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Design and selection of drug properties to increase the public health impact of next-generation seasonal malaria chemoprevention: a modelling study.
Get PDFBACKGROUND: Seasonal malaria chemoprevention (SMC) is recommended for disease control in settings with moderate to high Plasmodium falciparum transmission and currently depends on the administration of sulfadoxine-pyrimethamine plus amodiaquine. However, poor regimen adherence and the increased frequency of parasite mutations conferring sulfadoxine-pyrimethamine resistance might threaten the effectiveness of SMC. Guidance is needed to de-risk the development of drug compounds for malaria prevention. We aimed to provide guidance for the early prioritisation of new and alternative SMC drugs and their target product profiles.
METHODS: In this modelling study, we combined an individual-based malaria transmission model that has explicit parasite growth with drug pharmacokinetic and pharmacodynamic models. We modelled SMC drug attributes for several possible modes of action, linked to their potential public health impact. Global sensitivity analyses identified trade-offs between drug elimination half-life, maximum parasite killing effect, and SMC coverage, and optimisation identified minimum requirements to maximise malaria burden reductions.
FINDINGS: Model predictions show that preventing infection for the entire period between SMC cycles is more important than drug curative efficacy for clinical disease effectiveness outcomes, but similarly important for impact on prevalence. When children younger than 5 years receive four SMC cycles with high levels of coverage (ie, 69% of children receiving all cycles), drug candidates require a duration of protection half-life higher than 23 days (elimination half-life >10 days) to achieve reductions higher than 75% in clinical incidence and severe disease (measured over the intervention period in the target population, compared with no intervention across a range of modelled scenarios). High coverage is crucial to achieve these targets, requiring more than 60% of children to receive all SMC cycles and more than 90% of children to receive at least one cycle regardless of the protection duration of the drug.
INTERPRETATION: Although efficacy is crucial for malaria prevalence reductions, chemoprevention development should select drug candidates for their duration of protection to maximise burden reductions, with the duration half-life determining cycle timing. Explicitly designing or selecting drug properties to increase community uptake is paramount. FUNDING: Bill & Melinda Gates Foundation and the Swiss National Science Foundation
How age and sex affect treatment outcomes for children with severe malnutrition: A multi-country secondary data analysis.
Get PDFAge and sex influence the risk of childhood wasting. We aimed to determine if wasting treatment outcomes differ by age and sex in children under 5 years, enroled in therapeutic and supplementary feeding programmes. Utilising data from stage 1 of the ComPAS trial, we used logistic regression to assess the association between age, sex and wasting treatment outcomes (recovery, death, default, non-response, and transfer), modelling the likelihood of recovery versus all other outcomes. We used linear regression to calculate differences in mean length of stay (LOS) and mean daily weight gain by age and sex. Data from 6929 children from Kenya, Chad, Yemen and South Sudan was analysed. Girls in therapeutic feeding programmes were less likely to recover than boys (pooled odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.72-0.97, p = 0.018). This association was statistically significant in Chad (OR: 0.61, 95% CI: 0.39-0.95, p = 0.030) and Yemen (OR: 0.47, 95% CI: 0.27-0.81, p = 0.006), but not in Kenya and South Sudan. Multinomial analysis, however, showed no difference in recovery between sexes. There was no difference between sexes for LOS, but older children (24-59 months) had a shorter mean LOS than younger children (6-23 months). Mean daily weight gain was consistently lower in boys compared with girls. We found few differences in wasting treatment outcomes by sex and age. The results do not indicate a need to change current programme inclusion requirements or treatment protocols on the basis of sex or age, but future research in other settings should continue to investigate the aetiology of differences in recovery and implications for treatment protocols
Factors associated with initial AstraZeneca vaccine knowledge, attitudes, and uptake among hospital nurses: A cross-sectional study in Ghana's Upper East region.
Get PDFThe COVID-19 pandemic has caused over 171,657 confirmed cases and 1,462 deaths in Ghana, particularly among frontline health-workers involved in pandemic response. Prevention measures in Ghana include AstraZeneca 'Covishield' vaccination of health-workers, but research on factors affecting uptake of COVID-19 vaccines in Ghana were initially limited. Therefore, this study aimed to analyse knowledge, attitudes, and initial uptake of Covishield among nurses in the War Memorial Hospital in Navrongo, Upper East Region. We conducted a cross-sectional survey of 128 district hospital nurses using simple random sampling. We first calculated descriptive statistics and two composite variables summing either participant knowledge or attitude variables, with a threshold over 50% considered 'sufficient' or 'positive' respectively. We then analysed associations between demographic variables and Covishield knowledge, attitudes, or uptake using binomial logistic regression with a 95% confidence interval and p-value of <0.05 considered significant. All participants had heard of Covishield vaccine, with attitudes toward it generally positive (53%), and uptake high (72%). Reasons cited by the 28% unvaccinated included absence during vaccination, having already been infected with COVID-19, lack of trust in vaccine safety/efficacy, or pregnancy/breastfeeding. Education, residence, and family type were the only demographic factors significantly associated with nurses' knowledge about, attitudes towards, or uptake of COVID-19 vaccination. While 'positive' attitude was significantly associated with higher odds of being vaccinated (AOR 4.75; 95%CI 1.59-14.1), 'sufficient' knowledge was not (AOR 1.33; 95%CI 0.53-3.32). This is the first study in Ghana's resource-constrained Upper East region to examine health-worker perceptions of a novel vaccine and showed nurses' knowledge, attitudes, and uptake of COVID-19 vaccination were good overall. Further research is needed to determine how best to address hesitancy and understand findings that attitudes appeared more relevant than knowledge for uptake. Findings are relevant for local health authorities in improving vaccine availability and strengthening emergency risk communication and management of adverse events following immunisation
Patient and public involvement in abortion research: reflections from the Shaping Abortion for Change (SACHA) Study.
Get PDFPatient and public involvement (PPI) is limited within abortion-related research. Possible reasons for this include concerns about engaging with a stigmatised patient group who value confidentiality and may be reluctant to re-engage with services. Structural barriers, including limited funding for abortion-related research, also prevent researchers from creating meaningful PPI opportunities. Here, we describe lessons learnt on undertaking PPI as part of the Shaping Abortion for Change (SACHA) Study, which sought to create an evidence base to guide new directions in abortion care in Britain.Two approaches to PPI were used: involving patients and the public in the oversight of the research and its dissemination as lay advisors, and group meetings to obtain patients' views on interpretation of findings and recommendations. All participants observed the SACHA findings aligned with their own experiences of having an abortion in Britain. These priorities aligned closely with those identified in a separate expert stakeholder consultation undertaken as part of the SACHA Study. One additional priority which had not been identified during the research was identified by the PPI participants.We found abortion patients to be highly motivated to engage in the group meetings, and participation in them actively contributed to the destigmatisation of abortion by giving them a space to share their experiences. This may alleviate any ethical concerns about conducting research and PPI on abortion, including the assumption that revisiting an abortion experience will cause distress. We hope that our reflections are useful to others considering PPI in abortion-related research and service improvement
A Prognostic Model for Critically Ill Children in Locations With Emerging Critical Care Capacity.
Get PDFOBJECTIVES: To develop a clinical prediction model to risk stratify children admitted to PICUs in locations with limited resources, and compare performance of the model to nine existing pediatric severity scores. DESIGN: Retrospective, single-center, cohort study. SETTING: PICU of a pediatric hospital in Siem Reap, northern Cambodia. PATIENTS: Children between 28 days and 16 years old admitted nonelectively to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and laboratory data recorded at the time of PICU admission were collected. The primary outcome was death during PICU admission. One thousand five hundred fifty consecutive nonelective PICU admissions were included, of which 97 died (6.3%). Most existing severity scores achieved comparable discrimination (area under the receiver operating characteristic curves [AUCs], 0.71-0.76) but only three scores demonstrated moderate diagnostic utility for triaging admissions into high- and low-risk groups (positive likelihood ratios [PLRs], 2.65-2.97 and negative likelihood ratios [NLRs], 0.40-0.46). The newly derived model outperformed all existing severity scores (AUC, 0.84; 95% CI, 0.80-0.88; p < 0.001). Using one particular threshold, the model classified 13.0% of admissions as high risk, among which probability of mortality was almost ten-fold greater than admissions triaged as low-risk (PLR, 5.75; 95% CI, 4.57-7.23 and NLR, 0.47; 95% CI, 0.37-0.59). Decision curve analyses indicated that the model would be superior to all existing severity scores and could provide utility across the range of clinically plausible decision thresholds. CONCLUSIONS: Existing pediatric severity scores have limited potential as risk stratification tools in resource-constrained PICUs. If validated, our prediction model would be a readily implementable mechanism to support triage of critically ill children at admission to PICU and could provide value across a variety of contexts where resource prioritization is important
Multisectoral action to address noncommunicable diseases: lessons from three country case studies
Get PDFIntroduction: Multisectoral action is a central component of the global response to the rising prevalence of non-communicable diseases (NCDs). In this paper we aimed to unpack the definition of multisectoral action and provide an overview of the historical context, challenges, and recommendations alongside three country case studies: salt reduction in the UK, tobacco legislation in Nigeria, and regulation of edible oils in Iran.
Methods: We used an iterative review process to select three country case studies from a list of 20 potential cases previously identified by WHO. At our third round of review we unanimously agreed to focus on salt reduction in the UK, tobacco regulation in Nigeria, and edible oil regulation in Iran as these represented rich cases on diverse risk factors from three different world regions that we felt offered important lessons. We conducted literature reviews to identify further data for each case study.
Results: Across the three studies a number of important themes emerged. We found that multisectoral approaches demand the often difficult reconciliation of competing and conflicting values and priorities. Across our three chosen cases, commercial interests and free trade agreements were the most common obstacles to successful multisectoral strategies. We found that early consultative stakeholder engagement and strong political and bureaucratic leadership were necessary for success.
Discussion: The complex multi-rooted nature of NCDs requires a multisectoral approach, but the inevitable conflicts that this entails requires careful navigation
Managing microbial keratitis in resource-limited settings.
Get PDFIn resource-limited settings, the management of corneal infections (microbial keratitis) is challenging. Patients often delay seeking medical help, arriving in clinic with advanced disease, and diagnostic laboratory support may be unavailable
Leveraging healthcare standards-based improvement initiatives to support learning and continuous improvement: lessons from implementing the Ideal Clinic programme in Cape Town, South Africa
Get PDFBackground: This paper draws on the experiences of a group of health system leaders and researchers in leading and supporting, respectively, the implementation of the Ideal Clinic Realisation and Maintenance Framework (ICRMF) in Cape Town, South Africa. The ICRMF is a national standards-based quality improvement initiative that seeks to improve the quality of care in public primary healthcare (PHC) facilities. We share lessons learned on how efforts to improve healthcare standards can be leveraged for learning and meaningful system change.
Methods: A three-pronged approach to improving the implementation of the ICRMF was used in 15 PHC facilities across two sub-districts. The approach included (i) nurturing trust, (ii) changing the ICRMF assessment strategy, and (iii) promoting a collaborative and collective sense-making approach to understanding performance and addressing gaps. Routine ICRMF quantitative data and qualitative feedback from both the ICRMF assessment process and routine management meetings were used to reflect on the experience of using this approach and to draw lessons. The results and conclusions were further confirmed through member-checking.
Results: We found that using the three-pronged approach, the ICRMF assessments were able to facilitate deep and reflexive conversations about everyday health system challenges facing healthcare delivery in the sub-districts, while encouraging collective sensemaking and collaboration. The ICRMF was often perceived as a compliance-driven exercise with limited value on the actual quality of care. The three-pronged approach helped shift some of these perceptions and improved the experiences of facility managers in implementing the programme.
Conclusion: When supported by trusting relationships, reflexive processes and multidisciplinary ownership and collaboration, healthcare standards programmes such as the ICRMF can provide powerful avenues for learning and meaningful change. Our limited dataset could not demonstrate if our approach addresses the challenge of maintaining standards or not (which is linked to continuous improvement)
Economic Evaluation of Population-Based BRCA1 and BRCA2 Testing in Canada.
Get PDFIMPORTANCE: Population-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice.
OBJECTIVE: To estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada.
DESIGN, SETTING, AND PARTICIPANTS: For this economic evaluation, a Markov model was developed to compare the lifetime costs and outcomes of BRCA1/BRCA2 testing for all general population women aged 30 years compared with FH-based testing. BRCA carriers are offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and magnetic resonance imaging (MRI) and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk. The analyses were conducted from both payer and societal perspectives. This study was conducted from October 1, 2022, to February 20, 2024.
MAIN OUTCOMES AND MEASURES: Outcomes of interest were ovarian cancer, breast cancer, additional heart disease deaths, and incremental cost-effectiveness ratio ICER per quality-adjusted life-year (QALY). One-way and probabilistic-sensitivity-analyses (PSA) were undertaken to explore the uncertainty.
RESULTS: In the simulated cohort of 1 000 000 women aged 30 years in Canada, the base case ICERs of population-based BRCA testing were CAD 23 402.84) per QALY from the payer perspective or CAD 11 903.00) per QALY from the societal perspective compared with FH-based testing, well below the established Canadian cost-effectiveness thresholds. Population testing remained cost-effective for ages 40 to 60 years but not at age 70 years. The results were robust for multiple scenarios, 1-way sensitivity, and PSA. More than 99% of simulations from payer and societal perspectives were cost-effective on PSA (5000 simulations) at the CAD 36 254.25) per QALY willingness-to-pay threshold. Population-based BRCA testing could potentially prevent an additional 2555 breast cancers and 485 ovarian cancers in the Canadian population, corresponding to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1 000 000 population.
CONCLUSIONS AND RELEVANCE: In this economic evaluation, population-based BRCA testing was cost-effective compared with FH-based testing in Canada from payer and societal perspectives. These findings suggest that changing the genetic testing paradigm to population-based testing could prevent thousands of breast and ovarian cancers
Experiences of current UK service provision for co-occurring parental domestic violence and abuse, mental ill-health, and substance misuse: A reflexive thematic analysis
Get PDFDomestic violence and abuse (DVA), mental ill-health (MH), and substance misuse (SU) are inter-related public health problems negatively impacting families. Improved support requires an understanding of key stakeholders’ perspectives and experiences of current UK service provision. We conducted a qualitative research study to explore service users’, service providers’, and senior leadership/commissioners’ experiences of service provision for responding to parental DVA, MH, and SU in one locality. Six service users participated in individual, semi-structured interviews and ten service providers and senior leadership/commissioners attended two separate focus groups. We analysed data using reflexive thematic analysis. Five themes captured participants’ experiences: ‘it's hard to get the support I need, when I need it’; ‘almost all services come together around a family’; ‘it's all about the right relationships’; ‘addressing upstream drivers’; and ‘it's difficult providing support for multiple needs’. These highlighted the importance of: early support; a relational response; and addressing needs beyond parental DVA, MH, and SU. They also emphasised the barriers presented by siloed specialisms and overwhelmed practitioners. Our study is one of the first to consider multiple stakeholders’ perspectives on current UK service provision for co-occurring parental DVA, MH, and SU. It highlights key challenges for working at the intersection of these problems and suggests system-level change is needed to create the conditions to support families with multiple needs