Matthew Daubresse

Ambulatory diagnosis and treatment of nonmalignant pain in the United States, 2000-2010.

Background:Escalating rates of prescription opioid use and abuse have occurred in the context of efforts to improve the treatment of nonmalignant pain. Objective:The aim of the study was to characterize the diagnosis and management of nonmalignant pain in ambulatory, office-based settings in the United States between 2000 and 2010. Design, Setting, and Participants:Serial cross-sectional and multivariate regression analyses of the National Ambulatory Medical Care Survey (NAMCS), a nationally representative audit of office-based physician visits, were conducted. Measures:(1) Annual visit volume among adults with primary pain symptom or diagnosis; (2) receipt of any pain treatment; and (3) receipt of prescription opioid or nonopioid pharmacologic therapy in visits for new musculoskeletal pain. Results:Primary symptoms or diagnoses of pain consistently represented one-fifth of visits, varying little from 2000 to 2010. Among all pain visits, opioid prescribing nearly doubled from 11.3% to 19.6%, whereas nonopioid analgesic prescribing remained unchanged (26%–29% of visits). One-half of new musculoskeletal pain visits resulted in pharmacologic treatment, although the prescribing of nonopioid pharmacotherapies decreased from 38% of visits (2000) to 29% of visits (2010). After adjusting for potentially confounding covariates, few patient, physician, or practice characteristics were associated with a prescription opioid rather than a nonopioid analgesic for new musculoskeletal pain, and increases in opioid prescribing generally occurred nonselectively over time. Conclusions:Increased opioid prescribing has not been accompanied by similar increases in nonopioid analgesics or the proportion of ambulatory pain patients receiving pharmacologic treatment. Clinical alternatives to prescription opioids may be underutilized as a means of treating ambulatory nonmalignant pain.

Emergency Department Visits by Adults for Psychiatric Medication Adverse Events

IMPORTANCE In 2011, an estimated 26.8 million US adults used prescription medications for mental illness. OBJECTIVE To estimate the numbers and rates of adverse drug event (ADE) emergency department (ED) visits involving psychiatric medications among US adults between January 1, 2009, and December 31, 2011. DESIGN AND SETTING Descriptive analyses of active, nationally representative surveillance of ADE ED visits using the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance system and of drug prescribing during outpatient visits using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. PARTICIPANTS Medical records from national probability samples of ED and outpatient visits by adults 19 years or older were reviewed and analyzed. EXPOSURES Antidepressants, antipsychotics, lithium salts, sedatives and anxiolytics, and stimulants. MAIN OUTCOMES AND MEASURES National estimates of ADE ED visits resulting from therapeutic psychiatric medication use and of psychiatric medication ADE ED visits per 10,000 outpatient visits at which psychiatric medications were prescribed. RESULTS From 2009 through 2011, there were an estimated 89,094 (95% CI, 68,641-109,548) psychiatric medication ADE ED visits annually, with 19.3% (95% CI, 16.3%-22.2%) resulting in hospitalization and 49.4% (95% CI, 46.5%-52.4%) involving patients aged 19 to 44 years. Sedatives and anxiolytics, antidepressants, antipsychotics, lithium salts, and stimulants were implicated in an estimated 30,707 (95% CI, 23,406-38,008), 25,377 (95% CI, 19,051-31,704), 21,578 (95% CI, 16,599-26,557), 3620 (95% CI, 2311-4928), and 2779 (95% CI, 1764-3794) respective ADE ED visits annually. Antipsychotics and lithium salts were implicated in 11.7 (95% CI, 10.1-13.2) and 16.4 (95% CI, 13.0-19.9) ADE ED visits per 10,000 outpatient prescription visits, respectively, compared with 3.6 (95% CI, 3.2-4.1) for sedatives and anxiolytics, 2.9 (95% CI, 2.3-3.5) for stimulants, and 2.4 (95% CI, 2.1-2.7) for antidepressants. The commonly used sedative zolpidem tartrate was implicated in 11.5% (95% CI, 9.5%-13.4%) of all adult psychiatric medication ADE ED visits and in 21.0% (95% CI, 16.3%-25.7%) of visits involving adults 65 years or older, in both cases significantly more than any other psychiatric medication. CONCLUSIONS AND RELEVANCE Psychiatric medications are implicated in many ADEs treated in US EDs. Efforts to reduce ADEs should include adults of all ages but might prioritize medications causing high numbers and rates of ED visits.

Prevalence and treatment of pain in EDs in the United States, 2000 to 2010

OBJECTIVES To describe changes in the prevalence and severity of pain and prescribing of non-opioid analgesics in US emergency departments (EDs) from 2000 to 2010. METHODS Analysis of serial cross-sectional data regarding ED visits from the National Hospital Ambulatory Medical Care Survey. Visits were limited to patients ≥18 years old without malignancy. Outcome measures included annual volume of visits among adults with a primary symptom or diagnosis of pain, annual rates of patient-reported pain severity, and predictors of non-opioid receipt for non-malignant pain. RESULTS Rates of pain remained stable, representing approximately 45% of visits from 2000 through 2010. Patients reported pain as their primary symptom twice as often as providers reported a primary pain diagnosis (40% vs 20%). The percentage of patients reporting severe pain increased from 25% (95% confidence intervals [CI] 22%-27%) in 2003 to 40% (CI 37%-42%) in 2008. From 2000 to 2010, the proportion of pain visits treated with pharmacotherapies increased from 56% (CI 53%-58%) to 71% (CI 69%-72%), although visits treated exclusively with non-opioids decreased 21% from 28% (CI 27%-30%) to 22% (CI 20%-23%). The adjusted odds of non-opioid rather than opioid receipt were greater among visits for patients 18 to 24 years old (odds ratio [OR] 1.35, CI 1.24-1.46), receiving fewer medicines (OR 2.91, CI 2.70-3.15) and those with a diagnosis of mental illness (OR 2.24, CI 1.99-2.52). CONCLUSIONS Large increases in opioid utilization in EDs have coincided with reductions in the use of non-opioid analgesics and an unchanging prevalence of pain among patients.

The Food and Drug Administration Amendments Act and Postmarketing Commitments

The Food and Drug Administration Amendments Act and Postmarketing Commitments Because rare but potentially serious adverse events of prescription drugs are often discovered only after market approval,1 observational postmarketing studies constitute an important part of the US drug safety system.2 In most instances prior to 2007, the US Food and Drug Administration (FDA) could only request that drug manufacturers voluntarily agree to conduct postmarketing safety studies.2 An Office of Inspector General report3 in 2006 found inadequacies in drug companies’ fulfillment of these postmarketing studies and weaknesses in FDA’s regulatory authority to enforce these commitments. In 2007, Congress passed the Food and Drug Administration Amendments Act (FDAAA), which authorized the FDA to require postmarketing studies for a prescription drug’s approval and mandate adherence to study deadlines.2,4 We examined how fulfillment of these postmarketing studies has changed over time.

Impact of prescription drug monitoring programs and pill mill laws on high-risk opioid prescribers: A comparative interrupted time series analysis

BACKGROUND Prescription drug monitoring programs (PDMPs) and pill mill laws were implemented to reduce opioid-related injuries/deaths. We evaluated their effects on high-risk prescribers in Florida. METHODS We used IMS Healths LRx Lifelink database between July 2010 and September 2012 to identify opioid-prescribing prescribers in Florida (intervention state, N: 38,465) and Georgia (control state, N: 18,566). The pre-intervention, intervention, and post-intervention periods were: July 2010-June 2011, July 2011-September 2011, and October 2011-September 2012. High-risk prescribers were those in the top 5th percentile of opioid volume during four consecutive calendar quarters. We applied comparative interrupted time series models to evaluate policy effects on clinical practices and monthly prescribing measures for low-risk/high-risk prescribers. RESULTS We identified 1526 (4.0%) high-risk prescribers in Florida, accounting for 67% of total opioid volume and 40% of total opioid prescriptions. Relative to their lower-risk counterparts, they wrote sixteen times more monthly opioid prescriptions (79 vs. 5, p<0.01), and had more prescription-filling patients receiving opioids (47% vs. 19%, p<0.01). Following policy implementation, Floridas high-risk providers experienced large relative reductions in opioid patients and opioid prescriptions (-536 patients/month, 95% confidence intervals [CI] -829 to -243; -847 prescriptions/month, CI -1498 to -197), morphine equivalent dose (-0.88mg/month, CI -1.13 to -0.62), and total opioid volume (-3.88kg/month, CI -5.14 to -2.62). Low-risk providers did not experience statistically significantly relative reductions, nor did policy implementation affect the status of being high- vs. low- risk prescribers. CONCLUSIONS High-risk prescribers are disproportionately responsive to state policies. However, opioids-prescribing remains highly concentrated among high-risk providers.

Effect of direct-to-consumer advertising on asthma medication sales and healthcare use

RATIONALE The United States is one of only two countries that permit direct-to-consumer advertising (DTCA) of prescription drugs, and many questions remain regarding its effects. OBJECTIVES To quantify the association between asthma-related DTCA, pharmacy sales, and healthcare use. METHODS This was an ecological study from 2005 through 2009 using linked data from Nielsen (DTCA television ratings), the IMS Health National Prescription Audit (pharmacy sales), and the MarketScan Commercial Claims data (healthcare use) for 75 designated market areas in the United States. We used multilevel Poisson regression to model the relationship between DTCA and rates of prescriptions and use within and across designated market areas. Main outcome measures include (1) volume of total, new, and refilled prescriptions for advertised products based on pharmacy sales; (2) prescription claims for asthma medications; and asthma-related (3) emergency department use, (4) hospitalizations, and (5) outpatient encounters among the commercially insured. MEASUREMENTS AND MAIN RESULTS Four Food and Drug Administration-approved asthma medicines were advertised during the period examined: (1) fluticasone/salmeterol (Advair), (2) mometasone furoate (Asmanex), (3) montelukast (Singulair), and (4) budesonide/formoterol (Symbicort). After adjustment, each additional televised advertisement was associated with 2% (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.03) higher pharmacy sales rate from 2005 through 2009, although this effect varied across the three consistently advertised therapies examined. Among the commercially insured, DTCA was positively and significantly associated with emergency room visits related to asthma (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.04), but there was no relationship with hospitalizations or outpatient encounters. CONCLUSIONS Among this population, DTCA was associated with higher prescription sales and asthma-related emergency department use.

Impact of a drug utilization review program on high‐risk use of prescription controlled substances

Prescription drug abuse has prompted considerable concern. We evaluated a retrospective drug utilization review program to reduce controlled substance use among individuals with high‐risk utilization.

Effects of Televised Direct-to-Consumer Advertising for Varenicline on Prescription Dispensing in the United States, 2006–2009

INTRODUCTION Televised direct-to-consumer advertising (DTCA) for prescription drugs is controversial, especially for tobacco cessation products such as varenicline, given safety concerns that arose only after its market approval. We aim to quantify the extent to which DTCA influenced varenicline use. METHODS We linked monthly DTCA television ratings with monthly prescription data from IMS Healths National Prescription Audit across top 75 media markets in 2006-2009. We used Poisson models with Generalized Estimating Equations to analyze effects of exposures to DTCA for both varenicline and nicotine replacement therapies on rate of dispensed varenicline prescriptions among smokers, controlling for population characteristics and varenicline-related events. RESULTS Varenicline prescriptions increased dramatically following DTCA launch and declined sharply after safety risks were publicized and US Food and Drug Administration (FDA) issued an advisory. DTCA had significant impact on new prescription dispensing in the subsequent month: before the FDA advisory, one additional exposure to varenicline DTCA was associated with a 1.8% (rate ratio [RR] = 1.018 [1.015-1.021]) higher rate of new prescriptions; no effect was observed after the advisory (RR = 1.000 [0.997-1.003]). Prior to the advisory, cross-product effects of nicotine replacement therapy advertising on varenicline prescribing were negligible (RR = 1.002 [0.999-1.004]); after the advisory, effects were positive (RR = 1.015 [1.012-1.019]). CONCLUSIONS DTCA for varenicline had a significant impact on varenicline prescribing when the drugs safety profile was not well characterized, supporting arguments to limit DTCA for newly approved products whose real-world safety is unclear. IMPLICATIONS We examined the fluctuations in varenicline use in association with DTCA for varenicline and other tobacco cessation aids. To our knowledge this is the first study to quantify the effects of televised DTCA for varenicline and other tobacco cessation aids on varenicline prescription dispensing. We believe that understanding these relationships is critical for formulating effective public health policy and interventions.

Patterns of Buprenorphine-Naloxone Treatment for Opioid Use Disorder in a Multistate Population

Background: Buprenorphine-naloxone treatment for opioid use disorder has rapidly expanded, yet little is known about treatment outcomes among patients in the general population. Objective: To examine predictors of treatment duration, dosage, and continuity in a diverse community setting. Research Design: 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. Results: 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. Conclusions: 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.

Effect of Prescription Drug Coupons on Statin Utilization and Expenditures: A Retrospective Cohort Study

Drug coupons are widely used, but their effects are not well understood.