Mai N Nguyen-Huynh

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

CONTEXTnMore 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.nnnOBJECTIVEnTo 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.nnnDESIGN, SETTING, AND PARTICIPANTSnRetrospective, 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).nnnMAIN OUTCOME MEASURESnSerious 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.nnnRESULTSnDuring 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.nnnCONCLUSIONSnAmong 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.

Recent Trends in Cardiovascular Mortality in the United States and Public Health Goals

IMPORTANCEnHeart disease (HD) and cancer are the 2 leading causes of death in the United States. During the first decade of the 21st century, HD mortality declined at a much greater rate than cancer mortality and it appeared that cancer would overtake HD as the leading cause of death.nnnOBJECTIVESnTo determine whether changes in national trends had occurred in recent years in mortality rates due to all cardiovascular disease (CVD), HD, stroke, and cancer and to evaluate the gap between mortality rates from HD and cancer.nnnDESIGN, SETTING, AND PARTICIPANTSnThe Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data system was used to determine national trends in age-adjusted mortality rates due to all CVD, HD, stroke, and cancer from January 1, 2000, to December 31, 2011, and January 1, 2011, to December 31, 2014, overall, by sex, and by race/ethnicity. The present study was conducted from December 30, 2105, to January 18, 2016.nnnMAIN OUTCOMES AND MEASURESnComparison of annual rates of change and trend in gap between HD and cancer mortality rates.nnnRESULTSnThe rate of the decline in all CVD, HD, and stroke mortality decelerated substantially after 2011, and the rate of decline for cancer mortality remained relatively stable. Reported as percentage (95% CI), the annual rates of decline for 2000-2011 were 3.79% (3.61% to 3.97%), 3.69% (3.51% to 3.87%), 4.53% (4.34% to 4.72%), and 1.49% (1.37% to 1.60%) for all CVD, HD, stroke, and cancer mortality, respectively; the rates for 2011-2014 were 0.65% (-0.18% to 1.47%), 0.76% (-0.06% to 1.58%), 0.37% (-0.53% to 1.27%), and 1.55% (1.07% to 2.04%), respectively. Deceleration of the decline in all CVD mortality rates occurred in males, females, and all race/ethnicity groups. For example, the annual rates of decline for total CVD mortality for 2000-2011 were 3.69% (3.48% to 3.89%) for males and 3.98% (3.81% to 4.14%) for females; for 2011-2014, the rates were 0.23% (-0.71% to 1.16%) and 1.17% (0.41% to 1.93%), respectively. The gap between HD and cancer mortality persisted.nnnCONCLUSIONS AND RELEVANCEnDeceleration in the decline of all CVD, HD, and stroke mortality rates has occurred since 2011. If this trend continues, strategic goals for lowering the burden of CVD set by the American Heart Association and the Million Hearts Initiative may not be reached.

Inpatient statin use predicts improved ischemic stroke discharge disposition

Objective: To determine whether statin use is associated with improved discharge disposition after ischemic stroke. Methods: We used generalized ordinal logistic regression to analyze discharge disposition among 12,689 patients with ischemic stroke over a 7-year period at 17 hospitals in an integrated care delivery system. We also analyzed treatment patterns by hospital to control for the possibility of confounding at the individual patient level. Results: Statin users before and during stroke hospitalization were more likely to have a good discharge outcome (odds ratio [OR] for discharge to home = 1.38, 95% confidence interval [CI] 1.25–1.52, p < 0.001; OR for discharge to home or institution = 2.08, 95% CI 1.72–2.51, p < 0.001). Patients who underwent statin withdrawal were less likely to have a good discharge outcome (OR for discharge to home = 0.77, 95% CI 0.63–0.94, p = 0.012; OR for discharge to home or institution = 0.43, 95% CI 0.33–0.55, p < 0.001). In grouped-treatment analysis, an instrumental variable method using treatment patterns by hospital, higher probability of inpatient statin use predicted a higher likelihood of discharge to home (OR = 2.56, 95% CI 1.71–3.85, p < 0.001). In last prior treatment analysis, a novel instrumental variable method, patients with a higher probability of statin use were more likely to have a good discharge outcome (OR for each better level of ordinal discharge outcome = 1.19, 95% CI 1.09–1.30, p = 0.001). Conclusions: Statin use is strongly associated with improved discharge disposition after ischemic stroke.

Validation of the Stroke Prognostic Instrument-II in a Large, Modern, Community-Based Cohort of Ischemic Stroke Survivors

Background and Purpose— The risk of recurrent stroke in the modern era of secondary stroke prevention is not well defined. Several prediction models, including the Stroke Prognostic Instrument-II (SPI-II), have been created to identify patients at highest risk, but their performance in modern populations has been infrequently tested. We aimed to assess the 1-year risk of recurrence after hospital discharge in a recent, large, community-based cohort of patients with ischemic stroke and to validate the SPI-II prediction model in this cohort. Methods— From 2004 through 2006, 5575 patients with acute ischemic stroke were prospectively identified and followed for recurrent events. Kaplan-Meier statistics were used to analyze the cumulative incidence of recurrent ischemic stroke. Harrell c-statistic was calculated to determine the performance of SPI-II in predicting stroke or death at 1 year, and the log-rank test was used to compare the differences among low-, middle-, and high-risk groups. Results— Among 5575 patients with ischemic stroke, recurrence was observed in 221 during the subsequent year. Kaplan-Meier estimates of cumulative rates of recurrent stroke were 2.5%, 3.6%, and 4.8% at 3, 6, and 12 months, respectively. Rates of stroke or death for SPI-II in the low-, middle-, and high-risk groups were 8.2%, 24.5%, and 35.6%, respectively (trend, P=0.001). The c-statistic for SPI-II was 0.62 (95% CI, 0.61–0.64). Conclusions— The modern 1-year rate of recurrent stroke after hospital discharge is low but still substantial at 4.8%. SPI-II is a modestly effective tool in identifying patients with ischemic stroke at highest risk of developing recurrence or death.

Comparative Trends in Heart Disease, Stroke, and All-Cause Mortality in the United States and a Large Integrated Healthcare Delivery System

OBJECTIVESnHeart disease and stroke remain among the leading causes of death nationally. We examined whether differences in recent trends in heart disease, stroke, and total mortality exist in the United States and Kaiser Permanente Northern California (KPNC), a large integrated healthcare delivery system.nnnMETHODSnThe main outcome measures were comparisons of US and KPNC total, age-specific, and sex-specific changes from 2000 to 2015 in mortality rates from heart disease, coronary heart disease, stroke, and all causes. The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data system was used to determine US mortality rates. Mortality rates for KPNC were determined from health system, Social Security vital status, and state death certificate databases.nnnRESULTSnDeclines in age-adjusted mortality rates were noted in KPNC and the United States for heart disease (36.3% in KPNC vs 34.6% in the United States), coronary heart disease (51.0% vs 47.9%), stroke (45.5% vs 38.2%), and all-cause mortality (16.8% vs 15.6%). However, steeper declines were noted in KPNC than the United States among those aged 45 to 65 years for heart disease (48.3% KPNC vs 23.6% United States), coronary heart disease (55.6% vs 35.9%), stroke (55.8% vs 26.0%), and all-cause mortality (31.5% vs 9.1%). Sex-specific changes were generally similar.nnnCONCLUSIONSnDespite significant declines in heart disease and stroke mortality, there remains an improvement gap nationally among those aged less than 65 years when compared with a large integrated healthcare delivery system. Interventions to improve cardiovascular mortality in the vulnerable middle-aged population may play a key role in closing this gap.

Race-ethnicity on blood pressure control after ischemic stroke: a prospective cohort study

Disparities in health care access and socioeconomic status (SES) have been associated with racial-ethnic differences in blood pressure (BP) control. We examined post-ischemic stroke BP in a multiethnic cohort with good health care access. We included all hypertensive patients (nxa0=xa02972) from a randomized quality improvement trial on secondary stroke prevention, conducted in 14 Kaiser Permanente hospitals in Northern California from 2004-2006 (QUISP). Average age 73.2xa0±xa012.2xa0years; 52% female, 66% non-Hispanic white, 14% African-American, 11% Asian, 8% Hispanic, and 1% other. Demographics, diagnoses, health care utilization, BP measurements, and medications were obtained as part of routine care. We used random effects logistic regression models to examine race as a predictor of blood pressure control (<140/90xa0mm Hg) at 6xa0months post-discharge, adjusted for SES, age, gender, dementia, antihypertensive therapy, and attendance at follow-up visits. At 6xa0months, BP was controlled in 52.7% of blacks compared to 61.4% of whites (ORxa0=xa00.63, 95% CI, 0.48-0.82, Pxa0=xa0.001). Black race remained independently associated with poorer BP control in adjusted analysis, although blacks were as likely to attend post-discharge visits, and more likely to be on any antihypertensive therapy than whites. Greater difficulty in controlling BP and lifestyle differences may account for this difference.

Establishing a Carotid Artery Stenosis Disease Cohort for Comparative Effectiveness Research Using Natural Language Processing

Objective: Functional popliteal artery entrapment syndrome (FPAES) is a rare overuse condition described in physically active individuals that can be limb or performance threatening if untreated. We used provocative computed tomography angiography to guide partial debulking of the anterolateral quadrant of the medial head of the gastrocnemius muscle and reviewed outcomes of this technique in athletes. Methods: Athletes referred with symptoms of FPAES underwent computed tomography angiography with provocative plantar flexion and dorsiflexion to confirm compression. Surgery consisted of a posterior approach exposure, adhesiolysis, arterial side branch ligation, and partial excision of the gastrocnemius muscle compressing the artery with or without fasciotomies. Results: There were 36 athletes (mean age, 24 years; 53% female) who had a total of 56 limbs treated. Prior fasciotomies had already been performed in 31% of patients for chronic compartment syndrome. Involved sports included running (39%), soccer (28%), triathlete (8%), basketball (6%), gymnastics (3%), lacrosse (3%), diving (3%), tennis (3%), rugby (3%), water polo (3%), and skiing (3%). Bilateral symptoms were present in 27 (75%), but only 20 of 36 (56%) underwent bilateral surgery. Mean amount of gastrocnemius muscle removed was 6.8 cm. Six patients (17%) also underwent vascular reconstruction along with debulking because of arterial stenosis or occlusion at presentation. No nerve or vascular complications were noted, although two patients had wound or seroma complications (6%). At latest follow-up (mean, 16 months), 6 patients (17%) reported recurrence of symptoms; 25 of 30 (83%) athletes not undergoing vascular reconstruction reported full return to their preoperative competitive level of sport, whereas only 3 of 6 (50%) needing bypass returned to sport (P 1⁄4 .05). Conclusions: More than three-fourths of athletes limited by FPAES are able to return to prior competitive sport performance after fasciotomy and debulking of the anterolateral quadrant of the medial gastrocnemius. Need for arterial reconstruction significantly affects future ability to return to sport, and recognizing symptoms early in this highly specialized cohort is important in improving outcomes.