69832 research outputs found
Sort by
Assessing the resilience of a key health service: The response of acute surgical provision in England to the disruption of the COVID-19 pandemic.
Get PDFObjectiveInternational health systems had the opportunity to assess the resilience of core health services to severe disruption following the onset of the COVID-19 pandemic. This paper examines the resilience of a core health service to shocks from COVID-19. We compare outcomes following emergency admissions in England during the second (Winter 2020/21) and third (Winter 2021/22) major waves of COVID-19 with the first wave and historic admissions from 2016 to 2019.MethodsThis cohort study included adult emergency admissions for five common acute surgical conditions: appendicitis, symptomatic gallstone disease, intestinal obstruction, symptomatic diverticular disease, and abdominal wall hernia in 122 acute hospital Trusts in England. Participants were 647,367 admissions in the hospital episode statistics (HES) inpatient database including 34,560 in the second wave and 36,628 in the third wave. Outcome was all-cause mortality at 90 days.ResultsThere were 1308 deaths in wave two (3.8% of admissions) and 1235 (3.4%) in wave three compared with 3431 (3.4%) in the historic cohort and 577 (4.7%) in wave one. Compared with pre-COVID admissions, we found weak evidence of increased mortality in the second wave. There was no evidence of increased mortality in the third wave, compared to historic cohorts the case-mix adjusted odds ratios were: appendicitis 0.96 (95% CI 0.49-1.87); gallstone disease 1.27 (95% CI 0.94-1.72); diverticular disease 1.04 (95% CI 0.79-1.36); hernia 1.06 (95% CI 0.76-1.47); and intestinal obstruction 1.02 (95% CI 0.87-1.19).ConclusionsBy the end of wave three, outcomes for emergency admissions with five common acute conditions had returned to pre-pandemic levels. Lessons learnt during the disruption of the first wave of COVID-19 helped the NHS in England adapt emergency surgical services during subsequent waves. These findings emphasise the importance of maintaining, or quickly restoring core service capacity to help patient outcomes return to pre-pandemic levels
The epidemiology and clinical features of HIV and Trypanosoma cruzi (Chagas disease) co-infection: A systematic review and individual patient data analysis.
Get PDFBACKGROUND: Narrative descriptions of HIV and Trypanosoma cruzi, the causative agent of Chagas disease, co-infection exist in the literature but the breadth and depth of the data underlying these descriptions has not been previously thoroughly scrutinised and reactivation is poorly understood. The aim of this systematic review was to identify, synthesise and analyse the published literature on the epidemiology and clinical features of T. cruzi and HIV co-infection. METHODS: A systematic review of published literature on HIV and T. cruzi co-infection was conducted. Six international databases were searched: Medline, Embase, Global Health, Global Index Medicus (including LILACS, AIM, IMEMR, IMSEAR & WPRIM), Web of Science and Scopus. Articles reporting on HIV and T. cruzi co-infection, as defined by the authors, with no restrictions on study type, language or date of publication or reporting were included. RESULTS: 152 articles (62% case reports or series) were included, of which 110 reported individual patient data on 352 individuals with HIV and T. cruzi co-infection. Reported prevalence of co-infection varied by region and setting of screening, ranging from 0.2% to 5%. 86% of reactivations were reported in individuals with CD4 < 200 cells/mm3. CNS reactivation, typically presenting with meningoencephalitis and/or central nervous system (CNS) lesions, accounted for 85% of all published cases of reactivation. Myocarditis (accounting for 10% published reactivation cases) was less well characterised. Mortality of all reactivation cases was 67% (79% in those with CNS reactivation). CONCLUSION: T. cruzi reactivation mainly affects those with untreated HIV and lower CD4 counts. CNS reactivation is the most common clinical picture and confers high mortality. Prompt recognition of reactivation and immediate initiation of trypanocidal therapy (with benznidazole or nifurtimox) is recommended. Increased education and better awareness of the risks of co-infection are needed, as is systematic screening of individuals at-risk. TRIAL REGISTRATION: Prospero CRD42020216125
Plant-based analogues to meat and dairy for sustainable food systems.
No full textVarious strategies across food systems are needed for a systemic change, with dietary shifts representing a meaningful pathway-particularly in high-income nations. Plant-based analogues (PBAs) that mimic animal-based foods, represent a promising strategy to facilitate such shifts because they require minimal behaviour adjustments. This review aims to synthesise nutritional, health and environmental evidence on PBAs by examining their benefits, challenges, and research gaps to inform and support evidence-based policy and practice. PBAs generally have lower greenhouse gas emissions, land use and water use than their animal-based counterparts. Nutritionally, PBAs are complex, varying across product brands, product types, processing techniques and primary ingredients. The limited health evidence shows that consumption of plant-based meat analogues tends to be associated with positive health outcomes, while consumption of some plant-based drinks can be linked to micronutrient deficiencies. Fortified PBAs can contribute to daily recommended intakes and sometimes provide more micronutrients than their animal-based counterparts, while also providing more fibre, and less energy and saturated fat. Despite these potential benefits, debates persist around processing classifications and their health implications. Given this complex landscape, assessing what kind of role PBAs could play in our food systems will demand product-specific evaluation, targeted dietary recommendations, and expanding the range of healthier PBAs. To advance the field and accelerate dietary shifts without unintended consequences, critical considerations include strengthening the nutritional evidence-base, classifying PBAs further for dietary recommendations and informed regulatory approaches, understanding processing effects and use of additives, and standardising environmental outcomes and research beyond single ingredients
A Methodological Review of Simulation Studies Published in Pharmacoepidemiology and Drug Safety.
Get PDFPURPOSE: Simulation studies are used in pharmacoepidemiology for evaluating statistical methods in a controlled setting, whereby a known data-generating mechanism allows evaluation of the performance of different approaches and assumptions. This study aimed to review simulation studies performed in pharmacoepidemiology. METHODS: We conducted a review of all papers published in the journal of Pharmacoepidemiology and Drug Safety (PDS) over the period 2017-2024. We extracted data on study characteristics and key simulation choices such as the type of data-generating mechanism used, inferential methods tested and simulation size. RESULTS: Among 42 simulation studies included, 34 (81%) were informing comparative effectiveness/safety studies. Twenty-two studies (52%) used simulation in the context of a clinical condition, and 36 (86%) used Monte-Carlo simulation. Inputs not derived from empirical data alone (n = 22, 52%) or in combination with real-world data sources (n = 19, 45%) were most often used for data generation. The complexity of simulations was often relatively low: although 31 studies (74%) generated data based on other covariates, time-dependent covariates (n = 3) and effects (n = 4) were rarely implemented. Bias was the most often used performance measure (n = 26, 62%), although notably 18 studies (43%) did not report uncertainty in the method. CONCLUSION: Simulations contributed a relatively small number of articles (3.2% of 1320) to PDS over 2017-2024. Greater focus on evaluating methods and inferential approaches, using simulation studies that are appropriately complex given clinical realities, may be beneficial to the pharmacoepidemiology field
Artemether-lumefantrine versus pyronaridine-artesunate for the treatment of malaria in patients with mild to moderate COVID-19 in Kenya and Burkina Faso: a randomised open-label trial (MALCOV).
Get PDFBACKGROUND: It is unknown whether the choice of malaria treatment for uncomplicated malaria affects coronavirus disease 2019 (COVID-19) severity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, or duration of viral shedding. Several antimalarials exhibit antiviral activity against SARS-CoV-2 in vitro and have been suggested as potential therapeutic candidates for COVID-19, particularly pyronaridine-artesunate (PA), despite disappointing clinical results with chloroquine and hydroxychloroquine. METHODS: We conducted an open-label randomised trial comparing standard 3-day treatment with PA and artemether-lumefantrine (AL) in newly diagnosed SARS-CoV-2 infected patients aged ≥6 months with rapid diagnostic test or microscopy-confirmed non-severe malaria in Kenya and Burkina Faso. SARS-CoV-2 was assessed by RT-PCR on days 3, 7, 14, and 28, and symptom resolution was assessed daily for 14 days using FLU-PRO Plus. The primary endpoint was the proportion of participants with SARS-CoV-2 clearance by day 7. Secondary endpoints included SARS-CoV-2 clearance by days 14, 21, and 28, time to SARS-CoV-2 clearance over 28 days, median viral load on day 7, and time to symptom resolution. Complete case analysis was conducted using log-binomial regression for binary outcomes, Cox-regression for time-to-event outcomes, and negative binomial regression for count outcomes, all adjusted for disease severity and viral load at enrolment. The trial is registered with ClinicalTrials.gov NCT04695197. FINDINGS: From January 2021 to January 2022, 143 participants were randomised (PA = 69, AL = 74, intention-to-treat [ITT] population), including 117 with reverse transcription polymerase chain reaction (RT-PCR) confirmed (PA = 58, AL = 59, modified intention-to-treat [mITT] population) and 26 with rapid-antigen test confirmed SARS-CoV-2 infection. The median age was 19 years (interquartile range [IQR] 13-38), 66% were aged ≥15 years. Baseline characteristics were comparable. SARS-CoV-2 clearance by day 7 (primary endpoint) was 41% (22/54) with PA versus 58% (33/57) with AL (adjusted risk ratio [aRR] = 0.78, 95% confidence interval [CI] 0.45-1.35, p = 0.37); by day-14: PA = 80% (44/55) versus AL = 96% (55/57) (aRR = 0.86, 0.58-1.29, p = 0.47). Median (IQR) viral load on day 7 was higher with PA (855 [30-2883] versus AL:81 [12-209] copies/mL, p = 0.023). Time to SARS-CoV-2 clearance over 28 days was slower with PA (adjusted hazard ratio [aHR]: 0.55, 0.37-0.83, p = 0.004). Time to symptom clearance between treatments was similar (aHR = 1.01, 0.91-1.13, p = 0.79). Parasitological cure rates by day 42 were PA = 100% and AL = 99%. Five serious adverse events occurred (PA = 2, AL = 3) in three participants (PA = 1, AL = 2), including three hospitalisations (PA = 1, AL = 2), resulting in two deaths, both from respiratory failure (PA = 1, AL = 1). No serious adverse events (SAEs) were considered treatment-related. INTERPRETATION: Pyronaridine-artesunate in COVID-19 patients co-infected with malaria was associated with slower viral clearance than standard treatment with artemether-lumefantrine but similar symptom resolution. Both treatments were highly effective as antimalarials and should continue to be considered first- or second-line treatment options for uncomplicated malaria in patients with mild to moderate COVID-19. FUNDING: Gates Foundation
Restricted mean survival time in cluster randomized trials with a small number of clusters: Improving variance estimation of the intervention effect from the pseudo-values regression.
No full textIn randomized clinical trials with a time-to-event outcome, the intervention effect could be quantified by a difference in restricted mean survival time (ΔRMST) between the intervention and control groups, defined as the expected survival duration gain due to the intervention over a fixed follow-up period. In cluster randomized trials (CRTs), social units are randomized to intervention or control groups; the correlation between survival times of the individuals within the same cluster must be taken into account in the statistical analysis. In a previous work, we proposed the use of pseudo-values regression, based on generalized estimating equations (GEEs), for estimating ΔRMST in CRTs. We showed that this method correctly estimated the ΔRMST and controlled the type I error rate in CRTs with at least 50 clusters. Here, we propose methods for CRTs with a small number of clusters (<50). We evaluated the performance of four bias-corrections of the GEE sandwich variance estimator of the intervention effect. We also considered the use of a Student t distribution as an alternative to the normal distribution of the GEE Wald test statistic for testing the intervention effect and constructing the confidence interval. With a simulation study, assuming proportional or non-proportional hazards, we showed that the Student t distribution outperformed the normal distribution in terms of type I error rate, and the Fay and Graubard bias-corrected variance led to an appropriate type I error rate whatever the number of clusters. Therefore, we recommend the use of the Fay and Graubard variance estimator combined with a Student t distribution for the pseudo-values regression to correctly estimate the variance of the intervention effect. Finally, we provide an illustrative analysis of the DEMETER trial evaluating the use of a specific endotracheal tube for subglottic secretion drainage to prevent ventilator-associated pneumonia, by comparing each of the methods considered
Free and equal? The realities of lived experiences of food aid in the UK
Get PDFDrawing upon a large longitudinal qualitative study on lived experiences of food aid in England, we question contemporary academic and policy categorisations and portrayals of food aid. Contrary to ideas of a diverse food aid sector offering choice and dignity, we identify clear uniformity in the language participants use to describe different forms of food charity; any organisation which offers food for free or at very low cost to take away is predominantly described as a ‘food bank’. Simultaneously, however, we find marked inequalities in lived experiences of food charity by gender, age and race and ethnicity, and clear indications that demographically oriented exclusion is ever-present in food aid. We argue that the key fault line shaping lived experiences of the UK community food sector is not the ‘type’ of provision but demography (age, gender and parenthood, race and ethnicity) and yet inequalities remain broadly ignored in discussions of UK food aid. In doing so, we provide a critical contribution to scholarship on the changing nature of welfare pluralism and the lived experience of poverty today
Deep Learning for Automated Detection of Periportal Fibrosis in Ultrasound Imaging: Improving Diagnostic Accuracy in Schistosoma mansoni Infection
Get PDFThis study investigates advanced deep learning methods to improve the detection of periportal fibrosis (PPF) in medical imaging. Schistosoma mansoni infection affects over 54 million individuals globally, predominantly in sub-Saharan Africa, with around 20 million experiencing chronic complications. PPF, present in up to 42% of these cases, is a leading outcome of chronic liver disease, significantly contributing to morbidity and mortality. Early and accurate detection is critical for timely intervention, yet conventional ultrasound diagnosis remains highly operator-dependent. We adapted and trained a convolutional neural network (CNN) using ultrasound images to automatically identify and classify PPF severity. The proposed approach achieved a diagnostic accuracy of 80%. Sensitivity and specificity reached 84% and 76%, respectively, demonstrating robust generalisability across varying image qualities and acquisition settings. These findings highlight the potential of deep learning to reduce diagnostic subjectivity and support scalable screening programmes. Future work will focus on validation with larger datasets and multi-class fibrosis grading to enhance clinical utility
(Un)intended consequences: a social sciences stocktake of a decade of Global Action Plan-inspired antimicrobial governance
Get PDFAntimicrobial resistance (AMR) remains a major global health threat. Despite increasing international attention, AMR governance has often neglected social and equity dimensions, and there is a crucial need to synthesise evidence from social sciences and humanities scholarship to devise more people-centred approaches. In this Personal View, we report a qualitative stocktake of the intended and unintended consequences of the most recent phase of global AMR governance that started around the year 2000 and reached a high point with the 2015 Global Action Plan (GAP) on AMR. Our interdisciplinary analysis was guided by the five key objectives of current AMR governance, as organised in the 2015 GAP, to reduce AMR through awareness, surveillance, infection reduction, antimicrobial use optimisation, and research and innovation. The resulting assessment indicated mixed outcomes. Although the past decade witnessed unprecedented AMR-related action and investment, empirical studies highlight negative consequences of the decontextualised export of high-income governance frameworks and the neglect of upstream antibiotic-sensitive reforms of production, care, and innovation systems. Not embedding AMR within more general developmental and environmental challenges has also undermined local buy-in and contributed to the siloed status of AMR policies. For the next GAP, we recommend foregrounding equitable interventions; adopting a bottom-up, integrated perspective to incorporate local realities and solutions; and creating robust social sciences and humanities feedback loops for global AMR frameworks
Pay-it-forward intervention increased pneumococcal vaccine uptake among older adults in China: a randomized controlled trial.
No full textBACKGROUND: Pneumococcal vaccination reduces morbidity and mortality among older adults, yet coverage remains suboptimal in China. This study aimed to assess the effectiveness of a pay-it-forward intervention (covering two-thirds of the pneumococcal vaccination cost and offering the option to donate) in increasing pneumococcal vaccination among older adults (aged 60 years or older) in China, compared to standard-of-care self-paid vaccination.
METHODS: We used block randomization (block size = 4) to assign participants to a pay-it-forward arm and a standard-of-care arm in a 1:1 ratio. The primary outcome was pneumococcal vaccination. Secondary outcomes included influenza vaccine uptake, vaccine confidence, successful vaccine referral, and cost-effectiveness. Logistic regression analysis was used to compare PPSV-23 and influenza vaccination coverage and vaccine confidence between the two groups. The cost-effectiveness of the interventions was assessed using a micro-costing approach from the healthcare provider's perspective.
RESULTS: From January to September 2024, 221 older adults were randomized (110 in the pay-it-forward group and 111 in the standard-of-care group). Pneumococcal and influenza vaccine uptake were significantly higher in the pay-it-forward arm (70.9% and 30.0%) than in the standard-of-care arm (13.5% and 17.1%), with adjusted odds ratios of 17.20 (95% CI, 8.39-37.60) and 2.29 (95% CI, 1.17-4.65). The pay-it-forward group also exhibited greater confidence in the safety (4.29, 95% CI, 1.78-11.50), importance (5.15, 95% CI, 2.05-14.60), and effectiveness (7.14, 95% CI, 2.36-27.50) of the vaccine than that in the standard-of-care group. The pay-it-forward group had a higher successful vaccine referral rate (15.5% vs. 10.8%) and had a lower economic cost per person vaccinated (US 278.56) compared with the standard-of-care arm.
CONCLUSIONS: Our findings demonstrate that the pay-it-forward intervention significantly enhances pneumococcal and influenza vaccination coverage and improves vaccine confidence among the older adults. This study highlights the potential of the pay-it-forward intervention as an effective means to boost health service utilization.
TRIAL REGISTRATION: 2024-01-03, Chinese Clinical Trial Registry, ChiCTR2400079410