Introduction Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18–49: HR 3.57, CI 2.54–5.02), frailty (CFS 8 vs 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1–3: OR 7.00, CI 5.27–9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusions Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.

Background: Prevalence surveys have found a substantial burden of subclinical (asymptomatic but infectious) TB, from which individuals can progress, regress or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of TB disease. Methods: We created deterministic framework of TB disease with progression and regression between three states of pulmonary TB disease: minimal (non-infectious), subclinical, and clinical (symptomatic and infectious) disease. We estimated ranges for each parameter by considering all data from a systematic review in a Bayesian framework, enabling quantitative estimation of TB disease pathways. Findings: Twenty-four studies contributed data from 6030 individuals. Results suggested that, after five years, 24.7%(95% uncertainty interval, UI, 21.3%-28.6%) of individuals with prevalent subclinical disease at baseline had either progressed to clinical disease or died from TB, whereas 16.1%(95%UI, 13.8%-18.5%) had recovered after regressing to minimal disease. Over the course of five years 30% (95%UI, 27.2%-32.6%) of the subclinial cohort never developed symptoms. For those with clinical disease at baseline, 39%(95%UI, 35.8%-41.9%) and 10.3%(95%UI, 8.5%-12.4%) had died or recovered from TB, with the remainder in, or undulating between, the three disease states. The ten-year mortality of people with untreated prevalent infectious disease was 38%. Interpretation: Our results show that for people with subclinical disease, classic clinical disease is neither inevitable nor an irreversible outcome. As such, reliance on symptom- based screening means a large proportion of people with infectious disease may never be detected. Funding: TB Modelling and Analysis Consortium and European Research Council

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Background Childhood cancer is neglected within global health. Oxford Pediatrics Linking Oncology Research with Electives describes early outcomes following collaboration between low-and high-income paediatric surgery and oncology centres. The aim of this paper is twofold: to describe the development of a medical student-led research collaboration; and to report on the experience of Wilms' tumour (WT). Methods This cross-sectional observational study is reported as per STROBE guidelines. Collaborating centres included three tertiary hospitals in Tanzania, Rwanda and the UK. Data were submitted by medical students following retrospective patient note review of 2 years using a standardised data collection tool. Primary outcome was survival (point of discharge/death). Results There were 104 patients with WT reported across all centres over the study period (Tanzania n = 71, Rwanda n = 26, UK n = 7). Survival was higher in the high-income institution [87% in Tanzania, 92% in Rwanda, 100% in the UK (X 2 36.19, p \ 0.0001)]. Given the short-term follow-up and retrospective study design, this likely underestimates the true discrepancy. Age at presentation was comparable at the two African sites but lower in the UK (one-way ANOVA, F = 0.2997, p = 0.74). Disease was more advanced in Tanzania at presentation (84% stage III-IV cf. 60% and 57% in Rwanda and UK, respectively, X 2 7.57, p = 0.02). All patients had pre-operative chemotherapy, and a majority had nephrectomy. Post-operative morbidity was higher in lower resourced settings (X 2 33.72, p \ 0.0001). Methodology involving medical students and junior doctors proved time-and cost-effective. This collaboration was a valuable learning experience for students about global research networks. Conclusions This study demonstrates novel research methodology involving medical students collaborating across the global south and global north. The comparison of outcomes advocates, on an institutional level, for development in access to services and multidisciplinary treatment of WT.

Background School-level infection control measures in Germany during the early Coronavirus Disease 2019 (COVID-19) pandemic differed across the 16 federal states and lacked a dependable evidence base, with available evidence limited to regional data restricted to short phases of the pandemic. This study aimed to assess the (a) infection risks in students and staff; (b) transmission risks and routes in schools; (c) effects of school-level infection control measures on school and population infection dynamics; and (d) contribution of contacts in schools to population cases. Methods and findings For this retrospective observational study, we used German federal state (NUTS-2) and county (NUTS-3) data from public health and education agencies from March 2020 to April 2022. We assessed (a) infection risk as cumulative risk and crude risk ratios and (b) secondary attack rates (SARs) with 95% confidence interval (CI). We used (c) multiple regression analysis for the effects of infection control measures such as reduced attendance, mask mandates, and vaccination coverage as absolute reduction in case incidence per 100,000 inhabitants per 14 days and in percentage relative to the population, and (d) infection dynamic modelling to determine the percentage contribution of school contacts to population cases. We included (a) nationwide NUTS-2 data from calendar weeks (W) 46-50/2020 and W08/2021-W15/2022 with 3,521,964 cases in students and 329,283 in teachers; (b) NUTS-3 data from W09-25/2021 with 85,788 student and 9,427 teacher cases; and (c) detailed data from 5 NUTS-3 regions from W09/2020 to W27/2021 with 12,814 cases (39% male, 37% female; median age 14, range 5 to 63), 43,238 contacts and 4,165 secondary cases for students (for teachers, 14,801 [22% male, 50% female; median age 39, range 16 to 75], 5,893 and 472). Infection risk (a) for students and teachers was higher than the population risk in all phases of normal presence class and highest in the early 2022 omicron wave with 30.6% (95% CI 30.5% to 32.6%) of students and 32.7% (95% CI 32.6% to 32.8%) of teachers infected in Germany. SARs (b) for students and staff were below 5% in schools throughout the study period, while SARs in households more than doubled from 13.8% (95% CI 10.6% to 17.6%) W21-39/2020 to 28.7% (95% CI 27% to 30.4%) in W08-23/2021 for students and 10.9% (95% CI 7% to 16.5%) to 32.7% (95% CI 28.2% to 37.6%) for staff. Most contacts were reported for schools, yet most secondary cases originated in households. In schools, staff predominantly infected staff. Mandatory surgical mask wearing during class in all schools was associated with a reduction in the case incidence of students and teachers (c), by 56/100,000 persons per 14 days (students: 95% CI 47.7 to 63.4; teachers: 95% CI 39.6 to 71.6; p < 0.001) and by 29.8% (95% CI 25% to 35%, p < 0.001) and 24.3% (95% CI 13% to 36%, p < 0.001) relative to the population, respectively, as were reduced attendance and higher vaccination coverage. The contribution of contacts in schools to population cases (d) was 2% to 20%, lowest during school closures/vacation and peaked during normal presence class intervals, with the overall peak early during the omicron wave. Limitations include underdetection, misclassification of contacts, interviewer/interviewee dependence of contact-tracing, and lack of individual-level confounding factors in aggregate data regression analysis. Conclusion In this study, we observed that open schools under hygiene measures and testing strategies contributed up to 20% of population infections during the omicron wave early 2022, and as little as 2% during vacations/school closures; about a third of students and teachers were infected during the omicron wave in early 2022 in Germany. Mandatory mask wearing during class in all school types and reduced attendance models were associated with a reduced infection risk in schools.

BACKGROUNDKey stages in TB disease can be delineated by radiology, microbiology and symptoms, but transition between relevant stages remains unclear. We sought to quantify progression and regression across the spectrum of TB disease by systematically reviewing studies of individuals with untreated TB undergoing follow up.METHODSWe searched PubMED, EMBASE and Web of Science until December 31st 1960, the Index Medicus between 1895 and 1945, and extensive investigator collections without date restriction - in English and German. Eligible studies were observational cohorts and clinical trials, presenting adults/adolescents with TB or recent TB exposure, undergoing follow-up for at least 12 months without therapeutic intervention. Two authors independently reviewed titles/abstracts and full texts for inclusion. Quality was assessed with a modified Newcastle-Ottawa Score, excluding highly biased studies. Summary estimates were extracted to align with TB disease transitions in a conceptual model, and we used meta-analysis of proportions with random-effects to synthesise the extracted data. This study is registered with PROSPERO (CRD42019152585).FINDINGS10477 titles were screened and 1648 full texts reviewed. 223 met inclusion criteria. 109 were excluded for high risk of bias and 90 did not have extractable data. 24 studies (34 cohorts) were included. Progression from microbiologically negative to positive disease in those with radiographic TB evidence occurred at an annualized rate of 9.71% (95% CI:6.17-13.34) with “active” TB imaging, and 1.06% (95% CI:0.31-1.82) with “inactive” TB imaging. Reversion from microbiologically-positive to -undetectable in prospective cohorts occurred at an annualized rate of 12.40% (95% CI: 6.81-17.99). Studies reported symptoms poorly not allowing for direct estimation of transitions for subclinical (asymptomatic, culture positive) disease.INTERPRETATIONWe present the risk of progression in those with radiographic evidence of disease and the rate of self-cure for microbiologically positive disease to inform global disease burden estimates, clinical guidelines and policy decisions.

This review aimed to determine: whether EF is affected in children and adolescents (2-24-years-old) with perinatal HIV infection, perinatal HIV exposure without infection, and behaviourally acquired HIV. A systematic review (PROSPERO number: *) was conducted using 11 electronic databases (01.01.1981-09.07.2019) and 8 conference websites. Primary quantitative studies with EF scores on cognitive tasks and/or behavioural report measures were included. Meta-analyses were performed by EF subtype and subpopulations compared. 1789 records were found. Sixty-one studies were included in the narrative synthesis; 32 (N = 7884 participants) were included in meta-analyses. There was a distinct pattern of reduced EF in those with perinatal HIV infection on antiretroviral therapy compared to controls: pooled effect sizes were largest for verbal and visuospatial working memory, with smaller effects on planning, inhibitory control and set-shifting. Data were limited for other HIV-affected subpopulations. Perinatal HIV infection is associated with reduced EF with varying effect sizes for the different EF subtypes.

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