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Pragmatic Evaluation of an Improvement Program for People Living With Modifiable High-Risk COPD Versus Usual Care:Protocol for the Cluster Randomized PREVAIL Trial
Get PDFBackground: The burden of chronic obstructive pulmonary disease (COPD) is well established, but opportunities for earlier diagnosis and improved management are still missed. Compared to the general COPD population, patients with a history of exacerbations and suboptimal treatment (“modifiable high-risk”) are at greater risk of future exacerbations and adverse health outcomes. To date there is no systematic approach for identifying and treating this patient group. Methods: Two cluster randomized controlled trials (CRTs) in the United Kingdom and United States will assess the impact of a primary care-based quality improvement program (COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care [CONQUEST]), compared to routine care. In each trial, 126 primary care clusters will be randomized 1:1 to intervention or control arms. Three groups of modifiable high-risk patients will be identified using electronic medical records: undiagnosed with potential COPD, newly diagnosed COPD, and already diagnosed COPD. Eligible patients will be aged ≥40 years, have experienced ≥2 moderate/≥1 severe exacerbation(s) in the prior 24 months, including ≥1 in the last 12 months, and not be prescribed inhaled triple therapy. Patients in the undiagnosed group will also be required to have a positive smoking history. Primary trial outcomes will be the annual rate of exacerbations and the annual rate of major adverse cardiac or respiratory events, comparing the quality improvement program against routine care. Discussion: These will be the first CRTs assessing such a comprehensive primary care-based COPD quality improvement program. Intention-to-treat analysis of trial outcomes after 24 months will inform its effectiveness in targeting the identification, assessment, treatment, and follow-up of patients with modifiable high-risk COPD.</p
Transcranial alternating current stimulation for treating spinocerebellar ataxia type 3:A randomized controlled trial
Get PDFThere are no specific treatments for spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disease causing cerebellar dysfunction. Transcranial alternating current stimulation (tACS) can improve cerebellar motor functions, and it has been shown to be safe and effective in treating neurological diseases. This randomized controlled trial (RCT) explored the effects of tACS on SCA3 patients. Participants received either 40-min, 70 Hz, 2 mA tACS or sham stimulation daily for 2 weeks. The primary outcome was met by 80% of the active-tACS group (32/40) and 10% of the sham group (4/40). The active group also showed significantly greater reductions in the Scale for Assessment and Rating of Ataxia (SARA) scores. No serious adverse events occurred, indicating high safety. Therefore, tACS is effective, safe, and feasible for treating SCA3. The study is registered at ClinicalTrials.gov (NCT05557786).</p
Impact of Vgsc-1014 mutations on the feeding pattern of Phlebotomus argentipes
Get PDFKnockdown resistance alleles (kdr alleles) within the para voltage-gated sodium channel gene (Vgsc) are a common mechanism of DDT and pyrethroid resistance in insect vectors. In the primary Asian visceral leishmaniasis vector, Phlebotomus argentipes, two kdr alleles in codon 1014 of the Vgsc are associated with insecticide resistance, potentially presenting challenges to vector control efforts in the Indian subcontinent. Here, we screened Vgsc-1014 alleles and blood meal origin in P. argentipes females collected between September 2013 and August 2015 in Bangladesh (Mymensingh), to understand how Vgsc-1014 alleles could impact feeding patterns. The sand fly collection took place in parallel with the vector control agency’s biannual indoor residual spraying (IRS) programme. In this region, the wild-type leucine (wt-leucine) was the most common allele (66.7%), followed by the mutant serine (19.4%) and phenylalanine alleles (13.9%). Only 55 sand fly blood meals (13%) came from humans, with most of bovine origin (61%). However, sand flies that had fed on humans showed strongly contrasting Vgsc-1014 genotypic frequencies compared to those feeding on other blood sources. Whilst most (81%) P. argentipes with human blood possessed kdr genotypes with two mutant alleles, most (81%) sand flies feeding on other blood sources possessed genotypes with wt-leucine alleles (P<0.001). Significant spatial variation in kdr frequencies was detected, but there was no clear temporal trend nor effect of sampling year on any results, and no significant impact of recent IRS in any analyses. The association between human feeding and kdr alleles in parallel with pyrethroid spraying indicates a new mechanism of how kdr alleles might impact VL control programs.</p
Life from death:ethical implications of uterus transplantation from deceased donors in global health
Get PDFThe burden of multimorbidity-associated acute hospital admissions in Malawi and Tanzania:a prospective multicentre cohort study
Get PDFBackground: The global burden of multimorbidity—the coexistence of two or more long-term conditions—is increasing. Limited access to primary care in sub-Saharan Africa means acute hospital admission is often the sentinel multimorbidity presentation. This prospective multicentre cohort study aimed to describe the burden, constituent diseases, and outcomes of multimorbidity among patients acutely admitted to hospital in Malawi and Tanzania. Methods: Adults (ie, those aged ≥18 years) admitted to four hospitals (two tertiary and two district hospitals) with acute medical conditions were consecutively recruited within 24 h of presentation and followed up for 90 days. We estimated the prevalence of HIV infection, diabetes, hypertension, and chronic kidney disease using commercially available point-of-care tests, and captured self-reported and clinical diagnoses (n/N [%]). Health economic data were summarised by median and IQR and modelled using generalised linear models. All-cause 90-day mortality was summarised with Kalplan–Meier plots and analysed using Cox regression models. Findings: 1407 adults (657 [46·7%] were female and 750 [53·3%] were male; mean age was 52·3 years [SD 18·4]) were recruited. We examined multimorbidity prevalence in 1007 participants admitted to three hospitals that accept admissions directly from the community. Multimorbidity was found in 473 (47·0%) of 1007 participants and 292 (29·0%) had a single long-term condition. Outcomes at 90 days were determined for 1317 (93·6%) of 1407 participants. Adjusted 90-day mortality was higher in participants with multimorbidity (335 [41·7%] of 804; hazard ratio 1·5 [95% CI 1·1–2·1]) and those with one long-term condition (80 [28·3%] of 283; 1·5 [1·0–2·1]); compared with those with no long-term conditions (31 [13·5%] of 230). Health-related quality of life was lower in participants with multimorbidity compared with those with one long-term condition (median 0·402 [IQR –0·037 to 0·644] vs 0·557 [0·140 to 0·730]; p=0·005) at baseline, and at final observation (0·858 [0·667 to 1·00] vs 1·00 [0·589 to 1·00] respectively; p=0·01). In Tanzania, medical costs incurred by patients were higher in participants with multimorbidity compared with those with one long-term condition (relative effect 5·77 [95% CI 2·99–11·15]; p<0·0001). Interpretation: Multimorbidity is common in patients admitted to hospital in Malawi and Tanzania and associated with worse survival and increased cost. Multimorbidity is an urgent public health threat that requires fundamental health-care delivery reform to address population needs. Funding: National Institute for Health and Care Research and Wellcome Trust. Translations: For the Chichewa and Kiswahili translations of the abstract see Supplementary Materials section.</p
Equipping community health workers in Rwanda to deliver a gender transformative parenting program to prevent violence against women and children at scale
Get PDFIntroduction: In Rwanda, the Bandebereho program has demonstrated long-term reductions in intimate partner violence (IPV) and violence against children. Since 2019, the program has partnered with government to train community health workers (CHWs) to deliver at scale. Evidence on how to equip CHWs to deliver Bandebereho, or similar programs, with quality and fidelity is needed to support scaling. This study sought to assess the impact of training on CHWs and their capacity to deliver Bandebereho during scale up. Methods: A pre/post, follow-up study was conducted with 573 CHWs in Burera district. Data were collected at three time points over 20 months using self-administered questionnaires (pre/post) and a follow-up phone survey. Questionnaires gathered data on CHW attitudes about gender roles and violence, self-reported skills, knowledge and confidence to implement Bandebereho, and training impacts on partner relations and community work. Informed consent was obtained from all study participants. Results: The pre-survey was completed by 562 CHWs and 564 CHWs completed the post-survey after six to nine months. The phone survey was administered to 506 CHWs at follow-up (at 17–19 months). Analysis of changes between pre- and post-surveys found CHWs had more equitable gender attitudes after the training. Linear regression analysis found that CHWs with some secondary education (coefficient: −2.15, p < 0.01) and more than three years' experience (coefficient: −2.27, p < 0.001) were less likely to hold inequitable attitudes. At post-survey, CHWs reported a high level of preparedness to implement, regardless of gender. A majority reported improved partner relations, including greater partner support for their community work. At follow-up, a majority of CHWs reported a high degree of comfort and confidence implementing Bandebereho, and benefits to their work and personal relationships. Conclusions: The findings highlight the importance of investing in high-quality facilitator training, which allows sufficient time for facilitators' own transformation, to maintain quality and fidelity at scale. The findings underscore the importance of a slow and steady approach, with sufficient time to adapt, test, and refine IPV programs for scale, which can also support a progressive handover to government. The findings may support program originators who seek to scale proven IPV prevention programs with government in other settings.</p
Exploring the Interplay of Social and Physical Factors in Risk Dynamics and Transitions Across the Life-Course of Female Sex Workers in Blantyre, Malawi:A Longitudinal Narrative Study
Get PDFSexual risk amongst female sex workers (FSW) varies across the life-course and is influenced by socio-economic and interpersonal factors that affect behavioural choices and engagement in HIV/STI care. We explored transitions in the life-course of FSW to understand the dynamics of sexual risk in Blantyre, Malawi. We implemented a nested longitudinal qualitative study as part of the AMETHIST Consortium, a study testing approaches to reduce HIV transmission in sex work. We conducted consecutive narrative interviews with 30 FSW at three-time points over 12 months, with a three- to four-month break between each time point. We compared narratives to understand sex work transitions, HIV risk and engagement with HIV services. We identified factors (social and physical) related to sexual risk at the points of (1) transitions into sex work, (2) continuing sex work, and (3) breaks in sex work. At the entry stage, sexual risk was heightened when women lacked the knowledge and skills for protection against HIV/STI. Whilst continuing sex work, women’s immediate financial needs were prioritised over their HIV/STI risk. These behaviours occurred whether they were aware of the associated HIV/STI risk. During breaks, women perceived lower risk and reduced engagement in prevention strategies, particularly when they had stable partners, which paradoxically increased their risk. These narratives reveal how social context informs and limits access to health care while concurrently promoting risky behaviours. A multifaceted and dynamically responsive approach that considers risk differentiation from a temporal perspective can strengthen targeted interventions, effectively addressing the multiple challenges faced by FSW.</p
“The system brought beauty to our community”: Evaluating the impact of a physical address system in Mathare informal settlement, Nairobi, through ripple effect mapping
Get PDFIntroduction: Rapid urbanisation in Nairobi has led to the growth of informal settlements, characterised by overcrowding, poor infrastructure, and limited access to basic services. Often invisible in formal systems, these areas face weak accountability and restricted service access, worsening health and wellbeing. This paper evaluates the impact of a community-led Physical Address System (PAS) in improving visibility, access, and support for residents in the settlement of Kiamutisya in Mathare, Nairobi.Methods: Drawing on community-led data collection, the PAS introduced a unique address for each physical structure in Kiamutisya to support service delivery and emergency response, addressing the invisibility that residents face. We held three Ripple Effect Mapping (REM) workshops with community leaders, community health promoters and Accountability and Responsiveness in Informal Settlements for Equity (ARISE) Hub co-researchers. REM is a participatory evaluation method that captures the impacts of an intervention, both intended and unintended, from the perspective of the community. Data was coded using NVivo 12 and analysed thematically. Results: The PAS evaluation found direct impacts like better service delivery by community health promoters, and indirect benefits including stronger community identity, improved safety, and government engagement. It also noted ethical risks like data misuse and resident stigmatization. Key recommendations for policymakers and planners include using physical addresses to enhance service delivery and emergency response, formally integrating addresses into planning systems, and fostering community participation to improve equity in challenging urban environments.Conclusions: This study underscores the potential of community health systems to address structural vulnerabilities and build resilience in informal settlements. The PAS demonstrates the value of participatory approaches in creating sustainable, scalable models for urban health, reinforcing the critical role of communities as active agents in advancing health and well-being
The impact of sulfadoxine–pyrimethamine resistance on the effectiveness of intermittent preventive treatment for the prevention of malaria in pregnancy in Africa: an updated systematic review and meta-analysis
Get PDFBackground: Resistance of Plasmodium falciparum to sulfadoxine–pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine–pyrimethamine (ITPp-SP) in sub-Saharan Africa. We updated an aggregated-data meta-analysis to assess the associations between sulfadoxine–pyrimethamine resistance and the effectiveness of IPTp-SP to inform policy. Methods: We searched databases (Jan 1, 1990, to June 8, 2024) for observational studies or trials reporting data on malaria, low birthweight (<2500 g), anaemia, and other outcomes by IPTp-SP dose and matched these by year and location with studies that reported on molecular markers of sulfadoxine–pyrimethamine resistance. Studies including only women with HIV or combined interventions were excluded. We evaluated how sulfadoxine–pyrimethamine resistance influenced the adjusted risk ratio (aRR) between three and two doses of IPTp-SP for various outcomes using Poisson mixed-effects models that allowed for non-linear relationships. Initially, we performed a threshold analysis, stratified by region, to identify the resistance levels most predictive of altered effect of IPTp-SP doses on malaria parasitaemia at delivery (peripheral or placental parasitaemia by any test), our primary outcome. These resistance strata were then used in all subsequent models for other outcomes. All analyses were adjusted for malaria transmission intensity, HIV infection, percentage of paucigravidae, and insecticide-treated net use. Performance of models was evaluated using cross-validation. The trial was registered with PROSPERO (CRD42021250359). Findings: Overall, 122 studies involving 148 693 participants were included. For west and central Africa (69 studies comprising 63 745 participants), very low resistance was categorised as a prevalence of the dihydropteroate synthase (dhps) Lys540Glu mutation in the parasite population of less than 4%, and low resistance as a prevalence of Lys540Glu of 4% or higher. In east and southern Africa (53 studies comprising 84 948 participants), moderate resistance was categorised as a prevalence of the Lys540Glu mutation of less than 60% combined with a prevalence of the Ala581Gly mutation of less than 5%, high resistance as a prevalence of Lys540Glu of 60% or higher combined with a prevalence of Ala581Gly of less than 5%, and very high resistance as a prevalence of the Lys540Glu mutation of 60% or higher combined with a prevalence of Ala581Gly of 5% or higher. There was a marked trend towards lower efficacy of IPTp-SP on reducing malaria infection with increasing resistance levels. In west and central Africa, when comparing three versus two doses, the aRR was 0·71 (95% CI 0·65–0·78) in areas with very low resistance and 0·83 (0·72–0·95) in areas with low resistance (p=0·0144 for the difference between dose–response curves in very low vs low resistance). For east and southern Africa, the same trend was observed: the aRR was 0·63 (95% CI 0·57–0·69) in areas with moderate resistance, 0·89 (0·82–0·96) in areas with high resistance, and 0·93 (0·85–1·01) in areas with very high resistance (p<0·0001 for dose–response curves differences between moderate vs high and moderate vs very high resistance). This pattern was not seen for low birthweight. When comparing three versus two doses in west and central Africa, the aRR was 0·58 (95% CI 0·48–0·68) in areas with very low resistance and 0·56 (0·44–0·68) in areas with low resistance (p=0·72 for dose–response curves very low vs low resistance). For east and southern Africa, the aRR was 0·75 (95% CI 0·52–0·98) in areas with moderate resistance, 0·73 (0·69–0·78) in areas with high resistance, and 0·75 (0·63–0·87) in areas with very high resistance (p=0·80 for dose–response curves moderate vs high resistance; p=0·90 for moderate vs very high resistance). Dose comparisons in some resistance strata were limited by sample size.Interpretation: IPTp-SP antimalarial efficacy is greatly reduced in very high resistance areas. However, it remains effective at reducing low birthweight in these areas, possibly through non-malaria effects on fetal growth. While IPTp-SP use should continue in high SP-resistance areas, alternative malaria preventive strategies are urgently needed in these areas.Funding: WHO and WorldWide-Antimalarial-Resistance-Network.</p