Buprenorphine-naloxone treatment for opioid use disorder has rapidly expanded, yet little is known about treatment outcomes among patients in the general population.
To examine predictors of ...treatment duration, dosage, and continuity in a diverse community setting.
We examined QuintilesIMS Real World Data, an all-payer, pharmacy claims database, to conduct an analysis of individuals age 18 years and above initiating buprenorphine-naloxone treatment between January 2010 and July 2012 in 11 states. We used logistic regression to assess treatment duration longer than 6 months. We used accelerated failure time models to assess risk of treatment discontinuation. We used ordinary least squares regression to assess mean daily dosage. For patients with ≥3 fills, we also used logistic regression to assess whether ;an individual had a medication possession ratio of <80% and/or gaps in treatment >14 days. Models adjusted for individual demographics, prescribing physician specialty, state, and county-level variables.
Overall, 41% of individuals were retained in treatment for at least 6 months and the mean treatment length was 266 days. Compared with individuals who paid primarily for treatment with cash, adjusted odds of 6 month retention were significantly lower for individuals with primary payment from Medicaid fee-for-service, Medicare part D, and third-party commercial. There were substantial differences in 6-month retention across states with the lowest in Arizona and highest in New York. Low-possession ratios occurred for 30% of individuals and 26% experienced treatment episodes with gaps >14 days. Odds of low-possession and treatment gaps were largely similar across demographic groups and geographic areas.
Current initiatives to improve access and quality of buprenorphine-naloxone treatment should examine geographic barriers as well as the potential role of insurance benefit design in restricting treatment length.
The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i's) and lower extremity amputation is unclear.
To systematically review randomized control trials (RCTs) and observational ...studies quantifying risk of lower extremity amputations associated with SGLT2i use.
We searched PubMed, EMBASE, Scopus, and the Cochrane Central Register of Controlled Trials from January 2011 to February 2020 for RCTs and observational studies including lower extremity amputation outcomes for individuals with type 2 diabetes mellitus treated with SGLT2i's vs. alternative treatments or placebo.
Two reviewers independently extracted data.
Our primary outcome was risk of lower limb amputation. Secondary outcomes included peripheral arterial disease, peripheral vascular disease, venous ulcerations, and diabetic foot infections. We also evaluated the risk of bias. We conducted random and fixed effects relative risk meta-analysis of RCTs.
After screening 2,006 studies, 12 RCTs and 18 observational studies were included, of which 7 RCTs and 18 observational studies had at least one event. The random effects meta-analysis of 7 RCTs suggested the absence of a statistically significant association between SGLT2i exposure with evidence of substantial statistical heterogeneity (n = 424/23,716 vs n = 267/18,737 in controls; RR 1.28, CI's 0.93-1.76; I2 = 62.0%; p = 0.12) whereas fixed effects analysis showed an increased risk with statistical heterogeneity (RR 1.27, 1.09-1.48; I2 = 62%; p = 0.003). Subgroup analysis of canagliflozin vs placebo showed a statistically significantly increased risk in a fixed effects meta-analysis (n = 2 RCTs, RR 1.59, 1.26-2.01; I2 = 88%; p = 0.0001) whereas the meta-analysis of dapagliflozin or empagliflozin (n = 2 RCTs each) and a single RCT for ertugliflozin did not show a significantly increased risk. The findings from observational studies were too heterogeneous to be pooled in a meta-analysis and draw meaningful conclusions. Both randomized and observational studies were of generally good methodological quality.
Overall, there was no consistent evidence of SGLT2i exposure and increased risk of amputation. The increased risk of amputation seen in the large, long-term Canagliflozin Cardiovascular Assessment Study (CANVAS) trial for canagliflozin, and select observational studies, merits continued exploration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: A critical question in health care is the extent of scientific evidence that should be required to establish that a new therapeutic agent has benefits that outweigh its risks. Estimating ...the costs of this evidence of efficacy provides an important perspective. OBJECTIVE: To estimate costs and assess scientific characteristics of pivotal efficacy trials that supported the approval of new therapeutic agents by the US Food and Drug Administration (FDA) from 2015 to 2016. DESIGN AND SETTING: This study identified 59 novel therapeutic drugs using the annual summary reports from the FDA Center for Drug Evaluation and Research. ClinicalTrials.gov, FDA reviews, and peer-reviewed publications that were publicly available in 2017 were used to identify 52 characteristics of each efficacy trial. Costs were calculated with a global clinical trial cost assessment tool available to contract research organizations and pharmaceutical sponsors. MAIN OUTCOMES AND MEASURES: Estimated mean cost and 95% CIs based on industry benchmark data from 60 countries. Measures of trials’ scientific characteristics included trial design (no control group, placebo, and active drug), end point (surrogate outcome, clinical scale, and clinical outcome), patient enrollment, and treatment duration. RESULTS: A total of 138 pivotal clinical trials provided the basis for approval of 59 new therapeutic agents by the FDA from 2015 to 2016, with a median estimated cost of $19.0 million (interquartile range, $12.2 million-$33.1 million). Estimated costs ranged from less than $5 million for trials without a control group for 3 orphan drugs with fewer than 15 patients each to $346.8 million (95% CI, $252.0 million-$441.5 million) for a noninferiority trial with end points assessing clinical benefit. Twenty-six of 138 trials (18.8%) were uncontrolled, with a mean estimated cost of $13.5 million (95% CI, $10.1 million-$16.9 million). Trials designed with placebo or active drug comparators had an estimated mean cost of $35.1 million (95% CI, $25.4 million-$44.8 million). Costs also varied by trial end point, treatment duration, patient enrollment, and therapeutic area. CONCLUSIONS AND RELEVANCE: The highest-cost trials were those in which the new agent had to be proved to be noninferior with clinical benefit end points compared with an agent already available or those that required larger patient populations to achieve statistical power to document smaller treatment effects or accrue infrequently occurring end points.
National Trends in Ambulatory Oral Anticoagulant Use Barnes, Geoffrey D., MD, MSc; Lucas, Eleanor, BA; Alexander, G. Caleb, MD, MS ...
The American journal of medicine,
12/2015, Letnik:
128, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Abstract Background Four direct oral anticoagulants (DOACs) have been brought to market for the treatment of nonvalvular atrial fibrillation and venous thromboembolism. Many forces, including ...numerous positive trial results, emerging safety concerns, marketing, and promotion, may shape DOAC adoption by providers. However, relatively little is known regarding their ambulatory utilization compared with warfarin, as well as the degree to which they have decreased under-treatment of atrial fibrillation. Methods We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of outpatient office visits, to estimate the use of warfarin and DOACs between 2009 and 2014. Results Overall, visits with anticoagulation use increased from 2.05 (95% confidence interval CI, 1.82-2.27) to 2.83 (95% CI, 2.49-3.17) million (M) quarterly visits ( P < .001). Of these, DOAC use has grown to 4.21M (95% CI, 3.63M-4.79M; 38.2% of total) treatment visits in 2014 since their introduction in 2010. Use of all oral anticoagulants in treatment visits for atrial fibrillation has increased from 0.88M (95% CI, 0.74M-1.02M) to 1.72M (95% CI, 1.47M-1.97M; P < .001), with similar DOAC and warfarin use in 2014. Atrial fibrillation visits with anticoagulant use increased from 51.9% (95% CI, 50.4%-53.8%) to 66.9% (95% CI, 65.0%-69.3%) between 2009 and 2014 ( P < .001). In 2014, rivaroxaban was the most commonly prescribed DOAC for atrial fibrillation (47.9% of office visits), followed by apixaban (26.5%) and dabigatran (25.5%). Conclusions Direct oral anticoagulants have been adopted rapidly, matching the use of warfarin, and are associated with increased use of oral anticoagulation for patients with atrial fibrillation.
Little is known regarding the adoption of direct thrombin inhibitors in clinical practice. We examine trends in oral anticoagulation for the prevention of thromboembolism in the United States.
We ...used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of office-based providers, to quantify patterns of oral anticoagulant use among all subjects and stratified by clinical indication. We quantified oral anticoagulant expenditures using the IMS Health National Prescription Audit. Between 2007 and 2011, warfarin treatment visits declined from ≈2.1 million (M) quarterly visits to ≈1.6M visits. Dabigatran use increased from 0.062M quarterly visits (2010Q4) to 0.363M visits (2011Q4), reflecting its increasing share of oral anticoagulant visits from 3.1% to 18.9%. In contrast to warfarin, the majority of dabigatran visits have been for atrial fibrillation, though this proportion decreased from 92% (2010Q4) to 63% (2011Q4), with concomitant increases in dabigatran's off-label use. Among atrial fibrillation visits, warfarin use decreased from 55.8% visits (2010Q4) to 44.4% (2011Q4), whereas dabigatran use increased from 4.0% to 16.9%. Of atrial fibrillation visits, the fraction not treated with any oral anticoagulants has remained unchanged at ≈40%. Expenditures related to dabigatran increased rapidly from $16M in 2010Q4 to $166M in 2011Q4, exceeding expenditures on warfarin ($144M) in 2011Q4.
Dabigatran has been rapidly adopted into ambulatory practice in the United States, primarily for treatment of atrial fibrillation, but increasingly for off-label indications. We did not find evidence that it has increased overall atrial fibrillation treatment rates.
This Viewpoint details the development and regulatory path of aducanumab, a human IgG1 monoclonal antibody to treat Alzheimer disease, including termination of 2 clinical trials, identification of ...conflicting evidence of efficacy, and the FDA advisory committee vote against approval (final decision pending).
This Viewpoint proposes strategies to ensure adequate supply and distribution of medication in the US during and beyond the coronavirus pandemic, including development and funding of a national ...essential medicines supply, allocation strategies to prevent stockpiling, and funding of home delivery services to ensure adequate access for lower income and underserved populations.
IMPORTANCE: Prescription and over-the-counter medicines and dietary supplements are commonly used, alone and together, among older adults. However, the effect of recent regulatory and market forces ...on these patterns is not known. OBJECTIVES: To characterize changes in the prevalence of medication use, including concurrent use of prescription and over-the-counter medications and dietary supplements, and to quantify the frequency and types of potential major drug-drug interactions. DESIGN, SETTING, AND PARTICIPANTS: Descriptive analyses of a longitudinal, nationally representative sample of community-dwelling older adults 62 to 85 years old. In-home interviews with direct medication inspection were conducted in 2005-2006 and again in 2010-2011. The dates of the analysis were March to November 2015. We defined medication use as the use of at least 1 prescription or over-the-counter medication or dietary supplement at least daily or weekly and defined concurrent use as the regular use of at least 2 medications. We used Micromedex to identify potential major drug-drug interactions. MAIN OUTCOMES AND MEASURES: Population estimates of the prevalence of medication use (in aggregate and by therapeutic class), concurrent use, and major drug-drug interactions. RESULTS: The study cohort comprised 2351 participants in 2005-2006 and 2206 in 2010-2011. Their mean age was 70.9 years in 2005-2006 and 71.4 years in 2010-2011. Fifty-three percent of participants were female in 2005-2006, and 51.6% were female in 2010-2011. The use of at least 1 prescription medication slightly increased from 84.1% in 2005-2006 to 87.7% in 2010-2011 (P = .003). Concurrent use of at least 5 prescription medications increased from 30.6% to 35.8% (P = .02). While the use of over-the-counter medications declined from 44.4% to 37.9%, the use of dietary supplements increased from 51.8% to 63.7% (P < .001 for both). There were clinically significant increases in the use of statins (33.8% to 46.2%), antiplatelets (32.8% to 43.0%), and omega-3 fish oils (4.7% to 18.6%) (P < .05 for all). In 2010-2011, approximately 15.1% of older adults were at risk for a potential major drug-drug interaction compared with an estimated 8.4% in 2005-2006 (P < .001). Most of these interacting regimens involved medications and dietary supplements increasingly used in 2010-2011. CONCLUSIONS AND RELEVANCE: In this study, the use of prescription medications and dietary supplements, and concurrent use of interacting medications, has increased since 2005, with 15% of older adults potentially at risk for a major drug-drug interaction. Improving safety with the use of multiple medications has the potential to reduce preventable adverse drug events associated with medications commonly used among older adults.
Despite their increasingly important role in health care delivery, little is known about the availability, and characteristics, of community pharmacies in the United States.
(1) To examine trends in ...the availability of community pharmacies and pharmacy characteristics (24-hour, drive-up, home delivery, e-prescribing, and multilingual staffing) associated with access to prescription medications in the U.S. between 2007 and 2015; and (2) to determine whether and how these patterns varied by pharmacy type (retail chains, independents, mass retailers, food stores, government and clinic-based) and across counties.
Retrospective analysis using annual data from the National Council for Prescription Drug Programs. Pharmacy locations were mapped and linked to the several publically-available data to derive information on county-level population demographics, including annual estimates of total population, percent of population that is non-English speaking, percent with an ambulatory disability and percent aged ≥65 years. The key outcomes were availability of pharmacies (total number and per-capita) and pharmacy characteristics overall, by pharmacy type, and across counties.
The number of community pharmacies increased by 6.3% from 63,752 (2007) to 67,753 (2015). Retail chain and independent pharmacies persistently accounted for 40% and 35% of all pharmacies, respectively, while the remainder were comprised of mass retailer (12%), food store, (10%), clinic-based (3%) or government (<1%) pharmacies. With the exception of e-prescribing, there was no substantial change in pharmacy characteristics over time. While the number of pharmacies per 10,000 people (2.11) did not change between 2007 and 2015 at the national-level, it varied substantially across counties ranging from 0 to 13.6 per-capita in 2015. We also found that the majority of pharmacies do not offer accommodations that facilitate access to prescription medications, including home-delivery, with considerable variation by pharmacy type and across counties. For example, the provision of home-delivery services ranged from less than <1% of mass retailers to 67% of independent stores and was not associated with county demographics, including ambulatory disability population and percent of the population aged ≥65 years.
Despite modest growth of pharmacies in the U.S., the availability of pharmacies, and pharmacy characteristics associated with access to prescription medications, vary substantially across local areas. Policy efforts aimed at improving access to prescription medications should ensure the availability of pharmacies and their accommodations align with local population needs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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