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Genetically proxied inhibition of kidney function pathways and increased risk of type 2 diabetes in Africans: A Mendelian randomization study.
Get PDFObjectiveTo investigate the causal relationship between genetically predicted inhibition of specific kidney function drug targets and the risk of type 2 diabetes (T2D) in African populations using Mendelian randomization (MR).MethodsWe used MR, a genetic proxy approach, and utilized genome-wide association study data from African participants. This assessed the causal relationship between genetically predicted inhibition of specific pathways and T2D risk. The analysis was conducted using TwoSampleMR package implemented in R.ResultsWe found that inhibiting the vascular endothelial growth factor A (VEGFA) and Ras homolog enriched in brain (RHEB) was significantly linked to T2D risk in Africans (OR 2.66, 95% CI 1.34-3.78, p = 0.0017 and OR 2.25, 95% CI 1.34-3.28, p = 0.0010, respectively). Conversely, there was no evidence that solute-like carrier family 22 member A2 or claudin-14 were associated with an increased risk of T2D (OR = 0.95, 95% CI 0.61-1.48; OR = 1.56, 95% CI 0.71-2.20, respectively).ConclusionsInsight from this study could potentially mean that some of the drugs that are used for treatment of kidney diseases involving VEGFA and RHEB may potentially increase the risk of developing T2D among Africans. This highlights how it is critical to consider drug-drug interaction in kidney diseases in Africa
Effective coverage for maternal health: operationalising effective coverage cascades for antenatal care and nutrition interventions for pregnant women in seven low- and middle-income countries.
Get PDFBACKGROUND: Efforts to improve maternal health have focused on measuring health and nutrition service coverage. Despite improvements in service coverage, maternal mortality rates remain high. This suggests that coverage indicators alone do not fully capture the quality of care and may overestimate the health benefits of a service. Effective coverage (EC) cascades have been proposed as an approach to capture service quality within population-based coverage measures, but the proposed maternal health EC cascades have not been operationalised. This study aims to operationalise the effective coverage cascades for antenatal care (ANC) and maternal nutrition services using existing data from low- and middle-income countries (LMICs). METHODS: We used household surveys and health facility assessments from seven LMICs to estimate EC cascades for ANC and maternal nutrition services provided during ANC visits. We developed theoretical coverage cascades, defined health facility readiness and provision/experience of care scores and linked the facility-based scores to household survey data based on geographic domain and facility type. We then estimated the coverage cascade steps for each service by country. RESULTS: Service contact coverage for at least one ANC visit (ANC1) was high, ranging from 80% in Bangladesh to 99% in Sierra Leone. However, there was a substantial drop in coverage from service contact to readiness-adjusted coverage, and a further drop to quality-adjusted coverage for all countries. For ANC1, from service contact to quality-adjusted coverage, there was an average net decline of 52 percentage points. For ANC1 maternal nutrition services, there was an average net decline of 48 percentage points from service contact to quality-adjusted coverage. This pattern persisted across cascades. Further exploration revealed that gaps in service readiness including lack of provider training, and gaps in provision/experience of care such as limited nutrition counselling were core contributors to the drops in coverage observed. CONCLUSIONS: The cascade approach provided useful summary measures that identified major barriers to EC. However, detailed measures underlying the steps of the cascade are likely needed to support evidence-based decision-making with more actionable information. This analysis highlights the importance of understanding bottlenecks in achieving health outcomes and the inter-connectedness of service access and service quality to improve health in LMICs
High-dose vitamin D3 to improve outcomes in the convalescent phase of complicated severe acute malnutrition in Pakistan: a double-blind randomised controlled trial (ViDiSAM).
Get PDFWe have previously shown that high-dose vitamin D3 improved weight gain and neurodevelopmental indices in children receiving standard therapy for uncomplicated severe acute malnutrition (SAM). Here we present results of a randomised placebo-controlled trial in Lahore, Pakistan, to determine whether two oral doses of 200,000 international units (IU) vitamin D3 (the first administered on or before the day of hospital discharge and the second administered 14 days later) would benefit children aged 6-59 months during the convalescent phase of complicated SAM. Eligible participants were individually randomised to intervention vs. control arms with a one-to-one allocation ratio and stratification by hospital of recruitment using computer-generated random sequences. Double-blinding to treatment allocation was maintained by concealing allocation from participants' parents or guardians, their medical care providers, and all trial staff. The primary outcome was mean weight-for-height or -length z-score (WHZ) at 2-month follow-up. Secondary efficacy outcomes included mean WHZ at 6-month follow-up and mean lean mass index, Malawi Development Assessment Tool (MDAT) scores and serum 25-hydroxyvitamin D (25[OH]D) concentrations at 2- and 6-month follow-up. The trial has now completed. 259 children were randomised (128 to vitamin D, 131 to placebo), of whom 251 (96.9%) contributed data to analysis of the primary outcome (123 allocated to vitamin D, 128 to placebo). At 2-month follow-up, participants allocated to vitamin D had significantly higher mean serum 25(OH)D concentrations than those allocated to placebo (adjusted mean difference [aMD] 100.0 nmol/L, 95% confidence interval [CI] 72.2-127.8 nmol/L). This was not associated with an inter-arm difference in mean WHZ at 2-month follow-up (aMD 0.02, 95% CI -0.20 to 0.23), or in any anthropometric or neurodevelopmental secondary outcome assessed at 2- or 6-month follow-up. The intervention was safe. In conclusion, high-dose vitamin D3 elevated mean serum 25(OH)D concentrations in children receiving standard therapy for complicated SAM in Pakistan, but did not influence any anthropometric or neurodevelopmental outcome studied. The trial was registered at ClinicalTrials.gov with the identifier NCT04270643
Evaluation of health impacts of a disability-inclusive graduation programme among ultra-poor people with disabilities in Uganda: secondary analysis of a cluster randomized trial.
Get PDFBACKGROUND: People with disabilities experience significant health inequalities and barriers to healthcare access globally. While poverty alleviation interventions show promise for improving health outcomes, evidence specifically for people with disabilities remains limited. This study evaluated the effectiveness of a disability-inclusive graduation (DIG) programme on health outcomes among ultra-poor people with disabilities in Uganda. METHODS: We conducted a two-arm, parallel cluster-randomized controlled trial in four districts of Northern Uganda. Clusters were randomly assigned to either the DIG intervention (96 clusters) or control group (89 clusters). This analysis focused on households with people with disabilities, as identified by the Washington Group Short Set questions and verified by BRAC programme managers. Households in treatment clusters received up to 18 months DIG intervention between December 2020 and June 2022, combining asset transfers, cash support, skills training, financial inclusion activities, and disability-specific services including rehabilitation and assistive devices. The primary outcome was experience of illness/injury in the past 3 months, assessed at both first follow-up (immediately post-intervention) and second follow-up (about 16 months post-intervention), with secondary outcomes including unmet health needs, mental health status, unmet assistive product needs, and healthcare expenditure. Effects were estimated using linear mixed-effects regression or generalized estimating equations, reporting minimally-adjusted and fully-adjusted mean differences (FAMD) or odds ratios (FAOR) with 95% CIs. The trial was registered with RIDIE (RIDIE-STUDY-ID-626008898983a) and ISRCTN (ISRCTN-78592382). FINDINGS: At baseline, 691 participants (370 intervention, 321 control) were included. The DIG intervention did not significantly impact overall illness/injury prevalence at either first follow-up (41.18% vs 45.86%, FAOR 0.84, 95% CI 0.58-1.22) or second follow-up (55.65% vs 53.98%, FAOR 1.07, 95% CI 0.74-1.56). However, the intervention demonstrated a progressively strengthening effect on reducing unmet health needs, from marginal improvement immediately post-intervention (FAOR 0.56, 95% CI 0.31-1.02, p = 0.06) to significant reduction at 16 months post-intervention (FAOR 0.4, 95% CI 0.22-0.71, p = 0.002). Notably, the intervention produced temporal potential shifts in disease patterns, with malaria showing contrasting trends between follow-up periods. Sex-differentiated effects emerged by second follow-up, with females in the intervention group experiencing fewer injuries (FAOR for interaction 0.17, 95% CI 0.04-0.74, p = 0.02) but more pain-related conditions compared to males (FAOR for interaction 2.43, 95% CI 1.05-5.59, p = 0.04), though these subgroup findings require replication in future studies. No significant differences were observed in mental health outcomes or health expenditure. INTERPRETATION: This first randomized evaluation of a disability-inclusive graduation programme demonstrates that while economic empowerment alone may not reduce overall illness prevalence among people with disabilities, it can progressively improve healthcare access over time. The temporal evolution of effects and emerging sex-differentiated impacts highlight the need for sustained support and gender-sensitive approaches in future disability-inclusive poverty reduction programmes, with additional health-specific components to achieve broader improvements in health outcomes. FUNDING: PENDA, funded by the UK Foreign, Commonwealth and Development Office
Learning together for mental health: feasibility of measures to assess a whole-school mental health and wellbeing intervention in secondary schools.
Get PDFBACKGROUND: Population mental health in young people worsened during and since the COVID-19 pandemic. School environments can play a key role in improving young people's mental health. Learning Together for Mental Health is a whole-school intervention aiming to promote mental health and well-being among young people in secondary schools. Before progressing to a Phase III effectiveness evaluation of the intervention, it is critical to assess the feasibility of trial measures at baseline and follow-up. OBJECTIVE: To evaluate the feasibility of trial measures and procedures within a feasibility study of a whole-school intervention aiming to promote mental health and well-being among young people in secondary schools, including whether we met our progression criterion of survey response rates of 60% or more in two or more schools at baseline and follow-up. DESIGN AND METHODS: We conducted a feasibility study which included assessment of the indicative primary and secondary outcomes measures and procedures to be used in a future Phase III trial. SETTING AND PARTICIPANTS: Setting for our feasibility study included five state, mixed-sex secondary schools in southern England (one of which dropped out after baselines and one of which replaced this). We recruited year-7 students to participate in the baseline survey and year-10 students to participate in the follow-up survey at 12-month follow-up. Baseline and follow-up participants were different groups, as the focus was assessing feasibility of measures for the age groups that would be surveyed at baseline and follow-up in a Phase III randomised controlled trial. Our study was not powered or designed to estimate intervention effects. INTERVENTIONS: As part of our feasibility study, all schools received the Learning Together for Mental Health intervention for one academic school year. MAIN OUTCOME MEASURES: The indicative primary outcome measure trialled was the total difficulties score of the Strengths and Difficulties Questionnaire. Indicative secondary outcomes measures trialled were the: Warwick-Edinburgh Mental Well-being Scale; Short Moods and Feelings Questionnaire; Generalised Anxiety Disorder-7 scale; Eating Disorders Examination - Questionnaire Short, self-harm (single item from the Health Behaviour in School-aged Children study); bullying victimisation (Gatehouse Bullying Scale); cyberbullying (two items adapted from the Dose Adjustment for Normal Eating II questionnaire); substance use (National Health Service measure); and Beyond Blue School Climate Questionnaire. RESULTS: Trial measures and procedures were feasible to implement and were acceptable to year-7 and year-10 students, teachers and parents. At baseline, response rates ranged from 58% to 91% between schools. Only two students were opted out by parents, and no students opted out in advance. Students refusing consent on the day of survey was rare (7%). Twelve per cent of students were absent. The follow-up survey had an overall response rate of 66%, ranging from 44% to 91%. Only two students were opted out by parents, and three students opted out in advance. Overall, 12% opted out on the day. Twenty per cent of students were absent. Variation in response rate reflected specific problems at certain schools. Surveys took 40-45 minutes at baseline and 30 minutes at follow-up. The trial progression criterion concerning response rates was achieved, with three of four schools at baseline and two of four schools at follow-up having responses rates above 60%. LIMITATIONS: Our study involved a small, purposive sample of schools and students which are not representative of those in England. CONCLUSIONS: With some minor amendments, trial measures and procedures should be applied in a future Phase III effectiveness evaluation of the Learning Together for Mental Health intervention. FUTURE WORK: Survey response rates could be improved if baseline and follow-up surveys are not scheduled in the last weeks of term, on Fridays or near mock General Certificate of Secondary Education exams. Completion of some measures (such as Eating Disorders Examination - Questionnaire Short) among year-7 students may be improved if question wording is tailored to be age-appropriate. FUNDING: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR131594
Patient-reported harm from NHS treatment or care, or the lack of access to care: a cross-sectional survey of general population prevalence, impact and responses.
Get PDFOBJECTIVES: The aim of this article is to provide an estimate of the proportion of the general public reporting healthcare-related harm in Great Britain, its location, impact, responses post-harm and desired reactions from healthcare providers. DESIGN: We used a cross-sectional survey, using quota sampling. SETTING: This research was conducted in Great Britain. PARTICIPANTS: The survey had 10 064 participants (weighted analysis). RESULTS: In our survey 9.7% participants reported harm caused by the National Health Service (NHS) in the last 3 years through treatment or care (6.2%) or the lack of access to care (3.5%). The main location where the harm first occurred was hospitals. A total of 37.6% of participants reported a moderate impact and 44.8% a severe impact of harm. The most common response to harm was to share their experience with others (67.1%). Almost 60% sought professional advice and support, with 11.6% contacting the Patient Advice and Liaison Service (PALS). Only 17% submitted a formal complaint, and 2.1% made a claim for financial compensation. People wanted treatment or care to redress the harm (44.4%) and an explanation (34.8%). Two-thirds of those making a complaint felt it was not handled well and approximately half were satisfied with PALS. Experiences and responses differed according to sex and age (eg, women reported more harm). People with long-term illness or disability, those in lower social grades, and people in other disadvantaged groups reported higher rates and more severe impact of harm. CONCLUSIONS: We found that 9.7% of the British general population reported harm by the NHS, a higher rate than reported in two previous surveys. Our study used a broader and more inclusive definition of harm and was conducted during the COVID-19 pandemic, making comparison to previous surveys challenging. People responded to harm in different ways, such as sharing experiences with others and seeking professional advice and support. Mostly, people who were harmed wanted help to redress the harm or to gain access to the care needed. Low satisfaction with PALS and complaints services may reflect that these services do not always deliver the required support. There is a need to better understand the patient perspective following harm and for further consideration of what a person-centred approach to resolution and recovery might look like
GP remote consultations with marginalised patients and the importance of place during care: a qualitative study of the role of place in GP consultations.
Get PDFBACKGROUND: Since the COVID-19 pandemic, there has been an increase in the use of remote consultations in general practice in the UK. This leads to the displacement of the consultation outside of the physical general practice, and its 'emplacement' elsewhere, with underexplored consequences for inequities of health care in marginalised groups. AIM: To examine the place-making demands that remote consultations make on patients, and the ways that these affect their experiences of care, with a focus on the impact on patients from marginalised groups. DESIGN & SETTING: Ethnography and interview study (n = 15) undertaken at three fieldwork sites in London: a foodbank, a community development organisation, and a drop-in advice centre for migrants. Additionally, GPs (n = 5) working at practices in deprived areas of London, Digital Health Hub staff (n = 4), and staff at fieldwork sites (n = 3) were interviewed. METHOD: Ethnographic observation was undertaken for 84 hours at the fieldwork site services, and semi-structured interviews (n = 27) took place with service users and service providers. Interviews were conducted in-person and over the phone, and data were analysed through reflexive thematic analysis. RESULTS: The core themes emerging from the data included challenges securing privacy during remote consultations and the loss of formal healthcare spaces as important places of care. These findings were closely tied to resource access, leading to inequities in experiences of care. CONCLUSION: Remote GP consultations are not 'place-less' encounters, and inequities in access to suitable spaces may lead to inequities in experiences of care. Attention should be given to ensuring that patients without appropriate spaces for remote consultations are offered in-person care, or consultation times made more specific to allow for organisation of private space
Innate biosignature of treatment failure in human cutaneous leishmaniasis.
Get PDFThe quality and magnitude of the immune and inflammatory responses determine the clinical outcome of Leishmania infection, and contribute to the efficacy of antileishmanial treatments. However, the precise immune mechanisms involved in healing or in the chronic immunopathology of human cutaneous leishmaniasis (CL) are not well understood. Through sequential transcriptomic profiling of blood monocytes, neutrophils, and eosinophils over the course of systemic treatment with meglumine antimoniate, we revealed that a heightened and sustained Type-I interferon response signature is a hallmark of treatment failure (TF) in CL patients infected with Leishmania (Viannia) panamensis and L.V. braziliensis. The transcriptomes of pre-treatment, mid-treatment and end-of-treatment samples were interrogated to identify predictive and prognostic biomarkers of TF. A composite score derived from the expression of 11 differentially expressed genes (common between monocytes, neutrophils and eosinophils) is predictive of TF. Similarly, machine learning models constructed using data from pre-treatment as well as post-treatment samples, accurately classify treatment outcome into cure and TF. Results from this study instigate the evaluation of Type-I interferon responses as immunological targets for host-directed therapies for the treatment of CL, and highlight the feasibility of using transcriptional signatures as predictive biomarkers of outcome for therapeutic decision making
Socio-economic inequalities in all-cause mortality during the COVID-19 period in north-western Tanzania, 2018-2021.
Get PDFBACKGROUND: Evidence suggests that the COVID-19 pandemic has exacerbated social and demographic inequalities in the communities through pathways of unequal exposure, vulnerability, and susceptibility. In Tanzania, evidence on COVID-19-related mortality is limited to health facility data, with little to no information on the mortality patterns in the general population. This study assessed sociodemographic inequalities in all-cause mortality during the COVID-19 period in north-western Tanzania. METHODS: We utilized available longitudinal data from the Magu Health and Demographic Surveillance System (HDSS) from January 2018 to December 2021. We compared the crude death rates between subgroups of age, sex, area of residence, and wealth index for a period before (2018/2019) and during (2020/2021) the COVID-19 pandemic. To quantify how mortality risk varies across the subgroups we fitted a Cox proportional hazard model with an interaction of the COVID-19 period. RESULTS: Overall mortality declined from 5.9 in 2018/2019 to 5.4 and 5.5 deaths per 1000 person-years in 2020 and 2021, respectively. We observed an increase in differences in crude death rates by age groups, area of residence, and wealth quintiles during the COVID-19 period. In the Cox proportional hazards model, compared to adults aged 15-49, we observed greater mortality risk in children under five (AHR:2.9; 95%CI: 2.2-3.9), older individuals aged 50-64 years (AHR:3.02; 95%CI:2.11-4.33) and 65 + (AHR:18.65; 95%CI:14.28-24.35) during COVID-19 period. Males were also at greater risk of death compared to females (AHR:1.30; 95%CI:1.06-1.59). CONCLUSION: Despite the overall mortality decline during the pandemic, we observed an increased risk of mortality among vulnerable subgroups (aged 60 years) in the population. This highlights the need to take into account vulnerable subpopulations when addressing major public health issues in communities
Association of health knowledge with adoption of heart healthy behaviours: a cross-cohort analysis using data from the PURE Study.
Get PDFAIMS: This study aims to assess aspects of health knowledge: i) awareness of health effect of tobacco smoking and ii) awareness of preventive actions for heart disease and stroke, and their relationships with adoption of heart healthy behaviours (smoking cessation and utilisation of antihypertensive treatment). METHODS: In this multi-cohort study, we recruited adults aged 35 to 70 years from 21 countries. Data on health effects of tobacco smoking (10 questions) and health actions to prevent heart disease or stroke (11 questions) were collected at baseline. Logistic regression analyses were used to examine the relationship with the outcomes of smoking cessation and use of antihypertensive treatment adjusting for adjusting for possible confounders. RESULTS: Of the 12,962 included in the descriptive analysis, 50.0% were female, 42.9% had no or primary education, and 53.3 % were residing in low or lower middle-income country. Among current and former smokers, having knowledge of health effect of tobacco smoking on heart disease [Adjusted Odds Ratio (aOR): 1.70, 95% CI: 1.19, 2.43)], stroke (1.41, 1.08,1.86), and on heart disease in non-smokers exposed to others smoking (1.40, 1.06,1.86) were significantly and positively associated with smoking cessation compared to those who were not aware of health effects. Knowledge of the importance of reducing dietary salt aOR 1.62 (1.23,2.13), dietary fat aOR 1.56 (1.17,2.08) and exercising more aOR 1.48 (1.22,1.80) to prevent heart disease or stroke were positively associated with taking anti-hypertensive medication compared to those who were not aware of preventative actions. CONCLUSION: This study reinforces that better health knowledge shapes adoption of heart healthy behaviours such as smoking cessation and taking anti-hypertensive treatment even after accounting for baseline education and wealth