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Objective. To characterize the risk factors associated with overdose or serious opioid-induced respiratory depression (OIRD) among medical users of prescription opioids in a commercially insured population (CIP) and to compare risk factor profiles between the CIP and Veterans Health Administration (VHA) population. Subjects and Methods. Analysis of data from 18,365,497 patients in the IMS PharMetrics Plus health plan claims database (CIP) who were dispensed a prescription opioid in 2009 to 2013. Baseline factors associated with an event of serious OIRD among 7,234 cases and 28,932 controls were identified using multivariable logistic regression. The CIP risk factor profile was compared with that from a corresponding logistic regression among 817 VHA cases and 8,170 controls in 2010 to 2012. Results. The strongest associations with serious OIRD in CIP were diagnosed substance use disorder (odds ratio [OR] 5 10.20, 95% confidence interval [CI] 5 9.06-11.40) and depression (OR5 3.12, 95% CI52.84-3.42). Other strongly associated factors included other mental health disorders; impaired liver, renal, vascular, and pulmonary function; prescribed fentanyl, methadone, and morphine; higher daily opioid doses; and concurrent psychoactive medications. These risk factors, except depression, vascular disease, and specific opioids, largely aligned with VHA despite CIP being substantially younger, including more females and less chronic disease, and having greater prescribing prevalence of higher daily opioid doses, specific opioids, and most selected nonopioids. Conclusions. Risk factor profiles for serious OIRD among US medical users of prescription opioids with private or public health insurance were largely concordant despite substantial differences between the populations in demographics, clinical conditions, health care delivery systems, and clinical practices. [ABSTRACT FROM AUTHOR]

Aims To assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder. Methods We searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid-dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random-effects models for each outcome with two or more studies. Results Three RCTs ( n = 223) and 15 cohort OBSs ( n = 1923) met inclusion criteria. In meta-analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes. Conclusions Moderately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater harms. [ABSTRACT FROM AUTHOR]

Objective Develop a risk index to estimate the likelihood of life-threatening respiratory depression or overdose among medical users of prescription opioids. Subjects, Design, and Methods A case-control analysis of administrative health care data from the Veterans' Health Administration identified 1,877,841 patients with a pharmacy record for an opioid prescription between October 1, 2010 and September 30, 2012. Overdose or serious opioid-induced respiratory depression (OSORD) occurred in 817. Ten controls were selected per case ( n = 8,170). Items for an OSORD risk index (RIOSORD) were selected through logistic regression modeling, with point values assigned to each predictor. Modeling of risk index scores produced predicted probabilities of OSORD; risk classes were defined by the predicted probability distribution. Results Fifteen variables most highly associated with OSORD were retained as items, including mental health disorders and pharmacotherapy; impaired drug metabolism or excretion; pulmonary disorders; specific opioid characteristics; and recent hospital visits. The average predicted probability of experiencing OSORD ranged from 3% in the lowest risk decile to 94% in the highest, with excellent agreement between predicted and observed incidence across risk classes. The model's C-statistic was 0.88 and Hosmer-Lemeshow goodness-of-fit statistic 10.8 ( P > 0.05). Conclusion RIOSORD performed well in identifying medical users of prescription opioids within the Veterans' Health Administration at elevated risk of overdose or life-threatening respiratory depression, those most likely to benefit from preventive interventions. This novel, clinically practical, risk index is intended to provide clinical decision support for safer pain management. It should be assessed, and refined as necessary, in a more generalizable population, and prospectively evaluated. [ABSTRACT FROM AUTHOR]

Objective Prescription opioid use and deaths related to serious toxicity, including overdose, have increased dramatically in the United States since 1999. However, factors associated with serious opioid-related respiratory or central nervous system ( CNS) depression or overdose in medical users are not well characterized. The objective of this study was to examine the factors associated with serious toxicity in medical users of prescription opioids. Design Retrospective, nested, case-control analysis of Veterans Health Administration ( VHA) medical, pharmacy, and health care resource utilization administrative data. Subjects Patients dispensed an opioid by VHA between October 1, 2010 and September 30, 2012 (N = 8,987). Methods Cases (N = 817) experienced life-threatening opioid-related respiratory/ CNS depression or overdose. Ten controls were randomly assigned to each case (N = 8,170). Logistic regression was used to examine associations with the outcome. Results The strongest associations were maximum prescribed daily morphine equivalent dose ( MED) ≥ 100 mg (odds ratio [ OR] = 4.1, 95% confidence interval [ CI], 2.6-6.5), history of opioid dependence ( OR = 3.9, 95% CI, 2.6-5.8), and hospitalization during the 6 months before the serious toxicity or overdose event ( OR = 2.9, 95% CI, 2.3-3.6). Liver disease, extended-release or long-acting opioids, and daily MED of 20 mg or more were also significantly associated. Conclusions Substantial risk for serious opioid-related toxicity and overdose exists at even relatively low maximum prescribed daily MED, especially in patients already vulnerable due to underlying demographic factors, comorbid conditions, and concomitant use of CNS depressant medications or substances. Screening patients for risk, providing education, and coprescribing naloxone for those at elevated risk may be effective at reducing serious opioid-related respiratory/ CNS depression and overdose in medical users of prescription opioids. [ABSTRACT FROM AUTHOR]

Abstract: Background: Calendar blister packaging (CBP) that incorporates a day or date feature is a simple medication packaging technology that is designed to improve medication adherence and persistence. Objective: This study was conducted to assess the effect of a new calendar packaging technology on prescription refill adherence and persistence for daily, self-administered, long-term medication use. Methods: Anonymized pharmacy dispensing data from a large US mass merchandiser were analyzed. This retrospective cohort study included people aged 18 to 75 years who filled prescriptions for oral lisinopril or enalapril (control group) at a study pharmacy during 1 year before and after the switch of lisinopril packaging from vials to CBP. Cohorts were stratified into new and prevalent medication users. We used linear and logistic regression modeling and propensity score matching to assess the impact of CBP on refill adherence, using medication possession ratio (MPR) and proportion of days covered (PDC), and persistence using length of therapy (LOT). Results: Our sample comprised 76,321 new users and 249,040 prevalent users. Across all user, medication, and packaging groups, the mean unadjusted LOT decreased in the follow-up year, possibly due to economic recession. The LOT decline was attenuated in the CBP cohort. After adjustment for covariates, CBP use in new and prevalent medication users was associated with significantly higher LOT and PDC but not MPR. The odds of achieving PDC ≥80% were higher by 15% in new users (odds ratio [OR] = 1.15; 95% CI, 1.09–1.21) and 12% in prevalent users (OR = 1.12; 95% CI, 1.09–1.15) who switched to CBP, compared with continued vial use. Conclusions: CBP of medication prescribed for daily, self-administered, long-term use was associated with modest improvement in prescription refill adherence and persistence. An adherence strategy of even small effect size that is broadly implemented on a population level could significantly leverage therapeutic effect and provide substantial cumulative public health benefit. Clinical benefit, or harm, associated with use of CBP should be investigated. Usability assessments of CBP in patient subgroups may provide insight about differential impact on adherence and persistence. [Copyright &y& Elsevier]