PLoS Medicine最新文献

{"title":"Impact of active case finding for tuberculosis with mass chest X-ray screening in Glasgow, Scotland, 1950-1963: An epidemiological analysis of historical data.","authors":"Peter MacPherson, Helen R Stagg, Alvaro Schwalb, Hazel Henderson, Alice E Taylor, Rachael M Burke, Hannah M Rickman, Cecily Miller, Rein M G J Houben, Peter J Dodd, Elizabeth L Corbett","doi":"10.1371/journal.pmed.1004448","DOIUrl":"10.1371/journal.pmed.1004448","url":null,"abstract":"<p><strong>Background: </strong>Community active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening.</p><p><strong>Methods and findings: </strong>Case notifications for 1950 to 1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNRs) during and after a mass screening intervention implemented over 5 weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11 March 1957 to 12 April 1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults ≥15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950 to 1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI] [1.81, 2.11]) and 35% decline in the year after (RR: 0.65, 95% UI [0.59, 0.71]). Post-intervention (1958 to 1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95% UI [0.69, 0.85]), and there were an estimated 4,599 (95% UI [3,641, 5,683]) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined in young children (0 to 5 years) with the intervention. Limitations include the lack of data in historical reports on microbiological testing for tuberculosis, and uncertainty in contributory effects of other contemporaneous interventions including slum clearances, introduction of BCG vaccination programmes, and the ending of postwar food rationing.</p><p><strong>Conclusions: </strong>A single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) likely resulted in a major and sustained reduction in tuberculosis case notifications. Synthesis of evidence from other historical tuberculosis screening programmes is needed to confirm findings from Glasgow and to provide insights into ongoing efforts to successfully implement ACF interventions in today's high tuberculosis burden countries and with new screening tools and technologies.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584804","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":"Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.","authors":"Steven Perrin, Shafeeq Ladha, Nicholas Maragakis, Michael H Rivner, Jonathan Katz, Angela Genge, Nicholas Olney, Dale Lange, Daragh Heitzman, Cynthia Bodkin, Omar Jawdat, Namita A Goyal, Jeffrey D Bornstein, Carmen Mak, Stanley H Appel, Sabrina Paganoni","doi":"10.1371/journal.pmed.1004469","DOIUrl":"10.1371/journal.pmed.1004469","url":null,"abstract":"<p><strong>Background: </strong>The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS).</p><p><strong>Methods and findings: </strong>In this multicenter dose-escalating open-label Phase 2A study, 54 participants with a diagnosis of ALS received 6 infusions of tegoprubart administered intravenously every 2 weeks. The study was comprised of 4 dose cohorts: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 8 mg/kg. The primary endpoint of the study was safety and tolerability. Exploratory endpoints assessed the pharmacokinetics of tegoprubart as well as anti-drug antibody (ADA) responses, changes in disease progression utilizing the Revised ALS Functional Rating Scale (ALSFRS-R), CD154 target engagement, changes in pro-inflammatory biomarkers, and neurofilament light chain (NFL). Seventy subjects were screened, and 54 subjects were enrolled in the study. Forty-nine of 54 subjects completed the study (90.7%) receiving all 6 infusions of tegoprubart and completing their final follow-up visit. The most common treatment emergent adverse events (TEAEs) overall (>10%) were fatigue (25.9%), falls (22.2%), headaches (20.4%), and muscle spasms (11.1%). Mean tegoprubart plasma concentrations increased proportionally with increasing dose with a half-life of approximately 24 days. ADA titers were low and circulating levels of tegoprubart were as predicted for all cohorts. Tegoprubart demonstrated dose dependent target engagement associated and a reduction in 18 pro-inflammatory biomarkers in circulation.</p><p><strong>Conclusions: </strong>Tegoprubart appeared to be safe and well tolerated in adults with ALS demonstrating dose-dependent reduction in pro-inflammatory chemokines and cytokines associated with ALS. These results warrant further clinical studies with sufficient power and duration to assess clinical outcomes as a potential treatment for adults with ALS.</p><p><strong>Trial registration: </strong>Clintrials.gov ID:NCT04322149.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559201","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":"Incidence rates of hepatocellular carcinoma based on risk stratification in steatotic liver disease for precision medicine: A real-world longitudinal nationwide study.","authors":"Rongtao Lai, Scott Barnett, Xinrong Zhang, Leslie Yeeman Kam, Ramsey Cheung, Qing Xie, Mindie H Nguyen","doi":"10.1371/journal.pmed.1004479","DOIUrl":"10.1371/journal.pmed.1004479","url":null,"abstract":"<p><strong>Background: </strong>Detailed subgroup incidence rates for steatotic liver disease (SLD)-related hepatocellular carcinoma (HCC) are critical to inform practice and public health interventions but remain sparse. We aimed to fill in this gap.</p><p><strong>Methods and findings: </strong>In a retrospective cohort study of adults with SLD from the United States (US) Merative Marketscan Research Databases (1/2007 to 12/2021), we estimated HCC incidence stratified by sex, age, cirrhosis, diabetes mellitus (DM), and a combination of all these 4 factors. We excluded patients with significant alcohol use and chronic viral hepatitis. We analyzed data from 741,816 patients with SLD (mean age 51.5 ± 12.8 years, 46% male, 14.7% cirrhosis). During a 2,410,166 person-years (PY) follow-up, 1,740 patients developed HCC. The overall HCC incidence yielded 0.72 per 1,000 PY (95% confidence interval [CI, 0.68, 0.75]). The incidence was higher in males (0.95, 95% CI [0.89, 1.01]) compared to females (0.52, 95% CI [0.48, 0.56]) (p < 0.001). For those with cirrhosis, the incidence was significantly higher at 4.29 (95% CI [4.06, 4.51]) compared to those without cirrhosis (0.14, 95% CI [0.13, 0.16]) (p < 0.001). Additionally, the incidence was higher in patients with DM (1.19, 95% CI [1.12, 1.26]) compared to those without DM (0.41, 95% CI [0.38, 0.44]) (p < 0.001). Chronic kidney disease (CKD) was also associated with a higher HCC incidence of 2.20 (95% CI [2.00, 2.41]) compared to those without CKD (0.58, 95% CI [0.55, 0.62]) (p < 0.001). Similarly, individuals with cardiovascular disease (CVD) had a higher HCC incidence of 1.89 (95% CI [1.75, 2.03]) compared to those without CVD (0.51, 95% CI [0.48, 0.54]) (p < 0.001). Finally, the incidence of HCC was significantly higher in patients with non-liver cancer (3.90, 95% CI [3.67, 4.12]) compared to those without other cancers (0.29, 95% CI [0.26, 0.31]) (p < 0.001). On further stratification, HCC incidence incrementally rose by 10-year age intervals, male sex, cirrhosis, and DM, reaching 19.06 (95% CI [16.10, 22.01]) and 8.44 (95% CI [6.78, 10.10]) in males and females, respectively, but only 0.04 for non-diabetic, noncirrhotic aged <40 years patients in both sexes. The main limitation of this methodology is the potential misclassification of the International Classification of Diseases (ICD) codes inherent in claims database studies.</p><p><strong>Conclusions: </strong>This nationwide study provided robust granular estimates for SLD-related HCC incidence stratified by several key risk factors. In addition to cirrhosis, future surveillance strategies, prevention, public health initiatives, and future research models should also take into account the impact of sex, age, and DM.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511176","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":"The effect of protecting women against economic shocks to fight HIV in Cameroon, Africa: The POWER randomised controlled trial.","authors":"Aurélia Lépine, Sandie Szawlowski, Emile Nitcheu, Henry Cust, Eric Defo Tamgno, Julienne Noo, Fanny Procureur, Illiasou Mfochive, Serge Billong, Ubald Tamoufe","doi":"10.1371/journal.pmed.1004355","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004355","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Women in sub-Saharan Africa are disproportionately affected by the HIV epidemic. Young women are twice as likely to be living with HIV as men of the same age and account for 64% of new HIV infections among young people. Many studies suggest that financial needs, alongside biological susceptibility, are a leading cause of the gender disparity in HIV acquisition. New robust evidence suggests women adopt risky sexual behaviours to cope with economic shocks, the sudden decreases in household's income or consumption power, enhancing our understanding of the link between poverty and HIV. We investigated if health insurance protects against economic shocks, reducing the need for vulnerable women to engage in risky sexual behaviours and reducing HIV and sexually transmitted infection (STI) incidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method and findings: &lt;/strong&gt;We conducted a randomised controlled trial to test the effectiveness of a formal shock coping strategy to prevent HIV among women at high risk of HIV (registration number: ISRCTN 22516548). Between June and August 2021, we recruited 1,508 adolescent girls and women over age 15 years who were involved in transactional sex (n = 753) or commercial sex (n = 755), using snowball sampling. Participants were randomly assigned (1:1) to receive free health insurance for themselves and their economic dependents for 12 months either at the beginning of the study (intervention; n = 579; commercial sex n = 289, transactional sex n = 290) from November 2021 or at the end of the study 12 months later (control; n = 568; commercial sex n = 290, transactional sex n = 278). We collected data on socioeconomic characteristics of participants. Primary outcomes included incidence of HIV and STIs and were measured at baseline, 6 months after randomisation, and 12 months after randomisation. We found that study participants who engaged in transactional sex and were assigned to the intervention group were less likely to become infected with HIV post-intervention (combined result of 6 months post-intervention or 12 months post-intervention, depending on the follow-up data available; odds ratio (OR) = 0.109 (95% confidence interval (CI) [0.014, 0.870]); p = 0.036). There was no evidence of a reduction in HIV incidence among women and girls involved in commercial sex. There was also no effect on STI acquisition among both strata of high-risk sexual activity. The main limitations of this study were the challenges of collecting reliable STI incidence data and the low incidence of HIV in women and girls involved in commercial sex, which might have prevented detection of study effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The study provides to our knowledge the first evidence of the effectiveness of a formal shock coping strategy for HIV prevention among women who engage in transactional sex in Africa, reinforcing the importance of structural interventions to prevent HIV.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;The","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511179","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":"Leveraging behavioral economics strategies to close gaps in biomedical HIV prevention.","authors":"Jesse Heitner, Valerian Mwenda, Grace Umutesi, Ruanne V Barnabas","doi":"10.1371/journal.pmed.1004475","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004475","url":null,"abstract":"<p><p>Adolescent girls and young women (AGYW) in southern Africa face triple the HIV incidence of their male peers due to multiple factors, including economic deprivation and age-disparate relationships. A new study by Aurélia Lépine and colleagues has demonstrated that addressing healthcare costs among AGYW has the potential to reduce HIV incidence.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511177","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":"Adverse health outcomes in offspring of parents with alcohol-related liver disease: Nationwide Danish cohort study.","authors":"Peter Jepsen, Joe West, Anna Kirstine Kjær Larsen, Anna Emilie Kann, Frederik Kraglund, Joanne R Morling, Colin Crooks, Gro Askgaard","doi":"10.1371/journal.pmed.1004483","DOIUrl":"10.1371/journal.pmed.1004483","url":null,"abstract":"<p><strong>Background: </strong>Parental drinking can cause harm to the offspring. A parent's diagnosis of alcohol-related liver disease (ALD) might be an opportunity to reach offspring with preventive interventions. We investigated offspring risk of adverse health outcomes throughout life, their association with their parent's educational level and diagnosis of ALD.</p><p><strong>Methods and findings: </strong>We used nationwide health registries to identify offspring of parents diagnosed with ALD in Denmark 1996 to 2018 and age- and sex-matched comparators (20:1). We estimated the incidence rate ratios (IRRs) of hospital contacts with adverse health outcomes, overall and in socioeconomic strata. We used a self-controlled design to examine whether health outcomes were more likely to occur during the first year after the parent's ALD diagnosis. The 60,804 offspring of parents with ALD had a higher incidence rate of hospital contacts from age 15 to 60 years for psychiatric disease, poisoning, fracture or injury, alcohol-specific diagnoses, other substance abuse, and of death than comparators. Associations were stronger for offspring with low compared to high socioeconomic position: The IRR for admission due to poisoning was 2.2 versus 1.0 for offspring of an ALD parent with a primary level versus a highly educated ALD parent. Offspring had an increased risk for admission with psychiatric disease and poisoning in the year after their parent's ALD diagnosis. For example, among offspring whose first hospital contact with psychiatric disease was at age 13 to 25 years, the IRR in the first year after their parent's ALD diagnosis versus at another time was 1.29 (95% CI 1.13, 1.47). Main limitation was inability to include adverse health outcomes not involving hospital contact.</p><p><strong>Conclusions: </strong>Offspring of parents with ALD had a long-lasting higher rate of health outcomes associated with poor mental health and self-harm that increased shortly after their parent's diagnosis of ALD. Offspring of parents of low educational level were particularly vulnerable. This study highlights an opportunity to reach out to offspring in connection with their parent's hospitalization with ALD.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511175","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":"Medical imaging utilization in migrants compared with nonmigrants in a universal healthcare system: A population-based matched cohort study.","authors":"Giancarlo Di Giuseppe, Rinku Sutradhar, Priscila Pequeno, Marilyn L Kwan, Diana L Miglioretti, Rebecca Smith-Bindman, Jason D Pole","doi":"10.1371/journal.pmed.1004474","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004474","url":null,"abstract":"<p><strong>Background: </strong>Medical imaging is an integral part of healthcare. Globalization has resulted in increased mobilization of migrants to new host nations. The association between migration status and utilization of medical imaging is unknown.</p><p><strong>Methods and findings: </strong>A retrospective population-based matched cohort study was conducted in Ontario, Canada from April 1, 1995 to December 31, 2016. A total of 1,848,222 migrants were matched 1:1 to nonmigrants in the year of migration on age, sex, and geography. Utilization of computed tomography (CT), magnetic resonance imaging (MRI), radiography, and ultrasonography was determined. Rate differences per 1,000 person-years comparing migrants to nonmigrants were calculated. Relative rates were calculated using a recurrent event framework, adjusting for age, sex, and time-varying socioeconomic status, comorbidity score, and access to a primary care provider. Estimates were stratified by migration age: children and adolescents (≤19 years), young adults (20 to 39), adults (40 to 59), and older adults (≥60). Utilization rates of CT, MRI, and radiography were lower for migrants across all age groups compared with Ontario nonmigrants. Increasing age at migration was associated with larger differences in utilization rates. Older adult migrants had the largest gap in imaging utilization. The longer the time since migration, the larger the gap in medical imaging use. In multivariable analysis, the relative rate of imaging was approximately 20% to 30% lower for migrants: ranging from 0.77 to 0.88 for CT and 0.72 to 0.80 for MRI imaging across age groups. Radiography relative rates ranged from 0.84 to 0.90. All migrant age groups, except older adults, had higher rates of ultrasonography. The indication for imaging was not captured, thus it was not possible to determine if the imaging was necessary.</p><p><strong>Conclusions: </strong>Migrants utilized less CT, MRI, and radiography but more ultrasonography. Older adult migrants used the least amount of imaging compared with nonmigrants. Future research should evaluate whether lower utilization is due to barriers in healthcare access or health-seeking behaviors within a universal healthcare system.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511178","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":"Safety of single-dose bedaquiline combined with rifampicin for leprosy post-exposure prophylaxis: A Phase 2 randomized non-inferiority trial in the Comoros Islands.","authors":"Bouke Catherine de Jong, Said Nourdine, Auke Thomas Bergeman, Zahara Salim, Silahi Halifa Grillone, Sofie Marijke Braet, Mohamed Wirdane Abdou, Rian Snijders, Maya Ronse, Carolien Hoof, Achilleas Tsoumanis, Nimer Ortuño-Gutiérrez, Christian van der Werf, Alberto Piubello, Aboubacar Mzembaba, Younoussa Assoumani, Epco Hasker","doi":"10.1371/journal.pmed.1004453","DOIUrl":"10.1371/journal.pmed.1004453","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;To reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;From July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) &lt;450 ms and liver enzyme tests (ALT/AST) below 3× the upper limit of normal (ULN), before they were individually randomized 1:1 in an open-label design. Recruitment was sequential, by age group. Pediatric dosages were weight adjusted. Follow-up was done at day 1 post-dose (including ECG) and day 14 (including ALT/AST), with repeat of ALT/AST on the last follow-up at day 30 in case of elevation on day 14. The primary outcome was non-inferiority of BE-PEP based on a &lt;10 ms difference in QTc 24 h after treatment administration, both unadjusted and adjusted for baseline QTc. Of 408 screened participants, 313 were enrolled, starting with 187 adults, then 38 children aged 13 to 17 years, and finally 88 children aged 5 to 12 years, of whom 310 (99%) completed all visits. Across all ages, the mean QTc change on BE-PEP was from 393 ms to 396 ms, not significantly different from the change from 392 ms to 394 ms on SDR-PEP (difference between arms 1.8 ms, 95% CI -1.8, 5.3, p = 0.41). No individual's QTc increased by &gt;50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; -1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampici","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478608","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":"Risk of common psychiatric disorders, suicidal behaviours, and premature mortality following violent victimisation: A matched cohort and sibling-comparison study of 127,628 people who experienced violence in Finland and Sweden.","authors":"Amir Sariaslan, Joonas Pitkänen, Jonas Forsman, Ralf Kuja-Halkola, Isabell Brikell, Brian M D'Onofrio, Mikko Aaltonen, Henrik Larsson, Pekka Martikainen, Paul Lichtenstein, Seena Fazel","doi":"10.1371/journal.pmed.1004410","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004410","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Associations between violent victimisation and psychiatric disorders are hypothesised to be bidirectional, but the role of violent victimisation in the aetiologies of psychiatric disorders and other adverse outcomes remains unclear. We aimed to estimate associations between violent victimisation and subsequent common psychiatric disorders, suicidal behaviours, and premature mortality while accounting for unmeasured familial confounders.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;Using nationwide registers, we identified a total of 127,628 individuals born in Finland (1987 to 2004) and Sweden (1973 to 2004) who had experienced violent victimisation, defined as either hospital admissions or secondary care outpatient visits for assault-related injuries. These were age- and sex-matched with up to 10 individuals in the general population (n = 1,276,215). Additionally, we matched those who had experienced violent victimisation with their unaffected siblings (n = 132,408). Outcomes included depression, anxiety, personality disorders, alcohol use disorders, drug use disorders, suicidal behaviours, and premature mortality. Participants were followed from the victimisation date until the date of the outcome, emigration, death, or December 31, 2020, whichever occurred first. Country-specific associations were estimated using stratified Cox regression models, which also accounted for unmeasured familial confounders via sibling comparisons. The country-specific associations were then pooled using meta-analytic models. Among 127,628 patients (69.0% male) who had experienced violent victimisation, the median age at first violent victimisation was 21 (interquartile range: 18 to 26) years. Incidence of all outcomes was larger in those who were exposed to violent victimisation compared to population controls, ranging from 2.3 (95% confidence interval (CI) [2.2; 2.4]) per 1,000 person-years for premature mortality (compared with 0.6, 95% CI [0.6; 0.6], in controls) to 22.5 (95% CI [22.3; 22.8]) per 1,000 person-years for anxiety (compared with 7.3, 95% CI [7.3; 7.4], in controls). In adjusted models, people who had experienced violent victimisation were between 2 to 3 times as likely as their siblings to develop any of the outcomes, ranging from adjusted hazard ratio [aHR] 1.7 (95% CI [1.7; 1.8]) for depression to 3.0 (95% CI [2.9; 3.1]) for drug use disorders. Risks remained elevated 2 years post-victimisation, ranging from aHR 1.4 (95% CI [1.3; 1.5]) for depression to 2.3 (95% CI [2.2; 2.4]) for drug use disorders. Our reliance on secondary care data likely excluded individuals with milder assault-related injuries and less severe psychiatric symptoms, thus suggesting that our estimates may be conservative. Another limitation is the possibility of residual genetic confounding, as full siblings share on average about half of their co-segregating genes. However, the associations remained robust even after adjusting for both measured","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478555","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":"Manufactured meals: The challenges of ultraprocessed foods.","authors":"Alexandra Tosun","doi":"10.1371/journal.pmed.1004477","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004477","url":null,"abstract":"<p><p>In this Editorial on behalf of the PLOS Medicine Editors, Alexandra Tosun discusses how ultra-processed food has found itself at the center of a growing storm of criticism, the complexities of the ongoing nutrition debate and why stakeholders must be held to higher standards.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":null,"pages":null},"PeriodicalIF":15.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11478821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478554","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}