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Background Although the benefits outweigh risks, COVID-19 vaccines have been associated with an increased risk of myocarditis and pericarditis. This is a national US Veteran population-based report of confirmed myocarditis/pericarditis following mRNA COVID-19 vaccines using the VA’s near real-time active surveillance program. Methods A cohort evaluation of all adults administered one or more mRNA COVID-19 vaccine(s), including boosters, in the Veterans Health Administration (VHA) between December 14, 2020 and October 9, 2022. ICD-10-CM diagnosis codes were used to identify potential safety signals in near real-time through a database analysis. All potential cases of myocarditis/pericarditis identified in the database analysis underwent in-depth chart review and case validation by a team of pharmacists and expert clinicians. Our main outcome was the incidence rate of confirmed myocarditis/pericarditis among vaccine recipients (both overall and among those aged 18-39) within 21 days of either a first, second or booster dose of a mRNA COVID-19 vaccine. We calculated the ratio of observed events among COVID-19 vaccine recipients over expected events from historic vaccine recipient controls (2015-2020) in the VHA. We used confirmed cases to calculate incidence rates and 95% confidence intervals. Results Through October 9, 2022, 3,877,453 doses of BNT162b2 (Pfizer-BioNTech) and 4,221,397 doses of mRNA-1273 (Moderna) were administered as first or second dose across the VA, and 1,012,561 of BNT162b2 and 1,156,160 of mRNA-1273 booster doses were administered. Among all doses, the rapid cycle analysis identified 178 potential cases of myocarditis/pericarditis among vaccinees of any age and 22 potential cases among those aged 18-39. Of these, 33 cases including 6 cases among those 18-39 years old were confirmed after in depth chart review and validation, corresponding with an overall incidence rate per million ranging from 0.46 (95% CI: 0.01-2.55) for Moderna dose 1 to 6.91 (95% CI: 2.78-14.24) for Pfizer booster. Among those aged 18-39, incidence rates ranged from 7.1 (95% CI: 0.18-39.56) for Moderna dose #2 to 19.76 (95% CI: 5.38-50.58) for Pfizer dose #2. Confirmed cases were hospitalized for a mean of 4.1 days (range 1-15). The final disposition for 32/33 (97%) was discharge to home. Conclusions This report is a real-world demonstration of the VA’s active surveillance system for vaccines. Although the rapid cycle analysis initially identified 178 potential cases of myocarditis/pericarditis, only 1 out of 5 cases were confirmed to be related to a COVID-19 vaccine after chart review. These findings highlight the paramount importance of both active surveillance and chart validation for rare but serious adverse events related to COVID-19 vaccines.

Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS).We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD.Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables.MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages.Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

Background Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for suicidal behavior, but the effect of ADHD medication on suicidal behavior remains unclear. This study aimed to examine the associations between medication treatment for ADHD and risk of suicide attempts. Methods We identified a large cohort of patients with ADHD (N = 3,874,728, 47.8% female patients) using data from commercial health care claims from 2005 to 2014 in the United States. We used population-level and within-individual analyses to compare risk of suicide attempts during months when individuals received prescribed stimulant or nonstimulant medication relative to months when they did not receive medication. Results In both population-level and within-individual analyses, ADHD medication was associated with lower odds of suicide attempts (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66–0.73; and OR, 0.61; 95% CI, 0.57–0.66, respectively). Similar reductions were found in children to middle-aged adults and in clinically relevant subgroups, including patients with ADHD with preexisting depression or substance use disorder. The reduction was mainly seen for stimulant medication (OR, 0.72; 95% CI, 0.66–0.77); nonstimulant medication was not associated with statistically significant changes in risk of suicide attempts (OR, 0.94; 95% CI, 0.74–1.19). Sensitivity analyses assessing the influence of different exposure definitions, different outcome definitions, subsets of the cohort, and different analytic approaches provided comparable results. Conclusions Stimulant medication was associated with a reduced risk of suicide attempts in patients with ADHD, and nonstimulant medication is unlikely to increase the risk of suicide attempts.

Background Overdose due to concomitant use of opioids and benzodiazepines has been raised as a major public health concern, although little research has examined whether this risk extends to intentional overdose or other self-harm. This study examined whether prescription opioids and benzodiazepines interact to increase the rate of suicide attempt and intentional self-harm. Methods The study analyzed 4,762,438 users of opioids, benzodiazepines, both drugs concomitantly, or neither drug from the MarketScan Commercial Claims and Encounters databases (2014–2016). The four groups were matched using inverse probability of treatment weighting and a difference in difference design was used to examine associations with risk of suicide attempt, intentional self-harm and drug overdose, including suicide death resulting in a medical claim. Results There was a small association for opioids (HR=1.23; 95% CI 1.06–1.43) but a larger association for benzodiazepines (HR=2.55; 95% CI 2.12–3.05) with suicide attempt, intentional self-harm, and drug overdose. The medication interaction was opposite to the expected direction (HR=0.70; 95% CI 0.55–0.89), indicating that risk associated with concomitant use was lower than would be expected on an additive basis. Sensitivity analyses found no evidence of increased risk due to interaction between the two drug classes. Conclusions Increased risk of suicide attempt, intentional self-harm and drug overdose for concomitant use of opioids and benzodiazepines is in large part attributable to benzodiazepine use alone. In typically prescribed quantities, opioids and benzodiazepines may not represent a drug interaction in terms of yielding increased risk of suicide attempt and intentional self-harm resulting in medical care.

ImportanceSuicide is a leading cause of death in the United States, having increased more than 30% from 2000 to 2018. An inexpensive, safe, widely available treatment for preventing suicidal behavior could reverse this trend.ObjectiveTo confirm a previous signal for decreased risk of suicide attempt following prescription fills for folic acid in a national pharmacoepidemiologic study of patients treated with folic acid.Design, Setting, and ParticipantsA within-person exposure-only cohort design was used to study the dynamic association between folic acid (vitamin B9) prescription fills over a 24-month period and suicide attempts and intentional self-harm. Data were collected from a pharmacoepidemiologic database of US medical claims (MarketScan) for patients with private health insurance who filled a folic acid prescription between 2012 and 2017. The same analysis was repeated with a control supplement (cyanocobalamin, vitamin B12). Data were analyzed from August 2021 to June 2022.ExposureFolic acid prescription fills.Main Outcome and MeasureSuicide attempt or intentional self-harm resulting in an outpatient visit or inpatient admission as identified by codes from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification.ResultsData on 866 586 patients were collected; 704 514 (81.30%) were female, and 90 296 (10.42%) were 60 years and older. Overall, there were 261 suicidal events during months covered by a folic acid prescription (5 521 597 person-months) for a rate of 4.73 per 100 000 person-months, compared with 895 suicidal events during months without folic acid (8 432 340) for a rate of 10.61 per 100 000 person-months. Adjusting for age and sex, diagnoses related to suicidal behavior, diagnoses related to folic acid deficiency, folate-reducing medications, history of folate-reducing medications, and history of suicidal events, the hazard ratio (HR) for folic acid for suicide events was 0.56 (95% CI, 0.48-0.65), with similar results for the modal dosage of 1 mg of folic acid per day (HR, 0.57; 95% CI, 0.48-0.69) and women of childbearing age (HR, 0.60; 95% CI, 0.50-0.73). A duration-response analysis (1-mg dosage) revealed a 5% decrease in suicidal events per month of additional treatment (HR, 0.95; 95% CI, 0.93-0.97). The same analysis for the negative control, cyanocobalamin, found no association with suicide attempt (HR, 1.01; 95% CI, 0.80-1.27).Conclusions and RelevanceThis large-scale pharmacoepidemiologic study of folic acid found a beneficial association in terms of lower rates of suicide attempts. The results warrant the conduct of a randomized clinical trial with suicidal ideation and behavior as outcomes of interest. If confirmed, folic acid may be a safe, inexpensive, and widely available treatment for suicidal ideation and behavior.

Key Points Question What is the real-world experience with edaravone in patients with amyotrophic lateral sclerosis (ALS) within a national integrated health care system? Findings In this cohort study of data from 369 US veterans with documented or probable ALS, a significantly greater proportion of acute all-cause hospitalizations was associated with edaravone treatment and, among users receiving at least 6 months of treatment, an increased likelihood of ALS-related hospitalization was associated with edaravone treatment compared with riluzole-only treatment. Meaning While these findings should be interpreted with caution, in this evaluation, edaravone (mostly used with riluzole) was associated with more hospitalizations compared with riluzole-only therapy; more evidence is needed to evaluate edaravone treatment outcomes in real-world settings., Importance Using real-world data, the US Department of Veterans Affairs (VA) initiated a surveillance evaluation of edaravone after its approval for amyotrophic lateral sclerosis (ALS) in 2017. The use and safety of edaravone for patients with ALS in the VA health care system remain to be assessed. Objective To describe a pharmacovigilance surveillance initiative with edaravone to monitor patient characteristics, utilization (edaravone cycles and riluzole use), and safety and to evaluate safety/effectiveness. Design, Setting, and Participants This propensity score–matched cohort study used data on 369 patients with documented definite or probable ALS in the Veterans Health Administration (VHA) with at least 1 prescription for edaravone between August 1, 2017, and September 30, 2019. The analysis compared edaravone (alone or with riluzole) with riluzole only. For chronic users (≥6 months of drug), a time-to-event model evaluated ALS-related outcomes, with censoring at outcome, death, or end of evaluation. Patients with Parkinson disease, dementia, schizophrenia, or significant respiratory insufficiency per diagnosis codes within 2 years before prescription initiation were excluded. In overall matched cohorts, 223 patients treated with edaravone were 1:3 propensity score matched based on predefined confounders. For the chronic user subgroup analysis, 96 patients receiving edaravone and 424 patients receiving riluzole only were included. Exposures Edaravone (alone or with riluzole) vs riluzole only. Main Outcomes and Measures Patient characteristics, ALS drug use, and mortality. Acute outcomes (within 6 months of index) included proportion and mean time to event for death, discontinuation, or all-cause hospitalization, and outcomes for chronic users (receiving >6 months of treatment) included hazard ratios of outcomes related to disease-state progression. Results Of 369 patients who received edaravone, most were older (mean [SD] age, 64.6 [11.3] years), male (346 [93.8%]), and White (261 [70.7%]). As of September 2019, 59.9% of edaravone patients had discontinued treatment; of those, 49.5% (108 of 218) received only 1 to 3 treatment cycles. Approximately 30% (110 patients) died. In a matched evaluation, significantly more acute all-cause hospitalization events occurred with edaravone (35.4% vs 22.0% for riluzole only); 72.6% of the edaravone cohort received edaravone with riluzole. Among chronic users, edaravone patients (70.8% edaravone with riluzole) had an increased hazard ratio of ALS-associated hospitalization (2.51; 95% CI, 1.18-8.16). The death rate was lower with edaravone but the difference was not statistically significant. Conclusions and Relevance Early edaravone discontinuation was common in the VA. Although outcomes favored use of riluzole only in the matched analysis, results should be interpreted with caution, as unmeasured bias in observational data is likely., This cohort study uses real-world data to assess patient characteristics and use as well as the safety and effectiveness of edaravone among patients with amyotrophic lateral sclerosis in the US Department of Veterans Affairs Health Care System.

There is growing evidence that opioid prescribing in the United States follows a pattern in which patients who are at the highest risk of adverse outcomes from opioids are more likely to receive long-term opioid therapy. These patients include, in particular, those with substance use disorders (SUDs) and other psychiatric conditions. This study examined health insurance claims among 10,311,961 patients who filled prescriptions for opioids. Specifically, we evaluated how opioid receipt differed among patients with and without a wide range of preexisting psychiatric and behavioral conditions (ie, opioid and nonopioid SUDs, suicide attempts or other self-injury, motor vehicle crashes, and depressive, anxiety, and sleep disorders) and psychoactive medications (ie, antidepressants, benzodiazepines, hypnotics, mood stabilizers, antipsychotics, and medications used for SUD, tobacco cessation, and attention-deficit/hyperactivity disorder). Relative to those without, patients with all assessed psychiatric conditions and medications had modestly greater odds of subsequently filling prescriptions for opioids and, in particular, substantially greater risk of long-term opioid receipt. Increases in risk for long-term opioid receipt in adjusted Cox regressions ranged from approximately 1.5-fold for prior attention-deficit/hyperactivity disorder medication prescriptions (hazard ratio [HR] = 1.53; 95% confidence interval [CI], 1.48-1.58) to approximately 3-fold for prior nonopioid SUD diagnoses (HR = 3.15; 95% CI, 3.06-3.24) and nearly 9-fold for prior opioid use disorder diagnoses (HR = 8.70; 95% CI, 8.20-9.24). In sum, we found evidence of greater opioid receipt among commercially insured patients with a breadth of psychiatric conditions. Future studies assessing behavioral outcomes associated with opioid prescribing should consider preexisting psychiatric conditions.

The rate of suicide has been rising for 16 years and it is the 10th leading cause of death in the United States. Most suicides occur in the context of a psychiatric disorder (Bachmann, 2018 ), and yet the effect of many medications, including psychotropic medications, on suicide risk is intensely debated. The objective of this study is to develop a statistical surveillance methodology based on generalized mixed-effects regression models applied to analysis of large-scale medical claims and medical records that identifies drugs associated with increased and decreased risk of suicidal events. To this end, we use a within-person incident-user cohort design to simultaneously examine the relationship between 922 drugs and 43,978 suicidal events (suicide attempts and intentional self-harm, including fatalities if they resulted in a medical claim) using medical claims for private health insurance (MarketScan) from 2003–2014, for over 150 million people. Suicidal events were identified based on the following ICD-9 codes (E950-E959). Analysis of medical claims data for 922 drugs revealed statistically significant associations with suicidal events, including 10 drugs with increased rates and 44 with reduced rates following exposure. Among the strongest increased risk signals identified were alprazolam, butalbital, hydrocodone, and the codeine/promethazine mixture, and among the potentially most protective drugs were folic acid, mirtazapine, hydroxyzine, disulfiram, and naltrexone. Thirty of the 44 drugs with decreased risk are approved psychotropic medications providing both a degree of validation of the method and reassurance to clinicians about the effectiveness and safety of these drugs in suicidal patients. High-dimensional drug safety surveillance using extensive observational data is feasible and generates statistically and clinically significant signals of possible risks and benefits of drugs on suicide risk.Keywords: empirical Bayes, drug safety, suicide

PURPOSE The results of a study to assess the effectiveness and safety of hyperglycemia management provided by clinical pharmacy specialists (CPSs) versus usual care in outpatients with diabetes from 53 Veterans Affairs (VA) medical centers are reported. METHODS An historical cohort study of outpatients with baseline glycosylated hemoglobin (HbA1c) values of >9% who were referred to a CPS for management of hyperglycemia and primary care patients who were not referred to a CPS was conducted. The primary outcomes were change in HbA1c over time and time to reach an HbA1c value of

Importance The rate of youth suicide has increased over the past 15 years in the United States as has the rate of death due to opioid overdose in adults of parental age. Objective To explore the possible connection between parental use of prescription opioids and the increasing rate of youth suicide. Design, Setting, and Participants A pharmacoepidemiologic study was conducted from January 1, 2010, to December 31, 2016, linking medical claims for parental opioid prescriptions with medical claims for suicide attempts by their children. The study used MarketScan medical claims data covering more than 150 million privately insured people in the United States. The study included 121 306 propensity score–matched 30- to 50-year-old parents who used opioids and parents who did not use opioids and their 10- to 19-year-old children (148 395 children of parents who did not use opioids and 184 142 children of parents who used opioids). Propensity score matching was used to identify relevant control families based on demographic features and concomitant use of psychotropic medication. Exposures Opioid use in a parent was defined as having prescription fills covering more than 365 days of an opioid between 2010 and 2016. Main Outcomes and Measures Suicide attempt rate in the children of parents who used opioids and those who did not use opioids. Results A total of 148 395 children (75 575 sons and 72 820 daughters; mean [SD] age, 11.5 [1.6] years at the start of follow-up) had parents who did not use opioids and 184 142 children (94 502 sons and 89 640 daughters; mean [SD] age, 11.8 [1.8] years at the start of follow-up) with parents who did use opioids. There were 100 899 children aged 10 to 14 years and 47 496 children aged 15 to 19 years with parents who did not use opioids and 96 975 children aged 10 to 14 years and 87 163 children aged 15 to 19 years with parents who did use opioids. Of the children with parents who did not use opioids, 212 (0.14%) attempted suicide; of the children with parents who did use opioids, 678 (0.37%) attempted suicide. Parental use of opioids was associated with a doubling of the risk of a suicide attempt by their offspring (odds ratio [OR], 1.99; 95% CI, 1.71-2.33). The association remained significant after adjusting for child age and sex (OR, 1.85; 95% CI, 1.58-2.17), addition of child and parental depression and diagnoses of substance use disorder (OR, 1.46; 95% CI, 1.24-1.72), and addition of parental history of suicide attempt (OR, 1.45; 95% CI, 1.23-1.71). Geographical variation in opioid use did not change the association (OR, 2.00; 95% CI, 1.71-2.34). Conclusions and Relevance Children of parents who use prescription opioids are at increased risk for suicide attempts, which could be a contributing factor to the time trend in adolescent suicidality. The care of families with a parent who uses opioids should include mental health screening of their children.

Objective Our objective was to determine whether attention-deficit/hyperactivity disorder (ADHD) medication is associated with a decreased risk of unintentional injuries in children and adolescents in the United States across sexes, age groups and injury types. Method We used de-identified inpatient, outpatient, and filled prescription claims data from the Truven Health MarketScan Research Databases. Individuals were followed from January 1, 2005, date of first ADHD diagnosis, or medication prescription, or age 6 years, whichever occurred last, until December 31, 2014, first healthcare insurance disenrollment, or the first year at which their age was recorded as 19 years, whichever occurred first. A person was considered on ADHD medication during a given month if a prescription was filled in that month. The outcome was defined as emergency department visits for injuries, including traumatic brain injuries, with unintentional causes. Odds of having the outcome were compared between medicated and unmedicated months at the population-level and in within-individual analyses using logistic regression. Results Among 1,968,146 individuals diagnosed with ADHD or receiving ADHD medication, 87,154 had at least one event. At the population level, medication use was associated with a lower risk of injuries, both in boys (odds ratio [OR] = 0.85; 95% CI = 0.84−0.86) and girls (OR = 0.87; 95% CI = 0.85−0.89). Similar results were obtained from within-individual analysis among male (OR = 0.72; 95% CI = 0.70−0.74) and female (OR = 0.72; 95% CI = 0.69−0.75) children, and among male (OR = 0.64; 95% CI = 0.60−0.67) and female (OR = 0.65; 95% CI = 0.60−0.71) adolescents. Similar results were found for traumatic brain injuries. Conclusion ADHD medication use was associated with a reduction of different types of unintentional injuries in children and adolescents of both sexes.

Aims We compared the risk of mental health episodes requiring hospitalization (primary aim) or out-patient clinic visits (secondary aim) associated with varenicline versus the nicotine patch (NP) in an era prior to psychiatric boxed warnings. Design Retrospective cohort. Setting Department of Veterans Affairs (VA), USA. Participants VA patients with or without psychiatric comorbidities and a new prescription for varenicline (15 255) were propensity score-matched (1 : 2) to new users of NP (123 054) between 1 May 2006 and 30 September 2007, resulting in 11 774 and 23 548 patients in the varenicline and NP groups, respectively. Measurements The primary outcomes were hospitalizations with a primary discharge diagnosis of a range of mental health disorders: depression, schizophrenia, bipolar disorder, suicide attempt, post-traumatic stress disorder, other psychosis and drug-induced mental disorders. Secondary outcomes were out-patient clinic visits with a primary diagnosis of the above list of mental health disorders. Findings Background characteristics of the treatment groups were similar after matching. There was no statistically significant difference in risk of hospitalization for any of the studied mental health disorders with varenicline compared with NP. Among secondary outcomes there was an increased risk of out-patient clinic visits for schizophrenia among patients who received varenicline [hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.07, 1.51], this increase being evident only in those with a pre-existing mental health disorder. Conclusion In US VA patients studied prior to the boxed warning being implemented, use of varenicline for smoking cessation was not associated with a detectable increase compared with nicotine patches in hospitalization for any mental health outcomes. There was an increased rate of out-patient attendances with a primary diagnosis of schizophrenia amounting to five per 100 person years of treatment. This increase was found only in patients with a pre-existing mental health disorder.

IMPORTANCE: Guidelines for the pharmacological treatment of chronic insomnia in adults recognize that trazodone and other off-label medications are commonly prescribed despite poor evidence. The Department of Veterans Health Affairs (VA) fills high volumes of inexpensive, over-the-counter sedating antihistamines and older antidepressants in addition to benzodiazepines and zolpidem. Yet little is known about the comparative safety of these agents with regard to suicidal behavior. OBJECTIVES: To assess the comparative effectiveness of the safety of medications routinely used to treat insomnia in VA. DESIGN: Comparative effectiveness using propensity score-matched samples. SETTING: VA. PARTICIPANTS: VA patients without any history of suicidal ideation or behavior 12 months prior to first exposure. EXPOSURES: VA formularies and data were used to identify prescriptions for insomnia. Agents accounting for at least 1% of total insomnia fill volume were

This study examines the association between groundwater lithium and diagnoses of bipolar disorder and dementia in the United States, adjusting for local health care resources and demographics.

ObjectiveIndividuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures.MethodsWe followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication.ResultsPatients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24–2.42 males; OR = 2.31, 95% CI = 2.22–2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60–0.85) and without (OR = 0.71, 95% CI = 0.62–0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59–1.30) and without (OR = 1.01, 95% CI = 0.80–1.28) a seizure history.ConclusionsResults reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures.

Background An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting. Objective To investigate whether entacapone is associated with prostate cancer and to assess whether the associations are correlated with advanced disease at the time of cancer diagnosis. Methods Using data from the Department of Veterans Affairs healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014. Patients were followed on-treatment for occurrence of prostate cancer, identified via linkage to the VA cancer registry. Results Mean follow-up time was 3.1 and 4.0 years in the entacapone and control cohort, respectively. There were 17,666 subjects meeting study criteria (mean age, 74 (SD 8.6) years); the entacapone-treated group comprised 5,257 subjects. Twenty-three prostate cancer cases occurred in the entacapone cohort and ninety-seven in the control cohort. The overall incidence of prostate cancer was 1.8 per 1,000 person-years of risk. There was no difference in risk of prostate cancer between the cohorts for increased duration of entacapone intake (adjusted HR: 1.08; 95% confidence interval: 0.46–2.51 for cumulative exposure of ≥2 years). Time since starting drug therapy and cumulative dose (mg) also do not suggest a difference in prostate cancer risk between cohorts. Conclusions Prolonged therapy with entacapone was not associated with increased prostate cancer incidence; however, findings suggest a higher severity of prostate cancer.

The purpose of this study was to determine whether polymorphisms in the serotonin transporter (SLC6A4) and serotonin-2A receptor (HTR2A) genes are associated with response to escitalopram in patients with autism spectrum disorder (ASD).Forty-four participants with ASD were enrolled in a 6 week, forced titration, open label examination of the selective serotonin reuptake inhibitor (SSRI) escitalopram. Doses increased at weekly intervals starting at 2.5mg daily with a maximum possible dose of 20 mg daily achieved by the end of the study. If adverse events were experienced, participants subsequently received the previously tolerated dose for the duration of study. SLC6A4 (5-HTTLPR) and HTR2A (rs7997012) genotype groups were assessed in relation to treatment outcomes and drug doses.Insistence on sameness and irritability symptoms significantly improved over the course of the 6 week treatment period (p0.0001) in this open-label trial. There were no significant differences observed in the rate of symptom improvement over time across genotype groups. Similarly, dosing trajectory was not significantly associated with genotype groups.Previous studies have identified SLC6A4 and HTR2A associations with SSRI response in patients with depression and 5-HTTLPR (SLC6A4) associations with escitalopram response in ASD. We did not observe evidence for similar relationships in this ASD study.

Substance use disorders are major contributors to excess mortality among individuals with attention deficit hyperactivity disorder (ADHD), yet associations between pharmacological ADHD treatment and substance-related problems remain unclear. This study investigated concurrent and long-term associations between ADHD medication treatment and substance-related events.The authors analyzed 2005-2014 commercial health care claims from 2,993,887 (47.2% female) adolescent and adult ADHD patients. Within-individual analyses compared the risk of substance-related events (i.e., emergency department visits related to substance use disorders) during months in which patients received prescribed stimulant medication or atomoxetine relative to the risk during months in which they did not.In adjusted within-individual comparisons, relative to periods in which patients did not receive ADHD medication, male patients had 35% lower odds of concurrent substance-related events when receiving medication (odds ratio=0.65, 95% CI=0.64-0.67), and female patients had 31% lower odds of concurrent substance-related events (odds ratio=0.69, 95% CI=0.67-0.71). Moreover, male patients had 19% lower odds of substance-related events 2 years after medication periods (odds ratio=0.81, 95% CI=0.78-0.85), and female patients had 14% lower odds of substance-related events 2 years after medication periods (odds ratio=0.86, 95% CI= 0.82-0.91). Sensitivity analyses supported most findings but were less consistent for long-term associations among women.These results provide evidence that receiving ADHD medication is unlikely to be associated with greater risk of substance-related problems in adolescence or adulthood. Rather, medication was associated with lower concurrent risk of substance-related events and, at least among men, lower long-term risk of future substance-related events.

Importance Motor vehicle crashes (MVCs) are a major public health problem. Research has demonstrated that individuals with attention-deficit/hyperactivity disorder (ADHD) are more likely to experience MVCs, but the effect of ADHD medication treatment on the risk of MVCs remains unclear. Objective To explore associations between ADHD medication use and risk of MVCs in a large cohort of patients with ADHD. Design, Setting, and Participants For this study, a US national cohort of patients with ADHD (n = 2 319 450) was identified from commercial health insurance claims between January 1, 2005, and December 31, 2014, and followed up for emergency department visits for MVCs. The study used within-individual analyses to compare the risk of MVCs during months in which patients received ADHD medication with the risk of MVCs during months in which they did not receive ADHD medication. Exposures Dispensed prescription of ADHD medications. Main Outcomes and Measures Emergency department visits for MVCs. Results Among 2 319 450 patients identified with ADHD, the mean (SD) age was 32.5 (12.8) years, and 51.7% were female. In the within-individual analyses, male patients with ADHD had a 38% (odds ratio, 0.62; 95% CI, 0.56-0.67) lower risk of MVCs in months when receiving ADHD medication compared with months when not receiving medication, and female patients had a 42% (odds ratio, 0.58; 95% CI, 0.53-0.62) lower risk of MVCs in months when receiving ADHD medication. Similar reductions were found across all age groups, across multiple sensitivity analyses, and when considering the long-term association between ADHD medication use and MVCs. Estimates of the population-attributable fraction suggested that up to 22.1% of the MVCs in patients with ADHD could have been avoided if they had received medication during the entire follow-up. Conclusions and Relevance Among patients with ADHD, rates of MVCs were lower during periods when they received ADHD medication. Considering the high prevalence of ADHD and its association with MVCs, these findings warrant attention to this prevalent and preventable cause of mortality and morbidity.

PURPOSE: In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding. METHODS: We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding. RESULTS: For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone. CONCLUSIONS: Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth. Copyright © 2014 John Wiley & Sons, Ltd. Language: en

Objective To compare educational, occupational, legal, emotional, substance use disorder, and sexual behavior outcomes in young adults with persistent and desistent attention-deficit/hyperactivity disorder (ADHD) symptoms and a local normative comparison group (LNCG) in the Multimodal Treatment Study of Children with ADHD (MTA). Method Data were collected 12, 14, and 16 years postbaseline (mean age 24.7 years at 16 years postbaseline) from 476 participants with ADHD diagnosed at age 7 to 9 years, and 241 age- and sex-matched classmates. Probands were subgrouped on persistence versus desistence of DSM-5 symptom count. Orthogonal comparisons contrasted ADHD versus LNCG and symptom-persistent (50%) versus symptom-desistent (50%) subgroups. Functional outcomes were measured with standardized and demographic instruments. Results Three patterns of functional outcomes emerged. Post−secondary education, times fired/quit a job, current income, receiving public assistance, and risky sexual behavior showed the most common pattern: the LNCG group fared best, symptom-persistent ADHD group worst, and symptom-desistent ADHD group between, with the largest effect sizes between LNCG and symptom-persistent ADHD. In the second pattern, seen with emotional outcomes (emotional lability, neuroticism, anxiety disorder, mood disorder) and substance use outcomes, the LNCG and symptom-desistent ADHD group did not differ, but both fared better than the symptom-persistent ADHD group. In the third pattern, noted with jail time (rare), alcohol use disorder (common), and number of jobs held, group differences were not significant. The ADHD group had 10 deaths compared to one death in the LNCG. Conclusion Adult functioning after childhood ADHD varies by domain and is generally worse when ADHD symptoms persist. It is important to identify factors and interventions that promote better functional outcomes.

This study examined a model for mental health consultation, training and support designed to enhance the benefits of publicly-funded recreational after-school programs in communities of concentrated urban poverty for children's academic, social, and behavioral functioning. We assessed children's mental health needs and examined the feasibility and impact of intervention on program quality and children's psychosocial outcomes in three after-school sites (n = 15 staff, 89 children), compared to three demographically-matched sites that received no intervention (n = 12 staff, 38 children). Findings revealed high staff satisfaction and feasibility of intervention, and modest improvements in observed program quality and staff-reported children's outcomes. Data are considered with a public health lens of mental health promotion for children in urban poverty.

Objective:It is unknown whether prolonged childhood exposure to stimulant medication for the treatment of attention deficit hyperactivity disorder (ADHD) increases the risk for developing abnormalities in blood pressure or heart rate. The authors examined the association between stimulant medication and blood pressure and heart rate over 10 years. Method:A total of 579 children, ages 7–9, were randomly assigned to 14 months of medication treatment, behavioral therapy, the combination of the two, or usual community treatment. The controlled trial was followed by naturalistic treatment with periodic assessments. Blood pressure and heart rate data were first analyzed with linear regression models based on an intent-to-treat approach, using raw data and the blood pressure categories of prehypertension and hypertension. Currently medicated patients were then compared with never or previously medicated patients. Associations between cumulative stimulant exposure and blood pressure or heart rate were assessed. R...

Purpose On 16 December 2008, FDA issued a class warning for antiepileptic drugs and suicidal thoughts and behavior. The purpose of this study was to determine if the antiepileptic drug gabapentin increases risk of suicide attempt in patients to which it was prescribed for various indications. Methods We conducted a pharmacoepidemiologic study in which suicide attempt rates were compared before and after gabapentin was prescribed. We used the PharMetrics medical claims database to study the relationship between gabapentin and suicide attempts in a cohort of 131 178 patients with a 1-year window of information before and after initial prescription. Patients had diagnoses of epilepsy, pain disorders, bipolar illness, major depressive disorder, schizophrenia, and other psychiatric disorders. Results Overall, there was no significant difference in suicide attempt rates before (3.48/1000 patient years—PY) versus after (3.45/1000 PY) gabapentin prescription. Pre-prescription suicide attempt rates were five times higher in psychiatric populations compared with non-psychiatric populations leading us to analyze the two groups separately. No drug effect was detected in the non-psychiatric populations. Significant reductions in suicide attempt rates were seen for bipolar disorder (47.85/1000 PY versus 31.46/1000 PY), major depressive disorder (17.30/1000 PY versus 12.66/1000 PY), and other psychiatric disorders (12.84/1000 PY versus 10.14/1000 PY). Person–time analysis revealed an overall significant reduction in suicide attempt rates (2.01/1000 PY on drug versus 2.30/1000 PY off drug). Conclusions This study finds that gabapentin does not increase risk of suicide attempts in non-psychiatric populations and is associated with a reduction in suicide attempt risk in patients with psychiatric disorders. Copyright © 2010 John Wiley & Sons, Ltd.

Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation).At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events.Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months.Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)

Importance Adults with mental health conditions are more likely than those without to receive long-term opioid therapy. Less is known about opioid therapy among adolescents, especially those with mental health conditions. Objective To examine associations between preexisting mental health conditions and treatments and initiation of any opioid and long-term opioid therapy among adolescents. Design, Setting, and Participants A cohort of 1 224 520 incident opioid recipients without cancer diagnoses aged 14 to 18 years at first receipt was extracted from nationwide commercial health care claims data from January 1, 2003, to December 31, 2014. Analysis was conducted from August 19, 2016, to November 16, 2017. Associations between preexisting mental health conditions and treatments and any opioid receipt were examined by comparing recipients with nonrecipients matched on sex, calendar year and years of age of first enrollment, and months of enrollment (prior to the index month for recipients, ever for nonrecipients). Associations between preexisting mental health conditions and treatments and subsequent long-term opioid therapy were examined among recipients with at least 6 months’ follow-up using Cox proportional hazards regressions adjusted for demographics. Exposures Mental health condition diagnoses and treatments recorded in inpatient, outpatient, and filled-prescription claims prior to opioid receipt. Main Outcomes and Measures Opioid receipt, defined as any opioid analgesic prescription claim, and long-term opioid therapy, defined as more than 90 days’ supply within a 6-month window having no gaps in supply of more than 32 days. Results Of the 1 224 520 new opioid recipients included, the median age at first receipt was 17 years (interquartile range, 16-18 years), and 51.1% were female. Median follow-up after first receipt was 625 days (interquartile range, 255-1268 days). Adolescents with anxiety, mood, neurodevelopmental, sleep, and nonopioid substance use disorders and most mental health treatments were significantly more likely to receive any opioid (odds ratios from 1.13 [95% CI, 1.10-1.16] for nonopioid substance use disorders to 1.69 [95% CI, 1.58-1.81] for nonbenzodiazepine hypnotics). Among the 1 000 453 opioid recipients (81.7%) who had at least 6 months’ follow-up, the cumulative incidence of long-term opioid therapy was 3.0 (95% CI, 2.8-3.1) per 1000 recipients within 3 years after first opioid receipt. All preexisting mental health conditions and treatments were strongly associated with higher rates of long-term opioid therapy (adjusted hazard ratios from 1.73 [95% CI 1.54-1.95] for attention-deficit/hyperactivity disorder to 8.90 [95% CI, 5.85-13.54] for opioid use disorder). Conclusions and Relevance Commercially insured adolescents with many types of preexisting mental health conditions and treatments were modestly more likely to receive any opioid and were substantially more likely to subsequently transition to long-term opioid therapy relative to those without, although overall rates of long-term opioid therapy were low.

Background Factors leading to seroma following ventral incisional herniorrhaphy (VIH) are poorly understood. Methods Between 2004 and 2006, patients were prospectively randomized at 4 Veterans Affairs hospitals to undergo laparoscopic or open VIH. Patients who developed seromas within 8 weeks postoperatively were compared with those who did not. Multivariate analyses were performed to identify predictors of seroma. Results Of 145 patients who underwent VIH, 24 (16.6%) developed seromas. Patients who underwent open VIH had more seromas than those who underwent laparoscopic VIH (23.3% vs 6.8%, P = .011). Seroma patients had hernias that were never spontaneously reducible (0% vs 21%, P = .015), had more abdominal incisions preoperatively (mean, 2.4 vs 1.8; P = .037), and were less likely to have drain catheters placed than those without seromas (30.0% vs 63.1%, P = .011). In multivariate analyses, open VIH predicted seroma (odds ratio, 5.5; 95% confidence interval, 1.6–18.8), as well as the specific hospital at which the procedure was performed. Spontaneous resolution occurred in 71% of seromas; 29% required aspiration. Conclusions Procedural characteristics and hernia characteristics rather than patient comorbidities predicted seroma in VIH.

Background This study was undertaken to compare survival between primary and repeat lung transplant recipients and to identify survival predictors after repeat lung transplantation. Methods Data for 10,846 primary and 354 repeat lung transplant patients were extracted from the United Network for Organ Sharing registry. Propensity score matching was used to examine balance in the distribution of potential observed confounders and to match the sample in terms of the probability of repeat lung transplantation given pretransplant characteristics alone. Matching based on the propensity score was used to compare survival between the primary and repeat lung transplant groups. A Cox regression model was used to identify risk factors for death in the cohort of patients receiving lung transplant. Results Considerable bias between the primary and repeat lung transplant groups was found in the sample. Patients with high propensity scores tended to carry high-risk profiles. Propensity score matching revealed incomplete overlap of covariate distributions between primary and repeat transplant groups. For those subjects who could be matched for the set of potential confounding variables, no difference in survival time was observed between primary and repeat lung transplant patients. Functional status and serum creatinine level were the two clinically important risk factors for predicting the survival of repeat transplant patients. Conclusions The current study revealed that direct comparison of the survival of primary and repeat lung transplant patients is biased by nonoverlap in the distribution of potential confounders. Using propensity score matching we adjusted for this bias and found that there was no significant difference in survival between first and second transplants.

In 2003 and 2004, U.S. and European regulators issued public health warnings about a possible association between antidepressants and suicidal thinking and behavior. The authors assessed whether these warnings discouraged use of antidepressants in children and adolescents and whether they led to increases in suicide rates as a result of untreated depression.The authors examined U.S. and Dutch data on prescription rates for selective serotonin reuptake inhibitors (SSRIs) from 2003 to 2005 in children and adolescents (patients up to age 19), as well as suicide rates for children and adolescents, using available data (through 2004 in the United States and through 2005 in the Netherlands). They used Poisson regression analyses to determine the overall association between antidepressant prescription rates and suicide rates, adjusted for sex and age, during the periods preceding and immediately following the public health warnings.SSRI prescriptions for youths decreased by approximately 22% in both the United States and the Netherlands after the warnings were issued. In the Netherlands, the youth suicide rate increased by 49% between 2003 and 2005 and shows a significant inverse association with SSRI prescriptions. In the United States, youth suicide rates increased by 14% between 2003 and 2004, which is the largest year-to-year change in suicide rates in this population since the Centers for Disease Control and Prevention began systematically collecting suicide data in 1979.In both the United States and the Netherlands, SSRI prescriptions for children and adolescents decreased after U.S. and European regulatory agencies issued warnings about a possible suicide risk with antidepressant use in pediatric patients, and these decreases were associated with increases in suicide rates in children and adolescents.

Objective: In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination (Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. Method: For primary outcome measures (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. Results: At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication >50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. Conclusions: By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated.

Objective: To evaluate two hypotheses: that self-selection bias contributed to lack of medication advantage at the 36-month assessment of the Multimodal Treatment Study of Children With ADHD (MTA) and that overall improvement over time obscured treatment effects in subgroups with different outcome trajectories. Method: Propensity score analyses, using baseline characteristics and severity of attention-deficit/hyperactivity disorder symptoms at follow-up, established five subgroups (quintiles) based on tendency to take medication at the 36-month assessment. Growth mixture model (GMM) analyses were performed to identify subgroups (classes) with different patterns of outcome over time. Results: All five propensity subgroups showed initial advantage of medication that disappeared by the 36-month assessment. GMM analyses identified heterogeneity of trajectories over time and three classes: class 1 (34% of the MTA sample) with initial small improvement followed by gradual improvement that produced significant medication effects; class 2 (52%) with initial large improvement maintained for 3 years and overrepresentation of cases treated with the MTA Medication Algorithm; and class 3 (14%) with initial large improvement followed by deterioration. Conclusions: We failed to confirm the self-selection hypothesis. We found suggestive evidence of residual but not current benefits of assigned medication in class 2 and small current benefits of actual treatment with medication in class 1.

Objective: In late 2006, a U.S. Food and Drug Administration advisory committee recommended that the 2004 black box warning regarding suicidality in pediatric patients receiving antidepressants be extended to include young adults. This study examined the relationship between antidepressant treatment and suicide attempts in adult patients in the Veterans Administration health care system. Method: The authors analyzed data on 226,866 veterans who received a diagnosis of depression in 2003 or 2004, had at least 6 months of follow-up, and had no history of depression from 2000 to 2002. Suicide attempt rates overall as well as before and after initiation of antidepressant therapy were compared for patients who received selective serotonin reuptake inhibitors (SSRIs), new-generation non-serotonergic-specific (non-SSRI) antidepressants (bupropion, mirtazapine, nefazodone, and venlafaxine), tricyclic antidepressants, or no antidepressant. Age group analyses were also performed. Results: Suicide attempt rates were...

Background The purpose of this study was to identify predictors for survival after primary and repeat heart transplantations, and to compare their survival. Methods The United Network for Organ Sharing database provided 20,787 primary heart transplants and 594 repeat heart transplants (for those patients who had previously undergone a primary heart transplant). Cox regression models were used to separately determine predictors of survival in primary and retransplant patients and to compare their survival distributions. Propensity score matching was then used to compare the survival between primary and retransplant patients adjusted for potential confounders. Results Similar predictors of survival were found for primary and retransplant patients. The overall increased risk of death was 71% higher for retransplant versus primary transplant patients. Propensity score analysis showed that, in patients with characteristics most similar to primary transplant patients, the increased risk of death was 133%; however, for patients with characteristics most like retransplant patients, the increased risk of death was only 34%. Conclusions Survival after retransplantation is significantly reduced relative to survival after primary transplantation. The difference in survival between primary and repeat transplants is smallest among recipients who fit the profile of the typical repeat transplant patient. In general, these are younger patients with better functional status prior to listing, who received an organ from a younger donor.

Concern regarding the removal of African American children from their homes in McLean county and Peoria County Illinois, and placing them into Foster care have been the center of considerable debate and concern in the state of Illinois. As a result, a county- level (McLean and Peoria counties) investigation and intervention was performed. To evaluate the success of this intervention, we developed a mixed-effects Poisson regression model for the analysis of these data, and used it to obtain case-mix adjusted empirical Bayes estimates of county-specific changes (2000-2002) in Foster care placement rates in all counties in the state of Illinois. Results of the analysis revealed that four out of the 85 counties with African American residents in the state of Illinois exhibited significant decreases in Foster care placement rates relative to the change in the overall state-wide rate between 2000 and 2002. The two counties that received the intervention (McLean and Peoria) were among the four counties out of 85 counties that exhibited significant de- creases in Foster care placement rates (OR = 14.7, P < 0.0001). Conceptual and statistical aspects of this type of statistical profiling are presented and discussed.

We compared the risk of mental health episodes requiring hospitalization (primary aim) or out-patient clinic visits (secondary aim) associated with varenicline versus the nicotine patch (NP) in an era prior to psychiatric boxed warnings.Retrospective cohort.Department of Veterans Affairs (VA), USA.VA patients with or without psychiatric comorbidities and a new prescription for varenicline (15 255) were propensity score-matched (1 : 2) to new users of NP (123 054) between 1 May 2006 and 30 September 2007, resulting in 11 774 and 23 548 patients in the varenicline and NP groups, respectively.The primary outcomes were hospitalizations with a primary discharge diagnosis of a range of mental health disorders: depression, schizophrenia, bipolar disorder, suicide attempt, post-traumatic stress disorder, other psychosis and drug-induced mental disorders. Secondary outcomes were out-patient clinic visits with a primary diagnosis of the above list of mental health disorders.Background characteristics of the treatment groups were similar after matching. There was no statistically significant difference in risk of hospitalization for any of the studied mental health disorders with varenicline compared with NP. Among secondary outcomes there was an increased risk of out-patient clinic visits for schizophrenia among patients who received varenicline [hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.07, 1.51], this increase being evident only in those with a pre-existing mental health disorder.In US VA patients studied prior to the boxed warning being implemented, use of varenicline for smoking cessation was not associated with a detectable increase compared with nicotine patches in hospitalization for any mental health outcomes. There was an increased rate of out-patient attendances with a primary diagnosis of schizophrenia amounting to five per 100 person years of treatment. This increase was found only in patients with a pre-existing mental health disorder.

In 2002, 264 children and adolescents ages 5-14 died by suicide in the United States, the fifth leading cause of death. Of these suicides, 260 were in the 10-14 year age group, making suicide the third largest cause of death behind accidents and malignancy. Although 60% of suicides in the general population occur in the midst of a mood disorder, usually untreated, little is known about the relationship between treatment of mood disorders and youth suicide. The FDA recently linked adverse event reports of suicidal ideation among children and adolescents in randomized controlled trials to selective serotonin reuptake inhibitors (SSRIs) and consequently required a change in labeling that included a black box warning regarding SSRI use for all age groups. Given that the age-adjusted suicide rate is about six times higher in 15-19 year olds compared with 10-14 year olds, the risk-benefit ratio may be different in younger children. Therefore, this study examined the association between antidepressant medication prescription rate and suicide rate in children ages 5-14 prior to the FDA findings by analyzing associations at the county level across the United States.National county-level suicide rate data among children ages 5-14 were broken down by sex, income, and race during the period 1996-1998. National county-level antidepressant prescription rate data were expressed as number of pills prescribed per person. The primary outcome measure was the suicide rate in each county expressed as number of suicides for a given population size.After adjustment for sex, race, income, access to mental health care, and county-to-county variability in suicide rates, higher SSRI prescription rates were associated with lower suicide rates in children and adolescents.The aggregate nature of these observational data precludes a direct causal interpretation of the results. More SSRI prescriptions are associated with lower suicide rates in children and may reflect antidepressant efficacy, treatment compliance, better quality mental health care, and low toxicity in the event of a suicide attempt by overdose.

Object. Deep brain stimulation (DBS) to treat advanced Parkinson disease (PD) has been focused on one of two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). Authors of more than 65 articles have reported on bilateral DBS outcomes. With one exception, these studies involved pre- and postintervention comparisons of a single target. Despite the paucity of data directly comparing STN and GPI DBS, many clinicians already consider the STN to be the preferred target site. In this study the authors conducted a metaanalysis of the existing literature on patient outcomes following DBS of the STN and the GPI. Methods. This metaanalysis includes 31 STN and 14 GPI studies. Motor function improved significantly following stimulation (54% in patients whose STN was targeted and 40% in those whose GPI was stimulated), with effect sizes (ESs) of 2.59 and 2.04, respectively. After controlling for participant and study characteristics, patients who had undergone either STN or GPI DBS experienced comparable improved motor function following surgery (p = 0.094). The performance of activities of daily living improved significantly in patients with either target (40%). Medication requirements were significantly reduced following stimulation of the STN (ES = 1.51) but did not change when the GPI was stimulated (ES = −0.02). Conclusions. In this analysis the authors highlight the need for uniform, detailed reporting of comprehensive motor and nonmotor DBS outcomes at multiple time points and for a randomized trial of bilateral STN and GPI DBS.

Background Few studies have examined surgical risk factors and outcomes in American Indians and Alaska Natives (AI/ANs). My colleagues and I sought to determine if prevalence of preoperative risk factors for morbidity and mortality differed between male AI/AN and Caucasian surgical patients, and to determine if AI/ANs had an increased risk of surgical morbidity or mortality. Study design We obtained data from the Veterans Affairs National Surgical Quality Improvement Program on major, noncardiac, surgical procedures performed between 1991 and 2002 for all AI/AN men (n = 2,155) and a random sample of Caucasian men (n = 2,264), matched by facility. Chi-square and t -test analyses were used to assess differences in preoperative risk factors between the two groups. Logistic regression was used to determine whether AI/AN race was independently associated with 30-day morbidity (defined as 1 or more of 21 postoperative complications) or 30-day all cause mortality after adjustment for major risk factors. Results Prevalence of major preoperative risk factors for morbidity and mortality often differed between the groups. Compared with Caucasians, AI/AN race did not predict morbidity (adjusted odds ratio, 0.92; 95% CI, 0.75–1.13), but AI/ANs were at higher risk for 30-day all cause postoperative mortality (adjusted odds ratio, 1.56; 95% CI, 1.04–2.35). Conclusions Our results add postoperative mortality to health disparities experienced by AI/ANs. Future research should be conducted to identify other factors that contribute to this disparity.

In this paper, we propose an approach to modeling functional magnetic resonance imaging (fMRI) data that combines hierarchical polynomial models, Bayes estimation, and clustering. A cubic polynomial is used to fit the voxel time courses of event-related design experiments. The coefficients of the polynomials are estimated by Bayes estimation, in a two-level hierarchical model, which allows us to borrow strength from all voxels. The voxel-specific Bayes polynomial coefficients are then transformed to the times and magnitudes of the minimum and maximum points on the hemodynamic response curve, which are in turn used to classify the voxels as being activated or not. The procedure is demonstrated on real data from an event-related design experiment of visually guided saccades and shown to be an effective alternative to existing methods.

The aim of this study is to define the risk factors that predict adverse outcomes for patients undergoing pancreaticoduodenectomy for periampullary cancer in the Department of Veterans Affairs Healthcare System (VA). The VA National Surgical Quality Improvement Program prospectively collected data on 462 patients undergoing pancreaticoduodenectomy in 123 VA medical centers from 1990 to 2000. Independent variables included 68 preoperative and 12 intraoperative variables. The main outcome measures were 30-day postoperative mortality and morbidity, as measured by a set of 20 pre-defined complications. Predictive models for 30-day morbidity and mortality were constructed using logistic regression analysis. The 30-day morbidity rate was 45.9% (212/462). The 30-day postoperative mortality rate was 9.3% (43/462). Significant predictors of mortality included: preoperative serum albumin, American Society of Anesthesiologists classification, preoperative bilirubin >20mg/dl, and operative time. The use of preoperative biliary tract instrumentation did not predict postoperative death or septic complications. This study provides a set of preoperative risk factors that are predictive of adverse outcome following pancreaticoduodenectomy. These factors may assist in patient selection for this procedure and are likely to facilitate risk-adjusted comparison of pancreaticoduodenectomy outcomes between different health care systems.

To assess the feasibility of implementing the National Surgical Quality Improvement Program (NSQIP) methodology in non-VA hospitals.Using data adjusted for patient preoperative risk, the NSQIP compares the performance of all VA hospitals performing major surgery and anonymously compares these hospitals using the ratio of observed to expected adverse events. These results are provided to each hospital and used to identify areas for improvement. Since the NSQIP's inception in 1994, the VA has reported consistent improvements in all surgery performance measures. Given the success of the NSQIP within the VA, as well as the lack of a comparable system in non-VA hospitals, this pilot study was undertaken to test the applicability of the NSQIP models and methodology in the nonfederal sector.Beginning in 1999, three academic medical centers (Emory University, Atlanta, GA; University of Michigan, Ann Arbor, MI; University of Kentucky, Lexington, KY) volunteered the time of a dedicated surgical nurse reviewer who was trained in NSQIP methodology. At each academic center, these nurse reviewers used NSQIP protocols to abstract clinical data from general surgery and vascular surgery patients. Data were manually collected and then transmitted via the Internet to a secure web site developed by the NSQIP. These data were compared to the data for general and vascular surgery patients collected during a concurrent time period (10/99 to 9/00) within the VA by the NSQIP. Logistic regression models were developed for both non-VA and VA hospital data. To assess the models' predictive values, C-indices (0.5 = no prediction; 1.0 = perfect prediction) were calculated after applying the models to the non-VA as well as the VA databases.Data from 2,747 (general surgery 2,251; vascular surgery 496) non-VA hospital cases were compared to data from 41,360 (general surgery 31,393; vascular surgery 9,967) VA cases. The bivariate relationships between individual risk factors and 30-day mortality or morbidity were similar in the non-VA and VA patient populations for over 66% of the risk variables. C-indices of 0.942 (general surgery), 0.915 (vascular surgery), and 0.934 (general plus vascular surgery) were obtained following application of the VA NSQIP mortality model to the non-VA patient data. Lower C-indices (0.778, general surgery; 0.638, vascular surgery; 0.760, general plus vascular surgery) were obtained following application of the VA NSQIP morbidity model to the non-VA patient data. Although the non-VA sample size was smaller than the VA, preliminary analysis suggested no differences in risk-adjusted mortality between the non-VA and VA cohorts. CONCLUSIONS With some adjustments, the NSQIP methodology can be implemented and generates reasonable predictive models within non-VA hospitals.

In health research, count outcomes are fairly common and often these counts have a large number of zeros. In order to adjust for these extra zero counts, various modifications of the Poisson regression model have been proposed. Lambert (Lambert, D., Technometrics 34, 1-14, 1992) described a zero-inflated Poisson (ZIP) model that is based on a mixture of a binary distribution (πi ) degenerated at zero with a Poisson distribution (λi ). Depending on the relationship between πi and λi , she described two variants: a ZIP and a ZIP (τ ) model. In this paper, we extend these models for the case of clustered data (e.g., patients observed within hospitals) and describe random-effects ZIP and ZIP (τ ) models. These models are appropriate for the analysis of clustered extra-zero Poisson count data. The distribution of the random effects is assumed to be normal and a maximum marginal likelihood estimation method is used to estimate the model parameters. We applied these models to data from patients who underwent colon operations from 123 Veterans Affairs Medical Centers in the National VA Surgical Quality Improvement Program.

Objective Recent results from the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD; MTA) have demonstrated impairments in several functioning domains in adults with childhood ADHD. The childhood predictors of these adult functional outcomes are not adequately understood. The objective of the present study was to determine the effects of childhood demographic, clinical, and family factors on adult functional outcomes in individuals with and without childhood ADHD from the MTA cohort. Method Regressions were used to determine associations of childhood factors (age range 7–10 years) of family income, IQ, comorbidity (internalizing, externalizing, and total number of non-ADHD diagnoses), parenting styles, parental education, number of household members, parental marital problems, parent–child relationships, and ADHD symptom severity with adult outcomes (mean age 25 years) of occupational functioning, educational attainment, emotional functioning, sexual behavior, and justice involvement in participants with (n = 579) and without (n = 258) ADHD. Results Predictors of adult functional outcomes in ADHD included clinical factors such as baseline ADHD severity, IQ, and comorbidity; demographic factors such as family income, number of household members and parental education; and family factors such as parental monitoring and parental marital problems. Predictors of adult outcomes were generally comparable for children with and without ADHD. Conclusion Childhood ADHD symptoms, IQ, and household income levels are important predictors of adult functional outcomes. Management of these areas early on, through timely treatments for ADHD symptoms, and providing additional support to children with lower IQ and from households with low incomes, could assist in improving adult functioning.

This analysis discusses the association between the availability of psychiatric hospital beds and suicide rates in the United States.