Gaps in Evidence-Based Therapy Use in Insured Patients in the United States With Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease.

Background Evidence-based therapies are generally underused for cardiovascular risk reduction; however, less is known about contemporary patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Methods and Results Pharmacy and medical claims data from within Anthem were queried for patients with established atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Using an index date of April 18, 2018, we evaluated the proportion of patients with a prescription claim for any of the 3 evidence-based therapies on, or covering, the index date ±30 days: high-intensity statin, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonist. The potential benefit of achieving 100% adoption of all 3 evidence-based therapies was simulated using pooled treatment estimates from clinical trials. Of the 155 958 patients in the sample, 24.7% were using a high-intensity statin, 53.1% were using an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and 9.9% were using either an sodium glucose cotransporter-2 inhibitor or glucagon-like peptide-1 receptor agonists. Overall, only 2.7% of the population were covered by prescriptions for all 3 evidence-based therapies, and 37.4% were on none of them. Over a 12-month period, 70.6% of patients saw a cardiologist, while only 18% saw an endocrinologist. Increasing the use of evidence-based therapies to 100% over 3 years of treatment could be expected to reduce 4546 major atherosclerotic cardiovascular events (myocardial infarction, stroke, or cardiovascular death) in eligible but untreated patients. Conclusions Alarming gaps exist in the contemporary use of evidence-based therapies in this large population of insured patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. These data provide a call to action for patients, providers, industry, regulators, professional societies, and payers to close these gaps in care.

Antibiotic Use Among Residents Receiving Skilled Nursing Care in 29 U.S. Nursing Homes.

BACKGROUND: Data describing antibiotic use in U.S. nursing homes remain limited. We report antibiotic use among skilled nursing facility residents from 29 U.S. nursing homes and assessed correlations between antibiotics prescribed to residents in skilled care and nursing home characteristics. DESIGN: Retrospective cohort study. SETTING: Twenty-nine U.S. nursing homes in the same healthcare corporation. PARTICIPANTS: Residents receiving skilled care in 2016. MEASUREMENTS: We used pharmacy invoice and nursing home census data to calculate the days of antibiotic therapy per 1,000 days of skilled care (1,000 DOSC), the rate of antibiotic starts per 1,000 DOSC, the length of antibiotic therapy, and the average antibiotic spectrum index. We also assessed correlations between antibiotic use and nursing home characteristics. RESULTS: Antibiotics accounted for an average of 9.6% (±0.6%) of systemic medications prescribed among residents receiving skilled care. On average, 26.8% (±2.9%) of antibiotics were intravenous. Fluoroquinolones were prescribed at the highest rates (19% across all facilities), followed by beta-lactam/beta-lactamase inhibitors (11%), first- and second-generation cephalosporins, sulfonamides, and oral tetracyclines (each at 9%). Both the proportion of residents using enrolled in Medicare and number of unique prescribers responsible for systemic prescriptions positively correlated with the rate of antibiotic starts. CONCLUSIONS: Our study demonstrates that pharmacy invoices represent a useful and preexisting source of data for assessing antibiotic prescriptions among individuals receiving skilled nursing care. The correlation between the number of unique prescribers and antibiotic starts suggests that prescribers are central to efforts to improve antibiotic use in nursing homes.

A real-world data approach to determine the optimal dosing strategy for pembrolizumab.

INTRODUCTION: Cancer drug therapy costs continue to rise and threaten the sustainability of Canada's public healthcare system. Previous studies have calculated potential savings utilizing different dosing regimens of cancer treatments. Our objectives were to determine the financial impact of drug wastage and to explore cost-effective dosing regimens for pembrolizumab. METHODS: This was a retrospective study reviewing data for non-small cell lung cancer and melanoma patients at all six BC Cancer Regional Centres during fiscal years 2017 and 2018. Pembrolizumab waste amounts recorded in pharmacy wastage logs were totalled. Estimates of the number of vials used were compared between vial sharing and non-vial sharing practices to determine the cost differences. Costs for dosing regimens used during fiscal years 2017 and 2018 were compared to 2 mg/kg weight-based dosing (to a maximum of 200 mg), 2 mg/kg dosing rounding down within 5% and 10%, and flat dosing of 200 mg. RESULTS: There were a total of 202 non-small cell lung cancer and 182 melanoma patients with 2948 doses dispensed. Documented wastage was valued at $1,829,047.44 (8.65%) and across all six centres, vial sharing could reduce costs by $3,207,600.00 using the 100 mg vials. Compared to fiscal years 2017 and 2018, 2 mg/kg dosing (to a maximum of 200 mg) was the most cost-effective, decreasing costs by $222,719.20; flat dosing of 200 mg was the most expensive, increasing costs by $6,625,260.40. CONCLUSIONS: Having smaller vial sizes, practicing vial sharing, and using weight-based dosing all improve cost savings. Further investigations on the allocation of resources to optimize drug use and minimize wastage are needed.

The outcome of domiciliary medication reviews and their impact: a systematic review.

OBJECTIVES: Medication reviews in the domiciliary setting are becoming more prevalent internationally. Understanding the benefits of these reviews is essential to ensuring quality healthcare services. To date there has not been a systematic evaluation of the outcomes of these services and their impact on patients. A systematic review of the literature was undertaken with a view to understanding the impact of medication reviews in this setting. Controlled and uncontrolled studies were included. Outcomes were categorised according to the ECHO model. A narrative synthesis was developed. KEY FINDINGS: Nineteen out of 31 papers included demonstrated an improvement in outcome. Clinical outcomes were the most commonly measured and humanistic outcomes the least commonly measured. Domiciliary medication reviews (DMRs) services are presented as providing benefit. However, it is difficult to quantify the impact of services from the published outcomes. SUMMARY: Future work should focus on demonstrating the meaningful changes to patients that DMRs have enabled.

Antibiotic prescriptions in Italian hospitalised children after serial point prevalence surveys (or pointless prevalence surveys): has anything actually changed over the years?

BACKGROUND: Point prevalence surveys have been used in several studies to provide immediate and easily comparable information about antibiotic use and showed that about one third of hospitalised children had on ongoing antimicrobial prescription during their hospital admission. The aim of this study, as part of the Global Antimicrobial Resistance, Prescribing and Efficacy in Neonates and Children project, is to describe antimicrobial prescriptions among hospitalised children in four tertiary care hospitals in Italy to show if something has changed over the years. METHODS: Four tertiary care Italian's hospitals joined three Point Prevalence Surveys (PPSs) in three different period of the year. All children under 18 years of age with an ongoing antimicrobial prescription, admitted on the participating wards at 8 o'clock in the morning of the selecting day were enrolled. RESULTS: A total of 1412 patients (475 neonates and 937 children) were admitted in the days of three PPSs. Overall, among the total admitted patients, 565 patients (40%) had an ongoing antimicrobial prescription in the days of the survey A total of 718 antibiotics were administered in the 485 admitted children and 133 in neonates. The most common indications for antibiotic therapy in children was Lower respiratory tract infections (244/718, 34%), while in neonates were prophylaxis for medical problems (35/133, 26.3%), newborn prophylaxis for newborn risk factors (29/133, 21.8%) and prophylaxis for surgical disease (15/133, 11.3%). CONCLUSIONS: Based on our results, it appears that nothing has changed since the last PPS and that the quality improved targets, underlyined in previous studies, are always the same. Serial PPSs can be part of AMS strategies but they are not sufficient alone to produce changes in clinical practice.

Review of purchases of unapproved medications by the Veterans Health Administration.

PURPOSE: Many medications that were marketed prior to 1962 but lack Food and Drug Administration (FDA) approval are prescribed in the United States. Usage patterns of these "unapproved medications" are poorly elucidated, which is concerning due to potential lack of data on safety and efficacy. The purpose of this project was to characterize purchases of unapproved medications within the Veterans Health Administration (VHA) by type, frequency, and cost. METHODS: VHA purchasing databases were used to create a list of all products with National Drug Codes (NDCs) purchased nationwide in fiscal year 2016 (FY16). This list was compared to FDA databases to identify unapproved prescription medications. For each identified combination of active pharmaceutical ingredient (API) and route of administration ("API/route combination"), numbers of packages purchased and associated costs were added. RESULTS: VHA pharmacy purchasing records contained 3,299 unapproved products with NDCs in FY16. After excluding equipment, nutrition products, compounding ingredients, nonmedication products, and duplicate NDCs, there were 600 unique NDCs associated with 130 distinct API/route combinations. The most commonly acquired product was prescription sodium fluoride dental paste (350,775 packages). The greatest pharmaceutical expenditure was for sodium hyaluronate injection ($24.5 million). Unapproved products accounted for less than 1% of overall VHA pharmacy purchasing in FY16. CONCLUSION: VHA purchased many unapproved prescription products in FY16 but is taking action to address use of such products in consideration of safety and efficacy data and available alternatives.

The technical and economic impact of veterinary interventions aimed at reducing antimicrobial use on broiler farms.

Antimicrobial resistance is a global threat for both human and animal health. One of the main drivers of antimicrobial resistance is inappropriate antimicrobial use in livestock production. The aim of this study was to examine the technical and economic impact of tailor-made interventions, aimed at reducing antimicrobial use in broiler production. Historical (i.e., before intervention) and observational (i.e., after intervention) data were collected at 20 broiler farms. Results indicate that average daily gain and mortality generally increased after intervention, whereas feed conversion and antimicrobial use decreased. Economic performance after interventions was generally higher than before the interventions. Sensitivity analyses on price changes confirm the robustness of the findings.

[Surveillance of antibiotic agents according to § 23 of the German Infection Protection Act-data and results from hospitals in Frankfurt am Main, Germany, 2012-2017]. / Antibiotika-Verbrauchs-Surveillance nach § 23 Infektionsschutzgesetz ­ Daten und Erfahrungen aus den Krankenhäusern in Frankfurt am Main, 2012­2017.

BACKGROUND: Since 2011, German hospitals have been requested to record and evaluate antibiotic use in their institution. In this publication, the use of antibiotics in hospitals belonging to the administrative district Frankfurt/Main between 2012 and 2017 is presented and discussed with regards to the targets set in 2014. These targets are to improve the perioperative prophylaxis, reduce the use of cefuroxime, and increase the penicillin/cephalosporin ratio. METHODS: Since 2012, hospitals in Frankfurt/Main have been transmitting the defined daily doses (DDD) of all antibiotics used, the absolute number of patients, and their days of treatment. Since 2013, the data have also distinguished between intensive care and other units. The Frankfurt health authority calculated the total number of antibiotics and the DDD/100 patient days for all hospitals combined as well as for every hospital compared to each other. RESULTS: From 2012 to 2017, the number of absolute annual patient days increased from 1,592,161 to 1,615,180. Antibiotic use decreased from 1,073,975 DDD to 953,349 DDD, leading to a decrease from 67.5 DDD per 100 patient days to 59.0 DDD per 100 patient days. Cefuroxime was the most frequently used antibiotic in all hospitals. The use of cefuroxime showed a significant decrease between 2012 and 2017 (from 250,398 in 2012 to 165,160 DDD in 2017, a decrease of 34%). The use of ceftriaxone was reduced by 27%, ciprofloxacin by 9%, and levofloxacin by 16%. DISCUSSION: The targets set in 2014 were reached in the entirety of Frankfurt hospitals. However, there were significant differences between the hospitals taking part. The results were given as feedback to the hospitals in order to support their efforts in further improving antibiotic stewardship.

Variability in the community consumption of antibiotics: a problem in Europe, Spain and Asturias.

Increasing bacterial resistance is strictly correlated to the increasing use of antibiotics, currently constituting a public health problem. The aim of this study was to describe the consumption of antibiotics in Asturias, an autonomous community in northwestern Spain, and compare the results obtained with data from elsewhere in Spain and other European countries. A descriptive study was carried out on the use of antibacterial drugs for systemic use, ATC code J01 in Asturias in 2011-2015. Data were obtained from the prescription-billing information system charged to the Health Service of Asturias. The consumption data are expressed in daily doses per 1,000 inhabitants and day (DHD), and number of packages per thousand inhabitants per day. The average weighted consumption of antibiotics for systemic use in the Asturian community was 26.23 daily doses per 1000 inhabitants per day (DHD) in 2015. This figure was higher than that of the EU/EEA population, which was 22.4 DHD, and that of the whole of Spain at 22.2 DHD. There is a wide variability in consumption among the different areas of the Asturian region. This variability is common to the rest of the country and Europe. It can be explained by the influence of the data used in the indicators and by the variability in medical practice. Priority should be given to homologating consumer-monitoring information systems and implementing national strategies aimed at providing more information to medical practitioners, encouraging the appropriate use of antibiotics so as to reduce variability, consumption and resistance.

Cost-effectiveness of a clinical medication review in vulnerable older patients at hospital discharge, a randomized controlled trial.

Background Drug-related problems (DRP) following hospital discharge may cause morbidity, mortality and hospital re-admissions. It is unclear whether a clinical medication review (CMR) and counseling at discharge is a cost-effective method to reduce DRP. Objective To assess the effect of a CMR on health care utilization and to investigate whether CMR is a cost-effective method to reduce DRP in older polypharmacy patients discharged from hospital. Setting 24 community pharmacies in the Netherlands. Method A cluster-randomized controlled trial with an economic evaluation. Community pharmacies were randomized to those providing a CMR, counseling and follow-up at discharge and those providing usual care. Main outcome measures Change in the number of DRP after 1 year of follow-up and costs of health care utilization during follow-up. In 216 patients the use of health care was prospectively assessed. Missing data on effects and costs were imputed using multiple imputation techniques. Bootstrapping techniques were used to estimate the uncertainty around the differences in costs and incremental cost-effectiveness ratios. Results CMR resulted in a small reduction of DRP. The proportion of patients readmitted to the hospital during 6 months of follow-up was significantly higher in the intervention group than in the control group (46.4 vs. 20.9%; p < 0.05). Health care costs were higher in the intervention group, although not statistically significant. The costs of reducing one DRP by a CMR amounted to €8270. Conclusion A CMR in vulnerable older patients at hospital discharge led to a small reduction in DRP. Because of a significantly higher use of health care and higher number of re-hospitalisations post CMR, the present study data indicate that performing the intervention in this patient population is not cost-effective.

Factors Associated with the Initiation of Long-Acting Injectable Paliperidone Palmitate Versus Aripiprazole Among Medicaid Patients with Schizophrenia: An Observational Study.

INTRODUCTION: Factors underlying the selection of antipsychotics for patients with schizophrenia are poorly understood. This study investigated variables associated with initiation of treatment with the long-acting injectables paliperidone palmitate (LAI-PP) and aripiprazole LAI (LAI-AP) in Medicaid patients with schizophrenia. METHODS: Adults with at least one medical or pharmacy claim for LAI-PP or LAI-AP from 1 January 2013 to 31 December 2016 were selected from the IBM® MarketScan® Medicaid Database. The date of the first LAI-PP or LAI-AP claim was the index date. Patients who had at least two medical claims, on different days, for a schizophrenia diagnosis and at least 12 months of continuous health plan enrollment prior to index date were included in the analysis. Multivariable logistic regression was performed to determine the factors associated with the initiation of LAI-PP versus LAI-AP. RESULTS: Of included patients, 5501 initiated LAI-PP and 1449 initiated LAI-AP. Patients more likely to initiate LAI-PP versus LAI-AP were older, male, or African American (all p < 0.01). Patients with obesity (odds ratio [OR] 0.84; 95% confidence interval [CI] 0.71, 0.98), post-traumatic stress disorder (OR 0.76; 95% CI 0.63, 0.92), or prior oral antipsychotic use (OR 0.66; 95% CI 0.55, 0.79) were less likely to initiate LAI-PP; whereas, patients with nonorganic psychoses (OR 1.35; 95% CI 1.18, 1.55) or prior use of other injectable antipsychotics (OR 1.26; 95% CI 1.09, 1.47) were more likely to initiate LAI-PP versus LAI-AP. Patients with at least two all-cause hospitalizations were 1.37 times more likely to initiate LAI-PP vs LAI-AP (OR 1.37; 95% CI 1.18, 1.60). CONCLUSION: Factors associated with initiating LAI-PP and LAI-AP differed. Notably, patients who initiated LAI-PP had greater prior use of medical services than LAI-AP patients. Understanding prescribing practices may help optimize treatment strategies and improve disease management. FUNDING: Janssen Scientific Affairs, LLC.

Assessment of vancomycin utilization among Lebanese hospitals.

OBJECTIVES: To assess the appropriateness of vancomycin dosing and monitoring at Lebanese hospitals. METHODS: This was a multicenter retrospective study conducted at 3 Lebanese hospitals between January and March 2018. Patients 18 years of age and older treated with vancomycin for a systemic infection or prophylaxis were eligible for study enrollment. Consistency with the Infectious Diseases Society of America guidelines was evaluated to determine whether the dose of vancomycin was appropriate, as well as for the time of trough measurement, and the target concentration obtained. RESULTS: From a total of 120 patients who met the inclusion criteria, only 11 (12%) were given the appropriate maintenance dose of vancomycin with respect to actual body weight. The trough levels were monitored for 67 (55.8%) patients, with 20 (29.9%) of these patients achieving appropriate therapeutic trough levels of 15-20 mg/l. The trough concentration time measurement before the fourth dose was only carried out in 28 (41.8%) of the 67 patients. CONCLUSION: This study reveals a gap between the appropriate utilization of vancomycin with respect to the international guidelines in the studied Lebanese hospitals. It highlights the need for dosing and monitoring protocols suitable for vancomycin utilization in these hospitals.

Impact of Oncology Drug Shortages on Chemotherapy Treatment.

Prescription drug shortages began to increase markedly in the mid-2000s, including sterile injectable products such as chemotherapy drugs. Using Medicare claims linked to Surveillance Epidemiology and End Results (SEER), we examined outpatient chemotherapy use during shortage periods relative to the months before and after a shortage for newly diagnosed patients with breast, colorectal, leukemia, lung, lymphoma, ovarian, or pancreatic cancer (N = 182,470). For most drugs, we found little impact of shortages on either the fraction of patients receiving that drug or the quantity provided. In some cases, we found declines in utilization: 4% for doxorubicin and fluorouracil; 2.9% for oxaliplatin; and about 1% for cytarabine, dacarbazine, and leuprolide. Although shortages for a few drugs resulted in substantial reductions in use, in most cases, they resulted in little to no reduction. We discuss potential explanations for these counterintuitive findings, including potential limitations of current drug shortage reporting methods.

Comparative Effectiveness of Medication Therapy Management Eligibility Criteria Across Racial/Ethnic Groups.

BACKGROUND/OBJECTIVES: Previous research indicates that eligibility criteria for medication therapy management (MTM) services in Medicare prescription drug (Part D) plans, defined under the Medicare Modernization Act (MMA), are associated with racial/ethnic disparities and ineffective in identifying individuals with medication utilization issues. Our study's objective was to determine the comparative effectiveness of MTM eligibility criteria under MMA and in the Affordable Care Act (ACA) in identifying patients with medication utilization issues across racial/ethnic groups. DESIGN: ACA and MMA MTM eligibility criteria were compared on proportions of eligible individuals among patients with medication utilization issues. Multinomial logistic regression was conducted to control for patient/community characteristics. Need-based and demand-based analyses were used to determine disparities due to need and demand for healthcare. Main/sensitivity analyses were conducted for the range of eligibility thresholds. SETTING: Medicare data (2012-2013) linked to Area Health Resources Files. PARTICIPANTS: A total of 964 610 patients 65 years or older. MEASUREMENTS: Medication safety/adherence measures, developed primarily by the Pharmacy Quality Alliance, were used to determine medication utilization issues. RESULTS: Higher proportions of patients were eligible based on ACA than MMA MTM eligibility criteria. For example, in 2013, proportions based on ACA and MMA MTM eligibility criteria would be 99.7% and 26.2%, respectively, in the main analysis (p < .001); in the demand-based main analysis, ACA criteria were associated with 13.6% and 9.8%, respectively, higher effectiveness than MMA criteria among non-Hispanic blacks and Hispanics than non-Hispanic whites. CONCLUSION: ACA MTM eligibility criteria are more effective than MMA criteria in identifying older patients needing MTM, particularly among minorities. J Am Geriatr Soc 67:581-587, 2019.

Assessment of prior opioid tolerance among new users of fentanyl transdermal system in FDA's Sentinel System.

PURPOSE: Fentanyl transdermal system (FTS) is intended only for patients with prior opioid tolerance. The purpose of this study is to identify the proportion of new FTS users who had evidence of prior opioid tolerance, by dosage strength, in FDA's Sentinel System. METHODS: We identified new FTS episodes (183-day washout) from 2009 through 2013. Members were <65 years and enrolled in medical and pharmacy coverage for 183 days prior to initial FTS dispensing (index). We assessed the proportion of users with prior tolerance stratified by dosage strength of FTS using four definitions of opioid tolerance: ≥30-mg oxycodone equivalents/day in each of 7 consecutive days immediately prior to index; ≥30-mg oxycodone equivalents/day for any 7 days in the 30 days prior to index (secondary); any dose in each of 7 days in the 7 consecutive days immediately prior to index (tertiary); and any dose for any 7 days in the 30 days prior to index (quaternary). RESULTS: Of 44 450 episodes of 25 mcg/hr FTS, 37% met the primary definition, and 77% met the quaternary definition. Of 3507 episodes of 100 mcg/hr FTS, 57% and 74% met the primary and quaternary definitions, respectively. Those aged 25 to 34 years had the highest proportion of episodes with prior tolerance; those aged 55 to 64 accounted for more of the episodes overall. CONCLUSIONS: In Sentinel, many new users of FTS did not have evidence of prior opioid tolerance by the primary definition, ie, the product label definition, which is the minimum standard for the lowest FTS dose (12 mcg/hr), especially at the highest strength (100 mcg/hr). Validation of this metric is warranted, but our findings suggest the need for further prescriber education regarding appropriate prescribing of FTS.

A review of the Ghana National Health Insurance Scheme claims database: possibilities and limits for drug utilization research.

BACKGROUND: There are inadequate data on prescribed drug utilization in Sub-Saharan Africa (SSA). Drug utilization research (DUR) in this region is hampered by lack of access to databases that capture prescribed drug utilization such as health insurance claims, electronic medical records and disease registries. The primary objective of this MiniReview was to describe the content of the NHIS claims database in the context of the health care system in Ghana. We will also review the possibilities and limitations of analysing this novel database for drug utilization research (DUR) in Ghana. METHODS: We reviewed the history, composition of the database, coverage and health systems in Ghana. To demonstrate the application of the NHIS claims database for DUR, we reviewed the NHIS' drug formulary (NHIS medicines' list), assessed and quantified the utilization of the top 25 most commonly prescribed medicines and their distributions by age, sex, region of residence and by MDCs. RESULTS: As of December 2014, about 40% (~10.5 million) of the Ghanaian population were active beneficiaries of NHIS. There were 1.43 million unique patients in the NHIS claims database who received services from about 81 providers located in 9 out of the 10 regions in Ghana. The mean age of this sample of beneficiaries was 31 (standard deviation, 22) years, a third of whom were aged <18 years old. Nearly, 2 out of every 3 beneficiaries were females. On average, there were approximately 3 outpatient visits per beneficiary in 2015. There were about 522 unique drugs on the NHIS medicine list. Overall, analgesic was the most prescribed class of medicine (mostly paracetamol and diclofenac). Antimalarials, artemether-lumefantrine, were observed as the second most prescribed medicines followed by anti-infectives (metronidazole) and antihypertensives (amlodipine). CONCLUSION: The Ghana NHIS claims database is a great resource for DUR. This database could also be extended to facilitate pharmacoepidemiological and other health services' research especially if transformed into one of the existing standardized common data models.

Payments from drug companies to physicians are associated with higher volume and more expensive opioid analgesic prescribing.

BACKGROUND: While the rise in opioid analgesic prescribing and overdose deaths was multifactorial, financial relationships between opioid drug manufacturers and physicians may be one important factor. METHODS: Using national data from 2013 to 2015, we conducted a retrospective cohort study linking the Open Payments database and Medicare Part D drug utilization data. We created two cohorts of physicians, those receiving opioid-related payments in 2014 and 2015, but not in 2013, and those receiving opioid-related payments in 2015 but not in 2013 and 2014. Our main outcome measures were expenditures on filled prescriptions, daily doses filled, and expenditures per daily dose. For each cohort, we created a comparison group that did not receive an opioid-related payment in any year and was matched on state, specialty, and baseline opioid expenditures. We used a difference-in-differences analysis with linear generalized estimating equations regression models. RESULTS: We identified 6,322 physicians who received opioid-related payments in 2014 and 2015, but not in 2013; they received a mean total of $251. Relative to comparison group physicians, they had a significantly larger increase in mean opioid expenditures ($6,171; 95% CI: 4,997 to 7,346), daily doses dispensed (1,574; 95%CI: 1,330 to 1,818) and mean expenditures per daily dose ($0.38; 95% CI: 0.29 to 0.47). We identified 8,669 physicians who received opioid-related payments in 2015, but not in 2013 or 2014; they received a mean total of $40. Relative to comparison physicians, they also had a larger increase in mean opioid expenditures ($1,031; 95% CI: 603 to 1,460), daily doses dispensed (557; 95% CI: 417 to 697), and expenditures per daily dose ($0.06; 95% CI: 0.002 to 0.13). CONCLUSIONS: Our findings add to the growing public policy concern that payments from opioid drug manufacturers can influence physician prescribing. Interventions are needed to reduce such promotional activities or to mitigate their influence.

Initial Antihypertensive Treatment Strategies and Therapeutic Inertia.

In many hypertensive patients, treatment is not upgraded despite lack of blood pressure control because of therapeutic inertia. Information is limited, however, on the extent of this phenomenon in real-life medicine. We studied 125 635 patients (age 40-85 years) from the Lombardy region (Italy) who started antihypertensive treatment with 1 drug (n=100 982) or a 2-drug fixed-dose or free combination (n=24 653). A log-binomial regression model was used to estimate the prevalence ratio of combination therapy in relation to the initial treatment strategy. In the initial monotherapy group, patients under drug combinations were 22%, 27%, 32%, and 36% at 6 months, 1, 2, and 3 years later. In the initial combination treatment group, the corresponding percentages were 85%, 82%, 79%, and 78%. This translated into a markedly greater covariate-adjusted propensity of being under a multidrug prescription throughout the follow-up: 3.92 (95% CI, 3.84-4.00) after 6 months and 3.18 (3.12-3.25), 2.56 (2.51-2.60), and 2.23 (2.19-2.27) after 1, 2 and 3 years of treatment. In a propensity score analysis, initial 2-drug combination treatment was also associated with significant reductions in the risk of death (-20%, 11% to 28%) and hospitalization for cardiovascular events (-16%, 10% to 21%) compared with initial monotherapy. Thus, in real life, a large number of patients prescribed initial monotherapy fails to move to combination treatment, as recommended by guidelines. This implies that therapeutic inertia frequently prevents proper treatment uptitration, thereby playing a major role in the low rate of hypertension control that exists worldwide.

Effect of European Medicines Agency's restrictions on trimetazidine utilization in Portugal.

PURPOSE: Following safety concerns regarding trimetazidine, the European Medicines Agency (EMA) recommended restrictions on its use. Our objective was to determine the impact of regulatory actions on trimetazidine utilization in Portugal. METHODS: Retrospective interrupted time-series analysis of monthly ambulatory pharmacy reimbursement records for the Portuguese National Health Service between January 2006 and December 2015. Regulatory actions were identified by searching the EMA, Portuguese Medicines Authority, and European Commission's websites. Concurrent factors in the same period were also identified. The main outcome was the dispensing of trimetazidine-containing products per month in Portugal. RESULTS: Two interruption periods were defined in the series: May 2011, when EMA announced it would review trimetazidine safety, and June 2012 to January 2013, when EMA announced it had reached a final opinion recommending restrictions; the European Commission approved EMA's recommendation; the Portuguese Medicines Authority issued safety alerts, changed the summary of product characteristics, and approved a direct health-care professional letter; and a regional bulletin was issued. Interruption 1 had no effect on trimetazidine use, but interruption 2 resulted in decreases in level and trend-from 8.3 million defined daily doses in 2010 to 2.8 million in 2015. After interruption 2, trimetazidine use tended towards a lower steady state. CONCLUSIONS: There was a significant decrease in trimetazidine use in Portugal following a complex intervention that included safety alerts, changes to the summary of product characteristics, a direct health-care professional letter, and a regional drug bulletin. No effect was seen when EMA announced its review of trimetazidine safety.

Getting What We Pay For: How Do Risk-Based Payments to Medicare Advantage Plans Compare with Alternative Measures of Beneficiary Health Risk?

OBJECTIVE: To estimate the relative health risk of Medicare Advantage (MA) beneficiaries compared to those in Traditional Medicare (TM). DATA SOURCES/STUDY SETTING: Medicare claims and enrollment records for the sample of beneficiaries enrolled in Part D between 2008 and 2015. STUDY DESIGN: We assigned therapeutic classes to Medicare beneficiaries based on their prescription drug utilization. We then regressed nondrug health spending for TM beneficiaries in 2015 on demographic and therapeutic class identifiers for 2014 and used coefficients from this regression to predict relative risk of both MA and TM beneficiaries. PRINCIPAL FINDINGS: Based on prescription drug utilization data, beneficiaries enrolled in MA in 2015 had 6.9 percent lower health risk than beneficiaries in TM, but differences based on coded diagnoses suggested MA beneficiaries were 6.2 percent higher risk. The relative health risk based on drug usage of MA beneficiaries compared to those in TM increased by 3.4 p.p. from 2008 to 2015, while the relative risk using diagnoses increased 9.8 p.p. CONCLUSIONS: Our results add to a growing body of evidence suggesting MA receives favorable, or, at worst, neutral selection. If MA beneficiaries are no healthier and no sicker than similar beneficiaries in TM, then payments to MA plans exceed what is warranted based on their health status.