Denise M. Boudreau

Trends in long-term opioid therapy for chronic non-cancer pain

To report trends and characteristics of long‐term opioid use for non‐cancer pain.

De Facto Long-term Opioid Therapy for Noncancer Pain

ObjectivesThis paper describes characteristics of opioid use episodes for noncancer pain and defines thresholds for de facto long-term opioid therapy. MethodsCONSORT (CONsortium to Study Opioid Risks and Trends) includes adult members of 2 health plans serving over 1% of the US population. Opioid use episodes beginning in the years 1997 to 2005 were classified as acute, episodic, long-term/lower dose, or long-term/higher dose. ResultsOn the basis of evaluation of the likelihood of opioid use continuing, long-term opioid therapy was defined by episodes lasting longer than 90 days with 10+ opioid prescriptions or 120+ days supply of opioids dispensed. Long-term/higher dose episodes (<1.5% of all opioid use episodes) were characterized by daily or near daily use, a mean duration of about 1000 days, and an average daily dose of about 55 mg. They accounted for more than half the total morphine equivalents dispensed from the years 1997 to 2006. Short-acting, non-Schedule II opioids (eg, hydrocodone with acetaminophen) were, by far, the most commonly prescribed medications for acute, episodic, and long-term episodes. Long-acting (sustained-release) opioids were the predominately prescribed medication in a minority of long-term episodes (6% to 12%). DiscussionLong-term opioid therapy was characterized by the diversity in medications prescribed, dosage levels, and frequency of use. The proposed threshold for long-term opioid therapy provides a checkpoint for physicians to review whether an explicit decision to sustain opioid therapy has been reached, and to ensure that a documented treatment plan and provisions for monitoring medication use and patient outcomes are in place.

ADHD Medications and Risk of Serious Cardiovascular Events In Young and Middle-Aged Adults

CONTEXT More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND PARTICIPANTS Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). MAIN OUTCOME MEASURES Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias. RESULTS During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.

Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn

To determine the prevalence of persistent pulmonary hypertension of the newborn (PPHN) among infants whose mothers were exposed to antidepressants in the third trimester of pregnancy compared to the prevalence among infants whose mothers were not exposed to antidepressants in the third trimester.

Statin use and cancer risk: a comprehensive review

Importance of the field: HMG-CoA inhibitors (statins), a class of drugs that reduce cholesterol, are used to manage and prevent coronary heart disease. They are among the most commonly prescribed drugs worldwide. Contrary to early concerns over the carcinogenicity of statins, a growing body of evidence suggests statins may in fact have a chemopreventive potential against cancer. Areas covered in this review: In this paper, we review evidence on the association between statin use and cancer risk. Specifically, we report on clinical trials and observational studies that measured all cancer or site-specific cancers of the breast, colorectal, lung, prostate and reproductive organs associated with statin use. What the reader will gain: An understanding of the evidence, including strengths and limitations, to support an association between statins and cancer. Information on the current state of the field and future directions are also discussed. Take home message: Few strong or consistent associations between statins and cancer incidence overall or for any of the sites reviewed were detected. Data for any effects of statins on cancer prognosis and secondary prevention are lacking; with the exception of consistent evidence that statins are associated with reduced risk of advanced/aggressive prostate cancer. Statins appear safe in relation to cancer risk but any chemopreventive effect in humans remains to be established and should not be recommended outside the context of clinical trials. It is encouraging that numerous trials are ongoing. The prospect of reducing the incidence and burden of some of the most prevalent cancers with safe, affordable and tolerable medication that already reduces the risk of the leading cause of death and cardiovascular disease warrants further exploration in clinical trials and observational studies of prognosis and survival.

Design considerations, architecture, and use of the Mini-Sentinel distributed data system

We describe the design, implementation, and use of a large, multiorganizational distributed database developed to support the Mini‐Sentinel Pilot Program of the US Food and Drug Administration (FDA). As envisioned by the US FDA, this implementation will inform and facilitate the development of an active surveillance system for monitoring the safety of medical products (drugs, biologics, and devices) in the USA.

Age and Gender Trends in Long-Term Opioid Analgesic Use for Noncancer Pain

OBJECTIVES We describe age and gender trends in long-term use of prescribed opioids for chronic noncancer pain in 2 large health plans. METHODS Age- and gender-standardized incident (beginning in each year) and prevalent (ongoing) opioid use episodes were estimated with automated health care data from 1997 to 2005. Profiles of opioid use in 2005 by age and gender were also compared. RESULTS From 1997 to 2005, age-gender groups exhibited a total percentage increase ranging from 16% to 87% for incident long-term opioid use and from 61% to 135% for prevalent long-term opioid use. Women had higher opioid use than did men. Older women had the highest prevalence of long-term opioid use (8%-9% in 2005). Concurrent use of sedative-hypnotic drugs and opioids was common, particularly among women. CONCLUSIONS Risks and benefits of long-term opioid use are poorly understood, particularly among older adults. Increased surveillance of the safety of long-term opioid use is needed in community practice settings.

The association between 3-hydroxy-3-methylglutaryl conenzyme a inhibitor use and breast carcinoma risk among postmenopausal women: A case-control study

Statin use has increased dramatically in the U.S. in the past decade. Animal and mechanistic studies suggested that statins may have an inhibitory effect on cancer proliferation, including breast carcinoma. However, statins have been found to be carcinogenic in rodents and one clinical trial found an excess of breast carcinoma cases in the treatment group.

Trends in prescribed opioid therapy for non-cancer pain for individuals with prior substance use disorders

ABSTRACT Long‐term opioid therapy for non‐cancer pain has increased. Caution is advised in prescribing for persons with substance use disorders, but little is known about actual health plan practices. This paper reports trends and characteristics of long‐term opioid use in persons with non‐cancer pain and a substance abuse history. Using health plan data (1997–2005), the study compared age–sex‐standardized rates of incident, incident long‐term and prevalent long‐term prescription opioid use, and medication use profiles in those with and without substance use disorder histories. The CONsortium to Study Opioid Risks and Trends study included adult enrollees of two health plans, Kaiser Permanente of Northern California (KPNC) and Group Health Cooperative (GH) of Seattle, Washington. At KPNC (1999–2005), prevalence of long‐term use increased from 11.6% to 17.0% for those with substance use disorder histories and from 2.6% to 3.9% for those without substance use disorder histories. Respective GH rates (1997–2005), increased from 7.6% to 18.6% and from 2.7% to 4.2%. Among persons with an opioid disorder, KPNC rates increased from 44.1% to 51.1%, and GH rates increased from 15.7% to 52.4%. Long‐term opioid users with a prior substance abuse diagnosis received higher dosage levels, were more likely to use Schedule II and long‐acting opioids, and were more often frequent users of sedative‐hypnotic medications in addition to their opioid use. Since these patients are viewed as higher risk, the increased use of long‐term opioid therapy suggests the importance of improved understanding of the benefits and risks of opioid therapy among persons with a history of substance abuse, and the need for more careful screening for substance abuse history than is the usual practice.

Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65-79 years

Limited data are available regarding the incidence of breast carcinoma among users of relatively recently introduced forms of antihypertensive therapy. Although it has been suggested that women who have taken calcium channel blockers (CCBs) have an increased risk and that women who have taken angiotensin‐I‐converting enzyme (ACE) inhibitors have a decreased risk, currently, no conclusions can be drawn.