PLoS Medicine最新文献

{"title":"Analysis of retinal markers and incident amyotrophic lateral sclerosis: An optical coherence tomography-based cohort study.","authors":"Chunyang Pang, Yaojia Li, Wenhua Jiang, Haobo Xie, Wen Cao, Huan Yu, Zhiyang Lin, Yifan Cheng, Dongsheng Fan, Binbin Deng","doi":"10.1371/journal.pmed.1004545","DOIUrl":"10.1371/journal.pmed.1004545","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers are widely recognized as crucial breakthroughs in tackling amyotrophic lateral sclerosis (ALS). Among them, retina markers may hold promise due to the close retina-brain connection and non-invasive, portable detection methods. Thus, using optical coherence tomography (OCT), we investigated the link between baseline cell-level retinal features and future ALS risk.</p><p><strong>Methods and findings: </strong>Participants from the UK Biobank underwent OCT scans to assess retinal layers, macula, and optic disc parameters. Follow-up commenced two years after the baseline period (2006-2010), during which ALS cases were identified using International Classification of Diseases (ICD) codes from medical and assessment records. Cox proportional hazards models were applied to examine the relationship between retinal markers and incident ALS. Over a median follow-up of 14.11 years, 70 ALS cases occurred among 53,824 participants (incidence 10.58 per 100,000 person-years). Most participants were White (94.6%), 44.8% male, with a median age of 58 years. After adjusting for demographics and comorbidities affecting the retina, a standard deviation (SD) decrease of 15.19 µm in photoreceptor layer (PRL) thickness was associated with a 19% (95% confidence interval [7, 29]; p = 0.002) increased risk of ALS, while a SD increase of 26.11 µm in retinal pigment epithelium (RPE) thickness corresponded to a 20% (95% CI [7, 34]; p = 0.002) higher risk. Sensitivity analyses excluding follow-ups of less than 4 and 6 years yielded consistent results. Subgroup analyses showed these findings were more pronounced in smokers. The main limitation of this study is its single time point observational design.</p><p><strong>Conclusion: </strong>A thinner PRL and thicker RPE may precede the clinical diagnosis of ALS, offering potential clues for early diagnosis and insights into the disease's pathogenesis.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004545"},"PeriodicalIF":15.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12193630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498816","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":"Antimicrobial resistance in Africa: A retrospective analysis of data from 14 countries, 2016-2019.","authors":"Gilbert Osena, Geetanjali Kapoor, Erta Kalanxhi, Timothée Ouassa, Edwin Shumba, Sehr Brar, Yewande Alimi, Manuel Moreira, Martin Matu, Abdourahmane Sow, Eili Klein, Pascale Ondoa, Ramanan Laxminarayan","doi":"10.1371/journal.pmed.1004638","DOIUrl":"10.1371/journal.pmed.1004638","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) is a major global health issue that exacerbates the burden of infectious diseases and healthcare costs. However, the scarcity of national-level AMR data in African countries hampers our understanding of its scale and contributing factors in the region. To gain insights into AMR prevalence in Africa, we collected and analyzed retrospective AMR data from 14 countries.</p><p><strong>Methods and findings: </strong>We estimated bacterial AMR prevalence, defined as the proportion of resistant human isolates tested from antimicrobial susceptibility (AST) data collected retrospectively for 2016-2019 from 205 laboratories across 14 African countries. We generated 95% confidence intervals (CIs) for aggregated AMR estimates to account for data quality disparities across countries; the median data quality score was 73.1%, ranging from 56.4% to 80.8%. We assessed 819,584 culture records covering 9,266 pathogen-drug combinations, of which 187,832 (22.9%) were positive cultures with AST results. The most frequently cultured specimens were urine (32.0%) and purulent samples (28.1%), and the most frequently isolated pathogens were Escherichia coli (22.2%) and Staphylococcus aureus (15.0%). Aggregated AMR estimates did not change significantly across the years studied (p > 0.337); however, there were significant variations in AMR prevalence estimates in culture-positive samples across countries, regions, patient departments (inpatient/outpatient), and specimen sources (p < 0.05). Male sex (adjusted odds ratio [aOR] 1.15; 95% CI [1.09,1.21]; p < 0.0001), ages above 65 (aOR 1.28; 95% CI [1.16-1.41]; p < 0.0001), and inpatient department (aOR 1.24; 95% CI [1.13-1.35]; p < 0.0001) were associated with higher AMR prevalence among culture-positive samples. The lack of routine testing, as reflected in the low data volume from most contributing laboratories, and the absence of patient clinical information, represent significant limitations of this study.</p><p><strong>Conclusion: </strong>Analysis of the largest retrospective AMR dataset in Africa indicates high variability in AMR prevalence across countries, coupled with differences in AMR testing capacities, data quality, and AMR estimates. Gaps in AST practices and inadequate digital infrastructures for data collection and reporting represent barriers to estimating the true AMR burden in the region. These barriers warrant large-scale investments to expand healthcare access and strengthen bacteriology laboratory capacities.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004638"},"PeriodicalIF":15.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486762","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":"Maternal infections during pregnancy and offspring cognitive outcome: A nationwide full-sibling cohort study.","authors":"Anders Husby, Kim D Jakobsen, Jan Wohlfahrt, Mads Melbye","doi":"10.1371/journal.pmed.1004657","DOIUrl":"10.1371/journal.pmed.1004657","url":null,"abstract":"<p><strong>Background: </strong>Maternal infections are common during pregnancy, but it is unclear how they impact the cognitive outcome of the offspring, with many studies suggesting adverse effects. Using long-term follow-up of a nationwide sibling cohort in Denmark with information on maternal antimicrobial prescriptions in community pharmacies and in-patient hospitalizations for infection, we aimed to estimate the effect of maternal infections during pregnancy on offspring school grades and intelligence test results in adolescence.</p><p><strong>Methods and findings: </strong>From population-based national registries we defined a cohort of all full-siblings, born from January 1, 1996 to December 31, 2,003 in Denmark, and linked them to maternal filled prescription for antimicrobial pharmaceuticals and maternal hospitalizations for infection during pregnancy. Standardized examination grades in language and mathematics at the final year of compulsory schooling, in addition to intelligence test scores (calculated as IQ) for a nested sub-cohort of full brothers, were used as outcomes. Among 274,166 children in the full-sibling cohort, 80,817 (29.5%) had a mother who during her pregnancy filled a prescription for a systemic antimicrobial, while 5,628 (2.1%) had a mother who during her pregnancy was hospitalized due to an infection. We found no consistent difference in school grades in language (z-score difference, 0.0, 95% confidence interval [CI] [-0.0,0.0]; p = 0.920) and mathematics (z-score difference, -0.0, 95% CI [-0.0,-0.0]; p = 0.042), and in IQ (IQ-difference, 0.3, 95% CI [-0.2,0.7]; p = 0.217), in children whose mother filled one antimicrobial prescription compared with children whose mother did not fill any, when taking shared family factors into account, while many associations were consistently significant when not taking shared family factors into account. Furthermore, we found no indication of an impact of maternal in-patient hospitalizations for infections during pregnancy on school grades (z-score difference for language, -0.0, 95% CI [-0.1,0.0]; p = 0.103; z-score difference for mathematics, 0.0, 95% CI [-0.0,0.0]; p = 0.809) or IQ (IQ-difference, 0.4, 95% CI [-0.8,1.6]; p = 0.545), when also taking shared family factors into account. Similar findings were found when considering infections in bi-weekly exposure periods during gestation. The main limitations of the study were lacking information on within hospital pharmaceutical prescriptions and the underlying pathogenic microorganisms.</p><p><strong>Conclusions: </strong>Our study does not support major effects of common maternal infections during pregnancy on offspring cognitive outcomes, and support the safety of commonly prescribed antimicrobials during pregnancy with respect to the long-term cognitive outcomes of the offspring.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004657"},"PeriodicalIF":15.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486763","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 Fetal Region-specific Optimized Growth Standard (FROGS)-A fetal and birthweight centile calculator validated in a national population.","authors":"Natasha L Pritchard, Stephen Tong, Teresa MacDonald, Elizabeth McCarthy, Lisa Hui, Michael Bethune, Hannah G Gordon, Roxanne Hastie, Emerson Keenan, Michael Permezel, Susan P Walker, Anthea C Lindquist","doi":"10.1371/journal.pmed.1004634","DOIUrl":"10.1371/journal.pmed.1004634","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;There is no universally agreed upon obstetric growth standard for use during pregnancy. We aimed to design a simple novel growth standard, which incorporates key beneficial features identified in prior research.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We developed the Fetal Region-specific Optimized Growth Standard (FROGS), then validated it following International Federation of Gynaecology and Obstetrics (FIGO) guidelines. FROGS follows the shape of the fetal (ultrasound-based) Hadlock curve. It is region-specific; allowing adjustment for the mean birthweight and standard deviation of babies born at term in the local population where it will be applied. It provides an exact centile for each gestational day (rather than rounding off by weeks) and is optionally adjustable for fetal sex. Further, FROGS provides an 'estimate range' for the estimated fetal weight centile, assuming a 10% ultrasound measurement error. Following development, we validated FROGS in a retrospective cohort study by comparing its ability to identify small babies with an increased risk of adverse perinatal outcomes to four charts in current use: (1) population birthweight chart (Australian Institute of Health and Welfare, AIHW chart); (2) Hadlock's 1991 fetal chart; (3) Mikolajczyk's global fetal and birthweight centile chart; and (4) INTERGROWTH-21st fetal growth standards. To do this, we identified infants classified as small for gestational age (&lt;10th centile) by each chart. We then identified non-overlapping &lt;10th centile populations, i.e., infants classified as small by one chart, but not another. We compared rates of stillbirth and adverse perinatal outcomes between the non-overlapping populations. All charts except INTERGROWTH classified similar proportions of infants as &lt;10th centile (10.4% FROGS, 9.3% AIHW, 11.1% Hadlock, 10.9% global, 4.4% INTERGROWTH). Of the three charts that classified similar proportions as &lt;10th centile, infants classified by FROGS were at the highest risk of adverse perinatal outcomes. The infants classified as &lt;10th centile by only FROGS had significantly increased relative risk (RR) of stillbirth, compared to the infants classified as &lt;10th centile by only AIHW (RR 13.1, 95% CI 6.5-26.5), only Hadlock (RR 2.1, 95% CI 1.28-3.56) or only the global chart (RR 1.54, 95% CI 1.00-2.37). The FROGS chart outperformed these three charts in identifying infants at risk of other adverse perinatal outcomes associated with being small for gestational age, such as neonatal intensive care admission, Apgar scores &lt;7 at 5 min, and operative (instrumental) vaginal birth for suspected fetal compromise. The cohort of infants classified as small for gestational age by INTERGROWTH was, in size and risk, closer to the cohort classified as &lt;3rd centile by FROGS (3.4% of infants &lt;3rd). This study is limited in that it retrospectively assesses birthweight, which may have different implications to a prospective evaluation of estimat","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004634"},"PeriodicalIF":15.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337174","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":"Vaccination strategies, public health impact and cost-effectiveness of dengue vaccine TAK-003: A modeling case study in Thailand.","authors":"Jing Shen, Elizaveta Kharitonova, Anna Tytula, Justyna Zawieja, Samuel Aballea, Shibadas Biswal, Mayuri Sharma, Supattra Rungmaitree, Rosarin Sruamsiri, Derek Wallace, Riona Hanley","doi":"10.1371/journal.pmed.1004631","DOIUrl":"10.1371/journal.pmed.1004631","url":null,"abstract":"<p><strong>Background: </strong>Dengue is an increasing global problem associated with negative health and economic impacts. Vaccination is an important measure to reduce the significant public health and economic burden caused by dengue. Our study assesses the public health impact and cost-effectiveness of a new dengue vaccine, TAK-003, using Thailand as a case study.</p><p><strong>Methods and findings: </strong>We developed a dynamic transmission model with both host and vector populations, 4 serotype-specific infections, seasonality, and other key elements of dengue natural history. We estimated efficacy of TAK-003 from the DEN-301 trial. We first used the model to determine the optimal cohort age for different vaccination strategies with TAK-003, based on Thai dengue epidemiology. Secondly, we assessed the public health impact of a pragmatic strategy integrating TAK-003 into an existing national immunization program in Thailand. Cost-effectiveness was evaluated from a societal perspective using disability-adjusted life-years (DALYs) over a 20-year horizon. TAK-003 is estimated to prevent 41%-57% of symptomatic cases and 47%-70% of hospitalizations, with the greatest impact observed when routinely vaccinating children aged 6 years with 10 additional catch-up cohorts. This strategy resulted in 104,415 fewer DALYs and savings of US$1,786 million. If introduced into the national immunization program at 11 years of age (alongside the existing human papillomavirus vaccine), TAK-003 is estimated to prevent 44% of symptomatic cases and 53% of hospitalizations. This strategy prevented 87,715 DALYs and saved US$1,346 million. Sensitivity analyses demonstrated that the results were robust. The main limitations were inherent to the assumptions and simplifications made in the model, which are unavoidable when approximating the impact of vaccination in the real world.</p><p><strong>Conclusions: </strong>TAK-003 can considerably reduce dengue burden and lead to cost savings in Thailand. These benefits can be maximized by identifying optimal age cohorts for vaccination and adding catch-up programs. Our model can be used to assess the vaccination impact in other dengue-endemic countries.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004631"},"PeriodicalIF":15.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318465","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":"Making social sciences foundational to academic medicine.","authors":"Sahar Sadjadi, Lisa Barkley, Rebecca Jordan-Young, Helena Hansen","doi":"10.1371/journal.pmed.1004649","DOIUrl":"10.1371/journal.pmed.1004649","url":null,"abstract":"<p><p>Despite longstanding evidence of the enormous impact of socioeconomic conditions on population health, social sciences remain marginal to academic medicine. In this Perspective, we propose the integration of social sciences into the three pillars of academic medicine-education, research, and clinical practice-to build the theoretical and methodological foundations for identifying the mechanisms through which social and community factors shape health and disease, and to advance sustainable community engagement in the creation of medical knowledge.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004649"},"PeriodicalIF":15.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310696","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":"Community health worker-facilitated telehealth for moderate-severe hypertension care in Kenya and Uganda: A randomized controlled trial.","authors":"Matthew D Hickey, Asiphas Owaraganise, Sabina Ogachi, Norton Sang, Erick M Wafula, Jane Kabami, Nicole Sutter, Jennifer Temple, Anthony Muiru, Gabriel Chamie, Elijah Kakande, Maya L Petersen, Laura B Balzer, Diane V Havlir, Moses R Kamya, James Ayieko","doi":"10.1371/journal.pmed.1004632","DOIUrl":"10.1371/journal.pmed.1004632","url":null,"abstract":"<p><strong>Background: </strong>Hypertension is underdiagnosed and undertreated in sub-Saharan Africa. Improving hypertension treatment within primary health centers can improve cardiovascular disease outcomes; however, individuals with moderate-severe hypertension face additional barriers to care, including the need for frequent clinic visits to titrate medications. We conducted a pilot study to test whether a clinician-driven, community health worker (CHW)-facilitated telehealth intervention would improve hypertension control among adults with severe hypertension in rural Uganda and Kenya.</p><p><strong>Methods and findings: </strong>We conducted a pilot randomized controlled trial (RCT) of hypertension treatment delivered via telehealth by a clinician (adherence assessment, counseling, decision-making) and facilitated by a CHW in the participant's home, compared to clinic-based hypertension care (NCT04810650). We recruited adults ≥40 years with BP ≥ 160/100 mmHg at household screening by CHWs, with no restrictions by HIV status. After initial evaluation at the clinic, participants were randomized to telehealth or clinic-based hypertension follow-up. Randomization assignment was not blinded, except for the study statistician. All participants were treated using standard country guideline-based antihypertensive drugs. The primary outcome was hypertension control at 24 weeks (BP < 140/90 mmHg). We also assessed hypertension control at 48 weeks. In intention-to-treat analyses, we compared outcomes between randomized arms with targeted minimum loss-based estimation using sample-splitting to select optimal adjustment covariates (candidates: age, sex, baseline hypertension severity, and country). We screened 2,965 adults ≥40 years, identifying 266 (9%) with severe hypertension and enrolling 200 (98 telehealth arms, 102 clinic arms). Participants were 67% women, median age of 62 years (Q1-Q3 51-72); 14% with HIV. Week 24 blood pressure was measured in 96/99 intervention and 99/102 control participants; week 24 hypertension control was 77% in telehealth and 51% in clinic arms (risk difference (RD) 26%, 95% confidence interval (CI) [14%, 38%], p < 0.001). Week 48 hypertension control was 86% in telehealth and 44% in clinic arms (RD 42%, 95% CI [30%, 53%], p < 0.001). Three participants died (telehealth: 2, clinic: 1); all deaths were unrelated to the study interventions. Our study was limited by its small sample size, although findings are strengthened by being conducted in three primary health centers across two countries.</p><p><strong>Conclusion: </strong>In this pilot, RCT, clinician-driven, CHW-facilitated telehealth for hypertension management improved hypertension control and reduced severe hypertension compared to clinic-based care. Telehealth focused on individuals with moderate-severe hypertension is a promising approach to improve outcomes among those with the highest risk for CVD.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004632"},"PeriodicalIF":15.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235624","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 of initiating CYP2D6-metabolized opioids with risks of adverse outcomes in older adults receiving antidepressants: A retrospective cohort study.","authors":"Yu-Jung Jenny Wei, Almut G Winterstein, Siegfried Schmidt, Roger B Fillingim, Michael J Daniels, Steven T DeKosky, Stephan Schmidt","doi":"10.1371/journal.pmed.1004620","DOIUrl":"10.1371/journal.pmed.1004620","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The safety of pharmacokinetic opioid-antidepressant interactions may be affected by the sequence in which the drug is initiated. Previous literature showed that initiation of cytochrome P450 (CYP) 2D6-inhibiting versus CYP2D6-neutral antidepressants concomitantly with existing CYP2D6-metabolized opioids (i.e., antidepressant-triggered interaction) was associated with heightened risks of adverse outcomes (e.g., worsening pain). However, little is known about whether and to what extent the risks exist when CYP2D6-metabolized opioids are initiated on existing antidepressants (i.e., opioid-triggered interaction), a more common pattern of concomitant use of these two drugs. The study aims to examine the association of initiation of CYP2D6-metabolized opioids with risks of adverse outcomes among older nursing home residents who already received antidepressants.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We conducted a retrospective cohort study using a 100% Medicare nursing home sample linked to Medicare claims and Minimum Data Set (MDS) assessments from January 1, 2010, to December 31, 2021. Participants included long-term care residents 65 years of age or older who initiated CYP2D6-metabolized opioids while already receiving antidepressants for at least 30 days. The key exposure was the use of CYP2D6-inhibiting (versus CYP2D6-neutral) antidepressants concomitantly with CYP2D6-metabolized opioids, with day 1 of antidepressant-opioid concomitant use designated as cohort entry. Patients were followed from cohort entry until the end of 1 year, nursing home discharge, death, or study end (12/31/2021). Seven adverse outcomes included worsening pain, physical function, and depression, and counts of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose (OD). We identified 127,200 older nursing home long-term residents who initiated CYP2D6-metabolized opioids while already receiving antidepressants (mean [SD] age, 84.4 [8.7] years). After covariate adjustment via inverse probability of treatment weighting, use of CYP2D6-inhibiting (versus CYP2D6-neutral) antidepressants concomitantly with CYP2D6-metabolized opioids was associated with a higher risk of worsening pain (relative risk:1.04 [95% CI, 1.02, 1.06]; P &lt; 0.001; risk difference (RD): 1.1% [95% CI, 0.6%, 1.6%]) and a higher incidence rate of pain-related hospitalizations (incidence rate ratio [IRR]:1.13 [95% CI, 1.04, 1.22]; P = 0.003; RD: 1.21 [95% CI, 0.39, 1.89] per 1,000 patient-years) and pain-related ED visits (IRR = 1.17 [95% CI, 1.07, 1.29]; P = 0.003; RD: 0.85 [95% CI, 0.29, 1.41] per 1,000 patient-years), with no difference in physical function, depression, OUD, and OD. Main study limitations included unmeasured confounding and limited generalizability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This cohort study of older nursing home residents showed that initiation of CYP2D6-metabolized opioids on existing ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 6","pages":"e1004620"},"PeriodicalIF":15.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210026","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":"Assessment of lung function and severity grading in interstitial lung diseases (% predicted versus z-scores) and association with survival: A retrospective cohort study of 6,808 patients.","authors":"Piotr W Boros, Magdalena M Martusewicz-Boros, Katarzyna B Lewandowska","doi":"10.1371/journal.pmed.1004619","DOIUrl":"10.1371/journal.pmed.1004619","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary function tests (PFTs) are essential for predicting outcomes in interstitial lung disease (ILD). In 2022, an expert panel recommended using z-scores instead of the traditional % predicted cut-off values to interpret the severity of PFT abnormalities which may lead to discordant classifications in some patients. To assess the magnitude and prognostic impact of this phenomenon we compared these two approaches in predicting all-cause mortality in a large cohort of patients with ILDs.</p><p><strong>Methods and findings: </strong>We retrospectively analyzed data from a tertiary referral center for patients with ILDs. Absolute FEV1, FVC, TLC, and TLCO values from patients' first presentations were transformed and presented as % predicted and z-scores using the most recent global lung initiative (GLI) reference values. Results were categorized for severity according to % predicted and z-score levels. Predictors of all-cause mortality over a 14-year follow-up were determined using Kaplan-Meier survival analysis and Cox proportional hazards regression. Between January 2009 and March 2023, 6,808 patients with ILDs were evaluated at the National TB and Lung Diseases Research Institute in Warsaw, Poland. Most were diagnosed with sarcoidosis, fibrotic ILD, or non-fibrotic ILD. At their first presentation, 13.2% had airway obstruction, 23.1% had low FVC (indicative of restriction by spirometry), and 45.6% had a reduced lung transfer factor (TLCO). Reclassification of spirometric indices occurred in 26.8% of patients for FEV1 and 24.6% for FVC among those with abnormal results, with most being reassigned to a less severe categories. For TLCO, 28.1% of patients with reduced values were reclassified, with most shifting to more severe categories. During the follow-up, 1,525 (22.4%) of patients died. Both low FVC and low TLCO predicted all-cause mortality, with z-score thresholds showing stronger associations with mortality. A one-unit decrease in the FVC z-score was associated with a 10.3% increase in the risk of death, while a one-unit decrease in TLCO z-score was linked to an over 30% increase in mortality risk. Limitations of this retrospective single-center study include lack of data on cause-specific mortality, potential residual confounding, and limited generalizability to non-Caucasian or younger populations.</p><p><strong>Conclusions: </strong>The recently recommended use of z-scores leads to significant reclassification of lung function results in patients with ILDs, largely driven by age. This approach is justified by its stronger prognostic associations. Severe TLCO impairment remains a robust predictor of mortality in ILDs.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004619"},"PeriodicalIF":15.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182878","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":"Twenty-year outcomes after repeat doses of antenatal corticosteroids prior to 32 weeks' gestation: Follow-up of a randomised clinical trial.","authors":"Robyn W May, Anthony G B Walters, Greg D Gamble, Caroline A Crowther, Stuart R Dalziel, Carl L Eagleton, Christopher J D McKinlay, Barry J Milne, Jane E Harding","doi":"10.1371/journal.pmed.1004618","DOIUrl":"10.1371/journal.pmed.1004618","url":null,"abstract":"<p><strong>Background: </strong>For women who have received a course of antenatal corticosteroids ≥7 days prior and have ongoing risk of preterm birth within the next 7 days, repeat dose(s) of corticosteroids up to 32 weeks' gestation have been shown to reduce neonatal respiratory distress syndrome and serious health problems in the neonatal period but not other neonatal morbidities such as chronic lung disease, death, severe intraventricular haemorrhage or necrotising enterocolitis. Repeat antenatal corticosteroids were not associated with either benefit or harms in mid-childhood. However, this may have been too early to evaluate potential adverse effects on respiratory and other long-term outcomes. We aimed to assess if exposure to repeat dose(s) of antenatal corticosteroids administered to pregnant women up to 32 weeks' gestation has beneficial or harmful effects on respiratory and general health of the offspring in adulthood.</p><p><strong>Methods and findings: </strong>We assessed the adult offspring of New Zealand participants in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids for the Prevention of Neonatal Respiratory Disease (ACTORDS), a multicentre, placebo-controlled trial where women at risk of preterm birth within the next week, 7 or more days after having received a single course of corticosteroids were randomised to a repeat dose of intramuscular betamethasone or placebo, that could be repeated weekly if at ongoing preterm birth risk. Follow-up at 20 years included a health questionnaire and consent to access administrative data sources. The primary outcome was any asthma diagnosis. Secondary outcomes included neurodevelopmental, cardiovascular, mental and general health, functional difficulties and social outcomes. Of 352 infants born to 290 maternal trial participants, we assessed 214 (61%; 96 (45%) female) at mean (standard deviation) age 20.5 (1.5) years. The rate of any asthma diagnosis was similar in both groups (58/107 (54%) repeat bethamethasone versus 50/107 (47%) placebo; risk ratio adjusted for gestational age at trial entry, multiplicity and birth centre 1.13, 95% confidence interval, 0.87, 1.46). Differences between the groups for the secondary outcomes were generally small and confidence intervals included the possibility of no difference between groups.</p><p><strong>Conclusions: </strong>In this follow-up of a randomised clinical trial, our data suggest neither major harm nor benefit for the offspring in early adulthood following exposure to repeat dose(s) of antenatal corticosteroids compared with a single course prior to 32 weeks' gestation. Smaller effects cannot be excluded and follow-up of adult offspring from other trials of repeat antenatal corticosteroids is recommended.</p><p><strong>Trial registration: </strong>International Standard Randomized Controlled Trial, number ISRCTN48656428.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 5","pages":"e1004618"},"PeriodicalIF":15.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12118977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175490","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}