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Background: Concurrent opioid and benzodiazepine (BZD) use is a prevalent high‐risk prescribing behavior that increases the risk of opioid overdose. However, there is limited evidence on the relationship between timing of concurrent use and risk of opioid overdose. Objective: To evaluate the likelihood of opioid‐related overdose across levels of duration, recency, and daily dose of concurrent use. Design: A nested case‐control study was conducted using Truven MarketScan claims data (2009–2018). Participants: Commercially insured adults (age 18–64 years old) with a new opioid dispensing in 2010–2018. Main Measures: Cases of opioid‐related overdose were identified based on hospitalization diagnosis codes. Controls were matched to cases in a 10:1 ratio by age, sex, opioid start date, and cancer history. Concurrent use was classified based on duration, timing, and daily dose of overlapping opioids and BZDs during 90 days before the event. Conditional logistic regression models were used to evaluate the relationship between concurrent use and opioid‐related overdose. Key Results: Among 11,137,866 dispensed a new opioid, a total of 3388 patients experienced opioid‐related overdose and were matched to 33,893 controls. Cases and controls were 34 years old on average and 54% female. Patients with concurrent use were significantly more likely to have opioid‐related overdose compared to patients receiving opioids, BZDs, or neither (OR 9.28; 95% CI 7.87, 10.93). Longer concurrent use of 1–7, 8–30, and 31–90 days was associated with 4.6, 12.1, and 26.7‐fold higher likelihood of opioid‐related overdose (p < 0.01). Patients with overlapping prescriptions during previous 0–30, 31–60, and 61–90 days were 13.2, 6.0, and 3.2‐times more likely to experience an overdose (p < 0.01). Conclusions: Patients with an opioid‐related overdose were more likely to be prescribed concurrent opioid and BZD across all levels of duration, timing, and daily dose. Future policies and quality measures should be pursued to prevent concurrent use unless medically necessary. [ABSTRACT FROM AUTHOR]

Introduction Several dual bronchodilator fixed-dose inhaler medications were recently approved for the treatment of chronic obstructive pulmonary disease (COPD). These products combine a long-acting β2-agonist (LABA) and long-acting muscarinic antagonist (LAMA). In clinical trials, the separate mechanisms of the bronchodilators resulted in improved lung function. COPD treatment guidelines currently recommend combination LABA/LAMA as alternative therapy to combination LABA/inhaled corticosteroid (ICS). Evidence is limited on the comparative effectiveness of LABA/LAMA and LABA/ICS in COPD. The objective of this study was to compare real-world COPD exacerbation rates among patients treated with LABA/LAMA with those treated with LABA/ICS. Methods This was a retrospective observational study of COPD patients in the United States treated with LABA/LAMA or LABA/ICS combination. Insurance claims from January 1, 2004, through December 31, 2014, were used as the data source. Patients were required to have greater than one prescription filled for the combination medications, and they were followed from 30 days after drug initiation. Individuals were censored if they discontinued a study medication, initiated medication from the opposite cohort (LAMA or ICS), lost enrollment eligibility, or at the study period end. Exacerbation rates were compared using Poisson regression. Results There were 5384 patients in the LABA/LAMA cohort and 473,388 patients in the LABA/ICS cohort. The LABA/LAMA cohort was older, had more comorbidities, and more severe COPD. Unadjusted annual exacerbation rates were 2.87 events per person-year (standard deviation [SD] 5.14) in the LABA/LAMA cohort and 1.68 (SD 9.82) in the LABA/ICS cohort. The adjusted incidence rate ratio was 0.98 (95% confidence interval 0.95-1.01) for LABA/LAMA compared with LABA/ICS. Conclusions The LABA/LAMA combination had similar effectiveness to LABA/ICS as measured by exacerbation rates in COPD patients. As a result, characteristics other than effectiveness, such as symptom control, cost, patient preferences, and adverse events, may be important in selecting between the two regimens. [ABSTRACT FROM AUTHOR]

Objective To describe the suspected medications, types of reactions, and outcomes of adverse events ( AEs) most commonly reported to the United States Food and Drug Administration ( FDA) in children by age group. Methods All case reports submitted to the FDA Adverse Event Reporting System ( FAERS) between January 1, 2007, and August 27, 2012, for children (1 to < 12 yrs) and adolescents (12 to < 18 yrs) were examined. The most commonly reported suspected drugs were ranked. The corresponding AEs with serious outcome were compared and described between age groups. Results We identified a total of 78,623 reports in the FAERS database (53.8% in children and 46.2% in adolescents). Serious outcomes were noted in 40% of the children and 43% of the adolescents. The proportion of all case reports for central nervous system stimulants (lisdexamfetamine, 69.8%; methylphenidate, 68.0%) and analgesics (ibuprofen, 72.3%; acetaminophen, 68.6%) was higher in children, whereas tumor necrosis factor blockers (infliximab, 78.2%; adalimumab, 77.1%), atypical antipsychotics (aripiprazole 52.7%; risperidone 58.3%; quetiapine 72.1%) and oral contraceptives (levonogrestrel, 99.2%; drospirenone and ethinyl estradiol, 97.9%) were more commonly reported in adolescents. For most drugs, the types of reactions reported were similar but had different rank order across age groups, with the most dissimilar profiles being observed for isotretinoin and aripiprazole. Conclusions This study highlights high-risk medications and their AE profiles in children and adolescents. Our findings underscore the need for further confirmation of particular drug and AE pairs and the heterogeneity of AEs by age. [ABSTRACT FROM AUTHOR]

Pharmacogenomics has an important role in the evolution of personalized medicine, and its widespread uptake may ultimately depend on the interests and perspectives of key players in health care. Our aim was to summarize studies on stakeholder perspectives and attitudes toward pharmacogenomic testing. Thus, we conducted a review of original research studies that reported stakeholder views on pharmacogenomic testing using a structured approach in PubMed, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and EMBASE. A standardized data abstraction form was developed that included stakeholder group of interest-patients, general public, providers, and payers. Stakeholder views regarding barriers to pharmacogenetic implementation were organized into the following themes: ancillary information-related, clinical, economic, educational, ethical or legal, medical mistrust, and practicality. Of 34 studies that met our inclusion criteria, 37 perspectives were reported (15 on providers, 9 on the general public, 9 on patients, and 4 on payers). The most common topics that arose in studies of providers related to clinical usefulness of genetic data (n=11) and educational needs (n=11). Among the general public, the most common concerns were medical mistrust (n=5), insufficient education (n=5), and practicality (n=5). The most prevalent issues from the patient perspective were ethical or legal (n=6) and economic (n=5) issues. Among payers, leading issues were practicality (n=4) and clinical usefulness (n=3). There was overlap in the topics and concerns across stakeholder perspectives, including lack of knowledge about pharmacogenomic testing. Views on issues related to privacy, cost, and test result dissemination varied by stakeholder perspective. Limited research had been conducted in underrepresented groups. Efforts to address the issues raised by stakeholders may facilitate the implementation of pharmacogenomic testing into clinical practice. [ABSTRACT FROM AUTHOR]

Recent studies have suggested an increase in the number of retracted scientific publications. It is unclear how broadly the issue of misleading and fraudulent publications pertains to retractions of drug therapy studies. Therefore, we sought to determine the trends and factors associated with retracted publications in drug therapy literature. A Pub Med search was conducted to identify retracted drug therapy articles published from 2000-2011. Articles were grouped according to reason for retraction, which was classified as scientific misconduct or error. Scientific misconduct was further divided into data fabrication, data falsification, questions of data veracity, unethical author conduct, and plagiarism. Error was defined as duplicate publication, scientific mistake, journal error, or unstated reasons. Additional data were extracted from the retracted articles, including type of article, funding source, author information, therapeutic area, and retraction issue. A total of 742 retractions were identified from 2000-2011 in the general biomedical literature, and 102 drug studies met our inclusion criteria. Of these, 73 articles (72%) were retracted for a reason classified as scientific misconduct, whereas 29 articles (28%) were retracted for error. Among the 73 articles classified as scientific misconduct, those classified as unethical author conduct (32 articles [44%]) and data fabrication (24 articles [33%]) constituted the majority. The median time from publication of the original article to retraction was 31 months (range 1-130). Fifty percent of retracted articles did not state a funding source, whereas pharmaceutical manufacturer funding accounted for only 13 articles (13%) analyzed. Many retractions were due to repeat offenses by a small number of authors, with nearly 40% of the retracted studies associated with two individuals. We found that a greater proportion of drug therapy articles were retracted for reasons of misconduct and fraud compared with other biomedical studies. It is important for health care practitioners to monitor the literature for retractions so that recommendations for drug therapy and patient management may be modified accordingly. [ABSTRACT FROM AUTHOR]

Study Objective. To evaluate outcomes associated with six treatment regimens with theophylline versus each regimen without theophylline in patients with chronic obstructive pulmonary disease (COPD). Design. Retrospective cohort study. Setting. Veterans Affairs health care system. Patients. A total of 183,573 patients aged 45 years or older who had a diagnosis of COPD and were receiving respiratory drug therapy. Measurements and Main Results. Patients' treatment regimens were identified by using data from October 1, 2002-March 31, 2003, and patients were followed for events by using data from April 1, 2003-September 30, 2005. Data from October 1, 2001-September 30, 2002, were used to define the patients' baseline characteristics. Primary outcome measures were all-cause mortality, COPD exacerbations, and COPD-related hospitalizations. Two approaches were used: first, treatment assignment was based on drug therapy at baseline, and second, exposure was measured as a time-varying covariate. Treatment groups were stratified based on propensity to receive theophylline. Mortality was compared by using Cox proportional hazards models, and other outcomes were compared with use of negative binomial models. Comparisons were conducted within individual treatment regimens that were the same with the exception of theophylline. Patients treated with ipratropium plus theophylline (largest group) compared with those treated with ipratropium alone had a 1.11-fold increase in the risk of death (95% confidence interval [CI] 1.04-1.18). For each of the other regimens, the risk of mortality associated with theophylline was greater than that in the regimens without theophylline (hazard ratios [HRs] 1.17-1.31). In the time-varying exposure analysis, theophylline (HR 1.23, 95% CI 1.09-1.39) was associated with an increased mortality risk. Conclusion. Patients receiving regimens that included theophylline had slightly increased risks of mortality, COPD exacerbations, and COPD hospitalizations compared with patients receiving the same regimens without theophylline. However, the benefits of theophylline on other factors, including symptoms, quality of life, and activities of daily living, were not measured. Clinicians should consider all of the potential benefits and harms associated with theophylline when making treatment recommendations. [ABSTRACT FROM AUTHOR]

Objective. To determine if clopidogrel use before coronary artery bypass grafting (CABG) is associated with an increase in major bleeding, hemorrhage-related complications, or transfusion requirements. Methods. A structured literature search of English-language articles was conducted by using MEDLINE, EMBASE, and the Cochrane Collaboration Database for the period of January 1, 1990-April 30, 2007. Studies were included if they met the following criteria: randomized controlled trials, prospective observational trials, or retrospective trials; characteristics and outcomes of patients who were exposed to clopidogrel within 7 days before CABG were analyzed; at least 20 patients were enrolled; and reported outcomes were related to transfusion requirements, resource utilization, clinical events, or hemorrhage-related reoperation rates. Patients were considered exposed to clopidogrel if they discontinued the drug within a specified time frame that was designated in each study. The rates of the outcomes were compared between those patients exposed and those not exposed to clopidogrel. Results. Twenty-three studies, with data on 3505 patients exposed to clopidogrel before CABG, met the selection criteria. Results suggested that clopidogrel exposure within 7 days before CABG increased the risk of major bleeding and related complications, such as reoperation and blood product transfusions. For other outcomes such as mortality, myocardial infarction, or stroke, the studies' designs lacked statistical power to detect significant differences. In five of the 23 studies, antifibrinolytic therapy with aprotinin was evaluated; in the other studies, aprotinin may have been administered, but it was not discussed in detail. In these studies, the clopidogrel-exposed patients typically had significantly higher chest tube output volumes, reoperation rates due to bleeding, and greater transfusion requirements. Although aprotinin appeared to mitigate hemorrhagic risk, the drug has been temporarily suspended from the market due to safety concerns. Conclusion. Clopidogrel exposure within 7 days before CABG is associated with an increase in major bleeding, hemorrhage-related complications, and transfusion requirements, and leads to potentially greater consumption of health care resources. The overall risks and benefits for each patient should be considered before using the drug. [ABSTRACT FROM AUTHOR]

Study Objective. To systematically review the efficacy of azelastine nasal spray for the treatment of allergic rhinitis. Design. Meta-analysis of published randomized controlled trials reported in English. Data Source. Published literature from the PubMed-MEDLINE database. Patients. Patients aged at least 12 (United States) or 16 years (Europe) with allergic rhinitis or nonallergic vasomotor rhinitis. Measurements and Main Results. A global assessment of efficacy was used to estimate the number needed to treat for azelastine nasal spray compared with placebo or active comparators. The total symptom score was used to compare the effect size between azelastine and placebo. In five comparisons of azelastine and placebo, azelastine was most efficacious, with a summary number needed to treat of 5.0 (95% confidence interval [CI] 3.3-10.0). In reviewing 11 studies of azelastine versus active comparators, we found no significant difference between azelastine and active comparators (number needed to treat 66.7, 95% CI 14.3 to ∞ to 25]). Azelastine was more efficacious than placebo in terms of total symptom score (effect size of 0.36, 95% CI 0.26-0.46). Conclusion. Azelastine nasal spray was more efficacious than placebo in the treatment of allergic rhinitis. No significant differences were observed between azelastine and active comparators for the treatment of allergic rhinitis; however, when azelastine was compared with oral antihistamines as monotherapy, the trend favored azelastine. Because azelastine appears to be as efficacious as oral antihistamines, the choice of treatment for seasonal allergic rhinitis should depend on the patient's preference regarding the route of administration, adverse effects, and the cost of the drug. [ABSTRACT FROM AUTHOR]

Objectives. To characterize the services and activities performed by anticoagulation clinics (ACCs) across the United States, examine the anticipated impact that oral direct thrombin inhibitors (DTIs) will have on the clinical services of ACCs, and elicit possible management strategies to realign services provided by ACCs and opportunities for restructuring clinical services. Methods. A survey was developed in consultation with content experts in the field, pretested by several ACC providers, and subsequently refined. Surveys were mailed to 400 randomly selected ACC-based providers. Results. The final usable response rate was 34.5% (115 of 333 surveys). Respondents anticipated that the number of patient visits/month would decrease from a median of 336 (interquartile range [IQR] 151-775) to 150 (IQR 71-350, p<0.001) after the introduction of oral DTIs. In addition, time spent on many direct and indirect patient care activities currently performed by ACCs was expected to decline. Respondents indicated that ACCs may find new roles by providing guidance on individual suitability for therapy, managing the transition to oral DTIs, providing education for patients and health care providers on thrombotic disease state management, monitoring patients for recurrent thrombosis and risk of bleeding complications, monitoring patient compliance, and providing counseling and safety surveillance for patients receiving treatment with oral DTIs. Conclusion. The advent of oral DTIs is likely to have a significant impact on the structure and delivery of antithrombotic services. Clinics that are proactive and redesign their patient care services to consider emerging anticoagulant agents will be more likely to remain relevant and viable. [ABSTRACT FROM AUTHOR]

Study Objective. To quantify the relative risk of cardiovascular events associated with microalbuminuria in patients with both diabetes mellitus and hypertension. Design, A structured literature search from January 1990-December 2002 using MEDLINE, IPA, and CINAHL. Measurements and Main Results. We identified original studies that reported the presence or absence of microalbuminuria and estimates of risk associated with cardiovascular events in patients with both diabetes and hypertension. Abstracted information consisted of study design, patient demographics and risk factors, treatment regimens, and outcome variables. Point estimates and confidence intervals for relative risk were calculated from available data. Of 651 citations identified and reviewed based on title and abstract, 72 were selected for full review. Seven met the inclusion criteria. Because of lack of homogeneity among studies, the results were not conducive to pooling. Cardiovascular end points associated with the presence of microalbuminuria in these studies were all-cause mortality, cardiovascular mortality, and composite cardiovascular morbidity. The relative risk of cardiovascular end points associated with the presence of microalbuminuria ranged from 1.6 (95% confidence interval |CI] 1.2-2.2) to 7.9 (95% CI 2.5-25.3). Conclusion. From the limited information available, the risk of cardiovascular events and mortality is estimated to be 2-8 times higher when microalbuminuria is present in patients with diabetes and hypertension. Point estimates in relative risk of cardiovascular morbidity and mortality in patients with diabetes and hypertension were generally higher compared with studies estimating risk in those with only diabetes. Studies that examine the relationship between microalbuminuria (scaled as a continuous or ordinal variable) and cardiovascular events are necessary to clarify potential benefits of pharmacotherapies that reduce levels of urinary albumin. [ABSTRACT FROM AUTHOR]

Introduction: Several dual bronchodilator fixed-dose inhaler medications were recently approved for the treatment of chronic obstructive pulmonary disease (COPD). These products combine a long-acting β 2 -agonist (LABA) and long-acting muscarinic antagonist (LAMA). In clinical trials, the separate mechanisms of the bronchodilators resulted in improved lung function. COPD treatment guidelines currently recommend combination LABA/LAMA as alternative therapy to combination LABA/inhaled corticosteroid (ICS). Evidence is limited on the comparative effectiveness of LABA/LAMA and LABA/ICS in COPD. The objective of this study was to compare real-world COPD exacerbation rates among patients treated with LABA/LAMA with those treated with LABA/ICS., Methods: This was a retrospective observational study of COPD patients in the United States treated with LABA/LAMA or LABA/ICS combination. Insurance claims from January 1, 2004, through December 31, 2014, were used as the data source. Patients were required to have greater than one prescription filled for the combination medications, and they were followed from 30 days after drug initiation. Individuals were censored if they discontinued a study medication, initiated medication from the opposite cohort (LAMA or ICS), lost enrollment eligibility, or at the study period end. Exacerbation rates were compared using Poisson regression., Results: There were 5384 patients in the LABA/LAMA cohort and 473,388 patients in the LABA/ICS cohort. The LABA/LAMA cohort was older, had more comorbidities, and more severe COPD. Unadjusted annual exacerbation rates were 2.87 events per person-year (standard deviation [SD] 5.14) in the LABA/LAMA cohort and 1.68 (SD 9.82) in the LABA/ICS cohort. The adjusted incidence rate ratio was 0.98 (95% confidence interval 0.95-1.01) for LABA/LAMA compared with LABA/ICS., Conclusions: The LABA/LAMA combination had similar effectiveness to LABA/ICS as measured by exacerbation rates in COPD patients. As a result, characteristics other than effectiveness, such as symptom control, cost, patient preferences, and adverse events, may be important in selecting between the two regimens., (© 2017 Pharmacotherapy Publications, Inc.)