Use of a sequential multiple assignment randomized trial to test contingency management and an integrated behavioral economic and mindfulness intervention for buprenorphine-naloxone medication adherence for opioid use disorder.

BACKGROUND: Buprenorphine-naloxone is a medication shown to improve outcomes for individuals seeking treatment for opioid use disorder (OUD); however, outcomes are limited by low medication adherence rates. This is especially true during the early stages of treatment. METHODS: The present study proposes to utilize a sequential multiple assignment randomized trial design to compare two psychological interventions targeting buprenorphine-naloxone adherence: (1) contingency management (CM) and (2) brief motivational interviewing plus substance-free activities session plus mindfulness (BSM). Participants will be N = 280 adults who present to a university-based addictions clinic seeking treatment for OUD. Participants will be randomized to condition to receive 4 sessions of their assigned intervention (CM or BSM). Participants who are adherent, defined as attending physician appointments and having buprenorphine present in urine toxicology, will enter maintenance intervention for an additional 6 months. Those who are not adherent will be re-randomized to receive either the other intervention or both interventions. Follow-up will occur at 8 months post-randomization. CONCLUSIONS: This novel design will examine the benefit of sequential treatment decisions following non-adherence. The primary outcome of this study is buprenorphine-naloxone medication adherence, as assessed by physician visit attendance and presence of buprenorphine in urine. Results will elicit the relative efficacy of CM and BSM compared to one another and whether keeping the initial treatment approach when adding the alternative approach for initially non-adherent individuals is beneficial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080180.

Association of dyskalemias with short-term health care utilization in patients with advanced CKD.

BACKGROUND: Patients with advanced chronic kidney disease (CKD) are at high risk for dyskalemias, which may induce arrhythmias that require immediate emergent or hospital care. The association of dyskalemias with short-term hospital/emergency room (ER) visits in advanced CKD is understudied. OBJECTIVE: To assess the association of dyskalemias with short-term hospital/ER visits in an advanced CKD population. METHODS: From among 102,477 US veterans transitioning to dialysis from 2007 to 2015, we identified 21,366 patients with 2 predialysis outpatient eGFR < 30 ml/min/1.73m2 90-365 days apart (with the second eGFR serving as the index date) and at least 1 potassium (K) in the baseline period (1 year before index) and 1 outpatient K (oK) in the follow-up (1 year after the index but before dialysis initiation). We examined the association of time-varying hypokalemia (K < 3.5 mEq/L) and hyperkalemia (K > 5.5 mEq/L) vs referent (3.5-5.5 mEq/L) with separate hospital and ER visits within 2 calendar days following each oK value over the 1-year follow-up period from the index. We used generalized estimating equations with binary distribution and logit link to model the exposure-outcome relationship adjusted for various confounders. We conducted various subgroup and sensitivity analyses to test the robustness of our results. RESULTS: Over the 1-year follow-up, 125,266 oK measurements were observed, of which 6.8% and 3.7% were classified as hyper- and hypokalemia, respectively. In the multivariable-adjusted model, hyperkalemia (adjusted odds ratio [aOR] = 2.04; 95% CI = 1.88-2.21) and hypokalemia (aOR = 1.66; 95% CI = 1.48-1.86) were associated with significantly higher odds of hospital visits. Similarly, hyperkalemia (aOR = 1.83; 95% CI = 1.65-2.03) and hypokalemia (aOR = 1.24; 95% CI = 1.07-1.44) were associated with significantly higher odds of ER visits. Results were robust to subgroups and sensitivity analyses. CONCLUSIONS: In patients with advanced CKD, dyskalemias are associated with higher risk of hospital/ER visits. Interventions targeted at lowering the risk of dyskalemias might help in reducing the health care utilization and associated economic burden among patients with advanced CKD experiencing dyskalemias. DISCLOSURES: This study was supported by grant 5U01DK102163 from the National Institute of Health (NIH) to Kamyar Kalantar-Zadeh and Csaba P. Kovesdy and by resources from the US Department of Veterans Affairs. The data reported here have been supplied in part by the United States Renal Data System (USRDS). Support for VA/CMS data were provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, VA Information Resource Center (project numbers SDR 02-237 and 98-004). Opinions expressed in this article are those of the authors and do not necessarily represent the opinion of the Department of Veterans Affairs or the funding institution. Kovesdy has received honoraria from Akebia, Ardelyx, Astra Zeneca, Bayer, Boehringer-Ingelheim, Cara Therapeutics, Reata, and Tricida unrelated to this study. Kalantar-Zadeh has received honoraria and/or support from Abbott, Abbvie, ACI Clinical (Cara Therapeutics), Akebia, Alexion, Amgen, American Society of Nephrology, Astra-Zeneca, Aveo, BBraun, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media, Hofstra Medical School, International Federation of Kidney Foundations, International Society of Hemodialysis, International Society of Renal Nutrition & Metabolism, Japanese Society of Dialysis Therapy, Hospira, Kabi, Keryx, Kissei, Novartis, OPKO, National Institutes of Health, National Kidney Foundations, Pfizer, Regulus, Relypsa, Resverlogix, Dr Schaer, Sandoz, Sanofi, Shire, Veterans Affairs, Vifor, UpToDate, and ZS-Pharma, unrelated to this study. Gatwood has received research support from AstraZeneca, Merck & Co., and GlaxoSmithKline unrelated to this study. Obi has received research support from Relypsa/Vifor Pharma Inc. The remaining authors declare that they have no relevant financial interests.

Mediation analysis of racial disparities in triple-negative breast cancer incidence among postmenopausal women.

BACKGROUND: Triple-negative breast cancer (TNBC) is disproportionately higher in Black women relative to White women. The objective of this study was to examine to what extent the association between race/ethnicity and risk of TNBC is mediated by potentially modifiable factors. METHODS: A total of 128,623 Black and White women aged 50-79 years from the Women's Health Initiative were followed for a mean of 15.8 years. 643 incident TNBC cases (92 Black women and 551 White women) were confirmed by medical record review. Mediation analyses were conducted using an approach under a counterfactual framework. RESULTS: Black women had approximately twofold higher risk of TNBC compared with white women (HR = 1.93, 95% CI 1.52-2.45). We observed that 48% of the racial disparity was mediated by metabolic dysfunction defined by having 3 or more cardiometabolic risk factors including elevated waist circumference, having history of diabetes, high cholesterol and hypertension. The racial disparity was not significantly mediated by other factors studied, including socioeconomic, lifestyle or reproductive factors. CONCLUSION: Our study observed that approximately half of the racial disparity between postmenopausal Black and White women in TNBC incidence was driven by metabolic dysfunction.

Racial and Regional Disparities in Outcomes Among Veterans Initially Adherent to Oral Antidiabetic Therapies: an Observational Cohort Study.

BACKGROUND: Adherence to prescribed medications is connected with, but is not a guarantee of, improved disease management and health outcomes. It remains unclear whether underlying health disparities exist among patients adherent to therapy and whether differences in outcomes vary by race and residential areas of the country. OBJECTIVE: To determine the extent of racial and regional variation in outcomes within 5 years of oral antidiabetic drug initiation among veterans adherent to therapy. DESIGN: Retrospective cohort study of 83,265 US Veterans Health Administration data, 2002-2014 PATIENTS: US veterans with uncomplicated diabetes and taking oral antidiabetic agents MAIN MEASURES: Veterans initially adherent to oral antidiabetic therapy were followed for up to 5 years, and comparisons focused on differences between non-Hispanic White and non-Hispanic Black veterans across geographic region and residential type (urban or rural). Outcomes included composite cardiovascular events, composite cerebrovascular events, or all-cause mortality using Poisson and adjusted Cox proportional hazards models. KEY RESULTS: Cardiovascular event and all-cause mortality rates differed by race and region, while urban/rural differences were evident for cerebrovascular events and all-cause mortality. For non-Hispanic Blacks, the mortality rate was half that compared to non-Hispanic Whites (6.5 [95% CI 5.8-7.2] versus 13.3 [95% CI 12.9-13.8], p < 0.0001). Compared to the Northeast, all other regions had higher adjusted hazards for cardiovascular or cerebrovascular events (with a single exception), but no regional differences in all-cause mortality were observed. Models with interactions demonstrated that racial differences in cardiovascular events and all-cause mortality were isolated to the Midwest (HR 1.99 [95% CI 1.301-3.06; HR 1.64 [95% CI 1.210-2.215]) and South (HR 1.69 [85% CI 1.347-2.131]; HR 1.27 [95% CI 1.095-1.470]). CONCLUSIONS: Despite adherence to therapy, differences in outcomes are likely among veterans with diabetes based on race and geography. Localized analyses may uncover specific social determinants contributing to differences in outcomes.

Disparities in Initial Oral Antidiabetic Medication Adherence Among Veterans with Incident Diabetes.

BACKGROUND: Medication nonadherence is a prevalent public health issue, particularly among patients with diabetes mellitus (DM), and negatively affects health outcomes. Because of the prevalence of DM among U.S. veterans, it is crucial to understand how well these patients adhere to oral antidiabetic (OAD) medication and whether certain subgroups are more likely to be nonadherent. OBJECTIVE: To assess initial OAD medication use among veterans with uncomplicated DM and determine factors associated with adherence in the first 2 years of treatment. METHODS: This was a retrospective cohort study using data from the Veterans Affairs (VA) Corporate Data Warehouse from 2002 through 2014. The first diagnosis for uncomplicated DM was determined, and then medication use was assessed following OAD initiation. OAD use was assessed by proportion of days covered (PDC) for the first 2 years of therapy using outpatient VA pharmacy records. Adherence was determined both continuously and categorically, with a PDC of ≥ 80% used to indicate adherence. Logistic regression was used to determine if certain patient characteristics were associated with being adherent to OADs. RESULTS: A total of 148,544 veterans with uncomplicated DM were assessed, most of whom were white, aged ≥ 55 years, and initiated OAD therapy on metformin. A large portion resided in the southern part of the United States. In the first year, PDC averaged 79.2% (SD = 25.9), and 63.2% were adherent to OAD therapy; however, these numbers declined in the second year, when the average PDC was 71.3% (SD = 35.8), and only 59.1% were adherent. Over the course of both years, PDC averaged 75.3% (SD = 28.4), and 50.9% were adherent. The odds of being adherent were higher among older adults and significantly lower among veterans self-identifying as either African American (OR = 0.61; 95% CI = 0.59-0.63), Native American (OR = 0.67; 95% CI = 0.61-0.75), or Hawaiian/Pacific Islander (OR = 0.84; 95% CI = 0.76-0.92) when compared with whites. Veterans who were either divorced/separated (OR = 0.86; 95% CI = 0.83-0.88) or never married (OR = 0.89; 95% CI = 0.86-0.93) also had lower odds of being initially adherent to OAD therapy compared with those who reported being married. Being nonadherent in year 1 was highly predictive of remaining nonadherent in year 2 (OR = 12.8; 95% CI = 12.23-12.94), with only 22.2% nonadherent in the first year (8.2% overall) becoming adherent in the second year of therapy. Across both years, all minorities were less likely to be adherent (compared with whites), and average adherence differed among all geographic regions of the country. CONCLUSIONS: Within the first year of OAD therapy, medication adherence was suboptimal among veterans with DM, and second-year results indicate that adherence is likely to decline over time. Future studies should consider deeper regional and subgroup analysis to determine what contributes to variation in medication use in communities across the country. DISCLOSURES: This study was supported by a KL2 Career Development Grant from the University of Tennessee Health Science Center's Institute for Research, Innovation, Synergy and Health Equity and by resources from the U.S. Department of Veterans Affairs. Hung and Kovesdy are employees of the Department of Veterans Affairs. Opinions expressed are those of the study authors and do not necessarily reflect the views of the Department of Veterans Affairs. None of the authors declared significant relevant financial conflicts of interest. Results of this study were presented as a poster at the Academy of Managed Care Pharmacy Nexus Conference on October 3-6, 2016, in National Harbor, Maryland.

Efficacy of a Tobacco Quitline in Active Duty Military and TRICARE Beneficiaries: A Randomized Trial.

A higher proportion of military personnel than civilians smoke cigarettes. Few randomized trials of tobacco use interventions have been conducted in the U.S. military. We evaluated the efficacy of a tobacco quitline (QL) in 1298 active duty military personnel, their dependents, reservists, and retirees who smoke cigarettes. Participants were randomized to either a proactive (counselor-initiated) or reactive (participant-initiated) QL intervention for 8 weeks. The proactive condition included up to an 8-week supply of free nicotine replacement therapy, and the reactive condition included a 2-week supply. The primary outcome was 12-month smoking abstinence. The enrolled population was predominantly affiliated with the Air Force and Army. At the end of treatment, proactive treatment was associated with a greater odds of both prolonged (44.22% vs. 24.96%; odds ratio [OR] = 2.4, P < 0.0001) and 7-day point prevalence (49.92% vs. 28.20%; OR = 2.5, P < 0.0001) smoking abstinence, a difference that was maintained for prolonged smoking abstinence at 12 months (22.03% vs. 13.41%; OR = 1.8, P < 0.0001). Our findings provide evidence that a proactive QL with nicotine replacement therapy is highly efficacious among Air Force and Army active duty and TRICARE beneficiaries and would provide an effective telephonic treatment option for this population of smokers.

Preventing smoking initiation or relapse following 8.5 weeks of involuntary smoking abstinence in basic military training: trial design, interventions, and baseline data.

Smoking cessation is a primary method of reducing excess mortality and morbidity. Unfortunately, the vast majority of cessation attempts end in eventual relapse. Relapse-prevention interventions have shown some success at improving the long-term maintenance of tobacco abstinence among individuals motivated to abstain. However, involuntary tobacco abstinence (e.g., military training, hospitalization, incarceration) presents another opportunity for intervention to prevent relapse. During basic military training (BMT), tobacco use is strictly forbidden in all service branches, but tobacco relapse (and initiation) following BMT is extremely high. This paper reports on the design, intervention development, and baseline characteristics of a randomized controlled trial testing minimal interventions designed to prevent tobacco relapse among United States Air Force (USAF) personnel following BMT. Participants are randomized by squadron to receive either a standard smoking-cessation booklet, a new motivation-based booklet designed specifically for USAF personal, or the latter booklet combined with a brief, face-to-face motivational session. Primary outcomes will be self-reported tobacco use at 12 and 24month follow-up. Given that the Department of Defense is the world's largest employer, the potential of leveraging involuntary tobacco abstinence during BMT into extended abstinence has substantial public health significance.

Demographic and health factors associated with enrollment in posttrial studies: the Women's Health Initiative Hormone Therapy Trials.

BACKGROUND: After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants' decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied. PURPOSE: We examined how two re-enrollment campaigns and the passage of time altered features of the posttrial cohorts compared with the original Women's Health Initiative (WHI) Hormone Therapy clinical trials. METHODS: We examined associations that markers of sociodemography, health, lifestyle, and on-trial experiences had with re-enrollment and contrasted the characteristics of successive posttrial cohorts with those of the original enrollees. RESULTS: The posttrial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second posttrial follow-up less often had a history of cardiovascular disease (odds ratio (OR) = 0.36), hypertension (OR = 0.57), diabetes (OR = 0.59), or measured cognitive deficit (OR = 0.40). These women more often had graduated from high school (OR = 1.72) and had participated in other WHI trials (OR = 1.76). LIMITATIONS: We have examined experience with creating follow-up cohorts from participants in a single study. Thus, our findings may not apply to other cohorts and protocols. CONCLUSIONS: Posttrial enrollment in follow-up studies can be successful; however, the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may strengthen interpretation of findings.

Efficacy of a smoking quit line in the military: baseline design and analysis.

Thirty percent of all military personnel smoke cigarettes. Because of the negative health consequences and their impact on physical fitness, overall health, and military readiness, the Department of Defense has identified the reduction of tobacco use as a priority of US military forces. This study aims to evaluate the one-year efficacy of a proactive versus reactive smoking quit line in the US military with adjunctive nicotine replacement therapy (NRT) in both groups. This paper reports on the baseline variables of the first 1000 participants randomized, the design, and proposed analysis of the randomized two-arm clinical trial "Efficacy of a Tobacco Quit Line in the Military". Participants are adult smokers who are Armed Forces Active Duty personnel, retirees, Reservist, National Guard and family member healthcare beneficiaries. All participants are randomized to either the Counselor Initiated (proactive) group, receiving 6 counseling sessions in addition to an 8-week supply of NRT, or the Self-Paced (reactive) group, in which they may call the quit line themselves to receive the same counseling sessions, in addition to a 2-week supply of NRT. The primary outcome measure of the study is self-reported smoking abstinence at 1-year follow-up. Results from this study will be the first to provide evidence for the efficacy of an intensive Counselor Initiated quit line with provided NRT in military personnel and could lead to dissemination throughout the US Air Force, the armed forces population as a whole and ultimately to civilian personnel that do not have ready access to preventive health services.

Socioeconomic factors and diagnosis of uveal melanoma in the mid-southern United States.

PURPOSE: To establish the base incidence of uveal melanoma in the mid-southern United States and to explore the regional frequency of uveal melanoma diagnosis as a function of area-based socioeconomic measures (ABSM) aggregated at the level of small geographic units delimited by Zoning Improvement Plan (ZIP) codes. METHODS: Based on a retrospective chart review (1996-2007) of patients seen at our institutions with the diagnosis of uveal melanoma, the number of uveal melanoma cases was calculated for each ZIP-code in Arkansas, Mississippi, western Tennessee and Louisiana. The base incidence of uveal melanoma was calculated using the population size reported in the 2000 census as the population at risk for each geographic area. Data on the average house value and average household income reported in the 2000 census were used in a Poisson regression analysis to examine their effect on the frequency of uveal melanoma diagnosis. RESULTS: There were 327 (of 1,669) regional ZIP-codes that were the source of 457 patients with uveal melanoma. Higher ABSM, defined as greater average house value or household income, were positively associated with the number of observed melanoma cases per ZIP-code. The annualized incidence of uveal melanoma was at least 3.5 cases per million in the areas studied. CONCLUSION: Higher ABSM were associated with the increased frequency of uveal melanoma diagnosis in the regions studied. Extrapolating from similar trends observed with non-ocular cancers, this may signify a need for increased access to ophthalmologic care to ensure timely diagnosis.