The Lancet

Introduction Acute lower respiratory tract disease (aLRTD) is a leading cause of hospitalisation and death, particularly in older adults and adults with comorbidities, with acute lower respiratory tract infection (aLRTI; pneumonia and non-pneumonic LRTI) being a major component. Non-pulmonary complications and functional decline after aLRTI are recognised, but their pathogen-specific burden is poorly described. We aimed to quantify renal, hepatic, thromboembolic and functional complications, and mortality, after aLRTI hospitalisation, by clinical phenotype and pathogen. Methods We conducted a cohort study of adults (>18 years) admitted with aLRTD to two hospitals in Bristol, UK (01 August 2022-31 July 2024). aLRTD was classified as pneumonia, non-pneumonic LRTI (NP-LRTI) or no diagnosis of aLRTI. Pathogens were identified from standard-of-care and research microbiology. Outcomes were acute kidney injury (AKI), acute liver dysfunction, venous thromboembolism (VTE), in-hospital falls, reduced mobility at discharge, increased care requirements, and 30-day and 1-year mortality. Analyses were descriptive. Results Among 246,797 adult admissions, 21,456 aLRTD hospitalisations were included: 10,239 (47.7%) pneumonia, 7,742 (36.1%) NP-LRTI and 3,475 (16.2%) with no evidence of aLRTI. Of 19,152 tested aLRTD admissions, 8,503 (44.4%) had a positive microbiological/virological test, yielding 9,204 pathogen detections; 1,194 (6.2%) had co-infections, and SARS-CoV-2 was most frequent, with influenza the second most common in pneumonia and NP-LRTI. Pneumonia had greater severity than NP-LRTI and no diagnosis of aLRTI (median length of stay 6 vs 4 vs 4 days; ICU admission 3.4% vs 0.7% vs 0.5%, respectively). Overall, 22.2% developed AKI, 6.1% acute liver dysfunction, 0.6% DVT and 2.4% PE; 1.8% had a fall, 11.5% reduced mobility, and 16.6% required increased care at discharge. 30-day and 1-year mortality were highest for pneumonia (14.0% and 32.0%, respectively). Pathogen-specific analyses showed longer stays and higher complications and mortality rates for SARS-CoV-2 and Streptococcus pneumoniae, and shorter stays with lower complication and mortality rates for influenza and Haemophilus influenzae. Conclusions Non-cardiovascular complications and functional decline after aLRTI were common, particularly in pneumonic and SARS-CoV-2 or pneumococcal disease. These findings support routine surveillance for renal, hepatic, thromboembolic events, early mobilisation and rehabilitation, and consideration of multi-system outcomes when evaluating public health and economic value of vaccines and therapies.

Background In adults, cold-attributable mortality exceeds heat-attributable mortality roughly 17-fold. Child-specific evidence has begun to emerge only recently - a nationwide Brazilian case-crossover study located the minimum mortality temperature (MMT) for under-five deaths, and a 56-country survey-based analysis linked monthly temperature anomalies to under-five mortality - but no multi-country, climate-zone-resolved estimate of the childhood respiratory-infection MMT exists, and whether temperature variability is independently associated with childhood respiratory mortality at the global scale is unknown. We quantified both. Methods We combined Global Burden of Disease 2023 mortality estimates, lower respiratory infection (LRI) deaths at ages 0-19 years and asthma deaths at ages 0-24 years, 171 countries, 1990-2023 - with 0.5 deg monthly land temperature and diurnal temperature range (DTR) fields from C-LSAT/C-LDTR (1901-2023). Four exposure dimensions (annual mean, DTR, seasonal amplitude, interannual variability) entered two-way fixed-effects models with Driscoll-Kraay standard errors. A quadratic term in mean temperature located the MMT, with percentile confidence intervals from a 300-replication country-cluster bootstrap. Future-exposure leads, country-level detrending, and permutation tests assessed contemporaneous causality, applied to both the linear coefficients and the quadratic term generating the MMT; national pneumococcal conjugate vaccine (PCV3) coverage and ambient PM2.5 exposure series were added as time-varying mechanistic covariates. Results The childhood LRI MMT was 17.1 C (95% CI 14.7-19.8), the 36th percentile of the annual-temperature distribution; zone estimates were 24.7 C in tropical and 15.8 C in subtropical countries, with weak temperate and no subarctic identification. The quadratic term underpinning the MMT, however, failed both falsification checks - future temperatures reproduced the U-shape and country-level detrending erased it - so these MMT values describe a trend-level geographic pattern of the annual construct rather than a contemporaneous dose-response. Interannual temperature variability was positively associated with LRI (+0.278, 95% CI 0.102-0.454; p = 0.002) and asthma mortality (+0.836, 95% CI 0.447-1.226; p = 2.6 x 10^-5) per 1 C, but future-exposure models returned nearly identical significant coefficients and detrending erased significance, supporting only a trend-level association; adjustment for national PCV3 coverage and PM2.5 exposure left these estimates essentially unchanged. Annual mean temperature was likewise inversely associated with both outcomes at the trend level; DTR and seasonal amplitude showed no independent within-country effects. Conclusions This study provides the first multi-country, climate-zone-resolved geography of the optimal temperature for childhood respiratory survival, spanning 171 countries; because the underlying quadratic association is trend-level, the estimates are directional. The observed variability-mortality associations are trend-level signals rather than contemporaneous causal evidence; daily-scale, child-specific designs are required to determine whether short-term thermal variability affects paediatric respiratory mortality.

Background: Seasonal influenza, commonly known as flu, is an acute respiratory, highly contagious illness caused by influenza viruses. A clear understanding of influenza seasonality is crucial for guiding prevention and treatment strategies, including decisions on vaccination timing to prevent outbreaks. While well documented in temperate regions, data on influenza epidemiology in tropical areas, particularly sub-Saharan Africa, remain limited. We described the types, subtypes and positivity rate of seasonal influenza in Uganda during 2019-2023. Methods: We abstracted data from the National Influenza database on positive seasonal influenza cases confirmed by Polymerase Chain Reaction. The cases were disaggregated by age group, sex, region, month and year of reporting. Using Microsoft excel, we calculated the influenza positivity rate and disaggregated it by strain, sex, age, region and time. Test positivity rate was computed as the number of positive cases as a percentage of the total samples tested. Results: Among 17,957 individuals tested, the overall positivity rate for seasonal influenza was 5% (936 cases). Positivity was higher among males compared to females (7% vs. 4%), with children aged 5-9 years having the highest positivity rate (16%), while individuals aged 50-54 years had the lowest (1%). The median positivity rate was 4%, with a range of 1-16%. Regionally, the central region reported a positivity rate of 5%, with rates across all regions ranging from 5% to 8%. Over time, there was a gradual decline in positivity rates, decreasing from 16.5% in 2019 to 5.3% in 2023. Seasonal influenza exhibited bimodal peaks, with the primary peak occurring between March and May and a secondary peak from October to December. Influenza A was the predominant strain, accounting for 70% of seasonal influenza cases (669/936). Among the Influenza A subtypes, H3N2 was most common, representing 63% of cases (425/669). Conclusions: The declining seasonal influenza positivity rates from 2019 to 2023 and the predominance of Influenza A and H3N2 highlight the need for sustained surveillance in Uganda. Given Influenza A's high genetic variability and potential for novel strain emergence, monitoring circulating strains, informing vaccine development, and implementing targeted interventions for high-risk groups and regions are critical to controlling and preventing outbreaks.

Public genomic repositories can support antimicrobial resistance (AMR) surveillance, but unequal sampling can bias interpretation. We characterised AMR determinants, multicountry genomic cluster overlap and surveillance gaps across Africa using an NCBI Pathogen Detection snapshot retrieved on 24 August 2026 for 55 African Union member states. Records were validated and deduplicated by BioSample, and complete AMRFinderPlus calls were summarised across five United Nations M49 subregions and eight overlapping regional economic communities (RECs). Country-pair cluster overlap was assessed using the Jaccard index, while project-based and composition-standardised sensitivity analyses evaluated repository bias. The dataset contained 86,829 unique BioSamples from 51 states; South Africa, Malawi and Kenya contributed 55.8%. Complete extended-spectrum {beta}-lactamase calls were detected in 21,513 isolates and carbapenemase calls in 4,642. blaCTX-M-15 dominated the ESBL profile, while NDM and OXA types predominated. Seventy clusters contained carbapenemase-positive isolates from at least two countries. A shared REC covered all participating countries in 38 clusters, while 32 crossed REC boundaries. Normalised country-pair overlap was low, with a maximum Jaccard index of 9.5%. Project balancing reduced the Northern African carbapenemase estimate from 32.3% to 17.9% and the Eastern African ESBL estimate from 36.9% to 12.5%. Public repositories identify determinants and clusters for investigation but do not estimate prevalence or transmission. AMR surveillance should combine national confirmation, regional institution-led investigation where countries share an REC, and continent-wide coordination through Africa CDC for cross-REC signals, supported by representative One Health sampling, standardised metadata and sustained African sequencing capacity.

Study Objective Little is known about where in hospital care for multiple long-term conditions (MLTC) is delivered. We aimed to describe pathways of care (ward transfers) and outcomes for people admitted to hospital for unscheduled care by MLTC status and other key sociodemographic characteristics. Design and setting Analysis of routinely-collected electronic health records from a large acute UK hospital. Participants Adult unscheduled care admissions from 1st July 2018 to 30th June 2019. The presence of two or more of 59 long-term conditions was ascertained using ICD-10 codes from previous hospital discharges. Main outcome measures Markov state transition probabilities were derived for ward moves and compared for MLTC vs no MLTC, age, sex, ethnicity and neighbourhood deprivation. Outcomes (length of stay, death, readmission, move from definitive ward) and time spent in emergency and assessment departments were compared between subgroups. Results A total of 33,252 adults, mean age 56.0 (SD 21.9) years were analysed; 14,834 (42.4%) had MLTC. People with MLTC were more likely to die in hospital (4.2 vs 1.9%, p<0.001), transfer to internal medicine wards or older peoples medicine wards, were less likely to transfer to surgical wards, had longer median length of stay (1.83 vs 0.69 days, p<0.001), stayed longer in acute medical units (15.5 vs 9.6 hours, p<0.001), and were more likely to move from their definitive ward (18.2 vs 16.4%, p=0.002). Conclusion Unscheduled hospital care pathways are complex and differ for people with MLTC, who have worse outcomes and may be less likely to receive optimal care.

Purpose. Prognostic assessments after acute brain injury are largely narrative, and how prognostic language relates to subsequent care has not been measured at scale. We quantified where it is written and its association with a subsequent code-status limitation. Materials and Methods. Multidatabase observational study of adults with acute brain injury or a related neurologic emergency, using MIMIC-IV (2008-2019; discharge summaries and radiology reports) and a timestamped MIMIC-III cohort (notes and code-status orders). The exposure was documented prognostic language; outcomes were its association with a subsequent full-code-to-limitation transition, note-stream location, and completeness of documented command-following relative to structured Glasgow Coma Scale (GCS) motor scores. Results. Among 31,993 admissions (27,054 patients; median age, 69 years; 54.9% male), prognostic language in the timestamped cohort (MIMIC-III) was associated with a subsequent code-status limitation after multivariable adjustment (adjusted hazard ratio, 4.3; 95% CI, 2.9-6.5; unadjusted 14-day cumulative incidence, 40% vs 8.5%), including the comfort-measures component (3.9), a higher-risk subgroup (4.4), and after acute-physiology adjustment (4.1); the association was concentrated in the first 3 days. Non-prognostic severity language showed no comparable association (hazard ratios, 1.1-1.3). Prognostic language localized almost entirely to the narrative (4.9% of discharge summaries vs 0.015% of radiology reports); command-following was undocumented in 55.7% of summaries, and no final-24-hour GCS motor score was charted in 72.8%. Conclusions. Documented prognostic language after acute brain injury was written in the narrative, not structured fields, and was associated with a subsequent code-status limitation after multivariable adjustment. This observational association cannot establish causation but warrants prospective study.

Pneumococcal vaccination of older adults is primarily guided by age and clinical eligibility, despite substantial variation in individual risk of severe pneumonia. Here, we used longitudinal electronic health records from 787,538 adults aged [&ge;]65 years to evaluate the real-world effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) and quantify clinical benefit according to baseline risk of pneumonia hospitalization. We developed and validated a machine-learning model using pre-PCV20 data to estimate individual 12-month hospitalization risk and integrated these predictions into a propensity score matching framework. Overall vaccine effectiveness against pneumonia hospitalization was 16.5% (95% CI, 10.6-22.1), but this population-level estimate masked substantial heterogeneity in clinical benefit. The 60% at lowest predicted risk, characterized by younger age and fewer pulmonary and other chronic conditions, showed no measurable reduction in hospitalization (VE, 3.1%; 95% CI, -14.4 to 18.0) and had an estimated 1-year number needed to vaccinate (NNV) of 7,423, compared with 184 and 115 in the intermediate- and high-risk groups, respectively. These findings suggest that incorporating baseline risk into adult pneumococcal vaccination strategies could enable more targeted and potentially better-timed vaccination.

Background Lower respiratory infections (LRI) remain the leading infectious cause of death in children, and survival once ill is a direct tracer of health-system quality. Whether countries are converging toward the best survival performance achieved within their own region has never been tested at national level. We measured each country's distance to an empirical episode-fatality-ratio (EFR) frontier in 204 countries from 1990 to 2023. Methods For each country and year we computed EFR = LRI deaths/incident episodes using Global Burden of Disease (GBD) 2023 estimates for ages 0-19 years. Deaths span the full 1990-2023 series; episodes are observed for 1990, 2019 and 2023, with intermediate years linearly interpolated. The frontier was the 10th-percentile country EFR within each GBD super-region and year (sensitivity: 5th and 25th percentiles); the gap = EFR_country/EFR_frontier. We classified 33-year gap trajectories into catch-up phenotypes, ranked COVID-window (2019-2023) movers, cross-tabulated gap against avoidable deaths to build a priority list, and benchmarked upper respiratory infections (URI) at three time points as a near-zero-fatality contrast. Findings The median country's gap was 1.86 in 1990, 1.80 in 2019 and 1.86 in 2023; the share of countries more than twice their regional frontier was 44.6% in 1990 and 46.6% in 2023. Of 137 eligible countries, 67 narrowed and 69 widened their gap, with one unchanged. Nineteen countries achieved sustained catch-up, concentrated in North Africa and the Middle East (7) and Latin America (5), with China closing from 2.43 to 0.50, below its regional frontier; 28 countries regressed, led by Central Asia (Uzbekistan x3.5) and including the United States (x2.0). Over the COVID-19 window the median gap peaked at 2.00 in 2021 (+10.8% versus 2019, from unrounded medians) before returning to 1.86. Combining gap with avoidable deaths identifies two distinct policy problems: high-burden, moderate-gap giants (Nigeria 67,490 avoidable deaths, gap 2.4; India 54,109, gap 1.6) and extreme-gap outliers (Uzbekistan, gap 28.6). The Sub-Saharan Africa frontier fell further behind the High-income frontier (ratio 4.2 in 1990, 9.5 in 2023); the median Sub-Saharan African country sits 11.0 times the global 10th-percentile frontier but only 1.78 times its own regional frontier, so within-region benchmarking understates the region's true distance. URI gaps likewise did not converge (median 4.15 to 4.60). Interpretation Convergence toward the survival frontier is not the default national trajectory: over three decades the typical country made no net progress toward the best decile of its own region, and pandemic-era divergence was only partly reversed. National gap trajectories separate system-wide quality shortfalls from extreme outliers warranting audit, and expose a measurement trap in which regions whose frontiers stagnate appear closer to best practice than they are.

Abstract Preventable neonatal deaths remain a major public health problem in Zimbabwe, where near-universal antenatal and facility-delivery coverage coexist with a rising neonatal mortality rate. This study evaluated whether institutionalising three core "vital signs" of the community health system (a trained village health worker (VHW) workforce, functional community governance structures, and modified women's and men's participatory learning and action groups) reduces preventable neonatal deaths in Mashonaland West Province. An embedded QUAN (qual) mixed-methods design was used, with a two-arm, parallel-group cluster-randomised controlled trial as the dominant strand. Fifty-two ward-level clusters were randomised 1:1 to the institutionalised community health system package or to standard Ministry of Health and Child Care community services, and 984 pregnant women were enrolled between 1 September 2020 and 31 October 2021, with each mother-infant pair followed to 28 days after delivery, yielding 973 mother-infant pairs for intention-to-treat analysis. The primary outcome was neonatal death within 28 days of life, expressed per 1,000 live births. The primary analysis used a three-level mixed-effects log-binomial regression model with cluster and community-health-worker random intercepts, adjusted for pre-specified covariates. Supervised machine-learning classifiers with leave-one-cluster-out cross-validation, Cox proportional-hazards regression, and multilevel logistic models were fitted as supplementary analyses. An embedded longitudinal process evaluation used key informant interviews and focus group discussions, which were analysed thematically and integrated with the quantitative findings. The neonatal mortality rate was 44.8 per 1,000 live births in the intervention arm versus 110.1 per 1,000 in the control arm. The adjusted risk ratio for neonatal death was 0.43 (95% CI 0.26-0.70; p < 0.001), a 57% relative reduction, with a number needed to treat of 16 mother-infant pairs (95% CI 11-29). Low birthweight (<2,500 g), birth interval under two years, and low community women's literacy were the strongest risk factors, while trained VHWs, functional community governance, early antenatal care, and sustained participatory group attendance were independently protective. The women's and men's groups were protective in a dose-dependent manner, becoming significant at four or more cycles (about 14 meetings) (adjusted odds ratio 0.71; 95% CI 0.60-0.85; p = 0.001). A random forest classifier discriminated against neonatal deaths with a cross-validated area under the curve of 0.842 and a sensitivity of 0.912. Qualitative findings converged with the trial results, identifying male engagement, earlier care-seeking, danger-sign literacy, social-network activation, and community death audits as the behavioural and structural mechanisms of change. Institutionalising the community health system package (trained VHWs, functional governance, early antenatal engagement, and sustained participatory groups) was associated with a substantial reduction in preventable neonatal deaths. The findings suggest that in high-coverage, high-mortality settings, the binding constraint is structural rather than clinical, and that scaling functional community governance and workforce infrastructure in the most disadvantaged communities may accelerate progress toward neonatal survival targets. The principal limitations are a one-year follow-up period, the rarity of neonatal death, and concurrent national programming that only partially reached the control clusters. Trial registration: Pan African Clinical Trials Registry, PACTR202607591142118 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=PACTR202607591142118); registered retrospectively on 7 July 2026.

Background Respiratory infections remain the leading infectious cause of death among children and adolescents, yet the share of these deaths that could be averted with currently feasible care is not routinely quantified. Existing amenable-mortality frameworks rely on cause lists and population-level mortality benchmarks and do not exploit information on how many episodes occur. We propose an episode-fatality-ratio (EFR) frontier approach and apply it to lower respiratory infections (LRI), whooping cough (pertussis) and upper respiratory infections (URI) in 204 countries, 1990-2023. Methods For each cause, country and year we computed EFR = deaths/incident episodes using Global Burden of Disease (GBD) 2023 estimates for ages 0-19 years. The frontier was defined as the 10th-percentile country EFR within each GBD super-region, cause and year; avoidable deaths = max(0, deaths - episodes x frontier EFR). Primary estimates are deterministic; 95% uncertainty intervals (UIs) come from 2,000 Monte Carlo draws. Sensitivity analyses varied the frontier percentile, applied an aspirational global frontier, constructed pertussis counterfactuals, and recomputed all estimates within the single under-5 age band. Results In 2023, 333,803 childhood deaths from lower respiratory infections (95% UI 289,123-417,460; 46.9% of LRI deaths) were avoidable. Summing the three causes deterministically gives 391,034 avoidable deaths (46.5% of 840,444); the combined figure is a deterministic sum, and a UI is available for the LRI component only. The pertussis (43,958; 39.0%) and URI (13,273; 81.0%) estimates are secondary: their deterministic point values fall below their own Monte Carlo intervals and the underlying death estimates carry very wide uncertainty (global pertussis UI 12,545-321,874). Avoidable deaths fell from 1,050,468 (44.9%) in 1990, but between 2019 and 2023 the avoidable share for LRI+URI barely moved (48.7% to 47.7%) while absolute avoidable deaths fell 14.5%, a pattern consistent with stalled convergence to the frontier. Sub-Saharan Africa plus South Asia held 73.1% of avoidable deaths in 2023 versus 41.8% in 1990; ten countries accounted for 59.1%. Conclusion Nearly half of childhood respiratory-infection deaths remain avoidable relative to within-region best practice, and the residual burden is increasingly concentrated in low-income settings. In the pertussis counterfactual, most countries kept pace with their regional frontier, so further gains require advancing the frontier itself through quality-of-care improvements.

Background Childhood respiratory infectious deaths are partitioned across four Global Burden of Disease cause modules-26 etiological attributions within lower respiratory infections, tuberculosis, COVID-19, and whooping cough-never jointly reported. Whether the structure of this combined mortality spectrum has changed over time, and with what implications for intervention design, has not been quantified. We assembled and analyzed the integrated spectrum for children and adolescents aged 0-19 years, 1990-2023. Methods We integrated Global Burden of Disease Study 2023 (release v8352) estimates into a 29-node spectrum-26 lower respiratory infection etiologies plus tuberculosis, COVID-19, and pertussis-globally and across seven super-regions, with uncertainty propagated by summing bounds. We computed Shannon diversity, Herfindahl concentration, and effective cause counts; phenotyped pandemic-window collapse and rebound per cause; linked pathogen shares to WHO/UNICEF vaccine coverage; and mapped geographic concentration in sub-Saharan Africa and South Asia. Reporting follows GATHER. Results In 2023 the 29 causes jointly accounted for 965,330 deaths (95% uncertainty interval [UI] 680,096-1,342,437). Shannon diversity rose from 2.336 to 2.711 (+16.1%) between 1990 and 2023; the effective number of causes nearly doubled (5.57 to 9.94), inversely coupled to total deaths (Spearman rho = -0.997). Whooping cough ranked second (112,954 deaths; 95% UI 64,576-185,708; 11.7%) and showed the spectrum's only rebound above 100% (-57.4% collapse, +111.0% rebound). Tuberculosis ranked third (87,764; 57,779-124,912; 9.1%) with the highest concentration in sub-Saharan Africa and South Asia (87.1%). COVID-19 entered at rank five (52,899; 47,275-59,183; 5.5%). Nineteen of 29 causes exceeded the poverty-lock threshold (>80.59% of deaths in sub-Saharan Africa plus South Asia). Conclusions Childhood respiratory infectious mortality has become more diverse and more concentrated in poverty as it has declined. Single-pathogen interventions now address a shrinking share; the spectrum's structure argues for platform interventions-oxygen, antimicrobial access, referral-tailored jointly by age and geography, implying that pathogen-specific strategies alone cannot finish the remaining mortality agenda.

South Asian communities in the UK experience disproportionate maternal and child health inequalities linked to non-recommended infant feeding practices, limited health literacy, and socioeconomic constraints. Participatory learning and action (PLA) is effective in low- and middle-income countries, but high-income evidence is scarce. This pilot assessed the feasibility of a community facilitator-led PLA intervention to improve infant feeding among South Asian families in East London. A three-arm pilot feasibility cluster randomised controlled trial (ISRCTN10234623) was conducted in Tower Hamlets and Newham, East London (May-September 2022), with 12 wards randomised 1:1:1 to face-to-face PLA, online PLA, or usual care. Multilingual community facilitators delivered eight biweekly sessions over 14 weeks. Feasibility outcomes were assessed against prespecified Go/Stop criteria; exploratory outcomes included child feeding behaviours (Children's Eating Behaviour Questionnaire, CEBQ), parental feeding style (Parental Feeding Style Questionnaire, PFSQ), and child BMI Z-scores. Of 263 enrolled participants, 261 had a recorded trial arm allocation; consent to the pilot feasibility study was 70.7% (186/263; 95% CI 65.0-75.9%) meeting the [&ge;]50% Go criterion. Attendance was 37% (Tower Hamlets 59%, Newham 29%), below the [&ge;]80% Go threshold. Six-month retention was 54.8% (Tower Hamlets 78%, Newham 48.5%; 95% CI 41.8-55.3%), triggering the Definite Stop criterion. Significant baseline imbalances included BMI Z-score (p = 0.005), ethnicity, borough, and education; no between-arm BMI differences were observed at follow-up (p = 0.249). CEBQ and PFSQ baseline completion was 24.5% and 23.0%, with no usable follow-up data. PLA Phases 3 and 4 were not completed by any group; all participants providing feedback reported it acceptable. Recruitment was feasible and the intervention acceptable, but a Definite Stop criterion was triggered in Newham, no group completed the full PLA cycle, and outcome data were insufficient for evaluation. A definitive trial requires stratified randomisation, digitised multilingual data collection, participant reimbursement, and explicit PLA phase-completion criteria.

Background: The condition of a patient with acute stroke often changes within hours of ICU admission. Prognostic work here targets fixed endpoints predicted from admission data, and trajectory phenotyping assigns one label per patient. We used longitudinal ICU data to identify interpretable dynamic clinical states, characterize transitions between them, and relate the current state to later events. Methods: Retrospective cohort study of 6368 adults with acute stroke in MIMIC IV v3.1. The first 72 h were divided into twelve 6-hour windows, and a hidden Markov model was fitted to 21 neurological, physiological and organ support variables. State number was chosen against criteria fixed before fitting: statistical fit, restart stability, state occupancy and clinical interpretability. Generalized estimating equations related the current state to new mechanical ventilation and vasopressor use within 12 h, and to ICU death within 72 h. Eleven sensitivity analyses assessed the robustness of the state solution. Results: Four states were selected: neurologically preserved-low support, neurological impairment low support, impairment renal dysfunction and impairment-respiratory support (63.3%, 7.8%, 11.8% and 17.1% of windows). Within 72 h, 40.3% of patients changed state at least once, and transitions ran in both directions rather than along a single severity gradient. States were identified without outcome data, yet ICU mortality by last state ranged from 2.9% to 43.9%. Adjusted for age, sex, subtype and Charlson index, the current state remained associated with organ-support escalation and death. State prevalence differed by at most 1.1 percentage points between training and test sets, and 10 of 11 sensitivity analyses gave a stable four-state solution (ARI 0.754 0.955). Conclusions: The early ICU course of acute stroke can be represented as movement among a small number of clinically interpretable states. The representation was reproducible in a held out set and across admission eras, but requires validation in an independent database before any clinical use.

Background Severe acute respiratory infections (SARI) strain healthcare systems. Sentinel surveillance remains central to SARI monitoring, but routinely collected hospital discharge data offer a scalable, population-wide complement. In Finland, national registers now enable register-based surveillance, yet SARI case definitions remain unevaluated. Aim To evaluate whether routinely collected electronic health records can support register-based SARI surveillance and establish a national case definition. Methods We conducted a retrospective register-based study linking inpatient discharge data from the Finnish Care Register for Health Care (Hilmo) and laboratory-confirmed pathogen notifications from the National Infectious Diseases Register (NIDR). Admissions were aggregated into hospitalisation episodes using generic and pathogen-specific respiratory ICD-10 codes and linked to laboratory-confirmed respiratory pathogens within an admission-centred window. We assessed the impact of diagnostic coding position, laboratory linkage windows and alternative case definitions on age distribution, seasonality and epidemic trend detection. Results We included 145,435 respiratory hospitalisation episodes. Laboratory confirmations clustered around admission, and a -7-to-+3-day window was selected; 51,498 (35.4%) had a linked laboratory confirmation. Specific primary-position diagnoses preserved clear seasonality and age distributions consistent with SARI epidemiology, whereas secondary-position diagnoses showed attenuated seasonality. A combined case definition incorporating specific primary diagnoses and laboratory-supported syndromic episodes produced stable epidemic curves while improving sensitivity over laboratory confirmation alone. Conclusion National discharge and laboratory registers can support robust SARI surveillance in Finland when case definitions are carefully designed. A combined register-based definition balances specificity, sensitivity and feasibility, complementing sentinel surveillance and integrated respiratory monitoring. Keywords Severe acute respiratory infection (SARI); surveillance; electronic health records; ICD-10; case definition; Finland

Background: Ebola virus disease is a life-threatening illness caused by the Ebolavirus, with symptoms manifesting two to twenty-one days after infection. Although Uganda has faced multiple Ebola outbreaks, many patients survive only to encounter persistent challenges. Therefore, this study explored the post-discharge experiences of survivors following the 2022 Ebola Virus Disease outbreak in Uganda. Methods: An exploratory qualitative study comprising of in-depth participant interviews was conducted at Mubende Regional Referral Hospital in central Uganda. Interviews were face-to-face and data were analyzed manually by inductive content analysis. Ten male and female participants were Ebola Virus Disease survivors in Mubende district who had lived in the community for at least six months post-discharge from the Ebola Treatment Unit. Results: Four themes emerged: (i) Psychosocial Burdens and Social Exclusion, (ii) Economic Hardship and Loss of Financial Stability, (iii) Chronic Physical and Health Burdens Post-Recovery and (iv) Rebuilding Lives: Psychological, Social, and Medical Pathways to Recovery. Survivors faced significant emotional burdens such as survivor guilt, grief, trauma from loss, and anxiety about transmission risks. They experienced social isolation, stigma, and discrimination, which often led to their exclusion from community activities. Financially, they struggled with debt and the loss of livelihoods, compounded by ongoing health issues. Additionally, survivors endured chronic physical complications, including pain and fatigue, which hindered their recovery. Despite these challenges, survivors sought psychological, social, and medical pathways to recovery, including confirmation of their recovery, support from family and organizations, and health maintenance practices. Supportive medical care and community assistance were crucial in their physical and emotional rehabilitation. Conclusion: Ebola Virus Disease survivors in Uganda face significant psychosocial, health, social, and economic challenges post-discharge. The findings highlight the critical need for comprehensive medical and community-based support systems to aid survivors' recovery and well-being. Further research on long-term neurological effects and community reintegration programmes is needed to inform targeted interventions that support Ebola survivors and reduce stigma and discrimination.

Background. The clinical course of coronavirus disease 2019 (COVID-19), and the ability to anticipate which patients will require intensive care, were poorly characterized in Central Asia during the first pandemic wave. We aimed to describe the clinical features of hospitalized COVID-19 patients at the Tashkent State Medical University, Uzbekistan, and to identify risk factors for intensive care unit (ICU) admission. Methods. In this single-centre cross-sectional study, we reviewed the records of 2500 consecutive patients hospitalized between 11 April and 8 August 2020. Patients were grouped as asymptomatic or symptomatic, and symptomatic patients were compared by ICU versus non-ICU status. Groups were compared with chi-square or Fisher's exact and Mann-Whitney U tests. Univariable and multivariable logistic regression identified risk factors for ICU admission. Results. Of 2500 patients (median age 36 years; 60.9% male), 989 (39.6%) were asymptomatic and 1511 (60.4%) symptomatic. In total, 129 (5.2%) were admitted to the ICU and 38 (1.5%) died. ICU patients were older (median 56 vs 40.5 years) and more often had bilateral pneumonia, oxygen desaturation and cardiometabolic comorbidity. In the multivariable model (AUC 0.82), the independent predictors of ICU admission were ischemic heart disease (aOR 4.20), shortness of breath (aOR 3.22), hypertensive heart disease (aOR 2.93) and male sex (aOR 2.00). Conclusions. Older age, cardiometabolic comorbidity and respiratory compromise identified patients at high ICU risk. As one of the first clinical COVID-19 descriptions from Uzbekistan, these data provide a baseline for preparedness in Central Asia.

Introduction Postoperative analgesic management after minimally invasive cardiac surgery (MICS) should facilitate early recovery while providing adequate pain control. However, direct evidence comparing postoperative remifentanil- and fentanyl-based analgesic strategies after MICS remains limited. We compared these strategies and explored their associations with postoperative recovery, postoperative nausea and vomiting (PONV), and pain management. Methods This retrospective single-center observational cohort study included patients who underwent MICS via a right mini-thoracotomy between January 2023 and June 2026. Patients were categorized according to postoperative remifentanil- or fentanyl-based analgesia in the intensive care unit. Outcomes included time to extubation, PONV, postoperative pain assessed using the numerical rating scale (NRS), additional analgesic use, and intensive care unit length of stay. Multivariable logistic regression examined the association between postoperative opioid strategy and PONV, adjusting for age, sex, and smoking history. Results PONV occurred less frequently in the remifentanil group than in the fentanyl group (20.6% vs 45.0%, P = 0.004), and this association remained significant after adjustment (adjusted odds ratio, 0.23; 95% confidence interval, 0.10-0.56; P = 0.001). Time to extubation was shorter with remifentanil (median, 179 [interquartile range, 134-240.5] vs 247 [190.2-276.5] min; P < 0.001). In contrast, NRS pain scores on postoperative day 0 were higher with remifentanil (3 [1-6] vs 1 [0-2]; P < 0.001), and additional analgesics were used more frequently (80.6% vs 33.3%; P < 0.001). Pain scores on postoperative day 1 did not differ significantly between groups. Conclusion Postoperative remifentanil-based analgesia after MICS was associated with less PONV and earlier extubation but also with greater early postoperative pain and more frequent additional analgesic use than fentanyl-based analgesia. Appropriate transition to longer-acting analgesics with multimodal analgesia may help preserve the potential benefits of remifentanil while maintaining adequate postoperative pain control.

Introduction. By the end of 2023, many low-income countries had not reached 50% COVID-19 vaccine coverage, while most high-income countries had exceeded 80%. It remains unclear whether receiving vaccine deliveries translated into faster population coverage. We examined cross-national inequalities in the timing of the vaccine rollout and whether deliveries through the COVID-19 Vaccines Global Access (COVAX) facility were associated with subsequent national uptake. Methods. We conducted an observational study of 218 countries and territories using country-level data up to December 2023. We used generalized additive mixed models to identify country-level correlates of coverage at an early and a later stage of the pandemic, survival analysis to compare the time to 50% coverage between COVAX Advance Market Commitment (AMC) and non-AMC countries, and an event study to estimate the association between the timing of the first COVAX delivery and subsequent monthly coverage in AMC countries. Results. AMC-supported countries reached 50% coverage substantially more slowly than non-AMC countries. The hazard of reaching the threshold was 0.17 times that of non-AMC countries at month 1 (95% CI 0.07 to 0.41) and 0.53 times at month 18 (95% CI 0.33 to 0.85). One year after rollout began, 65.9% of AMC countries (95% CI 56.7 to 76.6) had not reached 50% coverage, compared with 21.1% of non-AMC countries (95% CI 15.1 to 29.5). The timing of COVAX deliveries was not significantly associated with subsequent national uptake in any post-delivery month. In the early stage of rollout, higher maternal mortality was associated with lower coverage, while a larger urban population was associated with higher coverage. By the end of the observation period, larger household size was associated with lower coverage, while higher health expenditure and a larger urban population were associated with higher coverage. Conclusion. Receiving COVAX deliveries was not, on its own, associated with faster coverage. Coverage differences were more consistently associated with country-level structural and health-system characteristics, while we found no significant association with the timing of the first COVAX delivery. Achieving vaccine equality likely requires strengthening the capacity of health systems to convert deliveries into administered doses, and preparedness efforts should invest in last-mile delivery capacity ahead of future emergencies.

Objectives Emergency department (ED) crowding is recognised as an important public health concern internationally, and is driven principally by exit block, the shortage of inpatient beds for patients requiring admission. This study aimed to evaluate whether a complex intervention targeting hospital occupancy improved ED patient flow, and quantified the change in attendances. Methods A controlled interrupted time series using weekly, publicly reported Public Health Scotland data from 1 January 2022 to 1 February 2026. The multi-component intervention focused on reducing hospital occupancy and included additional adult social care funding; engagement with regional social care providers; accelerated implementation of the Discharge without Delay programme; re-evaluation of whole-hospital escalation thresholds and response; resource and data supporting inpatient department reductions in length of stay; and additional investment in remote clinical assessment. The intervention commenced at a large tertiary ED on 01 February 2025. Primary outcomes were the proportions of attendances spending [&ge;]4, [&ge;]8 and [&ge;]12 hours in the ED. The secondary outcome was attendance volume. Segmented regression was fitted with a contemporaneous control series, seasonal terms and autoregressive moving average errors. Long waits were additionally illustrated as potentially avoided deaths. Results The analysis covered 161 pre-intervention and 52 post-intervention weeks. Relative to pre-intervention levels, the proportion of attendances waiting over 4 hours fell by 10.4% (95% CI 1.6 to 19.2%), by 16.4% (95%CI 1.3 to 31.5%) over 8 hours and by 24.3% (95%CI 2.6 to 46.1%) over 12 hours. Using established associations between long ED waits and excess mortality, by one-year the intervention was potentially associated with 54 fewer excess deaths (95%CI 19 to 93). Attendances rose by 3.8% (95%CI 1.3 to 6.4%) against the counterfactual. Conclusions A complex intervention targeting hospital occupancy was associated with a reduction in long ED waits despite rising attendances. Interventions addressing hospital occupancy can meaningfully improve ED crowding.

Purpose Despite the high documented prevalence of hunger and poor mental health in adolescent girls and young women (AGYW) in South Africa, this relationship remains understudied, with existing studies limited by their cross-sectional designs. This longitudinal study aimed to identify the association of hunger trajectories with anxiety and depressive symptoms, and hope in AGYW. Methods We used secondary data from the HIV Prevention Trials Network (HPTN) -068 conducted in rural Agincourt, South Africa. Complete data from 1779 AGYW collected at baseline (2011/12) and three annual follow-up visits were used. Hunger trajectories, measured using the Household Hunger Scale, were estimated via Group-Based Trajectory Modelling. Self-reported incident anxiety and depressive symptoms and hope were assessed based on AGYWs last two follow-up visits. Covariate adjusted modified Poisson regression models estimated the association between hunger trajectories and incident anxiety symptoms, incident depressive symptoms, and hope. Results Moderate-severe hunger was prevalent in 11.0%, 10.8%, and 6.0% of the households at baseline, follow-up 1, and 2, respectively. Incident anxiety symptoms were reported by 4.5%, incident depressive symptoms by 20.0% and hopelessness by 52.8% of the AGYW. Two hunger trajectories were identified- no hunger (82%) and marginal hunger (18%). Hunger trajectories were not associated with incident anxiety symptoms [RR:1.09, 95% CI: 0.55, 2.18], incident depressive symptoms [RR: 0.97; 95% CI: 0.72, 1.33] nor hope [RR: 1.00; 95% CI: 0.81, 1.23] in AGYW. Conclusion Better understanding of the factors that promote resiliency and mental health of AGYW in this setting is warranted to inform the design of interventions.