PLoS Medicine最新文献

{"title":"Measuring protective efficacy and quantifying the impact of drug resistance: A novel malaria chemoprevention trial design and methodology.","authors":"Andria Mousa, Gina Cuomo-Dannenburg, Hayley A Thompson, R Matthew Chico, Khalid B Beshir, Colin J Sutherland, David Schellenberg, Roly Gosling, Michael Alifrangis, Emma Filtenborg Hocke, Helle Hansson, Ana Chopo-Pizarro, Wilfred F Mbacham, Innocent M Ali, Mike Chaponda, Cally Roper, Lucy C Okell","doi":"10.1371/journal.pmed.1004376","DOIUrl":"10.1371/journal.pmed.1004376","url":null,"abstract":"<p><strong>Background: </strong>Recently revised WHO guidelines on malaria chemoprevention have opened the door to more tailored implementation. Countries face choices on whether to replace old drugs, target additional age groups, and adapt delivery schedules according to local drug resistance levels and malaria transmission patterns. Regular routine assessment of protective efficacy of chemoprevention is key. Here, we apply a novel modelling approach to aid the design and analysis of chemoprevention trials and generate measures of protection that can be applied across a range of transmission settings.</p><p><strong>Methods and findings: </strong>We developed a model of genotype-specific drug protection, which accounts for underlying risk of infection and circulating genotypes. Using a Bayesian framework, we fitted the model to multiple simulated scenarios to explore variations in study design, setting, and participant characteristics. We find that a placebo or control group with no drug protection is valuable but not always feasible. An alternative approach is a single-arm trial with an extended follow-up (>42 days), which allows measurement of the underlying infection risk after drug protection wanes, as long as transmission is relatively constant. We show that the currently recommended 28-day follow-up in a single-arm trial results in low precision of estimated 30-day chemoprevention efficacy and low power in determining genotype differences of 12 days in the duration of protection (power = 1.4%). Extending follow-up to 42 days increased precision and power (71.5%) in settings with constant transmission over this time period. However, in settings of unstable transmission, protective efficacy in a single-arm trial was overestimated by 24.3% if recruitment occurred during increasing transmission and underestimated by 15.8% when recruitment occurred during declining transmission. Protective efficacy was estimated with greater precision in high transmission settings, and power to detect differences by resistance genotype was lower in scenarios where the resistant genotype was either rare or too common.</p><p><strong>Conclusions: </strong>These findings have important implications for the current guidelines on chemoprevention efficacy studies and will be valuable for informing where these studies should be optimally placed. The results underscore the need for a comparator group in seasonal settings and provide evidence that the extension of follow-up in single-arm trials improves the accuracy of measures of protective efficacy in settings with more stable transmission. Extension of follow-up may pose logistical challenges to trial feasibility and associated costs. However, these studies may not need to be repeated multiple times, as the estimates of drug protection against different genotypes can be applied to different settings by adjusting for transmission intensity and frequency of resistance.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 5","pages":"e1004376"},"PeriodicalIF":15.8,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11081503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899585","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":"Sexual behaviour and incidence of sexually transmitted infections among men who have sex with men (MSM) using daily and event-driven pre-exposure prophylaxis (PrEP): Four-year follow-up of the Amsterdam PrEP (AMPrEP) demonstration project cohort.","authors":"Mark A M van den Elshout, Eline S Wijstma, Anders Boyd, Vita W Jongen, Liza Coyer, Peter L Anderson, Udi Davidovich, Henry J C de Vries, Maria Prins, Maarten F Schim van der Loeff, Elske Hoornenborg","doi":"10.1371/journal.pmed.1004328","DOIUrl":"10.1371/journal.pmed.1004328","url":null,"abstract":"<p><strong>Background: </strong>An increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension that condom use would decline and sexually transmitted infections (STIs) would increase. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP.</p><p><strong>Methods and findings: </strong>The Amsterdam PrEP demonstration project (AMPrEP) was a prospective, closed cohort study, providing oral daily PrEP and event-driven PrEP to MSM and transgender women from 2015 to 2020. Participants could choose their PrEP regimen and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in numbers of sex partners and condomless anal sex (CAS) acts with casual partners over time using negative binomial regression, adjusted for age. We assessed HIV incidence and changes in incidence rates (IRs) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis) and individual STIs over time using Poisson regression, adjusted for age and testing frequency. A total of 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (interquartile range [IQR] = 3.4-4.0). Median age was 40 years (IQR = 32-48), 315 participants (85.8%) self-declared ethnicity as white and 280 (76.3%) had a university or university of applied sciences degree. Overall median number of sex partners (past 3 months) was 13 (IQR = 6-26) and decreased per additional year on PrEP (adjusted rate ratio [aRR] = 0.86/year, 95% confidence interval [CI] = 0.83-0.88). Overall median number of CAS acts with casual partners (past 3 months) was 10 (IQR = 3-20.5) and also decreased (aRR = 0.92/year, 95% CI = 0.88-0.97). We diagnosed any STI in 1,092 consultations during 1,258 person years, resulting in an IR of 87/100 person years (95% CI = 82-92). IRs of any STI did not increase over time for daily PrEP or event-driven PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Study limitations include censoring follow-up due to COVID-19 measures and an underrepresentation of younger, non-white, practically educated, and transgender individuals.</p><p><strong>Conclusions: </strong>In this prospective cohort with a comparatively long follow-up period of 4 years, we observed very low HIV incidence and decreases in the numbers of casual sex partners and CAS acts over time. Although the STI incidence was high, it did not increase over time.</p><p><strong>Trial registration: </strong>The study was registered at the Netherlands Trial Register (NL5413) https://www.onderzoekmetmensen.nl/en/trial/22706.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 5","pages":"e1004328"},"PeriodicalIF":15.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892645","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":"ACcurate COnsensus Reporting Document (ACCORD) explanation and elaboration: Guidance and examples to support reporting consensus methods.","authors":"Patricia Logullo, Esther J van Zuuren, Christopher C Winchester, David Tovey, William T Gattrell, Amy Price, Niall Harrison, Keith Goldman, Alison Chisholm, Kirsty Walters, Paul Blazey","doi":"10.1371/journal.pmed.1004390","DOIUrl":"10.1371/journal.pmed.1004390","url":null,"abstract":"<p><strong>Background: </strong>When research evidence is limited, inconsistent, or absent, healthcare decisions and policies need to be based on consensus amongst interested stakeholders. In these processes, the knowledge, experience, and expertise of health professionals, researchers, policymakers, and the public are systematically collected and synthesised to reach agreed clinical recommendations and/or priorities. However, despite the influence of consensus exercises, the methods used to achieve agreement are often poorly reported. The ACCORD (ACcurate COnsensus Reporting Document) guideline was developed to help report any consensus methods used in biomedical research, regardless of the health field, techniques used, or application. This explanatory document facilitates the use of the ACCORD checklist.</p><p><strong>Methods and findings: </strong>This paper was built collaboratively based on classic and contemporary literature on consensus methods and publications reporting their use. For each ACCORD checklist item, this explanation and elaboration document unpacks the pieces of information that should be reported and provides a rationale on why it is essential to describe them in detail. Furthermore, this document offers a glossary of terms used in consensus exercises to clarify the meaning of common terms used across consensus methods, to promote uniformity, and to support understanding for consumers who read consensus statements, position statements, or clinical practice guidelines. The items are followed by examples of reporting items from the ACCORD guideline, in text, tables and figures.</p><p><strong>Conclusions: </strong>The ACCORD materials - including the reporting guideline and this explanation and elaboration document - can be used by anyone reporting a consensus exercise used in the context of health research. As a reporting guideline, ACCORD helps researchers to be transparent about the materials, resources (both human and financial), and procedures used in their investigations so readers can judge the trustworthiness and applicability of their results/recommendations.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 5","pages":"e1004390"},"PeriodicalIF":15.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11198995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867028","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":"Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR).","authors":"Ahmed M Arzika, Amza Abdou, Ramatou Maliki, Nassirou Beido, Boubacar Kadri, Abdoul N Harouna, Abdoul N Galo, Mankara K Alio, Elodie Lebas, Catherine E Oldenburg, Kieran S O'Brien, Cindi Chen, Lina Zhong, Zhaoxia Zhou, Daisy Yan, Armin Hinterwirth, Jeremy D Keenan, Travis C Porco, Thomas M Lietman, Thuy Doan","doi":"10.1371/journal.pmed.1004386","DOIUrl":"10.1371/journal.pmed.1004386","url":null,"abstract":"<p><strong>Background: </strong>Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting.</p><p><strong>Methods and findings: </strong>The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also fo","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 5","pages":"e1004386"},"PeriodicalIF":15.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11073710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863885","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":"Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.","authors":"Lyndon P James, Fayette Klaassen, Sedona Sweeney, Jennifer Furin, Molly F Franke, Reza Yaesoubi, Dumitru Chesov, Nelly Ciobanu, Alexandru Codreanu, Valeriu Crudu, Ted Cohen, Nicolas A Menzies","doi":"10.1371/journal.pmed.1004401","DOIUrl":"10.1371/journal.pmed.1004401","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST).</p><p><strong>Methods and findings: </strong>The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.03] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova's national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics.</p><p><strong>Conclusions: </strong>Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 5","pages":"e1004401"},"PeriodicalIF":15.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11101189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854257","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":"Physical activity across midlife and health-related quality of life in Australian women: A target trial emulation using a longitudinal cohort.","authors":"Binh Nguyen, Philip Clare, Gregore I Mielke, Wendy J Brown, Ding Ding","doi":"10.1371/journal.pmed.1004384","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004384","url":null,"abstract":"<p><strong>Background: </strong>There is little long-term causal evidence on the effect of physical activity on health-related quality of life. This study aimed to examine the associations between longitudinal patterns of physical activity over 15 years and health-related quality of life in both the physical and mental health domains, in a cohort of middle-aged Australian women.</p><p><strong>Methods and findings: </strong>We used data collected at 3-year intervals (1998 to 2019) from 11,336 participants in the Australian Longitudinal Study on Women's Health (ALSWH) (1946 to 1951 birth cohort). Primary outcomes were the physical (PCS) and mental health component summary (MCS) scores (range from 0 to 100; higher scores indicate higher perceived physical/mental health) from the SF-36 in 2019 (when women aged 68 to 73 years). Using target trial emulation to imitate a randomized controlled trial (RCT), we tested 2 interventions: (1) meeting the World Health Organization (WHO) physical activity guidelines consistently throughout the 15-year \"exposure period\" (2001 to 2016; when women aged 50-55 to 65-70 years; physical activity assessed every 3 years); and (2) not meeting the guidelines at the beginning of the exposure period but starting to first meet the guidelines at age 55, 60, or 65; against the control of not meeting the guidelines throughout the exposure period. Analysis controlled for confounding using marginal structural models which were adjusted for sociodemographic and health variables and conditions. Consistent adherence to guidelines during the exposure period (PCS: 46.93 [99.5% confidence interval [CI]: 46.32, 47.54]) and first starting to meet the guidelines at age 55 (PCS: 46.96 [99.5% CI: 45.53, 48.40]) were associated with three-point higher PCS (mean score difference: 3.0 [99.5% CI: 1.8, 4.1] and 3.0 [99.5% CI:1.2, 4.8]) than consistent non-adherence (PCS: 43.90 [99.5% CI: 42.79, 45.01]). We found a similar pattern for most SF-36 subscales but no significant effects of the interventions on MCS. The main limitations of the study were that it may not account for all underlying health conditions and/or other unmeasured or insufficiently measured confounders, the use of self-reported physical activity and that findings may not be generalizable to all mid-age women.</p><p><strong>Conclusions: </strong>Results from the emulated RCT suggest women should be active throughout mid-age, ideally increasing activity levels to meet the guidelines by age 55, to gain the most benefits for physical health in later life.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 5","pages":"e1004384"},"PeriodicalIF":15.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11065283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872871","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":"Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study.","authors":"Yi Sun, Rashmi Bhuyan, Anqi Jiao, Chantal C Avila, Vicki Y Chiu, Jeff M Slezak, David A Sacks, John Molitor, Tarik Benmarhnia, Jiu-Chiuan Chen, Darios Getahun, Jun Wu","doi":"10.1371/journal.pmed.1004395","DOIUrl":"10.1371/journal.pmed.1004395","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological findings regarding the association of particulate matter ≤2.5 μm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy.</p><p><strong>Methods and findings: </strong>A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 μg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP.</p><p><strong>Conclusions: </strong>Our findings add to the literatu","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 4","pages":"e1004395"},"PeriodicalIF":15.8,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865916","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":"Paucity of intellectual property rights information in the US biologics system a decade after passage of the Biosimilars Act.","authors":"Robin Feldman","doi":"10.1371/journal.pmed.1004381","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004381","url":null,"abstract":"In this Policy Forum piece, Robin Feldman discusses how current legislation contributes to informational deficits around drug patents for biologic drugs in the United States.","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 5","pages":"e1004381"},"PeriodicalIF":15.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140658551","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":"Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.","authors":"Sung-Mok Jung, Sara L Loo, E. Howerton, L. Contamin, Clair Smith, Erica C Carcelén, Katie Yan, Samantha J Bents, J. Levander, J. Espino, J. Lemaitre, Koji Sato, Clif McKee, Alison L Hill, Matteo Chinazzi, Jessica T. Davis, K. Mu, A. Vespignani, Erik T. Rosenstrom, Sebastian A Rodriguez-Cartes, Julie S. Ivy, Maria E. Mayorga, Julie L. Swann, G. España, S. Cavany, Sean M. Moore, T. A. Perkins, Shi Chen, Rajib Paul, Daniel Janies, J. Thill, A. Srivastava, Majd Al Aawar, Kaiming Bi, Shraddha Ramdas Bandekar, A. Bouchnita, S. Fox, L. A. Meyers, P. Porebski, S. Venkatramanan, A. Adiga, Benjamin Hurt, B. Klahn, J. Outten, Jiangzhuo Chen, H. Mortveit, Amanda Wilson, Stefan Hoops, P. Bhattacharya, D. Machi, Anil Vullikanti, B. Lewis, M. Marathe, Harry Hochheiser, Michael C. Runge, Katriona Shea, S. Truelove, Cécile Viboud, J. Lessler","doi":"10.1371/journal.pmed.1004387","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004387","url":null,"abstract":"BACKGROUND\u0000Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval).\u0000\u0000\u0000METHODS AND FINDINGS\u0000The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths.\u0000\u0000\u0000CONCLUSIONS\u0000COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":" 17","pages":"e1004387"},"PeriodicalIF":15.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140692849","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":"Mixed progress in global tobacco control.","authors":"Coral E Gartner, Wayne D Hall","doi":"10.1371/journal.pmed.1004392","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004392","url":null,"abstract":"","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"19 7","pages":"e1004392"},"PeriodicalIF":15.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140697318","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}