Assessing availability, prices, and market share of quality-assured malaria ACT and RDT in the private retail sector in Nigeria and Uganda.

BACKGROUND: An estimated 50% of suspected malaria cases in sub-Saharan Africa first seek care in the private sector, especially in private medicine retail outlets. Quality of care in these outlets is generally unknown but considered poor with many patients not receiving a confirmatory diagnosis or the recommended first-line artemisinin-based combination therapy (ACT). In 2010, a subsidy pilot scheme, the Affordable Medicines Facility malaria, was introduced to crowd out the use of monotherapies in favour of WHO-pre-qualified artemisinin-based combinations (WHO-PQ-ACTs) in the private health sector. The scheme improved the availability, market share, and cost of WHO-PQ-ACTs in countries like Nigeria and Uganda, but in 2018, the subsidies were halted in Nigeria and significantly reduced in Uganda. This paper presents findings from six retail audit surveys conducted from 2014 to 2021 in Nigeria and Uganda to assess whether the impact of subsidies on the price, availability, and market share of artemisinin-based combinations has been sustained after the subsidies were reduced or discontinued. METHODS: Six independent retail audits were conducted in private medicine retail outlets, including pharmacies, drug shops, and clinics in Nigeria (2016, 2018, 2021), and Uganda (2014, 2019, 2020) to assess the availability, price, and market share of anti-malarials, including WHO-PQ-ACTs and non-WHO-PQ-ACTs, and malaria rapid diagnostic tests (RDTs). RESULTS: Between 2016 and 2021, there was a 57% decrease in WHO-PQ-ACT availability in Nigeria and a 9% decrease in Uganda. During the same period, non-WHO-PQ-ACT availability increased in Nigeria by 41% and by 34% in Uganda. The price of WHO-PQ-ACTs increased by 42% in Nigeria to $0.68 and increased in Uganda by 24% to $0.95. The price of non-WHO-PQ-ACTs decreased in Nigeria by 26% to $1.08 and decreased in Uganda by 64% to $1.23. There was a 76% decrease in the market share of WHO-PQ-ACTs in Nigeria and a 17% decrease in Uganda. Malaria RDT availability remained low throughout. CONCLUSION: With the reduction or termination of subsidies for WHO-PQ-ACTs in Uganda and Nigeria, retail prices have increased, and retail prices of non-WHO-PQ-ACTs decreased, likely contributing to a shift of higher availability and increased use of non-WHO-PQ-ACTs.

Prevalence of antibiotic use for childhood diarrhoea in Uganda after an ORS scale-up intervention: a repeated cross-sectional study.

BACKGROUND: Diarrhoea kills 500,000 children every year despite availability of cheap and effective treatment. In addition, a large number are inappropriately treated with antibiotics, which do not benefit the patient but can contribute to the development of antibiotic resistance. We investigated whether the prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda changed following a national intervention to increase the use of oral rehydration salts (ORS), and whether any socioeconomic characteristics were associated with antibiotic use. METHODS: A cross-sectional survey was conducted among caregivers of children under the age of five and among private health care providers and drug sellers in Uganda in 2014. This was compared to a similar survey among private health care providers, and the national demographic and health survey in Uganda in 2016. Logistic regression was used to find associations between antibiotic use and socioeconomic characteristics, and chi-square test and independent sample t-test were used to find significant differences between groups. RESULTS: The prevalence of antibiotic use among children under the age of five with diarrhoea in Uganda decreased from 30.5% in 2014 to 20.0% (p < 0.001) in 2016. No associations between socioeconomic characteristics and the use of antibiotics were significant in both 2014 and 2016. CONCLUSIONS: The use of antibiotics in children with diarrhoeal disease decreased significantly in Uganda between 2014 and 2016. However, the extent of the contribution of the ORS scale-up programme to this decrease cannot be determined from this study.

Decentralizing oxygen availability and use at primary care level for children under-five with severe pneumonia, at 12 Health Centers in Ethiopia: a pre-post non-experimental study.

BACKGROUND: Pneumonia is the leading infectious cause of death in children worldwide, accounting for 15% of all deaths in children under the age of five. Hypoxemia is a major cause of death in patients suffering from pneumonia. There is strong evidence that using pulse oximetry and having reliable oxygen sources in health care facilities can reduce deaths due to pneumonia by one-third. Despite its importance, hypoxemia is frequently overlooked in resource-constrained settings. Aside from the limited availability of pulse oximetry, evidence showed that healthcare workers did not use it as frequently to generate evidence-based decisions on the need for oxygen therapy. As a result, the goal of this study was to assess the availability of medical oxygen devices, operating manuals, guidelines, healthcare workers' knowledge, and skills in the practice of hypoxemia diagnosis and oxygen therapy in piloted health centers of Ethiopia. METHODS: A pre-post non-experimental study design was employed. An interviewer-administered questionnaire was used to collect primary data and review medical record charts. A chi-square test with a statistical significance level of P < 0.05 was used as a cut-off point for claiming statistical significance. RESULTS: Eighty one percent of healthcare workers received oxygen therapy training, up from 6% at baseline. As a result of the interventions, knowledge of pulse oximetry use and oxygen therapy provision, skills such as oxygen saturation and practices of oxygen therapy have significantly improved among healthcare workers in the piloted Health Centers. In terms of availability of oxygen devices (e.g. cylinders, concentrators, and pulse oximeters) in the facilities, seven (58%) facilities did not have any at baseline, but due to the interventions, all facilities were equipped with the oxygen devices. CONCLUSIONS: Given the prevalence of pneumonia and hypoxemia, a lack of access to oxygen delivery devices, as well as a lack of knowledge and skills among healthcare workers in the administration of oxygen therapy, may represent an important and reversible barrier to improving child survival. Therefore, scaling up clinician training, technical support, availability of oxygen devices, guidelines, manuals, strengthening maintenance schemes, and close monitoring of healthcare workers and health facilities is strongly advised.

Private health care market shaping and changes in inequities in childhood diarrhoea treatment coverage: evidence from the analysis of baseline and endline surveys of an ORS and zinc scale-up program in Nigeria.

BACKGROUND: Nearly 90,000 under-five children die from diarrhoea annually in Nigeria. Over 90% of the deaths can be prevented with oral rehydration salt (ORS) and zinc treatment but coverage nationally was less than 34% for ORS and 3% for zinc with wide inequities. A program was implemented in eight states to address critical barriers to the optimal functioning of the health care market to deliver these treatments. In this study, we examine changes in the inequities of coverage of ORS and zinc over the intervention period. METHODS: Baseline and endline household surveys were used to measure ORS and zinc coverage and household assets. Principal component analysis was used to construct wealth quintiles. We used multi-level logistic regression models to estimate predictive coverage of ORS and zinc by wealth and urbanicity at each survey period. Simple measures of disparity and concentration indices and curves were used to evaluate changes in ORS and zinc coverage inequities. RESULTS: At baseline, 28% (95% CI: 22-35%) of children with diarrhoea from the poorest wealth quintile received ORS compared to 50% (95% CI: 52-58%) from the richest. This inequality reduced at endline as ORS coverage increased by 21%-points (P <  0.001) for the poorest and 17%-points (P <  0.001) for the richest. Zinc coverage increased significantly for both quintiles at endline from an equally low baseline coverage level. Consistent with the findings of the pairwise comparison of the poorest and the richest, the summary measure of disparity across all wealth quintiles showed a narrowing of inequities from baseline to endline. Concentration curves shifted towards equality for both treatments, concentration indices declined from 0.1012 to 0.0480 for ORS and from 0.2640 to 0.0567 for zinc. Disparities in ORS and zinc coverage between rural and urban at both time points was insignificant except that the use of zinc in the rural at endline was significantly higher at 38% (95%CI: 35-41%) compared to 29% (95%CI, 25-33%) in the urban. CONCLUSION: The results show a pro-rural improvement in coverage and a reduction in coverage inequities across wealth quintiles from baseline to endline. This gives an indication that initiatives focused on shaping healthcare market systems may be effective in reducing health coverage gaps without detracting from equity as a health policy objective.

Changes in the availability of medical oxygen and its clinical practice in Ethiopia during a national scale-up program: a time series design from thirty-two public hospitals.

BACKGROUND: Oxygen therapy is a lifesaving treatment, however, in Ethiopia, oxygen is not readily available in many healthcare facilities. In 2015, the Federal Ministry of Health launched a national roadmap to increase access to oxygen. This study aims to evaluate whether availability of oxygen and its clinical practice in public hospitals of Ethiopia changed during the time the roadmap was being implemented. METHODS: Between December 2015 and December 2019, a multifaceted approach was undertaken to increase access to oxygen in public facilities in Ethiopia. The activities included formation of new policies, development of guidelines, procurement and maintenance of oxygen equipment, and training of healthcare workers. To evaluate whether access and use of oxygen changed during this period, facility-based surveys were conducted between December 2015 to December 2019. Primary data, including medical record reviews, were collected from 32 public hospitals bi-annually. A chi-square test that claimed P < 0.05 used to assess the statistical significance differences. RESULTS: The study was conducted in 32 public hospitals of Ethiopia, where capacity building and technical support interventions implemented. Of these 32 facilities, 15 (46.9%) were general hospitals, 10 (31.2%) were referral hospitals, and 7 (21.9%) were primary hospitals. Functional availability of oxygen has shown a statistically significant increase from 62 to 100% in the pediatric in-patient departments of general and referral hospitals (p-value < 0.001). Similarly, functional availability of pulse oximetry has shown a statistically significant increase from 45 to 96%. With regard to clinical practices, the blood oxygen saturation (SpO2) measurement at diagnosis increased from 10.2 to 75%, and SpO2 measurement at admission increased 20.5 to 83%. CONCLUSIONS: Based on the intervention results, we conclude that multifaceted approaches targeting policy, healthcare workers' capacity, increased device procurement, and device maintenance programs with on-site mentorship, can improve the availability of medical oxygen and pulse oximetry, as well as clinical practice of oxygen therapy in health facilities. Therefore, ensuring device availability along with regular technical support and close follow-up of healthcare workers and facilities are critical, and these interventions should be scaled further.

BPG: Seamless, automated and interactive visualization of scientific data.

BACKGROUND: We introduce BPG, a framework for generating publication-quality, highly-customizable plots in the R statistical environment. RESULTS: This open-source package includes multiple methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it suitable for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for integration with computational pipelines. CONCLUSION: BPG provides a new approach for linking interactive and scripted data visualization and is available at http://labs.oicr.on.ca/boutros-lab/software/bpg or via CRAN at https://cran.r-project.org/web/packages/BoutrosLab.plotting.general.

VennDiagramWeb: a web application for the generation of highly customizable Venn and Euler diagrams.

BACKGROUND: Visualization of data generated by high-throughput, high-dimensionality experiments is rapidly becoming a rate-limiting step in computational biology. There is an ongoing need to quickly develop high-quality visualizations that can be easily customized or incorporated into automated pipelines. This often requires an interface for manual plot modification, rapid cycles of tweaking visualization parameters, and the generation of graphics code. To facilitate this process for the generation of highly-customizable, high-resolution Venn and Euler diagrams, we introduce VennDiagramWeb: a web application for the widely used VennDiagram R package. VennDiagramWeb is hosted at http://venndiagram.res.oicr.on.ca/ . RESULTS: VennDiagramWeb allows real-time modification of Venn and Euler diagrams, with parameter setting through a web interface and immediate visualization of results. It allows customization of essentially all aspects of figures, but also supports integration into computational pipelines via download of R code. Users can upload data and download figures in a range of formats, and there is exhaustive support documentation. CONCLUSIONS: VennDiagramWeb allows the easy creation of Venn and Euler diagrams for computational biologists, and indeed many other fields. Its ability to support real-time graphics changes that are linked to downloadable code that can be integrated into automated pipelines will greatly facilitate the improved visualization of complex datasets. For application support please contact Paul.Boutros@oicr.on.ca.

Determinants of malaria diagnostic uptake in the retail sector: qualitative analysis from focus groups in Uganda.

BACKGROUND: In Uganda, as in most other malaria-endemic countries, presumptive treatment for malaria based on symptoms without a diagnostic blood test is still very common. While diagnostic testing in public sector facilities is increasing, many people in Uganda who suspect malaria visit private sector outlets to purchase medications. Increasing the availability and uptake of rapid diagnostic tests (RDTs) for malaria in private outlets could help increase diagnostic testing for malaria but raises questions about the patient demand for and valuation of testing that are less critical for public sector introduction. METHODS: In preparation for a behaviour change campaign to encourage and sustain the demand for RDTs in drug shops, eight focus group discussions with a total of 84 community members were conducted in six districts across Uganda's Eastern Region in November-December 2011. Focus groups explored incentives and barriers to seeking diagnosis for malaria, how people react to test results and why, and what can be done to increase the willingness to pay for RDTs. RESULTS: Overall, participants were very familiar with malaria diagnostic testing and understood its importance, yet when faced with limited financial resources, patients preferred to spend their money on medication and sought testing only when presumptive treatment proved ineffective. While side effects did seem to be a concern, participants did not mention other potential costs of taking unnecessary or ineffective medications, such as money wasted on excess drugs or delays in resolution of symptoms. Very few individuals were familiar with RDTs. CONCLUSION: In order to boost demand, these results suggest that private sector RDTs will have to be made convenient and affordable and that targeted behaviour change campaigns should strive to increase the perceived value of diagnosis.

Chromatin decouples promoter threshold from dynamic range.

Chromatin influences gene expression by restricting access of DNA binding proteins to their cognate sites in the genome. Large-scale characterization of nucleosome positioning in Saccharomyces cerevisiae has revealed a stereotyped promoter organization in which a nucleosome-free region (NFR) is present within several hundred base pairs upstream of the translation start site. Many transcription factors bind within NFRs and nucleate chromatin remodelling events which then expose other cis-regulatory elements. However, it is not clear how transcription-factor binding and chromatin influence quantitative attributes of gene expression. Here we show that nucleosomes function largely to decouple the threshold of induction from dynamic range. With a series of variants of one promoter, we establish that the affinity of exposed binding sites is a primary determinant of the level of physiological stimulus necessary for substantial gene activation, and sites located within nucleosomal regions serve to scale expression once chromatin is remodelled. Furthermore, we find that the S. cerevisiae phosphate response (PHO) pathway exploits these promoter designs to tailor gene expression to different environmental phosphate levels. Our results suggest that the interplay of chromatin and binding-site affinity provides a mechanism for fine-tuning responses to the same cellular state. Moreover, these findings may be a starting point for more detailed models of eukaryotic transcriptional control.

Improving effective coverage of medical-oxygen services for neonates and children in health facilities in Uganda: a before-after intervention study.

BACKGROUND: Medical oxygen services are essential for the care of acutely unwell patients. We aimed to assess the effects of a multilevel, multicomponent health-system intervention on hypoxaemia detection, oxygen therapy, and mortality among neonates and children attending level IV health centres and hospitals in Uganda. METHODS: For this before-after intervention study, we included children who attended paediatric or neonatal wards of 24 level IV health centres and seven general or regional referral hospitals in the Busoga and North Buganda regions of Uganda between June 1, 2020, and June 30, 2022. All neonates younger than 1 month and children aged 1 month to 14 years were eligible for inclusion. We excluded neonates who were not sick but stayed in the maternity ward for routine postnatal care. The intervention involved clinical training, mentorship, and supportive supervision; provision of pulse oximeters and cylinder-based oxygen sources; biomedical-capacity support; and support to develop and disseminate oxygen supply strategies, oxygen therapy guidelines, and lists of essential oxygen supplies. Trained research assistants extracted individual patient data from case notes using a standardised electronic data collection form. Data were collected on health-facility details, age, sex, clinical signs and symptoms, admission diagnoses, pulse oximetry readings, oxygen therapy details, and final patient outcome. The primary outcome was the proportion of admitted neonates and children with a pulse oximetry oxygen saturation reading documented in their patient case notes on day 1 of health-facility admission (ie, pulse oximetry coverage). We used mixed-effects logistic regression to evaluate the effect of the intervention. FINDINGS: We obtained data on 71 997 eligible neonates and children admitted to 31 participating health facilities; the primary analysis included 10 001 patients in the pre-intervention period (ie, June 1 to Oct 30, 2020) and 51 329 patients in the post-intervention period (ie, March 1, 2021, to June 30, 2022). Because 1356 patients had missing data for sex, 4365 (46·7%) of 9347 in the pre-intervention group and 22 831 (46·2%) of 49 410 in the post-intervention group were female; 4982 (53·3%) in the pre-intervention group and 26 579 (53·8%) in the post-intervention group were male. The proportion of neonates and children with pulse oximetry at admission increased from 2365 (23·7%) of 10 001 in the pre-intervention period to 45 029 (87·7%) of 51 328 in the post-intervention period. Adjusted analysis indicated greater likelihood of a patient receiving pulse oximetry during the post-intervention period compared with the pre-intervention period (adjusted odds ratio 40·10, 95% CI 37·38-42·93; p<0·0001). INTERPRETATION: Large-scale improvements in hospital oxygen services are achievable and have the potential to improve clinical outcomes. Governments should be encouraged to develop national oxygen plans and focus investment on interventions that have been shown to be effective, including the introduction of pulse oximetry into routine hospital care and clinical and biomedical mentoring and support. FUNDING: Bill & Melinda Gates Foundation and ELMA Philanthropies. TRANSLATIONS: For the Luganda and Lusoga translations of the abstract see Supplementary Materials section.

Predicting the potential impact of scaling up four pneumonia interventions on under-five pneumonia mortality: A prospective Lives Saved Tool (LiST) analysis for Bangladesh, Chad, and Ethiopia.

Background: Pneumonia remains the leading cause of mortality in under-five children outside the neonatal period. Progress has slowed down in the last decade, necessitating increased efforts to scale up effective pneumonia interventions. Methods: We used the Lives Saved Tool (LiST), a modelling software for child mortality in low- and middle-income settings, to prospectively analyse the potential impact of upscaling pneumonia interventions in Bangladesh, Chad, and Ethiopia from 2023 to 2030. We included Haemophilus influenzae type B (Hib) vaccination, pneumococcal conjugate vaccine (PCV), oral antibiotics, pulse oximetry, and oxygen as pneumonia interventions in our analysis. Outcomes of interest were the number of pneumonia deaths averted, the proportion of deaths averted by intervention, and changes in the under-five mortality rate. Findings: We found that 19 775 lives of children under-five could be saved in Bangladesh, 76 470 in Chad, and 97 343 in Ethiopia by scaling intervention coverages to ≥90% by 2030. Our estimated reductions in pneumonia deaths among children under five range from 44.61% to 57.91% in the respective countries. Increased coverage of oral antibiotics, pulse oximetry, and oxygen show similar effects in all three countries, averting between 18.80% and 23.65% of expected pneumonia deaths. Scaling-up PCV has a prominent effect, especially in Chad, where it could avert 14.04% of expected pneumonia deaths. Under-five mortality could be reduced by 1.42 per 1000 live births in Bangladesh, 22.52 per 1000 live births in Chad, and 5.48 per 1000 live births in Ethiopia. Conclusions: This analysis shows the high impact of upscaling pneumonia interventions. The lack of data regarding coverage indicators is a barrier for further research, policy, and implementation, all requiring increased attention.

Hypoxaemia prevalence and management among children and adults presenting to primary care facilities in Uganda: A prospective cohort study.

Hypoxaemia (low blood oxygen) is common among hospitalised patients, increasing the odds of death five-fold and requiring prompt detection and treatment. However, we know little about hypoxaemia prevalence in primary care and the role for pulse oximetry and oxygen therapy. This study assessed the prevalence and management of hypoxaemia at primary care facilities in Uganda. We conducted a cross sectional prevalence study and prospective cohort study of children with hypoxaemia in 30 primary care facilities in Uganda, Feb-Apr 2021. Clinical data collectors used handheld pulse oximeters to measure blood oxygen level (SpO2) of all acutely unwell children, adolescents, and adults. We followed up a cohort of children aged under 15 years with SpO2<93% by phone after 7 days to determine if the patient had attended another health facility, been admitted, or recovered. Primary outcome: proportion of children under 5 years of age with severe hypoxaemia (SpO2<90%). Secondary outcomes: severe (SpO2<90%) and moderate hypoxaemia (SpO2 90-93%) prevalence by age/sex/complaint; number of children with hypoxaemia referred, admitted and recovered. We included 1561 children U5, 935 children 5-14 years, and 3284 adolescents/adults 15+ years. Among children U5, the prevalence of severe hypoxaemia was 1.3% (95% CI 0.9 to 2.1); an additional 4.9% (3.9 to 6.1) had moderate hypoxaemia. Performing pulse oximetry according to World Health Organization guidelines exclusively on children with respiratory complaints would have missed 14% (3/21) of severe hypoxaemia and 11% (6/55) of moderate hypoxaemia. Hypoxaemia prevalence was low among children 5-14 years (0.3% severe, 1.1% moderate) and adolescents/adults 15+ years (0.1% severe, 0.5% moderate). A minority (12/27, 44%) of severely hypoxaemic patients were referred; 3 (12%) received oxygen. We followed 87 children aged under 15 years with SpO2<93%, with complete data for 61 (70%), finding low rates of referral (6/61, 10%), hospital attendance (10/61, 16%), and admission (6/61, 10%) with most (44/61, 72%) fully recovered at day 7. Barriers to referral included caregiver belief it was unnecessary (42/51, 82%), cost (8/51, 16%), and distance or lack of transport (3/51, 6%). Hypoxaemia is common among acutely unwell children under five years of age presenting to Ugandan primary care facilities. Routine pulse oximetry has potential to improve referral, management and clinical outcomes. Effectiveness, acceptability, and feasibility of pulse oximetry and oxygen therapy for primary care should be investigated in implementation trials, including economic analysis from health system and societal perspectives.

Oxygen systems strengthening as an intervention to prevent childhood deaths due to pneumonia in low-resource settings: systematic review, meta-analysis and cost-effectiveness.

OBJECTIVES: Increasing access to oxygen services may improve outcomes among children with pneumonia living in low-resource settings. We conducted a systematic review to estimate the impact and cost-effectiveness of strengthening oxygen services in low-income and middle-income countries with the objective of including oxygen as an intervention in the Lives Saved Tool. DESIGN: We searched EMBASE and PubMed on 31 March 2021 using keywords and MeSH terms related to 'oxygen', 'pneumonia' and 'child' without restrictions on language or date. The risk of bias was assessed for all included studies using the quality assessment tool for quantitative studies, and we assessed the overall certainty of the evidence using Grading of Recommendations, Assessment, Development and Evaluations. Meta-analysis methods using random effects with inverse-variance weights was used to calculate a pooled OR and 95% CIs. Programme cost data were extracted from full study reports and correspondence with study authors, and we estimated cost-effectiveness in US dollar per disability-adjusted life-year (DALY) averted. RESULTS: Our search identified 665 studies. Four studies were included in the review involving 75 hospitals and 34 485 study participants. We calculated a pooled OR of 0.52 (95% CI 0.39 to 0.70) in favour of oxygen systems reducing childhood pneumonia mortality. The median cost-effectiveness of oxygen systems strengthening was $US62 per DALY averted (range: US$44-US$225). We graded the risk of bias as moderate and the overall certainty of the evidence as low due to the non-randomised design of the studies. CONCLUSION: Our findings suggest that strengthening oxygen systems is likely to reduce hospital-based pneumonia mortality and may be cost-effective in low-resource settings. Additional implementation trials using more rigorous designs are needed to strengthen the certainty in the effect estimate.

Drug and Therapeutics Committee (DTC) evolvement and expanded scope in Ethiopia.

As a key partner of Ministry of Health (MOH) Ethiopia, The Clinton Health Access Initiative (CHAI) had been implementing the Child Survival Project (CSP) since October 2015. Strengthening DTC was one of its focuses to improve overall supply chain management (SCM). The objective of this study are to review the evolution of DTCs in Ethiopia from their early years to current practice and identify the major driving and hindering factors for their functionality. A descriptive mixed study design was employed. The study made use of qualitative data supplemented with quantitative data, generated from both primary and secondary sources through key informant interviews and desk review methods. DTCs were introduced in Ethiopia in the early 1980s. The mandate of DTCs has been given to four different government organizations during that time. As a result, due to a lack of coordination among these organizations, its implementation was lagging. Recently, the government and its partners have given attention to DTCs. More than 5847 professionals underwent DTC training from 2016 onwards. DTC establishment in health facilities improved from 85% to 98% between 2015 and 2019 during baseline and end-line assessments carried out by CHAI/CSP. Similarly, DTC functionality in HFs improved from 20% to 63%. The CHAI/CSP regular supervision data analysis revealed that DTC establishment improved from 83% to 100% of HFs, while its functionality improved from 5% to 72% between 2016 and 2019, respectively. A chi-square test of independence examining the relationship between facility and pharmacy head training on DTCs and functionality of DTC in the same facility revealed a significant association between the two variables at p<0.0001. Conclusions: Providing consistent capacity building and availing strong monitoring and evaluation system improves functionality of DTCs. Moreover, national coordinating bodies for DTCs and similar structures at Regional Health Bureaus and woreda health offices should be established.

Engineered yeast tolerance enables efficient production from toxified lignocellulosic feedstocks.

Lignocellulosic biomass remains unharnessed for the production of renewable fuels and chemicals due to challenges in deconstruction and the toxicity its hydrolysates pose to fermentation microorganisms. Here, we show in Saccharomyces cerevisiae that engineered aldehyde reduction and elevated extracellular potassium and pH are sufficient to enable near-parity production between inhibitor-laden and inhibitor-free feedstocks. By specifically targeting the universal hydrolysate inhibitors, a single strain is enhanced to tolerate a broad diversity of highly toxified genuine feedstocks and consistently achieve industrial-scale titers (cellulosic ethanol of >100 grams per liter when toxified). Furthermore, a functionally orthogonal, lightweight design enables seamless transferability to existing metabolically engineered chassis strains: We endow full, multifeedstock tolerance on a xylose-consuming strain and one producing the biodegradable plastics precursor lactic acid. The demonstration of "drop-in" hydrolysate competence enables the potential of cost-effective, at-scale biomass utilization for cellulosic fuel and nonfuel products alike.

The prevalence of hypoxemia among pediatric and adult patients presenting to healthcare facilities in low- and middle-income countries: protocol for a systematic review and meta-analysis.

BACKGROUND: Hypoxemia is a severe condition associated with high rates of mortality, particularly in low- and middle-income countries (LMICs) with poor access to oxygen therapy. Despite its clinical significance, there have been few studies to describe the burden of hypoxemia. Thus, the primary objective of this study is to systematically describe the prevalence of hypoxemia among pediatric and adult patients in low- and middle-income countries. METHODS/DESIGN: Standard systematic review methods will be used. Bibliographic databases (MEDLINE, EMBASE, CINAHL) will be searched from 1998 onwards. The search strategy aims to identify studies that have measured peripheral blood oxygen saturation (SpO2) in children and adults presenting to health facilities in LMICs. Studies will be included if oxygen saturation measurements by pulse oximetry were measured. No studies will be excluded based on study design though patients recruited from intensive care units and post-operative care will be excluded. The primary outcome is the prevalence of hypoxemia on presentation to the healthcare facility. We define hypoxemia on the basis of SpO2 measurements, and use a threshold of SpO2 less than 90% at sea level though allow for a lower threshold for studies conducted at higher altitude and where justified. Standardized tools will be used to extract data on number of patients with SpO2 measurements, number of patients with hypoxemia, patient population characteristics, and study characteristics. Quality of the included studies will be assessed using the "Checklist for Prevalence Studies" developed by the Joanna Briggs Institute. If there are enough studies to do so, we will conduct meta-analysis using a random effects model to estimate prevalence of hypoxemia and conduct subgroup analyses by age and disease groups. DISCUSSION: Hypoxemia is a critical condition and understanding the burden of hypoxemia may support decision-making in LMICs to deploy pulse oximeters and oxygen treatments more efficiently to address diseases and patient populations with the highest burden. Previous studies on hypoxemia prevalence have focused too narrowly on a few diseases or specific patient populations (e.g., pneumonia in children under five) whereas any effort to improve access to oxygen requires understanding of the potential demand for oxygen for all diseases and population groups. Governments, UN agencies, donors, and NGOs are investing strongly to improve oxygen systems in LMICs. Effective oxygen system planning requires estimation of oxygen need, informed by robust data on hypoxemia prevalence and admission patterns at all the levels of the health system. This study aims to fill that gap by providing comprehensive estimates of hypoxemia prevalence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019136622.

Improved oxygen systems at hospitals in three Nigerian states: An implementation research study.

INTRODUCTION: Hypoxemia is a life-threatening condition and is commonly seen in children with severe pneumonia. A government-led, NGO-supported, multifaceted oxygen improvement program was implemented to increase access to oxygen therapy in 29 hospitals in Kaduna, Kano, and Niger states. The program installed pulse oximeters and oxygen concentrators, trained health care workers, and biomedical engineers (BMEs), and provided regular feedback to health care staff through quality improvement teams. OBJECTIVE: The aim of this study is to evaluate whether the program increased screening for hypoxemia with pulse oximetry and prescription of oxygen for patients with hypoxemia. METHODOLOGY: The study is an uncontrolled before-after interventional study implemented at the hospital level. Medical charts of patients under 5 admitted for pneumonia between January 2017 and August 2018 were reviewed and information on patient care was extracted using a standardized form. The preintervention period of this study was defined as 1 January to 31 October 2017 and the postintervention period as 1 February to 31 August 2018. The primary outcomes of the study were whether blood-oxygen saturation measurements (SpO2 ) were documented and whether children with hypoxemia were prescribed oxygen. RESULTS: A total of 3418 patient charts were reviewed (1601 during the preintervention period and 1817 during the postintervention period). There was a significant increase in the proportion of patients with SpO2 measurements after the interventions were conducted (adjusted odds ratio [aOR] 5.0; 4.3-5.7, P < .001). Before the interventions, only 13.7% (95% confidence interval [CI]: 12.2-15.3) of patients had SpO2 measurements and after the interventions, 82.4% (95% CI: 80.7-84.1) had SpO2 measurements. Oxygen administration for patients with clinical signs of hypoxemia also increased significantly (aOR 5.0; 4.2-5.9, P < .001)-from 22.8% (95% CI: 18.8-27.2) to 77.9% (95% CI: 73.9-81.5). CONCLUSION: Increasing pulse oximetry and oxygen therapy access and utilization in a low-resourced environment is achievable through a multifaceted program focused on strengthening government-owned systems.

A retrospective mixed-methods evaluation of a national ORS and zinc scale-up program in Uganda between 2011 and 2016.

BACKGROUND: In Uganda, diarrhoea was the third leading cause of mortality among children under the age of five in 2010. To address this issue, the Ministry of Health (MOH) formed a national Diarrhoea and Pneumonia Coordination Committee (DPCC) in 2011. One of the objectives of the DPCC for reducing diarrhoea mortality was to increase the use of oral rehydration salts (ORS) and zinc. This study aimed to describe and evaluate efforts by the DPCC to increase ORS and zinc coverage. METHODS: We conducted a retrospective mixed-methods evaluation to describe the activities conducted under the DPCC and evaluate the extent to which the committee's goal of increasing ORS and zinc use was achieved. We conducted secondary analysis using Uganda's Demographic and Health Survey from 2011 and 2016, analyzed cross-sectional private medicine outlet surveys from 2014 and 2016, analyzed ORS and zinc distribution data from the Uganda National Medical Stores, and reviewed program documents from DPCC partners. RESULTS: Nationally, the proportion of children under five with diarrhoea treated with ORS and zinc increased from 1% (95% confidence interval (CI) = 1%, 2%) in 2011 to 30% (95% CI = 27%, 32%) in 2016. Among private medicine outlets, the adjusted odds of having any zinc in-stock was 1.5 (95% CI = 1.14, 1.97) times higher in 2016 than in 2014, and the retail price for a complete treatment (2 ORS sachets and 10 zinc tablets) declined by $0.19 (95% CI = -0.31, -0.06), or 14%. CONCLUSIONS: Use of combined ORS and zinc for treatment of diarrhoea in children under five significantly increased in Uganda during the program period. The range of activities conducted by the various members of the DPCC likely contributed to the increase in the use of combined ORS and zinc.

Use of pulse oximetry during initial assessments of children under five with pneumonia: a retrospective cross-sectional study from 14 hospitals in Ethiopia.

BACKGROUND: Hypoxemia, a fatal condition characterized by low concentration of oxygen in the blood, is strongly associated with death among children with pneumonia. Ethiopia's Federal Ministry of Health launched its first National Oxygen and Pulse Oximetry Scale-up road map to improve access and utilization of pulse oximetry and oxygen. This study aimed to describe the use of pulse oximetry during the initial patient assessment among children under five diagnosed with pneumonia and serves as a benchmark to measure progress of the road map. METHODS: The study design was an observational study using retrospective review of patient medical records at 14 hospitals. Medical records of 443 children age 0-59 months with a primary diagnosis of pneumonia were randomly selected for review. The primary outcome was whether an arterial blood oxygen saturation (SpO2) measurement was recorded in the patient's medical record at the initial assessment. RESULTS: Overall, 10% (95% confidence interval CI = 4%-22%) of patient medical records had a SpO2 measurement. Admitted patients were more likely to have a SpO2 measurement recorded in their medical records than patients treated in the outpatient department (P<0.01). Among admitted patients, 19% (95% CI = 8%-38%) had a SpO2 measurement compared to 3% (95% CI = 1%-11%) of patients treated in the outpatient department. CONCLUSION: In Ethiopia, patients under five with a primary diagnosis of pneumonia are rarely screened for hypoxemia with a pulse oximeter, and hypoxemia may be severely underdiagnosed. Much needs to be done to improve the routine use of pulse oximetry.

An evaluation of a national oral rehydration solution and zinc scale-up program in Kenya between 2011 and 2016.

BACKGROUND: In Kenya, diarrheal disease is the second leading cause of death among children under five. The Government of Kenya launched a national plan to increase coverage of oral rehydration solution (ORS) and zinc by addressing demand and supply-side barriers. This study evaluates progress of ORS and zinc uptake in Kenya according to the national plan from 2011 to 2016. METHODS: In 2016, we conducted a nationally representative population-based household survey to estimate coverage of ORS and zinc for treatment of diarrhea cases among children under five. We also used ORS and zinc coverage data from the two most recent Kenya Demographic and Health Surveys in 2008/09 and 2014 to estimate annual changes in coverage rates during the program period. Based on these inputs, we used the Lives Saved Tool to estimate the number of diarrhea deaths averted between 2011 and 2016 due to increased use of ORS and zinc. RESULTS: The 2016 survey results showed that ORS coverage was 42% (95% confidence interval (CI) = 38%, 47%) and zinc coverage was 18% (95% CI = 15%, 23%). The estimated coverage for the combined use of ORS and zinc was 15% in 2016 (95% CI = 12%, 19%). Compared to 2011, an additional 3340 (sensitivity bounds = 2 670, 3 920) diarrhea deaths among children under five were averted due to increases in ORS and zinc coverage. CONCLUSIONS: Kenya was successful in catalyzing uptake of combined treatment with ORS and zinc, which rose from 0.8% in 2011 to 15% in 2016. Ongoing efforts are necessary to further build on these gains.