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Biomarkers for progressive multifocal leukoencephalopathy: emerging data for use of JC virus DNA copy number in clinical trials. 进行性多灶性白质脑病的生物标志物:在临床试验中使用JC病毒DNA拷贝数的新数据。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-05-01 DOI: 10.1016/S1474-4422(24)00099-1
Irene Cortese, Gina Norato, Patrick R Harrington, Therri Usher, Ilaria Mainardi, Guillaume Martin-Blondel, Paola Cinque, Eugene O Major, Virginia Sheikh
{"title":"Biomarkers for progressive multifocal leukoencephalopathy: emerging data for use of JC virus DNA copy number in clinical trials.","authors":"Irene Cortese, Gina Norato, Patrick R Harrington, Therri Usher, Ilaria Mainardi, Guillaume Martin-Blondel, Paola Cinque, Eugene O Major, Virginia Sheikh","doi":"10.1016/S1474-4422(24)00099-1","DOIUrl":"10.1016/S1474-4422(24)00099-1","url":null,"abstract":"<p><p>Progressive multifocal leukoencephalopathy is a rare but devastating demyelinating disease caused by the JC virus (JCV), for which no therapeutics are approved. To make progress towards addressing this unmet medical need, innovations in clinical trial design are needed. Quantitative JCV DNA in CSF has the potential to serve as a valuable biomarker of progressive multifocal leukoencephalopathy disease and treatment response in clinical trials to expedite therapeutic development, as do neuroimaging and other fluid biomarkers such as neurofilament light chain. Specifically, JCV DNA in CSF could be used in clinical trials as an entry criterion, stratification factor, or predictor of clinical outcomes. Insights from the investigation of candidate biomarkers for progressive multifocal leukoencephalopathy might inform approaches to biomarker development for other rare diseases.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 5","pages":"534-544"},"PeriodicalIF":46.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856968","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}
引用次数: 0
Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial. 洛斯玛匹莫德治疗面阔肌营养不良症(ReDUX4)的安全性和疗效:随机、双盲、安慰剂对照 2b 期试验。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-05-01 DOI: 10.1016/S1474-4422(24)00073-5
Rabi Tawil, Kathryn R Wagner, Johanna I Hamel, Doris G Leung, Jeffrey M Statland, Leo H Wang, Angela Genge, Sabrina Sacconi, Hanns Lochmüller, David Reyes-Leiva, Jordi Diaz-Manera, Jorge Alonso-Perez, Nuria Muelas, Juan J Vilchez, Alan Pestronk, Summer Gibson, Namita A Goyal, Lawrence J Hayward, Nicholas Johnson, Samantha LoRusso, Miriam Freimer, Perry B Shieh, S H Subramony, Baziel van Engelen, Joost Kools, Olof Dahlqvist Leinhard, Per Widholm, Christopher Morabito, Christopher M Moxham, Diego Cadavid, Michelle L Mellion, Adefowope Odueyungbo, William G Tracewell, Anthony Accorsi, Lucienne Ronco, Robert J Gould, Jennifer Shoskes, Luis Alejandro Rojas, John G Jiang
{"title":"Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.","authors":"Rabi Tawil, Kathryn R Wagner, Johanna I Hamel, Doris G Leung, Jeffrey M Statland, Leo H Wang, Angela Genge, Sabrina Sacconi, Hanns Lochmüller, David Reyes-Leiva, Jordi Diaz-Manera, Jorge Alonso-Perez, Nuria Muelas, Juan J Vilchez, Alan Pestronk, Summer Gibson, Namita A Goyal, Lawrence J Hayward, Nicholas Johnson, Samantha LoRusso, Miriam Freimer, Perry B Shieh, S H Subramony, Baziel van Engelen, Joost Kools, Olof Dahlqvist Leinhard, Per Widholm, Christopher Morabito, Christopher M Moxham, Diego Cadavid, Michelle L Mellion, Adefowope Odueyungbo, William G Tracewell, Anthony Accorsi, Lucienne Ronco, Robert J Gould, Jennifer Shoskes, Luis Alejandro Rojas, John G Jiang","doi":"10.1016/S1474-4422(24)00073-5","DOIUrl":"10.1016/S1474-4422(24)00073-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4-driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45·7 (SD 12·5) years. Least squares mean changes from baseline in DUX4-driven gene expression did not differ significantly between the losmapimod (0·83 [SE 0·61]) and placebo (0·40 [0·65]) groups (difference 0·43 [SE 0·56; 95% CI -1·04 to 1·89]; p=0·56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drug-related) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential impro","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 5","pages":"477-486"},"PeriodicalIF":46.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856970","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}
引用次数: 0
Surrogate endpoints for progressive multifocal leukoencephalopathy. 进行性多灶性白质脑病的替代终点。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-05-01 DOI: 10.1016/S1474-4422(24)00132-7
Joep Killestein, Mike P Wattjes
{"title":"Surrogate endpoints for progressive multifocal leukoencephalopathy.","authors":"Joep Killestein, Mike P Wattjes","doi":"10.1016/S1474-4422(24)00132-7","DOIUrl":"10.1016/S1474-4422(24)00132-7","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 5","pages":"455-456"},"PeriodicalIF":46.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859607","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}
引用次数: 0
A disease-specific therapy in facioscapulohumeral muscular dystrophy. 面肱骨肌营养不良症的特定疾病疗法
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-05-01 DOI: 10.1016/S1474-4422(24)00129-7
Nicol Voermans, John Vissing
{"title":"A disease-specific therapy in facioscapulohumeral muscular dystrophy.","authors":"Nicol Voermans, John Vissing","doi":"10.1016/S1474-4422(24)00129-7","DOIUrl":"10.1016/S1474-4422(24)00129-7","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 5","pages":"449-451"},"PeriodicalIF":46.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864795","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}
引用次数: 0
Factors affecting brain maturation trajectories in early childhood. 影响幼儿期大脑成熟轨迹的因素。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-05-01 DOI: 10.1016/S1474-4422(24)00089-9
Thiviya Selvanathan, Steven P Miller
{"title":"Factors affecting brain maturation trajectories in early childhood.","authors":"Thiviya Selvanathan, Steven P Miller","doi":"10.1016/S1474-4422(24)00089-9","DOIUrl":"10.1016/S1474-4422(24)00089-9","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 5","pages":"456-458"},"PeriodicalIF":46.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856597","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}
引用次数: 0
Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study. 唐氏综合征患者与常染色体显性遗传阿尔茨海默病患者 tau 扩散的比较:一项横断面研究。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-05-01 DOI: 10.1016/S1474-4422(24)00084-X
Julie K Wisch, Nicole S McKay, Anna H Boerwinkle, James Kennedy, Shaney Flores, Benjamin L Handen, Bradley T Christian, Elizabeth Head, Mark Mapstone, Michael S Rafii, Sid E O'Bryant, Julie C Price, Charles M Laymon, Sharon J Krinsky-McHale, Florence Lai, H Diana Rosas, Sigan L Hartley, Shahid Zaman, Ira T Lott, Dana Tudorascu, Matthew Zammit, Adam M Brickman, Joseph H Lee, Thomas D Bird, Annie Cohen, Patricio Chrem, Alisha Daniels, Jasmeer P Chhatwal, Carlos Cruchaga, Laura Ibanez, Mathias Jucker, Celeste M Karch, Gregory S Day, Jae-Hong Lee, Johannes Levin, Jorge Llibre-Guerra, Yan Li, Francisco Lopera, Jee Hoon Roh, John M Ringman, Charlene Supnet-Bell, Christopher H van Dyck, Chengjie Xiong, Guoqiao Wang, John C Morris, Eric McDade, Randall J Bateman, Tammie L S Benzinger, Brian A Gordon, Beau M Ances
{"title":"Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study.","authors":"Julie K Wisch, Nicole S McKay, Anna H Boerwinkle, James Kennedy, Shaney Flores, Benjamin L Handen, Bradley T Christian, Elizabeth Head, Mark Mapstone, Michael S Rafii, Sid E O'Bryant, Julie C Price, Charles M Laymon, Sharon J Krinsky-McHale, Florence Lai, H Diana Rosas, Sigan L Hartley, Shahid Zaman, Ira T Lott, Dana Tudorascu, Matthew Zammit, Adam M Brickman, Joseph H Lee, Thomas D Bird, Annie Cohen, Patricio Chrem, Alisha Daniels, Jasmeer P Chhatwal, Carlos Cruchaga, Laura Ibanez, Mathias Jucker, Celeste M Karch, Gregory S Day, Jae-Hong Lee, Johannes Levin, Jorge Llibre-Guerra, Yan Li, Francisco Lopera, Jee Hoon Roh, John M Ringman, Charlene Supnet-Bell, Christopher H van Dyck, Chengjie Xiong, Guoqiao Wang, John C Morris, Eric McDade, Randall J Bateman, Tammie L S Benzinger, Brian A Gordon, Beau M Ances","doi":"10.1016/S1474-4422(24)00084-X","DOIUrl":"10.1016/S1474-4422(24)00084-X","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In people with genetic forms of Alzheimer's disease, such as in Down syndrome and autosomal-dominant Alzheimer's disease, pathological changes specific to Alzheimer's disease (ie, accumulation of amyloid and tau) occur in the brain at a young age, when comorbidities related to ageing are not present. Studies including these cohorts could, therefore, improve our understanding of the early pathogenesis of Alzheimer's disease and be useful when designing preventive interventions targeted at disease pathology or when planning clinical trials. We compared the magnitude, spatial extent, and temporal ordering of tau spread in people with Down syndrome and autosomal-dominant Alzheimer's disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this cross-sectional observational study, we included participants (aged ≥25 years) from two cohort studies. First, we collected data from the Dominantly Inherited Alzheimer's Network studies (DIAN-OBS and DIAN-TU), which include carriers of autosomal-dominant Alzheimer's disease genetic mutations and non-carrier familial controls recruited in Australia, Europe, and the USA between 2008 and 2022. Second, we collected data from the Alzheimer Biomarkers Consortium-Down Syndrome study, which includes people with Down syndrome and sibling controls recruited from the UK and USA between 2015 and 2021. Controls from the two studies were combined into a single group of familial controls. All participants had completed structural MRI and tau PET (&lt;sup&gt;18&lt;/sup&gt;F-flortaucipir) imaging. We applied Gaussian mixture modelling to identify regions of high tau PET burden and regions with the earliest changes in tau binding for each cohort separately. We estimated regional tau PET burden as a function of cortical amyloid burden for both cohorts. Finally, we compared the temporal pattern of tau PET burden relative to that of amyloid.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;We included 137 people with Down syndrome (mean age 38·5 years [SD 8·2], 74 [54%] male, and 63 [46%] female), 49 individuals with autosomal-dominant Alzheimer's disease (mean age 43·9 years [11·2], 22 [45%] male, and 27 [55%] female), and 85 familial controls, pooled from across both studies (mean age 41·5 years [12·1], 28 [33%] male, and 57 [67%] female), who satisfied the PET quality-control procedure for tau-PET imaging processing. 134 (98%) people with Down syndrome, 44 (90%) with autosomal-dominant Alzheimer's disease, and 77 (91%) controls also completed an amyloid PET scan within 3 years of tau PET imaging. Spatially, tau PET burden was observed most frequently in subcortical and medial temporal regions in people with Down syndrome, and within the medial temporal lobe in people with autosomal-dominant Alzheimer's disease. Across the brain, people with Down syndrome had greater concentrations of tau for a given level of amyloid compared with people with autosomal-dominant Alzheimer's disease. Temporally, increases in tau were more strongly associat","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 5","pages":"500-510"},"PeriodicalIF":46.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863317","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}
引用次数: 0
Improving epilepsy diagnosis across the lifespan: approaches and innovations. 改善整个生命周期的癫痫诊断:方法与创新。
IF 46.5 1区 医学
Lancet Neurology Pub Date : 2024-05-01 DOI: 10.1016/S1474-4422(24)00079-6
Jacob Pellinen, Emma C Foster, Jo M Wilmshurst, Sameer M Zuberi, Jacqueline French
{"title":"Improving epilepsy diagnosis across the lifespan: approaches and innovations.","authors":"Jacob Pellinen, Emma C Foster, Jo M Wilmshurst, Sameer M Zuberi, Jacqueline French","doi":"10.1016/S1474-4422(24)00079-6","DOIUrl":"10.1016/S1474-4422(24)00079-6","url":null,"abstract":"<p><p>Epilepsy diagnosis is often delayed or inaccurate, exposing people to ongoing seizures and their substantial consequences until effective treatment is initiated. Important factors contributing to this problem include delayed recognition of seizure symptoms by patients and eyewitnesses; cultural, geographical, and financial barriers to seeking health care; and missed or delayed diagnosis by health-care providers. Epilepsy diagnosis involves several steps. The first step is recognition of epileptic seizures; next is classification of epilepsy type and whether an epilepsy syndrome is present; finally, the underlying epilepsy-associated comorbidities and potential causes must be identified, which differ across the lifespan. Clinical history, elicited from patients and eyewitnesses, is a fundamental component of the diagnostic pathway. Recent technological advances, including smartphone videography and genetic testing, are increasingly used in routine practice. Innovations in technology, such as artificial intelligence, could provide new possibilities for directly and indirectly detecting epilepsy and might make valuable contributions to diagnostic algorithms in the future.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"23 5","pages":"511-521"},"PeriodicalIF":46.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859343","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}
引用次数: 0
Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial. 阿托格潘用于传统口服预防治疗失败的成人发作性偏头痛预防治疗的安全性和有效性(ELEVATE):随机、安慰剂对照、3b 期试验。
IF 48 1区 医学
Lancet Neurology Pub Date : 2024-04-01 Epub Date: 2024-02-13 DOI: 10.1016/S1474-4422(24)00025-5
Cristina Tassorelli, Krisztián Nagy, Patricia Pozo-Rosich, Michel Lanteri-Minet, Sara Sacco, Tomáš Nežádal, Hua Guo, Rosa De Abreu Ferreira, Giovanna Forero, Joel M Trugman
{"title":"Safety and efficacy of atogepant for the preventive treatment of episodic migraine in adults for whom conventional oral preventive treatments have failed (ELEVATE): a randomised, placebo-controlled, phase 3b trial.","authors":"Cristina Tassorelli, Krisztián Nagy, Patricia Pozo-Rosich, Michel Lanteri-Minet, Sara Sacco, Tomáš Nežádal, Hua Guo, Rosa De Abreu Ferreira, Giovanna Forero, Joel M Trugman","doi":"10.1016/S1474-4422(24)00025-5","DOIUrl":"10.1016/S1474-4422(24)00025-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has been approved for the preventive treatment of migraine, but its efficacy and safety in people who have been failed by conventional oral preventive migraine treatments has not yet been evaluated in a dedicated clinical trial. The ELEVATE trial evaluated the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in participants for whom two to four classes of conventional oral preventive treatments have failed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;ELEVATE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3b trial done at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the UK, and the USA. Adults (18-80 years) with episodic migraine who had previously been failed by two to four classes of conventional oral treatments for migraine prevention were randomly assigned (1:1) using interactive web response technology to oral atogepant 60 mg once a day or placebo, stratified by baseline monthly migraine days, number of treatment classes participants have been failed by, and region. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the off-treatment hypothetical estimand (OTHE) population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods (whether on treatment or off treatment). The primary endpoint was analysed using a mixed model for repeated measures and a fixed-sequence procedure was used to control for multiple comparisons. The trial is registered with ClinicalTrials.gov (NCT04740827) and EudraCT (2019-003448-58), and is completed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between March 5, 2021, and Aug 4, 2022, 540 participants were screened, 315 were randomly assigned, and 313 participants (280 [89%] female, 33 [11%] male, and 300 [96%] White) received at least one dose of study intervention. In the OTHE population, which comprised 309 participants (155 assigned to placebo and 154 to atogepant), least squares mean changes from baseline in monthly migraine days across 12 weeks were -1·9 (SE 0·4) with placebo and -4·2 (0·4) with atogepant (least squares mean difference -2·4, 95% CI -3·2 to -1·5; adjusted p&lt;0·0001). The most common treatment-emergent adverse event with atogepant was constipation in 16 (10%) of 156 participants (vs four [3%] of 157 for placebo). Serious adverse events occurred in four [3%] of 156 participants in the atogepant group vs none in the placebo group, and treatment-emergent adverse events resulting in treatment discontinuation occurred in three [2%] in the atogepant group vs two [1%] in the placebo group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Atogepant 60 mg ","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"382-392"},"PeriodicalIF":48.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746848","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}
引用次数: 0
Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. 1990-2021 年影响神经系统疾病的全球、地区和国家负担:2021 年全球疾病负担研究的系统分析。
IF 48 1区 医学
Lancet Neurology Pub Date : 2024-04-01 Epub Date: 2024-03-14 DOI: 10.1016/S1474-4422(24)00038-3
{"title":"Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.","authors":"","doi":"10.1016/S1474-4422(24)00038-3","DOIUrl":"10.1016/S1474-4422(24)00038-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378-521), affecting 3·40 billion (3·20-3·62) individuals (43·1%, 40·5-45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7-26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6-38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5-32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7-2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm bir","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"344-381"},"PeriodicalIF":48.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143805","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}
引用次数: 0
Addressing neurological burden in the Americas. 解决美洲的神经负担问题。
IF 48 1区 医学
Lancet Neurology Pub Date : 2024-04-01 Epub Date: 2024-03-14 DOI: 10.1016/S1474-4422(24)00085-1
Amy Tausch, Kiran T Thakur, Renato Oliveira E Souza
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引用次数: 0
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