PLoS Medicine[JOURNAL]
Sun
200 papers
Clinical and economic impact of genome-wide non-invasive prenatal testing (NIPT) as a first-tier screening method compared to targeted NIPT and first-trimester combined testing: A modeling study.
van Prooyen Schuurman L, de Koning HJ, Meier E … +2 more , Galjaard RH, van Ravesteyn NT
PLoS Med · 2025 Nov · PMID 41191637 · Full text
BACKGROUND: Evidence on the diagnostic yield of genome-wide non-invasive prenatal testing (GW-NIPT) is growing, but its comparative clinical and economic impact as a first-tier screening strategy for fetal chromosomal ab...
BACKGROUND: Evidence on the diagnostic yield of genome-wide non-invasive prenatal testing (GW-NIPT) is growing, but its comparative clinical and economic impact as a first-tier screening strategy for fetal chromosomal abnormalities remains unassessed. We compared GW-NIPT with targeted NIPT and first-trimester combined testing (FCT), in a Dutch setting where all pregnancies also undergo a routine second-trimester anomaly ultrasound scan (scan), to guide policymakers on optimal prenatal screening approaches. METHODS AND FINDINGS: We developed a decision-analytic model for a cohort of 175,000 pregnancies, reflecting the Dutch obstetric population. All strategies screened for common trisomies 21 (Down syndrome), 18 (Edwards syndrome), and 13 (Patau syndrome); GW-NIPT additionally considered rare autosomal trisomies and structural aberrations. Model inputs were based on the TRIDENT-2 study data and historical FCT data. Base-case unit costs were €166 (scan), €191 (FCT), and €350 (NIPT). Sensitivity analyses were conducted to account for uncertainties in model parameters and potential country-specific variations. Outcomes included total screening costs, number of fetal chromosomal abnormalities diagnosed, number of invasive procedures, and expected procedure-related euploid fetal losses. We summarized economic results as cost per diagnosed case and incremental cost per additional diagnosis across strategies. GW-NIPT yielded the highest number of diagnoses (545) versus targeted NIPT (514) and FCT (452), and the lowest cost per diagnosed case (€152,785), compared with targeted NIPT (€159,852) and FCT (€170,050). Invasive tests required per diagnosis were lower for GW-NIPT and targeted NIPT (both 6) than for FCT (13), implying a lower risk of procedure-related miscarriage (iatrogenic miscarriage). Sensitivity analyses indicated that test uptake and unit costs strongly influenced outcomes. GW-NIPT remained the most favorable in terms of cost per diagnosis for NIPT prices up to €467. Key limitations include the use of a decision-analytic model without quality-of-life outcomes and the lack of comparisons against explicit cost-effectiveness thresholds. Therefore, the results should be interpreted as relative clinical and economic comparisons rather than cost-effectiveness judgements. CONCLUSIONS: Among the strategies evaluated, first-tier GW-NIPT had the greatest diagnostic yield and the lowest cost per diagnosis, improving detection rates and supporting reproductive autonomy at lower costs. Implementation decisions should also consider local pricing, laboratory capacity, and counseling resources. Future research that links screening outcomes to long-term health consequences (e.g., quality-adjusted life years or life-years), healthcare utilization, costs, and psychosocial outcomes will enable formal cost-effectiveness evaluations and support further refinement of prenatal screening policy.
Combining demographic shifts with age-based resistance prevalence to estimate future antimicrobial resistance burden in Europe and implications for targets: A modelling study.
Waterlow NR, Chandler CIR, Cooper BS … +5 more , Moore CE, Robotham JV, Sartorius B, Sharland M, Knight GM
PLoS Med · 2025 Nov · PMID 41187143 · Full text
BACKGROUND: Antimicrobial Resistance (AMR) is a global public health crisis. Evaluating intervention impact requires accurate estimates of how the AMR burden will change over time, given likely demographic shifts. This s...
BACKGROUND: Antimicrobial Resistance (AMR) is a global public health crisis. Evaluating intervention impact requires accurate estimates of how the AMR burden will change over time, given likely demographic shifts. This study aimed to provide an estimate of future AMR burden in Europe, investigating resistance variation by age and sex and the impact of interventions to achieve the proposed United Nations (UN) political declaration targets. METHODS AND FINDINGS: Using data from 12,807,473 bloodstream infection (BSI) susceptibility tests from routine surveillance in Europe, we estimate age- and sex-specific rates of change in BSI incidence for the 8 bacteria included in European Antimicrobial Resistance Surveillance Network (EARS-Net) surveillance over 2015-2019. This was used to project incidence rates by age and sex for 2022-2050 and, with demographic projections, to generate estimates of BSI burden (2022-2050). Two Bayesian hierarchical models were fitted across 38 bacteria-antibiotic combinations to the 2015-2019 resistance proportion of BSI by year and at the country-level with and without age and sex disaggregation. Inputting the incidence estimates into the "agesex" and "base" model, respectively, we sampled 1,000 model estimates of resistant BSI burden by age, sex, and country to determine the importance of age and sex disaggregation. We explored Intervention scenarios consisting of a 1, 5, or 20 per 100,000 per year reduction in infection incidence rate of change or 5 per 100,000 per year reduction in those older than 64 years. Overall, in Europe, BSI incidence rates are predicted to increase more in men than women across 6 of the 8 bacteria (Pseudomonas aeruginosa and Enterococcus faecium were the exception) and are projected to increase more dramatically in older age groups (74+ years) but stabilise or decline in younger age groups. We project huge country-level variation in resistance burden to 2050, with opposing trends in different countries for the same bacteria-antibiotic combinations (e.g., aminoglycoside-resistant Acinetobacter spp. ranged from a relative difference of 0.34 to 15.38 by 2030). Not accounting for age and sex results in differing resistance burden projections, with 47% of bacteria-antibiotic combinations estimated to have fewer resistant BSIs by 2030 compared to a model with age and sex. Not including age or sex resistance patterns results in fewer male cases for 76% (29/38) of the combinations compared to 11% (4/38) for women. We also saw age-based associations in projections with bigger differences at older ages. Achieving a 10% reduction in resistant BSI incidence by 2030 (equivalent to the UN 10% mortality target) was possible only for 68.4% (26/38) of bacteria-antibiotic combinations even with large reductions in BSI incidence rate of change of -20 per 100,000 per year. In some cases, a 10% reduction was followed by a rebound, with the resistant BSI burden exceeding previous levels by 2050. Limitations include reliance on European data and current trends, and the exclusion of factors such as comorbidities or ethnicity. CONCLUSIONS: Including country-specific, age- and sex-specific resistance levels alongside projected demographic shifts has a large impact on resistant BSI burden projections in Europe to 2030. Reducing this AMR infection burden by 10% will require substantial reductions in infection incidence rates.
Financial risk protection from vaccines in 52 Gavi-eligible low- and middle-income countries: A modeling study.
Jiao B, Sato R, Mak J … +16 more , Patenaude B, de Villiers M, Deshpande A, Gamkrelidze I, Gaythorpe KAM, Hallett TB, Jit M, Li X, Lopman B, Nayagam S, Razavi-Shearer D, Tam Y, Woodruff KH, Hogan D, Mengistu T, Verguet S
PLoS Med · 2025 Nov · PMID 41187138 · Full text
BACKGROUND: Poverty alleviation is a major global development goal. Vaccines have the potential to provide financial risk protection (FRP) by preventing illnesses and associated healthcare costs. We estimate the lifetime...
BACKGROUND: Poverty alleviation is a major global development goal. Vaccines have the potential to provide financial risk protection (FRP) by preventing illnesses and associated healthcare costs. We estimate the lifetime FRP benefits generated by major vaccines among individuals vaccinated between 2000 and 2030 in low- and middle-income countries (LMICs). METHODS AND FINDINGS: We developed a microsimulation model to quantify the number of cases of catastrophic health expenditure (CHE) averted by a range of vaccines in 52 Gavi-eligible countries, stratified by wealth quintile. Vaccines protecting against five pathogens were considered, i.e., hepatitis B (routine and birth dose vaccine), Haemophilus influenzae type B, rotavirus, measles (routine and supplementary campaign vaccine), and Streptococcus pneumoniae. Model inputs were obtained from secondary data sources, including infection reduction rates under various immunization coverage scenarios, out-of-pocket health expenditures, transportation costs, wage losses, and healthcare utilization associated with disease treatment and consumption expenditures. CHE cases were defined as exceeding 10% of annual consumption, with sensitivity analyses conducted using thresholds of 25% and 40%, as well as impoverishing health expenditures were estimated. All vaccines, singly and collectively, showed a large impact on FRP and could avert ~200 million CHE cases across 52 Gavi-eligible countries from 2000 to 2030. Importantly, about half of all CHE cases were prevented among the poorest quintiles. When evaluated at a 10% threshold for CHE, the first dose of measles vaccine stood out in averting around 1,400 CHE cases per 10,000 vaccinated individuals in the poorest quintile, that is a total of 44 million CHE cases averted. A key limitation is the assumption of uniform disease risks in the absence of vaccination across quintiles, which may underestimate benefits for poorer groups. CONCLUSIONS: Vaccines can provide substantial FRP benefits, particularly among the most disadvantaged populations. Sustained investments to ensure vulnerable populations receive vaccinations in LMICs can therefore not only improve health outcomes but also contribute to poverty reduction.
Cervical pessary versus vaginal progesterone in women with a multiple pregnancy and a short cervix: A randomised controlled trial.
van Dijk CE, van Gils AL, van Zijl MD … +17 more , Koullali B, van der Weide MC, van den Akker ES, Hermsen BJ, van Drongelen J, de Boer MA, van Baal WM, Vollebregt KC, van der Made FW, Gordijn SJ, Sueters M, Wijnberger LDE, Oudijk MA, Mol BWJ, Kazemier BM, Pajkrt E, Quadruple P Research Group
PLoS Med · 2025 Nov · PMID 41183078 · Full text
BACKGROUND: In absence of direct comparisons, consensus on the preferred preventive treatment for multiple pregnancies with a short cervix is lacking. Therefore, we compared the effectiveness of a cervical pessary and va...
BACKGROUND: In absence of direct comparisons, consensus on the preferred preventive treatment for multiple pregnancies with a short cervix is lacking. Therefore, we compared the effectiveness of a cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth (PTB) in women with a multiple pregnancy, no prior spontaneous PTB (sPTB) before 34 weeks' gestation, and an asymptomatic mid-trimester shortened cervix below 38 mm. METHODS AND FINDINGS: This open-label, superiority, multi-centre randomised controlled trial was conducted in 20 hospitals in the Netherlands. Women with a healthy multiple pregnancy and an asymptomatic cervical length (CL) below 38 mm between 16 and 22 weeks' gestation were eligible, with a target sample size of 332. Following an interim analysis, the study was halted for futility. A total of 276 multiples, including seven triplet pregnancies, were randomised 1:1 to receive either an Arabin cervical pessary (N = 138) or vaginal progesterone 200 mg daily (N = 138) until 36 weeks' gestation or earlier if indicated. The primary outcome was a composite adverse perinatal outcome, with secondary outcomes including rates of (s)PTB before 24, 28, 32, 34, and 37 weeks. Predefined subgroup analyses were conducted based on CL, parity, chorionicity, and number of foetuses. Among 531 neonates (pessary N = 269, progesterone N = 262), the composite adverse perinatal outcome occurred in 19.7% of neonates in the pessary group versus 13.7% in the progesterone group (crude RR 1.43; 95% CI [0.85,2.4], p = 0.18). The rates of (s)PTB were not significantly different between groups. In the subgroup with a CL of ≤25 mm, no significant difference in the composite perinatal outcome was found (41.1% versus 34.7%, RR 1.18; 95% CI [0.60,2.33], interaction p = 0.63). However, among nulliparous women, the composite outcome was more frequent in the pessary group compared to progesterone (30.0% versus 15.9%, RR 1.88; 95% CI [1.03,3.43], interaction p = 0.93). The study's main limitations include the inability to blind interventions, potentially introducing bias, and low self-reported medication compliance in the progesterone group, which may have led to overestimated adherence and underestimated progesterone's preventive potential in the per-protocol analysis. CONCLUSION: In women with multiple pregnancies and a midtrimester short cervix below 38 mm, we found no superiority of a cervical pessary compared to vaginal progesterone the prevention of perinatal complications. While progesterone may have a modest effect, future studies should focus on other interventions in multiple pregnancies such as a cerclage, both ultrasound- and physical examination-indicated. TRIAL REGISTRATION: This trial was registered at the International Clinical Trial Registry Platform (ICTRP, EUCTR2013-002884-24-NL, https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2013-002884-24-NL).
Raising the bar for causal inference: PLOS Medicine adopts the TARGET guidelines for target trial emulation studies.
Lumbard H, PLOS Medicine Staff Editors
PLoS Med · 2025 Oct · PMID 41171832 · Full text
The TARGET guidelines aim to improve transparency and consistency in reporting of observational studies that emulate target trials. In alignment with these goals, PLOS Medicine fully endorses the TARGET guidelines and no...
The TARGET guidelines aim to improve transparency and consistency in reporting of observational studies that emulate target trials. In alignment with these goals, PLOS Medicine fully endorses the TARGET guidelines and now asks that new submissions of target trial emulation studies adhere to them.
Associations between epileptic seizures in pregnancy and adverse pregnancy outcomes: A systematic review and meta-analysis.
Olalere O, Tariq S, Ajijola O … +23 more , Koh MD, Crabb K, Wilson A, Chatterjee A, Black M, Morris K, Bluett-Duncan M, Taylor E, Raju S, Junaid F, Bromley R, Moss N, Garcia-Finana M, Craig J, Wood A, Weckesser A, Dyson J, Nelson-Piercy C, Denny E, Roberts T, McNeill R, Thangaratinam S, Allotey J
PLoS Med · 2025 Oct · PMID 41171824 · Full text
BACKGROUND: Epileptic seizures during pregnancy may increase the risk of adverse pregnancy outcomes. Socioeconomic disparities in epilepsy incidence may extend to seizure control. We conducted a systematic review and met...
BACKGROUND: Epileptic seizures during pregnancy may increase the risk of adverse pregnancy outcomes. Socioeconomic disparities in epilepsy incidence may extend to seizure control. We conducted a systematic review and meta-analysis to assess the association between epileptic seizures during pregnancy and adverse pregnancy outcomes. We also evaluated the association between socioeconomic and individual-level factors and seizure occurrence. METHODS AND FINDINGS: We searched MEDLINE, Embase, CINAHL, and PsycINFO databases from inception to May 2025 for observational studies on pregnant women with epileptic seizures. We compared maternal and foetal outcomes in pregnant women with and without seizures and assessed the association between seizure occurrence and socioeconomic or individual-level factors. We used the Newcastle-Ottawa Scale to assess the risk of bias of included studies. Meta-analyses using random effects model were performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs). From 13,381 identified publications, 25 studies (24,596 pregnancies) are included in this analysis. In pregnant women with epilepsy, women with seizures compared to those without had increased odds of caesarean birth (OR 1.62, 95% CI 1.14 to 2.30, p = 0.007), peripartum depression (OR 2.20, 95% CI 1.04 to 4.65, p = 0.04), and small for gestational age baby (OR 1.32, 95% CI 1.03 to 1.69, p = 0.03). The odds of preterm birth (OR 1.66, 95% CI 1.29 to 2.15, p < 0.001), low birthweight (OR 1.47, 95% CI 1.12 to 1.93, p = 0.006), and small for gestational age baby (OR 1.44, 95% CI 1.19 to 1.74, p < 0.001) were higher in women with seizures compared to women without epilepsy. The risk of seizures was greater in pregnant women with epilepsy with low income compared to those with higher income (OR 1.57, 95% CI 1.22 to 2.02, p < 0.001), and in women with focal epilepsy compared to those with generalised epilepsy (OR 1.84, 95% CI 1.54 to 2.20, p < 0.001). The number of studies for some outcomes was small, limiting subgroup analyses and detection of heterogeneity. CONCLUSION: Epileptic seizures are associated with increased risks of adverse maternal and foetal outcomes. Risk assessment to identify women with epilepsy at highest risk of seizures is needed to optimise care.
Heart failure diagnosis: Impacts of atrial fibrillation on the diagnostic marker NT-proBNP.
Chen Y, McDowell G, Lip GYH
PLoS Med · 2025 Oct · PMID 41171700 · Full text
A recent PLOS Medicine study shows that atrial fibrillation lowers the specificity of the biomarker NT-proBNP for heart failure. Adjusted thresholds and better echocardiography access are therefore required for NT-proBNP...
A recent PLOS Medicine study shows that atrial fibrillation lowers the specificity of the biomarker NT-proBNP for heart failure. Adjusted thresholds and better echocardiography access are therefore required for NT-proBNP to remain as a high negative predictive value rule-out test in primary care.
NT-proBNP testing for heart failure diagnosis in people with atrial fibrillation: A diagnostic accuracy study.
Jones NR, Taylor KS, Ordóñez-Mena JM … +3 more , Goyder CR, Hobbs FDR, Taylor CJ
PLoS Med · 2025 Oct · PMID 41166233 · Full text
BACKGROUND: N-terminal pro-B-type natriuretic peptides (NT-proBNP) are important in the assessment of suspected heart failure (HF). However, NT-proBNP concentrations are elevated in atrial fibrillation (AF), creating dia...
BACKGROUND: N-terminal pro-B-type natriuretic peptides (NT-proBNP) are important in the assessment of suspected heart failure (HF). However, NT-proBNP concentrations are elevated in atrial fibrillation (AF), creating diagnostic uncertainty. The aim of this study was to assess the diagnostic accuracy of NT-proBNP for HF in people with AF, overall and by age, sex and BMI. METHODS AND FINDINGS: Retrospective study of all patients with a NT-proBNP test in their primary care electronic health record among English GP practices provided through the Clinical Practice Research Datalink (2004-2018) and linked to secondary care data. The accuracy of NT-proBNP for diagnosing HF within six months was assessed for people with and without AF at thresholds of 125, 400, 660 and 2,000 pg/mL, including by age, sex and BMI. Among 155,347 people who had an NT-proBNP test organized in primary care (median age 61 years), 17,403 (11.2%) had pre-existing AF. Of the 155,347 people included, 14,585 (9.4%) were subsequently diagnosed with HF, including 4,168/17,403 (23.9%) people with AF (median NT-proBNP = 1,852 pg/mL, interquartile range (IQR) [974, 3,459] pg/mL) and 10,417/137,944 (7.6%) without AF (1,110 pg/mL, IQR [434, 3,108] pg/mL). NT-proBNP discriminated better overall among people without AF (AUC = 0.877 (95% confidence interval (CI) [0.873, 0.881]) than with AF (AUC = 0.743 (95% CI [0.735, 0.751]). Among people with AF, NT-proBNP sensitivity and specificity at a 125 pg/mL threshold was 98.8% (95% CI [98.5%, 99.1]) and 13.2% (95% CI [12.6%, 13.7]) and at 400 pg/mL 93.2% (95% CI [92.4, 93.9]) and 35.5% (95% CI [34.7, 36.3]). Among people without AF the corresponding results were 92.9% (95% CI [92.4, 93.4]) and 53.8% (95% CI [53.6, 54.1]) at 125 pg/mL and 77.1% (95% CI [76.3, 77.9]) and 84.9% (95% CI [84.7, 85.1]) at 400 pg/mL. NT-proBNP discriminated less well among people with AF aged ≥65 years compared to <65years (e.g., AUC in people aged 65-75 years was 0.725, 95% CI [0.712, 0.739]). Increasing the threshold for a positive test among people with AF from 125 pg/mL to 660 pg/mL would reduce the number of false positive results by 26.0%, whilst retaining a negative predictive value of 91.5 (95% CI [90.8, 92.1]), albeit with a 10.6% increase in the proportion of those tested with AF having a missed or delayed HF diagnosis. The main limitation of the study is that it relies on routinely collected primary care data and people with an NT-proBNP result <400 pg/mL may not have been referred for further assessment, impacting upon the diagnostic accuracy below this threshold. CONCLUSIONS: NT-proBNP discriminates more accurately for HF among people without AF than with AF. A higher referral threshold could be considered in AF to account for higher median NT-proBNP levels but this would also increase missed HF diagnoses.
Differences in growth trajectories in breastfed HIV-exposed uninfected and HIV-unexposed infants in Kenya: An observational cohort study.
Tiwari R, Singa BO, Lihanda P … +10 more , Diakhate MM, Ochola E, Bunyige L, Sherry C, Richardson BA, Wamalwa D, Denno DM, John-Stewart GC, Aldrovandi GM, McGrath CJ
PLoS Med · 2025 Oct · PMID 41144576 · Full text
BACKGROUND: Children who are HIV-exposed and uninfected (CHEU) are at increased risk for poor growth compared to children who are HIV-unexposed (CHU). There are limited data on growth among CHEU in the era of preferred d...
BACKGROUND: Children who are HIV-exposed and uninfected (CHEU) are at increased risk for poor growth compared to children who are HIV-unexposed (CHU). There are limited data on growth among CHEU in the era of preferred dolutegravir-based antiretroviral therapy (ART) for pregnant and breastfeeding women living with HIV (WLWH). We aimed to compare child growth outcomes in the first two years of life between breastfed CHEU and CHU, and to examine maternal HIV factors associated with growth in CHEU. METHODS AND FINDINGS: We enrolled pregnant women in Kenya and followed them with their child to age 24 months. We measured anthropometry within 7 days of birth, at 3 and 6 weeks, and months 3, 6, 9, 12, 18, and 24. We compared length-for-age Z-scores (LAZ), weight-for-age Z-scores (WAZ), weight-for-length Z-scores (WLZ), head circumference-for-age Z-scores (HCZ), and mid-upper arm circumference-for-age Z-scores (MUAC), and stunting (LAZ < -2), underweight (WAZ < -2), and wasting (WLZ < -2) between groups using linear mixed effects or modified Poisson regression models adjusted for maternal age, education, depression, anemia, household wealth index, time-varying breastfeeding, time-varying food insecurity, parity, and child sex. Among 333 mother-child pairs with at least two child visits (CHEU = 171; CHU = 162), mothers of CHEU were older, less educated, and had lower wealth than mothers of CHU. Birth characteristics were similar between groups, with 9% preterm births and 6% low birthweight. All WLWH were on ART, 89.5% on dolutegravir-lamivudine-tenofovir, 76.6% initiating ART preconception, and 91.2% virally suppressed. The duration of breastfeeding was significantly shorter for CHEU than CHU (median 15 versus 17 months). CHEU had significantly lower LAZ at birth, 18- and 24-months than CHU. In multivariable analysis, growth trajectories for WLZ and HCZ were lower among CHEU than CHU in the first 24 months (interaction p = 0.001 and p = 0.009, respectively). There was no difference in trajectory in LAZ, WAZ, and MUACZ between groups. By 24 months, 31.5% of CHEU were stunted, 9.3% underweight, and 2.4% wasted, versus 27.2%, 3.2%, and 0.6% of CHU, respectively; only the difference in underweight prevalence was statistically significant. CHEU had a higher risk of being underweight from 9- to 24 months than CHU (adjusted Relative Risk at 24 months, 2.99 [95% CI: 1.08, 8.30]; p = 0.034). Growth was associated with maternal education, wealth, and breastfeeding and was lower among male infants. Among CHEU, maternal preconception ART was not associated with growth. Important limitations of this study include the possibility of unmeasured confounding and limited generalizability to contexts with differing prevalence of malnutrition, access to and uptake of ART, or breastfeeding practices. CONCLUSIONS: Despite breastfeeding and optimal maternal dolutegravir-based ART, CHEU experienced growth deficits compared to CHU in the first two years of life. Continued monitoring of the expanding CHEU population is essential in the context of rapidly evolving guidelines and policies to optimize their health and to identify and prevent future health disparities and disease risks.
Effectiveness of a brief intervention and text-based booster in the emergency department to reduce harmful and hazardous alcohol use: A pragmatic randomized adaptive clinical trial in Moshi, Tanzania.
Staton CA, Minja L, de Souza JVP … +9 more , Gallis JA, Santos PCP, Buono M, Sakita F, Ngowi K, Boshe J, Phillips AJ, Vissoci JRN, Mmbaga BT
PLoS Med · 2025 Oct · PMID 41144564 · Full text
BACKGROUND: Alcohol use contributes to over 3 million deaths annually. In Tanzania, there are no evidence-based culturally adapted interventions to address harmful alcohol use behaviors. Our hypothesis was that "Punguza...
BACKGROUND: Alcohol use contributes to over 3 million deaths annually. In Tanzania, there are no evidence-based culturally adapted interventions to address harmful alcohol use behaviors. Our hypothesis was that "Punguza Pombe Kwa Afya Yako" (PPKAY, Reduce Alcohol for your Health), a culturally adapted brief intervention with text-based boosters, is superior to usual care in reducing binge drinking at 3 months post discharge. METHODS AND FINDINGS: This manuscript reports. Stage 1 of our adaptive clinical trial which seeks to determine the effectiveness of the PPKAY+ booster to usual care; a subsequent stage will compare the PPKAY only to personalized and standard boosters. Adults who sought care for an acute injury at the Kilimanjaro Christian Medical Centre Emergency Department, self-disclosed alcohol use prior to the injury, scored ≥8 on the Alcohol Use Disorder Identification Test, and/or test positive by alcohol breathalyzer were offered enrollment. Participants were randomly assigned to PPKAY+ boosters (personalized or standard) or usual care at 1:1:1 allocation. Primary analyses followed the intention-to-treat principle. The PPKAY is a 15-min nurse delivered brief intervention using motivational interviewing techniques combined with a standardized or personalized text based reminder sent weekly to participants after hospital discharge and until 1 year post enrollment compared to a usual care arm. Follow-up was performed by blinded outcome assessors. Our pooled intervention arms PPKAY+ boosters were compared to usual care to determine the effectiveness of the intervention in reducing the number of binge drinking days, the trial's primary outcome, in the previous 4 weeks at 3 months after discharge. A total of 1,484 patients were screened for eligibility between October 12th 2020, and on April 14th 2023. 448 patients met inclusion criteria and consented to participate. 148 were randomized to usual care, and 300 to the pooled intervention arm. Reasons for attrition included loss to follow-up (n = 69), withdrawal (n = 6), and deaths (n = 4), with no differences between arms. Most participants were male (94%), from the Chagga tribe (59%) and had an average age of 36.4 years (SD 12.6) at baseline. At the 3-month follow-up, the intervention arm showed a notable reduction in mean predicted binge drinking days by 1.2 days (95% CI: [-2.3, -0.3]; p = 0.002) compared to the usual care group in a difference-in-differences analysis. Importantly, the self-reported nature of our primary outcome introduces the potential for social desirability bias, particularly in the absence of participant blinding, and should be considered a limitation when interpreting the findings. CONCLUSION: The reduction in binge drinking behavior at 3-month follow-up compared to usual care suggests our culturally adapted intervention is an effective alcohol intervention for patients acutely injured in Tanzania. According to the adaptive study design, the next phases of the trial will continue to compare the intervention arm with a paired down version without the text messages boosters. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04535011.
Correction: Vaccination strategies, public health impact and cost-effectiveness of dengue vaccine TAK-003: A modeling case study in Thailand.
Shen J, Kharitonova E, Tytula A … +8 more , Zawieja J, Aballea S, Biswal S, Sharma M, Rungmaitree S, Sruamsiri R, Wallace D, Hanley R
PLoS Med · 2025 Oct · PMID 41134752 · Full text
[This corrects the article DOI: 10.1371/journal.pmed.1004631.].
[This corrects the article DOI: 10.1371/journal.pmed.1004631.].
Estimating the effect on obesity of delaying tax-based interventions in Mexico: A modeling study.
Carnalla M, Reyes-Sánchez F, Alonso-Bastida A … +8 more , Reyes-García A, Hernández-Rojas A, García CG, Junquera-Badilla I, Basto-Abreu A, Swimburn B, Rivera JA, Barrientos-Gutiérrez T
PLoS Med · 2025 Oct · PMID 41129588 · Full text
BACKGROUND: The World Health Organization (WHO) launched the Acceleration Plan to STOP Obesity, highlighting the urgent need for timely implementation of proven interventions. Fiscal policies, including taxes on sugar-sw...
BACKGROUND: The World Health Organization (WHO) launched the Acceleration Plan to STOP Obesity, highlighting the urgent need for timely implementation of proven interventions. Fiscal policies, including taxes on sugar-sweetened beverages (SSB) and non-essential energy-dense foods (NEDF), are among the most cost-effective strategies to reduce obesity rates. Delays in adopting or strengthening these measures can undermine their impact, and the consequences of postponing such policies remain unmeasured. We aimed to estimate the expected impact of delaying doubling the SSB and NEDF tax in Mexico. METHODS AND FINDINGS: We simulated a closed cohort of Mexican adults aged 20 years and over from 2021 to 2040. The simulated sample corresponded to the combination of the 2020-22 Health and Nutrition Surveys, which contained anthropometric and demographic information representative at a national level. We projected annual average Body Mass Index (BMI), obesity prevalence, deaths averted, and years lived without obesity (YLWO) under four scenarios: status quo and doubling the current tax on SSB and NEDF in 2025, 2030, and 2035. BMI was projected from 2021 to 2040 using Hall's microsimulation weight change model, and a Mexican projection of total energy intake. To simulate deaths, we estimated the probability of all-cause mortality by BMI category from the National Population Council projections of the Mexican population by age and year. By 2040, doubling the taxes in 2025 resulted in an obesity prevalence of 41.6% (95% Uncertainty Interval [40.2,43.1]) in contrast to the status quo scenario (44.5%, 95% Uncertainty Interval [43.2,45.8]), and 170,600 deaths averted (95% Uncertainty Interval [130,900, 210,200]) and 25,031,900 (95% Uncertainty Interval [19,048,500, 31,015,300]) YLWO gained. A delayed intervention in 2035 resulted in an obesity prevalence of 41.7% (95% Uncertainty Interval [40.4,43.1]), 38,900 deaths averted (95% Uncertainty Interval [29,600, 48,200]), and 4,473,700 (95% Uncertainty Interval [3,378,900, 5,568,500]) YLWO gained. Our results apply only to individuals aged 20 years or older in 2021, excluding cohorts reaching age 20 between 2022 and 2040. CONCLUSIONS: Our results emphasize the urgency of advancing WHO's Acceleration Plan to STOP Obesity. Postponing evidence-based interventions is estimated to exacerbate the burden of obesity, mortality, and suffering.
Parental opioid prescriptions and the risk of opioid use in adolescents and young adults: The HUNT Study linked with prescription registry data.
Marcuzzi A, Ferreira P, Mork PJ … +5 more , Ferreira ML, Moe K, Gismervik S, Nordstoga AL, Lund Nilsen TI
PLoS Med · 2025 Oct · PMID 41129490 · Full text
BACKGROUND: Although opioids are usually not recommended for young people they are often prescribed. It is not clear whether family-level factors are related to the risk of opioid use among adolescents and young adults....
BACKGROUND: Although opioids are usually not recommended for young people they are often prescribed. It is not clear whether family-level factors are related to the risk of opioid use among adolescents and young adults. The aim of this study is to examine the association between parental opioid prescriptions and risk of opioid use in young people. METHODS AND FINDINGS: A prospective cohort study, including 21,470 adolescents and young adults (13-29 years) participating in the third (2006-2008) or fourth (2017-2019) survey of the population-based Young-HUNT or HUNT Study, Norway, paired with at least one participating parent. Opioid prescriptions were obtained by a linkage to the Norwegian Prescription Database. Parents' opioid prescriptions were defined as '0', '1', and '≥2' prescriptions over a period of 5 years. Analyses were also stratified according to parental chronic musculoskeletal (MSK) pain status (no, yes) assessed by the Standardised Nordic Questionnaire. Two outcomes were assessed: 1) any opioid prescription, and 2) persistent opioid prescriptions (i.e., at least three out of four quarters of the year). Analyses were adjusted for parental age, parental education level, parental body mass index, offspring age, and offspring participation survey. Follow-up started at the date of survey participation and ended at the date of prescription, emigration/death, or 7-year follow-up. If the mother or father had ≥2 opioid prescriptions, the hazard ratios (HR) for persistent opioid prescriptions in offspring were 2.60 (95% CI [1.86, 3.65]) and 2.37 (95% CI [1.56, 3.60]), respectively, compared to offspring whose parents did not receive any opioid prescriptions. There was no clear evidence that parental chronic MSK pain status influenced these associations. Comparing offspring of mothers with ≥2 versus no opioid prescriptions, the HR for any opioid prescription was 1.30 (95% CI [1.15, 1.47]) if the mother reported chronic MSK pain and 1.31 (95% CI [1.06, 1.62]) if she did not. Corresponding HRs associated with fathers' opioid prescription were 1.19 (95% CI [1.01, 1.41]) if the father reported chronic MSK pain and 1.21 (95% CI [0.98, 1.50]) if he did not. Residual confounding due to unmeasured factors cannot be excluded. CONCLUSIONS: Parental opioid prescription is related to an increased risk for opioid initiation and persistent use in offspring, irrespective of parental history of chronic MSK pain. These findings suggest that family-based strategies should be considered when managing pain and opioid use in young people.
Association between parental psychiatric conditions and offspring psychiatric, behavioral, and psychosocial outcomes: A Swedish population-based children-of-monozygotic twins study.
Zhou M, Larsson H, D'Onofrio BM … +6 more , Landén M, Kuja-Halkola R, Chang Z, Brikell I, Lichtenstein P, Pettersson E
PLoS Med · 2025 Oct · PMID 41118417 · Full text
BACKGROUND: Mental health problems tend to run in families, with studies showing transdiagnostic associations across generations. Nevertheless, if these associations were attributable to unmeasured familial (either envir...
BACKGROUND: Mental health problems tend to run in families, with studies showing transdiagnostic associations across generations. Nevertheless, if these associations were attributable to unmeasured familial (either environmental or genetic) factors that influence both generations, then treating the parental conditions would not break the intergenerational transmission. This study aims to investigate the associations between parental psychiatric conditions and offspring psychiatric, behavioral, and psychosocial outcomes, after controlling for unmeasured familial factors shared by offspring of monozygotic (MZ) twin parents (i.e., cousins). METHODS AND FINDINGS: We conducted a children-of-MZ twins study that consisted of 15,603 individuals (born to 7,742 MZ twin parents) born in Sweden between 1970 and 2000, and followed them from their date of birth to the date of the outcome or December 31, 2020, when the offspring were between 21 and 51 years old. The exposures were whether the MZ twin parents were diagnosed with any psychiatric condition, any internalizing condition, or any externalizing condition. The outcomes included register-based psychiatric conditions, behavioral problems, suicide, and psychosocial problems in the offspring. We performed stratified Cox regression for time-to-event outcomes and conditional logistic regression for binary outcomes to compare offspring exposed to an MZ twin parent with psychiatric conditions against their unexposed cousins. We adjusted for the highest parental educational level, maternal and paternal age at childbirth, offspring birth year, offspring sex, and psychiatric diagnosis of the nontwin parent. Offspring of parents with any parental psychiatric condition, internalizing condition, or externalizing condition had significantly higher probabilities for all the psychiatric, behavioral, and psychosocial outcomes, with hazard ratios (HRs) ranging from 1.34 (95% confidence interval [CI] [1.21, 1.49]; p < 0.001) to 2.53 (95% CI [1.96, 3.26]; p < 0.001) for time-to-event outcomes and odds ratios ranging from 1.33 (95% CI [1.17, 1.52]; p < 0.001) to 1.87 (95% CI [1.63, 2.14]; p < 0.001) for binary outcomes. Although these associations attenuated when comparing differentially exposed cousins whose parents were MZ twins (20 out of 27 associations were no longer statistically significant within cousin pairs), associations between broad spectra remained statistically significant. Specifically, across the main analysis and several sensitivity analyses, statistically significant within-twin-family associations remained between any parental psychiatric condition and any offspring psychiatric condition (HR = 1.28, 95% CI [1.13, 1.44]; p < 0.001), between parental internalizing conditions and any offspring psychiatric condition (HR = 1.26, 95% CI [1.09, 1.45]; p = 0.002), and between parental externalizing conditions and any offspring psychiatric condition (HR = 1.27, 95% CI [1.08, 1.51]; p = 0.005). The main limitations of this study were unmeasured confounders not shared by cousins, the lack of diagnostic data from primary care, and limited statistical power for some specific clustered outcomes. CONCLUSIONS: Although the intergenerational transmission between parental psychiatric conditions and offspring psychiatric, behavioral, and psychosocial outcomes appeared partially attributable to unmeasured familial (environmental or genetic) factors that influenced both generations, there was also evidence of either nonshared factors or direct causal effects. If the latter, then treating parental psychiatric conditions would reduce the risk of psychiatric vulnerability in offspring.
Impact of excessive social media use on adolescent depression and its consequences in France: An individual-based microsimulation model.
Hoertel N, Olfson M, Blanco C … +5 more , Biscond M, Limosin F, Sánchez-Rico M, Blachier M, Leleu H
PLoS Med · 2025 Oct · PMID 41118364 · Full text
BACKGROUND: Social media (SM) platforms have become increasingly prevalent in adolescents' lives, and concerns have arisen regarding their potential contribution to depression. This study examined whether excessive SM us...
BACKGROUND: Social media (SM) platforms have become increasingly prevalent in adolescents' lives, and concerns have arisen regarding their potential contribution to depression. This study examined whether excessive SM use contributes to rising adolescent depression rates and evaluated potential mitigation strategies. METHODS AND FINDINGS: We developed an individual-based microsimulation model of 18.6 million French adolescents born 1990-2012, tracking depression outcomes from 2000-2022 (analyses conducted August 2024-July 2025). The model incorporated 95 parameters, including demographics, SM use patterns, and established depression risk factors (childhood adversities, chronic physical conditions, physical inactivity, obesity, substance use). The main outcome was cumulative depression cases, and secondary outcomes were suicide deaths, health-adjusted life expectancy (HALE) loss, and associated costs. The model was well-calibrated and validated adequately against US-specific data. It showed that excessive SM use likely played an important role in the recent increase in rates of adolescent depression. Among French adolescents, simulations indicated that excessive SM use was associated with an additional cumulative lifetime 590,000 depression cases (95%CI [400,000, 760,000]), 799 suicide deaths (95%CI [547, 1,028]), 137,000 (95%CI [94,000, 176,000]) HALE loss years, and 3.94 (95%CI [2.70, 5.07]) billion euros, compared to scenarios without SM platforms. Key limitations are that microsimulation modeling cannot establish causality from observational data and the reliance on duration-based exposure measures without capturing content type or engagement quality. CONCLUSIONS: In this study, we estimated that limiting SM use to 1 h per day for all adolescents, replacing 30 min of SM use with 30 min of physical activity, or stopping its use for adolescents most at-risk for depression, would be associated with a reduction in cumulative lifetime prevalence of depression by 14.7%, 12.9%, and 12.0%, respectively, and diminished associated costs. Targeted SM interventions could potentially reduce adolescent depression burden, though real-world implementation and effectiveness require validation.
Prognostic significance of CD8+ T cell Spatial Biomarkers in ER+ and ER- breast cancer: A retrospective cohort study.
Walker AE, Gao X, Wang Q … +7 more , De la Cruz G, Li D, Perou CM, Saltz J, Marron JS, Hoadley KA, Troester MA
PLoS Med · 2025 Oct · PMID 41091832 · Full text
BACKGROUND: Tumor infiltrating lymphocytes (TILs) are prognostic in triple-negative breast cancer, but not estrogen receptor (ER) positive cancers which comprise 70%-80% of breast cancers. This is due to the relatively l...
BACKGROUND: Tumor infiltrating lymphocytes (TILs) are prognostic in triple-negative breast cancer, but not estrogen receptor (ER) positive cancers which comprise 70%-80% of breast cancers. This is due to the relatively low immune infiltration in ER-positive tumors. However, few studies have explored the prognostic impact of lower abundance TILs evaluated using spatial methods. The objective of this study was to explore whether the distribution of lymphocytes with respect to tumor cells predicts prognosis. METHODS AND FINDINGS: In this retrospective cohort study, we used multiplex immunofluorescent (IF)-stained images of tissue microarray cores (stained for cytokeratin [Ck], CD8, and FoxP3) obtained from 1,467 study participants to compute distance-based visual morphometry for epithelial and immune cells, including two new metrics, proximity and consistency. Proximity and consistency are defined as functions of the mean and variance of nearest neighbor distances between Ck+ tumor cells and CD8+ T cells. Prognostic significance of proximity and consistency were compared to lymphocyte counts using log-rank tests of differences in Kaplan-Meier survival curves and Cox proportional hazards models. Better recurrence-free survival (RFS) was observed for both ER+ and ER- breast cancers with high proximity and consistency of CD8+ T cells. Among ER- breast cancers, proximity had the highest RFS hazard ratio (HR 1.84, 95% CI [1.18, 2.87]; p = 0.0069) compared to count and consistency. Among ER-positive participants, RFS hazard ratios for proximity and consistency were 2.04 (95% CI [1.39, 2.98]; p = 0.0003) and 1.82 (95% CI [1.23, 2.69]; p = 0.0026), respectively. These associations were stronger than those observed for lymphocyte count (HR 1.35, 95% CI [0.92, 1.98]; p = 0.1289). Independent prognostic value was demonstrated by controlling clinical and demographic variables such as age, tumor grade, stage, ER status, progesterone receptor status, and human epidermal growth factor receptor 2 status. These IF-derived spatial metrics were also associated with established TILs metrics and RNA expression-based measures of tumor adaptive immune response. Though these results are promising, our exploration of the tumor immune microenvironment was limited by the small number of immune markers available for our data. CONCLUSIONS: Spatial characteristics described by proximity and consistency are frequently associated with recurrence irrespective of ER status. The prognostic significance of proximity in ER+ breast cancer implies that spatial parameters may identify individuals who would benefit from immune therapy; up to 75% of breast cancers experience T cell proximity suggestive of immune susceptibility.
Improving reporting of observational studies of interventions: The TARGET guideline.
Hansford HJ, McAuley JH, Cashin AG
PLoS Med · 2025 Oct · PMID 41091811 · Full text
Emulating a target trial when conducting an observational study of interventions can reduce the likelihood of design-related biases. The TARGET guideline aims to improve the reporting transparency of observational studie...
Emulating a target trial when conducting an observational study of interventions can reduce the likelihood of design-related biases. The TARGET guideline aims to improve the reporting transparency of observational studies emulating a target trial and help readers appraise and apply the results.
Open science must include effective results dissemination to study participants.
Tai KH, Legoff G, Le Louarn A … +2 more , Munung NS, Naudet F
PLoS Med · 2025 Oct · PMID 41091810 · Full text
Open science often centers around publications and data transparency. We highlight how and why disseminating results to study participants is essential for maximizing the values and benefits of open science.
Open science often centers around publications and data transparency. We highlight how and why disseminating results to study participants is essential for maximizing the values and benefits of open science.
Immunogenicity and safety of DS-5670d, an omicron XBB.1.5-targeting COVID-19 mRNA vaccine: A phase 3, randomized, active-controlled study.
Kawamoto A, Hashida M, Ishida K … +6 more , Furihata K, Ota A, Takahashi K, Sakakibara S, Nakano T, Takeshita F
PLoS Med · 2025 Oct · PMID 41082550 · Full text
BACKGROUND: DS-5670d is a monovalent lipid nanoparticle-messenger ribonucleic acid vaccine against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), containing an omicron XBB.1.5-derived antigen. This phase 3...
BACKGROUND: DS-5670d is a monovalent lipid nanoparticle-messenger ribonucleic acid vaccine against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), containing an omicron XBB.1.5-derived antigen. This phase 3 non-inferiority study assessed the immunogenicity and safety of a single dose of DS-5670d according to participant immune status. METHODS AND FINDINGS: Participants aged ≥12 years were stratified according to their history of both prior SARS-CoV-2 infection plus prior coronavirus disease 2019 vaccination (subpopulation A), prior infection only (subpopulation B), prior vaccination only (subpopulation C), or no history of either infection or vaccination (subpopulation D), and randomly assigned (1:1) to receive DS-5670d or monovalent BNT162b2 omicron XBB.1.5. The primary efficacy endpoint was geometric mean titer (GMT) of blood neutralizing activity against SARS-CoV-2 (omicron XBB.1.5) and seroresponse rate at day 29 after study vaccine administration in the combined ABC subpopulations (DS-5670d, n = 362 versus BNT162b2, n = 363). Prespecified non-inferiority margins required that the lower limit of the 95% confidence interval (CI) exceeded 0.67 for the GMT ratio and -10% for the difference in seroresponse. The adjusted GMT ratio was 1.218 (95% confidence interval [CI], 1.059, 1.401). Seroresponse rates were 87.3% (DS-5670d) and 82.9% (BNT162b2); adjusted difference 4.5% (95% CI, -0.70, 9.71). Both results exceeded the non-inferiority margins and the study met the primary endpoint. Immunogenicity data in the overall ABCD population also met non-inferiority criteria. There were no apparent immunogenicity differences according to age or sex, and analyses suggested that even unvaccinated persons achieved an adequate immune response following a single dose of DS-5670d. There were no major differences in the incidence or severity of adverse events between the study vaccination groups. The main study limitation was the short duration of follow-up. CONCLUSIONS: A single dose of DS-5670d was immunogenically non-inferior to BNT162b2 and acceptably safe in persons with or without a history of prior infection and/or vaccination. Trial registration Japan Registry of Clinical Trials (jRCT2031230424).
Why psychiatric bed capacity varies widely: Strategic questions on global mental health.
Seita A
PLoS Med · 2025 Oct · PMID 41071837 · Full text
A recent PLOS Medicine study reveals the wide variation in psychiatric bed numbers across the US. Globally, capacity differs 80-fold among OECD countries, reflecting history, policy, and care models. Without global stand...
A recent PLOS Medicine study reveals the wide variation in psychiatric bed numbers across the US. Globally, capacity differs 80-fold among OECD countries, reflecting history, policy, and care models. Without global standards and access, the efficiency and quality of psychiatric care remain uneven.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe