PLoS Medicine最新文献

{"title":"Development, characterization, and replication of proteomic aging clocks: Analysis of 2 population-based cohorts.","authors":"Shuo Wang, Zexi Rao, Rui Cao, Anne H Blaes, Josef Coresh, Rajat Deo, Ruth Dubin, Corinne E Joshu, Benoit Lehallier, Pamela L Lutsey, James S Pankow, Wendy S Post, Jerome I Rotter, Sanaz Sedaghat, Weihong Tang, Bharat Thyagarajan, Keenan A Walker, Peter Ganz, Elizabeth A Platz, Weihua Guan, Anna Prizment","doi":"10.1371/journal.pmed.1004464","DOIUrl":"10.1371/journal.pmed.1004464","url":null,"abstract":"<p><strong>Background: </strong>Biological age may be estimated by proteomic aging clocks (PACs). Previous published PACs were constructed either in smaller studies or mainly in white individuals, and they used proteomic measures from only one-time point. In this study, we created de novo PACs and compared their performance to published PACs at 2 different time points in the Atherosclerosis Risk in Communities (ARIC) study of white and black participants (around 75% white and 25% black).</p><p><strong>Medthods and findings: </strong>A total of 4,712 plasma proteins were measured using SomaScan in blood samples collected in 1990 to 1992 from 11,761 midlife participants (aged 46 to 70 years) and in 2011 to 2013 from 5,183 late-life participants (aged 66 to 90 years). The de novo ARIC PACs were constructed by training them against chronological age using elastic net regression in two-thirds of healthy participants in midlife and late life and validated in the remaining one-third of healthy participants at the corresponding time point. We also computed 3 published PACs. We estimated age acceleration for each PAC as residuals after regressing each PAC on chronological age. We also calculated the change in age acceleration from midlife to late life. We examined the associations of age acceleration and change in age acceleration with mortality through 2019 from all-cause, cardiovascular disease (CVD), cancer, and lower respiratory disease (LRD) using Cox proportional hazards regression in participants (irrespective of health) after excluding the training set. The model was adjusted for chronological age, smoking, body mass index (BMI), and other confounders. We externally validated the midlife PAC using the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 1 data. The ARIC PACs had a slightly stronger correlation with chronological age than published PACs in healthy participants at each time point. Associations with mortality were similar for the ARIC PACs and published PACs. For late-life and midlife age acceleration for the ARIC PACs, respectively, hazard ratios (HRs) per 1 standard deviation were 1.65 and 1.38 (both p < 0.001) for all-cause mortality, 1.37 and 1.20 (both p < 0.001) for CVD mortality, 1.21 (p = 0.028) and 1.04 (p = 0.280) for cancer mortality, and 1.68 and 1.36 (both p < 0.001) for LRD mortality. For the change in age acceleration, HRs for all-cause, CVD, and LRD mortality were comparable to the HRs for late-life age acceleration. The association between the change in age acceleration and cancer mortality was not significant. The external validation of the midlife PAC in MESA showed significant associations with mortality, as observed for midlife participants in ARIC. The main limitation is that our PACs were constructed in midlife and late-life participants. It is unknown whether these PACs could be applied to young individuals.</p><p><strong>Conclusions: </strong>In this longitudinal study, we found that the ARIC PACs and published ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 9","pages":"e1004464"},"PeriodicalIF":15.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330663","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":"HIV, malnutrition, and noncommunicable disease epidemics among tuberculosis-affected households in east and southern Africa: A cross-sectional analysis of the ERASE-TB cohort.","authors":"Claire Jacqueline Calderwood, Edson Tawanda Marambire, Leyla Larsson, Denise Banze, Alfred Mfinanga, Celina Nhamuave, Tejawsi Appalarowthu, Mishelle Mugava, Jorge Ribeiro, Peter Edwin Towo, Karlos Madziva, Justin Dixon, Kathrin Held, Lilian Tina Minja, Junior Mutsvangwa, Celso Khosa, Norbert Heinrich, Katherine Fielding, Katharina Kranzer","doi":"10.1371/journal.pmed.1004452","DOIUrl":"10.1371/journal.pmed.1004452","url":null,"abstract":"<p><strong>Background: </strong>As a result of shared social and structural risk factors, people in households affected by tuberculosis may have an increased risk of chronic conditions; at the same time, tuberculosis screening may be an opportunity for interventions. We sought to describe the prevalence of HIV, nutritional disorders, and noncommunicable diseases (NCDs) among members of tuberculosis-affected households in 3 African countries.</p><p><strong>Methods and findings: </strong>A part of a multicountry cohort study, we screened for tuberculosis, HIV, nutritional disorders (underweight, anaemia, overweight/obesity), and NCDs (diabetes, hypertension, and chronic lung disease) among members of tuberculosis-affected households aged ≥10 years in Mozambique, Tanzania, and Zimbabwe. We describe the prevalence of these conditions, their co-occurence within individuals (multimorbidity) and household-level clustering. Of 2,109 household contacts recruited, 93% (n = 1,958, from 786 households) had complete data and were included in the analysis. Sixty-two percent were female, median age was 27 years, and 0.7% (n = 14) were diagnosed with co-prevalent tuberculosis. Six percent of household members (n = 120) had previous tuberculosis, 15% (n = 294) were living with HIV, 10% (n = 194) had chronic lung disease, and 18% (n = 347) were anaemic. Nine percent of adults (n = 127) had diabetes by HbA1c criteria, 32% (n = 439) had hypertension. By body mass index criteria, 18% household members (n = 341) were underweight while 29% (n = 549) were overweight or obese. Almost half the household members (n = 658) had at least 1 modifiable tuberculosis risk factor. Sixty-one percent of adults (n = 822) had at least 1 chronic condition, 1 in 4 had multimorbidity. While most people with HIV knew their status and were on treatment, people with NCDs were usually undiagnosed and untreated. Limitations of this study include use of point-of-care HbA1c for definition of diabetes and definition of hypertension based on single-day measurements.</p><p><strong>Conclusions: </strong>Households affected by tuberculosis also face multiple other health challenges. Integrated approaches to tuberculosis screening may represent an opportunity for identification and treatment, including prioritisation of individuals at highest risk for tuberculosis to receive preventive therapy.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 9","pages":"e1004452"},"PeriodicalIF":15.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299316","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":"Correction: Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants.","authors":"Heidi Greulich, Tzu-Hsiu Chen, Whei Feng, Pasi A Jänne, James V Alvarez, Mauro Zappaterra, Sara E Bulmer, David A Frank, William C Hahn, William R Sellers, Matthew Meyerson","doi":"10.1371/journal.pmed.1004470","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004470","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pmed.0020313.].</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 9","pages":"e1004470"},"PeriodicalIF":15.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299314","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":"Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data.","authors":"Paris J Baptiste, Angel Y S Wong, Anna Schultze, Catherine M Clase, Clémence Leyrat, Elizabeth Williamson, Emma Powell, Johannes F E Mann, Marianne Cunnington, Koon Teo, Shrikant I Bangdiwala, Peggy Gao, Kevin Wing, Laurie Tomlinson","doi":"10.1371/journal.pmed.1004465","DOIUrl":"10.1371/journal.pmed.1004465","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 5.2 years. The primary composite outcome was cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using an inverse-probability-weighted Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (Pint = 0.422) or additive scale (Pint = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (Pint = 0.002) and additive scale (Pint &lt; 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (Pint = 0.306). However, there was heterogeneity on the additive scale (Pint = 0.023). Absolute risks were higher in Black indiv","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 9","pages":"e1004465"},"PeriodicalIF":15.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299315","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":"A comprehensive assessment of care competence and maternal experience of first antenatal care visits in Mexico: Insights from the baseline survey of an observational cohort study.","authors":"Svetlana V Doubova, Claudio Quinzaños Fresnedo, Martín Paredes Cruz, Diana Perez-Moran, Ricardo Pérez-Cuevas, Verónica Meneses Gallardo, Luis Rey Garcia Cortes, Megan Carolina Cerda Mancillas, Victoria Martínez Gaytan, Miguel Angel Romero Garcia, Gilberto Espinoza Anrubio, Claudia Elsa Perez Ruiz, Carlos A Prado-Aguilar, Augusto Sarralde Delgado, Margaret E Kruk, Catherine Arsenault","doi":"10.1371/journal.pmed.1004456","DOIUrl":"10.1371/journal.pmed.1004456","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Comprehensive antenatal care (ANC) must prioritize competent, evidence-based medical attention to ensure a positive experience and value for its users. Unfortunately, there is scarce evidence of implementing this holistic approach to ANC in low- and middle-income countries, leading to gaps in quality and accountability. This study assessed care competence, women's experiences during the first ANC visit, and the factors associated with these care attributes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;The study analyzed cross-sectional baseline data from the maternal eCohort study conducted in Mexico from August to December 2023. The study adapted the Quality Evidence for Health System Transformation (QuEST) network questionnaires to the Mexican context and validated them through expert group and cognitive interviews with women. Pregnant women aged 18 to 49 who had their first ANC visit with a family physician were enrolled in 48 primary clinics of the Instituto Mexicano del Seguro Social across 8 states. Care competence and women's experiences with care were the primary outcomes. The statistical analysis comprised descriptive statistics, multivariable linear and Poisson regressions. A total of 1,390 pregnant women were included in the study. During their first ANC visit, women received only 67.7% of necessary clinical actions on average, and 52% rated their ANC experience as fair or poor. Women with previous pregnancies (adjusted regression coefficient [aCoef.] -3.55; (95% confidence intervals [95% CIs]): -4.88, -2.22, p &lt; 0.001), at risk of depression (aCoef. -3.02; 95% CIs: -5.61, -0.43, p = 0.023), those with warning signs (aCoef. -2.84; 95% CIs: -4.65, -1.03, p = 0.003), common pregnancy discomforts (aCoef. -1.91; 95% CIs: -3.81, -0.02, p = 0.048), or those who had a visit duration of less than 20 minutes (&lt;15 minutes: aCoef. -7.58; 95% CIs: -10.21, -4.95, p &lt; 0.001 and 15 to 19 minutes: aCoef. -2.73; 95% CIs: -4.79, -0.67, p = 0.010) and received ANC in the West and Southeast regions (aCoef. -5.15; 95% CIs: -7.64, -2.66, p &lt; 0.001 and aCoef. -5.33; 95% CIs: -7.85, -2.82, p &lt; 0.001, respectively) had a higher probability of experiencing poorer care competence. Higher care competence (adjusted prevalence ratio [aPR] 1.004; 95% CIs:1.002, 1.005, p &lt; 0.001) and receiving care in a small clinic (aPR 1.19; 95% CIs: 1.06, 1.34, p = 0.003) compared to a medium-sized clinic were associated with a better first ANC visit experience, while common pregnancy discomforts (aPR 0.94; 95% CIs: 0.89, 0.98, p = 0.005) and shorter visit length (aPR 0.94; 95% CIs: 0.88, 0.99, p = 0.039) were associated with lower women's experience. The primary limitation of the study is that participants' responses may be influenced by social desirability bias, leading them to provide socially acceptable responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We found important gaps in adherence to ANC standards and that care competence during the first A","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 9","pages":"e1004456"},"PeriodicalIF":15.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127116","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":"Variability in performance of genetic-enhanced DXA-BMD prediction models across diverse ethnic and geographic populations: A risk prediction study.","authors":"Yong Liu, Xiang-He Meng, Chong Wu, Kuan-Jui Su, Anqi Liu, Qing Tian, Lan-Juan Zhao, Chuan Qiu, Zhe Luo, Martha I Gonzalez-Ramirez, Hui Shen, Hong-Mei Xiao, Hong-Wen Deng","doi":"10.1371/journal.pmed.1004451","DOIUrl":"10.1371/journal.pmed.1004451","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both genetic variants and clinical factors (such as sex, age, height, and weight), within 17,964 British white individuals from UKBB. Models based on regression with least absolute shrinkage and selection operator (LASSO), selected based on the coefficient of determination (R2) from a model selection subset of 5,973 individuals from British white population. These models were tested on 5 UKBB test sets and 12 independent cohorts of diverse ancestries, totaling over 15,000 individuals. Furthermore, we assessed the correlation of predicted BMDs with fragility fractures risk in 10 years in a case-control set of 287,183 European white participants without DXA-BMDs in the UKBB. With single-nucleotide polymorphism (SNP) inclusion thresholds at 5×10-6 and 5×10-7, the prediction models for FNK-BMD and SPN-BMD achieved the highest R2 of 27.70% with a 95% confidence interval (CI) of [27.56%, 27.84%] and 48.28% (95% CI [48.23%, 48.34%]), respectively. Adding genetic factors improved predictions slightly, explaining an additional 2.3% variation for FNK-BMD and 3% for SPN-BMD over clinical factors alone. Survival analysis revealed that the predicted FNK-BMD and SPN-BMD were significantly associated with fragility fracture risk in the European white population (P &lt; 0.001). The hazard ratios (HRs) of the predicted FNK-BMD and SPN-BMD were 0.83 (95% CI [0.79, 0.88], corresponding to a 1.44% difference in 10-year absolute risk) and 0.72 (95% CI [0.68, 0.76], corresponding to a 1.64% difference in 10-year absolute risk), respectively, indicating that for every increase of one standard deviation in BMD, the fracture risk will decrease by 17% and 28%, respectively. However, the model's performance declined in other ethnic groups and independent cohorts. The limitations of this study include differences in clinical factors distribution and the use of only SNPs as genetic factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In this study, we observed that combining genetic and clinical factors improves BMD prediction compared to clinical factors alone. Adjusting inclusion thresholds for genetic variants (e.g., 5×10-6 or 5×10-7) rather than solely considering genome-wide association study (GWAS)-significant variants can enhance the m","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004451"},"PeriodicalIF":15.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113855","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":"Comparison of oral anticoagulants for stroke prevention in atrial fibrillation using the UK clinical practice research Datalink Aurum: A reference trial (ARISTOTLE) emulation study.","authors":"Emma Maud Powell, Usha Gungabissoon, John Tazare, Liam Smeeth, Paris J Baptiste, Turki M Bin Hammad, Angel Y S Wong, Ian J Douglas, Kevin Wing","doi":"10.1371/journal.pmed.1004377","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004377","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Stroke prevention guidance for patients with atrial fibrillation (AF) uses evidence generated from randomised controlled trials (RCTs). However, applicability to patient groups excluded from trials remains unknown. Real-world patient data provide an opportunity to evaluate outcomes in a trial analogous population of direct oral anticoagulants (DOACs) users and in patients otherwise excluded from RCTs; however, there remains uncertainty on the validity of methods and suitability of the data. Successful reference trial emulation can support the generation of evidence around treatment effects in groups excluded or underrepresented in trials. We used linked United Kingdom primary care data to investigate whether we could emulate the pivotal ARISTOTLE trial (apixaban versus warfarin) and extend the analysis to investigate the impact of warfarin time in therapeutic range (TTR) on results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;Patients with AF in the UK Clinical Practice Research Datalink (CPRD Aurum) prescribed apixaban or warfarin from 1 January 2013 to 31 July 2019 were selected. ARISTOTLE eligibility criteria were applied to this population and matched to the RCT apixaban arm on baseline characteristics creating a trial-analogous apixaban cohort; this was propensity-score matched to warfarin users in the CPRD Aurum. ARISTOTLE outcomes were assessed using Cox proportional hazards regression stratified by prior warfarin exposure status during 2.5 years of patient follow-up and results benchmarked against the trial results before treatment effectiveness was further evaluated based on (warfarin) TTR. The dataset comprised 8,734 apixaban users and propensity-score matched 8,734 warfarin users. Results [hazard ratio (95% confidence interval)] confirmed apixaban noninferiority for stroke or systemic embolism (SE) [CPRD 0.98 (0.82,1.19) versus trial 0.79 (0.66,0.95)] and death from any cause [CPRD 1.03 (0.93,1.14) versus trial 0.89 (0.80,0.998)] but did not indicate apixaban superiority. Absolute event rates for stroke/SE were similar for apixaban in CPRD Aurum and ARISTOTLE (1.27%/year), whereas a lower event rate was observed for warfarin (CPRD Aurum 1.29%/year, ARISTOTLE 1.60%/year). Analysis by TTR suggested similar effectiveness of apixaban compared with poorly controlled warfarin (TTR &lt; 0.75) for stroke/SE [0.91 (0.73, 1.14)], all-cause death [0.94 (0.84, 1.06)], and superiority for major bleeding [0.74 (0.63, 0.86)]. However, when compared with well-controlled warfarin (TTR ≥ 0.75), apixaban was associated with an increased hazard for all-cause death [1.20 (1.04, 1.37)], and there was no significant benefit for major bleeding [1.08 (0.90, 1.30)]. The main limitation of the study's methodology are the risk of residual confounding, channelling bias and attrition bias in the warfarin arm, and selection bias and misclassification in the analysis by TTR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Analysis of nonintervention","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004377"},"PeriodicalIF":15.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113853","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":"Using real-world evidence to complement evidence from randomized controlled trials on oral anticoagulants for stroke prevention.","authors":"Mark J R Smeets, Suzanne C Cannegieter","doi":"10.1371/journal.pmed.1004449","DOIUrl":"https://doi.org/10.1371/journal.pmed.1004449","url":null,"abstract":"<p><p>Mark J. R. Smeets and Suzanne C. Cannegieter discuss the use of real world data to complement data generated by clinical trials of systemic anticoagulants.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004449"},"PeriodicalIF":15.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113854","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":"Antenatal care quality and detection of risk among pregnant women: An observational study in Ethiopia, India, Kenya, and South Africa.","authors":"Catherine Arsenault, Nompumelelo Gloria Mfeka-Nkabinde, Monica Chaudhry, Prashant Jarhyan, Tefera Taddele, Irene Mugenya, Shalom Sabwa, Katherine Wright, Beatrice Amboko, Laura Baensch, Gebeyaw Molla Wondim, Londiwe Mthethwa, Emma Clarke-Deelder, Wen-Chien Yang, Rose J Kosgei, Priyanka Purohit, Nokuzola Cynthia Mzolo, Anagaw Derseh Mebratie, Subhojit Shaw, Adiam Nega, Boikhutso Tlou, Günther Fink, Mosa Moshabela, Dorairaj Prabhakaran, Sailesh Mohan, Damen Haile Mariam, Jacinta Nzinga, Theodros Getachew, Margaret E Kruk","doi":"10.1371/journal.pmed.1004446","DOIUrl":"10.1371/journal.pmed.1004446","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Antenatal care (ANC) is an essential platform to improve maternal and newborn health (MNH). While several articles have described the content of ANC in low- and middle-income countries (LMICs), few have investigated the quality of detection and management of pregnancy risk factors during ANC. It remains unclear whether women with pregnancy risk factors receive targeted management and additional ANC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;This observational study uses baseline data from the MNH eCohort study conducted in 8 sites in Ethiopia, India, Kenya, and South Africa from April 2023 to January 2024. A total of 4,068 pregnant women seeking ANC for the first time in their pregnancy were surveyed. We built country-specific ANC completeness indices that measured provision of 16 to 22 recommended clinical actions in 5 domains: physical examinations, diagnostic tests, history taking and screening, counselling, and treatment and prevention. We investigated whether women with pregnancy risks tended to receive higher quality care and we assessed the quality of detection and management of 7 concurrent illnesses and pregnancy risk factors (anemia, undernutrition, obesity, chronic illnesses, depression, prior obstetric complications, and danger signs). ANC completeness ranged from 43% in Ethiopia, 66% in Kenya, 73% in India, and 76% in South Africa, with large gaps in history taking, screening, and counselling. Most women in Ethiopia, Kenya, and South Africa initiated ANC in second or third trimesters. We used country-specific multivariable mixed-effects linear regression models to investigate factors associated with ANC completeness. Models included individual demographics, health status, presence of risk factors, health facility characteristics, and fixed effects for the study site. We found that some facility characteristics (staffing, patient volume, structural readiness) were associated with variation in ANC completeness. In contrast, pregnancy risk factors were only associated with a 1.7 percentage points increase in ANC completeness (95% confidence interval 0.3, 3.0, p-value 0.014) in Kenya only. Poor self-reported health was associated with higher ANC completeness in India and South Africa and with lower ANC completeness in Ethiopia. Some concurrent illnesses and risk factors were overlooked during the ANC visit. Between 0% and 6% of undernourished women were prescribed food supplementation and only 1% to 3% of women with depression were referred to a mental health provider or prescribed antidepressants. Only 36% to 73% of women who had previously experienced an obstetric complication (a miscarriage, preterm birth, stillbirth, or newborn death) discussed their obstetric history with the provider during the first ANC visit. Although we aimed to validate self-reported information on health status and content of care with data from health cards, our findings may be affected by recall or other information biases.","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004446"},"PeriodicalIF":15.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082335","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":"A minimum data set-Core outcome set, core data elements, and core measurement set-For degenerative cervical myelopathy research (AO Spine RECODE DCM): A consensus study.","authors":"Benjamin M Davies, Xiaoyu Yang, Danyal Z Khan, Oliver D Mowforth, Alvaro Y Touzet, Aria Nouri, James S Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, Shekar N Kurpad, James D Guest, Lindsay Tetreault, Brian K Kwon, Timothy F Boerger, Ricardo Rodrigues-Pinto, Julio C Furlan, Robert Chen, Carl M Zipser, Armin Curt, James Milligan, Sukhivinder Kalsi-Rayn, Ellen Sarewitz, Iwan Sadler, Tammy Blizzard, Caroline Treanor, David Anderson, Nader Fallah, Olesja Hazenbiller, Carla Salzman, Zachary Zimmerman, Anne M Wandycz, Shirley Widdop, Margaret Reeves, Rye Raine, Sukvinder K Ryan, Ailish Malone, Ali Gharooni, Jefferson R Wilson, Allan R Martin, Michael G Fehlings, Angus G K McNair, Mark R N Kotter","doi":"10.1371/journal.pmed.1004447","DOIUrl":"10.1371/journal.pmed.1004447","url":null,"abstract":"<p><strong>Background: </strong>Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further \"how\" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research.</p><p><strong>Methods and findings: </strong>A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery.</p><p><strong>Conclusions: </strong>The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"21 8","pages":"e1004447"},"PeriodicalIF":15.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037458","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}