PLoS Med. [JOURNAL]
Sun
200 papers
Missing tissue, missing data: Resolving brain volume loss caused by anti-amyloid therapies.
Alves F, Ayton S
PLoS Med · 2026 Jan · PMID 41557594 · Full text
Anti-amyloid drugs modestly slow Alzheimer's disease progression, albeit with uncertainty of sustained benefit, particularly as they cause paradoxical acceleration of brain volume changes. Here, we examine explanations f...
Anti-amyloid drugs modestly slow Alzheimer's disease progression, albeit with uncertainty of sustained benefit, particularly as they cause paradoxical acceleration of brain volume changes. Here, we examine explanations for these volume changes and argue for transparent release of clinical trial data.
Glucagon-like peptide-1 receptor agonists for obesity: Growing popularity met with growing questions over safety.
Chao AM, Gilden A, Wadden TA
PLoS Med · 2026 Jan · PMID 41533690 · Full text
Glucagon-like peptide-1 (GLP-1)-based medications, such as semaglutide and tirzepatide, have transformed obesity care. However, rising use brings concerns about side effects, long-term outcomes, and unregulated products....
Glucagon-like peptide-1 (GLP-1)-based medications, such as semaglutide and tirzepatide, have transformed obesity care. However, rising use brings concerns about side effects, long-term outcomes, and unregulated products. Ensuring safe access requires oversight, monitoring, and coordinated clinical care.
Multiview deep-learning-enabled histopathology for prognostic and therapeutic stratification in stage II colorectal cancer: A retrospective multicenter study.
Zhao Z, Chen D, Wang R … +13 more , Zhang X, Wen X, Zheng X, Liu S, Chen H, Zhang Y, Huang D, Zheng C, Ma M, Xie D, Sun Y, He X, Cai M
PLoS Med · 2026 Jan · PMID 41532433 · Full text
BACKGROUND: Approximately 20% of patients with stage II colorectal cancer (CRC) experience tumor relapse despite standard surgical treatment. Histopathological analysis holds promise for postsurgical risk stratification...
BACKGROUND: Approximately 20% of patients with stage II colorectal cancer (CRC) experience tumor relapse despite standard surgical treatment. Histopathological analysis holds promise for postsurgical risk stratification and guiding adjuvant chemotherapy (ACT) decisions. The aim of this study was to use deep learning to extract explainable tissue biomarkers from whole-slide images. METHODS AND FINDINGS: In this retrospective cohort study, we developed and validated SurvFinder, an interpretable deep learning framework designed to autonomously identify tissue-based risk biomarkers from hematoxylin and eosin (H&E)-stained slides. The framework aims to support individualized risk stratification and explore associations with treatment outcomes. The present study included 6,950 H&E slides from 1,604 patients with stage II CRC across four independent cohorts in China. Patients were enrolled from 2012 to 2018 and followed for a minimum of 24 months. The primary outcome of the study was relapse-free survival (RFS). Our analyses identified tertiary lymphoid structures (TLSs) as critical prognostic features in stage II CRC. The multi-view integration of TLS characteristics by SurvFinder consistently demonstrated superior predictive and prognostic accuracy across four multicenter datasets (AUROC with 95% confidence interval [CI]: 0.827 [0.789,0.864], 0.805 [0.749,0.860], 0.805 [0.748,0.861], and 0.712 [0.621,0.804]), surpassing traditional clinical prognostic parameters (hazard ratio [HR]: 8.23, 95% CI: 5.43-12.47; p < 0.001). Using explainable AI (XAI) methods, we ensured model transparency and identified key TLS features-such as their location at the tumor periphery and their maturity state-as significant factors influencing prognosis and the efficacy of adjuvant therapy. The retrospective design without prospective validation and real-world clinical deployment is the main limitation of this study. CONCLUSIONS: Together, these results highlight the potential utility of deep learning-based histopathological analysis for automated risk stratification in stage II CRC. In particular, our findings support the relevance of TLSs as a histological biomarker with potential implications for personalizing ACT decisions.
Evaluating the clinical utility of large language models for hepatocellular carcinoma treatment recommendations: A nationwide retrospective registry study.
Yang K, Lee J, Jang JW … +2 more , Sung PS, Han JW
PLoS Med · 2026 Jan · PMID 41528959 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) management requires complex decision-making considering tumor burden, liver function, and patient's functional performance status. Large language models (LLMs) show promise in c...
BACKGROUND: Hepatocellular carcinoma (HCC) management requires complex decision-making considering tumor burden, liver function, and patient's functional performance status. Large language models (LLMs) show promise in clinical applications, but their utility in HCC treatment recommendations remains unexplored. We evaluated the clinical relevance of LLM-generated treatment recommendations by comparing concordance with real-world physician decisions and survival outcomes. METHODS AND FINDINGS: We analyzed 13,614 treatment-naive HCC patients diagnosed between 2008 and 2020 in the Korean Primary Liver Cancer Registry. Treatment recommendations were generated using ChatGPT 4o, Gemini 2.0, and Claude 3.5 with standardized prompts referencing the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver guidelines. Patients were classified as "matched" when LLM recommendations corresponded to actual treatments received. Overall survival (OS) was compared between matched and mismatched groups, stratified by the Barcelona Clinic Liver Cancer (BCLC) stage. Decision tree analysis identified factors influencing treatment selection patterns. Concordance rates between LLM recommendations and physician decisions were 31.1% (ChatGPT 4o), 32.7% (Gemini 2.0), and 26.8% (Claude 3.5). In BCLC-A patients, treatment concordance with LLM recommendations was associated with significantly improved survival (ChatGPT 4o HR: 0.743, 95% CI [0.665, 0.831], P < 0.001). Conversely, in BCLC-C patients, concordance was associated with worse survival outcomes (ChatGPT 4o HR: 1.650, 95% CI [1.523, 1.787], P < 0.001; Gemini 2.0 HR: 1.586, 95% CI [1.470, 1.711], P < 0.001; Claude 3.5 HR 1.483, 95% CI [1.366, 1.610], P < 0.001). In BCLC-B, concordance showed only modest or nonsignificant associations with survival across models. Decision tree analysis revealed that physicians prioritized liver function parameters, while LLMs emphasized tumor characteristics. In early-stage HCC, physicians avoided curative treatments when hepatic reserve was limited, whereas in advanced-stage HCC, physicians preferred locoregional therapies in patients with preserved liver function despite guideline recommendations for systemic therapy. This study is limited by its retrospective design, reliance on registry data without imaging information, and focus on guideline-era treatments, warranting future prospective validation. CONCLUSIONS: Concordance between LLM-generated and physician treatment decisions was associated with improved survival in early-stage HCC, whereas this association was not observed in advanced-stage disease. While LLMs may serve as adjunctive tools for guideline-concordant decisions in straightforward scenarios, their recommendations may reflect limited contextual awareness in complex clinical situations requiring individualized care. LLM recommendations should be interpreted cautiously alongside clinical judgment.
Distribution of capsule and O types in Klebsiella pneumoniae causing neonatal sepsis in Africa and South Asia: A meta-analysis of genome-predicted serotype prevalence to inform potential vaccine coverage.
Stanton TD, Keegan SP, Abdulahi JA … +80 more , Amulele AV, Bates M, Heinz E, Hooda Y, Hu W, Jain K, Kanwar S, Magobo R, Olwagen CP, Tembo JM, Sonda T, Strysko J, Tigoi CC, Amin SA, Bittinger K, Cornick J, Foster-Nyarko E, Gumbi W, Hotwani A, Iqbal N, Jones SM, Kabir F, Khan W, Musyani CL, McGann CM, Mittal V, Moustafa AM, Musicha P, Mwansa JCL, Ndumba ML, Odih EE, Omuoyo DO, Pearse O, Phillips LT, Planet PJ, Rasool AA, Rodrigues CMC, Sands K, Tanmoy AM, Theiller E, Zuza AM, Basu S, Chan GJ, Iregbu KC, Mazarati JB, Alemayehu SS, Walsh TR, Zahra R, Dramowski A, Fwoloshi S, Labi AK, Madrid L, Obeng-Nkrumah N, Ojok D, Wadugu BD, Whitelaw AC, Bethou A, Bhargava A, Jindal A, Nanavati RN, Prasad PS, Sastry A, Farooqi JQ, Ghanchi N, Jehan F, Khan E, Agarwal RK, Aiken AM, Berkley JA, Coffin SE, Feasey NA, Govender NP, Hamer DH, Madhi SA, Nisar MI, Saha SK, Saha S, Sankar MJ, Wyres KL, Holt KE
PLoS Med · 2026 Jan · PMID 41525325 · Full text
BACKGROUND: Klebsiella pneumoniae causes ~20% of sepsis in neonates, with ~40% crude mortality. A vaccine administered to pregnant women, protecting against ≥70% of K. pneumoniae infections, could avert ~400,000 cases an...
BACKGROUND: Klebsiella pneumoniae causes ~20% of sepsis in neonates, with ~40% crude mortality. A vaccine administered to pregnant women, protecting against ≥70% of K. pneumoniae infections, could avert ~400,000 cases and ~80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design. METHODS AND FINDINGS: We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20 K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and ≥70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5-10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n = 14 types). We estimate the top-5 (O1⍺β,2⍺, O1⍺β,2β, O2⍺, O2β, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%-92% per region), while the top-10 would cover ~99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time. CONCLUSIONS: Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover ≥70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development.
Public health impacts of increasing the minimum unit price for alcohol in Scotland: A model-based appraisal.
Holmes J, Morris D, Gillespie D … +5 more , Brennan A, Leeming G, Chen RKL, Wilson L, Angus C
PLoS Med · 2026 Jan · PMID 41505661 · Full text
BACKGROUND: Governments in several countries have introduced a minimum unit price (MUP) for alcohol. Evaluation studies suggest this has reduced alcohol-related harm, but MUPs must increase with inflation to remain effec...
BACKGROUND: Governments in several countries have introduced a minimum unit price (MUP) for alcohol. Evaluation studies suggest this has reduced alcohol-related harm, but MUPs must increase with inflation to remain effective. This paper estimates the impact of the impact of the Scottish Government's decision to increase its MUP from £0.50 to £0.65 in September 2024 and, alternative options where the MUP changes to between £0.40 and £0.80. It examines impacts on alcohol consumption, spending, and related health outcomes, how impacts vary across the population with regard to deprivation, and how drinkers move between lighter and heavier alcohol consumption groups. METHODS AND FINDINGS: Policy appraisal using the Sheffield Tobacco and Alcohol Policy Model, a dynamic microsimulation model that combines data on alcohol purchasing and consumption for 10 beverage types and 800 subgroups comprising adults in the Scottish population with price elasticities and an epidemiological model. Deprivation is measured using quintiles of the Scottish Index of Multiple Deprivation. Drinker group is categorised as moderate (<14 units/week, 1 UK unit = 8 g ethanol), hazardous (>14 to ≤35/ ≤50 units/week for women/men), and harmful (>35/50 units/week for women/men). The policy appraisal estimates that, compared to retaining Scotland's MUP at £0.50, increasing the MUP to £0.65 leads to an estimated 12.0% decrease in alcohol consumption, 2.1% decrease in alcohol spending, 3,385 fewer deaths overall, and 2,578 fewer deaths wholly attributable to alcohol over 20 years. Estimated effects are largest in the quintile of the population living in the most deprived areas. Increasing the MUP to £0.65 is also estimated to reduce the proportion of drinkers consuming at harmful levels by 29.4% and the proportion consuming at hazardous levels by 8.0%. Key limitations of the study include relying on data on alcohol consumption and spending collected before the COVID-19 pandemic, synthesising consumption and spending data from separate datasets, and assuming no supply-side responses (e.g., price changes above the MUP threshold). CONCLUSIONS: Increasing the threshold of an established MUP can lead to additional reductions in alcohol consumption, related harm, and health inequalities. Benefits accrue particularly to the most deprived and heaviest drinkers.
Context matters: Causality and global epidemiology of proton pump inhibitor safety.
Okabayashi S, Kaplan GG
PLoS Med · 2026 Jan · PMID 41499375 · Full text
Proton pump inhibitors revolutionized acid-related disorder therapy, yet widespread overuse has raised concerns about long-term safety. A recent study in PLOS Medicine presents new evidence assessing whether links betwee...
Proton pump inhibitors revolutionized acid-related disorder therapy, yet widespread overuse has raised concerns about long-term safety. A recent study in PLOS Medicine presents new evidence assessing whether links between their prolonged use and upper gastrointestinal cancer are causal.
Association between proton pump inhibitor use and upper gastrointestinal cancer: A matched case-control study accounting for reverse causation and confounding by indication.
Sawaid IO, Din Z, Golan E … +7 more , Ruppin E, Golan-Cohen A, Green I, Merzon E, Vinker S, Samson AO, Israel A
PLoS Med · 2026 Jan · PMID 41493925 · Full text
BACKGROUND: Proton pump inhibitors (PPIs) are widely used for acid-related disorders, but observational studies have raised concerns about a possible association between long-term PPI use and upper gastrointestinal (GI)...
BACKGROUND: Proton pump inhibitors (PPIs) are widely used for acid-related disorders, but observational studies have raised concerns about a possible association between long-term PPI use and upper gastrointestinal (GI) cancers. These associations may reflect confounding by indication and reverse causation. We aimed to evaluate the association between PPI use and upper GI cancer while explicitly addressing these biases. METHODS AND FINDINGS: We conducted a matched case-control study using electronic health records from a national health organization in Israel. Cases were 875 adults (age 63.0 ± 11.9 years, 62.5% male) with incident upper GI cancer (esophageal, gastric, or duodenal) diagnosed between 2003 and 2024; each case was matched to 10 cancer-free controls (n = 8,750). Matching was performed on age, sex, ethnic sector (general, Jewish ultra-orthodox, and Arab), socioeconomic status, and year of enrollment. PPI exposure was ascertained from pharmacy records and modeled in discrete pre-diagnosis windows (0-6 months, 6-12 months, 1-3 years, and 3-10 years). Multivariable conditional logistic regression estimated adjusted odds ratios (aORs) and confidence intervals (CIs), with covariates including age, smoking, body mass index, socioeconomic status, healthcare utilization, pregnancy history (in women), alcohol use, Helicobacter pylori diagnosis, and upper GI symptom-related diagnoses (e.g., gastroesophageal reflux, gastritis, peptic ulcer disease). In models without adjustment for symptom-related diagnoses, PPI use was associated with increased odds of cancer (e.g., esomeprazole aOR 4.01, 95% CI 3.20, 5.03, p < 0.001; omeprazole aOR 2.38, 95% CI 1.99, 2.85, p < 0.001). When exposure was modeled by time window, associations diminished for exposures >1 year before diagnosis. After excluding the final year before diagnosis and adjusting for symptom-related diagnoses, we did not detect a harmful association between PPI use and upper GI cancer. Remote use (>3 years) was instead associated with lower odds (e.g., omeprazole aOR 0.62, 95% CI 0.51, 0.75, p < 0.001), with similar patterns in a gastric-only subgroup (701 cases, 7,010 controls). Key limitations include potential residual confounding, lack of direct dietary and family-history data, and incomplete capture of over-the-counter PPI use. CONCLUSIONS: Apparent harmful associations between PPI use and upper GI cancer were concentrated in the months immediately preceding diagnosis and disappeared after adjusting for diagnostic context and excluding the final year before diagnosis. In these adjusted analyses, we found no evidence of increased odds with long-term PPI use, and remote use (>3 years before diagnosis) was associated with reduced cancer odds for omeprazole and lansoprazole. These findings underscore the importance of investigating new-onset upper GI symptoms rather than attributing malignancy risk to acid-suppressive therapy.
The nature and nurture of mental health problems in the family.
Wertz J, Richmond-Rakerd LS
PLoS Med · 2026 Jan · PMID 41493914 · Full text
Mental health problems are known to run in families, but it is not clear to what extent this reflects nature or nurture. By disentangling these influences, a recent PLOS Medicine article sheds light on how mental health...
Mental health problems are known to run in families, but it is not clear to what extent this reflects nature or nurture. By disentangling these influences, a recent PLOS Medicine article sheds light on how mental health problems are transmitted across generations.
Inequalities in cancer mortality between people with and without disability: A nationwide data linkage study of 10 million adults in Australia.
Yang Y, Afshar N, Aitken Z … +6 more , Bergin RJ, Summers P, Milne RL, Evans SM, Kavanagh A, Disney G
PLoS Med · 2026 Jan · PMID 41490345 · Full text
BACKGROUND: Cancer is a major yet under-recognised contributor to the mortality gap between people with and without disability. Our study aims to quantify these inequalities to inform cancer control efforts to reduce the...
BACKGROUND: Cancer is a major yet under-recognised contributor to the mortality gap between people with and without disability. Our study aims to quantify these inequalities to inform cancer control efforts to reduce the gap. METHODS AND FINDINGS: We used nationally-linked data (2011-2022) to construct a cohort of over 10 million adults in Australia aged 25-74 years. Disability was measured in 2011 Census as requiring assistance in core daily activities and cancer related deaths identified in national death registrations. We estimated age-standardised and age-specific cancer mortality rates, and absolute and relative mortality inequalities (rate differences and ratios) between people with and without disability. The study included 10,414,951 people. Of the 5,403,503 females, 185,801 (3.4%) reported disability; 183,594 of the 5,011,448 males (3.7%) reported disability. Over 93,940,222 person-years (9.2 years on average), 219,257 cancer-related deaths occurred. After age-standardisation, per 100,000 person-years, there were 314 (95% confidence intervals [CI]: 301, 328) more cancer related deaths in females and 410 (95% CI: 394, 427) more in males with disability (1.96 [95% CI: 1.92, 2.00], and 1.83 [95% CI: 1.80, 1.87] times higher, respectively) than those without disability. The largest absolute inequalities were for lung cancer in both females and males (67 [95% CI: 60, 73] and 103 [95% CI: 95, 111] more deaths per 100,000 person-years, respectively), followed by breast cancer in females (54 [95% CI: 49, 60] more deaths), prostate cancer in males (31 [95% CI: 26, 36] more deaths), and colorectal cancer in both sexes (30 more [95% CI: 25, 34] deaths in females and 44 [95% CI: 38, 49] more in males). By 5-year age group, lung cancer was the leading contributor to absolute inequalities in females and males aged 35 years and older. In females, across most age groups, breast cancer was the second largest contributor to absolute inequalities, followed by colorectal cancer. In males, colorectal cancer was the second largest contributor across most age groups, with prostate cancer contributing substantially to absolute inequalities in those aged 55 years and older. A substantial proportion of differences in cancer-related deaths between people with and without disability, across most age groups in both females and males were driven by cancers linked to smoking, obesity, and alcohol consumption. We found similar-sized relative inequalities between individuals with and without disability in mortality due to individual cancers in both sexes. The main limitation of the study was that disability status was measured at a single time point. CONCLUSIONS: People with disability had higher cancer mortality overall and in relation to specific cancers than people without disability. To close the gap, effort should prioritise interventions that work for people with disability across the cancer control pathway.
Sex-specific associations between surgery-induced weight loss and cancer outcomes: A post hoc analysis of the prospective, controlled Swedish Obese Subjects study.
Sjöholm K, Svensson PA, Andersson-Assarsson JC … +9 more , Jacobson P, Ahlin S, Karlsson C, Carlsson B, Kristensson FM, Karlsson P, Peltonen M, Carlsson LMS, Taube M
PLoS Med · 2026 Jan · PMID 41490246 · Full text
BACKGROUND: Obesity increases cancer risk, whereas surgery-induced weight loss is associated with reduced risk. Risk-based patient stratification may be needed to better understand and maximize benefits of weight loss in...
BACKGROUND: Obesity increases cancer risk, whereas surgery-induced weight loss is associated with reduced risk. Risk-based patient stratification may be needed to better understand and maximize benefits of weight loss interventions in individuals with obesity. To this end, comprehensive data from high-quality studies with extended follow-up are imperative. This study examines the link between bariatric surgery and long-term cancer outcomes, focusing on patient subgroups defined by previously suggested predictors of treatment benefit, such as sex and baseline insulin levels. METHODS AND FINDINGS: This post-hoc analysis used data from the Swedish Obese Subjects (SOS) study, a prospective, controlled intervention trial, designed to investigate the long-term effects of bariatric surgery-induced weight loss (ClinicalTrials.gov, NCT01479452). The study was conducted at 25 public surgical departments and 480 primary healthcare centers across Sweden. Between Sept 1, 1987, and Jan 31, 2001, 2,007 per-protocol patients with obesity who underwent bariatric surgery (gastric bypass, n = 266; gastric banding, n = 376; vertical banded gastroplasty, n = 1,365) and 2,040 matched controls, receiving standard nonsurgical obesity-related care, were recruited. Inclusion criteria were age 37-60 years and a body mass index (BMI) ≥34 kg/m2 for men and ≥38 kg/m2 for women. The primary outcome measures were cancer events and cancer-related deaths, captured through nearly complete data sourced from national Swedish health registries. Female-specific cancers were defined as gynecologic and breast cancers. Analyses were adjusted (adj) for baseline age, sagittal diameter, alcohol consumption, smoking, and serum insulin levels. The study was closed on December 31, 2022. Median follow-up was 26.8 years (interquartile range (IQR) [22.9, 29.6]) in the surgery group and 24.9 years (IQR [18.7, 28.8]) in the control group. Bariatric surgery was associated with a lower overall cancer incidence rate in women (adjusted hazard ratio (HRadj) = 0.78; 95% confidence interval (CI) [0.67, 0.90]; p = 0.001), but not in men (sex-treatment interaction p = 0.013). The HRadj for overall cancer mortality rate in women was 0.78 (95% CI [0.61, 1.00]; p = 0.050). In women, surgery was associated with a lower incidence rate of both obesity-related cancers (HRadj = 0.70; 95% CI [0.58, 0.85]; p < 0.001) and female-specific cancers (HRadj = 0.60; 95% CI [0.47, 0.75]; p < 0.001). Importantly, subgroup analyses showed that the associations between surgery and female-specific cancer incidence, as well as female-specific cancer-related mortality, were stronger in women with high baseline insulin levels (insulin-treatment interaction p = 0.021 and 0.039, respectively). The main limitation is that cancer was not a predefined study outcome. CONCLUSIONS: Bariatric surgery is associated with a lower risk of cancer and cancer-related mortality in women with obesity, with the strongest association observed for female-specific cancers in women with elevated baseline insulin levels. In men, bariatric surgery was not associated with overall cancer incidence or mortality. These findings support incorporating risk-based stratification to better tailor cancer prevention strategies in obesity care.
Taxation of foods high in fat, sugar, and sodium in India: A modelling study of health and economic impacts.
Roche M, Zhu J, Olney J … +5 more , Laydon DJ, Joe W, Sharma M, Steele L, Sassi F
PLoS Med · 2026 Jan · PMID 41490064 · Full text
BACKGROUND: Consumption of foods high in fat, sugar, and sodium (HFSS) and obesity are rapidly increasing in India. Taxing HFSS foods has been proposed as one of the policy interventions to promote healthier diets global...
BACKGROUND: Consumption of foods high in fat, sugar, and sodium (HFSS) and obesity are rapidly increasing in India. Taxing HFSS foods has been proposed as one of the policy interventions to promote healthier diets globally. This study estimates the effect of this approach on nutrient intake, diet-related disease, and associated health and economic burdens in India. METHODS AND FINDINGS: We use a nationally representative expenditure survey of 261,746 households, dietary requirements, and food composition tables to model individual nutrient intake. Consumer responsiveness to food price changes for three income terciles, captured in price elasticities, is estimated using an Almost Ideal Demand System model. Longer-term policy impacts are estimated through a novel dynamic microsimulation model, Health-GPS. Modelled policy outcomes include changes in risk exposures, disease incidence and burden, and total health expenditure. On average, 9.9% of total energy intake comes from HFSS items, based on the definition by the Food Safety and Standards Authority of India's Labelling and Display Amendment Draft Regulations 2022. Applying the highest Goods and Services Tax (GST) rate of 40% on HFSS items is associated with a persistent average per capita decrease of 0.1705 kg/m2 (95% CI: -0.1709, -0.1700) in body mass index and 45.8 mg (95% CI: -45.9, -45.7) in daily sodium intake. Over 30 years, this could reduce annual disease incidence by up to 1.72% (95% CI: -1.78%, -1.66%) on average and prevent 0.63 million (95% CI: -0.71, -0.55) disability-adjusted life years per year from ischaemic heart disease, chronic kidney disease, stroke, diabetes, and asthma, reducing total health expenditure by US$601 million (95% CI: -624, -578) per year. Larger absolute health gains accrue to higher-income individuals, reflecting higher baseline HFSS food intake. Given substitution patterns and a price-inelastic demand, the tax change is expected to generate a 92.0% (95% CI: 88.2%, 95.7%) increase in tax revenue from foods and beverages with only a minor effect on household spending (+1.0%, 95% CI: + 0.0%, + 1.9%). This analysis only captures the potential health impacts of changes in energy and sodium intakes. In addition, it does not model underlying temporal trends in disease incidence beyond those due to demographic changes, which would make our health impact estimates conservative if baseline disease risks were to increase in the future. CONCLUSIONS: Higher taxation of HFSS foods could help mitigate rising incidence of diet-related diseases and morbidity in India, reduce healthcare costs, and serve as an additional source of revenue for the government.
Correction: The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.
Sheppard JP, Koshiaris C, Stevens R … +9 more , Lay-Flurrie S, Banerjee A, Bellows BK, Clegg A, Hobbs FDR, Payne RA, Swain S, Usher-Smith JA, McManus RJ
PLoS Med · 2026 Jan · PMID 41490051 · Full text
[This corrects the article DOI: 10.1371/journal.pmed.1004223.].
[This corrects the article DOI: 10.1371/journal.pmed.1004223.].
Evaluation of economic strengthening in South Africa and its impact on HIV, sexually transmitted infections, and teenage births: A modelling study.
Johnson LF, Jamieson L, Kubjane M … +1 more , Meyer-Rath G
PLoS Med · 2025 Dec · PMID 41411229 · Full text
BACKGROUND: High incidence rates of HIV, sexually transmitted infections (STIs), and teenage pregnancy are major challenges facing South Africa. The role of socio-economic factors in driving these incidence rates is comp...
BACKGROUND: High incidence rates of HIV, sexually transmitted infections (STIs), and teenage pregnancy are major challenges facing South Africa. The role of socio-economic factors in driving these incidence rates is complex, with high socio-economic status protecting against some risk behaviours (condomless sex, early sexual debut, and casual/transactional sex in females) but increasing other risk behaviours (e.g., male engagement in casual and commercial sex). We aimed to model the effect of socio-economic status, and associated economic strengthening interventions, in South Africa. METHODS AND FINDINGS: We extended a previously-developed agent-based model of HIV, STIs, and fertility in South Africa to assess effects of education, employment, and per capita household income on sexual behaviours. We estimated these effects from literature and from calibration of the model to African randomized controlled trials of economic strengthening interventions. Population attributable fractions (PAFs) were calculated. We considered three intervention types, all targeting households with log per capita income below the national average: school support to reduce school dropout; vocational training for unemployed adults; and unconditional cash transfers. We estimate that low socio-economic status accounted for 13% of new HIV infections, 7% of incident STIs (gonorrhoea, chlamydia, and trichomoniasis) and 31% of teenage births in South Africa, over 2000-2020. However, because of uncertainties regarding effect sizes, confidence intervals around these PAFs are wide (1,50% for HIV; -1,19% for STIs; and 10,76% for teenage births). Over 2025-2040, none of the interventions are estimated to reduce HIV, STIs, or teenage births significantly, due to limited impact on secondary economic outcomes. The greatest impact would be that of school support on teenage births (a 5% reduction, 95% CI: -1,12%). Key limitations include the assumption of uniform STI treatment access across socio-economic strata, and the exclusion of possible socio-economic effects at a community level. CONCLUSIONS: Although poverty is likely to be a significant driver of HIV, STIs, and teenage pregnancy in South Africa, precise quantification is challenging. Recently trialled economic strengthening interventions have insufficient impact on socio-economic status to reduce HIV and STIs significantly at a population level.
Pediatric studies and labeling additions required by the U.S. FDA for novel drugs approved from 2011 to 2023: A retrospective cohort study.
McGonigle R, Naci H, Siebert M … +4 more , Ouvina M, Gutiérrez-Sacristán A, Wagner AK, Bourgeois FT
PLoS Med · 2025 Dec · PMID 41406177 · Full text
BACKGROUND: The U.S. Food and Drug Administration (FDA) has the authority to require that sponsors conduct pediatric studies for certain new drugs under the Pediatric Research Equity Act (PREA). Here, we evaluate the cha...
BACKGROUND: The U.S. Food and Drug Administration (FDA) has the authority to require that sponsors conduct pediatric studies for certain new drugs under the Pediatric Research Equity Act (PREA). Here, we evaluate the characteristics and completion of these studies and assess the addition of pediatric-specific evidence generated from these studies into drug labeling. METHODS AND FINDINGS: We performed a retrospective cohort study of all novel drugs approved by the FDA from 2011 to 2023 with at least one pediatric study requirement issued under PREA. Study status and outcomes were followed through 31 December 2024. We assessed completion of pediatric studies; addition of pediatric prescribing information to drug labels; and deviations from FDA-projected timelines. Of 552 novel drugs approved by the FDA between 2011 and 2023, 179 (32.4%) were subject to pediatric study requirements under PREA. Thirteen were later discontinued, resulting in a final cohort of 166 drugs and 338 pediatric study requirements. About half (51.8%) of the studies assessed efficacy. Among 222 studies with due dates by 31 December 2024, only 24.3% were completed by the original deadline. Over half (56.8%) received extensions of original timelines, by an average of 2.9 years (SD 2.0). At 10 years after drug approval, while 92.0% of studies were expected to have been completed, 59.5% had been completed. Of the 117 drugs with studies due by 31 December 2024, 54.7% (n = 64) had pediatric labeling updated with results from required studies. The mean time to addition of pediatric approval was 5.7 years (SD 2.6), whereas labeling additions reflecting lack of pediatric safety or benefit took an average of 8.3 years (SD 3.3) (p < 0.001). While 90.4% of drugs were expected to have all pediatric studies completed by 10 years, only 52.8% had any labeling changes reflecting data from the PREA-mandated studies. A limitation of this study is that publicly available FDA data provide limited detail on study design, execution, and reasons for delays, preventing assessment of study rigor and the factors contributing to delayed completion. CONCLUSIONS: PREA was implemented to advance pediatric drug research and fill a critical gap in pediatric labeling of new drugs. However, our findings reveal frequent delays in study completion and labeling updates, with just over half of labeling additions completed 10 years after drug approval. Strengthening reporting requirements and expanding the FDA's enforcement authority are essential to ensuring that children receive timely access to safe and effective therapies supported by high-quality evidence.
Effects of early water, sanitation, handwashing, and nutrition interventions on child development at school age: a follow-on study of a cluster-randomized trial in rural Bangladesh.
Tofail F, Pitchik HO, Islam M … +9 more , Khan R, Shoab AK, Akter F, Aktar S, Huda TMN, Rahman M, Winch PJ, Luby SP, Fernald LCH
PLoS Med · 2025 Dec · PMID 41401135 · Full text
BACKGROUND: A previous cluster-randomized controlled trial in Bangladesh found that individual or combined water, handwashing, sanitation, and nutrition interventions during pregnancy and after birth improved development...
BACKGROUND: A previous cluster-randomized controlled trial in Bangladesh found that individual or combined water, handwashing, sanitation, and nutrition interventions during pregnancy and after birth improved developmental outcomes of children at 1 and 2 years of age. In this study, we aimed to determine if these intervention effects were sustained for children at school age. METHODS AND FINDINGS: Clusters of pregnant women were enrolled between May 31, 2012 and July 7, 2013 and block-randomized into chlorinated drinking water (W); improved sanitation (S); handwashing with soap (H); combined WSH; nutrition counseling and provision of lipid-based supplements (N); combined WSH + N, or a double-sized passive control arm (C) with no intervention visits (N = 5,551). The primary outcomes of the main trial after the 2-year intervention were 7-day diarrhea prevalence and length-for-age z-score, measured in 4,584 children of enrolled pregnant women. We conducted a post hoc, follow-up of all initially enrolled mothers and their children 5 years after intervention completion, when children were 7 years old. Primary outcomes were child cognition assessed using the Wechsler Pre and Primary Scale of Intelligence (WPPSI-IV), along with assessments of fine motor abilities, behavior, school achievement, and executive function; secondary outcomes were maternal mental health and stimulation in the home environment. We conducted intention-to-treat analyses using generalized linear models to calculate unadjusted and adjusted comparisons between each arm and the control group, accounting for block-level clustering. Between September 2019 and February 2021, we re-enrolled 4,175 households from all 720 original clusters, with the full set of child development assessments conducted on 3,833 children across 718 clusters. Children in the WSH + N, N, and S arms had improved cognitive scores on one or more domains compared to the control arm, with adjusted effect sizes between 0.10 (95%CI: 0.00, 0.20) and 0.15 (0.03, 0.27). Children in the W, H, N, WSH, and WSH + N arms demonstrated improved prosocial behaviors (adjusted effect sizes between 0.20 (0.07, 0.33) and 0.31 (0.16, 0.46)) and reduced difficult behaviors (adjusted effect sizes between -0.15 (-0.28, -0.01) and -0.31 (-0.45, -0.17)). No intervention effects were observed for fine motor, executive functioning, or school achievement outcomes. Maternal depressive symptoms were improved in the WSH + N, H, and N arms (adjusted effect sizes between -0.14 (-0.24, -0.03) and -0.21 (-0.31, -0.11)), and the stimulating home environment was improved in all intervention arms (adjusted effect sizes between 0.17 (0.01, 0.33) and 0.40 (0.25, 0.56)). Children whose families had higher wealth at baseline and those who were male tended to have larger effect sizes on the FSIQ. Data collection for this study was interrupted by a 6-month pause at the start of the COVID-19 pandemic. The main limitation of this study is loss to follow-up. CONCLUSIONS: At 7 years of age, we found small, sustained benefits of early water, sanitation, handwashing, and nutrition interventions on child cognitive and socioemotional outcomes, the stimulating home environment, and maternal mental health. Future work to determine the mechanisms underlying these intervention effects will further inform the design of early interventions to improve child health and development. Trial registration: Follow-up trial: ClinicalTrials.gov, NCT04443855. Original WASH-Benefits Bangladesh (WASH-B): ClinicalTrials.gov, NCT01590095.
Safeguarding Open Science from exploitative practices.
Maupin D, Spick M, Geifman N
PLoS Med · 2025 Dec · PMID 41379828 · Full text
Open research and data transparency are a bulwark against unethical activities, but can also introduce integrity risks. As with all public goods, freely available data can be exploited, and here we set out the case for t...
Open research and data transparency are a bulwark against unethical activities, but can also introduce integrity risks. As with all public goods, freely available data can be exploited, and here we set out the case for the use of safeguarding practices.
From sex differences to sex inequalities in life expectancy: A cross-country observational benchmarking analysis.
Chang AY, Johnson EK, Bolongaita S … +9 more , Buse K, Hawkes SJ, Karlsson O, Knaul FM, Kruk ME, Norheim OF, Ogbuoji O, Watkins D, Jamison DT
PLoS Med · 2025 Dec · PMID 41379774 · Full text
BACKGROUND: The answer to whether females or males have better health, and which sex is the more disadvantaged, has depended in part on the metric and how the inequality is measured. This study introduces a new method fo...
BACKGROUND: The answer to whether females or males have better health, and which sex is the more disadvantaged, has depended in part on the metric and how the inequality is measured. This study introduces a new method for analyzing and interpreting sex inequalities in health outcomes-defined as the avoidable sex differences in health outcomes-that is systematic and potentially more objective. For this paper, we focus on life expectancy at different ages. METHODS AND FINDINGS: We introduce the adjusted sex ratio as a measure of sex inequalities and determining sex disadvantage. First, we calculated the sex ratio of life expectancy at ages 0, 5, 15, 35, 50, and 70. To understand what is achievable under favorable conditions, we identified countries in the 5th percentile of the highest life expectancy for each sex and used these values as benchmarks, and calculated the sex ratio of these best-performing countries ("frontier"). We calculated the country- and age-specific adjusted sex ratio by dividing country sex ratios by frontier sex ratios. This assumes that theoretically, under the current risk and healthcare environments, females all over the world have the potential to live up to the life expectancy of the females in the frontier countries, and separately, all males to their male-specific frontier. An adjusted ratio of greater than one indicates male disadvantage, while below one indicates female disadvantage. To avoid overinterpreting small differences, we defined a narrow range around equality (ratio of 1) within which we do not label either sex as disadvantaged. Before adjustment, males in all countries (except two) and at all ages had lower life expectancy than females. After adjustment, between 13% (at age 0) and 33% (at age 70) of the 237 countries shift from male to female disadvantage in life expectancy. More than half of the countries remain male-disadvantaged, indicating that males are generally disadvantaged in terms of life expectancy in most countries, even after our adjustments. India and approximately half of the countries in the Middle East and North Africa, North Atlantic, sub-Saharan Africa, and Western Pacific and Southeast Asia show female disadvantage. The number of countries with female disadvantage rises with age, especially in sub-Saharan Africa and Western Pacific and Southeastern Asia. Central and Eastern Europe show substantial male disadvantage across nearly all ages, even with adjustment. Our frontier selection and buffer range are empirical choices, and other definitions could be equally valid. Although our sex-specific benchmarks use the best-performing countries for each sex, they are not meant to represent purely biological differences, as observed sex gaps in life expectancy may also reflect unmeasured genetic variation, environmental exposures, and their interactions with sex. CONCLUSION: This study provides a novel, potentially more objective method for assessing sex inequalities in health outcomes, and presents the trends across countries, age, and time.
Heterogeneous impacts of HIV pre-exposure prophylaxis (PrEP) on drug resistance and phylogenetic cluster transmission dynamics in British Columbia, Canada: A retrospective cohort and simulation study.
McLaughlin A, Toy J, Montoya V … +7 more , Sereda P, Trigg J, Hull M, Brumme CJ, Barrios R, Montaner JSG, Joy JB
PLoS Med · 2025 Dec · PMID 41364728 · Full text
BACKGROUND: HIV pre-exposure prophylaxis (PrEP) prevents infection when used during periods of risk, however, its population-level effectiveness is hindered by incomplete uptake, adherence, and retention. Since oral PrEP...
BACKGROUND: HIV pre-exposure prophylaxis (PrEP) prevents infection when used during periods of risk, however, its population-level effectiveness is hindered by incomplete uptake, adherence, and retention. Since oral PrEP became available free-of-cost in British Columbia (BC), Canada, in January 2018, uptake has been rapid among eligible individuals, primarily comprising gay, bisexual, and other men who have sex with men (GBM), however, its effectiveness against HIV acquisition across subpopulations alongside potential effects on baseline drug resistance have not been estimated. We evaluated individual and population-level impacts of PrEP on HIV drug resistance and transmission in phylogenetic clusters, representing groups of individuals linked by recent outbreaks, to elucidate heterogeneity in its effectiveness. METHODS AND FINDINGS: Using a retrospective cohort design, we evaluated the frequencies of baseline drug resistance mutations and membership in phylogenetic clusters among newly HIV diagnosed people who ever filled a prescription for HIV PrEP (i.e., PrEP users) in BC (n = 39) compared to non-PrEP users (n = 566) diagnosed from 2018 to 2022 in the BC Drug Treatment Program with at least one sequence available. Newly HIV diagnosed PrEP users were significantly more likely than newly diagnosed non-PrEP users to be included in phylogenetic clusters (chi-squared test, p = 0.0075) and carry baseline nucleoside analogue reverse transcriptase inhibitor (NRTI) resistance mutation M184I/V (Fisher's exact test, adjusted p-value = 0.025). Subsequently, we quantified the population-level impacts of widespread PrEP availability on transmission based on the effective reproduction number (Re), compared across key populations living with HIV in BC and active phylogenetic clusters with at least one new case since 2018. We applied simulations of active clusters' growth based on their empirically observed Re with or without estimated PrEP impacts to estimate diagnoses averted via PrEP across clusters, with non-clustered cases grouped together. Most diagnoses were averted in large and medium GBM-predominant clusters. In a Poisson model, clusters with fewer diagnoses averted were associated with having a higher median age and lower proportion of new diagnoses with PrEP use, adjusted for cluster size at the end of 2017 and proportion residing in Vancouver Coastal Health Authority. These results must be interpreted in light of uncertainty owing to incomplete sampling, the use of consensus genomes, phylogenetic inference, and the assumptions of counterfactual simulations. CONCLUSIONS: We estimated that the oral PrEP program in BC from 2018 to 2022 averted approximately 20 new HIV diagnoses per year across phylogenetic clusters, while infrequently contributing to baseline drug resistance in instances where PrEP was inadvertently prescribed during acute infection or with incomplete adherence. These findings corroborate the broad effectiveness of PrEP, describe heterogeneity in its impacts on clusters' growth, and suggest groups for prioritized PrEP services.
Vaccines to prevent bacterial sexually transmitted infections: Promise, progress, and public health potential.
Gottlieb SL, Rees H, Peters RPH
PLoS Med · 2025 Dec · PMID 41364628 · Full text
Asymptomatic transmission, inequitable access to diagnostics, and rising antimicrobial resistance are major barriers to controlling the bacterial sexually transmitted infections (STIs) gonorrhea, chlamydia, and syphilis....
Asymptomatic transmission, inequitable access to diagnostics, and rising antimicrobial resistance are major barriers to controlling the bacterial sexually transmitted infections (STIs) gonorrhea, chlamydia, and syphilis. Developing vaccines against these infections has therefore become a key STI research priority, requiring innovative research, expedited clinical development, and increased investment.
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