Performance of the Universal Vital Assessment (UVA) mortality risk score in hospitalized adults with infection in Rwanda: A retrospective external validation study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Child health and the implementation of Community and District-management Empowerment for Scale-up (CODES) in Uganda: a randomised controlled trial.

INTRODUCTION: Uganda'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. METHODS: A 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. RESULTS: Intervention 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. CONCLUSION: Data-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 NUMBER: ISRCTN15705788.

The President's Emergency Plan for AIDS Relief and adult mortality: A replication study of HIV development assistance effects in Sub-Saharan African countries.

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).

Cash transfers and HIV/HSV-2 prevalence: A replication of a cluster randomized trial in Malawi.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Increasing Evidence-Based Interventions in Patients with Acute Infections in a Resource-Limited Setting: A Before-and-After Feasibility Trial in Gitwe, Rwanda.

OBJECTIVE: To evaluate whether a focused education program and implementation of a treatment bundle increases the rate of early evidence-based interventions in patients with acute infections. DESIGN: Single-center, prospective, before-and-after feasibility trial. SETTING: Emergency department of a sub-Saharan African district hospital. PATIENTS: Patients > 28 days of life admitted to the study hospital for an acute infection. INTERVENTIONS: The trial had three phases (each of four months). Interventions took place during the second (educational program followed by implementation of the treatment bundle) and third (provision of resources to implement treatment bundle) phases. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, and laboratory data were collected at study enrollment; 24, 48, and 72 hours after hospital admission; and at discharge. A total of 1,594 patients were enrolled (pre-intervention, n = 661; intervention I, n = 531; intervention II, n = 402). The rate of early evidence-based interventions per patient during Intervention Phase I was greater than during the pre-intervention phase (74 ± 17 vs. 79 ± 15%, p < 0.001). No difference was detected when data were compared between Intervention Phases I and II (79 ± 15 vs. 80 ± 15%, p = 0.58). No differences in the incidence of blood transfusion (pre-intervention, 6%; intervention I, 7%; intervention II, 7%) or severe adverse events in the first 24 hours (allergic reactions: pre-intervention, 0.2%; intervention I, 0%; intervention II, 0%; respiratory failure: pre-intervention, 2%; intervention I, 2%; intervention II, 2%; acute renal failure: pre-intervention, 2%; intervention I, 2%; intervention II, 1%) were observed. CONCLUSIONS: Our results indicate that a focused education program and implementation of an infection treatment bundle in clinical practice increased the rate of early evidence-based interventions in patients with acute infections (mostly malaria) admitted to a sub-Saharan African district hospital. Provision of material resources did not further increase this rate. While no safety issues were detected, this could be related to the very low disease severity of the enrolled patient population (www.clinicaltrials.gov: NCT02697513).

Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) Score With Excess Hospital Mortality in Adults With Suspected Infection in Low- and Middle-Income Countries.

Importance: The quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score has not been well-evaluated in low- and middle-income countries (LMICs). Objective: To assess the association of qSOFA with excess hospital death among patients with suspected infection in LMICs and to compare qSOFA with the systemic inflammatory response syndrome (SIRS) criteria. Design, Settings, and Participants: Retrospective secondary analysis of 8 cohort studies and 1 randomized clinical trial from 2003 to 2017. This study included 6569 hospitalized adults with suspected infection in emergency departments, inpatient wards, and intensive care units of 17 hospitals in 10 LMICs across sub-Saharan Africa, Asia, and the Americas. Exposures: Low (0), moderate (1), or high (≥2) qSOFA score (range, 0 [best] to 3 [worst]) or SIRS criteria (range, 0 [best] to 4 [worst]) within 24 hours of presentation to study hospital. Main Outcomes and Measures: Predictive validity (measured as incremental hospital mortality beyond that predicted by baseline risk factors, as a marker of sepsis or analogous severe infectious course) of the qSOFA score (primary) and SIRS criteria (secondary). Results: The cohorts were diverse in enrollment criteria, demographics (median ages, 29-54 years; males range, 36%-76%), HIV prevalence (range, 2%-43%), cause of infection, and hospital mortality (range, 1%-39%). Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. Compared with a low or moderate score, a high qSOFA score was associated with increased risk of death overall (19% vs 6%; difference, 13% [95% CI, 11%-14%]; odds ratio, 3.6 [95% CI, 3.0-4.2]) and across cohorts (P < .05 for 8 of 9 cohorts). Compared with a low qSOFA score, a moderate qSOFA score was also associated with increased risk of death overall (8% vs 3%; difference, 5% [95% CI, 4%-6%]; odds ratio, 2.8 [95% CI, 2.0-3.9]), but not in every cohort (P < .05 in 2 of 7 cohorts). High, vs low or moderate, SIRS criteria were associated with a smaller increase in risk of death overall (13% vs 8%; difference, 5% [95% CI, 3%-6%]; odds ratio, 1.7 [95% CI, 1.4-2.0]) and across cohorts (P < .05 for 4 of 9 cohorts). qSOFA discrimination (area under the receiver operating characteristic curve [AUROC], 0.70 [95% CI, 0.68-0.72]) was superior to that of both the baseline model (AUROC, 0.56 [95% CI, 0.53-0.58; P < .001) and SIRS (AUROC, 0.59 [95% CI, 0.57-0.62]; P < .001). Conclusions and Relevance: When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.

An overview of assessment methodology for obesity-related variables in infants at risk.

BACKGROUND: The first 2 years of a child's life are a particularly critical time period for obesity prevention. AIM: An increasing amount of research across the world is aimed at understanding factors that impact early childhood obesity and developing interventions that target these factors effectively. With this growing interest, new and interdisciplinary research teams are developing to meet this research need. Due to rapid growth velocity during this phase of the lifespan, typical assessments used in older populations may not be valid or applicable in infants, and investigators need to be aware of the pros and cons of specific methodological strategies. METHODS: This paper provides an overview of methodology available to assess obesity-related factors in the areas of anthropometry and body composition, nutrient intake, and energy expenditure in infants aged 0-2 years. RESULTS: Gold standard measures for body composition, such as dual-energy X-ray absorptiometry (DXA) or other imaging techniques, are costly, require highly trained personnel, and are limited for research application. Nutrient intake methodology primarily includes surveys and questionnaires completed via parent proxy report. In terms of energy expenditure, methods of calorimetry are expensive and may not differentiate between different activities. Questionnaires or physical activity sensors offer another way of energy expenditure assessment. However, questionnaires have a certain recall bias, while the sensors require further validation. CONCLUSIONS: Overall, in addition to understanding the pros and cons of each assessment tool, researchers should take into consideration the experience of the interdisciplinary team of investigators, as well as the cost and availability of measures at their institution.

Community and District Empowerment for Scale-up (CODES): a complex district-level management intervention to improve child survival in Uganda: study protocol for a randomized controlled trial.

BACKGROUND: Innovative and sustainable strategies to strengthen districts and other sub-national health systems and management are urgently required to reduce child mortality. Although highly effective evidence-based and affordable child survival interventions are well-known, at the district level, lack of data, motivation, analytic and planning capacity often impedes prioritization and management weaknesses impede implementation. The Community and District Empowerment for Scale-up (CODES) project is a complex management intervention designed to test whether districts when empowered with data and management tools can prioritize and implement evidence-based child survival interventions equitably. METHODS: The CODES strategy combines management, diagnostic, and evaluation tools to identify and analyze the causes of bottlenecks to implementation, build capacity of district management teams to implement context-specific solutions, and to foster community monitoring and social accountability to increase demand for services. CODES combines UNICEF tools designed to systematize priority setting, allocation of resources and problem solving with Community dialogues based on Citizen Report Cards and U-Reports used to engage and empower communities in monitoring health service provision and to demand for quality services. Implementation and all data collection will be by the districts teams or local Community-based Organizations who will be supported by two local implementing partners. The study will be evaluated as a cluster randomized trial with eight intervention and eight comparison districts over a period of 3 years. Evaluation will focus on differences in uptake of child survival interventions and will follow an intention-to-treat analysis. We will also document and analyze experiences in implementation including changes in management practices. DISCUSSION: By increasing the District Health Management Teams' capacity to prioritize and implement context-specific solutions, and empowering communities to become active partners in service delivery, coverage of child survival interventions will increase. Lessons learned on strengthening district-level managerial capacities and mechanisms for community monitoring may have implications, not only in Uganda but also in other similar settings, especially with regard to accelerating effective coverage of key child survival interventions using locally available resources. TRIAL REGISTRATION NUMBER: ISRCTN15705788 , Date of registration; 24 July 2015.

Improving child survival through a district management strengthening and community empowerment intervention: early implementation experiences from Uganda.

BACKGROUND: The Community and District Empowerment for Scale-up (CODES) project pioneered the implementation of a comprehensive district management and community empowerment intervention in five districts in Uganda. In order to improve effective coverage and quality of child survival interventions CODES combines UNICEF tools designed to systematize priority setting, allocation of resources and problem solving with Community dialogues based on Citizen Report Cards and U-Reports used to engage and empower communities in monitoring health service provision and to demand for quality services. This paper presents early implementation experiences in five pilot districts and lessons learnt during the first 2 years of implementation. METHODS: This qualitative study was comprised of 38 in-depth interviews with members of the District Health Teams (DHTs) and two implementing partners. These were supplemented by observations during implementation and documents review. Thematic analysis was used to distill early implementation experiences and lessons learnt from the process. RESULTS: All five districts health teams with support from the implementing partners were able to adopt the UNICEF tools and to develop district health operational work plans that were evidence-based. Members of the DHTs described the approach introduced by the CODES project as a more systematic planning process and very much appreciated it. Districts were also able to implement some of the priority activities included in their work plans but limited financial resources and fiscal decision space constrained the implementation of some activities that were prioritized. Community dialogues based on Citizen Report Cards (CRC) increased community awareness of available health care services, their utilization and led to discussions on service delivery, barriers to service utilization and processes for improvement. Community dialogues were also instrumental in bringing together service users, providers and leaders to discuss problems and find solutions. The dialogues however are more likely to be sustainable if embedded in existing community structures and conducted by district based facilitators. U report as a community feedback mechanism registered a low response rate. CONCLUSION: The UNICEF tools were adopted at district level and generally well perceived by the DHTs. The limited resources and fiscal decision space however can hinder implementation of prioritized activities. Community dialogues based on CRCs can bring service providers and the community together but need to be embedded in existing community structures for sustainability.

Modelling the potential impact and cost of scaling-up male circumcision in resource poor settings: A case of Uganda.

This study modelled estimates of the cost and impact of male circumcision (MC) under different scenarios using the Decision Maker's Program Planning Tool on data from Uganda. Results showed that the number of new adult HIV infections could be reduced by 23 000 if MC could be increased from the current 25% to 80% by 2015. The incidence of HIV could be reduced by 0.2 percentage points over the same period. If a scale up programme is to meet a target of 80% by 2015 then the annual number of MCs performed should be over twice as many as those performed in 2011. The discounted net cost per infection averted would be US$559 for the period 2011-2015 and the country would save US$6 841 per infection. A scale up of MC will reduce HIV prevalence and incidence substantially and it would be highly cost effective. The government should mobilise funding to meet high MC targets that would deliver the desired reduction in prevalence and incidence in a short period of time.

Human papillomavirus prevalence and cytopathology correlation in young Ugandan women using a low-cost liquid-based Pap preparation.

Screening for HPV-driven cervical dysplasia and neoplasia is a significant public health concern in the developing world. The purpose of this study was to use a manual, low-cost liquid-based Pap preparation to determine HPV prevalence in HIV-positive and HIV-negative young women in Kampala, Uganda and to correlate cervical cytopathology with HPV-DNA genotype. About 196 post-partum women aged 18-30 years underwent rapid HIV testing and pelvic examination. Liquid-based cervical cytology samples were processed using a low-cost manual technique. A DNA collection device was used to collect specimens for HPV genotyping. HIV and HPV prevalence was 18 and 64%, respectively. Overall, 49% of women were infected with a high-risk HPV genotype. The most common high-risk HPV genotypes were 16 (8.2%), 33 (7.7%), 35 (6.6%), 45 (5.1%), and 58 (5.1%). The prevalence of HPV 18 was 3.6%. HIV-positive women had an HPV prevalence of 86% compared to 59% in HIV-negative women (P = 0.003). The prevalence of HPV 16/18 did not differ by HIV status. HIV-positive women were infected with a significantly greater number of HPV genotypes compared to HIV-negative women. By multivariate analysis, the main risk factor for HPV infection was coinfection with HIV. HIV-positive women were four times more likely to have abnormal cytology than HIV-negative women (43% vs. 11.6%, P < 0.001). These data highlight that HIV infection is a strong risk factor for HPV infection and resultant abnormal cervical cytology. Notably, the manual low-cost liquid-based Pap preparation is practical in this setting and offers an alternate method for local studies of HPV vaccine efficacy.