Stickler Syndrome, Type 1

Physician-scientists at UPMC and the University of Pittsburgh found a way to use AI to accurately diagnose ear infections. The AI-powered smartphone app that diagnoses acute otitis media (AOM) could help decrease unnecessary antibiotic use in young children. Researchers published their outcomes in JAMA Pediatrics. AOM commonly has antibiotics prescribed to treat it, but can prove difficult to discern from other ear conditions without intensive training. This AI tool makes a diagnosis by assessing a short video of the eardrum captured by an otoscope connected to a smartphone camera. The researchers say this offers a simple and effective solution with potentially more accuracy than trained clinicians’ diagnoses. “Acute otitis media is often incorrectly diagnosed,” said senior author Dr. Alejandro Hoberma, professor of pediatrics and director of the Division of General Academic Pediatrics at Pitt’s School of Medicine and president of UPMC Children’s Community Pediatrics. “Underdiagnosis results in inadequate care and overdiagnosis results in unnecessary antibiotic treatment, which can compromise the effectiveness of currently available antibiotics. Our tool helps get the correct diagnosis and guide the right treatment.” Hoberman says about 70% of children have an ear infection before their first birthday. Despite the common nature of the condition, accurate diagnosis requires a trained eye. To develop a practical tool that improves accuracy, Hoberman and his team began by building and annotating a training library of 1,151 videos of the tympanic membrane from 635 children who visited outpatient UPMC pediatric offices between 2018 and 2023. Two trained experts reviewed the videos and made a diagnosis. Using 921 videos from the training library, the team taught two different AI models to detect AOM by looking at the features of the tympanic membrane. Features include shape, position, color and translucency. The remaining 230 videos helped to test how the models performed. Both models proved highly accurate, with sensitivity and specificity values totaling greater than 93%. Hoberman says previous studies of clinician diagnoses demonstrated accuracy ranging from 30% to 84%, depending on type of health care provider, level of training and age of the children being examined. “These findings suggest that our tool is more accurate than many clinicians,” said Hoberman. “It could be a game-changer in primary health care settings to support clinicians in stringently diagnosing AOM and guiding treatment decisions. “Another benefit of our tool is that the videos we capture can be stored in a patient’s medical record and shared with other providers,” said Hoberman. “We can also show parents and trainees — medical students and residents — what we see and explain why we are or are not making a diagnosis of ear infection. It is important as a teaching tool and for reassuring parents that their child is receiving appropriate treatment.” Hoberman hopes that the technology could soon be implemented widely across healthcare provider offices to enhance accurate diagnosis of AOM and support treatment decisions.

A new cell phone app developed by physician-scientists, which uses artificial intelligence (AI) to accurately diagnose ear infections, or acute otitis media (AOM), could help decrease unnecessary antibiotic use in young children, according to new research. A new cellphone app developed by physician-scientists at UPMC and the University of Pittsburgh, which uses artificial intelligence (AI) to accurately diagnose ear infections, or acute otitis media (AOM), could help decrease unnecessary antibiotic use in young children, according to new research published today in JAMA Pediatrics. AOM is one of the most common childhood infections for which antibiotics are prescribed but can be difficult to discern from other ear conditions without intensive training. The new AI tool, which makes a diagnosis by assessing a short video of the ear drum captured by an otoscope connected to a cellphone camera, offers a simple and effective solution that could be more accurate than trained clinicians. "Acute otitis media is often incorrectly diagnosed," said senior author Alejandro Hoberman, M.D., professor of pediatrics and director of the Division of General Academic Pediatrics at Pitt's School of Medicine and president of UPMC Children's Community Pediatrics. "Underdiagnosis results in inadequate care and overdiagnosis results in unnecessary antibiotic treatment, which can compromise the effectiveness of currently available antibiotics. Our tool helps get the correct diagnosis and guide the right treatment." According to Hoberman, about 70% of children have an ear infection before their first birthday. Although this condition is common, accurate diagnosis of AOM requires a trained eye to detect subtle visual findings gained from a brief view of the ear drum on a wriggly baby. AOM is often confused with otitis media with effusion, or fluid behind the ear, a condition that generally does not involve bacteria and does not benefit from antimicrobial treatment. To develop a practical tool to improve accuracy in the diagnosis of AOM, Hoberman and his team started by building and annotating a training library of 1,151 videos of the tympanic membrane from 635 children who visited outpatient UPMC pediatric offices between 2018 and 2023. Two trained experts with extensive experience in AOM research reviewed the videos and made a diagnosis of AOM or not AOM. "The ear drum, or tympanic membrane, is a thin, flat piece of tissue that stretches across the ear canal," said Hoberman. "In AOM, the ear drum bulges like a bagel, leaving a central area of depression that resembles a bagel hole. In contrast, in children with otitis media with effusion, no bulging of the tympanic membrane is present." The researchers used 921 videos from the training library to teach two different AI models to detect AOM by looking at features of the tympanic membrane, including shape, position, color and translucency. Then they used the remaining 230 videos to test how the models performed. Both models were highly accurate, producing sensitivity and specificity values of greater than 93%, meaning that they had low rates of false negatives and false positives. According to Hoberman, previous studies of clinicians have reported diagnostic accuracy of AOM ranging from 30% to 84%, depending on type of health care provider, level of training and age of the children being examined. "These findings suggest that our tool is more accurate than many clinicians," said Hoberman. "It could be a gamechanger in primary health care settings to support clinicians in stringently diagnosing AOM and guiding treatment decisions." "Another benefit of our tool is that the videos we capture can be stored in a patient's medical record and shared with other providers," said Hoberman. "We can also show parents and trainees -- medical students and residents -- what we see and explain why we are or are not making a diagnosis of ear infection. It is important as a teaching tool and for reassuring parents that their child is receiving appropriate treatment." Hoberman hopes that their technology could soon be implemented widely across health care provider offices to enhance accurate diagnosis of AOM and support treatment decisions. Other authors on the study were Nader Shaikh, M.D., Shannon Conway, Timothy Shope, M.D., Mary Ann Haralam, C.R.N.P., Catherine Campese, C.R.N.P., and Matthew Lee, all of UPMC and the University of Pittsburgh; Jelena Kova?evi?, Ph.D., of New York University; Filipe Condessa, Ph.D., of Bosch Center for Artificial Intelligence; and Tomas Larsson, M.Sc, and Zafer Cavdar, both of Dcipher Analytics. This research was supported by the Department of Pediatrics at the University of Pittsburgh School of Medicine.

“不节食不运动，轻轻松松瘦20斤，每周仅注射一次”，这样的宣传语怎能让人不心动？于是乎，司美格鲁肽成为了众多减肥人士梦寐以求的神药，甚至多国陷入了供应短缺的状态。司美格鲁肽的减肥效果究竟有多“神”？“网红减肥神药”的一炮而红，还要回溯到特斯拉CEO 埃隆·马斯克在社交媒体上晒出的自己“暴瘦”的图片——在度假照被嘲笑肥胖后，马斯克仅用了一个月的时间就成功减去20磅（约9kg）！而他自曝成功减肥的秘诀是：禁食与Wegovy（活性成分：司美格鲁肽 Semaglutide）。马斯克减肥前后对比图事实上，司美格鲁肽最初被批准用于降血糖。作为新型长效胰高糖素样肽-1（GLP-1）类似物，司美格鲁肽能有效地抑制胰高血糖素的释放，从而间接发挥降低血糖的作用。该药物的一大优点在于：体内半衰期在1周左右，因此能实现一周给药一次。凭此，“一周打一次”的司美格鲁肽迅速取代了上一代降糖药，并于2021年4月在我国上市。图源：网络司美格鲁肽能“跨界”减肥的原理并不复杂，或者说其控制体重的作用算是“顺带”——因其能够模拟胰高血糖素的作用，增加了人体对胰岛素的敏感性；在此基础上，饭后的饱腹感提升了，胃排空的速率减慢了，自然能够减少饥饿感、热量摄入以及体重。不可否认的是，司美格鲁肽用于减肥的效果，短时间来说确实是显著的。早在2021年，NEJM发布的全球性重磅临床试验显示：仅需每周给药一次2.4mg，在68周的持续用药之后，司美格鲁肽使得肥胖者的体重降低了15.3kg！此外，JAMA上的研究还将司美格鲁肽的减肥效果与另一常见减肥药“利拉鲁肽”进行了对比，结果发现，使用司美格鲁肽的参与者的体重平均降低了15.8%，显著优于利拉鲁肽组的6.4%。试验组与对照组的体重变化情况(图源：NEJM）人们使用抗肥胖药物的持久性如何？但除了药效之外，一个更令人在意的问题是：类似于司美格鲁肽的抗肥胖药物（AOM）持久性如何？为什么人们无法坚持服用减肥药呢？为了回答这一问题，来自美国克利夫兰医学中心的研究人员调查了多种AOMs的用药持久性以及无法坚持用药的原因。结果显示：随着随访时间的延长，坚持服用AOMs的比例显著下降，从3个月的44%降低到1年时的19%。为什么还有一大半的人放弃服用该药物呢？这是本研究试图回答的问题。https://doi-org.libproxy1.nus.edu.sg/10.1002/oby.23952研究者从俄亥俄州和佛罗里达州的大型卫生系统中2015年至2023年的电子健康记录里筛选出符合纳入标准的研究对象——最终确认了1911名患者，体重指数（BMI）≥30kg/m^2，且在该时间段内首次使用AOM。其中，AOMs为FDA批准的、用作慢性体重管理的药物以及剂型，包括芬特明-托吡酯、纳曲酮-安非他酮、奥利司他、司美格鲁肽注射液2.4mg和利拉鲁肽注射液3mg。整个队列的统计显示，有34%服用纳曲酮-安非他酮，26%服用芬特明-托吡酯，25%注射了司美格鲁肽，14%注利拉鲁肽以及0.9%的奥利司他。研究者在随访期间观察到，3个月时，整个队列中仍有44%的受试者在坚持使用AOM药物；到了6个月，该比例降低至33%；而在1年之后，仅剩19%的患者还在坚持服用AOM。具体来说，不同药物的持续率差异很大。比如，在3个月和6个月时，司美格鲁肽有着最高的持续率，分别为63%和56%，其次是利拉鲁肽的52%和37%。但在服用药物一年后，纳曲酮-安非他酮的持续率仅为10%，即使持续率最高的司美格鲁肽，也下滑一半以上，降至40%。不同药物的坚持用药占比为什么人们会停止使用AOM呢？首先，AOM并不平价，甚至算得上高昂，从每月200美元（芬特明-托吡酯）到1300美元（3.0mg利拉鲁肽和2.4mg司美格鲁肽）不等。而这些AOMs大多不属于医保报销的范畴，尤其是昂贵的新一代减肥药——胰高糖素样肽-1受体激动剂（GLP-1RA），相当于要“自费”减肥。此外，随着减肥神药的“一炮而红”，某些国家的司美格鲁肽甚至出现了短缺的现象，一定程度上也限制了患者获取药物的能力，导致AOMs的停用。其次，除了现实因素之外，司美格鲁肽等GLP-1药物可能引起的不良反应，也受到了越来越广泛的关注。此前，JAMA上刊登的、由哥伦比亚大学医学院科研人员开展的研究，给了大众“当头一棒”——包括司美格鲁肽在内的GLP-1激动剂恐存在一定的不良反应，与胰腺炎、胃轻瘫以及肠梗阻等胃肠道疾病的风险增加有关。该研究发现，与使用安非他酮+纳曲酮药物进行减肥的相比，两种GLP-1激动剂司美格鲁肽和利拉鲁肽诱发的4种胃肠道不良反应的发病率均更高，包括胆道疾病（比如胆囊炎、胆结石和胆总管结石）、胰腺炎（包括胆结石性胰腺炎）、肠梗阻和胃痉挛。GLP-1激动剂与安非他酮-纳曲酮使用者的胃肠道疾病发生风险FDA通报的最常见胃肠道不良反应包括：恶心、呕吐、腹泻、腹痛、消化不良、食欲下降等等，更有甚者可能会出现肠梗阻、胃轻瘫等更为严重的疾病。JAMA上刊登的另一项研究也对司美格鲁肽的副作用进行了报道，结果显示，使用司美格鲁肽治疗组出现胃肠道副作用的概率高达84.1%。第三，也是很关键的一点是，司美格鲁肽并非一打就瘦的“傻瓜针”，而需要配合饮食以及生活方式的管理。在停药之后，很容易出现反弹的现象——一项临床试验显示，在接受司美格鲁肽治疗的参与者停药一年后，减轻的体重恢复了超过50%。也就是说，坚持使用司美格鲁肽，确实可以保证体重的减轻；但一旦干预停止，反弹的可能性恐怕会更高。事实上，人体产生的内源性GLP-1与这些注射的人造GLP-1具有一定的差异。前者会在餐后释放，但不会持续很长时间，且会被身体迅速代谢掉；相比之下，后者的活性往往更高（甚至是内源性GLP-1的10倍），持续时间也会更长，让患者在注射后维持更长久的饱腹感。“吃得少、不易饿”，自然也会更瘦。然而，由于人为的干预，即外源性GLP-1的增加，身体检测到更高水平的“假”GLP-1后，合成的内源性GLP-1会随之减少。在突然停药之后，体内原本高水平的GLP-1骤然下降，饥饿和食欲会“报复性回归”，导致体重的迅速反弹。看来“坐躺瘦”的美梦在现阶段还是很难实现的，在用药之后的体重维持才是更大的考验！参考资料：[1] Gasoyan H, Pfoh ER, Schulte R, Le P, Rothberg MB. Early- and later-stage persistence with antiobesity medications: A retrospective cohort study. Obesity (Silver Spring). 2023 Dec 6. doi: 10.1002/oby.23952. Epub ahead of print. PMID: 38053443.[2] Khoo TK, Lin J. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Jul 1;385(1):e4.[3] Rubino DM,et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.[4] Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. Published online October 05, 2023. doi:10.1001/jama.2023.19574撰文 | Swagpp编辑 | Swagpp来源 | 梅斯医学精彩推荐：1、仅限男性！BMJ：「单身太久」或「分手频繁」容易引发高水平炎症风险2、想聪明多运动！斯坦福大学Nature发文：运动对大脑有保护作用，“换血”可升级抗炎能力，对神经发生和记忆大有裨益3、久坐伤身不用怕！《英国运动医学杂志》发现每天只需这样运动22分钟即可抵消久坐带来的死亡风险4、延寿新方法！Nature Aging证实：抑制特定自噬基因可以延长寿命、改善健康！5、首个！Cell Stem Cell：美国南加州大学开发出具备功能性小脑细胞的人脑类器官！本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！