PLoS Med. [JOURNAL]
Sun
200 papers
Maternal congenital heart disease and risk of child developmental vulnerability in early school age: A population-based cohort study.
Hossin MZ, Gadermann A, Nagy E … +4 more , Gill R, Petteni MG, Faxén J, Razaz N
PLoS Med · 2026 Jul · PMID 42391172 · Full text
BACKGROUND: While maternal congenital heart disease (CHD) is associated with increased risks of adverse pregnancy outcomes, its impact on long-term child development remains unknown. This study aimed to investigate if in...
BACKGROUND: While maternal congenital heart disease (CHD) is associated with increased risks of adverse pregnancy outcomes, its impact on long-term child development remains unknown. This study aimed to investigate if in-utero exposure to maternal CHD is associated with child developmental vulnerability at school entry. METHODS AND FINDINGS: This population-based cohort study included 256,629 singleton offspring born in British Columbia, Canada between January 1, 1995 and December 31, 2016, with follow up through linkage to teacher-rated Early Development Instrument (EDI) surveys administered in kindergarten around 5-6 years of age. Over 90% children enrolled in participating schools completed the questionnaire. Developmental vulnerability was defined as a score <10th percentile in any two of the five EDI domains: physical health and wellbeing, social competence, emotional maturity, language and cognitive development, and communication and general knowledge. The association between maternal CHD and child developmental vulnerability was examined using modified Poisson regression models, adjusted for maternal age at delivery, parity, country of birth, marital status, neighborhood income quintiles, preexisting psychiatric disorders, and pre-gestational diabetes. A counterfactual four-way decomposition method was used to quantify potential mediation and moderation by preterm birth. Of the 256,629 children (51.4% female) included in the analysis, 456 (0.2%) were exposed to maternal CHD. Developmental vulnerability was identified among 25.2% children exposed to maternal CHD compared with 16.6% among the unexposed. In the adjusted model, maternal CHD was associated with 28% higher risk of developmental vulnerability (aRR 1.28; 95% CI [1.11, 1.48]) compared with no maternal CHD. The increased risk was observed across multiple developmental domains related to physical health and wellbeing (aRR 1.31; 95% CI [1.11, 1.54]), social competence (aRR 1.22; 95% CI [1.02, 1.45]), language and cognitive development (aRR 1.39; 95% CI [1.13, 1.70]), and communication and general knowledge (aRR 1.33; 95% CI [1.09, 1.63]). Preterm birth mediated only about 8% of the overall association. Severe CHD was more strongly associated with developmental vulnerability (aRR 1.98; 95% CI [1.31, 3.00]) compared to mild CHD (aRR 1.19; 95% CI [1.00, 1.42]). However, the study had limited capacity to separate intrauterine effects from potential genetic and postnatal familial influences. Some degree of CHD misclassification is possible, which would likely bias the association toward the null. CONCLUSIONS: In this population-based study, maternal CHD was associated with child developmental vulnerability at school entry. While further research is required to elucidate the mechanisms, enhanced clinical monitoring and tailored support to reproductive age women with CHD may help reduce the risk of developmental vulnerability in their children.
Accelerometry-measured prolonged and interrupted sedentary behavior and cancer incidence and mortality: A cohort study of 91,292 UK Biobank participants.
Zhou Z, Trost SG, Ryde GC … +16 more , Parra-Soto S, Fang Z, Xu C, Lu Y, Wang K, Du M, Li Z, Lv Y, Gill JMR, Gray SR, Celis-Morales C, Gunter MJ, Giovannucci E, Pell JP, Song M, Ho FK
PLoS Med · 2026 Jul · PMID 42391119 · Full text
BACKGROUND: Current sedentary behavior (SB) guidelines primarily emphasize total time spent sedentary. We explored differences between interrupted and prolonged SB in relation to a range of cancer outcomes. METHODS AND F...
BACKGROUND: Current sedentary behavior (SB) guidelines primarily emphasize total time spent sedentary. We explored differences between interrupted and prolonged SB in relation to a range of cancer outcomes. METHODS AND FINDINGS: This study included 91,292 UK Biobank participants with valid accelerometer data. Participants were followed for a median of 12.38 years (interquartile range 11.56-13.15 years). A two-step approach based on a random forest model was used to classify SB. Multivariable Cox proportional hazards models were applied to overall incident cancers and cancer deaths, plus obesity-related and type-2 diabetes-related cancers, and 23 site-specific cancers. Models were adjusted for demographic, socioeconomic, lifestyle, dietary, and health-status factors, including age, ethnicity, deprivation, education, smoking, alcohol intake, diet, and morbidity count. Isotemporal substitution models were used to estimate the associated cancer risk when replacing prolonged SB with intermittent SB, or physical activity (PA). After adjusting for sociodemographic and lifestyle factors, each additional hour of prolonged SB was associated with a higher risk of overall cancer mortality (hazard ratio [HR] HR1hour 1.09; 95% confidence interval [CI] [1.06, 1.11]; p < 0.001). Replacing 1 hour per day of prolonged SB with light PA (HRLPA 0.88; 95% CI [0.79, 0.99]; p = 0.033) was associated with lower risk of overall cancer mortality. Similarly, replacing 30 min per day of prolonged SB with moderate PA (HRMPA 0.92; 95% CI [0.86, 0.99]; p = 0.024) was associated with a lower risk of overall cancer mortality. The main methodological limitations were observational design, residual confounding, healthy volunteer bias, and measurement imprecision due to having only 7 days of accelerometer wear. CONCLUSION: Cancer risk associated with SB is specific to prolonged SB. Replacing prolonged SB physical activity is associated with lower cancer risk.
Precision oncology's translation gap-Can molecular tumor boards bridge it?
Byrne MM, Kolesar JM
PLoS Med · 2026 Jun · PMID 42378308 · Full text
Precision oncology is revolutionizing cancer care, but isn't reaching enough patients. Molecular tumor boards (MTBs) translate complex genomic data to more effectively inform personalized care, and a new meta-analysis sh...
Precision oncology is revolutionizing cancer care, but isn't reaching enough patients. Molecular tumor boards (MTBs) translate complex genomic data to more effectively inform personalized care, and a new meta-analysis shows they boost clinical outcomes. But how can we feasibly and equitably expand the use of MTBs?
Improving suicide prevention in men.
Fazel S
PLoS Med · 2026 Jun · PMID 42378269 · Full text
Despite public health strategies focusing on men's mental health and suicide risk, rates of suicide among men remain concerningly high. Targeted, specialized approaches for high-risk individuals should be prioritized alo...
Despite public health strategies focusing on men's mental health and suicide risk, rates of suicide among men remain concerningly high. Targeted, specialized approaches for high-risk individuals should be prioritized alongside broader population-level strategies.
Multilevel onsite training and mentorship model to accelerate early childhood cancer diagnosis in Northwest Ethiopia: A quasi-experimental mixed method study.
Yimer MA, Toni AT, Teshager NW … +5 more , Worku DT, Alemayehu MA, Molla YM, Andualem Z, Tadesse AA
PLoS Med · 2026 Jun · PMID 42371922 · Full text
BACKGROUND: Childhood cancer survival in low-income countries remains below 20%, with late recognition and delayed referral commonly reported. In Northwest Ethiopia, care providers often lack the knowledge, skills, and s...
BACKGROUND: Childhood cancer survival in low-income countries remains below 20%, with late recognition and delayed referral commonly reported. In Northwest Ethiopia, care providers often lack the knowledge, skills, and support systems for recognizing early warning signs of pediatric malignancies. Community caregivers often present only after symptoms become advanced. The University of Gondar Comprehensive Specialized Hospital piloted a quality improvement initiative aimed at achieving earlier diagnoses. This study reports whether a multilevel onsite training and mentorship model could improve early recognition, referral practices, and timely diagnosis of childhood cancer in Northwest Ethiopia. METHODS AND FINDINGS: From January 2024 through September 2024, a quasi-experimental pre-post, mixed-methods study design was employed across three tiers of care: primary (e.g., health centers), secondary (general hospitals), and tertiary (specialized hospitals). Eighteen primary-level and 29 secondary-level clinicians completed intensive, on-site training (Ten and Seven days, respectively), while one thousand twenty health extension workers received pictorial outreach modules. A 6-month mentorship program combined monthly onsite visits with remote supervision. Mentees included general practitioners, nurses, health officers, and health extension workers mentored by a multidisciplinary team that included, for example, pediatric haemato-oncologists. Knowledge, attitude, and practice surveys and clinical chart reviews were conducted at baseline and 6 months post-implementation to evaluate patient-journey intervals. These quantitative assessments were integrated with qualitative interviews and focus groups grounded in the consolidated framework for implementation research. The intervention utilized specific curricula focusing on clinical recognition, referral protocols, and documentation. In this study, the participants had a 100% response rate. Median knowledge scores at primary and secondary levels rose from 54.6 (95% CI: 36.4, 63.6) to 90.90 (95% CI: 81.8, 100.0) and from 36.36 (95% CI: 27.3, 45.5) to 90.91 (95% CI: 61.4, 93.7), respectively. Median practice proficiency increased 87.5 (95% CI: 78.7, 100) to 100.00 (95% CI: 100.0, 100.0) at primary level and 68.75 (95% CI: 50.0, 87.5) to 93.8 (95% CI: 86.7, 100.0) at secondary level. The median interval from symptom onset to first health contact fell by 9.3% (from 27.0 days (95% CI: 16.0, 33.3) to 24.5 days (95% CI: 15.0, 32.0)), and the time from first contact to confirmed diagnosis decreased by 54.2%. Treatment initiation interval increased by 11.9%, reflecting ongoing infrastructural constraints. Qualitative findings underscored the roles of supportive leadership, diagnostic supply limitations, cultural beliefs, and referral coordination in shaping outcomes. This quasi-experimental pre-post design without a control group limits strong causal inference, especially in the presence of potential confounders like parallel public-health initiatives and seasonal variations in care-seeking. CONCLUSIONS: A context-tailored, multilevel training and mentorship model was associated with improved provider capacity and reduced diagnostic delays in Northwest Ethiopia. While the initiative demonstrated high fidelity and adaptability in conflict-affected settings, achieving timely treatment requires further investment in diagnostic infrastructure. These tools and protocols are well-positioned for national scale-up and integration into routine continuing medical education.
The well-worn path from armed conflict to measles resurgence.
Hagan JE
PLoS Med · 2026 Jun · PMID 42361064 · Full text
Armed conflict weakens immunization, surveillance, and socioeconomic resilience, increasing measles risk during and after war. Protecting routine vaccination in crises is a core emergency response.
Armed conflict weakens immunization, surveillance, and socioeconomic resilience, increasing measles risk during and after war. Protecting routine vaccination in crises is a core emergency response.
Association of armed conflict and global measles cases: A structural equation modeling analysis of 193 countries from 2000 to 2023.
Headley TY, Tozan Y
PLoS Med · 2026 Jun · PMID 42348569 · Full text
BACKGROUND: Global armed conflict and population displacement are increasing, yet their association with population health remains poorly understood. We developed and tested four theoretical models linking armed conflict...
BACKGROUND: Global armed conflict and population displacement are increasing, yet their association with population health remains poorly understood. We developed and tested four theoretical models linking armed conflict, population displacement, and socioeconomic development to measles burden across 193 countries from 2000 to 2023. METHODS AND FINDINGS: We analyzed longitudinal country-level data comprising 4,632 country-year observations, combining fixed-effects panel regression and structural equation modeling (SEM). Observed variables included battle-related deaths (BRDs) and forcibly displaced population sizes, while socioeconomic development was modeled as a latent variable incorporating gross domestic product (GDP) per capita, life expectancy, and mean years of schooling. Outcomes were total measles cases and incidence per million population. All four constructed models demonstrated excellent fit (Comparative Fit Index [CFI] 0.991-0.996; Tucker-Lewis Index [TLI] 0.976-0.989; Root Mean Square Error of Approximation [RMSEA] 0.046-0.062). Higher contemporaneous BRDs were associated with higher measles cases (β = 0.17; 95% Confidence Interval [CI] [0.14, 0.20]; p < 0.001), adjusting for population displacement and economic development. When prior-year BRDs were included as an observed variable, the direct effect of contemporaneous BRDs was no longer significant (β = 0.05; 95% CI [-0.01, 0.11]; p = 0.091), while the effect of prior-year BRDs was significantly associated with measles cases (β = 0.14; 95% CI [0.08, 0.20]; p < 0.001) but not incidence after accounting for displacement (β = 0.04; 95% CI [-0.02, 0.11]; p = 0.164). Each standard deviation (SD) increase in a country's standardized log-transformed BRDs was associated with an approximately 0.20 SD increase in measles cases, equivalent to 2,500 additional reported cases for every 3,700 BRDs. In all models, BRDs had a slight negative association with socioeconomic development (β = -0.10; 95% CI [-0.13, -0.07]; p < 0.001), and each SD increase in displaced population corresponded with a 0.20 SD decline in socioeconomic development (95% CI [-0.23, -0.17]; p < 0.001), which was the primary pathway by which displacement was associated with measles. Socioeconomic development, in turn, had a significant direct association with both measles cases and incidence, with each SD increase in socioeconomic development corresponding to a 0.32 to 0.34 and 0.34 to 0.36 SD reduction in cases and incidence, respectively (p < 0.001). Key limitations include reliance on national-level annual aggregates, possible under-reporting of both battle-related deaths and measles cases, and the possibility of unmeasured time-varying confounders that preclude causal interpretation. CONCLUSIONS: Armed conflict is associated with an increased measles burden, both directly and indirectly through associations with lower socioeconomic development and greater population displacement. These findings suggest that mitigating infectious disease risks in volatile settings requires a dual strategy: preserving the structural foundations of health and education while systematically integrating displaced populations into routine immunization programs. Future research using subnational and higher-frequency data is needed to clarify the precise mechanisms and timing of these associations across other vaccine-preventable diseases.
Cardiovascular outcomes and safety associated with statin therapy for primary prevention in older adults with type 2 diabetes: A target trial emulation study.
Chan L, Xu W, Chan EWY … +1 more , Wan EYF
PLoS Med · 2026 Jun · PMID 42340940 · Full text
BACKGROUND: There is limited evidence on the use of statins for primary prevention of cardiovascular disease (CVD) in older adults with type 2 diabetes due to underrepresentation of this population in randomized controll...
BACKGROUND: There is limited evidence on the use of statins for primary prevention of cardiovascular disease (CVD) in older adults with type 2 diabetes due to underrepresentation of this population in randomized controlled trials (RCTs). We aimed to determine the effectiveness and safety of statin therapy for primary CVD prevention among type 2 diabetes patients aged ≥75 years. METHODS AND FINDINGS: In this cohort study, territory-wide electronic health records (EHRs) from the Hospital Authority Clinical Management System in Hong Kong were used to emulate a sequence of nested target trials. Eligible patients were included in a rolling basis in each calendar month from January 2009 to December 2015, and thus we emulated 84 'nested monthly trials'. In each monthly trial, all type 2 diabetes patients aged ≥60 years with elevated low-density lipoprotein cholesterol (≥2.6 mmol/L) in the baseline calendar month were included; patients with a history of type 1 diabetes, CVDs, cancers, muscle-related disorders, or liver dysfunction were excluded from analysis. Eligible individuals were classified into statin initiators or noninitiators based on whether they initiated statin therapy at the time of enrollment. They were categorized into various age groups (60-74, 75-84, ≥85 years) for analysis, with those aged 60-74 years forming a benchmark group to test the validity of the emulated target trial. Patients were followed up until the outcome of interest, death, or the administrative end (December 2018), whichever occurred first. We estimated hazard ratios (HRs) comparing statin use versus nonuse for CVDs, all-cause mortality, muscle-related adverse events (AEs), and liver dysfunction using pooled logistic models, with inverse probability weighting to adjust for time-varying confounders related to treatment adherence, under the assumption of no unmeasured confounding. Propensity score matching was performed on eligible person-trials at baseline, incorporating demographic characteristics, clinical and laboratory parameters, comorbidities, medication history, and healthcare utilization as matching variables. Among 30,804 matched person-trials aged 75-84 years, a significant reduction in the incidence of CVDs (HR 0.69 (95% CI [0.65, 0.75]; p < 0.001)) and all-cause mortality (0.65 [0.60, 0.70], p < 0.001) was observed. In 3,798 matched person-trials aged ≥85 years, the benefits were consistently observed (CVDs: 0.65 [0.54, 0.77], p < 0.001; all-cause mortality: 0.61 [0.52, 0.71], p < 0.001). No substantially increased risks for muscle-related AEs or liver dysfunction were observed in both age groups. The effectiveness and safety of statins for the benchmark age group (60-74 years) were also confirmed. The remaining source of bias included the potential misclassification bias due to reliance on diagnosis coding in EHRs, as well as unmeasured confounding relating to lifestyle factors, social determinants, and information on the shared decision-making between physicians and patients. CONCLUSIONS: In type 2 diabetes patients aged ≥75 years, we found that statin use was associated with reduced risks of CVDs and all-cause mortality, including those aged over 85 years. No substantially increased risks for muscle-related adverse events and liver dysfunction were observed. Future studies, including RCTs, are warranted to confirm the effectiveness and safety of statin use in older adults with diabetes, and to determine optimal statin dosing and the comparative efficacy of different statin types, thereby improving CVD prevention in this population.
Multi-omics biomarkers of endothelial dysregulation preceding chronic lung allograft dysfunction: A prospective cohort study.
Iacono G, Begka C, Cardwell B … +9 more , Daunt C, Chatzis R, Pattaroni C, Butler A, Macowan M, Levvey B, Snell GI, Westall GP, Marsland BJ
PLoS Med · 2026 Jun · PMID 42335172 · Full text
BACKGROUND: Long-term survival of lung transplant recipients remains limited by chronic lung allograft dysfunction (CLAD). CLAD is only diagnosed following a persistent and substantial decline in lung function, after whi...
BACKGROUND: Long-term survival of lung transplant recipients remains limited by chronic lung allograft dysfunction (CLAD). CLAD is only diagnosed following a persistent and substantial decline in lung function, after which irreversible damage to the lungs has occurred, limiting opportunities to effectively intervene at an early stage. There is a critical need for earlier detection prior to its clinical manifestation. The immunological drivers of CLAD remain unclear, limiting the development of predictive biomarkers and new therapies. METHODS AND FINDINGS: In this hypothesis-generating, prospective cohort study, we profiled the microbial, metabolic, lipidomic, and gene expression dynamics of longitudinally collected broncho-alveolar lavages (BALs) from 56 CLAD-free lung transplant recipients up to 30 months post-transplant, and compared BALs from 13 CLAD-free patients to BALs from 13 patients who developed CLAD. In CLAD-free patients, the first 6 months post-transplant were hallmarked by diminished microbial diversity and increased abundance of Staphylococcus and Candida, coupled with upregulated innate and adaptive immune responses, and elevated nitric oxide metabolism (FDR < 0.05). This was superseded by homeostatic tissue repair and by the reactivation of T-cell genes such as CD3, GZMA, IL2RB, CD28, CD40LG, and LCK, after tapering of maintenance immunosuppression (FDR < 0.05). In patients who developed CLAD, disease onset was preceded by the increased abundance of sphingolipids and the upregulation of glycocalyx and immune cell recruitment genes such as HAPLN3, HS3ST3B1, SULF2, CHST2, CSGALNACT1, CXCR1, CSF3R, SELL, CXCL2, and CEACAM1 (FDR < 0.05), suggesting increased vascular dysfunction and immune cell graft infiltration prior to CLAD onset. Scoring against a publicly available lung single-cell dataset showed our bulk gene transcriptomics signature to be expressed by monocytes, endothelial, and T cells. In contrast to CLAD-free patients, this signature persisted after 1.5 months post-transplant and increased in intensity upon the start of lung function decline. Multi-omics integration highlighted sphingolipid molecules and genes involved in immune cell recruitment and endothelial function as candidate biomarkers associated with the onset of CLAD. This study is limited by its small sample size. CONCLUSIONS: We have identified immunological processes, metabolites, lipids, and genes associated with the onset of CLAD. Our findings are to be considered associative and not aimed at establishing causality. Future studies employing a targeted approach in independent validation cohorts, using, for example, quantitative polymerase chain reaction (PCR) and targeted mass-spectrometry, will be required to confirm these findings.
Comparisons of core component delivery in cardiac rehabilitation programs by country income classification and decade based on the 2025 Global Audit Update: A survey study.
Ghisi GLM, Carson RP, Turk Adawi K … +23 more , Ding R, Mampuya WM, Jiandani MP, Martinez J, Cruz Rivero M, Anchique CV, van Schalkwijk DL, Gallagher J, Akinci B, Candelaria D, Champaiboon J, Quesada-Chaves DF, Norekvål TM, Szadkowska I, Jug B, Kouidi E, Supervia M, Kim WS, Mettananda C, Mbau L, Aimakova GT, Grace SL, ICCPR Global Cardiac Rehabilitation Audit Update Investigators
PLoS Med · 2026 Jun · PMID 42335042 · Full text
BACKGROUND: Cardiovascular disease (CVD) remains a leading global health burden. Cardiac rehabilitation (CR) is essential to reducing morbidity and improving patient outcomes. Since the COVID-19 pandemic, CR delivery wor...
BACKGROUND: Cardiovascular disease (CVD) remains a leading global health burden. Cardiac rehabilitation (CR) is essential to reducing morbidity and improving patient outcomes. Since the COVID-19 pandemic, CR delivery worldwide has evolved, yet these changes have not been systematically charactemkjrized. The objective of this study was to characterize globally: (1) the delivery of core CR components, including risk factors assessed, patient education practices, and program resources; (2) differences in these elements by country income classification and relative to the initial 2016 Global CR Audit. METHODS AND FINDINGS: A cross-sectional Audit update was conducted. Program-level data were collected from May 1st to September 1st 2025 using a REDCap survey adapted from previous Audits. Eligible respondents were leads of phase II/post-discharge CR programs providing at least an initial assessment, structured aerobic exercise, and ≥1 additional core component. ICCPR associations and local leaders supported program identification. Main outcomes were core components delivered (10 assessed), risk factors assessed (14 assessed), patient education dose (hours/patient/program), and program resources (17 assessed). Generalized linear mixed models (GLMM) tested differences by income classification and (when applicable) changes since 2016. Of 7,025 programs identified globally, 1,505 (62% median country response rate) initiated a survey from 90/113 (80%) countries with CR. The median number of core components offered was 8/program (p25, p75 = 6, 10), with upper-middle income countries offering significantly more components overall (median = 9), and also high-income countries offering more than low-income countries (8 versus 6, p < 0.001; decade change not tested). Programs assessed 11 risk factors/program (median; p25, p75 = 8, 12). This significantly differed by country income class (GLMM p < 0.001), with programs in lower-middle income countries assessing fewer risk factors than those in both upper-middle-income (mean difference = 2.2; p < 0.001) and high-income countries (mean difference = 1.6, p < 0.001). There were significant increases in 2025 for glucose, sleep apnea and sedentariness, among others (ps < 0.01). Patient education dose was 3 hours/supervised program (median; p25, p75 = 1, 7), a significant reduction in many high-income countries since 2016 (p = 0.01). Globally, gym space, resistance training equipment, and individual assessment/counseling space were the most common resources (all >90%; median = 11; p25, p75 = 8, 14). Resource availability differed significantly by country income class (GLMM p < 0.001), with programs in upper-middle-income countries reporting more resources than those in high-income (mean difference = 1.5), lower-middle-income (mean difference = 2.6), and low-income countries (mean difference = 4.8; all p < 0.001). While there were no significant differences in total resources, resistance training equipment, electronic patient charts, body composition analyzers, and stress testing with O2 were more available in 2025, and the availability of administrative office space and group education room less so (ps < .01). Limitations include potential selection and ascertainment bias from incomplete program identification as well as variable, modest program response rates, limited representation from low-income settings, reliance on self-reported survey data, as well as measurement differences across Audit cycles, which may affect generalizability and precision of findings. CONCLUSIONS: CR programs worldwide continue to deliver guideline-concordant care, with education potentially shifting modality. However, modest inequities persist for resource-constrained programs.
Parental body mass index and offspring childhood body size and eating behaviour: A structural equation modelling analysis in the Norwegian Mother, Father and Child Cohort Study.
Bond TA, McAdams TA, Warrington NM … +9 more , Hannigan LJ, Eilertsen EM, Ayorech Z, Torvik FA, Davey Smith G, Lawlor DA, Ystrom E, Havdahl A, Evans DM
PLoS Med · 2026 Jun · PMID 42335027 · Full text
BACKGROUND: The intergenerational transmission of obesity-related traits could propagate an accelerating cycle of obesity, if parental adiposity causally influences offspring adiposity. The extent to which intergeneratio...
BACKGROUND: The intergenerational transmission of obesity-related traits could propagate an accelerating cycle of obesity, if parental adiposity causally influences offspring adiposity. The extent to which intergenerational obesity associations are due to such causal effects, as opposed to genetic confounding (inheritance), is unclear. We aimed to establish whether associations between parental peri-pregnancy body mass index (BMI) and offspring birth weight (BW), BMI until 8 years of age, and 8-year-old eating behaviour are due to genetic confounding. METHODS AND FINDINGS: Data were from the Norwegian Mother, Father and Child Cohort Study, a prospective population-based birth cohort born between 1999 and 2009 at 50 out of 52 hospital maternity units in Norway. We compared the strength of the associations of maternal pre-pregnancy BMI versus paternal BMI during pregnancy, with offspring outcomes including birth weight and BMI assessed between age 6 months and 8 years of age, and appetite-related eating behaviour traits assessed at age 8 years via the Child Eating Behaviour Questionnaire (CEBQ), adjusting for potential confounders including parity, parental/grandparental language group and parental age, smoking, education and income). We then used an extended children of twins structural equation model (SEM) to quantify the extent to which associations were due to genetic confounding. Up to 85,866 children (51.3% male) were included in linear regression models, whereas SEM models included up to 50,999 children. Maternal BMI was more strongly associated than paternal BMI with offspring BW, but the maternal-paternal difference decreased for offspring BMI after birth. Greater parental BMI was associated with obesity-related offspring eating behaviours. SEM results indicated that genetic confounding did not explain the association between parental BMI and offspring BW, but explained the majority of the association with offspring BMI from 6 months onwards. For 8-year BMI, genetic confounding explained 79% (95% CI [62, 95]; p = 1.9 × 10-12) of the covariance with maternal BMI and 94% (95% CI [72, 113]; p = 2.7 × 10-14) of the covariance with paternal BMI. Limitations of this study include selective recruitment and attrition, potential bias due to parental assortative mating, and that findings may not generalise beyond high-income country settings with high obesity prevalence. CONCLUSIONS: We found strong evidence that parent-child BMI associations may primarily be due to genetic confounding. When considered alongside prior evidence, this finding may argue against a strong causal effect of maternal or paternal adiposity on childhood adiposity via intrauterine or periconceptional mechanisms.
Prevalence and epidemiological patterns of Neisseria gonorrhoeae infection in sub-Saharan Africa, 1964-2025: Systematic review, meta-analyses, and meta-regressions.
Osman A, Akram H, Alemrayat B … +3 more , Al-Maraghi S, Harfouche M, Abu-Raddad LJ
PLoS Med · 2026 Jun · PMID 42335017 · Full text
BACKGROUND: Neisseria gonorrhoeae (NG) infection is a global health concern because of its morbidity and increasing antimicrobial resistance. Sub-Saharan Africa is believed to carry a disproportionately high burden of NG...
BACKGROUND: Neisseria gonorrhoeae (NG) infection is a global health concern because of its morbidity and increasing antimicrobial resistance. Sub-Saharan Africa is believed to carry a disproportionately high burden of NG infection, but the epidemiology of NG infection in this region has not been comprehensively synthesized. This study systematically reviewed and analyzed NG prevalence in sub-Saharan Africa to characterize prevalence patterns and identify populations at risk. METHODS AND FINDINGS: A systematic review was conducted and reported following PRISMA guidelines. Embase, PubMed, Scopus, and Web of Science were searched from inception to June 4, 2025. Eligible studies reported NG prevalence in sub-Saharan Africa. Random-effects meta-analyses generated pooled prevalence estimates, and random-effects meta-regression analyses identified associations and sources of heterogeneity. Nine hundred fifty publications contributed 1,604 prevalence measures spanning 1964-2025. In the general population, pooled urogenital prevalence was 3.2% (95% confidence interval (CI): 2.9-3.5), with substantial between-study heterogeneity and a wide prediction interval, indicating considerable variation in prevalence across settings. Prevalence was high in key populations: among female sex workers, 11.5% (95% CI: 9.9-13.2) for urogenital and 2.0% (95% CI: 0.4-4.5) for anorectal infection; and among men who have sex with men, 2.8% (95% CI: 2.4-3.3) for urogenital, 8.3% (95% CI: 5.8-11.0) for anorectal, and 5.7% (95% CI: 3.6-8.3) for oropharyngeal infection. Symptomatic men exhibited high urogenital prevalence (51.5%; 95% CI: 47.5-55.5), and symptomatic women showed 9.0% (95% CI: 7.7-10.4). Among women with adverse pregnancy or birth outcomes, urogenital prevalence was 8.6% (95% CI: 5.3-12.6). Meta-regression analyses explained over half of the variability in prevalence, showing a long-term decline of 1% per year, a clear population type gradient, subregional differences, and decreasing prevalence with increasing age, but no variation by sex. These findings may be affected by variability in data availability across countries, anatomical sites, and population groups, as well as heterogeneity across included studies. CONCLUSIONS: NG prevalence remains markedly high in this region but has declined over time. These findings highlight the need for strengthened surveillance, expanded prevention and diagnostic strategies, and continued monitoring of gonococcal antimicrobial resistance to support effective control efforts in sub-Saharan Africa.
Association between initial benzodiazepine prescribing patterns and time to benzodiazepine discontinuation: A population-based retrospective cohort study.
Bozinoff N, Hauck TS, Kleinman RA … +6 more , Sloan ME, Sproule BA, Vigod SN, Wyman J, Pequeno P, Gomes T
PLoS Med · 2026 Jun · PMID 42313778 · Full text
BACKGROUND: Long-term benzodiazepine use has been associated with increased risk of morbidity and mortality. Preventing long-term use through safer prescribing practices has received little attention to date. We sought t...
BACKGROUND: Long-term benzodiazepine use has been associated with increased risk of morbidity and mortality. Preventing long-term use through safer prescribing practices has received little attention to date. We sought to better understand associations between initial prescription characteristics and duration of benzodiazepine use. METHODS AND FINDINGS: This was a retrospective population-based cohort study of 1,820,808 adults in Ontario with incident benzodiazepine prescriptions between January 1, 2013 and December 31, 2020, with follow-up to December 31, 2021. The primary exposure was duration of the index prescription (≤7 days-referent group, 8-14 days, 15-30 days, or >30 days). Secondary exposures were: (a) duration of action of index benzodiazepine(s) prescription (short-acting, long-acting or both); (b) number of benzodiazepine dispensed on index (1 or 2+); and (c) mean daily dose of the index prescription in Diazepam Milligram Equivalents (DMEs). The primary outcome was time to benzodiazepine discontinuation in days. Multivariable models were adjusted for age, sex, anxiety, insomnia, and substance use disorders as well as other important comorbidities and socio-demographic characteristics. The median age at index was 53 years (Interquartile Range (IQR) 38-67), and 62.6% were women. The median time to discontinuation in women was 16 days (IQR: 6-29) while the median time to discontinuation in men was 19 days (IQR: 6-29). Lorazepam was the most commonly prescribed benzodiazepine on index (63.9%), followed by clonazepam (17.3%) and diazepam (5.8%). In multivariable Cox Proportional Hazards Models, longer index prescriptions were associated with a lower likelihood of benzodiazepine discontinuation (adjusted Hazard Ratio (aHR) 0.54 (95% Confidence Interval (CI) [0.54,0.54]) for 8-14 days; aHR 0.26 (95% CI [0.25,0.26] for 15-30 days and aHR 0.14 (95% CI [0.14,0.14]) for >30 days, compared to ≤7 days, respectively). Being prescribed two or more benzodiazepines versus 1 was also associated with a reduced likelihood of discontinuation (aHR 0.59 (95% CI [0.57,0.61])), as was being prescribed long-acting benzodiazepines (aHR 0.80 (95% CI [0.80,0.80])) or a combination of short and long acting benzodiazepine (aHR 0.84 (95% CI [0.80,0.88])) versus short-acting benzodiazepines alone. Mean daily doses of >5 to ≤10 DME and >10 to ≤20 DME were associated with an increased likelihood of discontinuation (aHR 1.03 (95% CI [1.03,1.03]); aHR: 1.03 (95% CI [1.03,1.04])), whereas doses >20 DME were associated with a reduced likelihood of discontinuation (aHR 0.98 (95% CI [0.97,0.98])) compared with ≤5 DME. Findings may be subject to bias from unmeasured confounding. CONCLUSION: This large population-based cohort study found that prescribing shorter courses of benzodiazepines, use of a single benzodiazepine, use of a short-acting agent, were associated with reduced likelihood of long-term benzodiazepine use. Findings suggest that simple changes to prescribing practices could reduce prolonged benzodiazepine use and the morbidity and mortality associated with long-term use of these medications.
The data transparency crisis in research: Lessons from systematic reviews and meta-analyses.
Martin-Rodriguez S, Fernandez-Gonzalo R, Moher D
PLoS Med · 2026 Jun · PMID 42302069 · Full text
Systematic reviews and meta-analyses underpin clinical guidelines and health policy, yet their validity may be compromised by limited access to underlying datasets and associated analytical code.Reliance on incomplete or...
Systematic reviews and meta-analyses underpin clinical guidelines and health policy, yet their validity may be compromised by limited access to underlying datasets and associated analytical code.Reliance on incomplete or inconsistently reported summary statistics forces researchers to use imputation and unverifiable assumptions, which can distort effect estimates and mislead clinical decision-making.The consequences extend beyond methodology: flawed evidence synthesis can influence treatment recommendations, healthcare spending, and patient safety, as illustrated by historical cases such as hormone replacement therapy.Despite widespread data-sharing policies, compliance remains low, enforcement weak, and monitoring almost non-existent, with many datasets remaining unavailable or inaccessible.This Policy Forum argues for strengthening enforceable data-sharing mechanisms, including clearer enforcement and pragmatic verification approaches within editorial workflows.
Comparison of count-based and clustering definitions of multimorbidity and their association with prevalence of multimorbidity, health profiles, and mortality: A cohort study of UK Biobank participants.
Silva GC, Fayosse A, Jacob L … +3 more , Sabia S, Singh-Manoux A, Landré B
PLoS Med · 2026 Jun · PMID 42284367 · Full text
BACKGROUND: Multimorbidity, the presence of several chronic conditions, is linked to higher mortality and healthcare use and thus poses a major challenge for aging populations. While most studies rely on simple counts of...
BACKGROUND: Multimorbidity, the presence of several chronic conditions, is linked to higher mortality and healthcare use and thus poses a major challenge for aging populations. While most studies rely on simple counts of conditions, clustering approaches have been proposed to describe patterns of co-occurring diseases. We aimed to evaluate the extent to which these methodological choices influence prevalence and association with health profiles and mortality. METHODS AND FINDINGS: Using UK Biobank baseline data (n = 474,397), collected between 2006 and 2010, we compared six count-based definitions of multimorbidity based on different condition lists (extended, most prevalent, or body systems) and thresholds (≥2 versus ≥3 conditions). We also applied a clustering analysis to characterize subtypes of multimorbidity among participants with at least two chronic conditions. We compared prevalence and associations with concurrent health outcomes (polypharmacy, self-rated health, frailty, falls, surgery, chronic pain), blood-based measures (C-reactive protein, Cystatin-C, HDL, LDL Cholesterol, IGF-1), and 3- and 10-year mortality risks. Analyses were undertaken separately in men and women using multivariable regression models adjusted for sociodemographic characteristics and body mass index. Multimorbidity prevalence ranged from 1.0% (cluster-based) to 35.3% (count-based). Count-based definitions using lists with more conditions yielded higher prevalence. Higher thresholds identified more severe health profiles on all measured health outcomes, blood-based measures, but not higher mortality risks. Associations with blood-based measures were more pronounced using clustering, with the highest differences from the standard definition distributed across clusters. Odds ratios for 3-year mortality ranged from 1.44 [1.26; 1.64] to 4.60 [3.73; 5.62] for men and 1.35 [1.07; 1.69] to 3.83 [2.78; 5.14] for women. For 10-year mortality, they ranged from 1.42 [1.34; 1.50] to 3.86 [3.46; 4.30] in men and 1.29 [1.21; 1.39] to 3.33 [2.93; 3.77] for women, with clustering identifying groups with low prevalence and high mortality risks. Findings should be interpreted in light of the selected nature of the UK Biobank cohort and the cross-sectional assessment of several health indicators. CONCLUSION: Operational definitions of multimorbidity substantially influence prevalence estimates, while associations with mortality appear more robust across count-based approaches. Clustering analyses provide complementary insights into heterogeneity within multimorbid populations. Future translational studies are warranted to determine how multimorbidity definitions can be optimized to ultimately improve clinical management and health outcomes in practice.
Placenta accreta spectrum in the 21st century: Challenging dogma and redefining disorder.
Jauniaux E, Bartels HC, Afshar Y
PLoS Med · 2026 Jun · PMID 42284360 · Full text
Placenta accreta spectrum (PAS) is a serious pregnancy complication caused by abnormal placental attachment to the uterus. In this Perspective, Eric Jauniaux and colleagues discuss emerging evidence that challenges our l...
Placenta accreta spectrum (PAS) is a serious pregnancy complication caused by abnormal placental attachment to the uterus. In this Perspective, Eric Jauniaux and colleagues discuss emerging evidence that challenges our long-held pathophysiological understanding of PAS, and argue that a critical reassessment of definition, diagnosis, and management is overdue.
Prediction of hospitalisation in young children with pneumonia in Malawi: A machine learning-based approach.
Staunton P, Makrooni MA, Chisale M … +9 more , Nyambolo B, Wu J, McCarthy D, Ledwidge M, Bin Nisar Y, Watson C, Mbakaya B, Seoighe C, Gallagher J
PLoS Med · 2026 Jun · PMID 42263118 · Full text
BACKGROUND: Globally, pneumonia remains the single biggest cause of mortality in children under 5 years of age. This study sought to train and test a prediction model for hospitalisation within 7 days after initial prese...
BACKGROUND: Globally, pneumonia remains the single biggest cause of mortality in children under 5 years of age. This study sought to train and test a prediction model for hospitalisation within 7 days after initial presentation in 2- to 59-month-old Malawian children with WHO-defined pneumonia in primary care and compare its performance to existing risk prediction models. METHODS AND FINDINGS: BIOTOPE is a cohort study of children with pneumonia in a primary healthcare setting in Malawi. The training cohort involved nine primary care centres and the testing cohort involved two primary care centres in Northern Malawi. The training cohort was recruited between December 2022 and April 2023 while the testing cohort was recruited in 2016. Participants were consecutive children aged 2-59 months presenting with cough and/or difficulty breathing and who were diagnosed as WHO-defined pneumonia in primary care of any severity. The training cohort was used to train and validate a machine learning model with a prespecified primary outcome defined as hospitalisation and/or death within 7 days as the outcome. This model was then further evaluated in the testing cohort. Median age was 15 months (interquartile range 8-27) in the training and 17 months (interquartile range 9-29) in the external testing cohort (52.1% and 54.4% male, respectively). Hospitalisation occurred in 14.3% (294) of the training cohort and 12.1% (55) of the testing cohort. There was one death in the training cohort only. WHO danger signs were present in 17.6% (360) and 15.9% (70) of children in the training and testing cohorts, respectively. The optimal machine learning model achieved an area under the receiver operating characteristic and precision recall curves of 0.87 and 0.57, respectively, in the testing cohort outperforming existing risk prediction models; furthermore, this model produced an expected calibration error of 0.16 (a logistic regression model using severity status as the response variable and the log odds of the machine learning model's calibrated probabilities produced an intercept estimate of -0.32 and a slope estimate of 1.13). Key limitations include the use of hospitalisation and/or death as a severity outcome, which may reflect health system factors rather than true disease severity, that mortality-based comparisons were not possible due to low mortality in these primary care cohorts, and that comparator tools were developed for hospital populations rather than primary care populations. CONCLUSION: This machine learning score outperformed traditional pneumonia risk scores in predicting hospitalisation within 7 days in Malawian children presenting to primary care. Traditional pneumonia risk scores diminish in performance when externally applied to new datasets suggesting they may not generalise well beyond their original derivation settings. Mortality-related findings are not applicable as there was only one death in this cohort. Overall these findings support the potential of machine learning to meaningfully improve early identification of children at risk of severe pneumonia in low-resource primary care settings. Further external validation and clinical impact studies are needed to confirm these results.
Molecular Tumor Boards clinical impact on patient care and structural features: A systematic review and meta-analysis.
Russo L, Giacobini E, Lentini N … +4 more , Osti T, Kamal M, Boccia S, Pastorino R
PLoS Med · 2026 Jun · PMID 42263112 · Full text
BACKGROUND: Molecular Tumor Boards (MTBs) bring together multidisciplinary experts to translate genomic data into clinical decisions in oncology, however, their overall clinical impact remains unclear. The aim of this sy...
BACKGROUND: Molecular Tumor Boards (MTBs) bring together multidisciplinary experts to translate genomic data into clinical decisions in oncology, however, their overall clinical impact remains unclear. The aim of this systematic review is to assess the clinical impact of MTB-recommended therapies on patients with cancer outcomes. METHODS AND FINDINGS: In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and CENTRAL up to July 2025. We included studies of any design, both single-arm studies and studies with a comparator group, that reported the clinical impact of MTBs in patients who received MTB-guided therapy. Meta-analyses were performed separately by study design, using hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), relative risks (RRs) for objective response rate (ORR) and disease control rate (DCR), and pooled proportions for PFS ratio ≥1.3. All meta-analyses were conducted using random-effects models based on the inverse variance method. We evaluated the risk of bias using the RoB 2.0 for RCTs and ROBINS-I for non-randomized studies. From 6,846 records, 78 studies (9,195 patients; 4,569 treated per MTB recommendations) were included. MTB-guided therapies were associated with reduced risk of death (HR 0.87; 95% CI [0.76, 1.01]; p = 0.069; I2 = 0.0% in RCTs; 0.62 in retrospective studies) and disease progression (HR 0.73; 95% CI [0.64, 0.84]; p < 0.001; I2 = 0.0% in RCTs; 0.63 in retrospective studies), as well as improved ORR (RR 1.75; 95% CI [1.24, 2.47]; p = 0.001; I2 = 0.0% in RCTs; 3.32 in retrospective studies) and DCR (RR 1.20; 95% CI [1.03, 1.40]; p = 0.018; I2 = 19.9% in RCTs; 1.65 in retrospective studies). Between 33% and 43% of patients achieved a PFS ratio ≥1.3. While the risk of bias for RCTs was low, except for one study that was rated as having some concerns, the overall risk of bias for non-randomized studies was rated as "serious" in most of the studies (n = 54). Limitations include substantial heterogeneity, predominance of non-randomized studies with risk of bias, and limitations in data reporting, which restrict causal inference. CONCLUSIONS: This meta-analysis provides robust evidence from RCTs supporting the clinical benefit of MTBs, although limited for OS. Methodological heterogeneity and study limitations from observational studies warrant cautious interpretation. Future high-quality RCTs and standardized reporting are needed to confirm these findings and guide the integration of MTBs into routine clinical practice and health system strategies.
Beyond associations: Navigating the safety of non-steroidal anti-inflammatory drugs (NSAIDs) in early pregnancy.
Yuen ASC, Man KKC
PLoS Med · 2026 Jun · PMID 42241474 · Full text
Pain and fever in pregnancy require treatment, but fetal safety concerns complicate analgesic choice. A recent PLOS Medicine study presents new evidence on the safety of first-trimester NSAID use and congenital malformat...
Pain and fever in pregnancy require treatment, but fetal safety concerns complicate analgesic choice. A recent PLOS Medicine study presents new evidence on the safety of first-trimester NSAID use and congenital malformation risk, but interpreting findings across studies is challenging.
Comparative impacts and cost-effectiveness of tuberculosis systematic screening strategies in prisons in Brazil, Colombia, and Peru: A mathematical modeling study.
Liu YE, Bampi JVB, Arthur RF … +21 more , Salindri AD, Busatto C, Jiménez PA, Pelissari DM, Johansen FDC, Arana-Narvaez R, Roca AFM, Solís Tupes WS, Jiu EM, Roca CAM, Abregú Contreras EA, Guizado VAA, Trujillo JT, Marcelino B, Gonzalez MA, Córdova Ayllon MC, Cohen T, Huaman MA, Goldhaber-Fiebert JD, Croda J, Andrews JR
PLoS Med · 2026 Jun · PMID 42241460 · Full text
BACKGROUND: Incarceration is a leading driver of tuberculosis in Latin America. Systematic screening in prisons may reduce tuberculosis burden, but optimal strategies and cost-effectiveness remain uncertain. We examined...
BACKGROUND: Incarceration is a leading driver of tuberculosis in Latin America. Systematic screening in prisons may reduce tuberculosis burden, but optimal strategies and cost-effectiveness remain uncertain. We examined the population-wide health impacts and cost-effectiveness of systematic screening in prisons in Brazil, Colombia, and Peru, comparing different timepoints, frequencies, and screening algorithms. METHODS AND FINDINGS: Using dynamic transmission models calibrated to Brazil, Colombia, and Peru, we simulated annual or biannual (twice-yearly) prison-wide screening, alone or combined with entry and exit screening from 2026 to 2035. We evaluated four algorithms: (1) symptom screening, (2) chest X-ray with computer-aided detection (CXR-CAD), (3) symptoms and CXR-CAD (follow-up testing if either is positive), and (4) GeneXpert Ultra (Xpert) with pooled sputum. Individuals screening positive then received individual Xpert. We projected impacts on within-prison and population-level tuberculosis incidence in 2035, along with discounted costs (2023 US dollars) and disability-adjusted life years (DALYs). Model projections showed that combined entry, exit, and biannual screening with CXR-CAD was highly impactful and cost-effective across countries, reducing tuberculosis incidence by 61%-87% in prisons and 18%-28% population-wide. Compared to only biannual CXR-CAD (the next best strategy), the incremental cost per DALY averted of adding entry and exit screening was $2,984 (Brazil), $2,925 (Colombia), and $645 (Peru). Adding symptom screening to CXR-CAD marginally increased benefit and was only cost-effective in Peru's higher-incidence prisons. Biannual screening alone remained cost-effective at prison incidence levels well below national averages, as well as at far lower willingness-to-pay thresholds. In settings without CXR-CAD, pooled Xpert was an impactful, cost-effective alternative. Key limitations include the model's simplified representation of tuberculosis disease states and lack of stratification by age, gender/sex, HIV, or drug resistance. CONCLUSIONS: These modeling results support immediate national-level adoption of prison-wide tuberculosis screening twice-yearly and at entry and exit, using CXR-CAD or pooled Xpert.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe