Improving assent in health research: a rapid systematic review.

BACKGROUND: Enrolment in a research study requires the participant's informed consent. In the case of minors, informed consent of the respective legal guardian is obtained in conjunction with informed assent of the underage p articipant. Since comprehension of the information provided may be limited, effective interventions to improve understanding should be identified. Thus, it is the objective of this study to review quantitative studies that tested interventions to improve the understanding of information provided during assent processes in health research. The studied population consisted of minors that participated or were willing to participate in research. The primary outcome was the level of comprehension after intervention. METHODS: A systematic search was conducted in eleven databases including regional databases: PubMed, Web of Science, ERIC, PsycINFO, CINAHL, POPLINE, AIM, LILACS, WPRIM, IMSEAR, and IMEMR and included references from inception of the database until July 2018 except PubMed which spanned the period from May 2013 to July 2018. Search terms focused on Informed Consent/Assent, Minors, and Comprehension. To complement the search, reference lists of retrieved publications were additionally searched. We included all quantitative studies that were conducted in minors, tested an intervention, covered assent processes in health research, and assessed comprehension. One reviewer screened titles, abstracts, and full-texts to determine eligibility and collected data on study design, population, intervention, methods, outcome, and for critical appraisal. Interventions comprised enhanced paper forms, interspersed questions, multimedia format, and others. RESULTS: Out of 7089 studies initially identified, 19 studies comprising 2805 participants and conducted in seven countries were included in the review. Fourteen studies (74 %) tested an intervention against control and ten (53 %) were randomized controlled trials. Heterogeneous methodology as well as incomplete outcome and statistical reporting impaired the reliability of the collected data. Positive effects were suggested for use of enhanced paper forms, interspersed questions, use of pie charts, and organizational factors. CONCLUSIONS: Improving assent in health research is an under-researched area with little reliable evidence. While some interventions are proposed to improve understanding in assent processes, further investigation is necessary to be able to give evidence-based recommendations. TRIAL REGISTRATION: PROSPERO ID: 106808.

Ensuring quality in AFRINEST and SATT: clinical standardization and monitoring.

BACKGROUND: Three randomized open-label clinical trials [Simplified Antibiotic Therapy Trial (SATT) Bangladesh, SATT Pakistan and African Neonatal Sepsis Trial (AFRINEST)] were developed to test the equivalence of simplified antibiotic regimens compared with the standard regimen of 7 days of parenteral antibiotics. These trials were originally conceived and designed separately; subsequently, significant efforts were made to develop and implement a common protocol and approach. Previous articles in this supplement briefly describe the specific quality control methods used in the individual trials; this article presents additional information about the systematic approaches used to minimize threats to validity and ensure quality across the trials. METHODS: A critical component of quality control for AFRINEST and SATT was striving to eliminate variation in clinical assessments and decisions regarding eligibility, enrollment and treatment outcomes. Ensuring appropriate and consistent clinical judgment was accomplished through standardized approaches applied across the trials, including training, assessment of clinical skills and refresher training. Standardized monitoring procedures were also applied across the trials, including routine (day-to-day) internal monitoring of performance and adherence to protocols, systematic external monitoring by funding agencies and external monitoring by experienced, independent trial monitors. A group of independent experts (Technical Steering Committee/Technical Advisory Group) provided regular monitoring and technical oversight for the trials. CONCLUSIONS: Harmonization of AFRINEST and SATT have helped to ensure consistency and quality of implementation, both internally and across the trials as a whole, thereby minimizing potential threats to the validity of the trials' results.

Ongoing trials of simplified antibiotic regimens for the treatment of serious infections in young infants in South Asia and sub-Saharan Africa: implications for policy.

BACKGROUND: The current World Health Organization (WHO) recommendation for treatment of severe infection in young infants is hospitalization and parenteral antibiotic therapy. Hospital care is generally not available outside large cities in low- and middle-income countries and even when available is not acceptable or affordable for many families. Previous research in Bangladesh and India demonstrated that treatment outside hospitals may be possible. RESEARCH: A set of research studies with common protocols testing simplified antibiotic regimens that can be provided at the lowest-level health-care facility or at home are nearing completion. The studies are large individually randomized controlled trials that are set up in the context of a program, which provides home visits by community health workers to detect serious illness in young infants with assessment and treatment at an outpatient health facility near home. This article summarizes the policy implications of the research studies. POLICY IMPLICATIONS: The studies are expected to result in information that would inform WHO guidelines on simple, safe and effective regimens for the treatment of clinical severe infection and pneumonia in newborns and young infants in settings where referral is not possible. The studies will also inform the inputs and process required to establish outpatient treatment of newborn and young infant infections at health facilities near the home. We expect that the information from research and the resulting WHO guidelines will form the basis of policy dialogue by a large number of stakeholders at the country level to implement outpatient treatment of neonatal infections and thereby reduce neonatal and infant mortality resulting from infection.

Cumulative exposure to cell-free HIV in breast milk, rather than feeding pattern per se, identifies postnatally infected infants.

BACKGROUND: We quantified the relationship between human immunodeficiency virus (HIV) RNA shedding in breast milk, cumulative RNA exposure, and postnatal transmission, relating timing of infection in the infant to estimated total volume of milk exposure. METHODS: Nested case-control study of 36 infants of HIV-infected mothers. Case patients were infants who acquired HIV infection through breastfeeding from age 6 through 28 weeks, and control subjects were uninfected infants matched on age at obtainment of a breast milk sample. Mothers and infants received peripartum single-dose nevirapine prophylaxis. Feeding data were collected daily; breast milk samples were collected and infant anthropometry was performed at 6 weeks and monthly thereafter. Volume of milk ingested was estimated using infant weight and feeding pattern. RESULTS: Before HIV acquisition in case patients, feeding pattern (exclusive breastfeeding; median duration, 65 vs 70 days; P = .6) and daily milk intake (mean volume, 638 vs 637 mL; P = .97) did not differ significantly between case patients and control subjects. Case mothers were more likely to shed virus (64% vs 9% always, 22% vs 20.5% intermittently, 14% vs 70.5% never shed; overall, P < .001). Case patients ingested ~15 times more HIV-1 RNA particles than did control subjects (196.5 vs 13 × 106 copies; P < .001). Allowing for maternal antenatal CD4 cell count and plasma HIV-1 load, child sex and duration of mixed breastfeeding, the association between HIV RNA exposure and infection remained statistically significant (P < .001). CONCLUSIONS: Postnatal acquisition of HIV-1 is more strongly associated with cumulative exposure to cell-free particles in breast milk than with feeding mode. Reducing breast milk viral load through antiretroviral therapy to mother or child can further decrease postnatal transmission in exclusively breastfed infants.

Too little, too late: comparison of nutritional status and quality of life of nutrition care and support recipient and non-recipients among HIV-positive adults in KwaZulu-Natal, South Africa.

OBJECTIVE: Compare the nutritional vulnerability, risk of malnutrition, nutritional status and quality of life (QoL) between recipients and non-recipients of nutrition care and support (NCS) of HIV-positive adults. METHODS: In 2009, a household-based cross-sectional study of HIV-positive adults, NCS recipients (n=97) and non-NCS recipients (n=203) from KwaZulu-Natal was conducted. Nutritional vulnerability (socio-economic status; food security; self-reported health status; nutritional knowledge and attitude), risk of malnutrition (nutrition assessment screening tool), anthropometry (body mass index; mid-upper arm circumference; waist-to-hip ratio) and QoL (general health; self-care; physical functioning) were compared between the two groups. RESULT: Although the result suggests a modest impairment of QoL, NCS recipients were twice as likely to have severe impairment of general health; self-care functioning and QoL. Overweight and obesity were common despite indications of high prevalence of food insecurity, possible-risk of malnutrition and diets predominantly of cereals. NCS recipients were more frequently taking anti-retroviral drugs, receiving social grants, reporting good eating plans and owning kitchen gardens. Non-NCS recipients had been generally sick, reported fatigue, nausea, appetite loss and diarrhoea. NCS recipients were twice as likely to experience oral thrush. CONCLUSION: Contextual factors such as low dietary diversity and household food insecurity that exacerbates nutritional vulnerability and malnutrition should be considered when providing NCS to fully achieve nutritional recovery and QoL of HIV-positive adults.