A multicenter randomized placebo controlled trial of rifampin to reduce pedal amputations for osteomyelitis in veterans with diabetes (VA INTREPID).

BACKGROUND: The prevalence of diabetes mellitus continues to inexorably rise in the United States and throughout the world. Lower limb amputations are a devastating comorbid complication of diabetes mellitus. Osteomyelitis increases the risk of amputation fourfold and commonly presages death. Antimicrobial therapy for diabetic foot osteomyelitis (DFO) varies greatly, indicating that high quality data are needed to inform clinical decision making. Several small trials have indicated that the addition of rifampin to backbone antimicrobial regimens for osteomyelitis outside the setting of the diabetic foot results in 28 to 42% higher cure rates. METHODS/DESIGN: This is a prospective, randomized, double-blind investigation of the addition of 6 weeks of rifampin, 600 mg daily, vs. matched placebo (riboflavin) to standard-of-care, backbone antimicrobial therapy for DFO. The study population are patients enrolled in Veteran Health Administration (VHA), ages ≥18 and ≤ 89 years with diabetes mellitus and definite or probable osteomyelitis of the foot for whom an extended course of oral or intravenous antibiotics is planned. The primary endpoint is amputation-free survival. The primary hypothesis is that using rifampin as adjunctive therapy will lower the hazard rate compared with the group that does not use rifampin as adjunctive therapy. The primary hypothesis will be tested by means of a two-sided log-rank test with a 5% significance level. The test has 90% power to detect a hazard ratio of 0.67 or lower with a total of 880 study participants followed on average for 1.8 years. DISCUSSION: VA INTREPID will test if a rifampin-adjunctive antibiotic regimen increases amputation-free survival in patients seeking care in the VHA with DFO. A positive finding and its adoption by clinicians would reduce lower extremity amputations and their associated physical and emotional impact and reduce mortality for Veterans and for the general population with diabetic foot osteomyelitis. Given that rifampin-adjunctive regimens are currently employed for therapy for the majority of DFO cases in Europe, and only in a small minority of cases in the United States, the trial results will impact therapeutic decisions, even if the null hypothesis is not rejected. TRIAL REGISTRATION: Registered January 6, 2017 at ClinicalTrials.gov, NCT03012529.

Assessing the impact of prescribing directives on opioid prescribing practices among Veterans Health Administration providers.

PURPOSE: The study aimed to test whether directives on opioid prescribing released by the Veterans Health Administration (VHA) or the Food and Drug Administration (FDA) had an impact on prescribing among VHA providers. METHODS: We used the VHA's linked pharmacy and patient medical records database to identify new prescriptions written for propoxyphene, fentanyl, and controlled release (CR) oxycodone between 1/1/2000 and 12/31/2009. We plotted the monthly proportion of these prescriptions that complied with components of four specific safety alerts or directives for these substances issued by the VHA or FDA between 1/1/2001 and 12/31/2008. We modeled compliance using interrupted time series analysis and a generalized additive model with the addition of an indicator variable to flag prescriptions that followed the directive's release date. RESULTS: A total of 32.2 million new prescriptions for fentanyl, oxycodone CR, and propoxyphene were written for VHA patients meeting inclusion criteria. Compliance with guidelines in the directives increased steadily throughout the entire study period, with no clinically meaningful inflection point near the date of each directive's release. Generalized additive modeling and interrupted time series analysis found that the indicator flag slightly improved the fit of the data, but visual inspection of the plots revealed no change at a level of practical significance. CONCLUSIONS: While prescribing compliance increased throughout the period, release of FDA and VHA alerts and guidelines did not appear to contribute to this change. Given the fivefold increase in the rate of drug-related overdose deaths since 1990, identifying effective methods to communicate safety messages and change prescriber behavior remains a priority for future work. Copyright © 2016 John Wiley & Sons, Ltd.

Incident severe thrombocytopenia in veterans treated with pegylated interferon plus ribavirin for chronic hepatitis C infection.

PURPOSE: We sought to determine the incidence and risks for severe thrombocytopenia (platelets < 50,000/µL) in United States Veteran patients treated with pegylated interferon (PEG-IFN) plus ribavirin for hepatitis C virus-positive (HCV) chronic liver disease (CLD). METHODS: Using a retrospective, observational cohort study design to analyze databases from the New England Veterans Healthcare System, we identified 979 patients diagnosed with HCV-positive CLD treated solely with PEG-IFN plus ribavirin. The cohort was stratified by pre-treatment platelet counts of 50,000-100,000/µL (N = 90), >100,000-150,000/µL (N = 162), and >150,000µL (N = 727). The cumulative incidence of severe thrombocytopenia and major bleeding events were determined for each baseline platelet group for 48 weeks following treatment initiation. Multivariable Cox regression was used to identify risk factors for incident severe thrombocytopenia. RESULTS: Overall, severe thrombocytopenia occurred in 6.1% (N = 60), but in 41.1% of patients with pre-treatment platelet counts 50, 000-100,000/µL compared with 11.7% (p < 0.001) and 0.55% (p < 0.001) in the two higher pre-treatment platelet groups. Most episodes occurred within the first 12 weeks of treatment. Median nadir count for these 60 patients was 35,000/µL (inter-quartile range 28,000, 44,000). Baseline platelet counts of 50,000-100,000/µL [adjusted hazard ratio (HR) = 3.81; 95%CI = 2.07-7.00] and hemoglobin <10 g/dL (adjusted HR = 3.39; 95%CI = 1.45-7.960) associated with severe thrombocytopenia. Major bleeding events during the 48-week observation period were rare (N = 5, 0.51%). CONCLUSIONS: The incidence of severe thrombocytopenia in a large, observational cohort of veteran patients with HCV CLD treated with PEG-IFN plus ribavirin was 6.1%. Low pre-treatment platelet counts and hemoglobin levels associated with early, incident severe thrombocytopenia.

Veterans Healthcare Administration providers' attitudes and perceptions regarding pragmatic trials embedded at the point of care.

Background The Veterans Healthcare Administration (VA) is implementing an adaptation of a pragmatic trial program, Point of Care Research (POC-R). The goal of POC-R is to embed research into clinical practice, contributing to a Learning Healthcare System. Provider acceptance and participation in POC-R is essential to its successful implementation. The purpose of this study is to evaluate provider's perceptions and beliefs regarding the POC-R program. Methods Provider focus groups and interviews were conducted at seven VA medical facilities involving 62 providers. A semi-structured script was used that included descriptions of four use cases and targeted questions regarding perceptions, concerns, and attitudes about the POC-R program. Sessions were audio-taped, de-identified, transcribed, and analyzed using systematic qualitative techniques to create response categories and overarching themes. Results The emergent themes were as follows: (1) POC-R is a valuable component of evidence-based practice, providing an opportunity to base clinical practice on more generalizable evidence as well as providing tools to improve local practice; (2) POC-R highlights the tension between the need for autonomy of practice and compliance with protocols; (3) POC-R may create increased time and burden resulting from added research responsibilities; (4) concern about the scientific validity and reliability of results; (5) potential for a negative impact on the provider-patient relationship; and (6) uncertainty regarding what constitutes equipoise, given differences in provider knowledge and preferences. Despite substantive concerns, barriers were generally felt to be solvable. Implementation should include provider education, careful attention to workflow for all arms of the study, inclusion of the entire team, and adequate oversight. Limitations The study design is qualitative with limited implications for causal inference. Participants are from the VA and may not be representative of other clinicians. Conclusion VA providers are supportive of the importance and value of pragmatic trials in general and of POC-R in particular. However, providers have significant concerns regarding the burden, ethics, and evidence regarding equipoise. Results are discussed in terms of implementation recommendations.

Thrombocytopenia and bleeding in veterans with non-hepatitis C-related chronic liver disease.

BACKGROUND: Thrombocytopenia in chronic liver disease (CLD) typically reflects disease severity and may indicate an increased risk for bleeding. AIMS: To describe the longitudinal course of thrombocytopenia and risks for bleeding in veteran patients with non-hepatitis C-related CLD. METHODS: We identified 2,349 patients with non-hepatitis C-related CLD from databases of the New England Veterans Healthcare System between 1999 and 2008. The cohort was stratified by baseline platelet counts of <50,000, 50-100,000, > 100,000-150,000, and >150,000/µl. Primary outcomes were the incidence and hazard rates for bleeding episodes requiring hospitalization and incident severe thrombocytopenia (<50,000/µl). RESULTS: Over a median follow-up of 3.3 years (IQR 1.2, 6.3), incident major bleeds, predominantly gastrointestinal, occurred in 254 patients (10.8 % of the cohort) and in 19.9 % of those with baseline platelets <50,000/µl. Incident severe thrombocytopenia occurred in 315 patients (13.4 % of cohort) and in 40.7 % of those with baseline platelet counts between 50,000 and 100,000/µl. Baseline platelet counts between 50,000 and 100,000/µl independently predicted bleeding [adjusted HR 2.89 (1.76, 4.73) p < 0.001] as did esophageal varices, hemoglobin ≤ 9.9 g %, and INR 1.4-2.0. Incident severe thrombocytopenia and minimum platelet counts <25,000/µl each associated with bleeding episodes, but the average of minimum platelet counts recorded for those who bled was 76,000/µl. CONCLUSIONS: Among veteran patients with non-hepatitis C-related CLD, baseline platelet counts of 50,000 to 100,000/µl increased subsequent risks for both incident severe thrombocytopenia and major bleeding events. Whereas associations between severe thrombocytopenia and bleeding most likely reflect CLD severity, liver-related coagulopathies, and co-morbid bleeding risks, interventions to enhance platelet production may be beneficial for such patients.

Risk of community-acquired pneumonia in veteran patients to whom proton pump inhibitors were dispensed.

BACKGROUND: Observational studies linking proton pump inhibitor (PPI) exposure with community-acquired pneumonia (CAP) have reported either modest or no associations. Accordingly, we studied PPI exposure and CAP in veteran patients, using a retrospective, nested case-control design. METHODS: From linked pharmacy and administrative databases of the New England Veterans Healthcare System, we identified 71985 outpatients newly prescribed PPIs between 1998 and 2007; 1544 patients met criteria for CAP subsequent to PPI initiation; 15440 controls were matched through risk-set sampling by age and time under observation. Crude and adjusted odds ratios comparing current with past PPI exposures, as well as tests for interactions, were conducted for the entire and stratified samples. RESULTS: Current PPI use associated with CAP (adjusted odds ratio [OR], 1.29 [95% confidence interval {CI}, 1.15-1.45]). Risks were not substantially altered by age or year of diagnosis. Dementia (n = 85; P = .062 for interaction) and sedative/tranquilizer use (n = 224; P = .049 for interaction) were likely effect modifiers increasing a PPI-CAP association; conversely, for some chronic medical conditions, PPI-associated CAP risks were reversed. PPI exposures between 1 and 15 days increased CAP risks, compared with longer exposures, but PPI initiation also frequently occurred shortly after CAP diagnoses. Prescribed PPI doses >1 dose/day also increased PPI-associated CAP risks. CONCLUSIONS: Among the veterans studied, current compared with past PPI exposures associated modestly with increased risks of CAP. However, our observations that recent treatment initiation and higher PPI doses were associated with greater risks, and the inconsistent PPI-CAP associations between patient subgroups, indicate that further inquiries are needed to separate out coincidental patterns of associations.

Rationale, design and methods of VA-BRAVE: a randomized comparative effectiveness trial of two formulations of buprenorphine for treatment of opioid use disorder in veterans.

BACKGROUND: To address the US opioid epidemic, there is an urgent clinical need to provide persons with opioid use disorder (OUD) with effective medication treatments for OUD (MOUD). Formulations of sublingual buprenorphine/naloxone (SL-BUP/NLX) are considered the standard of care for OUD including within the Veterans Healthcare Administration (VHA). However, poor retention on MOUD undermines its effectiveness. Long-acting injectable monthly buprenorphine (INJ-BUP) (e.g., Sublocade®) has the potential to improve retention and therefore reduce opioid use and overdose. Designing and conducting studies for OUD pose unique challenges. The strategies and solutions to some of these considerations in designing Cooperative Studies Program (CSP) 2014, Buprenorphine for Treating Opioid Use Disorder in Veterans (VA-BRAVE), a randomized, 20-site, clinical effectiveness trial comparing INJ-BUP to SL-BUP/NLX conducted within the VHA may provide valuable guidance for others confronted with similar investigation challenges. METHODS: This 52-week, parallel group, open-label, randomized controlled trial (RCT) evaluates the comparative effectiveness of two current FDA-approved formulations of buprenorphine: (1) daily SL-BUP/NLX vs. (2) monthly (28-day) INJ-BUP for Veterans with moderate to severe OUD (n = 952). The primary outcomes are (1) retention in MOUD and (2) opioid abstinence. Secondary outcomes include measures of other drug use, psychiatric symptoms, medical outcomes including prevalence rates of HIV, hepatitis B and C as well as social outcomes (housing instability, criminal justice involvement), service utilization and cost-effectiveness. Special considerations in conducting a comparative effectiveness trial with this population and during COVID-19 pandemic were also included. DISCUSSION: The evaluation of the extended-release formulation of buprenorphine compared to the standard sublingual formulation in real-world VHA settings is of paramount importance in addressing the opioid epidemic. The extent to which this new treatment facilitates retention, decreases opioid use, and prevents severe sequelae of OUD has not been studied in any long-term trial to date. Positive findings in this trial could lead to widespread adoption of MOUD, and, if proven superior INJ-BUP, by clinicians throughout the VHA and beyond. This treatment has the potential to reduce opioid use among Veterans, improve medical, psychological, and social outcomes, and save lives at justifiable cost. Trial registration Registered at Clinicaltrials.gov NCT04375033.

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen.

BACKGROUND: Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care. PURPOSE: We describe a novel randomized clinical trial that uses the informatics and statistics infrastructure of the Veterans Affairs Healthcare System (VA) to illustrate one key component (called the point-of-care clinical trial - POC-CT) of a 'learning healthcare system,' and settles a clinical question of interest to the VA. METHODS: This study is an open-label, randomized trial comparing sliding scale regular insulin to a weight-based regimen for control of hyperglycemia, using the primary outcome length of stay, in non-ICU inpatients within the northeast region of the VA. All non-ICU patients who require in-hospital insulin therapy are eligible for the trial, and the VA's automated systems will be used to assess eligibility and present the possibility of randomization to the clinician at the point of care. Clinicians will indicate their approval for informed consent to be obtained by study staff. Adaptive randomization will assign up to 3000 patients, preferentially to the currently 'winning' strategy, and all care will proceed according to usual practices. Based on a Bayesian stopping rule, the study has acceptable frequentist operating characteristics (Type I error 6%, power 86%) against a 12% reduction of median length of stay from 5 to 4.4 days. The adaptive stopping rule promotes implementation of a successful treatment strategy. LIMITATIONS: Despite clinical equipoise, individual healthcare providers may have strong treatment preferences that jeopardize the success and implementation of the trial design, leading to low rates of randomization. Unblinded treatment assignment may bias results. In addition, generalization of clinical results to other healthcare systems may be limited by differences in patient population. Generalizability of the POC-CT method depends on the level of informatics and statistics infrastructure available to a healthcare system. CONCLUSIONS: The methods proposed will demonstrate outcome-based evaluation of control of hyperglycemia in hospitalized veterans. By institutionalizing a process of statistically sound and efficient learning, and by integrating that learning with automatic implementation of best practice, the participating VA Healthcare Systems will accelerate improvements in the effectiveness of care.

Impact of supplemental site grants to increase African American accrual for the Selenium and Vitamin E Cancer Prevention Trial.

BACKGROUND: African American accrual to prevention trials at rates representative of the disease burden experienced by this population requires additional resources and focused efforts. PURPOSE: To describe the rationale, context, and criteria for selection of sites that received Minority Recruitment Enhancement Grants (MREGs) to increase African American recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT). To determine if African American accrual was higher among the 15 MREG sites when compared with similar nonawarded sites. METHODS: Changes in African American accrual at sites that received MREGs are compared with changes in a group of 15, frequency-matched, nonawarded sites using a quasi-experimental, post hoc analysis. Successful and unsuccessful recruitment strategies reported by the MREG sites are described. RESULTS: The increased number of African American participants accrued per month at MREG sites post-funding was higher than the change at comparison sites by a factor of 3.38 (p = 0.004, 95% CI: 1.51-7.57). An estimated 602 additional African American participants were recruited at MREG sites due to MREG funding, contributing to the overall 14.9% African American recruitment. Successful recruitment strategies most reported by MREG sites included increasing staff, transportation resources, recruiting through the media, mailings, and prostate cancer screening clinics during off-hours. LIMITATIONS: Comparison sites were chosen retrospectively, not by randomization. Although comparison sites were selected to be similar to MREG sites with regard to potential confounding factors, it is possible that unknown factors could have biased results. Cost-effective analyses were not conducted. CONCLUSIONS: MREG sites increased African American accrual in the post-funding period more than comparison sites, indicating MREG funding enhanced the sites' abilities to accrue African American participants. Targeted grants early in the accrual period may be a useful multi-site intervention to increase African American accrual for a prevention study where adequate African American representation is essential.

Adjunctive Rifampin Therapy For Diabetic Foot Osteomyelitis in the Veterans Health Administration.

Importance: Among patients diagnosed with diabetes, the lifetime incidence of foot ulcers is 15%. Infection is a common complication of foot ulcers, and 20% to 60% of infections result in diabetic foot osteomyelitis (DFO). Current treatment guidelines do not endorse any specific antibiotic agent for DFO, but small clinical trials suggest the addition of rifampin to antimicrobial regimens results in improved cure rates for osteomyelitis. Objective: To compare the clinical outcomes of patients treated for DFO in the Veterans Health Administration (VHA) with and without adjunctive rifampin. Design, Setting, and Participants: This observational cohort study used VHA databases to identify index DFO cases from January 1, 2009, through December 31, 2013, and analyzed patients alive and without high-level amputation at 90 days after diagnosis in whom antibiotic therapy was initiated within 6 weeks of diagnosis. Patients with death or major amputation within 90 days of diagnosis, who were not treated with systemic antibiotics dispensed by the VHA within 6 weeks of diagnosis, or who were treated at facilities where rifampin was not dispensed for DFO were excluded. The retrospective cohort to inform the planning of a multisite randomized clinical trial was first investigated in spring 2015; retrospective analysis was performed from February 2017 through September 2019. Exposures: Patients initiating rifampin therapy within 6 weeks of the DFO diagnosis and receiving the drug for at least 14 days within 90 days of diagnosis were considered treated with rifampin. Patients not administered rifampin within 90 days of diagnosis served as the comparator group. Main Outcomes and Measures: A combined end point of mortality or amputation within 2 years of diagnosis was analyzed. Differences in times to event were evaluated using log-rank tests. Differences in event rates were compared using χ2 tests and multivariable logistic regression. Results: The analysis population included 130 patients treated with rifampin and 6044 treated without rifampin (total of 6174; 6085 men [98.6%]; mean [SD] age, 64.9 [9.7] years). Lower event rates were observed among the rifampin group (35 of 130 [26.9%] vs 2250 of 6044 [37.2%]; P = .02). Patients treated with rifampin were younger (mean [SD] age, 62.2 [9.4] vs 64.9 [9.6] years), had fewer comorbidities (mean [SD] Charlson comorbidity index score, 3.5 [1.8] vs 4.0 [2.2]), had more infectious disease specialty consultations (63 of 130 [48.5%] vs 1960 of 6044 [32.4%]), and more often had Staphylococcus aureus identified in cultures (55 of 130 [42.3%] vs 1755 of 6044 [29.0%]) than patients not treated with rifampin. A logistic regression estimating the odds of events and controlling for these and other covariates yielded a significant association of rifampin (odds ratio, 0.65; 95% CI, 0.43-0.96; P = .04). Conclusions and Relevance: In this cohort study, patients administered rifampin experienced lower rates of death and amputation than patients not treated with rifampin, which remained significant after adjustment for confounders. These results coupled with existing evidence from small clinical trials suggest the addition of rifampin to current treatment regimens may be a useful antimicrobial option in the treatment of DFO.

The incidence and severity of hangover the morning after moderate alcohol intoxication.

AIMS: To determine the incidence and covariates of hangover following a night of moderate alcohol consumption at a targeted breath alcohol level. DESIGN: Data were combined from three randomized cross-over trials investigating the effects of heavy drinking on next-day performance. A total of 172 participants received either alcoholic beverage (mean=0.115 g% breath alcohol concentration) or placebo on one night and the other beverage a week later. The next day, participants completed a hangover scale. PARTICIPANTS: Participants were 54 professional merchant mariners attending a recertification course at Kalmar Maritime Academy (Kalmar, Sweden) and 118 university students or recent graduates recruited from greater Boston. SETTING: One trial was conducted at Kalmar Maritime Academy (Sweden); the other two were conducted at the General Clinical Research Center at Boston Medical Center. MEASUREMENTS: A nine-item scale assessed hangover. FINDINGS: Hangover was reported by 76% of participants. Neither alcoholic beverage type nor participant characteristics was associated with incidence of hangover. CONCLUSIONS: Our findings on the propensity of hangover suggest that 25-30% of drinkers may be resistant to hangover.

Characterizations of long-term oxycodone/acetaminophen prescriptions in veteran patients.

BACKGROUND: Long-term management of chronic pain with opioids may be stable over time or may be complicated by problematic dose increases, drug dependencies, and toxic effects. To determine clinical contexts in which stability or problems may occur, we examined the pharmacologic and clinical correlates of long-term prescriptions of oxycodone/acetaminophen, a commonly prescribed short-acting opioid formulation. METHODS: We analyzed linked, archival outpatient pharmacy and clinical databases from the New England Veterans Integrated Service Network between January 1, 1998, and June 30, 2001. Durations, doses, and dose changes of oxycodone/acetaminophen prescriptions and concurrent use of long-acting opioids, benzodiazepines, tricyclic antidepressants, and anticonvulsants were determined. RESULTS: In aggregate, 2195 patients (31% with cancer diagnoses per the International Classification of Diseases, Ninth Revision, Clinical Modification) received oxycodone/acetaminophen for more than 9 months at a mean prescribed daily dose of 3.9 tablets per day (range, 0.5-13.0 tablets per day) with minimal changes in daily prescribed mean dose over time. Patients with cancer were more likely than other patients to receive concurrent long-acting opioids. For patients without cancer, a higher mean daily dose was associated with duration, older age, human immunodeficiency virus (HIV) and/or AIDS, and with prescribed benzodiazepines and long-acting opioids; concurrent benzodiazepine prescriptions were associated with anticonvulsant prescriptions and with psychogenic pain and alcohol abuse and/or dependence diagnoses. CONCLUSIONS: In veteran patients who received long-term oxycodone/acetaminophen prescriptions, mean daily doses were typically modest and stable, likely reflecting a selection of patients with successful, long-term management. Among patients without cancer, however, associations of higher oxycodone/acetaminophen doses with benzodiazepine prescriptions, psychogenic pain, alcohol abuse, and HIV/AIDS may portend opioid prescription management problems.

Identifying Previously Undetected Harm: Piloting the Institute for Healthcare Improvement's Global Trigger Tool in the Veterans Health Administration.

BACKGROUND: Adverse event (AE) surveillance may be enhanced by the Institute for Healthcare Improvement's Global Trigger Tool (GTT). A pilot study of the GTT was conducted in one Veterans Health Administration (VA) facility to assess the rates, types, and harm of AEs detected and to examine the overlap in AE detection between the GTT and existing surveillance mechanisms. METHODS: GTT guidelines were followed and medical records were reviewed for 17 weeks of acute care hospitalizations. Investigators met monthly, first to adjudicate discordant reviewer categorizations of harm and later to categorize the AEs detected using standardized definitions. GTT-detected AEs were compared with incident reports, Patient Safety Indicators, and the VA Surgical Quality Improvement Program. RESULTS: Medical records were reviewed for 273 of 1980 eligible cases. Using the GTT, a total of 109 AEs were identified. More than 1 of 5 hospitalizations (21%) were associated with an AE. The majority of AEs detected (60%) were minor harms; there were no deaths attributable to medical care. Ninety-six of the 109 AEs (88%) were not detected by other measures. CONCLUSIONS: The GTT identified previously undetected AEs at one VA. The GTT has the potential to track AEs and guide quality improvement efforts in conjunction with existing AE surveillance mechanisms.

Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy.

IMPORTANCE: The unprecedented increase in unintentional overdose events that has occurred in tandem with escalating sales of prescription opioids over the past 2 decades has raised concerns about whether the therapeutic use of opioids has contributed to increases in overdose injury. Few controlled studies have examined the extent to which ecologic measures of increases in opioid prescribing and overdose injuries reflect risk among patients prescribed opioids, let alone whether some opioid regimens are safer than others. OBJECTIVE: To examine whether the risk of unintentional overdose injury is associated with the duration of opioid action (ie, long-acting vs short-acting formulations). DESIGN, SETTING, AND PARTICIPANTS: A propensity score-adjusted cohort study was conducted using population-based health care utilization data from the Veterans Administration Healthcare System. The patients were veterans with chronic painful conditions who began therapy with opioid analgesics between January 1, 2000, and December 31, 2009. MAIN OUTCOMES AND MEASURES: Unintentional overdoses that are explicitly coded using International Classification of Disease, Ninth Revision codes as drug or medication poisonings of accidental intent (E850.x-860.x) or undetermined intent (E980.x or drug poisoning [960.x-980.x] without an accompanying external cause of injury code). RESULTS: A total of 319 unintentional overdose events were observed. Patients initiating therapy with long-acting opioids were more than twice as likely to overdose compared with persons initiating therapy with short-acting opioids. After adjustment for age, sex, opioid dose, and other clinical characteristics, patients receiving long-acting opioids had a significantly higher rate of overdose injury than did those receiving short-acting opioids (hazard ratio [HR], 2.33; 95% CI, 1.26-4.32). The risk associated with long-acting agents was particularly marked during the first 2 weeks after initiation of treatment (HR, 5.25; 1.88-14.72). CONCLUSIONS AND RELEVANCE: To our knowledge, the findings of the present study provide the first evidence that the risk of unintentional overdose injury is related to the prescribed opioid's duration of action. If replicated in other cohorts, our findings suggest that clinicians weighing the benefits and risks of initiating different opioid regimens should consider not only the daily dose prescribed but also the duration of opioid action, favoring short-acting agents whenever possible, especially during the first 2 weeks of therapy.

Drinking goal choice and outcomes in a Web-based alcohol intervention: results from VetChange.

OBJECTIVES: The objectives of the paper are to describe characteristics of participants who chose moderation and abstinence drinking goals, and to examine post-treatment drinking outcomes based on patterns of goal choice during a Web-based alcohol intervention for returning U.S. Veterans. METHOD: We conducted a descriptive secondary analysis of a subsample of 305 of 600 Veterans who participated in a clinical trial of VetChange, an 8-module, cognitive-behavioural intervention. Participants self-selected abstinence or moderation drinking goals, initially at Module 3, and weekly during subsequent modules. Alcohol use and alcohol-related problems were measured using the Alcohol Use Disorders Identification Test (AUDIT), Quick Drink Screen (QDS), and Short Inventory of Problems (SIP-2R). RESULTS: Initial goal choices were 86.9% moderation and 13.1% abstinence. Approximately 20% of participants from each initial choice changed goals during the intervention; last goal choices were 68.6% moderation and 31.4% abstinence. Participants who initially chose moderation reported higher percent heavy drinking days at baseline; participants who initially chose abstinence were more likely to report recent substance abuse treatment and were older. Post-intervention levels of alcohol use and alcohol-related problems were significantly reduced in all goal-choice patterns (i.e., Moderation Only, Abstinence Only, Moderation to Abstinence, and Abstinence to Moderation; all measures p < 0.05 or less). Baseline drinking severity did not differentially relate to outcomes across goal-choice patterns. CONCLUSIONS: Participants in a Web-based alcohol intervention for returning U.S. Veterans demonstrated improvements in drinking regardless of whether they chose an abstinence or moderation drinking goal, and whether the goal was maintained or changed over the course of the intervention.

Retention of black and white participants in the selenium and vitamin E cancer prevention trial (SWOG-coordinated intergroup study S0000).

BACKGROUND: Disproportionally low retention of minority populations can adversely affect the generalizability of clinical research trials. We determine the overall retention rates for White and Black participants from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and explore participant and site characteristics associated with retention failure (study disengagement) for these groups. METHODS: A secondary analysis of 28,118 White (age ≥55), and 4,322 Black (age ≥ 50) SELECT participants used multivariate Cox regression to estimate overall retention rates and to calculate HRs and 95% confidence intervals (CI). RESULTS: Blacks had higher age-adjusted risk of disengagement than Whites (HR, 1.92; 95% CI, 1.77-2.08). Among Black participants, those ages 50 to 54 were at three times the risk of disengagement than those ≥65 years of age (HR, 3.61; 95% CI, 2.41-5.41). Blacks age ≥65 had 1.6 times the risk of disengagement than Whites age ≥65 (HR, 1.60; 95% CI, 1.38-1.87). By 6 years after randomization, 84% of Whites and 69% of Blacks remained engaged in the study. Current smoking status was an independent risk factor for study disengagement for both White and Black participants. For both groups, sites whose staffs missed SELECT training sessions or who received SELECT Retention and Adherence grants were associated with increased and decreased disengagement risks, respectively. CONCLUSIONS: SELECT retention was disproportionately lower for Blacks than for Whites. IMPACT: The observed difference in retention rates for Blacks and Whites and factors identified by race for study disengagement in SELECT may inform retention efforts for future long-term, cancer prevention trials.