EClinicalMedicine

PURPOSE: Cancer outcomes in sub-Saharan Africa are driven by delayed diagnosis and treatment initiation. We evaluated the magnitude and determinants of diagnostic and treatment delays among cancer patients in Kinshasa, Democratic Republic of the Congo (DRC). METHODS: We conducted a hospital-based cross-sectional study of 460 adults with confirmed cancer at Nganda Hospital Center in Kinshasa, DRC. Two outcomes were assessed: delay from symptom onset to diagnosis and delay from diagnosis to treatment initiation. Log-normal regression models were fitted for each outcome to estimate adjusted geometric mean ratios (aGMRs) and 95% confidence intervals (CIs). Covariates included demographic, socioeconomic, clinical, behavioral, and stigma-related factors. RESULTS: The median age was 55 years, and 76.2% of participants were women. Overall, 55.0% of participants experienced symptom-to-diagnosis delays >6 months, and 49.4% experienced diagnosis-to-treatment delays >3 months. Older age was associated with longer diagnostic delay (aGMR 1.55, 95% CI 1.03-2.31) and treatment delay (1.51, 1.07-2.14). Unemployment was strongly associated with both diagnostic delay (1.68, 1.15-2.47) and treatment delay (2.27, 1.54-3.33), as was hepatitis B co-infection (1.88, 1.06-3.34 and 2.42, 1.15-5.11, respectively). Longer diagnostic delay was additionally associated with informal trading (1.99, 1.21-3.28), taxi or motorbike transport (1.92, 1.25-2.94), and smoking history (2.25, 1.03-4.91), while high cancer-stereotype stigma was associated with longer treatment delay (1.56, 1.04-2.34). CONCLUSION: Substantial delays exist across the DRC cancer care continuum, driven by socioeconomic vulnerability, transport barriers, hepatitis B co-infection, and cancer-related stigma. These findings highlight the need for integrated interventions to improve timely diagnosis and treatment initiation, including strengthening financial protection, decentralizing cancer services, and reducing stigma in cancer care.

Background: Adults with severe mental health conditions (often referred to as severe mental illness, SMI) experience 15 to 20 year mortality gap relative to the general population, with lung cancer a significant contributor. National cancer policy targets earlier diagnosis but does not explicitly address how pathways function for this group. Aims: This study aimed to describe lung cancer risk, prevalence, screening eligibility, referral activity and diagnostic pathway performance for adults with SMI in South East London (SEL), and to examine where along the pathway inequalities arise. Methods: Co-designed with experts with lived experience and voluntary sector, this exploratory mixed-methods service evaluation combined quantitative analysis of routinely collected data from the Quality Outcomes Framework (QOF), SMI Register and Cancer Waiting Times Record (April 2023-March 2024) with semi-structured qualitative interviews (n=11 clinical staff) and focus groups (n=6 adults with lived experience of SMI). Quantitative and qualitative data were analysed using descriptive statistics and framework-based thematic analysis respectively, and findings were integrated using a joint display approach, organised by the Consolidated Framework for Implementation Research (CFIR). Results: Lung cancer prevalence was approximately double among adults with SMI (0.17% vs 0.09% in the general population). Despite Urgent Suspected Cancer (USC) referral rates being more than twice as high in the SMI population (63 vs 28 per 100,000), fewer cancers were detected via planned general practice (GP) routes (11% vs 20%), the 28-day Faster Diagnosis Standard was not met for any SMI patient diagnosed with lung cancer during the study period; overall FDS performance was 76% in the SMI population compared with 84% in the general population; and appointment non-attendance was more than double that in the general population (6% vs 3%). Qualitative findings identified individual, service and system-level mechanisms, including stigma, diagnostic overshadowing, fragmented coordination, and rigid pathway protocols, that compound disadvantage across lung cancer pathway stages. Conclusions: Inequality in lung cancer outcomes for adults with SMI accumulates across the pathway rather than arising at a single point of failure. Addressing this requires proportionate adaptations within existing cancer pathways, alongside routine reporting of cancer outcomes stratified by SMI population. Keywords: severe mental health conditions, lung cancer, health inequalities, cancer screening, diagnostic pathway, mixed methods

INTRODUCTION Severe acute brain injury (stroke, traumatic brain injury or hypoxic-ischemic encephalopathy; SABI) is increasingly recognized as a chronic condition with care and communication needs beyond the initial hospitalization. This study aimed to characterize post-acute care patterns among SABI survivors, focusing on healthcare utilization and outpatient communication. METHODS Data were collected from a prospective cohort of hospitalized SABI patients using surveys, chart reviews, and the ED Information Exchange database. Socioeconomic disadvantage was assessed using the Area Deprivation Index (ADI), and qualitative analysis of outpatient notes examined conversations around palliative care needs and goals-of-care. RESULTS Two-thirds of patients (140/222) survived until discharge, primarily to nursing facilities (39%) or inpatient rehabilitation (38%). Among 109 with one-year follow-up, there were 89 hospitalizations, 104 ED visits, and 28 deaths. Patients from the most disadvantaged neighborhoods had significantly higher odds of rehospitalization or ED use within 30 days (OR 3.37, p=0.036). ADI was not linked to one-year utilization. seen outpatient by primary care (40%), neurology/neurosurgery (57%), and palliative care (1%), but conversations rarely revisited prognosis or goals-of-care. CONCLUSIONS Our findings highlight the need for improved long-term care planning and communication, particularly for socioeconomically disadvantaged survivors of SABI.

Background: People affected by dementia experience intersecting care inequalities. We explored relationships between ethnicity and health and social care resource use among people with dementia in an ethnically diverse urban region. Methods: We conducted a retrospective observational cohort study using Discover-NOW, including patients with dementia between 1.4.2015 and 1.4.2025. We calculated ethnic density as the percentage of the Middle Layer Super Output Area (SOA) population self-identifying with the same ethnic group. Regression models, clustered by Local SOA, tested whether ethnic density moderated relationships between ethnicity and primary care, outpatient, inpatient, emergency and social care service use, controlling for sociodemographic characteristics, deprivation, comorbidities and time of diagnosis. Findings: We included 30,704 people with dementia. People from Black and Mixed ethnic groups used more primary care, and those from Asian ethnic groups less primary and secondary care, than White ethnic groups. Rates of local authority social care packages were similar across ethnic groups. High ethnic density predicted fewer GP consultations in Black ethnic groups, but more in South Asian groups. Interpretation: Among Black ethnic groups, primary care use was relatively high, especially in areas of low ethnic density, perhaps reflecting greater needs among communities at risk of racism and isolation. The trend towards increased primary care use among South Asian people in areas of higher ethnic density may reflect communities mitigating help-seeking hesitancy related to cultural and language barriers. Greater care integration could reduce care inequalities among minority ethnic communities who may experience fewer barriers to social relative to health care.

BackgroundThe emergency department (ED) serves as a critical entry point into hospital care and a sentinel indicator of health system performance. In-hospital mortality within 48 hours of ED admission represents acute care failures that are often preventable yet remain poorly characterized in sub-Saharan African (SSA) settings. This study aimed to identify the demographic, clinical, and hospital-related determinants of in-hospital mortality within 48 hours of admission to the Emergency and Urgent Care Department at the University Teaching Hospital (UTH), Lusaka, Zambia. MethodsA retrospective cross-sectional study was conducted using 385 patient records from UTHs Emergency and Urgent Care Department for the year 2021. Data were extracted from the District Health Information System 2 (DHIS2) using simple random sampling. Descriptive statistics, univariate, and multivariable logistic regression analyses were performed using STATA 16.1 MP. Variables with p<0.20 in univariate analysis were retained for adjusted modelling. Multicollinearity was assessed via variance inflation factors (VIF <5). Model fit was evaluated using the Hosmer-Lemeshow goodness-of-fit test and receiver operating characteristic (ROC) analysis. ResultsOf 385 patients, 175 (45.5%) died within 48 hours of admission. Patients who died were older (median age 45 vs. 37.5 years, p<0.001). In multivariable analysis, three variables were independently associated with 48-hour mortality: pulse rate (aOR = 0.98, 95% CI: 0.95-1.00, p = 0.036), Glasgow Coma Scale (GCS) score (aOR = 0.75, 95% CI: 0.63-0.90, p = 0.002), and out-of-hours admission between 00:00-07:59 (aOR = 11.44, 95% CI: 1.19-109.96, p = 0.035). Age was a significant predictor in univariate analysis but not in the adjusted model, indicating confounding. The model demonstrated good discriminatory ability (AUC = 0.81). ConclusionsReduced pulse rate, lower GCS score at admission, and out-of-hours presentation are independent determinants of 48-hour in-hospital mortality at UTH. These findings underscore the need for enhanced vital sign monitoring protocols, targeted staffing during overnight hours, and improved risk stratification tools in resource-constrained emergency care settings. The wide confidence interval for the time-of-admission finding warrants cautious interpretation and validation in future prospective studies.

Background: The Functional Outcome in Patients with Primary Intracerebral Hemorrhage (FUNC) score was initially validated for prediction of functional independence on the Glasgow Outcome Scale (GOS) 90 days after intracerebral hemorrhage (ICH), but recovery often extends beyond three months. Aims: Our objective was to extend the FUNC score for prediction of 12-month functional independence to strengthen its utility for family counseling and research methodology. Methods: We conducted a single-center prospective cohort study enrolling adult patients with primary ICH between February 2009 and January 2018. We calculated FUNC scores at admission and assessed GOS 12 months after ICH. The primary outcome was 12-month functional independence, defined as a GOS score [&ge;]4. We calculated the area under the receiver operating characteristic curve (AUC) of the FUNC score using logistic regression, handling missing GOS with multiple imputation by chained equations. We evaluated score calibration using a calibration curve and the Brier score, and we assessed clinical utility using decision curve analysis. We explored the statistical efficiency gains of using FUNC-based sliding dichotomy thresholds for favorable outcome definitions by running simulations of a clinical trial with 1:1 randomization. We ran 5000 simulations for each sample size (100 to 1000, in increments of 10) and treatment effect (odds ratio of 1.5, 2.0 and 2.5) combination and calculated efficiency gains for each respective treatment effect as the percentage reduction in sample size required to have 80% power using sliding versus fixed dichotomy thresholds. Results: A total of 535 patients were included (median [IQR] age 68 [54-79], 237 [44%] female, median [IQR] NIHSS 16 [6-25], median [IQR] FUNC 8 [6-9]). Overall, 99 of 445 (22%) patients with known 12-month GOS achieved functional independence. The FUNC score had an AUC of 0.79 (95%-CI: 0.75-0.84) for 12-month functional independence. The calibration plot was reasonable, with modest evidence of overestimation at low predicted probabilities, and the Brier score was 0.15. A net benefit was observed across 5-50% threshold probabilities. Sliding dichotomy had an efficiency gain of 27% for a treatment effect of OR=2.0, and a gain of 22% for a treatment effect of OR=2.5. The efficiency gain for a treatment effect of OR=1.5 could not be calculated because the fixed dichotomy did not reach 80% power despite a sample size of 1000 patients. Conclusions: The FUNC score's predictive performance for 12-month functional independence was comparable to its originally validated 3-month discrimination. Following external validation across centers, the FUNC score may be leveraged to counsel families on global measures of long-term functional independence and to implement sliding dichotomy methodology in ICH research.

Abstract Introduction: MET tyrosine kinase (TKI) therapy has improved outcomes in patients with non-small cell lung cancer (NSCLC) harboring MET alterations. However, primary and acquired resistance ultimately limits durability of response. This study evaluated the safety and efficacy of the MET inhibitor capmatinib with the MEK inhibitor trametinib in patients with metastatic MET-driven NSCLC who had progressed on prior treatment with at least one MET inhibitor. Methods: A multicenter phase I study evaluated capmatinib in combination with trametinib in patients with advanced stage NSCLC harboring activating MET alterations and prior exposure to at least one MET TKI. A 3+3 dose-escalation design was employed to assess safety and tolerability of the combination. Results: Three patients (n = 3) were enrolled in the study and completed a median of 3 cycles of therapy. Dose-limiting toxicities, including rash, edema, and nausea, necessitated dose reductions in the first two patients and initiation of the third patient at a lower dose level. Ultimately, all patients discontinued therapy due to treatment-related adverse events. The study was terminated early due to poor accrual and TRAEs. No radiographic objective responses were observed. Conclusions: In this phase I trial, capmatinib plus trametinib was associated with significant treatment-related adverse events and treatment was discontinued in all participants. Based on these findings, further investigation of this combination of MET and MEK inhibitors is not recommended.

Background and Aims SARS-CoV-2 infection is associated with an increased risk of cardiovascular, cerebrovascular and venous thromboembolism events. We aimed to assess the impact of COVID-19 vaccination prior to SARS-CoV-2 infection on the risk of these events post-infection. Methods Embase and MEDLINE were searched from January 2021 to 11 September 2025, supplemented by citation searching. Observational studies were included if they reported risks of cardiovascular, cerebrovascular, or venous thromboembolic events after SARS-CoV-2 infection between different vaccination groups (e.g. unvaccinated, vaccinated, or booster vaccinated), or reported risk of events after SARS-CoV-2 infection compared with no infection, stratified by vaccination status. Random-effects meta-analyses were conducted to estimate pooled hazard ratios (HRs) comparing vaccinated and unvaccinated individuals across prespecified outcomes. Results Twenty-three studies were included in the systematic review; most reported an association between vaccination and a reduced risk of post-infection vascular events. Ten studies were included across meta-analyses comparing vaccinated and unvaccinated individuals. Pre-infection vaccination was associated with significantly reduced risks of composite cardiovascular/cerebrovascular events (HR 0.60, 95% confidence intervals [CI] 0.51-0.69), stroke (HR 0.75, 95% CI 0.64-0.88), acute coronary syndrome (HR 0.70, 95% CI 0.52-0.95), arrhythmias (HR 0.82, 95% CI 0.69-0.98), and venous thromboembolism (HR 0.51, 95% CI 0.36-0.73). No statistically significant reduction was observed for heart failure (HR 0.72 [95% CI 0.47-1.10]). Conclusions Pre-infection COVID-19 vaccination is associated with lower risks of cardiovascular, cerebrovascular and venous thromboembolism events following SARS-CoV-2 infection in the pre- and post-Omicron eras, supporting its role within broader prevention strategies

Background: Wearing facemasks and practising social distancing slow the spread of respiratory pathogens. However, in the event of a new pandemic emerging, the willingness of populations to voluntarily adopt these behaviours is unclear. Methods: A discrete choice experiment was conducted among 2,006 UK-based adults. Participants were presented with hypothetical scenarios describing the emergence of a respiratory virus pandemic and were asked to choose when they would wear facemasks and practise social distancing. A mixed multinomial logit model was used to jointly estimate how disease severity and prevalence, uncertainty in these quantities, and individual-level characteristics influence behavioural choices. Findings: Participants were averse to facemasks and social distancing in the absence of pandemic risk. For each ten-unit increase in severity (10 additional hospitalisations/1,000 infections), the odds of always wearing a facemask outside the home increased by 15.9% (95%CI: 14.3%, 17.5%), relative to rarely/never, and the odds of avoiding all people as much as possible increased by 16.4% (14.6%, 18.2%), relative to not avoiding anyone. Greater disease prevalence, uncertainty in disease severity or disease prevalence, a university education, prior COVID-19 vaccination and non-white ethnicity were also associated with choosing to always wear facemasks and avoid all people as much as possible. The probability of participants choosing to rarely/never wear facemasks varied from 13.4% (11.9%, 14.9%) in the lowest-risk scenario to 1.4% (1.2%, 1.7%) in the highest-risk scenario. Interpretation: Perceived risks of disease and associated uncertainty drive intention of UK adults to adapt their behaviour in a future pandemic.

Background Microbiological confirmation of paediatric pulmonary tuberculosis is frequently unattainable, rendering chest radiography a critical yet underutilised diagnostic tool. Methods We conducted a retrospective diagnostic accuracy study of the qXR version 4.2.1 (Qure.ai), a paediatric optimized computer-aided detection (CAD) algorithm, for pulmonary tuberculosis. Diagnostic performance was assessed against microbiological (MRS) and clinical reference standards (ClRS). Bayesian latent class analysis (LCA) was applied to address the imperfection of both reference standards in children. Performance was quantified using area under the receiver operating characteristic curve (AUROC) and estimates of sensitivity and specificity. Results We included digital chest radiographs of 932 Gambian children (< 15 years) comprising 80 (9%) children with confirmed tuberculosis, 163 (17%) with unconfirmed tuberculosis, and 689 (74%) classified as unlikely tuberculosis. Against MRS, qXR demonstrated AUROC, sensitivity and specificity of 0.68 (95% CI, 0.61 to 0.75), 54% (95% CI, 43 to 64%), and 82% (95% CI, 79 to 84%), respectively. Against ClRS, the AUROC, sensitivity and specificity were 0.73 (95% CI, 0.69 to 0.77), 41% (95% CI, 34 to 49%), and 87% (95% CI, 84 to 89%), respectively. Bayesian LCA, assuming conditional independence, estimated sensitivity of 79% (95% CrI, 65 to 89%) and specificity of 82% (95% CrI, 79 to 84%). Assuming conditional dependence between qXR and expert radiologist, and between culture and Xpert, estimated sensitivity increased to 89% (95% CrI, 71 to 98%), with specificity remaining at 82% (95% CrI, 79 to 84%). Conclusions Paediatric optimized qXR algorithm provides a valuable complementary tool for diagnosis of paediatric pulmonary tuberculosis. Conventional reference standards likely underestimate the true diagnostic performance of CAD systems in children.

Abstract Background Cancer is an increasing public health challenge in Kenya, particularly in rural and underserved regions where surveillance systems and diagnostic capacity remain limited. Kilifi County, located along the Kenyan coast, lacks a population-based cancer registry, and data on the local cancer burden is not available. This study aimed to characterize the demographic distribution of patients, cancer burden in the county, and management of cancer cases diagnosed at Kilifi County Referral Hospital (KCRH) over ten years. Methods This retrospective study analyzed the patterns of cancer in Kilifi County using patient records from KCRH during the study period (January 1, 2014, to January 1, 2024). Results A total of 101 patients with cancer were identified, 58% female, with a mean age of 54 years. Most patients were from Kilifi North (47%), with a high proportion reporting no formal occupation (41%) or farming (26%). Esophageal and cervical cancers were the most common (18% each), followed by breast and prostate cancers (5% each), with other malignancies occurring infrequently. Histopathology was the primary diagnostic modality (88%). Staging data were incomplete in 70% of cases; among documented cases, the majority presented with advanced disease (21% stage IV). Due to limited local treatment capacity, approximately half of the patients were referred to tertiary centers for chemotherapy, radiotherapy, or surgery. At data cut-off, 43% had died, 25% were on treatment, and 29% were lost to follow-up, with only 2% completing treatment or under follow-up. Conclusions This study demonstrates a substantial cancer burden in Kilifi County and highlights critical gaps in diagnostic capacity, staging, and continuity of care. Strengthening cancer surveillance systems, expanding diagnostic and treatment infrastructure, and establishing a population-based cancer registry are essential to improving cancer outcomes and advancing equitable care in rural Kenya

Background: Large language models (LLMs) demonstrate strong performance in controlled medical environments such as multiple choice exams, but their utility in real-world clinical workflows remains unproven. The NHS Advice & Guidance (A&G) service, where Primary Care clinicians can submit text-based queries to specialists, provides an environment for evaluating the clinical performance of LLMs as a specialist. Methods: We compared responses from MedGemma 4B-IT, an open-weight model deployed locally on hospital infrastructure, against specialist neurologist responses across 50 adult neurology A&G cases from University College London Hospital. Two neurologists and two GPs rated 80 blinded and 20 unblinded responses for outcome, safety, efficacy, and feasibility using standardised criteria; outcome was a binary correct/incorrect, while other domains were scored 1-5. Inter-rater reliability was assessed using intraclass correlation coefficients. Results: Although there were no statistically significant differences between blinded specialist neurologists and LLM responses across any domain (outcome: 84% vs 82%, p=0.67; safety: 3.98 vs 4.02, p=0.85; efficacy: 4.06 vs 3.98, p=0.61; feasibility: 4.39 vs 4.20, p=0.45), 10% of LLM responses received concerning scores ([&le;]2 average score) compared to 0% of human responses, indicating potentially clinically important tail risk. Furthermore, unblinded results showed a preference for human responses, with human ratings being preferred across all domains. Only 51% of binary outcomes had unanimous agreement and inter-rater agreement was moderate across other domains (ICC 0.50-0.52). Conclusions: In this pilot study, aggregate scores between blinded human and LLM responses were similar, and no statistically significant differences were detected in this exploratory sample. However, aggregate metrics masked clinically important edge-case failures in LLM responses. Pronounced inter-rater variability and the potential impact of LLM/human syntax on blinded rater judgements highlight the challenges in establishing robust evaluation frameworks for clinical LLM deployment

Objectives: To describe secondary mental healthcare utilisation and associated costs among patients diagnosed with dementia or mild cognitive impairment (MCI). Design: Retrospective cohort study using routinely collected electronic health record data. Setting: Secondary mental healthcare services within a large NHS mental health provider in South London, UK. Participants: Adults aged 18 years or older with a recorded diagnosis of dementia or MCI between 1 January 2010 and 31 December 2020. Patients surviving less than one year after diagnosis were excluded. The final cohort comprised 16,081 individuals. Primary and secondary outcome measures: Service utilisation and NHS mental health service costs during the 12 months before and after diagnosis, including inpatient, outpatient and memory clinic contacts. Results: The proportion of patients with at least one recorded mental health service contact declined from 91% in the 12 months before diagnosis to 69% after diagnosis. Among service users, mean NHS mental health costs increased from GBP 1,497 to GBP 2,177 per person following diagnosis (mean increase GBP 680; p<0.001), driven primarily by inpatient care. Dementia diagnosis, younger age, male gender, living alone, greater cognitive impairment and higher clinical symptom burden were independently associated with higher costs. Ethnic differences in service use and costs were also observed. Conclusions: Although overall service engagement declined following diagnosis, costs increased among those continuing to access care, indicating greater intensity of service use. Understanding patterns of secondary mental healthcare utilisation and associated costs may help inform planning and resource allocation within dementia services.

The impact of social parameters on brain health among people with traumatic brain injury (TBI) has been extensively documented. However, translation of this evidence into policy and clinical practice remains limited. This may reflect a lack of coordinated and equity-driven approaches to brain health that integrate diverse stakeholder perspectives, limiting progress toward equity-oriented research and service delivery models. We conducted a convergent parallel mixed-methods study guided by the REporting guideline for PRIority SEtting of health research (REPRISE). We utilized the PROGRESS-Plus framework (Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, and context-specific parameters) to ensure systematic consideration of social parameters in the study. For Objective 1, we synthesized existing evidence on social parameters and brain health outcomes. For Objective 2, we surveyed people with lived experience of TBI, family members/friends, clinicians, researchers, and community leaders across the globe to assess their prioritization of social parameters relevant to brain health. For Objective 3, we integrated evidence synthesis and stakeholder input through a structured Round Robin consensus activity to prioritize actionable areas for feasibility and impact. The activity culminated in the development of a knowledge mobilization agenda designed to inform equity-centred policy, research, and clinical practice. In Objective 1, we identified 59 publications with evidence on the effect of PROGRESS-Plus parameters on brain health outcomes following TBI. Meta-research highlighted that education, age, and country-level indicators are prognostic for brain health after TBI. In Objective 2, the highest-ranked priorities of 113 stakeholders across four continents (North America, Europe, Africa, and Oceania) were education, access to benefits, and income. These priorities were at the centre of discussion in Objective 3, which comprised idea sharing, refinement and thematic clustering, and a final prioritization poll. The resulting final 15 priorities were organized into two tracks: Track A, actions feasible in the short term, and Track B, longer-term implementation priorities. Building on this priority-setting process, co-created with stakeholders around the globe, the findings provide a roadmap for integration of social parameters in TBI research, knowledge exchange, policy, and practice.

Malignant pleural effusion (MPE) frequently complicates advanced cancer and impairs quality of life. Chemical pleurodesis with agents such as bleomycin or povidone iodine is widely used, but comparative efficacy and safety remain uncertain. Bleomycin is an established agent but is costly and less available, whereas povidone iodine is affordable and easily accessible. This study aimed to systematically compare the efficacy and safety of bleomycin versus povidone iodine for pleurodesis in patients with malignant pleural effusions. We conducted a systematic review and meta-analysis following PRISMA guidelines. PubMed, Semantic Scholar, and the Google Scholar were searched through May 20th 2025. Studies included randomized controlled trials and cohort studies comparing bleomycin and povidone iodine for pleurodesis in patients with MPE. Seven studies with 392 patients (174 in the povidone iodine group, 218 in the bleomycin group) were included. Success rates for pleurodesis ranged from 71.1% to 100% for povidone iodine and 66.7% to 95.2% for bleomycin. Meta-analysis showed no significant difference in efficacy (RR = 1.04, 95% CI: 0.94-1.15, p = 0.50; I2 = 43%). Both agents were well tolerated, with similar rates of mild adverse events. This study showed no significant bias. Povidone iodine and bleomycin are equally effective and safe for pleurodesis in MPE. Given its lower cost and greater accessibility, povidone iodine may be preferred, especially in resource-limited settings.

Background: Mortality rates have declined across most high-income countries for decades, but recent evidence suggests a slowdown in improvements or a shift to increasing mortality, particularly among working-age populations. The international distribution and drivers of these trends remain incompletely understood. Methods: Mortality trends during 2012-2019 were analysed using all-cause and cause-specific data from 30 countries. Trends were estimated via linear regression. K-means clustering with Dynamic Time Warping identified countries and ICD-10 chapters with similar temporal trajectories. Results: Trends varied substantially by nation. While Japan, Switzerland, and the Republic of Korea maintained consistent declines in all-cause mortality rates, increases were concentrated in the United States, Canada, and the United Kingdom, most prominently in persons aged 30-59 years. However, cause-specific analysis showed that rising mortality was not confined to these countries: most countries exhibited increases in at least one ICD-10 chapter, with several European countries showing increases across multiple chapters. Across countries, a small set of causes recurred among increasing trends, including external causes (self-harm, drug poisoning) at younger ages and chronic conditions (cardiovascular and liver diseases, specific cancers) in mid-life. Notably, ill-defined causes of death consistently appeared among the increasing causes across countries and age groups. Conclusions: Mortality increases in the 2010s were geographically more widespread than previously recognized. The recurrent rise in mortality from ill-defined causes suggests that an important component of mortality change remains poorly characterized. These findings indicate that stalled health progress is a systemic challenge across many high-income societies.

BackgroundMultiple studies suggest bidirectional links between delirium and Alzheimers Disease and Related Dementias (ADRD). Although they establish a strong association between delirium and subsequent ADRD, it has not been explored using statistical causal inference which makes the best use of observational data to minimize biases. MethodsWe conducted an emulated clinical trial to estimate the effect of experiencing delirium during hospitalization between April 2017 and September 2019 on the cumulative incidence of ADRD over two years following hospital admission in patients 65 and older. The emulated trial used observational data from individuals in the Mass General Brigham Electronic Medical Record (EMR). We carried out statistical causal survival analysis using methods that adjust for confounding, censoring, competing risks, and immortal-time bias, including inverse propensity weighting (IPW) and g-formula approaches. ResultsOf the 6029 patients hospitalized in this time frame who were 65 or older with evidence of a PCP in the EMR, 5901 were included in the analysis based on no history of dementia diagnosis or medications 12 months prior to admission. At two years post-admission, the adjusted cumulative incidence of ADRD in individuals who did not experience delirium was 7.6% (95% Confidence Interval [CI] 4.0-12.1%) while it was 20.2% (95% CI 13.2-27.9%) for those who did experience delirium when calculated using the IPW method. ConclusionsOur emulated trial results argue for a strong association between delirium during hospitalization and the risk of developing ADRD in the two years following hospital admission in individuals 65 and older. Key PointsO_ST_ABSQuestionC_ST_ABSWe sought to answer whether statistical causal inference would show the same association between delirium and the onset of dementia in the two years following hospitalization. FindingsOur emulated trial results argue for a strong association between delirium during hospitalization and the risk of developing ADRD in the two years following hospital admission in individuals 65 and older. MeaningThe implications of demonstrating this relationship underscore the importance of delirium-mitigating interventions for long-term cognitive outcomes.

Background and Purpose Prognostication after acute ischemic stroke often relies on limited variables and simple risk scores, despite richer information being available at admission. We developed a multimodal AI model using admission data to predict modified Rankin Scale (mRS) outcomes and compared it to established tools. Methods In a retrospective study of ischemic stroke/TIA patients, we trained three modality-specific models on admission non-contrast head CT, history and physical notes, and structured clinical variables, and combined them in a weighted-average ensemble. We predicted binary (mRS 0-2 versus 3-6) and ordinal mRS (0-6) outcomes at discharge and 90 days. Performance on an external test cohort was compared with THRIVE and SPAN-100 scores using AUROC, AUPRC, Brier score, mean absolute error (MAE), and quadratic weighted kappa (QWK). Results A total of 6,915 patients were split into training, validation and testing cohorts in a 3:1:1 ratio. For discharge binary mRS (n=1596), the multimodal ensemble achieved significantly better discrimination (AUROC 0.859, AUPRC 0.858) with 25-61% lower Brier scores than THRIVE or SPAN?100 (all p<0.001). For 90?day binary mRS (n=207), the model also outperformed both THRIVE and SPAN-100 (AUROC 0.838, AUPRC 0.805, with 3-38% lower Brier scores). Ordinal mRS prediction showed similarly strong performance with significantly better QWK at discharge and numerically lower MAE. The multimodal ensemble model reassigned about one?third of patients to different risk categories versus THRIVE and was closer to the true discharge outcome in ~74% of discordant cases. Conclusions We developed a well-calibrated multimodal AI model for prediction of discharge and 90-day post-stroke functional outcomes using only data present at the time of admission. This model outperforms existing prognostic tools and can support early clinical decision-making.

Background: Despite rising enthusiasm for active case-finding for TB, there have been concerns about conducting simultaneous HIV screenings due to perceived stigma, although the evidence to support this concern is scarce. We assessed the acceptability of integrated HIV-TB community screening and characterised participants' motivations and prior testing history. Methods: The SLIM study was a non-interventional cross-sectional study conducted in Puducherry (February 2023 to January 2024). In two community health camp-style screening events (one urban and one peri-urban), adults 18 years and older were offered TB screening via portable chest X-ray with AI-assisted interpretation (qXR, Qure.ai), plus sputum testing (Truenat), alongside point-of-care HIV testing. Structured questionnaires captured sociodemographics, prior testing history, and motivations for participation. Acceptability was pre-specified as >50% uptake. Results: Of 273 eligible adults approached, 264 (96.7%) accepted integrated screening, nearly double our pre-specified threshold. Participants were predominantly low-income with limited formal employment. The dominant motivation was a desire to know one's health status (HIV: 74.8%; TB: 73.7%), followed by convenience (16 to 17%). Prior HIV and TB testing was rare (7 to 13% and 15 to 18%, respectively). Participation was uniformly high across demographic groups; however, the screened population skewed older and female (mean age 58 (standard deviation: 12.6) years; 67% female). Men under 45 comprised only 3.7% of participants, substantially below their 24.7% share in the Puducherry population per the most recent census. Conclusions: Integrated HIV-TB screening achieved near-universal uptake in a socioeconomically vulnerable population with little prior testing exposure, contradicting concerns that community HIV screening would be poorly accepted in India. Integrated community-based screening should be scaled up as a cornerstone of TB elimination in high-burden settings. Crucially, because TB incidence in India peaks in the 15 to 45 age group and disproportionately affects men, targeted strategies to bring younger men and women into community screenings are essential.

Background The majority of family dementia caregivers in the United States (U.S.) are now young and middleaged adults. However, little research has been conducted to understand how caregiver needs and preferences for support differ depending on their phase of adulthood. This study evaluated differences in mental health, caregiving readiness, desired supports, and intervention preferences among early (<46 years), middle (46 to 60 years), and late (>60 years) adulthood dementia caregivers. Methods A cross sectional survey was conducted with 202 family dementia caregivers aged 22 to 88. Caregivers completed validated measures of burden, anxiety, depression, well being, time pressure, dementia knowledge, caregiving preparedness, and positive aspects of caregiving. Desired supports and preferences for intervention format, program type, and frequency were assessed. Analyses examined both categorical adulthood phase and continuous age associations with caregiver outcomes, with alpha thresholds of p<.05. Results Early adulthood caregivers self reported higher anxiety symptoms (relative to late adulthood caregivers) and perceived time pressure (relative to middle and late adulthood caregivers). Relative to late adulthood caregivers only, early adulthood caregivers more frequently endorsed desired support for supplemental care and safety tools for the person with dementia, as well as willingness to engage in individual counseling and automated, digital supports. Relative to both middle adulthood and late adulthood caregivers, they also more frequently expressed desired support for their own mental health. Conclusions Dementia caregiving in early adulthood is associated with distinct psychological and practical support needs, suggesting life course informed interventions may enhance relevance and engagement.