 253 00:10:53,840 --> 00:10:56,760 ARDS WE MUST CONSIDER CONCEPTUAL 254 00:10:56,760 --> 00:10:59,600 INTERVENTIONS IN LIGHT OF 255 00:10:59,600 --> 00:11:00,840 NONCLASSICAL SKELETAL MUSCLE 256 00:11:00,840 --> 00:11:03,440 FUNCTIONS AND WITH THAT, WE WILL 257 00:11:03,440 --> 00:11:06,920 KICK OFF OUR SESSION ENTITLED 258 00:11:06,920 --> 00:11:08,840 PATHOGENESIS AND MUSCLE RECOVERY 259 00:11:08,840 --> 00:11:11,720 IN DISFUNCTION IN ARDS SURVIVORS 260 00:11:11,720 --> 00:11:13,960 AND I'M REALLY PLEASED TO 261 00:11:13,960 --> 00:11:16,160 INTRODUCE OUR FIRST SPEAKER. 262 00:11:16,160 --> 00:11:21,480 SUE BODINE IS FULL MEMBER IN 263 00:11:21,480 --> 00:11:23,680 AGING AND METABOLISM RESEARCH 264 00:11:23,680 --> 00:11:27,680 PROGRAM AND RESEARCH IS ON STUDY 265 00:11:27,680 --> 00:11:31,400 OF NEUROMUSCULAR SYSTEM AND 266 00:11:31,400 --> 00:11:35,560 VARIOUS STRESSORS EXERCISE MICRO 267 00:11:35,560 --> 00:11:38,120 GRAVITY DE-JENNERVATION AND 268 00:11:38,120 --> 00:11:39,480 AGING AND FOCUS OF LAB IS 269 00:11:39,480 --> 00:11:42,080 UNDERSTANDING MECHANISMS 270 00:11:42,080 --> 00:11:45,000 REGULATING SKELETAL MUSCLE SIZE 271 00:11:45,000 --> 00:11:47,320 AND FUNCTION UNDER ATROPHY AND 272 00:11:47,320 --> 00:11:49,280 MAJOR CONDITIONS AND FOCUS OF IT 273 00:11:49,280 --> 00:11:52,360 IS IDENTIFICATION OF IN VIVO 274 00:11:52,360 --> 00:11:55,960 SKELETAL MUSCLE SUBSTRATES AND 275 00:11:55,960 --> 00:11:56,880 LYINGACE IS [INDISCERNIBLE] AND 276 00:11:56,880 --> 00:11:59,680 LAB IS INVESTIGATING EFFECT OF 277 00:11:59,680 --> 00:12:01,800 AGING ON SKELETAL MUSCLE MASS 278 00:12:01,800 --> 00:12:03,320 AND FUNCTION AND IDENTIFICATION 279 00:12:03,320 --> 00:12:07,680 OF MECHANISMS UNDERLYING CORE 280 00:12:07,680 --> 00:12:10,080 RECOVERY OF MASS AND FUNCTION 281 00:12:10,080 --> 00:12:12,160 FOLLOWING ATROPHY IN AGE IN 282 00:12:12,160 --> 00:12:12,760 LABS. 283 00:12:12,760 --> 00:12:16,320 HER LAB IS A PRECLINICAL ANIMAL 284 00:12:16,320 --> 00:12:18,920 STUDY SITE INVOLVED IN MOLECULAR 285 00:12:18,920 --> 00:12:22,360 TRANSDUCERS OF PHYSICAL ACTIVITY 286 00:12:22,360 --> 00:12:24,120 CONSORTIUM OR MOTOR PACK. 287 00:12:24,120 --> 00:12:28,160 WITHOUT FURTHER ADO, DR. BODINE. 288 00:12:28,160 --> 00:12:29,800 >> THANK YOU CLARK AND JAIN FOR 289 00:12:29,800 --> 00:12:31,640 THE INVITATION TO PARTICIPATE IN 290 00:12:31,640 --> 00:12:39,480 THIS WONDERFUL WORKSHOP. 291 00:12:39,480 --> 00:12:41,240 NEXT SLIDE I WILL TALK ABOUT 292 00:12:41,240 --> 00:12:43,520 REGULATION OF MUSCLE MASS AND 293 00:12:43,520 --> 00:12:46,120 FUNCTIONS AND MECHANISMS 294 00:12:46,120 --> 00:12:48,920 UNDERLYING MUSCLE AT TROPHY. 295 00:12:48,920 --> 00:12:51,920 I WANT TO HIGHLIGHT MUSCLE IS A 296 00:12:51,920 --> 00:12:54,720 HIGHLY PLASTIC TISSUE AND 297 00:12:54,720 --> 00:12:56,440 MULTICELLULAR TISSUE AND AS SEEN 298 00:12:56,440 --> 00:12:59,040 IN THIS ILLUSTRATION, MUSCLE 299 00:12:59,040 --> 00:13:03,840 RELIES ON AN IN TACT MOTOR 300 00:13:03,840 --> 00:13:05,400 INNERVATION TO MAINTAIN MASS AND 301 00:13:05,400 --> 00:13:07,200 FUNCTION AND BESIDES MOTOR 302 00:13:07,200 --> 00:13:09,040 FUNCTION IT IS A SIGNIFICANT 303 00:13:09,040 --> 00:13:11,840 SENSORY ORGAN WITH MANY SENSORY 304 00:13:11,840 --> 00:13:15,280 RECEPTORS PROJECTING BACK TO THE 305 00:13:15,280 --> 00:13:19,920 BRAIN STEM AND OTHER ORGANS AND 306 00:13:19,920 --> 00:13:22,840 MUSCLE RELIES HEAVILY ON 307 00:13:22,840 --> 00:13:25,240 MECHANICAL LOADING AND MAINTAIN 308 00:13:25,240 --> 00:13:26,800 FUNCTION AND ELEMENTS ARE 309 00:13:26,800 --> 00:13:28,160 IMPORTANT FOR PRODUCING FORCE 310 00:13:28,160 --> 00:13:31,600 AND MUSCLE ALSO HAS A VERY 311 00:13:31,600 --> 00:13:34,600 HIGHLY STRUCTURED MICRO VASCULAR 312 00:13:34,600 --> 00:13:36,800 SYSTEM CRITICAL FOR DELIVERY OF 313 00:13:36,800 --> 00:13:40,040 OXYGEN AND NUTRIENTS AND WASTE 314 00:13:40,040 --> 00:13:43,720 REMOVAL AND MUSCLES HIGHLY 315 00:13:43,720 --> 00:13:46,880 METROBOLIC ORGAN DEPENDENT ON 316 00:13:46,880 --> 00:13:48,280 MITOCHONDRIA FOREIGN ERNL JI 317 00:13:48,280 --> 00:13:52,280 PRODUCTION AND IS A MAJOR 318 00:13:52,280 --> 00:13:54,520 REPOSITORY FOR GLUCOSE AND 319 00:13:54,520 --> 00:13:57,680 STORAGE OF GLUCOSE AS GLYCOGEN 320 00:13:57,680 --> 00:13:59,680 AND CLARK MENTIONED THAT MUSCLE 321 00:13:59,680 --> 00:14:02,360 IS HIGHLY RESPONSIVE TO HORMONES 322 00:14:02,360 --> 00:14:07,360 AND GROWTH FACTORS. AS A 323 00:14:07,360 --> 00:14:11,040 MULTINUCLEATED TISSUE HAS A STEM 324 00:14:11,040 --> 00:14:13,760 CELL POPULATION SATELLITE CELLS 325 00:14:13,760 --> 00:14:16,440 THAT ARE CAPABLE IN PRODUCING 326 00:14:16,440 --> 00:14:19,320 REGENERATION OF MUSCLE FIBERS 327 00:14:19,320 --> 00:14:21,280 AND THAT ARE CRITICAL FOR 328 00:14:21,280 --> 00:14:22,640 GROWTH. NEXT SLIDE. 329 00:14:22,640 --> 00:14:24,720 SO, MUSCLE WASTING CAN BE 330 00:14:24,720 --> 00:14:29,240 INDUCED BY A NUMBER OF 331 00:14:29,240 --> 00:14:29,520 STRESSORS. 332 00:14:29,520 --> 00:14:32,280 NEXT SLIDE. TWO OF THE MOST 333 00:14:32,280 --> 00:14:34,080 CRITICAL STRESSORS ARE EXTERNAL 334 00:14:34,080 --> 00:14:36,680 LOADING AND NEURAL ACTIVATION 335 00:14:36,680 --> 00:14:38,880 AND DECREASES IN EXTERNAL 336 00:14:38,880 --> 00:14:41,120 LOADING AND RECRUITMENT AND 337 00:14:41,120 --> 00:14:43,680 ACTIVATION OF MUSCLE INDUCE 338 00:14:43,680 --> 00:14:46,840 MUSCLE WASTING AND MITOCHONDRIAL 339 00:14:46,840 --> 00:14:48,160 DISFUNCTION CAN ALSO PLAY A ROLE 340 00:14:48,160 --> 00:14:53,240 IN REGULATION OF MUSCLE MASS. 341 00:14:53,240 --> 00:14:56,240 NEXT, OTHER FACTORS SUCH AS NEXT 342 00:14:56,240 --> 00:14:57,920 SLIDE. 343 00:14:57,920 --> 00:15:02,040 NEXT, INFLAMMATION AND TREATMENT 344 00:15:02,040 --> 00:15:06,120 INFLAMMATION WITH 345 00:15:06,120 --> 00:15:07,120 GLUCOCORTICOIDS AND VASCULAR 346 00:15:07,120 --> 00:15:09,280 INT 347 00:15:09,280 --> 00:15:11,720 INTERFUNCTION AND ORGAN FAILURES 348 00:15:11,720 --> 00:15:13,800 SUCH AS LIVER, RENAL AND HEART 349 00:15:13,800 --> 00:15:15,920 FAILURE CAN CONTRIBUTE TO MUSCLE 350 00:15:15,920 --> 00:15:18,440 WASTING AND LAST BUT NOT LEAST, 351 00:15:18,440 --> 00:15:21,840 AGING INDUCES PROLONGED OR A -- 352 00:15:21,840 --> 00:15:26,720 PROLONGED DECREASE IN MUSCLE 353 00:15:26,720 --> 00:15:27,240 MASS. 354 00:15:27,240 --> 00:15:28,600 NEXT. 355 00:15:28,600 --> 00:15:30,360 NEXT SLIDE. 356 00:15:30,360 --> 00:15:32,000 GENERALLY WHEN WE THINK OF 357 00:15:32,000 --> 00:15:33,920 REGULATION OF SKELETAL MUSCLE 358 00:15:33,920 --> 00:15:36,120 MASS, WE THINK OF THE BALANCE 359 00:15:36,120 --> 00:15:38,240 BETWEEN PROTEIN SYNTHESIS AND 360 00:15:38,240 --> 00:15:39,960 PROTEIN DEGRADATION AND WITH 361 00:15:39,960 --> 00:15:42,720 MUSCLE LOSS, THINKING THAT THE 362 00:15:42,720 --> 00:15:44,840 BALANCE GOES TOWARDS AN INCREASE 363 00:15:44,840 --> 00:15:47,480 IN PROTEIN DEGRADATION AND MOST 364 00:15:47,480 --> 00:15:49,440 PEOPLE THINK OF THIS AS DECREASE 365 00:15:49,440 --> 00:15:51,600 IN PROTEIN SYNTHESIS AND 366 00:15:51,600 --> 00:15:55,320 INCREASE IN PROTEIN DEGRADATION 367 00:15:55,320 --> 00:15:57,280 AND HOWEVER MORE RECENT DATA 368 00:15:57,280 --> 00:15:59,120 SHOWS PROTEIN SYNTHESIS CAN GO 369 00:15:59,120 --> 00:16:01,480 UP IN SOME CASES AND WE NEED TO 370 00:16:01,480 --> 00:16:03,120 KNOW AND NEED A BETTER 371 00:16:03,120 --> 00:16:06,320 UNDERSTANDING OF WHICH PROTEINS 372 00:16:06,320 --> 00:16:09,440 ARE IN FACT ARE BEING SUPPRESSED 373 00:16:09,440 --> 00:16:11,720 SYNTHESISWISE AND WHICH ARE 374 00:16:11,720 --> 00:16:15,400 INCREASED IN SYNTHESIS AND 375 00:16:15,400 --> 00:16:18,120 TRANSLATIONS DURING@TROPHY 376 00:16:18,120 --> 00:16:21,080 PROCESSES AND SHOWN HERE ARE 377 00:16:21,080 --> 00:16:23,920 MULTIPLE DEGRADATION PATHWAYS 378 00:16:23,920 --> 00:16:26,920 CRITICAL FOR DEGRADATION OF 379 00:16:26,920 --> 00:16:29,600 PROTEINS AND PROETEE OHM SYSTEM 380 00:16:29,600 --> 00:16:33,840 AND THEY ALL PLAY A ROLE IN THE 381 00:16:33,840 --> 00:16:35,640 DEGRADATION OF SPECIFIC PROTEINS 382 00:16:35,640 --> 00:16:38,520 AND OVER THE LAST 20 YEARS WE 383 00:16:38,520 --> 00:16:41,920 HAVE BEGUN TO UNDERSTAND SOME 384 00:16:41,920 --> 00:16:44,560 MOLECULAR PATHWAYS THAT ARE 385 00:16:44,560 --> 00:16:46,920 ACTIVATED OR SUPPRESSED 386 00:16:46,920 --> 00:16:47,600 UNDER@TROPHY CONDITIONS. 387 00:16:47,600 --> 00:16:49,080 NEXT SLIDE. 388 00:16:49,080 --> 00:16:52,520 YOU CAN SEE HERE NEXT THAT UNDER 389 00:16:52,520 --> 00:16:55,960 MECHANICAL LOADING OR CHANGES IN 390 00:16:55,960 --> 00:16:57,240 MECHANICAL LOADING AND 391 00:16:57,240 --> 00:16:59,680 ACTIVATION OF THE MUSCLE THROUGH 392 00:16:59,680 --> 00:17:01,840 THE NEUROMUSCULAR JUNCTION CAN 393 00:17:01,840 --> 00:17:04,200 HAVE EFFECTS ON PROTEIN 394 00:17:04,200 --> 00:17:07,680 SYNTHESIS PATHWAYS SPECIFICALLY 395 00:17:07,680 --> 00:17:12,400 MTOR PATHWAY AND OTHER NON-MTOR 396 00:17:12,400 --> 00:17:14,760 PATHWAYS COULD BE EFFECTED WITH 397 00:17:14,760 --> 00:17:16,920 DECREASES IN MECHANICAL LOADING 398 00:17:16,920 --> 00:17:19,560 AND SUPPRESSION OF AKT CAN 399 00:17:19,560 --> 00:17:21,640 EFFECT TRANSCRIPTION FACTORS 400 00:17:21,640 --> 00:17:26,480 SUCH AS FOXOS THAT CAN BECOME 401 00:17:26,480 --> 00:17:28,600 ACTIVATED TURNING ON VARIOUS 402 00:17:28,600 --> 00:17:31,160 TRANSCRIPTIONAL PROGRAMS THAT 403 00:17:31,160 --> 00:17:33,920 INCREASE PROTEIN DEGRADATION AND 404 00:17:33,920 --> 00:17:36,200 NEXT IS OTHER PAMPHLETS ALSO 405 00:17:36,200 --> 00:17:39,280 HERE INFLAMMATORY PATHWAYS COULD 406 00:17:39,280 --> 00:17:40,040 ACTIVATE. 407 00:17:40,040 --> 00:17:41,640 INFLAMMATION COULD ACTIVATE 408 00:17:41,640 --> 00:17:43,600 ADDITIONAL PATHWAYS THAT COULD 409 00:17:43,600 --> 00:17:45,840 CONTRIBUTE TO THE ACTIVATION 410 00:17:45,840 --> 00:17:48,000 EITHER SUPPRESSION OF PROTEIN 411 00:17:48,000 --> 00:17:50,360 SYNTHESIS AND/OR ACTIVATION OF 412 00:17:50,360 --> 00:17:51,960 PROTEIN DEGRADATION. 413 00:17:51,960 --> 00:17:55,840 YOU CAN SEE HERE GLUCOCORTICOIDS 414 00:17:55,840 --> 00:17:59,520 COULD INDUCE MUSCLE AT TROPHY. 415 00:17:59,520 --> 00:18:01,920 IN CRITICALLY ILL PATIENT, IT IS 416 00:18:01,920 --> 00:18:04,040 LIKELY MANY PATHWAYS ARE 417 00:18:04,040 --> 00:18:05,760 ACTIVATED WITH UNLOADING 418 00:18:05,760 --> 00:18:08,040 DECREASED NEURAL ACTIVATION AND 419 00:18:08,040 --> 00:18:09,760 INFLAMMATION THAT IS ALL 420 00:18:09,760 --> 00:18:12,880 CONTRIBUTING TO THIS ENHANCED 421 00:18:12,880 --> 00:18:15,320 BREAKDOWN OF SARCOMERES. 422 00:18:15,320 --> 00:18:15,880 NEXT SLIDE. 423 00:18:15,880 --> 00:18:17,760 TWO PROTEINS THAT HAVE BEEN 424 00:18:17,760 --> 00:18:22,320 SHOWN TO BE UPREGULATED UNDER A 425 00:18:22,320 --> 00:18:24,960 VARIETY OF ATROPHY AND 426 00:18:24,960 --> 00:18:31,600 CONDITIONS ARE E23 LYINGASES AND 427 00:18:31,600 --> 00:18:33,600 IMAGINE BOX [INDISCERNIBLE] AND 428 00:18:33,600 --> 00:18:37,400 THESE ARE E3 LYINGASES THAT 429 00:18:37,400 --> 00:18:40,840 IDENTIFY SPECIFIC SUBSTRATES AND 430 00:18:40,840 --> 00:18:44,960 ADDING UBIC WINATION TO THESE 431 00:18:44,960 --> 00:18:46,520 TARGETS. 432 00:18:46,520 --> 00:18:50,040 IT IS GENERALLY THOUGHT THAT 433 00:18:50,040 --> 00:18:53,120 ADDITION TO U- BIK WIT AN CHAINS 434 00:18:53,120 --> 00:18:55,920 LEADS TO PROTEIN DEGRADATION 435 00:18:55,920 --> 00:18:58,000 THROUGH THE PROETEOSOME AND CAN 436 00:18:58,000 --> 00:19:00,840 HAVE OTHER FUNCTIONS SUCH AS 437 00:19:00,840 --> 00:19:02,160 ALTERING ACTIVITY OF SPECIFIC 438 00:19:02,160 --> 00:19:05,400 PROTEIN OR LOCALIZATION WITHIN 439 00:19:05,400 --> 00:19:08,200 THE CELL. 440 00:19:08,200 --> 00:19:15,760 AND MURF AND MAFBX WERE 441 00:19:15,760 --> 00:19:16,920 IDENTIFIED THROUGH 442 00:19:16,920 --> 00:19:17,320 IMMOBILIZATION. 443 00:19:17,320 --> 00:19:17,840 NEXT. 444 00:19:17,840 --> 00:19:20,120 YOU CAN SEE HERE THEY ARE 445 00:19:20,120 --> 00:19:21,480 RELATIVELY LOW EXPRESSION IN 446 00:19:21,480 --> 00:19:25,720 NORMAL MUSCLE BUT BECOME HIGHLY 447 00:19:25,720 --> 00:19:28,240 UPREGULATED IN RESPONSE TO 448 00:19:28,240 --> 00:19:28,480 DISUSE. 449 00:19:28,480 --> 00:19:30,920 THEY HAVE BEEN SHOWN TO BE 450 00:19:30,920 --> 00:19:32,960 ACTIVATED UNDER A NUMBER OF 451 00:19:32,960 --> 00:19:33,680 CONDITIONS. 452 00:19:33,680 --> 00:19:37,000 NEXT, AS SEEN HERE. 453 00:19:37,000 --> 00:19:38,960 NEXT. 454 00:19:38,960 --> 00:19:42,240 DENERVATION AND FASTING AND 455 00:19:42,240 --> 00:19:45,680 GLUCOCORTICOID AND SEPSIS AND 456 00:19:45,680 --> 00:19:52,360 ACUTE LUNG INJURY AND MURF AND 457 00:19:52,360 --> 00:20:02,840 MAFBX ARE IN ANIMAL AND IN HUMAN 458 00:20:02,840 --> 00:20:03,360 HUMANS. 459 00:20:03,360 --> 00:20:06,520 HOW THEY ARE WORKING TO INDUCE 460 00:20:06,520 --> 00:20:09,720 AT TROPHY IS SOMETHING MY LAB 461 00:20:09,720 --> 00:20:12,600 HAS WORKED ON NEXT AND IT IS 462 00:20:12,600 --> 00:20:17,520 SUGGESTED THAT MURF BY ITSELF 463 00:20:17,520 --> 00:20:20,560 CONDITIONED INDUCE@TROPHY AND 464 00:20:20,560 --> 00:20:24,240 THEY CAN IN FACT INDUCE MUSCLE 465 00:20:24,240 --> 00:20:25,320 WASTING. NEXT. 466 00:20:25,320 --> 00:20:29,880 YOU CAN HIT IT AGAIN. NEXT. 467 00:20:29,880 --> 00:20:34,480 WE HAVE USED DIGLIDE PROTEOMICS 468 00:20:34,480 --> 00:20:38,240 TO IDENTIFY SPECIFIC TARGETS OF 469 00:20:38,240 --> 00:20:40,600 MURF1 AND IDENTIFYING PROTEINS 470 00:20:40,600 --> 00:20:48,360 THAT ARE IN FACT UB IQUITED AND 471 00:20:48,360 --> 00:20:49,800 THAT HAVE RESPONSE TO 472 00:20:49,800 --> 00:20:52,600 UPREGULATION OF MURF1. THEY ARE 473 00:20:52,600 --> 00:20:53,720 SHOWN HERE. 474 00:20:53,720 --> 00:20:57,840 NEXT, THIS TABLE SHOWS ALL 45 475 00:20:57,840 --> 00:21:01,280 PROTEINS THAT HAD UPREGULATED U- 476 00:21:01,280 --> 00:21:04,480 BIK WINATION IN RESPONSE TO MURF 477 00:21:04,480 --> 00:21:06,400 AND GENERALLY SUGGESTED THAT 478 00:21:06,400 --> 00:21:10,000 PRIMARY TARGETS IN MURF ARE 479 00:21:10,000 --> 00:21:11,880 HEAVY CHAINS AND DATA SUGGESTS 480 00:21:11,880 --> 00:21:16,360 NUMBER OF TARGETS FOR MURF AND 481 00:21:16,360 --> 00:21:20,120 TIGHTEN AND DEZ BIN ARE HIGHLY 482 00:21:20,120 --> 00:21:25,640 U- BIK WITTED PROTEINS WITH MURF 483 00:21:25,640 --> 00:21:27,760 DEREGULATING ASSEMBLY OF 484 00:21:27,760 --> 00:21:29,480 SARCOMERE AND PATHWAYS THAT 485 00:21:29,480 --> 00:21:32,240 MIGHT BE ACTIVATED IN RESPONSE 486 00:21:32,240 --> 00:21:36,680 TO MURF UPREGULATION AND NEXT I 487 00:21:36,680 --> 00:21:37,760 WANT TO SWITCH TO WORK WE HAVE 488 00:21:37,760 --> 00:21:43,880 DONE IN A MODEL OF UNLOADING AND 489 00:21:43,880 --> 00:21:44,160 RELOADING. 490 00:21:44,160 --> 00:21:47,080 TAIL SUSPENSION OR HIEM YEM 491 00:21:47,080 --> 00:21:49,000 LOADING MODEL AND USE THIS MODEL 492 00:21:49,000 --> 00:21:50,960 TO STUDY UNLOADING PROCESS AND 493 00:21:50,960 --> 00:21:53,240 LOOK AT WHAT HAPPENS DURING 494 00:21:53,240 --> 00:21:55,560 RELOADING AND RECOVERY OF MUSCLE 495 00:21:55,560 --> 00:21:56,760 AND LOOKING AT COMPARING EFFECT 496 00:21:56,760 --> 00:22:03,000 OF AGE BY LOOKING AT ADULT AND 497 00:22:03,000 --> 00:22:06,160 OLD FISHER BROWN NORWAY RATS. 498 00:22:06,160 --> 00:22:07,840 THESE SHOW LOSS OF MUSCLE MASS 499 00:22:07,840 --> 00:22:10,640 OVER 14 DAYS OF UNLOADING AND 500 00:22:10,640 --> 00:22:12,320 INCREASE OF MUSCLE MASS DURING 501 00:22:12,320 --> 00:22:15,080 14 DAYS OF RELOADING AND MUSCLES 502 00:22:15,080 --> 00:22:20,560 SHOWN HERE, THE SOLEOUS A 503 00:22:20,560 --> 00:22:22,480 PREDOMINANTLY SLOW MUSCLE IN THE 504 00:22:22,480 --> 00:22:22,680 RAT. 505 00:22:22,680 --> 00:22:26,680 PLAN TARRIS IS A MIXED EXTENSOR 506 00:22:26,680 --> 00:22:30,640 MUSCLE AND TIBIALIS INTERIOR IS 507 00:22:30,640 --> 00:22:33,480 A MIXED FLEXOR MUSCLE. YOU CAN 508 00:22:33,480 --> 00:22:35,360 SEE HERE IN THE ADULT IS THE 509 00:22:35,360 --> 00:22:38,960 MUSCLE SHOWING THE GREATEST LOSS 510 00:22:38,960 --> 00:22:42,520 IS THE SOLEOUS PREDOMINANTLY 511 00:22:42,520 --> 00:22:45,200 SLOW MUSCLE AND MUSCLE WITH 512 00:22:45,200 --> 00:22:48,400 LEAST LOSS OF MUSCLE MASS IS 513 00:22:48,400 --> 00:22:51,280 FLEXOR OR TIBIALIS INTERIOR AND 514 00:22:51,280 --> 00:22:52,920 FULL RECOVERY OF MASS WITHIN 14 515 00:22:52,920 --> 00:22:54,400 DAYS OF RELOADING. 516 00:22:54,400 --> 00:22:57,320 IN OLDER ANIMAL, NEXT. 517 00:22:57,320 --> 00:23:04,600 YOU CAN SEE THAT THE@TROPHY 518 00:23:04,600 --> 00:23:07,000 RESPONSE TO YOUNG AND OLD 519 00:23:07,000 --> 00:23:09,360 ANIMALS HOWEVER, UPON RELOADING 520 00:23:09,360 --> 00:23:12,760 YOU SEE ATTENUATED RECOVERY IN 521 00:23:12,760 --> 00:23:15,000 MUSCLE MASS WITH ALL OF THE 522 00:23:15,000 --> 00:23:17,320 MUSCLES WITH SOLEOUS BEING THE 523 00:23:17,320 --> 00:23:21,120 BEST AT RECOVERY AND TIBIALIS 524 00:23:21,120 --> 00:23:22,520 INTERIOR BEING ONE OF THE WORST. 525 00:23:22,520 --> 00:23:25,480 IT SHOWS MUSCLES MIGHT HAVE A 526 00:23:25,480 --> 00:23:28,720 SMALL AMOUNT OF AT TROPHY AND 527 00:23:28,720 --> 00:23:30,320 MIGHT NOT RECOVER WELL AND WE 528 00:23:30,320 --> 00:23:34,120 SEE MUSCLES WITH GREATEST 529 00:23:34,120 --> 00:23:35,920 PERCENTAGES AND LARGE TYPE 2B 530 00:23:35,920 --> 00:23:38,560 FIBERS HAVING WORST RECOVERY 531 00:23:38,560 --> 00:23:39,400 UPON RELOADING. 532 00:23:39,400 --> 00:23:39,600 NEXT. 533 00:23:39,600 --> 00:23:42,840 IN ADDITION TO MUSCLE MASS, WE 534 00:23:42,840 --> 00:23:44,720 LOOKED AT MUSCLE STRENGTH. IN 535 00:23:44,720 --> 00:23:47,040 ADULT ANIMALS YOU CAN SEE THAT 536 00:23:47,040 --> 00:23:50,400 RED DOTS SHOW RESPONSE TO 14 537 00:23:50,400 --> 00:23:51,880 DAYS UNLOADING AND IS A DECREASE 538 00:23:51,880 --> 00:23:55,120 IN STRENGTH. THIS IS ISOMETRIC 539 00:23:55,120 --> 00:24:00,160 TORQUE ABOVE THE ANKLE JOINT 540 00:24:00,160 --> 00:24:01,520 MEASURED USING AUR ORROUS SYSTEM 541 00:24:01,520 --> 00:24:04,200 AND ELOADING YOU SEE FULL 542 00:24:04,200 --> 00:24:09,280 RECOVERY OF STRENGTH AND IN OLD 543 00:24:09,280 --> 00:24:11,080 ANIMALS DROPPING FORCE IS 544 00:24:11,080 --> 00:24:13,280 GREATER THAN IN ADULT ANIMALS 545 00:24:13,280 --> 00:24:15,440 EVEN THOUGH AMOUNT OF@TROPHY IS 546 00:24:15,440 --> 00:24:18,280 SIMILAR AND NO RECOVERY OF 547 00:24:18,280 --> 00:24:20,960 MUSCLE STRENGTH OVER 14 DAYS OF 548 00:24:20,960 --> 00:24:23,000 RELOADING AND WOULD BE 549 00:24:23,000 --> 00:24:26,120 INTERESTING TO SEE WHAT IS 550 00:24:26,120 --> 00:24:29,200 RESPONSIBLE FOR THIS SIGNIFICANT 551 00:24:29,200 --> 00:24:31,680 DROP IN STRENGTH IN OLDER 552 00:24:31,680 --> 00:24:32,680 ANIMALS AND WHAT IS RESPONSIBLE 553 00:24:32,680 --> 00:24:37,120 FOR LACK OF RECOVERY. 554 00:24:37,120 --> 00:24:37,320 NEXT. 555 00:24:37,320 --> 00:24:41,320 ONE THING, WE LOOKEDALITY 556 00:24:41,320 --> 00:24:42,080 BASELINE DIFFERENCES BETWEEN OLD 557 00:24:42,080 --> 00:24:44,680 AND ADULT ANIMALS AND 558 00:24:44,680 --> 00:24:46,400 UNFORTUNATELY, THE DATA IS NOT 559 00:24:46,400 --> 00:24:47,080 SHOWING UP. 560 00:24:47,080 --> 00:24:50,040 WHAT WE SEE IS A SIGNIFICANT 561 00:24:50,040 --> 00:24:52,680 DIFFERENCE BETWEEN OLD AND YOUNG 562 00:24:52,680 --> 00:24:56,280 AT BASELINE WITH DIFFERENTIALLY 563 00:24:56,280 --> 00:24:59,760 EXPRESSED GENES HERE THAT IS 393 564 00:24:59,760 --> 00:25:02,120 IN THE UPREGULATED GENES THAT 565 00:25:02,120 --> 00:25:05,960 ARE DIFFERENTIALLY UPREGULATED 566 00:25:05,960 --> 00:25:09,640 AND 281 DIFFERENTIALLY 567 00:25:09,640 --> 00:25:11,360 DOWNREGULATED AND GENONTOLOGY 568 00:25:11,360 --> 00:25:14,960 PATHWAYS UPREGULATED IN OLD 569 00:25:14,960 --> 00:25:19,840 ANIMALS ARE INFLAMMATION T 570 00:25:19,840 --> 00:25:22,760 MEDIATED CYTOTOXICITY AND 571 00:25:22,760 --> 00:25:24,320 INSTABILITY AND DOWNREGULATED 572 00:25:24,320 --> 00:25:27,320 GENES HAVE CORRESPONDED TO 573 00:25:27,320 --> 00:25:31,320 VASCULAR OR ANGIOGENESIS AND 574 00:25:31,320 --> 00:25:33,440 EXCELLENT GUIDANCE AND DECREASES 575 00:25:33,440 --> 00:25:36,120 IN EXTRA CELLULAR MATRIX. WE 576 00:25:36,120 --> 00:25:38,560 LOOKED AT VARIOUS PROPERTIES AND 577 00:25:38,560 --> 00:25:39,440 MEASURED VARIOUS PROPERTIES OF 578 00:25:39,440 --> 00:25:40,480 THE MUSCLE. 579 00:25:40,480 --> 00:25:43,480 WE SEE ACTUALLY IN OLD ANIMALS 580 00:25:43,480 --> 00:25:45,120 INCREASE IN PROTEIN SYNTHESIS 581 00:25:45,120 --> 00:25:48,120 AND NOT A DECREASE. 582 00:25:48,120 --> 00:25:49,960 THIS HAS BEEN SEEN IN A NUMBER 583 00:25:49,960 --> 00:25:53,000 OF AGING MODELS WITH INCREASE IN 584 00:25:53,000 --> 00:25:57,040 MTOR ACTIVATION AND DON'T SEE 585 00:25:57,040 --> 00:26:00,160 ELEVATIONS IN PROETEOSOME 586 00:26:00,160 --> 00:26:03,320 ACTIVITY AT THIS AGE AND SEE 587 00:26:03,320 --> 00:26:06,040 SUPPRESSION OF PROETEOSOME 588 00:26:06,040 --> 00:26:09,000 ACTIVITY AND INCREASE IN 589 00:26:09,000 --> 00:26:12,960 AUTOPHAGY THAT IS IN RESPONSE TO 590 00:26:12,960 --> 00:26:15,760 INHIBITED PROETE OHM ACTIVITY 591 00:26:15,760 --> 00:26:17,760 AND AGGREGATES AND SIGNIFICANT 592 00:26:17,760 --> 00:26:23,000 ER STRESS INFLAMMATION AND 593 00:26:23,000 --> 00:26:26,120 INCREASED GENES SUGGESTING 594 00:26:26,120 --> 00:26:28,000 NEUROMUSCULAR JUNCTION, 595 00:26:28,000 --> 00:26:31,560 INSTABILITY AND/OR DENERVATION. 596 00:26:31,560 --> 00:26:32,520 NEXT. 597 00:26:32,520 --> 00:26:35,680 WHAT IS RESPONSIBLE FOR THIS 598 00:26:35,680 --> 00:26:37,200 LARGE DROP IN STRENGTH? 599 00:26:37,200 --> 00:26:38,880 ONE OF THE FIRST THINGS WE 600 00:26:38,880 --> 00:26:41,320 THOUGHT OF WAS NEUROMUSCULAR 601 00:26:41,320 --> 00:26:41,920 JUNCTION. 602 00:26:41,920 --> 00:26:42,120 NEXT. 603 00:26:42,120 --> 00:26:43,720 WE LOOKED AT GENES THAT HAVE 604 00:26:43,720 --> 00:26:48,120 BEEN ASSOCIATED WITH INACTIVITY 605 00:26:48,120 --> 00:26:51,920 OR DENERVATION AND THERE IS 606 00:26:51,920 --> 00:26:54,600 GENES HERE AND YOU CAN SEE HERE 607 00:26:54,600 --> 00:26:57,160 AT BASELINE THAT THERE IS RED 608 00:26:57,160 --> 00:26:59,680 BEING OLD ANIMALS AND INCREASE 609 00:26:59,680 --> 00:27:02,440 IN BASELINE EXPRESSION IN GENES 610 00:27:02,440 --> 00:27:04,640 UPON UNLOADING THESE GENES ALL 611 00:27:04,640 --> 00:27:08,560 GO UP AND IN SOME CASES LIKE 612 00:27:08,560 --> 00:27:11,680 NCAM AND ACETYL CHOLINE 613 00:27:11,680 --> 00:27:13,080 RECEPTORS INCREASE MORE IN THE 614 00:27:13,080 --> 00:27:15,840 OLD THAN IN THE ADULT AND 615 00:27:15,840 --> 00:27:17,280 INTERESTINGLY UPON RELOADING 616 00:27:17,280 --> 00:27:18,720 WHERE GENES ARE OFTEN SUPPRESSED 617 00:27:18,720 --> 00:27:21,840 IN ADULT ANIMALS UPON RELOADING, 618 00:27:21,840 --> 00:27:23,960 GENES STAY UP IN THE OLD AND 619 00:27:23,960 --> 00:27:26,000 SUGGESTING THAT THERE IS 620 00:27:26,000 --> 00:27:28,400 MAINTAINED OR THAT THERE IS 621 00:27:28,400 --> 00:27:30,520 POTENTIALLY EVEN -- THAT 622 00:27:30,520 --> 00:27:33,280 UNLOADING ITSELF IS INDUCING 623 00:27:33,280 --> 00:27:35,040 INCREASED NEUROMUSCULAR JUNCTION 624 00:27:35,040 --> 00:27:37,960 AND INSTABILITY AND POSSIBLY 625 00:27:37,960 --> 00:27:42,160 DENERVATION THAT IS ENHANCED OR 626 00:27:42,160 --> 00:27:45,920 EXACERBATED IN THE -- UPON 627 00:27:45,920 --> 00:27:46,720 RELOADING. 628 00:27:46,720 --> 00:27:47,200 NEXT. 629 00:27:47,200 --> 00:27:53,360 WE HAVE LOOKED AT DURING 630 00:27:53,360 --> 00:27:54,760 UNLOADING PERIOD WHAT IS 631 00:27:54,760 --> 00:27:58,400 DIFFERENT IN UNLOADING PERIOD 632 00:27:58,400 --> 00:28:08,960 BETWEEN YOUNG AND OLD ANIMALS -- 633 00:28:10,040 --> 00:28:13,080 YOUNG AND OLD DURING UNLOADING 634 00:28:13,080 --> 00:28:18,320 PROCESS AND LOOKING AT OVERLAP. 635 00:28:18,320 --> 00:28:23,040 AND WE SEE SIGNIFICANT OVERLAP 636 00:28:23,040 --> 00:28:25,720 BETWEEN YOUNG AND OLD AND ARE 637 00:28:25,720 --> 00:28:29,280 GENES DIFFERENTIALLY UPREGULATED 638 00:28:29,280 --> 00:28:31,880 IN OLD AND DOWNREGULATED IN OLD 639 00:28:31,880 --> 00:28:36,200 DURING UNLOADING RESPONSE 640 00:28:36,200 --> 00:28:39,440 AND@TROPHY RESPONSE LOOKS 641 00:28:39,440 --> 00:28:41,240 SIMILAR AND IS SOMETHING 642 00:28:41,240 --> 00:28:42,760 DIFFERENT WITH THE RESPONSE. 643 00:28:42,760 --> 00:28:45,920 NEXT, LOOKING AT GENES THIS IS 644 00:28:45,920 --> 00:28:49,840 MURF AND GAD45A IS SHOWN TO BE 645 00:28:49,840 --> 00:28:54,120 ACTIVATED WITH MUSCLE ATROPHY 646 00:28:54,120 --> 00:28:57,480 AND MIOGENERALIN AND SEE GENES 647 00:28:57,480 --> 00:28:59,960 ARE UPREGULATED DURING BASELINE 648 00:28:59,960 --> 00:29:01,280 DURING UNLOADING RESPONSE, THEY 649 00:29:01,280 --> 00:29:05,560 GO UP TO A GREATER DEGREE SUCH 650 00:29:05,560 --> 00:29:12,400 AS GAD 45A AND AGENERALINE AND 651 00:29:12,400 --> 00:29:14,240 REMAIN LOADING AND INCREASE 652 00:29:14,240 --> 00:29:15,440 EXPRESSION BEYOND WHAT WAS SEEN 653 00:29:15,440 --> 00:29:17,840 DURING UNLOADING AND IN THE CASE 654 00:29:17,840 --> 00:29:21,680 OF MURF1, WHAT IS INTERESTING IS 655 00:29:21,680 --> 00:29:25,080 IN ADULT ANIMALS, THIS GENE GETS 656 00:29:25,080 --> 00:29:26,920 SUPPRESSED AND USUALLY BELOW 657 00:29:26,920 --> 00:29:30,600 BASELINE AND IN OLDER ANIMALS, 658 00:29:30,600 --> 00:29:35,360 MURF1 IS STAYING ELEVATED AND 659 00:29:35,360 --> 00:29:39,560 INTERFERING WITH REMODELING 660 00:29:39,560 --> 00:29:42,920 PROCESS AND ASSEMBLY OF NEW 661 00:29:42,920 --> 00:29:45,080 SARCOMERES AND WE LOOKED AT 662 00:29:45,080 --> 00:29:48,440 DURING RELOADING PERIOD WHAT IS 663 00:29:48,440 --> 00:29:48,920 DIFFERENT. 664 00:29:48,920 --> 00:29:51,920 HERE I WANT TO SHOW WITH ADULT 665 00:29:51,920 --> 00:29:58,160 AND UNLOADING 83% OF GENES 666 00:29:58,160 --> 00:30:00,160 DIFFERENTIALLY UNREGULATED WITH 667 00:30:00,160 --> 00:30:02,520 LOADING AND RETURN BACK TO 668 00:30:02,520 --> 00:30:03,960 BASELINE WITHIN 3 DAYS AND IN 669 00:30:03,960 --> 00:30:07,560 OLD ANIMALS LESS THAN 64% OR 670 00:30:07,560 --> 00:30:11,280 LESS THAN THE GENES THAT ARE 671 00:30:11,280 --> 00:30:12,360 RETURNED TO BASELINE. 672 00:30:12,360 --> 00:30:17,120 THERE IS A DELAY IN PROCESS THAT 673 00:30:17,120 --> 00:30:21,880 RETURN TO BASELINE IN OLD 674 00:30:21,880 --> 00:30:22,240 ANIMALS. 675 00:30:22,240 --> 00:30:22,960 NEXT. 676 00:30:22,960 --> 00:30:25,000 SOME PROCESSES THAT SEEM DELAYED 677 00:30:25,000 --> 00:30:29,080 IN OLD ANIMALS ARE MITOCHONDRIAL 678 00:30:29,080 --> 00:30:30,960 FUNCTION AND ENERGY GENERATION 679 00:30:30,960 --> 00:30:36,680 AND MIGHT BE A DEFICIENCY IN 680 00:30:36,680 --> 00:30:39,360 BIOENERGETICS THAT COULD INHIBIT 681 00:30:39,360 --> 00:30:42,360 RECOVERY AND DECREASE IN MUSCLE 682 00:30:42,360 --> 00:30:44,840 CONTRACTION AND DEVELOPMENT AND 683 00:30:44,840 --> 00:30:47,120 DECREASE IN PROETEOSOME 684 00:30:47,120 --> 00:30:49,200 CATABOLISM AND THERE IS A 685 00:30:49,200 --> 00:30:51,400 PROTEIN WITH PROTEIN TURNOVER 686 00:30:51,400 --> 00:30:57,480 AND PROTEINSTASIS IN MUSCLES AND 687 00:30:57,480 --> 00:30:59,960 GLUTO THYMINE TRANSFER IN THESE. 688 00:30:59,960 --> 00:31:01,560 >> SORRY TO INTERRUPT. YOU ARE 689 00:31:01,560 --> 00:31:03,360 A FEW MINUTES OVER HERE. 690 00:31:03,360 --> 00:31:06,040 >> OKAY. I'M JUST FINISHING 691 00:31:06,040 --> 00:31:09,160 UP. WE ARE SEEING A DIFFERENCE 692 00:31:09,160 --> 00:31:12,280 AND CHANGE IN PROTEE OESTASIS IN 693 00:31:12,280 --> 00:31:15,840 ANIMALS AND I CAN FINISH UP 694 00:31:15,840 --> 00:31:16,520 HERE, NEXT. 695 00:31:16,520 --> 00:31:19,120 CURRENT KNOWLEDGE GAPS PRIMARY 696 00:31:19,120 --> 00:31:22,400 MECHANISMS UNDERLYING LOSS OF 697 00:31:22,400 --> 00:31:25,000 MUSCLE MASS AND LACK OF RECOVERY 698 00:31:25,000 --> 00:31:27,680 AND ARDS SURVIVORS ARE UNKNOWN 699 00:31:27,680 --> 00:31:30,680 AND AGE AND COMORBIDITIES ARE 700 00:31:30,680 --> 00:31:32,800 LIKELY HAVING MAJOR IMPACT ON 701 00:31:32,800 --> 00:31:35,000 EXTENT OF MUSCLE WASTING AND THE 702 00:31:35,000 --> 00:31:37,960 LACK OF RECOVERY OF MASS AND 703 00:31:37,960 --> 00:31:40,240 STRENGTH HOWEVER THE EFFECTS 704 00:31:40,240 --> 00:31:41,920 HAVE NOT DIRECTLY -- THANK YOU 705 00:31:41,920 --> 00:31:42,760 VERY MUCH. 706 00:31:42,760 --> 00:31:44,920 >> THANK YOU VERY MUCH, SUE, 707 00:31:44,920 --> 00:31:46,640 THAT WAS OUTSTANDING. 708 00:31:46,640 --> 00:31:48,000 WE HAVE SEVERAL QUESTIONS THAT 709 00:31:48,000 --> 00:31:49,560 ARE IN THE CHAT. WE HAVE A 710 00:31:49,560 --> 00:31:54,000 COUPLE OF MINUTES TO ANSWER 711 00:31:54,000 --> 00:31:54,520 THEM. 712 00:31:54,520 --> 00:31:58,000 SO, THIS IS A QUESTION THAT IS 713 00:31:58,000 --> 00:31:59,480 REGARDING SUPPLEMENTATION. ONE 714 00:31:59,480 --> 00:32:03,280 ISSUE THAT CAME UP IS THE 715 00:32:03,280 --> 00:32:04,720 INABILITY TO RECOVER AND YOU 716 00:32:04,720 --> 00:32:07,280 SHOWED US A LOT OF 717 00:32:07,280 --> 00:32:09,280 TRANSCRIPTOMIC CHANGES IN 718 00:32:09,280 --> 00:32:11,320 RECOVERY IN OLD VERSUS IN THE 719 00:32:11,320 --> 00:32:14,360 YOUNG. ONE QUESTION WAS IS THIS 720 00:32:14,360 --> 00:32:16,600 A DIFFERENCE POTENTIALLY IN 721 00:32:16,600 --> 00:32:18,800 PROTEIN INTAKE OR 722 00:32:18,800 --> 00:32:19,960 SUPPLEMENTATION DIETARY 723 00:32:19,960 --> 00:32:22,000 REQUIREMENTS OPPOSED TO 724 00:32:22,000 --> 00:32:25,040 SOMETHING INTRINSIC OR STRESS 725 00:32:25,040 --> 00:32:27,200 RELATED WITHIN THE OLDER MUSCLE 726 00:32:27,200 --> 00:32:28,800 VERSUS YOUNGER MUSCLE? 727 00:32:28,800 --> 00:32:30,280 COULD YOU COMMENT ON THAT A 728 00:32:30,280 --> 00:32:30,800 LITTLE MORE? 729 00:32:30,800 --> 00:32:33,440 >> YEAH. I MEAN, I SUSPECT 730 00:32:33,440 --> 00:32:34,840 THIS IS SOMETHING INTRINSIC TO 731 00:32:34,840 --> 00:32:37,200 THE MUSCLE AND I DON'T -- THESE 732 00:32:37,200 --> 00:32:40,360 ANIMALS ARE NOT ENERGY DEPRIVED 733 00:32:40,360 --> 00:32:43,120 AT ALL. THEIR EATING BEHAVIOR 734 00:32:43,120 --> 00:32:45,200 IS SIMILAR FOOD INTAKE AND THINK 735 00:32:45,200 --> 00:32:46,920 THIS IS SOMETHING INTRINSIC TO 736 00:32:46,920 --> 00:32:49,720 THE OLDER MUSCLE THAT IS 737 00:32:49,720 --> 00:32:53,360 PREVENTING RECOVERY OR 738 00:32:53,360 --> 00:32:55,680 ATTENUATING RECOVERY. 739 00:32:55,680 --> 00:32:57,520 >> THANK YOU VERY MUCH. 740 00:32:57,520 --> 00:32:58,680 ANOTHER QUESTION HERE AT THE 741 00:32:58,680 --> 00:33:00,320 BEGINNING THAT IS QUITE 742 00:33:00,320 --> 00:33:02,360 INTERESTING AND IS FROM JACK AND 743 00:33:02,360 --> 00:33:03,840 YOU DIDN'T SPEAK TO THIS 744 00:33:03,840 --> 00:33:05,000 DIRECTLY. I'M NOT SURE HOW MUCH 745 00:33:05,000 --> 00:33:06,800 OF IT WE CAN DISCUSS HERE. WE 746 00:33:06,800 --> 00:33:10,600 WANT TO KNOW TALKING ABOUT 747 00:33:10,600 --> 00:33:15,080 MUSCLE AS AN IMMUNOLOGICAL 748 00:33:15,080 --> 00:33:19,720 ORGAN. DO WE KNOW TO WHAT 749 00:33:19,720 --> 00:33:22,640 EXTENT MOBILITY PARALYSIS WOULD 750 00:33:22,640 --> 00:33:25,080 ALTER MUSCLES IMMUNOLOGICAL 751 00:33:25,080 --> 00:33:25,720 FUNCTION? 752 00:33:25,720 --> 00:33:26,760 THIS IS SOMETHING YOU SPOKE 753 00:33:26,760 --> 00:33:28,360 ABOUT HERE AND NOT SURE IF YOU 754 00:33:28,360 --> 00:33:29,880 ARE ABLE TO COMMENT ON THAT OR 755 00:33:29,880 --> 00:33:32,360 IF YOU LOOKED AT IT WITHIN YOUR 756 00:33:32,360 --> 00:33:32,560 CELLS. 757 00:33:32,560 --> 00:33:34,320 >> WE DID LOOK AT ACTIVITY 758 00:33:34,320 --> 00:33:37,320 LEVELS IN THE ANIMALS UPON 759 00:33:37,320 --> 00:33:38,840 RECOVERY OR RELOADING AND 760 00:33:38,840 --> 00:33:41,160 THINKING THAT THEY WERE MORE 761 00:33:41,160 --> 00:33:42,480 INACTIVE IN THEIR CAGE. 762 00:33:42,480 --> 00:33:44,120 ACTUALLY, THE FIRST COUPLE OF 763 00:33:44,120 --> 00:33:46,680 DAYS THEY WERE LESS ACTIVE. 764 00:33:46,680 --> 00:33:49,680 OVER THE COURSE OF A WEEK, THEIR 765 00:33:49,680 --> 00:33:51,720 ACTIVELY LEVELS AND OLD ANIMALS 766 00:33:51,720 --> 00:33:54,160 WERE AS ACTIVE IN THEIR KANL AS 767 00:33:54,160 --> 00:33:56,840 YOUNG ANIMALS AND WE ALSO PUT 768 00:33:56,840 --> 00:33:59,960 THEM ON A TREADMILL TO TRY TO 769 00:33:59,960 --> 00:34:01,680 INCREASE A SMALL AMOUNT OF 770 00:34:01,680 --> 00:34:01,960 ACTIVITY. 771 00:34:01,960 --> 00:34:04,720 THEY ARE NOT PARALYZED AND THEY 772 00:34:04,720 --> 00:34:07,520 CAN WALK. 773 00:34:07,520 --> 00:34:10,040 SO, I DON'T THINK THAT THEIR 774 00:34:10,040 --> 00:34:14,040 OVERALL BASELINE ACTIVITY IS THE 775 00:34:14,040 --> 00:34:14,280 PROBLEM. 776 00:34:14,280 --> 00:34:16,280 IT MAY TAKE MORE, YOU KNOW, 777 00:34:16,280 --> 00:34:20,440 LOADING OR ACTIVITY TO ENHANCE 778 00:34:20,440 --> 00:34:25,600 THE RECOVERY IN THESE OLDER 779 00:34:25,600 --> 00:34:25,880 ANIMALS. 780 00:34:25,880 --> 00:34:28,800 THEY ARE NOT PARALYZED IN THAT 781 00:34:28,800 --> 00:34:29,320 REGARD, YEAH. 782 00:34:29,320 --> 00:34:31,560 >> THERE IS A LOT OF QUESTIONS 783 00:34:31,560 --> 00:34:33,360 COMING UP, SUE, IN THE CHAT. 784 00:34:33,360 --> 00:34:35,640 THEY ARE REALLY INTERESTING FOR 785 00:34:35,640 --> 00:34:37,120 LATER AND UNFORTUNATELY WE HAVE 786 00:34:37,120 --> 00:34:39,320 TO MOVE ON TO THE NEXT SPEAKER 787 00:34:39,320 --> 00:34:40,760 AND WILL KEEP TRACK OF THIS AND 788 00:34:40,760 --> 00:34:42,680 BRING IT UP IN THE DISCUSSION. 789 00:34:42,680 --> 00:34:43,880 THANK YOU VERY MUCH. 790 00:34:43,880 --> 00:34:44,640 >> WELCOME. 791 00:34:44,640 --> 00:34:48,440 >> I WOULD LIKE TO INTRODUCE 792 00:34:48,440 --> 00:34:53,240 THE NEXT SPEAKER DR. LARS 793 00:34:53,240 --> 00:34:55,480 LARSON. 794 00:34:55,480 --> 00:35:06,000 -- TO STUDY MUSCLE CONTRACTION 795 00:35:09,320 --> 00:35:11,160 RANGING IN SINGLE UNIT MUSCLE 796 00:35:11,160 --> 00:35:14,200 CELL DOWN TO THE MOTOR PROTEINS 797 00:35:14,200 --> 00:35:16,000 THEMSELVES AND RESEARCH IS 798 00:35:16,000 --> 00:35:18,320 FOCUSED ON DELINEATING 799 00:35:18,320 --> 00:35:20,920 MECHANISMS IMPROVING DIAGNOSTICS 800 00:35:20,920 --> 00:35:23,080 EVALUATING INTERVENTIONS 801 00:35:23,080 --> 00:35:25,600 COMBINING NOVEL EXPERIMENTAL 802 00:35:25,600 --> 00:35:29,560 MODELS WITH CLINICAL STUDIES AND 803 00:35:29,560 --> 00:35:30,200 COLLABORATORS AROUND THE WORLD 804 00:35:30,200 --> 00:35:33,760 AND HE IS CURRENTLY A PROFESSOR 805 00:35:33,760 --> 00:35:36,120 AT INSTITUTE IN SWEDEN AND 806 00:35:36,120 --> 00:35:38,200 DIRECTOR OF MUSCLE BIOLOGY 807 00:35:38,200 --> 00:35:43,960 PROGRAM AT MMI IN BOSTON AND DR. 808 00:35:43,960 --> 00:35:48,680 LARS TALK IS VENTILATOR INDUCED 809 00:35:48,680 --> 00:35:51,200 LUNG INJURY AND ACQUIRED 810 00:35:51,200 --> 00:35:53,920 MIOPATHY IN MODERN CRITICAL 811 00:35:53,920 --> 00:35:54,120 CARE. 812 00:35:54,120 --> 00:35:55,840 >> THANK YOU FOR THE KIND 813 00:35:55,840 --> 00:35:57,320 INTRODUCTION AND INCLUDING IN 814 00:35:57,320 --> 00:35:58,640 THIS INTERESTING WORKSHOP THAT 815 00:35:58,640 --> 00:36:00,240 IS REALLY EXCITING. 816 00:36:00,240 --> 00:36:01,920 CAN WE GO BACK TO THE FIRST 817 00:36:01,920 --> 00:36:02,480 SLIDE? 818 00:36:02,480 --> 00:36:06,000 THIS IS THE ORIGINAL TITLE OF 819 00:36:06,000 --> 00:36:10,800 THE PRESENTATION IN PREMEETING 820 00:36:10,800 --> 00:36:12,320 WE THOUGHT TO TAKE ANOTHER 821 00:36:12,320 --> 00:36:13,560 APPROACH THAT IS PUBLISHED AND 822 00:36:13,560 --> 00:36:15,880 THAT IS INTERESTING AND CAN FIND 823 00:36:15,880 --> 00:36:19,680 IT AND LONGITUDINAL STUDY IN 824 00:36:19,680 --> 00:36:23,480 PATIENTS EXPOSED TO CONTROLLED 825 00:36:23,480 --> 00:36:25,080 MECHANIC INTERVENTION FOR 12 826 00:36:25,080 --> 00:36:28,240 DAYS AND 6 TIMES AND PAIRED 827 00:36:28,240 --> 00:36:30,240 BIOCONTRACTOR MEASUREMENTS AND 828 00:36:30,240 --> 00:36:32,440 THOSE IN-BETWEEN WERE GENE 829 00:36:32,440 --> 00:36:33,880 PROTEIN EXPRESSION AND ALL 830 00:36:33,880 --> 00:36:36,080 PATIENTS DEVELOPED WHAT WE CALL 831 00:36:36,080 --> 00:36:36,520 HALLMARK. 832 00:36:36,520 --> 00:36:39,720 FOR CRITICAL ILLNESS MODEL 833 00:36:39,720 --> 00:36:42,280 PREFERENTIAL LOSS OF MYOSIN. 834 00:36:42,280 --> 00:36:45,880 SEEING PATIENTS THAT DON'T HAVE 835 00:36:45,880 --> 00:36:47,160 THIS CENTRAL RESPIRATORY DRIVE 836 00:36:47,160 --> 00:36:50,360 HAS TO BE VENTILATED IN 837 00:36:50,360 --> 00:36:51,960 CONTROLLED MODE AND SOMETHING TO 838 00:36:51,960 --> 00:36:55,360 AVOID IN GENERAL ICU IT INDUCES 839 00:36:55,360 --> 00:36:58,000 MUCH MORE SEVERE LUNG INJURY AND 840 00:36:58,000 --> 00:36:59,800 THEY PUT THIS NOT SO COMMON 841 00:36:59,800 --> 00:37:04,280 MAYBE 1/3 OF PATIENTS EXPOSED TO 842 00:37:04,280 --> 00:37:06,200 LONG-TERM MECHANICAL 843 00:37:06,200 --> 00:37:08,080 INTERVENTION WITH MYOSIN LOSS 844 00:37:08,080 --> 00:37:12,360 AND THIS HAS A MUCH LESS LUNG 845 00:37:12,360 --> 00:37:12,640 INJURY. 846 00:37:12,640 --> 00:37:15,800 THAT IS IF YOU GO TO THE NEXT 847 00:37:15,800 --> 00:37:17,400 SLIDE, THEN WE SORT OF SWITCHED 848 00:37:17,400 --> 00:37:19,760 TO THE SCOPE OF THIS 849 00:37:19,760 --> 00:37:21,000 PRESENTATION BY FOCUSING ON 850 00:37:21,000 --> 00:37:24,920 WHICH I THINK IS A MAJOR 851 00:37:24,920 --> 00:37:25,760 PATHOPHYSIOLOGICAL FACTOR IN 852 00:37:25,760 --> 00:37:30,680 THIS ACQUIRED MI OP THINK AND 853 00:37:30,680 --> 00:37:33,680 CRITICAL CARE THAT WE CALL 854 00:37:33,680 --> 00:37:37,640 CRITICAL ILLNESS MIOPATHY AND 855 00:37:37,640 --> 00:37:40,200 LOOK AT THIS DISFUNCTION AND 856 00:37:40,200 --> 00:37:43,200 RESEARCH ON THREE DIFFERENT LEGS 857 00:37:43,200 --> 00:37:44,800 IMPROVED DIAGNOSTIC MONITORING 858 00:37:44,800 --> 00:37:47,560 AND MAJOR FOCUS IS ON DIFFERENT 859 00:37:47,560 --> 00:37:48,880 INTERVENTIONS AND SKIPPING OVER 860 00:37:48,880 --> 00:37:52,280 THE MONITORING DIAGNOSIS QUICKLY 861 00:37:52,280 --> 00:37:55,160 AND FOCUS ON MECHANISM 862 00:37:55,160 --> 00:37:55,520 INTERVENTIONS. 863 00:37:55,520 --> 00:37:56,160 NEXT SLIDE. 864 00:37:56,160 --> 00:37:59,360 AS FAR AS I KNOW, THIS IS THE 865 00:37:59,360 --> 00:38:02,200 FIRST PUBLICATION ON THIS 866 00:38:02,200 --> 00:38:09,360 CRITICAL ILLNESS MI MYOPATHY. 867 00:38:09,360 --> 00:38:10,520 CAME TO THE EMERGENCY ROOM AND 868 00:38:10,520 --> 00:38:13,240 HAD TO BE TRANSFER TODAY ICU. 869 00:38:13,240 --> 00:38:15,560 GIVEN MASSIVE DOSES OF STEROIDS 870 00:38:15,560 --> 00:38:18,240 AND HOOKED TO VENTILATOR TO 871 00:38:18,240 --> 00:38:20,320 ENSURE OXYGENATION TO CENTRAL 872 00:38:20,320 --> 00:38:22,720 NERVOUS SYSTEM AND AT THAT TIME 873 00:38:22,720 --> 00:38:23,800 [INDISCERNIBLE] PATIENT WOULD 874 00:38:23,800 --> 00:38:25,880 NOT WORK AGAINST THE VENTILATOR. 875 00:38:25,880 --> 00:38:33,440 WHEN INFECTION WAS CURED AND WE 876 00:38:33,440 --> 00:38:39,000 KNEW PATIENT FROM VENTILATOR WAS 877 00:38:39,000 --> 00:38:42,520 QUADROPLEGIC AND CRANIO FACIAL 878 00:38:42,520 --> 00:38:44,440 MUSCLES WERE IN TACT 879 00:38:44,440 --> 00:38:45,760 COMMUNICATING WITH SPATIAL 880 00:38:45,760 --> 00:38:47,440 FUNCTION AND [INDISCERNIBLE] WAS 881 00:38:47,440 --> 00:38:49,360 IN TACT AND SHE GRADUALLY 882 00:38:49,360 --> 00:38:51,040 RECOVERED AND CONSIDERED TO BE 883 00:38:51,040 --> 00:38:53,280 RARE CONDITION OF CLINICAL 884 00:38:53,280 --> 00:38:55,200 SIGNIFICANCE AND WE KNOW IT IS A 885 00:38:55,200 --> 00:38:57,120 VERY COMMON COURSE OF MUSCLE 886 00:38:57,120 --> 00:38:59,320 PARALYSIS IN THE ICU. 887 00:38:59,320 --> 00:39:01,760 FOR DECADES AND STILL FREQUENTLY 888 00:39:01,760 --> 00:39:07,080 BEING MISDIAGNOSED AS NEUROPATHY 889 00:39:07,080 --> 00:39:07,600 MISINTERPRETATION AND 890 00:39:07,600 --> 00:39:09,200 [INDISCERNIBLE] SIGNALS AND 891 00:39:09,200 --> 00:39:13,880 HEARD THIS IS THE FIRST TIME AND 892 00:39:13,880 --> 00:39:15,320 PROFESSOR AROUND NEUROLOGICAL 893 00:39:15,320 --> 00:39:17,200 CENTER AND HOSPITAL AND IT WAS 894 00:39:17,200 --> 00:39:19,840 AT THIS WAS ABOUT 30 YEARS AGO I 895 00:39:19,840 --> 00:39:24,000 WAS SETTING UP THIS SINGLE CELL 896 00:39:24,000 --> 00:39:27,720 CONTRACTOR MUSCLES IN PATIENTS 897 00:39:27,720 --> 00:39:30,040 WITH DIFFERENT NEUROMUSCULAR 898 00:39:30,040 --> 00:39:32,560 DISORDERS AND SMALL MUSCLE 899 00:39:32,560 --> 00:39:34,560 BIOPSIES AND CAME INTO THE LAB 900 00:39:34,560 --> 00:39:35,200 UNANNOUNCED THIS WOULD BE 901 00:39:35,200 --> 00:39:37,520 PERFECT TECHNIQUE TO STUDY OF 902 00:39:37,520 --> 00:39:38,840 PATIENT AND HE DID SOMETHING 903 00:39:38,840 --> 00:39:40,440 THAT NO ONE ELSE HAD DONE BEFORE 904 00:39:40,440 --> 00:39:44,800 AND TOOK A MUSCLE BIOPSY FROM A 905 00:39:44,800 --> 00:39:50,200 QUADROPLEGIC NEW ICU PATIENT AND 906 00:39:50,200 --> 00:39:53,200 TLIFRED MICROSCOPY AND THERE IS 907 00:39:53,200 --> 00:39:58,800 NO -- THE MOLECULAR MODEL IN THE 908 00:39:58,800 --> 00:40:02,560 SKELETAL MUSCLE. 909 00:40:02,560 --> 00:40:06,800 NEXT SLIDE. 1995 IN CHRISTMAS I 910 00:40:06,800 --> 00:40:09,480 WAS ON CALL AND GOING TO ANOTHER 911 00:40:09,480 --> 00:40:11,400 HOSPITAL TO LOOK AT PATIENT THAT 912 00:40:11,400 --> 00:40:13,800 WAS QUADROPLEGIC AND DIAGNOSIS 913 00:40:13,800 --> 00:40:16,240 AND ATYPICAL [INDISCERNIBLE] OF 914 00:40:16,240 --> 00:40:19,960 ACQUIRED NEUROPATHY AND WENT 915 00:40:19,960 --> 00:40:22,960 THERE AND THESE INDICATOR MOTOR 916 00:40:22,960 --> 00:40:24,360 AXONO PANELY AND REMEMBER WHAT 917 00:40:24,360 --> 00:40:27,000 THEY TOLD ME BEFORE. I TOOK A 918 00:40:27,000 --> 00:40:29,200 MUSCLE BIOPSY FROM THIS PATIENT 919 00:40:29,200 --> 00:40:33,720 AND TO THE LEFT HERE, YOU CAN 920 00:40:33,720 --> 00:40:36,800 SEE MUSCLE CELL FROM A NORMAL OR 921 00:40:36,800 --> 00:40:37,920 CONTROLLED PERSON THAT IS 922 00:40:37,920 --> 00:40:40,040 RELAXING AND THIS IS ACTIVATING 923 00:40:40,040 --> 00:40:42,400 THESE AND THESE CELLS DEVELOP 924 00:40:42,400 --> 00:40:44,240 SAME FORCE AS IN VIVO 925 00:40:44,240 --> 00:40:45,960 PREPARATION THAT IS FROM PATIENT 926 00:40:45,960 --> 00:40:49,200 THAT YOU CAN SEE PATTERNS 927 00:40:49,200 --> 00:40:51,320 LAUNCHED AND THESE DEVELOP 928 00:40:51,320 --> 00:40:52,840 [INDISCERNIBLE] ACTIVATION AND 929 00:40:52,840 --> 00:40:57,880 CELLS THAT LOOK AT EXPRESSION OF 930 00:40:57,880 --> 00:41:02,320 MYOSIN ISOFORMS AND SLOW AND TOO 931 00:41:02,320 --> 00:41:06,720 FAST AND THIS IS IN SLOW MYOSIN 932 00:41:06,720 --> 00:41:09,520 HERE AND WE SEE IT EVERY IT ENTO 933 00:41:09,520 --> 00:41:12,120 20 MUSCLE CELLS AND DIFFERENT 934 00:41:12,120 --> 00:41:15,400 JAIL SYSTEM AND 1, 2, 3 IS FROM 935 00:41:15,400 --> 00:41:18,880 A PATIENT WITH HEMIPLEGIA DUE TO 936 00:41:18,880 --> 00:41:20,720 [INDISCERNIBLE] AND NONPAR ETIC 937 00:41:20,720 --> 00:41:23,680 SIDE WE HAVE FULL EXPRESSION OF 938 00:41:23,680 --> 00:41:27,440 MYOSIN AND MYOSIN ASSOCIATED 939 00:41:27,440 --> 00:41:29,320 PROTEINS AND THERE IS ACTIN AND 940 00:41:29,320 --> 00:41:30,920 REGULATORY PROTEINS THAT ARE 941 00:41:30,920 --> 00:41:34,800 FULLY EXPRESSED. NEXT SLIDE, 942 00:41:34,800 --> 00:41:36,640 PLEASE. 943 00:41:36,640 --> 00:41:40,520 THIS IS AN EM PICTURE FROM 944 00:41:40,520 --> 00:41:42,320 NORMAL MUSCLE SEA LION AND IT 945 00:41:42,320 --> 00:41:46,320 HAD IS FROM PATIENT. SEA LION 946 00:41:46,320 --> 00:41:48,760 SEA LION WITH NO MOTOR PROTEINS 947 00:41:48,760 --> 00:41:51,840 AND NOT SURPRISING THAT PATIENTS 948 00:41:51,840 --> 00:41:54,200 ARE [INDISCERNIBLE]. 949 00:41:54,200 --> 00:41:55,120 NEXT SLIDE. 950 00:41:55,120 --> 00:41:58,080 THIS TIME WE DIDN'T HAVE 951 00:41:58,080 --> 00:41:59,680 SOPHISTICATED METHODS WE HAVE 952 00:41:59,680 --> 00:42:01,440 AVAILABLE NOW AND DEVELOPED IN 953 00:42:01,440 --> 00:42:06,440 THIS SESSION WE CAN LOOK AT 954 00:42:06,440 --> 00:42:09,760 ACTIN AND THREEMYCIN HEAVY 955 00:42:09,760 --> 00:42:14,360 ISOFORMS AND NOT FOR MYOSIN AND 956 00:42:14,360 --> 00:42:16,040 DISEASE THAT DOESN'T SHOW ANY 957 00:42:16,040 --> 00:42:18,720 NEITHER SLOW OR FAST MYOSIN IN 958 00:42:18,720 --> 00:42:21,560 MUSCLES AND WE HAVE PROTEIN 959 00:42:21,560 --> 00:42:23,200 SYNTHESIS IN PATIENTS. 960 00:42:23,200 --> 00:42:23,880 NEXT SLIDE. 961 00:42:23,880 --> 00:42:26,600 THIS IS JUST SHOWING A PATIENT 962 00:42:26,600 --> 00:42:28,920 FROM WHOM WE HAVE A BIOPSY ONE 963 00:42:28,920 --> 00:42:31,720 MONTH BEFORE WE WENT INTO THE 964 00:42:31,720 --> 00:42:35,640 ICU AND THEY BECOME QUADROPLEGIC 965 00:42:35,640 --> 00:42:39,120 WE HAVE MYOSIN AND NORMAL 966 00:42:39,120 --> 00:42:42,000 RECOVERY AND SURVIVED MYOCORDIAL 967 00:42:42,000 --> 00:42:43,880 FUNCTION DURING THIS TIME 968 00:42:43,880 --> 00:42:44,360 PERIOD. 969 00:42:44,360 --> 00:42:47,320 THIS IS -- WE HAVE ACTUALLY SEEN 970 00:42:47,320 --> 00:42:49,760 ONE PATIENT FROM WHOM BIOPSY WAS 971 00:42:49,760 --> 00:42:54,080 TAKEN PRIOR TO GOING INTO ICU. 972 00:42:54,080 --> 00:42:58,120 THEY BOTH HAVE SOME SORT OF 973 00:42:58,120 --> 00:43:00,000 IMMUNOLOGICAL DISORDER THAT IS 974 00:43:00,000 --> 00:43:01,440 UNCHARACTERIZED AND WE PROBABLY 975 00:43:01,440 --> 00:43:03,280 NEED SOMETHING AND DON'T KNOW 976 00:43:03,280 --> 00:43:07,840 WHAT. ANYWAY, IF YOU SURVIVE A 977 00:43:07,840 --> 00:43:11,280 PRIMARY STEEZ, NEXT SLIDE, 978 00:43:11,280 --> 00:43:11,840 PLEASE. 979 00:43:11,840 --> 00:43:15,840 THIS IS SHOWING REEXPIRATION OF 980 00:43:15,840 --> 00:43:18,280 4TH GENERATION CAPACITY AND 981 00:43:18,280 --> 00:43:19,440 UPREGULATION AND EXPRESSION OF 982 00:43:19,440 --> 00:43:22,520 MY FAVORITE PROTEINS. 983 00:43:22,520 --> 00:43:23,320 NEXT SLIDE. 984 00:43:23,320 --> 00:43:27,360 SO, FACTORS THAT HAVE BEEN TO BE 985 00:43:27,360 --> 00:43:30,320 SEPSIS BROKERS AND STEROIDS AND 986 00:43:30,320 --> 00:43:32,800 SEE THIS MYOPATHY IN PATIENTS 987 00:43:32,800 --> 00:43:35,480 WITHOUT ANY OF THESE FACTORS AND 988 00:43:35,480 --> 00:43:38,360 ARE LIKE YESTERDAY IN FIRE MAKES 989 00:43:38,360 --> 00:43:40,200 THINGS WORSE AND ONLY THING THAT 990 00:43:40,200 --> 00:43:42,080 PATIENTS HAVE IN COMMON WITH 991 00:43:42,080 --> 00:43:45,560 THIS CRITICAL ILLNESS MYOPANELY 992 00:43:45,560 --> 00:43:49,040 WITH MYOSIN IS LONG-TERM 993 00:43:49,040 --> 00:43:50,320 MECHANICAL VENTILATION AND 994 00:43:50,320 --> 00:43:52,160 COMPLETE IMMOBILIZATION THAT WE 995 00:43:52,160 --> 00:43:54,400 CALL MECHANICAL SILENCING 996 00:43:54,400 --> 00:43:57,840 MEANING NO WEIGHT BEARING AND NO 997 00:43:57,840 --> 00:43:59,640 INTERNAL STRAIN RELATING 998 00:43:59,640 --> 00:44:01,120 ACTIVATION CONTRACTING TO 999 00:44:01,120 --> 00:44:04,680 PROTEINS THAT IS UNIQUE FOR ICU 1000 00:44:04,680 --> 00:44:06,680 PATIENTS BEING PARALYZED 1001 00:44:06,680 --> 00:44:09,400 [INDISCERNIBLE] OR 1002 00:44:09,400 --> 00:44:09,800 [INDISCERNIBLE]. 1003 00:44:09,800 --> 00:44:13,840 NEXT SLIDE. NEXT SLIDE 1004 00:44:13,840 --> 00:44:14,360 UNDERSTANDING MECHANISMS 1005 00:44:14,360 --> 00:44:15,760 IMPORTANT TO GO INTO 1006 00:44:15,760 --> 00:44:17,840 EXPERIMENTAL ANIMAL MODEL. NEXT 1007 00:44:17,840 --> 00:44:19,680 SLIDE. SO MANY CONFOUNDING 1008 00:44:19,680 --> 00:44:23,200 FACTORS IN ICU PATIENTS STARTING 1009 00:44:23,200 --> 00:44:27,040 WITH THIS PORESINE MODEL AND 1010 00:44:27,040 --> 00:44:30,720 THEY WERE IMPORTANT FACTORS AND 1011 00:44:30,720 --> 00:44:33,640 WE EXPOSED THESE PIGS DURING 5 1012 00:44:33,640 --> 00:44:35,360 DAYS TO [INDISCERNIBLE] OF 1013 00:44:35,360 --> 00:44:40,240 COURSE AND MECHANICAL 1014 00:44:40,240 --> 00:44:40,560 VENTILATED. 1015 00:44:40,560 --> 00:44:43,720 WITH NEUROMUSCULAR BROKERS AND 1016 00:44:43,720 --> 00:44:50,920 IN 5 DAYS DON'T SEE MUSS MUSCLE 1017 00:44:50,920 --> 00:44:52,480 ATROPHY. 1018 00:44:52,480 --> 00:44:54,120 WE DON'T SEE A SIGNIFICANT DROP 1019 00:44:54,120 --> 00:44:56,720 HERE IN THE GROUPS AND WHEN WE 1020 00:44:56,720 --> 00:44:59,720 START TO ADD COURTI CO STEROIDS 1021 00:44:59,720 --> 00:45:03,160 AND SEPSIS COMBINED WE SEE 1022 00:45:03,160 --> 00:45:05,520 SIGNIFICANT DROP IN THESE AND 1023 00:45:05,520 --> 00:45:09,760 SHOW [INDISCERNIBLE] ACTS DUE TO 1024 00:45:09,760 --> 00:45:12,440 DEEP MUSCLE MEMBRANE 1025 00:45:12,440 --> 00:45:15,640 EXCITABILITY AND OFTEN MOTOR 1026 00:45:15,640 --> 00:45:19,960 AXON LOSS AND [INDISCERNIBLE] AT 1027 00:45:19,960 --> 00:45:22,440 THAT TIME TO DO THIS LOOKING AT 1028 00:45:22,440 --> 00:45:24,840 GENES EXPRESSING ROUTES AND PIGS 1029 00:45:24,840 --> 00:45:27,040 AND THESE ARE ROUTES SEEING NO 1030 00:45:27,040 --> 00:45:30,400 CHANGE IN MUSCLE FIBER SIZE OR 1031 00:45:30,400 --> 00:45:33,240 FOR GENERATING CAPACITY AND SOME 1032 00:45:33,240 --> 00:45:35,520 OF THE GENES WEPT UP AND DOWN 1033 00:45:35,520 --> 00:45:37,000 SIGNIFICANTLY THAT TO ME WAS A 1034 00:45:37,000 --> 00:45:39,920 LITTLE OVERSURPRISED AND THERE 1035 00:45:39,920 --> 00:45:41,960 WAS ALSO PROTECTIVE MECHANISMS 1036 00:45:41,960 --> 00:45:44,800 AND REASON WE DON'T WAIT UP 1037 00:45:44,800 --> 00:45:46,760 AFTER LONG NICE SLEEP WITH 1038 00:45:46,760 --> 00:45:50,960 MUSCLE WASTING AND WHY 1039 00:45:50,960 --> 00:45:54,040 HIBERNATING IN SPRING COMES UP 1040 00:45:54,040 --> 00:45:55,720 WITH WELL FUNCTIONING MUSCLES 1041 00:45:55,720 --> 00:45:58,440 AND HAVING COMPROMISED FUNCTION 1042 00:45:58,440 --> 00:46:01,560 YOU COULD SEE THERE WERE 1043 00:46:01,560 --> 00:46:07,720 DIFFERENCES AND FUNCTION WAS 1044 00:46:07,720 --> 00:46:08,080 COMPROMISED. 1045 00:46:08,080 --> 00:46:09,920 >> YOU HAVE FIVE MINUTES 1046 00:46:09,920 --> 00:46:10,240 REMAINING. 1047 00:46:10,240 --> 00:46:12,280 >> WOW. I BETTER SPEED UP 1048 00:46:12,280 --> 00:46:14,280 THEN. WE CAN SKIP OVER THIS 1049 00:46:14,280 --> 00:46:14,640 ONE. 1050 00:46:14,640 --> 00:46:17,280 LOOKING AT ANOTHER MUSCLE THAT 1051 00:46:17,280 --> 00:46:19,160 IS VENTLATORY MUSCLE AND 1052 00:46:19,160 --> 00:46:20,680 DIAPHRAGM THAT IS MUSCLE AND 1053 00:46:20,680 --> 00:46:22,120 VERY INTERESTED IN. 1054 00:46:22,120 --> 00:46:25,480 IT TERMS HOW QUICKLY WE CAN WEEN 1055 00:46:25,480 --> 00:46:27,160 PATIENT OFF VENTILATOR AND HERE 1056 00:46:27,160 --> 00:46:30,080 THE SITUATION IS COMPLETELY 1057 00:46:30,080 --> 00:46:30,400 DIFFERENT. 1058 00:46:30,400 --> 00:46:33,880 THOSE ARE CONTROLS AND OTHERS 1059 00:46:33,880 --> 00:46:35,000 WITH DIFFERENT INTERVENTION AND 1060 00:46:35,000 --> 00:46:38,400 ONLY COMMON DENOMINATOR HERE IS 1061 00:46:38,400 --> 00:46:39,000 MECHANICAL VENTILATION. 1062 00:46:39,000 --> 00:46:40,080 NEXT SLIDE. 1063 00:46:40,080 --> 00:46:41,920 WE WENT INTO DIFFERENT MODELS 1064 00:46:41,920 --> 00:46:45,720 THAT IS RODENT MODEL KEEPING 1065 00:46:45,720 --> 00:46:49,400 MECHANICAL VENTILATED AND 1066 00:46:49,400 --> 00:46:52,520 DENSELY MONITORED AND THIS IS BY 1067 00:46:52,520 --> 00:46:54,800 PROFESSOR ROCKEFELLER. NEXT 1068 00:46:54,800 --> 00:46:55,360 SLIDE. 1069 00:46:55,360 --> 00:46:58,600 THESE ARE TO BE MONITORED FROM 1070 00:46:58,600 --> 00:47:00,880 C02 AND [INDISCERNIBLE] GAS AND 1071 00:47:00,880 --> 00:47:03,640 EEG AND PRESSURE IN VENTLATORY 1072 00:47:03,640 --> 00:47:06,480 SYSTEM AND ECG MATERIAL AND 1073 00:47:06,480 --> 00:47:09,760 THESE ARE INVENOUS PRESSURE AND 1074 00:47:09,760 --> 00:47:11,640 MEASURE SATURATION AND 1075 00:47:11,640 --> 00:47:15,120 OXYGENATION IN LENS AND IN URINE 1076 00:47:15,120 --> 00:47:15,520 PRODUCTION. 1077 00:47:15,520 --> 00:47:16,840 NEXT SLIDE. 1078 00:47:16,840 --> 00:47:20,000 THESE WHEN EXPOSED TO LONG-TERM 1079 00:47:20,000 --> 00:47:22,920 MECHANICAL VENTILATION AND UP TO 1080 00:47:22,920 --> 00:47:27,200 THREE WEEKS LOOSE MYOSIN@TROPHY 1081 00:47:27,200 --> 00:47:29,800 AND 4TH GENERATION CAPACITY. 1082 00:47:29,800 --> 00:47:32,440 NEXT SLIDE. 1083 00:47:32,440 --> 00:47:35,480 MYOSIN IS FASTER MUSCLE AND 1084 00:47:35,480 --> 00:47:36,640 TRANSCRIPTION DOWNREGULATION 1085 00:47:36,640 --> 00:47:38,840 CONTRACTING PROTEINS AND LOOKING 1086 00:47:38,840 --> 00:47:41,080 ON EXPRESSION OF DIFFERENT 1087 00:47:41,080 --> 00:47:42,960 PROTEIN AGGRAVATION PATHWAYS 1088 00:47:42,960 --> 00:47:45,800 OVER TIME. 1089 00:47:45,800 --> 00:47:48,720 NEXT SLIDE. AGAIN, CRANIO 1090 00:47:48,720 --> 00:47:50,520 FACIAL MUSCLES IN LIMB MUSCLES 1091 00:47:50,520 --> 00:47:53,280 SEEING IN PATIENTS AND NEXT 1092 00:47:53,280 --> 00:47:54,160 SLIDE. 1093 00:47:54,160 --> 00:47:56,160 DIAPHRAGM WE SEE A DIFFERENT 1094 00:47:56,160 --> 00:47:59,320 PATTERN AND AS I SAID BEFORE, 1095 00:47:59,320 --> 00:48:01,760 DIAPHRAGM FUVENLGS DETERMINES 1096 00:48:01,760 --> 00:48:03,240 HOW QUICKLY WE CAN WEEN PATIENTS 1097 00:48:03,240 --> 00:48:06,160 OFF THE VENTILATOR AND 40% OF 1098 00:48:06,160 --> 00:48:09,040 TIME ON VENTILATOR IS WEENING 1099 00:48:09,040 --> 00:48:11,440 FROM THE VENTILATOR. 1100 00:48:11,440 --> 00:48:13,680 PATIENTS COST $64 PL IN US PRIOR 1101 00:48:13,680 --> 00:48:16,120 TO PANDEMIC. YOU CAN PROBE 1102 00:48:16,120 --> 00:48:18,840 SIGNIFICANT FACTORS DURING THE 1103 00:48:18,840 --> 00:48:19,080 PANDEMIC. 1104 00:48:19,080 --> 00:48:20,160 NEXT SLIDE. 1105 00:48:20,160 --> 00:48:23,520 IN THE DIAPHRAGM MUSCLE CELLS WE 1106 00:48:23,520 --> 00:48:26,200 SEE SAME THING, ATROPHIED AND 1107 00:48:26,200 --> 00:48:28,360 LOSS IN SPECIFIC [INDISCERNIBLE] 1108 00:48:28,360 --> 00:48:31,360 AND NO TRANSCRIPTION AND 1109 00:48:31,360 --> 00:48:31,720 DOWNREGULATION. 1110 00:48:31,720 --> 00:48:32,600 NEXT SLIDE. 1111 00:48:32,600 --> 00:48:34,400 THERE IS A DIFFERENT MECHANISM 1112 00:48:34,400 --> 00:48:38,560 HERE. IT IS MODIFICATIONS OF 1113 00:48:38,560 --> 00:48:40,880 MYOSIN THAT ARE VERY DIFFERENT 1114 00:48:40,880 --> 00:48:43,240 TECHNIQUES THEN. 1115 00:48:43,240 --> 00:48:48,000 NEXT SLIDE. I THINK THIS GETS 1116 00:48:48,000 --> 00:48:51,680 DIAGNOSTIC AND INTERVENTIONS AND 1117 00:48:51,680 --> 00:48:53,680 NEXT SLIDE. 1118 00:48:53,680 --> 00:48:55,960 WE LOOK AT DIFFERENT TYPES OF 1119 00:48:55,960 --> 00:49:01,160 INTERVENTION TARGETING MUSCLE 1120 00:49:01,160 --> 00:49:05,040 SILENCING AND LUNG INJURY. NEXT 1121 00:49:05,040 --> 00:49:09,400 SLIDE STARTED WITH SMALL 1122 00:49:09,400 --> 00:49:12,400 MOLECULE AND PROTEIN UPREGULATOR 1123 00:49:12,400 --> 00:49:13,640 AND MULTIPLE OTHER FUNCTIONS. 1124 00:49:13,640 --> 00:49:15,480 NEXT SLIDE. 1125 00:49:15,480 --> 00:49:18,120 WHAT WE CAN SEE THEN IS IF I 1126 00:49:18,120 --> 00:49:20,280 SIZE THEM DOWN SHOWN BEFORE AND 1127 00:49:20,280 --> 00:49:24,440 10 DAYS REPEATED WITH BP FIFTEEN 1128 00:49:24,440 --> 00:49:26,240 THAT IS IN DIAPHRAGM AND FORCE 1129 00:49:26,240 --> 00:49:28,640 THE GENERATION CAPACITY WAS 1130 00:49:28,640 --> 00:49:30,920 ALMOST DOUBLED. NEXT SLIDE. 1131 00:49:30,920 --> 00:49:33,960 PULLING OUT MYOSIN FROM SINGLE 1132 00:49:33,960 --> 00:49:36,280 CELLS AND ACTUALLY 4TH GENERATED 1133 00:49:36,280 --> 00:49:39,680 BY MYOSIN AND SAME THING AS 1134 00:49:39,680 --> 00:49:44,200 MOTOR PROTEIN LEVEL AND CELLULAR 1135 00:49:44,200 --> 00:49:45,920 LEVEL. NEXT SLIDE. 1136 00:49:45,920 --> 00:49:47,520 THESE ARE RELATION AND ALSO MANY 1137 00:49:47,520 --> 00:49:50,960 OTHER MONTHED FICTIONS. 1138 00:49:50,960 --> 00:49:53,080 NEXT SLIDE. 1139 00:49:53,080 --> 00:49:55,400 WE HAD A SIDE EFFECTS THAT WAS 1140 00:49:55,400 --> 00:49:57,120 IMPROVED SURVIVAL AND WE ARE NOT 1141 00:49:57,120 --> 00:50:01,040 QUICK ENOUGH TO REMOVE A MUCUS 1142 00:50:01,040 --> 00:50:03,400 PLUG AND HAVE ZERO MORTALITY AND 1143 00:50:03,400 --> 00:50:05,920 WITHOUT INTERVENTION, MORE THAN 1144 00:50:05,920 --> 00:50:06,840 60% OF [INDISCERNIBLE]. WE 1145 00:50:06,840 --> 00:50:08,800 DON'T KNOW WHY. THIS IS A SIDE 1146 00:50:08,800 --> 00:50:11,280 EFFECT WE CAN ACCEPT. 1147 00:50:11,280 --> 00:50:14,200 NEXT SLIDE. 1148 00:50:14,200 --> 00:50:20,040 WE TESTED BONE MARROW DERIVED 1149 00:50:20,040 --> 00:50:22,760 MESEN CHIMIAL STROMAL CELLS. 1150 00:50:22,760 --> 00:50:27,440 IT ALSO INCREASES DIAPHRAGM 1151 00:50:27,440 --> 00:50:29,960 MUSCLE CELL AND [INDISCERNIBLE] 1152 00:50:29,960 --> 00:50:32,120 LUNG INJURY AND HAS POSITIVE 1153 00:50:32,120 --> 00:50:35,400 EFFECT ON METABOLIZED 1154 00:50:35,400 --> 00:50:38,240 GENEGRESSION AND PROTEOMIC CELL. 1155 00:50:38,240 --> 00:50:40,160 NEXT SLIDE. TARGETING MUSCLE 1156 00:50:40,160 --> 00:50:43,760 CELL AND MECHANICAL SILENCING IS 1157 00:50:43,760 --> 00:50:46,800 ANECDOTAL OBSERVATION THAT IS 6 1158 00:50:46,800 --> 00:50:48,840 YEAR OLD BOY AND POST MORTAL 1159 00:50:48,840 --> 00:50:52,120 BIOPSY AND MUSCLE CELLS THAT 1160 00:50:52,120 --> 00:50:54,280 EXPRESS MYOSIN THAT ARE 1161 00:50:54,280 --> 00:50:56,680 INTERFUSED MUSCLE CELLS IN 1162 00:50:56,680 --> 00:50:58,320 MUSCLE SKIN AND SENSES AND 1163 00:50:58,320 --> 00:51:00,480 LENGTH CHANGES IN MUSCLE AND 1164 00:51:00,480 --> 00:51:05,400 CELLS ARE EXTRA FUELS OF FIBERS 1165 00:51:05,400 --> 00:51:07,560 SEVERELY TROPHIC MYOSIN WITH 1166 00:51:07,560 --> 00:51:09,240 THIS SIZE AND WHAT IS 1167 00:51:09,240 --> 00:51:12,360 DIFFERENCE? MECHANICAL LOADING 1168 00:51:12,360 --> 00:51:16,920 CELLS ON CONSTANT TENSION -- 1169 00:51:16,920 --> 00:51:18,920 IMPORTANT ROLE AND MUSCLE CELLS 1170 00:51:18,920 --> 00:51:23,120 ARE EXTREME IN CANCER SENSITIVE. 1171 00:51:23,120 --> 00:51:25,520 NEXT SLIDE. DOING SIMPLE 1172 00:51:25,520 --> 00:51:27,560 EXPERIMENTS MECHANICAL LOADING 1173 00:51:27,560 --> 00:51:30,440 AND SEEING RESTORATION ON MUSCLE 1174 00:51:30,440 --> 00:51:33,880 SIZE AND 4TH GENERATING CAPACITY 1175 00:51:33,880 --> 00:51:36,240 AND SAME THING WITH RESTORED 1176 00:51:36,240 --> 00:51:36,920 MUSCLE SIZE. 1177 00:51:36,920 --> 00:51:38,680 NEXT SLIDE. ELECTRICAL 1178 00:51:38,680 --> 00:51:40,240 STIMULATION AND SIMILAR EFFECT 1179 00:51:40,240 --> 00:51:42,680 THAT IS NOT AS DRAMATIC AS WE 1180 00:51:42,680 --> 00:51:45,640 HAD EXPECTED. NEXT SLIDE. 1181 00:51:45,640 --> 00:51:46,800 REMARKABLE OBSERVATION THOUGH. 1182 00:51:46,800 --> 00:51:51,760 WE COULD SEE THAT GLUTE4 1183 00:51:51,760 --> 00:51:54,880 SIGNALING IS EFFECTIVE IN ROUTES 1184 00:51:54,880 --> 00:51:58,000 CONTROL 8 DAYS IN COMPLETELY 1185 00:51:58,000 --> 00:52:02,640 IMMOBILE ROUTE AND DEPLETED 1186 00:52:02,640 --> 00:52:05,560 GLYCOGEN AND -- GLYCOGEN LEVELS 1187 00:52:05,560 --> 00:52:08,080 INCREASED IN CONTRALA THORRAL 1188 00:52:08,080 --> 00:52:11,040 SIDE THAT WAS NOT STIMULATED. 1189 00:52:11,040 --> 00:52:14,120 NEXT SLIDE. 1190 00:52:14,120 --> 00:52:16,920 EXPERIMENTS WE DID LONG TYPE AGO 1191 00:52:16,920 --> 00:52:17,720 LOOKING AT SPATIAL 1192 00:52:17,720 --> 00:52:20,320 [INDISCERNIBLE] AND EFFECTIVE BY 1193 00:52:20,320 --> 00:52:21,920 AGING AND SLOW MUSCLE BEING ABLE 1194 00:52:21,920 --> 00:52:24,840 TO DO THIS IDENTIFYING 1195 00:52:24,840 --> 00:52:27,040 [INDISCERNIBLE] VENTRAL ROOT AND 1196 00:52:27,040 --> 00:52:29,480 YOU ONLY HAVE ONE MOTOR NEURON 1197 00:52:29,480 --> 00:52:32,800 GOING TO MUSCLE AND STIMULATE IT 1198 00:52:32,800 --> 00:52:36,000 100 HERTZ 20 MILLISECOND UNTIL 4 1199 00:52:36,000 --> 00:52:37,320 STOPS -- THAT DOESN'T HAPPEN IN 1200 00:52:37,320 --> 00:52:39,880 THE CELL AND YOU HAVE TO MAKE 1201 00:52:39,880 --> 00:52:43,320 ITIS CHEEMIC AND THAT HAPPENED 1202 00:52:43,320 --> 00:52:45,960 AND IDENTIFY THESE CELLS AND IF 1203 00:52:45,960 --> 00:52:47,680 THIS CASE COMPLETELY DIFFERENT 1204 00:52:47,680 --> 00:52:47,920 STORY. 1205 00:52:47,920 --> 00:52:51,720 NO ACTIVATION AT ALL. NEXT 1206 00:52:51,720 --> 00:52:51,920 SLIDE. 1207 00:52:51,920 --> 00:52:53,040 >> [INDISCERNIBLE]. 1208 00:52:53,040 --> 00:52:54,920 >> YUP. ALMOST DONE. 1209 00:52:54,920 --> 00:52:57,440 WE SEE GLUTE FORCING SIGNAL 1210 00:52:57,440 --> 00:53:00,200 EFFECTIVE. NEXT SLIDE. 1211 00:53:00,200 --> 00:53:03,680 ALSO, WITH MECHANICAL LOADING WE 1212 00:53:03,680 --> 00:53:06,000 SEE SAME THING, CROSSOVER 1213 00:53:06,000 --> 00:53:08,440 EFFECTS. NEXT SLIDE. 1214 00:53:08,440 --> 00:53:11,440 NEUROMUSCULAR JUNCTION ADDITION 1215 00:53:11,440 --> 00:53:13,960 AND PRODUCING ACTUAL OUTGROWTH 1216 00:53:13,960 --> 00:53:16,280 IN THE STIMULATED UNSTIMULATED 1217 00:53:16,280 --> 00:53:19,880 SIDE THAT IS AT GENE LEVEL. 1218 00:53:19,880 --> 00:53:20,680 NEXT SLIDE. 1219 00:53:20,680 --> 00:53:25,000 WE CAN SEE THIS IS RELATED ALSO 1220 00:53:25,000 --> 00:53:30,840 TO -- I MEAN MORE THAN 6 FICHLT 1221 00:53:30,840 --> 00:53:32,960 -- WE TRIED TO LOOK AT 1222 00:53:32,960 --> 00:53:37,600 EXPRESSION OF MYOKINDS THAT ARE 1223 00:53:37,600 --> 00:53:40,840 DOWNREGULATED AND LOW BUT 1224 00:53:40,840 --> 00:53:44,640 INCREASED RESPONSE TO MECHANICAL 1225 00:53:44,640 --> 00:53:47,800 ELECTRICAL STIMULATION THAT IS 1226 00:53:47,800 --> 00:53:56,640 AS WELL AS IN [INDISCERNIBLE]. 1227 00:53:56,640 --> 00:53:58,640 NEXT SLIDE. I WILL SKIP OVER IT 1228 00:53:58,640 --> 00:54:00,960 AND COME TO THE CONCLUGS. 1229 00:54:00,960 --> 00:54:01,160 NEXT. 1230 00:54:01,160 --> 00:54:03,360 THERE IS NO MUSCLE THAT IS 1231 00:54:03,360 --> 00:54:03,680 EFFECTED. 1232 00:54:03,680 --> 00:54:05,680 NEXT SLIDE. 1233 00:54:05,680 --> 00:54:09,120 ALSO BONE. BONE LOSS AND 1234 00:54:09,120 --> 00:54:11,480 REDUCING STRENGTH TO BONE. 1235 00:54:11,480 --> 00:54:12,400 NEXT SLIDE. 1236 00:54:12,400 --> 00:54:17,000 I LOOK AT LEVEL AND THERE IS 1237 00:54:17,000 --> 00:54:18,440 GLYCOGEN LIVER OVER TIME AND 1238 00:54:18,440 --> 00:54:20,800 AFTER 8 DAYS ELECTRICAL 1239 00:54:20,800 --> 00:54:23,080 STIMULATION AND ONE MUSCLE AND 1240 00:54:23,080 --> 00:54:26,760 ONE LIMB ACTUALLY INCREASES 1241 00:54:26,760 --> 00:54:31,120 GLYCOGEN LEVEL IN THE LIVER. WE 1242 00:54:31,120 --> 00:54:35,080 THINK WE HAVE LUNG INJURY 1243 00:54:35,080 --> 00:54:38,880 INDUCED BY -- PERIPHERAL ORGANS 1244 00:54:38,880 --> 00:54:40,520 INTERACTS WITH OTHER ORGANS AND 1245 00:54:40,520 --> 00:54:42,560 NEXT SLIDE. DOING RIGHT NOW 1246 00:54:42,560 --> 00:54:46,120 TRYING TO -- NEXT SLIDE. 1247 00:54:46,120 --> 00:54:49,040 LOOKING AT SINGLE CELL RNA SEEK 1248 00:54:49,040 --> 00:54:52,360 IN MUSCLE BIOPSY AND MUSCLE 1249 00:54:52,360 --> 00:54:55,000 CELLS AND OTHER CELLS THAT 1250 00:54:55,000 --> 00:54:55,680 INTERACT ALSO. 1251 00:54:55,680 --> 00:54:58,160 NEXT SLIDE. TRYING TO 1252 00:54:58,160 --> 00:54:59,520 UNDERSTAND CROSSOVER EFFECT 1253 00:54:59,520 --> 00:55:00,560 BETTER. NEXT SLIDE. 1254 00:55:00,560 --> 00:55:05,400 WE TRY TO DO THIS BY USING ORGAN 1255 00:55:05,400 --> 00:55:07,440 CROSS-TOOL IN MICRO FLUID 1256 00:55:07,440 --> 00:55:08,560 [INDISCERNIBLE]. NEXT SLIDE. 1257 00:55:08,560 --> 00:55:09,760 THESE ARE PEOPLE TO THANK. THEY 1258 00:55:09,760 --> 00:55:12,880 HAVE BEEN WORKING IN LAB. NEXT 1259 00:55:12,880 --> 00:55:14,520 SLIDE. 1260 00:55:14,520 --> 00:55:17,400 OUR COLLABORATORS AND THANK YOU 1261 00:55:17,400 --> 00:55:19,240 FOR YOUR ATTENTION. 1262 00:55:19,240 --> 00:55:25,040 >> THANKS SO MUCH, DR. LARSON. 1263 00:55:25,040 --> 00:55:26,520 AMAZING BODY OF WORK IN 1264 00:55:26,520 --> 00:55:29,840 PRECLINICAL AND HUMAN STUDIES 1265 00:55:29,840 --> 00:55:30,200 HERE. 1266 00:55:30,200 --> 00:55:31,680 SO MUCH TO DISCUSS AND LOTS OF 1267 00:55:31,680 --> 00:55:34,080 GREAT QUESTIONS IN THE CHAT. I 1268 00:55:34,080 --> 00:55:37,200 THINK WE ARE AT OUR 20 MINUTES 1269 00:55:37,200 --> 00:55:37,640 HERE. 1270 00:55:37,640 --> 00:55:39,440 SO, MAYBE WHAT WE CAN DO IS 1271 00:55:39,440 --> 00:55:41,720 ADDRESS SOME OF THE QUESTIONS IF 1272 00:55:41,720 --> 00:55:44,680 IN OUR PANEL DISCUSSION THAT 1273 00:55:44,680 --> 00:55:47,880 STARTS AT 11:15. 1274 00:55:47,880 --> 00:55:50,720 KEEPING US ON TRACK HERE, I WILL 1275 00:55:50,720 --> 00:55:53,600 MOVE TOWARDS THE NEXT SPEAKER. 1276 00:55:53,600 --> 00:55:56,440 I WOULD LIKE TO INTRODUCE DR. 1277 00:55:56,440 --> 00:56:00,880 JASON DOLES. DR. DOLES IS AN 1278 00:56:00,880 --> 00:56:02,840 ASSOCIATE PROFESSOR AND VICE 1279 00:56:02,840 --> 00:56:05,080 CHAIR FOR DIVERSITY, EBBING 1280 00:56:05,080 --> 00:56:07,000 WITHIT AND INCLUSION IN 1281 00:56:07,000 --> 00:56:09,240 DEPARTMENT OF ANATOMY CELL 1282 00:56:09,240 --> 00:56:13,400 BIOLOGY AND PHYSIOLOGY AT 1283 00:56:13,400 --> 00:56:17,000 INDIANA SCHOOL OF MEDICINE AND 1284 00:56:17,000 --> 00:56:21,160 -- AND PHD IF IN BIOLOGY FROM 1285 00:56:21,160 --> 00:56:24,120 MIT. HIS RESEARCH PROGRAM 1286 00:56:24,120 --> 00:56:29,160 CENTERS AROUND THREE MAIN THEMES 1287 00:56:29,160 --> 00:56:33,080 CANCER COCK EXIA LAB USED 1288 00:56:33,080 --> 00:56:36,640 VARIETY OF CELL BASED MODELS AND 1289 00:56:36,640 --> 00:56:38,480 MODEL -- SPANNING BASIC 1290 00:56:38,480 --> 00:56:40,480 DISCOVERY TO PRECLINICAL 1291 00:56:40,480 --> 00:56:41,320 TRANSLATIONAL STUDIES. 1292 00:56:41,320 --> 00:56:45,000 DR. DOLES TALK IS ENTITLED A 1293 00:56:45,000 --> 00:56:48,080 ROLE FOR MUSCLE STEM CELLS IN 1294 00:56:48,080 --> 00:56:49,960 LONG-TERM TISSUE REPOLICING AND 1295 00:56:49,960 --> 00:56:52,440 RECOVERY FOLLOWING SURGICAL 1296 00:56:52,440 --> 00:56:52,760 SEPSIS. 1297 00:56:52,760 --> 00:56:54,480 DR. DOLES. 1298 00:56:54,480 --> 00:56:57,320 >> THANK YOU. CAN YOU HEAR ME, 1299 00:56:57,320 --> 00:56:57,560 CLARK. 1300 00:56:57,560 --> 00:56:58,000 >> YES. 1301 00:56:58,000 --> 00:56:59,120 >> WE GOOD? 1302 00:56:59,120 --> 00:56:59,680 >> YES. 1303 00:56:59,680 --> 00:57:02,000 >> THANK YOU TO ORGANIZERS AND 1304 00:57:02,000 --> 00:57:05,160 CLARK AND JAIN AND VERY MUCH TO 1305 00:57:05,160 --> 00:57:07,000 SUE AND LARS FOR SETTING UP 1306 00:57:07,000 --> 00:57:10,480 GETTING THE SESSION GOING ON A 1307 00:57:10,480 --> 00:57:12,680 VERY POSITIVE NOTE. 1308 00:57:12,680 --> 00:57:15,200 TODAY I WANT TO PIVOT YOU KNOW 1309 00:57:15,200 --> 00:57:18,640 FROM FOCUSING ON ACUTE INJURY OR 1310 00:57:18,640 --> 00:57:20,600 EVEN JUST OUTLINING LACK OF 1311 00:57:20,600 --> 00:57:22,600 RECOVERY IN CRITICALLY ILL 1312 00:57:22,600 --> 00:57:24,560 PATIENTS TO THINKING ABOUT WHAT 1313 00:57:24,560 --> 00:57:26,120 PROCESSES ARE ACTUALLY 1314 00:57:26,120 --> 00:57:29,400 CONTRIBUTING TO THE POOR 1315 00:57:29,400 --> 00:57:32,280 RECOVERY WHETHER MUSCLE MASS. 1316 00:57:32,280 --> 00:57:34,360 FAILURE TO RECOVER MASS OR 1317 00:57:34,360 --> 00:57:36,440 FAILURE TO RECOVER FUNCTION AND 1318 00:57:36,440 --> 00:57:39,120 ARGUE A ROLE FOR MUSCLE STEM 1319 00:57:39,120 --> 00:57:40,600 CELLS AND REGENERATIVE PROCESS 1320 00:57:40,600 --> 00:57:45,480 IN LIKELY ADDITION TO MYOFIBER 1321 00:57:45,480 --> 00:57:49,280 AND INTRINSIC BALANCES OF 1322 00:57:49,280 --> 00:57:51,440 ANANABOLIC AND CATABOLIC 1323 00:57:51,440 --> 00:57:53,240 PROCESSES AND WE WILL SEE AND 1324 00:57:53,240 --> 00:57:55,240 HOPEFULLY HAVE A DISCUSSION 1325 00:57:55,240 --> 00:57:56,720 LATER ON OR BREAKOUT SESSIONS 1326 00:57:56,720 --> 00:57:58,560 ABOUT WHETHER THIS IS AN 1327 00:57:58,560 --> 00:57:59,640 INTERESTING APPROACH OR WHETHER 1328 00:57:59,640 --> 00:58:03,600 IT IS POSSIBLY NOT FEASIBLE IN A 1329 00:58:03,600 --> 00:58:07,920 CLINICAL SETTING. 1330 00:58:07,920 --> 00:58:15,080 NEXT SLIDE, PLEASE A LITTLE 1331 00:58:15,080 --> 00:58:16,960 BACKGROUND TO SEPSIS IT OFTEN 1332 00:58:16,960 --> 00:58:18,920 OCCURS AND IS LIFE-THREATENING 1333 00:58:18,920 --> 00:58:21,440 AND NOT SURE IF MOST POPULAR BUT 1334 00:58:21,440 --> 00:58:25,760 SOME MODELS OF ACUTE RESIDENT 1335 00:58:25,760 --> 00:58:28,400 CHTORY DISTRESS SYNDROME INVOLVE 1336 00:58:28,400 --> 00:58:30,640 -- PRESENTING SIMILAR IN TERMS 1337 00:58:30,640 --> 00:58:33,280 OF ACUTE SEPSIS AND RECOVERY 1338 00:58:33,280 --> 00:58:34,480 DYNAMICS AND MUSCLE MASS AT 1339 00:58:34,480 --> 00:58:37,360 LEAST TO MODEL WE USE AND 1340 00:58:37,360 --> 00:58:38,120 WITHOUT TIMELY TREATMENT ALL 1341 00:58:38,120 --> 00:58:40,640 THESE ACUTE CRITICALLY ILL 1342 00:58:40,640 --> 00:58:44,440 INJURY MODELS LEAD TO TISSUE 1343 00:58:44,440 --> 00:58:46,360 DAMAGE AND MULTIORGAN FAILURE 1344 00:58:46,360 --> 00:58:49,080 AND SEPSIS AND ARDS IS IMPROVING 1345 00:58:49,080 --> 00:58:51,960 AND IS A RATHER OLD DIAGRAM AND 1346 00:58:51,960 --> 00:58:53,960 IMPROVEMENT OF CLINICAL 1347 00:58:53,960 --> 00:58:56,360 MANAGEMENT AND SEPSIS AND ARDS 1348 00:58:56,360 --> 00:58:57,720 SURVIVAL THERE IS INCREASED 1349 00:58:57,720 --> 00:58:59,520 NUMBER OF SURVIVORS AND LARGE 1350 00:58:59,520 --> 00:59:01,360 NUMBER OF SURVIVORS WHETHER YOU 1351 00:59:01,360 --> 00:59:04,560 WANT TO LOOK AT THOSE WHO ARE 1352 00:59:04,560 --> 00:59:07,840 JUST SEPTIC OR THOSE THAT SUFFER 1353 00:59:07,840 --> 00:59:08,600 FROM ARDS. 1354 00:59:08,600 --> 00:59:11,720 AT LEAST, YOU KNOW, DEPENDING ON 1355 00:59:11,720 --> 00:59:15,720 METRICS USED TO MEASURE IT, 1/3 1356 00:59:15,720 --> 00:59:18,040 TO A HALF OF PATIENTS SUFFER 1357 00:59:18,040 --> 00:59:22,080 FROM LONG-TERM CHRONIC ISSUES 1358 00:59:22,080 --> 00:59:26,280 WHETHER MUSCULOSKELETAL IN 1359 00:59:26,280 --> 00:59:29,120 NATURE OR RISK FOR INFECTION OR 1360 00:59:29,120 --> 00:59:32,120 COGNITIVE ISSUES AND IS SIMILAR 1361 00:59:32,120 --> 00:59:35,520 AND LOTS OF OVERLAP HEARING 1362 00:59:35,520 --> 00:59:38,720 ABOUT PICKS. 1363 00:59:38,720 --> 00:59:40,760 MODEL I WILL TALK ABOUT TODAY 1364 00:59:40,760 --> 00:59:42,800 HAS SIGNIFICANT CLINICAL AND 1365 00:59:42,800 --> 00:59:47,160 MOLECULAR OVERLAP WITH LONG-TERM 1366 00:59:47,160 --> 00:59:53,360 SUSTAINED MUSCLE DIS FUFRFUNCTI 1367 00:59:53,360 --> 00:59:55,120 SO, I LIKE AND PUT IT IN. I 1368 00:59:55,120 --> 00:59:56,680 DIDN'T HAVE TO. 1369 00:59:56,680 --> 00:59:57,680 I THINK LOTS OF PEOPLE THINK 1370 00:59:57,680 --> 01:00:00,720 ABOUT MUSCLES SOMETIMES SIMPLY 1371 01:00:00,720 --> 01:00:04,560 AS SOMETHING THAT IS AN ORGAN OR 1372 01:00:04,560 --> 01:00:06,200 TISSUE INVOLVED IN LOCOMOTION 1373 01:00:06,200 --> 01:00:08,960 AND IS LOTS OF OTHER 1374 01:00:08,960 --> 01:00:11,840 CONSEQUENCES ENDOCRINE OR 1375 01:00:11,840 --> 01:00:13,360 HORMONAL, ET CETERA AND THESE 1376 01:00:13,360 --> 01:00:15,200 ARE VERY SEVERE AND SOMETHING TO 1377 01:00:15,200 --> 01:00:19,200 BE TAKEN VERY SERIOUSLY IN THE 1378 01:00:19,200 --> 01:00:22,160 CLINICAL -- FROM A CLINICAL 1379 01:00:22,160 --> 01:00:24,720 PERSPECTIVE INCLUDING FUNCTIONAL 1380 01:00:24,720 --> 01:00:26,200 CHANGES IN STRENGTH AND MOBILITY 1381 01:00:26,200 --> 01:00:28,320 AND THIS GROUP DOESN'T HAVE TO 1382 01:00:28,320 --> 01:00:30,680 FORGET THAT SKELETAL MUSCLE AND 1383 01:00:30,680 --> 01:00:32,840 DIAPHRAGM IS SKELETAL MUSCLE AND 1384 01:00:32,840 --> 01:00:35,120 RESPIRATORY ISSUES ARE 1385 01:00:35,120 --> 01:00:37,920 ASSOCIATED WITH EFFECTS IN 1386 01:00:37,920 --> 01:00:38,600 DIAPHRAGM ASSOCIATION AND THAT 1387 01:00:38,600 --> 01:00:41,560 ARE ASSOCIATED WITH -- 1388 01:00:41,560 --> 01:00:43,560 RESISTANCE IN SOME CASES AND 1389 01:00:43,560 --> 01:00:47,200 PROTEIN TURNOVER, ET CETERA. 1390 01:00:47,200 --> 01:00:57,440 NEXT SLIDE. 1391 01:00:58,840 --> 01:01:01,640 SIMILAR TO ARDS AND IN MOUSE 1392 01:01:01,640 --> 01:01:03,680 MODELS WHERE YOU SEE RECOVERY 1393 01:01:03,680 --> 01:01:06,160 AND WOULD BE PROBABLY YOUNGER 1394 01:01:06,160 --> 01:01:09,120 MIDDLE AGED THAT GETS WORST IN 1395 01:01:09,120 --> 01:01:12,320 MICE AND RATS SHOWN BY SUE AND 1396 01:01:12,320 --> 01:01:13,800 OTHERS THERE IS EARLY PHASE 1397 01:01:13,800 --> 01:01:15,960 DRIVEN BY HIGHLY INFLAMMATORY 1398 01:01:15,960 --> 01:01:18,400 AND HIGHLY CAT BOLIC ENVIRONMENT 1399 01:01:18,400 --> 01:01:20,760 THAT IS ASSOCIATED USUALLY WITH 1400 01:01:20,760 --> 01:01:22,360 SEPSIS OR WHATEVER THE CRITICAL 1401 01:01:22,360 --> 01:01:25,640 INJURY IS. YOU ENHANCED 1402 01:01:25,640 --> 01:01:28,360 [INDISCERNIBLE] AND 1403 01:01:28,360 --> 01:01:29,960 GLUCOCORTICOID ATROPHY THAT IS 1404 01:01:29,960 --> 01:01:34,360 PART OF THE CLINICAL MANAGEMENT 1405 01:01:34,360 --> 01:01:38,120 OF SEPSIS. YOU SEE ISSUES WITH 1406 01:01:38,120 --> 01:01:42,080 MUSCLE STRUCTURE AND MEMBRANE 1407 01:01:42,080 --> 01:01:43,600 HYPOEXCITABILITY AND 1408 01:01:43,600 --> 01:01:45,440 NEUROMUSCULAR JUNCTION ISSUES 1409 01:01:45,440 --> 01:01:47,960 AND NERVES AND PHYSIOLOGICAL 1410 01:01:47,960 --> 01:01:49,920 IMPACTS ON CNS AND LATE PHASE 1411 01:01:49,920 --> 01:01:54,160 YOU SEE SIMILARITIES AND -- 1412 01:01:54,160 --> 01:01:56,200 ALTERED PROTEIN DISFUNCTION AND 1413 01:01:56,200 --> 01:01:58,720 I WILL FOCUS ON FAILURE TO 1414 01:01:58,720 --> 01:02:01,360 REPLETE TISSUE LO S AND 1415 01:02:01,360 --> 01:02:03,080 REGENERATIVE PROCESS AND HOW IT 1416 01:02:03,080 --> 01:02:05,640 CONTRIBUTES TO THAT. NEXT. BIG 1417 01:02:05,640 --> 01:02:07,440 QUESTIONS I HAD AT LEAST WHEN I 1418 01:02:07,440 --> 01:02:08,520 FIRST START TODAY THINK ABOUT 1419 01:02:08,520 --> 01:02:10,440 THIS IS FIRST OF ALL IS THE 1420 01:02:10,440 --> 01:02:13,800 RECOVERY OF MUSCLE MASS AND DOES 1421 01:02:13,800 --> 01:02:16,840 IT EVEN INVOLVE REGENERATION AND 1422 01:02:16,840 --> 01:02:20,120 LOOKING AT LITERATURE I WASN'T 1423 01:02:20,120 --> 01:02:23,520 SURE MUSCLE STEM CELLS PER-SE 1424 01:02:23,520 --> 01:02:25,040 AND REGENERATIVE PROCESS 1425 01:02:25,040 --> 01:02:27,160 INVOLVED AS ALL AND HOW DO THEY 1426 01:02:27,160 --> 01:02:30,200 CONTRIBUTE TO THE RECOVERY AND 1427 01:02:30,200 --> 01:02:33,320 LARS MENTIONED TOWARDS END OF 1428 01:02:33,320 --> 01:02:37,080 HIS TALK -- MUSCLE MICRO 1429 01:02:37,080 --> 01:02:38,440 ENVIRONMENT IS COMPLEX AND OTHER 1430 01:02:38,440 --> 01:02:41,400 CELLS IN MICRO ENVIRONMENT HOW 1431 01:02:41,400 --> 01:02:43,480 THEY CONTRIBUTE TO THE PROCESS 1432 01:02:43,480 --> 01:02:46,680 AND SIGNALING IN DEFICITS IN 1433 01:02:46,680 --> 01:02:48,560 STEM CELLS AND ENVIRONMENT TO 1434 01:02:48,560 --> 01:02:50,880 IMPROVE TISSUE RECOVERY. NEXT. 1435 01:02:50,880 --> 01:02:52,600 YOU CAN DO ANOTHER NEXT. 1436 01:02:52,600 --> 01:02:54,680 SOME OBSTACLES HAVE BEEN REALLY 1437 01:02:54,680 --> 01:02:57,040 AT LEAST FROM A RESEARCH 1438 01:02:57,040 --> 01:02:59,280 STANDPOINT HISTORIC FOCUS ON 1439 01:02:59,280 --> 01:03:02,400 ACCUSE PHASE ON SEPSIS THAT IS 1440 01:03:02,400 --> 01:03:06,040 PROBABLY TRUE IN ARDS FIELD AS 1441 01:03:06,040 --> 01:03:09,080 WELL AND HYPERCATABOLIC PHASE 1442 01:03:09,080 --> 01:03:11,440 AND IN MOUSE MODELS AND IN 1443 01:03:11,440 --> 01:03:14,120 HUMANS AND IS CHANGING IN RECENT 1444 01:03:14,120 --> 01:03:17,080 YEARS AND MODELING SEPSIS IN 1445 01:03:17,080 --> 01:03:19,800 ARDS AND MICE IS COMPLEX AND NOT 1446 01:03:19,800 --> 01:03:24,920 HUGE FAN USING MOUSE MODELS 1447 01:03:24,920 --> 01:03:26,600 STUDYING ACUTE SEPSIS AND 1448 01:03:26,600 --> 01:03:28,760 PRIORITIES AND MUSCLE RECOVERY 1449 01:03:28,760 --> 01:03:30,160 ASPECTS ARE MICE ARE APPROPRIATE 1450 01:03:30,160 --> 01:03:31,840 AND RATS ARE APPROPRIATE FOR 1451 01:03:31,840 --> 01:03:35,200 LOOKING AT SOME RECOVERY 1452 01:03:35,200 --> 01:03:37,400 DYNAMICS IN THOSE MODELS. 1453 01:03:37,400 --> 01:03:39,720 AND I THINK THAT IMPORTANTLY WE 1454 01:03:39,720 --> 01:03:41,640 ARE KIND OF AT A JUNCTURE IN 1455 01:03:41,640 --> 01:03:43,640 SCIENCE RIGHT NOW. THERE IS A 1456 01:03:43,640 --> 01:03:46,160 LOT OF OPPORTUNITIES THAT ALLOW 1457 01:03:46,160 --> 01:03:48,080 US TO UNDERSTAND MOLECULAR 1458 01:03:48,080 --> 01:03:49,600 MECHANISMS AND IN GREATER AND 1459 01:03:49,600 --> 01:03:51,080 FAR MORE DETAIL THAN WE WERE 1460 01:03:51,080 --> 01:03:53,480 ABLE TO 10 YEARS AGO INCLUDING 1461 01:03:53,480 --> 01:03:55,680 CELL SEQUENCING AND MENTIONING 1462 01:03:55,680 --> 01:03:57,760 ADVANCED IMAGING TECHNIQUES AND 1463 01:03:57,760 --> 01:04:00,120 OTHER WAYS OF MODELING AND 1464 01:04:00,120 --> 01:04:02,200 STUDYING THESE COMPLEX 1465 01:04:02,200 --> 01:04:02,720 PHENOMENON. 1466 01:04:02,720 --> 01:04:04,800 FROM AT LEAST MY PERSPECTIVE, 1467 01:04:04,800 --> 01:04:07,480 I'M A RELATIVE NEWCOMER TO 1468 01:04:07,480 --> 01:04:09,480 CRITICAL ILLNESS MYOPATHY FIELD 1469 01:04:09,480 --> 01:04:12,160 TAKING LESSONS FROM OTHER MUSCLE 1470 01:04:12,160 --> 01:04:14,880 WASTING DISORDERS WITH 1471 01:04:14,880 --> 01:04:15,680 OVERLAPPING AND SOMEWHAT 1472 01:04:15,680 --> 01:04:18,280 DISTINCT MECHANISMS CANCER CAR 1473 01:04:18,280 --> 01:04:21,080 CHASM YA AND SARCOPENIA USING IT 1474 01:04:21,080 --> 01:04:23,280 TO BETTER UNDERSTAND MUSCLE 1475 01:04:23,280 --> 01:04:25,160 DISFUNCTION AS CONSEQUENCE OF 1476 01:04:25,160 --> 01:04:26,920 ACUTE TRAUMA. 1477 01:04:26,920 --> 01:04:28,360 NEXT. 1478 01:04:28,360 --> 01:04:30,200 YOU CAN JUST GO FORWARD ANOTHER 1479 01:04:30,200 --> 01:04:31,520 ONE AND ONE MORE. 1480 01:04:31,520 --> 01:04:34,160 YEAH. SORRY HEAVY ON ANIMATION 1481 01:04:34,160 --> 01:04:35,720 THAT IS A LITTLE TRICKY. 1482 01:04:35,720 --> 01:04:37,280 FIRST THING IS WHETHER OR NO THE 1483 01:04:37,280 --> 01:04:41,760 TO MODEL LATE EFFECTS THAT ARE 1484 01:04:41,760 --> 01:04:45,200 LONG-TERM -- THIS LONG-TERM 1485 01:04:45,200 --> 01:04:46,640 DISFUNCTION IN MICE. 1486 01:04:46,640 --> 01:04:50,760 MODEL IN SURGICAL SEPSIS AND 1487 01:04:50,760 --> 01:04:54,080 PUNCTURE CECUM AND LIGATE IT 1488 01:04:54,080 --> 01:04:56,400 USING THIS VERSION FROM FOLKS AT 1489 01:04:56,400 --> 01:04:57,840 UNIVERSITY OF FLORIDA AND 1490 01:04:57,840 --> 01:04:59,800 COUPLED IT WITH DAILY CHRONIC 1491 01:04:59,800 --> 01:05:03,200 STRESS MODEL THAT IN CASES COULD 1492 01:05:03,200 --> 01:05:08,960 BE USED AS A -- MIMICKING 1493 01:05:08,960 --> 01:05:12,160 NEUROLOGICAL STRESS PHENOMENON 1494 01:05:12,160 --> 01:05:15,360 OCCURRING IN PATIENTS IN ICU 1495 01:05:15,360 --> 01:05:18,080 THAT ARE LIMITED IN MOBILITY AND 1496 01:05:18,080 --> 01:05:20,400 INDEED ADDITION OF DAILY CHRONIC 1497 01:05:20,400 --> 01:05:25,400 STRESS TO THIS MODEL AND CLP 1498 01:05:25,400 --> 01:05:29,760 MODEL DOES HAVE PROFOUND 1499 01:05:29,760 --> 01:05:32,320 ADDITIVE EFFECT NOT SIN ERNLY 1500 01:05:32,320 --> 01:05:35,120 EFFECT AND ADDING IN MICE THAT 1501 01:05:35,120 --> 01:05:36,920 EXHIBIT IN RED LINE AND GRAPH ON 1502 01:05:36,920 --> 01:05:40,320 RIGHT AND SHOWING THEY LOSE 1503 01:05:40,320 --> 01:05:46,080 WEIGHT ACUTELY AND RECOVER 1504 01:05:46,080 --> 01:05:49,440 SLOWLY OVER TIME AND THEY 1505 01:05:49,440 --> 01:05:54,160 RECOVER POORLY GOOD MODEL TO 1506 01:05:54,160 --> 01:05:56,960 STUDY THAT AND BOTTOM GRAPHS 1507 01:05:56,960 --> 01:05:59,520 SHOWING MUSCLE MASS RECOVER OF 1508 01:05:59,520 --> 01:06:02,920 INDIVIDUAL MODELS AND WE SEE 1509 01:06:02,920 --> 01:06:05,000 LESS RECOVERY OF MUSCLES THAT 1510 01:06:05,000 --> 01:06:07,320 ARE MORE HIGHLY ENRICHED WITH 1511 01:06:07,320 --> 01:06:09,640 LARGER TYPE 2B FIBERS PRA EVER 1512 01:06:09,640 --> 01:06:12,080 GOOD THING IS MICE -- I DON'T 1513 01:06:12,080 --> 01:06:14,200 HAVE TIME TO SHOW IT EXHIBITING 1514 01:06:14,200 --> 01:06:16,760 LONG-TERM ISSUES ASSOCIATED WITH 1515 01:06:16,760 --> 01:06:20,840 FUNCTION OR SUBSTANCE 1516 01:06:20,840 --> 01:06:22,080 ASSOCIATED. 1517 01:06:22,080 --> 01:06:26,760 POST SEPSIS SYNDROME THEY HAVE 1518 01:06:26,760 --> 01:06:30,120 VASCULAR ISSUES AND EVIDENCE OF 1519 01:06:30,120 --> 01:06:32,800 IMPAIRED MUSCLE REGENERATION. 1520 01:06:32,800 --> 01:06:36,320 NEXT SLIDE. BEFORE I DO THAT GO 1521 01:06:36,320 --> 01:06:40,120 ONE MORE TRACKING AND STUDYING 1522 01:06:40,120 --> 01:06:46,240 MUSCLE REGENERATION IN VIVO IS 1523 01:06:46,240 --> 01:06:51,680 USING USEFUL MODEL AND WE CAN 1524 01:06:51,680 --> 01:06:54,680 TRACK LOOKING ATTACKTIVATION AND 1525 01:06:54,680 --> 01:06:58,760 EXPANSION OF MUSCLE PROGENITORS 1526 01:06:58,760 --> 01:07:03,160 IN MICE. 1527 01:07:03,160 --> 01:07:04,000 NEXT SLIDE, PLEASE. 1528 01:07:04,000 --> 01:07:10,280 IN THIS CASE INDUCING INJURY AND 1529 01:07:10,280 --> 01:07:14,200 SEEING IN MICE 96 HOURS YOU SEE 1530 01:07:14,200 --> 01:07:18,600 RAPID EXPANSION OF 1531 01:07:18,600 --> 01:07:19,800 BIOLUMINESCENCE SIGNAL AND WE 1532 01:07:19,800 --> 01:07:23,120 HAVE POSITIVE CELLS INTO MUSCLE 1533 01:07:23,120 --> 01:07:24,840 BASELINE CONDITION LABELING THEM 1534 01:07:24,840 --> 01:07:27,720 THEY ARE TOO RARE AND SPARSE TO 1535 01:07:27,720 --> 01:07:29,120 SEE SIGNAL. 1536 01:07:29,120 --> 01:07:29,800 >> [INDISCERNIBLE]. 1537 01:07:29,800 --> 01:07:33,680 >> OKAY. IN MICE THAT ARE 1538 01:07:33,680 --> 01:07:35,960 PREVIOUSLY SEPTIC THERE IS 1539 01:07:35,960 --> 01:07:44,120 FAILURE TO ACTIVATE THESE CELLS. 1540 01:07:44,120 --> 01:07:49,320 INTERESTING THING HERE MUSCLE 1541 01:07:49,320 --> 01:07:54,240 CELLS ARE EFFECTED BY MICIS. 1542 01:07:54,240 --> 01:07:56,520 THERE IS INTRINSIC DEFEBLGS 1543 01:07:56,520 --> 01:07:58,800 ABILITIES TO DIFFERENTIATE AND 1544 01:07:58,800 --> 01:08:03,680 MOLECULAR DEFECTS IN CELLULAR 1545 01:08:03,680 --> 01:08:06,520 METABOLISM, ET CETERA DOES IT 1546 01:08:06,520 --> 01:08:08,520 MATTER? ARE THEY REQUIRED FOR 1547 01:08:08,520 --> 01:08:10,440 RECOVERY AND EXHIBIT MOLECULAR 1548 01:08:10,440 --> 01:08:12,960 CHANGES APPEARING TO BE 1549 01:08:12,960 --> 01:08:14,920 DYSFUNCTIONAL WITH TRACER ASSAYS 1550 01:08:14,920 --> 01:08:16,600 GOING FORWARD A COUPLE. NOT A 1551 01:08:16,600 --> 01:08:18,320 GIVEN THEY ARE IMPORTANT DURING 1552 01:08:18,320 --> 01:08:20,120 MUSCLE RECOVERY PHASE. 1553 01:08:20,120 --> 01:08:22,320 YOU KNOW, WHEN YOU HAVE 1554 01:08:22,320 --> 01:08:23,480 TRAUMATIC INJURIES YOU SEE A 1555 01:08:23,480 --> 01:08:26,280 FAILURE TO RECOVER IF IN THESE 1556 01:08:26,280 --> 01:08:28,520 EXPERIMENTAL INJURY MODELS OF 1557 01:08:28,520 --> 01:08:29,960 TRAUMATIC INJURY AND DOESN'T 1558 01:08:29,960 --> 01:08:32,320 APPEAR AS IF IMPORTANT FOR 1559 01:08:32,320 --> 01:08:34,160 LIFELONG MAINTENANCE AND 1560 01:08:34,160 --> 01:08:36,400 SEDENTARY MICE AND ARE THEY 1561 01:08:36,400 --> 01:08:38,800 INVOLVED IN SEPSIS AND POST 1562 01:08:38,800 --> 01:08:40,680 RECOVERY AT ALL AND TOOK 1563 01:08:40,680 --> 01:08:44,640 ADVANTAGE OF THIS -- REPORTER 1564 01:08:44,640 --> 01:08:48,080 AND WE HAVE WE TOOK OBLATION 1565 01:08:48,080 --> 01:08:50,320 STRATEGY AND GOT RID OF MUSCLE 1566 01:08:50,320 --> 01:08:53,560 STEM CELLS SUBJECTING INTO SAME 1567 01:08:53,560 --> 01:08:55,640 SEPSIS PROTOCOL AND GETTING RID 1568 01:08:55,640 --> 01:08:58,160 OF THEM ENTIRELY OBLATE MUSCLE 1569 01:08:58,160 --> 01:08:59,720 RECOVERY AND NEXT IS SPECIFIC TO 1570 01:08:59,720 --> 01:09:01,560 THE MUSCLE AND IS SPECIFIC IN 1571 01:09:01,560 --> 01:09:03,960 ALL OF THE OTHER TISSUES RECOVER 1572 01:09:03,960 --> 01:09:07,760 IN THIS MODEL AND NO IMPACT ON 1573 01:09:07,760 --> 01:09:11,080 RECOVERY AS WELL AND COULD 1574 01:09:11,080 --> 01:09:12,520 ARGUABLY LOSE WEIGHT IN MICE AND 1575 01:09:12,520 --> 01:09:16,240 STILL NOT UNCLEAR TO US AND THEY 1576 01:09:16,240 --> 01:09:17,840 DON'T RECOVER AS WELL. 1577 01:09:17,840 --> 01:09:19,960 NEXT. YEAH. THERE IS MORE TO 1578 01:09:19,960 --> 01:09:22,480 THE MUSCLE MICRO ENVIRONMENT IN 1579 01:09:22,480 --> 01:09:25,680 STEM CELLS AND GOING TO THE NEXT 1580 01:09:25,680 --> 01:09:26,120 SLIDE. 1581 01:09:26,120 --> 01:09:28,240 SINLE CELL SEQUENCING WE DID TO 1582 01:09:28,240 --> 01:09:30,080 BETTER UNDERSTAND WHAT IS 1583 01:09:30,080 --> 01:09:32,960 HAPPENING HERE AND TAKE-HOME 1584 01:09:32,960 --> 01:09:35,560 MESSAGE NOT ONLY DECREASE IN 1585 01:09:35,560 --> 01:09:38,040 STEM PROGENITOR CELLS INCREASED 1586 01:09:38,040 --> 01:09:41,480 ABUNDANCE AND IMPORTANCE ON 1587 01:09:41,480 --> 01:09:44,360 MACROPHAGES AND PRESENCE AND 1588 01:09:44,360 --> 01:09:47,760 PERSISTENCE OF MYELOSUPPRESSOR 1589 01:09:47,760 --> 01:09:49,480 CELLS SHOULDN'T BE THERE AND 1590 01:09:49,480 --> 01:09:51,240 T-CELL FUNCTION PROPORTIONS OF 1591 01:09:51,240 --> 01:09:53,520 THEM WE SHOULD ARGUE IS 1592 01:09:53,520 --> 01:09:56,920 CONSEQUENCE OF PERSISTENT MDC 1593 01:09:56,920 --> 01:09:59,080 AND ENDOTHELIAL CELLS THAT WE 1594 01:09:59,080 --> 01:10:01,240 ALSO SEE LOSS OF CELLS FOLLOWED 1595 01:10:01,240 --> 01:10:05,160 BY PHENOTYPE SWITCH. NEXT. 1596 01:10:05,160 --> 01:10:07,320 YOU CAN GO FORWARD ONE OR TWO 1597 01:10:07,320 --> 01:10:10,120 AND INTEGRATED ANALYSIS TO 1598 01:10:10,120 --> 01:10:11,960 UNDERSTAND IF WE COULD PREDICT 1599 01:10:11,960 --> 01:10:13,960 INTERVENTIONS THAT IS INFORMATIC 1600 01:10:13,960 --> 01:10:16,720 -- THIS IS BASICALLY, YOU KNOW, 1601 01:10:16,720 --> 01:10:19,160 CONCURRENT REGULATOR ANALYSIS OF 1602 01:10:19,160 --> 01:10:21,200 SINGLE CELL DATA FROM INDIVIDUAL 1603 01:10:21,200 --> 01:10:23,080 IMMUNE CELL POPULATIONS 1604 01:10:23,080 --> 01:10:25,800 TARGETING COMPOUNDS REVERSING 1605 01:10:25,800 --> 01:10:27,080 TRANSCRIPTIONAL SIGNATURES. 1606 01:10:27,080 --> 01:10:27,840 NEXT. 1607 01:10:27,840 --> 01:10:30,080 THIS IS MY FINAL SLIDE, I 1608 01:10:30,080 --> 01:10:32,400 BELIEVE. YUP. WE ARE 1609 01:10:32,400 --> 01:10:34,000 EVALUATING COMPOUNDS NOW TO SEE 1610 01:10:34,000 --> 01:10:36,640 HOW EFFECTIVE THEY ARE IN POST 1611 01:10:36,640 --> 01:10:39,520 SEPSIS TISSUE RECOVERY AND NEXT 1612 01:10:39,520 --> 01:10:41,360 IS A SUMMARY SLIDE HERE YOU CAN 1613 01:10:41,360 --> 01:10:43,360 GO FORWARD ON ALL OF THEM. I 1614 01:10:43,360 --> 01:10:44,560 COVERED THIS AND DON'T HAVE TO 1615 01:10:44,560 --> 01:10:46,160 GO OVER IT BUT WOULD LIKE TO 1616 01:10:46,160 --> 01:10:48,760 TALK ABOUT IMPLICATIONS ON NEXT 1617 01:10:48,760 --> 01:10:50,080 SLIDE AND OPPORTUNITIES MOVING 1618 01:10:50,080 --> 01:10:52,000 FORWARD, WE SEE EVIDENCE OF 1619 01:10:52,000 --> 01:10:53,480 FUNCTIONAL STEM CELL IMPAIRMENT 1620 01:10:53,480 --> 01:10:55,360 AND THINKING ABOUT WHETHER OR 1621 01:10:55,360 --> 01:10:58,280 NOT THERAPIES TARGETING STEM 1622 01:10:58,280 --> 01:11:01,320 CELL DEFICIENCIES IS TARGETING 1623 01:11:01,320 --> 01:11:05,280 COMPLICATIONS WITH 1624 01:11:05,280 --> 01:11:06,680 IMMUNOTHERAPIES AND THOSE 1625 01:11:06,680 --> 01:11:08,520 DYSREGULATED IN ACUTE PHASE AND 1626 01:11:08,520 --> 01:11:10,440 WE DON'T WANT TO IMPAIR ABILITY 1627 01:11:10,440 --> 01:11:12,640 TO ACUTELY MANAGE SEPSIS AND 1628 01:11:12,640 --> 01:11:14,880 WOULD LIKE TO FOCUS ON RECOVERY 1629 01:11:14,880 --> 01:11:17,000 AND A LOT OF THE PATHWAYS 1630 01:11:17,000 --> 01:11:19,280 APPEARING TO BE INVOLVED IN 1631 01:11:19,280 --> 01:11:20,920 ACUTE MUSCLE DISFUNCTION MIGHT 1632 01:11:20,920 --> 01:11:23,200 BE SOMETHING THAT WOULD, YOU 1633 01:11:23,200 --> 01:11:25,560 KNOW, INTERFERE WITH ABILITY TO 1634 01:11:25,560 --> 01:11:27,800 MANAGE SEPSIS CLINICALLY. ALSO, 1635 01:11:27,800 --> 01:11:31,160 IT IS POSSIBLE WE MIGHT NEED 1636 01:11:31,160 --> 01:11:33,720 CATABOLISM TO PROVIDE NUTRIENTS 1637 01:11:33,720 --> 01:11:36,280 TO OTHER ORGANS TO ASSIST IN 1638 01:11:36,280 --> 01:11:38,040 RECOVERY FROM SEPSIS AND MY 1639 01:11:38,040 --> 01:11:40,800 ARGUMENT WOULD BE TO -- MY 1640 01:11:40,800 --> 01:11:42,320 THOUGHTS ARE TO INTERVENE LATER 1641 01:11:42,320 --> 01:11:45,160 AND HELP WITH MUSCLE RECOVERY 1642 01:11:45,160 --> 01:11:47,040 RATHER THAN MESS WITH HIGHLY 1643 01:11:47,040 --> 01:11:48,320 COMPLICATED AND COMPLEX SCENARIO 1644 01:11:48,320 --> 01:11:50,640 OF ACUTE MUSCLE LOSS THAT WILL 1645 01:11:50,640 --> 01:11:52,600 REQUIRE MORE NUANCE AND 1646 01:11:52,600 --> 01:11:54,200 UNDERSTANDING OF MUSCLE MASS 1647 01:11:54,200 --> 01:11:56,560 VERSUS FUNCTION IN RECOVERY IN 1648 01:11:56,560 --> 01:12:00,200 ICU SURVIVORS DOING METABOLIC 1649 01:12:00,200 --> 01:12:03,240 STUDIES AND ARE OPPORTUNITIES TO 1650 01:12:03,240 --> 01:12:05,560 BOOST METABOLIC RECOVERY AND 1651 01:12:05,560 --> 01:12:09,440 INTERESTING IMPLICATIONS 1652 01:12:09,440 --> 01:12:13,360 PROGENITOR MICRO -- OR ALSO 1653 01:12:13,360 --> 01:12:15,000 DISRUPTED IN PATIENTS TAKING 1654 01:12:15,000 --> 01:12:17,640 APPROACH TO STUDY LONG TERM 1655 01:12:17,640 --> 01:12:19,120 SEPSIS DISNUFRNGS HEART AND LUNG 1656 01:12:19,120 --> 01:12:20,920 AND BONE MARROW OF SEPSIS MICE 1657 01:12:20,920 --> 01:12:22,000 AS WELL. 1658 01:12:22,000 --> 01:12:24,200 THAT IS THE END, I BELIEVE. 1659 01:12:24,200 --> 01:12:25,800 YEAH. JUST THANKING EVERYONE IN 1660 01:12:25,800 --> 01:12:27,360 THE LAB FOR HELPING OUT 1661 01:12:27,360 --> 01:12:29,200 COLLABORATORS BOTH AND WE HAVE A 1662 01:12:29,200 --> 01:12:32,080 FEW AT UP SOUTHWESTERN AND UW AS 1663 01:12:32,080 --> 01:12:34,760 WELL AS UNIVERSITY OF FLORIDA 1664 01:12:34,760 --> 01:12:37,960 GANG THAT IS LED BY PHIL EH RON 1665 01:12:37,960 --> 01:12:39,680 AND THANKS FOR LISTENING. 1666 01:12:39,680 --> 01:12:41,960 >> THANK YOU VERY MUCH, JASON. 1667 01:12:41,960 --> 01:12:44,320 THAT WAS REALLY INTERESTING. IT 1668 01:12:44,320 --> 01:12:47,000 IS A MASSIVE AMOUNT OF WORK THAT 1669 01:12:47,000 --> 01:12:49,080 IS PRESENTED IN A VERY SHORT AND 1670 01:12:49,080 --> 01:12:51,560 CONCISE AND EASY TO UNDERSTAND 1671 01:12:51,560 --> 01:12:52,120 TIMELINE. 1672 01:12:52,120 --> 01:12:53,240 THANKS VERY MUCH. 1673 01:12:53,240 --> 01:12:55,000 WE HAVE TIME FOR A COUPLE 1674 01:12:55,000 --> 01:12:57,160 QUESTIONS SPECIFICALLY. ONE IN 1675 01:12:57,160 --> 01:12:59,440 THE CHAT BASICALLY SAYS IT IS 1676 01:12:59,440 --> 01:13:01,720 SHOWN THAT STEM CELLS COULD 1677 01:13:01,720 --> 01:13:04,040 PROVIDE MITOCHONDRIAL MATERIAL 1678 01:13:04,040 --> 01:13:07,440 TO THE SATELLITE CELL AT ACUTE 1679 01:13:07,440 --> 01:13:09,160 PHASE OF SEPSIS IN THE MOUSE AND 1680 01:13:09,160 --> 01:13:11,560 ARE NECESSARY FOR MUSCLE 1681 01:13:11,560 --> 01:13:12,040 REGENERATION. 1682 01:13:12,040 --> 01:13:14,040 QUESTION IS, SHOULD STEM CELLS 1683 01:13:14,040 --> 01:13:16,400 BE GIVEN AT ACUTE PHASE OR 1684 01:13:16,400 --> 01:13:18,120 EFFECTIVENESS BE BETTER AT 1685 01:13:18,120 --> 01:13:18,840 RECOVERY PHASE? 1686 01:13:18,840 --> 01:13:20,280 >> I THINK YOU ARE TALKING 1687 01:13:20,280 --> 01:13:23,240 ABOUT THE BAPER FROM THE FRENCH 1688 01:13:23,240 --> 01:13:25,520 GROUP IN 2015. 1689 01:13:25,520 --> 01:13:29,680 THEY NOT ONLY SAW DIFFERENCES IF 1690 01:13:29,680 --> 01:13:31,760 INTRINSICALLY IN MITOCHONDRIA OF 1691 01:13:31,760 --> 01:13:36,080 STEM CELLS AND ARGUED BOOSTING 1692 01:13:36,080 --> 01:13:37,240 MITOCHONDRIA FUNCTION IN 1693 01:13:37,240 --> 01:13:38,440 SATELLITE CELLS COULD BE 1694 01:13:38,440 --> 01:13:39,800 IMPORTANT THERAPEUTIC STRATEGY 1695 01:13:39,800 --> 01:13:41,560 AND COULDN'T SEE FOLLOW UP FROM 1696 01:13:41,560 --> 01:13:43,600 THAT PARTICULAR GROUP. WHETHER 1697 01:13:43,600 --> 01:13:45,160 OR NOT SATELLITE CELLS COULD BE 1698 01:13:45,160 --> 01:13:48,600 SOURCE OF MITOCHONDRIA FOR 1699 01:13:48,600 --> 01:13:50,360 MYOFIBERS IS REALLY INTERESTING. 1700 01:13:50,360 --> 01:13:53,600 IT COULD BE USED PERHAPS 1701 01:13:53,600 --> 01:13:55,640 THERAPEUTICALLY IF THINKING OF 1702 01:13:55,640 --> 01:13:57,720 EXOGENOUS SATELLITE CELLS OR 1703 01:13:57,720 --> 01:13:59,320 EXOGENOUS TREATMENTS. I WOULD 1704 01:13:59,320 --> 01:14:01,120 PROBABLY DO THAT LATER. I DON'T 1705 01:14:01,120 --> 01:14:03,080 KNOW. I GUESS IT IS PURE 1706 01:14:03,080 --> 01:14:05,120 SPECULATION, I GUESS. I DON'T 1707 01:14:05,120 --> 01:14:05,320 KNOW. 1708 01:14:05,320 --> 01:14:07,280 >> THANK YOU. WHAT WE CAN DO, 1709 01:14:07,280 --> 01:14:08,840 I THINK, IS BRING SOME OF THIS 1710 01:14:08,840 --> 01:14:10,560 UP IN THE DISCUSSION THAT WE 1711 01:14:10,560 --> 01:14:11,000 HAVE HERE. 1712 01:14:11,000 --> 01:14:13,800 I THINK WHAT I WILL DO AT THIS 1713 01:14:13,800 --> 01:14:17,560 TIME IS JUST TRY TO SUMMARIZE 1714 01:14:17,560 --> 01:14:19,040 THE OUTSTANDING DATA AND 1715 01:14:19,040 --> 01:14:20,760 FANTASTIC IDEAS THAT SPEAKERS 1716 01:14:20,760 --> 01:14:23,280 HAVE BROUGHT TO THE TABLE. 1717 01:14:23,280 --> 01:14:25,480 THEN WE WILL MOVE FORWARD FOR 1718 01:14:25,480 --> 01:14:27,880 MORE IN-DEPTH DISCUSSION. 1719 01:14:27,880 --> 01:14:30,520 CLARK, PLEASE HOP IN HERE IF I 1720 01:14:30,520 --> 01:14:31,640 MISSED SOMETHING AND GENERAL 1721 01:14:31,640 --> 01:14:32,920 THEMES BRINGING FORWARD FROM 1722 01:14:32,920 --> 01:14:35,400 WORK WE HAVE SEEN TODAY IS AGE 1723 01:14:35,400 --> 01:14:36,960 IS HUGELY IMPORTANT AND IS 1724 01:14:36,960 --> 01:14:39,120 IMPACTING REALLY A BASELINE 1725 01:14:39,120 --> 01:14:42,040 MUSCLE STATUS AND BIOLOGICAL 1726 01:14:42,040 --> 01:14:42,440 FUNCTION. 1727 01:14:42,440 --> 01:14:45,200 THIS IS CRITICAL. THERE -- 1728 01:14:45,200 --> 01:14:48,080 ALTHOUGH THERE SEEMS TO BE A 1729 01:14:48,080 --> 01:14:49,840 SIMILAR LOSS, RATE OF LOSS OF 1730 01:14:49,840 --> 01:14:51,960 MUSCLE THAT IS SIMILAR IN OLD 1731 01:14:51,960 --> 01:14:54,000 AND YOUNG, CERTAINLY SIGNALING 1732 01:14:54,000 --> 01:14:56,960 THAT MEDIATES THAT LOSS IS 1733 01:14:56,960 --> 01:14:57,280 DIFFERENT. 1734 01:14:57,280 --> 01:14:59,560 THAT MEANS WE CAN'T APPROACH OLD 1735 01:14:59,560 --> 01:15:01,560 AND YOUNG NECESSARILY THE SAME 1736 01:15:01,560 --> 01:15:04,240 AND MOREOVER, THERE IS ACTUALLY 1737 01:15:04,240 --> 01:15:06,160 IMPEDIMENT OF RECOVERY OF THE 1738 01:15:06,160 --> 01:15:07,600 MUSCLE IN THE AGE COMPARED TO 1739 01:15:07,600 --> 01:15:08,120 THE YOUNG. 1740 01:15:08,120 --> 01:15:11,560 NOT ONLY ARE WE SEEING 1741 01:15:11,560 --> 01:15:13,480 DIFFERENCES IN CELLULAR 1742 01:15:13,480 --> 01:15:14,680 SIGNALING IN THE RACE THIS IS 1743 01:15:14,680 --> 01:15:17,200 BOTH AT LOSS AND RECOVERY. AGE 1744 01:15:17,200 --> 01:15:18,920 IS A HUGE CONSIDERATION AND 1745 01:15:18,920 --> 01:15:20,960 GIVEN AGE RANGE OF THE PATIENTS 1746 01:15:20,960 --> 01:15:24,440 IN THE ICU, WHAT WE DO FOR THE 1747 01:15:24,440 --> 01:15:26,320 YOUNG MAY KRERMLY NOT WORK FOR 1748 01:15:26,320 --> 01:15:28,840 THE OLD AND WORK ON PERSONALIZED 1749 01:15:28,840 --> 01:15:29,960 MEDICINE APPROACHES HERE. THAT 1750 01:15:29,960 --> 01:15:31,880 IS A BIG THEME, AGE IS CRITICAL. 1751 01:15:31,880 --> 01:15:34,000 THE OTHER REALLY INTERESTING 1752 01:15:34,000 --> 01:15:36,280 FACTOR THAT CAME OUT IS AS WE 1753 01:15:36,280 --> 01:15:38,120 TALKED BEFORE, DIFFERENT MUSCLES 1754 01:15:38,120 --> 01:15:39,560 SEEM TO RESPOND IN DIFFERENT 1755 01:15:39,560 --> 01:15:39,760 WAYS. 1756 01:15:39,760 --> 01:15:42,160 THIS CAN NOW ACTUALLY BE SHOWN 1757 01:15:42,160 --> 01:15:44,120 WITH SOME WORK THAT LARSON HAS 1758 01:15:44,120 --> 01:15:46,600 DONE FOR EXAMPLE AT A MOLECULAR 1759 01:15:46,600 --> 01:15:50,400 LEVEL AND SEE THAT WE ACTUALLY 1760 01:15:50,400 --> 01:15:51,840 LOSE MYOSIN IN PERIPHERAL 1761 01:15:51,840 --> 01:15:54,920 MUSCLES BUT ISSUE IN DIAPHRAGM 1762 01:15:54,920 --> 01:15:56,240 IS POSTTRANSLATIONAL 1763 01:15:56,240 --> 01:15:56,640 MODIFICATION. 1764 01:15:56,640 --> 01:15:59,560 WE HAVE, AGAIN, IMPAIRMENT OF 1765 01:15:59,560 --> 01:16:00,600 THE MECHANICAL MOTOR. 1766 01:16:00,600 --> 01:16:02,320 IF YOU WANT TO PUT THAT WAY. 1767 01:16:02,320 --> 01:16:04,280 THE REASON THAT WE ARE HAVING 1768 01:16:04,280 --> 01:16:07,000 THAT IMPAIRMENT IS LOSS VERSUS 1769 01:16:07,000 --> 01:16:07,920 IMPAIRED FUNCTION. 1770 01:16:07,920 --> 01:16:09,400 IT SEEMS TO BE DIFFERENT MUSCLE 1771 01:16:09,400 --> 01:16:10,760 TO MUSCLE. 1772 01:16:10,760 --> 01:16:12,200 THIS WILL BE HUGELY IMPORTANT AS 1773 01:16:12,200 --> 01:16:15,120 WELL WHEN WE LOOK AT THE 1774 01:16:15,120 --> 01:16:16,640 INDIVIDUAL AS A WHOLE. 1775 01:16:16,640 --> 01:16:18,680 LOADING IS CRITICAL AS 1776 01:16:18,680 --> 01:16:19,960 ELECTRICAL AND CAME OUT THAT WE 1777 01:16:19,960 --> 01:16:23,000 -- MUSCLES NEED TO BE ACTIVE TO 1778 01:16:23,000 --> 01:16:24,000 BE HEALTHY. 1779 01:16:24,000 --> 01:16:25,880 SO, THESE ARE THE THREE THEMES. 1780 01:16:25,880 --> 01:16:27,280 MOVING FORWARD TO THE OTHER END 1781 01:16:27,280 --> 01:16:29,000 OF THE SPECTRUM WHICH IS, YOU 1782 01:16:29,000 --> 01:16:31,040 KNOW, RECOVERY. THE QUESTION 1783 01:16:31,040 --> 01:16:33,560 COMES UP, SHOULD WE EVEN BE 1784 01:16:33,560 --> 01:16:36,320 TARGETING LOSS OF MUSCLE? 1785 01:16:36,320 --> 01:16:39,320 BECAUSE PERHAPS IF WE TRY TO 1786 01:16:39,320 --> 01:16:40,920 INHIBIT RELEASE OF AMINO ASS 1787 01:16:40,920 --> 01:16:42,760 SITS, ET CETERA, THIS WILL BE 1788 01:16:42,760 --> 01:16:44,400 HARMFUL TO THE ORGANISM THAT IS 1789 01:16:44,400 --> 01:16:46,120 TRYING TO SURVIVE CRITICAL 1790 01:16:46,120 --> 01:16:48,320 ILLNESS AND WE ARE LUCKY IN 1791 01:16:48,320 --> 01:16:49,680 MUSCLE IN THAT WE HAVE ANOTHER 1792 01:16:49,680 --> 01:16:52,760 END THAT IS RECOVERY AS JASON 1793 01:16:52,760 --> 01:16:54,400 WENT INTO. RECOVERY IS 1794 01:16:54,400 --> 01:16:56,280 IMPORTANT IN MUSCLE AGAIN. 1795 01:16:56,280 --> 01:16:58,080 WE ARE ADVANCING -- ADVANTAGE WE 1796 01:16:58,080 --> 01:16:59,600 CAN STICK ALL PROTEIN BACK IN 1797 01:16:59,600 --> 01:17:01,480 AND TRY TO MAKE IT BIGGER AND 1798 01:17:01,480 --> 01:17:03,560 FUNCTION BETTER AND WE CAN 1799 01:17:03,560 --> 01:17:05,880 REGENERATE IT AND MAKE NEW 1800 01:17:05,880 --> 01:17:06,120 MUSCLE. 1801 01:17:06,120 --> 01:17:08,000 STEM CELL IS ANOTHER POPULATION 1802 01:17:08,000 --> 01:17:09,480 WE CAN SPECIFICALLY TARGET IF IN 1803 01:17:09,480 --> 01:17:12,960 THE MUSCLE AND TRY TO MAINTAIN 1804 01:17:12,960 --> 01:17:14,840 HEALTH AND BRING BACK. WE HAVE 1805 01:17:14,840 --> 01:17:17,080 KEY THEMES, I THINK, THAT CAME 1806 01:17:17,080 --> 01:17:18,400 OUT IN THIS. 1807 01:17:18,400 --> 01:17:21,160 AGE AND -- AND IT IS HUGELY 1808 01:17:21,160 --> 01:17:21,480 IMPORTANT. 1809 01:17:21,480 --> 01:17:23,040 THE TYPE OF MUSCLE THAT YOU ARE 1810 01:17:23,040 --> 01:17:27,160 LOOKING AT IS GOING TO BE 1811 01:17:27,160 --> 01:17:28,680 MANIFESTING DIFFERENT THE 1812 01:17:28,680 --> 01:17:29,600 INSIDES DIFFERENTLY. 1813 01:17:29,600 --> 01:17:31,400 WE ARE LOOKING AT NOT JUST LOSS 1814 01:17:31,400 --> 01:17:33,200 BUT RECOVERY AND TRYING TO 1815 01:17:33,200 --> 01:17:35,440 TARGET 1 OR THE OTHER OR BOTH. 1816 01:17:35,440 --> 01:17:37,040 MAY BE DIFFERENT DEPENDING ON 1817 01:17:37,040 --> 01:17:39,360 AGE OF THE PATIENT AND MIGHT BE 1818 01:17:39,360 --> 01:17:41,760 EASIER TO RESCUE 1 VERSUS THE 1819 01:17:41,760 --> 01:17:44,000 OTHER. THAT IS MY SYNOPSIS. 1820 01:17:44,000 --> 01:17:46,120 CLARK, WANT TO ADD ANYTHING 1821 01:17:46,120 --> 01:17:46,360 ELSE? 1822 01:17:46,360 --> 01:17:48,840 >> REALLY GOOD AND CAN LINK 1823 01:17:48,840 --> 01:17:51,000 MAJOR POINTS TO A FEW QUESTIONS 1824 01:17:51,000 --> 01:17:51,720 IN THE CHAT. 1825 01:17:51,720 --> 01:17:55,680 ONE I WOULD LIKE TO ADD FOR OUR 1826 01:17:55,680 --> 01:17:58,240 DISCUSSION NOW LINKS BACK WITH 1827 01:17:58,240 --> 01:18:00,640 THE DISCUSSION IN SESSION 2 1828 01:18:00,640 --> 01:18:01,920 YESTERDAY. 1829 01:18:01,920 --> 01:18:05,200 IT IS ABOUT USING COMPLEX ANIMAL 1830 01:18:05,200 --> 01:18:08,600 MODELS THAT REPLICATE ICU 1831 01:18:08,600 --> 01:18:10,360 ENVIRONMENT AND THINK THAT DR. 1832 01:18:10,360 --> 01:18:11,800 LARSON HAS EXTENSIVE AMOUNT OF 1833 01:18:11,800 --> 01:18:13,680 EXPERIENCE IN THIS AREA AND 1834 01:18:13,680 --> 01:18:14,840 THINK WE SHOULD BRING FORWARD 1835 01:18:14,840 --> 01:18:16,280 THE DISCUSSION ABOUT, YOU KNOW, 1836 01:18:16,280 --> 01:18:17,960 HOW DO WE THINK ABOUT THESE 1837 01:18:17,960 --> 01:18:20,440 COMPLEX MODELS? 1838 01:18:20,440 --> 01:18:22,560 AND, YOU KNOW, THEY ARE 1839 01:18:22,560 --> 01:18:25,120 CHALLENGING TO SET UP. 1840 01:18:25,120 --> 01:18:28,000 THEY INFORM THE COMPLEXITY AND 1841 01:18:28,000 --> 01:18:30,720 HETEROGENEITY OF THE ICU 1842 01:18:30,720 --> 01:18:32,680 ENVIRONMENT AND HOW WE SHOULD BE 1843 01:18:32,680 --> 01:18:36,120 THINKING OF THOSE MODELS IN OUR 1844 01:18:36,120 --> 01:18:36,360 FIELD. 1845 01:18:36,360 --> 01:18:38,840 THE OTHER QUESTION OR SORT OF 1846 01:18:38,840 --> 01:18:41,040 ADD-ON, I THINK, IS TO THINK A 1847 01:18:41,040 --> 01:18:43,360 BIT MORE ABOUTISH AUTO YOU WITH 1848 01:18:43,360 --> 01:18:45,560 IMPAIRED REGENERATION. 1849 01:18:45,560 --> 01:18:48,240 SO, THERE IS REALLY KEY POINTS 1850 01:18:48,240 --> 01:18:49,800 THAT I THINK ARE BROUGHT UP 1851 01:18:49,800 --> 01:18:50,320 HERE. 1852 01:18:50,320 --> 01:18:52,760 ONE, I PUT IN THE CHAT RELATED 1853 01:18:52,760 --> 01:18:55,720 TO JASON'S WORK IN POST SEPSIS 1854 01:18:55,720 --> 01:18:58,720 MOUSE MODEL AND APPEARS TO BE 1855 01:18:58,720 --> 01:19:00,800 FAILURE OF STEM CELL ACTIVATION. 1856 01:19:00,800 --> 01:19:03,320 OF COURSE, YOUR WORK, JAIN, IN 1857 01:19:03,320 --> 01:19:06,400 THIS AREA IN HUMANS SHOWS IN 1858 01:19:06,400 --> 01:19:08,920 WEAK PATIENTS THAT HAVE SURVIVED 1859 01:19:08,920 --> 01:19:11,200 CRITICAL ILLNESS AND THOSE THAT 1860 01:19:11,200 --> 01:19:14,960 REMAIN WEAK APPEAR TO HAVE 1861 01:19:14,960 --> 01:19:16,280 IMPAIRED STEM CELL REGENERATION 1862 01:19:16,280 --> 01:19:18,240 AND THINK THAT ACTIVATION, 1863 01:19:18,240 --> 01:19:20,280 QUESTION HERE IS, WHAT IS 1864 01:19:20,280 --> 01:19:20,640 DRIVING THAT? 1865 01:19:20,640 --> 01:19:22,480 WHAT IS OCCURRING? 1866 01:19:22,480 --> 01:19:24,680 DR. LANGLY PUT A REALLY GOOD 1867 01:19:24,680 --> 01:19:26,680 QUESTION IN THE CHAT AS TO WHAT 1868 01:19:26,680 --> 01:19:29,000 IS HAPPENING HERE AND WHAT IS 1869 01:19:29,000 --> 01:19:30,240 THE MECHANISM? 1870 01:19:30,240 --> 01:19:32,920 ARE THERE -- IS THIS ROSS 1871 01:19:32,920 --> 01:19:36,520 INDUCED DAMAGE THAT IS EFFECTING 1872 01:19:36,520 --> 01:19:38,520 SKELETAL MUSCLE LONG TERM? 1873 01:19:38,520 --> 01:19:41,040 WHAT DO WE THINK THE MECHANISM 1874 01:19:41,040 --> 01:19:45,600 IS THAT WE MIGHT BE DRIVING AT? 1875 01:19:45,600 --> 01:19:45,800 GREAT. 1876 01:19:45,800 --> 01:19:47,600 MAYBE WE COULD START WITH THAT, 1877 01:19:47,600 --> 01:19:49,320 THAT QUESTION RIGHT THERE. SO, 1878 01:19:49,320 --> 01:19:51,680 MAYBE I WILL POSE THAT BACK TO 1879 01:19:51,680 --> 01:19:52,680 DR. DOLES. 1880 01:19:52,680 --> 01:19:55,160 WHAT DO YOU THINK MIGHT BE 1881 01:19:55,160 --> 01:19:57,080 DRIVING THAT IMPAIRED ACTIVATION 1882 01:19:57,080 --> 01:20:00,120 OF SATELLITE CELLS IN YOUR 1883 01:20:00,120 --> 01:20:00,400 MODEL? 1884 01:20:00,400 --> 01:20:02,960 >> YEAH. NO. I MEAN, I THINK 1885 01:20:02,960 --> 01:20:05,200 THAT IS A BIG -- I MEAN, IT IS A 1886 01:20:05,200 --> 01:20:07,320 BIG ONE. ONE THING WE NOTICED 1887 01:20:07,320 --> 01:20:09,800 AT LEAST FROM A WHOLE MUSCLE 1888 01:20:09,800 --> 01:20:11,560 STANDPOINT AND HAVEN'T LOOKED AT 1889 01:20:11,560 --> 01:20:14,440 SATELLITE CELLS SPECIFICALLY, WE 1890 01:20:14,440 --> 01:20:16,680 DON'T SEE PERSISTENT LOSS IF IN 1891 01:20:16,680 --> 01:20:19,240 MODEL AND LOOKING AT THAT IS 1892 01:20:19,240 --> 01:20:21,000 CONCURRENT WITH SATELLITE CELL 1893 01:20:21,000 --> 01:20:23,040 DISFUNCTION AND DON'T THINK 1894 01:20:23,040 --> 01:20:25,680 REQUIRED DRIVER OF SUSTAINED 1895 01:20:25,680 --> 01:20:26,760 SATELLITE CELL DISFUNCTION AND 1896 01:20:26,760 --> 01:20:30,560 WE DO SEE INCREASES IN DNA 1897 01:20:30,560 --> 01:20:33,080 DAMAGE MIGHT NOT BE ROSS DRIVEN 1898 01:20:33,080 --> 01:20:34,400 BUT DRIVEN BY SOMETHING ELSE, I 1899 01:20:34,400 --> 01:20:35,240 DON'T KNOW. 1900 01:20:35,240 --> 01:20:36,920 I THINK THAT THE IMPORTANT THING 1901 01:20:36,920 --> 01:20:40,360 IS WE DO SEE BOTH, YOU KNOW, 1902 01:20:40,360 --> 01:20:44,040 CELL INTRINSIC AND PERSISTENT 1903 01:20:44,040 --> 01:20:46,680 DEFECTS IN SATELLITE CELLS AND 1904 01:20:46,680 --> 01:20:48,720 NOT ONLY ARE DAMAGED AND 1905 01:20:48,720 --> 01:20:51,240 FUNCTIONING IN VIVO AND PULLING 1906 01:20:51,240 --> 01:20:52,800 OUT CULTURING THEM FOR WEEKS 1907 01:20:52,800 --> 01:20:54,560 THESE PERSIST AND CAN'T DO 1908 01:20:54,560 --> 01:20:58,080 NORMAL THING SUPPOSED TO DO IN 1909 01:20:58,080 --> 01:20:58,880 CULTURE AND [INDISCERNIBLE] ET 1910 01:20:58,880 --> 01:21:01,160 CETERA. SOMETHING IS HAPPENING 1911 01:21:01,160 --> 01:21:02,680 ALTERING NOW SOMEWHAT 1912 01:21:02,680 --> 01:21:04,960 PERMANENTLY HAVEN'T LOOKED SUPER 1913 01:21:04,960 --> 01:21:09,200 LONG TERM AT INTRINSIC FUNCTION 1914 01:21:09,200 --> 01:21:10,760 OF SATELLITE CELLS THAT WE HAVE 1915 01:21:10,760 --> 01:21:12,160 NOT QUITE TEASED OUT. 1916 01:21:12,160 --> 01:21:15,080 I'M NOT SURE ABOUT ROSS AS A -- 1917 01:21:15,080 --> 01:21:17,680 AS A CRITICAL DRIVER. 1918 01:21:17,680 --> 01:21:21,520 CERTAINLY, WE HAVE TO ADDRESS 1919 01:21:21,520 --> 01:21:24,120 ISSUES THAT ARE CELL AND 1920 01:21:24,120 --> 01:21:25,480 EXTRINSIC TO THE SATELLITE CELL. 1921 01:21:25,480 --> 01:21:27,680 >> ONE THING TO THINK ABOUT 1922 01:21:27,680 --> 01:21:30,320 ENVIRONMENT IN THE MUSCLES. 1923 01:21:30,320 --> 01:21:32,600 IN THE AGING ANIMALS, WE DON'T 1924 01:21:32,600 --> 01:21:34,720 SEE ANY IMPAIRMENT IN THE 1925 01:21:34,720 --> 01:21:37,120 ABILITY FOR PROTEIN SYNTHESIS 1926 01:21:37,120 --> 01:21:39,200 AND MYOFIBULAR PROTEINS ARE 1927 01:21:39,200 --> 01:21:41,880 BEING MADE AND NOT ASSEMBLED AND 1928 01:21:41,880 --> 01:21:46,080 NOT BEING FOLDED OR ASSEMBLED 1929 01:21:46,080 --> 01:21:48,000 PROPERLY INTO SARCOMERES AND YOU 1930 01:21:48,000 --> 01:21:49,920 MIGHT BE ABLE TO PRODUCE 1931 01:21:49,920 --> 01:21:52,160 PROTEINS AND MIGHT NOT BE ABLE 1932 01:21:52,160 --> 01:21:54,080 TO ASSEMBLE THEM CORRECTLY AND 1933 01:21:54,080 --> 01:21:58,680 WITH AGING THERE IS CHANGES IN 1934 01:21:58,680 --> 01:22:00,680 PROETEOSTASIS AEFFECTING 1935 01:22:00,680 --> 01:22:01,920 PROTEINS AND ADDING STEM CELLS 1936 01:22:01,920 --> 01:22:04,440 TO A BAD ENVIRONMENT MIGHT NOT 1937 01:22:04,440 --> 01:22:05,480 ENHANCE RECOVERY. 1938 01:22:05,480 --> 01:22:07,600 THERE IS A LOT WE STILL NEED TO 1939 01:22:07,600 --> 01:22:08,960 UNDERSTAND ABOUT WHAT IS 1940 01:22:08,960 --> 01:22:11,920 HAPPENING IN THESE PATIENTS POST 1941 01:22:11,920 --> 01:22:15,000 RECOVERY AND LARS MIGHT BE ABLE 1942 01:22:15,000 --> 01:22:20,120 TO ADDRESS THAT MORE. 1943 01:22:20,120 --> 01:22:22,360 >> ONE THING I WOULD LIKE TO 1944 01:22:22,360 --> 01:22:25,280 ADD IS LIFE-SAVING INTERVENTIONS 1945 01:22:25,280 --> 01:22:28,400 IN ICU HAVE ALSO NEGATIVE 1946 01:22:28,400 --> 01:22:30,720 CONSEQUENCES UNRELATE TODAY 1947 01:22:30,720 --> 01:22:33,800 SEPSIS AND OTHER INTERVENTIONS. 1948 01:22:33,800 --> 01:22:35,560 MAYBE ONE WAY TO REDUCE NEGATIVE 1949 01:22:35,560 --> 01:22:38,720 IN THE ELDERLY ESPECIALLY IS 1950 01:22:38,720 --> 01:22:40,640 REDUCING LUNG INDUCED INJURY BY 1951 01:22:40,640 --> 01:22:44,080 VENTILATOR THAT IS A LARGE 1952 01:22:44,080 --> 01:22:45,560 SAVING INTERVENTION. 1953 01:22:45,560 --> 01:22:49,000 AND THERE MAY BE OTHER WAYS. 1954 01:22:49,000 --> 01:22:52,800 AND LONG TIME AGO DURING POLIO 1955 01:22:52,800 --> 01:22:55,120 PANDEMIC, IRON LUNG WAS USED 1956 01:22:55,120 --> 01:22:56,360 WITH NEGATIVE PRESSURE 1957 01:22:56,360 --> 01:22:57,960 VENTILATION AND ONE COULD 1958 01:22:57,960 --> 01:23:01,520 MONITOR 50 PATIENTS AND ANOTHER 1959 01:23:01,520 --> 01:23:04,560 USING -- ONE IS MONITORING TWO 1960 01:23:04,560 --> 01:23:07,080 PATIENTS AND AT SAME TIME GET 1961 01:23:07,080 --> 01:23:10,880 LUNG INJURY AND FACTORS WITH 1962 01:23:10,880 --> 01:23:12,440 PERIPHERAL ORGANS AND NOT GOING 1963 01:23:12,440 --> 01:23:14,160 BACK TO IRON LUNG AND SOMETHING 1964 01:23:14,160 --> 01:23:16,000 THAT WE COULD THINK OF USING 1965 01:23:16,000 --> 01:23:17,760 DIFFERENT MODES OF VENTILATION 1966 01:23:17,760 --> 01:23:20,120 THAT INDUCES LESS LUNG INJURY. 1967 01:23:20,120 --> 01:23:23,520 I WAS ALSO VERY INTRIGUED ALSO 1968 01:23:23,520 --> 01:23:25,440 BY THE PRESENTATIONS YESTERDAY 1969 01:23:25,440 --> 01:23:29,160 ABOUT THE LUNG INDUCED LUNG 1970 01:23:29,160 --> 01:23:31,320 INJURY INFECTION CENTRAL NERVOUS 1971 01:23:31,320 --> 01:23:34,640 SYSTEM AS WELL AND THIS HAS SITO 1972 01:23:34,640 --> 01:23:38,360 TOXIC EFFECTS ON CELL TYPES AND 1973 01:23:38,360 --> 01:23:40,080 PERIPHERY AND CENTRAL NERVOUS 1974 01:23:40,080 --> 01:23:41,720 SYSTEM AND INTERVENTIONS TRY TO 1975 01:23:41,720 --> 01:23:44,640 TALK AND REDUCE NEGATIVE EFFECTS 1976 01:23:44,640 --> 01:23:49,880 OF MECHANICAL VENTILATION OF THE 1977 01:23:49,880 --> 01:23:53,000 LUNG REDUCING NEGATIVE EFFECTS 1978 01:23:53,000 --> 01:23:55,640 OF PERIPHERAL ORGANS AND 1979 01:23:55,640 --> 01:23:58,800 ACTUALLY MYOSIN AND 1980 01:23:58,800 --> 01:24:00,960 [INDISCERNIBLE] MUSCLES MODIFIED 1981 01:24:00,960 --> 01:24:02,680 THAT IMPAIRS FUNCTION BUT THEN 1982 01:24:02,680 --> 01:24:05,840 OF COURSE WHEN YOU HAVE 1983 01:24:05,840 --> 01:24:07,960 PREFERENTIAL MYOSIN LOSS, THIS 1984 01:24:07,960 --> 01:24:10,120 BECOMES NOT SO IMPORTANT. 1985 01:24:10,120 --> 01:24:12,960 AT THE SAME TIME, THE DIAPHRAGM 1986 01:24:12,960 --> 01:24:15,840 IS CONSTANTLY BEING MECHANICALLY 1987 01:24:15,840 --> 01:24:19,000 LOADED BY VENTILATOR AND WHEN WE 1988 01:24:19,000 --> 01:24:21,360 DID, THIS IS JUST A SIMPLE 1989 01:24:21,360 --> 01:24:23,760 EXPERIMENT NEEDING TO BE 1990 01:24:23,760 --> 01:24:26,000 REPEATED. WHEN WE DOUBLE NUMBER 1991 01:24:26,000 --> 01:24:28,040 OF MECHANICAL LOADINGS IN 1992 01:24:28,040 --> 01:24:30,320 MUSCLES WE HAVE NO MYOSIN LOSS 1993 01:24:30,320 --> 01:24:31,960 THERE IS STILL COMPROMISED 1994 01:24:31,960 --> 01:24:35,040 FUNCTION AND THINK IT MAY BE -- 1995 01:24:35,040 --> 01:24:37,320 THE LIMB MUSCLES BECOME LIKE A 1996 01:24:37,320 --> 01:24:38,680 DIAPHRAGM WHEN YOU ARE 1997 01:24:38,680 --> 01:24:42,040 CONSTANTLY LOADED. OF COURSE, 1998 01:24:42,040 --> 01:24:45,520 IT HAS A CROSS-EFFECTS ON 1999 01:24:45,520 --> 01:24:49,600 FUNCTION DOESN'T REDUCE LIMIT ON 2000 01:24:49,600 --> 01:24:51,120 FUNCTION THOUGH. 2001 01:24:51,120 --> 01:24:53,040 >> THOSE ARE REALLY, REALLY 2002 01:24:53,040 --> 01:24:55,800 INTERESTING POINTS. 2003 01:24:55,800 --> 01:25:03,720 AS YOU WERE TALKING ABOUT 2004 01:25:03,720 --> 01:25:07,720 MECHANICAL INTERVATION ON MUSCLE 2005 01:25:07,720 --> 01:25:09,120 WASTING AND THINKING OF PAST 2006 01:25:09,120 --> 01:25:11,480 THREE YEARS THINKING ABOUT 2007 01:25:11,480 --> 01:25:14,160 THROUGH COVID PANDEMIC AND WE -- 2008 01:25:14,160 --> 01:25:17,880 WORLDWIDE I THINK WE ARE USING A 2009 01:25:17,880 --> 01:25:20,680 MUCH HIGHER LEVEL OF HEATED HIGH 2010 01:25:20,680 --> 01:25:23,240 FLOW NASAL OXYGEN RATHER THAN 2011 01:25:23,240 --> 01:25:24,240 INVAESSIVE MECHANICAL 2012 01:25:24,240 --> 01:25:26,960 VENTILATION IN PATIENTS WITH 2013 01:25:26,960 --> 01:25:28,480 SEVERE ACUTE RESPIRATORY FAILURE 2014 01:25:28,480 --> 01:25:30,080 AND ARDS NOW. 2015 01:25:30,080 --> 01:25:33,040 I DON'T KNOW OF ANY STUDIES 2016 01:25:33,040 --> 01:25:34,720 DURING THE PANDEMIC THAT 2017 01:25:34,720 --> 01:25:37,120 COMPARED RATE OF MUSCLE WASTING 2018 01:25:37,120 --> 01:25:39,720 IN COVID PATIENTS WHO WERE 2019 01:25:39,720 --> 01:25:41,640 INVASIVELY MECHANICALLY 2020 01:25:41,640 --> 01:25:43,600 VENTILATED VERSUS THOSE ON HIGH 2021 01:25:43,600 --> 01:25:44,760 HEATED FLOW AND ANYONE IN THE 2022 01:25:44,760 --> 01:25:46,360 PANEL IF YOU KNOW OF THAT 2023 01:25:46,360 --> 01:25:47,760 INFORMATION AND COULD THINK OF 2024 01:25:47,760 --> 01:25:49,160 THAT, IT MIGHT BE INTERESTING 2025 01:25:49,160 --> 01:25:50,800 WAY TO GET AT THAT REALLY 2026 01:25:50,800 --> 01:25:52,160 IMPORTANT QUESTION. 2027 01:25:52,160 --> 01:25:53,880 ALTHOUGH, THERE IS CLEARLY GO TO 2028 01:25:53,880 --> 01:25:58,960 BE CONFOUNDING BY INDICATION 2029 01:25:58,960 --> 01:26:00,800 BECAUSE SICKER PATIENTS TEND TO 2030 01:26:00,800 --> 01:26:03,600 BE ON MECHANICAL VENTILATOR MORE 2031 01:26:03,600 --> 01:26:03,840 OFTEN. 2032 01:26:03,840 --> 01:26:06,000 >> I SKIP OVER THIS AND MAYBE 2033 01:26:06,000 --> 01:26:08,800 IT DOESN'T FULLY ADDRESS YOUR 2034 01:26:08,800 --> 01:26:10,120 QUESTION. IN BEGINNING OF 2035 01:26:10,120 --> 01:26:13,240 PANDEMIC 15 OUT OF 16 PATIENTS 2036 01:26:13,240 --> 01:26:15,720 AND COVID MODEL AND OTHER ONE 2037 01:26:15,720 --> 01:26:18,400 WAS BORDER LINE AND THERE WAS A 2038 01:26:18,400 --> 01:26:20,120 PAPER IN THE AGE RELATED 2039 01:26:20,120 --> 01:26:22,200 DIFFERENCES IN THE INCREASED 2040 01:26:22,200 --> 01:26:25,600 MORTALITY AND ELDERLY COVID 2041 01:26:25,600 --> 01:26:27,400 PATIENTS AND, OF COURSE, 2042 01:26:27,400 --> 01:26:30,640 ESPECIALLY IN THE BEGINNING, 2043 01:26:30,640 --> 01:26:31,760 THESE PATIENTS WERE VENTILATED 2044 01:26:31,760 --> 01:26:34,800 IN THE PRO ENPOSITION AND USE 2045 01:26:34,800 --> 01:26:37,880 CONTROLLED MECHANICAL 2046 01:26:37,880 --> 01:26:42,720 INTERVENTION AND USING -- WE HAD 2047 01:26:42,720 --> 01:26:47,320 THESE RATS YOUNG AND OLD 2048 01:26:47,320 --> 01:26:50,000 MECHANICALLY VENTILATED AND 2049 01:26:50,000 --> 01:26:50,840 CYTOKINES CONSIDERED TO BE VIRAL 2050 01:26:50,840 --> 01:26:53,080 EFFECT IN THE ELDERLY AND WENT 2051 01:26:53,080 --> 01:26:55,600 BACK AND CHECKED IN DIAPHRAGM OF 2052 01:26:55,600 --> 01:26:58,360 YOUNG AND OLD RAT AND YOUNG RATS 2053 01:26:58,360 --> 01:27:03,120 WE SAW AT GENE LEVEL 2054 01:27:03,120 --> 01:27:05,400 TRANSCRIPTION BIOREGULATOR 2055 01:27:05,400 --> 01:27:07,160 METABOLIC PATHWAY. 2056 01:27:07,160 --> 01:27:09,880 IN OLD ANIMALS IMMUNE RESPONSES 2057 01:27:09,880 --> 01:27:11,640 WERE SKYROCKETING. 2058 01:27:11,640 --> 01:27:15,320 ACTUALLY, YOU SEE A CYTOKINE 2059 01:27:15,320 --> 01:27:17,160 STORM AS RESPONSE TO MECHANICAL 2060 01:27:17,160 --> 01:27:19,600 VENTILATION AND PROBABLY HAVE A 2061 01:27:19,600 --> 01:27:23,240 LUNG MUCH MORE VULNERABLE TO 2062 01:27:23,240 --> 01:27:24,440 VENTILATOR INDUCED LUNG INJURY 2063 01:27:24,440 --> 01:27:28,560 AND FACTORS AND WE HAVE 2064 01:27:28,560 --> 01:27:39,120 INTERESTING AGE EFFECT AS WELL 2065 01:27:52,440 --> 01:27:52,760 -- 2066 01:27:52,760 --> 01:27:54,560 >> MAYBE THIS IS A QUESTION 2067 01:27:54,560 --> 01:27:58,360 REALLY THAT IS TO MAYBE TO THE 2068 01:27:58,360 --> 01:28:02,000 NIH LCHLTD BI STAFF TO WHAT 2069 01:28:02,000 --> 01:28:03,280 EXTENT THESE INFORMATIONAL 2070 01:28:03,280 --> 01:28:04,640 SESSIONS ARE GREAT GETTING 2071 01:28:04,640 --> 01:28:09,440 PEOPLE INTERESTED IN THIS HLBI 2072 01:28:09,440 --> 01:28:11,960 SUPPORTING -- P. PGS THAT WILL 2073 01:28:11,960 --> 01:28:14,200 ALLOW US TO -- IT SEEMS LIKE A 2074 01:28:14,200 --> 01:28:16,360 ONE PERSON OR LAB EFFORT TO DO 2075 01:28:16,360 --> 01:28:17,680 THIS. IS THIS SOMETHING ON 2076 01:28:17,680 --> 01:28:20,160 RADAR THAT WILL BE PRIORITY TO 2077 01:28:20,160 --> 01:28:24,320 ASSEMBLE TEAMS TO HAVE COMPLEX 2078 01:28:24,320 --> 01:28:28,440 MODELS AND ADJUST MULTIPLE 2079 01:28:28,440 --> 01:28:31,560 TISSUES AND RESEARCH TOGETHER? 2080 01:28:31,560 --> 01:28:34,680 JUST WONDERING. 2081 01:28:34,680 --> 01:28:38,160 >> I DON'T WANT TO SPEAK FOR 2082 01:28:38,160 --> 01:28:40,600 NHLBI THERE IS A LARGE FUNDED 2083 01:28:40,600 --> 01:28:43,640 OBSERVATIONAL STUDY THAT WILL BE 2084 01:28:43,640 --> 01:28:47,560 MULTICENTERED THAT IS NIGMS AND 2085 01:28:47,560 --> 01:28:49,680 NHLBI FUNDED LOOKING AT 2086 01:28:49,680 --> 01:28:51,840 COLLECTING BIOSAMPLES AND 2087 01:28:51,840 --> 01:28:53,920 PATIENTS WITH PNEUMONIA SEPSIS 2088 01:28:53,920 --> 01:28:58,720 AND ARDS THAT SHOULD BE GETTING 2089 01:28:58,720 --> 01:29:03,040 STARTED SOON AND MAY HELP. 2090 01:29:03,040 --> 01:29:04,880 WE WILL LET SESSION CHAIRS TALK 2091 01:29:04,880 --> 01:29:06,280 MORE ABOUT THIS AT THE END OF 2092 01:29:06,280 --> 01:29:07,680 THE SESSION AND WANT TO MOVE TO 2093 01:29:07,680 --> 01:29:09,440 A POINT THAT CAME UP IN THE 2094 01:29:09,440 --> 01:29:11,640 DISCUSSION A COUPLE TIMES HERE 2095 01:29:11,640 --> 01:29:16,600 THAT IS FROM TERRI HUH AND 2096 01:29:16,600 --> 01:29:18,040 LAUREN F. 2097 01:29:18,040 --> 01:29:21,120 ADDRESSING THIS ISSUE THAT TENDS 2098 01:29:21,120 --> 01:29:23,480 TO COME UP IN DISCUSSIONS WHEN 2099 01:29:23,480 --> 01:29:25,640 GETTING HEALTH OUTCOMES 2100 01:29:25,640 --> 01:29:27,480 RESEARCHERS AND CLINICAL 2101 01:29:27,480 --> 01:29:32,880 TRIALISTS AND MUSCLE BIOLOGISTS 2102 01:29:32,880 --> 01:29:33,120 TOGETHER. 2103 01:29:33,120 --> 01:29:35,480 THAT IS WHAT IS RELATIONSHIP 2104 01:29:35,480 --> 01:29:38,800 BETWEEN MUSCLE ATROPHY AND 2105 01:29:38,800 --> 01:29:41,200 FUNCTIONAL OUTCOMES IS TARGETING 2106 01:29:41,200 --> 01:29:43,640 ATROPHY IMPORTANT AT ALL OR SIZE 2107 01:29:43,640 --> 01:29:45,200 IMPORTANT? HOW DOES IT RELATE 2108 01:29:45,200 --> 01:29:46,520 TO PHYSICAL FUNCTION AND 2109 01:29:46,520 --> 01:29:47,400 RECOVERY? 2110 01:29:47,400 --> 01:29:50,320 WE HAVE REALLY EXPERT SKELETAL 2111 01:29:50,320 --> 01:29:51,840 MUSCLE BIOLOGISTS HERE ON THE 2112 01:29:51,840 --> 01:29:54,280 PANEL THAT MIGHT BE ABLE TO HELP 2113 01:29:54,280 --> 01:29:56,120 US THINK THROUGH THESE ISSUES 2114 01:29:56,120 --> 01:30:00,160 AND I MAYBE WILL TURN TO SUE TO 2115 01:30:00,160 --> 01:30:03,480 ANSWER THAT QUESTION. 2116 01:30:03,480 --> 01:30:06,560 >> YEAH. I THINK LARS CAN 2117 01:30:06,560 --> 01:30:07,920 ANSWER THIS TOO. 2118 01:30:07,920 --> 01:30:09,680 I THINK SIZE IS IMPORTANT AND WE 2119 01:30:09,680 --> 01:30:14,080 KNOW IN NORMAL MUSS THAT'LL 2120 01:30:14,080 --> 01:30:15,400 CROSS-SECTIONAL CORRELATES WITH 2121 01:30:15,400 --> 01:30:16,600 FORCE PRODUCTION AND MUSCLE HAS 2122 01:30:16,600 --> 01:30:20,680 TO BE ABLE TO BE ACTIVATED AND 2123 01:30:20,680 --> 01:30:26,000 IF THERE IS PROBLEMS WITH 2124 01:30:26,000 --> 01:30:27,240 NEUROMUSCULAR JUVENGS OR 2125 01:30:27,240 --> 01:30:28,520 ACTIVATION OF MUSCLE DOESN'T 2126 01:30:28,520 --> 01:30:32,840 MATTER HOW MUCH MUSCLE IS THERE 2127 01:30:32,840 --> 01:30:36,560 IF CAN'T BE ACTIVATED DON'T GET 2128 01:30:36,560 --> 01:30:39,120 FORCE PRODUCTION AND EFFECTING 2129 01:30:39,120 --> 01:30:41,600 FORCE TRANSDUCTION. 2130 01:30:41,600 --> 01:30:43,120 SO, IN THESE DISEASE CONDITIONS 2131 01:30:43,120 --> 01:30:47,360 OR ACUTE CONDITIONS, THEY DON'T 2132 01:30:47,360 --> 01:30:50,560 ALWAYS CORRELATE. 2133 01:30:50,560 --> 01:30:55,280 SO, YEAH. I MEAN IT IS COMPLEX 2134 01:30:55,280 --> 01:31:01,680 AND WE HAVE TO CONSIDER SIZE AND 2135 01:31:01,680 --> 01:31:05,520 INTERVATION AND HOW THESE 2136 01:31:05,520 --> 01:31:09,600 CROSS-BRIDGES ARE 2137 01:31:09,600 --> 01:31:12,520 INTERFUNCTIONING. 2138 01:31:12,520 --> 01:31:15,600 >> ALL RIGHT. 2139 01:31:15,600 --> 01:31:17,360 >> CAN I ASK -- I WANT TO ALSO 2140 01:31:17,360 --> 01:31:19,200 MAKE THE POINT HOW WE MEASURE 2141 01:31:19,200 --> 01:31:21,360 SIZE IN MUSCLE MASS IS ALSO 2142 01:31:21,360 --> 01:31:21,680 IMPORTANT. 2143 01:31:21,680 --> 01:31:23,440 I THINK IN HUMANS THAT HAS BEEN 2144 01:31:23,440 --> 01:31:27,040 A PROBLEM OF GETTING ACCURATE 2145 01:31:27,040 --> 01:31:28,880 MEASUREMENTS OF LEAN MUSCLE 2146 01:31:28,880 --> 01:31:29,200 MASS. 2147 01:31:29,200 --> 01:31:32,720 JUST SOMETIMES IN ANIMAL MODELS 2148 01:31:32,720 --> 01:31:35,040 JUST WEIGHING MUSCLE DOESN'T 2149 01:31:35,040 --> 01:31:37,360 REALLY REFLECT WHAT IS GOING ON 2150 01:31:37,360 --> 01:31:41,560 INSIDE AND HAVING BETTER WAYS OF 2151 01:31:41,560 --> 01:31:45,520 MEASURING MUSCLE MASS GETTING 2152 01:31:45,520 --> 01:31:48,120 BETTER INDICATION OF LEAN MASS 2153 01:31:48,120 --> 01:31:51,680 AND FUNCTIONAL MASS. 2154 01:31:51,680 --> 01:31:53,800 >> SO, I THINK I TRIED TO PUT 2155 01:31:53,800 --> 01:31:56,560 AN ANSWER IN THE CHAT RELATED TO 2156 01:31:56,560 --> 01:32:01,720 WHAT DR. BODEN JUST MENTIONED 2157 01:32:01,720 --> 01:32:03,840 AND THINK THAT THIS ISSUE OF 2158 01:32:03,840 --> 01:32:06,160 OUTCOMES AND FUNCTIONAL RECOVERY 2159 01:32:06,160 --> 01:32:07,600 AND DEFINING FUNCTIONAL RECOVERY 2160 01:32:07,600 --> 01:32:09,040 IS CRITICALLY IMPORTANT HERE. 2161 01:32:09,040 --> 01:32:12,160 SO, IF WE HAVE A -- IF WE DESIGN 2162 01:32:12,160 --> 01:32:14,520 A CLINICAL TRIAL FOCUSED ON 2163 01:32:14,520 --> 01:32:16,160 PHYSICAL FUFRJS RECOVERY 2164 01:32:16,160 --> 01:32:18,920 OUTCOMES SAY A 6 MINUTE WALK OR 2165 01:32:18,920 --> 01:32:21,920 SOMETHING SUCH, YOU MIGHT HAVE A 2166 01:32:21,920 --> 01:32:24,480 DRUG OR INTERVENTION IMPROVING 2167 01:32:24,480 --> 01:32:27,200 MUSCLE MASS OR MITIGATING MUSCLE 2168 01:32:27,200 --> 01:32:29,800 MASS MAKING MUSCLE MASS STRONGER 2169 01:32:29,800 --> 01:32:31,960 NOT DOG ANYTHING TO 6 MINUTE 2170 01:32:31,960 --> 01:32:35,000 WALK TEST AND CARDIOVASCULAR 2171 01:32:35,000 --> 01:32:38,640 COMPONENT TO 6 MINUTE WALK AND 2172 01:32:38,640 --> 01:32:41,840 PHYSICAL -- SO, I DO THINK WE 2173 01:32:41,840 --> 01:32:44,040 NEED TO BE VERY CAREFUL ABOUT 2174 01:32:44,040 --> 01:32:45,560 WHAT INTERVENTION IS AND WHAT WE 2175 01:32:45,560 --> 01:32:47,680 THINK WE ARE TARGETING IN THE 2176 01:32:47,680 --> 01:32:48,920 EXCEL TAR MUSCLE. 2177 01:32:48,920 --> 01:32:52,960 AND HOW WE MEASURE THAT IN A 2178 01:32:52,960 --> 01:32:55,840 CLINICAL OUTCOME. 2179 01:32:55,840 --> 01:32:58,240 >> DON'T FORGET THAT PHYSICAL 2180 01:32:58,240 --> 01:32:59,960 FUNCTION ALSO EMOTIONAL HOW 2181 01:32:59,960 --> 01:33:02,120 PATIENTS ARE FEELING COGNITIVELY 2182 01:33:02,120 --> 01:33:04,360 IMPACTED AND BECOMES REALLY 2183 01:33:04,360 --> 01:33:06,880 CHALLENGING TO MEASURE POST ICU. 2184 01:33:06,880 --> 01:33:09,720 WE DO A 6 MINUTE WALK TEST ONE 2185 01:33:09,720 --> 01:33:10,800 DAY AND THEY WILL DO EXCELLENT 2186 01:33:10,800 --> 01:33:14,240 AND DOING IT A FEW DAYS LATER 2187 01:33:14,240 --> 01:33:16,800 ANXIETY AND TRAUMATIC EVENT YOU 2188 01:33:16,800 --> 01:33:20,200 WILL GET HETERO JENAETY EVEN 2189 01:33:20,200 --> 01:33:25,520 WHEN FOLLOWING STANDARDIZED 2190 01:33:25,520 --> 01:33:25,880 PROTOCOL. 2191 01:33:25,880 --> 01:33:28,680 I WOULD LIKE TO MAYBE ASK DR. 2192 01:33:28,680 --> 01:33:30,960 LARSON A QUESTION AND TRY TO 2193 01:33:30,960 --> 01:33:32,160 LINK BACK TO THE SESSION 2194 01:33:32,160 --> 01:33:34,360 YESTERDAY THAT WAS FOCUSED ON 2195 01:33:34,360 --> 01:33:38,080 MECHANISMS OF NEUROCOGNITIVE 2196 01:33:38,080 --> 01:33:38,920 INJURY. 2197 01:33:38,920 --> 01:33:41,080 THE ROLE FOR COMPLEX ANIMAL 2198 01:33:41,080 --> 01:33:41,720 MODELS. 2199 01:33:41,720 --> 01:33:45,240 LARS, I'M INTERESTED TO KNOW 2200 01:33:45,240 --> 01:33:47,920 WHAT YOUR TAKE IS ON THE VALUE 2201 01:33:47,920 --> 01:33:52,080 OF THE MODELS THAT YOU HAVE 2202 01:33:52,080 --> 01:33:55,600 CREATED OF A PRECLINICAL ICU 2203 01:33:55,600 --> 01:33:57,200 ENVIRONMENT, NO. 1. 2204 01:33:57,200 --> 01:34:00,560 NO. 2, HAVE YOU LOOKED AT BRAIN 2205 01:34:00,560 --> 01:34:07,480 INJURY IN ANY OF YOUR MODELS? 2206 01:34:07,480 --> 01:34:09,880 >> I WILL START WITH A SECOND 2207 01:34:09,880 --> 01:34:11,720 QUESTION AND EXPERIMENTS ARE 2208 01:34:11,720 --> 01:34:13,680 DEMANDING AND WE HAVE TO BE 2209 01:34:13,680 --> 01:34:17,720 THERE 24 HOURS A DAY THOUGH. 2210 01:34:17,720 --> 01:34:20,560 IN 40 YEARS I DON'T THINK THEY 2211 01:34:20,560 --> 01:34:23,080 HAVE BEEN OPERATING AND WOKEN UP 2212 01:34:23,080 --> 01:34:25,680 FROM ANESTHESIA, SO TO SAY. 2213 01:34:25,680 --> 01:34:28,080 WE HAVE A SPECIAL ETHICAL XITEE. 2214 01:34:28,080 --> 01:34:30,200 ANYWAY, SO, WE ARE THERE 24 2215 01:34:30,200 --> 01:34:31,160 HOURS A DAY. 2216 01:34:31,160 --> 01:34:33,160 AT THE END, I THINK THAT WE ARE 2217 01:34:33,160 --> 01:34:36,560 INTERESTED IN MUSCLE AND I 2218 01:34:36,560 --> 01:34:38,960 COLLECT MORE THAN 92 AND AT END 2219 01:34:38,960 --> 01:34:41,560 OF THE EXPERIMENTS INCLUDING 2220 01:34:41,560 --> 01:34:52,120 BRAIN ONE WE FREEZE AND OTHER WE 2221 01:34:52,120 --> 01:34:53,760 FIXATE AND ARE THERE RAISING 2222 01:34:53,760 --> 01:34:56,440 HAND AND COLLECT A LOT OF TISSUE 2223 01:34:56,440 --> 01:35:01,120 AND LARGE BIOBANK FROM THIS. 2224 01:35:01,120 --> 01:35:02,960 WE HAVE TISSUE AND HAVEN'T 2225 01:35:02,960 --> 01:35:05,320 ANALYZED IT AND DON'T HAVE 2226 01:35:05,320 --> 01:35:06,920 EXPERTISE AND IF SOMEONE HAS 2227 01:35:06,920 --> 01:35:09,560 EXPERTISE WE ARE MORE THAN HAPPY 2228 01:35:09,560 --> 01:35:11,880 TO COLLABORATE AND USE OF MODELS 2229 01:35:11,880 --> 01:35:15,120 THOUGH AND THINK THAT PROBLEM 2230 01:35:15,120 --> 01:35:19,600 WITH CLINICAL STUDIES IS SO MANY 2231 01:35:19,600 --> 01:35:21,880 CONFOUNDING FACTORS AND FOCUSING 2232 01:35:21,880 --> 01:35:28,760 ON ICU CONDITION ITSELF. IT HAS 2233 01:35:28,760 --> 01:35:32,400 IMPACTS ON MUSCLE AND RAT MODEL 2234 01:35:32,400 --> 01:35:37,640 AND MODIFY IT AND MAKE IT LESS 2235 01:35:37,640 --> 01:35:37,920 INVASIVE. 2236 01:35:37,920 --> 01:35:42,120 WE SEE JEANO TYPE AND PHENOTYPE 2237 01:35:42,120 --> 01:35:52,200 IS SAME AS WE SEE IN ICU 2238 01:35:52,200 --> 01:35:56,120 PATIENTS AND STRONG SIMILARITIES 2239 01:35:56,120 --> 01:36:01,480 OF THESE COMMON DENOMINATOR IS 2240 01:36:01,480 --> 01:36:03,920 ICU CONDITION ITSELF AND MODEL 2241 01:36:03,920 --> 01:36:06,680 IS COMPLEX. 2242 01:36:06,680 --> 01:36:11,320 I THINK THAT ONLY ONE TRYING TO 2243 01:36:11,320 --> 01:36:13,280 REPLICATE MODEL AND KNOWING HOW 2244 01:36:13,280 --> 01:36:14,560 MUCH WORK IT WAS FROM BEGINNING 2245 01:36:14,560 --> 01:36:20,760 I WOULDN'T HAVE DONE IT EITHER 2246 01:36:20,760 --> 01:36:23,320 GIVING INFORMATION BITS AND 2247 01:36:23,320 --> 01:36:24,440 PIECE ABDZ WE THERE AND ANYONE 2248 01:36:24,440 --> 01:36:25,480 CAN DO IT. 2249 01:36:25,480 --> 01:36:32,240 IT IS A LOT OF WORK. THING FOR 2250 01:36:32,240 --> 01:36:35,760 ME IT HAS BEEN REWARDING. 2251 01:36:35,760 --> 01:36:37,960 WE HAVE LOTS OF TISSUE AND ARE 2252 01:36:37,960 --> 01:36:39,480 LOOKING AT -- SORRY. 2253 01:36:39,480 --> 01:36:42,360 >> I WAS GOING TO ASK, LARS 2254 01:36:42,360 --> 01:36:44,080 COULD YOU -- WOULD YOUR MODEL BE 2255 01:36:44,080 --> 01:36:48,560 ABLE TO BE ADAPTED TO ALLOW 2256 01:36:48,560 --> 01:36:51,720 ANIMALS TO RECOVER LOOKING AT 2257 01:36:51,720 --> 01:36:53,560 POST RECOVERY. 2258 01:36:53,560 --> 01:36:55,160 >> IN PRINCIPLE YES ABOUT YOU 2259 01:36:55,160 --> 01:36:56,320 IN PRACTICE EXPERIMENT I DON'T 2260 01:36:56,320 --> 01:36:58,440 WANT IT DO AND OTHER HAND OTHER 2261 01:36:58,440 --> 01:37:00,600 PATIENT IS VERY, VERY USEFUL AND 2262 01:37:00,600 --> 01:37:03,400 DID LONG TIME AGO AND FOLLOWED 2263 01:37:03,400 --> 01:37:05,520 PATIENTS LONGITUDINALLY AFTER 2264 01:37:05,520 --> 01:37:09,080 RECOVERY AND PATIENT HAS OWN 2265 01:37:09,080 --> 01:37:11,200 CONTROL AS WELL. 2266 01:37:11,200 --> 01:37:14,240 IT IS EASIER TO DO IN PATIENT 2267 01:37:14,240 --> 01:37:16,520 THAN RAT MODEL AND OUR MODEL IS 2268 01:37:16,520 --> 01:37:18,320 TERMINAL EXPERIMENT AND LOWEST 2269 01:37:18,320 --> 01:37:19,800 GRADE OR ANIMAL SUFFERING AS 2270 01:37:19,800 --> 01:37:23,560 WELL AND WOULD LIKE TO KEEP THAT 2271 01:37:23,560 --> 01:37:24,560 WAY AS WELL. 2272 01:37:24,560 --> 01:37:27,520 I WAS GOING TO BRING IT UP AND 2273 01:37:27,520 --> 01:37:30,040 ANIMAL MODELS ARE FABULOUS AND 2274 01:37:30,040 --> 01:37:32,000 LOOKING AT RECOVERY COMPONENT OF 2275 01:37:32,000 --> 01:37:36,920 THIS IN HUMANS ARE NOT PLEASANT 2276 01:37:36,920 --> 01:37:38,960 AND SERIAL BIOPSIES ARE POSSIBLE 2277 01:37:38,960 --> 01:37:40,800 AND YOUR INDIVIDUAL THAT YOU CAN 2278 01:37:40,800 --> 01:37:45,200 EXERCISE OR ELECTRICALLY 2279 01:37:45,200 --> 01:37:47,000 STIMULATE OR CHAFRJ DIET AND 2280 01:37:47,000 --> 01:37:51,080 INDIVIDUAL WHO IS NOT 2281 01:37:51,080 --> 01:37:52,920 PERSISTENTLY WEAK AND HEALTH AND 2282 01:37:52,920 --> 01:37:55,120 AGE AND -- YOU CAN DO 2283 01:37:55,120 --> 01:37:58,720 EXPERIMENTS IN HUMAN BEING 2284 01:37:58,720 --> 01:38:01,200 THEMSELVES POST ICU. 2285 01:38:01,200 --> 01:38:03,640 WE CAN PROBABLY DO CAUSE AND 2286 01:38:03,640 --> 01:38:07,200 EFFECT AND MECHANISTIC STUDIES 2287 01:38:07,200 --> 01:38:09,000 IN COMPLEX CREATURE ROLE IN THE 2288 01:38:09,000 --> 01:38:10,880 HUMAN AND THANKS FOR BRINGING IT 2289 01:38:10,880 --> 01:38:12,320 UP THAT WE OFTEN FORGET ABOUT 2290 01:38:12,320 --> 01:38:14,360 GOING BACK TO HUMANS TRYING TO 2291 01:38:14,360 --> 01:38:16,680 DO INTERVENTIONAL STUDIES WITHIN 2292 01:38:16,680 --> 01:38:19,120 HUMANS THAT ARE NOT JUST FARM 2293 01:38:19,120 --> 01:38:21,160 COLONL CAL BUT DOING LOADING AND 2294 01:38:21,160 --> 01:38:23,600 EXERCISE AND SEEING WHAT HAPPENS 2295 01:38:23,600 --> 01:38:25,920 TO SATELLITE AND SATELLITE CELL 2296 01:38:25,920 --> 01:38:28,000 IN INDIVIDUAL POST ICU RESPOND 2297 01:38:28,000 --> 01:38:31,600 THE SAME WAY TO HEAVY ISOMETRIC 2298 01:38:31,600 --> 01:38:33,640 IS EXERCISE THAT INDIVIDUAL WHO 2299 01:38:33,640 --> 01:38:35,920 DOESN'T HAVE PERSISTENT WEAKNESS 2300 01:38:35,920 --> 01:38:37,800 DOES. THERE ARE STUDIES WE CAN 2301 01:38:37,800 --> 01:38:43,880 DO IN PATIENT POPULATION. 2302 01:38:43,880 --> 01:38:45,360 >> WONDERFUL DISCUSSION. 2303 01:38:45,360 --> 01:38:47,280 WE HAVE FIVE MINUTES LEFT AND 2304 01:38:47,280 --> 01:38:48,840 THOUGHT THAT MAYBE WE COULD 2305 01:38:48,840 --> 01:38:50,720 SPEND THE LAST FEW MINUTES 2306 01:38:50,720 --> 01:38:52,200 TALKING ABOUT A QUESTION THAT 2307 01:38:52,200 --> 01:38:54,880 CAME INTO THE CHAT BY DR. SHAR 2308 01:38:54,880 --> 01:38:58,760 SHAR EARLY THAT IS A -- ALSO 2309 01:38:58,760 --> 01:39:01,360 ANOTHER GREAT TOPIC OF DEBATE 2310 01:39:01,360 --> 01:39:04,480 THAT CRITICAL CARE DOCTORS AND 2311 01:39:04,480 --> 01:39:07,760 MUSCLE PHYSIOLOGISTS DISCUSS AT 2312 01:39:07,760 --> 01:39:08,080 CONFERENCES. 2313 01:39:08,080 --> 01:39:10,800 I THINK THIS IS TRYING TO 2314 01:39:10,800 --> 01:39:13,720 PREVENT MUSCLE AT TROPHY OR 2315 01:39:13,720 --> 01:39:15,520 MUSCLE CATABOLISM IMPORTANT? 2316 01:39:15,520 --> 01:39:17,800 SHOULD WE JUST ACCEPT THAT THE 2317 01:39:17,800 --> 01:39:20,400 SKELETAL MUSCLE IS THERE? 2318 01:39:20,400 --> 01:39:23,520 THIS IS A TEEL LOGIC MECHANISM 2319 01:39:23,520 --> 01:39:25,520 IN PLACE TO PRESERVE AN ORGANISM 2320 01:39:25,520 --> 01:39:29,720 WHEN THERE IS A MAJOR CAT BOLIC 2321 01:39:29,720 --> 01:39:30,400 EVENT? 2322 01:39:30,400 --> 01:39:33,320 WHAT WOULD HAPPEN IF WE TRIED TO 2323 01:39:33,320 --> 01:39:35,960 PREVENT THIS CAT BOLIC EVENT? 2324 01:39:35,960 --> 01:39:40,000 MIGHT WE GET OURSELVES INTO MORE 2325 01:39:40,000 --> 01:39:43,160 TROUBLE THAN BENEFIT? 2326 01:39:43,160 --> 01:39:47,840 >> MAYBE I WILL ASK DR. BODINE 2327 01:39:47,840 --> 01:39:48,040 THAT. 2328 01:39:48,040 --> 01:39:50,880 >> [LAUGHING]. YOU ARE 2329 01:39:50,880 --> 01:39:51,160 PICKING. 2330 01:39:51,160 --> 01:39:51,560 >> I KNOW. 2331 01:39:51,560 --> 01:39:57,320 >> YEAH. I DON'T KNOW. 2332 01:39:57,320 --> 01:40:00,040 IS THERE A WAY TO SUPPLEMENT THE 2333 01:40:00,040 --> 01:40:03,520 PATIENT NUTRITIONALLY SO THEY 2334 01:40:03,520 --> 01:40:07,520 ARE NOT RELYING AS MUCH ON 2335 01:40:07,520 --> 01:40:13,040 MUSCLE BREAKDOWN? 2336 01:40:13,040 --> 01:40:15,680 OTHER CORING AN AND WHAT IS 2337 01:40:15,680 --> 01:40:19,080 HAPPENING IN LIVER AND TISSUES 2338 01:40:19,080 --> 01:40:22,120 AND PROTEIN BREAKDOWN IS GOOD 2339 01:40:22,120 --> 01:40:23,160 ALSO. 2340 01:40:23,160 --> 01:40:26,360 I DON'T KNOW YOU WANT COMPLETE 2341 01:40:26,360 --> 01:40:28,840 SUPPRESSION OF METABOLISM AND 2342 01:40:28,840 --> 01:40:34,360 WILL BE DIFFICULT TO DO. 2343 01:40:34,360 --> 01:40:41,040 JASON HAS HIS HAND UP. 2344 01:40:41,040 --> 01:40:43,560 >> I HAVE TO REMEMBER TO 2345 01:40:43,560 --> 01:40:45,440 UNMUTE. SUE, USING YOUR MICE 2346 01:40:45,440 --> 01:40:52,080 AND MICE THAT ARE DEFICIENT IN 2347 01:40:52,080 --> 01:40:54,840 MURF1 EXHIBIT LESS SKELETAL 2348 01:40:54,840 --> 01:40:56,800 MUSCLE WASTING FOR CONDITIONS 2349 01:40:56,800 --> 01:41:01,680 FOR OTHERS ON THE CALL. THEY 2350 01:41:01,680 --> 01:41:04,560 DIE ACTUALLY MORE READILY 2351 01:41:04,560 --> 01:41:08,880 ACUTELY TRYING SEPSIS THAT IS 2352 01:41:08,880 --> 01:41:10,120 UNPUBLISHED STUFF. 2353 01:41:10,120 --> 01:41:14,400 WE WERE INTERESTED IN STUDYING 2354 01:41:14,400 --> 01:41:19,440 RECOVERY AND OPPOSED TO -- IN A 2355 01:41:19,440 --> 01:41:25,000 CONDITION WHERE WE HAVE MILD 2356 01:41:25,000 --> 01:41:27,680 SEPSIS SO LESS THAN 20% ACUTE 2357 01:41:27,680 --> 01:41:29,600 MORTALITY ASSOCIATED WITH INSULT 2358 01:41:29,600 --> 01:41:32,760 OR LESS THAN 10% HALF OF MURF 2359 01:41:32,760 --> 01:41:34,280 MICE DIDN'T MAKE IT AND ARGUES 2360 01:41:34,280 --> 01:41:35,840 TO ME ACTIVE WASTING IS 2361 01:41:35,840 --> 01:41:38,080 IMPORTANT IN THE ACUTE PHASE. 2362 01:41:38,080 --> 01:41:40,040 AND IMPORTANT FOR THE RECOVERY 2363 01:41:40,040 --> 01:41:42,400 AS A NUTRIENT SOURCE FOR 2364 01:41:42,400 --> 01:41:45,600 SOMETHING AND NOT ACUTELY WITHIN 2365 01:41:45,600 --> 01:41:49,000 FIRST 20 BUT 24 TO 48 HOUR 2366 01:41:49,000 --> 01:41:50,560 WINDOW WHERE MICE WERE NOT -- 2367 01:41:50,560 --> 01:41:53,800 CLEARLY NOT RECOVERY AND REACHED 2368 01:41:53,800 --> 01:41:55,080 EXPERIMENTAL ENDPOINTS AND DON'T 2369 01:41:55,080 --> 01:41:58,240 KNOW WHAT YOU THINK ABOUT THAT, 2370 01:41:58,240 --> 01:41:58,440 SUE. 2371 01:41:58,440 --> 01:42:01,000 >> ONE THING I WOULD LIKE TO 2372 01:42:01,000 --> 01:42:04,040 ADD IS MAYBE IT IS IMPORTANT 2373 01:42:04,040 --> 01:42:08,000 SOURCE IN THE FIGHTING INFECTION 2374 01:42:08,000 --> 01:42:14,160 BUT I THINK THAT FIGHTING THE 2375 01:42:14,160 --> 01:42:18,560 CAUSE RELATED TO MODERN CRITICAL 2376 01:42:18,560 --> 01:42:20,960 CARE MECHANICAL VENTILATION 2377 01:42:20,960 --> 01:42:22,040 ITSELF AND LUNG INJURY COULDN'T 2378 01:42:22,040 --> 01:42:24,640 BE SOMETHING TO TRY TO AVOID, I 2379 01:42:24,640 --> 01:42:24,880 THINK. 2380 01:42:24,880 --> 01:42:27,480 THAT IS I THINK ACTUALLY A MAJOR 2381 01:42:27,480 --> 01:42:29,200 SOURCE AND MAYBE CHANGES THAT WE 2382 01:42:29,200 --> 01:42:30,200 SEE AS WELL. 2383 01:42:30,200 --> 01:42:34,000 I SEE NO REASON WHY ONE SHOULD 2384 01:42:34,000 --> 01:42:36,560 TRY TO AVOID THAT. 2385 01:42:36,560 --> 01:42:39,880 SOMETHING WE ARE TRYING TO DO 2386 01:42:39,880 --> 01:42:42,560 EXPONENTIALLY. SO FAR, IT LOOKS 2387 01:42:42,560 --> 01:42:45,160 PROMISING WITH SPECIFIC 2388 01:42:45,160 --> 01:42:46,960 INTERVENTIONS AND THESE BONE 2389 01:42:46,960 --> 01:42:49,920 MARROW DERIVED IN CHEMOSTROMAL 2390 01:42:49,920 --> 01:42:52,320 CELLS TARGETING INJURED LUNG 2391 01:42:52,320 --> 01:42:56,600 CELLS INDUCED BY MECHANICAL 2392 01:42:56,600 --> 01:43:00,360 VENTILA 2393 01:43:00,360 --> 01:43:00,680 VENTILATION. 2394 01:43:00,680 --> 01:43:01,760 >> GREAT DISCUSSION. I WILL 2395 01:43:01,760 --> 01:43:05,080 TRY TO HIT ONE MORE QUESTION IN 2396 01:43:05,080 --> 01:43:07,960 THE CHAT HERE. 2397 01:43:07,960 --> 01:43:10,920 THIS IS A QUESTION BROUGHT UP BY 2398 01:43:10,920 --> 01:43:13,560 MARK MOSS AND LAUREN. 2399 01:43:13,560 --> 01:43:16,280 IT IS THAT IF WE MEASURE MUSCLE 2400 01:43:16,280 --> 01:43:18,800 MASS OR STRENGTH OR FUNCTION AT 2401 01:43:18,800 --> 01:43:21,160 BEDSIDE OF CRITICALLY OLD 2402 01:43:21,160 --> 01:43:23,720 PATIENT, WHICH MUSCLE SHOULD WE 2403 01:43:23,720 --> 01:43:26,320 MEASURE? DIAPHRAGM BY 2404 01:43:26,320 --> 01:43:29,520 ULTRASOUND OR QUADRICEPS OR 2405 01:43:29,520 --> 01:43:31,920 ANKLE FLEXOR EXTENSOR? 2406 01:43:31,920 --> 01:43:33,920 WHAT SHOULD WE MEASURE? 2407 01:43:33,920 --> 01:43:35,160 WHAT IS IMPORTANT? 2408 01:43:35,160 --> 01:43:38,400 ANYONE ON THE PANEL WITH A 2409 01:43:38,400 --> 01:43:39,200 THOUGHT ABOUT THAT? 2410 01:43:39,200 --> 01:43:42,400 >> THANK YOU FOR ASKING. 2411 01:43:42,400 --> 01:43:45,080 DIAPHRAGM THAT I THINK IS HOW 2412 01:43:45,080 --> 01:43:46,880 QUICKLY THEY CAN TAKE PATIENT 2413 01:43:46,880 --> 01:43:50,080 OUT WITH AN ICU. 2414 01:43:50,080 --> 01:43:53,400 WHEN IT COMES TO LIMB MUSCLES, 2415 01:43:53,400 --> 01:43:56,440 PRIME OVER IS [INDISCERNIBLE] 2416 01:43:56,440 --> 01:44:01,120 MUSCLE CELL FOR WALKING, ET 2417 01:44:01,120 --> 01:44:01,520 CETERA. 2418 01:44:01,520 --> 01:44:04,240 SAME TIME MRC SCORES ARE USED TO 2419 01:44:04,240 --> 01:44:07,040 FOR DIAGNOSTIC PURPOSES I DON'T 2420 01:44:07,040 --> 01:44:09,880 UNDERSTAND HOW TO DO THIS 2421 01:44:09,880 --> 01:44:14,120 UNKROUSHS MECHANICAL EVENT 2422 01:44:14,120 --> 01:44:17,160 PATIENT THOUGH. 2423 01:44:17,160 --> 01:44:19,440 >> EXCELLENT. WE ARE ALMOST AT 2424 01:44:19,440 --> 01:44:23,600 TIME AND ONE MORE POINT TO MAKE 2425 01:44:23,600 --> 01:44:27,280 HERE THAT IS HAVING SOME 2426 01:44:27,280 --> 01:44:29,960 TRAINING IN GERIATRICS AS A 2427 01:44:29,960 --> 01:44:30,280 BYSTANDARD. 2428 01:44:30,280 --> 01:44:33,320 I HAVE LEARNED A BIT ABOUT 2429 01:44:33,320 --> 01:44:37,000 GERIATRICS FIELD. I THINK IT IS 2430 01:44:37,000 --> 01:44:40,960 IMPORTANT TO RECOGNIZE THAT KEY 2431 01:44:40,960 --> 01:44:42,840 EXPERIMENTS DR. BODINE SHOWED OF 2432 01:44:42,840 --> 01:44:46,600 DIFFERENT RESPONSE IN AGING MICE 2433 01:44:46,600 --> 01:44:48,360 IS DIFFERENT THAN YOUNGER 2434 01:44:48,360 --> 01:44:50,320 ANIMALS AND DOESN'T MEAN THAT 2435 01:44:50,320 --> 01:44:51,920 OLDER MICE WON'T RESPOND TO 2436 01:44:51,920 --> 01:44:52,520 INTERVENTIONS. 2437 01:44:52,520 --> 01:44:55,120 THERE IS A NUMBER OF STUDIES IN 2438 01:44:55,120 --> 01:44:58,480 OLDER HUMANS AND OLDER GERIATRIC 2439 01:44:58,480 --> 01:44:59,840 POPULATIONS WITH AGED MUSCLE 2440 01:44:59,840 --> 01:45:01,920 THAT ARE SHOWING OLDER HUMANS 2441 01:45:01,920 --> 01:45:05,880 CAN RESPOND TO INTERVENTIONS. 2442 01:45:05,880 --> 01:45:08,640 WE SHOULDN'T FEEL IT IS A LOST 2443 01:45:08,640 --> 01:45:11,200 CAUSE AND MIGHT BE A DIFFERENT 2444 01:45:11,200 --> 01:45:12,440 INTERVENTION BUT CRITICALLY 2445 01:45:12,440 --> 01:45:13,600 IMPORTANT POINT THAT I THOUGHT 2446 01:45:13,600 --> 01:45:16,960 WE COULD MAYBE FINISH WITH HERE. 2447 01:45:16,960 --> 01:45:21,000 SO -- ALL RIGHT. I THINK THAT 2448 01:45:21,000 --> 01:45:26,320 WE ARE AT TIME HERE. 2449 01:45:26,320 --> 01:45:28,640 >> THANK YOU, CLARK. TAKING A 2450 01:45:28,640 --> 01:45:31,640 15 MINUTE BREAK AND RECONVENING 2451 01:45:31,640 --> 01:45:33,600 AT 12 O'CLOCK EASTERN TIME. 2452 01:45:33,600 --> 01:45:35,480 THANK YOU, ALL. TAKE TIME TO 2453 01:45:35,480 --> 01:45:37,920 STRETCH OR GET A SIP OF WATER OR 2454 01:45:37,920 --> 01:46:04,640 ANYTHING AND SEE YOU SOON. 2455 01:46:04,640 --> 01:46:07,080 >> DR. MOSS IS HEAD OF THE 2456 01:46:07,080 --> 01:46:08,640 DIVISION OF PULMONARY SCIENCE 2457 01:46:08,640 --> 01:46:11,680 AND CRITICAL CARE MEDICINE AT 2458 01:46:11,680 --> 01:46:14,240 UNIVERSITY COLORADO SCHOOL OF 2459 01:46:14,240 --> 01:46:17,920 MEDICINE AND DR. STEPHANIE 2460 01:46:17,920 --> 01:46:24,120 TAILOR IS CHIEF DIVISION OF 2461 01:46:24,120 --> 01:46:26,280 MEDICINE AND STARTED POSITION 2462 01:46:26,280 --> 01:46:28,440 THIS MONTH AND CONGRATULATIONS 2463 01:46:28,440 --> 01:46:31,920 TO STEPHANIE AND WITHOUT FURTHER 2464 01:46:31,920 --> 01:46:37,640 ADO WEL COCOME MARK MOS AND 2465 01:46:37,640 --> 01:46:41,680 STEPHANIE TAILOR. 2466 01:46:41,680 --> 01:46:44,480 >> THANK YOU. SESSION 4 WE PUT 2467 01:46:44,480 --> 01:46:47,080 TOGETHER A CALL TO ACTION 2468 01:46:47,080 --> 01:46:47,840 SYNTHESIZING GREAT INFORMATION 2469 01:46:47,840 --> 01:46:49,400 YOU HEARD SO FAR THAT IS 2470 01:46:49,400 --> 01:46:59,080 RECOGNIZING WE HAVE COME SO FAR. 2471 01:46:59,080 --> 01:47:03,120 WE HAVE COME A LONG WAY 2472 01:47:03,120 --> 01:47:09,920 UNDERLYING MECHANISMS -- SUPPORT 2473 01:47:09,920 --> 01:47:16,040 ING INTERVENTIONS IN THE SETTING 2474 01:47:16,040 --> 01:47:19,440 WE ARE DEALING WITH SYNDROMES 2475 01:47:19,440 --> 01:47:22,960 AND DISEASES AND HARD TO KNOW 2476 01:47:22,960 --> 01:47:25,440 WHO SHOULD BE ENL ROLLED IN 2477 01:47:25,440 --> 01:47:26,880 TRIALS AND MULTICOMPLEX AND 2478 01:47:26,880 --> 01:47:31,680 THERE IS ISSUES WITH 2479 01:47:31,680 --> 01:47:33,360 IMPLEMENTATION AND QUESTIONS 2480 01:47:33,360 --> 01:47:38,520 COMING UP ALREADY WHAT TO 2481 01:47:38,520 --> 01:47:45,360 CONTROL AND BE HETEROENEOUS 2482 01:47:45,360 --> 01:47:48,480 OUTCOMES WE CARE ABOUT ARE HARD 2483 01:47:48,480 --> 01:47:50,240 TO MEASURE AVEND SOMETIMES DON'T 2484 01:47:50,240 --> 01:47:53,480 KNOW IF WE SHOULD CARE ABOUT 2485 01:47:53,480 --> 01:47:58,080 THEM OR NOT ASKING YOU TO 2486 01:47:58,080 --> 01:48:02,880 DECLARE LACK OF EVIDENCE 2487 01:48:02,880 --> 01:48:07,880 INTOLERABLE THINKING HOW TO 2488 01:48:07,880 --> 01:48:12,120 DESIGN TRIALS FOR INTERVENTIONS 2489 01:48:12,120 --> 01:48:17,720 FOR BRAIN DISFUNCTION IN NRDS 2490 01:48:17,720 --> 01:48:22,760 AND WE LIKE TO DO IT NOW AND 2491 01:48:22,760 --> 01:48:25,200 BROUGHT TOGETHER A LOT OF WORK 2492 01:48:25,200 --> 01:48:27,400 THAT WE HEARD ABOUT AS WELL AND 2493 01:48:27,400 --> 01:48:30,440 DISCUSSION WILL BE GREAT PLACE 2494 01:48:30,440 --> 01:48:35,240 TO DO THAT INTRODUCING OUR FIRST 2495 01:48:35,240 --> 01:48:39,040 SPEAKER WHO IS ASZANT PROFESSOR 2496 01:48:39,040 --> 01:48:47,800 OF MEDICINE AND BIOINFORMATICS 2497 01:48:47,800 --> 01:48:51,960 AND RESEARCH PROGRAM HAS NON 2498 01:48:51,960 --> 01:49:00,000 PATIENT TO UNDERSTAND WHAT 2499 01:49:00,000 --> 01:49:02,440 TREATMENTS HAVE BEST RESULTS FOR 2500 01:49:02,440 --> 01:49:06,240 PATIENTS AND TURNING IT TO DR. 2501 01:49:06,240 --> 01:49:07,240 SEMLER FOR HIS TALK. 2502 01:49:07,240 --> 01:49:10,240 >> THANK YOU FOR HAVING ME. I 2503 01:49:10,240 --> 01:49:15,800 WAS ABLE TO SIT IN THE LAST HOUR 2504 01:49:15,800 --> 01:49:24,560 AND LEARN MORE THAN IN PAST YEAR 2505 01:49:24,560 --> 01:49:29,280 COMBINED AND TRIALS AND HOW THEY 2506 01:49:29,280 --> 01:49:31,720 MIGHT INFORM BRAIN DISFUNCTION 2507 01:49:31,720 --> 01:49:34,960 AND APPRECIATIVE FOR FUNDING 2508 01:49:34,960 --> 01:49:38,960 FROM NIH AND DISCLOSURE IS I'M 2509 01:49:38,960 --> 01:49:43,720 AN INTENSIVE CLINICAL TRIALIST 2510 01:49:43,720 --> 01:49:45,680 BUT NOT EXPERT IN BRAIN 2511 01:49:45,680 --> 01:49:49,440 DISFUNCTION AND FORGIVE ME FOR 2512 01:49:49,440 --> 01:49:52,920 ERRORS I MIGHT HAVE. 2513 01:49:52,920 --> 01:49:53,840 NEXT SLIDE. 2514 01:49:53,840 --> 01:49:56,000 >> STARTING POINT CONCEPTUAL 2515 01:49:56,000 --> 01:49:59,160 FRAMEWORK WHAT WE ARE TALKING 2516 01:49:59,160 --> 01:50:02,360 ABOUT HERE BEGINS WITH A GOAL 2517 01:50:02,360 --> 01:50:05,160 AND ROUGH VERSION IS IDENTIFYING 2518 01:50:05,160 --> 01:50:08,520 PREVENTIONS TO TREAT SPEED 2519 01:50:08,520 --> 01:50:11,680 RECOVERY FROM. 2520 01:50:11,680 --> 01:50:15,760 WE HAVE TWO PATHWAYS TO THE GOAL 2521 01:50:15,760 --> 01:50:19,240 AND FIRST IS ONE WE THINK AND 2522 01:50:19,240 --> 01:50:29,800 TALK ABOUT A LOT DISCOVERIES AT 2523 01:50:29,800 --> 01:50:32,600 CELLULAR LEVEL IMPLEMENTING 2524 01:50:32,600 --> 01:50:36,080 CRITICAL PRACTICE TO IMPROVE 2525 01:50:36,080 --> 01:50:40,000 OUTCOMES AND TODAY'S TALK 2526 01:50:40,000 --> 01:50:44,840 FOCUSES ON OTHER PATHWAY THAT 2527 01:50:44,840 --> 01:50:47,680 PATHWAY IS REVERSE TRANSLATION 2528 01:50:47,680 --> 01:50:50,480 STARTING WITH PATIENT THAT IS 2529 01:50:50,480 --> 01:50:54,560 CRITICALLY ILL AND WHAT PATIENTS 2530 01:50:54,560 --> 01:50:56,280 MIGHT RECEIVE MIGHT EFFECT BRAIN 2531 01:50:56,280 --> 01:50:59,520 DISFUNCTION AND CLINICAL TRIALS 2532 01:50:59,520 --> 01:51:03,520 TO UNDERSTAND TREATMENT AND 2533 01:51:03,520 --> 01:51:05,960 OUTCOMES AND WALKING THAT BACK 2534 01:51:05,960 --> 01:51:15,400 TO BIOSPECIMENS AND TECHNIQUE 2535 01:51:15,400 --> 01:51:21,240 FRAMING ASPECTS OF RESEARCH 2536 01:51:21,240 --> 01:51:25,320 PORTFOLIO IS A POINT TO NOTE AND 2537 01:51:25,320 --> 01:51:30,400 CRITICAL ILLNESS TO DATE WE HAVE 2538 01:51:30,400 --> 01:51:32,880 TRIED TO WALK THINGS THROUGH 2539 01:51:32,880 --> 01:51:35,400 THAT TRANSLATION PATHWAY AND HAD 2540 01:51:35,400 --> 01:51:37,960 TROUBLE GETTING TO NEW DRUGS AND 2541 01:51:37,960 --> 01:51:40,160 DEVICES PROVING OUTCOMES FOR 2542 01:51:40,160 --> 01:51:45,360 ADULTS THAT IS ENGENDERING SENSE 2543 01:51:45,360 --> 01:51:47,520 OF ANILISM THAT I DON'T THINK IS 2544 01:51:47,520 --> 01:51:50,840 NECESSARY AND WE SHOULD KEEP 2545 01:51:50,840 --> 01:51:54,360 FOCUS ON FACT THAT WHEN WE 2546 01:51:54,360 --> 01:51:57,880 EXAMINE TREATMENTS THAT PATIENTS 2547 01:51:57,880 --> 01:52:01,840 RECEIVE IN IDENTIFYING 2548 01:52:01,840 --> 01:52:03,280 TREATMENTS PRODUCING DIFFERENT 2549 01:52:03,280 --> 01:52:06,640 OUTCOMES AND PLACE TO WORK 2550 01:52:06,640 --> 01:52:10,400 HARDER IS WALKING BACKWARDS TO 2551 01:52:10,400 --> 01:52:13,360 NSHS MECHANISMS FOR CRITICALLY 2552 01:52:13,360 --> 01:52:15,640 ILL PATIENTS USING THAT PATHWAY 2553 01:52:15,640 --> 01:52:18,800 MORE HEAVILY AND PORTFOLIO NOT 2554 01:52:18,800 --> 01:52:20,480 JUST BENCH TO BEDSIDE BUT 2555 01:52:20,480 --> 01:52:23,720 EXAMINING THINGS HAPPENING AT 2556 01:52:23,720 --> 01:52:25,640 BEDSIDE USING THAT LEVERAGE TO 2557 01:52:25,640 --> 01:52:28,120 GO BACKWARDS AND THAT IS 2558 01:52:28,120 --> 01:52:28,400 CRITICAL. 2559 01:52:28,400 --> 01:52:30,080 THIS FRAMING EFFECTS HOW WE 2560 01:52:30,080 --> 01:52:34,600 DESIGN CLINICAL TRIALS AND OUR 2561 01:52:34,600 --> 01:52:36,480 HISTORICAL REGULATORY FRAMEWORK 2562 01:52:36,480 --> 01:52:37,840 AND FRAMEWORKS FOR CLINICAL 2563 01:52:37,840 --> 01:52:39,480 TRIALS WAS DEVELOPED FOR 2564 01:52:39,480 --> 01:52:41,800 DEVELOPMENT OF NEW DRUGS AND 2565 01:52:41,800 --> 01:52:44,880 DEVICES LIVING IN THIS FORWARD 2566 01:52:44,880 --> 01:52:48,320 TRANSLATION MINDSET HEAVILY AND 2567 01:52:48,320 --> 01:52:50,760 IS NOT WELL SUITED. 2568 01:52:50,760 --> 01:52:52,360 NEXT SLIDE. THIS IS THE 2569 01:52:52,360 --> 01:52:55,320 FRAMEWORK AND BASIC FRAMEWORK 2570 01:52:55,320 --> 01:52:58,040 FOR CLINICAL TRIALS AND CLINICAL 2571 01:52:58,040 --> 01:53:00,480 CARE AND BUSY WORLD OF HOSPITAL 2572 01:53:00,480 --> 01:53:03,360 AND DIVERSITY OF PATIENTS AND 2573 01:53:03,360 --> 01:53:04,880 CLINICIANS USE TREATMENT A AND 2574 01:53:04,880 --> 01:53:11,160 SOME CLINICIANS USE TREATMENT B 2575 01:53:11,160 --> 01:53:12,920 NOW HERE TOTALLY SEPARATELY IS 2576 01:53:12,920 --> 01:53:16,440 THAT OF CLINICAL TRIALS 2577 01:53:16,440 --> 01:53:20,520 PRIORITIZING DRUGS AND DEVICES 2578 01:53:20,520 --> 01:53:25,600 IGNORING EXISTING THERAPIES 2579 01:53:25,600 --> 01:53:32,840 PATIENTS ARE GETTING AND SUBSET 2580 01:53:32,840 --> 01:53:35,160 OF PATIENT CARE AND PRACTICE AND 2581 01:53:35,160 --> 01:53:37,880 HIGHLY TRAINED RESEARCHER PERSON 2582 01:53:37,880 --> 01:53:39,080 ELDOESN'T MIMIC HOW 2583 01:53:39,080 --> 01:53:45,320 INTERVENTIONS WOULD BE USED TO 2584 01:53:45,320 --> 01:53:45,600 PRACTICE. 2585 01:53:45,600 --> 01:53:49,400 AS A RESULT TRIALS ARE NARROW 2586 01:53:49,400 --> 01:53:52,400 AND LONG AND EXPENSIVE AND 2587 01:53:52,400 --> 01:53:55,200 DESIGNED TO UNDERESTIMATE 2588 01:53:55,200 --> 01:53:56,920 BENEFIT AND UNDERESTIMATE HARM 2589 01:53:56,920 --> 01:54:03,240 AND ENRICHMENT AND INCREASINGLY 2590 01:54:03,240 --> 01:54:05,640 FOCUSED ON THIS AND THE SILOED 2591 01:54:05,640 --> 01:54:07,680 WORLD IS DEVELOPED FOR AND 2592 01:54:07,680 --> 01:54:08,760 STARTING WITH PATIENT AND 2593 01:54:08,760 --> 01:54:10,880 TREATMENT THEY ARE RECEIVING AND 2594 01:54:10,880 --> 01:54:12,840 DOING PARADIGM FOR CLINICAL 2595 01:54:12,840 --> 01:54:16,000 TRIALS AND WE ENVISION THAT. 2596 01:54:16,000 --> 01:54:18,800 NEXT SLIDE. BEING THIS KIND OF 2597 01:54:18,800 --> 01:54:21,320 SINGLE WORLD INSTEAD OF THESE 2598 01:54:21,320 --> 01:54:24,280 WORLDS SINGLE LEARNING HEALTH 2599 01:54:24,280 --> 01:54:29,480 SYSTEM PATIENTS CLINICIANS 2600 01:54:29,480 --> 01:54:31,480 RESEARCHERS DIET STATISTICIANS 2601 01:54:31,480 --> 01:54:33,840 IN ONE TEAM AND WORKPLACE COMMON 2602 01:54:33,840 --> 01:54:35,200 TREATMENTS AND CONDITIONS 2603 01:54:35,200 --> 01:54:36,640 PATIENTS ARE EXPOSE TODAY ALL 2604 01:54:36,640 --> 01:54:39,240 DAY EVERY DAY AT PRACTICE AND 2605 01:54:39,240 --> 01:54:40,640 USING RANDOMIZED TRIALS IMBEDDED 2606 01:54:40,640 --> 01:54:42,320 IN CLINICAL CARE TO UNDERSTAND 2607 01:54:42,320 --> 01:54:45,960 EFFECTS OF THOSE TREATMENTS ON 2608 01:54:45,960 --> 01:54:47,600 OUTCOMES FOR THE ENTIRE 2609 01:54:47,600 --> 01:54:49,640 DIVERSITY OF PATIENTS RECEIVING 2610 01:54:49,640 --> 01:54:50,840 TREATMENTS AND PRACTICE AND 2611 01:54:50,840 --> 01:54:55,360 SELECTED 5% ENROLLED IN REGULAR 2612 01:54:55,360 --> 01:55:01,600 CLINICAL TRIAL STUDYING 2613 01:55:01,600 --> 01:55:04,640 TREATMENTS TO BE ADMINISTERED 2614 01:55:04,640 --> 01:55:06,360 COULD GENERATE RESULTS 2615 01:55:06,360 --> 01:55:08,360 ADMINISTERED AND APPLY TO 2616 01:55:08,360 --> 01:55:10,120 PRACTICE AND NOT JUST GENERATING 2617 01:55:10,120 --> 01:55:11,920 KNOWLEDGE BUT IMPROVING CARE AND 2618 01:55:11,920 --> 01:55:18,160 STUDIES TO WHERE THIS IS 2619 01:55:18,160 --> 01:55:19,920 HAPPENING. 2620 01:55:19,920 --> 01:55:20,480 NEXT SLIDE. 2621 01:55:20,480 --> 01:55:24,000 WE NEED TO DO THIS WORK WORKING 2622 01:55:24,000 --> 01:55:26,160 TOWARDS VISION OF IMBEDDING 2623 01:55:26,160 --> 01:55:28,440 PRAGMATIC TRIALS INTO PRACTICE 2624 01:55:28,440 --> 01:55:30,520 TO UNDERSTAND EFFECT OF COMMON 2625 01:55:30,520 --> 01:55:32,280 TREATMENTS AND PATIENT OUTCOMES 2626 01:55:32,280 --> 01:55:33,680 THERE IS FIVE KEY THINGS AND 2627 01:55:33,680 --> 01:55:35,880 FIRST IS WE HAVE TO FIND WAYS TO 2628 01:55:35,880 --> 01:55:38,040 TREAT CLINICIANS TO DELIVER 2629 01:55:38,040 --> 01:55:39,280 INTERVENTIONS PART OF THE TRIAL 2630 01:55:39,280 --> 01:55:40,720 RATHER THAN IN A WAY THEY WOULD 2631 01:55:40,720 --> 01:55:42,800 IN CLINICAL PRACTICE RATHER THAN 2632 01:55:42,800 --> 01:55:45,240 HAVING INVENTIONS DELIVERED 2633 01:55:45,240 --> 01:55:49,840 EXCLUSIVELY BY RESEARCH PER SSO 2634 01:55:49,840 --> 01:55:50,040 EL. 2635 01:55:50,040 --> 01:55:52,880 TWO FINDING WAYS TO EFFICIENTLY 2636 01:55:52,880 --> 01:55:56,960 COLLECT LONG TERM OUTCOMES THAT 2637 01:55:56,960 --> 01:55:58,600 HAVE BRAIN AND MUSCLE 2638 01:55:58,600 --> 01:56:00,240 DISFUNCTION EXTENSIVE AND 2639 01:56:00,240 --> 01:56:02,360 INTEGRATED IN CLINICAL CARE AND 2640 01:56:02,360 --> 01:56:04,200 3 MOVING FROM ESTIMATING AVERAGE 2641 01:56:04,200 --> 01:56:06,680 TREATMENT EFFECTS TO ESTIMATING 2642 01:56:06,680 --> 01:56:09,760 INDIVIDUAL TREATMENT EFFECTS AS 2643 01:56:09,760 --> 01:56:11,760 STEP TOWARDS PERSONALIZED 2644 01:56:11,760 --> 01:56:14,120 MEDICINE AND 4 HAVING BETTER 2645 01:56:14,120 --> 01:56:16,800 WAYS INTEGRATING BIOMARKERS INTO 2646 01:56:16,800 --> 01:56:18,640 PRAGMATIC TRIALS TO WORK BACK TO 2647 01:56:18,640 --> 01:56:21,800 UNDERSTAND WHY TREATMENTS HAVE 2648 01:56:21,800 --> 01:56:26,000 EFFECTS THEY DID FIFTH IS 2649 01:56:26,000 --> 01:56:27,480 SOMETHING I WON'T TALK ABOUT 2650 01:56:27,480 --> 01:56:32,600 TODAY. WE NEED ETHICAL AND 2651 01:56:32,600 --> 01:56:36,240 REGULATORY FRAIM WORKS THAT ARE 2652 01:56:36,240 --> 01:56:38,040 DIFFERENT AND COMPARING 2653 01:56:38,040 --> 01:56:41,880 TREATMENTS OF PATIENTS THAT LE 2654 01:56:41,880 --> 01:56:48,920 WILL RECEIVE. 2655 01:56:48,920 --> 01:56:51,120 AT SCALE IN WAY THAT GENERALIZES 2656 01:56:51,120 --> 01:56:53,840 PRACTICE FINDING WAYS TO TREAT 2657 01:56:53,840 --> 01:56:55,840 CLINICIANS TO DELIVER TRIAL 2658 01:56:55,840 --> 01:56:59,080 INTERVENTIONS THAT IS EXAMPLE 2659 01:56:59,080 --> 01:57:01,840 HOW WE DID THIS. 2660 01:57:01,840 --> 01:57:04,080 I PICKED THIS BECAUSE IT IS AN 2661 01:57:04,080 --> 01:57:05,840 EMERGENCY PROCEDURE AND THERE IS 2662 01:57:05,840 --> 01:57:07,920 NO POSSIBLE WAY TO HAVE A 2663 01:57:07,920 --> 01:57:10,560 RESEARCH PERSON THERE TO DELIVER 2664 01:57:10,560 --> 01:57:13,040 TRIAL INTERVENTIONS. 2665 01:57:13,040 --> 01:57:15,400 THIS TRIAL RAN AT CENTERS ACROSS 2666 01:57:15,400 --> 01:57:17,480 UNITED STATES AND ENROLLED POOR 2667 01:57:17,480 --> 01:57:19,320 PATIENTS AND INTERVENTIONS WERE 2668 01:57:19,320 --> 01:57:21,160 ABLE TO BE SUCCESSFULLY 2669 01:57:21,160 --> 01:57:22,840 DELIVERED IN TREATING CLINICIANS 2670 01:57:22,840 --> 01:57:25,360 IN ABSENCE OF RESEARCH PERSON 2671 01:57:25,360 --> 01:57:27,880 ELAND DATA COLLECTED TRAINED 2672 01:57:27,880 --> 01:57:31,080 OBSERVERS IN CLINICAL 2673 01:57:31,080 --> 01:57:32,640 ENVIRONMENT AND TRIAL OCCURRED 2674 01:57:32,640 --> 01:57:34,560 AND IDEA OF RESEARCH AND 2675 01:57:34,560 --> 01:57:36,320 CLINICAL CARE INTEGRATED DON'T 2676 01:57:36,320 --> 01:57:38,720 HAVE TO BE SEPARATE TREATING 2677 01:57:38,720 --> 01:57:42,400 CLINICIANS ARE KEY ROLES IN 2678 01:57:42,400 --> 01:57:45,000 DELIVERING TRIAL INTERVENTIONS. 2679 01:57:45,000 --> 01:57:47,760 SUMMARY POINT ADMINISTERING 2680 01:57:47,760 --> 01:57:50,600 EVERY DAY CARE AND CLINICIANS 2681 01:57:50,600 --> 01:57:52,680 CAN DELIVER TRIAL INTERVENTIONS 2682 01:57:52,680 --> 01:57:56,240 WITHOUT RESEARCH PERSONNEL. 2683 01:57:56,240 --> 01:57:57,280 NEXT SLIDE. 2684 01:57:57,280 --> 01:57:59,160 THIS IS A EXAMPLE WE HAVE BEEN 2685 01:57:59,160 --> 01:58:02,880 ABLE TO DO FOR 10 TRIALS AND 2686 01:58:02,880 --> 01:58:06,200 MRNL PROCEDURE. 2687 01:58:06,200 --> 01:58:09,520 NEXT SLIDE INTEGRATING LONG TERM 2688 01:58:09,520 --> 01:58:13,520 PATIENT OUTCOMES COMPARATIVE 2689 01:58:13,520 --> 01:58:19,600 EFFECTIVENESS TRIALS IS EXAMPLE 2690 01:58:19,600 --> 01:58:24,880 OF THAT AND EACH OF WHOM IS 2691 01:58:24,880 --> 01:58:30,200 ENROLLED AS TRASH LAR 2692 01:58:30,200 --> 01:58:34,280 INTERBASING AND DURING EMERGENCY 2693 01:58:34,280 --> 01:58:37,840 PROCEDURE APPROACHING PATIENTS 2694 01:58:37,840 --> 01:58:44,280 AND FAMILIES. 2695 01:58:44,280 --> 01:58:47,400 PRAG MMATIC TRIAL. 2696 01:58:47,400 --> 01:58:51,680 BEING ABLE TO MARRY THOSE IN A 2697 01:58:51,680 --> 01:58:53,520 PRAGMATIC TRIAL DURING EMERGENCY 2698 01:58:53,520 --> 01:58:55,360 PROCEDURE LONG TERM OUTCOMES 2699 01:58:55,360 --> 01:58:56,280 IMPORTANT TO RESEARCH QUESTION 2700 01:58:56,280 --> 01:58:58,840 FINDING WAYS TO INTEGRATE THOSE. 2701 01:58:58,840 --> 01:59:00,000 NEXT SLIDE. 2702 01:59:00,000 --> 01:59:02,600 DOING THAT REPRODUCIBLY WE WILL 2703 01:59:02,600 --> 01:59:06,440 NEED EFFICIENCIES WE DON'T HAVE 2704 01:59:06,440 --> 01:59:09,800 TODAY OUTCOMES RELATIVE TO BRAIN 2705 01:59:09,800 --> 01:59:12,440 AND MUSCLE DISFUNCTION AND YOU 2706 01:59:12,440 --> 01:59:14,960 ARE TALKING ABOUT NOT SURE WHICH 2707 01:59:14,960 --> 01:59:18,240 ARE RELEVANT IN HEALTH 2708 01:59:18,240 --> 01:59:20,960 ELECTRONIC RECORD IN A WAY AND 2709 01:59:20,960 --> 01:59:24,360 APPROACHING THIS INCREASINGLY 2710 01:59:24,360 --> 01:59:28,920 MOBILE TOOLS CELL PHONES AND 2711 01:59:28,920 --> 01:59:32,760 PATIENTS CAN REPORT OUTCOMES AND 2712 01:59:32,760 --> 01:59:36,080 WEARABLES I THINK INCREASINGLY 2713 01:59:36,080 --> 01:59:39,240 FOCUS SHOULD BE ON MAKING SURE 2714 01:59:39,240 --> 01:59:41,080 OUTCOMES IMPORTANT TO PATIENTS 2715 01:59:41,080 --> 01:59:41,840 ARE [INDISCERNIBLE]. 2716 01:59:41,840 --> 01:59:42,320 >> [INDISCERNIBLE]. 2717 01:59:42,320 --> 01:59:44,440 >> THANK YOU EFFORT AT 2718 01:59:44,440 --> 01:59:48,280 VANDERBILT AND REPORTED OUTCOMES 2719 01:59:48,280 --> 01:59:51,960 IN ELECTRONIC HEALTH RECORD FOR 2720 01:59:51,960 --> 01:59:53,920 650,000 PATIENTS CLINICAL CARE 2721 01:59:53,920 --> 01:59:56,120 ARE REPORTING MEASURES WE WANT 2722 01:59:56,120 --> 02:00:00,280 FOR RESEARCH. NEXT SLIDE. 2723 02:00:00,280 --> 02:00:01,760 I WON'T DWELL ON THIS. 2724 02:00:01,760 --> 02:00:06,480 THIS IS A SEPARATE HOUR PRACH 2725 02:00:06,480 --> 02:00:08,800 TRYING TO ANALYZE TRIALS AND 2726 02:00:08,800 --> 02:00:10,560 OUTCOMES STATISTICAL METHODS CAN 2727 02:00:10,560 --> 02:00:12,640 DO THAT AND PRODUCE AN ANSWER 2728 02:00:12,640 --> 02:00:14,520 AND WE DON'T HAVE THOSE AND 2729 02:00:14,520 --> 02:00:16,360 SOMETHING TO FOCUS ON IN THE 2730 02:00:16,360 --> 02:00:18,040 FUTURE AND NEXT SLIDE. 2731 02:00:18,040 --> 02:00:19,680 SPEAKING OF STATISTICAL METHODS 2732 02:00:19,680 --> 02:00:22,800 WE KNOW WE NEED TO MOVE FROM 2733 02:00:22,800 --> 02:00:24,240 AVERAGE TREATMENT EFFECTS TO 2734 02:00:24,240 --> 02:00:24,920 INDIVIDUALIZED TREATMENT EFFECTS 2735 02:00:24,920 --> 02:00:28,520 AND WE HAVE WAYS OF DOING THAT 2736 02:00:28,520 --> 02:00:32,360 INSTEAD OF ENROLLING IN DIVERSE 2737 02:00:32,360 --> 02:00:34,440 POPULATION IN TRIAL AND A IS 2738 02:00:34,440 --> 02:00:39,480 BETTER THAN B ANSWER AND APRYING 2739 02:00:39,480 --> 02:00:42,960 THAT GOING FORWARD NEW WAYS 2740 02:00:42,960 --> 02:00:45,280 ENCOUNTERING PATIENTS USING 2741 02:00:45,280 --> 02:00:48,120 THOSE WHO ARE SIMILAR IN TRIALS 2742 02:00:48,120 --> 02:00:51,160 CAN WE KNOW WHAT IS BEFLT FROM 2743 02:00:51,160 --> 02:00:55,360 THIS PATIENT THAT DIFFERS FROM 2744 02:00:55,360 --> 02:00:56,840 OTHER PATIENTS WE TOOK 2745 02:00:56,840 --> 02:01:00,720 RANDOMIZED TRIALS USING THIS TO 2746 02:01:00,720 --> 02:01:06,040 DEVELOP ESTIMATES SECOND ACT 2747 02:01:06,040 --> 02:01:08,160 VALIDATED THOSE AND FOUND IN 2748 02:01:08,160 --> 02:01:13,120 NULL TRIAL PATIENTS BENEFITED 2749 02:01:13,120 --> 02:01:14,360 FROM XAIRTIVE EFFECTIVENESS 2750 02:01:14,360 --> 02:01:16,200 INTERVENTION AND MOVING TOWARDS 2751 02:01:16,200 --> 02:01:19,840 THIS BEING STANDARD APPROACH. 2752 02:01:19,840 --> 02:01:21,200 THESE ARE MEANT TO TELL WHAT YOU 2753 02:01:21,200 --> 02:01:23,840 TO DO FOR VISUAL PATIENT. 2754 02:01:23,840 --> 02:01:24,960 NEXT SLIDE. 2755 02:01:24,960 --> 02:01:27,600 I WILL MOVE QUICKLY THROUGH THIS 2756 02:01:27,600 --> 02:01:29,080 BIOMARKERS HAVE TO BE PIECE OF 2757 02:01:29,080 --> 02:01:31,240 THIS AND WHAT BIOMARKERS AND HOW 2758 02:01:31,240 --> 02:01:35,120 TO DO EFFICIENTLY IS EXAMPLE OF 2759 02:01:35,120 --> 02:01:37,520 INCLUDING URINARY AND BLOOD 2760 02:01:37,520 --> 02:01:40,320 BIOMARKERS PRAGMATIC TRIAL MORE 2761 02:01:40,320 --> 02:01:43,960 EFFORT AND EXPENSE AT BIOMARKERS 2762 02:01:43,960 --> 02:01:46,440 THAN PRAGMATIC TRIAL AND 2763 02:01:46,440 --> 02:01:48,440 EFFICIENCIES HAVE TO BE THERE TO 2764 02:01:48,440 --> 02:01:50,160 WHOLLY LEARN FROM TRIALS AND 2765 02:01:50,160 --> 02:01:52,440 FINAL TWO SLIDES TALKED ABOUT 2766 02:01:52,440 --> 02:01:54,200 BALANCE OF FORWARD AND REVERSE 2767 02:01:54,200 --> 02:01:56,480 TRANSLATION AND MEANS MORE 2768 02:01:56,480 --> 02:01:58,560 TRIALS COMPARING CURRENT 2769 02:01:58,560 --> 02:01:59,880 TREATMENTS AND GENE DIFFERENCES 2770 02:01:59,880 --> 02:02:02,880 IN TREATMENTS TO UNDERSTAND 2771 02:02:02,880 --> 02:02:06,680 BRAIN AND MUSCLE FUNCTION. 2772 02:02:06,680 --> 02:02:10,360 PROBLEMS WITH EXPLANATORY TRIALS 2773 02:02:10,360 --> 02:02:13,760 PRAGMATIC TRIALS CAN OVERCOME 2774 02:02:13,760 --> 02:02:15,960 AND LAST SLIDE PITCHING HIGH 2775 02:02:15,960 --> 02:02:18,640 RISK AND REWARD IDEA ON THIS IT 2776 02:02:18,640 --> 02:02:21,400 WOULD BE A PLATFORM AND GOAL IS 2777 02:02:21,400 --> 02:02:24,480 TO IMBED PRAGMATIC TRIALS IN 2778 02:02:24,480 --> 02:02:27,840 CLINICAL CARE COMPARING COMMON 2779 02:02:27,840 --> 02:02:29,000 INTERVENTIONS THAT MIGHT ALREADY 2780 02:02:29,000 --> 02:02:30,800 EFFECT BRAIN AND MUSCLE 2781 02:02:30,800 --> 02:02:31,680 DISFUNCTION. 2782 02:02:31,680 --> 02:02:35,240 EXAMPLES OF THAT 7 TAENVERSUS 2783 02:02:35,240 --> 02:02:38,400 [INDISCERNIBLE] TWO COMMON 2784 02:02:38,400 --> 02:02:39,240 ANTIBIOTICS ADMINISTERED IN 2785 02:02:39,240 --> 02:02:41,280 SEPSIS AND ONE PROBABLY CAUSES 2786 02:02:41,280 --> 02:02:43,160 BRAIN DISNUFRNGS WAYS WE DON'T 2787 02:02:43,160 --> 02:02:45,640 FULLY UNDERSTAND AND COMPARING 2788 02:02:45,640 --> 02:02:47,760 AND USING THOSE AS AN 2789 02:02:47,760 --> 02:02:50,080 OPPORTUNITY AND DIAPHRAGM 2790 02:02:50,080 --> 02:02:51,560 PROTECTIVE INTERVATION SLOW 2791 02:02:51,560 --> 02:02:54,120 TITLE VOLUME DIFFERENT 2792 02:02:54,120 --> 02:02:55,800 APPROACHES TO ANALGEEZIA 2793 02:02:55,800 --> 02:02:59,440 SEDATION IN THE ICU AND WHOLE 2794 02:02:59,440 --> 02:03:00,840 LAUNDRY LIST OF EVERYTHING YOU 2795 02:03:00,840 --> 02:03:04,240 HAVE AS A CLINICIAN MAKING A 2796 02:03:04,240 --> 02:03:05,760 CHOICE YOU HAVE WITHOUT EVIDENCE 2797 02:03:05,760 --> 02:03:08,480 USING POTENTIAL DIFFERENCES TO 2798 02:03:08,480 --> 02:03:09,720 WORK BACKWARDS UNDERSTANDING HOW 2799 02:03:09,720 --> 02:03:11,720 THESE EFFECT BRAIN AND MUSCLE 2800 02:03:11,720 --> 02:03:13,440 INFECTION AND EVERY TIME WE FIND 2801 02:03:13,440 --> 02:03:15,080 SOMETHING EFFECTING BRAIN AND 2802 02:03:15,080 --> 02:03:17,640 MUSCLE FUNCTION, STANDARDIZE 2803 02:03:17,640 --> 02:03:19,680 CARE AND MAKE SURE WE DELIVER 2804 02:03:19,680 --> 02:03:22,600 BEST CARE TO IMPROVE PATIENT 2805 02:03:22,600 --> 02:03:22,880 OUTCOMES. 2806 02:03:22,880 --> 02:03:24,280 NEXT SLIDE. THAT IS ALL. I 2807 02:03:24,280 --> 02:03:26,240 WANT TO THANK YOU. A LITTLE 2808 02:03:26,240 --> 02:03:27,440 RUSHED AND APPRECIATING YOUR 2809 02:03:27,440 --> 02:03:28,800 TIME AND ENJOYING OPPORTUNITY TO 2810 02:03:28,800 --> 02:03:39,840 TALK ABOUT ALL THIS WITH YOU. 2811 02:03:39,840 --> 02:03:42,960 >> THAT WAS GREAT, MATT. THANK 2812 02:03:42,960 --> 02:03:44,000 YOU SO MUCH. 2813 02:03:44,000 --> 02:03:45,880 MARK, DID YOU GET A CHANCE TO 2814 02:03:45,880 --> 02:03:47,280 LOOK THROUGH THE CHAT? 2815 02:03:47,280 --> 02:03:50,080 >> I DID, STEPHANIE. 2816 02:03:50,080 --> 02:03:51,080 >> OKAY. 2817 02:03:51,080 --> 02:03:53,200 >> MATT, A LOT OF GREAT 2818 02:03:53,200 --> 02:03:54,120 QUESTIONS AND ONE THING THAT 2819 02:03:54,120 --> 02:03:56,440 CAME UP THAT YOU MIGHT BE ABLE 2820 02:03:56,440 --> 02:08:15,280 TO ADDRESS IS A QUESTION 2821 02:08:15,280 --> 02:08:17,440 >> THANK YOU SO MUCH FOR THE 2822 02:08:17,440 --> 02:08:18,640 KIND INTRODUCTION. CAN YOU HEAR 2823 02:08:18,640 --> 02:08:19,760 ME ALL RIGHT? 2824 02:08:19,760 --> 02:08:20,840 >> THAT IS GREAT. 2825 02:08:20,840 --> 02:08:21,960 >> GREAT. LET'S GO TO THE NEXT 2826 02:08:21,960 --> 02:08:23,640 SLIDE. 2827 02:08:23,640 --> 02:08:25,920 I DON'T HAVE ANY CONFLICT OF 2828 02:08:25,920 --> 02:08:28,400 INTEREST TO DISCLOSE AND I DO 2829 02:08:28,400 --> 02:08:29,600 INVESTIGATIONS INVOLVING 2830 02:08:29,600 --> 02:08:30,360 IMPLEMENTATION SCIENCE 2831 02:08:30,360 --> 02:08:33,920 APPROACHES AND HAVE THE 2832 02:08:33,920 --> 02:08:35,520 RELATIONSHIP SEEN. NEXT SLIDE. 2833 02:08:35,520 --> 02:08:37,360 I HAVE A FEW OBJECTIVES FOR 2834 02:08:37,360 --> 02:08:39,560 SHORT TIME THAT WE HAVE 2835 02:08:39,560 --> 02:08:40,880 TOGETHER. YOU CAN TAB THROUGH 2836 02:08:40,880 --> 02:08:42,760 THESE 3 AND HOPEFULLY BY END OF 2837 02:08:42,760 --> 02:08:44,480 THE TIME YOU CAN UNDERSTAND 2838 02:08:44,480 --> 02:08:45,440 DIFFERENCE BETWEEN 2839 02:08:45,440 --> 02:08:47,600 IMPLEMENTATION OUTCOMES AND 2840 02:08:47,600 --> 02:08:48,160 EFFECTIVENESS OUTCOMES AND 2841 02:08:48,160 --> 02:08:49,960 COULDN'T ASK FOR A BETTER SETUP 2842 02:08:49,960 --> 02:08:51,960 AND HOPEFULLY YOU WILL BE PRIMED 2843 02:08:51,960 --> 02:08:54,120 TO HEAR ABOUT IMPLEMENTATION 2844 02:08:54,120 --> 02:08:56,600 SCIENCE AND EXPLAIN ROLE OF 2845 02:08:56,600 --> 02:08:59,040 QUASI EXPERIMENTAL DESIGNS IN 2846 02:08:59,040 --> 02:09:01,760 IMPLEMENTATION RESEARCH IN ARDS 2847 02:09:01,760 --> 02:09:03,680 LISTING CHALLENGES TO RESEARCH 2848 02:09:03,680 --> 02:09:06,640 IN ARDS. 2849 02:09:06,640 --> 02:09:07,880 NEXT SLIDE. 2850 02:09:07,880 --> 02:09:10,720 I DO QUALITATIVE MIXED METHODS 2851 02:09:10,720 --> 02:09:13,560 AND WE DO REFLEXIVITY STATEMENTS 2852 02:09:13,560 --> 02:09:15,680 TO HELP YOU UNDERSTAND WHO IS 2853 02:09:15,680 --> 02:09:17,280 TALKING TO YOU AND WHAT 2854 02:09:17,280 --> 02:09:19,720 PERSPECTIVES THERE ARE NEXT 2855 02:09:19,720 --> 02:09:19,960 SLIDE. 2856 02:09:19,960 --> 02:09:23,200 I WEAR HATS AS AN ANTHESE YOLS I 2857 02:09:23,200 --> 02:09:25,600 TRY TO GET PEOPLE TO NOT KILL 2858 02:09:25,600 --> 02:09:27,000 PATIENTS AND SPEND TIME DOING 2859 02:09:27,000 --> 02:09:29,200 HEALTH SERVICES RESEARCH. NEXT 2860 02:09:29,200 --> 02:09:31,440 SLIDE. I RUN A LAB FOCUSED ON 2861 02:09:31,440 --> 02:09:32,560 IMPLEMENTATION SCIENCE THAT WE 2862 02:09:32,560 --> 02:09:35,200 USE TO IMPROVE PERIOPERATIVE 2863 02:09:35,200 --> 02:09:37,480 CARE AND OTHER TYPES OF PATIENT 2864 02:09:37,480 --> 02:09:40,000 CARE AND NEXT SLIDE I RUN THE 2865 02:09:40,000 --> 02:09:41,680 PEN IMPLEMENTATION SCIENCE 2866 02:09:41,680 --> 02:09:43,280 CENTER WE MAKE SURE TO DO 2867 02:09:43,280 --> 02:09:45,160 RIGOROUS IMPLEMENTATION RESEARCH 2868 02:09:45,160 --> 02:09:47,520 TO SEE ACTUAL EXECUTION OF 2869 02:09:47,520 --> 02:09:49,200 INTERVENTIONS THAT ARE 2870 02:09:49,200 --> 02:09:52,000 EFFICACIOUS AND [INDISCERNIBLE]. 2871 02:09:52,000 --> 02:09:53,560 NEXT SLIDE. 2872 02:09:53,560 --> 02:09:56,720 YOU HEARD TERM IMPLEMENTATION 2873 02:09:56,720 --> 02:09:57,720 SCIENCE LEVEL SETTING BECAUSE 2874 02:09:57,720 --> 02:09:59,800 YOU DON'T KNOW WHAT THAT IS AND 2875 02:09:59,800 --> 02:10:01,200 TELLING WHAT YOU IT IS AND 2876 02:10:01,200 --> 02:10:04,920 HELPING GET CLINICIANS AND 2877 02:10:04,920 --> 02:10:06,920 ORGANIZATIONS TO CHANGE. 2878 02:10:06,920 --> 02:10:10,520 FAVORITE DEFINITION OF 2879 02:10:10,520 --> 02:10:12,960 IMPLEMENTATION SCIENCE COMES 2880 02:10:12,960 --> 02:10:18,600 FROM SCIENCE OF JERNL AND GOD 2881 02:10:18,600 --> 02:10:19,240 PARENT OF THE FIELD AND PROCESS 2882 02:10:19,240 --> 02:10:20,360 OF PLANNED HUMAN BEHAVIOR CHANGE 2883 02:10:20,360 --> 02:10:23,600 UNDER ORGANIZATIONAL CONSTRAINTS 2884 02:10:23,600 --> 02:10:24,360 WHAT IS IMPORTANT HERE SIGN 2885 02:10:24,360 --> 02:10:25,360 POSTING HERE WE ARE TRYING TO 2886 02:10:25,360 --> 02:10:27,360 CHANGE BEHAVIOR AND DOING IN 2887 02:10:27,360 --> 02:10:29,120 CONTEXT OF ORGANIZATION AND ALL 2888 02:10:29,120 --> 02:10:30,960 SCIENCES AND SOCIAL SCIENCES WE 2889 02:10:30,960 --> 02:10:33,960 THINK ABOUT WITH RESPECTIVE 2890 02:10:33,960 --> 02:10:35,680 BEHAVIOR CHANGE PSYCHOLOGY AND 2891 02:10:35,680 --> 02:10:37,240 SOCIOLOGY AND ANTHROPOLOGY, ALL 2892 02:10:37,240 --> 02:10:40,680 COME TO BARE AND ORGANIZATIONAL 2893 02:10:40,680 --> 02:10:43,880 SCIENCE AND ALL THAT IS CHANGE 2894 02:10:43,880 --> 02:10:45,080 MANAGEMENT AND IMPLEMENTATION 2895 02:10:45,080 --> 02:10:46,680 SCIENCE IS ALL OF THOSE PUT 2896 02:10:46,680 --> 02:10:47,960 TOGETHER AND IMPLEMENTATION 2897 02:10:47,960 --> 02:10:49,600 SCIENCE AND HEALTH APPLIES 2898 02:10:49,600 --> 02:10:51,320 SCIENCE OF IMPLEMENTATION AND 2899 02:10:51,320 --> 02:10:53,040 RELATED PROCESSES CHANGING 2900 02:10:53,040 --> 02:10:55,320 PATIENT BEHAVIOR THAT IS 2901 02:10:55,320 --> 02:10:57,240 DIFFERENT TO HEALTH CARE 2902 02:10:57,240 --> 02:10:59,800 SERVICES POSSIBLY SECONDARILY TO 2903 02:10:59,800 --> 02:11:00,840 HEALTH BEHAVIOR AND SHE IS NOT 2904 02:11:00,840 --> 02:11:03,200 INTO HERE THIS IDEA THAT I 2905 02:11:03,200 --> 02:11:05,000 CLASSICALLY CONCEIVED 2906 02:11:05,000 --> 02:11:06,160 IMPLEMENTATION SCIENCE IS ABOUT 2907 02:11:06,160 --> 02:11:09,560 CHANGING BEHAVIOR OF PEOPLE THAT 2908 02:11:09,560 --> 02:11:12,760 ARE DELIVERING SERVICES 2909 02:11:12,760 --> 02:11:14,320 IMPLEMENTATION SCIENCE IS 2910 02:11:14,320 --> 02:11:17,280 APPLIED TO PHYSICIANS AND HEALTH 2911 02:11:17,280 --> 02:11:20,520 CARE PROVIDER AND WHAT WE ARE 2912 02:11:20,520 --> 02:11:22,680 DOING HERE. 2913 02:11:22,680 --> 02:11:25,400 IF NOT AS NATURAL OF A FIT AND 2914 02:11:25,400 --> 02:11:27,600 SERIES MODELS AND FRAMEWORKS WE 2915 02:11:27,600 --> 02:11:31,080 HAVE NEED TO BE RESPONSIVE TO 2916 02:11:31,080 --> 02:11:31,280 THAT. 2917 02:11:31,280 --> 02:11:34,760 THAT IS AN EMERGING AREA IN THE 2918 02:11:34,760 --> 02:11:35,480 FIELD. 2919 02:11:35,480 --> 02:11:36,920 NEXT SLIDE. IMPLEMENTATION 2920 02:11:36,920 --> 02:11:38,840 SCIENCE IS ON TRANSLATIONAL 2921 02:11:38,840 --> 02:11:41,480 RESEARCH SPECTRUM PUTTING IN 2922 02:11:41,480 --> 02:11:43,800 LATE STAGE TRANSLATION AND LIKE 2923 02:11:43,800 --> 02:11:45,680 WHAT DR. SEMLER SAID ABOUT GOING 2924 02:11:45,680 --> 02:11:49,160 TO BEFRNL TO BEDSIDE AND BACK 2925 02:11:49,160 --> 02:11:51,400 AGAIN AND NEUROCONDITION OF 2926 02:11:51,400 --> 02:11:53,360 RESEARCH SPECTRUM GOING FROM 2927 02:11:53,360 --> 02:11:55,480 BENCH TO BEDSIDE AND 2928 02:11:55,480 --> 02:11:56,600 IMPLEMENTATION SCIENCE 2929 02:11:56,600 --> 02:11:57,920 PRESUPPOSES AN INTERVENTION THAT 2930 02:11:57,920 --> 02:11:59,760 WORKS AND CLASSICALLY TALK ABOUT 2931 02:11:59,760 --> 02:12:02,840 EVIDENCE COMING FROM RANDOMIZE 2932 02:12:02,840 --> 02:12:04,360 CHONDRTROLL TRIALS AND 2933 02:12:04,360 --> 02:12:06,160 PROBLEMIZE RTC AS PEOPLE HAVE AS 2934 02:12:06,160 --> 02:12:07,560 WELL AND IT ASSUMES THERE IS A 2935 02:12:07,560 --> 02:12:09,840 THING THAT OUGHT TO BE DONE. IT 2936 02:12:09,840 --> 02:12:11,200 TRIES TO FIGURE OUT HOW TO GET 2937 02:12:11,200 --> 02:12:18,320 PEOPLE AND SYSTEMS TO DO IT. 2938 02:12:18,320 --> 02:12:28,760 COLLEAGUES CONCEPTUALIZE 2939 02:12:29,280 --> 02:12:29,800 IMPLEMENTATION SEGUE TO HELP 2940 02:12:29,800 --> 02:12:30,440 PEOPLE UNDERSTAND WHETHER THING 2941 02:12:30,440 --> 02:12:30,920 THEY ARE INTERESTED IN 2942 02:12:30,920 --> 02:12:31,600 IMPLEMENTATION SCIENCE WAYS IT 2943 02:12:31,600 --> 02:12:33,120 WORKS IDENTIFY PRACTICE OF 2944 02:12:33,120 --> 02:12:34,520 INTEREST AND EARLY MOBILIZATION 2945 02:12:34,520 --> 02:12:38,000 DURING ICU STATE TO TRY TO 2946 02:12:38,000 --> 02:12:39,760 PREVENT WEAKNESS LATER AND ASK 2947 02:12:39,760 --> 02:12:41,960 QUESTION HOW IS IT SHOWING 2948 02:12:41,960 --> 02:12:44,960 EFFICACY IN RCT OR IDEAL WORLD 2949 02:12:44,960 --> 02:12:46,800 DOES IT WORK MEKNISTICALLY CAN 2950 02:12:46,800 --> 02:12:48,280 IT WORK? 2951 02:12:48,280 --> 02:12:49,400 WE HEARD GREAT SCIENCE EARLIER 2952 02:12:49,400 --> 02:12:52,080 IN THE CONFERENCE ABOUT 2953 02:12:52,080 --> 02:12:54,240 UNDERSTANDING PATHOPHYSIOLOGY 2954 02:12:54,240 --> 02:12:56,200 WEAKNESS AND CLINICAL ILLNESS AT 2955 02:12:56,200 --> 02:12:57,800 THIS LEVEL AND DOES INTERVENTION 2956 02:12:57,800 --> 02:12:59,200 WORK AT THAT LEVEL? 2957 02:12:59,200 --> 02:13:01,200 NOT SURE IF WE KNOW FOR SURE AND 2958 02:13:01,200 --> 02:13:03,560 IF WE DON'T KNOW WE WANT TO DO 2959 02:13:03,560 --> 02:13:05,920 THAT EFFICACY RESEARCH AND AT A 2960 02:13:05,920 --> 02:13:07,880 MECHANISTIC LEVEL MAKES SENSE TO 2961 02:13:07,880 --> 02:13:10,880 LOOK AT INTERVENTION AT ALL. IF 2962 02:13:10,880 --> 02:13:13,440 IT HAS SHOWN EFFICACY AT ALL WE 2963 02:13:13,440 --> 02:13:17,160 MOVE ON AND ASK OURSELVES IF IT 2964 02:13:17,160 --> 02:13:18,200 SHOWS EFFECTIVENESS IN REAL 2965 02:13:18,200 --> 02:13:21,000 WORLD DOES IT WORK AND 2966 02:13:21,000 --> 02:13:22,560 HETEROGENOUS DELIVERY SYSTEM HAS 2967 02:13:22,560 --> 02:13:24,560 IT BEEN SHOWN TO WORK? 2968 02:13:24,560 --> 02:13:26,480 IF NOT WE WOULD DO THAT 2969 02:13:26,480 --> 02:13:27,400 EFFECTIVENESS RESEARCH TO FIGURE 2970 02:13:27,400 --> 02:13:28,800 OUT THAT QUESTION AND IF WE KNOW 2971 02:13:28,800 --> 02:13:30,800 IT WORKS AND IS A MATTER OF 2972 02:13:30,800 --> 02:13:33,200 GETTING PEOPLE TO DO IT YOU FIND 2973 02:13:33,200 --> 02:13:34,760 YOURSELF IN LOWER RIGHT CORNER 2974 02:13:34,760 --> 02:13:37,040 THAT IS IMPLEMENTATION SCIENCE 2975 02:13:37,040 --> 02:13:38,480 INCREASINGLY WE ARE IN MIDDLE WE 2976 02:13:38,480 --> 02:13:40,200 ARE NOT SURE AND THINK IT MIGHT 2977 02:13:40,200 --> 02:13:41,400 WORK AND PEOPLE WANT US TO 2978 02:13:41,400 --> 02:13:43,000 REALLY DO IT. 2979 02:13:43,000 --> 02:13:45,480 WE GET INTO HYBRID EFFECTIVENESS 2980 02:13:45,480 --> 02:13:46,760 IMPLEMENTATION TRIALS I WILL 2981 02:13:46,760 --> 02:13:50,800 TELL YOU ABOUT. NEXT SLIDE. 2982 02:13:50,800 --> 02:13:52,800 LET'S TALK ABOUT STUDY DESIGN 2983 02:13:52,800 --> 02:13:54,320 CONSIDERATIONS FOR INTERVENTIONS 2984 02:13:54,320 --> 02:13:57,600 FOCUSED ON ARDS SURVIVORS AND 2985 02:13:57,600 --> 02:13:59,960 BRINGING [INDISCERNIBLE]. NEXT 2986 02:13:59,960 --> 02:14:00,640 SLIDE. 2987 02:14:00,640 --> 02:14:02,080 SO, PIECING IMPLEMENTATION 2988 02:14:02,080 --> 02:14:05,000 SCIENCE I WANT TO MAKE SURE 2989 02:14:05,000 --> 02:14:06,240 STUDENTS UNDERSTAND A DIFFERENCE 2990 02:14:06,240 --> 02:14:08,440 BETWEEN STUDY DESIGN AND 2991 02:14:08,440 --> 02:14:08,680 METHODS. 2992 02:14:08,680 --> 02:14:10,920 NEXT SLIDE. I WILL FOCUS ON 2993 02:14:10,920 --> 02:14:12,640 STUDY DESIGN AND I WILL MAKE A 2994 02:14:12,640 --> 02:14:14,960 NOD TO QUALITATIVE AND MIXED AND 2995 02:14:14,960 --> 02:14:17,920 OTHER TYPES OF METHODS AND 2996 02:14:17,920 --> 02:14:21,120 FOCUSED ON RESEARCH DESIGN HERE 2997 02:14:21,120 --> 02:14:22,480 OVERALL APPROACH TO RESEARCH 2998 02:14:22,480 --> 02:14:24,520 QUESTION AND UNDERSTANDING 2999 02:14:24,520 --> 02:14:25,600 RELATIONSHIP BETWEEN EXPOSURES 3000 02:14:25,600 --> 02:14:28,200 AND OUTCOME. NEXT SLIDE. 3001 02:14:28,200 --> 02:14:30,480 RCTS RANDOMIZED CONTROL TRIALS 3002 02:14:30,480 --> 02:14:33,600 WE LOVE. THEY ARE LOVELY ON SO 3003 02:14:33,600 --> 02:14:36,600 MANY LEVELS AND IS SIMPLE 3004 02:14:36,600 --> 02:14:37,120 CONCEPTUALLY. 3005 02:14:37,120 --> 02:14:39,080 NEXT SLIDE. THERE ARE PROBLEMS. 3006 02:14:39,080 --> 02:14:40,560 PEOPLE HAVE ALREADY IN THE 3007 02:14:40,560 --> 02:14:42,960 CONFERENCE NODDED TO PROBLEMS 3008 02:14:42,960 --> 02:14:45,800 WITH RCTS AND TAKING A DEEPER 3009 02:14:45,800 --> 02:14:48,440 DIVE THERE IS POTENTIAL FOR 3010 02:14:48,440 --> 02:14:50,280 CONTAMINATION DOG TRADITIONAL 3011 02:14:50,280 --> 02:14:52,000 PATIENT LEVEL RANDOMIZED CONTROL 3012 02:14:52,000 --> 02:14:54,200 TRIAL AND WHEN YOU GET INTO MORE 3013 02:14:54,200 --> 02:14:58,160 COMPLEX BEHAVIORAL INTERVENTIONS 3014 02:14:58,160 --> 02:15:02,200 AND QUESTIONS IN CHAT FROM PRIOR 3015 02:15:02,200 --> 02:15:04,800 TALK GREAT SIMPLE INTERVENTION 3016 02:15:04,800 --> 02:15:07,360 AND COMPLEX INTERVENTION GOING 3017 02:15:07,360 --> 02:15:10,880 BACK TO IDEA AND TRIAL FOCUSED 3018 02:15:10,880 --> 02:15:14,000 ON EARLY MOBILIZATION AND I 3019 02:15:14,000 --> 02:15:15,360 REMEMBER BEING A PARTICIPANT IN 3020 02:15:15,360 --> 02:15:17,720 STUDY AND TELLING US WE WANT YOU 3021 02:15:17,720 --> 02:15:20,720 TO MOBILIZE PATIENTS I DON'T 3022 02:15:20,720 --> 02:15:23,120 WANT TO TO EARLY MOBILIZATION OR 3023 02:15:23,120 --> 02:15:26,600 NOT IMMOBILIZING THEM SEEMS 3024 02:15:26,600 --> 02:15:29,280 UNETHICAL TO NOT MOBILIZE MR. 3025 02:15:29,280 --> 02:15:32,000 SMIDGE BUT TO MR. JONES AND 3026 02:15:32,000 --> 02:15:34,200 PROBLEMS ARE WITH TRYING TO KEEP 3027 02:15:34,200 --> 02:15:36,600 ARTIFICIAL SDIVENLGS AND YOU MAY 3028 02:15:36,600 --> 02:15:40,120 FIND PARTICIPANTS SABOTAGING 3029 02:15:40,120 --> 02:15:41,040 INADVERTENTLY OR MAYBE NOT 3030 02:15:41,040 --> 02:15:43,400 INTERVENTION AND ISSUES ARE WITH 3031 02:15:43,400 --> 02:15:45,120 CONTAMINATION THAT RCTS ARE NOT 3032 02:15:45,120 --> 02:15:47,280 WELL EQUIPPED TO DEAL WITH AND 3033 02:15:47,280 --> 02:15:48,880 OFTEN IN IMPLEMENTATION SCIENCE 3034 02:15:48,880 --> 02:15:51,240 YOU SEE CLUSTER DESIGNS AND MAY 3035 02:15:51,240 --> 02:15:53,440 SEE A UNIT AWARD RANDOMIZED TO 3036 02:15:53,440 --> 02:15:55,120 SOMETHING THAT YOU MAY SEE 3037 02:15:55,120 --> 02:15:57,720 HOSPITAL OR RANDOMIZED STUDENT 3038 02:15:57,720 --> 02:15:59,600 INTERVENTION THAT IS EASIER TO 3039 02:15:59,600 --> 02:16:01,560 PRESERVE AND YOU CAN RANDOMIZE 3040 02:16:01,560 --> 02:16:03,320 AT LEVEL OF CLINICIAN THAT IS 3041 02:16:03,320 --> 02:16:06,200 ANOTHER WAY TO TRY TO AVOID 3042 02:16:06,200 --> 02:16:08,200 CONTAMINATION AND SECONDARILY 3043 02:16:08,200 --> 02:16:09,800 STAKEHOLDERS HAVE FEELINGS ABOUT 3044 02:16:09,800 --> 02:16:11,200 RANDOMIZATION AND IF YOU ARE 3045 02:16:11,200 --> 02:16:12,800 TELLING YOUR STAKEHOLDERS THAT 3046 02:16:12,800 --> 02:16:15,360 YOU WANT TO TRIAL SOMETHING YOU 3047 02:16:15,360 --> 02:16:16,920 THINK IS EFFICACIOUS YOU HAVE 3048 02:16:16,920 --> 02:16:18,760 REASON TO BELIEVE IT WORKS. 3049 02:16:18,760 --> 02:16:20,800 YOU ARE TELLING THEM YOU KNOW 3050 02:16:20,800 --> 02:16:22,680 THERE IS A 50% CHANCE YOU WILL 3051 02:16:22,680 --> 02:16:24,920 GET THIS GREAT THING AND 50% 3052 02:16:24,920 --> 02:16:26,480 CHANCE YOU WON'T. PLEASE GIVE 3053 02:16:26,480 --> 02:16:28,360 US OUTCOMES ANYWAY. THAT 3054 02:16:28,360 --> 02:16:29,560 DOESN'T ALWAYS WORK. 3055 02:16:29,560 --> 02:16:32,160 SO, IT IS IMPORTANT WHEN YOU ARE 3056 02:16:32,160 --> 02:16:34,880 DOING ESPECIALLY COMPLEX 3057 02:16:34,880 --> 02:16:35,560 BEHAVIORAL INTERVENTION TO WORK 3058 02:16:35,560 --> 02:16:38,480 WITH STAKEHOLDERS IN CRAFTING 3059 02:16:38,480 --> 02:16:40,720 RESEARCH QUESTION AND CHOOSING A 3060 02:16:40,720 --> 02:16:42,160 STUDY DESIGN THAT THEY FEEL THEY 3061 02:16:42,160 --> 02:16:44,600 CAN ENDORSE AND PARTICIPATE IN. 3062 02:16:44,600 --> 02:16:47,160 THIRDLY, IT IS DIFFICULT TO 3063 02:16:47,160 --> 02:16:50,640 COMPLEX AND TO RULE OUT COMPLEX 3064 02:16:50,640 --> 02:16:53,120 INTERVENTIONS ALL AT ONCE AND 3065 02:16:53,120 --> 02:16:54,720 RCT WOULD SUGGEST TO GO FROM OFF 3066 02:16:54,720 --> 02:16:56,640 TO ON AND IF YOU HAVE SOMETHING 3067 02:16:56,640 --> 02:16:58,520 WITH MORE MOVING PIECES TO IT IT 3068 02:16:58,520 --> 02:17:02,760 CAN BE DIFFICULT TO DO THAT YOU 3069 02:17:02,760 --> 02:17:05,480 END UP WANTING TO LOOK AT 3070 02:17:05,480 --> 02:17:07,440 STAGGERED APPROACHES SO WHEN YOU 3071 02:17:07,440 --> 02:17:08,560 EXECUTE YOUR INTERVENTION YOU 3072 02:17:08,560 --> 02:17:12,000 ARE DOING IT WELL AND PAYING A 3073 02:17:12,000 --> 02:17:14,200 LOT OF ATTENTION TO FIDELITY AND 3074 02:17:14,200 --> 02:17:17,160 EASIER TO DO THAT IN COMPLEX 3075 02:17:17,160 --> 02:17:18,240 INTERVENTION STAGGERING 3076 02:17:18,240 --> 02:17:20,320 EXCLUSION AND 4TH, APPROACH TO 3077 02:17:20,320 --> 02:17:21,400 IMPLEMENTATION MAY NEED TO 3078 02:17:21,400 --> 02:17:23,560 DIFFER ACROSS SITES THAT IS NOD 3079 02:17:23,560 --> 02:17:25,240 TO QUESTION IN THE CHAT EARLIER 3080 02:17:25,240 --> 02:17:25,440 TOO. 3081 02:17:25,440 --> 02:17:28,320 IF YOU IMPLEMENT AT A COMMUNITY 3082 02:17:28,320 --> 02:17:29,240 HOSPITAL VERSUS ACADEMIC 3083 02:17:29,240 --> 02:17:31,280 HOSPITAL AND IMPLEMENTING AT 3084 02:17:31,280 --> 02:17:34,160 NURSING HOME VERSUS LONG-TERM 3085 02:17:34,160 --> 02:17:37,400 ACUTE CARE FACILITY APPROACH TO 3086 02:17:37,400 --> 02:17:38,320 IMPLEMENTATION MIGHT NEED TO 3087 02:17:38,320 --> 02:17:42,000 DIFFER PRESENTING PROBLEMS FOR 3088 02:17:42,000 --> 02:17:45,000 TRADITIONAL RCT. 3089 02:17:45,000 --> 02:17:46,400 NEXT SLIDE. 3090 02:17:46,400 --> 02:17:48,320 QUASI EXPERIMENTAL DESIGNS AND 3091 02:17:48,320 --> 02:17:50,160 PLACE FOR DESIGNS IN WORK 3092 02:17:50,160 --> 02:17:53,040 FOCUSED ON ARDS AND ARE DESIGNS 3093 02:17:53,040 --> 02:17:55,640 THAT DON'T EMPLOY TRADITIONAL 3094 02:17:55,640 --> 02:17:57,160 PATIENT LEVEL RANDOMIZATION AND 3095 02:17:57,160 --> 02:17:59,160 GOOD THINGS ABOUT QUASI 3096 02:17:59,160 --> 02:18:02,920 EXPERIMENTAL DESIGNS EASIER TO 3097 02:18:02,920 --> 02:18:07,280 EXECUTE AND EXPLAIN EVERYONE 3098 02:18:07,280 --> 02:18:08,960 GETS THE SAME AND NOT EVERYONE 3099 02:18:08,960 --> 02:18:11,960 GETS IT AT ONCE AND DIFFICULT TO 3100 02:18:11,960 --> 02:18:13,880 DO THAT PRACTICE MANAGERS AND 3101 02:18:13,880 --> 02:18:16,880 THOSE WORKING IN REAL WORLD 3102 02:18:16,880 --> 02:18:18,360 UNDERSTAND THAT RESEARCH TEAM 3103 02:18:18,360 --> 02:18:20,640 CAN'T EXECUTE AT 10 SITES AT 3104 02:18:20,640 --> 02:18:21,080 ONCE. 3105 02:18:21,080 --> 02:18:22,360 IT IS STRAIGHTFORWARD TO EXPLAIN 3106 02:18:22,360 --> 02:18:26,600 TO FOLKS AND TEND TO BE RELEVANT 3107 02:18:26,600 --> 02:18:29,240 TO PRACTICE. 3108 02:18:29,240 --> 02:18:33,560 YOU CHOOSE SITES LOOKS AT PLACES 3109 02:18:33,560 --> 02:18:34,760 WE PROVIDE. 3110 02:18:34,760 --> 02:18:37,120 WE COULD BE REALLY COMPLEX FROM 3111 02:18:37,120 --> 02:18:40,560 AN ANALYTIC PERSPECTIVE AND YOU 3112 02:18:40,560 --> 02:18:44,640 MAY BE EXPLANATORY ACT WITH 3113 02:18:44,640 --> 02:18:47,120 CONFOUNDING FACTORS TO ADDRESS 3114 02:18:47,120 --> 02:18:49,000 AND THEY HAVE [INDISCERNIBLE] ON 3115 02:18:49,000 --> 02:18:49,920 INTERNAL VALIDITY. 3116 02:18:49,920 --> 02:18:52,400 >> FIVE MINUTES REMAINING. 3117 02:18:52,400 --> 02:18:53,440 >> THANK YOU. 3118 02:18:53,440 --> 02:18:55,440 NEXT SLIDE. 3119 02:18:55,440 --> 02:19:00,800 ALL RIGHT. REAL BRIEF DETOUR 3120 02:19:00,800 --> 02:19:03,040 INTO HYBRID TRIALS AND 3121 02:19:03,040 --> 02:19:05,040 EFFECTIVENESS TRIALS MENTIONING 3122 02:19:05,040 --> 02:19:06,240 WHETHER INTERVENTION WORKS IN 3123 02:19:06,240 --> 02:19:07,880 REAL WORLD AND IMPLEMENTATION 3124 02:19:07,880 --> 02:19:09,560 TRIALS FOCUSED ON HOW TO GET 3125 02:19:09,560 --> 02:19:10,920 PEOPLE TO DO THE THING YOU WANT 3126 02:19:10,920 --> 02:19:13,440 THEM TO DO. IN THE MIDDLE THERE 3127 02:19:13,440 --> 02:19:15,520 ARE P HYBRID TRIALS. 3128 02:19:15,520 --> 02:19:16,320 NEXT SLIDE. 3129 02:19:16,320 --> 02:19:19,080 SO, THERE ARE REASONS TO DO 3130 02:19:19,080 --> 02:19:20,760 HYBRID TRIALS AND JEFF WHO IS A 3131 02:19:20,760 --> 02:19:22,600 FRIEND AND COLLABORATOR AT 3132 02:19:22,600 --> 02:19:25,800 UNIVERSITY OF ARKANSAS MEDICAL 3133 02:19:25,800 --> 02:19:28,040 SCIENCES ORIGINATED CONCEPT AND 3134 02:19:28,040 --> 02:19:30,480 IDEA OF HYBRID TRIAL TWO TRIALS 3135 02:19:30,480 --> 02:19:36,800 IN 1 IS SPEEDING PROGRESS ALONG 3136 02:19:36,800 --> 02:19:39,440 TRANSLATIONAL SPECTRUM. 3137 02:19:39,440 --> 02:19:41,480 ACKNOWLEDGING ULTIMATE GOAL OF 3138 02:19:41,480 --> 02:19:43,280 IMPLEMENTATION SCIENCE. 3139 02:19:43,280 --> 02:19:43,600 NEXT SLIDE. 3140 02:19:43,600 --> 02:19:46,760 HYBRID TRIALS ARE POPULAR AND 3141 02:19:46,760 --> 02:19:48,000 INCREASINGLY CITED AND 3142 02:19:48,000 --> 02:19:49,600 INCREASING APPROACH TO TRY TO 3143 02:19:49,600 --> 02:19:50,840 MAKE SURE THAT THOSE 3144 02:19:50,840 --> 02:19:52,560 EFFECTIVENESS THAT WE ARE DOING 3145 02:19:52,560 --> 02:19:54,880 IS INTO THE REAL WORLD. 3146 02:19:54,880 --> 02:19:56,160 NEXT SLIDE. 3147 02:19:56,160 --> 02:19:57,960 BRIEFLY THERE IS THREE TYPES OF 3148 02:19:57,960 --> 02:20:00,200 HYBRID TRIALS WITH DIFFERENTIAL 3149 02:20:00,200 --> 02:20:02,360 FOCUS ON EFFECTIVENESS VERSUS 3150 02:20:02,360 --> 02:20:03,880 IMPLEMENTATION AND EARLIER STAGE 3151 02:20:03,880 --> 02:20:06,040 THAT EVIDENCE IS, LESS CERTAIN 3152 02:20:06,040 --> 02:20:08,240 WE ARE IN EVIDENCE AND WHETHER 3153 02:20:08,240 --> 02:20:09,080 INTERVENTION AND INTEREST WORKS 3154 02:20:09,080 --> 02:20:11,880 AND WE ARE LIKELY TO DO TYPE 1 3155 02:20:11,880 --> 02:20:12,880 GATHERING A LITTLE INFORMATION 3156 02:20:12,880 --> 02:20:15,200 ABOUT IMPLEMENTATION AND MORE 3157 02:20:15,200 --> 02:20:17,120 CONFIDENT WE ARE IN EVIDENCE 3158 02:20:17,120 --> 02:20:18,480 BASE MORE QUESTION SHIFTS TO HOW 3159 02:20:18,480 --> 02:20:19,920 TO GET PEOPLE TO DO THE THING 3160 02:20:19,920 --> 02:20:24,360 AND YOU MOVE TO A TYPE 3. NEXT 3161 02:20:24,360 --> 02:20:28,880 SLIDE. 3162 02:20:28,880 --> 02:20:30,480 HYBRID TRIALS COMBINE TWO TRIAL 3163 02:20:30,480 --> 02:20:32,040 TYPES THAT ARE COMPLEX AND DO 3164 02:20:32,040 --> 02:20:34,040 YOU TWO TRIALS IN TANDEM USING 3165 02:20:34,040 --> 02:20:35,680 DIFFERENT METHODS AND WILL USE 3166 02:20:35,680 --> 02:20:37,640 DIFFERENT OUTCOMES AND INSTEAD 3167 02:20:37,640 --> 02:20:39,720 OF CLINICAL OUTCOMES LOOKING FOR 3168 02:20:39,720 --> 02:20:41,440 IN EFFECTIVENESS TRIAL YOU LOOK 3169 02:20:41,440 --> 02:20:47,920 FOR IMPLEMENTATION OUTCOMES 3170 02:20:47,920 --> 02:20:49,040 ACCEPTABILITY APPROPRIATENESS 3171 02:20:49,040 --> 02:20:49,480 AND FEASIBILITY. 3172 02:20:49,480 --> 02:20:51,720 NEXT SLIDE. GETTING BACK 3173 02:20:51,720 --> 02:20:54,600 QUICKLY TO QUASI EXPERIMENTAL 3174 02:20:54,600 --> 02:20:54,880 DESIGNS. 3175 02:20:54,880 --> 02:20:57,120 NEXT SLIDE. I LOVE THIS 3176 02:20:57,120 --> 02:20:59,360 DECISION TREE THAT APPLIES TO 3177 02:20:59,360 --> 02:21:01,160 IMPLEMENTATION RESEARCH AND 3178 02:21:01,160 --> 02:21:03,280 APPLIES TO RESEARCH FOCUSED ARDS 3179 02:21:03,280 --> 02:21:05,400 AND ONE WAY TO THINK ABOUT 3180 02:21:05,400 --> 02:21:06,920 CHOOSING QUASI EXPERIMENTAL 3181 02:21:06,920 --> 02:21:09,440 DESIGNS AND COLLEAGUES AT UCSF 3182 02:21:09,440 --> 02:21:12,080 AND THINKING ABOUT WHAT TYPES OF 3183 02:21:12,080 --> 02:21:13,400 OUTCOMES MAKE SENSE FOR YOUR 3184 02:21:13,400 --> 02:21:14,600 QUESTION OF INTEREST AND TIME 3185 02:21:14,600 --> 02:21:16,640 POINTS AND SITES AND THINKING 3186 02:21:16,640 --> 02:21:18,920 THROUGH WHAT GOOD QUASI 3187 02:21:18,920 --> 02:21:20,280 EXPERIMENTAL DESIGN MIGHT BE. 3188 02:21:20,280 --> 02:21:23,080 NEXT SLIDE. HIGHLIGHTING THREE 3189 02:21:23,080 --> 02:21:26,400 WE USE IN IMPLEMENTATION SCIENCE 3190 02:21:26,400 --> 02:21:28,360 AND WENLED TRIAL EACH SITE GETS 3191 02:21:28,360 --> 02:21:29,960 INTERVENTION STAGGERED OVER TIME 3192 02:21:29,960 --> 02:21:31,960 AND EACH SITE SERVES AS OWN 3193 02:21:31,960 --> 02:21:34,160 CONTROL AND STATISTICALLY IT IS 3194 02:21:34,160 --> 02:21:36,280 ELEGANT AND REALISTICALLY HARD 3195 02:21:36,280 --> 02:21:38,600 TO EXECUTE AND I'M IN THE MIDDLE 3196 02:21:38,600 --> 02:21:40,760 OF A TRIAL NOW NOT FOR FAINT AT 3197 02:21:40,760 --> 02:21:42,440 HEART BUT POWERFUL WAY TO LOOK 3198 02:21:42,440 --> 02:21:43,880 AT COMPLEX INTERVENTION ROLLING 3199 02:21:43,880 --> 02:21:46,880 OUT ACROSS SITES OVER TIME. 3200 02:21:46,880 --> 02:21:48,040 NEXT SLIDE. 3201 02:21:48,040 --> 02:21:49,400 INTERRUPTED TIME SERIES APPROACH 3202 02:21:49,400 --> 02:21:53,400 IS LOVELY WITH A SINGLE SITE TO 3203 02:21:53,400 --> 02:21:56,440 LOOK AT WHAT OUT COME THIS IS 3204 02:21:56,440 --> 02:21:57,920 QUANTITATIVE OUTCOME HERE AND 3205 02:21:57,920 --> 02:21:59,880 ASSESSING OVER TIME INSTITUTE 3206 02:21:59,880 --> 02:22:01,280 CHANGE AND LOOK FOR CHANGE IN 3207 02:22:01,280 --> 02:22:02,560 SLOPE OF INTERVENTION OVER TIME 3208 02:22:02,560 --> 02:22:04,920 AND YOU CAN DO IT AT ONE OR 3209 02:22:04,920 --> 02:22:06,000 MULTIPLE SITES AND NICE WHERE 3210 02:22:06,000 --> 02:22:08,480 YOU HAVE A CONTROL YOU HAVEN'T 3211 02:22:08,480 --> 02:22:09,840 INSTITUTED INTERVENTION AND YOU 3212 02:22:09,840 --> 02:22:11,200 CAN DO A DIFFERENCE IN 3213 02:22:11,200 --> 02:22:13,600 DIFFERENCES APPROACH. 3214 02:22:13,600 --> 02:22:15,480 NEXT SLIDE. 3215 02:22:15,480 --> 02:22:17,560 THIRD ONE DR. JORGE WILL COVER 3216 02:22:17,560 --> 02:22:20,200 AS WELL IS ADAPTIVE DESIGN AND 3217 02:22:20,200 --> 02:22:22,520 DESIGN AND PRE-SPECIFIED RULES 3218 02:22:22,520 --> 02:22:24,280 TO CHANGE EXPOSURE THAT YOU 3219 02:22:24,280 --> 02:22:27,120 ASSESS OUTCOMES CYCLICALLY BASED 3220 02:22:27,120 --> 02:22:28,560 ON HOW RESPONSIVE PARTICIPANTS 3221 02:22:28,560 --> 02:22:30,320 ARE TO THE INTERVENTION. 3222 02:22:30,320 --> 02:22:30,720 NEXT SLIDE. 3223 02:22:30,720 --> 02:22:33,480 THIS IS A EXAMPLE OF ADAPTIVE 3224 02:22:33,480 --> 02:22:36,040 TRIAL AND IMPLEMENTATION SCIENCE 3225 02:22:36,040 --> 02:22:38,880 AND AUTHORS CHOSE TO HAVE A 3226 02:22:38,880 --> 02:22:40,000 SPECIFIC INTERVENTION THAT IS 3227 02:22:40,000 --> 02:22:41,960 MEANT TO PREVENT SUICIDE IN VA 3228 02:22:41,960 --> 02:22:44,160 POPULATION AND LOOKED AT 3229 02:22:44,160 --> 02:22:46,200 IMPLEMENTATION IN SITE IS 3230 02:22:46,200 --> 02:22:47,200 IMPLEMENTED ADEQUATELY LEFT 3231 02:22:47,200 --> 02:22:49,040 ALONE IF DIDN'T CHOSE SPECIFIC 3232 02:22:49,040 --> 02:22:50,080 INTERVENTION FOR IMPLEMENTATION 3233 02:22:50,080 --> 02:22:52,520 AND IF THAT WORKS LEFT ALONE AND 3234 02:22:52,520 --> 02:22:54,200 IF DIDN'T CHOSE A DIFFERENT 3235 02:22:54,200 --> 02:22:56,400 APPROACH AND WHAT ADAPTIVE TRIAL 3236 02:22:56,400 --> 02:22:59,600 MIGHT LOOK LIKE WITH 6 DIFFERENT 3237 02:22:59,600 --> 02:23:01,880 ANALYTIC GROUPS AT THE END. 3238 02:23:01,880 --> 02:23:03,600 NEXT SLIDE, CHALLENGES AND WILL 3239 02:23:03,600 --> 02:23:06,760 WRAP UP AFTER THIS. NEXT SLIDE. 3240 02:23:06,760 --> 02:23:10,400 THIS IS NOT FOR FAINT OF HEART. 3241 02:23:10,400 --> 02:23:12,360 TAP FORWARD IF YOU COULD. WE 3242 02:23:12,360 --> 02:23:14,280 DON'T KNOW WHAT EVIDENCE IS 3243 02:23:14,280 --> 02:23:17,280 READY FOR TRANSLATION AND BASHED 3244 02:23:17,280 --> 02:23:18,960 RCT AND THEY HAVE UTILITY AND 3245 02:23:18,960 --> 02:23:20,600 HELP US TO UNDERSTAND WHETHER 3246 02:23:20,600 --> 02:23:21,600 INTERVENTIONS WORK AND IN 3247 02:23:21,600 --> 02:23:23,360 ABSENCE OF THAT HOW DO WE KNOW 3248 02:23:23,360 --> 02:23:24,800 WHEN SOMETHING IS READY TO 3249 02:23:24,800 --> 02:23:26,000 TRANSLATE. THERE IS A QUESTION 3250 02:23:26,000 --> 02:23:27,400 IN THE FIELD WHEN SOMETHING IS 3251 02:23:27,400 --> 02:23:29,520 READY FOR IMPLEMENTATION AND 3252 02:23:29,520 --> 02:23:31,000 SECONDARILY WE NEED TO DO 3253 02:23:31,000 --> 02:23:33,120 QUALITATIVE AND QUANTITATIVE 3254 02:23:33,120 --> 02:23:35,560 WORK DOING IMPLEMENTATION WORK 3255 02:23:35,560 --> 02:23:37,680 RESEARCH AND WE DON'T ALWAYS 3256 02:23:37,680 --> 02:23:38,960 THINK ABOUT THAT PIECE BUT 3257 02:23:38,960 --> 02:23:40,880 HAVING TEAMS TO DO THAT. 3258 02:23:40,880 --> 02:23:42,760 CERTAINLY WE HAVE TO FIGURE OUT 3259 02:23:42,760 --> 02:23:44,680 HOW TO BALANCE INTERNAL VALIDITY 3260 02:23:44,680 --> 02:23:47,320 SO WE CAN CREATE GENERALIZABLE 3261 02:23:47,320 --> 02:23:49,200 OR TRANSFERABLE KNOWLEDGE THAT 3262 02:23:49,200 --> 02:23:51,440 APPLIES ACROSS SETTINGS AND 3263 02:23:51,440 --> 02:23:54,040 FINALLY AND CERTAINLY NOT LEAST 3264 02:23:54,040 --> 02:23:56,200 IMPORTANT IS HAVING SITE OF 3265 02:23:56,200 --> 02:23:57,880 EQUITY AND IMPLEMENTATION TRYING 3266 02:23:57,880 --> 02:24:00,680 NO THE TO RECREATE GAPS AND 3267 02:24:00,680 --> 02:24:02,120 PRACTICE LEAVING BEHIND 3268 02:24:02,120 --> 02:24:03,720 IMPORTANT SETTINGS WHEN WE DO 3269 02:24:03,720 --> 02:24:04,560 THIS WORK. 3270 02:24:04,560 --> 02:24:06,560 NEXT SLIDE. 3271 02:24:06,560 --> 02:24:09,280 THAT IS ALL I HAVE. THANKS SO 3272 02:24:09,280 --> 02:24:09,600 MUCH. 3273 02:24:09,600 --> 02:24:12,280 >> THAT WAS AWESOME. MEGAN, 3274 02:24:12,280 --> 02:24:14,720 THANKS SO MUCH. 3275 02:24:14,720 --> 02:24:15,720 QUESTIONS COMING THROUGH THE 3276 02:24:15,720 --> 02:24:17,360 CHAT AND I HAVE A COUPLE 3277 02:24:17,360 --> 02:24:18,360 QUESTIONS FOR YOU. 3278 02:24:18,360 --> 02:24:21,600 ONE, RELATED TO -- SO, I THINK 3279 02:24:21,600 --> 02:24:23,640 IN RANDOM MUSCLE DISFUNCTION 3280 02:24:23,640 --> 02:24:27,200 AFTER ARDS WE ARE STUCK AT THAT 3281 02:24:27,200 --> 02:24:29,800 TOP NODE NOT HAVING A LOT OF 3282 02:24:29,800 --> 02:24:30,800 EVIDENCE; RIGHT? 3283 02:24:30,800 --> 02:24:31,960 MY PERSONAL THOUGHT WE DON'T 3284 02:24:31,960 --> 02:24:33,320 HAVE LOTS OF EVIDENCE WE ARE 3285 02:24:33,320 --> 02:24:36,000 MAYBE NOT IMPLEMENTING 3286 02:24:36,000 --> 02:24:38,280 INTERVENTIONS CORRECTLY AND WE 3287 02:24:38,280 --> 02:24:39,680 CAN TALK ABOUT THISSOID YAF 3288 02:24:39,680 --> 02:24:41,160 DESIGNING WITH IMPLEMENTATION IN 3289 02:24:41,160 --> 02:24:43,480 MIND AS A FIRST START TO TRY TO 3290 02:24:43,480 --> 02:24:46,320 SPEED TRANSLATION WITH SOME OF 3291 02:24:46,320 --> 02:24:47,440 THIS DISCOVERY. 3292 02:24:47,440 --> 02:24:49,520 >> I'M SO GLAD YOU ASKED THAT 3293 02:24:49,520 --> 02:24:50,800 QUESTION. THERE IS SOME 3294 02:24:50,800 --> 02:24:51,960 INTERVENTIONS THAT ARE PROBABLY 3295 02:24:51,960 --> 02:24:53,760 READY FOR IMPLEMENTATION MAYBE 3296 02:24:53,760 --> 02:24:55,960 AND POST IC CLINICS IN THERE. 3297 02:24:55,960 --> 02:24:57,600 THERE IS A LOT AND PREPONDERANCE 3298 02:24:57,600 --> 02:24:59,120 OF THE THINGS WE ARE INTERESTED 3299 02:24:59,120 --> 02:25:02,560 IN AT THAT EARLIER STAGE. IT IS 3300 02:25:02,560 --> 02:25:03,640 REALLY IMPORTANT TO WORK WITH 3301 02:25:03,640 --> 02:25:06,640 EITHER I WOULD SAY ENGINEERS OR 3302 02:25:06,640 --> 02:25:08,760 IMPLEMENTATION SCIENTISTS AND 3303 02:25:08,760 --> 02:25:11,080 FOLKS WITH WORKFLOW IN MIND TO 3304 02:25:11,080 --> 02:25:13,000 HELP YOU CRAFT INTERVENTION THAT 3305 02:25:13,000 --> 02:25:16,560 IS IMPLEMENTABLE AND ONE 3306 02:25:16,560 --> 02:25:18,520 APPROACH IS -- WHICH IS DESIGNED 3307 02:25:18,520 --> 02:25:20,600 BY -- I FORGOT HER FIRST NAME 3308 02:25:20,600 --> 02:25:22,840 BUT THE IDEA IS YOU ARE 3309 02:25:22,840 --> 02:25:23,920 DESIGNING INTERVENTION IN 3310 02:25:23,920 --> 02:25:26,160 PARTNERSHIP WITH STAKEHOLDERS 3311 02:25:26,160 --> 02:25:29,160 RAPIDLY ITERATING ON 3312 02:25:29,160 --> 02:25:31,480 INTERVENTION ITSELF AND YOU 3313 02:25:31,480 --> 02:25:33,080 DESIGN SOMETHING OPTIMALLY 3314 02:25:33,080 --> 02:25:34,600 IMPLEMENTABLE AND YOU ARE 3315 02:25:34,600 --> 02:25:36,320 TESTING A MEDICATION THAT NEEDS 3316 02:25:36,320 --> 02:25:38,640 TO BE DELIVERED 6 TIMES A DAY. 3317 02:25:38,640 --> 02:25:40,160 GUESS WHAT, THAT WON'T HAPPEN 3318 02:25:40,160 --> 02:25:42,560 AND WORKING WITH STAKEHOLDERS TO 3319 02:25:42,560 --> 02:25:44,880 COME UP WITH AN INTERVENTION 3320 02:25:44,880 --> 02:25:46,680 THAT COULD ACTUALLY BE 3321 02:25:46,680 --> 02:25:48,880 DOVE-TAILED INTO THE WORKFLOW OF 3322 02:25:48,880 --> 02:25:50,280 WHOEVER IT IS THAT WILL DELIVER 3323 02:25:50,280 --> 02:25:52,360 IT OR THAT WILL BE A RECIPIENT 3324 02:25:52,360 --> 02:25:55,920 OF IT. OUTCOMES ARE NOT 3325 02:25:55,920 --> 02:25:57,720 IMPLEMENTATION OUTCOMES BUT YOU 3326 02:25:57,720 --> 02:25:59,760 ARE AT LEAST CONSIDERING WHAT 3327 02:25:59,760 --> 02:26:01,520 WILL BE DONE TO GET THERE. 3328 02:26:01,520 --> 02:26:03,720 >> AWESOME. THANK YOU. I HAVE 3329 02:26:03,720 --> 02:26:05,960 ONE MORE QUESTION IF YOU DON'T 3330 02:26:05,960 --> 02:26:06,160 MIND. 3331 02:26:06,160 --> 02:26:06,840 >> OF COURSE. 3332 02:26:06,840 --> 02:26:08,640 >> IT IS TAKING THIS IDEA OF 3333 02:26:08,640 --> 02:26:16,840 FORWARD TRANSLATION AND REVERSE 3334 02:26:16,840 --> 02:26:17,160 TRANSLATION. 3335 02:26:17,160 --> 02:26:19,680 YOU KNOW, GIVEN LIMITED SOURCES 3336 02:26:19,680 --> 02:26:22,200 TO DO THIS WORK, HOW MUCH DO YOU 3337 02:26:22,200 --> 02:26:23,880 ACTUALLY CARE IF SOMETHING WORKS 3338 02:26:23,880 --> 02:26:27,840 AS AN IMPLEMENTATION SCIENTIST 3339 02:26:27,840 --> 02:26:29,920 AND PRACTICING BEDSIDE 3340 02:26:29,920 --> 02:26:31,480 CLINICIAN? IF SOMETHING WORKS 3341 02:26:31,480 --> 02:26:33,160 HOW MUCH DO YOU CARE ABOUT 3342 02:26:33,160 --> 02:26:34,160 WORKING BACKWOODS TO FIGURE OUT 3343 02:26:34,160 --> 02:26:35,960 WHY IT WORKS AND IF IT IS 3344 02:26:35,960 --> 02:26:38,600 POSSIBLE TO UNDERSTAND AT 3345 02:26:38,600 --> 02:26:39,760 BIOLOGICAL MECHANISM LEVEL THAT 3346 02:26:39,760 --> 02:26:42,640 SOMETHING WORKS AND WORKING ON 3347 02:26:42,640 --> 02:26:43,360 IMPLEMENTATION FROM THERE. 3348 02:26:43,360 --> 02:26:45,080 >> GOOD QUESTION. I LOVE THAT 3349 02:26:45,080 --> 02:26:46,800 QUESTION. IT REALLY DEPENDS WHO 3350 02:26:46,800 --> 02:26:48,760 YOUR STAKEHOLDERS ARE AND ONE 3351 02:26:48,760 --> 02:26:51,880 THING WE DO AT IMPLEMENTATION 3352 02:26:51,880 --> 02:26:54,200 SCIENCE IS ENGAGE DEEPLY AT 3353 02:26:54,200 --> 02:26:55,880 EVERY LEVEL WITH STAKEHOLDERS 3354 02:26:55,880 --> 02:26:58,040 NOT JUST TO DO WORK BUT DEFINE 3355 02:26:58,040 --> 02:26:59,760 INTERVENTION AND DEPENDING ON 3356 02:26:59,760 --> 02:27:02,920 RISK PROFILES OF INTERVENTION 3357 02:27:02,920 --> 02:27:04,960 YOU MIGHT GO INTO IMPLEMENTATION 3358 02:27:04,960 --> 02:27:06,240 AND SOMETHING LIKE EARLY 3359 02:27:06,240 --> 02:27:07,400 MOBILIZATION AND CRITICAL 3360 02:27:07,400 --> 02:27:08,960 ILLNESS WE KNOW IS GOOD FOR SO 3361 02:27:08,960 --> 02:27:11,320 MANY REASONS AND MAYBE NOT GOOD 3362 02:27:11,320 --> 02:27:13,720 FOR BRAIN DISNUFRNGS ARDS BUT 3363 02:27:13,720 --> 02:27:15,360 GOOD FOR OTHER REASONS THAT 3364 02:27:15,360 --> 02:27:16,960 THERE IS VERY LITTLE DOWNSIDE 3365 02:27:16,960 --> 02:27:18,480 AND THAT TYPE OF INTERVENTION 3366 02:27:18,480 --> 02:27:20,280 YOU MIGHT MOVE QUICKLY TOWARDS 3367 02:27:20,280 --> 02:27:22,040 LOOKING AT IMPLEMENTATION AND 3368 02:27:22,040 --> 02:27:23,760 WHAT ISSUES ARE INFLUENCING 3369 02:27:23,760 --> 02:27:25,880 PEOPLE AND SYSTEMS THAT WILL DO 3370 02:27:25,880 --> 02:27:28,360 INTERVENTION AND NEW DEVICE FOR 3371 02:27:28,360 --> 02:27:29,920 NEW DRUG AND SIGNIFICANT RISK 3372 02:27:29,920 --> 02:27:31,200 PROFILE I WOULD SAY FILL YOUR 3373 02:27:31,200 --> 02:27:33,120 ROLE A LITTLE BIT. WE PROBABLY 3374 02:27:33,120 --> 02:27:35,360 WANT TO KNOW MORE ABOUT EFFICACY 3375 02:27:35,360 --> 02:27:38,200 BEFORE WE DIVE INTO 3376 02:27:38,200 --> 02:27:38,560 IMPLEMENTATION. 3377 02:27:38,560 --> 02:27:40,360 >> OKAY. 3378 02:27:40,360 --> 02:27:42,760 >> DON'T WANT TO LOSE SIGHT OF 3379 02:27:42,760 --> 02:27:43,720 MECHANISM. YOU HAVE A GUIDELINE 3380 02:27:43,720 --> 02:27:46,000 AND BODY TELLING YOU TO GO DO 3381 02:27:46,000 --> 02:27:46,400 THE THING. 3382 02:27:46,400 --> 02:27:49,160 I DON'T THINK WE WANT TO LOSE 3383 02:27:49,160 --> 02:27:50,520 SIGHT WHERE WE CAN TRYING TO 3384 02:27:50,520 --> 02:27:51,520 UNDERSTAND HOW IT WORKS. 3385 02:27:51,520 --> 02:27:54,760 >> ABSOLUTELY. I AGREE. DR. 3386 02:27:54,760 --> 02:27:56,720 JER REGARD PUT IN THE CHAT AS 3387 02:27:56,720 --> 02:27:58,080 WELL UNDERSTANDING MECHANISM 3388 02:27:58,080 --> 02:28:00,600 THAT CAN CERTAINLY HELP TO 3389 02:28:00,600 --> 02:28:02,560 GENERALIZE ABILITY TO OTHER 3390 02:28:02,560 --> 02:28:02,880 CONDITIONS. 3391 02:28:02,880 --> 02:28:06,560 SO, I THINK FINDING THE RIGHT 3392 02:28:06,560 --> 02:28:09,720 BALANCE AND DR. HUH MENTIONS 3393 02:28:09,720 --> 02:28:10,240 REVERSE TRANSLATION 3394 02:28:10,240 --> 02:28:13,160 OPPORTUNITIES FOR TARGETING 3395 02:28:13,160 --> 02:28:14,840 POPULATIONS BENEFITING THE MOST 3396 02:28:14,840 --> 02:28:16,800 AND PRECISION MEDICINE THAT IS 3397 02:28:16,800 --> 02:28:17,760 ABSOLUTELY TRUE. 3398 02:28:17,760 --> 02:28:20,280 THANKS SO MUCH, DR. LANE FALL. 3399 02:28:20,280 --> 02:28:24,200 WE WILL INTRODUCE OUR NEXT 3400 02:28:24,200 --> 02:28:26,920 SPEAKER, DR. DALE WHO IS A 3401 02:28:26,920 --> 02:28:29,880 PROFESSOR OF PULMONARY CARE 3402 02:28:29,880 --> 02:28:35,680 MEDICINE AND REHABILITATIONS AT 3403 02:28:35,680 --> 02:28:37,080 JOHNS HOPKINS UNIVERSITY IN 3404 02:28:37,080 --> 02:28:38,880 BALTIMORE AND -- HE IS AN 3405 02:28:38,880 --> 02:28:41,000 ATTENDING PHYSICIAN IN MEDICAL 3406 02:28:41,000 --> 02:28:43,200 INTENSIVE CARE UNIT AT JOHNS 3407 02:28:43,200 --> 02:28:44,840 HOPKINS AND DIRECTOR AT CRITICAL 3408 02:28:44,840 --> 02:28:47,000 CARE PHYSICIAN MEDICINE 3409 02:28:47,000 --> 02:28:48,200 REHABILITATION PROGRAM AND THANK 3410 02:28:48,200 --> 02:28:52,920 YOU FOR BEING HERE DR. NEED HAM. 3411 02:28:52,920 --> 02:28:54,520 >> GREAT. YOU CAN HEAR ME AND 3412 02:28:54,520 --> 02:28:56,680 SEE MY SLIDES? CAN YOU HEAR ME? 3413 02:28:56,680 --> 02:28:59,040 >> YES, WE CAN, DALE. 3414 02:28:59,040 --> 02:29:02,200 >> GREAT. THANKS. 3415 02:29:02,200 --> 02:29:05,240 >> >> I WILL FOCUS ON IC-BASED 3416 02:29:05,240 --> 02:29:07,240 PHYSICAL REHABILITATION THAT IS 3417 02:29:07,240 --> 02:29:09,120 A KIND OF NICE CASE EXAMPLE FOR 3418 02:29:09,120 --> 02:29:11,280 -- THAT REALLY BUILDS ON LAST 3419 02:29:11,280 --> 02:29:12,680 COUPLE PRESENTATIONS AND IN 3420 02:29:12,680 --> 02:29:16,480 TERMS OF DISCLOSURES I'M 3421 02:29:16,480 --> 02:29:18,200 PRINCIPLE INVESTIGATOR ON 3422 02:29:18,200 --> 02:29:20,360 NIH-FUNDED RANDOMIZED TRIAL 3423 02:29:20,360 --> 02:29:24,040 NEARLY EARLY REHABILITATION AND 3424 02:29:24,040 --> 02:29:25,560 PROTEIN SUPPLEMENTATION APP AT 3425 02:29:25,560 --> 02:29:28,480 ICU AND WE HAVE SUPPORT FROM REC 3426 02:29:28,480 --> 02:29:31,240 MEDICAL DEVICES IN BAXTER THAT 3427 02:29:31,240 --> 02:29:33,040 WON'T INFLUENCE THE GIST OF 3428 02:29:33,040 --> 02:29:34,920 TODAY'S PRESENTATION AND KNOW IN 3429 02:29:34,920 --> 02:29:36,440 TERMS OF SPECIFIC INTERVENTION 3430 02:29:36,440 --> 02:29:38,480 THERE IS A REALLY GROWING BODY 3431 02:29:38,480 --> 02:29:41,720 OF DATA ON ICU-BASED REHAB 3432 02:29:41,720 --> 02:29:43,720 INTERVENTIONS AND IS MORE THAN 3433 02:29:43,720 --> 02:29:45,720 150 STUDIES INCLUDING MORE THAN 3434 02:29:45,720 --> 02:29:47,840 50 RANDOMIZED TRIALS WITH 3435 02:29:47,840 --> 02:29:50,320 PATIENTS WITH ACUTE RESPIRATORY 3436 02:29:50,320 --> 02:29:52,200 FAILURE REQUIRING MECHANICAL 3437 02:29:52,200 --> 02:29:54,160 INTERVENTION IN ICU AND SIGNALS 3438 02:29:54,160 --> 02:29:57,160 OF BENEFIT IN TERMS OF MUSCLE 3439 02:29:57,160 --> 02:30:00,200 AND PHYSICAL FUNCTION AND DELL 3440 02:30:00,200 --> 02:30:01,080 EARIUM AND COGNITION AND 3441 02:30:01,080 --> 02:30:03,000 CONDITIONAL RECOMMENDATIONS SUCH 3442 02:30:03,000 --> 02:30:06,600 AS SCCM PADDIS GUIDELINES THAT 3443 02:30:06,600 --> 02:30:08,760 SUPPORT THIS AND MORE AND MORE 3444 02:30:08,760 --> 02:30:10,840 STUDIES PUBLISHED WE ARE SEEING 3445 02:30:10,840 --> 02:30:11,960 CONFLICTING RESULTS. 3446 02:30:11,960 --> 02:30:15,240 THERE IS HETEROGENEITY AMONG 3447 02:30:15,240 --> 02:30:17,880 RESULTS AND RISK OF BIAS. IT IS 3448 02:30:17,880 --> 02:30:19,600 USEFUL TO DIG IN A LITTLE BIT 3449 02:30:19,600 --> 02:30:21,640 THINKING ABOUT THIS AS CANDIDATE 3450 02:30:21,640 --> 02:30:23,160 INTERVENTION AND WHAT ARE 3451 02:30:23,160 --> 02:30:24,040 CHALLENGES, GAPS AND 3452 02:30:24,040 --> 02:30:25,480 OPPORTUNITIES WE NEED TO THINK 3453 02:30:25,480 --> 02:30:25,720 ABOUT. 3454 02:30:25,720 --> 02:30:28,520 I WANT TO PRESENT TWO OR THREE 3455 02:30:28,520 --> 02:30:30,680 SYSTEMATIC REVIEWS BEFORE I DIVE 3456 02:30:30,680 --> 02:30:32,280 INTO GAPS AND OPPORTUNITIES AND 3457 02:30:32,280 --> 02:30:34,240 WHAT IS IMPORTANT IS THIS 3458 02:30:34,240 --> 02:30:36,400 SYSTEMATIC REVIEW OVER 20 YEARS 3459 02:30:36,400 --> 02:30:38,640 SUMMARIZED 43 RANDOMIZE TRIALEDS 3460 02:30:38,640 --> 02:30:43,160 AND 20 OF THEM LOOKED AT 3461 02:30:43,160 --> 02:30:44,440 PROTOCOLIZED APPROACHES TO PT 3462 02:30:44,440 --> 02:30:47,680 INTERVENTIONS AND 14 LOOKED AT 3463 02:30:47,680 --> 02:30:48,680 NEUROMUSCULAR ELECTRICAL 3464 02:30:48,680 --> 02:30:50,120 STIMULATION TALKED ABOUT IN 3465 02:30:50,120 --> 02:30:52,960 EARLIER TALKS IN THE CHAT AND 9 3466 02:30:52,960 --> 02:30:54,800 IN CYCLAR GOM ETTRY AND ALMOST 3467 02:30:54,800 --> 02:30:57,400 ALL STUDIES ARE RELATIVELY SMALL 3468 02:30:57,400 --> 02:30:59,760 AND 86% OF THEM DID NOT REPORT 3469 02:30:59,760 --> 02:31:04,600 THE DOSE THAT IS DELIVERED THAT 3470 02:31:04,600 --> 02:31:07,600 BROADHAM CONELLY PUT IN THE 3471 02:31:07,600 --> 02:31:07,800 CHAT. 3472 02:31:07,800 --> 02:31:11,360 WE SEE DECREASED UTILIZATION AND 3473 02:31:11,360 --> 02:31:13,400 COMING TO FUNCTIONAL OUTCOMES 3474 02:31:13,400 --> 02:31:15,240 COULDN'T EVALUATE STRENGTH AND 3475 02:31:15,240 --> 02:31:17,040 FUNCTION IN SYSTEMATIC REVIEW 3476 02:31:17,040 --> 02:31:20,520 AND LOTS OF HETEROGENEITY FOR 3477 02:31:20,520 --> 02:31:22,640 POST DISCHARGE OUTCOMES AND 3478 02:31:22,640 --> 02:31:25,320 LIMITATIONS LOOKING AT SUBGROUP 3479 02:31:25,320 --> 02:31:26,360 ANALYSIS THERE ARE DIFFERENCES 3480 02:31:26,360 --> 02:31:28,480 AMONG TYPES OF REHAB 3481 02:31:28,480 --> 02:31:29,880 INTERVENTIONS DELIVERED WITH 3482 02:31:29,880 --> 02:31:32,960 GREATER BENEFIT IN THOSE 3483 02:31:32,960 --> 02:31:36,160 PROTOCOLIZED PHYSIOTHERAPIST 3484 02:31:36,160 --> 02:31:39,480 BASED INTERVENTIONS AND 3485 02:31:39,480 --> 02:31:40,680 HETEROGENEITY AMONG PATIENT 3486 02:31:40,680 --> 02:31:41,560 CHARACTERISTICS AS WELL THAT 3487 02:31:41,560 --> 02:31:43,640 WILL ADDRESS HOW WE INTERPRET 3488 02:31:43,640 --> 02:31:45,440 AND THINK ABOUT THESE TRIALS AND 3489 02:31:45,440 --> 02:31:47,640 A SECOND SYSTEMATIC REVIEW WITH 3490 02:31:47,640 --> 02:31:49,680 60 TRIALS MORE THAN 5 THOUSAND 3491 02:31:49,680 --> 02:31:50,680 INUM NUMB PATIENTS THAT I WOULD 3492 02:31:50,680 --> 02:31:53,120 LIKE THIS ONE AND THEY DID A 3493 02:31:53,120 --> 02:31:54,680 SUBGROUP ANALYSIS BASED ON 3494 02:31:54,680 --> 02:31:57,000 CONTROL GROUPS. 3495 02:31:57,000 --> 02:31:58,480 HERE THEY LOOKED AT -- THEY DID 3496 02:31:58,480 --> 02:32:01,840 A METAANALYSIS WHERE CONTROL 3497 02:32:01,840 --> 02:32:05,160 GROUPS HAD LOWER DOSES OF IC 3498 02:32:05,160 --> 02:32:06,520 REHAB INTERVENTIONS THEY DEFINE 3499 02:32:06,520 --> 02:32:09,600 AS LESS THAN 5 TIMES A WEEK FOR 3500 02:32:09,600 --> 02:32:10,560 ASSESSMENTS AND MY EXPERIENCE IN 3501 02:32:10,560 --> 02:32:13,120 THE US IS THAT IS A VERY HIGH 3502 02:32:13,120 --> 02:32:15,320 DOSE INTERVENTION. THAT IS TO 3503 02:32:15,320 --> 02:32:17,200 FIND LOW DOSE FOR THIS. 3504 02:32:17,200 --> 02:32:19,040 TAKE THAT INTO CAN THE WHEN YOU 3505 02:32:19,040 --> 02:32:21,240 SEE FINDINGS. 3506 02:32:21,240 --> 02:32:24,640 MORE THAN 50% OF TRIALS HAVE 3507 02:32:24,640 --> 02:32:26,880 HIGH RISK OF BIAS COMPARED TO 3508 02:32:26,880 --> 02:32:29,480 LOW DOSE CONTROL GROUP AND 3509 02:32:29,480 --> 02:32:31,840 CONSISTENT SIGNALS OF BENEFIT OF 3510 02:32:31,840 --> 02:32:35,600 DECREASE IN RESOURCE UTILIZATION 3511 02:32:35,600 --> 02:32:38,520 MEASURES AND SMALL EFFECT AND NO 3512 02:32:38,520 --> 02:32:40,760 EFFECT FOR MUSCLE STRENGTH 3513 02:32:40,760 --> 02:32:43,560 ACROSS THIS AND HETEROGENEITY 3514 02:32:43,560 --> 02:32:45,720 DEPENDING ON RESULTS WITH TYPES 3515 02:32:45,720 --> 02:32:49,800 OF INTERVENTION AND 3516 02:32:49,800 --> 02:32:52,360 HETEROGENEITY AND OUTCOMES 3517 02:32:52,360 --> 02:32:54,440 REPORTING LED TO IMITATIONS IN 3518 02:32:54,440 --> 02:32:55,840 METAANALYSIS AND WHY WE ARE 3519 02:32:55,840 --> 02:32:59,880 HAVING SO-CALLED CONFLICTING 3520 02:32:59,880 --> 02:33:09,360 RESULTS -- FOR PREVENTING OR 3521 02:33:09,360 --> 02:33:14,320 TREATING DELL EARIUM AND PRIMARY 3522 02:33:14,320 --> 02:33:16,760 OUTCOME IS -- SYSTEMATIC REVIEW 3523 02:33:16,760 --> 02:33:20,520 FOR ICU REHAB INTERVENTIONS TO 3524 02:33:20,520 --> 02:33:23,080 PREVENT DELL EARIUM AND 300 3525 02:33:23,080 --> 02:33:24,720 STUDIES AND PATIENTS FOR 3526 02:33:24,720 --> 02:33:26,200 TREATMENT AND EVIDENCE THAT 3527 02:33:26,200 --> 02:33:29,600 EARLY MOBILIZATION REDUCED ODDS 3528 02:33:29,600 --> 02:33:33,320 OF INCIDENT DLEERIUM BY 50% 3529 02:33:33,320 --> 02:33:35,640 REDUCING DURATION OF DELL EARIUM 3530 02:33:35,640 --> 02:33:37,600 OF TREATMENT INTERVENTION BY TWO 3531 02:33:37,600 --> 02:33:39,120 DAYS AND WAS DIFFICULTIES 3532 02:33:39,120 --> 02:33:41,160 BECAUSE STUDIES DID NOT -- THERE 3533 02:33:41,160 --> 02:33:43,240 ARE MANY MORE STUDIES THAT 3534 02:33:43,240 --> 02:33:44,760 DIDN'T REPORT DATE NAH A 3535 02:33:44,760 --> 02:33:46,400 STANDARDIZED WAY TO BE 3536 02:33:46,400 --> 02:33:48,120 SYNTHESIZED IN METAANALYSIS AND 3537 02:33:48,120 --> 02:33:51,600 WERE ISSUES WITH RISK OF BIAS 3538 02:33:51,600 --> 02:33:52,920 AND HETEROGENEITY AND IS SIGNAL 3539 02:33:52,920 --> 02:33:54,280 THAT INTERVENTIONS THAT ARE 3540 02:33:54,280 --> 02:33:57,040 FOCUSED ON BODIES ALSO DO 3541 02:33:57,040 --> 02:33:59,880 IMPROVE COGNITION AS I ALWAYS 3542 02:33:59,880 --> 02:34:01,760 SAY HEAD BONE IS CONNECTED TO 3543 02:34:01,760 --> 02:34:03,640 BODY BONE AND RESEARCH DOES 3544 02:34:03,640 --> 02:34:05,560 REALLY NEED TO LOOK AT BOTH OF 3545 02:34:05,560 --> 02:34:08,760 THESE TOGETHER AND OT AND PT 3546 02:34:08,760 --> 02:34:10,520 COLLEAGUES IN ADDITION TO NURSES 3547 02:34:10,520 --> 02:34:14,600 NEED TO DO STANDARDIZED DLEERIUM 3548 02:34:14,600 --> 02:34:16,640 WITH INTERVENTIONS AND ROUTINE 3549 02:34:16,640 --> 02:34:21,000 CARE IN ICU AND FOCUSING ON 3550 02:34:21,000 --> 02:34:22,280 CHALLENGES AND GAPS AND 3551 02:34:22,280 --> 02:34:23,880 OPPORTUNITIES AND USING THIS 3552 02:34:23,880 --> 02:34:27,760 HERE AND PATIENT CHALLENGES 3553 02:34:27,760 --> 02:34:30,600 MOVING FIELD FORWARD AND DEFINE 3554 02:34:30,600 --> 02:34:33,080 WHOG TARGET POPULATION IS SICK 3555 02:34:33,080 --> 02:34:35,560 ENOUGH FOR MUSCLE BRAIN 3556 02:34:35,560 --> 02:34:37,000 IMPAIRMENTS AND LONG ENOUGH STAY 3557 02:34:37,000 --> 02:34:40,640 IN ICU IF ICU-BASED INTERVENTION 3558 02:34:40,640 --> 02:34:43,040 AND HEALTHY ENOUGH TO SURVIVE 3559 02:34:43,040 --> 02:34:44,200 HOSPITAL STAY TO SAFELY 3560 02:34:44,200 --> 02:34:45,880 PARTICIPATE IN INTERVENTIONS 3561 02:34:45,880 --> 02:34:48,240 THAT OFTEN REQUIRE ACTIVE 3562 02:34:48,240 --> 02:34:50,000 PATIENT PARTICIPATION AND THEY 3563 02:34:50,000 --> 02:34:52,000 HAVE PHYSIOLOGIC EFFECTS ON 3564 02:34:52,000 --> 02:34:53,800 PATIENTS WANTING THEM TO IDEALLY 3565 02:34:53,800 --> 02:34:55,880 BE ACTIVELY PARTICIPATING RATHER 3566 02:34:55,880 --> 02:34:57,920 THAN A PASSIVE INTERVENTION THAT 3567 02:34:57,920 --> 02:35:00,000 CALLS OUT TO NEUROINJURY AND USE 3568 02:35:00,000 --> 02:35:01,840 OF SEDATION AND HAVE MANY, MANY 3569 02:35:01,840 --> 02:35:03,600 SMALL STUDIES BUT WILL NEED 3570 02:35:03,600 --> 02:35:05,640 LARGER STUDIES AND I TALKED 3571 02:35:05,640 --> 02:35:08,320 ABOUT WE NEED TO MINIMIZE LOSS 3572 02:35:08,320 --> 02:35:10,320 TO FOLLOW UP AND THINK ABOUT 3573 02:35:10,320 --> 02:35:12,360 DEATH AND TRADITIONAL LOSS TO 3574 02:35:12,360 --> 02:35:13,880 FOLLOW UP AND RECOGNIZING THAT 3575 02:35:13,880 --> 02:35:17,200 PATIENTS MOVING TO A LONG-TERM 3576 02:35:17,200 --> 02:35:18,520 ACUTE CARE HOSPITAL MAY NO THE 3577 02:35:18,520 --> 02:35:20,880 BE ABLE TO HAVE PERFORMANCE 3578 02:35:20,880 --> 02:35:22,720 BASED ASSESSMENTS PERFORMED AND 3579 02:35:22,720 --> 02:35:24,480 NEED PEOPLE WHO SURVIVE AND 3580 02:35:24,480 --> 02:35:25,960 RECOVER AND WHAT ABOUT 3581 02:35:25,960 --> 02:35:26,840 INTERVENTION? 3582 02:35:26,840 --> 02:35:28,160 THIS IS VERY COMPLEX. 3583 02:35:28,160 --> 02:35:30,680 WHEN DO WE START REHAPPEN 3584 02:35:30,680 --> 02:35:31,080 INTERVENTION? 3585 02:35:31,080 --> 02:35:33,040 THERE IS ENOUGH DATA TELLING US 3586 02:35:33,040 --> 02:35:35,600 EARLIER IS BETTER AND DOSE 3587 02:35:35,600 --> 02:35:37,440 COMING TO REHAB IS COMPLICATED 3588 02:35:37,440 --> 02:35:39,240 AND WE HAVE TO THINK ABOUT 3589 02:35:39,240 --> 02:35:41,760 DURATION AND FREQUENCY AND 3590 02:35:41,760 --> 02:35:42,040 INTENSITY. 3591 02:35:42,040 --> 02:35:45,040 IN FACT, STEPHANIE AT JOHNS 3592 02:35:45,040 --> 02:35:47,360 HOPKINS JUST COMPLETED HER PHD 3593 02:35:47,360 --> 02:35:48,600 SPECIFICALLY FOCUSED ON QUESTION 3594 02:35:48,600 --> 02:35:52,160 OF INTENSITY ALONE FOR ICU REHAB 3595 02:35:52,160 --> 02:35:54,120 AND NEED TO THINK ABOUT 3596 02:35:54,120 --> 02:35:55,400 COORDINATION OF COMPLEX 3597 02:35:55,400 --> 02:35:57,120 INTERVENTION WITHIN ENTIRE 3598 02:35:57,120 --> 02:35:58,320 SYSTEM WHAT IS HAPPENING FOR 3599 02:35:58,320 --> 02:36:00,160 PATIENT CARE THAT IS VERY 3600 02:36:00,160 --> 02:36:02,360 COMPLICATED AND NEED TO THINK 3601 02:36:02,360 --> 02:36:03,360 ABOUT HOW LONG IT SHOULD 3602 02:36:03,360 --> 02:36:06,080 CONTINUE IN ICU ON HOSPITAL 3603 02:36:06,080 --> 02:36:07,280 FLOOR AFTER HOSPITAL DISCHARGE 3604 02:36:07,280 --> 02:36:09,080 AND NEED TO THINK ABOUT TYPES OF 3605 02:36:09,080 --> 02:36:10,480 INTERVENTION AND WHO WILL BE 3606 02:36:10,480 --> 02:36:12,160 PERFORMING IT. THERE IS MANY 3607 02:36:12,160 --> 02:36:14,040 DIFFERENT PEOPLE AND WE HAVE TO 3608 02:36:14,040 --> 02:36:16,400 REMIND OURSELVES THAT WORD 3609 02:36:16,400 --> 02:36:17,040 PHYSIOTHERAPY OR PHYSICAL 3610 02:36:17,040 --> 02:36:19,360 THERAPY IS THE NAME OF A 3611 02:36:19,360 --> 02:36:19,680 PROFESSION. 3612 02:36:19,680 --> 02:36:22,200 IT IS NOT THE NAME OF AN 3613 02:36:22,200 --> 02:36:23,800 INTERVENTION AND WE SHOULD 3614 02:36:23,800 --> 02:36:26,400 PLEASE STOP SAYING THAT PATIENT 3615 02:36:26,400 --> 02:36:28,840 NEEDS TO GET PHYSICAL THERAPY OR 3616 02:36:28,840 --> 02:36:34,360 PATIENT NEEDS TO GE MEDICINE OND 3617 02:36:34,360 --> 02:36:36,720 DOKTORRING DONE TO THEM AND ICU 3618 02:36:36,720 --> 02:36:38,640 REHAB INTERVENTIONS COMPLETELY 3619 02:36:38,640 --> 02:36:40,960 DIFFERENT AND TILT TABLE ALLOWS 3620 02:36:40,960 --> 02:36:43,200 GRADUATED WEIGHT BEARING AND 3621 02:36:43,200 --> 02:36:44,200 NEUROMUSCULAR ELECTRICAL 3622 02:36:44,200 --> 02:36:45,360 STIMULATION TALKED ABOUT A LOT 3623 02:36:45,360 --> 02:36:48,640 IN THE CHAT FOR THE EARLIER 3624 02:36:48,640 --> 02:36:51,360 SESSION AND IN-BED PSYCH LAR GOM 3625 02:36:51,360 --> 02:36:53,280 ETTRY THAT COULD BE PASSIVE OR 3626 02:36:53,280 --> 02:36:55,600 ACTIVE AND COMBINATION OF 3627 02:36:55,600 --> 02:36:57,480 ELECTRICAL STIMULATION WITH 3628 02:36:57,480 --> 02:36:59,480 INBED PSYCH LAR GOM ETTRY 3629 02:36:59,480 --> 02:37:01,240 FUNCTIONAL ELECTROSTIMULATION 3630 02:37:01,240 --> 02:37:02,880 AND WHAT MANY THINK ABOUT SAYING 3631 02:37:02,880 --> 02:37:04,560 P. T THAT IS FUNCTIONAL 3632 02:37:04,560 --> 02:37:08,280 MOBILITY WHERE PT IS BEHIND A 3633 02:37:08,280 --> 02:37:09,960 RESPIRATORY THERAPIST OUT FRONT 3634 02:37:09,960 --> 02:37:12,160 AND INTERACTIVE VIDEO GAMES 3635 02:37:12,160 --> 02:37:14,480 COINED AS WE HAVE. HYDROTHERAPY 3636 02:37:14,480 --> 02:37:16,560 AND MY HOSPITAL DOESN'T HAVE A 3637 02:37:16,560 --> 02:37:20,040 SWIMMING POOL. THIS IS IN THE 3638 02:37:20,040 --> 02:37:23,040 NENLERLANDS PATIENT ON 3639 02:37:23,040 --> 02:37:26,680 VENTILATOR ENDO TRACHIAL TUBE IN 3640 02:37:26,680 --> 02:37:29,920 POOL WITH PT AND THIS IS AN 3641 02:37:29,920 --> 02:37:31,200 OCCUPATIONAL THERAPIST WITH 3642 02:37:31,200 --> 02:37:32,960 COGNITIVE REHAB AND COLLEAGUE IN 3643 02:37:32,960 --> 02:37:34,400 JAPAN SHARING THIS PHOTOGRAPH 3644 02:37:34,400 --> 02:37:36,040 AND WE NEED TO REMIND OURSELVES 3645 02:37:36,040 --> 02:37:38,400 IT THIS IS A REALLY IMPORTANT 3646 02:37:38,400 --> 02:37:39,960 SLIDE AND FOR MOST 3647 02:37:39,960 --> 02:37:41,160 PHARMACEUTICALS WE KNOW EVERY 3648 02:37:41,160 --> 02:37:43,280 ROW IN THIS TABLE AND WHEN IT 3649 02:37:43,280 --> 02:37:46,600 COMES TO ICU REHAB ACTIVE 3650 02:37:46,600 --> 02:37:47,840 INGREEDIENT AND MECHANISM OF 3651 02:37:47,840 --> 02:37:50,320 ACTION AND PATHWAY OF ACTIVE 3652 02:37:50,320 --> 02:37:53,040 INGREEDIENT AND HALF LIFE HOW IT 3653 02:37:53,040 --> 02:37:54,440 INTERACTS WITH CO-INTERVENTIONS 3654 02:37:54,440 --> 02:37:56,520 AND MOST OF THOSE ARE NOT KNOWN 3655 02:37:56,520 --> 02:37:58,080 CONTINUING TO DO RANDOMIZED 3656 02:37:58,080 --> 02:37:59,120 TRIALS IN THE AREA. 3657 02:37:59,120 --> 02:38:01,280 WHAT ABOUT THE C AND COMPARISON 3658 02:38:01,280 --> 02:38:01,720 GROUP? 3659 02:38:01,720 --> 02:38:04,360 MANY TRIALS HAVE USED USUAL CARE 3660 02:38:04,360 --> 02:38:07,000 CONTROL GROUPS AND WE NEED TO 3661 02:38:07,000 --> 02:38:08,600 RECOGNIZE ARE THESE CONTROL 3662 02:38:08,600 --> 02:38:10,960 GROUPS TRULY REPRESENTATIVE? 3663 02:38:10,960 --> 02:38:14,840 MOST OF THE INTERVENTIONS ARE 3664 02:38:14,840 --> 02:38:17,240 COMPLEX TO DELIVER AND STUDY 3665 02:38:17,240 --> 02:38:18,560 SITES THAT PARTICIPATE HAVE AS 3666 02:38:18,560 --> 02:38:20,720 PART OF USUAL CARE RELATIVELY 3667 02:38:20,720 --> 02:38:23,120 ADVANCED ICU OR REHAB AND 3668 02:38:23,120 --> 02:38:24,480 REPRESENTATION OF THE CONTROL 3669 02:38:24,480 --> 02:38:25,800 GROUPS IN THOSE HOSPITALS MAY 3670 02:38:25,800 --> 02:38:27,720 NOT BE POSSIBLE. IF WE GO TO 3671 02:38:27,720 --> 02:38:31,680 OTHER HOSPITALS WHERE PTS HARDLY 3672 02:38:31,680 --> 02:38:33,800 EVEN ENTER ICU MIGHT NOT BE 3673 02:38:33,800 --> 02:38:35,120 POSSIBLE TO DELIVER INTERVENTION 3674 02:38:35,120 --> 02:38:36,960 AND NEED TO RECOGNIZE THAT USUAL 3675 02:38:36,960 --> 02:38:38,720 CARE CHANGES OVER TIME FROM 3676 02:38:38,720 --> 02:38:41,840 PLANNING OF RCT UNTIL ITS 3677 02:38:41,840 --> 02:38:45,160 COMPLETION AND BIG HETEROGENEITY 3678 02:38:45,160 --> 02:38:47,600 ACROSS STUDY SITES AND 3679 02:38:47,600 --> 02:38:48,360 CO-INTERVENTIONS ARE IMPORTANT 3680 02:38:48,360 --> 02:38:49,960 AND HEAD BONE IS CONNECTED TO 3681 02:38:49,960 --> 02:38:53,160 BODY BONE AND PROVIDING SEDATION 3682 02:38:53,160 --> 02:38:58,360 TO PATIENTS DELL EARYING STATUS 3683 02:38:58,360 --> 02:39:00,560 AND INTERVENTIONAL -- THESE ARE 3684 02:39:00,560 --> 02:39:01,920 IMPORTANT AND MAY EFFECT 3685 02:39:01,920 --> 02:39:03,400 EFFICACY OF INTERVENTION AND 3686 02:39:03,400 --> 02:39:05,840 FEASIBILITY YOU CAN'T DO ACTIVE 3687 02:39:05,840 --> 02:39:07,080 FUNCTIONAL MOBILITY INTERVENTION 3688 02:39:07,080 --> 02:39:09,960 IN SOMEONE WHO IS DEEPLY SEDATED 3689 02:39:09,960 --> 02:39:11,880 THAT WILL EFFECT FIDELITY TO THE 3690 02:39:11,880 --> 02:39:13,760 RESEARCH PROTOCOL AND IN TERMS 3691 02:39:13,760 --> 02:39:16,240 OF CORE OUTCOMES AND OUTCOME 3692 02:39:16,240 --> 02:39:18,880 CHALLENGES CORE OUTCOME SETS ARE 3693 02:39:18,880 --> 02:39:22,160 REALLY IMPORTANT TO REDUCE 3694 02:39:22,160 --> 02:39:24,200 HETEROGENEITY AND SPEAKER WILL 3695 02:39:24,200 --> 02:39:26,000 FINISH OFF CORE OUTCOME SET 3696 02:39:26,000 --> 02:39:28,200 SPECIFIC FOR ICU OR REHAB AND 3697 02:39:28,200 --> 02:39:31,960 TEXTED IN CHAT MANY TIMES ABOUT 3698 02:39:31,960 --> 02:39:34,280 NHLBI FUNDED EXISTING CORE 3699 02:39:34,280 --> 02:39:36,640 OUTCOME SET FOR ACCUSE 3700 02:39:36,640 --> 02:39:40,600 RESPIRATORY FAILURE AND RDS AND 3701 02:39:40,600 --> 02:39:43,000 PUBLISHED CORE OUTCOME SET AND 3702 02:39:43,000 --> 02:39:44,720 MEASUREMENT SET FOR DELL OOERIUM 3703 02:39:44,720 --> 02:39:47,320 IN THE ICU. THESE ARE AVAILABLE 3704 02:39:47,320 --> 02:39:48,920 AND WE NEED TO USE THEM. 3705 02:39:48,920 --> 02:39:51,520 >> FIVE MINUTES REMAINING. 3706 02:39:51,520 --> 02:39:53,840 >> FOCUS ON STRENGTH AND 3707 02:39:53,840 --> 02:39:55,680 FUNCTION AND INFORMATION ON 3708 02:39:55,680 --> 02:39:56,840 SYSTEMATIC REVIEWS AND LENGTH OF 3709 02:39:56,840 --> 02:39:58,760 STAY IN MORTALITY ARE NOT SAME 3710 02:39:58,760 --> 02:40:00,000 THINGS AND NEED TO RECOGNIZE 3711 02:40:00,000 --> 02:40:03,600 THAT PERFORMANCE-BASED MEASURES 3712 02:40:03,600 --> 02:40:04,880 6-MINUTE WALK TEST HAVE VERY 3713 02:40:04,880 --> 02:40:06,480 DIFFERENT OUTCOME MEASUREMENT 3714 02:40:06,480 --> 02:40:08,560 THAT PATIENT REPORTED OUTCOME OF 3715 02:40:08,560 --> 02:40:09,680 PHYSICAL FUNCTION ARE NOT 3716 02:40:09,680 --> 02:40:12,280 MEASURING SAME THINGS THAT ARE 3717 02:40:12,280 --> 02:40:13,880 COMPLEMENTARY NOT REDUNDANT AND 3718 02:40:13,880 --> 02:40:15,840 HOW DO WE BUILD BOTH IN? 3719 02:40:15,840 --> 02:40:17,720 WE NEED TO RECOGNIZE REQUIRED 3720 02:40:17,720 --> 02:40:21,520 EXPERTISE IN THE FEASIBILITY AND 3721 02:40:21,520 --> 02:40:22,160 COST. 3722 02:40:22,160 --> 02:40:24,040 MOST RESEARCH TEAMS AND ICS 3723 02:40:24,040 --> 02:40:26,440 DON'T KNOW HOW TO PERFORM MUSCLE 3724 02:40:26,440 --> 02:40:29,560 STRENGTH TESTING IN MECHANICALLY 3725 02:40:29,560 --> 02:40:31,240 VENTILATED PATIENT AND REQUIRE 3726 02:40:31,240 --> 02:40:34,000 EXPERTISE FOR PERFORMANCE-BASED 3727 02:40:34,000 --> 02:40:34,760 ASSESSMENTS AND RECOGNIZE ABOUT 3728 02:40:34,760 --> 02:40:36,280 TIMING AND LOCATION OF 3729 02:40:36,280 --> 02:40:37,640 ASSESSMENTS ESPECIALLY IF PEOPLE 3730 02:40:37,640 --> 02:40:40,680 ARE DISCHARGED TO LONG TERM 3731 02:40:40,680 --> 02:40:42,160 ACUTE CARE HOSPITALS AND NEED TO 3732 02:40:42,160 --> 02:40:43,840 RECOGNIZE THAT OUTCOMES NEED TO 3733 02:40:43,840 --> 02:40:46,560 BE PATIENT CENTERED AND NEED TO 3734 02:40:46,560 --> 02:40:50,040 HAVE PSYCHOMETRICS AND KNOW 3735 02:40:50,040 --> 02:40:51,400 MINIMUM IMPORTANT DIFFERENCES 3736 02:40:51,400 --> 02:40:54,400 AND LOTS OF GAPS SYSTEMATIC 3737 02:40:54,400 --> 02:40:55,800 REVIEWS TOLD US AND COUPLE 3738 02:40:55,800 --> 02:40:57,440 SLIDES LEFT TO TELL US WHAT GAPS 3739 02:40:57,440 --> 02:40:59,360 ARE AND TALKED A LOT ABOUT 3740 02:40:59,360 --> 02:41:01,560 EARLIER SESSIONS IN MECHANISMS 3741 02:41:01,560 --> 02:41:03,560 AND NEED LOTS OF MECHANISTIC 3742 02:41:03,560 --> 02:41:05,600 DATA HERE REQUIRING TEAM 3743 02:41:05,600 --> 02:41:07,640 COLLABORATION AND WE NEED SERIAL 3744 02:41:07,640 --> 02:41:10,520 MEASUREMENTS AND THOSE OF 3745 02:41:10,520 --> 02:41:12,760 PROTEIN METABOLISM AND 3746 02:41:12,760 --> 02:41:13,760 INFLAMMATION AND BODY 3747 02:41:13,760 --> 02:41:16,040 COMPOSITION AND ELECTRO 3748 02:41:16,040 --> 02:41:16,880 PHYSIOLOGY WE HAVEN'T TALKED 3749 02:41:16,880 --> 02:41:18,040 ABOUT VERY MUCH THAT IS HARD TO 3750 02:41:18,040 --> 02:41:20,040 DO ALL THOSE IN THE SAME STUDY 3751 02:41:20,040 --> 02:41:22,400 IN TERMS OF FEASIBILITY AND 3752 02:41:22,400 --> 02:41:25,640 RESOURCES AND EXPERTISE AND NEED 3753 02:41:25,640 --> 02:41:27,760 CONSENSUS AROUND WHAT CONTROL 3754 02:41:27,760 --> 02:41:29,360 GROUPS IN FUTURE TRIALS SHOULD 3755 02:41:29,360 --> 02:41:31,920 BE AND I HAVE A HALF DAY FREE OF 3756 02:41:31,920 --> 02:41:33,120 CHARGE MEETING THIS SATURDAY 3757 02:41:33,120 --> 02:41:36,840 WHERE THIS AIS ONE MENL LOGIC 3758 02:41:36,840 --> 02:41:39,640 ISSUES WE WILL ADDRESS AND CAROL 3759 02:41:39,640 --> 02:41:43,040 AND MICHELLE TWO FANTASTIC PT 3760 02:41:43,040 --> 02:41:45,040 COLLABORATORS AND THINK ABOUT 3761 02:41:45,040 --> 02:41:46,520 ISSUES OF REHAB DESIGN 3762 02:41:46,520 --> 02:41:48,520 DELIVERING OUTCOME MEASUREMENTS. 3763 02:41:48,520 --> 02:41:50,280 HAS TO BE MULTI-DISCIPLINARY AND 3764 02:41:50,280 --> 02:41:52,280 NEED EVERYBODY TO GET ENGAGED 3765 02:41:52,280 --> 02:41:54,160 AND REHAB PEOPLE TO UNDERSTAND 3766 02:41:54,160 --> 02:41:56,680 ICU AND ICU PEOPLE TO UNDERSTAND 3767 02:41:56,680 --> 02:41:58,680 REHAB. THAT IS WHY WE HAVE HAD 3768 02:41:58,680 --> 02:42:01,920 FOR 12 YEARS JOHNS HOPKINS 3769 02:42:01,920 --> 02:42:03,240 CRITICAL CARE REHAB CONFERENCE 3770 02:42:03,240 --> 02:42:08,360 AND OTS AND PTS TO BE MEASURING 3771 02:42:08,360 --> 02:42:10,280 DLEERIUM PART OF STANDARD CARE 3772 02:42:10,280 --> 02:42:12,000 AND RESEARCH AND COGNITIVE 3773 02:42:12,000 --> 02:42:14,040 SCREENING IN ALL FUTURE TRIALS 3774 02:42:14,040 --> 02:42:16,000 AND PATIENTS MAYBE STOP 3775 02:42:16,000 --> 02:42:17,680 EXCLUDING PATIENTS WITH IMPAIRED 3776 02:42:17,680 --> 02:42:19,320 BASELINE FUNCTION THAT IS REALLY 3777 02:42:19,320 --> 02:42:21,880 MOST PATIENTS COMING TO ICU AND 3778 02:42:21,880 --> 02:42:23,680 WE MIGHT NEED TO BE STRATIFYING 3779 02:42:23,680 --> 02:42:25,120 AND COMING TO INTERVENTIONS I 3780 02:42:25,120 --> 02:42:27,080 HAVE EXPLAINED HOW THERE IS SO 3781 02:42:27,080 --> 02:42:29,120 MANY TYPES OF INTERVENTIONS AND 3782 02:42:29,120 --> 02:42:30,320 SO MANY DIFFERENT PEOPLE WHO CAN 3783 02:42:30,320 --> 02:42:32,440 PROVIDE IT AND ISSUES AROUND 3784 02:42:32,440 --> 02:42:34,280 FREQUENCY AND INTENSITY AND 3785 02:42:34,280 --> 02:42:35,560 DURATION ALL NEED TO BE 3786 02:42:35,560 --> 02:42:36,680 CONSIDERED AND WE NEED TO 3787 02:42:36,680 --> 02:42:38,120 COMPARE THESE THINGS HEAD TO 3788 02:42:38,120 --> 02:42:39,920 HEAD AND NO WAY WE WILL FIGURE 3789 02:42:39,920 --> 02:42:42,560 THIS OUT WITHOUT HAVING DIRECT 3790 02:42:42,560 --> 02:42:44,160 COMPARISONS AS WELL AS 3791 02:42:44,160 --> 02:42:45,240 CO-INTERVENTIONS THAT WE TRIED 3792 02:42:45,240 --> 02:42:49,880 TO TACKLE THROUGH NHLBI FUNDED 3793 02:42:49,880 --> 02:42:51,640 NEXUS TRIAL OF PROTEIN 3794 02:42:51,640 --> 02:42:52,440 SUPPLEMENTATION WITH EXTRA 3795 02:42:52,440 --> 02:42:54,080 EXERCISE AND THINKING ABOUT 3796 02:42:54,080 --> 02:42:55,480 BUNDLED INTERVENTIONS AND CAN'T 3797 02:42:55,480 --> 02:42:57,560 DO ACTIVE INTERVENTIONS IF 3798 02:42:57,560 --> 02:42:59,160 PATIENTS ARE SEDATED THAT 3799 02:42:59,160 --> 02:43:01,440 REQUIRES BIG, BIG CULTURE CHANGE 3800 02:43:01,440 --> 02:43:03,440 THAT MAY REQUIRE CLUSTER 3801 02:43:03,440 --> 02:43:04,880 RANDOMIZED TRIALS AND STEP WEDGE 3802 02:43:04,880 --> 02:43:06,200 THAT WAS JUST TALKED ABOUT AND 3803 02:43:06,200 --> 02:43:08,400 NEED RESOURCES FOR COHORT 3804 02:43:08,400 --> 02:43:10,920 RETENTION AND CORE OUTCOME SETS 3805 02:43:10,920 --> 02:43:13,160 THAT WE ARE ALREADY ELUDING TO 3806 02:43:13,160 --> 02:43:17,720 IN MATT'S TALK. MY HIGH RISK 3807 02:43:17,720 --> 02:43:19,200 AND HIGH REWARD TIES IN NICELY 3808 02:43:19,200 --> 02:43:21,160 TO THE LAST COUPLE OF TALKS AND 3809 02:43:21,160 --> 02:43:23,760 COULD WE HAVE A BAYESIAN 3810 02:43:23,760 --> 02:43:25,200 ADAPTIVE PLATFORM TRIAL TO ALLOW 3811 02:43:25,200 --> 02:43:27,440 US TO THINK ABOUT ALL THESE 3812 02:43:27,440 --> 02:43:29,600 DIFFERENT TYPES OF INTERVENTIONS 3813 02:43:29,600 --> 02:43:31,000 AND THINK ABOUT THE DITCH WAYS 3814 02:43:31,000 --> 02:43:31,920 THAT WE DO DOSE. 3815 02:43:31,920 --> 02:43:33,880 I THINK THAT WE NEED TO PROCEED 3816 02:43:33,880 --> 02:43:37,080 IT WITH A STEP-LENLED RANDOMIZED 3817 02:43:37,080 --> 02:43:40,360 TRIAL TO GET ICUS UP TO SPEED 3818 02:43:40,360 --> 02:43:45,160 CHANGING CULTURE TO REDEUCE 3819 02:43:45,160 --> 02:43:46,880 SAIDDATION-REDUCED DELL EARIUM 3820 02:43:46,880 --> 02:43:50,040 AND PATIENT AS WAKE PERFORMING 3821 02:43:50,040 --> 02:43:51,560 REHAB INTERVENTIONS AND USING 3822 02:43:51,560 --> 02:43:52,840 MOST APPROACH TO LOOK AT 3823 02:43:52,840 --> 02:43:54,640 DIFFERENT WAYS OF LOOKING AT 3824 02:43:54,640 --> 02:43:56,080 MANY DIFFERENT INTERVENTIONS AND 3825 02:43:56,080 --> 02:43:57,640 I DON'T HAVE EXPERTISE AROUND 3826 02:43:57,640 --> 02:43:59,880 MOST OR PLATFORM TRIALS AND 3827 02:43:59,880 --> 02:44:02,080 [INDISCERNIBLE] IN THE ICU 3828 02:44:02,080 --> 02:44:03,600 TOGETHER WHEN WE DREAMT THIS UP 3829 02:44:03,600 --> 02:44:05,600 TOGETHER AND THERE ARE PEOPLE ON 3830 02:44:05,600 --> 02:44:07,280 THE ZOOM WHO HAVE EXACT 3831 02:44:07,280 --> 02:44:09,280 EXPERTISE IN TERMS OF CONTROL 3832 02:44:09,280 --> 02:44:10,800 GROUP THIS IS THE MEETING I WAS 3833 02:44:10,800 --> 02:44:13,720 TALKING ABOUT COMING TO ATS AND 3834 02:44:13,720 --> 02:44:16,120 INTERESTED IN CONTROL GROUPS AND 3835 02:44:16,120 --> 02:44:20,240 ICU REHAB AND COGNITION FREE OF 3836 02:44:20,240 --> 02:44:22,360 CHARGE A DAY AND UNDERSTANDING 3837 02:44:22,360 --> 02:44:23,960 REHAB AND REHAB PEOPLE TO 3838 02:44:23,960 --> 02:44:25,640 UNDERSTAND CRITICAL CARE IS 2 OR 3839 02:44:25,640 --> 02:44:28,120 3 OR 4 DAYS VIRTUAL CONFERENCE 3840 02:44:28,120 --> 02:44:30,240 WAND THAT I HAVE FINISHED ON 3841 02:44:30,240 --> 02:44:32,240 TIME. I'M HAPPY TO TAKE 3842 02:44:32,240 --> 02:44:33,520 QUESTIONS AND PARTICIPATE. 3843 02:44:33,520 --> 02:44:35,000 SORRY I TALKED QUICK AND WANTED 3844 02:44:35,000 --> 02:44:37,120 TO GET THROUGH ALL THIS AS QUICK 3845 02:44:37,120 --> 02:44:37,560 AS I COULD. 3846 02:44:37,560 --> 02:44:40,800 >> THAT WAS AMAZING AND IT DOES 3847 02:44:40,800 --> 02:44:42,720 NOT SURPRISE ME YOU ENDED ON 3848 02:44:42,720 --> 02:44:46,320 TIME. I'M SURE THAT YOU -- YOU 3849 02:44:46,320 --> 02:44:49,120 PACK AD I LOT IN THIS AND IT WAS 3850 02:44:49,120 --> 02:44:49,880 AN AMAZING TALK. 3851 02:44:49,880 --> 02:44:51,240 WHILE THE QUESTIONS ARE COMING 3852 02:44:51,240 --> 02:44:55,960 IN, I WANT TO ASK YOU 2 3853 02:44:55,960 --> 02:44:56,720 QUESTIONS. 3854 02:44:56,720 --> 02:44:58,400 FIRST IS THERE ARE A LOT OF 3855 02:44:58,400 --> 02:45:02,400 ISSUES YOU RAISED IN A VERY 3856 02:45:02,400 --> 02:45:03,400 IMPORTANT WAY. 3857 02:45:03,400 --> 02:45:06,040 IF YOU HAD TO PRIORITIZE ONE OR 3858 02:45:06,040 --> 02:45:09,360 TWO OF THEM, OF THE GAPS. 3859 02:45:09,360 --> 02:45:09,840 YEAH. 3860 02:45:09,840 --> 02:45:12,000 WHAT DO YOU THINK THEY ARE? 3861 02:45:12,000 --> 02:45:13,920 CONTROL GROUP ISSUE I THINK IS 3862 02:45:13,920 --> 02:45:14,600 IMPORTANT? 3863 02:45:14,600 --> 02:45:18,440 YOU SAID YOU WILL DEVOTE ETS 3864 02:45:18,440 --> 02:45:20,080 SYMPOSIUM AND FOCUSING ON ONE 3865 02:45:20,080 --> 02:45:22,080 ORE 2 WHAT COMES TO TOP OF LIST 3866 02:45:22,080 --> 02:45:24,320 OF WHAT PROBLEMS NEED TO BE 3867 02:45:24,320 --> 02:45:24,960 ADDRESSED FIRST? 3868 02:45:24,960 --> 02:45:27,840 >> I THINK IT WOULD HELP IF WE 3869 02:45:27,840 --> 02:45:29,080 COULD GET EXPERTISE TOGETHER TO 3870 02:45:29,080 --> 02:45:32,040 LOOK AT MECHANISMS OF HOW THESE 3871 02:45:32,040 --> 02:45:33,960 INTERVENTIONS MAY BE EFFECTING 3872 02:45:33,960 --> 02:45:35,760 PATIENTS SO THAT WE CAN DESIGN 3873 02:45:35,760 --> 02:45:38,640 INTERVENTIONS THAT WE THINK WILL 3874 02:45:38,640 --> 02:45:43,320 HAVE THE MOST BENEFIT AND FIELD 3875 02:45:43,320 --> 02:45:45,040 MATURING THIRD LAST BULLET POINT 3876 02:45:45,040 --> 02:45:46,600 HAVE TO COMPARE TRIALS LOTS AND 3877 02:45:46,600 --> 02:45:48,880 LOTS OF TRIALS AND THESE ARE NOT 3878 02:45:48,880 --> 02:45:51,720 DIFFERENT AND TEAM TRIAL 3879 02:45:51,720 --> 02:45:53,720 PUBLISHED IN NEW ENGLAND JOURNAL 3880 02:45:53,720 --> 02:45:55,760 THAT DR. MOS WROTE EDITORIAL ON 3881 02:45:55,760 --> 02:45:57,720 IS A FANTASTIC TRIAL TESTING 3882 02:45:57,720 --> 02:45:59,920 QUESTION OF INTENSITY AND 3883 02:45:59,920 --> 02:46:01,040 INTERVENTION GROUP IS VERY 3884 02:46:01,040 --> 02:46:02,760 SPECIFICALLY DESIGNED AND IS 3885 02:46:02,760 --> 02:46:04,520 VERY DIFFERENT THAN USUAL CARE. 3886 02:46:04,520 --> 02:46:06,800 BOTH INTERVENTION AND CONTROL 3887 02:46:06,800 --> 02:46:08,880 GROUP RECEIVE EARLY ONSET AND 3888 02:46:08,880 --> 02:46:11,120 HIGH FREQUENCY INTERVENTION. 3889 02:46:11,120 --> 02:46:13,240 DIFFERENCE BETWEEN TWO GROUPS IS 3890 02:46:13,240 --> 02:46:14,640 INTENSITY AND HOW INTERVENTION 3891 02:46:14,640 --> 02:46:16,840 IS DELIVERED AND WE WILL NEED A 3892 02:46:16,840 --> 02:46:18,840 LOT OF THE KINDS OF TRIALS THAT 3893 02:46:18,840 --> 02:46:21,360 IS WHY I WAS SUGGESTING A 3894 02:46:21,360 --> 02:46:23,600 PLATFORM WHERE WE COULD BEGIN TO 3895 02:46:23,600 --> 02:46:25,400 TEST MANY DIFFERENT THINGS. 3896 02:46:25,400 --> 02:46:28,080 IN A HEAD TO HEAD SORT OF BASIS 3897 02:46:28,080 --> 02:46:30,480 THAT ARE MY PROBABLY TOP 2. 3898 02:46:30,480 --> 02:46:32,360 >> SOUNDS GREAT. 3899 02:46:32,360 --> 02:46:36,320 ANOTHER THING I WILL ASK YOU IS 3900 02:46:36,320 --> 02:46:37,920 A DIFFICULT QUESTION, DALE. I 3901 02:46:37,920 --> 02:46:38,840 KNOW YOU HAVE THOUGHT ABOUT THIS 3902 02:46:38,840 --> 02:46:40,360 A LOT. 3903 02:46:40,360 --> 02:46:43,040 THERE IS A BALANCE BETWEEN DOING 3904 02:46:43,040 --> 02:46:44,960 SOME OF THE OBSERVATIONAL COHORT 3905 02:46:44,960 --> 02:46:48,320 TYPE OF STUDIES TO IDENTIFY 3906 02:46:48,320 --> 02:46:50,280 WHICH PATIENTS TRULY RESPOND OR 3907 02:46:50,280 --> 02:46:52,800 WHO, YOU KNOW, TREATMENT 3908 02:46:52,800 --> 02:46:55,360 ENRICHMENT STRATEGIES AND VERSUS 3909 02:46:55,360 --> 02:46:56,360 DOING RANDOMIZED CLINICAL TRIALS 3910 02:46:56,360 --> 02:46:58,520 AND WE ARE NOT REALLY SURE WHO 3911 02:46:58,520 --> 02:47:00,160 WE SHOULD BE ENROLLING. 3912 02:47:00,160 --> 02:47:01,920 HOW WOULD YOU BALANCE THOSE? 3913 02:47:01,920 --> 02:47:04,480 I MEAN, SHOULD WE DO MORE 3914 02:47:04,480 --> 02:47:05,720 OBSERVATIONAL THINGS AND NOT AS 3915 02:47:05,720 --> 02:47:07,680 MANY OF THE CLINICAL TRIALS NOW 3916 02:47:07,680 --> 02:47:10,360 TO TRY TO FIGURE OUT WHO TO 3917 02:47:10,360 --> 02:47:10,640 STUDY. 3918 02:47:10,640 --> 02:47:14,000 OR WOULD YOU SAY KEEP DOING THE 3919 02:47:14,000 --> 02:47:16,200 PRAGMATIC CLINICAL TRIALS AND 3920 02:47:16,200 --> 02:47:17,120 PLATFORM DESIGN WHERE WE CAN 3921 02:47:17,120 --> 02:47:19,080 FIGURE IT OUT ALONG THE WAY AND 3922 02:47:19,080 --> 02:47:20,680 REALIZE IT IS A TOUGH QUESTION. 3923 02:47:20,680 --> 02:47:22,840 >> I DON'T KNOW THE RIGHT 3924 02:47:22,840 --> 02:47:24,080 ANSWER. I WOULD LEAN TOWARDS I 3925 02:47:24,080 --> 02:47:25,920 THINK THAT WE HAVE LOTS OF 3926 02:47:25,920 --> 02:47:27,240 OBSERVATIONAL RESEARCH AND I 3927 02:47:27,240 --> 02:47:29,080 WOULD LEAN TOWARDS DOING MORE 3928 02:47:29,080 --> 02:47:31,680 RIGOROUS CLINICAL TRIALS AND 3929 02:47:31,680 --> 02:47:33,200 PLEASE STOP DOING UNBLINDED 3930 02:47:33,200 --> 02:47:35,200 TRIALS AND IS OKAY. WE MAY NEED 3931 02:47:35,200 --> 02:47:38,000 TO DO SINGLE CENTERED TRIALS FOR 3932 02:47:38,000 --> 02:47:39,400 EARLY STAGE INTERVENTIONS AND 3933 02:47:39,400 --> 02:47:41,720 THEY HAVE TO BE RIGOROUS THAN 3934 02:47:41,720 --> 02:47:44,720 TRIALS OF BEING TO DATE AND DO 3935 02:47:44,720 --> 02:47:46,000 MECHANISTIC PART OF THAT 3936 02:47:46,000 --> 02:47:46,360 TOGETHER. 3937 02:47:46,360 --> 02:47:47,800 I WOULD RATHER SEE 10 TRIALS 3938 02:47:47,800 --> 02:47:49,520 THAT BEGIN TO LOOK AT A NUMBER 3939 02:47:49,520 --> 02:47:53,560 OF DIFFERENT ASPECTS OF DOSE OR 3940 02:47:53,560 --> 02:47:55,360 TYPES OF INTERVENTIONS THAT FWIN 3941 02:47:55,360 --> 02:47:57,280 TO LOOK FOR SIGNALS FOR WHAT 3942 02:47:57,280 --> 02:48:01,280 COULD THEN BE PROGRESSED TOWARDS 3943 02:48:01,280 --> 02:48:04,080 LARGER TRIALS WOULD BE MY BIAS 3944 02:48:04,080 --> 02:48:06,200 WITH SOME MECHANISM BUILT IN. 3945 02:48:06,200 --> 02:48:08,040 IT WILL REQUIRE PARTNERSHIP TO 3946 02:48:08,040 --> 02:48:10,320 HAVE ALL NECESSARY SKILLS. 3947 02:48:10,320 --> 02:48:12,760 >> IN INTEREST, DALE, THAT IS 3948 02:48:12,760 --> 02:48:13,880 AWESOME. IN INTEREST, THERE IS 3949 02:48:13,880 --> 02:48:15,840 OTHER THINGS IN THE CHATS. WE 3950 02:48:15,840 --> 02:48:17,560 ARE KEEPING VERY CLOSE AND 3951 02:48:17,560 --> 02:48:19,520 WATCHING TO ADDRESS THOSE ISSUES 3952 02:48:19,520 --> 02:48:20,800 IN THE PANEL DISCUSSIONS. 3953 02:48:20,800 --> 02:48:23,800 I WANT TO TURN IT OVER TO 3954 02:48:23,800 --> 02:48:28,880 STEPHANIE TO INTRODUCE THE FINAL 3955 02:48:28,880 --> 02:48:32,440 SPEAKER OF THE SESSION. 3956 02:48:32,440 --> 02:48:35,680 >> THANK YOU. 3957 02:48:35,680 --> 02:48:37,480 FINAL SPEAKER IS [INDISCERNIBLE] 3958 02:48:37,480 --> 02:48:40,280 AND ASSISTANT PROFESSOR OF 3959 02:48:40,280 --> 02:48:42,480 EPIDEMIOLOGY AND MEDICINE IN 3960 02:48:42,480 --> 02:48:45,960 PULMONARY CRITICAL CARE. SORRY 3961 02:48:45,960 --> 02:48:50,200 HE IS THE DIRECTOR OF NIH PECK 3962 02:48:50,200 --> 02:48:54,120 CORI CLINICAL TRIALS OUTCOMES 3963 02:48:54,120 --> 02:48:57,600 LAB -- AT UNIVERSITY OF COLLEGE 3964 02:48:57,600 --> 02:49:04,680 LONDON AND PRIMARY FOCUS OF 3965 02:49:04,680 --> 02:49:11,920 RESEARCH AND IMPROVING PRAG. 3966 02:49:11,920 --> 02:49:14,080 YOU CAN SEE WHY WE THOUGHT HE 3967 02:49:14,080 --> 02:49:18,160 WAS A TREMENDOUS PERSON TO CLOSE 3968 02:49:18,160 --> 02:49:19,280 OUT THIS SESSION. 3969 02:49:19,280 --> 02:49:21,720 DR. JORGE, TAKE IT OVER. 3970 02:49:21,720 --> 02:49:23,400 >> THANK SO YOU MUCH, 3971 02:49:23,400 --> 02:49:23,800 STEPHANIE. 3972 02:49:23,800 --> 02:49:25,720 >> I HAVE LOTS OF OVERLAPPING 3973 02:49:25,720 --> 02:49:27,400 THEMES AND ADAPTING TO RESPOND 3974 02:49:27,400 --> 02:49:31,200 TO SOME QUESTIONS AND BARE WITH 3975 02:49:31,200 --> 02:49:32,680 ME. 3976 02:49:32,680 --> 02:49:35,640 NEXT SLIDE, PLEASE. 3977 02:49:35,640 --> 02:49:37,240 ACKNOWLEDGING FUNDING FROM PEK 3978 02:49:37,240 --> 02:49:39,840 ORRI AND NHLBI AND WHAT HAS BEEN 3979 02:49:39,840 --> 02:49:41,840 SAID IS GENERATING IN SUPPORT 3980 02:49:41,840 --> 02:49:43,720 AND I WILL THINK ABOUT IT AND I 3981 02:49:43,720 --> 02:49:45,080 HAVE PERSONAL FEES AND DON'T 3982 02:49:45,080 --> 02:49:46,600 THINK THEY ARE RELEVANT TO WHAT 3983 02:49:46,600 --> 02:49:50,720 I WILL SAY TODAY BUT TALK ABOUT 3984 02:49:50,720 --> 02:49:52,320 TRIALS TO LOTS OF PEOPLE. 3985 02:49:52,320 --> 02:49:55,360 I WILL TRY TO TALK ABOUT FOUR 3986 02:49:55,360 --> 02:49:56,640 BRIEFLY DISTINCT THINGS TODAY 3987 02:49:56,640 --> 02:49:58,880 AND IMBEDDING ARTICLES TO GIVE 3988 02:49:58,880 --> 02:50:01,160 PEOPLE WHO WANT TO EDUCATE 3989 02:50:01,160 --> 02:50:02,640 THEMSELVES GUIDANCE WHERE TO 3990 02:50:02,640 --> 02:50:04,000 LOOK AND MENTIONING AND STARTING 3991 02:50:04,000 --> 02:50:06,320 SAYING THINGS ABOUT OUTCOME 3992 02:50:06,320 --> 02:50:07,560 MEASURES LOTS HAS BEEN SAID 3993 02:50:07,560 --> 02:50:09,080 ALREADY AND PIVOTING AND TALKING 3994 02:50:09,080 --> 02:50:10,520 ABOUT HOW TO USE MORE WHAT I 3995 02:50:10,520 --> 02:50:13,480 THINK OF AS KIND OF REALINO 3996 02:50:13,480 --> 02:50:15,320 VATTIVE STATE OF THE ART 3997 02:50:15,320 --> 02:50:17,600 OBSERVATIONAL DATA METHODS AND 3998 02:50:17,600 --> 02:50:19,640 LAST COUPLE YEARS EMULATED 3999 02:50:19,640 --> 02:50:21,560 TRIALS AND WALKING THROUGH 4000 02:50:21,560 --> 02:50:23,880 EXAMPLE AND SHOULD USE TO INFORM 4001 02:50:23,880 --> 02:50:25,720 TRIAL DESIGN AS WELL AND GIVING 4002 02:50:25,720 --> 02:50:28,080 EXAMPLE IN A FEW YEARS AND 4003 02:50:28,080 --> 02:50:30,560 SPOILER ALERT MY HIGH RISK AWARD 4004 02:50:30,560 --> 02:50:32,800 OR IDEA IS ADAPTIVE PLATFORM 4005 02:50:32,800 --> 02:50:34,200 TRIAL THAT I WILL TALK ABOUT 4006 02:50:34,200 --> 02:50:36,080 WHAT I THINK THAT IS AND WILL 4007 02:50:36,080 --> 02:50:38,280 TRY TO ADD NUANCE THERE AND TALK 4008 02:50:38,280 --> 02:50:40,000 A LITTLE ABOUT WHY I THINK WE 4009 02:50:40,000 --> 02:50:44,680 HAVE TO PIVOT AWAY FROM P VALUE 4010 02:50:44,680 --> 02:50:46,440 BASED WORLD FULL-FLEJ BAYESIAN 4011 02:50:46,440 --> 02:50:47,880 AND WILL CONVINCE YOU TO GIVE 4012 02:50:47,880 --> 02:50:49,680 YOU A CHANCE IF YOU ARE NOT 4013 02:50:49,680 --> 02:50:51,280 ALREADY IN THAT DIRECTION. 4014 02:50:51,280 --> 02:50:52,680 NEXT SLIDE, PLEASE. 4015 02:50:52,680 --> 02:50:54,440 OKAY. VERY MUCH I THINK THAT 4016 02:50:54,440 --> 02:50:56,760 EVERYBODY KNOWS THE WHITE WHALE 4017 02:50:56,760 --> 02:50:58,520 OF THE CRITICAL CARE COMMUNITY 4018 02:50:58,520 --> 02:51:01,240 IS OUTCOME MEASURE AND 30 YEARS 4019 02:51:01,240 --> 02:51:03,320 FOCUSED ON DEATH AS PRIMARY 4020 02:51:03,320 --> 02:51:05,040 ENDPOINT WE WERE STRUGGLING AND 4021 02:51:05,040 --> 02:51:08,680 MOVED TO REALM OF FOCUSING ON 4022 02:51:08,680 --> 02:51:10,880 NONMORTALITY THAT IS CHALLENGING 4023 02:51:10,880 --> 02:51:14,200 IN ACUTE PHASE AND 90 DAYS AND 4024 02:51:14,200 --> 02:51:15,840 CHALLENGE RING IN LONG TERM AND 4025 02:51:15,840 --> 02:51:18,040 IT IS CHALLENGING WE KNOW WHAT 4026 02:51:18,040 --> 02:51:20,360 MATTERS LOTS OF CREDIT TO PEOPLE 4027 02:51:20,360 --> 02:51:21,720 ON THIS CALL AND COLLEAGUES AND 4028 02:51:21,720 --> 02:51:23,720 WHAT WE HAVE SEEN IS THIS 4029 02:51:23,720 --> 02:51:25,320 CONCEPT WE UNDERSTAND THERE IS 4030 02:51:25,320 --> 02:51:27,120 KINETICS AND ACUTE PHASE OF 4031 02:51:27,120 --> 02:51:30,320 CRITICAL ILLNESS AND LONG TERM 4032 02:51:30,320 --> 02:51:31,440 MULTIFACTORIAL TIME VARYING AND 4033 02:51:31,440 --> 02:51:32,800 HARD TO MEASURE THINGS THAT 4034 02:51:32,800 --> 02:51:34,360 MATTER TO PEOPLE AND HARD TO 4035 02:51:34,360 --> 02:51:36,600 MEASURE THEY HAVE TO COME FROM 4036 02:51:36,600 --> 02:51:38,800 INSTRUMENTS AND HAVE SUBJECTIVE 4037 02:51:38,800 --> 02:51:40,920 IMBEDDED IN THEM AND HAVE TO 4038 02:51:40,920 --> 02:51:42,680 MAKE A DECISION AT TRIAL STAGE 4039 02:51:42,680 --> 02:51:44,400 AND DECISION ABOUT WHAT ONE OR 4040 02:51:44,400 --> 02:51:46,960 TWO OUTCOME MEASURES TO HEDGE 4041 02:51:46,960 --> 02:51:48,280 EFFICACY DECISIONS ON AND MAKING 4042 02:51:48,280 --> 02:51:51,160 IT ABOUT A TIME HORIZON THAT IS 4043 02:51:51,160 --> 02:51:53,440 TRICKY AND YOU HAVE WHAT I CALL 4044 02:51:53,440 --> 02:51:56,000 COMPLIANCE ISSUES AND PEOPLE 4045 02:51:56,000 --> 02:51:58,080 LOSS FOLLOW UP AND SOME 4046 02:51:58,080 --> 02:51:59,080 PERMANENTLY HAVE LOSS TO FOLLOW 4047 02:51:59,080 --> 02:52:02,520 UP WHEN THEY DIE THAT IS REALLY 4048 02:52:02,520 --> 02:52:02,840 CHALLENGING. 4049 02:52:02,840 --> 02:52:03,920 NEXT SLIDE, PLEASE. 4050 02:52:03,920 --> 02:52:06,080 WHAT CAN WE DO? 4051 02:52:06,080 --> 02:52:07,560 RESEARCH OUT THERE AND THINK 4052 02:52:07,560 --> 02:52:11,120 ABOUT IN THREE BUCKETS CALL TO 4053 02:52:11,120 --> 02:52:12,520 INFERENCE METHODS AND PAPER THAT 4054 02:52:12,520 --> 02:52:14,560 WAS MENTIONED YOU CAN ANALYZE 4055 02:52:14,560 --> 02:52:16,320 GROUP THAT PEOPLE CALL ALWAYS 4056 02:52:16,320 --> 02:52:16,600 SURVIVORS. 4057 02:52:16,600 --> 02:52:18,600 I DO RESEARCH IN HERE. I LIKE 4058 02:52:18,600 --> 02:52:21,520 IT CONCEPTUALLY APPEALING AND 4059 02:52:21,520 --> 02:52:23,600 REQUIRES LOTS OF LONG-TERM DATA 4060 02:52:23,600 --> 02:52:26,000 AND STATISTICAL ASSUMPTIONS AND 4061 02:52:26,000 --> 02:52:27,200 DISCARDS LOTS OF PEOPLE. YOU 4062 02:52:27,200 --> 02:52:29,160 DON'T WANT TO DO THAT AND WANT 4063 02:52:29,160 --> 02:52:31,880 TO LEARN SOMETHING ABOUT 4064 02:52:31,880 --> 02:52:32,480 EVERYONE AND LOSE STATISTICAL 4065 02:52:32,480 --> 02:52:34,200 POWER THAT IS PERSISTENT 4066 02:52:34,200 --> 02:52:37,920 CHALLENGE FOR US STATISTICAL 4067 02:52:37,920 --> 02:52:40,360 APPROACHES JOINT MODELING AND 4068 02:52:40,360 --> 02:52:42,160 CHALLENGE IS THEY SOLVE DATA 4069 02:52:42,160 --> 02:52:44,480 ISSUE AND CREATE STATISTICAL 4070 02:52:44,480 --> 02:52:46,800 ISSUE AND EFFECT ESTIMATE WITH 4071 02:52:46,800 --> 02:52:49,160 NO REAL INTERPRETABILITY AND 4072 02:52:49,160 --> 02:52:51,400 CLINICAL TRANSLATION AND WE HAVE 4073 02:52:51,400 --> 02:52:58,800 FALLEN BY NECESSITY TOWARDS 4074 02:52:58,800 --> 02:53:01,880 COMPOSITE OUTCOMES AND NEXT 4075 02:53:01,880 --> 02:53:03,720 SLIDE, PLEASE. 4076 02:53:03,720 --> 02:53:06,240 SO, I WILL TALK ABOUT VENTILATOR 4077 02:53:06,240 --> 02:53:08,360 FREE DAYS AND WITH THIS WE HAVE 4078 02:53:08,360 --> 02:53:11,720 A MOVEMENT FROM MORTALITY BEING 4079 02:53:11,720 --> 02:53:13,760 TREATED 0 FREE DAYS TO NEGATIVE 4080 02:53:13,760 --> 02:53:16,360 1 AND NUMERICAL MOVE MAKING IT 4081 02:53:16,360 --> 02:53:18,200 HIERARCHICAL I LIKE IT AND 4082 02:53:18,200 --> 02:53:20,240 CHALLENGE WITH COMPOSITE 4083 02:53:20,240 --> 02:53:22,080 OUTCOMES NOT INTERPRETABLE 4084 02:53:22,080 --> 02:53:24,040 ACROSS TRIALS OR COMPARABLE AND 4085 02:53:24,040 --> 02:53:27,080 FIGURING HERE WE HAVE A Y AXIS 4086 02:53:27,080 --> 02:53:29,200 MEDIAN DAYS OF MECHANICAL 4087 02:53:29,200 --> 02:53:31,080 VENTILATION THAT RANGES FROM 4088 02:53:31,080 --> 02:53:33,480 TRIALS A THROUGH E AND 7 DAYS TO 4089 02:53:33,480 --> 02:53:35,760 18 AND ACROSS X AXIS WE HAVE 4090 02:53:35,760 --> 02:53:38,080 MORTALITY RATES FROM 0 TO 40 AND 4091 02:53:38,080 --> 02:53:42,040 ALL FIVE TRIALS HAVE SAME MEDIAN 4092 02:53:42,040 --> 02:53:44,080 VENTILATOR FREE DAYS OF MEDIAN 4093 02:53:44,080 --> 02:53:45,640 OF 10 NOT LEARNING WHAT IS 4094 02:53:45,640 --> 02:53:47,680 HAPPENING BUT GETTING A NET 4095 02:53:47,680 --> 02:53:49,640 SUMMARY AND CURRENT ENDPOINTS 4096 02:53:49,640 --> 02:53:51,720 FUNCTIONALLY ARE SOLVING 4097 02:53:51,720 --> 02:53:53,160 STATISTICAL PROBLEM WITH 4098 02:53:53,160 --> 02:53:55,160 TRADEOFF OF CONCEPTUAL PROBLEM 4099 02:53:55,160 --> 02:53:57,720 AND NEXT SLIDE SEEING AT 4100 02:53:57,720 --> 02:53:58,840 SUSTAINING LEVEL AND TRIAL LEVEL 4101 02:53:58,840 --> 02:54:00,640 AND MULTIPLE PEOPLE WITH SAME 4102 02:54:00,640 --> 02:54:02,480 VALUE OF OUTCOME MEASURE IN 4103 02:54:02,480 --> 02:54:05,280 TRIAL AND TWO HYPOTHETICAL 4104 02:54:05,280 --> 02:54:06,960 EXAMPLES VENTILATOR FREE DAYS 4105 02:54:06,960 --> 02:54:10,840 ASDOET AND AT 14 AND WE TROOID 4106 02:54:10,840 --> 02:54:13,120 TO MAP OUT RANDOM TRAJECTORIES 4107 02:54:13,120 --> 02:54:14,320 COULD BE DIFFERENT AND 4108 02:54:14,320 --> 02:54:15,480 STATISTICAL DISTRIBUTION YOU 4109 02:54:15,480 --> 02:54:16,920 WILL SEE SAME VALUES. 4110 02:54:16,920 --> 02:54:19,160 NEXT SLIDE, PLEASE. 4111 02:54:19,160 --> 02:54:21,160 SO, WE SPENT TIME OVER THE LAST 4112 02:54:21,160 --> 02:54:22,520 COUPLE YEARS THINKING ABOUT WHAT 4113 02:54:22,520 --> 02:54:26,160 WOULD BE WE STARTED DE NOVO 4114 02:54:26,160 --> 02:54:28,800 IDEAL LONG-TERM CRITICAL CARE 4115 02:54:28,800 --> 02:54:30,880 ENDPOINT THAT IS SUBJECTIVELY 4116 02:54:30,880 --> 02:54:32,400 RANKED ORDER AND MY 4117 02:54:32,400 --> 02:54:33,760 INTERPRETATION I THINK THAT MOST 4118 02:54:33,760 --> 02:54:36,000 IMPORTANT THING WE FIND A 4119 02:54:36,000 --> 02:54:37,920 NATURAL PLACE FOR DEATH AND 4120 02:54:37,920 --> 02:54:40,480 THINK OF HIERARCHICAL ENDPOINT 4121 02:54:40,480 --> 02:54:42,040 AND DECIDE THAT IS WHAT WE VALUE 4122 02:54:42,040 --> 02:54:44,360 MONTHEST TO ACCEPT IT AND THINGS 4123 02:54:44,360 --> 02:54:45,680 TO WORK THROUGH AS STAKEHOLDERS 4124 02:54:45,680 --> 02:54:49,720 IN THE COMMUNITY AND NEXT TWO 4125 02:54:49,720 --> 02:54:53,800 THINGS ARE TO ME INTERVIEW 4126 02:54:53,800 --> 02:54:55,280 RELATED WITH BEAUTIFUL DIAGRAM 4127 02:54:55,280 --> 02:54:57,200 AND TRAJECTORIES PEOPLE HAVE 4128 02:54:57,200 --> 02:55:00,600 WITH CRITICAL ILLNESS AND BLUE 4129 02:55:00,600 --> 02:55:03,840 JOURNAL AND FORGET TITLE JACK IF 4130 02:55:03,840 --> 02:55:05,640 YOU ARE LISTENING COMPELLING 4131 02:55:05,640 --> 02:55:07,760 FIGURE AND PEOPLE COMING INTO 4132 02:55:07,760 --> 02:55:09,160 RECOVERY AT DIFFERENT STARTING 4133 02:55:09,160 --> 02:55:11,640 POINTS DIFFERENT POST RECOVERY 4134 02:55:11,640 --> 02:55:12,960 AND KINETICS OR CONTINUUM 4135 02:55:12,960 --> 02:55:15,480 RECOVERY AND THINK THAT IDEAL 4136 02:55:15,480 --> 02:55:16,760 ENDPOINT ALLOWS US TO PICK THAT 4137 02:55:16,760 --> 02:55:20,080 UP AND IDEALLY IS SOMETHING OF A 4138 02:55:20,080 --> 02:55:22,120 MORE CONTINUOUS LEVEL AND FOCUS 4139 02:55:22,120 --> 02:55:24,360 ON ORDINAL OUTCOMES GOING FROM 0 4140 02:55:24,360 --> 02:55:27,760 TO 7 AND 0 TO 9 AND CEILING 4141 02:55:27,760 --> 02:55:30,160 EFFECTS TOUGH TO FIND MOVEMENT 4142 02:55:30,160 --> 02:55:33,320 IN IT AND NICE TO FIND SOMETHING 4143 02:55:33,320 --> 02:55:35,280 STATISTICALLY SIMPLE AND ROBUST 4144 02:55:35,280 --> 02:55:36,680 AND ADAPTABLE WHAT MATTERS TO 4145 02:55:36,680 --> 02:55:38,400 PEOPLE AND ALIGNING WITH 4146 02:55:38,400 --> 02:55:40,320 SOMETHING FAMILIAR TO REGULATORS 4147 02:55:40,320 --> 02:55:42,280 AND NEXT SLIDE, PLEASE. 4148 02:55:42,280 --> 02:55:43,960 WE HAVE PLAYED WITH GETTING 4149 02:55:43,960 --> 02:55:45,440 TOWARDS SOME OF THESE AND 4150 02:55:45,440 --> 02:55:47,080 PERHAPS NOT PERFECTLY AND 4151 02:55:47,080 --> 02:55:48,680 DEFINITELY NOT PERFECTLY DAYS 4152 02:55:48,680 --> 02:55:52,480 ALIVE OUT OF THE HOSPITAL AND 4153 02:55:52,480 --> 02:55:55,280 HOSPITAL FREE DAYS CONCEPT OF 4154 02:55:55,280 --> 02:55:56,520 STATISTICS [INDISCERNIBLE] 4155 02:55:56,520 --> 02:55:57,760 DEMANDS IDEAL QUANTITY TO TARGET 4156 02:55:57,760 --> 02:55:59,320 THAT GETS THERE AND IS ABOUT 4157 02:55:59,320 --> 02:56:01,320 WHAT PEOPLE WANT AND YOU CAN 4158 02:56:01,320 --> 02:56:03,480 START TO MANIPULATE IT FOUR 4159 02:56:03,480 --> 02:56:06,680 DIFFERENT PEOPLE AND STAKEHOLDER 4160 02:56:06,680 --> 02:56:08,440 POPULATIONS FOCUSING BEING OUT 4161 02:56:08,440 --> 02:56:09,840 INSTITUTION AND FREE DAYS 4162 02:56:09,840 --> 02:56:11,640 GETTING OUT OF REHABILITATION OR 4163 02:56:11,640 --> 02:56:13,760 GETTING OUT OF MEDICATION THAT 4164 02:56:13,760 --> 02:56:14,960 IS FLEXIBLE AND IS NICE 4165 02:56:14,960 --> 02:56:17,440 MEASURING IN TRIALS THAT 180 4166 02:56:17,440 --> 02:56:19,240 DAYS IS A BEAUTIFUL CONTINUOUS 4167 02:56:19,240 --> 02:56:22,400 OUTCOME AND STARTING TO THINK 4168 02:56:22,400 --> 02:56:24,920 ABOUT ME AND MEDIAN DIFFERENCE 4169 02:56:24,920 --> 02:56:27,160 AND RELATIVE SCALES AND RATIO TO 4170 02:56:27,160 --> 02:56:30,240 WIN ODDS AND SOMETHING WE ARE 4171 02:56:30,240 --> 02:56:32,520 TINKERING WITH AND PATIENT 4172 02:56:32,520 --> 02:56:36,320 CENTERED MEANINGFUL TO 4173 02:56:36,320 --> 02:56:39,360 REGULATORS AND PATIENT CAREGIVER 4174 02:56:39,360 --> 02:56:39,880 RS. 4175 02:56:39,880 --> 02:56:42,720 COLLEAGUE FIRST AUTHOR PAPER K 4176 02:56:42,720 --> 02:56:46,080 AWARD HLVI TRYING TO RANK ORDER 4177 02:56:46,080 --> 02:56:48,120 OR QUALITY RANK DAYS. I'M 4178 02:56:48,120 --> 02:56:49,480 EXCITED ABOUT WHERE THAT WORK 4179 02:56:49,480 --> 02:56:51,480 GOES AND IT WILL SOLVE PROBLEMS 4180 02:56:51,480 --> 02:56:53,800 AND IS BASED ON ONE INSTRUMENT 4181 02:56:53,800 --> 02:56:57,000 THAT MAY NOT CAPTURE EVERY 4182 02:56:57,000 --> 02:56:57,280 DOMAIN. 4183 02:56:57,280 --> 02:56:58,880 NEXT SLIDE, PLEASE. 4184 02:56:58,880 --> 02:57:01,320 HARD PIVOT. I WANT TO TALK 4185 02:57:01,320 --> 02:57:04,240 ABOUT MOVING FROM OBSERVATION TO 4186 02:57:04,240 --> 02:57:07,560 EXPERIMENTATION BETTER. I'M 4187 02:57:07,560 --> 02:57:09,360 IMPRESSED WITH HOW WELL TARGET 4188 02:57:09,360 --> 02:57:12,160 TRIALS ARE DOG AND IDEA IS THREE 4189 02:57:12,160 --> 02:57:14,240 FOLD AND HEARING MORTAL TIME 4190 02:57:14,240 --> 02:57:18,200 BIAS AND GOAL OF RANDOMIZED 4191 02:57:18,200 --> 02:57:21,000 TRIAL IS CONCEPT OF -- GROUPS 4192 02:57:21,000 --> 02:57:23,240 ARE MORE OR LESS IDENTICAL AT 4193 02:57:23,240 --> 02:57:24,160 BASELINE AND OBSERVATIONAL 4194 02:57:24,160 --> 02:57:26,480 RESEARCH IS WORKING WITH A 4195 02:57:26,480 --> 02:57:28,120 COHORT AND BEING CAREFUL ON 4196 02:57:28,120 --> 02:57:29,280 SOMEONE'S STARTING POINT AND YOU 4197 02:57:29,280 --> 02:57:32,240 ARE ASSUMING PEOPLE ARE MORE OR 4198 02:57:32,240 --> 02:57:35,720 LESS RANDOMIZED AT BASELINE. 4199 02:57:35,720 --> 02:57:36,720 NEXT SLIDE. 4200 02:57:36,720 --> 02:57:38,880 TALKING ABOUT ODD ELEMENTS OF IT 4201 02:57:38,880 --> 02:57:41,200 PAPER WRITTEN BY PEOPLE ON THE 4202 02:57:41,200 --> 02:57:43,200 CALL AND INCREDIBLY ELEGANT 4203 02:57:43,200 --> 02:57:45,480 WISHING TO DO IT FOR EVERY 4204 02:57:45,480 --> 02:57:48,760 TRIAL. NEXT SLIDE, PLEASE. 4205 02:57:48,760 --> 02:57:51,200 NEXT ELEMENT OF EMULATED TRIAL 4206 02:57:51,200 --> 02:57:53,520 IS TAKING TABLE MAPPING OUT 4207 02:57:53,520 --> 02:57:54,880 PERFECT TRIAL TO RUN IN THIS 4208 02:57:54,880 --> 02:57:57,640 EXAMPLE IS PREVENT AND MAKING 4209 02:57:57,640 --> 02:57:59,200 OBSERVATIONAL ANALYSIS IDENTICAL 4210 02:57:59,200 --> 02:58:03,560 TO IT OR MIRROR IT AS MUCH AS 4211 02:58:03,560 --> 02:58:04,400 POSSIBLE ELIGIBILITY CRITERIA 4212 02:58:04,400 --> 02:58:06,720 AND OMIZING TREATMENT STRATEGIES 4213 02:58:06,720 --> 02:58:08,560 AND MAPPING TO EXPOSURES AND 4214 02:58:08,560 --> 02:58:11,000 CONTROL GROUPS WE SEE IN 4215 02:58:11,000 --> 02:58:13,760 OBSERVATIONAL COHORT. NEXT 4216 02:58:13,760 --> 02:58:18,120 SLIDE, PLEASE. 4217 02:58:18,120 --> 02:58:20,480 CONTINUE AND GET TO THE LAST 4218 02:58:20,480 --> 02:58:22,160 THIRD ELEMENT YOU CAN'T DO 4219 02:58:22,160 --> 02:58:26,040 UNADJUSTED ANALYSIS YOU WOULD 4220 02:58:26,040 --> 02:58:28,360 CONVENTIONALLY DO IN RCT AND 4221 02:58:28,360 --> 02:58:31,640 THERE IS BALANCING WAY TO 4222 02:58:31,640 --> 02:58:33,520 APPROACH THIS PROPENSITY SCORES 4223 02:58:33,520 --> 02:58:35,800 AND THEY ARE GOOD AT THIS IF YOU 4224 02:58:35,800 --> 02:58:37,240 DO FIRST AND SECOND STEP 4225 02:58:37,240 --> 02:58:39,440 ELEMENTS CORRECTLY. NEXT SLIDE, 4226 02:58:39,440 --> 02:58:40,040 PLEASE. 4227 02:58:40,040 --> 02:58:41,320 I WILL SHOW YOU HOW CLOSE YOU 4228 02:58:41,320 --> 02:58:43,480 CAN GET. THIS IS A NICE PANEL 4229 02:58:43,480 --> 02:58:46,560 THAT I THINK SHOWS THAT YOU HAVE 4230 02:58:46,560 --> 02:58:49,000 IN THE MIDDLE COLUMNS TREATMENT 4231 02:58:49,000 --> 02:58:50,760 EFFECTS FROM OBSERVATIONAL STUDY 4232 02:58:50,760 --> 02:58:53,000 AND RANDOMIZED TRIAL AND LAST 4233 02:58:53,000 --> 02:58:55,760 COLUMN TO THE RIGHT YOU HAVE A 4234 02:58:55,760 --> 02:58:58,200 DIFFERENCE AND DIFFERENCE AND 4235 02:58:58,200 --> 02:59:02,640 THEY ARE QUITE CLOSE ACROSS 4236 02:59:02,640 --> 02:59:03,840 ELEMENTS AND LEARNING FROM 4237 02:59:03,840 --> 02:59:07,240 OBSERVATION AT DATA WHAT IS 4238 02:59:07,240 --> 02:59:11,720 BASELINE MORTALITY RATE WHAT IS 4239 02:59:11,720 --> 02:59:14,480 CLINICAL DELTA IN POWER 4240 02:59:14,480 --> 02:59:15,680 REGULATIONS SUPPLEMENTING 4241 02:59:15,680 --> 02:59:17,120 AUGMENTING WHAT WE DO IN PILOT 4242 02:59:17,120 --> 02:59:18,720 TRIALS AND WOULD LOVE TO SEE 4243 02:59:18,720 --> 02:59:22,440 MORE OF IT IN EXPECTATION DONE 4244 02:59:22,440 --> 02:59:24,920 FOR FUTURE TRIALS. 4245 02:59:24,920 --> 02:59:27,040 NEXT SLIDE, PLEASE PIVOTING 4246 02:59:27,040 --> 02:59:30,040 AGAIN. LONG TIME FOCUSED ON 4247 02:59:30,040 --> 02:59:32,120 FIXED TRIAL AGAIN AND YOU HEARD 4248 02:59:32,120 --> 02:59:34,600 IN LAST COUPLE TALKS A MOVEMENT 4249 02:59:34,600 --> 02:59:36,880 TOWARDS THIS WHERE WE HAVE TO GO 4250 02:59:36,880 --> 02:59:38,680 REMAP CAP AND PLATFORMS BROUGHT 4251 02:59:38,680 --> 02:59:40,640 UP DURING PANDEMIC HAVE SHOWN 4252 02:59:40,640 --> 02:59:42,480 HOW MUCH WE CAN LEARN AND REMAP 4253 02:59:42,480 --> 02:59:45,480 CAP IS PUBLISHED 25TH ARTICLE 4254 02:59:45,480 --> 02:59:47,840 AND RCT MORE RECENTLY THAT IS 4255 02:59:47,840 --> 02:59:50,120 AMAZING AND IDEA BEHIND ADAPTIVE 4256 02:59:50,120 --> 02:59:52,000 TRIAL IS KEEPING ON LEARNING AND 4257 02:59:52,000 --> 02:59:56,040 LOOKING AT DATA AND COUPLE 4258 02:59:56,040 --> 03:00:00,080 HUNDRED PATIENTS OR 1 PATIENTS 4259 03:00:00,080 --> 03:00:02,560 ADAPTING INPUTS AND PERPETUAL 4260 03:00:02,560 --> 03:00:04,680 PERSISTENT LEARNING NEXT SLIDE. 4261 03:00:04,680 --> 03:00:06,200 TAPPING THROUGH THESE BOXES 4262 03:00:06,200 --> 03:00:09,680 MOVING AND IDEA IS THAT YOU 4263 03:00:09,680 --> 03:00:12,240 START TO RANDOMIZE PEOPLE AND 4264 03:00:12,240 --> 03:00:14,080 CONTROL ARM AND INTERVENTION 1, 4265 03:00:14,080 --> 03:00:15,880 2, 3, OR 4 WHATEVER YOUR 4266 03:00:15,880 --> 03:00:17,600 POPULATION ALLOWS AND TAKE A 4267 03:00:17,600 --> 03:00:20,120 LOOK AT 100 AND TREATMENT EFFECT 4268 03:00:20,120 --> 03:00:22,320 DISTRIBUTION WE ARE STARTING TO 4269 03:00:22,320 --> 03:00:24,800 SEE IF DOESN'T BE COMPELLING AND 4270 03:00:24,800 --> 03:00:26,920 YOU CAN ADJUST RANDOMIZATION 4271 03:00:26,920 --> 03:00:28,560 PROBABILITIES AND KEEP ON GOING 4272 03:00:28,560 --> 03:00:30,800 SUCH THAT YOU START TO MIX 4273 03:00:30,800 --> 03:00:33,280 SUBGROUPS AND ADD PLATFORMS INTO 4274 03:00:33,280 --> 03:00:35,640 IT. YOU CAN ADD MULTIPLE 4275 03:00:35,640 --> 03:00:38,360 DOMAINS AND PLATFORM TRIALS HAVE 4276 03:00:38,360 --> 03:00:39,960 ANTIBIOTIC AND VENTILATION 4277 03:00:39,960 --> 03:00:43,400 DOMAIN AND ORGAN FAILURE AND AI 4278 03:00:43,400 --> 03:00:45,040 DOMAIN. YOU CAN TEST MULTIPLE 4279 03:00:45,040 --> 03:00:47,880 INDIVIDUALS IN A FACTORIAL WAY 4280 03:00:47,880 --> 03:00:49,360 THAT COULD GET VERY COMPLEX. 4281 03:00:49,360 --> 03:00:50,680 NEXT SLIDE, PLEASE. 4282 03:00:50,680 --> 03:00:55,080 THIS IS A DIAGRAM THAT I WON'T 4283 03:00:55,080 --> 03:00:56,680 WALK THROUGH TOO MUCH. NUMBERS 4284 03:00:56,680 --> 03:00:58,360 AND STATISTICS. 4285 03:00:58,360 --> 03:01:00,280 >> FIVE MINUTE ROOEZ MAINING. 4286 03:01:00,280 --> 03:01:01,120 >> GOT IT. 4287 03:01:01,120 --> 03:01:03,160 WHAT YOU CAN SEE IN FIRST COLUMN 4288 03:01:03,160 --> 03:01:06,880 IS EQUAL SHADING OR EQUAL SIZED 4289 03:01:06,880 --> 03:01:08,400 BOXES THAT START TO CHANGE THAT 4290 03:01:08,400 --> 03:01:10,760 IS PROBABILITY OF BEING 4291 03:01:10,760 --> 03:01:12,600 RANDOMIZED IN DIFFERENT ARMS 4292 03:01:12,600 --> 03:01:15,120 CHANGING HAPPENING STATISTICIAN 4293 03:01:15,120 --> 03:01:18,480 AND INFORMATICS SYSTEM PEOPLE 4294 03:01:18,480 --> 03:01:19,840 CONSTANTLY WATCHING AND LEARNING 4295 03:01:19,840 --> 03:01:22,360 AND NEXT SLIDE, PLEASE. 4296 03:01:22,360 --> 03:01:23,880 POINTS I WANT TO MAKE CLOSING 4297 03:01:23,880 --> 03:01:25,280 THIS OUT DESIGNING TRIAL THAT 4298 03:01:25,280 --> 03:01:27,160 CAN LEARN AND ADAPT AND RUN LIKE 4299 03:01:27,160 --> 03:01:29,720 THAT INVESTING MORE TRIAL 4300 03:01:29,720 --> 03:01:31,120 INFRASTRUCTURE NOT TRIALS THAT 4301 03:01:31,120 --> 03:01:35,520 ARE IN STADIUMS THAT GUITAR 4302 03:01:35,520 --> 03:01:37,680 BUILT LAST YEAR FOR WORLD CUP 4303 03:01:37,680 --> 03:01:39,400 AND CAN'T HELP THAT THIS IS WHAT 4304 03:01:39,400 --> 03:01:41,440 WE WERE DOING FOR A LONG TIME 4305 03:01:41,440 --> 03:01:44,040 AND TRIALS BUILDING STATIUM FOR 4306 03:01:44,040 --> 03:01:46,160 SINGLE GAIN AND HAVE TO MOVE 4307 03:01:46,160 --> 03:01:50,120 AWAY FROM PULLING TALENT AND 4308 03:01:50,120 --> 03:01:51,440 INFORMATICS INFRASTRUCTURE HOW 4309 03:01:51,440 --> 03:01:53,600 TO LEARN AND BE ADAPTIVE 4310 03:01:53,600 --> 03:01:55,480 BRINGING ME TO NEXT POINT NEXT 4311 03:01:55,480 --> 03:01:56,200 SLIDE, PLEASE. 4312 03:01:56,200 --> 03:01:58,000 WON'T TRY TO TEACH YOU WHAT 4313 03:01:58,000 --> 03:01:59,360 BAYESIAN IS BUT CONVINCING YOU 4314 03:01:59,360 --> 03:02:01,520 WHY YOU SHOULD GIVE IT A CHANCE 4315 03:02:01,520 --> 03:02:02,680 LAND TEACH YOU WHAT BAYESIAN IS 4316 03:02:02,680 --> 03:02:04,960 IF YOU WANT TO TALK ABOUT IT. 4317 03:02:04,960 --> 03:02:06,600 FIGURED IT WASN'T BEST ENDING OR 4318 03:02:06,600 --> 03:02:09,480 TALK. WHAT WE HAVE TO DO AT A 4319 03:02:09,480 --> 03:02:10,680 PHILOSOPHICAL LEVEL IS THINKING 4320 03:02:10,680 --> 03:02:12,200 ABOUT WHAT LEVEL OF EVIDENCE DO 4321 03:02:12,200 --> 03:02:14,880 WE NEED TO MAKE MOVE ON TESTING 4322 03:02:14,880 --> 03:02:16,720 NEW THERAPY AND WE ARE MOVING 4323 03:02:16,720 --> 03:02:19,800 INTO PHASE 2 OR 3 AND LONG 4324 03:02:19,800 --> 03:02:22,640 RELIED ON CONCEPT OF .5 OR NOT 4325 03:02:22,640 --> 03:02:25,120 AND NOTHING FUNDMENTMENT ALLEY 4326 03:02:25,120 --> 03:02:27,200 DIFFERENT BAYESIAN OR FREQUENCY 4327 03:02:27,200 --> 03:02:28,760 TRIAL AND CALCULATING TREATMENT 4328 03:02:28,760 --> 03:02:30,360 EFFECTS AND WHAT IS DIFFERENT IS 4329 03:02:30,360 --> 03:02:32,000 PROCESSING THINKING ABOUT MOVING 4330 03:02:32,000 --> 03:02:34,160 ON EVIDENCE AND BAYESIAN IS IF 4331 03:02:34,160 --> 03:02:36,480 YOU REMEMBER Z SCORES NORMAL 4332 03:02:36,480 --> 03:02:38,080 DISTRIBUTION AND LINE AND 4333 03:02:38,080 --> 03:02:39,600 PERCENT TO THE RIGHT AND PERCENT 4334 03:02:39,600 --> 03:02:41,240 TO THE LEFT AND THINKING ABOUT 4335 03:02:41,240 --> 03:02:43,640 THAT PERCENT TO LEFT OR RIGHT IS 4336 03:02:43,640 --> 03:02:46,480 AROUND NULL AND ODDS RATIO OF 1 4337 03:02:46,480 --> 03:02:51,520 AND HOW MUCH DISTRIBUTION IS 4338 03:02:51,520 --> 03:02:53,720 SUGGESTIVE BENEFIT OR EQUIPOISE 4339 03:02:53,720 --> 03:02:55,600 OR HARM AND DESIGNING TO MOVE 4340 03:02:55,600 --> 03:02:58,320 AND ADAPTIVE BAYESIAN TRIALS ARE 4341 03:02:58,320 --> 03:03:00,320 DOING THAT OBSERVING PROBABILITY 4342 03:03:00,320 --> 03:03:01,800 DISTRIBUTIONS COMING IN AND 4343 03:03:01,800 --> 03:03:03,880 DECIDING IF IT IS ENOUGH TO 4344 03:03:03,880 --> 03:03:04,080 MOVE. 4345 03:03:04,080 --> 03:03:05,480 NEXT SLIDE, PLEASE. 4346 03:03:05,480 --> 03:03:07,760 I LIKE THAT WAY OF THINKING 4347 03:03:07,760 --> 03:03:09,120 BECAUSE I'M KIND OF DRIVEN BY 4348 03:03:09,120 --> 03:03:10,200 THIS EXAMPLE. 4349 03:03:10,200 --> 03:03:11,920 IF YOU HAVE NEVER READ THIS 4350 03:03:11,920 --> 03:03:14,720 PAPER IT IS ONE OF MY FAVORITES 4351 03:03:14,720 --> 03:03:16,600 USING IT A LOT WHEN I TEACH AND 4352 03:03:16,600 --> 03:03:18,680 WHAT DO WE WANT WHEN WALKING 4353 03:03:18,680 --> 03:03:19,920 INTO NEW TREATMENT WE WANT TO 4354 03:03:19,920 --> 03:03:23,080 KNOW FIRST IS IT BETTER THAN 4355 03:03:23,080 --> 03:03:26,840 WHAT WE USE NOW? IF NOT IS IT 4356 03:03:26,840 --> 03:03:30,520 INFERIOR? IDEAL TRIAL ANSWERS 4357 03:03:30,520 --> 03:03:33,200 QUESTIONS AND IS THERE A 4358 03:03:33,200 --> 03:03:33,600 COMMENT? 4359 03:03:33,600 --> 03:03:36,800 WAY WE ARE DOING THINGS P 4360 03:03:36,800 --> 03:03:38,200 VALUE-BASED TRIALS ALLOWING TO 4361 03:03:38,200 --> 03:03:39,960 ANSWER QUESTIONS SIMULTANEOUSLY. 4362 03:03:39,960 --> 03:03:40,920 NEXT SLIDE, PLEASE. 4363 03:03:40,920 --> 03:03:42,720 I THINK IT IS BECAUSE WE ARE 4364 03:03:42,720 --> 03:03:44,680 MOVING AWAY FROM SCIENTIFIC 4365 03:03:44,680 --> 03:03:46,560 QUESTION AND QUESTIONS ARE 4366 03:03:46,560 --> 03:03:48,200 ASKING IS TRIAL IN PREVIOUS 4367 03:03:48,200 --> 03:03:50,760 SLIDE FORCING INTO STATISTICAL 4368 03:03:50,760 --> 03:03:52,240 FRAMEWORK DOESN'T ANSWER THAT 4369 03:03:52,240 --> 03:03:54,080 START TO THINK ABOUT NULL 4370 03:03:54,080 --> 03:03:56,840 HYPOTHESES THAT ARE RIGID AND GO 4371 03:03:56,840 --> 03:03:59,240 SO FAR TO SAY NONSENSICAL AND 4372 03:03:59,240 --> 03:04:01,920 THIS IS A NICE QUOTE THAT SAYS 4373 03:04:01,920 --> 03:04:06,520 ONCE TO ME AND PHILOSOPHICAL 4374 03:04:06,520 --> 03:04:07,880 PERSPECTIVES THEY CAN'T BE -- 4375 03:04:07,880 --> 03:04:10,000 THAT IS NOT WHAT P VALUES DO FOR 4376 03:04:10,000 --> 03:04:13,080 US THEY TELL US HOW COMPATIBLE 4377 03:04:13,080 --> 03:04:14,520 ALTERNATIVE AND NULL HYPOTHESIS 4378 03:04:14,520 --> 03:04:17,240 ARE. THAT IS NOT SCIENTIFIC 4379 03:04:17,240 --> 03:04:20,040 QUESTION. NEXT SLIDE, PLEASE. 4380 03:04:20,040 --> 03:04:20,720 SCIENTIFIC QUESTION IS WHETHER 4381 03:04:20,720 --> 03:04:22,040 OR NOT THERE IS A TREATMENT 4382 03:04:22,040 --> 03:04:24,440 EFFECT WE CAN OBSERVE THAT IS 4383 03:04:24,440 --> 03:04:26,720 ACTIONABLE OR MEANINGFUL AND ARE 4384 03:04:26,720 --> 03:04:28,400 THREE DISTRIBUTION AND LOOK LIKE 4385 03:04:28,400 --> 03:04:32,160 THEY DIDN'T COME UP FULLY. 4386 03:04:32,160 --> 03:04:35,240 BUT THERE IS SOME THAT IS FROM 4387 03:04:35,240 --> 03:04:37,880 REMAP CAP AND HOW THEY MAKE 4388 03:04:37,880 --> 03:04:39,920 EFFICACY DECISIONS UP TOP. 99% 4389 03:04:39,920 --> 03:04:42,240 OF CLINICAL TRIAL DISTRIBUTIONS 4390 03:04:42,240 --> 03:04:43,920 TO THE RIGHT SUGGESTING BENEFIT 4391 03:04:43,920 --> 03:04:45,720 THEY SAY IS SUPERIOR AND IF 4392 03:04:45,720 --> 03:04:47,880 LEVEL OF INFERIORITY THEY WILL 4393 03:04:47,880 --> 03:04:50,320 HAVE FUTILITY THAT IS IN THE 4394 03:04:50,320 --> 03:04:52,920 MIDDLE AND JUMPING OVER THIS 4395 03:04:52,920 --> 03:04:54,520 WITH FULL WALK THROUGH OVER 4396 03:04:54,520 --> 03:04:55,240 TIME. 4397 03:04:55,240 --> 03:04:56,800 SORRY ABOUT THAT. 4398 03:04:56,800 --> 03:04:58,960 BOTTOM IS EQUIVALENT TREATMENT 4399 03:04:58,960 --> 03:05:02,080 EFFECT DISTRIBUTION SAME AS 95% 4400 03:05:02,080 --> 03:05:03,440 CONFIDENCE INTERVAL LOOKING AT 4401 03:05:03,440 --> 03:05:06,000 IT VISUALLY INSTEAD OF TWO 4402 03:05:06,000 --> 03:05:08,240 NUMBERS IS HOW WE MAKE DECISIONS 4403 03:05:08,240 --> 03:05:10,120 AND WANT FROM A TRIAL THAT 4404 03:05:10,120 --> 03:05:11,560 ALLOWS ALL QUESTIONS REGARDLESS 4405 03:05:11,560 --> 03:05:13,240 WHAT TRIAL PANS OUT AND WHAT I 4406 03:05:13,240 --> 03:05:15,320 THINK WE HAVE NOT DONE FOR THE 4407 03:05:15,320 --> 03:05:18,280 LAST 30 OR 40 YEARS. 4408 03:05:18,280 --> 03:05:19,640 NEXT SLIDE, PLEASE. 4409 03:05:19,640 --> 03:05:22,120 AND IF I HAVE NOT CONVINCED YOU 4410 03:05:22,120 --> 03:05:24,120 GIVING A CHANCE I WILL CLOSE WE 4411 03:05:24,120 --> 03:05:25,720 HAVE TO FOR NO OTHER REASON THAT 4412 03:05:25,720 --> 03:05:27,880 WHAT WE ARE DOING IS NOT WORKING 4413 03:05:27,880 --> 03:05:30,720 AND OLDER PAPER ALMOST A DECADE 4414 03:05:30,720 --> 03:05:32,680 NOW AND ONLY DIFFERENCE IS 4415 03:05:32,680 --> 03:05:35,200 DENOMINATOR PROBABLY TOWARDS 200 4416 03:05:35,200 --> 03:05:39,720 NOW AND LOOKING AT ATS AND 4417 03:05:39,720 --> 03:05:41,320 MULTIPLE SOCIETY CLINICAL 4418 03:05:41,320 --> 03:05:44,200 GUIDELINES AND PROMOTES WITH 4419 03:05:44,200 --> 03:05:46,120 EVIDENCE BASED IS PRONE 4420 03:05:46,120 --> 03:05:48,280 POSITIONING AND LONG TIME WITH 4421 03:05:48,280 --> 03:05:51,160 SUCCESS AND CAN'T DO IN ACUTE 4422 03:05:51,160 --> 03:05:56,840 PHASE WILL BE HARDER IN 4423 03:05:56,840 --> 03:05:57,800 LONG-TERM PHASE KNOWLEDGE GAPS 4424 03:05:57,800 --> 03:05:59,800 TWO THINGS TO FOCUS ON IS 4425 03:05:59,800 --> 03:06:03,200 FINDING P MULTICOMPONENT OUTCOME 4426 03:06:03,200 --> 03:06:05,120 MEASURE AND PATIENTS MOVING INTO 4427 03:06:05,120 --> 03:06:07,080 OUTCOME WE CAN ACTUALLY MAKE 4428 03:06:07,080 --> 03:06:08,760 SENSE OF GETTING TREATMENT 4429 03:06:08,760 --> 03:06:10,880 EFFECT AND FIGURING OUT WHAT 4430 03:06:10,880 --> 03:06:13,160 COMPONENTS OF THAT IS AND WILL 4431 03:06:13,160 --> 03:06:15,000 BE COMPLEX AND KNOWING 4432 03:06:15,000 --> 03:06:16,840 COMPONENTS THAT ARE RELEVANT AND 4433 03:06:16,840 --> 03:06:19,640 KNOWLEDGE GAP IS THRESHOLD 4434 03:06:19,640 --> 03:06:21,440 MOVING ON FROM EVIDENCE WE HAVE 4435 03:06:21,440 --> 03:06:22,640 TO CHOOSE SOMETHING TO RESPOND 4436 03:06:22,640 --> 03:06:24,480 TO AND THINK THAT CURRENT 4437 03:06:24,480 --> 03:06:27,600 APPROACH OF 99% EVIDENCE IS HIGH 4438 03:06:27,600 --> 03:06:29,200 AND UNDERSTAND WHY REMAP CAP DID 4439 03:06:29,200 --> 03:06:31,280 IT FIRST IN THE FIELD AND DON'T 4440 03:06:31,280 --> 03:06:35,440 KNOW IF 75% IS TOO LOW ALL DAY 4441 03:06:35,440 --> 03:06:36,680 LONG MAKE PROBABILISTIC 4442 03:06:36,680 --> 03:06:38,160 DECISIONS AND KNOW YOU DO 4443 03:06:38,160 --> 03:06:40,920 CLINICALLY DAUGHTER TELLS ME 4444 03:06:40,920 --> 03:06:44,520 WANTS TO WEAR NEW SHOES 75% 4445 03:06:44,520 --> 03:06:45,720 CHANCE OF RAIN DECISION WILL BE 4446 03:06:45,720 --> 03:06:49,600 NO MOVING FROM PHASE 2 OR 3 4447 03:06:49,600 --> 03:06:51,160 TRIAL DON'T HAVE THAT ANSWER BUT 4448 03:06:51,160 --> 03:06:53,600 AS A COMMUNITY WE CAN MOVE 4449 03:06:53,600 --> 03:06:55,360 TOWARD AND DECIDE AND NEXT 4450 03:06:55,360 --> 03:06:56,000 SLIDE, PLEASE. 4451 03:06:56,000 --> 03:06:58,080 HIGH RISK AND REWARD BEING 4452 03:06:58,080 --> 03:06:59,080 REPETITIVE NOW AND OTHER 4453 03:06:59,080 --> 03:07:01,320 SPEAKERS PLEASED TO SEE WHEN WE 4454 03:07:01,320 --> 03:07:04,880 TOOK A STAB AT IT WE ARRIVED AND 4455 03:07:04,880 --> 03:07:07,560 I DON'T THINK IT HAS TO BE 4456 03:07:07,560 --> 03:07:08,880 FOCUSED JUST NECESSARILY ON LONG 4457 03:07:08,880 --> 03:07:10,200 TERM BUT IDEAL TRIAL IS 4458 03:07:10,200 --> 03:07:13,160 SOMETHING THAT INTEGRATES WITH 4459 03:07:13,160 --> 03:07:16,600 NEW CONSORTIUM THAT IS COMING 4460 03:07:16,600 --> 03:07:19,400 TESTING SHORT-TERM THERAPIES OR 4461 03:07:19,400 --> 03:07:20,960 LONG-TERM THERAPIES AND 4462 03:07:20,960 --> 03:07:22,480 REPOSTORY AND INTEGRATION AND 4463 03:07:22,480 --> 03:07:24,880 THINK THIS IS SOMETHING THAT 4464 03:07:24,880 --> 03:07:26,200 NHLBI COULD LEAD THE FIELD IN 4465 03:07:26,200 --> 03:07:28,880 AND IF LISTENING I WOULD SAY 4466 03:07:28,880 --> 03:07:30,880 CANADA AND SCOTLAND AND DENMARK 4467 03:07:30,880 --> 03:07:32,440 ARE ALL FUNDING AT NATIONAL 4468 03:07:32,440 --> 03:07:34,360 LEVEL AND THERE IS NO REASON WE 4469 03:07:34,360 --> 03:07:35,280 HAVE SHOWN IT EITHER. 4470 03:07:35,280 --> 03:07:38,400 I AM SORRY THAT I SPOKE FAST. I 4471 03:07:38,400 --> 03:07:40,120 INHERENTLY DO BUT WANTED TO SAY 4472 03:07:40,120 --> 03:07:42,320 A LOT AND THANKS SO MUCH. 4473 03:07:42,320 --> 03:07:43,480 APPRECIATE BEING HERE. IT HAS 4474 03:07:43,480 --> 03:07:45,160 BEEN REALLY INTERESTING. 4475 03:07:45,160 --> 03:07:47,400 >> AWESOME, MICHAEL. THANKS SO 4476 03:07:47,400 --> 03:07:49,040 MUCH. WE ALL LEARNED A LOT IN 4477 03:07:49,040 --> 03:07:52,280 ADDITION TO THE FACT THAT YOU 4478 03:07:52,280 --> 03:07:54,600 ARE VERY, VERY MEAN DAD ABOUT 4479 03:07:54,600 --> 03:07:56,200 YOUR DAUGHTER'S SHOES AND LOTS 4480 03:07:56,200 --> 03:07:59,240 OF QUESTIONS TO GET INTO. A FEW 4481 03:07:59,240 --> 03:08:00,920 EARLY QUESTIONS FOCUSED ON DAYS 4482 03:08:00,920 --> 03:08:02,880 ALIVE OUTSIDE OF THE HOSPITAL 4483 03:08:02,880 --> 03:08:04,680 AND HOSPITAL-FREE DAYS MEASURE 4484 03:08:04,680 --> 03:08:08,680 THAT I THINK PROBABLY ASKING 4485 03:08:08,680 --> 03:08:11,440 ABOUT GETTING GRANULAR ABOUT 4486 03:08:11,440 --> 03:08:13,400 DEFINING THAT. DR. CONNOLLY 4487 03:08:13,400 --> 03:08:15,680 ASKED ABOUT CAPTURING BURDEN OF 4488 03:08:15,680 --> 03:08:17,280 DISABILITY AND SUPPORT NEEDS AND 4489 03:08:17,280 --> 03:08:20,040 FURTHER IN REFINING DAYS AT HOME 4490 03:08:20,040 --> 03:08:21,720 WHETHER GOOD OR BAD DAYS AT HOME 4491 03:08:21,720 --> 03:08:23,520 AND MAYBE I DON'T KNOW IF YOU 4492 03:08:23,520 --> 03:08:26,280 CAN SPEAK TO OUTCOMES RESEARCHER 4493 03:08:26,280 --> 03:08:28,480 KNOWING KATIE'S WORK? 4494 03:08:28,480 --> 03:08:29,440 >> GREAT QUESTION. 4495 03:08:29,440 --> 03:08:33,280 WE -- I THINK ATTRACTION TO THAT 4496 03:08:33,280 --> 03:08:34,760 INHERENTLY HAS BEEN THAT IT IS 4497 03:08:34,760 --> 03:08:37,480 WHEN YOU THINK OF GUIDELINES FOR 4498 03:08:37,480 --> 03:08:39,200 PRAGMATIC TRIALS IT IS PERHAPS 4499 03:08:39,200 --> 03:08:41,520 ONE OF MOST PRAGMATIC ENDPOINTS 4500 03:08:41,520 --> 03:08:43,440 YOU CAN GET AND DON'T NEED A LOT 4501 03:08:43,440 --> 03:08:44,520 OF INFORMATION AND SELF-REPORT 4502 03:08:44,520 --> 03:08:46,960 IS TRICKY. YOU CAN CALL SOMEONE 4503 03:08:46,960 --> 03:08:48,560 UP. HAVE YOU BEEN IN HOSPITAL 4504 03:08:48,560 --> 03:08:51,760 FOR LAST 90 DAYS? BECOMES LESS 4505 03:08:51,760 --> 03:08:52,760 PRAGMATIC LOSING ATTRACTION WHEN 4506 03:08:52,760 --> 03:08:55,040 YOU WANT TO INTEGRATE ALL 4507 03:08:55,040 --> 03:08:57,280 DIFFERENT ELEMENTS OF CAREGIVER 4508 03:08:57,280 --> 03:08:59,000 BURDEN AND HOW PATIENTS HAVING 4509 03:08:59,000 --> 03:09:01,320 GOOD OR BAD DAYS AND SPECIFIC 4510 03:09:01,320 --> 03:09:04,360 DOMAINS AND I DON'T REALLY KNOW 4511 03:09:04,360 --> 03:09:06,400 A PERFECT WAY TO DO IT. 4512 03:09:06,400 --> 03:09:08,480 KATIE HAS BEEN DOING A CONCEPT 4513 03:09:08,480 --> 03:09:11,840 WE HEARD FOR THE LAST COUPLE 4514 03:09:11,840 --> 03:09:13,520 DAYS SEQUENTIAL SERIAL FOLLOW 4515 03:09:13,520 --> 03:09:16,080 UPS CONTACTING PEOPLE REGULAR 4516 03:09:16,080 --> 03:09:16,760 INTERVALS AND HAVING 4517 03:09:16,760 --> 03:09:17,640 [INDISCERNIBLE] AND WE HAVE 4518 03:09:17,640 --> 03:09:19,960 TALKED ABOUT WAYS THAT SHE 4519 03:09:19,960 --> 03:09:21,880 PROPOSED WAYS DON'T WANT TO TAKE 4520 03:09:21,880 --> 03:09:23,880 IDEAS IT IS HER TALKING ABOUT 4521 03:09:23,880 --> 03:09:26,360 WAYS TEXTING PEOPLE AND HAS BEEN 4522 03:09:26,360 --> 03:09:28,920 CLEVER GETTING PEOPLE TO RESPOND 4523 03:09:28,920 --> 03:09:29,880 ELECTRONICALLY AND ONE THING 4524 03:09:29,880 --> 03:09:31,560 MATT SAID FIGURING OUT 4525 03:09:31,560 --> 03:09:32,960 REASONABLE SET OF INSTRUMENTS IN 4526 03:09:32,960 --> 03:09:35,360 WAY TO BEHAVIORALLY NUNL PEOPLE 4527 03:09:35,360 --> 03:09:36,880 TO RESPOND WE CAN START TO GET 4528 03:09:36,880 --> 03:09:39,320 THERE AND ADDS LAYER OF 4529 03:09:39,320 --> 03:09:40,680 COMPLEXITY THAT IS REAL. 4530 03:09:40,680 --> 03:09:43,000 >> YEAH. THAT IS GREAT AND 4531 03:09:43,000 --> 03:09:45,480 KIND OF FOLLOWING A FOLLOW UP TO 4532 03:09:45,480 --> 03:09:47,360 THE NEXT QUESTION SOMEONE ASKED 4533 03:09:47,360 --> 03:09:50,200 ABOUT LOSS TO FOLLOW UP AND 4534 03:09:50,200 --> 03:09:52,520 HANDLING THAT STATISTICALLY AND 4535 03:09:52,520 --> 03:09:54,520 WONDERING IF YOU HAVE BRILLIANT 4536 03:09:54,520 --> 03:09:55,960 IDEAS ABOUT BEST WAY TO HANDLE 4537 03:09:55,960 --> 03:09:57,920 LOSS OF FOLLOW UP AND 4538 03:09:57,920 --> 03:09:59,000 POPULATIONS THAT ARE PRONE TO 4539 03:09:59,000 --> 03:10:01,320 NOT HAVING FULL FOLLOW UP. 4540 03:10:01,320 --> 03:10:08,040 >> I AM SAD TO SAY THAT GRANTS 4541 03:10:08,040 --> 03:10:10,640 LATER MY WHOLE PHD I DON'T -- 4542 03:10:10,640 --> 03:10:13,640 MORE I TRY TO STUDY IT I FEEL IT 4543 03:10:13,640 --> 03:10:17,120 IS SUBOPTIMAL AND COMING TO 4544 03:10:17,120 --> 03:10:18,680 TERMS STARTING TO NOT LIKE 4545 03:10:18,680 --> 03:10:20,080 COMPOSITE ENDPOINTS THEY ARE 4546 03:10:20,080 --> 03:10:21,520 RIGHT ANSWER AND WE HAVE TO 4547 03:10:21,520 --> 03:10:23,360 FIGURE OUT HOW TO PUT THEM 4548 03:10:23,360 --> 03:10:23,720 TOGETHER. 4549 03:10:23,720 --> 03:10:25,960 I'M NOT A FAN AS MUCH AS I USED 4550 03:10:25,960 --> 03:10:28,680 TO BE OF LOTS OF STATISTICAL 4551 03:10:28,680 --> 03:10:31,960 APPROACHES AND THEY TRANSFORM 4552 03:10:31,960 --> 03:10:34,480 DATA INTO AN EFFECT ESTIMATE 4553 03:10:34,480 --> 03:10:35,920 WITH STATISTICAL ASSUMPTIONS 4554 03:10:35,920 --> 03:10:38,520 THAT ARE HARD TO UNDERSTAND AND 4555 03:10:38,520 --> 03:10:40,440 THESE ARE ALWAYS INHERENT THINGS 4556 03:10:40,440 --> 03:10:42,400 TO THEM. 4557 03:10:42,400 --> 03:10:45,160 OTHER ONES LIKE ADVERSE 4558 03:10:45,160 --> 03:10:47,440 PROBABILITY WAITING AND JOINT 4559 03:10:47,440 --> 03:10:50,200 MODELING MAKE ASSUMPTION AND 4560 03:10:50,200 --> 03:10:51,440 ESTIMATE REPRESENTS 4561 03:10:51,440 --> 03:10:52,600 COUNTERFACTUAL POPULATION IF NO 4562 03:10:52,600 --> 03:10:54,200 ONE DIED OF THIS REASON THAT IS 4563 03:10:54,200 --> 03:10:55,760 AN ODD CONCEPT WHEN YOU THINK 4564 03:10:55,760 --> 03:10:56,520 ABOUT IT. 4565 03:10:56,520 --> 03:10:58,760 SO, I FEEL THEY GET TOO FAR AWAY 4566 03:10:58,760 --> 03:11:02,240 FROM WHAT WE ACTUALLY WANT TO 4567 03:11:02,240 --> 03:11:02,640 KNOW. 4568 03:11:02,640 --> 03:11:04,600 SO, THAT IS NOT A GREAT ANSWER. 4569 03:11:04,600 --> 03:11:06,160 I WILL ACKNOWLEDGE IT IS A HARD 4570 03:11:06,160 --> 03:11:09,000 -- I DON'T THINK THERE IS A GOOD 4571 03:11:09,000 --> 03:11:14,000 ANSWER BUT SUBOPTIMAL SOLUTION. 4572 03:11:14,000 --> 03:11:14,560 >> FAIR. 4573 03:11:14,560 --> 03:11:16,000 >> WE SHOULD PROBABLY. 4574 03:11:16,000 --> 03:11:17,840 >> DO PANEL DISCUSSION, YEAH. 4575 03:11:17,840 --> 03:11:18,120 PERFECT. 4576 03:11:18,120 --> 03:11:19,480 >> LET'S DO THAT. 4577 03:11:19,480 --> 03:11:22,120 SO, WHAT I THOUGHT WE WOULD DO 4578 03:11:22,120 --> 03:11:25,120 IS THIS IS -- THIS HAS BEEN 4579 03:11:25,120 --> 03:11:26,400 REALLY GREAT AND WANT TO COMMEND 4580 03:11:26,400 --> 03:11:31,200 4 SPEAKERS ON GIVING SUCCINCT 4581 03:11:31,200 --> 03:11:33,520 AND PROVOCATIVE TALKS NOT ALWAYS 4582 03:11:33,520 --> 03:11:35,560 EASIEST THING TO DO. STEPHANIE 4583 03:11:35,560 --> 03:11:37,400 AND I TALKED ABOUT GIVING A 4584 03:11:37,400 --> 03:11:39,360 BRIEF SUMMARY OF MAJOR ISSUES 4585 03:11:39,360 --> 03:11:42,960 THAT ARE RAISED AND ACTUALLY I 4586 03:11:42,960 --> 03:11:46,960 THINK FLOWS VERY NICELY. 4587 03:11:46,960 --> 03:11:49,160 IT SPEAKS TO STRENGTH OF TALKS 4588 03:11:49,160 --> 03:11:53,040 AND SO THE THING OR ISSUES 4589 03:11:53,040 --> 03:11:55,680 GETTING RAISED FIRST IS CONCEPT 4590 03:11:55,680 --> 03:11:58,040 OF REVERSE TRANSLATION AND WHAT 4591 03:11:58,040 --> 03:12:01,240 PEOPLE THAT STUDY AT BEDSIDE DO 4592 03:12:01,240 --> 03:12:02,920 TO HELP FUEL BASIC SCIENCE 4593 03:12:02,920 --> 03:12:05,920 RESEARCH AND WHY IT MATTERS AND 4594 03:12:05,920 --> 03:12:07,240 GENERALIZABILITY AND TARGETING 4595 03:12:07,240 --> 03:12:08,920 CERTAIN POPULATIONS THAT GOT 4596 03:12:08,920 --> 03:12:11,000 RAISED AND WE GOT INTO THE WHOLE 4597 03:12:11,000 --> 03:12:13,360 STUDY DESIGN CONCEPTS OF WHAT DO 4598 03:12:13,360 --> 03:12:14,400 WE STUDY? 4599 03:12:14,400 --> 03:12:16,480 WHAT ARE INTERVENTIONS THAT NEED 4600 03:12:16,480 --> 03:12:22,240 TO BE INVESTIGATED? 4601 03:12:22,240 --> 03:12:23,800 MATT TALKED ABOUT PICKING SOME 4602 03:12:23,800 --> 03:12:26,120 AND THINGS USED IN PRACTICE THAT 4603 03:12:26,120 --> 03:12:27,720 CAN EFFECT BRAIN AND MUSCLE 4604 03:12:27,720 --> 03:12:32,080 OUTCOMES AND WE TALKED ABOUT 4605 03:12:32,080 --> 03:12:34,320 ALSO HOW TO MOVE FORWARD WITH 4606 03:12:34,320 --> 03:12:35,440 THE TREATMENT AND SOMETHING THAT 4607 03:12:35,440 --> 03:12:37,120 MICHAEL TALKED ABOUT AND HOW DO 4608 03:12:37,120 --> 03:12:40,520 WE TALK ABOUT WHAT WE SHOULD BE 4609 03:12:40,520 --> 03:12:41,760 STUDYING? 4610 03:12:41,760 --> 03:12:43,720 DALE RAISED EXTREMELY IMPORTANT 4611 03:12:43,720 --> 03:12:46,040 ISSUES FOCUSED ON REHAB THAT I 4612 03:12:46,040 --> 03:12:49,080 THINK CAN BE EXPANDED. 4613 03:12:49,080 --> 03:12:50,960 INTENSITY DURATION AND WHO 4614 03:12:50,960 --> 03:12:52,760 PERFORMS IT AND HOW LONG IS 4615 03:12:52,760 --> 03:12:53,960 PERFORMED AND WHERE IT IS 4616 03:12:53,960 --> 03:12:57,440 PERFORMED AND WHO, ET CETERA. 4617 03:12:57,440 --> 03:13:00,440 ALL THESE QUESTIONS THAT ARE 4618 03:13:00,440 --> 03:13:02,280 IMPORTANT NOT ONLY TO REHAB BUT 4619 03:13:02,280 --> 03:13:04,480 OTHER INTERVENTIONS THAT WE DO. 4620 03:13:04,480 --> 03:13:06,760 THEN HOW DO WE IMPLEMENT 4621 03:13:06,760 --> 03:13:11,240 INTERVENTIONS AT EARLY STAGES? 4622 03:13:11,240 --> 03:13:13,120 MEGAN RAISED ISSUES ABOUT 4623 03:13:13,120 --> 03:13:15,640 LOOKING AT WORKFLOWS IN MIND AND 4624 03:13:15,640 --> 03:13:18,280 COMBINING IMPLEMENTATION SCIENCE 4625 03:13:18,280 --> 03:13:19,760 TYPES OF INTERVENTIONS. 4626 03:13:19,760 --> 03:13:21,360 WHAT DO WE STUDY? 4627 03:13:21,360 --> 03:13:23,920 LOTS OF QUESTIONS ARE OUT THERE 4628 03:13:23,920 --> 03:13:25,600 AND IN A VERY POSITIVE GOOD WAY 4629 03:13:25,600 --> 03:13:28,840 AND WHO TO STUDY AS DALE SAID 4630 03:13:28,840 --> 03:13:30,440 WOULD BE SECOND OP AND ABLE TO 4631 03:13:30,440 --> 03:13:31,680 PARTICIPATE AND ONE THING TO 4632 03:13:31,680 --> 03:13:36,160 TALK ABOUT IS MEASURING BASELINE 4633 03:13:36,160 --> 03:13:38,640 NUFRNGS REHAPPEN TRIALS AND WHAT 4634 03:13:38,640 --> 03:13:40,680 RIGHT CONTROL GROUP IS AND AS 4635 03:13:40,680 --> 03:13:42,320 DALE SAID I THINK IS A VERY 4636 03:13:42,320 --> 03:13:43,600 IMPORTANT QUESTION. 4637 03:13:43,600 --> 03:13:46,560 WHAT IS THE RIGHT STUDY DESIGN? 4638 03:13:46,560 --> 03:13:47,680 MICHAEL AND OTHER PEOPLE WERE 4639 03:13:47,680 --> 03:13:50,160 TALK BEING T I THINK IT IS 4640 03:13:50,160 --> 03:13:51,760 INTERESTING THAT WE DIDN'T HAVE 4641 03:13:51,760 --> 03:13:53,320 PEOPLE THAT ALL TALKED TOGETHER. 4642 03:13:53,320 --> 03:13:55,120 PEOPLE THAT ARE LEADERS IN THE 4643 03:13:55,120 --> 03:13:57,480 FIELD CAME UP WITH SIMILAR 4644 03:13:57,480 --> 03:13:59,040 SOLUTIONS FOR THE END. 4645 03:13:59,040 --> 03:14:00,520 BUT, YOU KNOW, DIFFERENT TYPES 4646 03:14:00,520 --> 03:14:01,960 OF STUDY DESIGNS. 4647 03:14:01,960 --> 03:14:05,640 HOW DO WE CONTROL FOR 4648 03:14:05,640 --> 03:14:06,160 CO-INTERVENTIONS? 4649 03:14:06,160 --> 03:14:07,880 ONCE WE FIGURED OUT WHAT 4650 03:14:07,880 --> 03:14:09,680 INTERVENTIONS DO HOW DO WE 4651 03:14:09,680 --> 03:14:12,120 DELIVER IN PROPER WAY ACROSS ICU 4652 03:14:12,120 --> 03:14:14,480 AND ON THE FLOOR AND GOING HOME 4653 03:14:14,480 --> 03:14:17,520 IN LONG-TERM CARE FACILITIES AND 4654 03:14:17,520 --> 03:14:19,120 THERE IS A TREATMENT FIDELITY 4655 03:14:19,120 --> 03:14:20,880 WITH COMPLEX INTERVENTIONS AND 4656 03:14:20,880 --> 03:14:23,120 IN PRAGMATIC TRIALS WE HAVE TO 4657 03:14:23,120 --> 03:14:25,560 BE VERY CAREFUL AND WATCH VERY 4658 03:14:25,560 --> 03:14:27,040 CLOSELY TREATMENT FIDELITY. IF 4659 03:14:27,040 --> 03:14:29,520 YOU DON'T GET SEPARATION BETWEEN 4660 03:14:29,520 --> 03:14:33,800 GROUPS IT WILL BE HARDER TO FIND 4661 03:14:33,800 --> 03:14:34,920 EFFECT SIZE. 4662 03:14:34,920 --> 03:14:38,040 LAST PART THAT IS I THINK ALSO 4663 03:14:38,040 --> 03:14:39,240 EXTREMELY IMPORTANT IS RIGHT 4664 03:14:39,240 --> 03:14:41,000 OUTCOME VARIABLES AND HOW TO 4665 03:14:41,000 --> 03:14:42,080 MEASURE THESE THINGS WHETHER 4666 03:14:42,080 --> 03:14:44,280 THEY ARE APPS OR WEARABLES AND 4667 03:14:44,280 --> 03:14:47,720 CHANGES IN THE EMR AND COMPOSITE 4668 03:14:47,720 --> 03:14:50,120 OUTCOMES AND HOW DO WE ADJUST 4669 03:14:50,120 --> 03:14:52,920 FOR A LOSS TO FOLLOW UP? 4670 03:14:52,920 --> 03:14:56,680 THEN I THINK THAT THE LAST PART 4671 03:14:56,680 --> 03:14:59,760 OF THIS IS WHO PERFORMS 4672 03:14:59,760 --> 03:15:00,960 INTERVENTIONS AND JOE RAISED 4673 03:15:00,960 --> 03:15:02,600 THIS. IT IS SOMETHING THAT IS A 4674 03:15:02,600 --> 03:15:04,800 BIT NEAR AND DEAR TO MY HEART 4675 03:15:04,800 --> 03:15:06,520 THAT WE JUST WENT THROUGH A 4676 03:15:06,520 --> 03:15:08,480 PANDEMIC AND PEOPLE ARE LEAVING 4677 03:15:08,480 --> 03:15:10,000 HEALTH CARE AND HAVING YOU KNOW 4678 03:15:10,000 --> 03:15:13,200 WHO IS GOING TO BE ABLE -- WHO 4679 03:15:13,200 --> 03:15:15,080 WILL STILL BE AROUND TO DO THESE 4680 03:15:15,080 --> 03:15:16,000 INTERVENTIONS IS I THINK 4681 03:15:16,000 --> 03:15:17,680 SOMETHING THAT IS IMPORTANT AND 4682 03:15:17,680 --> 03:15:20,000 TO JUST SUMMARIZE KIND OF 4683 03:15:20,000 --> 03:15:20,920 REVERSE TRANSLATION AND WHAT DO 4684 03:15:20,920 --> 03:15:21,920 WE STUDY? 4685 03:15:21,920 --> 03:15:24,080 WHO DO WE STUDY? 4686 03:15:24,080 --> 03:15:25,880 WHAT ARE RIGHT STUDY DESIGNS AND 4687 03:15:25,880 --> 03:15:28,400 HOW DO WE MAKE SURE TREATMENT 4688 03:15:28,400 --> 03:15:30,240 INTERVENTION IS DONE IN A 4689 03:15:30,240 --> 03:15:30,960 FIDELITY WAY? 4690 03:15:30,960 --> 03:15:33,040 WHAT ARE RIGHT OUTCOMES AND 4691 03:15:33,040 --> 03:15:36,400 THESE ARE I THINK BASIC 4692 03:15:36,400 --> 03:15:36,840 SUMMARIES. 4693 03:15:36,840 --> 03:15:41,120 FIRST QUESTION I WOULD LIKE TO 4694 03:15:41,120 --> 03:15:43,040 A 4695 03:15:43,040 --> 03:15:43,240 ASK. 4696 03:15:43,240 --> 03:15:44,120 PLEASE CHIME IN WITH QUESTIONS 4697 03:15:44,120 --> 03:15:46,120 IF IN THE CHAT AND I WAS TALKING 4698 03:15:46,120 --> 03:15:48,760 ABOUT HOW WE MEASURE BASELINE 4699 03:15:48,760 --> 03:15:56,760 FUNCTION IN REHAB TRIALS. 4700 03:15:56,760 --> 03:15:57,960 LY ASK DALE THAT DIRECTLY. MATT 4701 03:15:57,960 --> 03:15:58,920 HAD TO GO. 4702 03:15:58,920 --> 03:16:00,320 DALE, THAT IS SOMETHING YOU HAVE 4703 03:16:00,320 --> 03:16:03,160 THOUGHT ABOUT A LOT. HOW DO WE 4704 03:16:03,160 --> 03:16:04,960 MEASURE BASELINE FUNCTION? 4705 03:16:04,960 --> 03:16:08,560 >> LOWEST HANGING FRUIT IS NOW 4706 03:16:08,560 --> 03:16:11,080 STUDIES USE EXISTING INSTRUMENT 4707 03:16:11,080 --> 03:16:14,640 AND ENROLL PEOPLE PATIENTS HAVE 4708 03:16:14,640 --> 03:16:20,880 HIGH INDEX SCORES THAT CAN BE 4709 03:16:20,880 --> 03:16:22,360 EVALUATED IN APPROXIMATELY BY 4710 03:16:22,360 --> 03:16:23,960 FAMILY MEMBER AND TIME OF 4711 03:16:23,960 --> 03:16:27,920 CONSENT THAT IS BASIC WAY IN 4712 03:16:27,920 --> 03:16:31,480 FUNDED RANDOMIZED TRIAL GOING ON 4713 03:16:31,480 --> 03:16:34,760 NOW WE HAVE A WALKING DISTANCE 4714 03:16:34,760 --> 03:16:39,360 PRIOR TO ICU AND ONE BLOCHL 4715 03:16:39,360 --> 03:16:43,400 BASED ON EXISTING INSTRUMENT. 4716 03:16:43,400 --> 03:16:46,800 THEY ARE PERFECT WAYS AND 4717 03:16:46,800 --> 03:16:49,960 ENROLLING PEOPLE WITH PERFECT 4718 03:16:49,960 --> 03:16:52,880 BASELINE FUNCTION AT LEAST USING 4719 03:16:52,880 --> 03:16:54,840 EXISTING INSTRUMENTS MOVING 4720 03:16:54,840 --> 03:16:58,080 FURTHER DOWN SCALE AND 4721 03:16:58,080 --> 03:17:02,160 STRATIFYING AND THINK THAT IS A 4722 03:17:02,160 --> 03:17:03,920 FEASIBLE WAY AND PEOPLE HAVE 4723 03:17:03,920 --> 03:17:04,640 BETTER IDEAS. 4724 03:17:04,640 --> 03:17:08,760 >> DO YOU HAVE A QUESTION? 4725 03:17:08,760 --> 03:17:14,440 WANT TO CHIME IN. 4726 03:17:14,440 --> 03:17:18,200 >> HIGHLIGHTING JACKS QUESTION 4727 03:17:18,200 --> 03:17:20,160 MATTER IF WE MEASURE BASELINE 4728 03:17:20,160 --> 03:17:22,080 FUNCTION AND RANDOMIZE ACROSS 4729 03:17:22,080 --> 03:17:24,280 BOTH GROUPS EVENLY IS IT SUPER 4730 03:17:24,280 --> 03:17:25,840 IMPORTANT TO MEASURE BASELINE 4731 03:17:25,840 --> 03:17:28,320 FUNCTION? 4732 03:17:28,320 --> 03:17:35,240 >> I THINK IT IS. 4733 03:17:35,240 --> 03:17:39,320 INTERVENTION MIGHT HAVE A BIG 4734 03:17:39,320 --> 03:17:42,920 IMPACT OUTCOME AND THINK 4735 03:17:42,920 --> 03:17:45,760 UNDERSTANDING OUTCOMES WE WANT 4736 03:17:45,760 --> 03:17:47,360 TO KNOW SOMETHING ABOUT BOOIS 4737 03:17:47,360 --> 03:17:49,040 LINE STATUS FOR INTERP 4738 03:17:49,040 --> 03:17:49,720 RECEIPTING IT. 4739 03:17:49,720 --> 03:17:54,360 YOU KNOW, TWO RANDOMIZED TRIALS 4740 03:17:54,360 --> 03:17:57,840 PUBLISHED IN LANCIT IN MEDICAL 4741 03:17:57,840 --> 03:18:04,680 PATIENTS IN US AND CANADA 4742 03:18:04,680 --> 03:18:08,080 ENROLLED PATIENTS -- 13 OF 4743 03:18:08,080 --> 03:18:13,720 PEOPLIN DEPENDENT LY -- I WOULD 4744 03:18:13,720 --> 03:18:17,160 UNDERSTAND DIFFERENTLY BASED ON 4745 03:18:17,160 --> 03:18:19,840 KNOWING THAT BASED ON FUNCTION. 4746 03:18:19,840 --> 03:18:21,400 I APPRECIATE WHAT JACK IS SAYING 4747 03:18:21,400 --> 03:18:23,240 THAT IS IMPORTANT AND NOT DOING 4748 03:18:23,240 --> 03:18:25,160 SUPER LARGE TRIAL SUCH IT WILL 4749 03:18:25,160 --> 03:18:29,320 MAKE ITS WAY OUT IN THE WASH. 4750 03:18:29,320 --> 03:18:30,840 THAT IS MY FEELING. 4751 03:18:30,840 --> 03:18:33,040 >> GREAT. THANKS. 4752 03:18:33,040 --> 03:18:37,120 ANOTHER QUESTION FROM ME TO YOU 4753 03:18:37,120 --> 03:18:40,240 AND MICHAEL AND MARK. 4754 03:18:40,240 --> 03:18:44,520 EVERYONE PROPOSED PLATFORM 4755 03:18:44,520 --> 03:18:46,680 ADAPTIVE TRIAL WITH 4756 03:18:46,680 --> 03:18:48,600 IMPLEMENTATION FOCUS THINK THAT 4757 03:18:48,600 --> 03:18:52,520 IS FEASIBLE IN NEAR TERM WITH 4758 03:18:52,520 --> 03:18:53,560 REGULATORY CONDITIONS AND TRIALS 4759 03:18:53,560 --> 03:18:55,800 AND STRUCTURES AND FUNDING MOON 4760 03:18:55,800 --> 03:18:57,600 SHOT PIE IN SKY LOTS OF THINGS 4761 03:18:57,600 --> 03:19:00,760 HAVE TO CHANGE BEFORE WE GET 4762 03:19:00,760 --> 03:19:03,040 THE 4763 03:19:03,040 --> 03:19:03,240 THERE. 4764 03:19:03,240 --> 03:19:06,720 >> I DON'T MIND FIRST WE HAVE 4765 03:19:06,720 --> 03:19:13,120 BENEFIT OF MULTIPLE OTHER 4766 03:19:13,120 --> 03:19:18,560 COUNTRIES REMARKABLE TEAM AT 4767 03:19:18,560 --> 03:19:20,560 TORONTO GO LIVE AND LEARNED LAST 4768 03:19:20,560 --> 03:19:23,960 THREE YEARS GOING TOGETHER WE 4769 03:19:23,960 --> 03:19:27,040 CAN JOIN THEM BIG PROPONENT OF 4770 03:19:27,040 --> 03:19:28,560 MULTINATIONAL PLATFORM TRIAL AND 4771 03:19:28,560 --> 03:19:31,880 REMAP CAP I DON'T KNOW HOW THEY 4772 03:19:31,880 --> 03:19:35,320 ARE FUNDED HE NO REASON THAT 4773 03:19:35,320 --> 03:19:36,320 FUNDING AGENCY CAN'T GET 4774 03:19:36,320 --> 03:19:38,040 TOGETHER WORKING INTERNATIONALLY 4775 03:19:38,040 --> 03:19:40,080 AND I THINK WE COULD -- THERE IS 4776 03:19:40,080 --> 03:19:41,880 A REASON TO RELEARN AND WE CAN 4777 03:19:41,880 --> 03:19:43,480 ADAPT AND PARTNER UP AND THERE 4778 03:19:43,480 --> 03:19:45,960 IS HUGE POTENTIAL THERE IN 4779 03:19:45,960 --> 03:19:49,080 SAMPLE SIZE ALONE BEYOND 4780 03:19:49,080 --> 03:19:50,440 ANYTHING ELSE. 4781 03:19:50,440 --> 03:19:52,760 >> I WILL GIVE TWO CENTS 4782 03:19:52,760 --> 03:19:53,960 STEPHANIE. I AGREE WITH MICHAEL 4783 03:19:53,960 --> 03:19:57,760 AND THINK IT IS A WAY TO GO. I 4784 03:19:57,760 --> 03:19:58,920 THINK THAT PEOPLE SOMETIMES WHEN 4785 03:19:58,920 --> 03:20:01,040 THERE IS A NEW IDEA COMING UP 4786 03:20:01,040 --> 03:20:02,440 PEOPLE ARE LIKE THIS IS GREAT 4787 03:20:02,440 --> 03:20:04,400 AND LET'S DO THIS. WILL ANSWER 4788 03:20:04,400 --> 03:20:08,360 ALL PROBLEMS AND CENTRAL IRB IS 4789 03:20:08,360 --> 03:20:10,040 GOOD EXAMPLE IF WE HAVE THIS 4790 03:20:10,040 --> 03:20:12,280 WON'T HAVE ISSUES AT ALL AND 4791 03:20:12,280 --> 03:20:13,640 ISSUES CHANGED A LITTLE BIT AND 4792 03:20:13,640 --> 03:20:15,880 THINK IT IS A WAY TO GO AND 4793 03:20:15,880 --> 03:20:17,040 DESIGNING THESE AND GETTING THEM 4794 03:20:17,040 --> 03:20:20,240 TO BE ALIGNED EFFECTIVELY AND 4795 03:20:20,240 --> 03:20:25,040 HOW YOU IMPLEMENT IT AMICHAEL 4796 03:20:25,040 --> 03:20:26,400 NOT SURE IF YOU SAID 4797 03:20:26,400 --> 03:20:27,600 SPECIFICALLY BUT TAKES A LONG 4798 03:20:27,600 --> 03:20:28,960 TIME TO DO THAT MAYBE THREE 4799 03:20:28,960 --> 03:20:32,840 YEARS OR SO. WE CAN LEARN FROM 4800 03:20:32,840 --> 03:20:43,120 OTHER PEOPLE. 4801 03:20:44,640 --> 03:20:50,240 THIS WILL BE A HEAVY LIFT BUT 4802 03:20:50,240 --> 03:20:56,120 THINK IT WOULD BE WORTH THE 4803 03:20:56,120 --> 03:20:57,480 EFFORT. 4804 03:20:57,480 --> 03:21:01,080 THERE IS A QUESTION I HAD AND 4805 03:21:01,080 --> 03:21:04,560 WILL ASK MEGAN YOU MIGHT BE 4806 03:21:04,560 --> 03:21:07,160 INTUBATING OR TAKING CARE OF 4807 03:21:07,160 --> 03:21:09,920 PATIENTS AND NOT SURE IF SHE IS 4808 03:21:09,920 --> 03:21:11,320 STILL ON THE CALL BUT QUESTION 4809 03:21:11,320 --> 03:21:13,280 IS IT GOT RAISED ABOUT 4810 03:21:13,280 --> 03:21:15,040 OBSERVATIONAL STUDIES LOOKING AT 4811 03:21:15,040 --> 03:21:16,680 PEOPLE THAT ARE EXCEPTIONALLY 4812 03:21:16,680 --> 03:21:20,360 RESILIENT AND WHAT WE CAN LEARN 4813 03:21:20,360 --> 03:21:23,280 FROM PEOPLE THAT DON'T DEVELOP 4814 03:21:23,280 --> 03:21:24,760 ISSUES AND WHAT IS DIFFERENT 4815 03:21:24,760 --> 03:21:26,800 ABOUT THEM. MEGAN, HOW WOULD WE 4816 03:21:26,800 --> 03:21:31,120 DESIGN THAT OR IDENTIFY PEOPLE 4817 03:21:31,120 --> 03:21:34,400 EARLY ENOUGH THAT MIGHT BE A 4818 03:21:34,400 --> 03:21:37,600 STUDY IN ITS OWN WAY WHO PEOPLE 4819 03:21:37,600 --> 03:21:39,640 ARE THAT DON'T RUN INTO THE 4820 03:21:39,640 --> 03:21:41,840 PROBLEMS MEGAN MIGHT NOT BE ON 4821 03:21:41,840 --> 03:21:44,200 THE CALL. DALE, WANT TO ADDRESS 4822 03:21:44,200 --> 03:21:44,600 THAT? 4823 03:21:44,600 --> 03:21:45,960 IMPORTANT AREA TO LOOK AT? 4824 03:21:45,960 --> 03:21:50,000 IF SO, HOW WOULD WE DO THAT? 4825 03:21:50,000 --> 03:21:55,760 >> SURE. BORROWING ON EARLIER 4826 03:21:55,760 --> 03:21:58,080 EXAMPLES ABOUT TEACHING AND I 4827 03:21:58,080 --> 03:22:00,680 THINK ABOUT A PATIENT OF MINE IN 4828 03:22:00,680 --> 03:22:04,160 RESEARCH STUDY LONGITUDINAL 4829 03:22:04,160 --> 03:22:04,720 RELATIVELY COMPREHENSIVE 4830 03:22:04,720 --> 03:22:06,080 COGNITIVE TESTING THIS PERSON 4831 03:22:06,080 --> 03:22:07,520 SAID FAMILY SAID THEY WOULDN'T 4832 03:22:07,520 --> 03:22:10,440 WANT TO LIVE PRACTICING NURSE 4833 03:22:10,440 --> 03:22:13,120 AND COGNITIVE IMPAIRMENT 4834 03:22:13,120 --> 03:22:14,840 INDEPENDENT PERSON AND THEY HAD 4835 03:22:14,840 --> 03:22:18,400 CARDIAC ARREST IN ICU AND 4836 03:22:18,400 --> 03:22:21,720 LONGEST DURATION OF DLEERIUM I 4837 03:22:21,720 --> 03:22:25,200 HAD SEEN MONTHS AND DIFFERENT 4838 03:22:25,200 --> 03:22:28,600 SERVICES LOOKED LIKE DLEERIUM 4839 03:22:28,600 --> 03:22:30,280 AND LOOKED LIKE SOMETHING ELSE 4840 03:22:30,280 --> 03:22:33,000 WASN'T CATATONIA OR SOMETHING. 4841 03:22:33,000 --> 03:22:35,520 SHE WAS IN STUDY AND ENDED UP 4842 03:22:35,520 --> 03:22:38,720 STILL TESTING MONTHS LATER AT 4843 03:22:38,720 --> 03:22:40,880 SCORES WELL ABOVE NORMAL VALUES 4844 03:22:40,880 --> 03:22:43,040 BACK TO WORK AND SHE FELT SHE IS 4845 03:22:43,040 --> 03:22:45,560 PERFORMING RELATIVELY NORMAL AND 4846 03:22:45,560 --> 03:22:47,200 WONDERED WHAT IS DIFFERENT ABOUT 4847 03:22:47,200 --> 03:22:50,600 THIS PERSON? HOW MANY TIMES 4848 03:22:50,600 --> 03:22:52,120 HAVE I MAYBE MADE 4849 03:22:52,120 --> 03:22:53,760 RECOMMENDATIONS TO FAMILY 4850 03:22:53,760 --> 03:22:55,520 MEMBERS IN PERHAPS IN YOUNGER 4851 03:22:55,520 --> 03:22:57,880 YEARS WITH GREATER CONFIDENCE 4852 03:22:57,880 --> 03:22:58,840 THAN MAYBE I HAVE. 4853 03:22:58,840 --> 03:23:00,400 I THIS I IT IS IMPORTANT TO 4854 03:23:00,400 --> 03:23:02,120 LEARN FROM THIS AND THINK AS 4855 03:23:02,120 --> 03:23:04,680 JASON WAS SAYING WE WILL NEED TO 4856 03:23:04,680 --> 03:23:06,360 EXPAND MEASUREMENT TOOLS TO BE 4857 03:23:06,360 --> 03:23:08,520 MANY THINGS OTHER THAN WHAT WE 4858 03:23:08,520 --> 03:23:10,520 TYPICALLY MEASURE. WE NEED 4859 03:23:10,520 --> 03:23:13,120 OTHER DETERMINANTS OF HEALTH 4860 03:23:13,120 --> 03:23:16,240 RATHER THAN FIZZ LOGIC AND 4861 03:23:16,240 --> 03:23:17,760 MEDICAL THINGS SOCIAL 4862 03:23:17,760 --> 03:23:19,760 DETERMINANTS OF HEALTH THINKING 4863 03:23:19,760 --> 03:23:22,000 OF FEASIBLE WAYS TO MEASURE 4864 03:23:22,000 --> 03:23:24,520 THOSE THINGS AND MEASURING THEM 4865 03:23:24,520 --> 03:23:26,640 ROUTINELY AND THINK THAT SMALL 4866 03:23:26,640 --> 03:23:30,440 SAMPLES AND PATIENTS MAY HELP US 4867 03:23:30,440 --> 03:23:33,240 BEGINNING TO STIMULATE AROUND 4868 03:23:33,240 --> 03:23:37,960 THAT GOING TO DATA AND 4869 03:23:37,960 --> 03:23:39,640 RETROSPECTIVELY COLLECTING DATA 4870 03:23:39,640 --> 03:23:40,720 ELEMENTS AND TREATMENT EFFECTS 4871 03:23:40,720 --> 03:23:42,640 AND DON'T HAVE DETAILED ANSWER 4872 03:23:42,640 --> 03:23:45,640 BUT VALUABLE AND INSIGHTFUL WILL 4873 03:23:45,640 --> 03:23:47,720 EFFECT CLINICAL CARE AND 4874 03:23:47,720 --> 03:23:48,960 DESIGNING INTERVENTIONS AND 4875 03:23:48,960 --> 03:23:50,560 UNDERSTANDING DATA AND THINK IT 4876 03:23:50,560 --> 03:23:51,760 IS A GREAT IDEA. 4877 03:23:51,760 --> 03:23:55,400 >> STEPHANIE, HAVE A QUESTION 4878 03:23:55,400 --> 03:23:58,000 THAT YOU WANT TO RAISE? 4879 03:23:58,000 --> 03:23:59,520 I HAVE ONE BUT WHY DON'T YOU. 4880 03:23:59,520 --> 03:24:03,520 >> I WILL JUMP IN WITH ONE 4881 03:24:03,520 --> 03:24:05,360 QUICKLY. WE TALK ABOUT TRIALS 4882 03:24:05,360 --> 03:24:07,040 AND MICHAEL BROUGHT UP 4883 03:24:07,040 --> 03:24:08,640 OBSERVATIONAL DATA AND WAYS TO 4884 03:24:08,640 --> 03:24:10,720 USE OBSERVATIONAL DATA WITH 4885 03:24:10,720 --> 03:24:13,640 TARGET TRIAL EMULATION AND 4886 03:24:13,640 --> 03:24:17,760 REANALYZING TRIALS WITH BAYESIAN 4887 03:24:17,760 --> 03:24:19,720 ANALYSIS FRAMEWORKS AND DO YOU 4888 03:24:19,720 --> 03:24:22,440 THINK THAT, THAT -- WE SHOULD 4889 03:24:22,440 --> 03:24:24,600 ALSO BROADEN OUR MINDS IN TERMS 4890 03:24:24,600 --> 03:24:27,400 HOW WE LOOK AT OBSERVATIONAL 4891 03:24:27,400 --> 03:24:29,320 DATA AND LOOKING AT WHAT 4892 03:24:29,320 --> 03:24:30,960 INTERVENTIONS MIGHT BE 4893 03:24:30,960 --> 03:24:31,240 EFFECTIVE? 4894 03:24:31,240 --> 03:24:32,560 IS THERE A BIG OPPORTUNITY FOR 4895 03:24:32,560 --> 03:24:34,520 THAT OR THINKING IT IS STILL 4896 03:24:34,520 --> 03:24:36,320 TRIALS ALL THE WAY? 4897 03:24:36,320 --> 03:24:38,040 >> NOT SURE IF ANYBODY -- I CAN 4898 03:24:38,040 --> 03:24:41,680 PUT IN CHAT ARTICLE IN JAMA THIS 4899 03:24:41,680 --> 03:24:43,520 WE'RE THERE IS 32 TRIALS AND 4900 03:24:43,520 --> 03:24:46,200 THEY DID EMULATED TRIALS AND 4901 03:24:46,200 --> 03:24:47,560 RESULTS ARE NOT DISSIMILAR TO 4902 03:24:47,560 --> 03:24:50,720 WHAT I SHOWED IN ANDREW'S PAPER. 4903 03:24:50,720 --> 03:24:53,240 SO, I MEAN, THINGS YOU NEVER 4904 03:24:53,240 --> 03:24:54,840 KNOW TRUTH EVEN IN A TRIAL AND 4905 03:24:54,840 --> 03:24:56,800 THINK THERE IS STILL VALUE IN 4906 03:24:56,800 --> 03:24:58,960 TRIALS IN LEARNING FROM THEM. 4907 03:24:58,960 --> 03:25:01,440 SCIENCE IS GETTING REALLY G I 4908 03:25:01,440 --> 03:25:03,760 MEAN, THERE IS ALWAYS AEND USER 4909 03:25:03,760 --> 03:25:05,200 AND UP TO THE PERSON EXECUTING 4910 03:25:05,200 --> 03:25:09,240 IT BUT ARE REALLY GOOD PEOPLE 4911 03:25:09,240 --> 03:25:10,640 THROUGHOUT. MIGUEL AND 4912 03:25:10,640 --> 03:25:11,320 [INDISCERNIBLE] AND HAVE BEEN 4913 03:25:11,320 --> 03:25:14,000 SEVERAL PAPERS IN THE PANDEMIC 4914 03:25:14,000 --> 03:25:17,200 THAT PERFECTLY REPLICATE RESULTS 4915 03:25:17,200 --> 03:25:19,640 OF RANDOMIZED TRIALS I USED TO 4916 03:25:19,640 --> 03:25:22,520 BE A CHEMIST BUT I'M QUITE 4917 03:25:22,520 --> 03:25:24,520 IMPRESSED RECENTLY AND WILL PUT 4918 03:25:24,520 --> 03:25:26,120 IT IN THE CHAT. 4919 03:25:26,120 --> 03:25:27,400 >> THANKS, MICHAEL. 4920 03:25:27,400 --> 03:25:29,280 >> GLAD YOU COULD POINT THAT 4921 03:25:29,280 --> 03:25:29,480 OUT. 4922 03:25:29,480 --> 03:25:31,040 >> QUESTION FOR MICHAEL ALSO. 4923 03:25:31,040 --> 03:25:33,080 I WILL LET YOU TYPE. ONE I WANT 4924 03:25:33,080 --> 03:25:36,720 TO SAY IS I THINK YOUR ANALOGY 4925 03:25:36,720 --> 03:25:40,000 OF THE FOOTBALL OR SOCCER 4926 03:25:40,000 --> 03:25:41,480 STADIUMS IN QATAR IS A REALLY 4927 03:25:41,480 --> 03:25:43,560 GOOD ONE. HAVING BEEN TO FOUR 4928 03:25:43,560 --> 03:25:45,400 OF THEM I WENT TO ACTUALLY THE 4929 03:25:45,400 --> 03:25:47,360 WORLD CUP. IT IS INTERESTING 4930 03:25:47,360 --> 03:25:50,320 BECAUSE OUTSIDES ARE VERY 4931 03:25:50,320 --> 03:25:52,120 DIFFERENT AND THERE IS ONE BUILT 4932 03:25:52,120 --> 03:25:54,920 FROM SHIPPING CONTAINERS AND 4933 03:25:54,920 --> 03:25:57,160 INSIDE OF THE STADIUMS WERE VERY 4934 03:25:57,160 --> 03:25:59,040 MUCH THE SAME AND WASN'T THAT 4935 03:25:59,040 --> 03:26:00,600 EVERYTHING WAS TOTALLY 4936 03:26:00,600 --> 03:26:01,560 DIFFERENT. 4937 03:26:01,560 --> 03:26:03,200 THERE WAS STANDARDIZATION TO IT 4938 03:26:03,200 --> 03:26:05,720 BUT WITH ADAPTATION ON OUTSIDE. 4939 03:26:05,720 --> 03:26:06,080 >> YEAH. 4940 03:26:06,080 --> 03:26:09,440 >> YOU CAN BETTER HAVE AN 4941 03:26:09,440 --> 03:26:12,480 ANALOGY THAT MAYBE YOU REALIZED 4942 03:26:12,480 --> 03:26:14,360 AND QUESTION I SHOULD HAVE. 4943 03:26:14,360 --> 03:26:15,360 >> [INDISCERNIBLE]. 4944 03:26:15,360 --> 03:26:16,120 >> OH, OKAY. 4945 03:26:16,120 --> 03:26:17,640 >> SORRY NOT TO TAKE YOUR 4946 03:26:17,640 --> 03:26:19,440 QUESTION SCOMBL I WILL TALK TO 4947 03:26:19,440 --> 03:26:21,920 DEREK ABOUT IT AND LET HIM KNOW. 4948 03:26:21,920 --> 03:26:23,920 QUESTION IS ABOUT OUTCOME 4949 03:26:23,920 --> 03:26:25,880 VARIABLES AND COMPOSITE OUTCOMES 4950 03:26:25,880 --> 03:26:28,840 AND RAISING ISSUE ABOUT WHAT DO 4951 03:26:28,840 --> 03:26:32,120 WE DO WITH SHORT-TERM ENDPOINTS 4952 03:26:32,120 --> 03:26:34,400 AND [INDISCERNIBLE] WE TRIED TO 4953 03:26:34,400 --> 03:26:37,000 IDENTIFY SURROGATE OUTCOMES IN 4954 03:26:37,000 --> 03:26:39,280 ICU FOREVER. THEY DON'T WORK 4955 03:26:39,280 --> 03:26:41,640 VERY WELL. WHAT IS YOUR THOUGHT 4956 03:26:41,640 --> 03:26:43,680 ABOUT DEVELOPMENT OF OR TRYING 4957 03:26:43,680 --> 03:26:46,360 TO DEVELOP BETTER SURROGATE 4958 03:26:46,360 --> 03:26:48,200 OUTCOMES SO WE DON'T -- SO THAT 4959 03:26:48,200 --> 03:26:50,320 NOT EVERY STUDY HAS TO FOLLOW 4960 03:26:50,320 --> 03:26:53,240 PEOPLE FOR FIVE YEARS, ET 4961 03:26:53,240 --> 03:26:53,520 CETERA? 4962 03:26:53,520 --> 03:26:57,080 >> YEAH. I KNOW IT IS ANOTHER 4963 03:26:57,080 --> 03:26:59,280 ONE OF THOSE PURSUITS THAT HAVE 4964 03:26:59,280 --> 03:27:04,040 BEEN KIND OF FRUITLESS. WE ARE 4965 03:27:04,040 --> 03:27:07,200 THINKING ABOUT SUR GASSY AND -- 4966 03:27:07,200 --> 03:27:09,200 AND USING THIS GROWING KIND OF 4967 03:27:09,200 --> 03:27:13,160 USING WHAT I CALL MULTICOMPONENT 4968 03:27:13,160 --> 03:27:15,120 RISK SCORES AND MULTIVARIABLE 4969 03:27:15,120 --> 03:27:17,280 RISK SCORES DON'T PROVE TO BE 4970 03:27:17,280 --> 03:27:19,400 GOOD SEROGATES BUT LIKE CONCEPT 4971 03:27:19,400 --> 03:27:21,320 THEY WANT TO FIGURE OUT MONTH 2 4972 03:27:21,320 --> 03:27:24,680 OR 3 THAT IS A DIFFERENT TIME 4973 03:27:24,680 --> 03:27:26,520 HORIZON WHAT IS SOMEBODY'S RISK 4974 03:27:26,520 --> 03:27:27,640 PROFILE AND IS THAT SOMETHING WE 4975 03:27:27,640 --> 03:27:30,240 ARE SEEING TWO YEARS LATER? I 4976 03:27:30,240 --> 03:27:32,560 DON'T KNOW HOW TO TIE TOGETHER 4977 03:27:32,560 --> 03:27:34,880 SUR GASSY MEASURES AND 4978 03:27:34,880 --> 03:27:36,080 STATISTICS IS QUITE GOOD AND 4979 03:27:36,080 --> 03:27:38,040 CAUSAL DEVELOPMENT IN THE LAST 4980 03:27:38,040 --> 03:27:40,560 COUPLE YEARS AND THINK IT IS 4981 03:27:40,560 --> 03:27:41,560 WORTH REVISITING SOME HISTORICAL 4982 03:27:41,560 --> 03:27:44,200 -- IF WE HAVE DATA WE CAN 4983 03:27:44,200 --> 03:27:46,240 REVISIT SOME CONTESTANTS BETTER 4984 03:27:46,240 --> 03:27:49,960 AND DON'T RECALL SEEING 4985 03:27:49,960 --> 03:27:51,400 SURROGATES ANALYSIS IN CLINICAL 4986 03:27:51,400 --> 03:27:53,000 CARE AND STATS THAT ARE FIRST 4987 03:27:53,000 --> 03:27:55,480 THOUGHT THAT STATS ARE TIMED AND 4988 03:27:55,480 --> 03:27:57,520 SO I THINK IT IS WORTH 4989 03:27:57,520 --> 03:27:59,560 REVISITING AND MAYBE THAT IS 4990 03:27:59,560 --> 03:28:02,200 ALSO A RESEARCH PRIORITY THAT 4991 03:28:02,200 --> 03:28:03,680 COMES FROM THE TALK AND HAPPY TO 4992 03:28:03,680 --> 03:28:09,120 HELP IF YOU HAVE THOUGHTS ABOUT 4993 03:28:09,120 --> 03:28:09,320 DATA. 4994 03:28:09,320 --> 03:28:11,440 NOT A PERFECT ANSWER BUT COULD 4995 03:28:11,440 --> 03:28:12,920 BE PROMISING. 4996 03:28:12,920 --> 03:28:15,040 >> I THINK IT IS -- I THINK IT 4997 03:28:15,040 --> 03:28:19,760 IS AN AREA THAT NEEDS TO BE 4998 03:28:19,760 --> 03:28:20,080 DEVELOPED. 4999 03:28:20,080 --> 03:28:20,360 >> YEAH. 5000 03:28:20,360 --> 03:28:22,040 >> TALKING ABOUT WHAT WE 5001 03:28:22,040 --> 03:28:24,320 MEASURE IN OUTCOMES THAT IS VERY 5002 03:28:24,320 --> 03:28:27,640 IMPORTANT THAT DIFFERENT THINGS 5003 03:28:27,640 --> 03:28:29,520 MEASURE DIFFERENT DOMAINS. 5004 03:28:29,520 --> 03:28:29,800 >> YEAH. 5005 03:28:29,800 --> 03:28:31,680 >> THEY ARE NOT RIGHT OR WRONG 5006 03:28:31,680 --> 03:28:33,640 BUT MEASURING DIFFERENT THINGS 5007 03:28:33,640 --> 03:28:35,200 AND WE HAVE TO DESIGN STUDIES 5008 03:28:35,200 --> 03:28:38,360 THAT ARE ANSWERING QUESTIONS 5009 03:28:38,360 --> 03:28:40,080 THAT WE CAN AND WANT TO ANSWER 5010 03:28:40,080 --> 03:28:42,800 AND THEREFORE ALIGN RIGHT 5011 03:28:42,800 --> 03:28:44,840 OUTCOME VARIABLE WHAT RIGHT 5012 03:28:44,840 --> 03:28:45,520 STUDY IS. 5013 03:28:45,520 --> 03:28:47,720 QUESTION IS: ARE THERE -- IS 5014 03:28:47,720 --> 03:28:51,400 THERE NEED FOR DEVELOPMENT OF 5015 03:28:51,400 --> 03:28:55,200 OTHER OUTCOMES THAT COULD BE 5016 03:28:55,200 --> 03:28:57,200 USED FOR SURROGATE OUTCOMES, ET 5017 03:28:57,200 --> 03:28:57,520 CETERA? 5018 03:28:57,520 --> 03:28:59,600 I THINK ANSWER IS YES, 5019 03:28:59,600 --> 03:28:59,960 PERSONALLY. 5020 03:28:59,960 --> 03:29:00,400 >> YEAH. 5021 03:29:00,400 --> 03:29:02,800 >> BUT, I -- JUST BECAUSE 5022 03:29:02,800 --> 03:29:03,520 SOMETHING IS DIFFICULT DOESN'T 5023 03:29:03,520 --> 03:29:05,560 MEAN WE SHOULDN'T TRY TO DO IT. 5024 03:29:05,560 --> 03:29:08,040 >> I WANT TO TIE BACK THAT I 5025 03:29:08,040 --> 03:29:10,040 THINK JIM AND KARLA YESTERDAY 5026 03:29:10,040 --> 03:29:12,840 HAD REALLY GREAT INFORMATION AND 5027 03:29:12,840 --> 03:29:14,960 IDEAS ABOUT DIFFERENCES AND JIM 5028 03:29:14,960 --> 03:29:16,960 ESPECIALLY WITH STANDARDIZED 5029 03:29:16,960 --> 03:29:18,120 COGNITIVE FUNCTIONING VERSUS 5030 03:29:18,120 --> 03:29:20,640 WHAT IT TAKES TO PERFORM AND IS 5031 03:29:20,640 --> 03:29:23,200 VALUABLE TO PEOPLE AND JASON 5032 03:29:23,200 --> 03:29:24,320 TALKING ABOUT SOCIAL 5033 03:29:24,320 --> 03:29:25,880 DETERMINANTS THAT WE HAVE TO 5034 03:29:25,880 --> 03:29:28,040 BUILD INTO RESEARCH MUCH MORE 5035 03:29:28,040 --> 03:29:30,040 AND PEOPLE LIKE JASON CAN GUIDE 5036 03:29:30,040 --> 03:29:33,840 US INTO WHAT TO DO AND JOHNS 5037 03:29:33,840 --> 03:29:35,840 HOPKINS AND EPIDEMIOLOGIST THAT 5038 03:29:35,840 --> 03:29:39,440 WILL GET NIH FUNDED R01 THAT 5039 03:29:39,440 --> 03:29:40,920 WILL BUILD ON PRIOR RESEARCH TO 5040 03:29:40,920 --> 03:29:43,200 LOOK AT ROLE OF HEALTH 5041 03:29:43,200 --> 03:29:44,200 EXPECTATIONS AND VERY, VERY 5042 03:29:44,200 --> 03:29:46,040 DIFFERENT. WHAT YOU ARE 5043 03:29:46,040 --> 03:29:49,520 EXPECTING EARLY ON MIGHT HAVE 5044 03:29:49,520 --> 03:29:53,960 BIG IMPACT HOW YOU PERCEIVE LIFE 5045 03:29:53,960 --> 03:29:56,160 AFTERWARDS INCLUDING DIIAD 5046 03:29:56,160 --> 03:29:58,160 ANALYSIS LOOKING AT PATIENTS 5047 03:29:58,160 --> 03:29:59,560 CAREGIVER SPOUSE AND WHAT 5048 03:29:59,560 --> 03:30:00,720 EXPECTATIONS ARE AND WHAT 5049 03:30:00,720 --> 03:30:03,400 ALLISON IS ALSO TRYING TO MODIFY 5050 03:30:03,400 --> 03:30:05,000 THIS IS THIS SOMETHING WE CAN 5051 03:30:05,000 --> 03:30:07,880 MODIFY AS CLINICIANS HELPING 5052 03:30:07,880 --> 03:30:11,200 PEOPLE EXPECT WHAT TO GET FROM 5053 03:30:11,200 --> 03:30:13,280 ICU CLINIC WHEN GETTING TO 5054 03:30:13,280 --> 03:30:15,800 FOLLOW UP CLINIC AND LEADING 5055 03:30:15,800 --> 03:30:18,680 EDGE IF WE DON'T KNOW ANSWERS 5056 03:30:18,680 --> 03:30:20,640 AND IN TURN SHOULD HELP INFORM 5057 03:30:20,640 --> 03:30:21,920 THAT AND ONE VARIABLE TO 5058 03:30:21,920 --> 03:30:24,720 UNDERSTAND TO LOOK AT PATIENT 5059 03:30:24,720 --> 03:30:26,600 REPORTED OUTCOMES LONGER. 5060 03:30:26,600 --> 03:30:29,080 >> AWESOME. I THINK WE MIGHT 5061 03:30:29,080 --> 03:30:31,880 HAVE TIME FOR ONE MORE QUESTION. 5062 03:30:31,880 --> 03:30:34,360 DALE, YOU BROUGHT IT UP A LITTLE 5063 03:30:34,360 --> 03:30:35,640 BIT IN YOUR TALK AND DR. SHAR 5064 03:30:35,640 --> 03:30:37,880 SHAR ASKED A QUESTION ABOUT 5065 03:30:37,880 --> 03:30:39,400 TIMING OF INTERVENTION DELIVERY 5066 03:30:39,400 --> 03:30:43,480 AND WHETHER TO BE FOCUSED ON -- 5067 03:30:43,480 --> 03:30:44,920 OUR INTERVENTIONS IMPROVING 5068 03:30:44,920 --> 03:30:46,920 BRAIN AND MUSCLE DISFUNCTION AND 5069 03:30:46,920 --> 03:30:48,840 SHOULD THEY BE IN ACUTE OR 5070 03:30:48,840 --> 03:30:50,720 WEENING PHASE OR RECOVERY PHASE? 5071 03:30:50,720 --> 03:30:54,080 I THOUGHT I THINK IT WAS JASON 5072 03:30:54,080 --> 03:30:56,320 WHOSE BIOLOGICAL MODELS ARGUMENT 5073 03:30:56,320 --> 03:30:59,240 IS FOCUSING ON RECOVERY AND 5074 03:30:59,240 --> 03:31:00,880 INJURY BREAKDOWN FOR MUSCLES 5075 03:31:00,880 --> 03:31:03,720 MIGHT BE ADAPTIVE AND FOCUSING 5076 03:31:03,720 --> 03:31:05,520 ON RECOVERY PHASE AND INTERESTED 5077 03:31:05,520 --> 03:31:07,520 IN WHAT YOU THINK ABOUT TRIAL 5078 03:31:07,520 --> 03:31:09,280 DESIGN AND INTERVENTION DELIVERY 5079 03:31:09,280 --> 03:31:09,520 TIMING. 5080 03:31:09,520 --> 03:31:11,200 >> FOR ME, I THINK THERE IS 5081 03:31:11,200 --> 03:31:13,040 ENOUGH DATA THAT EARLIER IS 5082 03:31:13,040 --> 03:31:13,280 BETTER. 5083 03:31:13,280 --> 03:31:15,200 I THINK THAT IS NOT AN IMPORTANT 5084 03:31:15,200 --> 03:31:16,240 QUESTION FOR THE FIELD. 5085 03:31:16,240 --> 03:31:18,200 I RECOGNIZE THAT PEOPLE MAY 5086 03:31:18,200 --> 03:31:19,680 DISAGREE WITH ME. 5087 03:31:19,680 --> 03:31:22,080 I THINK THAT WE SEE CONSISTENTLY 5088 03:31:22,080 --> 03:31:23,880 THAT INTERVENTIONS STARTING IN 5089 03:31:23,880 --> 03:31:27,200 DAY 1, 2, OR 3 HAVE BETTER 5090 03:31:27,200 --> 03:31:29,000 OUTCOMES THAN SAME INTERVENTION 5091 03:31:29,000 --> 03:31:30,320 STARTING AROUND DAY 7 LOOKING 5092 03:31:30,320 --> 03:31:33,040 FOR EXAMPLE UNIVERSITY OF 5093 03:31:33,040 --> 03:31:35,320 CHICAGO'S RANDOMIZED CONTROL 5094 03:31:35,320 --> 03:31:40,920 TRIAL 2009 PUBLISHED IN LANCIT 5095 03:31:40,920 --> 03:31:43,760 AND RESPIRATORY -- LOOKING AT 5096 03:31:43,760 --> 03:31:45,040 SAME INTERVENTION THAT WAS 5097 03:31:45,040 --> 03:31:46,400 DELIVERED EARLIER RATHER THAN 5098 03:31:46,400 --> 03:31:48,200 LATER AND PRIMARY OUTCOME IN 5099 03:31:48,200 --> 03:31:50,560 LAST RANDOMIZED TRIAL PUBLISHED 5100 03:31:50,560 --> 03:31:52,880 WEEKS AGO IS IMPROVED COGNITION 5101 03:31:52,880 --> 03:31:55,040 ONE YEAR LATER FROM EARLY ONSET 5102 03:31:55,040 --> 03:31:58,680 OF OT AND PT INTERVENTIONS 5103 03:31:58,680 --> 03:32:00,280 MECHANICALLY VENTILATED PATIENTS 5104 03:32:00,280 --> 03:32:02,240 WALKED IN DAY 2 IN THEIR STUDY 5105 03:32:02,240 --> 03:32:05,000 WITH LIKE SEDATION SO OTS AND 5106 03:32:05,000 --> 03:32:09,400 PTS COULD ACCESS PEOPLES 5107 03:32:09,400 --> 03:32:11,360 COGNITION FOR MOBILITY IN DAILY 5108 03:32:11,360 --> 03:32:13,320 LIVING AND BEFORE WE HAD MANY 5109 03:32:13,320 --> 03:32:14,960 PROBLEMS THAT IS GOOD AND NEEDS 5110 03:32:14,960 --> 03:32:17,080 TO BE PAIRED WITH WAKEFULNESS SO 5111 03:32:17,080 --> 03:32:18,880 THERE IS A BENEFIT ON THE BRAIN 5112 03:32:18,880 --> 03:32:19,600 AND BODY. 5113 03:32:19,600 --> 03:32:22,120 >> DO YOU THINK THAT DEPENDS ON 5114 03:32:22,120 --> 03:32:24,680 WHAT TYPE OF INTERVENTION IS 5115 03:32:24,680 --> 03:32:26,400 BEING DELIVERED OR IS -- DO YOU 5116 03:32:26,400 --> 03:32:28,040 THINK CONCEPTUALLY? 5117 03:32:28,040 --> 03:32:31,040 >> I THINK CONCEPTUALLY FOR 5118 03:32:31,040 --> 03:32:31,840 FUNCTIONAL INTERVENTIONS. 5119 03:32:31,840 --> 03:32:34,320 I WOULD PROBABLY EVEN ARGUE FOR 5120 03:32:34,320 --> 03:32:36,920 PASSIVE INTERVENTIONS LIKE 5121 03:32:36,920 --> 03:32:40,000 NEUROMUSCULAR ELECTRICAL 5122 03:32:40,000 --> 03:32:42,040 STIMULATION IN DED PSYCHOGOMTRY 5123 03:32:42,040 --> 03:32:44,680 AND WE COULD DO A LARGER 5124 03:32:44,680 --> 03:32:45,800 RANDOMIZED TRIAL BUT HAVE ENOUGH 5125 03:32:45,800 --> 03:32:49,120 SMALLER TRIALS SHOWING THAT 5126 03:32:49,120 --> 03:32:52,160 EARLY COMPARED TO LATE WERE LATE 5127 03:32:52,160 --> 03:32:53,680 PATIENTS GETTING BED REST FOR 5128 03:32:53,680 --> 03:32:56,040 DAYS CONSISTENTLY IMPROVES 5129 03:32:56,040 --> 03:32:58,160 PATIENT OUTCOMES AND THAT IS NOT 5130 03:32:58,160 --> 03:32:59,640 SUCH AN IMPORTANT QUESTION AND 5131 03:32:59,640 --> 03:33:01,600 SATURDAY BEFORE START OF ATS WE 5132 03:33:01,600 --> 03:33:03,280 WILL HAVE A BUNCH OF EXPERTS 5133 03:33:03,280 --> 03:33:06,080 COMING TOGETHER TO SPECIFICALLY 5134 03:33:06,080 --> 03:33:09,560 BE EXPRESSING THEIR THOUGHTS ON 5135 03:33:09,560 --> 03:33:16,640 THAT SORT OF IN A DELPI LIKE 5136 03:33:16,640 --> 03:33:18,280 MANNER WHAT EXPERTS THINK RATHER 5137 03:33:18,280 --> 03:33:20,560 THAN MY BIASED OPINION. GO 5138 03:33:20,560 --> 03:33:20,760 AHEAD. 5139 03:33:20,760 --> 03:33:22,560 >> I WILL TRY TO GET ONE MORE 5140 03:33:22,560 --> 03:33:24,520 QUESTION IN. WE ACTUALLY HAVE 5141 03:33:24,520 --> 03:33:26,600 FIVE YOU KNOW A MINUTE. 5142 03:33:26,600 --> 03:33:29,920 MEGAN, ARE YOU STILL BACK ON THE 5143 03:33:29,920 --> 03:33:30,560 CALL? 5144 03:33:30,560 --> 03:33:32,200 >> AWESOME. QUESTION I HAVE 5145 03:33:32,200 --> 03:33:34,520 THAT BUILDS ON WHAT DALE SAID IS 5146 03:33:34,520 --> 03:33:38,640 I AGREE, DALE. IT ALWAYS MAKES 5147 03:33:38,640 --> 03:33:44,160 SENSE TO START SOMETHING EAR 5148 03:33:44,160 --> 03:33:44,440 EARLIER. 5149 03:33:44,440 --> 03:33:45,800 QUESTION FOR MEGAN IS PEOPLE 5150 03:33:45,800 --> 03:33:47,040 DON'T SPEND THAT MUCH TIME IN 5151 03:33:47,040 --> 03:33:49,480 THE ICU. I THINK THAT SOME OF 5152 03:33:49,480 --> 03:33:52,200 THESE INTERVENTIONS NEED TO BE 5153 03:33:52,200 --> 03:33:53,960 IMPLEMENTED FOR LONGER PERIODS 5154 03:33:53,960 --> 03:33:54,800 OF TIME. 5155 03:33:54,800 --> 03:33:56,760 WHETHER IT IS ON THE FLOOR OF 5156 03:33:56,760 --> 03:33:58,960 THE HOSPITAL OR THEN THEY GO TO 5157 03:33:58,960 --> 03:34:03,840 A LONG-TERM CARE FACILITY THAT 5158 03:34:03,840 --> 03:34:07,400 YOU LOSE CONTROL OVER THE 5159 03:34:07,400 --> 03:34:10,280 INTERVENTION AND PEOPLE 5160 03:34:10,280 --> 03:34:13,120 DISAPPEARING LEAVE THE NEXT DAY 5161 03:34:13,120 --> 03:34:14,960 IMBEDDED IN LONG TERM CARE 5162 03:34:14,960 --> 03:34:16,320 FACILITY AND NOT A LOT OF TIME 5163 03:34:16,320 --> 03:34:18,720 OR PLANNING TO COORDINATE THAT 5164 03:34:18,720 --> 03:34:21,760 FROM IMPLEMENTATION SCIENCE 5165 03:34:21,760 --> 03:34:25,680 STANDPOINT, HOW DO WE WORK IT TO 5166 03:34:25,680 --> 03:34:27,240 PROLONG DURATION OF 5167 03:34:27,240 --> 03:34:28,520 INTERVENTIONS OR MAKE SURE THAT 5168 03:34:28,520 --> 03:34:31,320 THE INTERVENTIONS ARE CONTINUED 5169 03:34:31,320 --> 03:34:34,040 ONCE THEY LEAVE THE HOSPITAL? 5170 03:34:34,040 --> 03:34:35,840 >> SO, I THINK THERE IS A 5171 03:34:35,840 --> 03:34:37,880 COUPLE WAYS TO THINK ABOUT THAT. 5172 03:34:37,880 --> 03:34:39,560 ONE, INCREASING TREND THAT WE 5173 03:34:39,560 --> 03:34:42,320 ARE SEEING IS CERT CAL 5174 03:34:42,320 --> 03:34:44,480 INTEGRATION ACROSS PAYERS AND 5175 03:34:44,480 --> 03:34:47,760 SETTINGS AND STRIKES ME VERTICAL 5176 03:34:47,760 --> 03:34:51,000 INTEGRATION -- PAYER PAYING FOR 5177 03:34:51,000 --> 03:34:53,320 HOSPITAL STAY OWNING LTAC AND 5178 03:34:53,320 --> 03:34:55,440 SNIFF AND HAVE EMR THAT 5179 03:34:55,440 --> 03:34:57,400 POTENTIALLY IS CAPTURING DATA 5180 03:34:57,400 --> 03:34:58,880 ACROSS ALL SETTINGS AT VERY 5181 03:34:58,880 --> 03:35:00,520 LEAST YOU MIGHT HAVE DATA KANT 5182 03:35:00,520 --> 03:35:02,480 TOO YOU ARE THAT IS USEFUL FROM 5183 03:35:02,480 --> 03:35:04,040 STUDY DESIGN PERSPECTIVE WOULD 5184 03:35:04,040 --> 03:35:07,080 BE USEFUL TO ENGAGE STAKEHOLDERS 5185 03:35:07,080 --> 03:35:09,040 UP FRONT AND FIGURE OUT HOW TO 5186 03:35:09,040 --> 03:35:12,160 CREATE SOMETHING THAT IS 5187 03:35:12,160 --> 03:35:13,960 WORKABLE AND THINKING BACK TO 5188 03:35:13,960 --> 03:35:15,240 SIMILAR POINTS TO MAKE SURE YOU 5189 03:35:15,240 --> 03:35:19,680 HAVE CONTROLS IN PLACE TO PICK 5190 03:35:19,680 --> 03:35:22,080 UP IF YOU HAVE DROPOFF IN 5191 03:35:22,080 --> 03:35:25,120 EARLIER INTERVENTION AND IS 5192 03:35:25,120 --> 03:35:27,360 THERE AN ANSWER TO THAT OTHER 5193 03:35:27,360 --> 03:35:29,760 THAN BIG TEAM FROM OUTSET THAT 5194 03:35:29,760 --> 03:35:31,120 HAS ALL THOSE TRANSITION POINTS 5195 03:35:31,120 --> 03:35:33,200 TO LOOK FOR WAYS TO SMOOTH 5196 03:35:33,200 --> 03:35:34,760 TRANSITION AND COLLECTION OF 5197 03:35:34,760 --> 03:35:35,720 DATA ACROSS SETTINGS. 5198 03:35:35,720 --> 03:35:38,520 WE HAVE TO DO IT. PATIENTS ARE 5199 03:35:38,520 --> 03:35:41,000 GOING THROUGH THAT. 5200 03:35:41,000 --> 03:35:42,320 >> YEAH. 5201 03:35:42,320 --> 03:35:43,840 >> STEPHANIE, TURNING IT TO YOU 5202 03:35:43,840 --> 03:35:45,600 TO TURN IT OVER TO. 5203 03:35:45,600 --> 03:35:45,840 >> YEAH. 5204 03:35:45,840 --> 03:35:47,320 >> LOOKS LIKE WE ARE OUT OF 5205 03:35:47,320 --> 03:35:49,880 TIME AND THANKS TO THE PANEL AND 5206 03:35:49,880 --> 03:35:51,240 AMAZING SET OF SPEAKERS AND TO 5207 03:35:51,240 --> 03:35:53,480 THE REST OF THE SESSION. YOU 5208 03:35:53,480 --> 03:35:54,520 ASKED GREAT QUESTIONS. 5209 03:35:54,520 --> 03:35:58,600 I WILL EXCEPTED IT BACK OVER TO 5210 03:35:58,600 --> 03:36:02,280 TERRI AND TIM. 5211 03:36:02,280 --> 03:36:08,400 >> THANK YOU, SESSION 4. 5212 03:36:08,400 --> 03:36:11,000 WHAT A WAY TO FINISH UP. MY 5213 03:36:11,000 --> 03:36:12,160 GOODNESS. DON'T KNOW IF ANYONE 5214 03:36:12,160 --> 03:36:14,760 ELSE IS FEELING PRESSURE IN YOUR 5215 03:36:14,760 --> 03:36:16,680 HEAD AND FROM ALL OF THE GREAT 5216 03:36:16,680 --> 03:36:19,960 IDEAS AND THOUGHTS. 5217 03:36:19,960 --> 03:36:22,960 SO, A DEEP BREATH. WE WILL 5218 03:36:22,960 --> 03:36:24,720 TRANSITION INTO THE NEXT AND 5219 03:36:24,720 --> 03:36:29,600 FINAL PHASE OF OUR WORKSHOP. 5220 03:36:29,600 --> 03:36:30,880 AND I RECOGNIZE PEOPLE MIGHT 5221 03:36:30,880 --> 03:36:33,000 HAVE TO TAKE A COUPLE MINUTES 5222 03:36:33,000 --> 03:36:35,640 AWAY BIO BREAK OR GETTING A 5223 03:36:35,640 --> 03:36:37,560 LITTLE BLOOD FLOW TO YOUR LEGS 5224 03:36:37,560 --> 03:36:37,640 BUT MOVING INTO BREAKOUT ROOM 5225 03:36:37,640 --> 03:36:41,400 >> WELCOME BACK. 5226 03:36:41,400 --> 03:36:44,840 THAT TIME WENT REALLY QUICKLY 5227 03:36:44,840 --> 03:36:46,520 AND WE WILL MOVE TO THE REPORT 5228 03:36:46,520 --> 03:36:48,200 OUT PHASE NOW. EACH ROOM WILL 5229 03:36:48,200 --> 03:36:50,400 HAVE FIVE MINUTES TO PRESENT 5230 03:36:50,400 --> 03:36:53,000 THEIR THOUGHTS AND KIND OF 5231 03:36:53,000 --> 03:36:55,800 HIGH-LEVEL POINTS. 5232 03:36:55,800 --> 03:36:59,640 THEN WE WILL HAVE FIVE MINUTES 5233 03:36:59,640 --> 03:37:01,680 FOR QUESTIONS FROM THE CHAT AND 5234 03:37:01,680 --> 03:37:04,600 ANYONE FROM THE PANEL. WE ARE A 5235 03:37:04,600 --> 03:37:06,840 TIGHT KNIT GROUP NOW OF 52. 5236 03:37:06,840 --> 00:00:00,000 TURNING IT TO LAUREN