PLoS Medicine最新文献

{"title":"Long-term mortality outcome of a primary care-based mobile health intervention for stroke management: Six-year follow-up of a cluster-randomized controlled trial.","authors":"Xingxing Chen, Enying Gong, Jie Tan, Elizabeth L Turner, John A Gallis, Shifeng Sun, Siran Luo, Fei Wu, Bolu Yang, Yutong Long, Yilong Wang, Zixiao Li, Yun Zhou, Shenglan Tang, Janet P Bettger, Brian Oldenburg, Xiaochen Zhang, Jianfeng Gao, Brian S Mittman, Valery L Feigin, Ruitai Shao, Shah Ebrahim, Lijing L Yan","doi":"10.1371/journal.pmed.1004564","DOIUrl":"10.1371/journal.pmed.1004564","url":null,"abstract":"<p><strong>Background: </strong>Despite growing evidence of primary care-based interventions for chronic disease management in resource-limited settings, long-term post-trial effects remain inconclusive. We investigated the association of a 12-month system-integrated technology-enabled model of care (SINEMA) intervention with mortality outcomes among patients experiencing stroke at 6-year post-trial.</p><p><strong>Methods and findings: </strong>This study (clinicltiral.gov registration number: NCT05792618) is a long-term passive observational follow-up of participants and their spouse of the SINEMA trial (clinicaltrial.gov registration number: NCT03185858). The original SINEMA trial was a cluster-randomized controlled trial conducted in 50 villages (clusters) in rural China among patients experiencing stroke during July 2017-July 2018. Village doctors in the intervention arm received training, incentives, and a customized mobile health application supporting monthly follow-ups to participants who also received daily free automated voice-messages. Vital status and causes of death were ascertained using local death registry, standardized village doctor records, and verbal autopsy. The post-trial observational follow-up spanned from 13- to 70-months post-baseline (up to April 30, 2023), during which no intervention was requested or supported. The primary outcome of this study was all-cause mortality, with cardiovascular and stroke cause-specific mortality also reported. Cox proportional hazards models with cluster-robust standard errors were used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs), adjusting for town, age, and sex in the main analysis model. Analyses were conducted on an intention-to-treat basis. Of 1,299 patients experiencing stroke (mean age 65.7 years, 42.6% females) followed-up to 6 years, 276 (21.2%) died (median time-to-death 43.0 months [quantile 1-quantile 3: 26.7-56.8]). Cumulative incidence of all-cause mortality was 19.0% (121 among 637) in the intervention arm versus 23.4% (155 among 662) in the control arm (HR 0.73; 95% CI 0.59, 0.90; p = 0.004); 14.4% versus 17.7% (HR 0.73; 95% CI 0.58, 0.94; p = 0.013) for cardiovascular cause-specific mortality; and 6.0% versus 7.9% (HR 0.71; 95% CI 0.44, 1.15; p = 0.16) for stroke cause-specific mortality. Although multisource verification was used to verify the outcomes, limitations exist as the survey- and record-matching-based nature of the study, unavailability of accurate clinical diagnostic records for some cases and the potential confounders that may influence the observed association on mortality.</p><p><strong>Conclusions: </strong>Despite no observed statistically difference on stroke cause-specific mortality, the 12-month SINEMA intervention, compared with usual care, significantly associated with reduced all-cause and cardiovascular cause-specific mortality during 6 years of follow-up, suggesting potential sustained long-term benefits to patients experi","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 3","pages":"e1004564"},"PeriodicalIF":15.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732735","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":"Pharmacogenetics and adverse drug reports: Insights from a United Kingdom national pharmacovigilance database.","authors":"Emma F Magavern, Maia Megase, Jack Thompson, Gabriel Marengo, Julius Jacobsen, Damian Smedley, Mark J Caulfield","doi":"10.1371/journal.pmed.1004565","DOIUrl":"10.1371/journal.pmed.1004565","url":null,"abstract":"<p><strong>Background: </strong>Adverse drug reactions (ADRs) harm patients and are costly for healthcare systems. Genetic variation contributes to variability in medication response and prospective knowledge of these variants can decrease risk of ADRs, as shown in the PREPARE trial. Reduction in ADRs would affect only those reactions to drugs contained in well-validated pharmacogene-drug pairs. The scope of ADRs represented by these drugs on a population scale is unclear. The objective of this study was to characterize the pharmacogene-drug-associated ADR reporting landscape from a national regulatory pharmacovigilance dataset to elucidate the scale of potential ADR mitigation by pharmacogenomics (PGx) implementation.</p><p><strong>Methods and findings: </strong>All publicly available Yellow Card ADR reports to the United Kingdom Medicines and Healthcare Products Regulatory Agency, from 1963 to 2024, were compiled using programmatic data extraction. The ADRs were analysed with descriptive statistics, stratified by PGx status and by associated genes. Prescribing prevalence from the literature was compared with age range matched ADR reports for PGx-associated drugs. There were 1,345,712 ADR reports, attributed to 2,499 different substances. 115,789 adverse drug reports (9%) were associated with drugs for which ADR risk can be modified based on pharmacogenomic prescribing guidance. Seventy-five percent of these (n = 87,339) were due to medicines which interact with only three pharmacokinetic pharmacogenes (CYP2C19, CYP2D6, SLCO1B1). Forty-seven percent of all the PGx mitigatable ADRs identified were attributed to psychiatric medications (n = 54,846), followed by 24% attributed to cardiovascular medications (n = 28,279). Those experiencing PGx mitigatable ADRs, as compared with non-PGx mitigatable ADRs, were older and the ADRs more often consisted of severe non-fatal reactions. Many PGx-associated psychiatric drug ADRs were overrepresented as compared with prescribing prevalence, but fatal cardiac arrhythmias were uncommon consequences, comprising only 0.4% of these ADRs (n = 172 of n = 48,315 total ADRs). Limitations of this data source include under reporting of ADRs and reporting bias. These findings are based on analysis of the Yellow Card dataset described and may not represent all ADRs from a generalised patient population.</p><p><strong>Conclusions: </strong>Nine percent of all reported ADRs are associated with drugs where a genetic variant can cause heightened risk of an ADR and inform prescribing. A panel of only three pharmacogenes could potentially mitigate three in every four PGx modifiable ADRs. Based on our findings, Psychiatry may be the single highest impact specialty to pilot PGx to reduce ADRs and associated morbidity, mortality and costs.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 3","pages":"e1004565"},"PeriodicalIF":15.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731570","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":"Evaluation of postural therapy using lateral position according to fetal back orientation on breech presentation and breech recurrence (BRLT study): An open-label randomized controlled trial.","authors":"Hiroki Shinmura, Youhei Tsunoda, Takashi Matsushima, Ryuhei Kurashina, Asako Watanabe, Eika Harigane, Nozomi Ouchi, Shunji Suzuki","doi":"10.1371/journal.pmed.1004555","DOIUrl":"10.1371/journal.pmed.1004555","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In Japan, the lateral position method is known as a postural therapy for breech presentation wherein the mother lies down in lateral position according to the orientation of the fetal back. Few studies have formally tested lateral position management for breech presentation, and no method exists to prevent breech recurrence after cephalic version. We hypothesized that postural management comprising a combination of opposite-side lateral position for breech presentation and same-side lateral position after cephalic version demonstrates a clinically relevant effect size on breech presentation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We conducted a stratified, open-label randomized controlled trial at an academic hospital in Kawasaki, Japan. A total of 200 women diagnosed with breech presentation between 28 +  0 and 30 +  0 gestational weeks were randomized to postural management (n =  100) or control (no intervention, n =  100) group. The intervention was instruction every 2 weeks on lying in the lateral position on the opposite-side of fetal back for breech presentation and on the same-side of fetal back for head-first presentation. The primary outcome was the rate of fetuses in breech presentation at 37 weeks of gestation, and the secondary outcomes were cesarean delivery, cesarean delivery for breech presentation, head presentation 2, 4, and 6 weeks later, breech presentation recurrence, and adverse events. Breech presentation rate at 37 gestational weeks was 11% in the intervention group, using the combination of the opposite-side and same-side lateral positions, compared with 19% in the control group. However, we found no statistical significance in the intention-to-treat analysis (11% [11/100] versus 19% [19/100]; relative risk, 0.58 [95% CI, 0.29 to 1.15]; p =  0.11). In the control group, 23 participants (23%) unknowingly took the same posture as the intervention group, and the prespecified per-protocol analysis excluding crossover found the same direction of effect but with statistical significance. In the intention-to-treat analysis, the intervention group had a higher cephalic version rate 2 weeks after the instruction (69% [69/100] versus 54% [54/100]; relative risk, 0.67 [95% CI, 0.47 to 0.96]; p =  0.029), and lower breech presentation recurrence rates (2% [2/91] versus 10% [9/88]; relative risk, 0.22 [95% CI, 0.048 to 0.97]; p =  0.031) than the control group. Regarding adverse events in the intervention group, three participants experienced discomfort and one participant complained of pain in the lateral abdomen; these symptoms resolved spontaneously.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;For breech presentation at the beginning of the third trimester, providing postural therapy instruction on opposite-side lateral positioning and same-side lateral positioning was associated with 8% reduction of breech fetuses at 37 gestational weeks compared with the control group, but this primary endpoint did no","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 3","pages":"e1004555"},"PeriodicalIF":15.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factor analysis and creation of an externally-validated prediction model for perioperative stroke following non-cardiac surgery: A multi-center retrospective and modeling study.","authors":"Yulong Ma, Siyuan Liu, Faqiang Zhang, Xuhui Cong, Bingcheng Zhao, Miao Sun, Huikai Yang, Min Liu, Peng Li, Yuxiang Song, Jiangbei Cao, Yingfu Li, Wei Zhang, Kexuan Liu, Jiaqiang Zhang, Weidong Mi","doi":"10.1371/journal.pmed.1004539","DOIUrl":"10.1371/journal.pmed.1004539","url":null,"abstract":"<p><strong>Background: </strong>Perioperative stroke is a serious and potentially fatal complication following non-cardiac surgery. Thus, it is important to identify the risk factors and develop an effective prognostic model to predict the incidence of perioperative stroke following non-cardiac surgery.</p><p><strong>Methods and findings: </strong>We identified potential risk factors and built a model to predict the incidence of perioperative stroke using logistic regression derived from hospital registry data of adult patients that underwent non-cardiac surgery from 2008 to 2019 at The First Medical Center of Chinese PLA General Hospital. Our model was then validated using the records of two additional hospitals to demonstrate its clinical applicability. In our hospital cohorts, 223,415 patients undergoing non-cardiac surgery were included in this study with 525 (0.23%) patients experiencing a perioperative stroke. Thirty-three indicators including several intraoperative variables had been identified as potential risk factors. After multi-variate analysis and stepwise elimination (P < 0.05), 13 variables including age, American Society of Anesthesiologists (ASA) classification, hypertension, previous stroke, valvular heart disease, preoperative steroid hormones, preoperative β-blockers, preoperative mean arterial pressure, preoperative fibrinogen to albumin ratio, preoperative fasting plasma glucose, emergency surgery, surgery type and surgery length were screened as independent risk factors and incorporated to construct the final prediction model. Areas under the curve were 0.893 (95% confidence interval (CI) [0.879, 0.908]; P < 0.001) and 0.878 (95% CI [0.848, 0.909]; P < 0.001) in the development and internal validation cohorts. In the external validation cohorts derived from two other independent hospitals, the areas under the curve were 0.897 and 0.895. In addition, our model outperformed currently available prediction tools in discriminative power and positive net benefits. To increase the accessibility of our predictive model to doctors and patients evaluating perioperative stroke, we published an online prognostic software platform, 301 Perioperative Stroke Risk Calculator (301PSRC). The main limitations of this study included that we excluded surgical patients with an operation duration of less than one hour and that the construction and external validation of our model were from three independent retrospective databases without validation from prospective databases and non-Chinese databases.</p><p><strong>Conclusions: </strong>In this work, we identified 13 independent risk factors for perioperative stroke and constructed an effective prediction model with well-supported external validation in Chinese patients undergoing non-cardiac surgery. The model may provide potential intervention targets and help to screen high-risk patients for perioperative stroke prevention.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 3","pages":"e1004539"},"PeriodicalIF":15.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674671","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":"Product reformulation in non-alcoholic beverages and foods after the implementation of front-of-pack warning labels in Mexico.","authors":"Juan Carlos Salgado, Lilia S Pedraza, Alejandra Contreras-Manzano, Tania C Aburto, Lizbeth Tolentino-Mayo, Simon Barquera","doi":"10.1371/journal.pmed.1004533","DOIUrl":"10.1371/journal.pmed.1004533","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In late March 2020, the Mexican government announced an updated norm to include front-of-pack warning labels for packaged foods and non-alcoholic beverages. Warning labels came into effect in October 2020. To avoid displaying warning labels, producers can reformulate their products by reducing the content of calories or critical nutrients targeted by the policy (added sugars, saturated fat, and sodium) or removing non-caloric sweeteners or added caffeine. The objective of this study is to assess changes in the percentage of products above warning-label cutoffs for calories and critical nutrients and changes in the content of calories and critical nutrients associated with warning labels in Mexico.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We used nutritional panel data collected by the Mexican National Institute of Public Health from ≈1,000 top-purchased products, which represented ≥60% of the market share for each of the included food groups according to household purchases in the Nielsen Consumer Panel commercial dataset for Mexico in 2016. Nutritional panel data is available for three periods: 2016-2017, T0 (pre-policy); Jul-Sep 2020, T1 (post-warning-label announcement); and Feb-Apr 2021, T2 (post-warning-label implementation). We assessed changes in T1 versus T0 (potential anticipatory reformulation before the warning-label implementation) and T2 versus T0 (reformulation after the warning-label implementation) by food group using generalized estimating equations for the percentage of products above warning-label cutoffs or containing non-caloric sweeteners or added caffeine, and fixed-effects linear models and quantile regressions for the content of calories and critical nutrients. Included food groups were cereal-based desserts, bread and other cereals, salty snacks, sweetened beverages, solid dairy, liquid dairy, instant food, and candies. At T0, the food group level with the lowest percentage of products with at least one calorie/nutrient content above warning-label cutoffs was instant food (77.8%); at T2, this fell to 52.6%. Based on our statistical models, we found that all food groups showed reductions in at least one type of warning label. The most common reductions in the percentage of products exceeding warning-label cutoffs were for sodium (up to -63.1 percentage points for bread and other cereals; 95% CI: -77.5, -48.6; p-value &lt; 0.001), saturated fat (up to -26.3 percentage points for salty snacks; 95% CI: -35.8, -16.8; p-value &lt; 0.001), and products containing non-caloric sweeteners (up to -29.0 percentage points for solid dairy; 95% CI: -40.7, -17.2; p-value &lt; 0.001). The reductions in products above warning-label cutoffs were coupled with reductions in products' content of calories and critical nutrients. According to quantile regressions, these reductions mostly occurred at the 50th-75th percentiles. Product reformulation mainly occurred in T2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our findings ","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 3","pages":"e1004533"},"PeriodicalIF":15.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659474","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":"Direct and indirect impacts of the COVID-19 pandemic on life expectancy and person-years of life lost with and without disability: A systematic analysis for 18 European countries, 2020-2022.","authors":"Sara Ahmadi-Abhari, Piotr Bandosz, Martin J Shipley, Joni V Lindbohm, Abbas Dehghan, Paul Elliott, Mika Kivimaki","doi":"10.1371/journal.pmed.1004541","DOIUrl":"10.1371/journal.pmed.1004541","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The direct and indirect impacts of the COVID-19 pandemic on life expectancy (LE) and years of life lost with and without disability remain unclear. Accounting for pre-pandemic trends in morbidity and mortality, we assessed these impacts in 18 European countries, for the years 2020-2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We used multi-state Markov modeling based on several data sources to track transitions of the population aged 35 or older between eight health states from disease-free, combinations of cardiovascular disease, cognitive impairment, dementia, and disability, through to death. We quantified separately numbers and rates of deaths attributable to COVID-19 from those related to mortality from other causes during 2020-2022, and estimated the proportion of loss of life expectancy and years of life with and without disability that could have been avoided if the pandemic had not occurred. Estimates were disaggregated by COVID-19 versus non-COVID causes of deaths, calendar year, age, sex, disability status, and country. We generated the 95% uncertainty intervals (UIs) using Monte Carlo simulations with 500 iterations. Among the 289 million adult population in the 18 countries, person-years of life lost (PYLL) in millions were 4.7 (95% UI 3.4-6.0) in 2020, 7.1 (95% UI 6.6-7.9) in 2021, and 5.0 (95% UI 4.1-6.2) in 2022, totaling 16.8 (95% UI 12.0-21.8) million. PYLL per capita varied considerably between the 18 countries ranging between 20 and 109 per 1,000 population. About 60% of the total PYLL occurred among persons aged over 80, and 30% in those aged 65-80. If the pandemic were avoided, over half (9.8 million (95% UI 4.7-15.1)) of the 16.8 million PYLL were estimated to have been lived without disability. Of the total PYLL, 11.6-13.2 million were due to registered COVID-19 deaths and 3.6-5.3 million due to non-COVID mortality. Despite a decrease in PYLL attributable to COVID-19 after 2021, PYLL associated with other causes of death continued to increase from 2020 to 2022 in most countries. Lower income countries had higher PYLL per capita as well as a greater proportion of disability-free PYLL during 2020-2022. Similar patterns were observed for life expectancy. In 2021, LE at age 35 (LE-35) declined by up to 2.8 (95% UI 2.3-3.3) years, with over two-thirds being disability-free. With the exception of Sweden, LE-35 in the studied countries did not recover to 2019 levels by 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The considerable loss of life without disability and the rise in premature mortality not directly linked to COVID-19 deaths during 2020-2022 suggest a potential broader, longer-term and partially indirect impact of the pandemic, possibly resulting from disruptions in healthcare delivery and services for non-COVID conditions and unintended consequences of COVID-19 containment measures. These findings highlight a need for better pandemic preparedness in Europe, ideally, as part of a more c","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 3","pages":"e1004541"},"PeriodicalIF":15.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606407","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":"Effects of a community-driven water, sanitation, and hygiene intervention on diarrhea, child growth, and local institutions: A cluster-randomized controlled trial in rural Democratic Republic of Congo.","authors":"John P Quattrochi, Kevin Croke, Caleb Dohou, Luca Stanus Ghib, Yannick Lokaya, Aidan Coville, Eric Mvukiyehe","doi":"10.1371/journal.pmed.1004524","DOIUrl":"10.1371/journal.pmed.1004524","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diarrhea and growth faltering in early childhood reduce survival and impair neurodevelopment. We assessed whether a national program combining (i) funds for latrine and water upgrades; (ii) institutional strengthening; and (iii) behavior change campaigns reduced diarrhea and stunting, and strengthened local institutions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and findings: &lt;/strong&gt;We collaborated with program implementers to conduct a cluster-randomized controlled trial in four provinces of the Democratic Republic of Congo (DRC). Three hundred thirty-two rural villages were grouped into 121 clusters to minimize geographic spillovers. Between 15 March and 30 June 2018, we randomly assigned, after stratifying by province and cluster size, 50 intervention and 71 control clusters. Masking of participants and interviewers was not possible. Primary outcomes were length-for-age Z-score among children under 5 years of age, caregiver-reported diarrhea in last 7 days among children under 5 years of age, and an index of community WASH institutions. The primary analysis was on an intention-to-treat basis, using a binary variable indicating whether the participant was in an intervention or control cluster. Three thousand two hundred eighty-three households were interviewed between November 2022 and April 2023, median 3.6 years post-intervention. The intervention had no effect on diarrhea (adjusted mean difference -0.01 [95% -0.05 to 0.03]). Diarrhea prevalence was high overall, at 38% in the treatment group and 42% in the control group. The intervention had no effect on length-for-age Z-scores in children (adjusted mean difference -0.01 [95% CI -0.15 to 0.12]). In the control group, the mean length-for-age Z-score was -2.18 (1.60 SD). Villages in the intervention group had a 0.40 higher score on the WASH institutions index (95% CI 0.16-0.65). The percentage of villages in the intervention group with an active water, sanitation, and hygiene (or just water) committee was 21 pp higher than the control group. Households in the intervention group were 24 pp (95% CI 12-36) more likely to report using an improved water source, 18 pp (95% CI 10-25) more likely to report using an improved sanitation facility, and reported more positive perceptions of water governance (adjusted difference 0.19 SD [95% CI 0.04-0.34]). The trial had several limitations, including incomplete (86%) adherence in the implementation group, the absence of baseline measures, and the reliance on self-reported outcomes for some measures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The DRC's national rural WASH program increased access to improved water and sanitation infrastructure, and created new WASH institutions, all of which persisted for at least 3.6 years. However, these effects were not sufficient to reduce diarrhea or growth faltering.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;The Pan African Clinical Trials Registry PACTR202102616421588 (https://pactr.samrc.ac.za/TrialDisplay.a","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 3","pages":"e1004524"},"PeriodicalIF":15.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574610","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":"Submicroscopic malaria in pregnancy and associated adverse pregnancy events: A case-cohort study of 4,352 women on the Thailand-Myanmar border.","authors":"Mary Ellen Gilder, Makoto Saito, Warat Haohankhunnatham, Clare L Ling, Gornpan Gornsawun, Germana Bancone, Cindy S Chu, Peter R Christensen, Mallika Imwong, Prakaykaew Charunwatthana, Nay Win Tun, Aung Myat Min, Verena I Carrara, Stephane Proux, Nicholas J White, François Nosten, Rose McGready","doi":"10.1371/journal.pmed.1004529","DOIUrl":"10.1371/journal.pmed.1004529","url":null,"abstract":"<p><strong>Background: </strong>Malaria in pregnancy detected by microscopy is associated with maternal anaemia, reduced fetal growth, and preterm birth, but the effects of lower density (i.e., submicroscopic) malaria infections are poorly characterised. This analysis was undertaken to investigate associations between submicroscopic malaria at the first antenatal care (ANC) visit and these adverse pregnancy events on the Thailand-Myanmar border.</p><p><strong>Methods: </strong>Blood samples taken from refugee and migrant pregnant women presenting for their first ANC visit were analysed retrospectively for malaria using ultrasensitive PCR (uPCR, limit of detection 22 parasites/mL). The relationships between submicroscopic malaria and subsequent microscopically detectable malaria, anaemia, birth weight, and preterm birth were evaluated using inverse probability weighting for stratified random sampling.</p><p><strong>Results: </strong>First ANC visit samples from 4,352 asymptomatic women (median gestational age 16.5 weeks) attending between October 1st 2012 and December 31st 2015 were analysed. The weighted proportion of women with submicroscopic malaria infection was 4.6% (95% CI 3.9-5.6), comprising 59.8% (49.5-69.4) Plasmodium vivax, 6.5% (4.0-10.5) Plasmodium falciparum, 1.8% (0.9-3.6) mixed, and 31.9% (22.2-43.5) infections which could not be speciated. Submicroscopic parasitaemia at first ANC visit was associated with subsequent microscopically detected malaria (adjusted hazard ratio [HR] 12.9, 95% CI 8.8-18.8, p < 0.001) and lower birth weight (adjusted predicted mean difference -275 g, 95% CI -510 to -40, p = 0.022). There was no association with preterm birth. Submicroscopic P. falciparum mono-infection (adjusted HR 2.8, 95% CI 1.2-6.6, p = 0.023) and coinfection with P. falciparum and P. vivax (adjusted HR 10.3, 95% CI 2.6-40.4, p = 0.001) was associated with increased risk of maternal anaemia, but submicroscopic P. vivax mono-infection was not. That uPCR was conducted for only a part of the cohort due to cost constraints is a limitation.</p><p><strong>Conclusions: </strong>In low transmission settings, uPCR identifies substantially more malaria infections at antenatal screening than conventional diagnostic methods. On the Thailand-Myanmar border, submicroscopic malaria at first antenatal consultation was associated with higher risks of microscopically diagnosed malaria later in pregnancy, anaemia, and reduced birth weight.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 3","pages":"e1004529"},"PeriodicalIF":15.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558550","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":"Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank.","authors":"Meng Zhu, Xia Zhu, Yuting Han, Zhimin Ma, Chen Ji, Tianpei Wang, Caiwang Yan, Ci Song, Canqing Yu, Dianjianyi Sun, Yue Jiang, Jiaping Chen, Ling Yang, Yiping Chen, Huaidong Du, Robin Walters, Iona Y Millwood, Juncheng Dai, Hongxia Ma, Zhengdong Zhang, Zhengming Chen, Zhibin Hu, Jun Lv, Guangfu Jin, Liming Li, Hongbing Shen","doi":"10.1371/journal.pmed.1004534","DOIUrl":"10.1371/journal.pmed.1004534","url":null,"abstract":"<p><strong>Background: </strong>Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain.</p><p><strong>Methods and findings: </strong>We constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the China Kadoorie Biobank (CKB). The optimal PRSs with the highest discriminatory ability were used to define genetic risk, and their site-specific and cross-cancer associations were assessed. We modeled 10-year absolute risk trajectories for each cancer across risk strata defined by PRSs and modifiable risk scores and quantified the explained relative risk (ERR) of PRSs with modifiable risk factors for different cancers. More than 60% (50/80) of the PRSs demonstrated significant associations with the corresponding cancer outcomes. Optimal PRSs for nine common cancers were identified, with each standard deviation increase significantly associated with corresponding cancer risk (hazard ratios (HRs) ranging from 1.20 to 1.76). Compared with participants at low genetic risk and reduced modifiable risk scores, those with high genetic risk and elevated modifiable risk scores had the highest risk of incident cancer, with HRs ranging from 1.97 (95% confidence interval (CI): 1.11-3.48 for cervical cancer, P = 0.020) to 8.26 (95% CI: 1.92-35.46 for prostate cancer, P = 0.005). We observed nine significant cross-cancer associations for PRSs and found the integration of PRSs significantly increased the prediction accuracy for most cancers. The PRSs contributed 2.6%-20.3%, while modifiable risk factors explained 2.3%-16.7% of the ERR in the Chinese population.</p><p><strong>Conclusions: </strong>The integration of existing evidence has facilitated the development of PRSs associated with nine common cancer risks in the Chinese population, potentially improving clinical risk assessment.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 2","pages":"e1004534"},"PeriodicalIF":15.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527982","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":"Understanding the quality of ethnicity data recorded in health-related administrative data sources compared with Census 2021 in England.","authors":"Cameron Razieh, Bethan Powell, Rosemary Drummond, Isobel L Ward, Jasper Morgan, Myer Glickman, Chris White, Francesco Zaccardi, Jonathan Hope, Veena Raleigh, Ashley Akbari, Nazrul Islam, Thomas Yates, Lisa Murphy, Bilal A Mateen, Kamlesh Khunti, Vahe Nafilyan","doi":"10.1371/journal.pmed.1004507","DOIUrl":"10.1371/journal.pmed.1004507","url":null,"abstract":"<p><strong>Background: </strong>Electronic health records (EHRs) are increasingly used to investigate health inequalities across ethnic groups. While there are some studies showing that the recording of ethnicity in EHR is imperfect, there is no robust evidence on the accuracy between the ethnicity information recorded in various real-world sources and census data.</p><p><strong>Methods and findings: </strong>We linked primary and secondary care NHS England data sources with Census 2021 data and compared individual-level agreement of ethnicity recording in General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR), Hospital Episode Statistics (HES), Ethnic Category Information Asset (ECIA), and Talking Therapies for anxiety and depression (TT) with ethnicity reported in the census. Census ethnicity is self-reported and, therefore, regarded as the most reliable population-level source of ethnicity recording. We further assessed the impact of multiple approaches to assigning a person an ethnic category. The number of people that could be linked to census from ECIA, GDPPR, HES, and TT were 47.4m, 43.5m, 47.8m, and 6.3m, respectively. Across all 4 data sources, the White British category had the highest level of agreement with census (≥96%), followed by the Bangladeshi category (≥93%). Levels of agreement for Pakistani, Indian, and Chinese categories were ≥87%, ≥83%, and ≥80% across all sources. Agreement was lower for Mixed (≤75%) and Other (≤71%) categories across all data sources. The categories with the lowest agreement were Gypsy or Irish Traveller (≤6%), Other Black (≤19%), and Any Other Ethnic Group (≤25%) categories.</p><p><strong>Conclusions: </strong>Certain ethnic categories across all data sources have high discordance with census ethnic categories. These differences may lead to biased estimates of differences in health outcomes between ethnic groups, a critical data point used when making health policy and planning decisions.</p>","PeriodicalId":49008,"journal":{"name":"PLoS Medicine","volume":"22 2","pages":"e1004507"},"PeriodicalIF":15.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517164","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}