Hacsi Horvath

Effectiveness of semen washing to prevent human immunodeficiency virus (HIV) transmission and assist pregnancy in HIV-discordant couples: a systematic review and meta-analysis

OBJECTIVE To evaluate the effectiveness of semen washing in human immunodeficiency virus (HIV)-discordant couples in which the male partner is infected. DESIGN Systematic review and meta-analysis. SETTING Not applicable. PATIENT(S) Forty single-arm open-label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen. INTERVENTION(S) Semen washing followed by IUI, IVF, or IVF/ICSI. MAIN OUTCOME MEASURE(S) PRIMARY OUTCOME HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy. RESULT(S) No HIV transmission occurred in 11,585 cycles of assisted reproduction with the use of washed semen among 3,994 women. Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women after 2,863 cycles of assisted reproduction with the use of washed semen. Studies that measured HIV transmission to infants reported no cases of vertical transmission. Overall, 56.3% of couples (2,357/4,184) achieved a clinical pregnancy with the use of washed semen. CONCLUSION(S) Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help to further reduce the spread of HIV.

Interventions for treating patients with chikungunya virus infection-related rheumatic and musculoskeletal disorders: A systematic review.

Background Chikungunya virus infection (CHIKV) is caused by a mosquito-borne alphavirus. CHIKV causes high fever and painful rheumatic disorders that may persist for years. Because little is known about interventions for treating CHIKV-related illness, we conducted a systematic review. Methods We used Cochrane methods. We searched PubMed, EMBASE, Cochrane Library, LILACS and other sources from the earliest records to March 2016. We had no language restrictions. We included randomized controlled trials assessing any intervention for treating acute or chronic CHIKV-related illness. Our primary outcomes were pain relief, global health status (GHS) or health related quality of life (HRQL), and serious adverse events (SAEs). We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality. Results We screened 2,229 records and found five small trials with a total of 402 participants. Patients receiving chloroquine (CHQ) had better chronic pain relief than those receiving placebo (relative risk [RR] 2.67, 95% confidence interval [CI] 1.23 to 5.77, N = 54), but acute pain relief was marginally not different between groups (mean difference [MD] 1.46, 95% CI 0.00 to 2.92, N = 54). SAEs were similar (RR = 15.00, 95% CI 0.90 to 250.24, N = 54). Comparing CHQ with paracetamol (PCM), CHQ patients had better pain relief (RR = 1.52, 95% CI 1.20 to 1.93, N = 86). Compared with hydroxychloroquine (HCHQ), disease-modifying anti-rheumatic drugs (DMARDs) reduced pain (MD = -14.80, 95% CI -19.12 to -10.48, N = 72). DMARDs patients had less disability (MD = -0.74, 95% CI -0.92 to -0.56, N = 72) and less disease activity (MD = -1.35; 95% CI -1.70 to -1.00; N = 72). SAEs were similar between DMARDs and HCHQ groups (RR = 2.84, 95% CI 0.12 to 67.53, N = 72). Comparing meloxicam (MXM) with CHQ, there was no difference in pain relief (MD = 0.24, 95% CI = -0.81 to 1.29; p = 0.65, N = 70), GHS or HRQL (MD = -0.31, 95% CI -2.06 to 1.44, N = 70) or SAEs (RR = 0.85, 95% CI 0.30 to 2.42, N = 70). Finally, a four-arm trial (N = 120) compared aceclofenac (ACF) monotherapy to ACF+HCHQ, ACF+ prednisolone (PRD), or ACF+HCHQ+PRD. Investigators found reduced pain (p<0.001) and better HRQL (p<0.001) in the two patient groups receiving PRD, compared to those receiving ACF monotherapy or ACF+HCHQ. Trials were at high risk of bias. GRADE evidence quality for all outcomes was very low. Conclusion Results from these small trials provide insufficient evidence to draw conclusions about the efficacy or safety of CHIKV interventions. Physicians should be cautious in prescribing and policy-makers should be cautious in recommending any intervention reviewed here. Rigorous trials with sufficient statistical power are urgently needed, with results stratified by disease stage and symptomology.

Dolutegravir Plus Two Nucleoside Reverse Transcriptase Inhibitors versus Efavirenz Plus Two Nucleoside Reverse Transcriptase Inhibitors As Initial Antiretroviral Therapy for People with HIV: A Systematic Review.

Background Dolutegravir (DTG) is a once-daily unboosted second-generation integrase-inhibitor that along with two nucleoside reverse transcriptase inhibitors is one of several regimens recommended by the United States, United Kingdom and European Union for first-line antiretroviral treatment of people with HIV infection. Our objective was to review the evidence for the efficacy and safety of DTG-based first-line regimens compared to efavirenz (EFV)-based regimens. Methods We conducted a systematic review. We comprehensively searched a range of databases as well as conference abstracts and a trials registry. We used Cochrane methods in screening and data collection and assessed each study’s risk of bias with the Cochrane tool. We meta-analyzed data using a fixed-effects model. We used GRADE to assess evidence quality. Results From 492 search results, we identified two randomized controlled trials, reported in five peer-reviewed articles and one conference abstract. One trial tested two DTG-based regimens (DTG + abacavir (ABC) + lamivudine (3TC) or DTG + tenofovir + emtricitabine) against an EFV-based regimen (EFV+ ABC+3TC). The other trial tested DTG+ABC+3TC against EFV+ABC+3TC. In meta-analysis, DTG-containing regimens were superior to EFV-containing regimens at 48 weeks and at 96 weeks (RR = 1.10, 95% CI 1.04–1.16; and RR = 1.12, 95% CI 1.04–1.21, respectively). In one trial, the DTG-containing regimen was superior at 144 weeks (RR = 1.13, 95% CI 1.02–1.24). DTG-containing regimens were superior in reducing treatment discontinuation compared to those containing EFV at 96 weeks and at 144 weeks (RR = 0.27, 95% CI 0.15–0.50; and RR = 0.28, 95% CI 0.16–0.48, respectively). Risk of serious adverse events was similar in each regimen at 96 weeks (RR = 1.15, 95% CI 0.80–1.63) and 144 weeks (RR = 0.93, 95% CI 0.68–1.29). Risk of bias was moderate overall, as was GRADE evidence quality. Conclusions DTG-based regimens should be considered in future World Health Organization guidelines for initial HIV treatment.

Effectiveness of School-Based Teen Pregnancy Prevention Programs in the USA: a Systematic Review and Meta-Analysis

School-based programs have been a mainstay of youth pregnancy prevention efforts in the USA. We conducted a systematic review and meta-analysis to assess their effectiveness. Eligible studies evaluated the effect on pregnancy rates of programs delivered in elementary, middle, or high schools in the USA and Canada, published between January 1985 and September 2016. The primary outcome was pregnancy; secondary outcomes were delay in sexual initiation, condom use, and oral contraception use. Randomized controlled trials (RCTs) and non-RCTs with comparator groups were eligible. We developed a comprehensive search strategy, applied to major bibliographic databases, article bibliographies, gray literature, and contact with authors. We calculated risk ratios (RR) with 95% confidence intervals (CI) for each outcome and pooled data in random effects meta-analysis. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess evidence quality. Ten RCTs and 11 non-RCTs conducted from 1984 to 2016 yielded 30 unique pooled comparisons for pregnancy, of which 24 were not statistically significant. Six showed statistically significant changes in pregnancy rates: two with increased risk (RR 1.30, 95% CI 1.02–1.65; and RR 1.39, 95% CI 1.10–1.75) and four with decreased risk ranging from RR 0.56, 95% CI 0.41–0.77, to RR 0.75, 95% CI 0.58–0.96. All studies were at high risk of bias, and the quality of evidence was low or very low. Identified evidence indicated no consistent difference in rates of pregnancies between intervention recipients and controls.

Reducing the global burden of Preterm Birth through knowledge transfer and exchange: a research agenda for engaging effectively with policymakers

Preterm birth (PTB) is the world’s leading cause of death in children under 5 years. In 2013, over one million out of six million child deaths were due to complications of PTB. The rate of decline in child death overall has far outpaced the rate of decline attributable to PTB. Three key reasons for this slow progress in reducing PTB mortality are: (a) the underlying etiology and biological mechanisms remain unknown, presenting a challenge to discovering ways to prevent and treat the condition; (ii) while there are several evidence-based interventions that can reduce the risk of PTB and associated infant mortality, the coverage rates of these interventions in low- and middle-income countries remain very low; and (c) the gap between knowledge and action on PTB—the “know-do gap”—has been a major obstacle to progress in scaling up the use of existing evidence-based child health interventions, including those to prevent and treat PTB.In this review, we focus on the know-do gap in PTB as it applies to policymakers. The evidence-based approaches to narrowing this gap have become known as knowledge transfer and exchange (KTE). In our paper, we propose a research agenda for promoting KTE with policymakers, with an ambitious but realistic goal of reducing the global burden of PTB. We hope that our proposed research agenda stimulates further debate and discussion on research priorities to soon bend the curve of PTB mortality.

Training for Better Management: Avante Zambézia, PEPFAR and Improving the Quality of Administrative Services; Comment on “Implementation of a Health Management Mentoring Program: Year-1 Evaluation of Its Impact on Health System Strengthening in Zambézia Province, Mozambique”

The United States Presidents Emergency Plan for AIDS Relief (PEPFAR) emphasizes health systems strengthening as a cornerstone of programmatic success. Health systems strengthening, among other things, includes effective capacity building for clinical care, administrative management and public health practice. Avante Zambézia is a district-level in-service training program for administrative staff. It is associated with improved accounting practices and human resources and transportation management but not monitoring and evaluation. We discuss other examples of successful administrative training programs that vary in the proportion of time that is spent learning on the job and the proportion of time spent in classrooms. We suggest that these programs be more rigorously evaluated so that lessons learned can be generalized to other countries and regions.

Yield of community-based tuberculosis targeted testing and treatment in foreign-born populations in the United States: A systematic review

Objective To synthesize outputs and outcomes of community-based tuberculosis targeted testing and treatment (TTT) programs in foreign-born populations (FBP) in the United States (US). Methods We systematically searched five bibliographic databases and other key resources. Two reviewers independently applied eligibility criteria to screen citations and extracted data from included studies. We excluded studies that contained <50% FBP participants or that examined steps only after diagnosis of latent TB infection (LTBI). We stratified studies as majority FBP (50–90%) and predominantly FBP (>90%). We used random-effects meta-analytic models to calculate pooled proportions and 95% confidence intervals (CI) for community-based TTT cascade steps (e.g., recruited, tested and treated), and used them to create two hypothetical cascades for 100 individuals. Results Fifteen studies conducted in 10 US states met inclusion criteria. Studies were heterogeneous in recruitment strategies and mostly recruited participants born in Latin America. Of 100 hypothetical participants (predominantly FBP) reached by community-based TTT, 40.4 (95% CI 28.6 to 50.1) would have valid test results, 15.7 (95% CI 9.9 to 21.8) would test positive, and 3.6 (95% CI 1.4 to 6.0) would complete LTBI treatment. Likewise, of 100 hypothetical participants (majority FBP) reached, 77.9 (95% CI 54.0 to 92.1) would have valid test results, 26.5 (95% CI 18.0 to 33.5) would test positive, and 5.4 (95% CI 2.1 to 9.0) would complete LTBI treatment. Of those with valid test results, pooled proportions of LTBI test positive for predominantly FBP and majority FBP were 38.9% (95% CI 28.6 to 49.8) and 34.3% (95% CI 29.3 to 39.5), respectively. Conclusions We observed high attrition throughout the care cascade in FBP participating in LTBI community-based TTT studies. Few studies included cascade steps prior to LTBI diagnosis, limiting our review findings. Moreover, Asia-born populations in the US are substantially underrepresented in the FBP community-based TTT literature.

Effectiveness of community-based condom distribution interventions to prevent HIV in the United States: A systematic review and meta-analysis

Background Despite significant public health implications, the extent to which community-based condom distribution interventions (CDI) prevent HIV infection in the United States is not well understood. Methods We systematically reviewed research evidence applying Cochrane Collaboration methods. We used a comprehensive search strategy to search multiple bibliographic databases for relevant randomized controlled trials (RCTs) and non-RCTs published from 1986–2017. We focused on CDI that made condoms widely available or accessible in community settings. Eligible outcomes were HIV infection (primary), sexually transmitted infections, condom use, and multiple sexual partnership. Two reviewers independently screened citations to assess their eligibility, extracted study data, and assessed risk of bias. We calculated risk ratios (RR) with 95% confidence intervals (CI) and pooled them using random-effects models. We assessed evidence quality using GRADE. Results We reviewed 5,110 unique records. Nine studies (including one RCT) met eligibility criteria. Studies were conducted in 10 US states between 1989 and 2011. All studies were at high risk of bias. Interventions were categorized into three groups: “Ongoing” (unlimited access to condoms), “Ongoing-plus” (unlimited access to condoms, with co-interventions), and “Coupon-based” (coupons redeemed for condoms). No studies reported incident HIV. Ongoing CDI (four non-RCTs) modestly reduced condomless sex (RR 0.88, 95% CI 0.78 to 0.99). Ongoing-plus CDI (two non-RCTs) significantly reduced multiple sexual partnership (RR 0.37, 95% CI 0.16 to 0.87). Of two coupon-based studies, one (non-RCT) showed reduction in condomless sex in female participants (Odds Ratio 0.67, 95% CI 0.47 to 0.96), while the other one (RCT) showed no effect on STI incidence (RR 0.91, 95% CI 0.63 to 1.31). Evidence quality was “very low” for all outcomes. Conclusions CDI may reduce some risky sexual behaviors, but the evidence for any reduction is limited and of low-quality. Lack of biological outcomes precludes assessing the link between CDI and HIV incidence.

Preterm birth: the role of knowledge transfer and exchange

BackgroundPreterm birth (PTB) is the leading cause of death in children under age five. Healthcare policy and other decision-making relevant to PTB may rely on obsolete, incomplete or inapplicable research evidence, leading to worsened outcomes. Appropriate knowledge transfer and exchange (KTE) strategies are an important component of efforts to reduce the global PTB burden. We sought to develop a ‘landscape’ analysis of KTE strategies currently used in PTB and related contexts, and to make recommendations for optimising programmatic implementation and for future research.MethodsIn the University of California, San Francisco’s Preterm Birth Initiative, we convened a multidisciplinary working group and examined KTE frameworks. After selecting a widely-used, adaptable, theoretically-strong framework we reviewed the literature to identify evidence-based KTE strategies. We analysed KTE approaches focusing on key PTB stakeholders (individuals, families and communities, healthcare providers and policymakers). Guided by the framework, we articulated KTE approaches that would likely improve PTB outcomes. We further applied the KTE framework in developing recommendations.ResultsWe selected the Linking Research to Action framework. Searches identified 19 systematic reviews, including two ‘reviews of reviews’. Twelve reviews provided evidence for KTE strategies in the context of maternal, neonatal and child health, though not PTB specifically; seven reviews provided ‘cross-cutting’ evidence that could likely be generalised to PTB contexts.For individuals, families and communities, potentially effective KTE strategies include community-based approaches, ‘decision aids’, regular discussions with providers and other strategies. For providers, KTE outcomes may be improved through local opinion leaders, electronic reminders, multifaceted strategies and other approaches. Policy decisions relevant to PTB may best be informed through the use of evidence briefs, deliberative dialogues, the SUPPORT tools for evidence-informed policymaking and other strategies.Our recommendations for research addressed knowledge gaps in regard to partner engagement, applicability and context, implementation strategy research, monitoring and evaluation, and infrastructure for sustainable KTE efforts.ConclusionsEvidence-based KTE, using strategies appropriate to each stakeholder group, is essential to any effort to improve health at the population level. PTB stakeholders should be fully engaged in KTE and programme planning from its earliest stages, and ideally before planning begins.

Yield of testing and treatment for tuberculosis among foreign-born persons during contact investigations in the United States: A semi-systematic review

Background Contact investigation is an important strategy for maintaining control of tuberculosis (TB) in the United States. However, testing and treatment outcomes specifically to foreign-born populations are poorly understood. We reviewed literature on testing and LTBI identified during contact investigations in foreign-born populations living in the US. Methods We conducted a comprehensive search of peer-reviewed and grey literature using Cochrane systematic review methods. We included studies with adult and adolescent populations that were at least 50% foreign-born. Pooled proportions and 95% confidence intervals (CIs) were calculated via inverse-variance weighted meta-analysis, and cumulative proportions were calculated as products of adjacent step proportions. Results We identified 22 studies published between 1997 and 2014 that included at least 50% foreign-born participants. From studies of predominantly (>90%) foreign-born populations, almost all identified contacts were recruited and had valid test results, and 54.8% (95% CI 45.1–62.5%) of contacts with valid test results tested positive. From studies of majority (50% to 90%) foreign-born populations, 78.4% (95% CI 78.0–78.9%) of identified contacts were recruited, 92.0% (95% CI 91.6–92.3%) of recruited contacts had valid test results, and 38.5% (95% CI 31.9%-44.2%) of persons with valid results tested positive. These proportions varied by test type in studies of predominantly foreign-born populations. For every 1000 contacts identified in predominantly foreign-born populations, we estimate that 535 (95% CI 438 to 625) will test positive, and 354 (95% CI 244 to 453) will complete LTBI treatment. For every 1000 contacts identified in majority foreign-born populations, these estimates are 276 (95% CI 230 to 318), and 134 (95% CI 44 to 264), respectively. Conclusions Contact investigation is a high yield activity for identifying and treating foreign-born persons with LTBI, but must be complemented by other tuberculosis control activities in order to achieve continued progress toward TB elimination.