Ethical Considerations for Engaging Children and Adolescents Living with HIV in Research in African Countries: A Systematic Review.

Research engaging children and adolescents living with HIV (CALWH) is critical for youth-friendly services and HIV care, and researchers need to ensure that such engagement is ethical. We conducted a systematic review to identify key ethical considerations for the engagement of CALWH in research. The review focused on primary research articles conducted in African countries that examined ethical issues in CALWH engaged in research. Ten studies met the inclusion criteria; the following seven key domains were extracted: 1) justifications for engaging CALWH in research; 2) community involvement; 3) informed consent/assent; 4) caregiver involvement; 5) perceptions of benefits; 6) perception of the risks of involvement; and 7) confidentiality. These domains can inform the ethical engagement of CALWH in research.

Individualized Assessment of Risk of Complications after Benign Hysterectomy.

STUDY OBJECTIVES: The primary objective of this study is to identify patient characteristics associated with postoperative complications or readmissions after hysterectomy for a benign indication. DESIGN: Retrospective cohort. SETTING: The Surgical Gynecologic Scorecard Database includes performance metrics and patient outcomes for hysterectomies across 7 sites in Ontario, Canada. PARTICIPANTS: Individuals who underwent hysterectomy for benign gynecologic indication and were recorded in the Surgical Gynecologic Scorecard Database between July 2016 and June 2019 were included in this study. MEASUREMENTS AND MAIN RESULTS: Two outcomes of interest were considered: (1) complications grade II or greater on the Clavien-Dindo classification scale and (2) emergency room visits or hospital readmissions within 6 weeks after operation. Logistic models were generated to determine the associations between outcome of interest and potential predictors using a mixed-step AIC selection algorithm. A total of 2792 patients underwent hysterectomy for a benign indication during the study period, with a mean age of 52.6 ± 11.7 years and mean body mass index of 29.0 ± 0.7 kg/m2. The most common indications for surgery were abnormal uterine bleeding (33.3%) and myomas (33.6%). Previous cesarean delivery (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.04-1.42), American Society of Anesthesiologists class ≥3 (aOR, 2.31; 95% CI, 1.42-3.99), preoperative anemia (aOR, 1.51; 95% CI, 1.12-2.02), and laparotomic approach (aOR, 1.73; 95% CI, 1.30-2.29) were associated with increased odds of complication. Perioperative complications (aOR, 2.95; 95% CI, 2.12-4.08), preoperative anemia (aOR, 1.43; 95% CI, 1.03-1.98), and vaginal (aOR, 1.94; 95% CI, 1.26-2.96) or laparotomic (aOR, 1.64; 95% CI, 1.10-2.43) approach were associated with increased odds of emergency room visit or readmission to hospital. CONCLUSION: This study identified several important risk factors for complications after hysterectomy. The utility of these data is important to help improve counseling for patients undergoing a hysterectomy and potentially optimize modifiable risk factors when identified preoperatively.

Cost Utility of Supporting Family-Based Care to Prevent HIV and Deaths among Orphaned and Separated Children in East Africa: A Markov Model-Based Simulation.

Purpose. Strengthening family-based care is a key policy response to the more than 15 million orphaned and separated children who have lost 1 or both parents in sub-Saharan Africa. This analysis estimated the cost-effectiveness of family-based care environments for preventing HIV and death in this population. Design. We developed a time-homogeneous Markov model to simulate the incremental cost per disability-adjusted life year (DALY) averted by supporting family-based environments caring for orphaned and separated children in western Kenya. Model parameters were based on data from the longitudinal OSCAR's Health and Well-Being Project and published literature. We used a societal perspective, annual cycle length, and 3% discount rate. Incremental cost-effectiveness ratios were simulated over 5- to 15-y horizons, comparing family-based settings to street-based "self-care." Parameter uncertainty was addressed via deterministic and probabilistic sensitivity analyses. Results. Under base-case assumptions, family-based environments prevented 422 HIV infections and 298 deaths in a simulated cohort of 1,000 individuals over 10 y. Compared with street-based self-care, family-based care had an incremental cost of $2,528 per DALY averted (95% confidence interval [CI]: 1,798, 2,599) and $2,355 per quality-adjusted life year gained (95% CI: 1,667, 2,413). The probability of family-based care being highly cost-effective was >80% at a willingness-to-pay (WTP) threshold of $2,250/DALY averted. Households receiving government cash transfers had minimally higher cost-effectiveness ratios than households without cash transfers but were still cost-effective at a WTP threshold of twice Kenya's GDP per capita. Conclusions. Compared with the status quo of street-based self-care, family-based environments offer a cost-effective approach for preventing HIV and death among orphaned children in lower-middle income countries. Decision makers should consider increasing resources to these environments in tandem with social protection programs. Highlights: UNICEF and more than 200 other international organizations endorsed efforts to redirect services toward family-based care as part of the 2019 UN Resolution on the Rights of the Child; yet this study is one of the first to quantify the cost-effectiveness of family-based care environments serving some of the world's most vulnerable children.This health economic modeling analysis found that family-based environments would prevent 422 HIV infections and 298 deaths in a cohort of 1,000 orphaned and separated children over a 10-y time horizon.Compared with street-based "self-care," family-based care resulted in an incremental cost of $2,528 per DALY averted (95% CI: 1,798, 2,599) and $2,355 per quality-adjusted life year gained (95% CI: 1,667, 2,413) after 10 y.Annual per-child expenditures for children living in family-based care environments in sub-Saharan Africa could potentially be increased by at least 25% and remain highly cost-effective.

Sex differences in health status, healthcare utilization, and costs among individuals with elevated blood pressure: the LARK study from Western Kenya.

BACKGROUND: Elevated blood pressure is the leading risk factor for global mortality. While it is known that there exist differences between men and women with respect to socioeconomic status, self-reported health, and healthcare utilization, there are few published studies from Africa. This study therefore aims to characterize differences in self-reported health status, healthcare utilization, and costs between men and women with elevated blood pressure in Kenya. METHODS: Data from 1447 participants enrolled in the LARK Hypertension study in western Kenya were analyzed. Latent class analysis based on five dependent variables was performed to describe patterns of healthcare utilization and costs in the study population. Regression analysis was then performed to describe the relationship between different demographics and each outcome. RESULTS: Women in our study had higher rates of unemployment (28% vs 12%), were more likely to report lower monthly earnings (72% vs 51%), and had more outpatient visits (39% vs 28%) and pharmacy prescriptions (42% vs 30%). Women were also more likely to report lower quality-of-life and functional health status, including pain, mobility, self-care, and ability to perform usual activities. Three patterns of healthcare utilization were described: (1) individuals with low healthcare utilization, (2) individuals who utilized care and paid high out-of-pocket costs, and (3) individuals who utilized care but had lower out-of-pocket costs. Women and those with health insurance were more likely to be in the high-cost utilizer group. CONCLUSIONS: Men and women with elevated blood pressure in Kenya have different health care utilization behaviors, cost and economic burdens, and self-perceived health status. Awareness of these sex differences can help inform targeted interventions in these populations.

Estimation of cumulative number of post-treatment Lyme disease cases in the US, 2016 and 2020.

BACKGROUND: Lyme disease (LD) is an infectious multi-system illness caused by the bacterial genus Borrelia and spread by bites of infected ticks. Although most patients are successfully treated by timely antibiotic therapy, it is broadly accepted that a sizeable number of patients experience treatment failure and continue to suffer long-term, debilitating symptoms, including pain, fatigue, cognitive dysfunction and other symptoms. This is known as post-treatment LD (PTLD), for which diagnosis is not standardized and treatment remains controversial. The prevalence and societal burden of PTLD is unknown. METHODS: In an effort to help characterize the LD landscape, we estimated the number of PTLD cases in the US in 2016 and 2020 using Monte-Carlo simulation techniques, publically-available demographic datasets, uncertainty in the inputs and realistic assumptions about incidence and treatment failure rates. RESULTS: Depending on the input assumptions, PTLD prevalence estimates for 2016 ranged from 69,011 persons (95% CI 51,796 to 89,312) to 1,523,869 (CI 1,268,634 to 1,809,416). Prevalence in 2020 is predicted to be higher than 2016, and may be as high as 1,944,189 (CI 1,619,988 to 2,304,147) cases. CONCLUSIONS: The cumulative prevalence of PLTD in the United States is estimated to be high and continues to increase. These findings will be of interest to epidemiologists and health economists studying disease burden in the US and elsewhere, and justify funding to study PTLD diagnosis and treatment.

Bridging Income Generation with Group Integrated Care for cardiovascular risk reduction: Rationale and design of the BIGPIC study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with >80% of CVD deaths occurring in low and middle income countries (LMICs). Diabetes mellitus and pre-diabetes are risk factors for CVD, and CVD is the major cause of morbidity and mortality among individuals with DM. There is a critical period now during which reducing CVD risk among individuals with diabetes and pre-diabetes may have a major impact. Cost-effective, culturally appropriate, and context-specific approaches are required. Two promising strategies to improve health outcomes are group medical visits and microfinance. METHODS/DESIGN: This study tests whether group medical visits integrated into microfinance groups are effective and cost-effective in reducing CVD risk among individuals with diabetes or at increased risk for diabetes in western Kenya. An initial phase of qualitative inquiry will assess contextual factors, facilitators, and barriers that may impact integration of group medical visits and microfinance for CVD risk reduction. Subsequently, we will conduct a four-arm cluster randomized trial comparing: (1) usual clinical care, (2) usual clinical care plus microfinance groups only, (3) group medical visits only, and (4) group medical visits integrated into microfinance groups. The primary outcome measure will be 1-year change in systolic blood pressure, and a key secondary outcome measure is 1-year change in overall CVD risk as measured by the QRISK2 score. We will conduct mediation analysis to evaluate the influence of changes in social network characteristics on intervention outcomes, as well as moderation analysis to evaluate the influence of baseline social network characteristics on effectiveness of the interventions. Cost-effectiveness analysis will be conducted in terms of cost per unit change in systolic blood pressure, percent change in CVD risk score, and per disability-adjusted life year saved. DISCUSSION: This study will provide evidence regarding effectiveness and cost-effectiveness of interventions to reduce CVD risk. We aim to produce generalizable methods and results that can provide a model for adoption in low-resource settings worldwide.

Optimizing linkage and retention to hypertension care in rural Kenya (LARK hypertension study): study protocol for a randomized controlled trial.

BACKGROUND: Hypertension is the leading global risk factor for mortality. Hypertension treatment and control rates are low worldwide, and delays in seeking care are associated with increased mortality. Thus, a critical component of hypertension management is to optimize linkage and retention to care. METHODS/DESIGN: This study investigates whether community health workers, equipped with a tailored behavioral communication strategy and smartphone technology, can increase linkage and retention of hypertensive individuals to a hypertension care program and significantly reduce blood pressure among them. The study will be conducted in the Kosirai and Turbo Divisions of western Kenya. An initial phase of qualitative inquiry will assess facilitators and barriers of linkage and retention to care using a modified Health Belief Model as a conceptual framework. Subsequently, we will conduct a cluster randomized controlled trial with three arms: 1) usual care (community health workers with the standard level of hypertension care training); 2) community health workers with an additional tailored behavioral communication strategy; and 3) community health workers with a tailored behavioral communication strategy who are also equipped with smartphone technology. The co-primary outcome measures are: 1) linkage to hypertension care, and 2) one-year change in systolic blood pressure among hypertensive individuals. Cost-effectiveness analysis will be conducted in terms of costs per unit decrease in blood pressure and costs per disability-adjusted life year gained. DISCUSSION: This study will provide evidence regarding the effectiveness and cost-effectiveness of strategies to optimize linkage and retention to hypertension care that can be applicable to non-communicable disease management in low- and middle-income countries. TRIAL REGISTRATION: This trial is registered with (NCT01844596) on 30 April 2013.

TREAT Asia Quality Assessment Scheme (TAQAS) to standardize the outcome of HIV genotypic resistance testing in a group of Asian laboratories.

The TREAT Asia (Therapeutics, Research, Education, and AIDS Training in Asia) Network is building capacity for Human Immunodeficiency Virus Type-1 (HIV-1) drug resistance testing in the region. The objective of the TREAT Asia Quality Assessment Scheme - designated TAQAS - is to standardize HIV-1 genotypic resistance testing (HIV genotyping) among laboratories to permit rigorous comparison of results from different clinics and testing centres. TAQAS has evaluated three panels of HIV-1-positive plasma from clinical material or low-passage, culture supernatant for up to 10 Asian laboratories. Laboratory participants used their standard protocols to perform HIV genotyping. Assessment was in comparison to a target genotype derived from all participants and the reference laboratory's result. Agreement between most participants at the edited nucleotide sequence level was high (>98%). Most participants performed to the reference laboratory standard in detection of drug resistance mutations (DRMs). However, there was variation in the detection of nucleotide mixtures (0-83%) and a significant correlation with the detection of DRMs (p<0.01). Interpretation of antiretroviral resistance showed approximately 70% agreement among participants when different interpretation systems were used but >90% agreement with a common interpretation system, within the Stanford University Drug Resistance Database. Using the principles of external quality assessment and a reference laboratory, TAQAS has demonstrated high quality HIV genotyping results from Asian laboratories.