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Evaluation of Attractive Targeted Sugar Baits, a new outdoor vector control strategy against malaria: Results from a cluster randomised open-label parallel arm controlled trial in Southwestern Mali.
BACKGROUND: The Attractive Targeted Sugar Bait (ATSB) is a new malaria outdoor vector control tool targeting sugar-feeding behaviours of vector mosquitoes. In Mali, a two-year open-label two-arm cluster randomised controlled trial compared the efficacy and safety of ATSB plus insecticide treated mosquito nets (ITN) versus ITN alone on malaria burden. METHODS: 76 clusters were formed, of which 38 were randomly allocated to the intervention. Cohort studies and household surveys were performed to assess clinical malaria incidence (primary outcome) in children aged 5 to 14 years and malaria infection prevalence in individuals aged 6 months or older, respectively. Primary analyses were performed on an intention-to-treat basis. The trial was designed to detect a minimum 30% reduction in the two outcomes over a two-year period with a power of at least 80%. The trial is registered at ClinicalTrial.gov (NCT04149119). FINDINGS: The proportion of sleeping buildings with at least 2 ATSB ranged between 70% and 80%. Coverage of ATSB in good condition was lower (50% or less). Over the two-year trial period, the clinical malaria incidence rate in the control and intervention arm was 0.726 and 0.660 cases per person-year, respectively, with no statistical evidence for an intervention effect (Incidence Rate Ratio (IRR) = 0.90; 95%CI 0.77, 1.05; p = 0.188). Malaria infection prevalence was approximately 37% in both arms (Odds Ratio (OR) = 0.96; 95%CI 0.76, 1.21; p = 0.729). In clusters with coverage of stations in good condition above 80%, there was evidence for a 26% reduction in malaria incidence compared to control clusters after controlling for confounders (adjusted IRR = 0.74; 95%CI 0.61, 0.90; p = 0.002). INTERPRETATION: Overall, the trial did not demonstrate evidence of additional protection against malaria of ATSB compared to using ITN alone. Suboptimal coverage and maintenance of ATSB in good condition in the field may explain the lack of an intervention effect
Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotes.
Trypanosoma cruzi is a protozoan parasite that is the etiological agent of Chagas disease, which is endemic to Latin America with reported cases in non-endemic regions such as Europe, Asia, and Oceania due to migration. During its lifecycle, T. cruzi alternates between replicative and non-replicative infective lifeforms. Metacyclogenesis is the most studied transition of the T. cruzi life cycle, where replicative epimastigotes differentiate into infective metacyclic trypomastigotes inside the gut of the triatomine vector. This early-branching organism expresses a divergent pre-replication complex (pre-RC) where the only conserved component is the MCM2-7 protein family. Given the role of pre-RC components in cell cycle regulation, we investigated whether MCM expression and location could be involved in proliferation control in epimastigotes and during metacyclogenesis. Using CRISPR/Cas9, we tagged MCM subunits and tracked their expression and subcellular localization. Our findings reveal that MCM subunits are consistently expressed and localized to the nucleus throughout the epimastigote cell cycle, including in G1/G0-arrested cells. However, MCM subunits are degraded during metacyclogenesis as cells enter the G0 state, marking the transition to replication arrest. Therefore, epimastigotes arrested in G1/G0 can either maintain MCM complex expression and resume the cell cycle when conditions become favorable, or they can undergo metacyclogenesis, exiting the cell cycle and entering a G0 state, where MCM subunits are degraded as part of the replication repression mechanism
A household randomized-control trial of insecticide-treated screening for malaria control in unimproved houses in Tanzania.
BACKGROUND: Installing insecticidal netting on open eaves, windows, and holes in walls of unimproved houses is a potential malaria control tool. It prevents mosquito house-entry, induces lethal and sub-lethal effects on malaria vectors, and may reduce malaria transmission. Therefore, a household epidemiological trial was conducted to assess the efficacy of insecticide-treated screening (ITS) on malaria infection and indoor vectors in Tanzania. METHODS: In Chalinze district, Tanzania, 421 households were randomized into two arms. In June-July 2021, one group of households' houses was fitted with ITS (incorporated with deltamethrin and piperonyl butoxide) on eaves, windows, and wall holes, while the second group did not receive screening. After installation, consenting household members (aged ≥ 6 months) were tested for malaria infection using quantitative polymerase chain reaction after the long rainy season (June/July 2022, primary outcome) and the short rainy season (January/February 2022, secondary outcome). Secondary outcomes included indoor total mosquito per trap/night (June-July 2022), adverse effects after one month of ITS installation (August 2021), and chemical bioavailability and retention of ITS samples after one year of field use (June/July 2022). At the end of the trial, the control group received ITS. RESULTS: Malaria prevalence among residents in the ITS arm was 19.9% (50/251) and 28.3% (65/230) in the control arm after the long rains, however, this difference was not significant [adjusted odds ratio (OR) 0.67 (95% CI 0.35-1.28), p = 0.227]. Similarly, no protection was seen for ITS after the short rains, [OR 1.27 (95% CI 0.68-2.38), p = 0.452]. However, school-age children in the ITS arm had lower malaria after the long rains [OR 0.11 (95% CI 0.02-0.73), p = 0.022]. No serious adverse effects were reported. The mean number of female Anopheles mosquitoes caught per trap/night was not significantly different between arms [1.7 vs 2.4, crude relative risk: 0.71 (95% CI 0.16-3.09), p = 0.650]. ITS showed reduced chemical bioavailability and retention post-field use. The trial reported high household refusals (17-30%) in both arms in both surveys. CONCLUSION: The trial was inconclusive because households' refusal resulted in low power. A large cluster randomized trial of the intervention, preferably with screens treated with longer-lasting insecticides installed in houses, is needed. TRIAL REGISTRY: The trial was registered at ClinicalTrials.gov (NCT05125133) on October 2021
Improving HIV case finding using spatial data infrastructures in Anambra State, Nigeria: a pre-post intervention study
Background:
The heightened HIV prevalence in Nigeria is partly associated with challenges in accessing people living with HIV in geographically isolated and unidentified regions. Spatial Data Infrastructure (SDI) is an innovation that has shown promise for HIV case-finding in unidentified settlements. This study reports the use of SDI to improve HIV case identification in Anambra North Senatorial District, Nigeria.
Methods:
This study utilised a pre-post intervention study design to analyse data from the implementation of HIV testing services (HTS). Settlements for HTS were identified in the district using SDIs, such as microplans and hotspot maps. Community teams captured areas’ names and geolocations using a custom application. Geographical Information Systems technology was overlayed on coordinates to generate microplans and hotspot maps, which were used for targeted tests and new case identification.
Results:
Our study showed varying trends across the periods when SDIs were utilised and when they were not. The use of SDI greatly enhanced HIV case identification and provided a strategic framework for HTS implementation. Overall, the period when SDI was used recorded relatively higher new cases than before. Local Government Areas with more rural settlements that leveraged SDI significantly upscaled their case identification.
Conclusions:
SDI can facilitate HIV case identification. Our study revealed twice as many cases identified across the periods compared. Our pioneering use of SDI for HIV case finding in Nigeria offers promise for efficient HTS implementation in high-burden and yet-to-be-identified locations
Performance of Foundation Models vs Physicians in Textual and Multimodal Ophthalmological Questions.
IMPORTANCE: There is an increasing amount of literature evaluating the clinical knowledge and reasoning performance of large language models (LLMs) in ophthalmology, but to date, investigations into its multimodal abilities clinically-such as interpreting images and tables-have been limited. OBJECTIVE: To evaluate the multimodal performance of the following 7 foundation models (FMs): GPT-4o (OpenAI), Gemini 1.5 Pro (Google), Claude 3.5 Sonnet (Anthropic), Llama-3.2-11B (Meta), DeepSeek V3 (High-Flyer), Qwen2.5-Max (Alibaba Cloud), and Qwen2.5-VL-72B (Alibaba Cloud) in answering offline Fellowship of the Royal College of Ophthalmologists part 2 written multiple-choice textual and multimodal questions, with head-to-head comparisons with physicians. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted between September 2024 and March 2025 using questions sourced from a textbook used as an examination preparation resource for the Fellowship of the Royal College of Ophthalmologists part 2 written examination. EXPOSURE: FM performance. MAIN OUTCOMES AND MEASURES: The primary outcome measure was FM accuracy, defined as the proportion of answers generated by the model matching the textbook's labeled letter answer. RESULTS: For textual questions, Claude 3.5 Sonnet (accuracy, 77.7%) outperformed all other FMs (followed by GPT-4o [accuracy, 69.9%], Qwen2.5-Max [accuracy, 69.3%], DeepSeek V3 [accuracy, 63.2%], Gemini Advanced [accuracy, 62.6%], Qwen2.5-VL-72B [accuracy, 58.3%], and Llama-3.2-11B [accuracy, 50.7%]), ophthalmology trainees (difference, 9.0%; 95% CI, 2.4%-15.6%; P = .01) and junior physicians (difference, 35.2%; 95% CI, 28.3%-41.9%; P < .001), with comparable performance with expert ophthalmologists (difference, 1.3%; 95% CI, -5.1% to 7.4%; P = .72). GPT-4o (accuracy, 69.9%) outperformed GPT-4 (OpenAI; difference, 8.5%; 95% CI, 1.1%-15.8%; P = .02) and GPT-3.5 (OpenAI; difference, 21.8%; 95% CI, 14.3%-29.2%; P < .001). For multimodal questions, GPT-4o (accuracy, 57.5%) outperformed all other FMs (Claude 3.5 Sonnet [accuracy, 47.5%], Qwen2.5-VL-72B [accuracy, 45%], Gemini Advanced [accuracy, 35%], and Llama-3.2-11B [accuracy, 25%]) and the junior physician (difference, 15%; 95% CI, -6.7% to 36.7%; P = .18) but was weaker than expert ophthalmologists (accuracy range, 70.0%-85.0%; P = .16) and trainees (accuracy range, 62.5%-80%; P = .35). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that for textual questions, current FMs exhibited notable improvements in ophthalmological knowledge reasoning when compared with older LLMs and ophthalmology trainees, with performance comparable with that of expert ophthalmologists. These models demonstrated potential for medical assistance for answering ophthalmological textual queries, but their multimodal abilities remain limited. Further research or fine-tuning models with diverse ophthalmic multimodal data may lead to more capable applications with multimodal functionalities
Expert perspectives on exposure-response functions for urban health policy: Lessons from a UBDPolicy workshop.
Policy-makers require robust, quantitative evidence in order to better align urban and transport planning practices with public health goals. Epidemiologically derived exposure-response functions can quantify the association between urban health determinants and human health outcomes. They are therefore a crucial input in quantitative health risk assessments, providing to policy-makers actionable evidence on how healthier, more sustainable cities may be achieved. The Urban Burden of Disease Policy (UBDPolicy) project convened a two-day workshop to discuss recent developments, ongoing challenges, and future directions for exposure-response functions and their application to quantitative health risk assessment. The workshop discussions centred around air pollution, transport noise, non-optimal temperature, greenspace and physical activity as primary pathways through which urban and transport planning impact human health. Based on this workshop, we provide an expert-guided perspective on how to enhance both our conceptual understanding of exposure-response functions and their practical application in urban health risk assessment. We also identify pathway-specific as well as cross-cutting (e.g., quantifying multiple exposures, need for population sub-group evidence) research needs relevant to environmental health more broadly. We propose several future research directions as an agenda for advancing urban environmental health
Safe and respectful? Birth attendants' hand hygiene compliance and its determinants using nationally representative data from Kenya, Malawi and Nepal.
BACKGROUND: In low and middle-income countries (LMICs), infections acquired during childbirth contribute significantly to maternal and neonatal mortality. Hand hygiene (HH) is critical in preventing the spread of infections, yet compliance remains inadequate. This study investigates birth attendants' HH compliance during labour, delivery, and postpartum in LMICs, using nationally representative data from Service Provision Assessments (SPAs) in Kenya, Malawi, and Nepal. METHODS: We analysed 1565 observed deliveries across 517 health facilities, resulting in 3919 HH opportunities. The outcomes were hand washing or hand disinfectant use: (1) before any initial examination, (2) before aseptic procedures during labour, (3) after birth. We used descriptive statistics to assess HH compliance and multivariate multilevel mixed-effect logistic regressions to investigate determinants, accounting for facility and individual clustering. FINDINGS: Hand hygiene compliance varied significantly across countries, with Kenya showing the lowest rates, while Malawi and Nepal had higher compliance levels. Supportive and effective communication towards pregnant women was significantly associated with an increase in HH compliance before the vaginal examination (Kenya - OR: 5.94, 95% CI 1.68-21.0; Malawi - OR: 2.19, 95% CI 1.04-4.65) and before aseptic procedures (Kenya - OR: 4.03, 95% CI 1.81-8.96; Malawi - OR: 4.01, 95% CI 1.69-9.50; Nepal - OR: 2.66, 95% CI 1.30-5.44). HH compliance during aseptic procedures during labour was also associated with recent IPC training in Malawi (OR: 3.48,95%CI 1.44-8.41) and facility infrastructure (OR: 6.14,95%CI 1.07-35.3). CONCLUSION: Low hand hygiene compliance during birth, especially before aseptic procedures, can lead to healthcare-associated infections with serious consequences for mothers and newborns. Future research should investigate further the association between effective communication and hand hygiene
Replicating a COVID-19 study in a national England database to assess the generalisability of research with regional electronic health record data.
OBJECTIVES: To assess the degree to which we can replicate a study between a regional and a national database of electronic health record data in the UK. The original study examined the risk factors associated with hospitalisation following COVID-19 infection in people with diabetes. DESIGN: A replication of a retrospective cohort study. SETTING: Observational electronic health record data from primary and secondary care sources in the UK. The original study used data from a large, urbanised region (Greater Manchester Care Record, Greater Manchester, UK-2.8 m patients). This replication study used a national database covering the whole of England, UK (NHS England's Secure Data Environment service for England, accessed via the BHF Data Science Centre's CVD-COVID-UK/COVID-IMPACT Consortium-54 m patients). PARTICIPANTS: Individuals with a diagnosis of type 1 diabetes or type 2 diabetes prior to a positive COVID-19 test result. The matched controls (3:1) were individuals who had a positive COVID-19 test result, but who did not have a diagnosis of diabetes on the date of their positive COVID-19 test result. Matching was done on age at COVID-19 diagnosis, sex and approximate date of COVID-19 test. PRIMARY AND SECONDARY OUTCOME MEASURES: Hospitalisation within 28 days of a positive COVID-19 test. RESULTS: We found that many of the effect sizes did not show a statistically significant difference, but that some did. Where effect sizes were statistically significant in the regional study, then they remained significant in the national study and the effect size was the same direction and of similar magnitude. CONCLUSIONS: There is some evidence that the findings from studies in smaller regional datasets can be extrapolated to a larger, national setting. However, there were some differences, and therefore replication studies remain an essential part of healthcare research
Temporal Trends in Outcomes and Predictors of Length of Stay following Lung Cancer Resection over 10 Years with Enhanced Recovery After Surgery.
OBJECTIVES: Enhanced Recovery After Surgery aims to accelerate recovery, with length of stay as a key metric. This study assessed temporal trends in short-term outcomes within a maturing programme and identified factors associated with increased hospital stay. METHODS: Data were prospectively collected for consecutive patients undergoing lung cancer resection following a 14-step protocol between 2013 and 2023. Primary outcome was length of stay. Secondary outcomes included 30-day mortality, morbidity, re-admission, and reoperation rates. Predictors of length of stay were analysed using linear regression. RESULTS: We included 2192 patients; procedures included lobectomy (61%), wedge resection (23%), segmentectomy (10%), pneumonectomy (3.5%), and bi-lobectomy (2.7%), Video-assisted thoracoscopic surgery was used in 80% of cases. Median length of stay decreased from 5 to 4 days (p < 0.001), while protocol adherence increased from 10/14 to 12/14 (p = 0.01). In-hospital mortality (2.9% to 1.0%, p < 0.001) and major-morbidity (12.2% to 5.6%, p < 0.001) both declined. In multivariable linear regression, factors associated with longer stay included age (β = 0.17, CI 0.13-0.20, p < 0.001), higher American Society of Anesthesiologists score (β = 1.12, CI 1.04-2.2, p = 0.02), open surgery (β = 1.0, CI 0.17-2.2, p = 0.043), thoracoscopic-to-open converted surgery (β = 1.49, CI 0.96-1.9, p = 0.03) and intensive care (β = 3.4, CI 2.5-4.3, p < 0.001). Protective factors were early mobilisation (β=-0.90, CI -1.9-0.33, p = 0.005) and opioid avoidance (β=-0.72, CI -2.4-0.99, p = 0.038). CONCLUSIONS: Sustained use of an Enhanced Recovery After Surgery programme was associated with shorter hospitalisation and reduced morbidity. Factors associated with length of stay can identify patients at risk of delayed recovery and prioritise elements for optimisation within recovery pathways
Mapping the Nature, Drivers, Effects and Responses to Corruption in the Procurement of Pharmaceuticals in Anglophone Africa: A Scoping Review of Literature
Expenditure on pharmaceuticals comprises a large share of health budgets. It involves many different actors, often working out of the public gaze, making the process ‘corruption-attractive’ and hard to monitor. Given the indispensable contributions of pharmaceuticals to health outcomes, it is essential that they are available at the right time and at the lowest prices. This requires the process to be as transparent and accountable as possible. But first, it is important to understand the system and the obtainable corruption concerns that impact it, as well as what works. This is the essence of a scoping review on the subject, focusing on Anglophone sub-Saharan Africa (SSA). We focused on the literature written in English from 2008 onward. After screening, 52 publications were reviewed, and the findings were synthesised and presented thematically. Findings from the reviewed literature demonstrate that corruption is widespread in pharmaceutical procurement, with consequences for revenue generation, utilisation and public confidence in health facilities, as well as the finances and health outcomes of service users. There is a need to devise a multi-dimensional approach to interventions, as most of the reviewed literature reckoned