London School of Hygiene & Tropical Medicine

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    69832 research outputs found

    Mastering online ophthalmology exams: essential tips for success

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    Aproaching an online exam may be different from previous exam experiences, and involves both knowledge and self preparation. Examiners and a top-performing candidate have contributed these tips

    The Gastein prescription: health as Europe's path to renewal

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    Case fatality rate and determinants of maternal death among pregnant women with SARS-CoV-2 infection: A population-based cohort study in Bahia, Brazil.

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    Objectives To estimate the case fatality rate (CFR) of SARS-CoV-2 infection among pregnant women in Bahia, Brazil, and to identify individual- and community-level factors associated with maternal death. Methods We conducted a population-based retrospective cohort study including all women at ≥20 weeks of gestation with laboratory-confirmed SARS-CoV-2 infection between 2020 and 2022. CFRs were estimated overall and stratified by sociodemographic and clinical characteristics. Multilevel logistic regression models were used to identify individual- and contextual-level determinants of maternal mortality. Results The overall CFR was 2.2%. Higher fatality rates were observed among older women, those with lower educational attainment, fewer prenatal visits, cesarean delivery, and unvaccinated status. Independent predictors of death included multiparity, fewer prenatal visits, cesarean section, infection during the third trimester, limited availability of obstetric beds, and higher regional maternal mortality ratios. Study limitations include the use of secondary surveillance data and lack of information on comorbidities and behavioral factors. Conclusion Social, clinical, and healthcare access factors significantly influenced SARS-CoV-2-related maternal deaths in Bahia. Preventing maternal deaths in future respiratory epidemics will require expanding vaccination coverage, ensuring comprehensive prenatal and obstetric care, and promoting evidence-based decisions regarding delivery mode, particularly in regions historically burdened by high maternal mortality

    TOAST: a novel tool for designing targeted gene amplicons and an optimised set of primers for high-throughput sequencing in tuberculosis genomic studies.

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    BACKGROUND: Amplicon sequencing of Mycobacterium tuberculosis resistance-associated genes offers a cost-effective alternative to whole-genome sequencing for rapid profiling of infections and guiding clinical management. However, existing assays require frequent manual updates to accommodate emerging resistance mutations, limiting scalability and responsiveness. RESULTS: We present TOAST (Tuberculosis Optimised Amplicon Sequencing Tool), a novel software tool that automates primer design by integrating mutation frequencies from a curated database of over 68,000 drug-resistant M. tuberculosis genomes. TOAST prioritises regions with the highest clinical relevance, accounting for single-nucleotide polymorphisms, insertions, and deletions. The software supports customisation of design parameters such as amplicon length, melting temperature, and GC content, while screening for undesirable primer properties, including self-dimers and off-target binding. Using TOAST, we designed a multiplex panel of 33 amplicons targeting mutations associated with resistance to 13 anti-TB drugs. These amplicons covered over 97% of resistance mutations in a 68 K isolate database and were validated using Oxford Nanopore sequencing of two clinical samples, achieving high uniform coverage with a minimum sequencing depth exceeding 50-fold across all targets. CONCLUSIONS: TOAST represents a major advancement in targeted TB sequencing by integrating large-scale clinical genomic data directly into assay design. This enables rapid, high-coverage, and adaptable amplicon sequencing, enhancing diagnostic precision and surveillance capabilities for drug-resistant TB. TOAST’s framework is also extensible to other pathogens, supporting broader applications in infectious disease genomics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-025-12247-9

    Assessing hepatitis C self-testing within differentiated care models in Cameroon: Feasibility, acceptability, and linkage to care for key and priority populations.

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    Hepatitis C virus (HCV) infection remains a global public health concern, with limited care coverage in resource-limited settings. HCV self-testing (HCVST) offers a potential strategy to expand screening, diagnosis, and treatment. This study evaluated the feasibility and acceptability of HCVST among at-risk populations in Cameroon. Between 26-06-2023 and 01-03-2024, adults (≥21 years) were recruited through four HCVST service models targeting specific populations: people living with HIV at antiretroviral therapy clinics, men who have sex with men and people who inject drugs at drop-in-centers, and adults ≥45 years attending chronic disease clinics. Participants were randomly assigned either blood-based or oral-fluid self-test kits, with the option to test on-site or off-site, with or without assistance. Reactive results were linked to confirmatory testing and HCV treatment. Descriptive and multivariable analyses assessed acceptability and feasibility outcomes of HCVST. Of 2,653 clients offered HCVST, 99.7% (n = 2,644) accepted, 97.7% tested on-site, and 80.9% performed unassisted self-testing. Most (91.7%) found HCVST easy to use, citing rapid results (60.4%), simplicity (45.8%), and confidentiality (23.1%). Nearly all (98.7%) would recommend HCVST, with 45.9% favoring unassisted home-testing. Satisfaction with HCVST varied by care model, increased with higher HCV knowledge (aOR 1.07, 1.04-1.11), and decreased for retired clients (aOR 0.65, 0.44-0.96), blood-based tests (aOR 0.59, 0.50-0.70) and assisted testing (aOR 0.32, 0.25-0.40). Difficulties in result interpretation were rare (3.1%) but higher with off-site testing (aRR 3.76, 1.69-8.36). The HCVST seroprevalence was 4.4% (n = 117), highest at chronic disease clinics (12.2%). Among 117 clients with reactive results, 93.2% linked to confirmatory testing, 72 were treatment-eligible, and 71 (98.6%) initiated therapy, with 74.6% achieving cure. Men had greater attrition along the care cascade (aOR: 3.77, 1.10-12.91). HCVST was highly acceptable and feasible, increasing testing uptake and care engagement in Cameroon. Findings can guide rollout through differentiated, population-specific delivery models

    Organisational and management factors and related end-users' perspectives relevant to newborn and stillbirth data at different levels of the health system: findings of the IMPULSE study in Uganda, Ethiopia, Tanzania, and the Central African Republic.

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    BACKGROUND: As few studies systematically analysed organisational and management factors related to newborn and stillbirth data quality, we sought to identify specific gaps in these factors to provide evidence for planning tailored actions. METHODS: We performed a cross-sectional survey in 12 regions and 4 city administrations in the Central African Republic (CAR), Ethiopia, Tanzania, and Uganda between November 2022 and July 2024, collecting data related to organisational and management factors at different health system levels through the Every Newborn - Measurement Improvement for Newborn & Stillbirth Indicators (EN-MINI) tools. We reported the results as frequencies/normalised PRISM scores, both on the overall sample and by country, and conducted exploratory subgroup analyses by region. RESULTS: We included 151 sites (56 data offices; 95 facilities) and 108 health/data professional respondents. Availability of written documents describing the routine health information system (RHIS) mission, roles, and responsibilities (71.4% in the CAR to 94.1% in Tanzania; P = 0.380), and designated staff for internal data quality review (83.3% in Ethiopia to 100% in the CAR, Tanzania, or Uganda; P = 0.245) showed high percentages and low heterogeneity across countries at data office level. Most of the other measures explored - i.e. those related to governance, planning, financing, capacity development, relevant guidelines, data quality assurance systems, feedback mechanisms and supportive supervision - showed high heterogeneity across countries, with Ethiopia and Uganda, followed by Tanzania, showing the highest percentages, and the CAR showing the lowest. We observed low percentages in all countries at the data office level in the domains of financing (budget for RHIS supplies: 0% in the CAR to 35.3% in Tanzania; P = 0.079) and capacity development (availability of a report with RHIS training needs: 0% in the CAR to 41.2% in Tanzania; P = 0.333; training schedule: 17.6% in Tanzania to 42.9% in Uganda; P = 0.412). Subgroup analyses suggested high within-country heterogeneity. Needs for improvement in management and organisational factors were reported by most respondents (72.7% in Ethiopia to 100% in the CAR; P = 0.629). CONCLUSIONS: Our findings reveal a need for tailored interventions to improve organisational and management aspects at different levels of the health system, to ensure better quality and use of newborn and stillbirth data

    A rapid review of the causes of diagnostic and treatment delays for tuberculosis in low-burden countries.

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    Background Delays in diagnosing and treating tuberculosis (TB) have significant implications. We undertook a rapid review to explore factors associated with delays at all stages of the diagnostic and treatment pathways in low-burden settings. Methods We searched databases (Embase, Medline, CENTRAL, Cinahl, PubMed, Cochrane Database of Systematic Reviews, and Web of Science) for qualitative and quantitative evidence (2010-25) from countries with low TB burden (incidence rate <40/100 000 in 2020). Included studies were assessed on their robustness and relevance. Due to the rapid review design, we did not conduct formal quality appraisal. Results The review included 3 reviews, 5 qualitative studies, 18 cohort studies, and 13 cross sectional studies (n = 41) with varying robustness and relevance. By synthesizing data using a patient pathway, we uncovered patient- and healthcare-related factors that contribute to delays such as medical history, health behaviours, level of patient and physician suspicion of TB, service location (primary care), and timing of TB testing. Having extrapulmonary TB was associated with greater total delay. Conclusions We have identified patient and health service factors that are consistently associated with patient, diagnostic, and total delay from TB symptom onset to initiation of treatment in low-burden settings. Factors amenable to change should be the focus of public health interventions aimed at reducing TB diagnostic delay

    Characterization of 843 children with Zika-related microcephaly in the first three years of life: An individual participant data meta-analysis of 12 cohorts in the Zika Brazilian Cohorts consortium.

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    One of the main gaps in characterizing the congenital Zika syndrome (CZS) up to now is the small number of participants in individual studies. Pooling the data together overcomes the sample size-related limitations of individual studies and provides an opportunity for investigating heterogeneity between studies and, as appropriate, to better characterize the CZS. This study aims to describe adverse anthropometric, clinical, and neuroimaging outcomes in Brazilian children with Zika-related microcephaly.Individual participant data meta-analysis of 12 cohorts of the Zika Brazilian Cohorts Consortium (ZBC-Consortium), using primary data from children with Zika-related microcephaly, born between January/2015 and July/2018. We included 843 children with microcephaly at birth, at first evaluation, or over follow-up. Of 601 children with microcephaly at birth, 217 (36.1%) had moderate and 384 (63.9%) had severe microcephaly. Postnatal microcephaly occurred in 172 (20.4%) children. There was heterogeneity across studies. Severe microcephaly ranged from 11-87.5%; prematurity from 10-20% in most sites; low birth weight from 10-43.8%. Deficit of social attention, hyperreflexia, and persistence of primitive reflexes were reported in at least 50% of the children in the larger cohorts. Epilepsy ranged from 30-80% of the children and dysphagia, from 22.2-67.7%. Calcifications and ventriculomegaly were the most consistent and frequent abnormality (around 80%). Cortical atrophy or other development disorders were reported in around 50% of the children. The frequency of fundal, optical nerve and hearing abnormalities ranged from 0-67.1%, 0-36.5% and 0-50%, respectively. This large sample size allowed us to describe the spectrum of severity and of manifestations of Congenital Zika Syndrome

    Public engagement, evidence review and survey to adapt a whole-school intervention to prevent bullying in English primary schools [version 1; peer review: 2 approved].

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    BACKGROUND: Bullying increases during primary school and causes multiple mental/physical health harms. Whole-school interventions offer a feasible means of reducing bullying but few have been evaluated in primary schools. We previously trialled the Learning Together intervention in secondary schools comprising local needs assessment, student and staff participation in decision-making through 'action groups', restorative practice, and a social and emotional skills curriculum. This intervention was effective in preventing bullying and improving mental wellbeing. We aimed to adapt Learning Together for primary schools (Learning Together Primary Schools (LTPS)). This paper reports on how we adapted intervention materials to produce the LTPS intervention through a review of research evidence, online survey, and patient and public involvement and engagement (PPIE). METHODS: We conducted a rapid review of existing systematic reviews, online survey of primary schools in south-east England, and multiple PPIE workshops. PPIE was conducted with two primary schools (10 staff members and 20 pupils), with a group of 10 pupils from five primary schools, and with a group of six parents with primary-school-aged children. CONCLUSIONS: We refined our initial plans for LTPS, developing an intervention appropriate for primary schools and supported by full materials, training and external facilitation. We retained key components including restorative practice and action groups and made several refinements, including guidance for action group implementation to accommodate for primary schools' smaller capacities. No refinements were made to the intervention theory of change. We found that it is possible to refine and elaborate interventions to provide full materials and support via processes drawing on evidence review, a survey and PPIE. Although not all PPIE suggestions could be acted upon, PPIE proved valuable in ensuring the feasibility and acceptability of the intervention in primary schools. Future work will include a pilot trial to assess whether progression to a full trial is justified. STUDY REGISTRATION: ISRCTN10215449 https://doi.org/10.1186/ISRCTN10215449

    Disparities in uptake of Shingrix® vaccine in immunosuppressed individuals in England: a population-based cohort study.

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    BACKGROUND: Herpes zoster (shingles) impacts health and quality of life, particularly in immunosuppressed individuals. The UK Shingrix® zoster vaccination programme has been available for eligible immunosuppressed individuals since 2021. Understanding Shingrix® uptake in immunosuppressed adults is critical for equitable vaccine delivery. METHODS: We conducted a population-based cohort study using primary care records from English practices contributing to Clinical Practice Research Datalink (CPRD) Aurum (1 September 2021-31 August 2023). We included immunosuppressed adults (70-79 years) with at least one year of prior registration. Our primary outcome was uptake of at least one dose of Shingrix®. Secondary outcomes were two-dose completion, inadvertent Zostavax® receipt (live attenuated vaccine contraindicated in immunosuppression), and co-administration of Shingrix® with seasonal influenza vaccine. We used multivariable logistic regression to estimate associations between potential uptake-related factors and vaccine uptake. RESULTS: We included 86,197 immunosuppressed adults, 17.3 % received at least one Shingrix® dose. Of those, 41.5 % received two doses. Uptake was lower in older individuals, people from minority ethnic groups (e.g. Black vs. White OR 0.53, 95 %CI 0.43-0.66), and the most vs. least deprived quintile (OR 0.61, 95 %CI 0.56-0.67). While many factors showed strong relative differences, absolute differences were often modest. Absolute differences exceeded 5 %, highlighting substantial disparity in vaccine coverage, for dementia (10.3 % vs 17.5 %), severe mental illness (10.8 % vs 17.4 %), Black ethnicity (10.0 % vs 18.0 %), care home residence (5.8 % vs 17.5 %), and deprivation (most 13.3 % vs least 21.3 %). CONCLUSIONS: Our study highlights suboptimal Shingrix® vaccine uptake during initial UK roll-out to immunosuppressed adults. Both relative and absolute differences reveal particularly low uptake among older people, those living with dementia or severe mental illness, and individuals from more deprived or minority ethnic backgrounds. Our results suggest a need for targeted strategies to improve access and reduce disparities in this vulnerable group

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