1 00:00:08,775 --> 00:00:10,910 WELCOME TO THE CLINICAL CENTER GRAND ROUNDS, 2 00:00:10,977 --> 00:00:14,714 A WEEKLY SERIES OF EDUCATIONAL LECTURES FOR PHYSICIANS AND 3 00:00:14,781 --> 00:00:17,350 HEALTH CARE PROFESSIONALS BROADCAST FROM THE CLINICAL 4 00:00:17,417 --> 00:00:20,320 CENTER AT THE NATIONAL INSTITUTES OF HEALTH IN 5 00:00:20,387 --> 00:00:22,122 BETHESDA, MD. 6 00:00:22,188 --> 00:00:25,658 THE NIH CLINICAL CENTER IS THE WORLD'S LARGEST HOSPITAL TOTALLY 7 00:00:25,725 --> 00:00:29,362 DEDICATED TO INVESTIGATIONAL RESEARCH AND LEADS THE GLOBAL 8 00:00:29,429 --> 00:00:32,298 EFFORT IN TRAINING TODAY'S INVESTIGATORS AND DISCOVERING 9 00:00:32,365 --> 00:00:34,467 TOMORROW'S CURES. 10 00:00:34,534 --> 00:00:43,309 LEARN MORE BY VISITING US ONLINE AT HTTP://CLINICALCENTER.NIH.GOV 11 00:00:43,376 --> 00:00:44,711 IT IS MY 12 00:00:44,778 --> 00:00:46,346 GREAT PLEASURE TO WELCOME YOU 13 00:00:46,413 --> 00:00:50,617 TO TODAY'S CLINICAL CENTER 14 00:00:50,683 --> 00:00:51,885 CONTEMERARY CLINICAL MEDICINE 15 00:00:51,951 --> 00:00:54,320 GREAT TEACHERS GRAND ROUNDS. 16 00:00:54,387 --> 00:00:55,822 THE HOPKINS CME ACTIVITY CODE 17 00:00:55,889 --> 00:00:56,923 FOR TODAY'S GRAND ROUNDS WHICH 18 00:00:56,990 --> 00:00:58,458 HAS BEEN SHOWN ON THE SLIDES 19 00:00:58,525 --> 00:01:01,528 PRIOR TO GETTING STARTED IS 20 00:01:01,594 --> 00:01:01,728 50535. 21 00:01:01,795 --> 00:01:04,063 PLEASE TEXT THIS CODE TO THE 22 00:01:04,130 --> 00:01:05,532 JOHNS HOPKINS CME PHONE NUMBER 23 00:01:05,598 --> 00:01:08,234 TO RECEIVE CME CREDIT FOR THIS 24 00:01:08,301 --> 00:01:08,535 LECTURE. 25 00:01:08,601 --> 00:01:10,503 WE ALSO KINDLY INVITE TO YOU 26 00:01:10,570 --> 00:01:11,871 PROVIDE FEEDBACK ON TODAY'S 27 00:01:11,938 --> 00:01:13,640 LECTURE BY SCANNING THE QR CODE 28 00:01:13,706 --> 00:01:15,875 SHOWN ON THE CME SLIDE, FOR 29 00:01:15,942 --> 00:01:18,111 THOSE APPLYING FOR CME, YOU WILL 30 00:01:18,178 --> 00:01:20,747 RECEIVE THE FEEDBACK SURVEY LINK 31 00:01:20,814 --> 00:01:21,114 VIA E-MAIL. 32 00:01:21,181 --> 00:01:23,416 THE SURVEY WILL BE USED TO 33 00:01:23,483 --> 00:01:24,651 PROVOID US WITH IMPORTANT 34 00:01:24,717 --> 00:01:25,685 FEEDBACK ABOUT THIS PRESENTATION 35 00:01:25,752 --> 00:01:28,254 AND ALLOWS YOU TO SUBMIT ANY 36 00:01:28,321 --> 00:01:29,422 SUGGESTIONS FOR FUTURE GRAND 37 00:01:29,489 --> 00:01:31,157 ROUNDS TOPICS. 38 00:01:31,224 --> 00:01:32,325 FOLLOWING THE PRESENTATION, 39 00:01:32,392 --> 00:01:34,027 QUESTIONS WILL BE TAKEN FROM THE 40 00:01:34,093 --> 00:01:35,795 MICROPHONES IN THE AISLES, 41 00:01:35,862 --> 00:01:37,397 ADDITIONALLY VIDEOCAST VIEWERS 42 00:01:37,464 --> 00:01:39,833 MAY SUBMIT QUESTIONS AT ANY TIME 43 00:01:39,899 --> 00:01:41,367 CURING THE LECTURE BOY SCROLLING 44 00:01:41,434 --> 00:01:43,837 DOWN AND CLICKING THE LIVE 45 00:01:43,903 --> 00:01:46,172 FEEDBACK BUTTON ON THE VIDEOCAST 46 00:01:46,239 --> 00:01:46,439 WEB SITE. 47 00:01:46,506 --> 00:01:48,107 SECOND WORLD WAR QUESTIONS WILL 48 00:01:48,174 --> 00:01:50,176 BE ANSWERED AS TIME PERMITS AT 49 00:01:50,243 --> 00:01:51,277 THE END OF THE DISCUSSION. 50 00:01:51,344 --> 00:01:56,182 TODAY WE ARE HONORED TO HAVE 51 00:01:56,249 --> 00:01:58,184 DR. TUHINA NEOGI, CHIEF OF 52 00:01:58,251 --> 00:02:01,254 RHEUMATOLOGY AT BOSTON MEDICAL 53 00:02:01,321 --> 00:02:03,423 CENTER, SECTION CHIEF OF 54 00:02:03,490 --> 00:02:04,858 RHEUMATOLOGY AT BOSTON 55 00:02:04,924 --> 00:02:09,963 UNIVERSITY SCHOOL OF MEDICINE. 56 00:02:10,029 --> 00:02:12,799 DR. NEOGI EARNED HER HD IN 1998 57 00:02:12,866 --> 00:02:15,935 FROM CABBEDDA AND/OR Ph.D. IN 58 00:02:16,002 --> 00:02:18,238 BOSTON MASSACHUSETTS IN 2 THINE. 59 00:02:18,304 --> 00:02:19,105 COMPLOATED FELLOWSHIP AT 60 00:02:19,172 --> 00:02:20,273 RHEUMATOLOGY AT THE UNIVERSITY 61 00:02:20,340 --> 00:02:22,308 OF TORONTO SHORTLY AFTER SHE 62 00:02:22,375 --> 00:02:23,610 BEGAN AT THE SCHOOL OF MEDICINE 63 00:02:23,676 --> 00:02:28,715 AS A RESEARCH FELLOW IN 2003. 64 00:02:28,781 --> 00:02:30,950 WORKINGROLES UNTIL 2016 WHICH HE 65 00:02:31,017 --> 00:02:32,252 WAS PROMOTED TO PROFESSOR OF 66 00:02:32,318 --> 00:02:33,786 MEDICINE AND EPIDEMIOLOGY. 67 00:02:33,853 --> 00:02:35,755 IN 2019 SHE BEGAN HER ROLE AS 68 00:02:35,822 --> 00:02:37,490 CHIEF OF THE SECTION FOR 69 00:02:37,557 --> 00:02:38,858 RHEUMATOLOGY AT BMC. 70 00:02:38,925 --> 00:02:42,795 A AS A HIEWMATOLOGYIST AND 71 00:02:42,862 --> 00:02:51,170 EPIDEMIOLOGIST, DR. NEOGI IS AN 72 00:02:51,237 --> 00:02:53,673 EXPERT IN DISEASES, GOWT, 73 00:02:53,740 --> 00:02:55,408 ARTHRITIS AND METHOD LOGICAL 74 00:02:55,475 --> 00:02:57,377 ISSUES OF RELEVANCE FOR 75 00:02:57,443 --> 00:02:57,844 RHEUMATIC DISEASES. 76 00:02:57,911 --> 00:03:02,215 HER WORK WAS RECOGNIZED WITH THE 77 00:03:02,282 --> 00:03:03,550 2014 ORNERY KONKLE INVESTIGATOR 78 00:03:03,616 --> 00:03:04,817 AWARD FOR PROMISING AND 79 00:03:04,884 --> 00:03:06,019 INDEPENDENT CONTRIBUTIONS TO 80 00:03:06,085 --> 00:03:07,086 RHEUMATOLOGY RESEARCH. 81 00:03:07,153 --> 00:03:13,726 IN 2022 SHE WAS AWARDED THE 82 00:03:13,793 --> 00:03:14,594 OSTEOARTHRITIS AWARD IN 83 00:03:14,661 --> 00:03:17,430 RECOGNITION OF HER CONTRIBUTIONS 84 00:03:17,497 --> 00:03:20,533 FOR OSTEOARTHRITIS RESEARCH AND 85 00:03:20,600 --> 00:03:22,669 AN HONORARY DOCTORAL FROM 86 00:03:22,735 --> 00:03:23,236 SWEDEN. 87 00:03:23,303 --> 00:03:24,871 HE HAS LED COMIEW CLASSISK 88 00:03:24,938 --> 00:03:26,573 CRITERIA FOR SEVERAL HIEWMATTIC 89 00:03:26,639 --> 00:03:29,676 DECS AND LED NATIONAL GUIDELINES 90 00:03:29,742 --> 00:03:33,980 FOR GOWT AND AFTIO ARTHRITIS. 91 00:03:34,047 --> 00:03:35,481 DR. NEOGI MENTORS EARLY STAGE 92 00:03:35,548 --> 00:03:36,883 RESEARCHERS IN RECOGNITION FOR 93 00:03:36,950 --> 00:03:40,053 HER EXCELLENCE SHE WAS AWARDED 94 00:03:40,119 --> 00:03:43,022 THE 2016 ROBERT DAWSON EVANS 95 00:03:43,089 --> 00:03:43,590 RESEARCH MENTORING AWARD. 96 00:03:43,656 --> 00:03:47,260 PAST CHAIR OF THE FDA ARGTDRITIS 97 00:03:47,327 --> 00:03:51,564 COMMITTEE AND HAS SERVED ON THE 98 00:03:51,631 --> 00:03:54,734 BOARD OF CRYSTAL ASSOCIATED 99 00:03:54,801 --> 00:03:56,336 DISEASES ON NETWORK, ACR, AND 100 00:03:56,402 --> 00:03:57,036 INTERNATIONAL ASSOCIATION FOR 101 00:03:57,103 --> 00:03:58,638 THE STUDY OF PAIN AMONG MOTHERS. 102 00:03:58,705 --> 00:04:00,206 PLEASE JOIN ME IN WELCOMING OUR 103 00:04:00,273 --> 00:04:03,343 SPEAKER FOR HER TALK ENTITLED 104 00:04:03,409 --> 00:04:05,244 PAIN MECHANISMS IN ARTHRITIS AND 105 00:04:05,311 --> 00:04:09,315 PLEASE WELCOME OUR SPEAKER 106 00:04:09,382 --> 00:04:10,917 DR. TUHINA NEOGI. 107 00:04:10,984 --> 00:04:11,217 [ APPLAUSE ] 108 00:04:11,284 --> 00:04:13,119 >> THANK YOU VERY MUCH FOR THAT 109 00:04:13,186 --> 00:04:14,287 KIND INVITATION AND FOR THIS 110 00:04:14,354 --> 00:04:16,889 INVITATION TO SPEC TO YOU. 111 00:04:16,956 --> 00:04:19,492 I UNDERSTAND IT'S A BUSY TIME OF 112 00:04:19,559 --> 00:04:22,095 YEAR AND I HEARD THIS MORNING 113 00:04:22,161 --> 00:04:23,730 THAT NIAMS IS HAVING THE HOLIDAY 114 00:04:23,796 --> 00:04:25,999 PARTIES AND I GOT A LOT OF 115 00:04:26,065 --> 00:04:27,500 E-MAILS AND MESSAGES WITH 116 00:04:27,567 --> 00:04:29,435 REGRETS THAT PEOPLE COULD NOT 117 00:04:29,502 --> 00:04:31,270 ATTEND TODAY SO I'M HAPPY TO 118 00:04:31,337 --> 00:04:32,905 WILL BE ARCHIVED. 119 00:04:32,972 --> 00:04:35,508 AND ALSO FOR THOSE THAT WILL BE 120 00:04:35,575 --> 00:04:37,844 WATCHING, WE WILL TAKE QUESTIONS 121 00:04:37,910 --> 00:04:39,078 BY E-MAIL. 122 00:04:39,145 --> 00:04:42,115 IF WE CAN GET THIS MOVING EMPLOY 123 00:04:42,181 --> 00:04:43,983 OKAY, SO, I'M FIRST GOING TO 124 00:04:44,050 --> 00:04:45,618 JUST PROVIDE A BROAD PERSPECTIVE 125 00:04:45,685 --> 00:04:49,622 OF WHY THESE ARE IMPORTANT 126 00:04:49,689 --> 00:04:50,023 QUESTIONS. 127 00:04:50,089 --> 00:04:51,691 SO ACCORDING TO THE LATEST 128 00:04:51,758 --> 00:04:53,593 GLOBAL BURDEN OF DEC STUDY, 129 00:04:53,660 --> 00:04:56,462 ABOUT 600 MILLION PEOPLE WORLD 130 00:04:56,529 --> 00:04:57,930 WIDE HAVE OSTEOARTHRITIS 131 00:04:57,997 --> 00:05:02,135 REFLECTING 10% OF ADULT 132 00:05:02,201 --> 00:05:05,738 POPULATIONS. 133 00:05:05,805 --> 00:05:07,073 I'M SORRY THE CLICKER IS NOT 134 00:05:07,140 --> 00:05:09,709 MOVING FORWARD SO IS THERE A WAY 135 00:05:09,776 --> 00:05:11,644 TO HAVE THE KEYBOARD FUNCTION TO 136 00:05:11,711 --> 00:05:12,745 MOVE THE SLIDES FORWARD SO I'M 137 00:05:12,812 --> 00:05:14,681 NOT HAVING TO CLICK AT THE 138 00:05:14,747 --> 00:05:25,291 BOTTOM OF THE SCREEN EACH TIME? 139 00:05:46,412 --> 00:05:48,414 IN OSTEOARTHRITIS THE PAIN IS 140 00:05:48,481 --> 00:05:49,449 INTERMITTENT ACTIVITY WEIGHT 141 00:05:49,515 --> 00:05:50,616 BEARING AREYALATED BUT OVERTIME 142 00:05:50,683 --> 00:05:52,351 THE PAIN CAN BECOME MORE SEVERE 143 00:05:52,418 --> 00:05:54,787 AND MORE PERSPIOF THENT VENLT 144 00:05:54,854 --> 00:05:57,690 IN TERMS OF THE BURDEN OF 145 00:05:57,757 --> 00:05:58,758 DISEASE, CURRENTLY IN THE U.S. 146 00:05:58,825 --> 00:06:00,593 JOINT PAIN ARE THE NUMBER 1 147 00:06:00,660 --> 00:06:02,228 LEADING REASON FOR DOCTOR'S 148 00:06:02,295 --> 00:06:06,099 OFFICE VISITS, SO THIS IS 149 00:06:06,165 --> 00:06:08,034 LARGELY CONTRIBUTED TO BY OFTIO 150 00:06:08,101 --> 00:06:08,968 ARTHRITIS AND LOW BACK PAIN. 151 00:06:09,035 --> 00:06:10,837 IN THE PAST IT USED TO BE 152 00:06:10,903 --> 00:06:12,805 HYPERTENSION AND PEOPLE DON'T GO 153 00:06:12,872 --> 00:06:15,742 TO THEIR DOCTORS BECAUSE THEY 154 00:06:15,808 --> 00:06:18,010 FEEL THE BLOOD PRESSURE, THEY GO 155 00:06:18,077 --> 00:06:18,745 BECAUSE THE PHYSICIAN TOLD THEM 156 00:06:18,811 --> 00:06:25,685 TO COME BACK FOR THE BPs TO BE 157 00:06:25,752 --> 00:06:25,918 CORRECT. 158 00:06:25,985 --> 00:06:29,589 IN WORLD WIDE, MUSK LO SKELETAL 159 00:06:29,655 --> 00:06:30,189 RELATED DISEASES, WITH 160 00:06:30,256 --> 00:06:31,557 OSTEOARTHRITIS AND LOW BACK PAIN 161 00:06:31,624 --> 00:06:32,759 BEING THE LARGEST CONTRIBUTORS 162 00:06:32,825 --> 00:06:35,895 ARE THE SECOND LEADING CAUSE OF 163 00:06:35,962 --> 00:06:37,396 YEARS LIVED WITH DISABILITY, SO 164 00:06:37,463 --> 00:06:38,464 ALL THESE DISEASES DON'T 165 00:06:38,531 --> 00:06:39,499 NECESSARILY KILL YOU, THOUGH 166 00:06:39,565 --> 00:06:42,835 THERE ARE DATA TO SUGGEST OR 167 00:06:42,902 --> 00:06:44,003 THAT DEMONSTRATE THAT 168 00:06:44,070 --> 00:06:46,205 OSTEOARTHRITIS IS ASSOCIATED 169 00:06:46,272 --> 00:06:47,173 WITH HIGHER MORTALITY, PEOPLE 170 00:06:47,240 --> 00:06:48,741 LIVING WITH DECADES WITH THESE 171 00:06:48,808 --> 00:06:49,208 PAINFUL CONDITIONS. 172 00:06:49,275 --> 00:06:52,912 AND IN TERMS OF SOCIETAL COST 173 00:06:52,979 --> 00:06:54,981 BURDEN, OSTEOARTHRITIS IS THE 174 00:06:55,047 --> 00:06:55,882 THIRD LEADING HOSPITAL DISCHARGE 175 00:06:55,948 --> 00:06:58,050 DIAGNOSIS IN THE U.S. 176 00:06:58,117 --> 00:07:02,088 THIS IS AFTER CHILD BIRTH 177 00:07:02,155 --> 00:07:03,222 RELATED HOSPITALIZATIONS WHICH 178 00:07:03,289 --> 00:07:04,524 IS NUMBER 1 AND QUUBS QUENT 179 00:07:04,590 --> 00:07:07,860 HOSPITAL IEGZATIONS WHICH IS 180 00:07:07,927 --> 00:07:08,594 NUMBER 2. 181 00:07:08,661 --> 00:07:10,129 FOR ME THINKING BACK TO MY 182 00:07:10,196 --> 00:07:11,097 INTERNAL MEDICINE DAYS, I WAS 183 00:07:11,164 --> 00:07:12,532 SHOCKED WHEN I SAW THIS 184 00:07:12,598 --> 00:07:13,966 STATISTIC BECAUSE I WAS THINKING 185 00:07:14,033 --> 00:07:17,103 HEART ATTACKS AND FAILURE WOULD 186 00:07:17,170 --> 00:07:17,804 BE UP THERE. 187 00:07:17,870 --> 00:07:19,705 SO THIS ILLUSTRATES THAT THE 188 00:07:19,772 --> 00:07:21,207 BURDEN OF OSTEOARTHRITIS THAT A 189 00:07:21,274 --> 00:07:24,043 HUGE AMOUNT OF U.S. HOSPITAL 190 00:07:24,110 --> 00:07:26,813 EXPENDITURES ARE SPENT ON JOINT 191 00:07:26,879 --> 00:07:28,214 REPLACEMENT SURGERY THAT,'S WHY 192 00:07:28,281 --> 00:07:30,683 OA IS THE THIRD LEADING HOSPITAL 193 00:07:30,750 --> 00:07:31,117 DISCHARGE DIAGNOSIS. 194 00:07:31,184 --> 00:07:31,851 IN TERMS OF WHAT WE HAVE TO 195 00:07:31,918 --> 00:07:39,659 OFFER OUR PATIENTS IN THE LATEST 196 00:07:39,725 --> 00:07:40,526 TREATMENT GUIDELINES FROM THE 197 00:07:40,593 --> 00:07:43,563 CORE FOUNDATION I WAS IN, THE 198 00:07:43,629 --> 00:07:44,797 OPTIONS ARE MAINTAINING HEALTHY 199 00:07:44,864 --> 00:07:46,265 WEIGHT, SO LOSING WEIGHT IF 200 00:07:46,332 --> 00:07:48,034 YOU'RE OBESE OR OVERWEIGHT AND 201 00:07:48,100 --> 00:07:49,836 PHYSICAL ACTIVITY. 202 00:07:49,902 --> 00:07:51,771 GENERAL HEALTHY LIFESTYLE 203 00:07:51,838 --> 00:07:54,407 FACTORS CORE FOUNDATIONAL 204 00:07:54,473 --> 00:07:55,875 MANAGEMENT STRATEGIES AND THEN 205 00:07:55,942 --> 00:07:58,311 WE HAVE TOPICAL AGENTS, SOME 206 00:07:58,377 --> 00:08:01,547 ORAL THERAPIES FOR SYMPTOM 207 00:08:01,614 --> 00:08:04,383 MANAGEMENT AND SOME 208 00:08:04,450 --> 00:08:05,318 INTERARTICULAR THERAPIES, SO FOR 209 00:08:05,384 --> 00:08:07,086 SUCH A HUGE BURDEN DEC, WE OHM 210 00:08:07,153 --> 00:08:09,288 HAVE A FEW HANDFUL OF THING THAT 211 00:08:09,355 --> 00:08:14,760 HAVE GOOD EVIDENCE TO SUPPORT 212 00:08:14,827 --> 00:08:14,994 THEM. 213 00:08:15,061 --> 00:08:17,063 A CONSEQUENCE OF NOT HAVING GOOD 214 00:08:17,129 --> 00:08:18,030 MANAGEMENT OPTION SYSTEM 215 00:08:18,097 --> 00:08:20,700 ILLUSTRATED HERE IN A STUDY I 216 00:08:20,766 --> 00:08:21,400 DID WITH ANDREW--DR. ANDREW 217 00:08:21,467 --> 00:08:24,136 STOKE WHO IS IS A COLLEAGUE AT 218 00:08:24,203 --> 00:08:25,771 THE BU SCHOOL OF HEALTH. 219 00:08:25,838 --> 00:08:28,074 WE WERE INTERESTED IN LOOKING AT 220 00:08:28,140 --> 00:08:29,008 PATTERNS OF PRESCRIPTION 221 00:08:29,075 --> 00:08:32,178 MEDICATION USE BY PEOPLE WHO 222 00:08:32,245 --> 00:08:33,179 HAVE ARTHRITIS, LARGELY 223 00:08:33,246 --> 00:08:35,781 OSTEOARTHRITIS, GIVEN THE LARGE 224 00:08:35,848 --> 00:08:39,986 PREVALENCE OF OSTEOARTHRITIS, 225 00:08:40,052 --> 00:08:44,123 AND WE USED THE NEXT HANES DATA 226 00:08:44,190 --> 00:08:44,924 FROM 2015-20 FLEAN. 227 00:08:44,991 --> 00:08:48,728 THE ORANGE DATA POINTS ARE 228 00:08:48,794 --> 00:08:49,528 EXCLUSIVE NONNARCOTICS 229 00:08:49,595 --> 00:08:51,597 ANALGESICS, AND THE BLUE ARE 230 00:08:51,664 --> 00:08:53,032 OPIOID ANNAL GEEDZICS SO YOU CAN 231 00:08:53,099 --> 00:08:55,601 SEE THAT THE PREVALENCE OF 232 00:08:55,668 --> 00:08:56,235 PRESCRIPTIONS WAS FAIRLY 233 00:08:56,302 --> 00:08:59,472 CONSTANT IN THE LATE 90S, AND 234 00:08:59,538 --> 00:09:00,172 THEN SOMETHING HAPPENED. 235 00:09:00,239 --> 00:09:05,645 ALL OF A SUDDEN IN ABOUT THE 236 00:09:05,711 --> 00:09:08,147 MID2000S, PREKRIPGZS FOR NSAIDS 237 00:09:08,214 --> 00:09:09,815 AND COX2 INHIBITORS WENT DOWN. 238 00:09:09,882 --> 00:09:12,018 AND FOR THOSE WHO HAVE BEEN 239 00:09:12,084 --> 00:09:13,619 AROUND LONG ENOUGH, YOU MAY 240 00:09:13,686 --> 00:09:16,589 RECOGNIZE THAT THIS IS WHEN VIOX 241 00:09:16,656 --> 00:09:18,891 CAME OFF THE MARKET, 242 00:09:18,958 --> 00:09:20,660 CARDIOVASCULAR RISK, PEOPLE WERE 243 00:09:20,726 --> 00:09:22,862 HAVING MIs AND DYING AND THE 244 00:09:22,929 --> 00:09:25,197 RISKS ASSOCIATE WIDE NSAIDS, GI 245 00:09:25,264 --> 00:09:27,833 BLEED, RENAL FAILURE, HEART, YOU 246 00:09:27,900 --> 00:09:29,468 KNOW CARDIOVASCULAR ADVERSE 247 00:09:29,535 --> 00:09:32,872 EEIVETS WERE INCREASINGLY BEING 248 00:09:32,939 --> 00:09:34,006 RECOGNIZED SO, APPROPRIATELY 249 00:09:34,073 --> 00:09:36,509 PHYSICIANS STARTED REDUCING THE 250 00:09:36,575 --> 00:09:37,810 PRESCRIPTIONS FOR NSAIDS AND 251 00:09:37,877 --> 00:09:39,145 COX2 INHIBITORS THAT WERE ON THE 252 00:09:39,211 --> 00:09:40,179 MARKET. 253 00:09:40,246 --> 00:09:42,114 BUT PEOPLE WITH OSTEOARTHRITIS 254 00:09:42,181 --> 00:09:44,283 AND OTHER FORMS OF ARTHRITIS 255 00:09:44,350 --> 00:09:46,252 STILL HAD PAIN AND SO WHAT 256 00:09:46,319 --> 00:09:46,519 HAPPENED? 257 00:09:46,585 --> 00:09:48,387 AND THAT'S WHERE YOU SEE THE 258 00:09:48,454 --> 00:09:50,756 RISE IN OPIOID PRESCRIPTIONS. 259 00:09:50,823 --> 00:09:53,759 GIVEN THE HIGH PREVALENCE OF 260 00:09:53,826 --> 00:09:55,394 OSTEOARTHRITIS, YOU KNOW A LARGE 261 00:09:55,461 --> 00:09:56,462 BURDEN OF PRESCRIPTIONS FOR 262 00:09:56,529 --> 00:10:00,900 OPIOIDS AT THIS TIME IS FOR MSK 263 00:10:00,967 --> 00:10:04,503 PAIN LARGELY DOMINATED BY 264 00:10:04,570 --> 00:10:05,938 OSTEOARTHRITIS AND BACK PAIN. 265 00:10:06,005 --> 00:10:08,040 SO I SUBMIT AS PART OF THE 266 00:10:08,107 --> 00:10:13,913 COMBINATION AS PAIN AS A FIFTH 267 00:10:13,980 --> 00:10:15,881 VITAL SIGN, AND PLUS THE 268 00:10:15,948 --> 00:10:19,652 COMPANIES PUSHING THE THESE HIGH 269 00:10:19,719 --> 00:10:20,853 OPIDS, IT HAS ALL CONTRIBUTED TO 270 00:10:20,920 --> 00:10:23,789 TO THE STAGE OF THE HIGH 271 00:10:23,856 --> 00:10:25,257 RESCRIPGZS AND THEN OPIOID 272 00:10:25,324 --> 00:10:25,791 EPIDEMIC. 273 00:10:25,858 --> 00:10:29,395 SO NOW LET'S THINK ABOUT WHAT 274 00:10:29,462 --> 00:10:31,630 ARE CAUSING--WHAT'S CAUSING 275 00:10:31,697 --> 00:10:32,765 SYMPTOMS IN OSTEOARTHRITIS. 276 00:10:32,832 --> 00:10:33,666 SO THE DISEASE ITSELF WE CAN 277 00:10:33,733 --> 00:10:36,502 THINK OF IT IN TERMS OF 278 00:10:36,569 --> 00:10:39,138 STRUCTURE, TISSUE FUNCTION AND 279 00:10:39,205 --> 00:10:39,672 PATHOLOGY. 280 00:10:39,739 --> 00:10:40,206 SO HISTOLOGICALLY, 281 00:10:40,272 --> 00:10:43,275 HISTOLOGICALLY HERE, YOU CAN SEE 282 00:10:43,342 --> 00:10:44,110 CARTILAGE AND BONE 283 00:10:44,176 --> 00:10:46,112 ABNORMALITIES, THERE'S A LOT OF 284 00:10:46,178 --> 00:10:48,481 MOLECULAR MECHANISMS THAT HAVE 285 00:10:48,547 --> 00:10:49,882 BEEN UNDERSTOOD INCLUDING 286 00:10:49,949 --> 00:10:52,485 CYTOKINES AND MMPs, ET CETERA, 287 00:10:52,551 --> 00:10:54,320 OSTEOARTHRITIS IS NOT JUST A 288 00:10:54,387 --> 00:10:56,522 DISEASE OF BONE AND CARTILAGE, 289 00:10:56,589 --> 00:10:57,723 DISEASE OF THE WHOLE JOINT. 290 00:10:57,790 --> 00:10:59,725 IF WE WERE TO RENAME IT TODAY, 291 00:10:59,792 --> 00:11:02,928 IT MIGHT BE CALLED LIKE TOTAL 292 00:11:02,995 --> 00:11:04,697 JOINT FAILURE, LIKE RENAL 293 00:11:04,764 --> 00:11:05,531 FAILURE, HEART FAILURE, IT'S ALL 294 00:11:05,598 --> 00:11:06,732 THE TISSUES IN THE JOINT SO WE 295 00:11:06,799 --> 00:11:11,937 CAN LOOK AT IT ON IMAGING, MRI, 296 00:11:12,004 --> 00:11:12,772 RADIO GRAPH, PATHOLOGY, ET 297 00:11:12,838 --> 00:11:13,005 CETERA. 298 00:11:13,072 --> 00:11:15,141 BUT HOW DOES THIS RELATE TO THE 299 00:11:15,207 --> 00:11:16,742 ILLNESS, SO THE DISEASE, WE 300 00:11:16,809 --> 00:11:19,078 THINK OF A PATHOLOGY AND 301 00:11:19,145 --> 00:11:20,813 STRUCTURE BUT THE ILLNESS IS THE 302 00:11:20,880 --> 00:11:22,348 HUMAN RESPONSE TO THAT DISEASE. 303 00:11:22,415 --> 00:11:24,283 HOW DOES THAT PATHOLOGY 304 00:11:24,350 --> 00:11:25,317 STRUCTURAL ABNORMALITIES, HOW 305 00:11:25,384 --> 00:11:27,820 DOES THAT CONTRIBUTE TO THE PAIN 306 00:11:27,887 --> 00:11:28,888 EXPERIENCE THEIR FUNCTIONING, 307 00:11:28,954 --> 00:11:34,193 THEIR QUALITY OF LIFE IN SO, IN 308 00:11:34,260 --> 00:11:35,461 OSTEOARTHRITIS, WE HAVE SEVERAL 309 00:11:35,528 --> 00:11:36,962 ASSPECS OF SYMPTOMS THAT WE 310 00:11:37,029 --> 00:11:37,997 INSWIER ABOUT. 311 00:11:38,064 --> 00:11:41,434 WE CAN ABOUT SYMPTOMS, TYPICALLY 312 00:11:41,500 --> 00:11:43,402 PAIN, WITH REGARDS TO SEVERITY, 313 00:11:43,469 --> 00:11:45,271 FREQUENCY AND CHANGE OVER TIME. 314 00:11:45,337 --> 00:11:46,472 HAS IT WORSENED? 315 00:11:46,539 --> 00:11:48,007 HOW HAS THE PATTERN CHANGED IN 316 00:11:48,074 --> 00:11:51,010 PATTERNS ARE VERY IMPORTANT TO 317 00:11:51,077 --> 00:11:52,011 PATIENTS FOR SELF-MANAGEMENT. 318 00:11:52,078 --> 00:11:53,579 IF THEY KNOW WHAT TRIGGERS THEIR 319 00:11:53,646 --> 00:11:54,814 PAIN, THEY CAN MODIFY THEIR 320 00:11:54,880 --> 00:11:56,048 ACTIVITY. 321 00:11:56,115 --> 00:11:58,284 IF I SKI FOR MORE THAN HOUR, MY 322 00:11:58,350 --> 00:11:59,218 KNEE'S GOING TO HURT. 323 00:11:59,285 --> 00:12:02,354 IF I PLAY TENNIS, YOU KNOW 324 00:12:02,421 --> 00:12:04,190 THERE'S THINGS THAT FOR PHYSICAL 325 00:12:04,256 --> 00:12:05,024 ACTIVITY, WEIGHT BEARING 326 00:12:05,091 --> 00:12:06,525 ACTIVITIES THAT THEY MIGHT KNOW 327 00:12:06,592 --> 00:12:08,294 ABOUT, BUT WHAT'S MORE 328 00:12:08,360 --> 00:12:09,428 TROUBLESOME FOR PATIENTS IS WHEN 329 00:12:09,495 --> 00:12:11,864 THE PAIN IS UNPREDICTABLE, THEY 330 00:12:11,931 --> 00:12:12,731 CAN'T MODIFY ACTIVITY IF THEY 331 00:12:12,798 --> 00:12:13,899 DON'T KNOW WHEN THE PAIN'S GOING 332 00:12:13,966 --> 00:12:16,836 TO HIT THEM CAN THAT CAN BE VERY 333 00:12:16,902 --> 00:12:18,504 DISABLING, IT REALLY IMPACTS 334 00:12:18,571 --> 00:12:19,538 THEIR ABILITY TO PARTICIPATE IN 335 00:12:19,605 --> 00:12:21,974 THEIR QUALITY OF LIFE EMPLOY IN 336 00:12:22,041 --> 00:12:23,742 ADDITION THESE SYMPTOMS HAVE 337 00:12:23,809 --> 00:12:26,045 BROAD IMPACT, BROAD INTERFERENCE 338 00:12:26,112 --> 00:12:28,047 ON OTHER AREAS, THEIR PHYSICAL 339 00:12:28,114 --> 00:12:28,948 FUNCTION, THEIR SLEEP, 340 00:12:29,014 --> 00:12:30,483 COGNITION, THEIR MOOD, AND MANY 341 00:12:30,549 --> 00:12:33,052 PEOPLE HAVE WIDE SPREAD PAIN, SO 342 00:12:33,119 --> 00:12:35,488 OSTEOARTHRITIS OF THE KNEE ISN'T 343 00:12:35,554 --> 00:12:37,089 USUALLY JUST AN ISOLATED 344 00:12:37,156 --> 00:12:38,924 SYMPTOMATIC AREA, OFTEN PEOPLE 345 00:12:38,991 --> 00:12:44,029 HAVE COMORBID PANE ELSEWHERE. 346 00:12:44,096 --> 00:12:47,600 SO WHAT CAUSES PAIN? 347 00:12:47,666 --> 00:12:51,036 THERE'S A WELL KNOWN IMAGE FROM 348 00:12:51,103 --> 00:12:52,037 DICK HEART SHOWING THE 349 00:12:52,104 --> 00:12:54,640 TRANSMISSION OF A NOXIOUS 350 00:12:54,707 --> 00:12:56,142 STIMPLUS FROM THE STIMULUS GOING 351 00:12:56,208 --> 00:12:59,145 UP TO THE BRAIN BUT IT'S NOT 1 352 00:12:59,211 --> 00:12:59,912 SIMPLE 1 LANE HIGHWAY GOING UP 353 00:12:59,979 --> 00:13:01,280 TO THE BRAIN MUCH BUT THIS 354 00:13:01,347 --> 00:13:02,982 CONCEPT IS USEFUL IN 355 00:13:03,048 --> 00:13:04,416 UNDERSTANDING WHY WE HAVE A 356 00:13:04,483 --> 00:13:06,085 QUICK RESPONSE, EXCUSE ME, A 357 00:13:06,152 --> 00:13:08,721 QUICK RESPONSE TO NOXIOUS 358 00:13:08,787 --> 00:13:08,954 STIMULI. 359 00:13:09,021 --> 00:13:12,057 IF YOU TOUCH A HOT STOVE THERE'S 360 00:13:12,124 --> 00:13:13,125 INSTANDPOINT PREFLEX TO REMOVE 361 00:13:13,192 --> 00:13:14,560 YOUR HAND SO YOU DON'T DAMAGE IT 362 00:13:14,627 --> 00:13:14,793 FURTHER. 363 00:13:14,860 --> 00:13:17,429 WHEN YOU GO FOR A JOG AND YOU 364 00:13:17,496 --> 00:13:19,064 TWIST YOUR ANKLE, YOU LIMP AND 365 00:13:19,131 --> 00:13:21,167 OFFLOAD THE JOINT SO THE JOINT 366 00:13:21,233 --> 00:13:22,668 IS HEAL ITSELF, SO THOSE ARE 367 00:13:22,735 --> 00:13:24,603 APPROPRIATE RESPONSES TO AN 368 00:13:24,670 --> 00:13:27,373 ACUTE STIMULUS AND THAT'S ACUTE 369 00:13:27,439 --> 00:13:29,808 PAIN TO NOT ALLOW THE TISSUE TO 370 00:13:29,875 --> 00:13:30,776 HAVE FURTHER DAMAGE AND ALLOW 371 00:13:30,843 --> 00:13:33,279 THE TISSUE TO HEAL. 372 00:13:33,345 --> 00:13:35,781 SO WHEN WE THINK ABOUT THAT 373 00:13:35,848 --> 00:13:40,352 NORMAL RESPONSE, THAT'S NORMAL 374 00:13:40,419 --> 00:13:42,221 SENSATION, WE HAVE NO CEPTIVE 375 00:13:42,288 --> 00:13:44,924 STIMULI, SO HEAT, SHARP, 376 00:13:44,990 --> 00:13:48,027 ELECTRICAL, CHEMICAL, THESE ALL 377 00:13:48,093 --> 00:13:49,562 STIMULATE NOCI SEPTORSORS WHICH 378 00:13:49,628 --> 00:13:50,963 ACTIVATES, LIKE YOU GET ACTION 379 00:13:51,030 --> 00:13:52,631 POTENTIALS AND THEN THIS GOES UP 380 00:13:52,698 --> 00:13:54,466 THROUGH TO THE DORSAL ROOT 381 00:13:54,533 --> 00:13:57,102 GANGLION AND THAT IS THEN 382 00:13:57,169 --> 00:13:58,237 TRANSMITTED, THERE'S A SIGNAL 383 00:13:58,304 --> 00:14:03,442 AND EXPERIENCED AS PAIN. 384 00:14:03,509 --> 00:14:07,012 IN CONTRAST, LIGHT TOUCH 385 00:14:07,079 --> 00:14:08,781 ACTIVATES LOW THRESHOLD MECHAN O 386 00:14:08,847 --> 00:14:10,783 RECEPTOR ANDS THAT'S INTERPRET 387 00:14:10,849 --> 00:14:12,051 THE AS TOUCH. 388 00:14:12,117 --> 00:14:12,985 WHEN THESE MECHANISMS GET 389 00:14:13,052 --> 00:14:15,554 ALTERED YOU GET CENTRAL 390 00:14:15,621 --> 00:14:21,360 SENSITIZATION, SO WITH CENTRAL 391 00:14:21,427 --> 00:14:22,027 SENSITIZATION, THESE 392 00:14:22,094 --> 00:14:23,762 NOCISEPTORSORS MAY FIRE WITH 393 00:14:23,829 --> 00:14:25,631 LOWER THAN REGULAR THRESHOLD 394 00:14:25,698 --> 00:14:27,933 STIMULI, SO THEY MIGHT RESPOND 395 00:14:28,000 --> 00:14:29,602 TO LOWER THRESHOLDS OF TIMUE 396 00:14:29,668 --> 00:14:29,802 LIE. 397 00:14:29,868 --> 00:14:31,704 YOU GET MORE ACTION PROTENTIALS, 398 00:14:31,770 --> 00:14:33,205 SO SOMETHING THAT WAS NORMALLY 399 00:14:33,272 --> 00:14:37,443 WOULD BE PAINFUL CAN NOW BE MORE 400 00:14:37,509 --> 00:14:38,644 PAINFUL, HYPER ALGEESIA. 401 00:14:38,711 --> 00:14:43,949 IN ADDITION YOU CAN NOW HAVE LOW 402 00:14:44,016 --> 00:14:44,516 THRESHOLD MECHANO RECEPTORS 403 00:14:44,583 --> 00:14:48,020 RESPONDING IN SUCH A WAY THAT 404 00:14:48,087 --> 00:14:49,922 THE SIGNALS ARE NOW BEING 405 00:14:49,989 --> 00:14:52,258 INTERPRETED AS PAIN, SO 406 00:14:52,324 --> 00:14:53,158 ALODENNIA, SOMETHING THAT SHOULD 407 00:14:53,225 --> 00:14:56,762 NOT BE PAINFUL AND NOW BEING 408 00:14:56,829 --> 00:14:57,663 EXPERIENCED AS PAIN. 409 00:14:57,730 --> 00:15:00,933 SO WITH THAT IN MIND, 1 OF THE 410 00:15:01,000 --> 00:15:02,568 BIG CONUNDRUMS IN OSTEOARTHRITIS 411 00:15:02,635 --> 00:15:05,237 HAS BEEN THE SO CALLED STRUCTURE 412 00:15:05,304 --> 00:15:05,671 SYMPTOM DISCORDANCE. 413 00:15:05,738 --> 00:15:07,473 THAT IS PEOPLE WHO MIGHT HAVE 414 00:15:07,539 --> 00:15:11,410 KNEE PAIN, MIGHT NOT HAVE A MUCH 415 00:15:11,477 --> 00:15:13,579 SHOWING UP ON THEIR X-RAY AS 416 00:15:13,646 --> 00:15:14,613 STRUCTURAL DAMAGE BUT THEN 417 00:15:14,680 --> 00:15:16,715 PEOPLE WHO HAVE BAD LOOKING 418 00:15:16,782 --> 00:15:18,183 X-RAYS MIGHT NOT HAVE A LOT OF 419 00:15:18,250 --> 00:15:19,051 KNEE PAIN. 420 00:15:19,118 --> 00:15:20,185 SO THE OVERLAP BETWEEN THOSE 421 00:15:20,252 --> 00:15:22,621 WITH KNEE PAIN AND WITH RADIO 422 00:15:22,688 --> 00:15:24,056 GRAPHIC STRUCTURAL DAMAGE 423 00:15:24,123 --> 00:15:25,791 APPARENT ON RADIO GRAFS, THAT 424 00:15:25,858 --> 00:15:27,726 OVERLAP MAY NOT BE COMPLETE. 425 00:15:27,793 --> 00:15:29,161 AND SO WHY IS THAT. 426 00:15:29,228 --> 00:15:31,730 AND THAT HAS LED TO MANY YEARS 427 00:15:31,797 --> 00:15:33,365 OF DISCUSSION ABOUT WELL, MAYBE 428 00:15:33,432 --> 00:15:34,333 PATHOLOGY DOESN'T HAVE THAT MUCH 429 00:15:34,400 --> 00:15:37,903 TO DO WITH PAIN AND 430 00:15:37,970 --> 00:15:38,404 OSTEOARTHRITIS. 431 00:15:38,470 --> 00:15:41,140 SO FOR ME AS A--THIS WAS 1 OF 432 00:15:41,206 --> 00:15:43,442 THE FIRST QUESTIONS THAT I TRULY 433 00:15:43,509 --> 00:15:46,712 TRIED TO ADDRESS AND UNDERSTAND, 434 00:15:46,779 --> 00:15:48,714 FOR ME AS AN EPIDEMIOLOGIST, I 435 00:15:48,781 --> 00:15:50,883 REALLY THOUGHT ABOUT, WELL, WHY 436 00:15:50,949 --> 00:15:52,685 DO PEOPLE EXPERIENCE PAIN IN 437 00:15:52,751 --> 00:15:53,052 DIFFERENT WAYS? 438 00:15:53,118 --> 00:15:54,720 AND SO IF YOU THINK ABOUT IT, IF 439 00:15:54,787 --> 00:15:56,522 I WERE TO PUNCH 1 PERSON WITH 440 00:15:56,588 --> 00:15:57,623 THE SAME FORCE AND ANOTHER 441 00:15:57,690 --> 00:16:00,359 PERSON WITH THE SAME FORCE, THEY 442 00:16:00,426 --> 00:16:02,928 MIGHT EXPERIENCE IT DIFFERENTLY 443 00:16:02,995 --> 00:16:06,198 BECAUSE THEY HAVE DIFFERENT 444 00:16:06,265 --> 00:16:06,999 GENETIC SUSCEPTIBILITY, THEY 445 00:16:07,066 --> 00:16:09,935 SLEPT DIFFERENTLY, THEIR MOOD IS 446 00:16:10,002 --> 00:16:11,804 DIFFERENT, THEIR SOCIOLOGICAL 447 00:16:11,870 --> 00:16:12,571 CULTURAL EXPECTATIONS ARE 448 00:16:12,638 --> 00:16:13,172 DIFFERENT. 449 00:16:13,238 --> 00:16:14,039 ALL SORTS OF THINGS DIFFER 450 00:16:14,106 --> 00:16:15,541 BETWEEN PEOPLE EMPLOY SO WHAT IF 451 00:16:15,607 --> 00:16:15,974 WE DID THIS. 452 00:16:16,041 --> 00:16:17,609 WHAT IF I LOOK AT PEOPLE WHO HAD 453 00:16:17,676 --> 00:16:19,812 PAIN IN 1 KNEE AND NO PAIN IN 454 00:16:19,878 --> 00:16:22,681 THE OTHER KNEE. 455 00:16:22,748 --> 00:16:27,486 IN THAT WAY, THEIR SLEEP, THEIR 456 00:16:27,553 --> 00:16:29,188 MOOD, GENETICS, BPI, SEX, ALL OF 457 00:16:29,254 --> 00:16:31,557 THOSE THINGS ARE THE SAME FOR 458 00:16:31,623 --> 00:16:32,024 BOTH KNEES. 459 00:16:32,091 --> 00:16:33,692 SO IF THE KNEES HAVE DIFFERENCE 460 00:16:33,759 --> 00:16:35,661 IN PAIN, THERE MUST BE SOMETHING 461 00:16:35,728 --> 00:16:37,162 GOING ON AT THE KNEE AND WHEN 462 00:16:37,229 --> 00:16:38,597 YOU DO THAT KIND OF ANALYSIS AND 463 00:16:38,664 --> 00:16:42,434 I DID THIS IN 2 LARGE COHORTS 464 00:16:42,501 --> 00:16:43,302 THE MULTICENTER OSTEOARTHRITIS 465 00:16:43,369 --> 00:16:44,970 STUDY OR MOST WHICH HAS ABOUT 466 00:16:45,037 --> 00:16:47,406 3000 OLDER ADULTS AND THE 467 00:16:47,473 --> 00:16:48,407 FRAMINGHAM HEART STUDY, A 468 00:16:48,474 --> 00:16:49,241 COMMUNITY SAMPLE, YOU KNOW THIS 469 00:16:49,308 --> 00:16:52,978 IS THE FESTER COHORT STUDY IN 470 00:16:53,045 --> 00:16:54,813 THE WORLD OVER 70, 75 YEARS IN 471 00:16:54,880 --> 00:16:55,681 THE FIELD NOW. 472 00:16:55,748 --> 00:16:58,150 WE HAD RADIO GRAFS, AND THE 473 00:16:58,217 --> 00:17:03,555 X-AXIS SHOWS THE SEVERITY OF 474 00:17:03,622 --> 00:17:05,991 RADIO GRAPHIC DISEASE WITH KL 475 00:17:06,058 --> 00:17:08,327 GRADE AND 4 BEING BASICALLY END 476 00:17:08,394 --> 00:17:09,395 STAGE BONE ON BONE EMPLOY SO 477 00:17:09,461 --> 00:17:10,729 WHEN YOU DO THIS KIND OF 478 00:17:10,796 --> 00:17:13,699 ANALYSIS, YOU CAN SEE THERE'S A 479 00:17:13,766 --> 00:17:15,100 VERY NICE DOSE RESPONSE 480 00:17:15,167 --> 00:17:17,436 RELATIONSHIP BETWEEN RADIO 481 00:17:17,503 --> 00:17:18,670 GRAPHIC SEVERITY OF THE KNEE AND 482 00:17:18,737 --> 00:17:21,206 THE LIKELIHOOD OF HAVING PAIN IN 483 00:17:21,273 --> 00:17:21,473 THAT KNEE. 484 00:17:21,540 --> 00:17:23,509 SO WHEN YOU CAN GET RID OF ALL 485 00:17:23,575 --> 00:17:24,376 THE BETWEEN PERSON DIFFERENCES 486 00:17:24,443 --> 00:17:25,778 IN THE PAIN EXPERIENCE, YOU CAN 487 00:17:25,844 --> 00:17:27,246 SHOW A VERY STRONG RELATIONSHIP 488 00:17:27,312 --> 00:17:32,351 BETWEEN STRUCTURE AND PAIN. 489 00:17:32,418 --> 00:17:34,520 SO THIS STUDY SHOWS PROOF OF 490 00:17:34,586 --> 00:17:35,954 CONCEPT THAT THERE ARE TISSUES 491 00:17:36,021 --> 00:17:37,456 WITHIN THE JOINT THAT ARE 492 00:17:37,523 --> 00:17:38,357 PAINFUL, THIS STUDY, I DON'T 493 00:17:38,424 --> 00:17:40,793 KNOW HOW IT WAS DONE, 25 YEARS 494 00:17:40,859 --> 00:17:44,329 AGO, IT WOULD NOT BE IRB 495 00:17:44,396 --> 00:17:46,098 APPROVED TODAY, THIS IS A STUDY 496 00:17:46,165 --> 00:17:49,034 WHERE 1 OR 2 ORTHOPEDIC SURGEON 497 00:17:49,101 --> 00:17:52,704 BROTHERS, 1 PERFORMED AN AWAKE, 498 00:17:52,771 --> 00:17:54,907 UNANESTHETIZED ARGT ROUGH ATOM 499 00:17:54,973 --> 00:17:55,507 SCOPPIC MANIPULATION IN THE 500 00:17:55,574 --> 00:17:56,809 OTHER BROTHER, I DON'T KNOW WHO 501 00:17:56,875 --> 00:17:58,444 WAS OLDER, WHO WAS YOUNGER BUT 502 00:17:58,510 --> 00:18:00,846 WE CAN MAKE A GUESS AND THEY 503 00:18:00,913 --> 00:18:01,613 INTERROGATED DIFFERENT TISSUES 504 00:18:01,680 --> 00:18:03,515 IN THE JOINT. 505 00:18:03,582 --> 00:18:04,383 THEY DIDN'T ENTERIGATE BONE 506 00:18:04,450 --> 00:18:05,617 BECAUSE WE KNOW BONE IS PAINFUL, 507 00:18:05,684 --> 00:18:07,820 IF YOU BREAK YOUR BONE, IT'S 508 00:18:07,886 --> 00:18:08,420 PAINFUL. 509 00:18:08,487 --> 00:18:10,189 WHAT THEY DEMONSTRATED IS 510 00:18:10,255 --> 00:18:11,690 CARTILAGE BEING HEALTHY 511 00:18:11,757 --> 00:18:13,759 CARTILAGE BEING ANEURAL WAS NOT 512 00:18:13,826 --> 00:18:14,660 PAINFUL. 513 00:18:14,726 --> 00:18:17,463 SO THAT'S AN IMPORTANT THING. 514 00:18:17,529 --> 00:18:20,866 PAIN ISN'T COMING FROM HEALTHY 515 00:18:20,933 --> 00:18:21,700 CARTILAGE IN OSTEOARTHRITIS, 516 00:18:21,767 --> 00:18:25,737 THERE IS DAMAGE IN TO THEART 517 00:18:25,804 --> 00:18:28,807 LEDGE BUT HEALTHY CARTILAGE IS 518 00:18:28,874 --> 00:18:29,074 A-NEURAL. 519 00:18:29,141 --> 00:18:31,510 BUT WHAT IS PAINFUL IS YOU HAVE 520 00:18:31,577 --> 00:18:34,513 LIGAMENTS, THE FAT PAD, THE SIN 521 00:18:34,580 --> 00:18:37,716 OVIUM LIGAMENTS, OUTER ASPECTS 522 00:18:37,783 --> 00:18:38,951 OF THE MENISCUS, LOTS OF TISSUES 523 00:18:39,017 --> 00:18:43,989 THAT ARE PAINFUL THAT HAVE 524 00:18:44,056 --> 00:18:44,723 NOCISEPTORSORS, THE CHANGE IN 525 00:18:44,790 --> 00:18:46,925 OSTEOARTHRITIS IS A LOT OF 526 00:18:46,992 --> 00:18:47,793 ABNORMALITIES IN THESE TISSUE 527 00:18:47,860 --> 00:18:49,127 ARE COMMON EMPLOY SO IN THIS 528 00:18:49,194 --> 00:18:50,329 PAPER BY MARTIN ENGLAND 529 00:18:50,395 --> 00:18:51,630 PUBLISHED IN THE NEW ENGLAND 530 00:18:51,697 --> 00:18:53,932 JOURNAL OF MEDICINE IN 2008, 531 00:18:53,999 --> 00:18:55,501 HE'S FROM SWEDEN AND HE CAME AND 532 00:18:55,567 --> 00:18:58,837 WORKED WITH US IN BOSTON AND HE 533 00:18:58,904 --> 00:19:01,607 USE THE FRAMINGHAM DATA WHERE WE 534 00:19:01,673 --> 00:19:03,108 HAD MRIs AND X-RAYS AND HE 535 00:19:03,175 --> 00:19:06,778 LOOKEDDA THE PEOPLE WHO HAD 536 00:19:06,845 --> 00:19:07,713 RADIO GRAPHIC OFTIO ARTHRITIS 537 00:19:07,779 --> 00:19:09,815 AND DIVIDED THEM UP WHETHER THEY 538 00:19:09,882 --> 00:19:11,083 HAD MENISICAL TEARS AND LOOKED 539 00:19:11,149 --> 00:19:12,684 TO SEE AMONG PEOPLE, WHAT'S THE 540 00:19:12,751 --> 00:19:14,887 FREQUENCY OF KNEE PAIN. 541 00:19:14,953 --> 00:19:17,589 AND THE IMIEDING THOUGHT AT THE 542 00:19:17,656 --> 00:19:19,758 TIME IS MENISICAL TEARS CAUSE 543 00:19:19,825 --> 00:19:19,958 PAIN. 544 00:19:20,025 --> 00:19:22,194 WELL, IN THIS SAMPLE, THE 545 00:19:22,261 --> 00:19:23,962 PROPORTION THAT HAD PAIN AMONG 546 00:19:24,029 --> 00:19:25,030 KNEES WITH MENISICAL TEARS WAS 547 00:19:25,097 --> 00:19:27,633 THE SAME AS THE PROPORTION QUHO 548 00:19:27,699 --> 00:19:29,001 DIDN'T HAVE PAIN. 549 00:19:29,067 --> 00:19:30,435 AND THIS IS IMPORTANT CLINICALLY 550 00:19:30,502 --> 00:19:32,371 BECAUSE WE NOW HAD OVER 20-25 551 00:19:32,437 --> 00:19:35,274 YEARS OF CLINICAL TRIALS, 552 00:19:35,340 --> 00:19:36,942 DEMONSTRATING THAT ARGT ROUGH 553 00:19:37,009 --> 00:19:38,877 ATOM SCOPPIC PARTIAL 554 00:19:38,944 --> 00:19:40,546 MENISSECTOMY A VERY COMMON 555 00:19:40,612 --> 00:19:42,147 ORTHOPEDIC SURGERY IS NO BETTER 556 00:19:42,214 --> 00:19:44,750 THAN PT OR SHAM SURGERY. 557 00:19:44,816 --> 00:19:46,351 YET THESE PROCEDURES CONTINUE TO 558 00:19:46,418 --> 00:19:47,753 BE DONE. 559 00:19:47,819 --> 00:19:48,520 SO THIS HIGHLIGHTS HOW DIFFICULT 560 00:19:48,587 --> 00:19:50,856 IT IS FOR KNOWLEDGE TRANSLATION 561 00:19:50,923 --> 00:19:57,529 TO IMPACT CLINICAL CARE. 562 00:19:57,596 --> 00:19:59,231 THAT'S MENISICAL TEARS, SO WHAT 563 00:19:59,298 --> 00:19:59,765 ABOUT OTHER ISSUES. 564 00:19:59,831 --> 00:20:01,934 SO WE DID ANOTHER FRAMINGHAM 565 00:20:02,000 --> 00:20:03,635 STUDY OF OTHER ISSUES. 566 00:20:03,702 --> 00:20:10,208 WE LOOKED AT KNEES FREE OF 567 00:20:10,275 --> 00:20:10,842 OSTEOARTHRITIS. 568 00:20:10,909 --> 00:20:11,209 PRISTINE KNEES. 569 00:20:11,276 --> 00:20:18,116 HERE YOU CAN SEE ON MREFRESH 570 00:20:18,183 --> 00:20:18,750 --MRI, YOU CAN 571 00:20:18,817 --> 00:20:20,986 SEE THEY HAD SOME KIND OF 572 00:20:21,053 --> 00:20:23,155 ABNORMALITY ON MRI. 573 00:20:23,221 --> 00:20:24,656 IN ADDITION THE ABNORMALITY 574 00:20:24,723 --> 00:20:33,966 AMONG THE KNEES, 90% WAS THE 575 00:20:34,032 --> 00:20:35,133 SAME PREVALENCE 90%. 576 00:20:35,200 --> 00:20:36,568 IT'S DIFFICULT TO IDENTIFY WHAT 577 00:20:36,635 --> 00:20:37,936 STRUCTURES ARE CAUSING PAIN IN 578 00:20:38,003 --> 00:20:39,204 ANY GIVEN INDIVIDUAL WHEN WE DO 579 00:20:39,271 --> 00:20:40,906 THESE VERY LARGE STUDIES WHERE 580 00:20:40,973 --> 00:20:43,575 WE CAN'T CONTROL FOR ALL OF 581 00:20:43,642 --> 00:20:46,411 THOSE BETWEEN PERSON 582 00:20:46,478 --> 00:20:46,912 DIFFERENCES. 583 00:20:46,979 --> 00:20:49,181 STUDIES OVERALL HAVE SHOWN THAT 584 00:20:49,247 --> 00:20:50,849 BONE MARROW LESIONS AND SIN 585 00:20:50,916 --> 00:20:53,085 OIVITIS OR INFLAMMATION OF THE 586 00:20:53,151 --> 00:20:55,320 SYNOVIAL LINING ARE 2 OF THE 587 00:20:55,387 --> 00:20:56,321 MOST FREQUENTLY IDENTIFIED 588 00:20:56,388 --> 00:21:00,859 TISSUES AS CONTRIBUTING TO THE 589 00:21:00,926 --> 00:21:02,527 PAIN PRESENCE IN OSTEOARTHRITIS. 590 00:21:02,594 --> 00:21:03,495 SO ALL THIS PAINTS A PICTURE 591 00:21:03,562 --> 00:21:04,863 THAT THERE ARE MULTIPLE 592 00:21:04,930 --> 00:21:09,434 CONTRIBUTORS TO PAIN AND 593 00:21:09,501 --> 00:21:09,835 OSTEOARTHRITIS. 594 00:21:09,901 --> 00:21:13,305 WHILE WE AS RESEARCHERS MIGHT BE 595 00:21:13,372 --> 00:21:15,674 INTERESTED IN DISENTANGLING THE 596 00:21:15,741 --> 00:21:17,142 OA PATHOLOGY RELATED TO PAIN, WE 597 00:21:17,209 --> 00:21:18,443 NEED TO RECK THERE ARE A WHOLE 598 00:21:18,510 --> 00:21:19,845 HOST OF THE OTHER THINGS THAT 599 00:21:19,911 --> 00:21:20,445 CONTRIBUTE TO THAT EXPERIENCE. 600 00:21:20,512 --> 00:21:22,214 SO FOR ME AS A CLINICIAN, 1 OF 601 00:21:22,280 --> 00:21:23,448 THE THINGS I DO ROUTINELY WITH 602 00:21:23,515 --> 00:21:26,151 ALL OF MY PATIENTS, IS ASSESS 603 00:21:26,218 --> 00:21:28,120 HOW GOOD THEIR SLEEP IS, WHAT'S 604 00:21:28,186 --> 00:21:31,289 THE THEIR MOOD, COPING SKILLS 605 00:21:31,356 --> 00:21:34,926 ARE, DO THEY HAVE ANY 606 00:21:34,993 --> 00:21:35,994 CATASTROPHIZING TRAITS, WHAT'S 607 00:21:36,061 --> 00:21:36,695 THEIR PHYSICAL ACTIVITY, ALL 608 00:21:36,762 --> 00:21:38,664 THESE OTHER THINGS THAT ARE NOT 609 00:21:38,730 --> 00:21:39,965 WITHIN THE PERVIEW OF 610 00:21:40,032 --> 00:21:41,466 RHEUMATOLOGY BECAUSE IF I CAN'T 611 00:21:41,533 --> 00:21:43,402 OPTIMIZE THOSE THINGS OR HELP 612 00:21:43,468 --> 00:21:44,369 OPTIMIZE THOSE THINGS, OTHER 613 00:21:44,436 --> 00:21:46,538 THINGS I DO ARE NOT GOING TO 614 00:21:46,605 --> 00:21:50,409 HAVE AS GOOD A PAIN EFFECT AS IF 615 00:21:50,475 --> 00:21:51,910 I COULD ALSO OPTIMIZE THESE 616 00:21:51,977 --> 00:21:52,177 THINGS. 617 00:21:52,244 --> 00:21:57,716 SO 1 OF THE AREAS THAT HAD NOT 618 00:21:57,783 --> 00:22:01,286 BEEN REALLY EVALUATED INDEPTH 619 00:22:01,353 --> 00:22:01,820 ARE THESE NEUROBIOLOGICAL 620 00:22:01,887 --> 00:22:02,521 MECHANISMS. 621 00:22:02,587 --> 00:22:04,456 AND YOU KNOW IT'S QUITE CLEAR, 622 00:22:04,523 --> 00:22:05,924 CLINICALLY, IF YOU THINK ABOUT 623 00:22:05,991 --> 00:22:09,961 IT, THAT THERE'S ALWAYS BEEN 624 00:22:10,028 --> 00:22:12,330 CLUES THERE ARE ALTERATIONS IN 625 00:22:12,397 --> 00:22:14,032 NEUROBIOLOGICAL MECH NIMS IN OA 626 00:22:14,099 --> 00:22:17,302 PAIN, EARLY FOR EXAMPLE IN OA 627 00:22:17,369 --> 00:22:19,337 THERE MIGHT BE MEDIAL LOCALIZED 628 00:22:19,404 --> 00:22:20,639 PAIN, THE MEDIAL ASPECT OF THE 629 00:22:20,706 --> 00:22:22,374 JOINT IS THE MOST COMMON SIDE 630 00:22:22,441 --> 00:22:23,742 EFFECTED BUT AT LATER STAGES THE 631 00:22:23,809 --> 00:22:26,511 PAIN CAN BE MORE DIFFUSE, THERE 632 00:22:26,578 --> 00:22:28,580 CAN BE REFERRED PAIN, WHY IS 633 00:22:28,647 --> 00:22:28,780 THAT? 634 00:22:28,847 --> 00:22:31,883 THE JOINT ISN'T UP HERE IN THE 635 00:22:31,950 --> 00:22:32,150 MIDTHIGH. 636 00:22:32,217 --> 00:22:33,351 SO THERE'S CLINICAL CLUES THERE 637 00:22:33,418 --> 00:22:36,021 ARE OTHER THINGS GOING ON. 638 00:22:36,088 --> 00:22:39,591 SO, WHAT IS THE EVIDENT FOR PAIN 639 00:22:39,658 --> 00:22:40,225 SENSITIZATION AND 640 00:22:40,292 --> 00:22:40,892 OSTEOARTHRITIS, WHAT IS THE 641 00:22:40,959 --> 00:22:42,494 EVIDENT THAT THERE'S ALTERATIONS 642 00:22:42,561 --> 00:22:43,428 IN THE NERVOUS SYSTEM THAT, 643 00:22:43,495 --> 00:22:44,930 CONTRIBUTE TO THE PAIN 644 00:22:44,996 --> 00:22:46,031 EXPERIENCE, WELL, I'M GOING TO 645 00:22:46,098 --> 00:22:48,834 FIRST START WITH AN OLD STUDY 646 00:22:48,900 --> 00:22:50,535 THAT SHOWS A VERY INTERESTING 647 00:22:50,602 --> 00:22:52,671 THING ABOUT CONTRA LATERAL KNEE 648 00:22:52,738 --> 00:22:55,307 EFFECTS WHEN YOU'RE TREATING A 649 00:22:55,373 --> 00:22:56,007 PARTICULAR KNEE. 650 00:22:56,074 --> 00:22:59,544 SO IN THIS INTERVENTION, STUDY, 651 00:22:59,611 --> 00:23:00,912 THERE WAS LIDOCAINE INJECTED 652 00:23:00,979 --> 00:23:02,714 INTO THE PAINFUL KNEE AND YOU 653 00:23:02,781 --> 00:23:07,052 CAN SEE THAT THERE WAS A PAIN 654 00:23:07,119 --> 00:23:07,319 REDUCTION. 655 00:23:07,385 --> 00:23:08,653 SO THIS ALSO SUPPORTS THE FACT 656 00:23:08,720 --> 00:23:09,554 THAT THERE'S SOMETHING IN THE 657 00:23:09,621 --> 00:23:12,457 KNEE THAT IS PAINFUL, INYECT 658 00:23:12,524 --> 00:23:13,859 LIDOCAINE, YOU REDUCE THE PAIN 659 00:23:13,925 --> 00:23:15,260 EMPLOY SOMETHING INSIDE THE KNEE 660 00:23:15,327 --> 00:23:16,695 WAS CAUSING PAIN. 661 00:23:16,762 --> 00:23:17,629 BUT WHAT'S REALLY TRIKING, I 662 00:23:17,696 --> 00:23:19,965 THINK MORE IMPORTANT IN THIS 663 00:23:20,031 --> 00:23:21,633 TRIAL, IS THAT THE CONTRA 664 00:23:21,700 --> 00:23:23,101 LATERAL KNEE THAT WAS NOT 665 00:23:23,168 --> 00:23:24,770 INJECTED ALSO HAD A PAIN 666 00:23:24,836 --> 00:23:25,070 IMPROVEMENT. 667 00:23:25,137 --> 00:23:26,738 SO WHY ARE YOU GETTING PAIN 668 00:23:26,805 --> 00:23:29,007 IMPROVEMENT IN THE KNEE THAT 669 00:23:29,074 --> 00:23:30,041 WASN'T INJECTED. 670 00:23:30,108 --> 00:23:34,579 AND SO THAT IMPLIES THAT SOME 671 00:23:34,646 --> 00:23:36,081 MODIFICATION WAS GOING ON, 672 00:23:36,148 --> 00:23:37,816 MODULATION WAS GOING ON IN THE 673 00:23:37,883 --> 00:23:38,817 NERVOUS SYSTEM. 674 00:23:38,884 --> 00:23:40,485 SO IN ANIMAL MODELS, CAN YOU DO 675 00:23:40,552 --> 00:23:43,054 ALL SORTS OF TESTING, 676 00:23:43,121 --> 00:23:44,189 NEUROPHYSIOLOGIC TESTING SO 677 00:23:44,256 --> 00:23:47,459 HERE'S A JOINT, THEY CAN DO 678 00:23:47,526 --> 00:23:48,994 ELECTROPHYSIOLOGIC, YOU KNOW PUT 679 00:23:49,060 --> 00:23:50,929 NEEDLES ON NERVES, THEY CAN DO 680 00:23:50,996 --> 00:23:53,165 NOXIOUS STIMULI, LIKE ROTATING 681 00:23:53,231 --> 00:23:58,170 AND THE YOINT AND THEN GETTING 682 00:23:58,236 --> 00:23:59,004 ACTION POTENTIALS. 683 00:23:59,070 --> 00:24:06,978 HERE THEY'RE INJECTING 684 00:24:07,045 --> 00:24:07,879 MONO[INDISCERNIBLE] ACETATE, SO 685 00:24:07,946 --> 00:24:10,015 WHEN YOU INJECT SOMETHING 686 00:24:10,081 --> 00:24:11,783 INFLAMMATORY YOU DO THIS NOXIOUS 687 00:24:11,850 --> 00:24:13,752 MOVEMENT OF THE JOINT, YOU CAN 688 00:24:13,819 --> 00:24:14,553 RECORD THOSE ACTION POTENTIALS 689 00:24:14,619 --> 00:24:16,087 AND THE MORE OF THE NOXIOUS 690 00:24:16,154 --> 00:24:19,024 STUFF YOU GIVE, THE MORE ACTION 691 00:24:19,090 --> 00:24:19,591 PROTENTIALS ARE FIRING. 692 00:24:19,658 --> 00:24:22,527 WE CAN'T DO THIS, IN HUMANS, WE 693 00:24:22,594 --> 00:24:24,296 CAN'T JUST STICK NEEDLES IN THE 694 00:24:24,362 --> 00:24:26,665 PINEAL CORD AND ON THEIR NERVES, 695 00:24:26,731 --> 00:24:28,533 READILY AND SO, WHEN I SOMETIMES 696 00:24:28,600 --> 00:24:29,801 PRESENT OUR DATA, I WILL HAVE 697 00:24:29,868 --> 00:24:31,536 BASIC SCIENTISTS COME UP TO ME 698 00:24:31,603 --> 00:24:32,771 AND JUST INTERROGATE THE SPINAL 699 00:24:32,838 --> 00:24:34,506 CORD, YOU WILL KNOW WHAT'S GOING 700 00:24:34,573 --> 00:24:36,741 ON IN CAN'T REALLY DO THAT IN 701 00:24:36,808 --> 00:24:37,542 HUMANS. 702 00:24:37,609 --> 00:24:39,578 SO WE HAVE TO USE INDIRECT TOOLS 703 00:24:39,644 --> 00:24:42,614 AND THE CLASS OF TOOLS ARE 704 00:24:42,681 --> 00:24:43,748 CALLED QUANTITATIVE SENSORY 705 00:24:43,815 --> 00:24:46,051 TESTING, THEY'RE A SERIES OF 706 00:24:46,117 --> 00:24:48,553 NEUROPHYSICAL TOOLS TO TRY TO 707 00:24:48,620 --> 00:24:50,055 MAKE INFERENCES ABOUT THESE 708 00:24:50,121 --> 00:24:50,856 VARIOUS PATHWAYS. 709 00:24:50,922 --> 00:24:54,726 SO HERE, IF WE'VE GOT PERIPHERAL 710 00:24:54,793 --> 00:24:55,560 AND NOCICEPTIVE INPUT, THE 711 00:24:55,627 --> 00:24:59,865 SIGNAL GOES UP TO THE SPINAL 712 00:24:59,931 --> 00:25:00,799 INCORD DORSAL ROOT AND THE 713 00:25:00,866 --> 00:25:04,035 SYMPTOM UP TO THE BRAIN AND 714 00:25:04,102 --> 00:25:05,737 THERE'S ALSO DESCENDING 715 00:25:05,804 --> 00:25:06,438 MODLATTORY PATHWAYS, SO IF WE 716 00:25:06,504 --> 00:25:09,274 UPON TO LOOK AT THE PEREVERERAL 717 00:25:09,341 --> 00:25:13,111 NOCISEPTORSORS AND WHETHER OR 718 00:25:13,178 --> 00:25:14,246 NOT THEY ARE WORKING 719 00:25:14,312 --> 00:25:16,214 ABNORMALITIES NORMALLY, SORT OF 720 00:25:16,281 --> 00:25:18,617 MORE FACILITATION OF SIGNALS, WE 721 00:25:18,683 --> 00:25:22,754 CAN USE A HAND HELD OGOMETER AND 722 00:25:22,821 --> 00:25:25,423 MEASURE PAIN THRESHOLD IN 723 00:25:25,490 --> 00:25:28,293 OSTEOARTHRITIS BECAUSE IT'S 724 00:25:28,360 --> 00:25:29,961 LARGELY A BIOMECHANICAL DRIVEN 725 00:25:30,028 --> 00:25:33,064 DISEASE AND BIO-MEDIATED BUT THE 726 00:25:33,131 --> 00:25:34,399 MECHANICAL STIMUE IS THOUGHT TO 727 00:25:34,466 --> 00:25:37,102 BE MOST IMPORTANT THAT'S WHY WE 728 00:25:37,168 --> 00:25:38,236 USE PAIN THRESHOLDS. 729 00:25:38,303 --> 00:25:41,106 THERE'S ANOTHER STIMULI WE CAN 730 00:25:41,172 --> 00:25:43,608 USE, NOXIOUS STIMULI BUT WE 731 00:25:43,675 --> 00:25:48,013 THINK A MECHANICAL STIMULUS IS 732 00:25:48,079 --> 00:25:49,314 MOST RELEVANT FOR OA. 733 00:25:49,381 --> 00:25:51,182 SO IF WE DO A SITE LIKE THE KNEE 734 00:25:51,249 --> 00:25:53,752 WE GET A SENSE OF PERIPHERAL 735 00:25:53,818 --> 00:25:57,789 SENSITIZATION, ARE THOSE SIGNALS 736 00:25:57,856 --> 00:26:03,061 HAVING FACILITATED--IS THERE 737 00:26:03,128 --> 00:26:03,561 ASCENDING FACILITATION? 738 00:26:03,628 --> 00:26:06,331 WHEN WE TEST THE PRESSURE SITE 739 00:26:06,398 --> 00:26:08,233 LIKE THE TRAPEZUOUS OR HEALTHY 740 00:26:08,300 --> 00:26:09,367 FOREARM, THAT CAN GIVE US AN 741 00:26:09,434 --> 00:26:14,072 IDEA OF THE CENTRAL NERVOUS SIZE 742 00:26:14,139 --> 00:26:14,873 AND CENTRAL SENSITIZATION. 743 00:26:14,940 --> 00:26:16,942 WE CAN ALSO INTERROGATE THE 744 00:26:17,008 --> 00:26:18,810 CENTRAL NERVOUS SYSTEM WITH A 745 00:26:18,877 --> 00:26:19,577 PROTOCOL CALLED TEMPORAL 746 00:26:19,644 --> 00:26:23,348 SUMMATION WHERE YOU USE A SERIES 747 00:26:23,415 --> 00:26:26,217 OF WEIGHTED PROBES AND YOU APPLY 748 00:26:26,284 --> 00:26:27,852 THESE PROBES ONCE PERSECOND OVER 749 00:26:27,919 --> 00:26:29,020 A PERIOD OF TIME AND IF YOU 750 00:26:29,087 --> 00:26:31,623 THINK ABOUT IT HERE, IF YOU'RE 751 00:26:31,690 --> 00:26:32,457 APPLYING THE SAME STIMULUS, YOU 752 00:26:32,524 --> 00:26:34,426 SHOULD GET THE SAME ACTION TO 753 00:26:34,492 --> 00:26:36,261 TENTIAL AND THE SAME SEN 754 00:26:36,328 --> 00:26:37,295 ILLEGALSENNATION, BUT FOR 755 00:26:37,362 --> 00:26:39,831 SOMEONE WHERE THERE'S ARK 756 00:26:39,898 --> 00:26:44,002 SENDING FACILITATION, WHERE THE 757 00:26:44,069 --> 00:26:45,637 SIGNALS ARE GOING, THE ACTION 758 00:26:45,704 --> 00:26:49,474 POTENTIALS ARE BEING FIRED, MORE 759 00:26:49,541 --> 00:26:50,809 READILY THAN THOSE ACTION 760 00:26:50,875 --> 00:26:52,210 POTENTIALS CAN BUILD UP ON EACH 761 00:26:52,277 --> 00:26:56,781 OTHER AND OVERTIME ON THAT TRAIN 762 00:26:56,848 --> 00:26:58,817 OF STIMULI THE PAIN EXPERIENCE 763 00:26:58,883 --> 00:26:59,084 INCREASES. 764 00:26:59,150 --> 00:27:00,952 AND THEN FINALLY WE CAN ALSO TRY 765 00:27:01,019 --> 00:27:02,687 TO EXAMINE THE DESCENDING 766 00:27:02,754 --> 00:27:05,623 MODLATTORY PATHWAY WITH THE 767 00:27:05,690 --> 00:27:07,292 PARADIGM CALLED PARADIGM PAIN 768 00:27:07,359 --> 00:27:08,493 MODULATION WHERE YOU FIRST 769 00:27:08,560 --> 00:27:09,160 ASSESS THE PRESSURE PAIN 770 00:27:09,227 --> 00:27:11,796 THRESHOLD AND THEN YOU APPLY A 771 00:27:11,863 --> 00:27:13,565 SECOND PAINFUL CONDITIONING 772 00:27:13,631 --> 00:27:16,434 STIMULUS AND THE THEORY IS THAT 773 00:27:16,501 --> 00:27:18,670 THAT PAINFUL CONDITION STIMULUS 774 00:27:18,737 --> 00:27:20,772 ACTIVATES THESE DESCENDING 775 00:27:20,839 --> 00:27:21,906 INHIBITORY MODLATTORY PATHWAYS 776 00:27:21,973 --> 00:27:24,009 SO THAT WHEN YOU CHECK THE 777 00:27:24,075 --> 00:27:26,177 PRESSURE PAIN THRESHOLD, AGAIN, 778 00:27:26,244 --> 00:27:28,013 IT IMPROVES, IT'S LIKE THIS 779 00:27:28,079 --> 00:27:31,349 PARADIGM OF PAIN INHIBITS PAIN. 780 00:27:31,416 --> 00:27:32,751 SO I'M JUST GOING TO GO THROUGH 781 00:27:32,817 --> 00:27:34,953 A COUPLE OF STUDIES THAT WE DID 782 00:27:35,020 --> 00:27:38,189 USING THESE MEASURES IN 783 00:27:38,256 --> 00:27:41,459 OSTEOARTHRITIS USING THE 784 00:27:41,526 --> 00:27:42,060 MULTICENTER OFTOSTEOARTHRITIS 785 00:27:42,127 --> 00:27:44,262 STUDY A MENTIONED A FEW MOMENTS 786 00:27:44,329 --> 00:27:47,332 AGO, A LARGE COHORT OF ADULTS AT 787 00:27:47,399 --> 00:27:49,234 RISK FOR KNEE OSTEOARTHRITIS, 788 00:27:49,300 --> 00:27:51,136 ONLY COHORT IN THE WORLD WHERE 789 00:27:51,202 --> 00:27:52,270 WE HAVE THESE MEASURES 790 00:27:52,337 --> 00:27:52,704 LONGITUDINALLY. 791 00:27:52,771 --> 00:27:54,139 WE STARTED AT YEAR 5 OF THIS 792 00:27:54,205 --> 00:27:57,108 COHORT AND WE'RE IN 2024 GOING 793 00:27:57,175 --> 00:27:58,410 INTO THE 20th YEAR IN THE 794 00:27:58,476 --> 00:28:00,211 FIELD WITH THIS COHORT. 795 00:28:00,278 --> 00:28:04,149 SO AGAIN, JUST REMINDING YOU 796 00:28:04,215 --> 00:28:06,151 WE'RE TRYING TO UNDERSTAND 797 00:28:06,217 --> 00:28:07,452 WHETHER THERE'S ABNORMALITIES 798 00:28:07,519 --> 00:28:14,659 AND SIGNALS ANYTHING UP OR 799 00:28:14,726 --> 00:28:16,261 ABNORMALITIES GOING UP OR DOWN. 800 00:28:16,327 --> 00:28:18,530 AND THE FIRST THING I WILL SHOW 801 00:28:18,596 --> 00:28:20,165 YOU IS THE PRESSURE THRESHOLD. 802 00:28:20,231 --> 00:28:22,300 WE LOOKED AT THE KNEE. 803 00:28:22,367 --> 00:28:23,902 FOR ANALYSIS WE DIVIDED THIS 804 00:28:23,968 --> 00:28:26,704 INTO TERTILES BECAUSE THERE'S NO 805 00:28:26,771 --> 00:28:29,808 BIOLOGIC THRESHOLD TO SAY WHICH 806 00:28:29,874 --> 00:28:30,508 APT IS NORMAL. 807 00:28:30,575 --> 00:28:33,511 SO THE LOWEST IS THE MOST PAIN 808 00:28:33,578 --> 00:28:37,115 SENSITIZED SO AS YOU APPLY THE 809 00:28:37,182 --> 00:28:38,850 OGOM EATER, THE POINT AT WHICH 810 00:28:38,917 --> 00:28:40,385 IT CHANGES TO PAIN IS CONSIDERED 811 00:28:40,452 --> 00:28:40,952 THE THRESHOLD. 812 00:28:41,019 --> 00:28:43,521 SO IF THE PERSON IS EXPERIENCING 813 00:28:43,588 --> 00:28:46,324 SLIGHT PAIN VERY QUICKLY, THEY 814 00:28:46,391 --> 00:28:48,293 HAVE A LOW THRESHOLD, THEY'RE 815 00:28:48,359 --> 00:28:49,627 MORE SENSITIZED O IN THESE 816 00:28:49,694 --> 00:28:51,930 ANALYSIS, THOSE THAT HAVE THE 817 00:28:51,996 --> 00:28:53,098 LOWEST PRESSURE PAIN THRESHOLD 818 00:28:53,164 --> 00:28:55,133 HAD THE HIGHEST RISK OF HAVING 819 00:28:55,200 --> 00:28:56,434 FREQUENT KNEE PAIN OR SEVERITY 820 00:28:56,501 --> 00:28:57,869 IN A DOSE RESPONSE RELATIONSHIP 821 00:28:57,936 --> 00:29:00,171 AND THIS IS ADJUSTED FOR ALL 822 00:29:00,238 --> 00:29:00,672 POTENTIAL CONFOUNDERS. 823 00:29:00,738 --> 00:29:04,943 WHEN WE DO IT AT THE WRIST AS AN 824 00:29:05,009 --> 00:29:06,010 INDICATION OF CENTRAL 825 00:29:06,077 --> 00:29:08,179 SENSITIZATION, WE FIND THE SAME 826 00:29:08,246 --> 00:29:08,880 PATTERN. 827 00:29:08,947 --> 00:29:11,082 SO BOTH PERIPHERAL AND 828 00:29:11,149 --> 00:29:12,283 SENSITIZATION ARE ASSOCIATE WIDE 829 00:29:12,350 --> 00:29:12,884 PAIN. 830 00:29:12,951 --> 00:29:14,619 WE THEN LOOKED AT A MORE 831 00:29:14,686 --> 00:29:18,389 SPECIFIC MEASURE FOR CENTRAL 832 00:29:18,456 --> 00:29:19,023 SENSITIZATION, AGAIN, ASCENDING 833 00:29:19,090 --> 00:29:22,293 FACILITATION AT THE CENTRAL 834 00:29:22,360 --> 00:29:24,028 NERVOUS SYSTEM LEVEL, WITH 835 00:29:24,095 --> 00:29:25,096 TEMPERRAL SUMMATION. 836 00:29:25,163 --> 00:29:28,032 AND HERE, CONTRARY TO OUR 837 00:29:28,099 --> 00:29:31,102 HYPOTHESIS, WE DID NOT FIND THAT 838 00:29:31,169 --> 00:29:32,470 TEMPORAL SUMMATION WAS ASSOCIATE 839 00:29:32,537 --> 00:29:36,407 WIDE PRESENCE OF RADIO GRAPHIC 840 00:29:36,474 --> 00:29:36,774 OSTEOARTHRITIS. 841 00:29:36,841 --> 00:29:38,543 MY HYPOTHESIS WAS THAT IF YOU 842 00:29:38,610 --> 00:29:40,512 HAVE RAD YE GRAPHIC OA, THAT 843 00:29:40,578 --> 00:29:41,246 MIGHT INDUCE SENSITIZATION AND 844 00:29:41,312 --> 00:29:43,248 WE SHOULD SEE THAT SENSITIZATION 845 00:29:43,314 --> 00:29:44,482 HAS A HIGHER ASSOCIATION WITH 846 00:29:44,549 --> 00:29:46,351 PRESENCE OF RADIO GRAPHIC OA. 847 00:29:46,417 --> 00:29:47,986 WE DID NOT FIEND THAT. 848 00:29:48,052 --> 00:29:49,654 INSTEAD WE FOUND THAT IT WAS 849 00:29:49,721 --> 00:29:52,157 ASSOCIATED WITH HAVING SYMPTOMS, 850 00:29:52,223 --> 00:29:53,858 FREQUENT KNEE PAIN AND MOST 851 00:29:53,925 --> 00:29:58,363 STRONGLY WITH XEE PAIN SEVERITY. 852 00:29:58,429 --> 00:30:01,799 SO WE WERE REALLY PUZZLED BY WHY 853 00:30:01,866 --> 00:30:04,102 ISN'T ASSOCIATED WITH RADIO 854 00:30:04,169 --> 00:30:05,069 GRAPHIC OA? 855 00:30:05,136 --> 00:30:07,372 I THOUGHT WELL, MAYBE IT'S KIND 856 00:30:07,438 --> 00:30:08,606 OF A HODGEPODGE OF EVERYTHING 857 00:30:08,673 --> 00:30:10,008 GOING ON IN THE JOINT, IT'S LATE 858 00:30:10,074 --> 00:30:10,842 IN THE GAME. 859 00:30:10,909 --> 00:30:12,210 IT'S CLOSE, THERE'S A LOT GOING 860 00:30:12,277 --> 00:30:14,879 ON IN THE JOANT AND WE CAN'T 861 00:30:14,946 --> 00:30:17,081 DISENTANGLE WHAT MIGHT BE 862 00:30:17,148 --> 00:30:19,417 RELATED TO SENSITIZATION, AND IN 863 00:30:19,484 --> 00:30:20,718 THINKING ABOUT ANIMAL MODELS, 864 00:30:20,785 --> 00:30:22,387 YOU CAN INDUCE SENSITIZATION 865 00:30:22,453 --> 00:30:25,190 THROUGH CHRONIC JOINT INJURY, OR 866 00:30:25,256 --> 00:30:26,124 CHRONIC INFLAMMATION. 867 00:30:26,191 --> 00:30:29,761 AND THE HUMAN EQUIVALENT WILL BE 868 00:30:29,827 --> 00:30:33,932 A MECHANICAL STIMULUS TO KIND OF 869 00:30:33,998 --> 00:30:36,201 BE PARALLEL TO JOINT INJURY SUCH 870 00:30:36,267 --> 00:30:38,469 AS BONE MARROW LESIONS OR 871 00:30:38,536 --> 00:30:39,704 INFLAMMATORY LESIONS WOULD BE 872 00:30:39,771 --> 00:30:40,605 SIN OIVITIS OR 873 00:30:40,672 --> 00:30:41,239 CERTAINLY--CERTAINLY FUSION AND 874 00:30:41,306 --> 00:30:44,576 IN DOING THIS ANALIS WE FOUND 875 00:30:44,642 --> 00:30:47,512 THAT BONE MARROW WAS NOT 876 00:30:47,579 --> 00:30:50,081 ASSOCIATE WIDE LESIONS BUT 877 00:30:50,148 --> 00:30:50,982 INFLAMMATORY LESIONS WERE. 878 00:30:51,049 --> 00:30:52,483 SO BONE MARROW LESIONS WE KNOW 879 00:30:52,550 --> 00:30:54,319 ARE ASSOCIATE WIDE PAIN IN OA 880 00:30:54,385 --> 00:30:56,087 BUT THE MECHANISM BY WHICH BONE 881 00:30:56,154 --> 00:30:57,789 MARROW LESIONS CONTRIBUTE TO 882 00:30:57,855 --> 00:30:59,324 PAIN IS NOT THROUGH 883 00:30:59,390 --> 00:31:00,959 SENSITIZATION, IT'S THROUGH SOME 884 00:31:01,025 --> 00:31:01,993 OTHER MECHANISM. 885 00:31:02,060 --> 00:31:03,127 FOR THESE INFLAMMATORY LESIONS, 886 00:31:03,194 --> 00:31:04,796 WE KNOW THEY CONTRIBUTE TO PAIN 887 00:31:04,862 --> 00:31:06,998 AND OA AND AT LEAST 1 OF THE 888 00:31:07,065 --> 00:31:07,532 MECHANISMS BY WHICH THEY 889 00:31:07,599 --> 00:31:10,635 CONTRIBUTE TO PAIN IS THROUGH 890 00:31:10,702 --> 00:31:11,035 SENSITIZATION. 891 00:31:11,102 --> 00:31:13,271 SO TO KIND OF PUT THIS 892 00:31:13,338 --> 00:31:14,739 ALTOGETHER SO FAR, WHAT WE'VE 893 00:31:14,806 --> 00:31:16,140 LEARNED IN THESE SERIES OF 894 00:31:16,207 --> 00:31:20,511 STUDIES WE'VE DONE IS WITH THESE 895 00:31:20,578 --> 00:31:23,214 MEASURES, OF PAIN SENSITIZATION, 896 00:31:23,281 --> 00:31:24,916 THESE MEASURES ARE ASSOCIATE 897 00:31:24,983 --> 00:31:26,651 WIDE PAIN SEVERITY, THEY'RE NOT 898 00:31:26,718 --> 00:31:27,685 ASSOCIATED WITH THE MERE 899 00:31:27,752 --> 00:31:30,121 PRESENCE OF RADIO GRAPHIC OA. 900 00:31:30,188 --> 00:31:31,889 I DIDN'T SHOW THESE DATA BUT 901 00:31:31,956 --> 00:31:33,524 THEY ARE ALSO NOT ASSOCIATED 902 00:31:33,591 --> 00:31:34,826 WITH DURATION OF OA. 903 00:31:34,892 --> 00:31:37,128 I THOUGHT, OKAY, MAYBE IT'S NOT 904 00:31:37,195 --> 00:31:38,429 MERE PRESENCE OF OA BUT THE 905 00:31:38,496 --> 00:31:39,631 LONGER YOU HAVE OA, THE MORE 906 00:31:39,697 --> 00:31:41,032 LIKELY IT IS THAT YOU HAVE 907 00:31:41,099 --> 00:31:42,634 SENSITIZATION AND THAT WAS NOT 908 00:31:42,700 --> 00:31:43,901 THE CASE. 909 00:31:43,968 --> 00:31:46,037 BUT WE DID FIND SPECIFIC 910 00:31:46,104 --> 00:31:46,738 ASSOCIATIONS WITH INFLAMMATION 911 00:31:46,804 --> 00:31:51,209 BUT NOT BONE MARROW LESIONS. 912 00:31:51,276 --> 00:31:52,977 SO THESE FINDINGS OF NOT BEING 913 00:31:53,044 --> 00:31:55,613 ASSOCIATED WITH RADIO GRAPHIC OR 914 00:31:55,680 --> 00:31:57,115 DURATION OF OA MADE US TART 915 00:31:57,181 --> 00:31:59,317 THINKING ABOUT WELL, IS THIS A 916 00:31:59,384 --> 00:32:00,518 STATE THAT'S INDUCIBLE BY 917 00:32:00,585 --> 00:32:03,121 PATHOLOGY, OR IS IT A TRAIT 918 00:32:03,187 --> 00:32:06,324 THAT'S UNMASKED ONCE YOU HAVE 919 00:32:06,391 --> 00:32:07,292 PATHOLOGY. 920 00:32:07,358 --> 00:32:08,459 SORRY, ARE YOU PREDISPOSED TO 921 00:32:08,526 --> 00:32:12,497 HAVING A CERTAIN PAIN EXPERIENCE 922 00:32:12,563 --> 00:32:14,098 BECAUSE YOU HAVE THIS AS AN 923 00:32:14,165 --> 00:32:15,500 UNDERLYING TRAIT AND THAT'S WHY 924 00:32:15,566 --> 00:32:17,735 SOME PEOPLE WITH THE SAME AMOUNT 925 00:32:17,802 --> 00:32:21,572 OF RADIO GRAPHIC OA HAVE MORE 926 00:32:21,639 --> 00:32:21,973 PAIN THAN OTHERS. 927 00:32:22,040 --> 00:32:24,842 SO IF YOU LOOK IN THE LITERATURE 928 00:32:24,909 --> 00:32:26,144 AROUND THE TIME WE WERE ASKING 929 00:32:26,210 --> 00:32:27,545 THIS QUESTION, THERE WASN'T A 930 00:32:27,612 --> 00:32:29,247 LOT THAT LOOKED AT THIS BECAUSE 931 00:32:29,314 --> 00:32:31,316 MOST THINGS WERE DONE IN A CROSS 932 00:32:31,382 --> 00:32:32,050 SECTIONAL MANNER. 933 00:32:32,116 --> 00:32:34,719 SO IN THIS STUDY FROM A DANISH 934 00:32:34,786 --> 00:32:36,187 GROUP, THEY--I WILL SAY WHAT THE 935 00:32:36,254 --> 00:32:37,322 CONCLUSION IS BEFORE I SHOW THE 936 00:32:37,388 --> 00:32:38,656 FIGURE WHICH IS VERY BUSY, THEY 937 00:32:38,723 --> 00:32:40,892 FOUND THERE WAS LOWER PREC PAIN 938 00:32:40,958 --> 00:32:44,329 THRESHOLD IN PEOPLE OF OFTIO 939 00:32:44,395 --> 00:32:46,597 OSTEOARTHRITIS THAN PEOPLE IN 940 00:32:46,664 --> 00:32:47,065 HELICONTROLS. 941 00:32:47,131 --> 00:32:47,765 HEALTHY CONTROLS MEAN THEY 942 00:32:47,832 --> 00:32:48,766 DEPARTMENT HAVE OA AND THEY 943 00:32:48,833 --> 00:32:49,767 DIDN'T HAVE PAIN. 944 00:32:49,834 --> 00:32:51,336 SO ANY DIFFERENCE WEAN THESE 2 945 00:32:51,402 --> 00:32:53,004 GROUPS, YOU DON'T KNOW IF IT'S 946 00:32:53,071 --> 00:32:56,874 DUE TO PAIN, DUE TO OA OR THE 947 00:32:56,941 --> 00:32:58,376 COMBINATION OF THE 2. 948 00:32:58,443 --> 00:33:02,013 SO ON THIS LEFT SIDE IS THE 949 00:33:02,080 --> 00:33:03,815 PAINFUL KNEE, ON THIS RIGHT SIDE 950 00:33:03,881 --> 00:33:05,249 IS THE NONPAINFUL KNEE, THE 951 00:33:05,316 --> 00:33:07,251 BLACK BARS ARE PAINFUL 952 00:33:07,318 --> 00:33:08,486 THRESHOLDS IN OA PEOPLE AND 953 00:33:08,553 --> 00:33:10,922 WHITE BARS ARE IN THOSE HEALTHY 954 00:33:10,988 --> 00:33:12,156 CONTROLS, YOU CAN SEE THE 955 00:33:12,223 --> 00:33:13,491 PRESSURE PAIN AND PLEAS HOLD 956 00:33:13,558 --> 00:33:14,992 WITH THE PEOPLE WITH OA LOWER AT 957 00:33:15,059 --> 00:33:18,062 ALL SITES ON THE PAINFUL KNEE, 958 00:33:18,129 --> 00:33:20,598 AND THE NONPAINFUL KNEE, IN 959 00:33:20,665 --> 00:33:23,901 ADDITION AT THE ARM AND AT THE 960 00:33:23,968 --> 00:33:25,470 TIBIALIS INTERIOR, SO IT SEEMS 961 00:33:25,536 --> 00:33:28,239 LIKE A FLOABAL PHENOMENON, THESE 962 00:33:28,306 --> 00:33:29,474 PEOPLE HAVE LOWER PAIN 963 00:33:29,540 --> 00:33:30,742 THRESHOLDS NO MATTER WHERE YOU 964 00:33:30,808 --> 00:33:31,809 LOOK, THIS IS CROSS SECTIONAL 965 00:33:31,876 --> 00:33:33,444 AND WE DON'T KNOW IF IT'S 966 00:33:33,511 --> 00:33:38,082 CHICKEN OR THE EGG. 967 00:33:38,149 --> 00:33:38,883 OR ALISA [INDISCERNIBLE] WHO 968 00:33:38,950 --> 00:33:40,785 CAME AND DID A RESEARCH POST DOC 969 00:33:40,852 --> 00:33:41,986 WITH ME WAS ABOUTED IN THIS 970 00:33:42,053 --> 00:33:46,758 QUESTION AS WELL AND WE WANTED 971 00:33:46,824 --> 00:33:48,593 TO UNDERSTAND ABOUT PAIN 972 00:33:48,659 --> 00:33:48,993 SUSCEPTIBILITY. 973 00:33:49,060 --> 00:33:49,794 SO IS THIS A TRAIT? 974 00:33:49,861 --> 00:33:51,028 WE WANTED TO UNDERSTAND, OKAY, 975 00:33:51,095 --> 00:33:53,498 WE UNDERSTAND THERE ARE CERTAIN 976 00:33:53,564 --> 00:33:54,665 JOINT PATHOLOGIES THAT 977 00:33:54,732 --> 00:33:57,101 CONTRIBUTE TO PAIN BUT THERE ARE 978 00:33:57,168 --> 00:33:58,269 UNDERLYING FEATURES INHERENT IN 979 00:33:58,336 --> 00:34:00,138 AN INDIVIDUAL THAT PREDISPOSE 980 00:34:00,204 --> 00:34:03,775 THEM TO HAVING A WORSE PAIN 981 00:34:03,841 --> 00:34:04,008 OUTCOME. 982 00:34:04,075 --> 00:34:06,644 ONE OF THE KEY QUESTIONS IN 983 00:34:06,711 --> 00:34:07,278 OSTEOARTHRITIS AND GENERALLY FOR 984 00:34:07,345 --> 00:34:09,313 PAIN IS WHY DO PEOPLE TRANSITION 985 00:34:09,380 --> 00:34:11,315 FROM ACUTE TO CHRONIC PAIN WHEN 986 00:34:11,382 --> 00:34:13,217 THE ACUTE INJURY, WHEN THE ACUTE 987 00:34:13,284 --> 00:34:14,652 INSULT IS GONE, WHY DO SOME 988 00:34:14,719 --> 00:34:17,188 PEOPLE HAVE CHRONIC PAIN IN AND 989 00:34:17,255 --> 00:34:18,923 IN OSTEOARTHRITIS WHY DO PEOPLE 990 00:34:18,990 --> 00:34:21,025 GO FROM HAVING INTERMITTENT 991 00:34:21,092 --> 00:34:23,394 WEIGHT TO BEARING PAIN TO 992 00:34:23,461 --> 00:34:24,562 CHRONIC PERSISTENT PAIN IN SO WE 993 00:34:24,629 --> 00:34:26,497 SAID, OKAY, WE WANT TO,A 994 00:34:26,564 --> 00:34:27,665 ASSESSES OUR QUANTITATIVE 995 00:34:27,732 --> 00:34:28,499 SENSORY TESTING MEASURES, BUT WE 996 00:34:28,566 --> 00:34:30,902 ALSO WANT TO LOOK AT MAYBE 997 00:34:30,968 --> 00:34:33,204 THERE'S A GROUPING OF FEATURES, 998 00:34:33,271 --> 00:34:37,642 LIKE IF YOU HAVE POOR MOOD, POOR 999 00:34:37,708 --> 00:34:39,076 COGNITION, POOR SLEEP, WIDE 1000 00:34:39,143 --> 00:34:40,912 SPREAD PAIN, MAYBE THERE'S A 1001 00:34:40,978 --> 00:34:42,079 CLUSTER OF FEATURES THAT 1002 00:34:42,146 --> 00:34:43,681 PREDISPOSE TO YOU DEVELOPING 1003 00:34:43,748 --> 00:34:44,682 PERSISTENT PAIN. 1004 00:34:44,749 --> 00:34:45,750 SO WE LOOKEDDA THE A BUNCH OF 1005 00:34:45,817 --> 00:34:47,618 PEOPLE WHO DID NOT HAVE 1006 00:34:47,685 --> 00:34:49,387 PERSISTENT KNEE PAIN AT BASE 1007 00:34:49,454 --> 00:34:49,587 LINE. 1008 00:34:49,654 --> 00:34:52,023 HAD ALL THESE MEASURES TAKEN AND 1009 00:34:52,089 --> 00:34:54,425 THEN WE FOLLOWED THEM FOR 2 1010 00:34:54,492 --> 00:34:54,625 YEARS. 1011 00:34:54,692 --> 00:35:00,498 AND WHAT WE FOUND WAS THAT THE 1012 00:35:00,565 --> 00:35:02,900 GROUP THAT WAS PREDOMINATED 1013 00:35:02,967 --> 00:35:06,504 BASED ON PAIN PRESSURE THRESHOLD 1014 00:35:06,571 --> 00:35:08,906 HAD A RISK OF DEVELOPING PAIN 2 1015 00:35:08,973 --> 00:35:09,407 YEARS LATER. 1016 00:35:09,474 --> 00:35:12,877 SO WHEY DID IN THIS STUDY AND WE 1017 00:35:12,944 --> 00:35:16,314 USED AN AGNOSTIC APPROACH CALLED 1018 00:35:16,380 --> 00:35:16,914 LATENT CLASS ANALYSIS. 1019 00:35:16,981 --> 00:35:20,084 SO WE DID NOT TRY TO GROUP THESE 1020 00:35:20,151 --> 00:35:21,452 TOGETHER TO SAY WHICH 1021 00:35:21,519 --> 00:35:22,186 COMBINATIONS OF THESE GO 1022 00:35:22,253 --> 00:35:22,720 TOGETHER. 1023 00:35:22,787 --> 00:35:25,423 WE LET THE DATA SPEAK FOR ITSELF 1024 00:35:25,490 --> 00:35:28,226 AND HERE'S A SPIDER GRAM SHOWING 1025 00:35:28,292 --> 00:35:31,796 1 GROUP PREDOMINATED BY PRESSURE 1026 00:35:31,863 --> 00:35:33,431 THRESHOLDS SENSITIZATION, AND 1 1027 00:35:33,498 --> 00:35:34,532 GROUP WITH TEMPORAL SUMMATION 1028 00:35:34,599 --> 00:35:36,367 AND THE OTHER GROUP HAS LESS OF 1029 00:35:36,434 --> 00:35:37,568 THESE BUT CLINICALLY WHAT I 1030 00:35:37,635 --> 00:35:39,403 THOUGHT WAS REALLY INTERESTING 1031 00:35:39,470 --> 00:35:41,472 IS, THESE GROUPS DO NOT DIFFER 1032 00:35:41,539 --> 00:35:45,176 ON PREVALENCE FOR SLEEP, 1033 00:35:45,243 --> 00:35:46,944 DEPRESSIVE SLEEP OR WIDE SPREAD 1034 00:35:47,011 --> 00:35:47,445 PAIN. 1035 00:35:47,512 --> 00:35:49,247 SO ALTHOUGH, MOOD, LEAP, PLAW, 1036 00:35:49,313 --> 00:35:50,982 BLAH, PLAW, ALL THOSE ARE 1037 00:35:51,048 --> 00:35:52,149 IMPORTANT FOR THE PAIN 1038 00:35:52,216 --> 00:35:53,351 EXPERIENCE, THEY'RE NOT 1039 00:35:53,417 --> 00:35:55,319 PREDISPOSING PEOPLE TO 1040 00:35:55,386 --> 00:35:57,054 DEVELOPING CHRONIC PERSISTENT 1041 00:35:57,121 --> 00:35:57,288 PAIN. 1042 00:35:57,355 --> 00:35:58,856 AND SO WHEN YOU DO THESE 1043 00:35:58,923 --> 00:36:01,926 ANALYSIS, WE FIND THAT THIS DARK 1044 00:36:01,993 --> 00:36:03,461 BLUE GROUP, THE BLUE THRESHOLD 1045 00:36:03,528 --> 00:36:04,996 GROUP IS THE ONLY GROUP THAT HAD 1046 00:36:05,062 --> 00:36:07,532 THE 2 FOLD INCREASE RISK OF 1047 00:36:07,598 --> 00:36:08,032 PERSISTENT, DEVELOPING 1048 00:36:08,099 --> 00:36:08,799 PERSISTENT KNEE PAIN MUCH THE 1049 00:36:08,866 --> 00:36:10,434 REST OF THE GROUPS HAD NO 1050 00:36:10,501 --> 00:36:11,035 INCREASED RISK. 1051 00:36:11,102 --> 00:36:12,336 SO HAD IS STARTING TO CONTRIBUTE 1052 00:36:12,403 --> 00:36:14,071 TO THIS CONCEPT OF A TRAIT. 1053 00:36:14,138 --> 00:36:16,440 AND WHEN THIS WAS PRESENTED AT 1054 00:36:16,507 --> 00:36:20,111 AN NIH PAIN SYMPOSIUM, THIS WAS 1055 00:36:20,177 --> 00:36:23,814 HIGHLIGHTED AS 1 OF THE MOST 1056 00:36:23,881 --> 00:36:24,749 IMPORTANT INSIGHTS INTO--NOT 1057 00:36:24,815 --> 00:36:26,217 JUST FOR OA PAIN BUT 1058 00:36:26,284 --> 00:36:27,618 UNDERSTANDING THIS ACUTE TO 1059 00:36:27,685 --> 00:36:28,319 CHRONIC PAIN TRANITION AND 1060 00:36:28,386 --> 00:36:30,354 HIGHLIGHTS THE NEED FOR 1061 00:36:30,421 --> 00:36:31,122 LONGITUDINAL DATA TO ADDRESS 1062 00:36:31,188 --> 00:36:31,822 THESE IMPORTANT QUESTIONS. 1063 00:36:31,889 --> 00:36:36,827 SO WHAT ARE CONSEQUENCES OF 1064 00:36:36,894 --> 00:36:38,863 SENSITIZATION, SO A CONUNDRUM IS 1065 00:36:38,930 --> 00:36:42,233 YOIBT REPLACEMENT IS GRIT BUT 1066 00:36:42,300 --> 00:36:43,534 ABOUT 15-20% OF PEOPLE STILL 1067 00:36:43,601 --> 00:36:45,036 HAVE PAIN AFTER THEIR KNEE IS 1068 00:36:45,102 --> 00:36:45,369 REPLACED. 1069 00:36:45,436 --> 00:36:46,971 SO WHY IS THAT? 1070 00:36:47,038 --> 00:36:48,873 YOU'VE REMOVED THE PAINFUL 1071 00:36:48,940 --> 00:36:51,475 TISSUE, AND YET THEY STILL HAVE 1072 00:36:51,542 --> 00:36:52,043 PAIN. 1073 00:36:52,109 --> 00:36:55,112 SO WHY IS THAT IN SO 1074 00:36:55,179 --> 00:36:56,213 [INDISCERNIBLE] WHO IS A POST 1075 00:36:56,280 --> 00:36:59,150 DOC WITH ME, HE'S NOW FACULTY AT 1076 00:36:59,216 --> 00:37:01,752 UNIVERSITY OF TEXAS IN EL PASO, 1077 00:37:01,819 --> 00:37:06,257 WE DID THIS STUDY IN A COHORT OF 1078 00:37:06,324 --> 00:37:07,658 PEOPLE WHERE WE--HAD JOINT 1079 00:37:07,725 --> 00:37:08,492 REPLACEMENTS AND WE BROUGHT THEM 1080 00:37:08,559 --> 00:37:10,895 BACK A YEAR AFTER THEY HAD JOINT 1081 00:37:10,962 --> 00:37:12,196 REPLACEMENT AND WE DID 1082 00:37:12,263 --> 00:37:13,497 QUANTITATIVE SENSORY TESTING AND 1083 00:37:13,564 --> 00:37:15,333 WOE FOUND THAT AFTER THEIR KNEE 1084 00:37:15,399 --> 00:37:17,802 REPLACE AM, HAVING TEMPORAL 1085 00:37:17,868 --> 00:37:19,136 SUMMATION AND INADEQUATE 1086 00:37:19,203 --> 00:37:21,105 DESCENDING MODULATION, THAT'S 1087 00:37:21,172 --> 00:37:23,174 THAT CONDITION TO PAIN 1088 00:37:23,240 --> 00:37:26,243 MODULATION PARADIGM, THESE WERE 1089 00:37:26,310 --> 00:37:29,714 ASSOCIATED WITH WOMACK STANDARD 1090 00:37:29,780 --> 00:37:30,481 MEASUREMENT OF PAIN. 1091 00:37:30,548 --> 00:37:32,049 SO THIS IS AGAIN POINTING TO 1092 00:37:32,116 --> 00:37:34,885 CLUES THAT THESE NERVOUS SYSTEM 1093 00:37:34,952 --> 00:37:35,519 ABNORMALITIES ARE CONTRIBUTING 1094 00:37:35,586 --> 00:37:37,955 NOT ONLY TO THE PANE EXPERIENCE 1095 00:37:38,022 --> 00:37:40,758 IN OA, THE DEVELOPMENT OF 1096 00:37:40,825 --> 00:37:43,094 PERSISTENCE IN OA BUT MAY ALSO 1097 00:37:43,160 --> 00:37:44,428 CONTRIBUTE TO PERSISTENT OA 1098 00:37:44,495 --> 00:37:48,833 AFTER REMOVING REMOVING THE DIE 1099 00:37:48,899 --> 00:37:49,066 TISSUE. 1100 00:37:49,133 --> 00:37:50,201 I'VE ALWAYS BEEN INTEREST INDEED 1101 00:37:50,267 --> 00:37:53,137 SAYING WELL, OKAY, IF THERE'S 1102 00:37:53,204 --> 00:37:55,039 ABNORMAL 8S TO SIGNALS GOING UP 1103 00:37:55,106 --> 00:37:56,974 TO THE BRAIN, ARE THERE 1104 00:37:57,041 --> 00:37:57,908 ABNORMALITIES GOING DOWN TO THE 1105 00:37:57,975 --> 00:38:00,244 JOINT AND THE FUNCTION AND IS IT 1106 00:38:00,311 --> 00:38:02,880 RESILIENCEALATED TO A SORT OF A 1107 00:38:02,947 --> 00:38:06,083 COMMON PROBLEM AT THE CORTICALE 1108 00:38:06,150 --> 00:38:08,319 LEVEL OR SENSITIZATION, SOMEHOW 1109 00:38:08,386 --> 00:38:12,423 AFFECTING THE EFFECTOR MOTOR 1110 00:38:12,490 --> 00:38:12,723 FUNCTIONING. 1111 00:38:12,790 --> 00:38:13,658 SO JOSH STEFANIC ON THE RIGHT, 1112 00:38:13,724 --> 00:38:16,794 HE WAS MY MENTEE, HE HAD AN NIH 1113 00:38:16,861 --> 00:38:18,562 K ASH WARD TO DO THIS WORK AND 1114 00:38:18,629 --> 00:38:20,131 NOW HES OWN MENTEE PAT IS 1115 00:38:20,197 --> 00:38:23,968 CONTINUING ON THIS WORK WITH 1116 00:38:24,035 --> 00:38:24,135 US. 1117 00:38:24,201 --> 00:38:26,170 SO WE HAD POSED THIS QUESTION, 1118 00:38:26,237 --> 00:38:27,872 THIS PAIN SENSITIZATION HAVE A 1119 00:38:27,938 --> 00:38:29,940 DIRECT EFFECT ON PHYSICAL 1120 00:38:30,007 --> 00:38:31,575 FUNCTION, NOT THROUGH PAIN 1121 00:38:31,642 --> 00:38:31,842 SEVERITY? 1122 00:38:31,909 --> 00:38:33,911 SO YOU KNOW YOU CAN SEE THAT 1123 00:38:33,978 --> 00:38:35,579 OKAY, YOUR SENSITIZED, YOU HAVE 1124 00:38:35,646 --> 00:38:37,081 MORE PAIN SEVERITY, YOU HAVE 1125 00:38:37,148 --> 00:38:39,784 MORE PAIN, YOU HAVE POOR 1126 00:38:39,850 --> 00:38:40,251 FUNCTIONING. 1127 00:38:40,317 --> 00:38:42,787 BUT IS THERE A DIFFERENT--IS 1128 00:38:42,853 --> 00:38:44,155 THERE ANOTHER PATHWAY THROUGH 1129 00:38:44,221 --> 00:38:45,756 WHICH PAIN SENSITIZATION MAY BE 1130 00:38:45,823 --> 00:38:47,158 AFFECTING PAIN FUNCTIONING AND 1131 00:38:47,224 --> 00:38:48,793 WITH THESE ANALYSIS, WE FOUND 1132 00:38:48,859 --> 00:38:52,463 THAT THOSE, THOSE THAT WERE MOST 1133 00:38:52,530 --> 00:38:54,165 SENSITIZED, THE LOWEST TERTILES 1134 00:38:54,231 --> 00:38:56,667 HAD THE WORST SELF-REPORTED 1135 00:38:56,734 --> 00:38:58,202 FUNCTIONING BASED ON THE WOMAC 1136 00:38:58,269 --> 00:39:00,071 SCALE AND THE LOWEST PRESSURE 1137 00:39:00,137 --> 00:39:02,139 PAIN THRESHOLDS ALSO HAD THE 1138 00:39:02,206 --> 00:39:04,341 SLOWEST WALKING SPEED, THE 1139 00:39:04,408 --> 00:39:07,845 SLOWEST GAIT SPEED SORE POOR 1140 00:39:07,912 --> 00:39:10,114 PHYSICAL PERFOR THE PURPOSANCE 1141 00:39:10,181 --> 00:39:12,650 BASED MEASUREMENT OF FUNCTION. 1142 00:39:12,717 --> 00:39:14,652 WE ALSO FOUND THAT THESE 1143 00:39:14,719 --> 00:39:16,887 MEASURES OF SENSITIZATION WERE 1144 00:39:16,954 --> 00:39:17,855 ASSOCIATED WITH LOWER STRENGTH 1145 00:39:17,922 --> 00:39:21,525 IN THOSE LEGS AND MUSCLE CO 1146 00:39:21,592 --> 00:39:23,761 CONTRACT WHICH IS AN ABNORMAL 1147 00:39:23,828 --> 00:39:26,731 FUNCTIONING OF THE MUSCLES THAT 1148 00:39:26,797 --> 00:39:27,631 CAN BE DETRIMENTAL IN 1149 00:39:27,698 --> 00:39:28,132 OSTEOARTHRITIS. 1150 00:39:28,199 --> 00:39:30,468 BUT IN TERMS OF THAT QUESTION OF 1151 00:39:30,534 --> 00:39:31,769 DOES MAIN SENSITIZATION 1152 00:39:31,836 --> 00:39:33,871 CONTRIBUTE TO PHYSICAL FUNCTION 1153 00:39:33,938 --> 00:39:36,173 DIRECTLY INDEPENDENT OF PAIN 1154 00:39:36,240 --> 00:39:37,508 SEVERITY, WE FOUND THAT THE 1155 00:39:37,575 --> 00:39:39,243 EFFECTS OF PAIN SENSITIZATION 1156 00:39:39,310 --> 00:39:41,378 WERE NOT COMPLETELY MEDIATED BY 1157 00:39:41,445 --> 00:39:44,315 PAIN SEVERITY, MEANING THERE IS 1158 00:39:44,381 --> 00:39:46,117 SOME DIRECT EFFECT OF PAIN 1159 00:39:46,183 --> 00:39:46,650 SENSITIZATION ON FUNCTION. 1160 00:39:46,717 --> 00:39:48,619 AND SO THIS LEADS TO A WHOLE 1161 00:39:48,686 --> 00:39:55,226 HOST OF OTHER QUESTIONS ABOUT 1162 00:39:55,292 --> 00:39:58,996 MOVEMENT EVOKED PAIN AND HYPER 1163 00:39:59,063 --> 00:40:02,566 SENSITIVE ALGEEZIA, SO MOVEMENT 1164 00:40:02,633 --> 00:40:07,638 EVOKED PAIN, WHY WOULD THAT BE 1165 00:40:07,705 --> 00:40:08,539 PAINFUL? 1166 00:40:08,606 --> 00:40:09,874 ARE THERE ABNORMALITIES INVOLVE 1167 00:40:09,940 --> 00:40:12,610 WIDE THAT? 1168 00:40:12,676 --> 00:40:19,784 AND MORE CLINICALLY, IS THE 1169 00:40:19,850 --> 00:40:20,851 HYPOINDUCED ALGEEZIA, I DON'T 1170 00:40:20,918 --> 00:40:23,287 KNOW IF ANYONE IN HER 1171 00:40:23,354 --> 00:40:25,322 EXPERIENCES THE RUNNER'S HIGH, I 1172 00:40:25,389 --> 00:40:26,991 DON'T GET IT BUT I STILL 1173 00:40:27,057 --> 00:40:29,360 EXERCISE, BUT THIS CAN BE 1174 00:40:29,426 --> 00:40:30,895 CONTRIBUTE TO THE HYPOALGEEZIA, 1175 00:40:30,961 --> 00:40:33,130 AND IT CAN INDUCE SOME KIND OF 1176 00:40:33,197 --> 00:40:34,064 PAIN RELIEVING MECHANISMS BUT 1177 00:40:34,131 --> 00:40:35,866 SOME PATES HAVE A--NOT PATIENTS, 1178 00:40:35,933 --> 00:40:40,771 SOME PEOPLE HAVE A PARADOCKSICAL 1179 00:40:40,838 --> 00:40:41,372 EXERCISE INCUESED HYPER 1180 00:40:41,438 --> 00:40:42,006 ALGEEZIA, THEY EXPERIENCE MORE 1181 00:40:42,072 --> 00:40:43,407 PAIN AND SO THINK ABOUT WHAT I 1182 00:40:43,474 --> 00:40:46,577 SAID ABOUT OUR CURRENT 1183 00:40:46,644 --> 00:40:48,512 MANAGEMENT LANDSCAPE FOR OA, THE 1184 00:40:48,579 --> 00:40:50,548 NUMBER 1 THING IS PHYSICAL 1185 00:40:50,614 --> 00:40:52,149 ACTIVITY AND GOING TO PHYSICAL 1186 00:40:52,216 --> 00:40:52,449 THERAPY. 1187 00:40:52,516 --> 00:40:54,084 WHAT IF WE ARE SETTING UP OUR 1188 00:40:54,151 --> 00:40:55,119 PATIENTS FOR FAILURE BECAUSE 1189 00:40:55,186 --> 00:40:56,487 WE'RE SENDING EVERYONE OFF TO DO 1190 00:40:56,554 --> 00:40:59,190 PHYSICAL ACTIVITY TO EXERCISE TO 1191 00:40:59,256 --> 00:41:01,258 GO TO PHYSICAL THERAPY BUT THOSE 1192 00:41:01,325 --> 00:41:02,493 PEOPLE HAVE EXERCISE INDUCED 1193 00:41:02,560 --> 00:41:05,029 HYPER ALGEEZIA BECAUSE SOME OF 1194 00:41:05,095 --> 00:41:06,063 THESE MECHANISMS ARE ABNORMAL 1195 00:41:06,130 --> 00:41:07,264 ARE SET UP FOR FAILURE, THAT'S 1196 00:41:07,331 --> 00:41:08,365 NOT GOING TO HELP THEM. 1197 00:41:08,432 --> 00:41:09,600 WE NEED TO ADDRESS THAT FIRST 1198 00:41:09,667 --> 00:41:12,236 BEFORE THEY CAN BENEFIT FROM 1199 00:41:12,303 --> 00:41:12,870 THOSE INTERVENTIONS. 1200 00:41:12,937 --> 00:41:14,972 AND SO THAT'S AN AREA THAT WE'RE 1201 00:41:15,039 --> 00:41:16,774 STUDYING IN THIS 20th YEAR IN 1202 00:41:16,841 --> 00:41:19,009 THE FIELD IN THE MULTICENTER 1203 00:41:19,076 --> 00:41:19,910 ARTHRITIS STUDY. 1204 00:41:19,977 --> 00:41:22,479 I WILL BRIEFLY A THIS IS NOT 1205 00:41:22,546 --> 00:41:24,181 JUST UNIQUE TO HAND, TO ME, 1206 00:41:24,248 --> 00:41:27,017 WE'VE ALSO BEEN STUDYING IN THIS 1207 00:41:27,084 --> 00:41:28,219 THE HAND, AND [INDISCERNIBLE] ON 1208 00:41:28,285 --> 00:41:31,255 THE RIGHT IS ARGUABLILY 1 OF THE 1209 00:41:31,322 --> 00:41:34,391 WORLD'S MOST EXPERT HAND OTH 1210 00:41:34,458 --> 00:41:35,426 CLINICAL RESEARCHERS AND 1211 00:41:35,492 --> 00:41:38,562 [INDISCERNIBLE] IS HER Ph.D. 1212 00:41:38,629 --> 00:41:41,599 STUDENT WORKING ON THE NORHAND 1213 00:41:41,665 --> 00:41:44,468 COHORT IN NORWAY IN OSLOW AND 1214 00:41:44,535 --> 00:41:45,669 THEY USE THE SAME PROTOCOL. 1215 00:41:45,736 --> 00:41:48,272 SO I HAVE A P30 GRANT WHERE PART 1216 00:41:48,339 --> 00:41:51,175 OF OUR CCR MANDATE IS I ACTsA 1217 00:41:51,242 --> 00:41:52,176 A RESOURCE FOR THESE MEASURES 1218 00:41:52,243 --> 00:41:54,378 AND TO TRAIN OTHER GROUPS SO WE 1219 00:41:54,445 --> 00:41:55,746 CAN HAVE HARMONIZED MEASURES 1220 00:41:55,813 --> 00:41:56,280 ACROSS DIFFERENT STUDIES 1221 00:41:56,347 --> 00:41:57,715 SOPHISTICATEDY THEY DO THE SAME 1222 00:41:57,781 --> 00:42:01,051 MEASURES AND THEY FOUND MANY OF 1223 00:42:01,118 --> 00:42:02,887 THE SAME TYPES OF THINGS WITH 1224 00:42:02,953 --> 00:42:04,922 RELATIONSHIP TO SIN OIVITIS, ET 1225 00:42:04,989 --> 00:42:05,956 CETERA, PAIN, FUNCTION, ET 1226 00:42:06,023 --> 00:42:06,190 CETERA. 1227 00:42:06,257 --> 00:42:09,560 AND I'M ALSO ANYTHING TO MENTION 1228 00:42:09,627 --> 00:42:11,528 BRIEFLY HERE THAT YOU KNOW 1229 00:42:11,595 --> 00:42:13,631 THERE'S A CONNECTION BETWEEN 1230 00:42:13,697 --> 00:42:15,799 OBESITY AND OSTEOARTHRITIS AND 1231 00:42:15,866 --> 00:42:18,402 AT THE KNEE A LOT OF THINKING IS 1232 00:42:18,469 --> 00:42:20,237 OH IT'S THE LOAD THROUGH THE 1233 00:42:20,304 --> 00:42:20,871 KNEE. 1234 00:42:20,938 --> 00:42:21,672 IT'S EXCESS WEIGHT, YOU'RE 1235 00:42:21,739 --> 00:42:23,607 LOADING THE KNEE MORE. 1236 00:42:23,674 --> 00:42:25,876 BUT THERE'S ALSO ASSOCIATION OF 1237 00:42:25,943 --> 00:42:26,610 OBESITY WITH HAND PAIN. 1238 00:42:26,677 --> 00:42:28,679 WHY THAT WOULD BE, IT'S NOT LIKE 1239 00:42:28,746 --> 00:42:29,980 OBESITY IS LOADING THE JOINTS SO 1240 00:42:30,047 --> 00:42:32,750 THERE'S ALSO A QUESTION OF A LOW 1241 00:42:32,816 --> 00:42:33,918 GRADE SYSTEMIC INFLAMMATION SO 1242 00:42:33,984 --> 00:42:38,355 IN THE MORHAND STUDY, WE--WITH 1 1243 00:42:38,422 --> 00:42:41,592 OF THE OTHER MENTEES, WE DID A 1244 00:42:41,659 --> 00:42:43,093 MEDIATION ANALYSIS AND WE FOUND 1245 00:42:43,160 --> 00:42:45,396 THAT LEPTIN IS AN IMPORTANT 1246 00:42:45,462 --> 00:42:48,899 MEDIATOR OF THAT OBESITY TO 1247 00:42:48,966 --> 00:42:49,400 HAND-PAIN RELATIONSHIP. 1248 00:42:49,466 --> 00:42:51,168 AND I'VE BEEN TALKING A LOT 1249 00:42:51,235 --> 00:42:52,236 ABOUT OSTEOARTHRITIS BUT THE 1250 00:42:52,303 --> 00:42:55,673 TITLE WAS PAIN MECHANISMS IN 1251 00:42:55,739 --> 00:42:57,174 ARTHRITIS SO RHEUMATOID 1252 00:42:57,241 --> 00:42:58,976 ARTHRITIS IS PROTOTYPICAL 1253 00:42:59,043 --> 00:43:01,512 INFLAMMATORY ARTHRITIS, MANY OF 1254 00:43:01,578 --> 00:43:02,713 THE SAME FINDINGS HERE, SO 1255 00:43:02,780 --> 00:43:04,515 YVONNE LEE ON THE LEFT THERE IS 1256 00:43:04,581 --> 00:43:06,917 A RHEUMATOLOGIST AT NORTHWEST 1257 00:43:06,984 --> 00:43:08,752 EXPEN ANDY WAS HER RHEUMATOLOGY 1258 00:43:08,819 --> 00:43:10,387 FELLOW. 1259 00:43:10,454 --> 00:43:14,658 WE WERE INTERESTED IN ASKING 1260 00:43:14,725 --> 00:43:15,192 THESE SAME QUESTIONS. 1261 00:43:15,259 --> 00:43:17,461 AND WE FOUND IN RHEUMATOID 1262 00:43:17,528 --> 00:43:18,996 ARTHRITIS, THE MORE PAIN YOU 1263 00:43:19,063 --> 00:43:20,664 HAVE, THE MORE PAIN SEVERITY YOU 1264 00:43:20,731 --> 00:43:22,633 HAVE WHY UOF THE LIKE IN 1265 00:43:22,700 --> 00:43:24,868 OSTEOARTHRITIS EVEN AFTER 1266 00:43:24,935 --> 00:43:25,769 ACCOUNTING FOR INFLAMMATORY 1267 00:43:25,836 --> 00:43:26,036 MEASURES. 1268 00:43:26,103 --> 00:43:29,273 I WAS ALSO INTERESTED IN 1269 00:43:29,340 --> 00:43:31,275 UNDERSTANDING WHETHER PAIN 1270 00:43:31,342 --> 00:43:33,077 SENSITIZATION IMPACTS HOW WE 1271 00:43:33,143 --> 00:43:35,346 MEASURE DISEASE ACTIVITY IN 1272 00:43:35,412 --> 00:43:36,880 RHEUMATOID ARTHRITIS. 1273 00:43:36,947 --> 00:43:39,616 DISEASE ACTIVITY FOR THOSE WHO 1274 00:43:39,683 --> 00:43:42,753 HAVE RHEUMATOID ARTHRITIS OR NOT 1275 00:43:42,820 --> 00:43:45,189 RHEUMATOLOGIST OR FAR ENOUGH 1276 00:43:45,255 --> 00:43:46,523 AWAY FROM RHEUMATOLOGY FOR 1277 00:43:46,590 --> 00:43:47,691 INTERNAL MEDICINE, YOU MAY 1278 00:43:47,758 --> 00:43:48,926 RECALL THAT DEC ACTIVITY 1279 00:43:48,993 --> 00:43:49,793 MEASURES DRIVE OUR TREATMENT 1280 00:43:49,860 --> 00:43:53,030 DECISION WHEN IS WE USE DEC 1281 00:43:53,097 --> 00:43:55,366 MODIFYING AGENTS, BIOLOGICS AND 1282 00:43:55,432 --> 00:43:56,467 PUSH THE IMMUNOSUPPRESSION, IF 1283 00:43:56,533 --> 00:43:57,701 SOMEONE HAS HIGH DISEASE 1284 00:43:57,768 --> 00:43:59,136 ACTIVITY, MODERATE DISEASE 1285 00:43:59,203 --> 00:44:03,173 ACTIVITY, WE PUSH 1286 00:44:03,240 --> 00:44:04,108 IMMUNOSUPPRESSION BUT SOME OF 1287 00:44:04,174 --> 00:44:06,243 THOSE DISEASE ACTIVITIES 1288 00:44:06,310 --> 00:44:08,045 MEASURES INCLUDE TENDER JOINT 1289 00:44:08,112 --> 00:44:09,813 COUNT AND PATIENT FLOABAL, 1290 00:44:09,880 --> 00:44:11,548 TENDER JOINT COUNT IS JUST ABOUT 1291 00:44:11,615 --> 00:44:13,283 INFLAMMATION, IT'S PAIN WHEN YOU 1292 00:44:13,350 --> 00:44:15,352 SQUEEZE THE JOINT WHA. IF THAT 1293 00:44:15,419 --> 00:44:17,121 PAIN ISN'T DUE TO INFLAMMATION. 1294 00:44:17,187 --> 00:44:19,456 WHAT IF THIS INFLAMMATION 1295 00:44:19,523 --> 00:44:22,426 SYMPTOM DISCORDANCE THAT HAS A 1296 00:44:22,493 --> 00:44:23,260 MAJOR CLINICAL IMPLICATION, WE 1297 00:44:23,327 --> 00:44:25,462 SHOULD NOT BE PUSHING 1298 00:44:25,529 --> 00:44:26,397 IMMUNOSUPPRESSION WHEN THERE'S 1299 00:44:26,463 --> 00:44:27,364 ACTIVITY MEASURES BEING DRIVEN 1300 00:44:27,431 --> 00:44:30,200 BY PAIN THAT'S NOT DUE TO 1301 00:44:30,267 --> 00:44:30,534 INFLAMMATION. 1302 00:44:30,601 --> 00:44:32,102 WE NEED TO THINK ABOUT THE 1303 00:44:32,169 --> 00:44:34,505 MULTIPLE CONTRIBUTORS TO PAIN. 1304 00:44:34,571 --> 00:44:36,306 AND THIS SLIDE JUST SHOWS THAT 1305 00:44:36,373 --> 00:44:39,109 IF THERE'S MEASURES OF 1306 00:44:39,176 --> 00:44:40,511 SENSITIZATION, THOSE PEOPLE HAVE 1307 00:44:40,577 --> 00:44:43,480 LOWER RATES OF HAVING A GOOD 1308 00:44:43,547 --> 00:44:45,416 RESPONSE TO THERAPY, SO ALL OF 1309 00:44:45,482 --> 00:44:46,417 THESE DIFFERENT MEASURES HAVE 1310 00:44:46,483 --> 00:44:49,086 LOWER RESPONSE AND IF YOU HAVE A 1311 00:44:49,153 --> 00:44:50,687 COMBINATION OF MEASURES THAT ARE 1312 00:44:50,754 --> 00:44:53,157 MOST SENSITIZED, YOU HAVE THE 1313 00:44:53,223 --> 00:44:54,358 LOWEST RESPONSE TO 1314 00:44:54,425 --> 00:44:56,026 IMMUNOSUPPRESSIVE THERAPY, SO 1315 00:44:56,093 --> 00:44:57,061 LOTS OF CLINICAL IMPLICATIONS. 1316 00:44:57,127 --> 00:44:59,363 AND THEN FINALLY, I'M JUST GOING 1317 00:44:59,430 --> 00:45:01,899 TO END WITH IMPLICATIONS FOR 1318 00:45:01,965 --> 00:45:03,967 TREATMENT, THERE'S LOTS OF 1319 00:45:04,034 --> 00:45:05,836 ACTIVE WORK ON WHAT TO TARGET IN 1320 00:45:05,903 --> 00:45:08,072 ALL OF THESE PATHWAYS THAT WE'RE 1321 00:45:08,138 --> 00:45:10,140 TALKING ABOUT, LOTS OF EMERGING 1322 00:45:10,207 --> 00:45:12,643 PAIN TARGETS THAT ARE BEING 1323 00:45:12,709 --> 00:45:14,845 TESTED, NERVE GROWTH FACTOR HAS 1324 00:45:14,912 --> 00:45:17,247 BEEN THE MOST EXSITTING 1 FOR 1325 00:45:17,314 --> 00:45:18,015 OSTEOARTHRITIS BUT AS I WILL 1326 00:45:18,082 --> 00:45:20,551 SHOW YOU IN A MOMENT, ALL 1327 00:45:20,617 --> 00:45:22,519 PROGRAMS HAVE STOPPED, TRIP V1 1328 00:45:22,586 --> 00:45:26,090 IS TOPICAL CAP ASSESSINGIN IS 1329 00:45:26,156 --> 00:45:27,758 WHAT WE'RE USING AND COUPLE 1330 00:45:27,825 --> 00:45:35,265 YEARS AGO, DAVID [INDISCERNIBLE] 1331 00:45:35,332 --> 00:45:37,868 WON THE NOBEL PRIZE FOR THESE 1332 00:45:37,935 --> 00:45:38,635 TRIALS. 1333 00:45:38,702 --> 00:45:41,004 THERE ARE LOTS OF TRIALS FOR 1334 00:45:41,071 --> 00:45:43,040 PAIN AND OSTEOARTHRITIS AND AS I 1335 00:45:43,107 --> 00:45:45,375 SAID THE NG F WERE THE MOST 1336 00:45:45,442 --> 00:45:46,677 PROMISING, MOST CLOSE TO COMING 1337 00:45:46,743 --> 00:45:49,446 TO FRUITION FOR THE CLINICAL, 1338 00:45:49,513 --> 00:45:52,049 FOR CLINICAL INDICATION BUT THEN 1339 00:45:52,116 --> 00:45:53,050 THEY WERE PULLED OFF--THE 1340 00:45:53,117 --> 00:45:54,284 SPONSORS PULLED OUT FROM THESE 1341 00:45:54,351 --> 00:45:56,320 PROGRAMS BECAUSE THERE WAS AN 1342 00:45:56,386 --> 00:45:57,020 ADVERSE JOINT EFFECT, ADVERSE 1343 00:45:57,087 --> 00:46:02,493 EFFECTS IN THE YOINT AND SO, 1344 00:46:02,559 --> 00:46:04,728 ANOTHER 1 BITES THE DUST. 1345 00:46:04,795 --> 00:46:09,433 SO WE'RE FAR OFF FROM HAVING 1346 00:46:09,500 --> 00:46:10,934 PAIN TARGETS COMING TO THE 1347 00:46:11,001 --> 00:46:12,136 MARKET EMPLOY BUT ALSO WE HAVE 1348 00:46:12,202 --> 00:46:13,237 TO TAKE A STEP BACK AND REMEMBER 1349 00:46:13,303 --> 00:46:16,106 THAT WE HAVE TO BE CAUTIOUS WITH 1350 00:46:16,173 --> 00:46:24,615 MANAGING PAIN BECAUSE 1351 00:46:24,681 --> 00:46:25,549 NOCICEPTION NEEDED FOR PREVENT 1352 00:46:25,616 --> 00:46:25,749 HARM. 1353 00:46:25,816 --> 00:46:27,885 SO WE HAVE TO BE REALISTIC ABOUT 1354 00:46:27,951 --> 00:46:28,152 THE GOALS. 1355 00:46:28,218 --> 00:46:29,853 ZERO PAIN IS NOT THE GOAL. 1356 00:46:29,920 --> 00:46:31,321 WE HAVE TO BE REALISTIC THAT 1357 00:46:31,388 --> 00:46:32,656 WE'RE TRYING TO MANAGE THE 1358 00:46:32,723 --> 00:46:33,857 SYMPTOM SO PEOPLE CAN FUNCTION 1359 00:46:33,924 --> 00:46:35,893 WELL AND HAVE GOOD QUALITY OF 1360 00:46:35,959 --> 00:46:37,060 LIFE, BUT NOT 0 PAIN BECAUSE 1361 00:46:37,127 --> 00:46:40,697 THAT CAN DAMAGE THE JOINT. 1362 00:46:40,764 --> 00:46:42,499 THE OTHER CHALLENGE IS HOW TO 1363 00:46:42,566 --> 00:46:43,300 TARGET PAIN THERAPIES. 1364 00:46:43,367 --> 00:46:44,735 I JUST TALKED A LOT ABOUT 1365 00:46:44,801 --> 00:46:46,069 MULTILE CONTRIBUTORS TO PAIN, I 1366 00:46:46,136 --> 00:46:47,905 JUST TALKED ABOUT THE CLINICAL 1367 00:46:47,971 --> 00:46:50,340 IMPLICATIONS AND RHEUMATOID 1368 00:46:50,407 --> 00:46:51,842 ARTHRITIS, DON'T KEEP PUSHING 1369 00:46:51,909 --> 00:46:53,277 THE DMARKS AND BIOLOGICS IF THE 1370 00:46:53,343 --> 00:46:54,678 PAIN ISN'T DUE TO INFLAMMATION 1371 00:46:54,745 --> 00:46:56,180 BUT HOW DO WE KNOW WHAT THEIR 1372 00:46:56,246 --> 00:46:57,314 PAIN IS DUE TO? 1373 00:46:57,381 --> 00:46:58,682 SO THIS IS A THEY--THE RETINAL 1374 00:46:58,749 --> 00:47:00,617 LOCATIONERAL EXAMPLE OF 4 PEOPLE 1375 00:47:00,684 --> 00:47:05,255 AND I'VE GOT OA NOC ISEPTORSION 1376 00:47:05,322 --> 00:47:06,390 HERE, I COULD MOVE IT TO 1377 00:47:06,456 --> 00:47:07,758 TREATMENT, IF I HAVE A TREATMENT 1378 00:47:07,824 --> 00:47:11,128 THAT'S GOING TO TARGET OA TISSUE 1379 00:47:11,195 --> 00:47:15,098 THAT CONTRIBUTES TO NOCISEPGZ, I 1380 00:47:15,165 --> 00:47:17,134 DON'T WANT TO ENROLL PERSON 1 IN 1381 00:47:17,201 --> 00:47:17,634 MY TRIAL. 1382 00:47:17,701 --> 00:47:22,005 WE DON'T HAVE A WAY OF 1383 00:47:22,072 --> 00:47:23,440 DISENTANGLING HOW MUCH OF EACH 1384 00:47:23,507 --> 00:47:24,741 PERSON'S PAIN IS CONTRIBUTED TO 1385 00:47:24,808 --> 00:47:25,175 BY WHICH MECHANISM. 1386 00:47:25,242 --> 00:47:26,810 SO WE NEED TO DO MORE WORK IN 1387 00:47:26,877 --> 00:47:28,645 THIS AREA AND WE NEED TO HAVE 1388 00:47:28,712 --> 00:47:31,682 MEASURES IN CLINICAL TRIALS TO 1389 00:47:31,748 --> 00:47:32,616 TEST RESPONSE PHENOTYPE. 1390 00:47:32,683 --> 00:47:34,918 SO IN SUMMARY, PAIN IS 1391 00:47:34,985 --> 00:47:35,986 MULTIFACTORIAL, NO MATTER WHAT 1392 00:47:36,053 --> 00:47:37,054 DEC WE'RE TALKING ABOUT, WE HAVE 1393 00:47:37,120 --> 00:47:39,056 TO CONSIDER AND MANAGE OTHER 1394 00:47:39,122 --> 00:47:39,523 CONTRIBUTORS TO PAIN. 1395 00:47:39,590 --> 00:47:42,159 WE HAVE TO BE REALISTIC WITH OUR 1396 00:47:42,226 --> 00:47:45,796 PATIENTS ABOUT GOALS OF SYMPTOMS 1397 00:47:45,862 --> 00:47:47,564 AND FUNCTION. 1398 00:47:47,631 --> 00:47:51,201 WE HAVE A DIRE NEED FOR DISEASE 1399 00:47:51,268 --> 00:47:52,502 MANAGEMENT AND PAIN OPTIONS AND 1400 00:47:52,569 --> 00:47:55,906 WE NEED TO MOVE TOWARDS A 1401 00:47:55,973 --> 00:47:57,274 MECHANISM-BASED APPROACH TO 1402 00:47:57,341 --> 00:47:57,841 MANAGEMENT. 1403 00:47:57,908 --> 00:47:58,709 AND ANOTHER BULLET HERE, I DON'T 1404 00:47:58,775 --> 00:48:01,445 THINK THERE WILL BE A SINGLE 1405 00:48:01,511 --> 00:48:02,746 MAGIC BULLET FOR OA. 1406 00:48:02,813 --> 00:48:04,081 IN CARDIOVASCULAR DISEASE WE 1407 00:48:04,147 --> 00:48:08,652 DON'T EXPECT 1 SINGLE DRUG TO 1408 00:48:08,719 --> 00:48:09,286 MANAGE CARDIOVASCULAR DISEASE, 1409 00:48:09,353 --> 00:48:11,722 WE MANAGE THEIR DIABETES, 1410 00:48:11,788 --> 00:48:12,789 SMOKING, CHOLESTEROL, ALCOHOL, 1411 00:48:12,856 --> 00:48:14,024 ALL THAT, ET CETERA, ET CETERA, 1412 00:48:14,091 --> 00:48:21,665 AND WE NEED THE SAME MODE IN 1413 00:48:21,732 --> 00:48:22,165 MANAGING OSTEOARTHRITIS. 1414 00:48:22,232 --> 00:48:23,634 AND WITH THAT I WILL BE HAPPY TO 1415 00:48:23,700 --> 00:48:34,044 TAKE ANY QUESTIONS. 1416 00:48:36,013 --> 00:48:36,413 [ APPLAUSE ] 1417 00:48:36,480 --> 00:48:39,983 NHI, I'M AN INFECT YOWZ DEC 1418 00:48:40,050 --> 00:48:41,518 SPECIALIST, BUT I MANAGE PATIENT 1419 00:48:41,585 --> 00:48:42,686 BHOS HAVE PAIN, WE THOUGH A LOT 1420 00:48:42,753 --> 00:48:44,788 OF THINGS AT A LOT OF 1421 00:48:44,855 --> 00:48:46,089 MEDICATIONS AT PATIENTS TO 1422 00:48:46,156 --> 00:48:53,297 MANAGE PAIN FROM THEIR JOINTS 1423 00:48:53,363 --> 00:48:55,265 INCLUDING ANTIDEPRESSANTS, LOW 1424 00:48:55,332 --> 00:48:57,234 DOSE ANTIDEPRESSANTS, I WAS 1425 00:48:57,301 --> 00:48:58,268 WONDERING AFTER CONDUCTING THOSE 1426 00:48:58,335 --> 00:49:07,311 TRIALS DO THOSE DO ANYTHING THIS 1427 00:49:07,377 --> 00:49:10,213 DULOX ETINE TO CHANGE THE PAIN 1428 00:49:10,280 --> 00:49:12,949 THRESHOLD SORE ARE WE CHANGING 1429 00:49:13,016 --> 00:49:15,152 THE NOCICEPTIVE IN THOSE 1430 00:49:15,218 --> 00:49:15,952 PATIENTS? 1431 00:49:16,019 --> 00:49:16,353 NDPRAIT QUESTION. 1432 00:49:16,420 --> 00:49:17,888 THERE HAVEN'T BEEN ENOUGH 1433 00:49:17,954 --> 00:49:20,624 STUDIES IN OSTEOARTHRITIS TO 1434 00:49:20,691 --> 00:49:26,930 UNDERSTAND THE MECHANISMS TO 1435 00:49:26,997 --> 00:49:28,632 WHICH D ULOXETINE, IS IT'S 1 OF 1436 00:49:28,699 --> 00:49:31,468 THE APPROVED DRUGS TO TREAT 1437 00:49:31,535 --> 00:49:31,835 OSTEOARTHRITIS. 1438 00:49:31,902 --> 00:49:35,605 IT COULD HAVE EFFECTS, IT COULD 1439 00:49:35,672 --> 00:49:36,606 IMPROVING MOOD YOU'RE IMPROVING 1440 00:49:36,673 --> 00:49:38,108 PAIN, SO WE DON'T KNOW, THE 1441 00:49:38,175 --> 00:49:41,144 THINKING IS THAT IT'S AFFECTING 1442 00:49:41,211 --> 00:49:42,512 CENTRAL MECHANISMS AND THIS IS 1443 00:49:42,579 --> 00:49:43,914 AGAIN WHY THE RESPONSE 1444 00:49:43,980 --> 00:49:44,581 PHENOTYPES ARE IMPORTANT SO 1445 00:49:44,648 --> 00:49:47,617 THERE WAS A STUDY IN PAINFUL 1446 00:49:47,684 --> 00:49:49,553 DIABETIC PAINFUL NEUROPATHY 1447 00:49:49,619 --> 00:49:51,555 WHERE PEOPLE WITH INADEQUATE 1448 00:49:51,621 --> 00:49:55,559 CONDITION MODULATION, SO 1449 00:49:55,625 --> 00:49:57,427 INADEQUATE DESCENDING INHIBITORY 1450 00:49:57,494 --> 00:50:02,032 PATHWAYS, THEY WERE THE 1S THAT 1451 00:50:02,099 --> 00:50:05,035 RESPONDED TO DULOXETINE, IF THAT 1452 00:50:05,102 --> 00:50:09,740 PATHWAY WAS ADEQUATELY 1453 00:50:09,806 --> 00:50:10,474 FUNCTIONING THEN DULOXETINE 1454 00:50:10,540 --> 00:50:12,109 DIDN'T HELP THOSE INDIVIDUALS. 1455 00:50:12,175 --> 00:50:13,377 SO THOSE ARE THE STUDIES WE NEED 1456 00:50:13,443 --> 00:50:15,312 TO DO TO UNDERSTAND WHO WOULD 1457 00:50:15,379 --> 00:50:18,415 BENEFIT FROM DULOXETINE EMPLOY. 1458 00:50:18,482 --> 00:50:18,782 >> THANK YOU. 1459 00:50:18,849 --> 00:50:21,084 WONDERFUL TALK, I LEARN SO MUCH. 1460 00:50:21,151 --> 00:50:21,585 >> THANK YOU. 1461 00:50:21,651 --> 00:50:24,588 YOU KNOW EVEN IF YOU'RE NOT A 1462 00:50:24,654 --> 00:50:26,156 RHEUMATOLOGIST, OR PT OR 1463 00:50:26,223 --> 00:50:27,858 WHATEVER, WHATEVER, ALMOST 1464 00:50:27,924 --> 00:50:29,025 EVERYBODY'S GOING TO HAVE PAIN 1465 00:50:29,092 --> 00:50:30,627 IN A JOINT IN THEIR LIFETIME SO 1466 00:50:30,694 --> 00:50:36,032 IT'S PERSONALLY REEL KEEPSAKES 1467 00:50:36,099 --> 00:50:38,402 VAPT. 1468 00:50:38,468 --> 00:50:39,136 -- RELEVANT. 1469 00:50:39,202 --> 00:50:43,206 >> SO AS I STUMBLE UP HERE WITH 1470 00:50:43,273 --> 00:50:46,443 MY PAINFUL KNEES ... [LAUGHTER] 1471 00:50:46,510 --> 00:50:48,111 --THANK YOU THAT WAS AN 1472 00:50:48,178 --> 00:50:48,945 EXCELLENT PRESENTATION, WE THANK 1473 00:50:49,012 --> 00:50:52,149 YOU FOR SHARING YOUR WORK AND 1474 00:50:52,215 --> 00:50:54,518 INSIGHTS, AND AS YOU POINT OUT 1475 00:50:54,584 --> 00:50:56,453 ALL OF US, OUR KNEES DO SEEM TO 1476 00:50:56,520 --> 00:50:57,087 GO OUT. 1477 00:50:57,154 --> 00:51:00,090 WE HAVE A QUESTION FROM THE 1478 00:51:00,157 --> 00:51:01,458 VIDEOCAST AUDIENCE, THE FIRST IS 1479 00:51:01,525 --> 00:51:02,426 THE ROLE OF COMPLIMENTARY 1480 00:51:02,492 --> 00:51:04,060 MEDICINE AND TREATMENT AND IF SO 1481 00:51:04,127 --> 00:51:07,164 WHAT ARE THE BIOLOGICAL DOSES OF 1482 00:51:07,230 --> 00:51:08,698 THESE COMPLIMENTARY TREATMENTS 1483 00:51:08,765 --> 00:51:08,965 HAD? 1484 00:51:09,032 --> 00:51:14,905 >> THAT'S A WHEL --WHOLE TOPIC N 1485 00:51:14,971 --> 00:51:15,138 ITS OWN. 1486 00:51:15,205 --> 00:51:20,977 SO FIRST OF ALL, I THINK THERE 1487 00:51:21,044 --> 00:51:23,513 ARE SOME NEED TO REALLY EXPAND 1488 00:51:23,580 --> 00:51:24,781 OUR THINKING ABOUT PAIN 1489 00:51:24,848 --> 00:51:26,450 MANAGEMENT AND NOT JUST 1490 00:51:26,516 --> 00:51:30,420 PHARMAICOLOG BEINGLY, AND I 1491 00:51:30,487 --> 00:51:31,521 THINK THERE ARE--THERE'S A GREAT 1492 00:51:31,588 --> 00:51:32,456 INTEREST FROM PATIENTS AND I 1493 00:51:32,522 --> 00:51:33,824 THINK THERE'S A DPRAIT INTEREST 1494 00:51:33,890 --> 00:51:35,826 IN HAVING SAFE OPTIONS, SO THERE 1495 00:51:35,892 --> 00:51:38,628 ARE SOME DATA FOR EXAMPLE, 1496 00:51:38,695 --> 00:51:39,930 REGARDING ACCUPUNCTURE AND IN 1497 00:51:39,996 --> 00:51:41,665 THE AMERICAN COLLEGE OF 1498 00:51:41,731 --> 00:51:42,866 RHEUMATOLOGY TREATMENT 1499 00:51:42,933 --> 00:51:44,701 GUIDELINES WE CONDITIONALLY 1500 00:51:44,768 --> 00:51:45,368 RECOMMENDED ACCUPUNCTURE BECAUSE 1501 00:51:45,435 --> 00:51:46,403 THERE ARE POSITIVE TRIALS BUT 1502 00:51:46,470 --> 00:51:49,873 THERE ARE ALSO SOME TRIALS THAT 1503 00:51:49,940 --> 00:51:50,941 QUESTION ITS TRUE EFFICACY. 1504 00:51:51,007 --> 00:51:52,542 SO 1 TRIAL IN PARTICULAR THAT I 1505 00:51:52,609 --> 00:51:55,479 THOUGHT WAS VERY WELL DONE IS A 1506 00:51:55,545 --> 00:51:59,249 TRIAL WHERE THEY RANDOMIZE TO 1507 00:51:59,316 --> 00:52:00,517 TRUE ACCUPUNCTURE, AND FACTORIAL 1508 00:52:00,584 --> 00:52:04,020 DESIGN WITHIN EACH ARM, YOU'RE 1509 00:52:04,087 --> 00:52:05,322 RANDOMIZED TO THE ACCUPUNCTURIST 1510 00:52:05,388 --> 00:52:09,159 BEING POSITIVE AND OPTIMISTIC 1511 00:52:09,226 --> 00:52:10,360 VERSUS VERY NEUTRAL, AND THERE 1512 00:52:10,427 --> 00:52:13,096 WAS NO DIFFERENCE BETWEEN TRUE 1513 00:52:13,163 --> 00:52:15,632 AND SHAM BUT THE GROUPS THAT 1514 00:52:15,699 --> 00:52:16,666 HAVE THE OPTIMISTIC 1515 00:52:16,733 --> 00:52:18,869 ACCUPUNCTURIST HAD THE BETTER 1516 00:52:18,935 --> 00:52:20,604 PAIN RESPONSE. 1517 00:52:20,670 --> 00:52:22,038 NOW WITH ACCUPUNCTURE BEING 1518 00:52:22,105 --> 00:52:23,373 SAFE, ET CETERA, ALTHOUGH 1519 00:52:23,440 --> 00:52:24,574 WHETHER INSURERS COVER IT, ET 1520 00:52:24,641 --> 00:52:26,443 CETERA THERE'S A COST ISSUE TO 1521 00:52:26,510 --> 00:52:29,112 IT, THAT'S WHY THERE WAS A 1522 00:52:29,179 --> 00:52:29,913 CONDITIONAL RECOMMENDATION 1523 00:52:29,980 --> 00:52:30,780 BECAUSE THERE WERE POSITIVE 1524 00:52:30,847 --> 00:52:32,849 TRIALS BUT ALSO EVEN IF IT'S A 1525 00:52:32,916 --> 00:52:34,384 THERAPEUTIC ALLIANCE AT LEFT 1526 00:52:34,451 --> 00:52:36,152 THERE'S NO DOUBT SIDE TO IT. 1527 00:52:36,219 --> 00:52:37,554 I THINK THERE'S A LOT OF 1528 00:52:37,621 --> 00:52:39,089 CHALLENGES IN DOING TRIALS FOR 1529 00:52:39,155 --> 00:52:42,692 SOME OF THE COMPLIMENTARY AND 1530 00:52:42,759 --> 00:52:43,293 ALTERNAATIVE THERAPIES BECAUSE 1531 00:52:43,360 --> 00:52:45,195 SOME OF IT DOES NEED TO BE 1532 00:52:45,262 --> 00:52:46,396 PERSONALIZED BUT CERTAINLY LOTS 1533 00:52:46,463 --> 00:52:52,035 OF ROOM AND SCOPE FOR THAT TYPE 1534 00:52:52,102 --> 00:52:56,673 OF STUDY. 1535 00:52:56,740 --> 00:52:58,074 DR. HELEN LENG EVINE, THE HEAD 1536 00:52:58,141 --> 00:53:03,780 OF THE NI, KREBS --NICCH, SHE HE 1537 00:53:03,847 --> 00:53:06,783 LOTS OF STUDIES ON YOGA AND 1538 00:53:06,850 --> 00:53:09,185 STRETCHING AND INFLAMMA TORRORY 1539 00:53:09,252 --> 00:53:10,787 MARKERS AND CYTOKINES, SO THERE 1540 00:53:10,854 --> 00:53:13,256 ARE LOTS OF INTERESTING STUDIES 1541 00:53:13,323 --> 00:53:15,792 ABOUT YOGA AND TAI KHIHIGH, AND 1542 00:53:15,859 --> 00:53:17,694 MEDICATION AND MECHANISMS BY 1543 00:53:17,761 --> 00:53:20,030 WHICH THOSE COULD IMPROVE 1544 00:53:20,096 --> 00:53:22,299 FUNCTIONING AND LET'S NOT FORGET 1545 00:53:22,365 --> 00:53:23,533 EXERCISE, DAILY WALKING, SO WHEN 1546 00:53:23,600 --> 00:53:24,534 WE TELL PEOPLE TO EXERCISE WE 1547 00:53:24,601 --> 00:53:26,202 HAVE TO THINK OF IT AS A 1548 00:53:26,269 --> 00:53:27,571 PRESCRIPTION, NOT JUST GO 1549 00:53:27,637 --> 00:53:29,105 EXERCISE, THEY'RE GOING TO THINK 1550 00:53:29,172 --> 00:53:31,641 LIKE JANE FONDA, LET'S GO RUN A 1551 00:53:31,708 --> 00:53:33,677 MARATHON, NO DAILY WALKING, 1552 00:53:33,743 --> 00:53:34,844 SOMETIMES I PRESCRIBE 2 MINUTES 1553 00:53:34,911 --> 00:53:37,047 OF WALKING PER DAY, YOU WOULD 1554 00:53:37,113 --> 00:53:38,281 NOT BELIEVE HOW SEDENTARY SOME 1555 00:53:38,348 --> 00:53:39,683 PEOPLE ARE AND SHOULD PEOPLE 1556 00:53:39,749 --> 00:53:41,384 CANNOT WALK FOR CONTINUOUS 2 1557 00:53:41,451 --> 00:53:44,554 MINUTES OR 5 MINUTES AND I DO A 1558 00:53:44,621 --> 00:53:45,822 DOSE ESCALATION OF HOW MUCH 1559 00:53:45,889 --> 00:53:47,057 WALKING THEY NEED TO DO EVERY 1560 00:53:47,123 --> 00:53:49,025 DAY, THINK ABOUT THEIR 1561 00:53:49,092 --> 00:53:50,961 ENVIRONMENT, ARE THERE BUS STOPS 1562 00:53:51,027 --> 00:53:52,762 AND BENCHES THEY CAN STOP AT 1563 00:53:52,829 --> 00:53:54,030 BECAUSE PEOPLE HAVE FEAR OF 1564 00:53:54,097 --> 00:53:55,732 GOING OUT TOO FAR AND NOT BEING 1565 00:53:55,799 --> 00:53:56,967 ABLE TO MAKE IT HOME. 1566 00:53:57,033 --> 00:53:58,702 SO THIS IS WHY RHEUMATOLOGY IS 1567 00:53:58,768 --> 00:53:59,669 GREAT, YOU GET KNOW YOUR 1568 00:53:59,736 --> 00:54:01,204 PATIENTS SO WELL AND YOU HELP 1569 00:54:01,271 --> 00:54:01,871 THEM PROBLEM SOLVE AND THINK 1570 00:54:01,938 --> 00:54:05,175 ABOUT HOW TO ENGAGE IN HEALTHY 1571 00:54:05,241 --> 00:54:07,744 LIFESTYLE BEHAVIORS. 1572 00:54:07,811 --> 00:54:08,878 >> THANK YOU. 1573 00:54:08,945 --> 00:54:09,512 ANOTHER QUESTION. 1574 00:54:09,579 --> 00:54:12,682 EMPLOY WOULD YOU PLEASE COMMENT 1575 00:54:12,749 --> 00:54:20,190 ON ROLES OF VITAMIN D, K, AND 1576 00:54:20,256 --> 00:54:22,392 TREATMENTS OF LESIONS IN OA 1577 00:54:22,459 --> 00:54:22,859 MUCH. 1578 00:54:22,926 --> 00:54:25,061 >> YIKES, SO WHOLE OTHER TOPICS. 1579 00:54:25,128 --> 00:54:27,163 SO TRAUMATIC LESIONS, ACL TEARS, 1580 00:54:27,230 --> 00:54:28,865 MENISICAL TEARS, THOSE ARE AT 1581 00:54:28,932 --> 00:54:31,534 HIGH RISK FOR DEVELOPING 1582 00:54:31,601 --> 00:54:32,002 OSTEOARTHRITIS. 1583 00:54:32,068 --> 00:54:33,036 TENNIERS LATER AFTER SUCH AS 1584 00:54:33,103 --> 00:54:36,606 INJURY, OFTEN WILL HAVE 1585 00:54:36,673 --> 00:54:37,574 DEVELOPED OSTEOARTHRITIS, FIRST 1586 00:54:37,641 --> 00:54:40,844 OF ALL, I WILL REITERATE ARGT 1587 00:54:40,910 --> 00:54:47,917 ROUGH ATOM SCOPPIC PARTIAL 1588 00:54:47,984 --> 00:54:51,287 MENISICAL REPAIR SHOULD NOT BE 1589 00:54:51,354 --> 00:54:51,688 CONSIDERED FIRST. 1590 00:54:51,755 --> 00:54:53,623 VITAMIN D, SEVERAL TRIALS, NO 1591 00:54:53,690 --> 00:54:56,893 DATA TO SUPPORT ITS EFFICACY IN 1592 00:54:56,960 --> 00:54:57,594 OA. 1593 00:54:57,661 --> 00:55:00,230 OFTIO POROSE ICE, VERY 1594 00:55:00,296 --> 00:55:03,366 INTERESTING, THERE'S THIS 1595 00:55:03,433 --> 00:55:04,167 INVERSION RELATIONSHIP, BUT IT'S 1596 00:55:04,234 --> 00:55:04,934 HEARD HATFIELD ORDER TO KNOW 1597 00:55:05,001 --> 00:55:08,772 BECAUSE PEOPLE WHO ARE OBESE ARE 1598 00:55:08,838 --> 00:55:11,608 AT ENCREED RISK FOR 1599 00:55:11,675 --> 00:55:13,143 OSTEOARTHRITIS, PEOPLE WHO ARE 1600 00:55:13,209 --> 00:55:18,214 OBESE HAVE HIGHER BMD, BUT 1601 00:55:18,281 --> 00:55:20,850 PEOPLE WHO HAVE LOW BMD HAVE 1602 00:55:20,917 --> 00:55:22,318 INCREASED RISK OF 1603 00:55:22,385 --> 00:55:22,686 OSTEOARTHRITIS. 1604 00:55:22,752 --> 00:55:23,520 PEOPLE WITH OSTEOARTHRITIS HAVE 1605 00:55:23,586 --> 00:55:26,389 A HIGHER RISK OF FALL ANDS 1606 00:55:26,456 --> 00:55:29,192 FACTORS, I THINK BMD IS NOT 1607 00:55:29,259 --> 00:55:30,860 ENOUGH ALONE FOR TRUE 1608 00:55:30,927 --> 00:55:32,362 UNDERSTANDING OF BONE HEALTH AND 1609 00:55:32,429 --> 00:55:34,431 QUALITY, THERE'S ALTERATIONS IN 1610 00:55:34,497 --> 00:55:37,300 AT THE JOINT IN BONE 1611 00:55:37,367 --> 00:55:41,104 MINERALIZATION, STIFFNESS, 1612 00:55:41,171 --> 00:55:41,705 MECHANICAL PROPERTIES, 1613 00:55:41,771 --> 00:55:42,972 SARCOPENIA, SARCO PENIA OOH 1614 00:55:43,039 --> 00:55:45,241 BEESITY, IT'S A WHOLE 1615 00:55:45,308 --> 00:55:46,676 COMPLICATED TOPIC BUT I WILL PUT 1616 00:55:46,743 --> 00:55:49,713 IN A PLUG FOR THE VITAMIN K. 1617 00:55:49,779 --> 00:55:51,214 MY FIRST PROJECT THAT ALLOWED ME 1618 00:55:51,281 --> 00:55:52,749 TO GET FUNDED TO START MY 1619 00:55:52,816 --> 00:55:55,151 RESEARCH TRAINING CAREER WAS IN 1620 00:55:55,218 --> 00:55:56,686 VIT- MIN K AND OSTEOARTHRITIS. 1621 00:55:56,753 --> 00:56:00,590 AND THERE'S A NOW A RESURGENCE 1622 00:56:00,657 --> 00:56:01,591 BECAUSE THERE'S BEEN O GENIC 1623 00:56:01,658 --> 00:56:03,460 NUMBER OF THETIC GENETIC GWAS 1624 00:56:03,526 --> 00:56:08,431 STUDIES THAT HAVE IESHES 1625 00:56:08,498 --> 00:56:09,332 DENTIFIED VITAMIN K DEFICIENCY 1626 00:56:09,399 --> 00:56:11,935 IN THESE, SO THERE'S BEEN A 1627 00:56:12,001 --> 00:56:13,670 RESURMING ENSEL OF VITAMIN K, 1628 00:56:13,737 --> 00:56:16,139 BUT IN OTHER THAN THAT NO OTHER 1629 00:56:16,206 --> 00:56:17,741 VITAMINS HAVE BEEN REALLY SHOWN 1630 00:56:17,807 --> 00:56:20,610 TO BE IMPORTANT OR EFFECTIVE AND 1631 00:56:20,677 --> 00:56:23,480 SOME INTEREST IN OMEG THAT 3 1632 00:56:23,546 --> 00:56:26,483 FATTY ACIDS AND TURMERIC, BUT 1633 00:56:26,549 --> 00:56:29,085 BETTER WELL POWERED TRIALS NEED 1634 00:56:29,152 --> 00:56:30,453 TO BE DONE. 1635 00:56:30,520 --> 00:56:31,387 >> THANK YOU. 1636 00:56:31,454 --> 00:56:32,355 A COMMENT MORE THAN A QUESTION 1637 00:56:32,422 --> 00:56:34,257 BUT MAYBE HAVE A COMMENT ON IT, 1638 00:56:34,324 --> 00:56:35,625 WHEN COMPARING CHANGE NOTHING 1639 00:56:35,692 --> 00:56:39,796 PAIN FROM 1 SITE TO ANOTHER, THE 1640 00:56:39,863 --> 00:56:42,298 OSTEOARTHRITIS KNEE VERSUS THE 1641 00:56:42,365 --> 00:56:44,334 NONOA NEED PLEASE CONSIDER 1642 00:56:44,400 --> 00:56:46,936 COMPENSATION FROM THE NON OA 1643 00:56:47,003 --> 00:56:48,404 KNEE WHEN MEASURING CHANGES. 1644 00:56:48,471 --> 00:56:49,439 >> YES, WE DO THAT. 1645 00:56:49,506 --> 00:56:51,107 >> I BELIEVE THAT'S ALL WE HAVE 1646 00:56:51,174 --> 00:56:51,808 FROM VIDEOCAST. 1647 00:56:51,875 --> 00:56:56,379 NI WILL JUST ADD 1 OTHER THING, 1648 00:56:56,446 --> 00:56:59,949 THAT I THINK WILL BE SORT OF 1649 00:57:00,016 --> 00:57:03,219 INTERESTING TO FOLLOW IS THERE 1650 00:57:03,286 --> 00:57:05,588 WAS A RECENT FDA APPROVED 1651 00:57:05,655 --> 00:57:09,225 FORMULATION OF CULT RASEEN 1652 00:57:09,292 --> 00:57:10,760 CALLED LODOCO, FOR HEART DEC 1653 00:57:10,827 --> 00:57:11,127 PREVEPGZ. 1654 00:57:11,194 --> 00:57:12,962 THE TRIAL WHEN IT WAS PUBLISHED 1655 00:57:13,029 --> 00:57:14,764 THEY DID A POST HOC ANALYSIS 1656 00:57:14,831 --> 00:57:15,899 WHERE THEY WERE ABLE TO DEMON 1657 00:57:15,965 --> 00:57:19,369 TRAIT THAT THOSE IN THE CULTURE 1658 00:57:19,435 --> 00:57:22,038 ARM HAD ALMOST A 40% REDUCTION 1659 00:57:22,105 --> 00:57:23,573 IN JOINT REPLACEMENT OVER FOLLOW 1660 00:57:23,640 --> 00:57:24,874 UP THAN THE PLACEBO ARM. 1661 00:57:24,941 --> 00:57:26,142 AND THIS WAS VERY SIMILAR TO 1662 00:57:26,209 --> 00:57:30,013 WHAT WAS SEEN IN THE CANT OS 1663 00:57:30,079 --> 00:57:31,514 TRIAL OF [INDISCERNIBLE], WHICH 1664 00:57:31,581 --> 00:57:33,950 IS AN IL1 BETAAN TAGANIST SO 1665 00:57:34,017 --> 00:57:38,688 THESE ARE 2 LARGE CARDIOVASCULAR 1666 00:57:38,755 --> 00:57:39,689 DISEASE TRIALS THAT 1667 00:57:39,756 --> 00:57:41,658 EN--STRATEGIES DENTALLY FOUND A 1668 00:57:41,724 --> 00:57:43,393 JOINT REPLACEMENT EFFECT LIKE A 1669 00:57:43,459 --> 00:57:47,897 BENEFIT OF IL1 BETA AND CULT 1670 00:57:47,964 --> 00:57:48,331 RASEEN, REPLACEMENT. 1671 00:57:48,398 --> 00:57:50,567 SO COLT RASEEN IS SOMETHING 1672 00:57:50,633 --> 00:57:51,401 THAT'S WIDELY AVAILABLE, ET 1673 00:57:51,467 --> 00:57:54,504 CETERA, SO FOR MY PATIENTS WHERE 1674 00:57:54,571 --> 00:57:56,472 THEY HAVE A CARDIOVASCULAR 1675 00:57:56,539 --> 00:58:00,009 INDICATION, THEY ME MEET THE 1676 00:58:00,076 --> 00:58:02,145 INDICATION FOR LODOCO, AND WE'RE 1677 00:58:02,212 --> 00:58:03,513 STRUGGLING WITH MANAGING THEIR 1678 00:58:03,580 --> 00:58:04,814 SYMPTOMS, I THINK CULT RASEEN 1679 00:58:04,881 --> 00:58:06,249 MIGHT BE AN OPTION WHERE IT'S 1680 00:58:06,316 --> 00:58:07,450 SAFE AND APPROPRIATE. 1681 00:58:07,517 --> 00:58:09,185 AND IT HIGHLIGHTS THAT IN 1682 00:58:09,252 --> 00:58:10,486 OSTEOARTHRITIS THERE HAVE BEEN 1683 00:58:10,553 --> 00:58:12,589 MANY TRIALS OF CULT RASEEN THAT 1684 00:58:12,655 --> 00:58:13,857 HAVE BEEN NEGATIVE AND I THINK 1685 00:58:13,923 --> 00:58:16,025 IT'S BECAUSE OUR TRIALS ARE TOO 1686 00:58:16,092 --> 00:58:17,393 SMALL, TOO SHORT OF DURATION AND 1687 00:58:17,460 --> 00:58:20,530 THE WAY WE ENROLL PEOPLE IN THE 1688 00:58:20,597 --> 00:58:22,232 TRIALS IS TOO HETEROGENIUS TO 1689 00:58:22,298 --> 00:58:22,799 FIND THAT SIGNAL. 1690 00:58:22,866 --> 00:58:24,500 AND THE REASON THAT TRIAL AND 1691 00:58:24,567 --> 00:58:27,070 CANT OS TRIALS AND WE ALSO HAD 1692 00:58:27,136 --> 00:58:28,771 IL1 BETA INHIBITION TRIALS THAT 1693 00:58:28,838 --> 00:58:30,206 WERE TOO MAUL, TOO SHORT OF 1694 00:58:30,273 --> 00:58:31,908 DURATION AND DIDN'T FIND A 1695 00:58:31,975 --> 00:58:35,645 SIGNAL AND CANT OS AND LODOCO 2 1696 00:58:35,712 --> 00:58:37,180 FOUND THESE SIGNALS BECAUSE THEY 1697 00:58:37,247 --> 00:58:38,314 WERE LARGE ENOUGH, 10,000 1698 00:58:38,381 --> 00:58:39,382 PEOPLE, 5000 PEOPLE AND LONG 1699 00:58:39,449 --> 00:58:41,117 ENOUGH TO PICK UP THE SIGNATURES 1700 00:58:41,184 --> 00:58:44,654 UNTIL DESPITE THE NOISE AND SO, 1701 00:58:44,721 --> 00:58:46,623 IN OSTEOARTHRITIS, I FEAR WE'VE 1702 00:58:46,689 --> 00:58:48,024 THROWN AWAY PROMISING THERAPIES 1703 00:58:48,091 --> 00:58:50,827 BECAUSE OUR TRIAL ENROLLMENT AND 1704 00:58:50,894 --> 00:58:56,799 TOO HETEROGENIUS TO PICK UP 1705 00:58:56,866 --> 00:58:57,367 THESE SIGNALS. 1706 00:58:57,433 --> 00:59:02,872 I CAN GO ON BUT I WILL LET EVEN 1707 00:59:02,939 --> 00:59:03,039 GO. 1708 00:59:03,106 --> 00:59:03,539 [ APPLAUSE ] 1709 00:59:03,606 --> 00:59:05,108 I WAS REMISS AND I WANTED TO 1710 00:59:05,174 --> 00:59:07,310 THANK THE NIH FOR ALL OF THIS 1711 00:59:07,377 --> 00:59:08,177 WONDERFUL FUNDING THAT SUPPORTED 1712 00:59:08,244 --> 00:59:10,513 THIS WORK ALONG THE WAY. 1713 00:59:10,580 --> 00:59:12,215 >> ON BEHALF OF THE GREAT 1714 00:59:12,282 --> 00:59:12,649 TEACHERS COMMITTEE. 1715 00:59:12,715 --> 00:59:14,083 THANK YOU THAT WAS FANTASTIC. 1716 00:59:14,150 --> 00:59:15,818 I LEARNED A LOT THAT I HAD 1717 00:59:15,885 --> 00:59:17,887 FORGOTTEN ABOUT PAIN MECHANISMS. 1718 00:59:17,954 --> 00:59:19,656 WE DID HAVE OVER A HUNDRED 1719 00:59:19,722 --> 00:59:24,527 PEOPLE ON THE VIDEOCAST, SO, I 1720 00:59:24,594 --> 00:59:25,962 THINK--WE DID HAVE OVER A 1721 00:59:26,029 --> 00:59:27,230 HUNDRED PEOPLE ON THE VIDEOCAST, 1722 00:59:27,297 --> 00:59:29,832 SO I THINK YOUR MESSAGE KNOT OUT 1723 00:59:29,899 --> 00:59:31,034 TO A BROADER COMMUNITY THAN WAS 1724 00:59:31,100 --> 00:59:34,037 HERE TODAY AND THANK YOU AGAIN. 1725 00:59:34,103 --> 00:59:34,337 NTHANK YOU. 1726 00:59:34,404 [ APPLAUSE ]