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gen_477397e7c8c420cc5e7032dc13932cb8 | Examining the level and variation in the efficiency of county health systems in Kenya, and how it can be improved | Medical Research Council | KEMRI Wellcome Trust Research Programme | HRCS22_01633 | This research aims to measure the level of efficiency of the 47 county health systems in Kenya, and to examine its determinants. It also aims to examine the potential for efficiency gains and how this can in turn result in increased fiscal space for the Kenyan health sector. Further, the research aims to test the application, and explore methodological refinements of current efficiency measurement methods to LMIC settings, and at sub-national levels of the system (such as counties/districts) rather than health facility level (such as hospitals). We will use two frontier methods to measure the technical efficiency (and its determinants) of county health systems. First, we will use the double bootstrap Data Envelopment Analysis technique. Data envelopment analysis (DEA) is a non-parametric mathematical linear programming technique that has been widely used in low and middle income countries (LMICs) due to its flexible nature. Stochastic frontier analysis (SFA) is a parametric econometric approach that uses regression analysis to estimate a production or cost function, that accounts for error, but can be computationally complex. Bootstrap DEA will generate bias corrected efficiency scores, which will then be subjected to truncated regression analysis to examine the determinants of efficiency. To further explore the determinants of efficiency, we will select 2 counties that are found to be efficient and 2 inefficient counties that are lower than the 75th percentile in efficiency rank, and carry out in-depth qualitative inquiry through in-depth interviews and document reviews. This component of the study answer questions about how identified factors interact with and influence health system efficiency, and how these might be leveraged on to improve health system efficiency. Lastly, we will examine the potential for efficiency gains using DEA, and excel based models | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_d6012a09ab0cfb33779eeb031a1e7faf | Infection, inflammation and hepcidin-mediated iron deficiency anaemia in African children | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_01722 | The 2016 Global Burden of Disease analysis estimates that 1.225 billion people suffer from iron deficiency anaemia (IDA) and it is the fourth largest contributor to years lived with disability (YLD) globally. The burden is concentrated in sub-Saharan Africa and South Asia. Iron is crucial for neural development and early deficiencies during fetal and infant growth cause irreparable damage to brain development. Until now IDA has been largely attributed to diets low in iron and to infections such as malaria and intestinal helminths. However carefully controlled trials of iron supplements (often with deworming and malaria control) have very poor efficacy in Africa. The discovery of hepcidin - the master regulator of iron - throws a new light on the causes of IDA and may guide future therapeutic pathways. We have recently shown that even low-grade inflammation is a major contributor to ID in rural African children due to hepcidin/ferroportin-mediated blockade of intestinal absorption of iron. IDA is likely further exacerbated by EPO resistance. This project seeks to identify the sources of persistent low-grade inflammation in well and sick Gambian children. It will additionally try to understand the complex interacting mechanisms linking iron absorption, distribution and erythropoiesis to the effects of inflammation mediated through hepcidin, erythropoietin (EPO) and the newly discovered hormone erythroferrone (ERFE) which signals to the liver that the bone marrow requires iron. Finally we will conduct a randomised controlled trial to test whether it is possible to circumvent the hepcidin-induced blockade of iron absorption by administering iron in the form of haem. Another arm of this trial will be a proof-of-principle trial to assess the impact of reducing inflammation by co-administering azithromycin and galacto-oligosaccharides with iron. These studies, if successful, would suggest the need for a radical revision of current policies to combat IDA | 2.1 Biological and endogenous factors / Research Grant | 6project_grants_public
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gen_67a03f2d3ada67b73f7de4f7d46706a0 | Phase III, Multicentre, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy of Probiotic Supplementation for Prevention of Neona | Medical Research Council | Indian Council for Medical Res (ICMR) | HRCS22_01846 | Neonatal infections (pneumonia, septicaemia, meningitis) are responsible for more than a quarter of the 1 million neonatal deaths every year in India(1). Low Birth Weight (LBW) is a very important indirect cause of death in neonates, accounting for 40% to 80% of neonatal deaths (2-3). Management of neonatal sepsis with antibiotics faces the problem of drug resistance and immune-modulation/immune-potentiating with the use of probiotics may prove to be an option. Available evidence suggests a beneficial effect of probiotics treatment on reducing the incidence and all -cause mortality due to NEC (4-5.). In our pilot study supplementation with probiotics VSL#3 in LBW infants was associated with a non-significant overall 21% reduction in the risk of suspected sepsis (PSBI). In the post-hoc analyses using physician's diagnosis of sepsis as the outcome measure, there was a 33% overall reduction in risk of sepsis. However, in the un-prespecified sub-group of infants weighing 1.5-1.99 kg, there was a 100% reduction, with no cases observed in the group receiving probiotic supplementation (6). Following on from the evidence on VLBW and premature infants and based on the positive results of the above mentioned pilot study, we propose to test the hypothesis, with sufficient power and a precise definition of the outcome measure to conclusively evaluate the role of probiotics among LBW infants in a multicentre double blind placebo controlled trial. | 3.3 Nutrition and chemoprevention / Research Grant | 6project_grants_public
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gen_7a537b0ab3b7752ee4525651213e3ff3 | High Dose Oral Rifampicin to Improve Survival from Adult TB Meningitis - (HARVEST) Trial | Medical Research Council | Infectious Diseases Institute (IDI) | HRCS22_01848 | Tuberculous meningitis, the most severe form of TB, results in death or neurological disability in >50% of those affected, and mortality is 2-3 fold greater in HIV-infected patients. Rifampicin, a primary TB medication, only achieves in cerebrospinal fluid (CSF) 10-20% of the levels observed in blood. We propose a phase III randomized, double-blind placebo-controlled clinical trial evaluating whether ~3.5x higher oral dose rifampicin has a 6-month survival benefit as the primary endpoint, additionally pharmacokinetic measurements and safety are included as important secondary endpoints. This trial builds up a series of phase II trials conducted in Indonesia by our team members which demonstrated that higher rifampicin IV doses were associated with lower mortality. In follow up oral rifampicin phase II trials, based on pharmacokinetic analyses, the optimal oral dose is estimated to be approximately 35 mg/kg/day. In the prior phase II trials as well as in pulmonary TB trials, there were not excess adverse events observed with higher dose rifampicin therapy at doses of 35 mg/kg/day. To simplify future implementation, we will use a single (flat) increase in rifampicin for all participants of 900mg in Indonesia and 1200mg in Uganda/South Africa, corresponding a total rifampicin dose of approx. 35mg/kg, during the first 8 weeks of treatment. This can easily be added to fixed dose combination therapy provided by most national TB programs. | 6.1 Pharmaceuticals / Research Grant | 6project_grants_public
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gen_38515e5f983819c08693833c505a0c33 | Integrating Refugees into National Health Systems: Enhancing Equity and Strengthening Sustainable Health Services for All. | Medical Research Council | American University of Beirut | HRCS22_01945 | This study will employ a comparative case study approach focusing on three countries currently hosting large numbers of refugees: Lebanon (1.1m), Jordan (655,624), and Uganda (940,800). We plan to focus on Syrian refugees in Lebanon and Jordan, and South Sudanese refugees in Uganda. Our research will seek to: (i) understand the perceptions and experiences of stakeholders (international, regional, and national) as well as host populations and refugee populations towards refugees' integration into national health systems including how these stakeholders understand the meaning of integration and how desirable various actors believe it to be (ii) identify the factors that have shaped the adoption and implementation of policies supporting the integration of refugees into national health systems in these three countries (iii) assess how the pattern and extent of refugee integration has affected health services received by both refugee and host populations and (iv) assess financial flows and the financial sustainability of services. We will then convene national, regional and international policy and decision-makers to reflect upon the findings from these analyses, and identify their implications for future policy and practice. Within each of the three country cases, we will employ a mixed-method, qualitative and quantitative, approach that will be tailored to match local circumstances. We plan to identify timelines for the development of refugee policies (generally and in regard to access to national health services) and will conduct a policy analysis to understand how policies and practices evolved and why. We will then use existing datasets and primary data collection within district level cases, to explore how different aspects of refugee integration into national health systems over time has affected availability, access to health services, quality of health care, and felt experiences of seeking care, as well as financial sustainability. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_231b7e92191f4ab00b09286a127ea22f | Adolescents' Resilience and Treatment nEeds for Mental health in Indian Slums (ARTEMIS) | Medical Research Council | The George Inst for Global Health India | HRCS22_02027 | The proposed trial will be a hybrid effectiveness-implementation cluster randomised trial with wards/blocks (only urban slums will be included) being the unit of allocation. The trial will implement a mobile-technology enabled mental health services delivery model for adolescents living in slums in two Indian cities - New Delhi and Hyderabad. Duration of the trial will be for 36 months. It will train primary healthcare workers and doctors to screen, diagnose, and manage adolescents suffering from depression and increased suicide risk, and also inquire and manage those identified at high risk of intimate partner violence leading to stress/depression. Besides task sharing, the complex intervention will also include an anti-stigma campaign. We hypothesise that: (1) a community-based anti-stigma campaign will lead to significant improvements in community's behaviours toward adolescents with mental disorders; (2) a mobile device-based decision support system for primary health care staff will significantly lower depression and suicide risk in adolescents. Forty wards (only slums will be included) will be randomized to intervention or control group and we aim to recruit 2560 adolescents into the study, in total. Standardized tools will be used to screen for depression and suicide risk and management will be done using evidence-based WHO guidelines. The primary outcomes will be assessed at the end of 12 months of intervention. Process evaluation will be done throughout the intervention, but the detailed evaluation will follow the intervention. Economic evaluation will use statistical modelling to ascertain cost-effectiveness. If successful, the trial could be scaled up across other areas of India or even other low and middle income countries with the help of the government and other key stakeholders. | 6.6 Psychological and behavioural / Research Grant | 6project_grants_public
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gen_5b435c65b1c8580ae6b51a0e381e3cf8 | Crowdsourcing with adolescents in Senegal to address social norms limiting their access to sexual and reproductive health services | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02034 | The overall aim of this research project is to co-develop an intervention with adolescents aged 15 to 19 in order to address the social norms that limit their access to available sexual and reproductive health (SRH) services. The proposed research will take place in two regions of Senegal, one peri-urban area in Dakar region and one rural area in Kedougou region (South West Senegal). These regions are experiencing rapid population increases due to urbanisation and a thriving gold mining sector, respectively. In parallel with urbanisation and migration, there is likely to be an increase in sex work and other high-risk sexual behaviours. With SRH needs of adolescents already underserved, the health systems and health authorities of the two regions will need to plan an increase of service delivery and uptake to meet increased demand. In this project we will use qualitative formative research and crowdsourcing, an innovative approach to intervention co-development. Specifically, we will examine sexual and reproductive health policies and programmes available to adolescents living in the two regions. We will conduct focus group discussions and semi-structured interviews with adolescents and SRH service providers to explore the norms underlying barriers to service use. We will collect stories of service use and through a panel of adolescents from each region will select the most important three barriers to access. We will then launch an open call for one-month to crowdsource ideas on interventions to address the selected social norms. Adolescents will be able to submit an intervention idea to one or all of the key barriers. The winners of this call, selected in collaboration with an established steering committee, will be supported in further developing an intervention to increase uptake of sexual and reproductive health services. The steering committee will rank the final interventions, with a winning entry selected based on established criteria | 3.1 Primary prevention interventions to modify behaviours or promote well-being / Research Grant | 6project_grants_public
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gen_d7e769cf811f27ab80003e2763b868a1 | Project HASHTAG: Health Action in Schools for a Thriving Adolescent Generation | Medical Research Council | Stellenbosch University | HRCS22_02037 | Background. Adolescents suffer a high burden of disease, mostly injuries and mental disorders. Universal school interventions offer opportunities to address early symptoms and risk factors. We conducted a systematic review and meta-analysis of such interventions, finding that most are 'single-issue' interventions from high-income countries, focused on substances or violence. Aim. Project HASHTAG aims to address the evidence gap by developing and adapting a multicomponent gender-sensitive intervention in low- and middle-income countries targeting negative health outcomes by promoting positive mental health; preventing common mental disorders; and preventing risk behaviours in young at-risk adolescents. Methods. Project HASHTAG will comprise two strategies: 1) a school assessment, planning and action process, Thriving Environment in Schools (TES), to improve school climate; and 2) a group psychosocial intervention, Thrive Together (TT), to equip adolescents 11-12 years old with skills identified as effective components in reducing negative health outcomes. The study will be conducted in 2 low-resource settings in South Africa and Nepal. The development phase aims to co-produce a TES outline and TT draft, together with adolescents, parents, teachers, and other stakeholders in 2 schools per country. This will be achieved through focus groups, interviews and observations, to inform the work of an intervention development group. The aim of the feasibility phase is to assess the feasibility and acceptability of the TT and TES strategies, outcome measures, and intervention processes. To achieve this, we will implement and evaluate both strategies in 4 schools per country, using baseline and follow-up quantitative assessments to measure mental health and risk behaviour outcomes. Qualitative interviews and observations will be conducted to assess acceptability, feasibility, fidelity and barriers to the programme. Process data will be collected to assess feasibility. | 3.1 Primary prevention interventions to modify behaviours or promote well-being / Research Grant | 6project_grants_public
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gen_10a932e9e6a618e716ff107d92257b7f | Prevention of Addiction and Mental Ill Health in Adolescents in Georgia (PAMAd) | Medical Research Council | Curatio International Foundation | HRCS22_02050 | The study will first inform how the PAMAd service (package of interventions) is designed in collaboration with potential service beneficiaries (CA and their family members), service providers, main stakeholders and policy makers at national level and also generate evidence on effectiveness of CA targeted service (clinical effectiveness and unit costs of PAMAd service). Proposed research project will use pre and post-test design without control groups (Shadish WR, et al.2002) with nested process evaluation. A controlled design will not be feasible because the research is being undertaken within a developing EC supported service with well-estabished plans and a strict timeline. This offers an unique opportunity for implementation research in a real-world setting that will be an integral part of the PAMAd piloting/development work. This will allow exploration of how the interventions are developed and conducted, mechanisms through which the interventions produce change, and what contextual factors may act as barriers or facilitators to PAMAd implementation. This will be mixed methods research. Quantitative interviews with structured questionnaires will be used to determine socio-demographic status, living conditions, measure outcomes to determine effectiveness of the service and to collect cost data on service. Qualitative data (from in-depth interviews and focus group discussions) will be used to obtain depth of understanding and more comprehensively address the research questions. Data will also be collected on utilization of mental and physical health services, and social services; financial, economic and other barriers to care for common mental health and drug related problems, drug related risks awareness and risk behaviors. Qualitative data from service users and providers, different stakeholders will capture all factors important for duplication of the service in different areas and make it clear for decision makers how feasible its introduction will be. | 3.1 Primary prevention interventions to modify behaviours or promote well-being / Research Grant | 6project_grants_public
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gen_302b609aa9fa8f72caa8fd286ec6784b | A Novel High Intensity Short Interval Dance Intervention for Non Communicable Disease(NCD) Prevention in Asian Indian Adolescent Girls-THANDAV | Medical Research Council | Madras Diabetes Research Foundation | HRCS22_02201 | The proposal aims to study the effect of the THANDAV intervention on physical activity, fitness levels,body weight and fat % in Asian Indian adolescent girls using digital technology. High intensity interval training (HIIT) is a form of cardiovascular exercise plan alternating short periods of intense aerobic exercise with less intense recovery periods. Effective HIIT regimens can range anywhere from 4 to 20 minutes. Research has shown that HIIT regimens produced significant reductions in whole body fat mass, weight and improvement in cardiovascular fitness in both adults and adolescents. Various socio- cultural (such as not being allowed out late in the evenings) and environmental factors (such as lack of availability of safe places to exercise) prevent Asian Indian adolescent girls from exercising. Moreover, the term exercise has a 'male connotation' in India and exercising outdoors can lead to cultural 'inappropriateness'. However, dance is a culturally acceptable form of exercise, especially for girls. It is actively encouraged in the adolescent age group and is culturally looked upon as healthy, fun, appropriate and 'cool'. We thus incorporated the principles of HIIT in various Indian dance forms to produce this novel intervention called 'THANDAV'. The 10-min THANDAV routine will be developed in association with seasoned choreographers to ensure the ease and safety of the steps being performed. There will be a 2-min high intensity (80-100% of max heart rate (HR)) portion followed by a 30-sec low intensity (40-60% max HR) and four such repetitions will constitute a single 10-min routine. The 'THANDAV' website will offer details about the project and educational content after registration. Once women/girls are part of this online community, it will enable them to post their queries, talk about their experiences, watch 'THANDAVITES' dance videos and share their own on this webpage. | 3.1 Primary prevention interventions to modify behaviours or promote well-being / Research Grant | 6project_grants_public
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gen_ea5cc4d087289dbef89e168db4e2f55f | BRIGHT-SAM: BRaIn development, Growth and HealTh in children with Severe Acute Malnutrition | Medical Research Council | National Institute for Medical Research | HRCS22_02203 | The use of ready-to-use therapeutic foods (RUTF) for community-based management of children with severe acute malnutrition (SAM) is well-established and saves lives. However, current RUTF formulations result in a low ratio of n3/n6 essential fatty acids (EFAs) and other data show that low levels of the n3 EFA, docosahexaenoic acid, are associated with impaired cognitive function. An RUTF has been developed with an EFA content which should improve n3/n6 EFA ratio. We will test this for acceptability among children with SAM and their caregivers and we will assess the EFA profile and variability before and after the interventions, and compare with that of control children. Current recommendations for SAM treatment include provision of psychosocial (PS) interventions to help caregivers improve cognitive function of their children. However, to date these have had little impact: interventions shown to be efficacious have been too intensive and costly for scale-up and those scaled-up widely for children without SAM had little benefit. A short intervention focussing on the most high-risk children may have greater benefit. We will work with caregivers, local health staff, and local organizations working to promote child development to design a short, focussed PS intervention which can be offered in parallel with RUTF for community-based SAM treatment. Our long-term plan is to conduct a well-powered 2X2 factorial clinical trial of the novel RUTF and the PS intervention to determine their individual and any synergistic effects on cognitive development of children with SAM. The development project will aid this by: finalising the interventions, determining contextual factors influencing intervention delivery and uptake, determining variability in EFA and development outcomes to aid sample size calculations; engagement with local health care staff managing SAM and providers of child development interventions to ensure that our interventions are appropriate and locally own | 6.1 Pharmaceuticals / Research Grant | 6project_grants_public
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gen_ca92a97e9b7166d61d83a1d77dade8b3 | Feasibility of implementing an integrated hybrid model of service delivery for AGYW sexual and reproductive health in South Africa | Medical Research Council | Wits Health Consortium (Pty) Ltd | HRCS22_02206 | Adolescent girls and young women face significant health challenges such as HIV infection, unwanted teenage pregnancies and sexually transmitted diseases. However sexual and reproductive health service utilization remains low among this age group. Hence, there is a need to focus on determining optimal service delivery models that are responsive to current barriers faced by AGYW. This study aims to determine the feasibility of implementing an integrated hybrid model of service delivery for adolescent girls and young women (AGYW) sexual and reproductive health (SRH) at selected facilities in South Africa over a 24 month period. The service delivery model proposed will be a hybrid model comprising of both integration of contraceptive, STI/HIV transmission prevention and mental health screening with linkage by health connectors to care services for HIV treatment, PrEP and psychosocial support. Prior to implementing such an intervention, the feasibility of implementation needs to be determined through determining acceptability (client and provider), demand, practicality and adaptations needed. Hence, the principle research questions that the study aims to address include: (1)What level of service integration for SRH already exists at selected health facilities for adolescent girls and young women?, (2) Would an integrated SRH service be acceptable to health care providers and adolescent girls and young women?, (3) Would SRH service integration be practical in terms of time, space, workload, task-shifting, training and resources in a limited resource setting? and (4) What system changes are needed to implement an integrated hybrid model. This study will inform the development of a full trial to implement and evaluate the effectiveness of an integrated hybrid model of service delivery for AGYW SRH at community health care level. | 7.1 Individual care needs / Research Grant | 6project_grants_public
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gen_a0a5d8eb64de7917cb1d2f4aab919d29 | Latent rheumatic heart disease in West Africa: a pilot multi-country study | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02207 | This trial development grant (TDG) aims at generating epidemiological and feasibility data data to inform the design of a multicentric trial in West Africa to test the efficacy of penicillin to prevent the progression of latent RHD towards overt clinical disease. This is urgently needed to formulate long awaited guidelines for the management of latent RHD. There is little information on the burden of RHD in West Africa as most of . This TDG will determine the prevalence of latent RHD in three West African countries (Senegal, The Gambia, Nigeria), by carrying out mass screening at community level using handheld EC (HHEC) by non expert users. Study activities are divided in two phases, i.e. a training phase (3 months) and a screening phase (4 months). Two trainees from each country (1 expert cardiologist +1 nurse/midwife) will follow a 2-week intensive training on HHEC in Uganda. Each pair of trainees will become trainer for 3 additional health staff in its own country and continue on-site practical training for 6-10 weeks under the supervision (online) of the Ugandan expert. At the end of the training, each study team should have four trained non-expert staff (including 1 nurse, 1 midwife, and 1 community health worker) with two operators scanning in parallel. In each site, a total of 3,000 school children (5-18y) and 3,000 adults aged 19-40 years (pregnant and non pregnant women and their partners/relative men) will be screened in a pre-defined peri-urban community. Each suspect RHD case identified by HHEC will be referred for standard EC by a cardiologist. Confirmed latent RHD will be referred for regular EC monitoring while symptomatic RHD will be referred for appropriate care at the nearest teaching hospital. Quantitative and qualitative data will be collected on the feasibility and acceptability of the proposed approach in each site through continuous engagement with stakeholders and end users. | 4.2 Evaluation of markers and technologies / Research Grant | 6project_grants_public
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gen_a1d385019124dfb077ba0df187b90886 | Enhancing brain development by early iron supplementation of African infants: An enabling pilot study | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02208 | Growth and organisation of the human brain is maximally active in late fetal life and early infancy. Breast milk contains very little iron and babies born to iron deficient mothers lack the full endowment of hepatic iron that usually subsidises the needs for growth and brain development in early infancy. We have recently shown that, by 5m of age, breastfed infants in rural Africa have extremely low levels of circulating iron with 95% lying below the US reference range. There is extensive evidence from human and animal studies that early iron deficiency causes irreversible deficits in psychomotor development and cognition. Hence, we plan to conduct a large-scale RCT that will introduce iron supplements much earlier than in prior and on-going trials. To inform a go/no go decision and to refine the trial design we first need to conduct an enabling trial that will address the following key questions: Can provision of a daily iron supplement as paediatric drops starting at 6wks of age reverse the profound decline in serum iron and other measures of iron status seen in rural African infants? Can we introduce supplementary iron without undermining exclusive breast-feeding? Would iron supplementation at this age alter the infant gut microbiome potentially causing diarrhoea? Does iron supplementation (through competition for divalent metal transport systems) impair zinc and/or copper status; and hence indicate a need for triple supplementation? These questions will be addressed in a pilot 'experimental medicine' two-arm RCT comparing daily iron versus placebo in 100 rural Gambian infants receiving intervention or placebo from 6wk to 5m. | 4.1 Discovery and preclinical testing of markers and technologies / Research Grant | 6project_grants_public
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gen_083eac5a74b0e6bfb598c735024c8b1e | MICA: The third, Intensive care bundle with blood pressure reduction in acute cerebral haemorrhage (INTERACT3) trial | Medical Research Council | George Institute for Global Health | HRCS22_02216 | INTERACT3 is an international, multicentre, stepped-wedge, cluster randomised, blinded outcome assessed, clinical trial (Phase III-IV). The objective is to determine the effectiveness of a goal-directed care bundle of active management involving intensive BP lowering, glycaemic control, early treatment of pyrexia, and reversal of anticoagulation, against a practice of usual care, on the standard clinical outcome of functional recovery in patients with acute spontaneous ICH. The primary outcome measure is an ordinal shift analysis of all 7-levels (scores) on the modified Rankin scale (mRS, categories 0 to 6: 0=no symptoms, 1=no significant disability, 2=slight disability, 3= moderate disability, 4=moderate severe disability, 5=severe disability, 6=death) at 6 months. Secondary outcomes include early functional neurological recovery (according to a shift analysis of scores on the National Institutes of Health stroke scale [NIHSS] at 7 days), health-related quality of life (HRQoL) using the EuroQoL Group 5-Dimension self-report questionnaire (EQ-5D) at 6 months, duration of hospitalisation, and residence. This research will be conducted through a global network of investigators from nine LMICs. The stepped-wedge cluster randomised design has been chosen to avoid contamination, facilitate hospital-wide implementation, and maximise adherence as the complex intervention under investigation becomes usual standard of care. A consecutive recruiting approach is involved to minimise bias in patient selection into the study. A mixed consent process is proposed according to local/national rules and regulations. Besides an individual standard consent for the data collection and follow-up, a cluster guardian consent is required for patients to receive the randomised care bundle to be implemented for acute ICH patients across multiple wards as a systems of care approach. | 4.1 Discovery and preclinical testing of markers and technologies / Research Grant | 6project_grants_public
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gen_02d755937309fe0aa9ab4c6e6679d88a | A feasibility and pilot trial of enteral probiotic administration in preterm infants admitted to a neonatal unit in Nigeria | Medical Research Council | University of Ibadan | HRCS22_02219 | Our proposal is based on a fixed effects meta-analysis of 23 RCTs of preterm infants in 10 LMICs (n=4,783; Deshpande 2017). Probiotics reduced all cause mortality (RR 0.73 [95% CI 0.59 to 0.90]; P=0.003), necrotising enterocolitis (RR 0.46 [0.34 to 0.61]; P<0.00001), late-onset sepsis (RR 0.80 [0.71 to 0.91]; P=0.0009) and time to full enteral feeds (-1.95 days; [-3.44 to -0.45]; P<0.00001). No adverse effects were ascribed to probiotics in the systematic review and there are only limited case reports of adverse effects in preterm/VLBW infants. Based on global clinical trial evidence, probiotic administration has becoming routine in many neonatal units in industrialised countries. The meta-analysis included only two studies in Africa (Egypt and South Africa) and neither may be representative of other neonatal units in the sub-continent. Probiotics effects likely differ according to host characteristics, exposure to environmental microbes and nosocomial pathogens, antibiotic use and feeding practices. There is an urgent need to test this intervention in low-resource settings with the highest rates of neonatal mortality. For selection of probiotic for neonates, network meta-analysis advises the inclusion of Lactobacilli and Bifidobacterium spp. to simulate the gut flora in the healthy, breast-fed infant and use of multistrain preparations that have greater beneficial effects including the prevention of NEC. For this initial study, we have selected a product that contains three probiotic strains (L acidophilus, B infantis, B bifidum) suspended in oil, manufactured in South Africa and with a long shelf life at room temperature. This probiotic is used extensively in highly vulnerable infants in neonatal practice in the UK and no significant safety concerns have arisen. This proposal aims to ultimately address the evidence gap regarding the potential health benefits of probiotics in preterm/VLBW infants in a low resource setting in sSA. | 6.1 Pharmaceuticals / Research Grant | 6project_grants_public
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gen_a06c36db975df5a6d6dea4884511fd99 | Concentration and fragmentation: analysing the implications of the structure of Georgia's private healthcare market for quality and accessibility | Medical Research Council | Curatio International Foundation | HRCS22_02313 | To inform decisionmakers on how to engage effectively with the private sector, better evidence is needed of how healthcare markets are structured, the risks of different market structures for patients and for the health system as a whole. This evidence can help design health system policies to (i) shape the market to avoid excessive concentration or fragmentation, and (ii) design appropriate private sector engagement strategies, including by healthcare purchasing agencies. Our study will generate new evidence on the structure of the healthcare market in Georgia, a lower-middle income country where the health system is highly privatized. Applying economic theories of market performance we will: - Describe the Georgian healthcare market in terms of business models and the extent of vertical and horizontal integration. This will use publicly available information (national statistical yearbook, company financial reports, national health accounts), social insurance claims data and key informant interviews - Analyse the demand, supply and policy factors driving the observed market structure and business models, and elaborate a set of "theories of harm" about the risks of concentration and fragmentation and their potential influence on health system outcomes by different provider types. - Assess quantitative, and where necessary, qualitative evidence about the risks of fragmentation and concentration, looking at the extent to which individual outcomes such as price and intensity of treatment, and system level outcomes such as accessibility, approaches to quality assurance and the costs of contracting and regulating, differ by provider business model and market structure. - Conduct structured policy dialogues to test our interpretations of the data and identify potential policy levers to shape the private healthcare sector, engaging key stakeholders from government and the private sector. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_0bf4b85a5197144f7d0e838e27c6cc26 | Understanding male engagement in child health and nutrition in urban informal settlements: A formative participatory exploration | Medical Research Council | KEMRI Wellcome Trust Research Programme | HRCS22_02326 | Improving child health requires primary prevention, quality health services and community action. Whilst there is recognition that the health system encompasses both the suppliers of policy, services, and interventions, and the communities and households intended to benefit from them; in health systems research the focus has primarily been on the supply-side with little attention given to the demand-side of this equation. Gender roles and relations play an important role in child health and nutritional status. In many sub-Saharan African (sSA) settings, childcare and health is primarily a female domain with men largely absent or only involved in perceived severe or serious cases. Similarly, intentionally or unintentionally, child health programmes in sSA countries predominantly focus on women. While women are perceived as responsible for children, paradoxically they must negotiate decision-making and resources with other family members, including men. By exclusively focusing on women without considering family dynamics or the broader social context, these programmes may inadvertently reinforce harmful gender divisions and practices related to child health and nutrition. Evidence suggests that programmes targeting women might be more effective if men's roles are considered and transformed to affirm more equitable gender relations. Furthermore, following treatment in the formal health system, ill or recovering children are 'discharged back' into their homes and communities. Without proper understanding of the intricacies and dynamics operating at the household and community levels, hospital-initiated interventions are likely to be less effective and sustainable. Focusing on user-centred perspectives and the demand-side of the health system, the proposed work seeks to answer if and how participatory approaches can strengthen male involvement in child health and nutrition for better outcomes. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_81a0a381f6ec9b4b97c27b89eff7cc00 | Identifying the health systems changes necessary to sustain and scale up the integration of mental health services into primary care in Lagos, Nigeria | Medical Research Council | Lagos State Univ Coll of Med LAUSCOM | HRCS22_02328 | STATEMENT OF THE PROBLEM: There are policy and ethical implications of developing effective heath programmes without sustainability and scale-up. This feasibility study aims to identify the strategies to facilitate the health system changes necessary to sustain and scale up mental health services in primary care in Lagos, Nigeria. SPECIFIC QUESTIONS TO BE ADRESSED BY THE PROJECT 1) what is the state of implementation of the MeHPriC Project and what are the factors that are currently underlying its implementation?; 2) What are the dynamic interactions between the different components of the programme as regards contexts (inner and outer), implementation processes, implementation actors and intervention outputs and outcomes?; 3) How do these components influence the sustainability of the programme; and 4) What strategies may be required to facilitate the changes necessary for sustainability and scale-up METHODOLOGY There are 5 phases of the study. 1. In Phase 1, Through review of policy documents and in-depth interviews we will develop specific hypothetical pathways that link the programme inputs to processes, outputs and outcomes within the health system 2. In Phase 2, we will conduct a quantitative survey amongst the stakeholders to assess readiness to change, sustainability, feasibility and acceptability 3. In Phase 3, we will conduct a brief process and outcome evaluation of the implementation, and through in-depth interviews, and institutional ethnographies, we will examine the stakeholders' perception about the health systems constraints to delivering, scaling up and sustaining the intervention. 4. In Phase 4, we will conduct a Theory of Change (ToC) workshop to identify health system changes that will improve sustainability in the delivery of the intervention. 5. In Phase 5, we will analysis and present the project report to the funders and the stakeholders | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_5d4c4c5a7b7e619832e8031f838701a4 | A systems approach to examining health sector responses to cholera epidemics in Kenya | Medical Research Council | Strathmore University | HRCS22_02329 | Technical Summary Kenya has experienced an increased disease burden due to cholera outbreaks characterized by continuous transmission in the refugee camp settings of Garissa and Turkana, and sporadic transmission in cities such as Nairobi and Mombasa. However, while inquiry has been made regarding how the health sector has responded to and how populations have been impacted by epidemics such as cholera, not enough attention has been paid to causal relationships between the unique components of the health systems leading to an inadequate understanding of how the building blocks of the health systems interact in disease surveillance and epidemic response. Consequently, this research effort focuses on examining the health sector responses to these epidemics, developing a systems-theory-based description of the said responses, and based on the results, provide recommendations that may help break the epidemic's continuous and cyclical nature. The study will be conducted in Turkana and Garissa in Kenya, as well as in Nairobi. These are counties that have diverse levels of health system sophistication and recent experiences of cholera epidemics. Moreover, the study draws on several systems analytic frameworks - specifically Rasmussen's Risk Management Framework and its attendant AcciMap, the Analytic Hierarchy Process tool, and Cognitive Work Analysis - to determine the actors and their decisions, as well as their inter-relationships, linkages and dependencies. Thus, the study appropriates systems-oriented research techniques and applies them in a novel fashion to the assessment of health service delivery. The findings of this study are expected to guide interventions aimed at improving disease surveillance and epidemic response, and to act as a primer for the research community by assessing the utility of systems-thinking approaches in such settings. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_616b48f87f61ad34e5d97364ab410e72 | Examining effects of decision-making space and its practices on health systems performance in Tanzania | Medical Research Council | University of Dar es Salaam | HRCS22_02342 | Many low and middle income countries (LMICs), including Tanzania, have been implementing decentralisation since 1990s as a process to strengthen health systems and its performance through improved efficiency, quality of services and a means of promoting democracy and accountability. While decentralisation is widely practiced in LMICs empirical studies have predominantly focused on understanding the extent of the decision-making authority provided by the central government to the authorities at the lower levels. A few studies which have examined the actual use of decision-making space have focused on the influence of decentralisation on one or few health systems functional areas rather than addressing multiple functional areas. Other studies have only been conducted in a few districts making it difficult to explore how the exercise of the decision space vary across the districts and the factors that account for the variations. Additionally, studies examining the evidence for the effectiveness of decentralisation on improving health system performance are scarce and results are mixed. We aim to better understand how and if decentralized local authorities use decentralisation opportunities for improving health systems performance. Specific objectives are to: (i) analyse the decision-making authorities transferred from the central government to institutions at the periphery in the decentralised health system in Tanzania; (ii) assess the actual decision-making space exercised by local government officials and district health managers within the decentralised health system; (iii) assess performance of the decentralised district health systems; (iv) investigate effects of the decision-making space on health systems performance in Tanzania; (v) engage decision makers at the national and district levels aiming at informing policy and improving the practice of decision space within the decentralized health systems | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_eea8f20f4ca1030a45c8a293ee297574 | Understanding the consequences for quality and efficiency of expanding services through the private sector in South Africa | Medical Research Council | University of the Witwatersrand | HRCS22_02343 | The private sector provides a large proportion of health services in many low- and middle-income countries (LMICs), particularly for primary health care (PHC), even for the poor. But the role of the private sector in expanding universal health coverage (UHC) in LMICs is contentious. Supporters of private care provision argue that competition makes private providers more responsive, exert more effort, and provide better quality care. Yet the empirical evidence supporting this is mixed. There is also limited evidence that the demand for care is responsive to quality or costs, a pre-condition for a functioning competitive market. These dynamics are also likely to vary between countries. These questions are central to current policy proposals in South Africa, where the government plans to expand access to quality primary care services by contracting private providers. This study aims to address these questions and inform current policy debates by undertaking a detailed investigation of a self-contained market for PHC services among the urban poor in South Africa. The study has five components: (1) a detailed description of the structure of the market for PHC in Soweto; (2) an audit study of PHC providers in the market using standardised patients, allowing us to describe the relative performance of public and private providers in terms of access, quality and efficiency of treatment; (3) an investigation of the relationship between measures of market competition and performance; (4) a study of the determinants of patients' choices of PHC providers; and (5) a field experiment testing the impact of subsidised care and information about quality on demand. By describing the market structure, the differentiation strategies of providers, and the key determinants of the demand for healthcare, we will provide robust and innovative evidence that will lay out the grounds for designing future regulatory and contracting arrangements with the private sector. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_f94b42d390f12bd3822aa39bba3485ff | An inter-disciplinary approach to understanding and intervening on contextual factors that shape HIV-risk for young women and men in South Africa | Medical Research Council | South African Medical Research Council | HRCS22_02420 | Background: South Africa remains the epicentre globally of the HIV-epidemic, driven by harsh contexts of gender inequalities, poverty and community violence. Understandings of how these impact on the syndemic of HIV-acquisition risk, intimate partner violence (IPV), poor mental health and substance misuse, for young women and men remain limited, and there remain no effective HIV-prevention interventions for young people who are out of school. Aim: To understand how contextual factors shape the syndemic of HIV-acquisition risk, in South Africa, and how these can be challenged in participatory interventions to reduce HIV-risk. Methods: To understand the relationship between contextual factors and the syndemic of HIV-acquisition risk we will undertake secondary analysis of South African data sets using spatial epidemiological techniques. We will also recruit 16 youth peer research associates (YPRAs) aged 18-24 from two communities, and through participatory methods understand their perspectives. We will then co-develop with the YPRA an intervention that responds to their needs and priorities, and undertake a mixed methods pilot randomised control trial of the intervention. We will assess feasibility, acceptability and potential effects sizes through this pilot. Outcome: At the end of the project we will have an intervention that is ready for a larger scale evaluation, as well as a better understanding of the contextual factors shape the syndemic of HIV-acquisition risk for young people. Expertise: An experienced inter-disciplinary team of social psychologists, statisticians, social epidemiologists, gender, mental health, and violence experts, and HIV-clinicians. | 3.1 Primary prevention interventions to modify behaviours or promote well-being / Research Grant | 6project_grants_public
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gen_66ee2592e45bfbdb91ec99c697599873 | Nutrition and the epigenome: early environmental factors influencing human developmental programming | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02477 | A seasonal 'experiment of nature' in rural Gambia has revealed the presence of DNA methylation (DNAm) hotspots sensitive to periconceptional environment. These are enriched for metastable epialleles, endogenous retroviruses and parent-of-origin-specific methylation (PofOm) suggesting establishment in the early embryo. This is further supported by analysis of public IVF and gametic DNAm datasets which show distinctive patterns of early embryo DNAm dynamics along with enrichment for regions hypomethylated in sperm. Several loci are linked to disease outcomes, including obesity, thyroid disease and cancer. Genetic analysis suggests the greater part of DNAm variance at many season-of-conception (SoC)-associated loci is explained by gene-environment interactions, suggesting they may have evolved to sense the environment, record the information and adapt the phenotype accordingly. Such 'programmed' epigenetic states would be maladaptive if there is a mismatch with the postnatal environment, with implications for the developmental origins of health and disease. This grant seeks to establish a unique prospective SoC cohort of 600 babies to assess exposures within +/-15 days of conception in order to: a) define nutritional and other SoC exposures (methylation pathway metabolites; agnostic metabolomics; fecal microbiome); b) understand and characterise key features of SoC-sensitive loci to gain insights into genetic and other mechanisms underpinning their establishment; c) confirm and delineate the role of gene-environment interactions as a potential driver of SoC-sensitivity and look for signatures of genetic selection; d) assess the influence of SoC on the placental transcriptome (trophoblasts/mesenchymal cells) with particular attention to genomic imprinting and PofOm; e) assess effects of the above on placental and fetal growth and development. This work will establish an open-access Early Developmental Epigenetic BioResource for researchers worldwide. | 2.4 Surveillance and distribution / Research Grant | 6project_grants_public
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gen_d6e5a101ac85554bcb081496bea9584c | Understanding and measuring pregnancy-related anxiety in low- and middle-income contexts: A pilot study in northern Ghana | Medical Research Council | University for Development Studies | HRCS22_02499 | Women's anxiety during pregnancy is widespread and has been associated with poor mental and physical health outcomes for both mothers and their children. One type of anxiety which seems to be particularly problematic is anxiety about the pregnancy itself. We know little about pregnancy-related anxiety in LMICs and there are no measures of pregnancy-related anxiety which have been validated for use in any LMIC. To address this gap, we will conduct a systematic review to get a clear overview of levels of pregnancy-related anxiety and relations with maternal and neonatal mortality. We will also conduct a mixed-methods study to measure how pregnancy-related anxiety is conceptualized and to adapt and validate the Pregnancy Related Anxiety Scale among pregnant women in the Northern Region of Ghana. To do this, we will conduct 15 focus groups (n = 150) and collect survey data from 575 pregnant women attending antenatal care in Mion, Savelugu, and Tamale Metropolitan Districts. We will hire one PDRA and 5 RAs to assist with the systematic review and qualitative and quantitative data collection. We will use inductive thematic analysis to analyse the focus group data. We will use exploratory factor analysis, correlations, and t-tests to establish construct validity, convergent validity, and test-retest reliability of the adapted scale. We will also consult with a local advisory committee to ensure the use of appropriate methods and measures, and to establish face validity of our adapted measure. This project is directly linked with UN Sustainable Development Goal #3 (good health and wellbeing). Without a clear understanding of what underlies pregnancy-related anxiety and how to measure it, we cannot develop and implement effective interventions nor can we evaluate whether any implemented interventions are effective. This project will pave the way for future work promoting mental health during pregnancy and reducing associated maternal mortality and morbidity. | 2.3 Psychological, social and economic factors / Research Grant | 6project_grants_public
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gen_fd679e6b38a0acdead398406441f2e81 | Oral Vitamin D supplementation as a safe, affordable treatment for profound vitamin D deficiency in pregnancy | Medical Research Council | CBCI Society for Medical Education | HRCS22_02500 | We aim to address to the extent supplementation with 2000 IU/day vitamin D3 corrects deficiency in pregnant women in India, which has not previously been tested. We propose this is linked to lack of awareness amongst stakeholders of the benefits of offering higher vitamin D doses than current Indian RDA (<500 IU/day). Aim 1: In a pilot study determine whether the highest acceptable level of vitamin D supplementation approved by the Govt. of India leads to repletion of pregnant women at St. John's Medical College Hospital, Bangalore. Study design: Pregnant women (n=186-200) will receive 2000 IU vitamin D/day from end of the 1st trimester to term. Vitamin D status will be monitored in pregnancy [T1, T2, T3] in serum (5ml), and in the baby by sensitive LC-MS. Samples: Cord blood from a subset of babies will be sued to study the impact of maternal intervention on innate secreted cytokine responses as a measure of newborn immunity, powered on our immune data from the USA VDAART trial. Aim 2: Form a cross India network comprising scientists, clinicians, health care workers, policy makers to discuss realizing the known benefits of vitamin D supplementation in pregnancy. We will invite international experts to a workshop to discuss heterogeneity globally and within India on vitamin D dose and supplementation regimens; a meta-analysis of vitamin D studies in India in the context of global vitamin D trial outcomes and a projected review with the potential to influence national strategy are planned. Days 1-2: A closed 2-day workshop discussing whether vitamin D dose and timing regimen is the same across different clinical (e.g. skeletal vs non-skeletal), biochemical and immune outcomes. We anticipate strong representation of vitamin D interests across India. Day 3: This session will be open to all interested parties across India to ensure knowledge dissemination and transfer, and to help understand the depth of interest in vitamin D and existing concerns in India | 6.1 Pharmaceuticals / Research Grant | 6project_grants_public
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gen_91d501031e530c6fbcc381b3f41f57a8 | Capacity building for a Centre of Design, Innovation and Translational Excellence (CITE) for clinical trials of healthcare technologies in SS Africa | Medical Research Council | Makerere University | HRCS22_02505 | Great strides have been taken to reduce global maternal and neonatal mortality. However, due to numerous factors such as limited access to resources including funding, healthcare providers among others, means that maternal and neonatal mortality have remained stubbornly high in sub-Saharan Africa. Advances in technological innovations, including contextually appropriate devices coupled with mobile health technologies offer the opportunity to improve healthcare outcomes in maternal and neonatal health. For instance, improved and timely diagnostics, therapy and monitoring can improve outcomes for mothers with conditions such as preeclampsia, postpartum haemorrhage and pneumonia and hypothermia for neonates. In Uganda, researchers, students and innovators have developed many contextually appropriate solutions with some winning international awards. such devices include: (1) Maternal (postpartum haemorrhage (PPH) Wrap (https://challenges.openideo.com/challenge/reproductive-health/ideas/maternal-wrap-a-first-aid-postpartum-hemorrhage-belt); (2) The EPED strip: The Early Pre-Eclampsia Detection strip (https://bigideascontest.org/winners/early-preeclampsia-detection-strip/); and (3) Mama Ope a smart jacket for early diagnosis and monitoring of pneumonia in children aged between 0 and 5 years (http://mamaope.com/en/). Such great innovations have found a great challenge in translation to useful products due to limited capacity in clinical evaluation and translational expertise in the country. Our aim is to strengthen propose our proposed interdisciplinary Centre of Design, Innovation and Translational Excellence (CITE) in collaboration with University of Edinburgh. We propose to map existing knowledge about the systems and processes for clinical evaluation of locally made Investigational Medical Devices (IMD) amongst key stakeholders in Uganda and to strengthen local research capacity through training on clinical trial design. | 3.5 Resources and infrastructure (prevention) / Research Grant | 6project_grants_public
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gen_1d8b4b877270e7d308fb7e8cf8ccd086 | Reducing infection risks in maternity and neonatal wards through improved environmental hygiene: an exploratory study in The Gambia. | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02506 | The aim of this research is to explore the links between environmental hygiene and infection risks in maternity and neonatal units in two hospitals in the Gambia. We will use the learning derived from this preliminary work to convene a network of researchers to build the case for a future African trial of this intervention against an infectious outcome across multiple neonatal units. The specific objectives are 1. To establish baseline measurements of environmental contamination in the maternity and neonatal units in two hospitals in The Gambia, including two-weekly variability in such measures; 2. To develop a contextually appropriate cleaning training package specifically for newborn units in LMICs, with a focus on sub-Saharan Africa 3. To pilot this training package intervention in two large hospitals in The Gambia and measure potential impact on environmental cleanliness. 4. To establish a network of researchers and relevant WASH/IPC stakeholders, including the regional Maternal-Newborn Infection network and Infection Control Africa Network (ICAN), and build collaborations to support a future West African trial of the same cleaning intervention across multiple regional neonatal units, bringing together academic partners in West Africa and the UK. Cleaning in newborn care units including NICUs has some important technical differences to cleaning other hospital areas. Due to the intense vulnerability of patients and the delicacy of medical equipment, typically different cleaning staff, chemical agents and physical methods are typically used. We will observe use of cleaning products and techniques, and hand hygiene as well as measure environmental contamination before and after the introduction of a cleaning training package intervention. | 3.2 Interventions to alter physical and biological environmental risks / Research Grant | 6project_grants_public
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gen_a625673d2919a2b7decd897415f181fc | Adolescent mental, sexual and reproductive health and wellbeing policy, program and primary care implementation priorities in West Africa | Medical Research Council | Ghana College of Physicians and Surgeons | HRCS22_02510 | The principal research question of this study is: "what and why are adolescent wellbeing policy and program priorities in countries in West Africa, what mental, sexual and reproductive health services are available at primary health care level for adolescent health and wellbeing; are they proven effective, what and why are the mechanisms by which these services are funded and how efficiently are available resources used to deliver these services". The study design is a multi-country case study in West Africa with the case is defined as: "Country level adolescent mental, sexual and reproductive health and wellbeing policy and implementation priorities, financing, technical and allocative efficiency of primary health care service provision". The three countries purposively selected for this study to reflect the anglophone francophone language divide in the sub-region as well as stable and more fragile contexts are Niger, Burkina Faso and Ghana. Specific groups to be studied will be adolescents (in and out of school) and their families and communities, national and sub-national level policy makers and frontline health workers. Within each country one region and two rural and two urban districts within the region will be selected for the sub-national level study. In each district four sub-district level primary care facilities will be randomly selected along with their surrounding communities. The conceptual framework of the study draws on several policy analysis and econometric frameworks including Leichter's scheme for analyzing context and the political economy framework of 4 I's (interests, institutions, ideas and ideology). Methods of data collection and analysis include desk review, key informant interviews, focus group discussions, participant and non participant observation, conversations, resource mapping, revenue and expenditure records analysis and Data Envelopment Analysis (DEA) or Stochastic frontier analysis (SFA). | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_2355cf34df175e087a29e54d99db74fa | If I Were Thabo: Optimisation and feasibility trial of a gender transformative sexual and reproductive health intervention in South Africa and Lesotho | Medical Research Council | Stellenbosch University | HRCS22_02512 | A key social determinant of sexual and reproductive health-related (SRH) morbidity and mortality in Southern Africa is unequal gender norms. The importance of working with men as well as women using Gender-Transformative (GT) approaches, in order to reduce gender inequality and improve SRH outcomes for all is well-recognised. However, a recent systematic review showed that only 8% of SRH interventions that target adolescent men are GT. We aim to develop and feasibility test a co-produced relationships and sexuality education intervention, If I Were Thabo, for 13-14 years old adolescents, to address gender inequality as a social determinant of SRH. The study will be conducted in the Eastern Cape, South Africa, and Maseru District, Lesotho, two countries where adolescent pregnancy and HIV rates are among the highest in the world. There are two phases to the project; a development phase followed by a cluster randomised feasibility trial. The aim of the development phase is to work with stakeholders to co-produce and optimise intervention materials and outcome measures for use in the trial. This will involve working with adolescents, their caregivers, teachers and other stakeholders to develop materials for the feasibility testing phase. The aim of the feasibility trial is to determine the value and feasibility of conducting an effectiveness trial of Thabo in schools and community groups in LE and SA. To achieve this we will implement the Thabo intervention in both settings using a cluster randomised design in 10 clusters, and measure baseline, 3 month and 9 month outcomes. We will measure self-reported engagement in unprotected sex as the primary outcome. Secondary outcomes will include knowledge, attitudes, skills, intentions relating to avoiding adolescent pregnancy, and self-reported HIV and STI diagnosis. Qualitative interviews, focus groups and observational data will be gathered to assess acceptability, feasibility, fidelity and barriers to the programme. | 3.1 Primary prevention interventions to modify behaviours or promote well-being / Research Grant | 6project_grants_public
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gen_42ecc64bc4961485414088e6bd111f13 | Strengthening the quality of adolescent primary healthcare in South Africa: preliminary work on a complex public health intervention | Medical Research Council | University of Cape Town | HRCS22_02513 | Over half the world's adolescents live in countries like South Africa, with high levels of communicable and non-communicable diseases, obesity, high adolescent fecundity and unmet need for contraception. Although at increased risk, adolescents are marginalised and face barriers in accessing healthcare. In South Africa many policies set out to right this, nevertheless, adolescent-specific service provision is lacking especially with regards to inter-sectoral collaboration. The Knowledge Translation Unit has developed a PACK Adolescent health systems strengthening intervention which covers the comprehensive and integrated primary healthcare of a 10 to 19 year old. At 6 clinics and 12 schools in South Africa, we will conduct a situational analysis of adolescent primary healthcare using observations of non-clinical healthcare processes and clinical consultations, interviews with policymakers and community-based organisations and focus groups with managers, clinicians and adolescents. Two theory of change workshops with key stakeholders will help adapt the intervention using minimum components that incorporate an understanding of adolescent health needs across clinics and schools. The customised intervention will then be piloted in 6 schools and 12 clinics. A parallel, mixed methods process evaluation will include observations of consultations and interviews with adolescents and clinicians. A survey questionnaire will be completed by end-users 6 months after implementation to assess the intervention's reach. Impact will be assessed through monitoring routine data of adolescents accessing healthcare in schools and clinics. We will engage with stakeholders in the design, adaptation, pilot and implementation phases through an advisory board of national and provincial stakeholders in health, education and social services, as well as adolescents themselves, to ensure that the study and the intervention speak to the needs of adolescents and their healthcare providers. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_e11c80763c6105790dbc691a3f47f4fd | Building a sustainable model to promote menstrual, sexual and reproductive health (MSRH) amongst secondary school girls in Tanzania | Medical Research Council | Mwanza Intervention Trials Unit | HRCS22_02514 | The project addresses a critical evidence gap in how to comprehensively address menstrual, sexual, and reproductive health (MSRH) challenges of adolescent girls in Tanzania. Poor MSRH is associated with subsequent psychosocial (high levels of shame, depression, anxiety) and physical (pain, increased risk of reproductive and urinary tract infections) ill health, and poor school outcomes (including poor performance, participation, and completion). Our Theory of Change builds on a model which was developed after a qualitative metasynthesis of 76 studies and over 6,000 women and girls. The model shows how the social and cultural context underpin social support, behavioural expectations, knowledge, and the physical and economic environment that affect elements of girls' menstrual experience, including practices and perceptions, confidence to participate, and menstrual-anxiety, all ultimately impacting on girls' mental and physical health and education. The project will be conducted in four phases. An initial inception phase (Phase 1) will be followed by a formative phase (Phase 2) to iteratively refine an existing MSRH intervention and collaboratively design strategies to embed the intervention into government structures thereby promoting scaleability. In Phase 3 we will pilot and evaluate the refined intervention and implementation strategies using a before-after mixed methods design to assess (a) feasibility (including cost per student, school and district), sustainability, and acceptability and (b) effect on MSRH practice and perceptions and the overall school climate. In the final phase (Phase 4) we will collaboratively synthesise the research findings. Our phased project approach will enable us to develop a scaleable MSRH intervention that fits within Tanzanian government structures to improve MSRH practices and perceptions and the school climate to ensure the psychosocial wellbeing and optimal school participation and performance of secondary school girls. | 3.2 Interventions to alter physical and biological environmental risks / Research Grant | 6project_grants_public
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gen_4dcac5332114637177cfc2c8bbc1f621 | Impact of prophylactic CPAP in the delivery room (DR-CPAP) on neonates <1500g in a low-resource setting: A feasibility trial | Medical Research Council | Mbale Clinical Research Institute | HRCS22_02591 | Complications of prematurity are the leading cause of deaths in children under the age of five and the majority occur in low income countries. The predominant reason for these preterm deaths is respiratory distress syndrome (RDS). In high-income countries (HICs), the use of early CPAP, within 15 minutes of delivery, can reduce the need for mechanical ventilation and surfactant in the treatment of RDS. In low-resource settings, where access to mechanical ventilation or artificial surfactant is limited, when CPAP fails there are limited options for care. We hypothesise that initiation of early prophylactic CPAP in the delivery room (DR-CPAP) will reduce the rate of CPAP failure and therefore the neonatal mortality rate in low-resource settings. This project will develop and test for feasibility, acceptability and safety a protocol for DR-CPAP, which if successful can later be tested for efficacy in a future trial. The feasibility of initiating CPAP in VLBW neonates within 15 minutes of delivery in this low-resource setting will be evaluated. The acceptability of administering CPAP in the delivery room will be assessed. The safety of DR-CPAP will be evaluated through adverse events. This project will ensure that deferred consent with prior assent is acceptable to both the mothers and the medical staff for a trial of neonatal emergency care. We will pilot low-cost third party randomisation and assess if neonates can randomised within 15 minutes of delivery to allow initiation of DR-CPAP within a suitable timeframe. This study will validate secondary outcomes for the future trial. The strong involvement of health leaders, medical staff, and mothers at all stages will ensure that if successful, the intervention will be both acceptable to the communities and more effectively scaled-up. Together these findings will allow us to design a large and robust multi-centre unblinded randomised controlled trial to evaluate the impact of DR-CPAP on mortality in VLBW infants. | 6.3 Medical devices / Research Grant | 6project_grants_public
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gen_3b0381a25647d59d20e3348aa3826957 | Patient-led support groups in the management of hypertension and diabetes in low-resource settings: mixed methods study of an innovative model | Medical Research Council | African Population and Health Research Center | HRCS22_02592 | The long term ambition of this project is to improve the lives of low and middle-income people living with untreated hypertension and diabetes across Africa through a patient-led model of care. Our work is motivated by the rising burden of hypertension and diabetes in a rapidly urbanising Africa and scarce public resources for managing patients. Patient support groups have gained considerable interest as a strategy to reach low-income patients, however, there is insufficient evidence to scale up such groups widely. We have seen a window of opportunity in long-lived experiences of 6 patient groups in the slums of Nairobi and we want to interview these patients and co-design a model of care and evaluate the feasibility of conducting a large trial. We plan to conduct this through three interrelated work packages. The first work package will be a mixed methods approach starting with ethnographies, focus group discussions, in-depth interviews and survey of patients in the groups. Key informant interviews of healthcare providers will also be conducted. A literature review to assess the adaptability of the models in Africa will follow. This formative work will inform the design of a model that we will pilot (work package 2) in two communities in Nairobi slums. The novel data from the pilot will inform design, sample size, logistical considerations for a multi-country trial. We have assembled a multi-disciplinary team to undertake this task. The last work package (work package 3) entails networking with stakeholders to disseminate findings and for investigators to plan the design of a large trial. We anticipate this work to be completed in 24 months. | 7.3 Management and decision making / Research Grant | 6project_grants_public
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gen_253df1104a294b0ad6fe2cecab7a29f4 | Complex intervention to optimise adolescent BMI pre-conception to address the double burden of malnutrition: A RCT in rural and urban South Africa | Medical Research Council | Wits Health Consortium | HRCS22_02609 | South Africa faces a complex health burden with rising non-communicable disease against a background of prevalent infection. Malnutrition, undernutrition alongside overweight/obesity, is widely prevalent, imposing risks along the life course especially among adolescent girls. We propose an intervention to optimise adolescent BMI pre-conception to address the double burden of malnutrition, using established research sites: rural Agincourt and Soweto. We hypothesise that, by optimising change in BMI of adolescent girls at-risk, we can realise a triple return on investment: improved nutrition, reduced metabolic risk, and moderated peri-conceptional exposures to offset transgenerational risk for metabolic conditions. We ask: 1. In high-risk nulliparous adolescent girls, can a community health worker-delivered intervention of nutrition (multi-micronutrient supplementation) and lifestyle change, with a conditional-cash transfer (i) achieve directionally-appropriate changes in BMI?, (ii) improve micronutrient status?, and (iii) influence individual behaviours? 2. Will these changes impact individual metabolic disease risk? 3. In those adolescent women who become pregnant, will reductions in variance of BMI from improved BMI status during the peri-conceptional period impact maternal glucose during pregnancy and new-born birth weight and adiposity? Further: is the intervention package cost-effective; can findings contribute to strategies to tackle the adolescent double burden of malnutrition and reduce trans-generational risk for metabolic disease? We will enrol 1248 underweight or overweight/obese girls 14-19y using age-/sex-appropriate cut-offs. After baseline assessment/randomisation, participants will be reassessed after 18-24 months follow-up. If a participant becomes pregnant, a reassessment will be conducted in pregnancy (<18weeks) and further measures collected during pregnancy and birth. We include both process and economic evaluations. | 3.1 Primary prevention interventions to modify behaviours or promote well-being / Research Grant | 6project_grants_public
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gen_833483a3b797d0af3da128dc5c173ac1 | Nutrition-sensitive epigenetic mechanisms in the early human embryo - developing insights from stem cell and organoid models | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02610 | A seasonal 'experiment of nature' in rural Gambia has revealed the presence of DNA methylation (DNAm) hotspots sensitive to periconceptional environment. These are enriched for metastable epialleles, endogenous retroviruses and parent-of-origin-specific methylation (PofOm) suggesting establishment in the early embryo. This is further supported by analysis of public IVF and gametic DNAm datasets which show distinctive patterns of early embryo DNAm dynamics along with enrichment for regions hypomethylated in sperm. Several loci are linked to disease outcomes, including obesity, thyroid disease and cancer. Genetic analysis suggests the greater part of DNAm variance at many season-of-conception (SoC)-associated loci is explained by gene-environment interactions, suggesting they may have evolved to sense the environment, record the information and adapt the phenotype accordingly. Such 'programmed' epigenetic states would be maladaptive if there is a mismatch with the postnatal environment, with implications for the developmental origins of health and disease. This grant will allow me to gain a deeper understanding of early embryonic epigenetic processes and the techniques that are available to interrogate these, through joining a group at the University of Cambridge that has pioneered work in this area. I will use this knowledge and links with researchers working in the Department of Genetics to devise experiments to test key aspects of our nutritional programming hypothesis in developmental cell and gastruloid models, enabling me to probe the roles of specific nutrients, genetic variation, specific transcription factors (e.g. ZFPs), and chromatin remodelling via histone modifications. | 1.1 Normal biological development and functioning / Research Grant | 6project_grants_public
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gen_61e7ee6934863ca7044e0f6f5f26b569 | Duration of protection and density of colonisation following pneumococcal conjugate vaccination with a booster dose | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02653 | Global control of pneumococcal disease is hampered by the cost of PCV. More than 20 countries are projected to 'transition' from GAVI vaccine subsidies in the next 5 years. Continuation of PCV programmes will require substantial increases in country expenditure on PCV. Gambia introduced a three-dose PCV schedule without a booster dose (a '3+0' schedule), with large reductions in vaccine-type (VT) invasive pneumococcal disease (IPD) and pneumonia. Now that VT IPD is controlled, a cluster-randomised trial has begun comparing the ongoing use of the 3+0 schedule with transition to a two-dose schedule with a booster dose at 9 months of age (a '1+1' schedule). Theoretically, the 1+1 schedule will stimulate greater herd protection given its likely greater effect to prevent acquisition of pneumococcal bacteria. The ongoing study measures the effect of the two schedules on acquisition of pneumococcal carriage to 18 months of age as well as immunological measures. Despite this and other studies of the 1+1 schedule that are underway, significant gaps in knowledge remain, and none of the current studies will determine the duration of the effect of the booster dose to prevent acquisition of VT pneumococci, the effect of the booster dose on density of VT colonisation, nor whether anti-pneumococcal IgG concentration or function are associated with rates of VT acquisition. The proposed study will extend randomised follow-up of 784 participants measuring VT acquisition with repeated nasopharyngeal specimens to 28 months of age, VT colonisation density at age 10 months by qPCR and pneumococcal microarray serotyping, and opsonophagocytic activity in additional participants to compare with the effect of IgG concentration on rates of acquisition. Our findings will inform WHO policy on PCV scheduling, allow mechanistic interpretation of the trial results, and provide duration of protection and force-of-infection inputs into mathematical modeling of the booster dose effect. | 3.4 Vaccines / Research Grant | 6project_grants_public
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gen_d3bd0c6fc044e0a3ea8d3c62db41f0ee | Doctors under siege: Making sense of the rising incidence of violence against doctors in India. | Medical Research Council | Gokhale Inst of Politics and Economics | HRCS22_02673 | Society grants medical professionals' status, respect, and privilege with the expectation that physicians would be competent, altruistic, moral, and conscientious. A well-functioning social contract and a harmonious relationship between the medical profession and the people it serves is essential for a country's health system to fulfill its mandate - in India this social contract seems to be breaking down. Globally, many societies have seen major transformations in their social contracts with the medical profession, however in India, this historically stable social contract is unraveling with a dramatic rise in violent attacks on doctors. We contend that this unraveling deserves critical examination to understand what underpins it - we argue that this understanding is an essential first step to inform changes to the nature of the medical profession's relationship with Indian society. This is the objective of our study. We will conduct an exploratory, qualitative study using in-depth interviews with purposefully selected participants to unpack how various societal actors experience and understand these acts of violence. Through comparing the understandings and experiences of different actors we will reveal the cleavages and disconnects in the current social contract, and the implications going forward. While the inquiry will be inductive, it will be guided by theoretical understandings around social conflict and foregrounded by the socio-economic-political processes shaping the society and the medical profession in India. Insights from our study will be of interest to social and health policy makers, and to the medical profession in India and beyond. We will share our insights widely within the medical profession with a view to trigger conversations and critical reflections about the state of social contract. We will also use study insights to work with stakeholders in India to inform the development of innovative and practical health system interventions. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_eedd5125a586004fada1a8fde287dcb5 | Developing an mHealth intervention to strengthen the community mental health system in the context of the COVID-19 pandemic in Peru | Medical Research Council | Cayetano Heredia University | HRCS22_02674 | The COVID-19 pandemic and the mandatory social distancing have made visible the challenges the Peruvian health system faces to provide remote care. People with mental disorders are particularly vulnerable in this context, due to the impact of the pandemic on their health, as well as the limitations in accessing services. As a result, the Ministry of Health in Peru published guidelines to providing mental health care through telemedicine. In this context, which is simultaneously a great challenge and opportunity for the community mental health system in Peru, we proposed a two-year project with the following objectives: (1) To assess the impact of the pandemic on the community mental health system in Peru, (2) To identify the strategies implemented to preserve the provision of mental health care during the pandemic and assess, using the Learning Health Systems framework, the readiness to deliver remote mental care, (3) To co-design and evaluate the performance of an mHealth intervention to deliver remote care within the community mental health system in Peru. To achieve this, the study comprises 3 phases: (1) the formative phase, centered around the first two aims, will involve the review of local and international guidelines and evidence produced during the pandemic and a qualitative study with stakeholders. (2) The intervention development phase to co-design along with stakeholders the mHealth intervention based on the formative phase. Finally, (3) the pilot of our intervention, assessing implementation and clinical outcomes. The pilot will recruit 60 participants (30 users and 30 relatives) who will receive the intervention delivered by 15 health providers. Recruitment will take place at 3 Community Mental Health Centers. Data will be collected at 3 different time points: (i) before starting, (ii) during and (iii) after finishing the intervention, through questionnaires, in-depth interviews, as well as data generated through the mHealth platform. | 2.3 Psychological, social and economic factors / Research Grant | 6project_grants_public
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gen_7bea01300256253bac06fc70ef3b2649 | Strengthening the health system for a people-centred community orientation in South Africa. A formative study. | Medical Research Council | University of KwaZulu-Natal | HRCS22_02675 | Health systems in sub-Saharan Africa are typically fragile, reactive and vertically organised - being ill-equipped to deal with multiple co-existing health problems, such as malaria, tuberculosis, HIV and non-communicable diseases; as well as emerging shocks such as COVID-19. The Lancet Commission on the future of health in sub-Saharan Africa identified health systems reforms towards people-centred systems as necessary for achieving longer and healthier lives in this region. People-centredness focuses on prevention and health promotion - empowering people to be more in control of their health and that of their communities. Strengthening of the community sub-system - a historically neglected component of the health system, comprising households, civic groups, community structures and other sectors - is central to strengthening a people-centred health system. While there is political will on the part of the South African Department of Health to make a shift towards a people-centred community-oriented health system, visible in policies promoting re-engineering of primary health care (PHC) in particular; there is a knowledge gap on how to implement these reforms operationally. To provide academic direction to closing this knowledge gap, the applicants have partnered with the KwaZulu-Natal provincial Department of Health and NGOs to provide strategic academic direction to achieve these reforms operationally. Through this foundation grant, we will conduct a formative investigation of the barriers, needs and opportunities for strengthening of the pillars of the health system as conceptualized by the Lancet Commission of Quality Health systems. Guided by Realist Evaluation (RE), this formative work will inform the co-development of Initial Programme Theories (IPT) which will provide logical conceptual models for strengthening of these key pillars, including multisectoral approaches.Testing and refining these models will form the scope of work for a full-stage proposal. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_3422cc2e13123f66fd290d014a5fb403 | Promoting Universal Health Coverage for Amputees through Social Enterprise and Engineering Innovation | Medical Research Council | Makerere University | HRCS22_02677 | In Uganda, as in many other LMICs, prosthetics services have been developed, and supported by international NGOs (e.g. ICRC), in humanitarian responses to conflict. When support is withdrawn, post-conflict, health systems struggle to integrate and maintain such services. Despite the government's commitment to universal health coverage, Ugandan citizens usually have to provide the cost of materials or devices. Local suppliers are scarce and orders from abroad are only made when a user has paid a percentage of the cost. This drives up costs, compromises quality, introduces delays, uncertainties and additional visit. It also makes maintenance a great challenge leading to poor device utilisation. In reality, many amputees do not have access to prosthetic services, although data on access is extremely poor. The Ugandan government adopted the Public Private Partnership (PPP) as a model for health system strengthening, where foreign partners make a significant contribution to public resources. Until now the PPP approach has only been utilised in the not-for-profit hospitals and large research institutions and has not been tested in public services. Our aim is to determine how engineering and social innovation can improve Uganda's ability to deliver universal health coverage in prosthetic services. We will integrate innovations in prosthesis design, coupled with fine-resolution modelling of demand, to pilot new, distributed prosthesis service models, characterised through our collaboration with Joint Medical Stores via a PPP model. To achieve our objectives, the following work packages are planned: (1) Promoting universal health coverage through health system strengthening and social enterprise; (2) Mapping clinical need, service distribution and quality, and scoping modelling of future services; (3) Evaluating the introduction of appropriate new technology into the Ugandan supply chain; and (4) Engagement and development of a proposal for a follow-on proposal. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_0b4fb628510513c6891cac82e4c03105 | Learning health systems: fostering participatory learning and action to equip rural health workers as change agents for maternal and newborn care. | Medical Research Council | South African Medical Research Council | HRCS22_02686 | Our study aims to create a culture of organizational learning within rural health facilities towards maternal and newborn health (MNH) care quality improvements. We will evaluate an innovative health system strengthening approach in rural KwaZulu-Natal, South Africa (SA) using participatory learning and action (PLA) groups. Evaluation sites are two rural districts, comprising 9 district hospitals and 2 community health centres. Districts were selected on the basis of low population density, long distances between levels of care, poor road infrastructure, lack of health resources, and poor MNH indicators. We will use implementation research methods to co-design and document intervention implementation via a mixed methods approach. A before-after evaluation design will assess the effect of PLA on organizational learning culture and person-centered MNH care. Pre-implementation, in-depth interviews with health personnel at all levels of participating districts exploring challenges of MNH care provision, and interviews with rural women as recipients of care, will inform the development of the intervention. Baseline and end-line cross-sectional surveys will measure facilities' performance as learning organisations, and womens' experiences of patient-centred MNH care. Two validated tools, 1) Dimensions of Learning Organisation questionnaire, will measure facilities' performance in terms of team learning, management support, and leadership, and 2) the Person-centred Maternity Care score (PCMC) will measure womens' MNH care experiences and their perceptions of newborn care in terms of dignity and respect, autonomy and supportive care. These will provide quantitative measures of change over the implementation period. A process evaluation using qualitative case study methodology will rigorously document the intervention implementation. An economic evaluation will determine budgetary implications of replicating this intervention routinely in rural districts in SA. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_91184a03ca8f605c6c98c39751790358 | Developing Strategies to coordinate HEalthcare provision between The GAmbia and Senegal (SHEGAS) | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02688 | An increasingly mobile global population (there were an estimated 1 billion international and national migrants in 2019) poses challenges to policymakers, who must ensure their health systems can provide good quality healthcare to an increasing number of patients with diverse health needs. This is a particular challenge for policymakers in Low- and Middle-Income Countries (LMIC), particularly those in Africa, who already have over-stretched health systems, and who face fast-increasing rates of population mobility. This is particularly critical in the time of the Coronavirus Disease 2019 (Covid-19) pandemic. However, there is little relevant literature LMIC policymakers can draw on to inform their decisions. This research will adopt a participatory approach to co-develop a health systems strategy to coordinate people movement between The Gambia and Senegal - two countries with close political ties, a common pre-colonial history, and a different colonial and post-colonial history, leading to different political systems and official languages. We will adopt a mixed methods approach to first of all determine the volume of cross-border healthcare use, the influence of history on current population mobility and healthcare provision and use, to examine pre-exisiting formal and informal coordination mechanisms between different West African countries (including The Gambia and Senegal), and to explore the impact of the Covid-19 pandemic on cross-border health system coordination. We will use this information to co-develop a health system-wide strategy for responding to cross-border movement of patients between The Gambia and Senegal, in collaboration with policymakers from both countries, through the use of participatory multi-criteria mapping approach. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_2f9919a737c976935b938e05a25093ba | Measuring unanticipated opportunity costs of South Africa's COVID-19 response for children, mothers, and people living with non-communicable diseases | Medical Research Council | Wits Health Consortium (Pty) Ltd | HRCS22_02713 | Before the COVID-19 epidemic, SA's life expectancy was on an upward trajectory, with gains towards 2030 SDG targets. In response to the epidemic, the government instituted a lockdown to flatten the curve. Though there have been benefits, there are questions about the impact on non-COVID-19 health outcomes. Rapid decision making has also left community perspectives behind. SAMRC Centre for Health Economics and Decision Science-PRICELESS SA & the MRC/Wits Agincourt Unit have partnered to investigate this. Our hypotheses are firstly, that during COVID-19 epidemic there has been and will continue to be a decrease in supply and demand of routine health services which may impact on morbidity and mortality for individuals with HT, Diabetes, pregnant mothers and children under 5. Secondly, the perspective of health workers and community members regarding provision and access to routine health services during the COVID-19 epidemic will differ from that of public policy makers. The proposal aims to quantitatively measure the impact of diverting a workforce who are managing COVID-19, on routine preventive and curative health services. This will include supply and demand side perspectives. We will also qualitatively evaluate the views of the public and of healthcare workers in rural and urban areas. This will be a mixed-method study with a multi-disciplinary approach that will quantify health service opportunity costs due to the COVID-19 response. We will use a time series analysis of health services headcount data, addressing geographical and equity impacts, and qualitative interviews to understand the perspective of the public and health workers. The results will enable policymakers to make evidence-based decisions regarding resource allocation, between maintaining health services and mitigating the epidemic, that are also responsive to community needs and priorities. Our robust track record of policy action research over a decade in SA predicts a successful outcome. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_14eb09d49c92711a1085bfafcccafa09 | SARS-CoV-2 infection, transmission dynamics and household impact in Malawi (SCATHIM) | Medical Research Council | University of Malawi | HRCS22_02717 | Sub-Saharan African countries have adopted prevention measures similar to those used in developed countries to combat the SARS-CoV-2 virus (COVID-19) pandemic, although their social, cultural and economic contexts are markedly dissimilar. Limited empirical data exist on SARS-CoV-2 transmission dynamics and the feasibility of prevention measures in diverse African households, to guide the adaptation of the preventive measures. We aim to determine the transmission dynamics, determinants and socio-economic impact of SARS-CoV-2 infection in households located in urban medium-density, urban high-density and rural-high density locations in Malawi, Africa. Our specific objectives are to (1) measure the secondary attack rates of SARS-CoV-2 infection within households of symptomatic and asymptomatic index cases, (2) assess how SARS CoV-2 susceptibility and clinical outcomes among household contacts of index cases are influenced by socio-demographic, nutritional and anti-SARS CoV-2 immunological status; co-infections (HIV, TB, malaria) and their treatments, and household environment, (3) assess the acceptability, feasibility, adoption and effectiveness of personal protective equipment among household members of index cases, (4) describe lived experiences of caregivers of SARS-CoV-2 index cases, and (5) estimate the direct and indirect costs associated with SARS-CoV-2 prevention and care in households of index cases. Through this study, we will generate contextually-relevant empirical data for identifying high risk individuals; predicting the intensity of SARS-CoV-2 transmission and the impact of preventive measures; and designing appropriate social safety nets for households affected by SARS-CoV-2. Our research team's existing engagement with policy makers and local health department will facilitate knowledge translation and enhance their pandemic response capacity. | 2.3 Psychological, social and economic factors / Research Grant | 6project_grants_public
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gen_d78cc0b99ed8b7ea24bef86ac7c48761 | To investigate the spectrum, determinants and long-term outcome of SARS-CoV-2 in African children, immune responses and protective role of prior sHCoV | Medical Research Council | University of Cape Town Lung Institute | HRCS22_02720 | To prospectively investigate SARS-CoV-2 in African children, we will leverage 2 ongoing cohorts: (i) the Drakenstein Child Health Study (DCHS), a birth cohort study with comprehensive longitudinal measurement of risk factors, a very well phenotyped population and large biobank of samples. Children will be followed for 3 study visits with repeated sampling through the epidemic and at any intercurrent illness. (ii) study of children hospitalized with pneumonia at the largest childrens hospital in Sub-Saharan Africa. Children will be tested for SARS-CoV-2 and for other viral pathogens by PCR of nasal samples. Clinical features, risk factors, nasal specimens and blood samples (serum, Paxgene, PBMCs) will be collected in children. PCR for SARS-CoV-2 and other respiratory viruses will be done on nasal samples. Serology for SARS-CoV-2 will be done in all children; in DCHS we will also investigate the role of prior seasonal coronavirus (sHCoV) infection using biobanked samples to investigate serological responses to sHCoV and potential cross protection for SARS-CoV-2. Immune markers, cytokines and RNA expression profiles will be measured to identify SARS-CoV-2 associated inflammation compared to other viral infections or asymptomatic illness. All children will be followed at 12 months for long-term health outcomes. This study design will enable us to investigate symptomatic and asymptomatic SARS-CoV-2 and serological responses, including cross-reactivity and cross-protection from sHCoV. We will also be able to compare clinical, immunological and inflammatory profiles and long term outcome of children with COVID, with asymptomatic infection, and with other viral-pneumonia, in a LMIC community and hospital setting. | 2.1 Biological and endogenous factors / Research Grant | 6project_grants_public
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gen_6859c540590f0117e2cd7e34b836b99a | Evaluation of low birth weight infant post-discharge outcomes and development of community-based follow-up and monitoring strategies in Africa | Medical Research Council | Aga Khan University, Kenya | HRCS22_02738 | Globally, every year 2.5 million newborns die. Low birth weight (LBW) infants (birth weight< 2,500g) who constitute 15% of all newborns, have the highest risk of mortality and adverse long-term growth, health and neurodevelopmental outcomes. They include both preterm and intrauterine growth restricted infants and majority are born in low-and middle-income countries (LMICs) in sub-Saharan Africa and Southern Asia. Over the past two decades, interventions to improve facility-based care in LMICs for LBW infants have been tested and implemented, but the scarcity of longitudinal data to determine the predictors of poor outcomes and inform the design and timing of interventions have hampered progress in improving their post-discharge outcomes. LBW infants in impoverished communities are particularly vulnerable and community-based strategies to monitor and address gaps in their care in a timely manner have the potential to improve their outcomes. Community-based peer support for mothers is effective in improving breast feeding practices in infants in low resource settings and has the potential to improve post-discharge survival outcomes for LBW infants. We propose to evaluate the predictors of stunting and neurodevelopmental impairment among LBW infants using a cohort of well-characterised mother-infant dyads recruited from one rural and two urban health facilities in Kenya and The Gambia over a period of 30 months. In addition, using a mixed methods approach, we will explore the feasibility and acceptability of embedding mother-to-mother peer support for LBW infants in community-level quality improvement strategies for maternal and child health in Kenya over a 12-month period. The data from these two studies will enable us to refine a community-based package of interventions for LBW infants and inform the design of a cluster randomised trial to rigorously evaluate the impact of these interventions on LBW infant survival, growth and neurodevelopmental outcomes. | 8.1 Organisation and delivery of services / Research Grant | 6project_grants_public
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gen_48d0cb4fdcb3cad21d7f47725486f2b9 | Host-virus interactions in KSHV-related malignancies: evaluating the role of STIP1 as a therapeutic target | Medical Research Council | Rhodes University | HRCS22_02739 | Molecular chaperones are essential for protein homeostasis. Hsp90 and Hsp70 function as broad host factors for viral protein folding and are essential for both KSHV latent and lytic replication cycles. As such, we believe KSHV is exquisitely sensitive to perturbations in molecular chaperone systems and inhibition of these pathways is a viable therapeutic strategy. However, targeting molecular chaperones directly is not without issue, due to cells having the ability to circumvent chaperone inhibition by activating alternative stress pathways. For example, resistance to the cellular stress response triggered by Hsp90 inhibition can be overcome by upregulating other chaperones, including Hsp70. To circumvent this issue, we will target alternative components of the stress complexes. Co-chaperones are accessory proteins that fine-tune the function of Hsp70-Hsp90 complexes. Specifically, the co-chaperone STIP1 (also known as HOP) couples the de novo and stress-related protein folding pathways of Hsp70, to the conformational regulation cycle of Hsp90. Therefore, inhibiting STIP1 function is a potential mechanism to simultaneously perturb both Hsp70 and Hsp90 function in viral infection. Our preliminary data suggest that STIP1 is required for survival of latently KSHV infected PEL cells and production of lytic virions. During lytic KSHV replication we determined that STIP1 become enriched in host networks regulating translation and ribosome biogenesis, cytoskeletal remodelling, and metabolism, all of which are necessary for KSHV infection. In addition, four KSHV-encoded proteins were associated with STIP1 during lytic replication. Based on this, this project will aim to understand the mechanisms by which STIP1 regulates the identified host and viral pathways, while concurrently extending the analysis of STIP1 as a therapeutic target in KSHV-infected cells and identifying hit compounds that inhibit STIP1 which could be developed into antiviral agents in future. | 2.1 Biological and endogenous factors / Research Grant | 6project_grants_public
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gen_bfc56ae67e7702f03548d849eb1652da | Development and pilot testing of an m-health intervention to reduce COVID-19 associated psychosocial distress among Nigerian healthcare workers | Medical Research Council | Obafemi Awolowo University | HRCS22_02740 | The advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease (COVID-19) across the globe has brought severe disproportionate distress on individuals, communities, health resources, and nations. The distress is increasingly eroding the mental health and wellbeing of patients and caregivers in contexts with precariously fragile health resources. Nigeria with all health parameters below the WHO standard is no exception. COVID-19 related distress in Nigeria is rapidly jeopardising the mental health and wellbeing of health workers, especially doctors and nurses who spend relatively more time with patients. Doctors and nurses, hereafter referred to as healthcare workers (HWs), are brutally besieged by long working hours, psychological distress, fatigue, and occupational burnout. Also, the HWs' exposure to the virus is exponentially increasing while some of the control measures, like social distancing, imposed by the government are depleting their social capital and social connectedness, further undermining their mental health and wellbeing. However, m-health intervention is increasingly seen by some experts as a game-changer in the context of solutions to mental health and wellbeing challenges. Therefore, this project investigates COVID-19 associated psychosocial distress and evaluate the feasibility and pilot-testing of a guided m-health intervention among Nigeria's HWs. The study will use mixed-method to collect data for pilot-testing a guided m-health intervention to reduce Covid-19 associated psychosocial distress among the HWs in selected tertiary hospitals, Southwest Nigeria. The findings of this project would provide useful information on the feasibility of using such intervention for improving the psychosocial health of Nigerian HWs. | 7.1 Individual care needs / Research Grant | 6project_grants_public
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gen_676761ae23c8340d11d6169719025221 | Two-way risk communication mobile application versus traditional methods of adverse drug reaction reporting in Uganda: a randomized controlled trial | Medical Research Council | Makerere University | HRCS22_02798 | There is an urgent need to improve pharmacovigilance in Uganda. Despite efforts to improve reporting using web- and paper-methods, adverse drug reaction (ADR) reporting by healthcare professionals (HCPs) remains critically low. We aim to complete a cluster-randomised controlled trial to evaluate the effectiveness of a mobile application in addition to traditional web- and paper-based methods for ADR-reporting by HCPs. Our goal is to recruit 3820 HCPs from 382 ART-sites in Uganda to evaluate the Med Safety(R) mobile application, developed by the European Union WEB-RADR programme to embed digital PV in healthcare. Med Safety(R) is available in English and Luganda and has been implemented in limited settings in Uganda since February 2020. We aim to discover the barriers and facilitators to Med Safety(R) uptake, its effectiveness in improving PV, and the cost-effectiveness of rolling it out to HCPs at ART-sites. Our study will have two arms: HCPs enrolled at ART-sites in the intervention arm will be trained in the use of Med Safety(R), paper- and web-based ADR-reporting methods and those in the control arm will be trained in the use of paper- and web-based ADR-reporting only. HCPs will be encouraged to report ADRs through onsite awareness campaigns, reminder WhatsApp and mobile phone short messages. To-date we have enrolled 243 HCPs from 45 intervention sites and 386 HCPs from 41 control sites, using funding from Makerere University. We are requesting funds from the MRC to deliver the rest of this project. The work will deliver important insights into the practicality, acceptability and effectiveness of mobile application-driven ADR-reporting in a resource-limited setting and increase our knowledge of the safety of dolutegravir-regimens and isoniazid preventive therapy among people living with HIV in Uganda. This work underpins potential national roll-out of Med Safety(R) among HCPs in collaboration with Uganda's National Pharmacovigilance Centre. | 7.3 Management and decision making / Research Grant | 6project_grants_public
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gen_06c6ecea0ed0536adf1d12eef879141c | Healthcare and Socio-economic Impacts of COVID-19 on Patients with Diabetes in Tanzania and Kenya | Medical Research Council | Ifakara Health Institute | HRCS22_02810 | This project will provide much-needed, timely and unique evidence from rural and urban areas of neighbouring East African Countries (Tanzania and Kenya) with different approaches to the control of COVID-19. The project aims to explore the experiences of people with type 2 diabetes (T2D) and healthcare providers on managing T2D during COVID-19. Guided by the World Health Organization Social Determinants of Health and Wellbeing Framework [1] , it will focus on how the pandemic has impacted patients' and healthcare providers' ability to manage T2D, the socio-economic burden of T2D, and patients' response to COVID-19 itself. It will also identify policy gaps in each country in relation to health and social care of T2D during COVID-19. The study will foster multidisciplinary collaboration and capacity building by close working between scientists from Africa and UK throughout delivery of five interrelated workpackages (WPs). WP1 will employ questionnaires (N=500 in each country) and in-depth interviews (N=30 in each country) to explore patients' experiences of healthcare access, and T2D self management, socio-economic challenges and knowledge, attitude and practices related to COVID-19 in rural and urban settings in each country. WP2 will use a desk review and field research to estimate the individual and societal economic burden of T2D. In WP3, IDIs with local healthcare providers (N=15 in each country) will explore their perspectives on T2D management during COVID-19. In WP4, a policy landscape analysis in each country will employ a desk review and key informant interviews to identify policy gaps, priority setting and action for T2D during COVID-19. WP5 will use a multi-stage participatory process involving key stakeholders in which evidence from WPs 1-4 will be synthesised to develop context-specific national policy recommendations and health education messages for T2D management during COVID-19. | 2.3 Psychological, social and economic factors / Research Grant | 6project_grants_public
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gen_2c212af183572baecb85a93cdc6d40c7 | The Impact of COVID-19 Control measures on NCD risk factors and Metabolic health: A comparison of 3 Caribbean countries | Medical Research Council | University of the West Indies | HRCS22_02824 | Low and middle income countries (LMICs) have a disproportionate burden of noncommunicable diseases (NCDs) and limited resources for prevention and treatment. The COVID-19 pandemic has served to highlight and also exacerbate these disparities. With limited resources for tertiary level care and no evidence-based treatments or effective vaccines, LMIC governments employed a range of public health measures to control the spread of COVID-19, many of which interfered with daily routines and food systems. These control measure may have beneficial and detrimental effects on NCD risk factors, physical measurements (blood pressure and weight), mental & metabolic health. The Caribbean's high NCD burden and heterogeneity in COVID-19 incidence & implementation of COVID-19 control measures provides a unique opportunity to investigate the effect of specific policies on NCD health practices and explore differential effects by gender, urban/rural residence and socioeconomic status. We plan to administer a telephone survey to hospital out-patients who had blood taken for metabolic studies (glucose and lipids) at tertiary hospitals prior to the outbreak in three island territories -Jamaica, Barbados and Trinidad & Tobago (n= 1460) to investigate the effect of COVID-19 control measures on NCD risk factor practices and mental health. Participants will be invited for repeat laboratory testing to evaluate the effect of COVID-19 control measures on metabolic health. Blood pressure and weight will be abstracted from outpatient visit records prior to and following the epidemic. The effect of COVID-19 control measures on NCD risk factors, physical measures, mental and metabolic health has not been examined in the region. Through multi-island comparisons we can investigate the impact of specific government policies and help LMICs limit adverse outcomes in persons at risk of or living with NCDs while containing future COVID-19 outbreaks or other national disasters. | 2.4 Surveillance and distribution / Research Grant | 6project_grants_public
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gen_942fe357e14805c1a47cfa34a4a226d4 | HPV, STI and AMR in West Africa: estimating population burden and understanding exposures to accelerate vaccine impact and drive new interventions | Medical Research Council | London School of Hygiene and Tropical Medicine | HRCS22_02905 | This multi-stage, probability-based, cluster survey will be undertaken within an established Health and Demographic Surveillance System in The Gambia. It will generate key data on the population prevalence of human papilloma viruses - associated with cervical cancer, other sexually transmitted infections, viral hepatitis, and HIV; also, on associated risk factors in 15 to 49-year-old females. These data are expected to accelerate progress towards achieving the targets set out in relation to Sustainable Development Goal 3 - addressing health and wellbeing, in females in West Africa. Specifically, baseline prevalence data on HPV, at the point of national vaccine rollout, are essential if vaccine impact is to be predicted, measured, and maximized, through considering alternative vaccination schedules, and new vaccines as they become available. Data on sexually transmitted infections, important causes of neonatal death, stillbirth, and infertility and on their antimicrobial resistance patterns, will allow syndromic treatment guidelines to be adapted to the setting - thus reducing the drivers of further resistance. The data are also expected to provide advocacy for the implementation of strategies, such as for the prevention of congenital syphilis, which are known to be effective but not currently provided as part of antenatal care in The Gambia and other countries is West Africa. Quantifying the ongoing burden of hepatitis B in women of child-bearing age, despite a well-established vaccination programme, will determine progress toward elimination targets, and drive work to improve the timeliness of neonatal hepatitis B vaccination. Prevalence data on hepatitis C and HIV both amendable to prevention and treatment strategies, will be complemented by a study of health systems factors which aims to identify the barriers to implementation of proven interventions in The Gambia and sub-region. | 4.4 Population screening / Research Grant | 6project_grants_public
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gen_2497b399a10afd516fdcbb835051b1bc | C-it DU-it: Community Data Use for Integrated ANC | Department of Health and Social Care | LVCT Health Healthy Societies | HRCS22_05095 | Facility and community health data is rapidly changing from paper to electronic across Kenya. Multiple digital systems are being developed, but these do not link. Community health volunteers (CHVs) and facility staff need to work together using data to monitor and improve uptake of services. Antenatal care (ANC) is an example of a service where this is important as Kenya in adopting WHO’s ambitious target of 8 ANC contacts. This research will demonstrate how to link the data and use it, providing missing evidence on the impact, costs and scale-up of data linkage and use. Our intervention targets the interface between the community and the facility. Data linkage for data use is at its heart with ANC picked as an example of what is possible. Our short name C-it DU-it (pronounced “see-it; do-it”) is an acronym intended to convey ‘seeing’ linked data (C-it) and ‘doing’ or acting on the data (DU-it). Our aim is to strengthen community health systems in Kenya through ANC data linkage and use, learning lessons for other contexts. Our objectives are to: 1.To increase ANC uptake and quality in Western Kenya by a.linking community and facility digital ANC data systems, creating a system able to track an individual woman throughout pregnancy and schedule appointments (‘C-it’) b.strengthening the capacity of community work improvement teams to use ‘C-it’ data for quality improvement and of CHVs to deliver community-based ANC contacts (‘DU-it’). 2.To co-develop research strategies with county policymakers that address evidence gaps to scale-up community health systems strengthening through ‘C-it DU-it’: 3.To strengthen the capacity of communities, county managers, Kenyan researchers, and institutions to set the community health research agenda and deliver major implementation research. Our research will be conducted in 4 counties in Western Kenya. A realist evaluation will tell us how, why and for whom the approach worked or did not work. Understanding the relationship between the county context, how people responded and outcomes (e.g., political agendas; team working; motivation; local pregnancy beliefs) makes it easier to adapt the approach to other contexts. A pragmatic cluster-randomised controlled trial in Homa Bay will tell us the impact of linking digital data and the added value (if any) of combining this with training work improvement teams in data use. We will measure the impact on the number of ANC visits and the effects on pregnancy outcomes and quality of care. Health economic evaluation will identify whether C-it DU it reduces health expenditure for pregnant women accessing and engaging with ANC care and whether the intervention is cost effective. Scale-up We will adapt and scale-up the interventions using toolkits developed in the trial county to control clusters and 3 additional counties. There will be a chance to refine as results from our research emerge. Two Kenyan partners with excellent reputations and national influence are leading this study. LVCT piloted the approach and is a lead player in strengthening community health system and scale-up. KEMRI conducts large health systems trials in Western Kenya. Liverpool School of Tropical Medicine will support us in our research and our data digitisation experts will develop and test systems for data linkage adapted to each county. We will work with the county teams and hundreds of community health volunteers that identify pregnancy and refer women to ANC services. | 8.1 Organisation and delivery of services / GHPSR | 6project_grants_public
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gen_201c9a1786a10172416d9d284dcfc6e7 | Community Voices in Health Governance - Translating Public Participation Into Practice in a World of Pluralistic Health System | Department of Health and Social Care | University of Cape Town | HRCS22_05098 | India, Brazil and South Africa are countries with public health care systems, that assure some space, even if nominal, for citizen participation in its daily routines. This proposal focuses on ongoing changes in these systems, which increasingly rely on new ways of combining public and private provision, calling attention to the actual and potential role of institutionalized channels for public participation in contributing to system effectiveness. The central argument relies on the role of citizen participation in fostering the alignment of bureaucracies, politicians and health professionals around the goals of improving population health and wellbeing. The research program will produce a better understanding concerning: a) How citizen participation is working in these systems; b) How is it adapting to ongoing changes; c) What is needed in term of resources, institutional design, community involvement and public officials training to fulfill its potential contribution. Since the 2000’s, large cities in these countries began to expand access to health care based on models of purchasing public health care. These experiences are growing, with private and philanthropic providers hired to manage public facilities and deliver public services. There is preliminary evidence suggesting that under certain conditions these experiences are contributing to a quick expansion and improved access to care in peripheral and poor areas of big cities (Coelho et al 2019, Seem, & NandraJ 2021, Schütz 2020). Despite these initial positive results there is widespread resistance to this modality of pluralistic service provision, based on the idea that it introduces a private logic in the public system (England 2004; Witter et al 2012). Reynolds (2018) also caution that public servants lack the skills or experience to negotiate such contracts and that “unless substantial capacity is developed and mechanisms for monitoring — including by local health committees — established, the potential for dysfunctionality and fraud is great.” From our perspective, pluralistic modalities of public service provision may contribute to the improvement of public administration agility, but at the same time may create a coalition between state and private actors to the detriment of population health interests. For us, the strengthening of the public health care system in LMIC countries will need to address deficiencies related to the six building blocks of the WHO model: infrastructure, human resources, technology, medicines, financial resources, and evaluation systems and will be facilitated once community governance mechanisms crosscut all the building blocks providing glue to ensure community voice is harnessed for health system responsiveness to citizens needs and equity. In this scenario, we propose a multi country study focused on mapping and improving the state of community participation mechanisms in selected districts in the cities of Mumbai, Bengaluru, São Paulo, Fortaleza, Gqebhera and Cape Town, where pluralistic models of managing and providing services are either in place or in the making. This research seeks to understand the crucial role community participation can play in pluralistic health systems and how it could strengthen and enhance Universal Health System, helping to create an accountable health system with democratic governance. It seeks to identify a model for effective and meaningful participation within the pluralistic health system. | 8.1 Organisation and delivery of services / GHPSR | 6project_grants_public
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gen_b4d89fd8b4017aa8877611b42a46d9b1 | Implementation of the COmmunity HEalth System InnovatiON Project, COHESION - I | Department of Health and Social Care | Cayetano Heredia University | HRCS22_05108 | The COmmunity HEalth System InnovatiON (COHESION) project was a 3-year project that started in 2016 as a collaboration between research teams from Mozambique, Nepal, Peru and Switzerland. It enabled formative research to be conducted at policy, health system and community levels using tracer chronic conditions that included non-communicable diseases (NCDs) (diabetes and hypertension), and a specific neglected tropical disease (NTDs) (Schistosomiasis in Mozambique, Leprosy in Nepal and Neurocysticercosis in Peru). The results from this formative research were utilised as part of a process for identifying adequate interventions through a participatory approach with communities, primary healthcare (PHC) workers, and regional health authorities. Meetings with different stakeholders were carried out between 2017 and 2018 to propose context-relevant interventions oriented to address the challenges of providing care for people affected by NCDs and NTDs. During the meetings, participants provided feedback regarding problems and potential solutions for chronic care and health services in general and proposed possible areas of intervention. Upon completion of all the meetings, each country identified the main components to be included in their interventions that were focussed on communities, health workers and facilities. Taking the work forward, this proposed Project (COHESION-I) has two main objectives: first, the implementation and evaluation of the context specific co-created interventions in the three countries – Mozambique, Nepal and Peru (Component 1), and secondly, explore the possibilities to translate the experience and the lessons learnt to other countries (India) for adaptation of the COHESION approach in a different context (Component 2). 1.1Component 1 We propose to work in six communities in Mozambique, Nepal and Peru. Two communities (A&B) where we worked as part of the formative research will receive the co-created/co-designed intervention encompassing activities with the community’s health service users and health providers. Two other communities (C&D) will receive a co-designed only intervention of the same duration, the idea is evaluate if interventions that were co-created in other communities will work in new communities with similar characteristics. Finally, two different communities (E&F) will receive no intervention (“usual care arm”) to enable meaningful comparisons between intervention arms and usual care. The current project will enable us to evaluate the impact of a co-designed strategy in terms of (a) improved responsiveness of PHC and patient satisfaction, and (b) improved health care provision for chronic conditions. We will compare the impacts of the co-designed intervention to those of the non-co designed intervention and usual care. 1.2Component 2 In India, we will follow the approach taken in COHESION study and conduct a policy analysis, health system assessment and community perception study. A co-creation process will follow this to develop context-relevant interventions to improve the provision of care for people affected by NCDs and NTDs. The co-created interventions will be pilot tested in the field for feasibility, acceptability, and preliminary effectiveness. If the COHESION approach proved to be locally adaptable in India, a protocol for the COHESION methodology will be developed that can be adapted to different settings. | 8.1 Organisation and delivery of services / GHPSR | 6project_grants_public
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gen_faf16b0543fea2c65c533517eb6686c2 | Strengthening health systems by addressing community health workers’ mental wellbeing and agency | Department of Health and Social Care | BRAC James P. Grant School of Public Health, BRAC University | HRCS22_05118 | Community Health Workers (CHWs) are the backbone of the health system. In remote rural and slum settings, they are often the only point of contact with formal health services for many communities. COVID-19 has demonstrated how CHWs are critical in ensuring adaptability of health systems during crises. Supporting CHWs is fundamental to improve their resilience and agency, maintain trusting relationships with communities and the sustainability and responsiveness of the broader health system. Despite this, CHWs are under-prioritised and lack support. Limited available support focuses on additional service provision, often overwhelming CHWs and neglecting their wellbeing. Evidence across LMICs suggests that CHWs face many job related stressors: physical, including regular risks; and emotional, including trauma and pressure due to the scale of community demands for help in under-resourced contexts. Yet, these stressors remain invisible to health systems, which offer little or no support to preserve CHWs wellbeing, risking their effectiveness and retention. Our research aims to develop a holistic support package for community health workers (including training, supervision, physical and emotional support) to address a multitude of job-related stressors with a specific focus on psychosocial support to contribute to enhanced CHW wellbeing, agency and resilience. Our research will take a co-production approach, situating CHWs as peer-researchers who are central to data collection, analyses and co-designing of solutions with collaborators, working across sectors. We will: 1) develop an evidence base through analysis of existing policies and practices on support for wellbeing of CHWs; interdisciplinary research with CHWs to understand their experiences and challenges, including qualitative, participatory (photo voice, stepping stones, body mapping), quantitative surveys, and participatory evaluation methods; 2) utilize the evidence generated to co-produce a package of interventions with CHWs and key stakeholders, to support CHWs wellbeing, with a specific focus on mental wellbeing to promote agency of CHWs and resilience of health systems; and 3) pilot and evaluate interventions for cost, equity, feasibility and scale up. This work brings together global and national expertise in health systems strengthening, gender, mental health and participatory health research from Bangladesh (BRAC JPGSPH) and Kenya (LVCT Health, APHRC), and partners in the UK (LSTM) who have a proven track record of CHWs research and implementation. Collaborators include representatives from Community Development Organization, Associations of CHWs, Ministries of Health, National Institute of Mental Health, and the Divisions of Mental Health and Community Health Services at national and county levels. Capacity strengthening of CHWs and health systems actors will be embedded throughout. | 7.1 Individual care needs / GHPSR | 6project_grants_public
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gen_08506b1104dd062a5e75254e37b26168 | Calling time on avoidable morbidity from asthma in African children | Department of Health and Social Care | University of KwaZulu-Natal | HRCS22_05425 | Research question In a poor rural population in KwaZulu-Natal using a pragmatic adaptive randomised controlled trial in 2028 children and adolescents to answer the questions: a) Is a combination inhaled steroid/ fast onset long acting 2 agonist (ICS/LABA) clinically effective? b) Is the ICS/LABA cost-effective compared to standard of care as per South African Asthma Guidelines? I will establish an observatory for asthma in adolescents in Africa by answering the following questions: a) What is the prevalence and what are the risk factors for asthma in children and adolescents in Africa? Background In Africa, over 50 million children suffer from asthma. Mortality is unacceptably high and far exceeds that seen in high income regions of the world - for example the rate of asthma deaths is as high as 100 times that in the UK. A major contributor to the high and largely preventable morbidity and mortality from asthma in Africa is lack of access to effective and affordable inhaled therapies. Even the very first step of asthma treatment as recommended by the Global Initiative for Asthma -h; inhaled corticosteroid/fast onset 2 agonist (ICS/LABA) as required -h; is out of reach for the great majority in Africa. This global inequality has been ignored for too long due to a lack of high-quality burden of disease data and robust clinical and health economic data to guide policy. Aims and objectives To determine the clinical and cost effectiveness of ICS/LABA compared to standard asthma care The determine the prevalence and risk factors for asthma in adolescents in Africa To create an observatory for asthma for Africa To establish opportunities for early career researcher in Africa to strengthen research capacity To advocate for access and effective medications for asthma for African children and adolescents.Design and methods a) Individually randomised controlled adaptive trial of a single inhaler-based approach to asthma management. Population: Children and adolescents 6 -18 years, with 1 asthma exacerbation in the preceding 12 months.Intervention: A pragmatic strategy using an (ICS/LABA) inhaler for asthma exacerbations as well as for maintenance treatment. Control: Standard care for asthma.Primary outcome: Severe asthma exacerbations defined as events requiring treatment with systemic corticosteroids (oral or intravenous).Time: 12 months' follow-up. b) Multi-country cross-sectional study of three African countries to determine the prevalence and risk factors for asthma using standardised methodology from the Global Asthma Network (GAN) using self-administered written and video questionnaires. Additional questions on risk factors adapted to the African context will be included. Timelines: I propose to have relevant approvals/engagements (12 months), data collection (42 months), data analysis (48 months) and reporting/dissemination (60 months). Outputs and dissemination Effective and accessible asthma treatment Creation of an asthma observatory to improve the care of children and adolescents with asthma Masters and PhD opportunities for early career researchers Community engagement, publications and policy briefs Dissemination through Pan African Thoracic Society, Global Asthma Network and the International Union of Tuberculosis and Lung Disease through WHO engagement for access to affordable asthma therapy for all | 6.1 Pharmaceuticals / NIHR Professorships | 6project_grants_public
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gen_f1c6fda9cb13b725cb0fd1b713ed14f3 | Psychosocial, Pharmacological, and Legal Interventions for Improving the Psychosocial Outcomes of Children with Substance Misusing Parents | Department of Health and Social Care | Saint Louis University | HRCS22_09156 | Global estimates indicate approximately 5-10 per cent of children are raised in families where parents misuse alcohol or other drugs. Extensive research documents the adverse health, developmental and psychosocial outcomes for children raised in these families. Parental substance misuse also typically co-occurs with multiple family risk factors, including parental psychopathology and domestic violence. The prevalence and complexities associated with parental substance misuse has led to the development of a range of approaches that aim to improve child health and developmental outcomes. Estimates suggest that for every dollar invested into substance misuse treatment, there are significant cost savings. While there is a number of reviews on different interventions (~ 25), a critical limitation of the current evaluation and review literature is the lack of an updated integration and synthesis of the comparative effectiveness of intervention models. Without a clear understanding of the comparative effectiveness, practitioners and policy-makers face difficulties in making informed and reliable choices between interventions. This review will provide a comprehensive up-to-date review of psychosocial, pharmacological and legal interventions in the context of parental substance misuse and their impact on child psychosocial outcomes. The review will use network meta-analysis to synthesise the comparative effectiveness of different intervention approaches. | 6.1 Pharmaceuticals / ESP | 6project_grants_public
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gen_69c0a193ee13b6fb14ea87c8667f6fe5 | Physical interventions to interrupt or reduce the spread of respiratory viruses | Department of Health and Social Care | Cochrane Acute Respiratory Infections Group | HRCS22_09162 | Acute respiratory infection (ARI) is the leading cause of infectious disease morbidity and mortality and imposes a significant burden on healthcare systems. Viral epidemics or pandemics of ARIs pose a global threat, such as severe acute respiratory syndrome (SARS) in 2003, influenza (H1N1) in 2009, and the current coronavirus pandemic (COVID-19). ARIs are complex syndromes. Agent-specific interventions or preventive measures are seldom completely effective. Physical methods have clear advantages in reducing ARI transmission: they can be implemented quickly, independent of specific infective agents, at local, or wider geographic or social sectors, and are relatively cheap. This review assesses a range of interventions to prevent infection including physical barriers (e.g. masks), hygiene (e.g. handwashing), and distancing. For COVID-19, these are vitally important strategies that need a solid and reliable evidence-base. The previous update of the review in November 2020 was partly funded by the World Health Organization. It has been cited 740 times and has contributed to global decision-making. It has also been cited in a guideline.1 This review is amongst the most highly accessed during the pandemic, and it is imperative it is kept up to date with evidence from recent trials in the context of COVID-19, e.g. DANMASK.2 1. [S1-Guideline: Prevention of infection by wearing masks] Bartenschlager, Becker, Brandt, Dittmer, Eckerle, Liese, Mattner, Vogel, Wessels, Ziebuhr Deutsche Gesellschaft für Hygiene und Mikrobiologie, Gesellschaft für Virologie, Publication date: November 2020 2. https://clinicaltrials.gov/ct2/show/NCT04337541 | 3.1 Primary prevention interventions to modify behaviours or promote well-being / ESP | 6project_grants_public
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gen_a7e46f85eae7e2fb6d3fc75bf238e521 | Individual-level interventions for reducing occupational stress in healthcare workers | Department of Health and Social Care | AMC Medical Research B.V. | HRCS22_09169 | In the UK, one in ten workers are employed in health and social care. In 2020, 104,000 healthcare workers suffered from work-related stress, depression or anxiety. This is around half of all ill health among healthcare workers.(1) Financial and non-financial costs are high and quality of care is in jeopardy. Total economic costs are shared between individuals, employers and government/taxpayers. Preventing occupational stress among healthcare workers is therefore a priority. The review “Preventing occupational stress in healthcare workers” (2015; 41studies) found that cognitive behavioural therapy and mental and physical relaxation may reduce stress more than no intervention. This review has been used in WHO guidance (2) and also has the potential to guide future policy and practice. Its findings are dated and of low certainty, currently a major limitation. Therefore, this review needs to be updated, starting with individual-level interventions. We expect around 20 additional RCTs. The author team is experienced in conducting and updating Cochrane reviews in a timely manner and involves a representative of the population of interest. The lead author can dedicate working time when there is some funding available. References/Other: 1 Health and Safety Executive (HSE) (2020) Human health and social work activities statistics in Great Britain 2020. HSE. https://www.hse.gov.uk/statistics/ 2 World Health Organization, Wolf J., Prüss-Ustün, A., Ivanov I., Mugdal S. et al. ( 2018) . Preventing disease through a healthier and safer workplace. World Health Organization. https://apps.who.int/iris/handle/10665/272980. License: CC BY-NC-SA 3.0 IGO | 6.6 Psychological and behavioural / ESP | 6project_grants_public
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gen_fcad1299ca937d2d814e05a424d9ee70 | Semaphorin/plexin interactions in regenerative neurogenesis in zebrafish | Biotechnology and Biological Sciences Research Council | Technical University Dresden | HRCS22_10421 | Zebrafish, in contrast to mammals, show regeneration of neurons after spinal cord injury. The immune reaction to injury promotes regenerative neurogenesis in zebrafish, but how cross-talk between immune cells and neural progenitors occurs is poorly understood. We hypothesize that immune cells signal directly to neural progenitor cells via semaphorins to promote neurogenesis. In pilot studies using single cell RNAseq we determined that reactive macrophages show a 6-fold increase in sema4ab expression and that spinal progenitor cells express the receptors plexinb1a and plexinb1b after injury. We will determine spatiotemporal expression patterns of sema4ab and its ligands, and determine their functional roles by assessing progenitor cell proliferation and neuronal differentiation in mutants for ligand and receptors. To establish whether direct signalling occurs, we will expose neural progenitors to recombinant Sema4ab ex vivo and quantify regulation of neurogenesis-associated genes. To distinguish between effects in immune cell and neural progenitors, we will conditionally ablate plexinb1 function only in neural progenitor cells in vivo and determine regenerative outcome. This project will elucidate at the fundamental level if and how immune cells directly influence spinal progenitor cells after injury. This will provide targets for future interventions in non-regenerating mammals. | 1.1 Normal biological development and functioning / Responsive Mode | 6project_grants_public
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gen_7ce0f781326a413bf3e672a10718548d | Africa Research Universities Alliance, Centre of Excellence for Non-Communicable Diseases | Economic and Social Research Council | University of Nairobi | HRCS22_11558 | The project seeks to develop a strong collaborative research and training platform, the ARUA Centre of Excellence on Non-Communicable Diseases (ACE-NCD), anchored at five ARUA member universities: Nairobi, Makerere, Ibadan, Ghana and Witwatersrand - working closely with other universities on the continent and UK universities. Specifically, ACE-NCD shall seek to 1. Form a strong network of researchers broadly addressing the problem of NCDs in Africa. Researchers will be drawn from ACE-NCD universities, University of Glasgow and University of Leicester, as well as regional and international universities. Research teams' activities will revolve around six initial thematic areas: Prevention, mechanics of disease, multi-morbidity, bio-banking/biomarkers, models of care, and big data. 2. Bring on board other ARUA and non-ARUA African Universities, especially those that are less-research intensive. Each ACE-NCD spoke university will serve as a regional hub, actively engaging universities within their countries and regions: Ghana and Ibadan targetting West Africa, Nairobi and Makerere focussing on Eastern and Central Africa, and Witwatersrand on Southern Africa. Once on-board, these additional universities will actively collaborate with all members institutions across the continent and indeed the world. This approach will ensure the organic structured growth of the network leading to intra-Africa research capacity-building in NCDs. 3. Provide training and capacity-building in support of NCD research through Masters and PhD programmes (where students will be co-supervised by faculty drawn from the network) and post-doctoral training attached to existing and new research projects. 4. Develop and mount targeted short courses and capacity-building workshops and seminars offered both face-to-face and through e-learning. 5. Develop strong research collaborations with other global networks, initially with the World Universities Network where NCDs is one of its four key pillars and in which Nairobi and Ghana are active members with existing related research projects. 6. Build strong collaborations with African governments, policy-makers, non-university, research institutions, professionals, private sector players, and civil society through the regional hub approach for co-design and co-production to ensure relevance, usefulness, high quality of the research outputs. 7. Develop a vibrant research culture across the network, breaking down traditional silos within and across the member universities to form multi-institutional, multi-disciplinary research teams working to develop fundable high-impact research projects that address the challenges within the identified research themes. These projects will also build upon and strengthen on-going related research activities in member institutions. Supporting activities will include identification, dissemination and exploitation of funding opportunities, training on writing winning grant proposals, support in proposal preparation. | 2.6 Resources and infrastructure (aetiology) / Research Grant | 3networking_collaborative
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gen_114483ea722399c85085658dbff6b5fb | Demonstrating impact of mosquito-assisted larviciding (autodissemination) as a complementary malaria intervention in rural Tanzania | Wellcome Trust | Ifakara Health Institute | HRCS22_11808 | Long-lasting insecticide treated nets (LLINs) and indoor residual spraying (IRS) have significantly reduced malaria burden across sub-Saharan Africa [1], but are increasingly threatened by challenges such as mosquito resistance against common public health insecticides [2]. This necessitates innovative complementary tools to sustain the gains [3]. Mosquito-driven autodissemination of pyriproxyfen (PPF) has previously been demonstrated to effectively reduce populations of the dengue vector, Aedes aegypti in field trials [4, 5]. In recent years, we have demonstrated similar potential against dominant malaria vectors, Anopheles gambiae and An. arabiensis under semi-field settings in Tanzania [6, 7]. This approach could potentially complement disease control by targeting mosquitoes in aquatic habitats [8]. However, it still needs field-validation and optimization for low-income endemic communities. Here, I propose to optimize the PPF-autodissemination technology and demonstrate its entomological impact as a complementary intervention in Tanzanian villages where malaria persists despite widespread LLINs use. I will also simulate potential epidemiological impact and develop practical community-engagement approaches for scaling-up the technology. Unlike most insecticides for malaria control, Pyriproxyfen has lower resistance risk [9], and can control both susceptible and resistant mosquitoes through adult emergence inhibition and sterilization [10]. This project will cost-effectively accelerate overall malaria elimination goals. | 3.2 Interventions to alter physical and biological environmental risks | 6project_grants_public
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gen_5c12662be0c6811f00de24a36bf7ab34 | Skills Developments Grant - Travel award - Advances in Ewing Ssarcoma Research conference 14 October 2022 | Bone Cancer Research Trust | Essen University Hospital | HRCS22_11840 | Poster presentation: ATR inhibitors in Ewing Sarcoma – Targeting DNA damage repair | 5.1 Pharmaceuticals | 1fellowships_scholarships
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gen_5ee5639c77f625a091c5c8c530ac627a | Skills Developments Grant - Travel award - Advances in Ewing Ssarcoma Research conference 14 October 2022 | Bone Cancer Research Trust | Georgetown University | HRCS22_11851 | Oral presentation: Neuropeptide Y and its Y5 receptor in Ewing sarcoma metastasis | 2.1 Biological and endogenous factors | 1fellowships_scholarships
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gen_bf2fe0f960ab3ef9cf072c371ec0152d | Gordon Research Conference | Ataxia UK | McMaster University | HRCS22_11882 | Sponsorship of CAG Triplet Repeat Disorders Gordon Research Conference and Seminar 2023 | HRCS Research Uncodeable | 3networking_collaborative
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gen_0ea836ee661b74669e424848b841d63b | OA fee for terminated award | Wellcome Trust | Stellenbosch University | HRCS22_11931 | In South Africa, where access to mental health services is poor, the risk of developing mental health issues among children and adolescents is high. Accordingly, there is an urgent need to implement cost-, and time-effective interventions to address these issues in child-friendly, and child-accessible settings. Evidence suggests that CBT-based interventions have potential to mitigate the onset of mental illness by addressing symptoms of anxiety and depression in younger children, and thus may be considered primary preventative interventions. We aim to determine the acceptability and feasibility of a culturally-specific and context-sensitive CBT-based psychoeducational programme to support psychological well-being amongst children and adolescents (11-14 years) in an impoverished area of the Western Cape. As such, our study seeks to develop (using core CBT principles of existing evidence-based programmes) a school-based universal intervention to reduce symptoms of anxiety and depression amongst adolescents and to determine if this intervention is acceptable and can feasibly be delivered by NGO school-based counsellors. We will: 1. Develop a CBT-based intervention programme for anxiety and depression. 2. Train NGO counsellors to deliver and pilot the intervention to primarily establish feasibility and acceptability, and, as a secondary outcome, preliminary effectiveness at reducing symptoms of anxiety and depression. | 6.6 Psychological and behavioural | 6project_grants_public
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gen_72b562c447ae0b7f17d5243434562dd2 | TUF Urolink Fellowship | The Urology Foundation | Unknown | HRCS22_11938 | Visit to University Teaching Hospital, Lusaka, Zambia | HRCS Research Uncodeable | 1fellowships_scholarships
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gen_739095f6c25491109758813620f0670e | OA fee for Innovator Award | Wellcome Trust | Rare Partners (Italy) | HRCS22_11950 | The availability of funding will allow completion of a first exploratory clinical trial on sirolimus. This would be the first trial with the drug in thalassemia, will involve about 20 patients and will explore a surrogate end point known as an important point in thalassemia, namely HbF. The trial will also explore other end points, trying to evaluate meaningful clinical end points at a preliminary stage. The final goal of the project is a substantial decrease of the transfusion need, of great interest for the thalassemia patients. A reduction of transfusion need would dramatically improve the quality of life and reduce the iron overload, caused by repeated transfusions of red blood cells. The strategy for the future clinical development of sirolimus in thalassemia will be designed taking into account the results of this first pivotal trial. An additional important output of the study of particular significance would be the advancement toward personalised medicine (ex vivo test to predict in vivo results) and the possible combination of agents acting on HbF to improve treatment approaches. The available data, obtained so far in vitro on human preparations, strongly support this view and would be confirmed and expanded by the planned experiments. | 5.2 Cellular and gene therapies | 6project_grants_public
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gen_e86be71603b0f1c86b31a51e8b816180 | Open access for terminated award | Wellcome Trust | Fred Hutchinson Cancer Center | HRCS22_11959 | Oral cholera vaccines (OCV), administered in two doses, have emerged recently as a powerful tool for short-term outbreak control. When resources are limited, single-dose vaccination has been used as a way to stretch the supply, however, previous studies have shown that a single dose of vaccine is less effective, and wanes faster. In addition, studies have shown reduced effectiveness of the OCV in children under five years old, who are disproportionally affected by cholera. Determining who, how, and when to vaccinate are pressing decisions that public health officials usually take during an unfolding epidemic, often resulting in a sub-optimal use of resources. We will use mathematical models paired with optimization algorithms to determine optimal vaccine allocation, thereby providing public health officials with an evidence-based rationale for vaccine distribution. Our specific aims are: 1) To construct data-driven mathematical models of cholera transmission, infection and vaccination. 2) To determine optimal vaccine allocation strategies. 3) To develop and disseminate a free, user-friendly, decision-making tool to inform public health officials, in real time, about the best use of limited OCV supplies. This research will benefit countries with scarce resources for which making the best use of each dose of vaccine is a top priority. | 3.4 Vaccines | 6project_grants_public
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gen_ad49e314a76030fb3c296c7d3a6010c3 | Open access for terminated award | Wellcome Trust | Associação Brasileira de Saúde Coletiva | HRCS22_12000 | No abstract available for this analysis | HRCS Research Uncodeable | 5out_of_scope
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gen_c067ed8dbbb26d95c34f21714301083d | Identification of key immunogenic post-translational modifications in Trichohyalin: a potential major autoantigen in Alopecia Areata | Alopecia UK | University College Dublin | HRCS22_12096 | This project is aimed at discovery of HF-associated autoantigens in AA. Strong evidence for TCHH as a major AA autoantigen in humans as well as in several other mammals is intriguing. Given that TCHH is a substrate for immunogenic PTMs citrullination and deamidation, we speculate that there might be an abnormal immune response against normal antigens that becomes immunogenic at a certain stage of their maturation i.e., during early stages of anagen. We hypothesize that in the initial stages of TCHH maturation, either before or during loss of immune-privilege (IP), key PTMs in TCHH may prompt an active immune response against anagen HF in AA. The presentation of modified TCHH peptides on MHC molecules locally could be an initial activation event of the (auto)immune response in AA. To evaluate this hypothesis, we aim to address the following key questions in this proposal. 1. Which amino acid residues undergoes citrullination and deamidation modifications in TCHH during its maturation in the IRS during anagen? 2. Which post-translational modifications in THH could be potentially immunogenic? 3. Will theimmunogenic peptides identified(in 2 above)be able to induce cellular and antibody immunoreactivity in AA? | 1.1 Normal biological development and functioning | 6project_grants_public
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gen_02f0665c6fa261e36b02cb73dcb0ea86 | Decoding Genetic Studies from Pakistan - A Review of International, Regional and Local Guidelines and Compliance. | Wellcome Trust | Aga Khan University | HRCS22_12151 | I conducted research for my Masters thesis to explore, identify and examine ethical guidelines available for genetic studies and to then analyse and describe the extent to which researchers in Pakistan, comply with existing ethical standards specified for genetic research. I report in my thesis that there are no guidelines for genetic research, gene therapy or gene editing in Pakistan. I also found some other patterns in the studies reviewed that I would like to present in the form of a publication in a peer reviewed journal as I feel they will provide a foundation of behavioural practises of researchers in Pakistan. I would also like to use the findings as a starting point to develop and propose guidelines for researchers for genetic research, gene therapy and gene editing in Pakistan. I want to propose guidelines that can be incorporated effectively into practise for which I will need to identify effective training, implementation and monitoring of the guidelines. Key goals: 1. Develop a better understanding of the ethical review process of international collaborations in the UK 2. Produce a draft of a paper for submission to a peer reviewed journal 3. Propose an outline of guidelines for researchers in Pakistan | No Research Activity assigned | 1fellowships_scholarships
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gen_d44bb0eeec670b5039b1042c16dfeef5 | Analysis of the mitochondrial dysfunction in FXN deficient neurons to generate a drug screening test | Ataxia UK | Spanish National Research Council | HRCS22_12153 | The main genetic cause of Friedreich’s ataxia (FA) is a GAA triplet expansion within the first intron of the frataxin (fxn) gene. More than 30 repetitions are considered pathogenic, and most FA patients have 600-900 repeats. Most FA animal models show very mild phenotype, likely due to the difficulty in recreating the pathological expansion. To address this, Jackson laboratories have developed a new humanized mouse model using a human YAC FXN with more than 800 GAA repeats, on a mouse fxn knockout background – the YG8JR model. This mouse model is still being characterised, but evidence so far suggests that it better mimics the ataxia phenotype seen in people with FA. Cerebellar granular neurons (CGNs) are affected in FA, and others have shown mitochondrial dysfunction and deficits in energy production in these cells in other models. Dr Herranz Martín and colleagues plan to use this mouse model to characterize the dysfunction in the mitochondrial respiration in CGN. Their aim is to select a few defective mitochondrial parameters which can be used as a quick readout for FA drug screening. | 2.1 Biological and endogenous factors | 6project_grants_public
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gen_cbfad69536755c5eb5f0e3a0bfdaf899 | Motor and cognitive outcomes of non-invasive transcranial alternate current stimulation by entrainment of cerebellar oscillations | Ataxia UK | University of Brescia | HRCS22_12176 | Transcranial alternative current stimulation (tACS) is a non-invasive brain stimulation technique, which is thought to modulate physiologically relevant brain oscillations by a desired frequency. Cerebellar ataxias are characterised by loss of Purkinje cells, which have been shown to oscillate in the gamma frequency band (30-80Hz) (Zhurhaj et al., Eur J Neurosci, 2005). In this study, the Dr Borroni and colleagues will evaluate whether a single 60 minute session of cerebellar tACS at gamma frequency (50Hz) is superior to cerebellar tDCS or sham treatment at improving motor and cognitive outcomes. They will perform a triple-cross over study, with all patients receiving tACS, tDCS or sham treatment in a randomized order. The researchers will use two clinical rating scales to assess the treatments: the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). They will also use wearable sensors so that they can measure more subtle changes in ataxia. In particular, they will look at changes in participant’s steps and the smoothness of movements. This study will help determine whether tACS could be a more effective brain stimulation technique for ataxia for use in future trials. | 6.5 Radiotherapy and other non-invasive therapies | 6project_grants_public
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gen_581ce066bd7ee036e9a34e41e3c45b87 | Advancing African Neuroscience Report | Wellcome Trust | University of Cape Town | HRCS22_12201 | The purpose of the Showcasing African Neuroscience meeting was to facilitate a dynamic and interactive stakeholder engagement process that would: highlight the best examples of research in basic and clinical African neuroscience, explore potential for enhancing the interface between them in the African research-context, and provide a platform to highlight the significant potential for new discovery from within the continent. Wellcome Trust supports a wide range of research, looking for potential areas of growth and opportunity, globally. Potential in the African neuroscience research-landscape was identified as one such area. Through conversations, a survey with African neuroscientists, and assistance from other groups already embedded in this landscape, the concept for a strategic meeting was born, with the aim of showcasing exciting neuroscience in African ecosystems, articulating prevailing challenges, and discussing ways to overcome them. The African neuroscience community led the engagement process, with support from Wellcome. A subsequent series of workshops drilled further into issues raised, starting discussions on how best to address them. This report builds on these discussions. In it, we highlight early advances in neuroscience research in Africa, and outline a framework for further development of African neuroscience to explore the unique challenges facing brain health and development. | 2.6 Resources and infrastructure (aetiology) | 3networking_collaborative
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gen_302bffaf5ea5325e4e91c04354d17b21 | Opinions of patients with psychosis, caregivers and key stakeholders on informed consent for research involving people with mental health conditions | Wellcome Trust | University of Botswana | HRCS22_12234 | Research involving people with mental health conditions (PWMHC) has its unique ethical challenges. Conducting research among human participants requires obtaining informed consent. However, PWMHC may have impaired decision-making capacity, which may invalidate consent. Often, surrogates are resorted to for consent which may undermine the autonomy of PWMHC. As a result, this study investigates participants' opinions from Low-and-Middle Income Countries (LMICs) on informed consent for research involving PWMHC. It is expected that the outcome will contribute to academic literature and discussions on this issue. This study will be in three stages. The first will be a systematic review of empirical studies on informed consent for research involving PWMHC. This will guide the second study, which will utilise qualitative methods to explore the views of patients with psychosis and their caregivers on informed consent for research involving PWMHC. In-depth interviews will be conducted among 15 patients and caregivers dyads who will be purposefully selected from Sbrana Psychiatric Hospital (SPH) in Botswana. The third will involve in-depth interviews with 15 key stakeholders involved in mental health research and policy. Data will be collected using an interview schedule developed and piloted by the researchers and analysed with the NViVo Software using the Framework Method. | 8.3 Policy, ethics and research governance | 6project_grants_public
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gen_66b93a78d1bdd82b873b841ca728e463 | NanoSCA3: Development of brain-targeted nanobodies for application in spinocerebellar ataxia type 3 therapy | Ataxia UK | i3S consortium | HRCS22_12235 | SCA3 is caused by the expansion of a polyglutamine segment in the ataxin-3 protein, which accumulates protein aggregates. Small variable domains of camelid heavy-chain-only antibodies, known as nanobodies, show promise as therapeutic anti-aggregation agents for other neurodegenerative disorders, such as Parkinson’s Disease, Huntington’s Disease and Alzheimer’s Disease. This group holds a collection of ataxin-3-targeting nanobodies, seven of which impact on pathogenic ataxin-3 aggregation in vitro. In this project, they will investigate the neuroprotective potential of these nanobodies in cellular and Drosophila models of SCA3. Promising nanobodies will be engineered for blood brain barrier transmission and optimised for safe use in humans. If this project is successful, then these optimised nanobodies would then need to be tested in SCA3 mouse models, before eventually being tested in a clinical treatment trial in people with SCA3. | 5.1 Pharmaceuticals | 6project_grants_public
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gen_6fce11c9c8b47b6bee4d40bf4f715117 | Identifying ethical issues in conducting research with transwomen in India | Wellcome Trust | George Institute for Global Health | HRCS22_12258 | Research on trans communities including transwomen is extremely limited in India, inspite of the huge social and political injustices that they have suffered over ages. Trans communities are often a closed community and in India many of them become part of 'gharanas'. The gharana system is an institutionalized lifestyle, which defies the heteronormative idea of a family and is a place that makes transgenders feel safe and confident in their expression of identity. However, not everyone belongs to a gharana. In this project we will collaborate with a transwoman-led non-governmental organization in Kolkata, India. The main objective is to understand the ethical challenges of conducting research on transwomen and to develop a framework for undertaking ethical research with transwomen in India using qualitative research methods. We will interact with transwomen, understand ethical issues in conducting research with transwomen and identify and validate an appropriate ethical framework in consultation with transwomen using qualitative research methodology. We will use a feminist approach and the standpoint theory that postulates that an individual's perspectives are shaped by their social and political experiences. Narrative analysis of the qualitative data will be used to develop the final ethical framework in consultation with transwomen, prior to dissemination. | No Research Activity assigned | 6project_grants_public
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gen_ae0ace450b4fb3919b3389caaca3094d | The role of governance and ethical considerations of mental health research on children and adolescents: A pragmatic framework using mixed method Delphi process | Wellcome Trust | Jos University Teaching Hospital | HRCS22_12272 | The prevalence of children and adolescents (C&A) with mental health conditions is increasing globally. More attention is given to infectious diseases and a paucity of mental health research on C&A exists. This area remains neglected because of lack of effective governance, particularly in LMICs. Effective C&A mental health system is dependent on research governance structures, necessitating the need for an effective governance framework which guides ethical considerations in research and health systems for C&A. This study aims to assess the extent to which governance frameworks impacts mental health research on C&A, identify governance framework beneficial for C&A in LMICs and generate a consensus that examines indicators which guide ethical practice and good governance. A systematic review will be used to identify existing governance framework. Thereafter, a mixed method Delphi process comprising minimum 30 experts who meet the following criteria: diversity of expertise, independence, decentralization, and aggregation from LMICs and HICs across the six regions of the World Health Organization will be used to determine a consensus for effective governance for mental health research on C&A. Outputs generated from this study will be disseminated via seminars/ webinars conferences, publications, and academic and non-academic meetings to facilitate adoption by stakeholders and policymakers. | 8.3 Policy, ethics and research governance | 6project_grants_public
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gen_5d50dc46398fcdc8edba60e4878bece0 | A randomised, single blinded, prospective study to compare simulated daylight photodynamic therapy with natural daylight photodynamic therapy for treatment of actinic keratoses. | British Skin Foundation | St. Vincent's University Hospital | HRCS22_12286 | Actinic keratoses (AKs) are dysplastic epidermal lesions considered to be potential precursors of squamous cell carcinoma (SCC). Various studies have 2011 and 2015 inclusive there were 70 deaths per year attributed to keratinocyte cancers. Thus treatment of AKs prior to conversion to SCC is important. Photodynamic therapy (PDT) is a widely approved therapy for AKs. A protocol using daylight to treat AKs is widely practised. Daylight PDT (d-PDT) is very dependent on geographical location (latitude), weather conditions and time of year. It has to date been studied mostly in Nordic countries. In Denmark, a country at similar latitude to Ireland (55 degrees versus 53 degrees north) it is only possible to perform d-PDT from April to October due to low temperatures. Conventional PDT (c-PDT) is an alternative to d-PDT outside of these months but the main drawback for patients is pain. As a result, patients prefer d-PDT and in fact in Copenhagen, where they routinely offer d-PDT from April to October they have found that patients will frequently opt to defer their treatment until a time of year when d-PDT is an option. Artificial white light (AWL) has been investigated as an alternative PDT treatment to overcome this. We propose that a treatment room with 4000K white light LED flood lamps which would be orientated to provide uniform power distribution across treatment areas would mimic d-PDT and enable us to effectively treat AKs year round. | No Research Activity assigned | 6project_grants_public
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gen_e5cbf809314bead4da65e98371267b99 | Opend Data Commons Spinal Cord Injury | Spinal Research | University of Alberta | HRCS22_12288 | Workshop to provide information and training on Open Data Commons on SCI to all in the filed. | HRCS Research Uncodeable | 3networking_collaborative
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gen_22f090e2c04a8004ccaa0bc097434243 | Exploring the feasibility, acceptability and potential impact of an ultra-brief online well-being programme for caregivers of children with tuberous sclerosis complex (TSC) in South Africa and the United Kingdom | Tuberous Sclerosis Association | University of Cape Town | HRCS22_12292 | Background. To date, very little attention has been given to the mental health and well-being of caregivers of children with disabilities and chronic conditions, including caregivers of children with tuberous sclerosis complex (TSC). Acceptance and commitment therapy (ACT) has shown promise in improving the well-being of caregivers of children with complex needs. Objectives. Our pilot study will explore the feasibility, acceptability, and potential impact of a 3-session online caregiver well-being programme (Well-Beans for Caregivers Programme). Methods. Local TSC organisations and advocates will review the programme materials and protocol before the study commences. The identified community hubs will also assist with the recruitment of caregivers of children with TSC (aged 2 to 11), living in either South Africa or the United Kingdom. The programme will be delivered online by two trained facilitators to a group of 10 caregivers and two observer trainees. The group will meet once a week for 3 weeks. Using an electronic data collection platform, feedback will be sought from caregivers, facilitators, and observers after each session. Additionally, caregivers will complete a set of wellness forms (pre-, post, and follow-up). All participants will join a focus group after programme completion. To increase the scientific rigour of the study, the programme will be delivered twice, with the second group acting as the waitlist control for the study. Outcomes. We will use various measures and focus groups to gather quantitative and qualitative data from multiple informants. This small scale study is an important first step in finding scalable and sustainable ways to support the well-being of caregivers with children with TSC. Importantly, it addresses the following identified gaps in TSC research: (1) research from a low/middle-income country, (2) non-pharmacological intervention research focused on caregiver wellness, (3) qualitative research, and (4) utilising technologies to increase the accessibility of support to families. | 6.6 Psychological and behavioural | 6project_grants_public
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gen_9dea8c67c35d45933af769c06614fecc | Aetiologies, clinical presentation and neuro-cognitive outcomes of non-HIV associated encephalitis in Cameroon - exploring a neglected disease in a low income African country. | The Encephalitis Society | Filariasis and other Tropical Diseases Research Centre (CRFilMT) | HRCS22_12332 | Acute infectious encephalitis is a frequent infectious disease associated with high mortality rates. It is caused by different etiologic agents and manifests with a wide range of clinical signs. Encephalitis management guidelines in low- and middle-income countries (LMIC) are limited by the absence of local epidemiological data leading to delays or even absence of adequate treatment. Today’s empirical treatment based on non-specific signs and symptoms is a “blind” treatment strategy contributing to mortality. Therefore, there is an urgent need to identify the etiological agents of encephalitis in LMIC. We intend to investigate the aetiologies and pathogen-specific elements in the clinical presentation of encephalitis in HIV-negative adults from urban and rural areas in Cameroon. To achieve this goal, we will perform microbiologic analysis on cerebrospinal fluid, as well as inflammatory, biochemical, and cerebral imaging. Additionally, we will describe survival rates, and outcomes of encephalitis in terms of physical and neuropsychological sequelae. Finally, we will associate these clinical observations with the pathogen type, initial radiologic findings. The results will allow us to adapt diagnostic algorithms and treatment protocols to the regional variations in pathogen distribution. They will also emphasize the need for long-term follow-up and rehabilitation of survivors | 4.2 Evaluation of markers and technologies | 6project_grants_public
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gen_a14710be55e22900e602294257c2f45a | Getting ready to solve the unsolved for SLC26A4 | Royal National Institute for Deaf People | Radboud University Nijmegen Medical Centre | HRCS22_12333 | [none] | 2.1 Biological and endogenous factors | 6project_grants_public
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gen_1397089b0e2f0dcf8974ad882f290bbe | Developing a novel host transcript-based test to diagnose scrub typhus in children with acute encephalitis syndrome | The Encephalitis Society | National Institute of Mental Health and Neurosciences | HRCS22_12359 | Encephalitis, swelling or inflammation of the brain, is a serious global health problem, leading to death of up to one-third of people affected by it, and around half of survivors not recovering fully. Recent research has shown scrub typhus as a major cause of encephalitis in children in India. Scrub typhus is an infection caused by bacteria that affects around 1 million people each year, especially in southeast Asia. Early diagnosis of scrub typhus encephalitis is important, as it is treatable, so starting antibiotics early can prevent death and long-term health problems. Currently, scrub typhus diagnostics have problems (such as delays in performing lumbar puncture) that can lead to results being slow and/or unreliable. This research will start to address these challenges. I will examine the body’s responses (host transcripts) in the blood of children with scrub typhus encephalitis. I will compare these responses to those of patients with other causes of encephalitis and clinically similar brain infections. I will identify patient transcript responses unique to scrub typhus brain infection and use these transcripts to begin to develop a fast and accurate diagnostic blood test for scrub typhus encephalitis This test will offer prompt and accurate diagnosis, leading to earlier appropriate treatment and improved patient outcomes. | 4.2 Evaluation of markers and technologies | 6project_grants_public
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gen_9f94ce80c375c26954cef1b127471e4a | Physiological characteristics of stimulation sites in auditory brainstem and cochlear implants | Royal National Institute for Deaf People | New York University | HRCS22_12365 | No abstract available for this analysis. | No Research Activity assigned | 6project_grants_public
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gen_c731116f5cb1d58c832f38a7ae8ca4a4 | Role of striatum in tinnitus pathophysiology | Royal National Institute for Deaf People | National University of Central Buenos Aires | HRCS22_12366 | No abstract available for this analysis. | No Research Activity assigned | 6project_grants_public
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gen_92401146eaf24fc58fdf847ced2d747f | iPSC-derived human spiral ganglion models: a pilot study | Royal National Institute for Deaf People | University of Zurich | HRCS22_12367 | [none] | 1.1 Normal biological development and functioning | 6project_grants_public
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gen_c71c4a42b096f7c7b55fbb36bf74de3a | Targeting cellular senescence to slow age-related hearing loss | Royal National Institute for Deaf People | University Medical Center Groningen | HRCS22_12368 | [none] | 2.1 Biological and endogenous factors | 6project_grants_public
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gen_6c817fc243ef9a3f0cf66bdcfaff8b93 | Mechanism-based Approach to Optimization of Noise Reduction in Hearing Aids: Influence of Individual Traits on Outcomes and Preference | Royal National Institute for Deaf People | Purdue University System | HRCS22_12369 | [none] | 1.2 Psychological and socioeconomic processes | 6project_grants_public
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gen_d616e1269ff8fb481c15e8046e452221 | Study of otos genes expression and function in the zebrafish inner ear | Royal National Institute for Deaf People | Mount Desert Island Biological Laboratory | HRCS22_12370 | No abstract available for this analysis. | No Research Activity assigned | 6project_grants_public
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gen_6956ecca0f9c41477114e28cd48ac1cd | Assessment of hearing disability in children with auditory neuropathy using novel objective methods | Royal National Institute for Deaf People | Bionics Institute | HRCS22_12371 | [none] | 2.1 Biological and endogenous factors | 6project_grants_public
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gen_be95528c11f43eec9c3d52fd6b91a711 | Investigating the dysregulation of cellular metabolism in hidradenitis suppurativa patients and whether metformin can reverse this altered metabolism | British Skin Foundation | Trinity College Dublin | HRCS22_12383 | Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting approximately 1% of the population. It is characterised by painful nodules and lesions in intertriginous areas of skin. Despite having similar prevalence to psoriasis, the disease is under-recognised, under-diagnosed and its pathogenesis is poorly understood. As a result, treatment options are limited and inadequate, and there is a pressing need for research into its pathogenesis to yield better treatment options. In recent years, immunometabolism has emerged as a major research field, since it became apparent that immune cell function is regulated via metabolic pathways. Although at the centre of other inflammatory diseases, no studies have investigated a dysregulated cellular metabolism in HS. Hence novel therapeutic targets may be uncovered. Furthermore, metformin, which can modulate cellular metabolism has demonstrated efficacy in treating HS. Our preliminary data showed that metabolism was dysregulated in the peripheral blood of HS patients. In addition, transcriptomic analysis of skin samples revealed striking differences in metabolic pathways in lesional HS skin compared with healthy skin. We will confirm our preliminary data showing dysregulated metabolism in peripheral blood of HS patients and identify the specific immune cell type/s responsible. We will then determine whether metformin treatment is associated with a reversal of the altered metabolism in HS. Finally, using available single cell RNA-sequencing data, we will further analyse altered expression of metabolic genes and pathways in HS lesional skin. This study will identify metabolic pathways that may be dysregulated in HS and represent potential therapeutic targets. | 2.1 Biological and endogenous factors | 6project_grants_public
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gen_b11ccc745636637bf2303c58b440e910 | Data-driven drug discovery for AT – interrogation of dysfunctional pathways at single-cell resolution in cerebellar organoids | Ataxia-Telangiectasia Society | QIMR Berghofer Medical Research Institute | HRCS22_12390 | Interrogation of dysfunctional pathways at single-cell resolution in cerebellar organoids | 1.1 Normal biological development and functioning | 6project_grants_public
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gen_17e5b3f919876a82f19877c0946da0d0 | Study of natural killer cells in AT pathogenesis and their therapeutic implications | Ataxia-Telangiectasia Society | University of Rome Tor Vergata | HRCS22_12391 | Study of natural killer cells in AT pathogenesis and their therapeutic implications | 2.1 Biological and endogenous factors | 6project_grants_public
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gen_fb15e591049c7d9e4d03dacf038216bb | Implementing an hospital-based encephalitis surveillance in Senegal to decipher main causes of viral encephalitis in a West-African Low-Income Country. | The Encephalitis Society | Institut Pasteur de Dakar | HRCS22_12397 | The main objective of the project is to characterize the aetiology and the clinics of the encephalitis hospitalized in Senegal. To reach this objective, three specific aims have been identified: Specific aim 1: Detect and estimate prevalence of the different viruses associated to encephalitis. Specific aim 2: Describe the clinical features specific to each viral infection and the population under investigation | 2.1 Biological and endogenous factors | 6project_grants_public
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gen_310f131b168c26beedde33e215fd4a0e | Genetics of Mitochondrial Diseases | Medical Research Foundation | Venetian Institute of Molecular Medicine | HRCS22_12411 | In “Mitofight” we are engaged in developing suitable therapeutic approaches against mitochondrial disorders in mouse models with a particular but not exclusive emphasis on Pearson syndrome and related conditions associated with instability of mtDNA. The creation of mouse models has to be followed by their characterisation in vivo and ex vivo, and eventually, to the evaluation of any beneficial effect induced by therapeutic strategies. In order to accomplish these goals Massimo Zeviani started his laboratory at VIMM dedicated to the investigation of our mouse disease models both in their behaviour (locomotor proficiency, orientation in space, cognitive functions) and after their culling (to study pathological changes in different tissues). In the frame of this project, we have characterized a knockin mouse reproducing the most common recessive mutation in the mitochondrial DNA Polymerase (POLGA467T). We demonstrated that the mutant POLG has severely impaired DNA binding, polymerase, and proofreading activities. In addition, mutant protein has reduced affinity for the accessory subunit POLG2, which makes POLG amenable of degradation by the LONP1 protease. This study highlights a new mechanism contributing to the pathogenesis of POLG-related disorders. In addition, we have produced a Y955C mouse model reproducing the most common dominant mutation of the patients. The initial characterization of this model showed that the mutant homozygous mice were embryonic lethal with complete penetrance. In contrast, the heterozygous did not show any obvious clinical phenotype. Post-mortem analysis showed only a partial increase of mtDNA content in skeletal muscle and liver in KI vs WT littermates. Older animals (around two years of age) showed spongiosis in several brain areas and inflammatory infiltrates in skeletal muscle. No major phenotypes were observed in other organs, such as liver, kidney and heart. No mtDNA 2 depletion or deletions were observed in any organ. In order to trigger a more severe phenotype, we challenged two-year old Y933C mice with a high-fat, ketogenic diet, for two months. No differences were observed between wild-type and mutant animals. We also tried to challenge the animals by administering AZT, a nucleoside analogue which causes mtDNA depletion in humans, in the drinking water, but again, we did not observe any obvious effect on the clinical phenotype or on mtDNA amount/quality. In collaboration with Maria Falkenberg, University of Gothenburg, we investigated the molecular pathogenesis of the mouse Y933C and humanY955C mutations in vitro. The data are clearcut and show that both mutant proteins have a DNA binding capacity similar to the wildtype counterparts, but that capacity to incorporate nucleotides is severely impaired. In addition, we demonstrated that the mutant protein has a dominant effect and inhibits the wild-type form. Future studies will be aimed at using additional challenges to trigger a more severe phenotype (eg: inducing fever by LPS administration) and in developing gene editing approaches to correct the mutation. | 2.1 Biological and endogenous factors | 6project_grants_public
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gen_65f565f0cd0cd67973b42941e739ad1e | Depression Update: Dissemination Activiies | Wellcome Trust | Fundmed Pesquisa, Ensino e Inovacao | HRCS22_12423 | A Lancet-World Psychiatric Association Commission on Depression reflecting the work developed over three years by a group of world experts was launched in February 2022. The Commission's state of the art overview of depression provides a timely and unique opportunity for dissemination of knowledge and awareness-raising activities regarding depression. Key goals: 1) Support the organization of a global Commission launch webinar (completed February 16, 2022); 2) Organize and support regional webinars focusing on state of the art knowledge on depression involving policy makers, researchers, individuals with lived experience of depression, and clinicians; 3) Provide materials for dissemination of state of the art knowledge on depression by the World Psychiatric Association and other key partners. | No Research Activity assigned | 3networking_collaborative
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