69832 research outputs found
Sort by
Standards for the conduct and reporting of health technology assessments: Ghana reference case of HTA and economic evaluations.
Get PDFBACKGROUND: The methods of economic evaluation and HTA should be based on best practices and standards, tailored to unique country contexts that can be systematically applied to inform decisions. This paper outlines standards for the conduct of economic evaluations for HTA in Ghana. METHODS: A five-step process was followed to develop the HTA reference case as a methodological and reporting benchmark. These include (a) a review of literature and evidence synthesis, (b) a review of country policies, (c) a review and adaption of international frameworks, (d) expert/stakeholder consultations, and (e) the development of a methodological framework. A series of stakeholder consultations were done to refine, finalize, and validate the outcomes of the processes to generate a finalized reference case. RESULTS: The Ghana reference case is made up of 14 components comprising: evidence synthesis, evaluation type, perspectives on cost, perspectives of outcomes, choice of comparator, data sources, outcome measures, discount rate, uncertainty, equity considerations, time horizon, heterogeneity, transparency, and budget impact. These provide methodological considerations and reporting requirements for economic evaluations for HTA. It provides a framework to ensure the best research methods are adopted to harmonize the evidence-generation process with the expectations of policy and decision-makers and ensure that policy decisions are based on uniform evidence. CONCLUSION: Recommendations set out in this reference case when followed can provide context-specific evidence to support a rigorous and transparent system for evaluating healthcare interventions and technologies. It will support decision-making, ultimately improving the quality and efficiency of healthcare delivery in the country
Strategies to sustain HIV prevention interventions among adolescents and young adults: analysis of data from a crowdsourcing open call in Nigeria.
Get PDFBackground Crowdsourcing is a process whereby a large group, including experts and non-experts, collaborate to solve a problem and then share the solution with the public. Crowdsourcing can be used to identify strategies to sustain HIV services in low-and-middle-income countries. This study aims to identify innovative adolescent and young adult (AYA) solutions through a crowdsourcing open call to sustain HIV services. Methods Building on HIV prevention services developed by AYA from an initial open call, we organized a crowdsourcing open call to identify innovative, AYA-led strategies to sustain these services through partnerships with the community. The open call question was, 'How might we sustain the 4 Youth by Youth HIV prevention services while nurturing our existing relationships, practices, procedures and services that will last in our communities?'. All submissions were assessed based on prespecified judging criteria. Qualitative data were analyzed using thematic analysis and categorized into strategies for sustaining AYA-friendly HIV prevention services in Nigeria. Results We received 102 eligible submissions from AYA. Twenty-three submissions met the mean score threshold and were qualitatively analyzed. Through this analysis, we identified four strategies for sustaining AYA-friendly HIV prevention services in Nigeria: AYA engagement and leadership in research, digital health solutions, financing and efficiency, and partnerships. Conclusion This open call highlights how strategies developed by AYA may sustain AYA-friendly HIV prevention services. Our findings offer key insights for maintaining HIV prevention services in Nigeria and other similar settings
Interactions between live attenuated influenza vaccine and nasopharyngeal microbiota among children aged 24-59 months in The Gambia: a phase 4, open-label, randomised controlled trial.
Get PDFBACKGROUND: Live attenuated influenza vaccines (LAIVs) alter nasopharyngeal microbiota in adults. It is poorly understood why LAIV immunogenicity varies across populations, but it could be linked to the microbiome. We aimed to investigate the interactions between intranasal immunisation with LAIV and nasopharyngeal microbiota composition in children from The Gambia. METHODS: We conducted a phase 4, open-label, randomised controlled trial in Sukuta, The Gambia. Children aged 24-59 months with no underlying illness or history of respiratory illness for at least 14 days before recruitment were eligible. Participants were randomly assigned (2:1) by use of a computer-generated sequence in permuted blocks of 15, stratified by sex, to receive trivalent LAIV either on day 0 (intervention group) or after active follow-up at day 21 (control group). The investigator team was initially masked to block size and randomisation sequence; however, group allocation was later revealed to the team. Microbiome profiles were characterised from nasopharyngeal samples collected from all participants on days 0, 7, and 21 by use of 16S rRNA sequencing. The primary outcomes were the effect of LAIV on nasopharyngeal microbiome profiles on day 7 and day 21, and the association between the nasopharyngeal microbiome at baseline and LAIV-induced mucosal IgA responses at day 21, assessed with permutational ANOVA tests. Asymptomatic respiratory viral co-infection at baseline and year of recruitment (2017 or 2018) were included as covariates. This trial is registered with ClinicalTrials.gov (NCT02972957) and is closed. FINDINGS: Between Feb 8 and April 12, 2017, and Jan 15 and March 28, 2018, 343 children were screened for eligibility, of whom 220 (64%) children were randomly assigned to the intervention group and 110 (32%) to the control group. 213 (97%) children in the intervention group and 108 (98%) in the control group completed the study and were included in the final analysis. Although we did not observe an independent effect of LAIV on microbial community composition at days 7 or 21, we found that LAIV had an effect dependent on the year of recruitment. LAIV affected microbial community composition in 2018 (R2 1·97% [95% CI 0·85-5·94]; p=0·037), but not in 2017 (1·23% [0·49-4·46]; p=0·091). We also found that viral co-infection at baseline had an effect on microbial composition at day 7, regardless of recruitment year (R2 1·01% [95% CI 0·28-3·01]; p=0·026). Nasopharyngeal microbial community composition at baseline had no effect on mucosal IgA responses to LAIV administration (R2 0·51% [95% CI 0·23-2·49]; p=0·46). INTERPRETATION: Our findings suggest that the effect of LAIVs on nasopharyngeal microbiota composition in children is modest and temporary; therefore, LAIVs could be used as an intervention to curb influenza in children from low-income and middle-income countries, without causing long-lasting perturbations in nasopharyngeal microbiota. However, nasopharyngeal microbiota at the time of vaccination might not explain the variability observed between individuals in LAIV-induced IgA responses. FUNDING: The Wellcome Trust, UK National Institute for Health Research, and Chief Scientist Office Scotland
Use of minimally invasive tissue sampling to determine the contribution of diarrheal diseases to under-five mortality and associated co-morbidities and co-infections in children with fatal diarrheal diseases in Africa and Bangladesh.
Get PDFAchieving the Sustainable Development Goal of reducing child mortality to <25 deaths per 1000 live births by 2030 requires strategies to prevent diarrheal disease-related morbidity and mortality. Accurate etiological diagnosis is essential. This study used postmortem diagnostics to investigate the contribution of diarrhea to under-5 mortality and examine co-morbidities and co-infections in Africa and South Asia. Child Health and Mortality Prevention Surveillance (CHAMPS) generates data on child deaths through minimally invasive tissue sampling, clinical record review, and verbal autopsies. Multidisciplinary panels assign cause(s) of death using WHO International Classification of Diseases. This analysis included deaths among children aged 1-59 months enrolled from 18 December 2016-31 December 2023 across six African sites (Ethiopia, Mali, Kenya, Sierra Leone, Mozambique, South Africa) and Bangladesh. Of 1517 deaths assessed, diarrhea was in the causal pathway in 240 (15.8%). The proportion of diarrhea-related deaths was highest in Ethiopia (41.0%, 34/83), followed by Bangladesh, (30.0%, 3/10), Mozambique (21.7%, 56/258), Mali (17.5%, 18/103), Kenya (13.9%, 51/366), Sierra Leone (12.8%, 46/358), and South Africa (9.4%, 32/339). Diarrhea was underlying cause in 44.2% (106/240) of cases and immediate/antecedent cause in 58.3% (140/240), with some deaths involving multiple roles in the causal chain. When diarrhea was underlying cause, sepsis (33.0%) and lower respiratory infections (25.5%) were common downstream conditions; when an antecedent/immediate cause, leading underlying causes were malnutrition (64.3%) and HIV (13.6%). No pathogen was identified in 49.6% (119/240) of diarrhea-related deaths; among these, diarrhea was underlying cause in 42.9%. Among the 121 pathogen-attributed deaths, the most frequent were EAEC (34.7%), typical EPEC (15.7%), Shigella/EIEC (14.0%), ST-ETEC (12.4%), rotavirus (26.4%), and adenovirus (non-40/41: 19.0%; 40/41: 5.0%). These pathogens were frequently identified as co-infections. Diarrheal disease accounted for a substantial share of child deaths across CHAMPS sites. Reducing mortality will require preventing diarrhea and addressing key contributors such as malnutrition and HIV
Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics.
Get PDFBACKGROUND: Plasmodium vivax forms dormant liver stages (hypnozoites) that can reactivate weeks to months after primary infection. Radical cure requires a combination of antimalarial drugs to kill both the blood-stage and liver-stage parasites. Hypnozoiticidal efficacy of the liver-stage drugs primaquine and tafenoquine cannot be estimated directly because hypnozoites are undetectable. We aimed to estimate hypnozoiticidal efficacy from clinical trial data, and quantify the community-level impact of implementing case management with radical cure. METHODS: We calibrated a novel P vivax Recurrence Model to publicly available data from prospective clinical trials to estimate the hypnozoiticidal efficacy of different supervised primaquine (3·5 mg/kg or 7 mg/kg over 7 or 14 days) and tafenoquine (5 mg/kg or 7·5 mg/kg single dose) regimens in patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity. We used an existing P vivax Individual-Based Model to quantify the 5-year impact of case management with unsupervised primaquine or tafenoquine regimens across various transmission settings. FINDINGS: We estimated median hypnozoiticidal efficacies of 99·1% (95% credible interval 96·0-100) for primaquine 7 mg/kg over 14 days; 96·3% (90·8-99·7) for primaquine 7 mg/kg over 7 days; 72·3% (68·1-76·3) for primaquine 3·5 mg/kg over 7 or 14 days; 62·4% (49·1-76·3) for tafenoquine 5 mg/kg single dose; and 87·5% (62·1-99·3) for tafenoquine 7·5 mg/kg single dose. 5 years of community-level tafenoquine case management was estimated to reduce P vivax transmission by 74-79% where pre-intervention prevalence as measured by PCR was low (<2%) and by 17-20% where prevalence as measured by PCR was high (around 35%). Similar 5-year reductions were estimated with primaquine case management only when adherence to the primaquine regimen was above 50%. INTERPRETATION: Substantial reductions in prevalence as measured by PCR were predicted with primaquine and tafenoquine regimens if these could be implemented with high coverage and adherence. The benefits of preventing P vivax relapses need to be balanced against the risks of inducing severe haemolysis in patients with G6PD deficiency. FUNDING: Bill & Melinda Gates Foundation and Horizon Europe
Universal health coverage for women of reproductive ages: a survey-based comprehensive assessment of service utilisation and health expenditure in Tanzania.
Get PDFINTRODUCTION: Universal health coverage (UHC) for women of reproductive ages is a critical component of country and global health strategies but most evidence in high-fertility settings is limited to maternity care. Our study aimed to comprehensively assess women's health service utilisation and expenditure, including an equity dimension.
METHODS: We conducted a household survey among 15-49 years as a nested study within the Magu health and demographic surveillance study, northwest Tanzania, during 2020-2021. Data were collected on self-reported health, fertility, utilisation of health services, health expenditure and health insurance. We analysed key indicators by household wealth quintiles, place of residence and health insurance, using logistic regression models controlling for age and other confounders.
RESULTS: Among 8665 women aged 15-49 years (response rate 81%), 3.0% reported poor or very poor health, 13% gave birth in the preceding year, and health insurance coverage was 5.1%. Coverage of antenatal (99.5%) and institutional delivery care (88%) were high; 7.3% of women reported at least one outpatient visit in the last 4 weeks, of which 81% were for their own non-maternal healthcare; 9.3% had been admitted to a hospital during the last year, and 74% of these admissions were for deliveries. The total average annual health expenditure per woman was about TZS 16 860 (US10.00) per year on self-treatment. The poorest women had poorer self-reported health, lower coverage of maternity care, lower utilisation of services for their own healthcare and lower health insurance coverage, and limited their expenditure by making greater use of nearby public services than richer women.
CONCLUSION: Women spent more financial resources on their own non-maternal healthcare than maternity care with poorer women still facing disadvantages for their own healthcare. Health insurance programmes were hardly but were associated with an increase in service use. Comprehensive assessments of women's health needs, service use and expenditures with an equity focus are crucial for shaping UHC strategies tailored to women of reproductive ages
Agreement between parent reported and clinical coding of asthma, eczema and allergic rhinitis: The multi-ethnic Born in Bradford cohort.
Get PDFBACKGROUND: Discrepancies between parent reports and electronic health records (EHRs) challenge the accurate estimation of childhood allergic disease prevalence. This study aimed to: (1) compare parent reports of asthma, eczema, and allergic rhinitis with GP-recorded diagnoses; (2) identify factors associated with reporting differences; and (3) assess the predictive validity of parent reports for future diagnoses. METHODS: Data were analyzed from 2594 children (aged 4-5 years) in the UK Born in Bradford (BiB) cohort. Parent-reported symptoms and diagnoses from questionnaires were compared against diagnoses in primary care EHRs. Agreement was assessed using prevalence estimates and agreement metrics. Logistic and Poisson regression models were used to identify factors influencing reporting and to evaluate predictive validity. RESULTS: Agreement varied by condition. For parent-reported "ever-diagnosed" asthma, agreement with GP records was good (Kappa = 0.68), while for recent eczema symptoms, it was poor (Kappa = 0.07), though this improved after adjusting for prevalence (PABAK = 0.66). Parent reports were highly reliable for ruling out diagnoses. Factors including ethnicity and GP visit frequency were associated with reporting discrepancies. Parent reports at age 4-5 strongly predicted a future GP diagnosis, increasing the risk fivefold for asthma and threefold for allergic rhinitis. CONCLUSION: Neither parent reports nor EHRs alone capture the full picture of childhood allergic disease. Parent reports offer crucial insights into symptom burden and future risk, while EHRs provide objective diagnostic data. An integrating approach, combining both sources, is essential for comprehensive epidemiological research and a more complete understanding of disease burden
Prevalence and factors associated with mental health challenges among adolescents with HIV and viral non-suppression in rural northern Uganda.
Get PDFINTRODUCTION: Adolescents living with HIV (ALWH) face significant mental health challenges, such as depression and anxiety, which negatively impact their HIV treatment outcomes. This study investigated the prevalence and factors associated with mental health challenges among adolescents with unsuppressed viral loads in Northern Uganda. METHODS: In 2021, 121 dyads of caregivers and ALWH (10 to 18 years) with unsuppressed viral loads were recruited from five community-based HIV clinics in Kitgum district. They were assessed for mental health challenges using the Revised Child Anxiety and Depression Scale (RCADS-25), the Patterson Suicide Risk Assessment Tool and the Clinician-administered Post-traumatic Stress Disorder Scale for Children and Adolescents (CAPS-CA). Bivariate and multivariate analysis of the data was carried out using STATA version 18. RESULTS: Emotional problems were observed in 61.97% of participants. Among these, depression was present in 45.45% of individuals, and all participants diagnosed with depression also exhibited significant comorbid anxiety symptoms. Notably, 16.52% of participants experienced anxiety without comorbid depression. Having food security (OR = 0.03; p = 0.003), and the absence of recurrent infections (OR = 0.47; p = 0.023) were protective against mental health challenges. However, significant post-traumatic stress symptoms were independently associated with mental health challenges (OR = 1.33; p < 0.0001). No significant association was observed between emotional problems and gender (χ2 = 0.009; p = 0.94). CONCLUSION: These results emphasize the importance of addressing underlying socio-economic and psychological factors to improve mental health well-being. Targeted interventions focused on reducing barriers to resources and providing mental health support are essential for fostering equitable mental health outcomes
Molecular docking and molecular dynamics simulation studies of inhibitor candidates against Anopheles gambiae 3-hydroxykynurenine transaminase and implications on vector control.
Get PDFIsoxazole and oxadiazole derivatives inhibiting 3-hydroxykynurenine transaminase (3HKT) are potential larvicidal candidates. This study aims to identify more suited potential inhibitors of Anopheles gambiae 3HKT (Ag3HKT) through molecular docking and molecular dynamics simulation. A total of 958 compounds were docked against Anopheles gambiae 3HKT (PDB ID: 2CH2) using Autodock vina and Autodock4. The top three identified hits were subjected to 300 ns molecular dynamics simulation using AMBER 18 and ADMET analysis using SWISSADME predictor and ADMETSAR. Replacement of alkyl attachment on C5 of isoxazole or oxadiazole derivative with a cycloalkyl group yielded compounds with lower binding energy than their straight chain counterparts. The top three compounds were brominated compounds, 2-[3-(4-bromophenyl)-1,2-oxazol-5-yl]cyclopentane-1-carboxylic acid, 2-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]cyclopentane-1-carboxylic acid, 3-[3-(4-bromo-2-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopentane-1-carboxylic acid, and they had binding energies of -8.58, -8.25, and -8.18 kcal/mol in virtual screening against 2CH2 protein target, respectively. These compounds were predicted to be less toxic than temephos, a standard larvicide and more biodegradable than previously reported inhibitors. The three compounds exhibited a greater stabilizing effect on 2CH2 protein target than 4-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid, a previously reported inhibitor candidate with good larvicidal activity on Aedes aegypti. Further thermodynamic calculations revealed that the top three compounds possessed total binding energies (ΔGbind) of -26.64 kcal/mol, -24.26 kcal/mol and -14.11 kcal/mol, respectively, as compared to -12.02 kcal/mol for 4-[3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid. These compounds could be better larvicides than previously reported isoxazole or oxadiazole derivatives and safer than temephos
Memory B cell proliferation drives differences in neutralising responses between ChAdOx1 and BNT162b2 SARS-CoV-2 vaccines.
Get PDFINTRODUCTION: Vaccination against COVID-19 has been pivotal in reducing the global burden of the disease. However, Phase III trial results and observational studies underscore differences in efficacy across vaccine technologies and dosing regimens. Notably, mRNA vaccines have exhibited superior effectiveness compared to Adenovirus (AdV) vaccines, especially with extended dosing intervals. METHODS: Using in-host mechanistic modelling, this study elucidates these variations and unravels the biological mechanisms shaping the immune responses at the cellular level. We used data on the change in memory B cells, plasmablasts, and antibody titres after the second dose of a COVID-19 vaccine for Australian healthcare workers. Alongside this dataset, we constructed a kinetic model of humoral immunity which jointly captured the dynamics of multiple immune markers, and integrated hierarchical effects into this kinetics model, including age, dosing schedule, and vaccine type. RESULTS: Our analysis estimated that mRNA vaccines induced 2.1 times higher memory B cell proliferation than AdV vaccines after adjusting for age, interval between doses and priming dose. Additionally, extending the duration between the second vaccine dose and priming dose beyond 28 days boosted neutralising antibody production per plasmablast concentration by 30%. We also found that antibody responses after the second dose were more persistent when mRNA vaccines were used over AdV vaccines and for longer dosing regimens. DISCUSSION: Reconstructing in-host kinetics in response to vaccination could help optimise vaccine dosing regimens, improve vaccine efficacy in different population groups, and inform the design of future vaccines for enhanced protection against emerging pathogens