HIV retention in care: results and lessons learned from the Positive Pathways Implementation Trial.

BACKGROUND: Sustained, routine care is vital to the health of people with HIV (PWH) and decreasing transmission of HIV. We evaluated whether the identification of PWH at-risk of falling out of care and prompts for outreach were effective in retaining PWH in care in the United States. METHODS: In this cluster randomized controlled trial, 20 AIDS Healthcare Foundation Healthcare Centers (HCCs) were randomized to the intervention (n = 10) or control (n = 10) arm; all maintained existing retention efforts. The intervention included daily automated flags in CHORUS™, a mobile app and web-based reporting solution utilizing electronic health record data, that identified PWH at-risk of falling out of care to clinic staff. Among flagged PWH, the association between the intervention and visits after a flag was assessed using logistic regression models fit with generalized estimating equations (independent correlation structure) to account for clustering. To adjust for differences between HCCs, models included geographic region, number of PWH at HCC, and proportions of PWH who self-identified as Hispanic or had the Ryan White Program as a payer. RESULTS: Of 15,875 PWH in care, 56% were flagged; 76% (intervention) and 75% (control) resulted in a visit, of which 76% were within 2 months of the flag. In adjusted analyses, flags had higher odds of being followed by a visit (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.97, 1.21) or a visit within 2 months (OR: 1.07, 95% CI: 0.97, 1.17) at intervention than control HCCs. Among at-risk PWH with viral loads at baseline and study end, the proportion with < 50 copies/mL increased in both study arms, but more so at intervention (65% to 74%) than control (62% to 67%) HCCs. CONCLUSION: Despite challenges of the COVID-19 pandemic, adding an intervention to existing retention efforts, and the reality that behavior change takes time, PWH flagged as at-risk of falling out of care were marginally more likely to return for care at intervention than control HCCs and a greater proportion achieved undetectability. Sustained use of the retention module in CHORUS™ has the potential to streamline retention efforts, retain more PWH in care, and ultimately decrease transmission of HIV. TRIAL REGISTRATION: The study was first registered at Clinical Trials.gov (NCT04147832, https://clinicaltrials.gov/show/NCT04147832 ) on 01/11/2019.

Examining the Implementation of Conditional Financial Incentives Using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework to Improve HIV Outcomes among Persons Living with HIV (PLWH) in Louisiana.

Economic strengthening interventions are needed to support HIV outcomes among persons living with HIV (PLWH). The Baton Rouge Positive Pathway Study (BRPPS), a mixed method implementation science study, was conducted to assess key RE-AIM components tied to the provision of conditional financial incentives among PLWH in Baton Rouge, Louisiana. Seven hundred and eighty-one (781) PLWH enrolled at four HIV clinic sites were included in the final analyses. Participants completed an initial baseline survey, viral load test, and were contacted at 6 and 12 months (±1 month) post-enrollment for follow-up labs to monitor viral load levels. Participants received up to USD140 in conditional financial incentives. The primary analyses assessed whether participation in the BRPPS was associated with an increase in the proportion of participants who were: (a) engaged in care, (b) retained in care and (c) virally suppressed at baseline to 6 and 12 months post-baseline. We constructed a longitudinal regression model where participant-level outcomes at times t0 (baseline) and t1 (6- or 12-month follow-up) were modeled as a function of time. A secondary analysis was conducted using single-level regression to examine which baseline characteristics were associated with the outcomes of interest at 12-month follow-up. Cost analyses were also conducted with three of the participating clinics. Most participants identified as Black/African American (89%). Fewer than half of participants reported that they were unemployed or made less than USD5000 annually (43%). Over time, the proportion of participants engaged in care and retained in care significantly increased (70% to 93% and 32% to 64%, p < 0.00). However, the proportion of virally suppressed participants decreased over time (59% to 34%, p < 0.00). Implementation costs across the three sites ranged from USD17,198.05 to USD396,910.00 and were associated with between 0.37 and 1.34 HIV transmissions averted at each site. Study findings provide promising evidence to suggest that conditional financial incentives could help support engagement and retention in HIV care for a high need and at risk for falling out of HIV care population.

A Layer Plus Approach to Implementation Research and Collaboration for Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention.

In 2020, the HIV prevention clinical trials, HPTN (HIV Prevention Trials Network) 083 and 084, reported that long-acting injectable cabotegravir (CAB-LA) for HIV prevention was statistically superior to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in cisgender men and transgender women who have sex with men, and cisgender women. However, clinical efficacy does not translate to real-world effectiveness and clinical practice as evidenced by current global use of oral PrEP. There are ~626,000 users of PrEP, which is significantly below the 3 million goal set by UNAIDS for 2020. Implementation will be key to ensuring that CAB-LA reaches those who desire to use it. We describe the Layer Plus Approach for CAB-LA for PrEP dissemination and implementation. The "Layer" is focused on integrating CAB-LA into existing PrEP models of care and understanding the best delivery channels that could be established in existing programs. Important implications of layering include preparing health professionals to provide CAB-LA, improving access for potential users, and addressing existing PrEP structural and facility barriers. "Plus," which accounts for the existing disparities in PrEP access and use, means expanding CAB-LA to reach individuals for whom HIV prevention options have not been accessible or who have lapsed on oral PrEP. Implications for Plus include the development of new structures, systems, policies, and processes. A key aspect to the Approach is building collaborations to aid successful implementation. The Layer Plus Approach is a simple but strategic framework or a tailored approach to guide dissemination research and implementation.

Increased risks for random errors are common in outcomes graded as high certainty of evidence.

OBJECTIVES: The aim of article was to assess the risk for random errors in outcomes graded as high certainty of evidence (CoE). STUDY DESIGN AND SETTING: We randomly selected 100 Cochrane reviews with dichotomous outcomes rated as high CoE using Grading of Recommendations Assessment, Development, and Evaluation. To detect increased risks for random errors, two investigators independently conducted trial sequential analysis using conventional thresholds for type I (α = 0.05) and type II (ß = 0.10) errors. We dually regraded all outcomes with increased risks for random errors and conducted multivariate logistic regression analyses to determine predictors of increased risks for random errors. RESULTS: Overall, 38% (95% confidence interval: 28-47%) of high CoE outcomes had increased risks for random errors. Outcomes assessing harms were more frequently affected than outcomes assessing benefits (47% vs. 12%). Regrading of outcomes with increased random errors showed that 74% should have been downgraded based on current guidance. Regression analyses rendered small absolute risk differences (P = 0.009) and low number of events (P = 0.001) as significant predictors of increased risks for random errors. CONCLUSION: Decisionmakers need to be aware that outcomes rated as high CoE often have increased risks for false-positive or false-negative findings.

Tuberculosis Knowledge, Awareness, and Stigma Among African-Americans in Three Southeastern Counties in the USA: a Qualitative Study of Community Perspectives.

To inform strategies to address the tuberculosis (TB) excess among US-born African-Americans, we sought to understand the TB experience in the most highly affected southeastern communities. We conducted semi-structured interviews and focus groups in three communities with a TB excess-urban (Georgia and Tennessee) and rural (North Carolina). Participants from five groups provided diverse perspectives-African-Americans: patients with TB disease or latent TB infection (LTBI), or at high risk of contracting TB; and local community leaders and TB program staff. Few differences emerged between sites. Many participants demonstrated low levels of knowledge and awareness and held many misconceptions about TB. Patients expressed a preference for verbal communication of medical information. Patients reported fear of stigmatization and shunning, but few experienced discrimination. Patient trust for TB program staff was high, though community leaders often assumed the opposite. The findings will help guide interventions to improve knowledge and awareness regarding TB, including specific attention to the role of public and private health care providers in dispelling persistent misinformation about TB. The insight from these communities will help build the scientific foundation required to effectively eliminate health inequities.

Average effect estimates remain similar as evidence evolves from single trials to high-quality bodies of evidence: a meta-epidemiologic study.

OBJECTIVES: The objective of our study was to use a diverse sample of medical interventions to assess empirically whether first trials rendered substantially different treatment effect estimates than reliable, high-quality bodies of evidence. STUDY DESIGN AND SETTING: We used a meta-epidemiologic study design using 100 randomly selected bodies of evidence from Cochrane reports that had been graded as high quality of evidence. To determine the concordance of effect estimates between first and subsequent trials, we applied both quantitative and qualitative approaches. For quantitative assessment, we used Lin's concordance correlation and calculated z-scores; to determine the magnitude of differences of treatment effects, we calculated standardized mean differences (SMDs) and ratios of relative risks. We determined qualitative concordance based on a two-tiered approach incorporating changes in statistical significance and magnitude of effect. RESULTS: First trials both overestimated and underestimated the true treatment effects in no discernible pattern. Nevertheless, depending on the definition of concordance, effect estimates of first trials were concordant with pooled subsequent studies in at least 33% but up to 50% of comparisons. The pooled magnitude of change as bodies of evidence advanced from single trials to high-quality bodies of evidence was 0.16 SMD [95% confidence interval (CI): 0.12, 0.21]. In 80% of comparisons, the difference in effect estimates was smaller than 0.5 SMDs. In first trials with large treatment effects (>0.5 SMD), however, estimates of effect substantially changed as new evidence accrued (mean change 0.68 SMD; 95% CI: 0.50, 0.86). CONCLUSION: Results of first trials often change, but the magnitude of change, on average, is small. Exceptions are first trials that present large treatment effects, which often dissipate as new evidence accrues.

The predictive validity of quality of evidence grades for the stability of effect estimates was low: a meta-epidemiological study.

OBJECTIVE: To determine the predictive validity of the U.S. Evidence-based Practice Center (EPC) approach to GRADE (Grading of Recommendations Assessment, Development and Evaluation). STUDY DESIGN AND SETTING: Based on Cochrane reports with outcomes graded as high quality of evidence (QOE), we prepared 160 documents which represented different levels of QOE. Professional systematic reviewers dually graded the QOE. For each document, we determined whether estimates were concordant with high QOE estimates of the Cochrane reports. We compared the observed proportion of concordant estimates with the expected proportion from an international survey. To determine the predictive validity, we used the Hosmer-Lemeshow test to assess calibration and the C (concordance) index to assess discrimination. RESULTS: The predictive validity of the EPC approach to GRADE was limited. Estimates graded as high QOE were less likely, estimates graded as low or insufficient QOE more likely to remain stable than expected. The EPC approach to GRADE could not reliably predict the likelihood that individual bodies of evidence remain stable as new evidence becomes available. C-indices ranged between 0.56 (95% CI, 0.47 to 0.66) and 0.58 (95% CI, 0.50 to 0.67) indicating a low discriminatory ability. CONCLUSION: The limited predictive validity of the EPC approach to GRADE seems to reflect a mismatch between expected and observed changes in treatment effects as bodies of evidence advance from insufficient to high QOE.

Models of Cancer Survivorship Care: Overview and Summary of Current Evidence.

INTRODUCTION: This article, derived from a Technical Brief prepared for the Agency for Healthcare Research and Quality, presents an overview on current models of care for survivors of adult-onset cancer who have completed active treatment. METHODS: This article integrates reviewed literature on background, context, research gaps, and future research directions for survivorship care models. We also conducted a systematic literature review of current evidence from studies of survivorship care models. RESULTS: Our systematic review identified nine empirical studies of survivorship care models, covering multiple models types and illustrating the heterogeneity in this field. The literature review indicated considerable heterogeneity in models of survivorship care, components of models, survivor populations, and target outcomes. Models of survivorship care are highly individualized to the institution or setting where they are provided. "Usual care" is often uncoordinated and highly varied across cancer survivors and within cancer programs. Anticipated shortages in the oncology workforce may require the expanded use of nurse practitioners and physician assistants and shared care with primary care providers to deliver survivorship care to the growing number of survivors. Concerns associated with survivorship care models include payment considerations, adequacy of training, and the potential for lack of coordination and fragmented care. CONCLUSION: There is substantial variation in survivorship care models. The optimal nature, timing, intensity, format, and outcomes of survivorship care models are uncertain and require further research. Specific research questions need to be addressed by the survivorship community to better understand the advantages and limitations of survivorship models.

Grades for quality of evidence were associated with distinct likelihoods that treatment effects will remain stable.

OBJECTIVES: We sought to determine whether producers or users of systematic reviews using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach or a close variation give the same meanings to terms intended to convey uncertainty about treatment effects when interpreting grades for the quality or strength of evidence. STUDY DESIGN AND SETTING: Following exploratory interviews with stakeholders and user testing, we conducted an international Web-based survey among producers and users of systematic reviews. For each quality grade (high, moderate, low, very low/insufficient), we asked participants to assign a minimum likelihood that treatment effects will not change substantially as new studies emerge. Using multivariate analysis of covariance, we tested whether the estimated likelihoods differed between producers and users. RESULTS: In all, 244 participants completed the survey. The associated minimum likelihoods that treatment effects will not change substantially for high, moderate, and low grades of quality of evidence (QOE) were 86% [95% confidence interval (CI): 85%, 87%], 61% (95% CI: 59%, 63%), and 34% (95% CI: 32%, 36%), respectively (very low was preset at 0%). Likelihoods for each grade were similar between producers and users of systematic reviews (P > 0.05 for all comparisons). CONCLUSION: GRADE is, in general, a suitable method to convey uncertainties for systematic review producers to users. The wide ranges of likelihoods associated with GRADE terms suggest that current definitions of levels of QOE that rely exclusively on qualitative certainty expressions should be augmented by numerical predictions once such data are available.

Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) and 2 or more prior antidepressant treatment failures (often referred to as treatment-resistant depression [TRD]). These patients are less likely to recover with medications alone and often consider nonpharmacologic treatments such as rTMS. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and the International Pharmaceutical Abstracts for studies comparing rTMS with a sham-controlled treatment in TRD patients ages 18 years or older. STUDY SELECTION: We included 18 good- or fair-quality TRD studies published from January 1, 1980, through March 20, 2013. DATA EXTRACTION: We abstracted relevant data, assessed each study's internal validity, and graded strength of evidence for change in depressive severity, response rates, and remission rates. RESULTS: rTMS was beneficial compared with sham for all outcomes. rTMS produced a greater decrease in depressive severity (high strength of evidence), averaging a clinically meaningful decrease on the Hamilton Depression Rating Scale (HDRS) of more than 4 points compared with sham (mean decrease = -4.53; 95% CI, -6.11 to -2.96). rTMS resulted in greater response rates (high strength of evidence); those receiving rTMS were more than 3 times as likely to respond as patients receiving sham (relative risk = 3.38; 95% CI, 2.24 to 5.10). Finally, rTMS was more likely to produce remission (moderate strength of evidence); patients receiving rTMS were more than 5 times as likely to achieve remission as those receiving sham (relative risk = 5.07; 95% CI, 2.50 to 10.30). Limited evidence and variable treatment parameters prevented conclusions about which specific treatment options are more effective than others. How long these benefits persist remains unclear. CONCLUSIONS: For MDD patients with 2 or more antidepressant treatment failures, rTMS is a reasonable, effective consideration.

Behavioral counseling after screening for alcohol misuse in primary care: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.

BACKGROUND: Alcohol misuse, which includes the full spectrum from risky drinking to alcohol dependence, is a leading cause of preventable death in the United States. PURPOSE: To evaluate the benefits and harms of behavioral counseling interventions for adolescents and adults who misuse alcohol. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and reference lists of published literature (January 1985 through January 2012, limited to English-language articles). STUDY SELECTION: Controlled trials at least 6 months' duration that enrolled persons with alcohol misuse identified by screening in primary care settings and evaluated behavioral counseling interventions. DATA EXTRACTION: One reviewer extracted data and a second checked accuracy. Two independent reviewers assigned quality ratings and graded the strength of the evidence. DATA SYNTHESIS: The 23 included trials generally excluded persons with alcohol dependence. The best evidence was for brief (10- to 15-minute) multicontact interventions. Among adults receiving behavioral interventions, consumption decreased by 3.6 drinks per week from baseline (weighted mean difference, 3.6 drinks/wk [95% CI, 2.4 to 4.8 drinks/wk]; 10 trials; 4332 participants), 12% fewer adults reported heavy drinking episodes (risk difference, 0.12 [CI, 0.07 to 0.16]; 7 trials; 2737 participants), and 11% more adults reported drinking less than the recommended limits (risk difference, 0.11 [CI, 0.08 to 0.13]; 9 trials; 5973 participants) over 12 months compared with control participants (moderate strength of evidence). Evidence was insufficient to draw conclusions about accidents, injuries, or alcohol-related liver problems. Trials enrolling young adults or college students showed reduced consumption and fewer heavy drinking episodes (moderate strength of evidence). Little or no evidence of harms was found. LIMITATIONS: Results may be biased to the null because the behavior of control participants could have been affected by alcohol misuse assessments. In addition, evidence is probably inapplicable to persons with alcohol dependence and selective reporting may have occurred. CONCLUSION: Behavioral counseling interventions improve behavioral outcomes for adults with risky drinking. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Translating evidence-based interventions into practice: the design and development of the Merck Childhood Asthma Network, Inc. (MCAN).

Pediatric asthma is a multifactorial disease, requiring complex, interrelated interventions addressing children, families, schools, and communities. The Merck Childhood Asthma Network, Inc. (MCAN) is a nonprofit organization that provides support to translate evidence-based interventions from research to practice. MCAN developed the rationale and vision for the program through a phased approach, including an extensive literature review, stakeholder engagement, and evaluation of funding gaps. The analysis pointed to the need to identify pediatric asthma interventions implemented in urban U.S. settings that have demonstrated efficacy and materials for replication and to translate the interventions into wider practice. In addition to this overall MCAN objective, specific goals included service and system integration through linkages among health care providers, schools, community-based organizations, patients, parents, and other caregivers. MCAN selected sites based on demonstrated ability to implement effective interventions and to address multiple contexts of pediatric asthma prevention and management. Selected MCAN program sites were mature institutions or organizations with significant infrastructure, existing funding, and the ability to provide services without requiring a lengthy planning period. Program sites were located in communities with high asthma morbidity and intended to integrate new elements into existing programs to create comprehensive care approaches.