Viral blood-borne infections testing and linkage to care cascade among persons who experience homelessness in the United States: a systematic review and meta-analysis.

BACKGROUND: Persons who experience homelessness remain at increased risk for three viral blood-borne infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). We assessed the yield of testing and linkage to care programs targeting this population for these infections in the United States (US). METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Central for peer-reviewed articles through August 27, 2020. Additionally, we searched the grey literature. Two individuals independently reviewed all relevant studies to check for eligibility and extracted data for each step in the care cascade. We used random-effects model to generate weighted pooled proportions to assess yield at each step. Cumulative proportions were calculated as products of adjacent-step pooled proportions. We quantitatively synthesized data from the studies that focused on non-drug injecting individuals. RESULTS: We identified 24 studies published between 1996-2019 conducted in 19 US states. Seventeen studies screened for HIV, 12 for HCV, and two screened for HBV. For HIV, 72% of approached were recruited, 64% had valid results, 4% tested positive, 2% were given results, and 1% were referred and attended follow-up. Of positives, 25% were referred to treatment and started care. For HCV, 69% of approached were recruited, 63% had valid results, 16% tested positive, 14% were given results, and 3% attended follow-up. Of positives, 30% were referred for treatment and 19% started care. The yield at each care cascade step differs widely by recruitment strategy (for example, for HIV: 71.6% recruited of reached under service-based with zero yield under healthcare facility-based and outreach). CONCLUSIONS: A very large proportion of this population reached for HIV and HCV care were lost in the follow-up steps and never received treatment. Future programs should examine drop-out reasons and intervene to reduce health disparities in this population.

Indirect COVID-19 health effects and potential mitigating interventions: Cost-effectiveness framework.

BACKGROUND: The COVID-19 pandemic led to important indirect health and social harms in addition to deaths and morbidity due to SARS-CoV-2 infection. These indirect impacts, such as increased depression and substance abuse, can have persistent effects over the life course. Estimated health and cost outcomes of such conditions and mitigation strategies may guide public health responses. METHODS: We developed a cost-effectiveness framework to evaluate societal costs and quality-adjusted life years (QALYs) lost due to six health-related indirect effects of COVID-19 in California. Short- and long-term outcomes were evaluated for the adult population. We identified one evidence-based mitigation strategy for each condition and estimated QALYs gained, intervention costs, and savings from averted health-related harms. Model data were derived from literature review, public data, and expert opinion. RESULTS: Pandemic-associated increases in prevalence across these six conditions were estimated to lead to over 192,000 QALYs lost and to approach $7 billion in societal costs per million population over the life course of adults. The greatest costs and QALYs lost per million adults were due to adult depression. All mitigation strategies assessed saved both QALYs and costs, with five strategies achieving savings within one year. The greatest net savings over 10 years would be achieved by addressing depression ($242 million) and excessive alcohol use ($107 million). DISCUSSION: The COVID-19 pandemic is leading to significant human suffering and societal costs due to its indirect effects. Policymakers have an opportunity to reduce societal costs and health harms by implementing mitigation strategies.

Hepatitis B prevalence association with sexually transmitted infections: a systematic review and meta-analysis.

Background Hepatitis B vaccination is recommended for persons with current or past sexually transmitted infections (STI). Our aim is to systematically assess the association of hepatitis B virus (HBV) sero-markers for current or past infection with syphilis, chlamydia, gonorrhoea, or unspecified STIs. METHODS: We conducted a systematic review and meta-analysis. PubMed, Embase, and Web of Science from 1982 to 2018 were searched using medical subject headings (MeSH) terms for HBV, STIs and epidemiology. We included studies conducted in Organisation for Economic Cooperation and Development countries or Latin America that permit the calculation of prevalence ratios (PRs) for HBV and STIs and extracted PRs and counts by HBV and STI status. RESULTS: Of 3144 identified studies, 43 met inclusion requirements, yielding 72 PRs. We stratified outcomes by HBV sero-markers [surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), combined], STI pathogen (syphilis, gonorrhoea/chlamydia, unspecified), and STI history (current, past) resulting in 18 potential outcome groups, for which results were available for 14. For the four outcome groups related to HBsAg, PR point estimates ranged from 1.65 to 6.76. For the five outcome groups related to anti-HBc, PRs ranged from 1.30 to 1.82; and for the five outcome groups related to combined HBV markers, PRs ranged from 1.15 to 1.89). The median HBsAg prevalence among people with a current or past STI was 4.17; not all studies reported HBsAg. Study settings and populations varied. CONCLUSION: This review found evidence of association between HBV infection and current or past STIs.

Change in Condom Use in Populations Newly Aware of HIV Diagnosis in the United States and Canada: A Systematic Review and Meta-Analysis.

HIV-infected individuals "aware" of their infection are more likely to use condoms, compared to HIV-infected "unaware" persons. To quantify this likelihood, we undertook a systematic review and meta-analysis of U.S. and Canadian studies. Twenty-one eligible studies included men who have sex with men (MSM; k = 15), persons who inject drugs (PWID; k = 2), and mixed populations of high-risk heterosexuals (HRH; k = 4). Risk ratios (RR) of "not always using condoms" with partners of any serostatus were lower among aware MSM (RR 0.44 [not significant]), PWID (RR 0.70) and HRH (RR 0.27); and, in aware MSM, with partners of HIV-uninfected or unknown status (RR 0.46). Aware individuals had lower "condomless sex likelihood" with HIV-uninfected or unknown status partners (MSM: RR 0.58; male PWID: RR 0.44; female PWID: RR 0.65; HRH: RR 0.35) and with partners of any serostatus (MSM only, RR 0.72). The association diminished over time. High risk of bias compromised evidence quality.

Potential Contributions of Clinical and Community Testing in Identifying Persons with Undiagnosed HIV Infection in the United States.

BACKGROUND: An estimated 166,155 individuals in the United States have undiagnosed HIV infection. We modeled the numbers of HIV-infected individuals who could be diagnosed in clinical and community settings by broadly implementing HIV screening guidelines. SETTING: United States. METHODS: We modeled testing for general population (once lifetime) and high-risk populations (annual): men who have sex with men, people who inject drugs, and high-risk heterosexuals. We used published data on HIV infections, HIV testing, engagement in clinical care, and risk status disclosure. RESULTS: In clinical settings, about 76 million never-tested low-risk and 2.6 million high-risk individuals would be tested, yielding 36,000 and 55,000 HIV diagnoses, respectively. In community settings, 30 million low-risk and 4.4 million high-risk individuals would be tested, yielding 75,000 HIV diagnoses. CONCLUSION: HIV testing in clinical and community settings diagnoses similar numbers of individuals. Lifetime and risk-based testing are both needed to substantially reduce undiagnosed HIV.

Healthcare facility-based strategies to improve tuberculosis testing and linkage to care in non-U.S.-born population in the United States: A systematic review.

CONTEXT: An estimated 21% of non-U.S.-born persons in the United States have a reactive tuberculin skin test (TST) and are at risk of progressing to TB disease. The effectiveness of strategies by healthcare facilities to improve targeted TB infection testing and linkage to care among this population is unclear. EVIDENCE ACQUISITION: Following Cochrane guidelines, we searched several sources to identify studies that assessed strategies directed at healthcare providers and/or non-U.S.-born patients in U.S. healthcare facilities. EVIDENCE SYNTHESIS: Seven studies were eligible. In a randomized controlled trial (RCT), patients with reactive TST who received reminders for follow-up appointments were more likely to attend appointments (risk ratio, RR = 1.05, 95% confidence interval 1.00-1.10), but rates of return in a quasi-RCT study using patient reminders did not significantly differ between study arms (P = 0.520). Patient-provider language concordance in a retrospective cohort study did not increase provider referrals for testing (P = 0.121) or patient testing uptake (P = 0.159). Of three studies evaluating pre and post multifaceted interventions, two increased TB infection testing (from 0% to 77%, p < .001 and RR 2.28, 1.08-4.80) and one increased provider referrals for TST (RR 24.6, 3.5-174). In another pre-post study, electronic reminders to providers increased reading of TSTs (RR 2.84, 1.53-5.25), but only to 25%. All seven studies were at high risk of bias. CONCLUSIONS: Multifaceted strategies targeting providers may improve targeted TB infection testing in non-U.S.-born populations visiting U.S. healthcare facilities; uncertainties exist due to low-quality evidence. Additional high-quality studies on this topic are needed.

Supportive interventions to improve retention on ART in people with HIV in low- and middle-income countries: A systematic review.

OBJECTIVES: To determine whether supportive interventions can increase retention in care for patients on antiretroviral therapy (ART) in low- and middle-income countries (LMIC). DESIGN: Systematic review and meta-analysis. METHODS: We used Cochrane Collaboration methods. We included randomised controlled trials (RCT) and observational studies with comparators conducted in LMIC. Our principal outcomes were retention, mortality and the combined outcome of lost-to-follow-up (LTFU) or death. RESULTS: We identified seven studies (published in nine articles); six of the studies were from Sub-Saharan Africa. We found four types of interventions: 1) directly observed therapy plus extra support ("DOT-plus"), 2) community-based adherence support, 3) adherence clubs and 4) extra care for patients with low CD4 count. One RCT of a community-based intervention showed significantly improved retention at 12 months (RR 1.14, 95% CI 1.02 to 1.27), and three observational studies found significantly improved retention for paediatric patients followed for 12 to 36 months (RR 1.07, 95 CI 1.03 to 1.11), and for adult patients at 12 (RR 1.38, 95% CI 1.13 to 1.70) and 60 months (RR 1.07, 95% CI 1.07 to 1.08). One observational study of adherence clubs showed significantly reduced LTFU or mortality (RR 0.20, 95% CI 0.12 to 0.33). A cluster RCT of an extra-care intervention for high-risk patients also showed a significant increase in retention (RR 1.06, 95% CI 1.01 to 1.10), and an observational study of extra nursing care found a significant decrease in LTFU or mortality (RR 0.76, 95% CI 0.66 to 0.87). CONCLUSIONS: Supportive interventions are associated with increased ART programme retention, but evidence quality is generally low to moderate. The data from this review suggest that programmes addressing psychosocial needs can significantly help retain patients in care.

The discordance between evidence and health policy in the United States: the science of translational research and the critical role of diverse stakeholders.

BACKGROUND: There is often a discordance between health research evidence and public health policies implemented by the United States federal government. In the process of developing health policy, discordance can arise through subjective and objective factors that are unrelated to the value of the evidence itself, and can inhibit the use of research evidence. We explore two common types of discordance through four illustrative examples and then propose a potential means of addressing discordance. DISCUSSION: In Discordance 1, public health authorities make recommendations for policy action, yet these are not based on high quality, rigorously synthesised research evidence. In Discordance 2, evidence-based public health recommendations are ignored or discounted in developing United States federal government policy. Both types could lead to serious risks of public health and clinical patient harms. We suggest that, to mitigate risks associated with these discordances, public health practitioners, health policy-makers, health advocates and other key stakeholders should take the opportunity to learn or expand their knowledge regarding current research methods, as well as improve their skills for appropriately considering the strengths and limitations of research evidence. This could help stakeholders to adopt a more nuanced approach to developing health policy. Stakeholders should also have a more insightful contextual awareness of these discordances and understand their potential harms. In Discordance 1, public health organisations and authorities need to acknowledge their own historical roles in making public health recommendations with insufficient evidence for improving health outcomes. In Discordance 2, policy-makers should recognise the larger impact of their decision-making based on minimal or flawed evidence, including the potential for poor health outcomes at population level and the waste of huge sums. In both types of discordance, stakeholders need to consider the impact of their own unconscious biases in championing evidence that may not be valid or conclusive. CONCLUSION: Public health policy needs to provide evidence-based solutions to public health problems, but this is not always done. We discuss some of the factors inhibiting evidence-based decision-making in United States federal government public health policy and suggest ways these could be addressed.

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.

Care Cascade for targeted tuberculosis testing and linkage to Care in Homeless Populations in the United States: a meta-analysis.

BACKGROUND: Homelessness increases the risk of tuberculosis (TB) disease and latent TB infection (LTBI), but persons experiencing homelessness often lack access to testing and treatment. We assessed the yield of TB testing and linkage to care for programs targeting homeless populations in the United States. METHODS: We conducted a comprehensive search of peer-reviewed and grey literature, adapting Cochrane systematic review methods. Two reviewers independently assessed study eligibility and abstracted key data on the testing to care cascade: number of persons reached, recruited for testing, tested for LTBI, with valid test results, referred to follow-up care, and initiating care. We used random effects to calculate pooled proportions and 95% confidence intervals (CI) of persons retained in each step via inverse-variance weighted meta-analysis, and cumulative proportions as products of adjacent step proportions. RESULTS: We identified 23 studies published between 1986 and 2014, conducted in 12 states and 15 cities. Among studies using tuberculin skin tests (TST) we found that 93.7% (CI 72.4-100%) of persons reached were recruited, 97.9% (89.3-100%) of those recruited had tests placed, 85.5% (78.6-91.3%) of those with tests placed returned for reading, 99.9% (99.6-100%) of those with tests read had valid results, and 24.7% (21.0-28.5%) with valid results tested positive. All persons testing positive were referred to follow-up care, and 99.8% attended at least one session of follow-up care. Heterogeneity was high for most pooled proportions. For a hypothetical cohort of 1000 persons experiencing homelessness reached by a targeted testing program using TST, an estimated 917 were tested, 194 were positive, and all of these initiated follow-up care. CONCLUSIONS: Targeted TB testing of persons experiencing homelessness appears effective in detecting LTBI and connecting persons to care and potential treatment. Future evaluations should assess diagnostic use of interferon gamma release assays and completion of treatment, and costs of testing and 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.

Do School-Based Programs Prevent HIV and Other Sexually Transmitted Infections in Adolescents? A Systematic Review and Meta-analysis.

We systematically reviewed the literature to assess the effectiveness of school-based programs to prevent HIV and other sexually transmitted infections (STI) among adolescents in the USA. We searched six databases including PubMed for studies published through May 2017. Eligible studies included youth ages 10-19 years and assessed any school-based programs in the USA that reported changes in HIV/STI incidence or testing. We used Cochrane tool to assess the risk of bias and GRADE to determine the evidence quality for each outcome. Three RCTs and six non-RCTs, describing seven interventions, met study inclusion criteria. No study reported changes in HIV incidence or prevalence. One comprehensive intervention, assessed in a non-RCT and delivered to pre-teens, reduced STI incidence into adulthood (RR 0.36, 95% CI 0.23-0.56). A non-RCT examining chlamydia and gonorrhea incidence before and after a condom availability program found a significant effect at the city level among young men 3 years later (RR 0.43, 95% CI 0.23-0.80). The remaining four interventions found no effect. The effect on STI prevalence was also not significant (pooled RR 0.83 from two non-RCTs, RR 0.70 from one RCT). Only one non-RCT showed an increase in HIV testing (RR 3.19, 95% CI 1.24-8.24). The quality of evidence for all outcomes was very low. Studies, including the RCTs, were of low methodological quality and had mixed findings, thus offering no persuasive evidence for the effectiveness of school-based programs. The most effective intervention spanned 6 years, was a social development-based intervention with multiple components, rather than a sex education program, and started in first grade.

Ritonavir-Boosted Darunavir Plus Two Nucleoside Reverse Transcriptase Inhibitors versus Other Regimens for Initial Antiretroviral Therapy for People with HIV Infection: A Systematic Review.

BACKGROUND: Darunavir is a second-generation protease-inhibitor used with ritonavir (DRV/r) and two nucleoside reverse-transcriptase inhibitors as an option in first-line antiretroviral treatment (ART). METHODS: We systematically reviewed randomized controlled trials (RCTs) of DRV/r versus other regimens in patients initiating ART. We searched five bibliographic databases and other key resources. We had no language limitations. We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality. We report findings in terms of risk ratio (RR) with 95% confidence intervals (CI). FINDINGS: Three RCTs met inclusion criteria. In plasma viral load suppression, DRV/r outperformed ritonavir-boosted lopinavir at 48 weeks (RR 1.13, 95% CI 1.03-1.25), 96 weeks (RR 1.11, 95% CI 1.02-1.21), and 192 weeks (RR 1.20, 95% CI 1.07-1.35). DRV/r was similar to dolutegravir at 48 weeks (RR 0.96, 95% CI 0.87-1.06) but less effective at 96 weeks (RR 0.84, 95% CI 0.75-0.93). At 96 weeks, DRV/r underperformed raltegravir (RR 0.94, 95% CI 0.88-0.99) but was similar to ritonavir-boosted atazanavir (RR 1.02, 95% CI 0.96-1.09). Overall bias risk was moderate. Evidence quality was also moderate. INTERPRETATION: Initial ART regimens using DRV/r should be considered in future World Health Organization guidelines.

Preterm birth: the role of knowledge transfer and exchange.

BACKGROUND: Preterm 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. METHODS: In 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. RESULTS: We 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. CONCLUSIONS: Evidence-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.

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.

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.

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.

Interventions for preventing mother-to-child HIV transmission: protocol of an overview of systematic reviews.

INTRODUCTION: Various interventions to prevent mother-to-child-transmission (MTCT) of HIV have been investigated and implemented. A number of systematic reviews assessing the efficacy of interventions for the prevention of MTCT of HIV reported antiretroviral prophylaxis, caesarean section before labour and before ruptured membranes, and complete avoidance of breastfeeding were efficacious for preventing MTCT of HIV. Recent WHO guidelines recommend lifelong antiretroviral therapy for all pregnant women for treatment of the woman's own HIV infection and for prevention of MTCT of HIV. Therefore, the objective of this overview is to evaluate the currently available systematic reviews of interventions for preventing MTCT of HIV, and to identify the current best evidence-based interventions for reducing the risk of MTCT of HIV. METHODS AND ANALYSIS: We will include only peer-reviewed systematic reviews of randomised or quasi-randomised controlled trials assessing the effects of interventions for preventing MTCT of HIV that target both HIV-infected women and children aged 2 years and younger born to HIV-infected women. We will search the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effectiveness, Ovid MEDLINE and EMBASE. We will assess review eligibility, the methodological quality of included systematic reviews using A Measurement Tool to Assess The Systematic Reviews and will extract data, comparing our results and resolving discrepancies by consensus. Finally, we will independently assess the certainty of the evidence using Grades of Recommendation, Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: Ethics approval is not required. We will publish the results in a peer-reviewed journal and present at conferences, which will inform future research and will be useful for healthcare managers, administrators and policymakers to guide resource allocation decisions and optimisation of interventions to prevent the MTCT of HIV.

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.

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.