Formulating the Future Research Agenda for Postexposure Prophylaxis for HIV: Methodological Challenges and Potential Approaches

Background. During a World Health Organization-convened Guideline Development Group meeting, recommendations for postexposure prophylaxis (PEP) for human immunodeficiency virus were made and research gaps identified. Methods. We used the PEP clinical management pathway and the Grading of Evidence, Assessment, Development and Evaluation (GRADE) system as a framework to formulate future research questions, describe the most feasible study design, and identify potential biases. Results. Three key study design formats were identified to address 12 research questions: (1) survey- and interview-driven research to identify barriers to access to PEP and related clinical care; (2) establishment of a global PEP registry to generate data to inform the choice of an optimal PEP drug regimen, record drug toxicities arising from specific PEP regimens, and track follow-up and linkage to care (including transition from PEP to preexposure prophylaxis); and (3) randomized controlled trials to determine the optimal adherence promotion strategies necessary for successful outcomes following PEP. Conclusions.  Positioning key clinical and programmatic research questions within the GRADE framework facilitates the formulation of an evidence-based research agenda and future revisions of guideline

Micronutrient supplementation in adults with HIV infection.

Background Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and minerals. Some micronutrients play critical roles in maintenance of the immune system, and routine supplementation could therefore be beneficial. This is an update of a Cochrane Review previously published in 2010. Objectives To assess whether micronutrient supplements are effective and safe in reducing mortality and HIV-related morbidity of HIV-positive adults (excluding pregnant women). Search methods We performed literature searches from January 2010 to 18 November 2016 for new randomized controlled trials (RCTs) of micronutrient supplements since the previous review included all trials identified from searches prior to 2010. We searched the CENTRAL (the Cochrane Library), Embase, and PubMed databases. Also we checked the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov trials registers. We also checked the reference lists of all new included trials. Selection criteria We included RCTs that compared supplements that contained either single, dual, or multiple micronutrients with placebo, no treatment, or other supplements. We excluded studies that were primarily designed to investigate the role of micronutrients for the treatment of HIV-positive participants with metabolic morbidity related to highly active antiretroviral therapy (HAART). Primary outcomes included all-cause mortality, morbidity, and disease progression. Data collection and analysis Two review authors independently selected trials for inclusion, and appraised trial quality for risk of bias. Where possible, we presented results as risk ratios (RR) for dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean differences (MD) for continuous variables, each with 95% confidence intervals (CIs). Since we were often unable to pool the outcome data, we tabulated it for each comparison. We assessed the certainty of the evidence using the GRADE approach. Main results We included 33 trials with 10,325 participants, of which 17 trials were new trials. Ten trials compared a daily multiple micronutrient supplement to placebo in doses up to 20 times the dietary reference intake, and one trial compared a daily standard dose with a high daily dose of multivitamins. Nineteen trials compared supplementation with single or dual micronutrients (such as vitamins A and D, zinc, and selenium) to placebo, and three trials compared different dosages or combinations of micronutrients. Multiple micronutrients We conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials, 1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400 participants), and ART-naive adults with concurrent active tuberculosis (3 trials, 1429 participants). Routine multiple micronutrient supplementation may have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI 0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence). Routine supplementation for up to two years may have little or no effect on the average of mean CD4+ cell count (MD 26.40 cells/mm³, 95% CI −22.91 to 75.70; 6 trials, 1581 participants, low certainty evidence), or the average of mean viral load (MD −0.1 log10viral copies, 95% CI −0.26 to 0.06; 4 trials, 840 participants, moderate certainty evidence). One additional trial in ART-naïve adults did report an increase in the time to reach a CD4+ cell count < 250 cells/mm³ after two years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1 trial, 439 participants). However, the trial authors reported this effect only in the trial arm that received multiple micronutrients plus selenium (not either supplementation alone), which is inconsistent with the findings of other trials that used similar combinations of micronutrients and selenium. In one additional trial that compared high-dose multiple micronutrient supplementation with standard doses in people on ART, peripheral neuropathy was lower with high dose supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI 0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to increased adverse events (elevated alanine transaminase (ALT) levels) in the high dose group. Single or dual micronutrients None of the trials of single or dual micronutrient supplements were adequately powered to assess for effects on mortality or morbidity outcomes. No clinically significant changes in CD4 cell count (data not pooled, 14 trials, 2370 participants, very low or low certainty evidence) or viral load (data not pooled, seven studies, 1334 participants, very low or low certainty evidence), were reported. Supplementation probably does increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D: 4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty evidence) and may also increase blood concentrations of vitamin A (data not pooled, 3 trials, 495 participants, low certainty evidence), especially in those who are deficient. Authors' conclusions The analyses of the available trials have not revealed consistent clinically important benefits with routine multiple micronutrient supplementation in people living with HIV. Larger trials might reveal small but important effects. These findings should not be interpreted as a reason to deny micronutrient supplements for people living with HIV where specific deficiencies are found or where the person's diet is insufficient to meet the recommended daily allowance of vitamins and minerals

Scope and geographical distribution of African medical journals active in 2005

Objectives: To identify all African medical journals actively publishing in 2005, and to create a geodatabase of these to evaluate and monitor future journal activity.Design: A search was done for relevant African medical journals on electronic databases, library catalogues and internet sites, and a list was compiled of active journals. A survey was conducted via questionnaire of editors of all listed African medical journals defined as having an editorial base on the continent.Results: One hundred and fifty-eight African medical journals were identified, published in 33 countries. One hundred and fifty-three editors were surveyed via email, post and/or fax. There was a 39% response rate from editors based in 17 countries. Fifty-one journals were published in English, 7 in French and 1 in Portuguese. Most journals were owned by an association or a society and were funded from a combination of sources. Journals covered general medical and specialist medical interest equally. Most (41 of 59 journals) had a circulation below 1 000, and most (52/59) published 4 or fewer issues a year. Almost all the journals included original research, and articles were peer reviewed. Few were indexed on Medline (N = 18) and EMBASE (N = 10). Plotting journal location using Geographic Information Systems (GIS) software provided a snapshot view of current journal activity. Conclusions: This study is likely to represent the most comprehensive list of current African medical journals. It confirms growth in African health care research and journal activity on the continent. Limited inclusion in international databases and accessibility to African researchers remain challenges in achieving publication of high-quality African research in high-quality African journals.South African Medical Journal Vol. 96(6) 2006: 533-53

Does Male Circumcision Prevent HIV Infection?

Siegfried discusses the first reported randomized controlled trial of whether circumcision protects against HIV, published in PLoS Medicine

Clinician-Scientists in Canada: Barriers to Career Entry and Progress

BACKGROUND: Clinician-scientists play an important role in translating between research and clinical practice. Significant concerns about a decline in their numbers have been raised. Potential barriers for career entry and progress are explored in this study. METHODS: Case-study research methods were used to identify barriers perceived by clinician-scientists and their research teams in two Canadian laboratories. These perceptions were then compared against statistical analysis of data from Canadian Institutes of Health Research (CIHR) databases on grant and award performance of clinician-scientists and non-clinical PhDs for fiscal years 2000 to 2008. RESULTS: Three main barriers were identified through qualitative analysis: research training, research salaries, and research grants. We then looked for evidence of these barriers in the Canada-wide statistical dataset for our study period. Clinician-scientists had a small but statistically significant higher mean number of degrees (3.3) than non-clinical scientists (3.2), potentially confirming the perception of longer training times. But evidence of the other two barriers was equivocal. For example, while overall growth in salary awards was minimal, awards to clinician-scientists increased by 45% compared to 6.3% for non-clinical PhDs. Similarly, in terms of research funding, awards to clinician-scientists increased by more than 25% compared with 5% for non-clinical PhDs. However, clinician-scientist-led grants funded under CIHR's Clinical thematic area decreased significantly from 61% to 51% (p-value<0.001) suggesting that clinician-scientists may be shifting their attention to other research domains. CONCLUSION: While clinician-scientists continue to perceive barriers to career entry and progress, quantitative results suggest improvements over the last decade. Clinician-scientists are awarded an increasing proportion of CIHR research grants and salary awards. Given the translational importance of this group, however, it may be prudent to adopt specific policy and funding incentives to ensure the ongoing viability of the career path

Adolescent experiences in a vaccine trial: A pilot study

Little is known about how adolescents experience clinical trials. We assessed the experiences of South African adolescent participants in a clinical trial, employing semi-structured interviews to gather qualitative data on the experiences and effects of trial participation. Despite misunderstanding certain concepts regarding assent and trial processes subsequent to enrolment, participants reported positive experiences overall. Subjects’ motivations for participation included: an ability to help others; receipt of healthcare; and free blood screening. Participants expressed fears associated with trial procedures, such as phlebotomy; however, these apprehensions diminished as the trial progressed. We found that conducting qualitative research within a trial site is feasible, and can provide insight into the uptake and acceptability of interventions

Practice-based evidence: evaluating the quality of occupational therapy patient records as evidence for practice

Background: Occupational therapy patient records are required for legal purposes, but may also be used to produce evidence for practice. Our aim was to establish how comprehensively occupational therapists documented patient records. Methodology: We conducted a descriptive cross-sectional study of occupational therapists at public health facilities in a South African province. Trained raters audited five randomly-drawn records per participant using a checklist developed for the study. The maximum possible score was nine and the lowest was zero. Audits were checked for consistency. Results: Forty-nine occupational therapists participated and 240 records were audited. Records contained information on intervention (96%) and changes occurring at impairment (82%) and activity and participation levels (64%). Documentation of baseline assessment (impairment level: 20%; activity and participation level: 10.4%) and re-assessment (impairment level: 7%; activity and participation level: 0.0%) was limited. Audit scores were significantly better in the work practice area (H=16.10, p=0.003) and among therapists in urban areas (U=24.50, p<0.001).There was a significant negative correlation between audit score and number of clients seen per month (rs=-0.46, p<0.001). Conclusion: The low audit scores suggest that the records did not contain sufficient information to produce robust evidence. Manageable ways of documenting occupational therapy practice need to be devised

Improving HIV test uptake and case finding with assisted partner notification services.

OBJECTIVE: Despite the enormous expansion of HIV testing services (HTS), an estimated 40% of people with HIV infection remain undiagnosed. To enhance the efficiency of HTS, new approaches are needed. The WHO conducted a systematic review on the effectiveness of assisted partner notification in improving HIV test uptake and diagnosis, and the occurrence of adverse events, to inform the development of normative guidelines. METHODS: We systematically searched five electronic databases through June 2016. We also contacted experts in the field and study authors for additional information where needed. Eligible studies compared assisted HIV partner notification services to passive or no notification. Where multiple studies reported comparable outcomes, meta-analysis was conducted using a random-effects model to produce relative risks (RRs) or risk ratios and 95% confidence intervals (CIs). RESULTS: Of 1742 citations identified, four randomized controlled trials and six observational studies totalling 5150 index patients from eight countries were included. Meta-analysis of three individually randomized trials showed that assisted partner notification services resulted in a 1.5-fold increase in HTS uptake among partners compared with passive referral (RR = 1.46; 95% CI: 1.22-1.75; I = 0%). The proportion of HIV-positive partners was 1.5 times higher with assisted partner notification than with passive referral (RR = 1.47; 95% CI: 1.12-1.92; I = 0%). Few instances of violence or harm occurred. CONCLUSION: Assisted partner notification improved partner testing and diagnosis of HIV-positive partners, with few reports of harm. WHO strongly recommends voluntary assisted HIV partner notification services to be offered as part of a comprehensive package of testing and care

Comparison of an interactive with a didactic educational intervention for improving the evidence-based practice knowledge of occupational therapists in the public health sector in South Africa: a randomised controlled trial

Background: Despite efforts to identify effective interventions to implement evidence-based practice (EBP), uncertainty remains. Few existing studies involve occupational therapists or resource-constrained contexts. This study aimed to determine whether an interactive educational intervention (IE) was more effective than a didactic educational intervention (DE) in improving EBP knowledge, attitudes and behaviour at 12 weeks. Methods: A matched pairs design, randomised controlled trial was conducted in the Western Cape of South Africa. Occupational therapists employed by the Department of Health were randomised using matched-pair stratification by type (clinician or manager) and knowledge score. Allocation to an IE or a DE was by coin-tossing. A self-report questionnaire (measuring objective knowledge and subjective attitudes) and audit checklist (measuring objective behaviour) were completed at baseline and 12 weeks. The primary outcome was EBP knowledge at 12 weeks while secondary outcomes were attitudes and behaviour at 12 weeks. Data collection occurred at participants’ places of employment. Audit raters were blinded, but participants and the provider could not be blinded. Results: Twenty-one of 28 pairs reported outcomes, but due to incomplete data for two participants, 19 pairs were included in the analysis. There was a median increase of 1.0 points (95% CI = -4.0, 1.0) in the IE for the primary outcome (knowledge) compared with the DE, but this difference was not significant (P = 0.098). There were no significant differences on any of the attitude subscale scores. The median 12-week audit score was 8.6 points higher in the IE (95% CI = -7.7, 27.0) but this was not significant (P = 0.196). Within-group analyses showed significant increases in knowledge in both groups (IE: T = 4.0, P <0.001; DE: T = 12.0, P = 0.002) but no significant differences in attitudes or behaviour. Conclusions: The results suggest that the interventions had similar outcomes at 12 weeks and that the interactive component had little additional effect