Nature Medicine最新文献

{"title":"Digital phenotyping could help detect autism","authors":"Catherine Lord, Rujuta B. Wilson","doi":"10.1038/s41591-023-02557-4","DOIUrl":"10.1038/s41591-023-02557-4","url":null,"abstract":"Researchers have developed a screening tool for autism that uses computer vision and machine learning to analyze autism-related behaviors — but greater reliability and robust validation will be needed if such tools are to be used in primary care settings.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 10","pages":"2412-2413"},"PeriodicalIF":82.9,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41151817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence","authors":"Mia Moore, Sarah Stansfield, Deborah J. Donnell, Marie-Claude Boily, Kate M. Mitchell, Peter L. Anderson, Sinead Delany-Moretlwe, Linda-Gail Bekker, Nyaradzo M. Mgodi, Connie L. Celum, Dobromir Dimitrov","doi":"10.1038/s41591-023-02564-5","DOIUrl":"10.1038/s41591-023-02564-5","url":null,"abstract":"Pre-exposure prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate and emtricitabine administered orally daily is effective in preventing human immunodeficiency virus (HIV) acquisition in both men and women with sufficient adherence; however, the adherence–efficacy relationship in cisgender women has not been well established. We calculated the adherence–efficacy curve for cisgender women by using HIV incidence and plasma TFV concentration data from three trials (FEM-PrEP, VOICE and Partners PrEP). We imputed TFV diphosphate (TFV-DP) concentrations, a measure of long-term adherence, from TFV quantification by using data from the HIV Prevention Trials Network 082 study, which measured both TFV-DP and TFV concentrations. Two, four and seven pills per week reduced HIV incidence by 59.3% (95% credible interval (CrI) 29.9–95.8%), 83.8% (95% CI 51.7–99.8%) and 95.9% (95% CI 72.6–100%), respectively. Our adherence–efficacy curve can be validated and updated by HIV prevention studies that directly measure TFV-DP concentrations. The curve suggests that high adherence confers high protection in cisgender women. However, the lower efficacy with partial adherence highlights the need for new PrEP products and interventions to increase adherence. Pre-exposure prophylaxis (PrEP) with daily antiretrovirals to prevent human immunodeficiency virus type 1 acquisition has not been shown to be consistently effective in cisgender women. Modeling adherence to daily PrEP clarifies how robust protection can be achieved.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 11","pages":"2748-2752"},"PeriodicalIF":82.9,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine","authors":"Deirdre K. Tobias, Jordi Merino, Abrar Ahmad, Catherine Aiken, Jamie L. Benham, Dhanasekaran Bodhini, Amy L. Clark, Kevin Colclough, Rosa Corcoy, Sara J. Cromer, Daisy Duan, Jamie L. Felton, Ellen C. Francis, Pieter Gillard, Véronique Gingras, Romy Gaillard, Eram Haider, Alice Hughes, Jennifer M. Ikle, Laura M. Jacobsen, Anna R. Kahkoska, Jarno L. T. Kettunen, Raymond J. Kreienkamp, Lee-Ling Lim, Jonna M. E. Männistö, Robert Massey, Niamh-Maire Mclennan, Rachel G. Miller, Mario Luca Morieri, Jasper Most, Rochelle N. Naylor, Bige Ozkan, Kashyap Amratlal Patel, Scott J. Pilla, Katsiaryna Prystupa, Sridharan Raghavan, Mary R. Rooney, Martin Schön, Zhila Semnani-Azad, Magdalena Sevilla-Gonzalez, Pernille Svalastoga, Wubet Worku Takele, Claudia Ha-ting Tam, Anne Cathrine B. Thuesen, Mustafa Tosur, Amelia S. Wallace, Caroline C. Wang, Jessie J. Wong, Jennifer M. Yamamoto, Katherine Young, Chloé Amouyal, Mette K. Andersen, Maxine P. Bonham, Mingling Chen, Feifei Cheng, Tinashe Chikowore, Sian C. Chivers, Christoffer Clemmensen, Dana Dabelea, Adem Y. Dawed, Aaron J. Deutsch, Laura T. Dickens, Linda A. DiMeglio, Monika Dudenhöffer-Pfeifer, Carmella Evans-Molina, María Mercè Fernández-Balsells, Hugo Fitipaldi, Stephanie L. Fitzpatrick, Stephen E. Gitelman, Mark O. Goodarzi, Jessica A. Grieger, Marta Guasch-Ferré, Nahal Habibi, Torben Hansen, Chuiguo Huang, Arianna Harris-Kawano, Heba M. Ismail, Benjamin Hoag, Randi K. Johnson, Angus G. Jones, Robert W. Koivula, Aaron Leong, Gloria K. W. Leung, Ingrid M. Libman, Kai Liu, S. Alice Long, William L. Lowe Jr, Robert W. Morton, Ayesha A. Motala, Suna Onengut-Gumuscu, James S. Pankow, Maleesa Pathirana, Sofia Pazmino, Dianna Perez, John R. Petrie, Camille E. Powe, Alejandra Quinteros, Rashmi Jain, Debashree Ray, Mathias Ried-Larsen, Zeb Saeed, Vanessa Santhakumar, Sarah Kanbour, Sudipa Sarkar, Gabriela S. F. Monaco, Denise M. Scholtens, Elizabeth Selvin, Wayne Huey-Herng Sheu, Cate Speake, Maggie A. Stanislawski, Nele Steenackers, Andrea K. Steck, Norbert Stefan, Julie Støy, Rachael Taylor, Sok Cin Tye, Gebresilasea Gendisha Ukke, Marzhan Urazbayeva, Bart Van der Schueren, Camille Vatier, John M. Wentworth, Wesley Hannah, Sara L. White, Gechang Yu, Yingchai Zhang, Shao J. Zhou, Jacques Beltrand, Michel Polak, Ingvild Aukrust, Elisa de Franco, Sarah E. Flanagan, Kristin A. Maloney, Andrew McGovern, Janne Molnes, Mariam Nakabuye, Pål Rasmus Njølstad, Hugo Pomares-Millan, Michele Provenzano, Cécile Saint-Martin, Cuilin Zhang, Yeyi Zhu, Sungyoung Auh, Russell de Souza, Andrea J. Fawcett, Chandra Gruber, Eskedar Getie Mekonnen, Emily Mixter, Diana Sherifali, Robert H. Eckel, John J. Nolan, Louis H. Philipson, Rebecca J. Brown, Liana K. Billings, Kristen Boyle, Tina Costacou, John M. Dennis, Jose C. Florez, Anna L. Gloyn, Maria F. Gomez, Peter A. Gottlieb, Siri Atma W. Greeley, Kurt Griffin, Andrew T. Hattersley, Irl B. Hirsch, Marie-France Hivert, Korey K. Hood, Jami L. Josefson, Soo Heon Kwak, Lori M. Laffel, Siew S. Lim, Ruth J. F. Loos, Ronald C. W. Ma, Chantal Mathieu, Nestoras Mathioudakis, James B. Meigs, Shivani Misra, Viswanathan Mohan, Rinki Murphy, Richard Oram, Katharine R. Owen, Susan E. Ozanne, Ewan R. Pearson, Wei Perng, Toni I. Pollin, Rodica Pop-Busui, Richard E. Pratley, Leanne M. Redman, Maria J. Redondo, Rebecca M. Reynolds, Robert K. Semple, Jennifer L. Sherr, Emily K. Sims, Arianne Sweeting, Tiinamaija Tuomi, Miriam S. Udler, Kimberly K. Vesco, Tina Vilsbøll, Robert Wagner, Stephen S. Rich, Paul W. Franks","doi":"10.1038/s41591-023-02502-5","DOIUrl":"10.1038/s41591-023-02502-5","url":null,"abstract":"Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine. A systematic review of evidence, across the key pillars of prevention, diagnosis, treatment and prognosis, outlines milestones that need to be met to enable the broad clinical implementation of precision medicine in diabetes care.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 10","pages":"2438-2457"},"PeriodicalIF":82.9,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10735053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial","authors":"Lars Krogvold, Ida Maria Mynarek, Erica Ponzi, Freja Barrett Mørk, Trine Witzner Hessel, Trine Roald, Nina Lindblom, Jacob Westman, Peter Barker, Heikki Hyöty, Johnny Ludvigsson, Kristian F. Hanssen, Jesper Johannesen, Knut Dahl-Jørgensen","doi":"10.1038/s41591-023-02576-1","DOIUrl":"10.1038/s41591-023-02576-1","url":null,"abstract":"Previous studies showed a low-grade enterovirus infection in the pancreatic islets of patients with newly diagnosed type 1 diabetes (T1D). In the Diabetes Virus Detection (DiViD) Intervention, a phase 2, placebo-controlled, randomized, parallel group, double-blind trial, 96 children and adolescents (aged 6–15 years) with new-onset T1D received antiviral treatment with pleconaril and ribavirin (n = 47) or placebo (n = 49) for 6 months, with the aim of preserving β cell function. The primary endpoint was the mean stimulated C-peptide area under the curve (AUC) 12 months after the initiation of treatment (less than 3 weeks after diagnosis) using a mixed linear model. The model used longitudinal log-transformed serum C-peptide AUCs at baseline, at 3 months, 6 months and 1 year. The primary endpoint was met with the serum C-peptide AUC being higher in the pleconaril and ribavirin treatment group compared to the placebo group at 12 months (average marginal effect = 0.057 in the linear mixed model; 95% confidence interval = 0.004–0.11, P = 0.037). The treatment was well tolerated. The results show that antiviral treatment may preserve residual insulin production in children and adolescent with new-onset T1D. This provides a rationale for further evaluating antiviral strategies in the prevention and treatment of T1D. European Union Drug Regulating Authorities Clinical Trials identifier: 2015-003350-41 . Results from the DiViD Intervention, a phase 2 randomized, placebo-controlled trial, showed that antiviral treatment with pleconaril and ribavirin for 6 months resulted in higher endogenous insulin production in children and adolescents with new-onset type 1 diabetes.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 11","pages":"2902-2908"},"PeriodicalIF":82.9,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to modernize medical evidence for the misinformation era","authors":"Clare Watson","doi":"10.1038/s41591-023-02537-8","DOIUrl":"10.1038/s41591-023-02537-8","url":null,"abstract":"Systematic reviews and meta-analyses are used by clinicians and policymakers to synthesize medical evidence, but they can amplify falsified or poor-quality clinical trial data. In this era of contested evidence, new approaches are needed.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 10","pages":"2383-2386"},"PeriodicalIF":82.9,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organ-sparing precision treatment for muscle-invasive bladder cancer","authors":"Roger Li","doi":"10.1038/s41591-023-02575-2","DOIUrl":"10.1038/s41591-023-02575-2","url":null,"abstract":"The response to neoadjuvant treatment can be used to stratify individuals with muscle-invasive bladder cancer according to their risk of progression, enabling bladder-sparing approaches for some — and heralding a shift from the existing one-size-fits-all approach.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 11","pages":"2709-2710"},"PeriodicalIF":82.9,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial","authors":"Nizar J. Bahlis, Caitlin L. Costello, Noopur S. Raje, Moshe Y. Levy, Bhagirathbhai Dholaria, Melhem Solh, Michael H. Tomasson, Michael A. Damore, Sibo Jiang, Cynthia Basu, Athanasia Skoura, Edward M. Chan, Suzanne Trudel, Andrzej Jakubowiak, Cristina Gasparetto, Michael P. Chu, Andrew Dalovisio, Michael Sebag, Alexander M. Lesokhin","doi":"10.1038/s41591-023-02589-w","DOIUrl":"10.1038/s41591-023-02589-w","url":null,"abstract":"Multiple myeloma (MM) is a plasma cell malignancy expressing B cell maturation antigen (BCMA). Elranatamab, a bispecific antibody, engages BCMA on MM and CD3 on T cells. The MagnetisMM-1 trial evaluated its safety, pharmacokinetics and efficacy. Primary endpoints, including the incidence of dose-limiting toxicities as well as objective response rate (ORR) and duration of response (DOR), were met. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). Eighty-eight patients with relapsed or refractory MM received elranatamab monotherapy, and 55 patients received elranatamab at efficacious doses. Patients had received a median of five prior regimens; 90.9% were triple-class refractory, 29.1% had high cytogenetic risk and 23.6% received prior BCMA-directed therapy. No dose-limiting toxicities were observed during dose escalation. Adverse events included cytopenias and cytokine release syndrome. Exposure was dose proportional. With a median follow-up of 12.0 months, the ORR was 63.6% and 38.2% of patients achieving complete response or better. For responders, the median DOR was 17.1 months. All 13 patients evaluable for minimal residual disease achieved negativity. Even after prior BCMA-directed therapy, 53.8% achieved response. For all 55 patients, median PFS was 11.8 months, and median OS was 21.2 months. Elranatamab achieved durable responses, manageable safety and promising survival for patients with MM. ClinicalTrials.gov Identifier: NCT03269136 . In the first-in-human trial of elranatamab, patients with refractory or relapsed multiple myeloma who received the bispecific antibody against BCMA and CD3 experienced no dose-limiting toxicities during dose escalation, and the agent showed promising clinical efficacy.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 10","pages":"2570-2576"},"PeriodicalIF":82.9,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discontinued CRISPR gene therapy for sickle-cell disease improves symptoms","authors":"Thiago Carvalho","doi":"10.1038/d41591-023-00088-6","DOIUrl":"10.1038/d41591-023-00088-6","url":null,"abstract":"Nature Medicine explores the latest translation and clinical research news, with results from a clinical trial of Novartis'' discontinued gene therapy to restore fetal hemoglobin. Nature Medicine explores the latest translation and clinical research news, with results from a clinical trial of Novartis'' discontinued gene therapy to restore fetal hemoglobin.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 11","pages":"2669-2670"},"PeriodicalIF":82.9,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41138844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic epidemiology of Clostridioides difficile in individuals admitted to an intensive care unit","authors":"","doi":"10.1038/s41591-023-02550-x","DOIUrl":"10.1038/s41591-023-02550-x","url":null,"abstract":"Whole-genome sequencing of Clostridioides difficile from a densely sampled intensive care unit (ICU) population showed that many of these patients harbor toxigenic C. difficile. This carriage did not lead to high levels of cross-transmission but was associated with a greatly increased risk of developing clinically overt C. difficile infection.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 10","pages":"2418-2419"},"PeriodicalIF":82.9,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial","authors":"Matthew D. Galsky, Siamak Daneshmand, Sudeh Izadmehr, Edgar Gonzalez-Kozlova, Kevin G. Chan, Sara Lewis, Bassam El Achkar, Tanya B. Dorff, Jeremy Paul Cetnar, Brock O. Neil, Anishka D’Souza, Ronac Mamtani, Christos Kyriakopoulos, Tomi Jun, Mahalya Gogerly-Moragoda, Rachel Brody, Hui Xie, Kai Nie, Geoffrey Kelly, Amir Horwitz, Yayoi Kinoshita, Ethan Ellis, Yohei Nose, Giorgio Ioannou, Rafael Cabal, G. Kenneth Haines, Li Wang, Kent W. Mouw, Robert M. Samstein, Reza Mehrazin, Nina Bhardwaj, Menggang Yu, Qianqian Zhao, Seunghee Kim-Schulze, Robert Sebra, Jun Zhu, Sacha Gnjatic, John Sfakianos, Sumanta K. Pal","doi":"10.1038/s41591-023-02568-1","DOIUrl":"10.1038/s41591-023-02568-1","url":null,"abstract":"Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"29 11","pages":"2825-2834"},"PeriodicalIF":82.9,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41134402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}