Virginia P. Quinn

ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults

BACKGROUND Adverse-event reports from North America have raised concern that the use of drugs for attention deficit-hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events. METHODS We conducted a retrospective cohort study with automated data from four health plans (Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology), with 1,200,438 children and young adults between the ages of 2 and 24 years and 2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs. We identified serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) from health-plan data and vital records, with end points validated by medical-record review. We estimated the relative risk of end points among current users, as compared with nonusers, with hazard ratios from Cox regression models. RESULTS Cohort members had 81 serious cardiovascular events (3.1 per 100,000 person-years). Current users of ADHD drugs were not at increased risk for serious cardiovascular events (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.31 to 1.85). Risk was not increased for any of the individual end points, or for current users as compared with former users (adjusted hazard ratio, 0.70; 95% CI, 0.29 to 1.72). Alternative analyses addressing several study assumptions also showed no significant association between the use of an ADHD drug and the risk of a study end point. CONCLUSIONS This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low. (Funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration.).

Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer

PURPOSE Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) -positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. PATIENTS AND METHODS Within six health care delivery systems, we identified women >or= 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. RESULTS Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged >or= 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). CONCLUSION Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.

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.

The Kaiser Permanente prenatal smoking-cessation trial: when more isn't better, what is enough?

INTRODUCTION The effectiveness of low-cost smoking interventions targeted to pregnant women has been demonstrated, although few gains in absolute cessation rates have been reported in the past decade. Under conditions of typical clinical practice, this study examined whether outcomes achieved with brief counseling from prenatal care providers and a self-help booklet could be improved by adding more resource-intensive cognitive-behavioral programs. DESIGN Randomized Clinical Trial. SETTING A large-group-model managed care organization. PARTICIPANTS 390 English-speaking women 18 years of age or older who self-reported to be active smokers at their initial prenatal appointment. INTERVENTION Participants were randomized to one of three groups: (1) a self-help booklet tailored to smoking patterns, stage of change, and lifestyle of pregnant smokers; (2) the booklet plus access to a computerized telephone cessation program based on interactive voice response technology; or (3) the booklet plus proactive telephone counseling from nurse educators using motivational interviewing techniques and strategies. No attempt was made to change smoking-related usual care advice from prenatal providers. MAIN OUTCOME MEASURE Biochemically confirmed abstinence measured by level of cotinine in urine samples obtained during a routine prenatal visit at approximately the 34th week of pregnancy. RESULTS Twenty percent of participants were confirmed as abstinent with no significant differences found between intervention groups. Multivariate baseline predictors of cessation included number of cigarettes smoked per day, confidence in ability to quit, exposure to passive smoke, and educational level. No differential intervention effects were found within strata of these predictors or by baseline stage of readiness to change. Cessation rates among heavier smokers were strikingly low in all intervention groups. CONCLUSION Neither a computerized telephone cessation program nor systematic provision of motivational counseling improved cessation rates over a tailored self-help booklet delivered within the context of brief advice from prenatal providers. Innovative strategies need to be developed to increase the effectiveness of existing prenatal smoking interventions. Special attention should be paid to the needs of heavier smokers.

Spontaneous quitting: self-initiated smoking cessation in early pregnancy.

This article reviews the empirical literature on spontaneous quitting of cigarette smoking among pregnant women. We define spontaneous quitting and discuss its prevalence and the characteristics that differentiate spontaneous quitters from women who continue to smoke during pregnancy. We examine the success of these women in abstaining throughout their pregnancy, and their pattern of relapse back to smoking during the postpartum period. We review studies that have tested strategies to maintain abstinence among spontaneous quitters, and we conclude the article with gaps identified in the literature that warrant further study.

Statin use and risk of prostate cancer in the California Men's Health Study cohort.

Statins have known anticarcinogenic effects, however, evidence for long-term statin use as effective chemoprevention for prostate cancer is inconsistent. We examined the association between statin use and risk of prostate cancer among 69,047 eligible participants in the California Mens Health Study, a prospective cohort of Northern and Southern California Kaiser Permanente (KP) members, ages 45 to 69 years, initiated in 2002. Prostate cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and since 1994 in Northern California), was treated as time-varying and defined as the cumulative days dispensed of any statin from the first dispensing until a prostate cancer diagnosis, radical prostatectomy, termination of membership, or end of study (December 31, 2004). Cox proportional hazards models with age as the time scale were used to estimate rate ratios, while controlling for confounding variables. During follow-up, 888 prostate cancer cases, including 131 advanced cases, were identified. There was no association between ever statin use or <5 years use and prostate cancer. Conversely, ≥5 years use was associated with a 28% lower risk for prostate cancer compared with nonuse (adjusted rate ratio, 0.72; 95% confidence interval, 0.53-0.99). This association did not differ markedly for advanced disease. However, the association did seem to be restricted to those who regularly take nonsteroidal anti-inflammatory drugs. Our findings suggest that long-term statin use might be associated with a reduced risk of prostate cancer but perhaps only among regular nonsteroidal anti-inflammatory drug users. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2218–25)

Prevalence of Extreme Obesity in a Multiethnic Cohort of Children and Adolescents

OBJECTIVE To estimate the prevalence of extreme obesity in a large, multiethnic contemporary cohort of children and adolescents. STUDY DESIGN In a cross-sectional study, measured weight and height were extracted from electronic medical records of 710,949 patients aged 2 to 19 years (87.8% of eligible patients) who were enrolled in an integrated prepaid health plan in 2007 and 2008. Prevalence of extreme obesity was defined as body mass index (BMI)-for-age>or=1.2 times 95th percentile or BMI>or=35 kg/m2. RESULTS Extreme obesity was observed in 7.3% of boys and 5.5% of girls. The prevalence peaked at 10 years of age in boys and at 12 years of age with a bimodal distribution in girls (second peak at 18 years; P value for sex x age interaction=.036). The prevalence of extreme obesity varied in ethnic/racial and age groups, with the highest prevalence in Hispanic boys (as high as 11.2%) and African-American girls (as high as 11.9%). CONCLUSION Extreme obesity in Southern California youth is frequently observed at relatively young ages. The shift toward extreme body weights is likely to cause an enormous burden of adverse health outcomes once these children and adolescents grow older.

Initial validation of an exercise "vital sign" in electronic medical records.

PURPOSE The objective of this study is to describe the face and discriminant validity of an exercise vital sign (EVS) for use in an outpatient electronic medical record. METHODS Eligible patients were 1,793,385 adults 18 yr and older who were members of a large health care system in Southern California. To determine face validity, median total self-reported minutes per week of exercise as measured by the EVS were compared with findings from national population-based surveys. To determine discriminant validity, multivariate Poisson regression models with robust variance estimation were used to examine the ability of the EVS to discriminate between groups of patients with differing physical activity (PA) levels on the basis of demographics and health status. RESULTS After 1.5 yr of implementation, 86% (1,537,798) of all eligible patients had an EVS in their electronic medical record. Overall, 36.3% of patients were completely inactive (0 min of exercise per week), 33.3% were insufficiently active (more than 0 but less than 150 min·wk), and 30.4% were sufficiently active (150 min or more per week). As compared with national population-based surveys, patient reports of PA were lower but followed similar patterns. As hypothesized, patients who were older, obese, of a racial/ethnic minority, and had higher disease burdens were more likely to be inactive, suggesting that the EVS has discriminant validity. CONCLUSIONS We found that the EVS has good face and discriminant validity and may provide more conservative estimates of PA behavior when compared with national surveys. The EVS has the potential to provide information about the relationship between exercise and health care use, cost, and chronic disease that has not been previously available at the population level.

Postpartum Return to Smoking: Who Is at Risk and When

Purpose. Despite high rates of spontaneous and assisted smoking cessation during pregnancy, postpartum maintenance is disappointingly low. Predictors of return to smoking remain unclear, thus limiting the development of interventions that could protect the health of women and their children. This study followed women who had participated in a prenatal smoking cessation intervention trial and successfully stopped smoking to address two aims: (1) describe the probability of relapse in confirmed quitters during the first 6 months after the birth, and (2) identify factors that increase relapse. Design. Prospective design during pregnancy and retrospective report at 6 months postpartum used survival analysis with return to smoking as the dependent variable and the Cox proportional hazards regression technique. Measures. Questionnaires were used at the first prenatal visit and telephone interviews at the 26th week of pregnancy and 6 months postpartum. Nonsmoking after the 20th week was measured by urine cotinine tests (m = 3); nonsmoking postpartum was measured by retrospective self-report. Setting. The setting was an HMO-based group practice in Los Angeles. Subjects. Subjects were white, black, and Hispanic women (n = 127) available for follow-up. Results. The proportion of the sample classified as relapsers at 6 months postpartum was 62.9%. The final model identified the following risk factors for smoking: taking puffs in late pregnancy and having friends who smoke at the first prenatal visit, less confidence in mid-pregnancy that they could maintain nonsmoking postpartum, and a partner who smokes postpartum. Conclusions. Intervention should begin in late pregnancy, and smoking networks, including partner smoking, should be addressed.

Mammography Surveillance and Mortality in Older Breast Cancer Survivors

PURPOSE There are more than 2,000,000 breast cancer survivors in the United States today. While surveillance for asymptomatic recurrence and second primary is included in consensus recommendations, the effectiveness of this surveillance has not been well characterized. Our purpose is to estimate the effectiveness of surveillance mammography in a cohort of breast cancer survivors with complete ascertainment of surveillance mammograms and negligible losses to follow-up. PATIENTS AND METHODS We enrolled 1,846 stage I and II breast cancer patients who were at least 65 years old at six integrated health care delivery systems. We used medical record review and existing databases to ascertain patient, tumor, and therapy characteristics, as well as receipt of surveillance mammograms. We linked personal identifiers to the National Death Index to ascertain date and cause of death. We matched four controls to each breast cancer decedent to estimate the association between receipt of surveillance mammogram and breast cancer mortality. RESULTS One hundred seventy-eight women died of breast cancer during 5 years of follow-up. Each additional surveillance mammogram was associated with a 0.69-fold decrease in the odds of breast cancer mortality (95% CI, 0.52 to 0.92). The protective association was strongest among women with stage I disease, those who received mastectomy, and those in the oldest age group. CONCLUSION Given existing recommendations for post-therapy surveillance, trials to compare surveillance with no surveillance are unlikely. This large observational study provides support for the recommendations, suggesting that receipt of surveillance mammograms reduces the rate of breast cancer mortality in older patients diagnosed with early-stage disease.