Cost-effectiveness of community-based screening and treatment of moderate acute malnutrition in Mali.

IntroductionModerate acute malnutrition (MAM) causes substantial child morbidity and mortality, accounting for 4.4% of deaths and 6.0% of disability-adjusted life years (DALY) lost among children under 5 each year. There is growing consensus on the need to provide appropriate treatment of MAM, both to reduce associated morbidity and mortality and to halt its progression to severe acute malnutrition. We estimated health outcomes, costs and cost-effectiveness of four dietary supplements for MAM treatment in children 6-35 months of age in Mali.MethodsWe conducted a cluster-randomised MAM treatment trial to describe nutritional outcomes of four dietary supplements for the management of MAM: ready-to-use supplementary foods (RUSF; PlumpySup); a specially formulated corn-soy blend (CSB) containing dehulled soybean flour, maize flour, dried skimmed milk, soy oil and a micronutrient pre-mix (CSB++; Super Cereal Plus); Misola, a locally produced, micronutrient-fortified, cereal-legume blend (MI); and locally milled flour (LMF), a mixture of millet, beans, oil and sugar, with a separate micronutrient powder. We used a decision tree model to estimate long-term outcomes and calculated incremental cost-effectiveness ratios (ICERs) comparing the health and economic outcomes of each strategy.ResultsCompared to no MAM treatment, MAM treatment with RUSF, CSB++, MI and LMF reduced the risk of death by 15.4%, 12.7%, 11.9% and 10.3%, respectively. The ICER was US$9821 per death averted (2015 USD) and US$347 per DALY averted for RUSF compared with no MAM treatment.ConclusionMAM treatment with RUSF is cost-effective across a wide range of willingness-to-pay thresholds.Trial registrationNCT01015950

COVID-19-Related Testing, Knowledge and Behaviors among Severe and Chronic Non-Communicable Disease Patients in Neno District, Malawi: A Prospective Cohort Study

COVID-19-related knowledge and behaviors remain essential for controlling the spread of disease, especially among vulnerable patients with advanced, chronic diseases. We prospectively assessed changes over 11 months in COVID-19-related testing, knowledge, and behaviors among patients with non-communicable diseases in rural Malawi using four rounds of telephone interviews between November 2020 to October 2021. The most commonly reported COVID-19-related risks among patients included visiting health facilities (35–49%), attending mass gatherings (33–36%), and travelling outside the district (14–19%). Patients reporting having experienced COVID-like symptoms increased from 30% in December 2020 to 41% in October 2021. However, only 13% of patients had ever received a COVID-19 test by the end of the study period. Respondents answered 67–70% of the COVID-19 knowledge questions correctly, with no significant changes over time. Hand washing, wearing face masks and maintaining a safe distance were the most frequently reported strategies to prevent the spreading of COVID-19. Wearing face masks significantly improved over time (p < 0.001). Although the majority reported accurate knowledge about COVID-19 and enhanced adherence to infection prevention measures over time, patients commonly visited locations where they could be exposed to COVID-19. Government and other stakeholders should increase COVID-19 testing accessibility to primary and secondary facilities

Phenotype Fingerprinting Suggests the Involvement of Single-Genotype Consortia in Degradation of Aromatic Compounds by Rhodopseudomonas palustris

Anaerobic degradation of complex organic compounds by microorganisms is crucial for development of innovative biotechnologies for bioethanol production and for efficient degradation of environmental pollutants. In natural environments, the degradation is usually accomplished by syntrophic consortia comprised of different bacterial species. This strategy allows consortium organisms to reduce efforts required for maintenance of the redox homeostasis at each syntrophic level. Cellular mechanisms that maintain the redox homeostasis during the degradation of aromatic compounds by one organism are not fully understood. Here we present a hypothesis that the metabolically versatile phototrophic bacterium Rhodopseudomonas palustris forms its own syntrophic consortia, when it grows anaerobically on p-coumarate or benzoate as a sole carbon source. We have revealed the consortia from large-scale measurements of mRNA and protein expressions under p-coumarate, benzoate and succinate degrading conditions using a novel computational approach referred as phenotype fingerprinting. In this approach, marker genes for known R. palustris phenotypes are employed to determine the relative expression levels of genes and proteins in aromatics versus non-aromatics degrading condition. Subpopulations of the consortia are inferred from the expression of phenotypes and known metabolic modes of the R. palustris growth. We find that p-coumarate degrading conditions may lead to at least three R. palustris subpopulations utilizing p-coumarate, benzoate, and CO2 and H2. Benzoate degrading conditions may also produce at least three subpopulations utilizing benzoate, CO2 and H2, and N2 and formate. Communication among syntrophs and inter-syntrophic dynamics in each consortium are indicated by up-regulation of transporters and genes involved in the curli formation and chemotaxis. The N2-fixing subpopulation in the benzoate degrading consortium has preferential activation of the vanadium nitrogenase over the molybdenum nitrogenase. This subpopulation in the consortium was confirmed in an independent experiment by consumption of dissolved nitrogen gas under the benzoate degrading conditions

CD133 Is a Marker of Bioenergetic Stress in Human Glioma

Mitochondria dysfunction and hypoxic microenvironment are hallmarks of cancer cell biology. Recently, many studies have focused on isolation of brain cancer stem cells using CD133 expression. In this study, we investigated whether CD133 expression is regulated by bioenergetic stresses affecting mitochondrial functions in human glioma cells. First, we determined that hypoxia induced a reversible up-regulation of CD133 expression. Second, mitochondrial dysfunction through pharmacological inhibition of the Electron Transport Chain (ETC) produced an up-regulation of CD133 expression that was inversely correlated with changes in mitochondrial membrane potential. Third, generation of stable glioma cells depleted of mitochondrial DNA showed significant and stable increases in CD133 expression. These glioma cells, termed rho0 or ρ0, are characterized by an exaggerated, uncoupled glycolytic phenotype and by constitutive and stable up-regulation of CD133 through many cell passages. Moreover, these ρ0 cells display the ability to form “tumor spheroids” in serumless medium and are positive for CD133 and the neural progenitor cell marker, nestin. Under differentiating conditions, ρ0 cells expressed multi-lineage properties. Reversibility of CD133 expression was demonstrated by transfering parental mitochondria to ρ0 cells resulting in stable trans-mitochondrial “cybrid” clones. This study provides a novel mechanistic insight about the regulation of CD133 by environmental conditions (hypoxia) and mitochondrial dysfunction (genetic and chemical). Considering these new findings, the concept that CD133 is a marker of brain tumor stem cells may need to be revised

Cost-effectiveness of community-based screening and treatment of moderate acute malnutrition in Mali.

IntroductionModerate acute malnutrition (MAM) causes substantial child morbidity and mortality, accounting for 4.4% of deaths and 6.0% of disability-adjusted life years (DALY) lost among children under 5 each year. There is growing consensus on the need to provide appropriate treatment of MAM, both to reduce associated morbidity and mortality and to halt its progression to severe acute malnutrition. We estimated health outcomes, costs and cost-effectiveness of four dietary supplements for MAM treatment in children 6-35 months of age in Mali.MethodsWe conducted a cluster-randomised MAM treatment trial to describe nutritional outcomes of four dietary supplements for the management of MAM: ready-to-use supplementary foods (RUSF; PlumpySup); a specially formulated corn-soy blend (CSB) containing dehulled soybean flour, maize flour, dried skimmed milk, soy oil and a micronutrient pre-mix (CSB++; Super Cereal Plus); Misola, a locally produced, micronutrient-fortified, cereal-legume blend (MI); and locally milled flour (LMF), a mixture of millet, beans, oil and sugar, with a separate micronutrient powder. We used a decision tree model to estimate long-term outcomes and calculated incremental cost-effectiveness ratios (ICERs) comparing the health and economic outcomes of each strategy.ResultsCompared to no MAM treatment, MAM treatment with RUSF, CSB++, MI and LMF reduced the risk of death by 15.4%, 12.7%, 11.9% and 10.3%, respectively. The ICER was US$9821 per death averted (2015 USD) and US$347 per DALY averted for RUSF compared with no MAM treatment.ConclusionMAM treatment with RUSF is cost-effective across a wide range of willingness-to-pay thresholds.Trial registrationNCT01015950

Impact of facilitating continued accessibility to cancer care during COVID-19 lockdown on perceived wellbeing of cancer patients at a rural cancer center in Rwanda.

During the COVID-19 pandemic in Rwanda, Partners In Health Inshuti Mu Buzima collaborated with the Butaro Cancer Center of Excellence (BCCOE) to mitigate disruptions to cancer care by providing patients with free transportation to treatment sites and medication delivery at patients' local health facilities. We assessed the relationship between facilitated access to care and self-reported wellbeing outcomes. This cross-sectional telephone survey included cancer patients enrolled at BCCOE in March 2020. We used linear regression to compare six dimensions of quality of life (EORTC QLQ-C30), depression (PHQ-9), anxiety (GAD-7), and financial toxicity (COST) among patients who did and did not receive facilitated access to care. We also assessed access to cancer care and whether patient wellbeing and its association with facilitated access to care differed by socioeconomic status. Of 214 respondents, 34.6% received facilitated access to care. Facilitated patients were more likely to have breast cancer and be on chemotherapy. Facilitation was significantly associated with more frequent in-person clinical encounters, improved perceived quality of cancer care, and reduced transportation-related barriers. Facilitated patients had significantly better global health status (β = 9.14, 95% CI: 2.3, 16.0, p <0.01) and less financial toxicity (β = 2.62, 95% CI: 0.2,5.0, p = 0.03). However, over half of patients reported missing or delaying appointment. Patient wellbeing was low overall and differed by patient socioeconomic status, with poor patients consistently showing worse outcomes. Socioeconomic status did not modify the association between facilitated access to care and wellbeing indicators. Further, facilitation did not lead to equitable wellbeing outcomes between richer and poorer patients. Facilitated access to care during COVID-19 pandemic was associated with some improvements in access to cancer care and patient wellbeing. However, cancer patients still experienced substantial disruptions to care and reported low overall levels of wellbeing, with socioeconomic disparities persisting despite facilitated access to care. Implementing more robust, equity-minded facilitation and better patient outreach programs during health emergencies may promote better care and strengthen patient care overall and effect better patients' outcomes

Attitudes toward COVID-19 Vaccination: Staff and Patient Perspectives at Six Health Facilities in Sierra Leone

Sierra Leone is a West African country with a population of over 8 million. With more than half of Sierra Leone’s population living in rural areas, it is important to understand rural populations’ access to and attitudes toward the COVID-19 vaccine. In November 2021, the rate of vaccination coverage in Sierra Leone was only 7% for one dose and 4% for two doses. Understanding perspectives of health facility staff and patients can help strengthen future vaccine campaigns. We conducted a cross-sectional study, between March 2022 and May 2022, of clinical staff, non-clinical staff, and adult (>18 years) patients/caregivers attending six Ministry of Health and Sanitation (MoHS) facilities supported by Partners In Health, four in the Kono district and two in the Western Urban Area district, the capital of Sierra Leone. We assessed the opportunity to vaccinate, vaccine uptake, and intention to vaccinate. Out of the 2015 participants, 11.4% were clinical staff, 18.8% were non-clinical staff, and 69.8% were patients/caregivers. Less than half of the patients/caregivers had the opportunity to be vaccinated (42%), and 22% of patients/caregivers were fully vaccinated. Among the unvaccinated population, 44% would refuse a vaccine if offered to them at no cost. Lack of access to COVID-19 vaccines and to official education messaging, especially for patients and caregivers, is still an underlying problem in Sierra Leone for vaccine uptake, rather than a lack of willingness to be vaccinated

Attitudes toward COVID-19 Vaccines among Patients with Complex Non-Communicable Disease and Their Caregivers in Rural Malawi

Current low COVID-19 vaccination rates in low- and middle-income countries reflect an inequitable global vaccine distribution; however, local attitudes towards the COVID-19 vaccine are an important factor to meet vaccination benchmarks. We describe attitudes toward the uptake of the COVID-19 vaccine and perceptions among patients with NCDs and their caregivers using cross-sectional data collected through telephone interviews in Neno, Malawi. Out of 126 survey respondents, 71% were patients, and 29% were caregivers. Twenty-two percent of respondents had received at least one dose at the interview (95% CI: 15–30%), with 19% being fully vaccinated. Only 24% (95% CI: 12–40%) of unvaccinated respondents reported that they would accept an approved vaccine if it were offered today. Vaccines were perceived as unsafe or designed to harm and commonly associated with death, severe disability, infertility, and evil. However, over two-thirds reported high levels of trust in health care workers (73%) and community health workers (72%) as sources of information for the COVID-19 vaccine. Although the uptake of COVID-19 vaccine in this vulnerable population was three times than the national average, a low intention to be vaccinated persists among the unvaccinated. Strong trust in health care workers suggests that community engagement could help increase vaccine acceptance

Time to complete hepatitis C cascade of care among patients identified during mass screening campaigns in rural Rwanda: a retrospective cohort study

Background Since the discovery of direct-acting antivirals, treatment for hepatitis C virus (HCV) is increasingly accessible in low-resource settings, but quality of care in these settings is not known. We described progression through the cascade of care among individuals who screened positive for HCV antibodies during a mass screening campaign in Kirehe and Kayonza, two rural Rwandan districts, in September 2019. Methods This retrospective cohort study used routine clinical data to assess proportions of participants completing each stage of the cascade of care, including: (a) screening positive on rapid diagnostic test; (b) return of initial viral load results; (c) detectable viral load; (d) treatment assessment; (e) treatment initiation; (f) return of sustained virological response (SVR12) results; and (g) achieving SVR12. We proposed three indicators to assess timely care provision and used medians and interquartile ranges (IQR) to describe the time to complete the cascade of care. Results Overall, 666 participants screened HCV positive, among them, 452 (68.1%) were female and median age was 61 years (IQR: 47, 70). Viral load results were returned for 537 (80.6%) participants of whom 448 (83.4%) had detectable viral loads. Of these, 398 (88.8%) were assessed for treatment, 394 (99%) were initiated, but only 222 (56.3%) had results returned for SVR12. Among those with SVR12 results, 208 (93.7%) achieved SVR12. When assessing timely care provision, we found 65.9% (95% CI: 62.0, 69.7) of initial viral load results were returned ≤ 30 days of screening; 45% (95% CI: 40.1, 49.8) of people with detectable viral load completed treatment assessment ≤ 90 days of initial viral load results; and 12.5% (95% CI: 9.2, 16.3) of SVR12 results were returned ≤ 210 days of treatment initiation among those who initiated treatment. The overall median time from screening to SVR12 assessment was 437 days. Conclusion Despite high rates of SVR12 among those who completed all stages of the cascade of care, we identified gaps and delays in the treatment cascade. Improving communication between viral load testing hubs and health facilities could reduce the turn-around time for viral load testing, and actively monitor timeliness of care provision could improve quality of HCV care.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacultyResearche