Opportunities to Increase Science of Diversity and Inclusion in Clinical Trials: Equity and a Lack of a Control.

The United States witnessed a nearly 4-fold increase in personal health care expenditures between 1980 and 2010. Despite innovations and obvious benefits to health, participants enrolled in clinical trials still do not accurately represent the racial and ethnic composition of patients nationally or globally. This lack of diversity in cohorts limits the generalizability and significance of results among all populations and has deep repercussions for patient equity. To advance diversity in clinical trials, robust evidence for the most effective strategies for recruitment of diverse participants is needed. A major limitation of previous literature on clinical trial diversity is the lack of control or comparator groups for different strategies. To date, interventions have focused primarily on (1) community-based interventions, (2) institutional practices, and (3) digital health systems. This review article outlines prior intervention strategies across these 3 categories and considers health policy and ethical incentives for substantiation before US Food and Drug Administration approval. There are no current studies that comprehensively compare these interventions against one another. The American Heart Association Strategically Focused Research Network on the Science of Diversity in Clinical Trials represents a multicenter, collaborative network between Stanford School of Medicine and Morehouse School of Medicine created to understand the barriers to diversity in clinical trials by contemporaneous head-to-head interventional strategies accessing digital, institutional, and community-based recruitment strategies to produce informed recruitment strategies targeted to improve underrepresented patient representation in clinical trials.

Bariatric Surgery and Inflammatory Bowel Disease: National Trends and Outcomes Associated with Procedural Sleeve Gastrectomy vs Historical Bariatric Surgery Among US Hospitalized Patients 2009-2020.

PURPOSE: The association between bariatric surgery and IBD-related inpatient outcomes is not well characterized. We report, analyze, and compare inpatient trends and outcomes among encounters with a history of bariatric surgery (Hx-MBS) compared to those receiving bariatric surgery during index admission (PR-MBS) admitted from 2009 to 2020. METHODS: Retrospective cohort design: the 2009-2020 National Inpatient Sample (NIS) databases were used to identify hospital encounters with patients aged ≥ 18 years with a history of MBS (Hx-MBS) or with procedure coding indicating MBS procedure (PR-MBS) according to International Classification of Diseases, Ninth (ICD-9-CM/ ICD-9-PCS) or Tenth Revision (ICD-10-CM/ICD-10-PCS) Clinical Modification/Procedure Coding System during index admission (ICD-9-CM: V4586; ICD-10-CM: Z9884; ICD-9-PR: 4382, 4389; ICD-10-PR: 0DB64Z3, 0DB63ZZ). Pearson χ2 analysis, analysis of variance, multivariable regression analyses, and propensity matching on independent variables were conducted to analyze significant associations between variables and for primary outcome inflammatory bowel disease-related admission, and secondary outcomes: diagnosis of nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, or chronic mesenteric ischemia during admission. RESULTS: We identified 3,365,784 (76.20%) Hx-MBS hospitalizations and 1,050,900 hospitalizations with PR-MBS (23.80%). Propensity score matching analysis demonstrated significantly higher odds of inflammatory bowel disease, and chronic mesenteric ischemia for Hx-MBS compared to PR-MBS, and significantly lower odds of nonalcoholic steatohepatitis and nonalcoholic fatty liver disease for Hx-MBS compared to PR-MBS. CONCLUSION: In our study, Hx-MBS was associated with significantly increased odds of inflammatory bowel disease and other GI pathologies compared to matched controls. The mechanism by which this occurs is unclear. Additional studies are needed to examine these findings.

Development of a Single-Institution Virtual Internal Medicine Subinternship With Near-Peer Teaching in Response to the COVID-19 Pandemic.

PROBLEM: In March 2020, medical students at the University of Washington School of Medicine were removed from clinical settings in response to the COVID-19 pandemic. As subinternships are required for graduation and an important way to prepare for internship, a virtual subinternship was created to include practical elements of in-person learning and to address limited teaching faculty from COVID-19 inpatient surges. APPROACH: A virtual, interactive subinternship was developed with case-based teaching sessions, communication and critical literature evaluation skill building, professional development, and creation of independent learning plans. Near-peer teachers (NPTs) were selected from graduating senior medical students who matched into internal medicine. In addition to teaching topics from the Clerkship Directors of Internal Medicine curriculum, NPTs engaged in course development, recruited teaching faculty, gathered feedback, and facilitated small groups. Participating students completed pre- and postcourse surveys. OUTCOMES: The 10 students (100%) enrolled in the course who completed both surveys indicated significant improvement in mean scores across 4 domains: evaluating medical literature (3.1/5 to 4.5/5; +1.4, P < .001); developing individual learning plans (3.6/5 to 4.7/5; +1.1, P = .001); perceived ability to efficiently evaluate patients with common internal medicine concerns (3.7/5 to 4.6/5; +0.9, P = .004); and formulating initial diagnostic and therapeutic plans (3.6/5 to 4.6/5; +1.0, P < .001). Themes extracted from open-ended responses included initial skepticism of an online format, the course exceeding expectations, and feeling prepared for internship. NEXT STEPS: Although a virtual subinternship lacks direct patient care, students reported improvement in all 4 domains studied. Future courses would benefit from greater use of simulation and role-playing scenarios for practical skills. The experience with NPTs was encouraging, aiding in the success of the subinternship. The role of NPTs should be cultivated to fill gaps in content delivery and enhance the development of students as educators.

Genetic Variation in Toll-Like Receptor 5 and Colonization with Flagellated Bacterial Vaginosis-Associated Bacteria.

Bacterial vaginosis (BV) is a vaginal dysbiotic condition linked to negative gynecological and reproductive sequelae. Flagellated bacteria have been identified in women with BV, including Mobiluncus spp. and BV-associated bacterium-1 (BVAB1), an uncultivated, putatively flagellated species. The host response to flagellin mediated through Toll-like receptor 5 (TLR5) has not been explored in BV. Using independent discovery and validation cohorts, we examined the hypothesis that TLR5 deficiency-defined by a dominant negative stop codon polymorphism, rs5744168-is associated with an increased risk for BV and increased colonization with flagellated bacteria associated with BV (BVAB1, Mobiluncus curtisii, and Mobiluncus mulieris). TLR5 deficiency was not associated with BV status, and TLR5-deficient women had decreased colonization with BVAB1 in both cohorts. We stimulated HEK-hTLR5-overexpressing NF-κB reporter cells with whole, heat-killed M. mulieris or M. curtisii and with partially purified flagellin from these species; as BVAB1 is uncultivated, we used cervicovaginal lavage (CVL) fluid supernatant from women colonized with BVAB1 for stimulation. While heat-killed M. mulieris and CVL fluid from women colonized with BVAB1 stimulate a TLR5-mediated response, heat-killed M. curtisii did not. In contrast, partially purified flagellin from both Mobiluncus species stimulated a TLR5-mediated response in vitro We observed no correlation between vaginal interleukin 8 (IL-8) and flagellated BVAB concentrations among TLR5-sufficient women. Interspecies variation in accessibility of flagellin recognition domains may be responsible for these observations, as reflected in the potentially novel flagellin products encoded by Mobiluncus species versus those encoded by BVAB1.

Mechanisms of Endogenous HIV-1 Reactivation by Endocervical Epithelial Cells.

Pharmacological HIV-1 reactivation to reverse latent infection has been extensively studied. However, HIV-1 reactivation also occurs naturally, as evidenced by occasional low-level viremia ("viral blips") during antiretroviral treatment (ART). Clarifying where blips originate from and how they happen could provide clues to stimulate latency reversal more effectively and safely or to prevent viral rebound following ART cessation. We studied HIV-1 reactivation in the female genital tract, a dynamic anatomical target for HIV-1 infection throughout all disease stages. We found that primary endocervical epithelial cells from several women reactivated HIV-1 from latently infected T cells. The endocervical cells' HIV-1 reactivation capacity further increased upon Toll-like receptor 3 stimulation with poly(I·C) double-stranded RNA or infection with herpes simplex virus 2 (HSV-2). Notably, acyclovir did not eliminate HSV-2-induced HIV-1 reactivation. While endocervical epithelial cells secreted large amounts of several cytokines and chemokines, especially tumor necrosis factor alpha (TNF-α), CCL3, CCL4, and CCL20, their HIV-1 reactivation capacity was almost completely blocked by TNF-α neutralization alone. Thus, immunosurveillance activities by columnar epithelial cells in the endocervix can cause endogenous HIV-1 reactivation, which may contribute to viral blips during ART or rebound following ART interruption.IMPORTANCE A reason that there is no universal cure for HIV-1 is that the virus can hide in the genome of infected cells in the form of latent proviral DNA. This hidden provirus is protected from antiviral drugs until it eventually reactivates to produce new virions. It is not well understood where in the body or how this reactivation occurs. We studied HIV-1 reactivation in the female genital tract, which is often the portal of HIV-1 entry and which remains a site of infection throughout the disease. We found that the columnar epithelial cells lining the endocervix, the lower part of the uterus, are particularly effective in reactivating HIV-1 from infected T cells. This activity was enhanced by certain microbial stimuli, including herpes simplex virus 2, and blocked by antibodies against the inflammatory cytokine TNF-α. Avoiding HIV-1 reactivation could be important for maintaining a functional HIV-1 cure when antiviral therapy is stopped.

The cost-effectiveness of depression treatment for co-occurring disorders: a clinical trial.

The authors aimed to determine the economic value of providing on-site group cognitive behavioral therapy (CBT) for depression to clients receiving residential substance use disorder (SUD) treatment. Using a quasi-experimental design and an intention-to-treat analysis, the incremental cost-effectiveness and cost-utility ratio of the intervention were estimated relative to usual care residential treatment. The average cost of a treatment episode was $908, compared to $180 for usual care. The incremental cost effectiveness ratio was $131 for each point improvement of the BDI-II and $49 for each additional depression-free day. The incremental cost-utility ratio ranged from $9,249 to $17,834 for each additional quality adjusted life year. Although the intervention costs substantially more than usual care, the cost effectiveness and cost-utility ratios compare favorably to other depression interventions. Health care reform should promote dissemination of group CBT to individuals with depression in residential SUD treatment.

A report on eight early-stage state and regional projects testing value-based payment.

To help contain health care spending and improve the quality of care, practitioners and policy makers are trying to move away from fee-for-service toward value-based payment, which links providers' reimbursement to the value, rather than the volume, of services delivered. With funding from the Robert Wood Johnson Foundation, eight grantees across the country are designing and implementing value-based payment reform projects. For example, in Salem, Oregon, the Physicians Choice Foundation is testing "Program Oriented Payments," which include incentives for providers who follow a condition-specific program of care designed to meet goals set jointly by patient and provider. In this article we describe the funding rationale and the specific objectives, strategies, progress, and early stages of implementation of the eight projects. We also share some early lessons and identify prerequisites for success, such as ensuring that providers have broad and timely access to data so they can meet patients' needs in cost-effective ways.

Group cognitive-behavioral therapy for clients with major depression in residential substance abuse treatment.

OBJECTIVE: The BRIGHT (Building Recovery by Improving Goals, Habits, and Thoughts) study was a community-based effectiveness trial that compared residential substance abuse treatment with residential treatment plus group cognitive-behavioral therapy (CBT)for depression. This brief report focuses on the subgroup of participants with major depression. METHODS: The authors used a quasi-experimental design and an intent-to-treat analysis. Out of 299 participants enrolled, 135 had major depression. Primary outcomes were change in depression symptoms, mental health functioning, and days of alcohol use and problematic substance use. RESULTS: At the three-month follow-up, participants with major depression reported less severe depression and better functioning, compared with participants with major depression who received usual care. At six months, functioning continued to be higher and problem substance use was lower. CONCLUSIONS: Group CBT was an effective treatment for major depression for clients in residential substance abuse treatment. These results extend the effectiveness of group CBT for major depression to a new setting, patient population, and type of provider.

An effectiveness trial of group cognitive behavioral therapy for patients with persistent depressive symptoms in substance abuse treatment.

CONTEXT: Although depression frequently co-occurs with substance abuse, few individuals entering substance abuse treatment have access to effective depression treatment. OBJECTIVE: The Building Recovery by Improving Goals, Habits, and Thoughts (BRIGHT) study is a community-based effectiveness trial that compared residential substance abuse treatment with residential treatment plus group cognitive behavioral therapy for depression delivered by substance abuse treatment counselors. We hypothesized that intervention clients would have improved depression and substance use outcomes compared with those of clients receiving usual care. DESIGN: A nonrandomized controlled trial using a quasi-experimental intent-to-treat design in which 4 sites were assigned to alternate between the intervention and usual care conditions every 4 months for 2½ years. SETTING: Four treatment programs in Los Angeles County. PARTICIPANTS: We screened 1262 clients for persistent depressive symptoms (Beck Depression Inventory-II score >17). We assigned 299 clients to receive either usual care (n = 159) or usual care plus the intervention (n = 140). Follow-up rates at 3 and 6 months after the baseline interview were 88.1% and 86.2%, respectively, for usual care and 85.7% and 85.0%, respectively, for the intervention group. INTERVENTION: Sixteen 2-hour group sessions of cognitive behavioral therapy for depression. MAIN OUTCOME MEASURES: Change in depression symptoms, mental health functioning, and days of alcohol and problem substance use. RESULTS: Intervention clients reported significantly fewer depressive symptoms (P < .001 at 3 and 6 months) and had improved mental health functioning (P < .001 at 3 months and P < .01 at 6 months). At 6 months, intervention clients reported fewer drinking days (P < .05) and fewer days of problem substance use (P < .05) on days available. CONCLUSIONS: Providing group cognitive behavioral therapy for depression to clients with persistent depressive symptoms receiving residential substance abuse treatment is associated with improved depression and substance use outcomes. These results provide support for a new model of integrated care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01191788.

The effect of dental care on cardiovascular disease outcomes: an application of instrumental variables in the presence of heterogeneity and self-selection.

Studies show a relationship between oral inflammatory processes and cardiovascular risk factors, suggesting that dental care may reduce the risk of cardiovascular disease (CVD) events. However, due to the differences between men and women in the development and presentation of CVD, such effects may vary by sex. We use a valid set of instrumental variables to evaluate these issues and include a test of essential heterogeneity. CVD events include new occurrences of heart attack (including death from heart attack), stroke (including death from stroke), angina, and congestive heart failure. Controls include age, race, education, marital status, foreign birthplace, and cardiovascular risk factors (health status, body mass index, alcohol use, smoking status, diabetes status, high-blood-pressure status, physical activity, and depression). Our analysis finds no evidence of essential heterogeneity. We find the minimum average treatment effect for women to be -0.01, but find no treatment effect for men. This suggests that women who receive dental care may reduce their risk of future CVD events by at least one-third. The findings may only apply to married middle-aged and older individuals as the data set is only representative for this group.

Exploring productivity outcomes from a brief intervention for at-risk drinking in an employee assistance program.

Brief intervention (BI) research has traditionally examined alcohol and drug use outcomes; however it is unknown whether BIs can also impact on-the-job productivity. This exploratory study examines changes in workplace productivity and related costs for clients receiving a BI for at-risk drinking in the employee assistance program (EAP). Participants were 44 clients attending the EAP for behavioral health concerns, screened for at-risk drinking, assigned to BI+Usual Care (n=25) or UC alone (n=19), and who completed 3-month follow-up. Absenteeism, presenteeism, and productivity costs were derived as outcomes. At follow-up, participants in the BI+UC group had improved productivity when at work (presenteeism) compared to the UC group. The estimated cost savings from improved productivity for the BI+UC group was $1200 per client over the UC group. Groups did not differ by absenteeism (missed days of work). Preliminary evidence suggests the broad impact BIs may have. Implications for future BI research are discussed.

Taking stock of pay-for-performance: a candid assessment from the front lines.

Pay-for-performance (P4P) has been widely adopted, but it remains unclear how providers are responding and whether results are meeting expectations. Physician organizations involved in the California Integrated Healthcare Association's (IHA) P4P program reported having increased physician-level performance feedback and accountability, speeded up information technology adoption, and sharpened their organizational focus and support for improvement in response to P4P; however, after three years of investment, these changes had not translated into breakthrough quality improvements. Continued monitoring is required to determine whether early investments made by physician organizations provide a basis for greater improvements in the future.