Population assessment of health system performance in 16 countries.

Objective: To demonstrate how the new internationally comparable instrument, the People's Voice Survey, can be used to contribute the perspective of the population in assessing health system performance in countries of all levels of income. Methods: We surveyed representative samples of populations in 16 low-, middle- and high-income countries on health-care utilization, experience and confidence during 2022-2023. We summarized and visualized data corresponding to the key domains of the World Health Organization universal health coverage framework for health system performance assessment. We examined correlation with per capita health spending by calculating Pearson coefficients, and within-country income-based inequities using the slope index of inequality. Findings: In the domain of care effectiveness, we found major gaps in health screenings and endorsement of public primary care. Only one in three respondents reported very good user experience during health visits, with lower proportions in low-income countries. Access to health care was rated highest of all domains; however, only half of the populations felt secure that they could access and afford high-quality care if they became ill. Populations rated the quality of private health systems higher than that of public health systems in most countries. Only half of respondents felt involved in decision-making (less in high-income countries). Within countries, we found statistically significant pro-rich inequalities across many indicators. Conclusion: Populations can provide vital information about the real-world function of health systems, complementing other system performance metrics. Population-wide surveys such as the People's Voice Survey should become part of regular health system performance assessments.

Site-specific protein conjugates incorporating Para-Azido-L-Phenylalanine for cellular and in vivo imaging.

This work features the use of amber suppression-mediated unnatural amino acid (UAA) incorporation into proteins for various imaging purposes. The site-specific incorporation of the UAA, p-azido-L-phenylalanine (pAzF), provides an azide handle that can be used to complete the strain promoted azide-alkyne click cycloaddition (SPAAC) reaction to introduce an imaging modality such as a fluorophore or a positron emission tomography (PET) tracer on the protein of interest (POI). Such methodology can be pursued directly in mammalian cell lines or on proteins expressed in vitro, thereby conferring a homogeneous pool of protein conjugates. A general procedure for UAA incorporation to use with a site-specific protein labeling method is provided allowing for in vitro and in vivo imaging applications based on the representative proteins PTEN and PD-L1. This approach would help elucidate the cellular or in vivo biological activities of the POI.

Measuring people's views on health system performance: Design and development of the People's Voice Survey.

Todd Lewis and co-authors discuss development and use of the People's Voice Survey for health system assessment.

Improving health and social systems for all children in LMICs: structural innovations to deliver high-quality services.

Despite health gains over the past 30 years, children and adolescents are not reaching their health potential in many low-income and middle-income countries (LMICs). In addition to health systems, social systems, such as schools, communities, families, and digital platforms, can be used to promote health. We did a targeted literature review of how well health and social systems are meeting the needs of children in LMICs using the framework of The Lancet Global Health Commission on high-quality health systems and we reviewed evidence for structural reforms in health and social sectors. We found that quality of services for children is substandard across both health and social systems. Health systems have deficits in care competence (eg, diagnosis and management), system competence (eg, timeliness, continuity, and referral), user experience (eg, respect and usability), service provision for common and serious conditions (eg, cancer, trauma, and mental health), and service offerings for adolescents. Education and social services for child health are limited by low funding and poor coordination with other sectors. Structural reforms are more likely to improve service quality substantially and at scale than are micro-level efforts. Promising approaches include governing for quality (eg, leadership, expert management, and learning systems), redesigning service delivery to maximise outcomes, and empowering families to better care for children and to demand quality care from health and social systems. Additional research is needed on health needs across the life course, health system performance for children and families, and large-scale evaluation of promising health and social programmes.

Semi-syntheses and interrogation of indole-substituted Aspidosperma terpenoid alkaloids.

We demonstrated here a series of Aspidosperma terpenoid alkaloids can be quickly prepared using semisynthesis from naturally sourced tabersonine, featuring multiple oxygen-based substituents on the indole ring such as hydroxy and methoxy groups. This panel of complex compounds enabled the exploration of indole modifications to optimize the indole alkaloids' anticancer activity, generating lead compounds (e.g., with C15-hydroxy, C16-methoxy, and/or C17-methoxy derivatizations) that potently inhibit cancer cell line growth in the single-digit micromolar range. These results can help guide the development of Aspidosperma terpenoid alkaloid therapeutics. Furthermore, this synthetic approach features late-stage facile derivatization on complex natural product molecules, providing a versatile path to indole derivatization of this family of alkaloids with diverse chemical functionalities for future medicinal chemistry and chemical biology discoveries.

Concentration Dependence of a Hydrogel Phase Formed by the Deprotonation of the Imidazole Side Chain of Glycylhistidylglycine.

Upon deprotonation of its imidazole group at ∼pH 6, the unblocked tripeptide glycylhistidylglycine (GHG) self-assembles into very long crystalline fibrils on a 10-1000 µm scale which are capable of forming a volume spanning network, that is, hydrogel. The critical peptide concentration for self-assembly at a pH of 6 lies between 50 and 60 mM. The fraction of peptides that self-assemble into fibrils depends on the concentration of deprotonated GHG. While IR spectra seem to indicate the formation of fibrils with standard amyloid fibril ß-sheet structures, vibrational circular dichroism spectra show a strongly enhanced amide I' signal, suggesting that the formed fibrils exhibit significant chirality. The fibril chirality appears to be a function of peptide concentration. Rheological measurements reveal that the rate of gelation is concentration-dependent and that there is an optimum gel strength at intermediate peptide concentrations of ca. 175 mM. This paper outlines the unique properties of the GHG gel phase which is underlain by a surprisingly dense fibril network with an exceptionally strong modulus that make them potential additives for biomedical applications.

Deficiency of the Fanconi anemia E2 ubiqitin conjugase UBE2T only partially abrogates Alu-mediated recombination in a new model of homology dependent recombination.

The primary function of the UBE2T ubiquitin conjugase is in the monoubiquitination of the FANCI-FANCD2 heterodimer, a central step in the Fanconi anemia (FA) pathway. Genetic inactivation of UBE2T is responsible for the phenotypes of FANCT patients; however, a FANCT patient carrying a maternal duplication and a paternal deletion in the UBE2T loci displayed normal peripheral blood counts and UBE2T protein levels in B-lymphoblast cell lines. To test whether reversion by recombination between UBE2T AluYa5 elements could have occurred in the patient's hematopoietic stem cells despite the defects in homologous recombination (HR) in FA cells, we constructed HeLa cell lines containing the UBE2T AluYa5 elements and neighboring intervening sequences flanked by fluorescent reporter genes. Introduction of a DNA double strand break in the model UBE2T locus in vivo promoted single strand annealing (SSA) between proximal Alu elements and deletion of the intervening color marker gene, recapitulating the reversion of the UBE2T duplication in the FA patient. To test whether UBE2T null cells retain HR activity, the UBE2T genes were knocked out in HeLa cells and U2OS cells. CRISPR/Cas9-mediated genetic knockout of UBE2T only partially reduced HR, demonstrating that UBE2T-independent pathways can compensate for the recombination defect in UBE2T/FANCT null cells.

The tripeptide GHG as an unexpected hydrogelator triggered by imidazole deprotonation.

The tripeptide glycyl-histidyl-glycine (GHG) self-assembles into long, crystalline fibrils forming a strong hydrogel (G'∼ 50 kPa) above a critical concentration of 40 mM upon the deprotonation of its imidazole group. Spectroscopic data reveal a mixture of helically twisted ß-sheets and monomers to coexist in the gel phase.

Clinical performance among recent graduates in nine low- and middle-income countries.

OBJECTIVES: Recent studies have identified large and systematic deficits in clinical care in low-income countries that are likely to limit health gains. This has focused attention on effectiveness of pre-service education. One approach to assessing this is observation of clinical performance among recent graduates providing care. However, no studies have assessed performance in a standard manner across countries. We analysed clinical performance among recently graduated providers in nine low- or middle-income countries. METHODS: Service Provision Assessments from Haiti, Kenya, Malawi, Namibia, Nepal, Rwanda, Senegal, Tanzania, and Uganda were used. We constructed a Good Medical Practice Index that assesses completion of essential clinical actions using direct observations of care (range 0-1), calculated index scores by country and clinical cadre, and assessed the role of facility and clinical characteristics using regression analysis. RESULTS: Our sample consisted of 2223 clinicians with at least one observation of care. The Good Medical Practice score for the sample was 0.50 (SD = 0.20). Nurses and midwives had the highest score at 0.57 (SD = 0.20), followed by associate clinicians at 0.43 (SD = 0.18), and physicians at 0.42 (SD = 0.16). The average national performance varied from 0.63 (SD = 0.18) in Uganda to 0.39 (SD = 0.17) in Nepal, persisting after adjustment for facility and clinician characteristics. CONCLUSIONS: These results show substantial gaps in clinical performance among recently graduated clinicians, raising concerns about models of clinical education. Competency-based education should be considered to improve quality of care in LMICs. Observations of care offer important insight into the quality of clinical education.

OBJECTIFS: Des études récentes ont identifié des déficits importants et systématiques dans les soins cliniques dans les pays à faible revenu, susceptibles de limiter les progrès en matière de santé. Cela a attiré l'attention sur l'efficacité de la formation initiale. Une des approches permettant cette évaluation a été l'observation de la performance clinique des diplômés récents dispensant des soins. Cependant, aucune étude n'a évalué la performance de manière standard dans tous les pays. Nous avons analysé les performances cliniques de prestataires récemment diplômés dans neuf pays à revenu faible ou intermédiaire. MÉTHODES: Des évaluations de la fourniture de services en Haïti, au Kenya, au Malawi, en Namibie, au Népal, au Rwanda, au Sénégal, en Tanzanie et en Ouganda ont été utilisées. Nous avons construit un indice de bonne pratique médicale qui évalue l'achèvement des actions cliniques essentielles à l'aide d'observations directes des soins (plage de 0 à 1), calculé les scores d'index par pays et par cadre clinique, et évalué le rôle de l'établissement et des caractéristiques cliniques à l'aide d'une analyse de régression. RÉSULTATS: Notre échantillon était constitué de 2.223 cliniciens avec au moins une observation des soins. Le score de bonne pratique médicale pour l'échantillon était de 0,50 (écart-type = 0,20). Les infirmières et les sages-femmes avaient le score le plus élevé de 0,57 (écart-type = 0,20), suivies des cliniciens associés avec 0,43 (écart-type = 0,18) et des médecins avec 0,42 (écart-type = 0,16). La performance moyenne nationale variait de 0,63 (écart-type = 0,18) en Ouganda à 0,39 (écart-type = 0,17) au Népal, persistant après ajustement en fonction des caractéristiques de l'établissement et du clinicien. CONCLUSIONS: Ces résultats montrent des écarts substantiels dans les performances cliniques des cliniciens récemment diplômés, ce qui soulève des inquiétudes concernant les modèles de formation clinique. Une éducation axée sur les compétences devrait être envisagée pour améliorer la qualité des soins dans les PRFM. Les observations des soins offrent des informations importantes sur la qualité de la formation clinique.

Caregiving can be costly: A qualitative study of barriers and facilitators to conducting kangaroo mother care in a US tertiary hospital neonatal intensive care unit.

BACKGROUND: Preterm birth is a leading cause of morbidity and mortality in children under five and often requires a newborn to have an extended stay in a neonatal intensive care unit (NICU). Maternal engagement, such as visiting the NICU to provide kangaroo mother care (KMC), can improve outcomes for preterm infants but requires significant investment of time and resources. This study sought to understand barriers and facilitators to provision of KMC in the NICU. METHODS: We conducted semi-structured in-depth interviews with mothers of preterm infants (N = 20) at a large academic medical center in Massachusetts. A series of open-ended interview questions were designed to elicit all aspects of mothers' experiences and to understand how these experiences influence provision of KMC. All interviews were recorded and transcribed verbatim. We conducted an inductive thematic analysis to identify themes in the data with a focus on the barriers and facilitators of KMC provision in the NICU. RESULTS: Findings show that engaging in KMC is heavily influenced by the mental, emotional, and physical effects of preterm birth on the birth mother, such as stress around preterm birth and difficulty recovering from birth. These challenges are compounded by structural barriers such as costly accommodations, unreliable transportation, lack of child care, and inadequate maternity leave policies that limit the frequency and duration of KMC and parental ability to provide care. CONCLUSIONS: A complex array of mental, emotional, physical, and structural factors determine a mother's ability to visit the NICU and provide kangaroo mother care. Providing social supports, such as improved maternity leave policies and reliable hospital access through child care, accommodation, and transportation services, may address the structural barriers that inhibit KMC, reduce burdensome costs, and improve the health of mothers and their preterm infants.

AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia.

Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene.

Environmental Conditions and Vehicle Disturbance Influence Stress Behaviors in a Working Harris's Hawk (Parabuteo unicinctus).

Harris's hawk (Parabuteo unicinctus) is used for pest control, as their presence can deter wild birds such as gulls. Working Harris's hawk on UK waste sites is permitted in accordance with regulations and legislation. This study investigated the general environment of a waste site compound yard where a single Harris's hawk was flown for pest control. The hawk's behaviors were evaluated in an ethogram, alongside environmental measures, and disturbance levels. Data was analyzed using Generalised Linear Latent Variable Models (GLLVM) to elucidate the effects of disturbance and environment on hawk behaviors. Results suggested cloudy conditions encouraged grooming responses that were normal and relaxed in their nature. Rain, sun and wind conditions increased recognized stress behaviors. Frequency of disturbance by construction vehicles inside the compound increased stress behaviors, such that keepers are recommended to revise welfare conditions. Increased stress behaviors by birds worked in dynamic environments like waste recycling yards could potentially elicit damaging illness such as feather breaking behavior. Reducing stress factors for Harris's hawk in industrial working yards combined with amending husbandry practices will improve welfare for the species.

User-reported quality of care: findings from the first round of the People's Voice Survey in 14 countries.

High-quality care is essential for improving health outcomes, although many health systems struggle to maintain good quality. We use data from the People's Voice Survey-a nationally representative survey conducted in 14 high-income, middle-income, and low-income countries-to describe user-reported quality of most recent health care in the past 12 months. We described ratings for 14 measures of care competence, system competence, and user experience and assessed the relationship between visit quality factors and user recommendation of the facility. We disaggregated the data by high-need and underserved groups. The proportion of respondents rating their most recent visit as high quality ranged from 25% in Laos to 74% in the USA. The mean facility recommendation score was 7·7 out of 10. Individuals with high needs or who are underserved reported lower-quality services on average across countries. Countries with high health expenditure per capita tended to have better care ratings than countries with low health expenditure. Visit quality factors explained a high proportion of variation in facility recommendations relative to facility or demographic factors. These results show that user-reported quality is low but increases with high national health expenditure. Elevating care quality will require monitoring and improvements on multiple dimensions of care quality, especially in public systems.

The path to universal health coverage in five African and Asian countries: examining the association between insurance status and health-care use.

Despite major efforts to achieve universal health coverage (UHC), progress has lagged in many African and Asian countries. A key strategy pursued by many countries is the use of health insurance to increase access and affordability. However, evidence on insurance coverage and on the association between insurance and UHC is mixed. We analysed nationally representative cross-sectional data collected between 2022 and 2023 in Ethiopia, Kenya, South Africa, India, and Laos. We described public and private insurance coverage by sociodemographic factors and used logistic regression to examine the associations between insurance status and seven health-care use outcomes. Health insurance coverage ranged from 25% in India to 100% in Laos. The share of private insurance ranged from 1% in Ethiopia to 13% in South Africa. Relative to the population with private insurance, the uninsured population had reduced odds of health-care use (adjusted odds ratio 0·68, 95% CI 0·50-0·94), cardiovascular examinations (0·63, 0·47-0·85), eye and dental examinations (0·54, 0·42-0·70), and ability to get or afford care (0·64, 0·48-0·86); private insurance was not associated with unmet need, mental health care, and cancer screening. Relative to private insurance, public insurance was associated with reduced odds of health-care use (0·60, 0·43-0·82), mental health care (0·50, 0·31-0·80), cardiovascular examinations (0·62, 0·46-0·84), and eye and dental examinations (0·50, 0·38-0·65). Results were highly heterogeneous across countries. Public health insurance appears to be only weakly associated with access to health services in the countries studied. Further research is needed to improve understanding of these associations and to identify the most effective financing strategies to achieve UHC.

Primary health care in practice: usual source of care and health system performance across 14 countries.

Primary health care (PHC) is central to attainment of the Sustainable Development Goals, yet comparable cross-country data on key aspects of primary care have not been widely available. This study analysed data from the People's Voice Survey, which was conducted in 2022 and 2023 in 14 countries. We documented usual source of care across countries and examined associations of usual source of care with core PHC services, quality ratings, and health system confidence. We found that 75% of respondents had a usual source of care, and that 40% of respondents accessed usual care in the public sector at primary level. 44% rated their usual source of care as very good or excellent. Access to PHC-linked screenings and treatments varied widely within and across countries. Having any usual source of care was associated with higher take-up of preventive services, greater access to treatment including mental health services, and greater health system endorsement. Strengthening links between health system users and primary care providers could improve take-up of preventive care and increase user satisfaction with health system performance.

Population confidence in the health system in 15 countries: results from the first round of the People's Voice Survey.

Population confidence is essential to a well functioning health system. Using data from the People's Voice Survey-a novel population survey conducted in 15 low-income, middle-income, and high-income countries-we report health system confidence among the general population and analyse its associated factors. Across the 15 countries, fewer than half of respondents were health secure and reported being somewhat or very confident that they could get and afford good-quality care if very sick. Only a quarter of respondents endorsed their current health system, deeming it to work well with no need for major reform. The lowest support was in Peru, the UK, and Greece-countries experiencing substantial health system challenges. Wealthy, more educated, young, and female respondents were less likely to endorse the health system in many countries, portending future challenges for maintaining social solidarity for publicly financed health systems. In pooled analyses, the perceived quality of the public health system and government responsiveness to public input were strongly associated with all confidence measures. These results provide a post-COVID-19 pandemic baseline of public confidence in the health system. The survey should be repeated regularly to inform policy and improve health system accountability.

Health system quality and COVID-19 vaccination: a cross-sectional analysis in 14 countries.

The social and behavioural determinants of COVID-19 vaccination have been described previously. However, little is known about how vaccinated people use and rate their health system. We used surveys conducted in 14 countries to study the health system correlates of COVID-19 vaccination. Country-specific logistic regression models were adjusted for respondent age, education, income, chronic illness, history of COVID-19, urban residence, and minority ethnic, racial, or linguistic group. Estimates were summarised across countries using random effects meta-analysis. Vaccination coverage with at least two or three doses ranged from 29% in India to 85% in Peru. Greater health-care use, having a regular and high-quality provider, and receiving other preventive health services were positively associated with vaccination. Confidence in the health system and government also increased the odds of vaccination. By contrast, having unmet health-care needs or experiencing discrimination or a medical mistake decreased the odds of vaccination. Associations between health system predictors and vaccination tended to be stronger in high-income countries and in countries with the most COVID-19-related deaths. Access to quality health systems might affect vaccine decisions. Building strong primary care systems and ensuring a baseline level of quality that is affordable for all should be central to pandemic preparedness strategies.

Health service quality in 2929 facilities in six low-income and middle-income countries: a positive deviance analysis.

BACKGROUND: Primary care is of insufficient quality in many low-income and middle-income countries. Some health facilities perform better than others despite operating in similar contexts, although the factors that characterise best performance are not well known. Existing best-performance analyses are concentrated in high-income countries and focus on hospitals. We used the positive deviance approach to identify the factors that differentiate best from worst primary care performance among health facilities across six low-resource health systems. METHODS: This positive deviance analysis used nationally representative samples of public and private health facilities from Service Provision Assessments of the Democratic Republic of the Congo, Haiti, Malawi, Nepal, Senegal, and Tanzania. Data were collected starting June 11, 2013, in Malawi and ending Feb 28, 2020, in Senegal. We assessed facility performance through completion of the Good Medical Practice Index (GMPI) of essential clinical actions (eg, taking a thorough history, conducting an adequate physical examination) according to clinical guidelines and measured with direct observations of care. We identified hospitals and clinics in the top decile of performance (defined as best performers) and conducted a quantitative, cross-national positive deviance analysis to compare them with facilities performing below the median (defined as worst performers) and identify facility-level factors that explain the gap between best and worst performance. FINDINGS: We identified 132 best-performing and 664 worst-performing hospitals, and 355 best-performing and 1778 worst-performing clinics based on clinical performance across countries. The mean GMPI score was 0·81 (SD 0·07) for the best-performing hospitals and 0·44 (0·09) for the worst-performing hospitals. Among clinics, mean GMPI scores were 0·75 (0·07) for the best performers and 0·34 (0·10) for the worst performers. High-quality governance, management, and community engagement were associated with best performance compared with worst performance. Private facilities out-performed government-owned hospitals and clinics. INTERPRETATION: Our findings suggest that best-performing health facilities are characterised by good management and leaders who can engage staff and community members. Governments should look to best performers to identify scalable practices and conditions for success that can improve primary care quality overall and decrease quality gaps between health facilities. FUNDING: Bill & Melinda Gates Foundation.

Associations between women's empowerment, care seeking, and quality of malaria care for children: A cross-sectional analysis of demographic and health surveys in 16 sub-Saharan African countries.

Background: Fever and malaria are highly prevalent among children under five across sub-Saharan Africa, but utilization and quality of care for febrile illness remain insufficient. Many studies examine socioeconomic and demographic determinants of care seeking; however, few assess how women's empowerment influences care seeking and quality. We examine associations of women's empowerment with: a) care utilization for children with fever and malaria and b) the quality of that care in 16 sub-Saharan African countries. Methods: This cross-sectional study used data from Demographic and Health Surveys conducted between 2010 and 2018. We constructed indices for economic, educational, sociocultural, and health-related empowerment and calculated the proportion of children with fever and malaria who sought care and received a range of recommended clinical actions. We used multivariable Poisson hurdle models to assess associations between empowerment, utilization, and number of components of quality care, controlling for socioeconomic and demographic factors. Results: Our sample consisted of 25 871 febrile children, 4731 of whom had malaria diagnosed by rapid diagnostic test. Empowerment among mothers of children with fever was 0.50 (interquartile range, 0.38-0.63). In both the fever and malaria groups, over 30% of children were not taken for care. Among care seekers, febrile children received on average 0.47 (SD = 0.37) of components of quality care, and children with malaria received 0.38 (SD = 0.34). Multidimensional women's empowerment was significantly associated with care seeking and quality among febrile children, and with quality among children with malaria. Associations persisted after adjustment for socioeconomic and demographic characteristics. Conclusions: Results demonstrate substantial gaps in women's empowerment and poor utilization and quality of care for fever and malaria among children. Increased women's empowerment is associated with seeking care and, separately, obtaining high-quality care. To improve health outcomes, consideration of how empowering women can promote care seeking and extract quality from the health system is warranted.

Best and worst performing health facilities: A positive deviance analysis of perceived drivers of primary care performance in Nepal.

Primary care services are on average of low quality in Nepal. However, there is marked variation in performance of basic clinical and managerial functions between primary health care centers. The determinants of variation in primary care performance in low- and middle-income countries have been understudied relative to the prominence of primary care in national health plans. We used the positive deviance approach to identify best and worst performing primary health care centers in Nepal and investigated perceived drivers of best performance. We selected eight primary health care centers in Province 1, Nepal, using an index of basic clinical and operational activities to identify four best and four worst performing primary health care centers. We conducted semi-structured, in-depth interviews with managers and clinical staff from each of the eight primary health care centers for a total of 32 interviews. We identified the following factors that distinguished best from worst performers: 1) Managing the facility effectively, 2) engaging local leadership, 3) building active community accountability, 4) assessing and responding to facility performance, 5) developing sources of funding, 6) compensating staff fairly, 7) managing clinical staff performance, and 8) promoting uninterrupted availability of supplies and equipment. These findings can be used to inform quality improvement efforts and health system reforms in Nepal and other similarly under-resourced health systems.