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Prior studies demonstrated that deletion of the protein phosphatase Phlpp1 in Ctsk-Cre expressing cells enhances bone mass, characterized by diminished osteoclast activity and increased coupling to bone formation. Due to non-specific expression of Ctsk-Cre, the definitive mechanism for this observation was unclear. To further define the role of bone resorbing osteoclasts, we performed ovariectomy (Ovx) and Sham surgeries on Phlpp1 cKOCtsk and WT mice. Micro-CT analyses confirmed enhanced bone mass of Phlpp1 cKOCtsk Sham females. In contrast, Ovx induced bone loss in both groups, with no difference between Phlpp1 cKOCtsk and WT mice. Histomorphometry demonstrated that Ovx mice lacked differences in osteoclasts per bone surface, suggesting that estradiol (E2) is required for Phlpp1 deficiency to have an effect. We performed high throughput unbiased transcriptional profiling of Phlpp1 cKOCtsk osteoclasts and identified 290 differentially expressed genes. By cross-referencing these differentially expressed genes with all estrogen response element (ERE) containing genes, we identified IGFBP4 as potential estrogen-dependent target of Phlpp1. E2 induced PHLPP1 expression, but reduced IGFBP4 levels. Moreover, genetic deletion or chemical inhibition of Phlpp1 was correlated with IGFBP4 levels. We then assessed IGFBP4 expression by osteoclasts in vivo within intact 12-week-old females. Modest IGFBP4 immunohistochemical staining of TRAP+ osteoclasts within WT females was observed. In contrast, TRAP+ bone lining cells within intact Phlpp1 cKOCtsk females robustly expressed IGFBP4, but levels were diminished within TRAP+ bone lining cells following Ovx. These results demonstrate that effects of Phlpp1 conditional deficiency are lost following Ovx, potentially due to estrogen-dependent regulation of IGFBP4.

Strengthening district-level management may be an important lever for improving key public health outcomes in low-income settings; however, previous studies have not established the statistical associations between better management and primary healthcare system performance in such settings. To explore this gap, we conducted a cross-sectional study of 36 rural districts and 226 health centers in Ethiopia, a country which has made ambitious investment in expanding access to primary care over the last decade. We employed quantitative measure of management capacity at both the district health office and health center levels and used multiple regression models, accounting for clustering of health centers within districts, to estimate the statistical association between management capacity and a key performance indicator (KPI) summary score based on antenatal care coverage, contraception use, skilled birth attendance, infant immunization, and availability of essential medications. In districts with above median district management capacity, health center management capacity was strongly associated (p < 0.05) with KPI performance. In districts with below median management capacity, health center management capacity was not associated with KPI performance. Having more staff at the district health office was also associated with better KPI performance (p < 0.05) but only in districts with above median management capacity. The results suggest that district-level management may provide an opportunity for improving health system performance in low-income country settings.

Purpose To determine if tangent visual fields gathered during assessment of superior visual field deficits caused by blepharoptosis and dermatochalasis offer good correlation to clinical exam in a time and cost efficient manner. Methods Prospective, observational case series. Subjects included all patients referred to a single surgeon (CCN) who underwent surgical correction of blepharoptosis and/or dermatochalasis. Preoperatively and postoperatively, upper margin-to-reflex distances were assessed. Tangent visual fields were performed in a timed fashion and analyzed for degrees of intact vision in the vertical meridian and degrees squared of area under the curve. Data were compared by Student t-tests and Pearson correlation coefficients. Results Mean preoperative superior visual fields with the eyelid in the natural position measured 8° in the vertical meridian. Measurements in the vertical meridian and area under the curve showed excellent correlation (r = 0.87). Patients with ptosis showed strong correlation between margin-to-reflex distance and superior visual fields. Patients completed field testing faster than reported times for automated or Goldmann testing. Finally, tangent screens were the least expensive type of equipment to purchase. Conclusions Tangent visual fields are a rapid and inexpensive way to test for functional loss of superior visual field in patients with upper eyelid malposition. Our data revealed potential differences between tangent screen results and published results for automated or Goldmann visual field testing which warrants further studies.

We summarized the recently published, peer-reviewed literature that examined the impact of investments in social services or investments in integrated models of health care and social services on health outcomes and health care spending. Of 39 articles that met criteria for inclusion in the review, 32 (82%) reported some significant positive effects on either health outcomes (N = 20), health care costs (N = 5), or both (N = 7). Of the remaining 7 (18%) studies, 3 had non-significant results, 2 had mixed results, and 2 had negative results in which the interventions were associated with poorer health outcomes. Our analysis of the literature indicates that several interventions in the areas of housing, income support, nutrition support, and care coordination and community outreach have had positive impact in terms of health improvements or health care spending reductions. These interventions may be of interest to health care policymakers and practitioners seeking to leverage social services to improve health or reduce costs. Further testing of models that achieve better outcomes at less cost is needed.

Background Primary health care services are fundamental to improving health and health equity, particularly in the context of low and middle-income settings where resources are scarce. During the past decade, Ethiopia undertook an ambitious investment in primary health care known as the Ethiopian Health Extension Program that recorded impressive gains in several health outcomes. Despite this progress, substantial disparities in health outcomes persist across the country. The objective of this study was to understand how variation in the implementation of the primary health care efforts may explain differences in key health outcomes. Methods and Findings We conducted a qualitative study of higher-performing and lower-performing woredas using site visits and in-depth interviews undertaken in 7 woredas. We classified woredas as higher-performing or lower-performing based on data on 5 indicators. We conducted a total of 94 open-ended interviews; 12–15 from each woreda. The data were analyzed using the constant comparative method of qualitative data analysis. Substantial contrasts were apparent between higher-performing and lower-performing woredas in use of data for problem solving and performance improvement; collaboration and respectful relationships among health extension workers, community members, and health center staff; and coordination between the woreda health office and higher-level regulatory and financing bodies at the zonal and regional levels. We found similarities in what was reported to motivate or demotivate health extension workers and other staff. Additionally, higher-performing and lower-performing woredas shared concerns about hospitals being isolated from health centers and health posts. Participants from both woredas also highlighted a mismatch between the urban health extension program design and the urban-dwelling communities’ expectations for primary health care. Conclusions Data-informed problem solving, respectful and supportive relationships with the community, and strong support from zonal and regional health bureaus contributed to woreda performance, suggesting avenues for achieving higher performance in primary health care.

Background Primary healthcare systems in sub-Saharan Africa have undergone substantial development in an effort to expand access to appropriate facilities through a well-functioning referral system. The objective of this study was to evaluate the current patterns of seeking prior care before arriving at a health center or a hospital as a key aspect of the referral system of the primary health care unit (PHCU) in three regions in Ethiopia. We examined what percentage of patients had either sought prior care or had been referred to the present facility and identified demographic and clinical factors associated with having sought prior care or having been referred. Methods and Findings We conducted a cross-sectional study using face-to-face interviews in the local language with 796 people (99% response rate) seeking outpatient care in three primary health care units serving approximately 100,000 people each and reflecting regional and ethnic diversity; 53% (N = 418) of the sample was seeking care at hospital outpatient departments, and 47% of the sample was seeking care at health centers (N = 378). We used unadjusted and adjusted logistic regression to identify factors associated with having been referred or sought prior care. Our findings indicated that only 10% of all patients interviewed had been referred to their current place of care. Among those in the hospital population, 14% had been referred; among those in the health center population, only 6% had been referred. Of those who had been referred to the hospital, most (74%) had been referred by a health center. Among those who were referred to the health center, the plurality portion (32%) came from a nearby hospital (most commonly for continued HIV treatment or early childhood vaccinations); only 18% had come from a health post. Among patients who had not been formally referred, an additional 25% in the hospital sample and 10% in the health center sample had accessed some prior source of care for their present health concern. In the adjusted analysis, living a longer distance from the source of care and needing more specialized care were correlated with having sought prior care in the hospital sample. We found no factors significantly associated with having sought prior care in the health center sample. Conclusions The referral system among health facilities in Ethiopia is used by a minority of patients, suggesting that intended connections between health posts, health centers, and hospitals may need strengthening to increase the efficiency of primary care nationally.

BACKGROUND: Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and country-specific barriers to complete childhood vaccination. METHODS: Using data from the Demographic and Health Surveys (DHS) for Burundi, Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, we looked at the prevalence of complete vaccination for polio, measles, Bacillus Calmette-Guérin (BCG) and DTwPHibHep (DTP) as recommended by the WHO among children ages 12 to 23 months. We conducted multivariable logistic regression within each country to estimate associations between complete vaccination status and health care access and sociodemographic variables using backwards stepwise regression. RESULTS: Vaccination varied significantly by country. In all countries, the majority of children received at least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and Uganda less than 50% of children received a complete schedule of recommended vaccines. Being delivered in a public or private institution compared with being delivered at home was associated with increased odds of complete vaccination status. Sociodemographic covariates were not consistently associated with complete vaccination status across countries. CONCLUSIONS: Although no consistent set of predictors accounted for complete vaccination status, we observed differences based on region and the location of delivery. These differences point to the need to examine the historical, political, and economic context of each country in order to maximize vaccination coverage. Vaccination against these childhood diseases is a critical step towards reaching the Millennium Development Goal of reducing under-five mortality by two-thirds by 2015 and thus should be a global priority.

MAIN OBJECTIVE: Few studies have examined the long-term, impact of large-scale interventions to strengthen primary care services for women and children in rural, low-income settings. We evaluated the impact of the Ethiopian Millennium Rural Initiative (EMRI), an 18-month systems-based intervention to improve the performance of 30 primary health care units in rural areas of Ethiopia. METHODS: We assessed the impact of EMRI on maternal and child survival using The Lives Saved Tool (LiST), Demography (DemProj) and AIDS Impact Model (AIM) tools in Spectrum software, inputting monthly data on 6 indicators 1) antenatal coverage (ANC), 2) skilled birth attendance coverage (SBA), 3) post-natal coverage (PNC), 4) HIV testing during ANC, 5) measles vaccination coverage, and 6) pentavalent 3 vaccination coverages. We calculated a cost-benefit ratio of the EMRI program including lives saved during implementation and lives saved during implementation and 5 year follow-up. RESULTS: A total of 134 lives (all children) were estimated to have been saved due to the EMRI interventions during the 18-month intervention in 30 health centers and their catchment areas, with an estimated additional 852 lives (820 children and 2 adults) saved during the 5-year post-EMRI period. For the 18-month intervention period, EMRI cost $37,313 per life saved ($42,366 per life if evaluation costs are included). Calculated over the 18-month intervention plus 5 years post-intervention, EMRI cost $5,875 per life saved ($6,671 per life if evaluation costs are included). The cost effectiveness of EMRI improves substantially if the performance achieved during the 18 months of the EMRI intervention is sustained for 5 years. Scaling up EMRI to operate for 5 years across the 4 major regions of Ethiopia could save as many as 34,908 lives. SIGNIFICANCE: A systems-based approach to improving primary care in low-income settings can have transformational impact on lives saved and be cost-effective.

IntroductionThe lack of trained mental health workers is a primary contributor to the mental health treatment gap worldwide. Despite the great need to recruit and retain mental health workers in low-income countries, little is known about how these workers perceive their jobs and what drives them to work in mental health care. Using qualitative interviews, we aimed to explore factors motivating mental health workers in order to inform interventions to increase recruitment and retention.MethodsWe conducted 28 in-depth, open-ended interviews with staff in Ghana's three public psychiatric hospitals. We used the snowballing method to recruit participants and the constant comparative method for qualitative data analysis, with multiple members of the research team participating in data coding to enhance the validity and reliability of the analysis. The use of qualitative methods allowed us to understand the range and depth of motivating and demotivating factors.ResultsRespondents described many factors that influenced their choice to enter and remain in mental health care. Motivating factors included 1) desire to help patients who are vulnerable and in need, 2) positive day-to-day interactions with patients, 3) intellectual or academic interest in psychiatry or behavior, and 4) good relationships with colleagues. Demotivating factors included 1) lack of resources at the hospital, 2) a rigid supervisory hierarchy, 3) lack of positive or negative feedback on work performance, and 4) few opportunities for career advancement within mental health.ConclusionsBecause many of the factors are related to relationships, these findings suggest that strengthening the interpersonal and team dynamics may be a critical and relatively low cost way to increase worker motivation. The data also allowed us to highlight key areas for resource allocation to improve both recruitment and retention, including risk pay, adequate tools for patient care, improved hospital work environment, and stigma reduction efforts.

Background Experts have suggested that intersectoral partnerships between prayer camps and biomedical care providers may be an effective strategy to address the overwhelming shortage of mental health care workers in Africa and other low-income settings. Nevertheless, previous studies have not explored whether the prayer camp and biomedical staff beliefs and practices provide sufficient common ground to enable cooperative relationships. Therefore, we sought to examine the beliefs and practices of prayer camp staff and the perspective of biomedical care providers, with the goal of characterizing interest in—and potential for—intersectoral partnership between prayer camp staff and biomedical care providers. Methods We conducted 50 open-ended, semi-structured interviews with prophets and staff at nine Christian prayer camps in Ghana, and with staff within Ghana’s three public psychiatric hospitals. We used the purposive sampling method to recruit participants and the constant comparative method for qualitative data analysis. Results Prayer camp staff expressed interest in collaboration with biomedical mental health care providers, particularly if partnerships could provide technical support introducing medications in the prayer camp and address key shortcomings in their infrastructure and hygienic conditions. Nevertheless, challenges for collaboration were apparent as prayer camp staff expressed strong beliefs in a spiritual rather than biomedical explanatory model for mental illness, frequently used fasting and chained restraints in the course of treatment, and endorsed only short-term use of medication to treat mental illness—expressing concerns that long-term medication regimens masked underlying spiritual causes of illness. Biomedical providers were skeptical about the spiritual interpretations of mental illness held by faith healers, and were concerned by the use of chains, fasting, and the lack of adequate living facilities for patients in prayer camps; many, however, expressed interest in engaging with prayer camps to expand access to clinical care for patients residing in the camps. Conclusions The findings demonstrate that biomedical care providers are interested in engaging with prayer camps. Key areas where partnerships may best improve conditions for patients at prayer camps include collaborating on creating safe and secure physical spaces and delivering medication for mental illness to patients living in prayer camps. However, while prayer camp staff are willing to engage biomedical knowledge, deeply held beliefs and routine practices of faith and biomedical healers are difficult to reconcile Additional discussion is needed to find the common ground on which the scarce resources for mental health care in Ghana can collaborate most effectively.

There was a typographical error in the sixth author's name. The correct spelling is Yigeremu Abebe.

Background Poverty due to illness has become a substantial social problem in rural China since the collapse of the rural Cooperative Medical System in the early 1980s. Although the Chinese government introduced the New Rural Cooperative Medical Schemes (NRCMS) in 2003, the associations between different health insurance benefit package designs and healthcare utilization remain largely unknown. Accordingly, we sought to examine the impact of health insurance benefit design on health care utilization. Methods and Findings We conducted a cross-sectional study using data from a household survey of 15,698 members of 4,209 randomly-selected households in 7 provinces, which were representative of the provinces along the north side of the Yellow River. Interviews were conducted face-to-face and in Mandarin. Our analytic sample included 9,762 respondents from 2,642 households. In each household, respondents indicated the type of health insurance benefit that the household had (coverage for inpatient care only or coverage for both inpatient and outpatient care) and the number of outpatient visits in the 30 days preceding the interview and the number of hospitalizations in the 365 days preceding the household interview. People who had both outpatient and inpatient coverage compared with inpatient coverage only had significantly more village-level outpatient visits, township-level outpatient visits, and total outpatient visits. Furthermore, the increased utilization of township and village-level outpatient care was experienced disproportionately by people who were poorer, whereas the increased inpatient utilization overall and at the county level was experienced disproportionately by people who were richer. Conclusion The evidence from this study indicates that the design of health insurance benefits is an important policy tool that can affect the health services utilization and socioeconomic equity in service use at different levels. Without careful design, health insurance may not benefit those who are most in need of financial protection from health services expenses.

BACKGROUND: Multiple interventions have been launched to improve the quality, access, and utilization of primary health care in rural, low-income settings; however, the success of these interventions varies substantially, even within single studies where the measured impact of interventions differs across sites, centers, and regions. Accordingly, we sought to examine the variation in impact of a health systems strengthening intervention and understand factors that might explain the variation in impact across primary health care units. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a mixed methods positive deviance study of 20 Primary Health Care Units (PHCUs) in rural Ethiopia. Using longitudinal data from the Ethiopia Millennium Rural Initiative (EMRI), we identified PHCUs with consistently higher performance (n = 2), most improved performance (n = 3), or consistently lower performance (n = 2) in the provision of antenatal care, HIV testing in antenatal care, and skilled birth attendance rates. Using data from site visits and in-depth interviews (n = 51), we applied the constant comparative method of qualitative data analysis to identify key themes that distinguished PHCUs with different performance trajectories. Key themes that distinguished PHCUs were 1) managerial problem solving capacity, 2) relationship with the woreda (district) health office, and 3) community engagement. In higher performing PHCUs and those with the greatest improvement after the EMRI intervention, health center and health post staff were more able to solve day-to-day problems, staff had better relationships with the woreda health official, and PHCU communities' leadership, particularly religious leadership, were strongly engaged with the health improvement effort. Distance from the nearest city, quality of roads and transportation, and cultural norms did not differ substantially among PHCUs. CONCLUSIONS/SIGNIFICANCE: Effective health strengthening efforts may require intensive development of managerial problem solving skills, strong relationships with government offices that oversee front-line providers, and committed community leadership to succeed.