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.

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.

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.

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.

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.

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.

A randomized placebo-controlled trial of D-cycloserine and exposure therapy for posttraumatic stress disorder.

D-Cycloserine (DCS) is a partial NMDA receptor agonist that has been shown to enhance therapeutic response to exposure-based treatments for anxiety disorders, but has not been tested in the treatment of combat-related posttraumatic stress disorder (PTSD). The aim of this randomized, double-blind, placebo-controlled trial was to determine whether DCS augments exposure therapy for PTSD in veterans returning from Iraq and Afghanistan and to test whether a brief six-session course of exposure therapy could effectively reduce PTSD symptoms in returning veterans. In contrast to previous trials using DCS to enhance exposure therapy, results indicated that veterans in the exposure therapy plus DCS condition experienced significantly less symptom reduction than those in the exposure therapy plus placebo condition over the course of the treatment. Possible reasons for why DCS was associated with poorer outcome are discussed. Clinicaltrials.gov Registry #: NCT00371176; A Placebo-Controlled Trail of D-Cycloserine and Exposure Therapy for Combat-PTSD; www.clinicaltrials.gov/ct2/results?term=NCT00371176.

Proton pump inhibitor discontinuation in long-term care.

OBJECTIVES: To determine factors associated with proton pump inhibitor (PPI) discontinuation in long-term care. DESIGN: Retrospective cohort analysis. SETTING: Veterans Affairs (VA) long-term care facilities. PARTICIPANTS: Veterans admitted for nonhospice care in 2005 with a length of stay of 7 days or more who were prescribed a PPI within 7 days of admission (N = 10,371). MEASUREMENTS: Prescribed medications and comorbidities were determined from VA pharmacy and administrative databases and functional status from Minimum Data Set records. Associations between participant characteristics and PPI discontinuation were determined using Cox proportional hazard ratios (HRs), censoring at death, discharge, or 180 days after admission. RESULTS: Participants were predominantly male (97%) and had a median age of 73 (interquartile range 60-81). There were 2,749 (27%) PPI discontinuations; 43% of these occurred within 28 days of admission. Hospitalizations (HR = 1.22, 95% confidence interval (CI) = 1.01-1.46), preadmission PPI use (HR = 1.35, 95% CI = 1.16-1.56), and lowest functional status (HR = 1.22, 95% CI = 1.03-1.45) were associated with early PPI discontinuation in adjusted models. Participants with gastric acid-related disease (HR = 0.53, 95% CI 0.46-0.61), diabetes mellitus (HR = 0.82, 95% CI 0.72-0.94), and those who were prescribed six or more medications (6-7 medications, HR = 0.78, 95% CI = 0.66-0.92; 8-10 medications, HR = 0.64, 95% CI = 0.54-0.76; ≥ 11 medications 0.51, 95% CI = 0.42-0.62) were less likely to have early discontinuation. No PPI discontinuer had PPIs resumed during the study, and few (9%) had histamine-2 receptor antagonist substitutions. CONCLUSION: Although there may be clinical uncertainty regarding PPI discontinuation, more than one-quarter of participants prescribed a PPI upon admission to long-term care had it discontinued within 180 days. Targeting individuals prescribed PPIs for medication appropriateness review may reduce prescribing of potentially nonindicated medications.

Proton pump inhibitors and risk for recurrent Clostridium difficile infection.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used gastric acid suppressants, but they are often prescribed without clear indications and may increase risk of Clostridium difficile infection (CDI). We sought to determine the association between PPI use and the risk of recurrent CDI. METHODS: Retrospective, cohort study using administrative databases of the New England Veterans Healthcare System from October 1, 2003, through September 30, 2008. We identified 1166 inpatients and outpatients with metronidazole- or vancomycin hydrochloride-treated incident CDI, of whom 527 (45.2%) received oral PPIs within 14 days of diagnosis and 639 (54.8%) did not. We determined the hazard ratio (HR) for recurrent CDI, defined by a positive toxin finding in the 15 to 90 days after incident CDI. RESULTS: Recurrent CDI was more common in those exposed to PPIs than in those not exposed (25.2% vs 18.5%). Using Cox proportional survival methods, we determined that the adjusted HR of recurrent CDI was greater in those exposed to PPIs during treatment (1.42; 95% confidence interval [CI], 1.11-1.82). Risks among exposed patients were highest among those older than 80 years (HR, 1.86; 95% CI, 1.15-3.01) and those receiving antibiotics not targeted to C difficile during follow-up (HR, 1.71; 95% CI, 1.11-2.64). [corrected] CONCLUSIONS: Proton pump inhibitor use during incident CDI treatment was associated with a 42% increased risk of recurrence. Our findings warrant further studies to examine this association and careful consideration of the indications for prescribing PPIs during treatment of CDI.

Does opioid therapy affect quality of care for diabetes mellitus?

OBJECTIVE: To examine whether veterans who received chronic opioid therapy had worse diabetes performance measures than patients who did not receive opioids. STUDY DESIGN: Retrospective cohort study. METHODS: We identified all patients with diabetes mellitus receiving care in US Department of Veterans Affairs facilities during 2004. Cases received at least 6 prescriptions for chronic opioids during 2004, while controls were randomly selected from among patients with diabetes who received no opioids. We compared process measures (glycosylated hemoglobin and low-density lipoprotein cholesterol levels tested and an eye examination performed) and outcome measures (glycosylated hemoglobin level < or =9.0% and low-density lipoprotein cholesterol level < or =130 mg/dL) between groups. RESULTS: Cases (n = 47,756) had slightly worse diabetes performance measures than controls (n = 220,912) after adjustment for covariates. For example, 86.4% of cases and 89.0% of controls had a glycosylated hemoglobin test during fiscal year 2004 (adjusted odds ratio, 0.69; P <.001). Among cases, receipt of higher-dose opioids was associated with additional decrement in diabetes performance measures, with a dose-response relationship. CONCLUSIONS: Chronic opioid therapy among patients within the Veterans Affairs system is associated with slightly worse diabetes performance measures compared with patients who do not receive opioids. However, patients receiving higher dosages of opioids had additional decrements in diabetes performance measures; these patients may be appropriate targets for interventions to improve their care for pain and diabetes.

Association of elevated alanine aminotransferase with BMI and diabetes in older veteran outpatients.

AIMS: We determined age-stratified associations of elevated alanine aminotransferase (ALAT), as a likely indicator of non-alcoholic steatonecrosis (NASH), with body mass index (BMI) and diabetes among older male, veteran outpatients. METHODS: Administrative files at three, urban Veteran Administration Healthcare Systems were surveyed. 47.916 male outpatients, mean age 69.2 years, without ICD-9CM documented liver diseases or alcohol- or drug-abuse, had the highest of one or more ALAT results analyzed. Logistic regression determined age-stratified predictors of elevated ALAT among groups <50 ("younger-aged"), 50-70 ("middle-aged") and >70 ("older-aged"). BMI, diabetes and "statin" use were predictors. RESULTS: 1272 (2.7%) patients had their highest ALAT greater than the upper limit of normal (mean=98.4U/L). 4.9% of all diabetics and 15.2, 6.1 and 3.4% of the "younger-aged", middle-aged" and "older-aged" diabetics, respectively, had elevated ALATs. BMI values from 25 to <30 and 30 to 45, compared with those from >20 to <25, predicted elevated ALAT in the two younger groups. In contrast, among "older-aged" patients, diabetes independently predicted elevated ALAT, whereas BMI did not. CONCLUSIONS: The cross-sectional findings support previous epidemiologic data associating ALAT elevations with obesity and diabetes, and provide new evidence that in elderly male patients, ALAT elevations, absent other known liver diseases, may selectively associate with diabetes.