Evaluating scientific confidence in the concordance of in vitro and in vivo protective points of departure.

To fulfil the promise of reducing reliance on mammalian in vivo laboratory animal studies, new approach methods (NAMs) need to provide a confident basis for regulatory decision-making. However, previous attempts to develop in vitro NAMs-based points of departure (PODs) have yielded mixed results, with PODs from U.S. EPA's ToxCast, for instance, appearing more conservative (protective) but poorly correlated with traditional in vivo studies. Here, we aimed to address this discordance by reducing the heterogeneity of in vivo PODs, accounting for species differences, and enhancing the biological relevance of in vitro PODs. However, we only found improved in vitro-to-in vivo concordance when combining the use of Bayesian model averaging-based benchmark dose modeling for in vivo PODs, allometric scaling for interspecies adjustments, and human-relevant in vitro assays with multiple induced pluripotent stem cell-derived models. Moreover, the available sample size was only 15 chemicals, and the resulting level of concordance was only fair, with correlation coefficients <0.5 and prediction intervals spanning several orders of magnitude. Overall, while this study suggests several ways to enhance concordance and thereby increase scientific confidence in vitro NAMs-based PODs, it also highlights challenges in their predictive accuracy and precision for use in regulatory decision making.

Effectiveness of community case management of malaria on severe malaria and inpatient malaria deaths in Zambia: a dose-response study using routine health information system data.

BACKGROUND: Community case management of malaria (CCM) has been expanded in many settings, but there are limited data describing the impact of these services in routine implementation settings or at large scale. Zambia has intensively expanded CCM since 2013, whereby trained volunteer community health workers (CHW) use rapid diagnostic tests and artemether-lumefantrine to diagnose and treat uncomplicated malaria. METHODS: This retrospective, observational study explored associations between changing malaria service point (health facility or CHW) density per 1000 people and severe malaria admissions or malaria inpatient deaths by district and month in a dose-response approach, using existing routine and programmatic data. Negative binomial generalized linear mixed-effect models were used to assess the impact of increasing one additional malaria service point per 1000 population, and of achieving Zambia's interim target of 1 service point per 750 population. Access to insecticide-treated nets, indoor-residual spraying, and rainfall anomaly were included in models to reduce potential confounding. RESULTS: The study captured 310,855 malaria admissions and 7158 inpatient malaria deaths over 83 districts (seven provinces) from January 2015 to May 2020. Total CHWs increased from 43 to 4503 during the study period, while health facilities increased from 1263 to 1765. After accounting for covariates, an increase of one malaria service point per 1000 was associated with a 19% reduction in severe malaria admissions among children under five (incidence rate ratio [IRR] 0.81, 95% confidence interval [CI] 0.75-0.87, p < 0.001) and 23% reduction in malaria deaths among under-fives (IRR 0.77, 95% CI 0.66-0.91). After categorizing the exposure of population per malaria service point, there was evidence for an effect on malaria admissions and inpatient malaria deaths among children under five only when reaching the target of one malaria service point per 750 population. CONCLUSIONS: CCM is an effective strategy for preventing severe malaria and deaths in areas such as Zambia where malaria diagnosis and treatment access remains challenging. These results support the continued investment in CCM scale-up in similar settings, to improve access to malaria diagnosis and treatment.

Nurses' strategies for overcoming barriers to fundamental nursing care in patients with COVID-19 caused by infection with the SARS-COV-2 virus: Results from the 'COVID-NURSE' survey.

AIMS: To identify strategies used by registered nurses and non-registered nursing care staff in overcoming barriers when providing fundamental nursing care for non-invasively ventilated inpatients with COVID-19. DESIGN: Online survey with open-ended questions to collect qualitative data. METHODS: In August 2020, we asked UK-based nursing staff to describe any strategies they employed to overcome barriers to delivering care in 15 fundamental nursing care categories when providing care to non-invasively ventilated patients with COVID-19. We analysed data using Framework Analysis. RESULTS: A total of 1062 nurses consented to participate in our survey. We derived four themes. 1) Communication behaviours included adapting verbal and non-verbal communication with patients, using information technology to enable patients' significant others to communicate with staff and patients, and establishing clear information-sharing methods with other staff. 2) Organizing care required clustering interventions, carefully managing supplies, encouraging patient self-care and using 'runners' and interdisciplinary input. 3) Addressing patients' well-being and values required spending time with patients, acting in loco familiae, providing access to psychological and spiritual support, obtaining information about patients' wishes early on and providing privacy and comforting/meaningful items. 4) Management and leadership behaviours included training, timely provision of pandemic information, psychological support, team huddles and facilitating regular breaks. CONCLUSIONS: Our respondents identified multiple strategies in four main areas of clinical practice. Management and leadership are crucial to both fundamental care delivery and the well-being of nurses during pandemics. Grouping strategies into these areas of action may assist nurses and leaders to prepare for pandemic nursing. IMPACT: As these strategies are unlikely to be exclusive to the COVID-19 pandemic, their global dissemination may improve patient experience and help nurses deliver fundamental care when planning pandemic nursing. However, their effectiveness is unknown. Therefore, we are currently evaluating these strategies in a cluster randomized controlled trial.

Provoking a Cultural Shift in Data Quality.

Ecological studies require quality data to describe the nature of ecological processes and to advance understanding of ecosystem change. Increasing access to big data has magnified both the burden and the complexity of ensuring quality data. The costs of errors in ecology include low use of data, increased time spent cleaning data, and poor reproducibility that can result in a misunderstanding of ecosystem processes and dynamics, all of which can erode the efficacy of and trust in ecological research. Although conceptual and technological advances have improved ecological data access and management, a cultural shift is needed to embed data quality as a cultural practice. We present a comprehensive data quality framework to evoke this cultural shift. The data quality framework flexibly supports different collaboration models, supports all types of ecological data, and can be used to describe data quality within both short- and long-term ecological studies.

Cardiotoxicity Hazard and Risk Characterization of ToxCast Chemicals Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes from Multiple Donors.

Heart disease remains a significant human health burden worldwide with a significant fraction of morbidity attributable to environmental exposures. However, the extent to which the thousands of chemicals in commerce and the environment may contribute to heart disease morbidity is largely unknown, because in contrast to pharmaceuticals, environmental chemicals are seldom tested for potential cardiotoxicity. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes have become an informative in vitro model for cardiotoxicity testing of drugs with the availability of cells from multiple individuals allowing in vitro testing of population variability. In this study, we hypothesized that a panel of iPSC-derived cardiomyocytes from healthy human donors can be used to screen for the potential cardiotoxicity hazard and risk of environmental chemicals. We conducted concentration-response testing of 1029 chemicals (drugs, pesticides, flame retardants, polycyclic aromatic hydrocarbons (PAHs), plasticizers, industrial chemicals, food/flavor/fragrance agents, etc.) in iPSC-derived cardiomyocytes from 5 donors. We used kinetic calcium flux and high-content imaging to derive quantitative measures as inputs into Bayesian population concentration-response modeling of the effects of each chemical. We found that many environmental chemicals pose a hazard to human cardiomyocytes in vitro with more than half of all chemicals eliciting positive or negative chronotropic or arrhythmogenic effects. However, most of the tested environmental chemicals for which human exposure and high-throughput toxicokinetics data were available had wide margins of exposure and, thus, do not appear to pose a significant human health risk in a general population. Still, relatively narrow margins of exposure (<100) were estimated for some perfuoroalkyl substances and phthalates, raising concerns that cumulative exposures may pose a cardiotoxicity risk. Collectively, this study demonstrated the value of using a population-based human in vitro model for rapid, high-throughput hazard and risk characterization of chemicals for which little to no cardiotoxicity data are available from guideline studies in animals.

A new approach method for characterizing inter-species toxicodynamic variability.

Inter-species differences in toxicodynamics are often a critical source of uncertainty in safety evaluations and typically dealt with using default adjustment factors. In vitro studies that use cells from different species demonstrated some success for estimating the relationships between life span and/or body weight and sensitivity to cytotoxicity; however, no apparent investigation evaluated the utility of these models for risk assessment. It was hypothesized that an in vitro model using dermal fibroblasts derived from diverse species and individuals might be utilized to inform the extent of inter-species and inter-individual variability in toxicodynamics. To test this hypothesis and characterize both inter-species and inter-individual variability in cytotoxicity, concentration-response cytotoxicity screening of 40 chemicals in primary dermal fibroblasts from 68 individuals of 54 diverse species was conducted. Chemicals examined included drugs, environmental pollutants, and food/flavor/fragrance agents; most of these were previously assessed either in vivo or in vitro for inter-species or inter-individual variation. Species included humans, the typical preclinical species and representatives from other orders of mammals and birds. Data demonstrated that both inter-species and inter-individual components of variability contribute to the observed differences in sensitivity to cell death. Further, it was found that the magnitude of the observed inter-species and inter-individual differences was chemical-dependent. This study contributes to the paradigm shift in risk assessment from reliance on in vivo toxicity testing to higher-throughput in vitro or alternative approaches, extending the strategy to replace use of default adjustment factors with experimental characterization of toxicodynamic inter-individual variability and to also address toxicodynamic inter-species variability.

Fundamental nursing care in patients with the SARS-CoV-2 virus: results from the 'COVID-NURSE' mixed methods survey into nurses' experiences of missed care and barriers to care.

BACKGROUND: Patient experience of nursing care is associated with safety, care quality, treatment outcomes, costs and service use. Effective nursing care includes meeting patients' fundamental physical, relational and psychosocial needs, which may be compromised by the challenges of SARS-CoV-2. No evidence-based nursing guidelines exist for patients with SARS-CoV-2. We report work to develop such a guideline. Our aim was to identify views and experiences of nursing staff on necessary nursing care for inpatients with SARS-CoV-2 (not invasively ventilated) that is omitted or delayed (missed care) and any barriers to this care. METHODS: We conducted an online mixed methods survey structured according to the Fundamentals of Care Framework. We recruited a convenience sample of UK-based nursing staff who had nursed inpatients with SARS-CoV-2 not invasively ventilated. We asked respondents to rate how well they were able to meet the needs of SARS-CoV-2 patients, compared to non-SARS-CoV-2 patients, in 15 care categories; select from a list of barriers to care; and describe examples of missed care and barriers to care. We analysed quantitative data descriptively and qualitative data using Framework Analysis, integrating data in side-by-side comparison tables. RESULTS: Of 1062 respondents, the majority rated mobility, talking and listening, non-verbal communication, communicating with significant others, and emotional wellbeing as worse for patients with SARS-CoV-2. Eight barriers were ranked within the top five in at least one of the three care areas. These were (in rank order): wearing Personal Protective Equipment, the severity of patients' conditions, inability to take items in and out of isolation rooms without donning and doffing Personal Protective Equipment, lack of time to spend with patients, lack of presence from specialised services e.g. physiotherapists, lack of knowledge about SARS-CoV-2, insufficient stock, and reluctance to spend time with patients for fear of catching SARS-CoV-2. CONCLUSIONS: Our respondents identified nursing care areas likely to be missed for patients with SARS-CoV-2, and barriers to delivering care. We are currently evaluating a guideline of nursing strategies to address these barriers, which are unlikely to be exclusive to this pandemic or the environments represented by our respondents. Our results should, therefore, be incorporated into global pandemic planning.

The potential role of patent and proprietary medicine vendors' associations in improving the quality of services in Nigeria's drug shops.

BACKGROUND: Patent and Proprietary Medicine Vendors (PPMVs) play a major role in Nigeria's health care delivery but regulation and monitoring of their practice needs appreciable improvement to ensure they deliver quality services. Most PPMVs belong to associations which may be useful in improving their regulation. However, little is known about how the PPMV associations function and how they can partner with relevant regulatory agencies to ensure members' compliance and observance of good practice. This study sought to describe the PPMV associations' structure and operations and the regulatory environment in which PPMVs function. With this information we explore ways in which the associations could help improve the coverage of Nigeria's population with basic quality health care services. METHODS: A mixed methods study was conducted across four rural local government areas (LGAs) (districts) in two Nigerian states of Bayelsa and Oyo. The study comprises a quantitative data collection of 160 randomly selected PPMVs and their shops, eight PPMV focus group discussions, in-depth interviews with 26 PPMV association executives and eight regulatory agency representatives overseeing PPMVs' practice. RESULTS: The majority of the PPMVs in the four LGAs belonged to the local chapters of National Association of Patent and Proprietary Medicine Dealers (NAPPMED). The associations were led by executive members and had regular monthly meetings. NAPPMED monitored members' activities, provided professional and social support, and offered protection from regulatory agencies. More than 80% of PPMVs received at least one monitoring visit in the previous 6 months and local NAPPMED was the organization that monitored PPMVs the most, having visited 68.8% of respondents. The three major regulators, who reached 30.0-36.3% of PPMVs reported lack of human and financial resources as the main challenge they faced in regulation. CONCLUSIONS: Quality services at drug shops would benefit from stronger monitoring and regulation. The PPMV associations already play a role in monitoring their members. Regulatory agencies and other organizations could partner with the PPMV associations to strengthen the regulatory environment and expand access to basic quality health services at PPMV shops in Nigeria.

Population-based toxicity screening in human induced pluripotent stem cell-derived cardiomyocytes.

The potential for cardiotoxicity is carefully evaluated for pharmaceuticals, as it is a major safety liability. However, environmental chemicals are seldom tested for their cardiotoxic potential. Moreover, there is a large variability in both baseline and drug-induced cardiovascular risk in humans, but data are lacking on the degree to which susceptibility to chemically-induced cardiotoxicity may also vary. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes have become an important in vitro model for drug screening. Thus, we hypothesized that a population-based model of iPSC-derived cardiomyocytes from a diverse set of individuals can be used to assess potential hazard and inter-individual variability in chemical effects on these cells. We conducted concentration-response screening of 134 chemicals (pharmaceuticals, industrial and environmental chemicals and food constituents) in iPSC-derived cardiomyocytes from 43 individuals, comprising both sexes and diverse ancestry. We measured kinetic calcium flux and conducted high-content imaging following chemical exposure, and utilized a panel of functional and cytotoxicity parameters in concentration-response for each chemical and donor. We show reproducible inter-individual variability in both baseline and chemical-induced effects on iPSC-derived cardiomyocytes. Further, chemical-specific variability in potency and degree of population variability were quantified. This study shows the feasibility of using an organotypic population-based human in vitro model to quantitatively assess chemicals for which little cardiotoxicity information is available. Ultimately, these results advance in vitro toxicity testing methodologies by providing an innovative tool for population-based cardiotoxicity screening, contributing to the paradigm shift from traditional animal models of toxicity to in vitro toxicity testing methods.

Malaria testing and treatment knowledge among selected rural patent and proprietary medicine vendors (PPMV) in Nigeria.

BACKGROUND: Malaria is a leading cause of illness and death in Nigeria, but access of poor people to quality anti-malarial services remains low especially in the rural areas. Patent and proprietary medicine vendors (PPMVs) provide the majority of malaria treatment in rural areas, but little is known about their knowledge of malaria testing and treatment of uncomplicated malaria as recommended in the 2011 National Malaria Control Programme policy. METHODS: A cross-sectional survey was conducted in two purposively selected states (Oyo and Bayelsa) in Nigeria with each state representing a different geographic and linguistic-ethnic region in the southern part of the country. Two rural LGAs were randomly selected from each state and data were collected from 160 randomly selected PPMVS (40 per LGA) using a structured questionnaire. Data were analysed using descriptive statistics. RESULTS: The 2011 National Policy on Malaria Diagnosis and Treatment is mostly unknown to PPMVs. Although most PPMVs (89%) knew that artemisinin-based combination therapy (ACT) is recommended in the national policy, 91% also thought non-ACT were endorsed. The proportion of PPMVs who stated they would treat a malaria case with an artemisinin-based combination at the correct dose was 33% for a child under five, 47% for an adult male and 14% for a pregnant woman in her second trimester. The proportion of PPMVs who reported they would diagnose a case of malaria prior to treatment using a malaria rapid diagnostic test (RDT) kit was 1.9% for children under five, 7.5% for adult males and 3.1% for pregnant women in their first trimester due to lack of knowledge. Almost two-thirds (65.6%) would correctly refer children with severe malaria to health facility. CONCLUSIONS: Substantial knowledge gaps on the use of RDTs and treatment with artemisinin-based combinations exist among rural PPMVs. Given existing evidence regarding the effectiveness of private retail outlets in malaria case management, PPMVs should be provided with competency-based training and supervision to improve the quality of care they provide.

Peroxisomal Pex3 activates selective autophagy of peroxisomes via interaction with the pexophagy receptor Atg30.

Pexophagy is a process that selectively degrades peroxisomes by autophagy. The Pichia pastoris pexophagy receptor Atg30 is recruited to peroxisomes under peroxisome proliferation conditions. During pexophagy, Atg30 undergoes phosphorylation, a prerequisite for its interactions with the autophagy scaffold protein Atg11 and the ubiquitin-like protein Atg8. Atg30 is subsequently shuttled to the vacuole along with the targeted peroxisome for degradation. Here, we defined the binding site for Atg30 on the peroxisomal membrane protein Pex3 and uncovered a role for Pex3 in the activation of Atg30 via phosphorylation and in the recruitment of Atg11 to the receptor protein complex. Pex3 is classically a docking protein for other proteins that affect peroxisome biogenesis, division, and segregation. We conclude that Pex3 has a role beyond simple docking of Atg30 and that its interaction with Atg30 regulates pexophagy in the yeast P. pastoris.

Effectiveness of educational outreach in infectious diseases management: a cluster randomized trial in Uganda.

BACKGROUND: Integrated Infectious Diseases Capacity Building Evaluation (IDCAP) teams designed and implemented two health worker in-service training approaches: 1) an off-site classroom-based integrated management of infectious diseases (IMID) course with distance learning aspects, and 2) on-site support (OSS), an educational outreach intervention. We tested the effects of OSS on workload and 12 facility performance indicators for emergency triage assessment and treatment, HIV testing, and malaria and pneumonia case management among outpatients by two subgroups: 1) mid-level practitioners (MLP) who attended IMID training (IMID-MLP) and 2) health workers who did not (No-IMID). METHODS: Thirty-six health facilities participated in the IDCAP trial, with 18 randomly assigned to Arm A and 18 to Arm B. Two MLP in both arms received IMID. All providers at Arm A facilities received nine monthly OSS visits from April to December 2010 while Arm B did not. From November 2009 to December 2010, 777,667 outpatient visits occurred. We analyzed 669,580 (86.1 %) outpatient visits, where provider cadre was reported. Treatment was provided by 64 IMID-MLP and 1,515 No-IMID providers. The effect of OSS was measured by the difference in pre/post changes across arms after controlling for covariates (adjusted ratio of relative risks = a RRR). RESULTS: The effect of OSS on patients-per-provider-per-day (workload) among IMID-MLP (aRRR = 1.21; p = 0.48) and No-IMID (aRRR = 0.90; p = 0.44) was not statistically significant. Among IMID-MLP, OSS was effective for three indicators: malaria cases receiving an appropriate antimalarial (aRRR = 1.26, 99 % CI = 1.02-1.56), patients with negative malaria test result prescribed an antimalarial (aRRR = 0.49, 99 % CI = 0.26-0.92), and patients with acid-fast bacilli smear negative result receiving empiric treatment for acute respiratory infection (aRRR = 2.04, 99 % CI = 1.06-3.94). Among No-IMID, OSS was effective for two indicators: emergency and priority patients admitted, detained or referred (aRRR = 2.12, 99 % CI = 1.05-4.28) and emergency patients receiving at least one appropriate treatment (aRRR = 1.98, 99 % CI = 1.21-3.24). CONCLUSION: Effects of OSS on workload were not statistically significant. Significant OSS effects on facility performance across subgroups were heterogeneous. OSS supported MLP who diagnosed and treated patients to apply IMID knowledge. For other providers, OSS supported team work to manage emergency patients. This evidence on OSS effectiveness could inform interventions to improve health workers' capacity to deliver better quality infectious diseases care.

Phosphorylation of mitophagy and pexophagy receptors coordinates their interaction with Atg8 and Atg11.

The selective autophagy receptors Atg19 and Atg32 interact with two proteins of the core autophagic machinery: the scaffold protein Atg11 and the ubiquitin-like protein Atg8. We found that the Pichia pastoris pexophagy receptor, Atg30, also interacts with Atg8. Both Atg30 and Atg32 interactions are regulated by phosphorylation close to Atg8-interaction motifs. Extending this finding to Saccharomyces cerevisiae, we confirmed phosphoregulation for the mitophagy and pexophagy receptors, Atg32 and Atg36. Each Atg30 molecule must interact with both Atg8 and Atg11 for full functionality, and these interactions occur independently and not simultaneously, but rather in random order. We present a common model for the phosphoregulation of selective autophagy receptors.

Disease diagnosis in primary care in Uganda.

BACKGROUND: The overall burden of disease (BOD) especially for infectious diseases is higher in Sub-Saharan Africa than other regions of the world. Existing data collected through the Health Management Information System (HMIS) may not be optimal to measure BOD. The Infectious Diseases Capacity Building Evaluation (IDCAP) cooperated with the Ugandan Ministry of Health to improve the quality of HMIS data. We describe diagnoses with associated clinical assessments and laboratory investigations of outpatients attending primary care in Uganda. METHODS: IDCAP supported HMIS data collection at 36 health center IVs in Uganda for five months (November 2009 to March 2010) prior to implementation of the IDCAP interventions. Descriptive analyses were performed on a cross-sectional dataset of 209,734 outpatient visits during this period. RESULTS: Over 500 illnesses were diagnosed. Infectious diseases accounted for 76.3% of these and over 30% of visits resulted in multiple diagnoses. Malaria (48.3%), cough/cold (19.4%), and intestinal worms (6.6%) were the most frequently diagnosed illnesses. Body weight was recorded for 36.8% of patients and less than 10% had other clinical assessments recorded. Malaria smears (64.2%) and HIV tests (12.2%) accounted for the majority of 84,638 laboratory tests ordered. Fewer than 30% of patients for whom a laboratory investigation was available to confirm the clinical impression had the specific test performed. CONCLUSIONS: We observed a broad range of diagnoses, a high percentage of multiple diagnoses including true co-morbidities, and underutilization of laboratory support. This emphasizes the complexity of illnesses to be addressed by primary healthcare workers. An improved HMIS collecting timely, quality data is needed. This would adequately describe the burden of disease and processes of care at primary care level, enable appropriate national guidelines, programs and policies and improve accountability for the quality of care.

Reduction of malaria case incidence following the introduction of clothianidin-based indoor residual spraying in previously unsprayed districts: an observational analysis using health facility register data from Côte d'Ivoire, 2018-2022.

BACKGROUND: Indoor residual spraying (IRS) using neonicotinoid-based insecticides (clothianidin and combined clothianidin with deltamethrin) was deployed in two previously unsprayed districts of Côte d'Ivoire in 2020 and 2021 to complement standard pyrethroid insecticide-treated nets. This retrospective observational study uses health facility register data to assess the impact of IRS on clinically reported malaria case incidence. METHODS: Health facility data were abstracted from consultation registers for the period September 2018 to April 2022 in two IRS districts and two control districts that did not receive IRS. Malaria cases reported by community health workers (CHWs) were obtained from district reports and District Health Information Systems 2. Facilities missing complete data were excluded. Controlled interrupted time series models were used to estimate the effect of IRS on monthly all-ages population-adjusted confirmed malaria cases and cases averted by IRS. Models controlled for transmission season, precipitation, vegetation, temperature, proportion of cases reported by CHWs, proportion of tested out of suspected cases and non-malaria outpatient visits. RESULTS: An estimated 10 988 (95% CI 5694 to 18 188) malaria cases were averted in IRS districts the year following the 2020 IRS campaign, representing a 15.9% reduction compared with if IRS had not been deployed. Case incidence in IRS districts dropped by 27.7% (incidence rate ratio (IRR) 0.723, 95% CI 0.592 to 0.885) the month after the campaign. In the 8 months after the 2021 campaign, 14 170 (95% CI 13 133 to 15 025) estimated cases were averted, a 24.7% reduction, and incidence in IRS districts dropped by 37.9% (IRR 0.621, 95% CI 0.462 to 0.835) immediately after IRS. Case incidence in control districts did not change following IRS either year (p>0.05) and the difference in incidence level change between IRS and control districts was significant both years (p<0.05). CONCLUSION: Deployment of clothianidin-based IRS was associated with a reduction in malaria case rates in two districts of Côte d'Ivoire following IRS deployment in 2020 and 2021.

Establishing a health information workforce: innovation for low- and middle-income countries.

BACKGROUND: To address the shortage of health information personnel within Botswana, an innovative human resources approach was taken. University graduates without training or experience in health information or health sciences were hired and provided with on-the-job training and mentoring to create a new cadre of health worker: the district Monitoring and Evaluation (M&E) Officer. This article describes the early outcomes, achievements, and challenges from this initiative. METHODS: Data were collected from the district M&E Officers over a 2-year period and included a skills assessment at baseline and 12 months, pre- and post-training tests, interviews during stakeholder site visits, a survey of achievements, focus group discussions, and an attrition assessment. RESULTS: An average of 2.7 mentoring visits were conducted for M&E Officers in each district. There were five training sessions over 18 months. Knowledge scores significantly increased (p < 0.05) during the three trainings in which pre/post tests were administered. Over 1 year, there were significant improvements (p < 0.05) in self-rated skills related to computer literacy, checking data validity, implementing data quality procedures, using data to support program planning, proposing indicators, and writing M&E reports. Out of the 34 district M&E Officers interviewed during site visits, most were conducting facility visits to review data (27/34; 79%), comparing data sets over time (31/34; 91%), backing up data (32/34; 94%), and analyzing data (32/34; 94%). Common challenges included late facility reports (28/34; 82%), lack of transportation (22/34; 65%), inaccurate facility reports (10/34; 29%), and colleagues' misunderstanding of M&E (10/34; 29%). Six posts were vacated in the first year (6/51; 12%). A total of 49 Officers completed the achievements survey; of these, common accomplishments related to improvements in data management (35/49; 71%), data quality (31/49; 63%), data use (29/49; 59%), and capacity development (26/49; 53%). CONCLUSIONS: The development of a cadre of district M&E Officers has contributed positively to the health information system in Botswana. In the absence of tertiary training related to health information, on-the-job training and mentoring of university graduates can be an effective approach for developing a new professional cadre of M&E expertise and for strengthening capacity within a national health system.

Pre-endoscopic Rockall and Blatchford scores to identify which emergency department patients with suspected gastrointestinal bleed do not need endoscopic hemostasis.

BACKGROUND: The pre-endoscopic Rockall Score (RS) and the Glasgow-Blatchford Scores (GBS) can help risk stratify patients with upper gastrointestinal bleed who are seen in the Emergency Department (ED). The RS and GBS have yet to be validated in a United States patient population for their ability to discriminate which ED patients with upper gastrointestinal bleed do not need endoscopic hemostasis. OBJECTIVE: We sought to determine whether patients who received a score of zero on either score (the lowest risk) in the ED still required upper endoscopic hemostasis during hospitalization. METHODS: Retrospective electronic medical record chart review was performed during a 3-year period (2007-2009) to identify patients with suspected upper gastrointestinal bleed by ED final diagnosis of gastrointestinal hemorrhage and related terms at a single urban academic ED. The RS and GBS were calculated from ED chart abstraction and the hospital records of admitted patients were queried for subsequent endoscopic hemostasis. RESULTS: Six hundred and ninety patients with gastrointestinal bleed were identified and 86% were admitted to the hospital. One hundred and twenty-two patients had an RS equal to zero; 67 (55%; 95% confidence interval [CI] 46-63%) of these patients were admitted to the hospital and 11 (16%; 95% CI 9-27%) received endoscopic hemostasis. Sixty-three patients had a GBS equal to zero; 15 (24%; 95% CI 15-36%) were admitted to the hospital and 2 (13%; 95% CI 4-38%) received endoscopic hemostasis. CONCLUSIONS: Some patients who were identified as lowest risk by the GBS or RS still received endoscopic hemostasis during hospital admission. These clinical decision rules may be insufficiently sensitive to predict which patients do not require endoscopic hemostasis.

Using routine health data to evaluate the impact of indoor residual spraying on malaria transmission in Madagascar.

INTRODUCTION: Indoor residual spraying (IRS) and insecticide-treated bed nets (ITNs) are cornerstone malaria prevention methods in Madagascar. This retrospective observational study uses routine data to evaluate the impacts of IRS overall, sustained IRS exposure over multiple years and level of spray coverage (structures sprayed/found) in nine districts where non-pyrethroid IRS was deployed to complement standard pyrethroid ITNs from 2017 to 2020. METHODS: Multilevel negative-binomial generalised linear models were fit to estimate the effects of IRS exposure overall, consecutive years of IRS exposure and spray coverage level on monthly all-ages population-adjusted malaria cases confirmed by rapid diagnostic test at the health facility level. The study period extended from July 2016 to June 2021. Facilities with missing data and non-geolocated communes were excluded. Facilities in IRS districts were matched with control facilities by propensity score analysis. Models were controlled for ITN survivorship, mass drug administration coverage, precipitation, enhanced vegetation index, seasonal effects and district. Predicted cases under a counterfactual no IRS scenario and number of cases averted by IRS were estimated using the fitted models. RESULTS: Exposure to IRS overall reduced case incidence by an estimated 30.3% from 165.8 cases per 1000 population (95% CI=139.7 to 196.7) under a counterfactual no IRS scenario, to 114.3 (95% CI=96.5 to 135.3) over 12 months post-IRS campaign in nine districts. A third year of IRS reduced malaria cases 30.9% more than a first year (incidence rate ratio (IRR)=0.578, 95% CI=0.578 to 0.825, p<0.001) and 26.7% more than a second year (IRR=0.733, 95% CI=0.611 to 0.878, p=0.001). There was no significant difference between the first and second year (p>0.05). Coverage of 86%-90% was associated with a 19.7% reduction in incidence (IRR=0.803, 95% CI=0.690 to 0.934, p=0.005) compared with coverage ≤85%, although these results were not robust to sensitivity analysis. CONCLUSION: This study demonstrates that non-pyrethroid IRS appears to substantially reduce malaria incidence in Madagascar and that sustained implementation of IRS over three years confers additional benefits.

Process and Methodological Considerations for Observational Analyses of Vector Control Interventions in Sub-Saharan Africa Using Routine Malaria Data.

Progress in malaria control has stalled in recent years. With growing resistance to existing malaria vector control insecticides and the introduction of new vector control products, national malaria control programs (NMCPs) increasingly need to make data-driven, subnational decisions to inform vector control deployment. As NMCPs are increasingly conducting subnational stratification of malaria control interventions, including malaria vector control, country-specific frameworks and platforms are increasingly needed to guide data use for vector control deployment. Integration of routine health systems data, entomological data, and vector control program data in observational longitudinal analyses offers an opportunity for NMCPs and research institutions to conduct evaluations of existing and novel vector control interventions. Drawing on the experience of implementing 22 vector control evaluations across 14 countries in sub-Saharan Africa, as well as published and gray literature on vector control impact evaluations using routine health information system data, this article provides practical guidance on the design of these evaluations, makes recommendations for key variables and data sources, and proposes methods to address challenges in data quality. Key recommendations include appropriate parameterization of impact and coverage indicators, incorporating explanatory covariates and contextual factors from multiple sources (including rapid diagnostic testing stockouts; insecticide susceptibility; vector density measures; vector control coverage, use, and durability; climate and other malaria and non-malaria health programs), and assessing data quality before the evaluation through either on-the-ground or remote data quality assessments. These recommendations may increase the frequency, rigor, and utilization of routine data sources to inform national program decision-making for vector control.

Improved clinical and laboratory skills after team-based, malaria case management training of health care professionals in Uganda.

BACKGROUND: Deployment of highly effective artemisinin-based combination therapy for treating uncomplicated malaria calls for better targeting of malaria treatment to improve case management and minimize drug pressure for selecting resistant parasites. The Integrated Management of Malaria curriculum was developed to train multi-disciplinary teams of clinical, laboratory and health information assistants. METHODS: Evaluation of training was conducted in nine health facilities that were Uganda Malaria Surveillance Programme (UMSP) sites. From December 2006 to June 2007, 194 health professionals attended a six-day course. One-hundred and one of 118 (86%) clinicians were observed during patient encounters by expert clinicians at baseline and during three follow-up visits approximately six weeks, 12 weeks and one year after the course. Experts used a standardized tool for children less than five years of age and similar tool for patients five or more years of age. Seventeen of 30 laboratory professionals (57%) were assessed for preparation of malaria blood smears and ability to interpret smear results of 30 quality control slides. RESULTS: Percentage of patients at baseline and first follow-up, respectively, with proper history-taking was 21% and 43%, thorough physical examination 18% and 56%, correct diagnosis 51% and 98%, treatment in compliance with national policy 42% and 86%, and appropriate patient education 17% and 83%. In estimates that adjusted for individual effects and a matched sample, relative risks were 1.86 (95% CI: 1.20,2.88) for history-taking, 2.66 (95%CI: 1.60,4.41) for physical examination, 1.77 (95%CI: 1.41,2.23) for diagnosis, 1.96 (95%CI: 1.46,2.63) for treatment, and 4.47 (95%CI: 2.68,7.46) for patient education. Results were similar for subsequent follow-up and in sub-samples stratified by patient age. Quality of malaria blood smear preparation improved from 21.6% at baseline to 67.3% at first follow-up (p < 0.008); sensitivity of interpretation of quality control slides increased from 48.6% to 70.6% (p < 0.199) and specificity increased from 72.1% to 77.2% (p < 0.736). Results were similar for subsequent follow-up, with the exception of a significant increase in specificity (94.2%, p < 0.036) at one year. CONCLUSION: A multi-disciplinary team training resulted in statistically significant improvements in clinical and laboratory skills. As a joint programme, the effects cannot be distinguished from UMSP activities, but lend support to long-term, on-going capacity-building and surveillance interventions.