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The US budget for global health funding, which was by far the largest of similar funding in the world, increased from US $1.3 billion in 2001 to more than US $10 billion in recent years. More than 54% of this funding was allocated to the Global Fund to Fight HIV/AIDS through the US President's Emergency Plan for AIDS Relief (PEPFAR) in Africa. However, recent studies indicate contradictory results regarding the effectiveness of PEPFAR. One by Bendavid, Holmes, Bhattacharya, and Miller shows positive effects of PEPFAR in reducing adult mortality in Africa, while another by Duber, Coates, Szekeras, Kaji, and Lewis finds that there are no significant differences in reducing adult mortality in countries that received PEPFAR funding vs countries that did not. Due to their potential impact on policy decisions regarding critical global health funding, we wanted to assess why the results are discrepant. To do this, we replicated the Bendavid study. The replication provides verification that the study replicable and that the analytic choices of the authors are robust to different assumptions or restrictions. This allows us to assess the different choices and data available to the two research groups and draw some conclusions about why the results may be different. Then, focusing on two of the prominently discrepant studies, i.e., the Bendavid study (1998-2008) and the Duber study (2000-2006), we establish why the two studies are in disagreement. We apply appropriate individual-level and country-level analytical methodology as used by Bendavid over the analytical time period used for the Duber study (2000-2006), which originally focused on nationally aggregated data and differed in some key focus countries. For our first objective, we replicated the original Bendavid study findings and our findings support their conclusion that between 1998-2008 all-cause mortality decreased significantly more (OR = 0.84, CI, 0.72-0.99) in countries that implemented PEPFAR. For our second objective (Bendavid's data and methodology applied to Duber's study period), we found reduction in all cause adult mortality to be borderline insignificant (OR = 0.87 CI, 0.75-1.01, p = 0.06), most possibly reflecting the abbreviated fewer number of events and sample size over a shorter period. Therefore, our overall analyses are consistent with the conclusion of positive impact of the PEPFAR program in reducing adult mortality. We believe that the discrepancy observed in the original studies mainly a reflection of shortcomings in the analytical approach necessitated by the Duber study's nationally aggregated dataset or \"may reflect a lack of data quality\" in the Duber study (Duber, et al. 2010).

Approximately two-thirds of HIV-infected individuals reside in sub-Saharan Africa. The region accounts for 68% of the new HIV infections occurring worldwide with almost one-half of these infections being among young adults aged 12-24 years. Cowan and colleagues conducted a community-based, multi-component HIV intervention aimed at youth in rural Zimbabwe. Despite some changes in knowledge and attitudes, the community-based intervention did not affect the prevalence of HIV or HSV-2. We selected this frequently cited study for replication since it incorporates individual-, community-, and structural- level intervention components that are often considered in global HIV/AIDS prevention programs. Additionally, the intervention could be easily scaled-up, which is especially important in the context of limited resources. Although this study indicated no intervention effects in reducing HIV, the authors acknowledged some key methodological challenges. Our replication analysis provided important insights regarding the impact of these challenges to the interpretation of the results of this study. Our replication study focused on replicating Cowan's findings and assessing the robustness of Cowan's results to alternative analytical models based on their study design. We determined how out-migration occurring during Cowan's study may have affected the population characteristics, the intervention exposure level, and the study findings. While the original intervention targeted knowledge and attitudes as a mechanism to decrease HIV/HSV-2, the Cowan study evaluated the intervention effects on knowledge, attitudes, and prevalence of HIV or HSV-2 separately. To better identify the pathway describing the interrelationship among the intervention and knowledge, attitudes, and prevalence of HIV or HSV-2, we assessed whether increases in knowledge or attitudes were associated with decreased HIV or HSV-2 prevalence. We replicated the original findings with minor discrepancies during the pure replication. Our additional analyses revealed that the study population characteristics changed over time in ways that may have affected outcomes. These changes also affected the levels of intervention exposure, with 48.7% males and 75.5% females of the intervention group receiving low-level exposure. Both genders with higher level intervention exposure experienced higher increments in multiple knowledge, attitude, and sexual risk behavior outcomes. Unfortunately, these did not translate to a significant reduction in HIV or HSV-2 regardless of the level and combination of knowledge and attitude domains. However, males receiving high-level intervention exposure compared to control indicated significantly lower odds of having HIV or HSV-2 under a Bayesian modeling paradigm. Our findings suggest a more robust conclusion on the study intervention effects. Further study based on a design that more consistently maximizes the exposure level of the intervention is necessary and should ideally be an evaluated goal in similar studies. Evaluation of the intervention impact for key subgroups of the target population is important and would better advise the use and scale-up of the evaluated interventions in various contexts. Our observation of a consistent lack of relationship between knowledge/attitudes and HIV/HSV-2 suggests a need to explore and include relevant additional and or complementary interventions, e.g., promoting effective skills in reducing risky sexual behaviors and addressing cultural and structural bottlenecks that may reduce HIV/HSV-2 risk among youth.

Self-medication with antimicrobial agents is a common form of self-care among patients globally with the prevalence and nature differing from country to country. Here we assessed the prevalence and predictors of antimicrobial self-medication in post-conflict northern Uganda. A cross-sectional study was carried out using structured interviews on 892 adult (≥18 years) participants. Information on drug name, prescriber, source, cost, quantity of drug obtained, and drug use was collected. Households were randomly selected using multistage cluster sampling method. One respondent who reported having an illness within three months in each household was recruited. In each household, information was obtained from only one adult individual. Data was analyzed using STATA at 95% level of significance. The study found that a high proportion (75.7%) of the respondents practiced antimicrobial self-medication. Fever, headache, lack of appetite and body weakness were the disease symptoms most treated through self-medication (30.3%). The commonly self-medicated antimicrobials were coartem (27.3%), amoxicillin (21.7%), metronidazole (12.3%), and cotrimoxazole (11.6%). Drug use among respondents was mainly initiated by self-prescription (46.5%) and drug shop attendants (57.6%). On average, participants obtained 13.9±8.8 (95%CI: 12.6-13.8) tablets/capsules of antimicrobial drugs from drug shops and drugs were used for an average of 3.7±2.8 days (95%CI: 3.3-3.5). Over half (68.2%) of the respondents would recommend self-medication to another sick person. A high proportion (76%) of respondents reported that antimicrobial self-medication had associated risks such as wastage of money (42.1%), drug resistance (33.2%), and masking symptoms of underlying disease (15.5%). Predictors of self-medication with antimicrobial agents included gender, drug knowledge, drug leaflets, advice from friends, previous experience, long waiting time, and distance to the health facility. Despite knowledge of associated risks, use of self-medication with antimicrobial drugs in management of disease symptoms is a common practice in post-conflict northern Uganda.

Purpose Obstructive sleep apnea (OSA) presents perioperative challenges with increased risk for complications. Floppy eyelid syndrome (FES) is associated with OSA yet has not been addressed perioperatively. The current standard for perioperative OSA screening includes assessing patient risk factors or the STOP-BANG tool, which requires an active participant. We aimed to confirm a connection between FES and OSA in presurgical patients and develop a screening method appropriate for patients with perioperative OSA risk. Materials and Methods 162 presurgical pre-anesthesia clinic patients were enrolled. Screening questions determined eligibility. Those who were pregnant or aged < 19 were excluded. Control group included those with a STOP-BANG score < 3. Experimental group included those with BMI > 35 and OSA diagnosis. Examiners photographed participants’ eyes with vertical and horizontal retraction while two blinded ophthalmologists used a grading scale to review grade of eyelid laxity. Results Differences in habitus, ASA score, and hypertension as a comorbidity were significant. Sensitivity of FES screening was 52% (CI 37–66%) and specificity was 56% (CI 46–66%) for reviewer 1. For reviewer 2, sensitivity was 48% (CI 28–69%) and specificity was 72% (CI 60–81%). Negative predictive value was 86% (CI 81–90) for reviewer 1 and 88% (CI 83–92%) for reviewer 2. Inter-rater agreement was moderate. Conclusion While specificity and sensitivity were lower than anticipated, negative predictive value was high. Given this strong negative predictive value, our findings indicate using eyelid retraction to screen for FES has perioperative clinical utility. These findings encourage further research addressing the connection of lid laxity/FES to OSA. Key Points • Aimed to investigate if a FES screening tool could identify perioperative OSA risk. • Negative predictive value for FES with OSA was 86%. • Observing periocular lid laxity has clinical utility; is feasible in any patient. Graphical abstract

We previously derived a Universal Vital Assessment (UVA) score to better risk-stratify hospitalized patients in sub-Saharan Africa, including those with infection. Here, we aimed to externally validate the performance of the UVA score using previously collected data from patients hospitalized with acute infection in Rwanda. We performed a secondary analysis of data collected from adults ≥18 years with acute infection admitted to Gitwe District Hospital in Rwanda from 2016 until 2017. We calculated the UVA score from the time of admission and at 72 hours after admission. We also calculated quick sepsis-related organ failure assessment (qSOFA) and modified early warning scores (MEWS). We calculated amalgamated qSOFA scores by inserting UVA cut-offs into the qSOFA score, and modified UVA scores by removing the HIV criterion. The performance of each score determined by the area under the receiver operator characteristic curve (AUC) was the primary outcome measure. We included 573 hospitalized adult patients with acute infection of whom 40 (7%) died in-hospital. The admission AUCs (95% confidence interval [CI]) for the prediction of mortality by the scores were: UVA, 0.77 (0.68-0.85); modified UVA, 0.77 (0.68-0.85); qSOFA, 0.66 (0.56-0.75), amalgamated qSOFA, 0.71 (0.61-0.80); and MEWS, 0.74 (0.64, 0.83). The positive predictive values (95% CI) of the scores at commonly used cut-offs were: UVA >4, 0.35 (0.15-0.59); modified UVA >4, 0.35 (0.15-0.59); qSOFA >1, 0.14 (0.07-0.24); amalgamated qSOFA >1, 0.44 (0.20-0.70); and MEWS >5, 0.14 (0.08-0.22). The 72 hour (N = 236) AUC (95% CI) for the prediction of mortality by UVA was 0.59 (0.43-0.74). The Chi-Square test for linear trend did not identify an association between mortality and delta UVA score at 72 hours (p = 0.82). The admission UVA score and amalgamated qSOFA score had good predictive ability for mortality in adult patients admitted to hospital with acute infection in Rwanda. The UVA score could be used to assist with triage decisions and clinical interventions, for baseline risk stratification in clinical studies, and in a clinical definition of sepsis in Africa.

In Uganda, men who have sex with men (MSM) are at high risk for HIV. Between May 2008 and February 2009 in Kampala, Uganda, we used respondent driven sampling (RDS) to recruit 295 MSM≥18 years who reported having had sex with another man in the preceding three months. The parent study conducted HIV and STI testing and collected demographic and HIV-related behavioral data through audio computer-assisted self-administered interviews. We conducted a nested qualitative sub-study with 16 men purposively sampled from among the survey participants based on responses to behavioral variables indicating higher risk for HIV infection. Sub-study participants were interviewed face-to-face. Domains of inquiry included sexual orientation, gender identity, condom use, stigma, discrimination, violence and health seeking behavior. Emergent themes included a description of sexual orientation/gender identity categories. All groups of men described conflicting feelings related to their sexual orientation and contextual issues that do not accept same-sex identities or behaviors and non-normative gender presentation. The emerging domains for facilitating condom use included: lack of trust in partner and fear of HIV infection. We discuss themes in the context of social and policy issues surrounding homosexuality and HIV prevention in Uganda that directly affect men's lives, risk and health-promoting behaviors.

In this paper we perform a replication analysis of \"Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial\" by Sarah Baird and others published in \"The Lancet\" in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13-22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution.

Clinical laboratories are crucial in addressing the high rates of communicable and non-communicable diseases seen in sub-Saharan Africa (SSA). However, the most basic information, such as the number and quality of clinical laboratories in SSA, is not available. The objective of this study was to create a practical method for obtaining this information in SSA towns and cities using an initial survey in Kampala, Uganda. Kampala city was divided into 5 partially-overlapping regions. Each region was assigned to 2-3 surveyors who identified and surveyed laboratories in their respective regions; in person and on foot. A modified version of the World Health Organization - African Region (WHO/AFRO) Laboratory Strengthening Checklist was used to obtain baseline measures of quality for all clinical laboratories within Kampala city. The surveyors also measured other attributes of each laboratory, such as their affiliation (government, private etc), designation (national hospital, district hospital, standalone etc), staff numbers, and type of staff. The survey team identified and surveyed 954 laboratories in Kampala city. 96% of laboratories were private. Only 45 (5%) of the laboratories met or surpassed the lowest quality standards defined by the WHO/AFRO-derived laboratory strengthening tool (1-star). These 45 higher-quality laboratories were, on average, larger and had a higher number of laboratory-specific staff (technologists, phlebotomists etc) than the other 909 laboratories. 688 (72%) of the 954 laboratories were not registered with the Ministry of Health (MoH). This comprehensive evaluation of the number, scope, and quality of clinical laboratories in Kampala is the first published survey of its kind in sub-Saharan Africa. The survey findings demonstrated that laboratories in Kampala that had qualified personnel and those that had higher testing volumes, tended to be of higher-quality.

Background Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes. Methods A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS), virological failure and immunological success (VF/IS). virological success and immunological failure (VS/IF) and both virological and immunological failure (VF/IF). Results From March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR) was 5.0 years (2.1 - 7.0) and 49% (61/124) were female. The median [95% confidence interval (CI)] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2), -1.2 (-2.1, -0.5) and -2.06 (-2.9, -1.2) respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0) and 5.6 (5.2-5.8) copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7) to + 1.22 (SD 1.2) and from -1.99 (1.7) to + 0.76 (2.4) respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3) to - 0.41 (1.2) and -2.25 (1.2) to -1.16 (1.3) respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6)], age [OR 4.6 95% CI (1.14 -19.1)] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7)] were associated with successful treatment outcome. Conclusions HIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to completely suppress virus. Older children initiating HAART with severe immune suppression were less likely to achieve a successful treatment outcome. These data emphasize the importance of initiating HAART early to ensure adequate immune and growth responses.

IntroductionUganda’s district-level administrative units buttress the public healthcare system. In many districts, however, local capacity is incommensurate with that required to plan and implement quality health interventions. This study investigates how a district management strategy informed by local data and community dialogue influences health services.MethodsA 3-year randomised controlled trial (RCT) comprised of 16 Ugandan districts tested a management approach, Community and District-management Empowerment for Scale-up (CODES). Eight districts were randomly selected for each of the intervention and comparison areas. The approach relies on a customised set of data-driven diagnostic tools to identify and resolve health system bottlenecks. Using a difference-in-differences approach, the authors performed an intention-to-treat analysis of protective, preventive and curative practices for malaria, pneumonia and diarrhoea among children aged 5 and younger.ResultsIntervention districts reported significant net increases in the treatment of malaria (+23%), pneumonia (+19%) and diarrhoea (+13%) and improved stool disposal (+10%). Coverage rates for immunisation and vitamin A consumption saw similar improvements. By engaging communities and district managers in a common quest to solve local bottlenecks, CODES fostered demand for health services. However, limited fiscal space-constrained district managers’ ability to implement solutions identified through CODES.ConclusionData-driven district management interventions can positively impact child health outcomes, with clinically significant improvements in the treatment of malaria, pneumonia and diarrhoea as well as stool disposal. The findings recommend the model’s suitability for health systems strengthening in Uganda and other decentralised contexts.Trial registration numberISRCTN15705788.