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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.

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.

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.

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.

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.

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.

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.

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...

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.

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.

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.

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.

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.

Background Deep brain stimulation (DBS) improves motor symptoms in Parkinson9s disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target. Methods Neuropsychological functioning was assessed in patients with Parkinson9s disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered. Results Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up. Conclusions In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL. Trial registration number NCT00056563 and NCT01076452.

Background:A part of the prospective, multi-institutional National Veterans Affairs Surgical Quality Improvement Program was developed to predict 30-day mortality and morbidity for patients undergoing a major pulmonary resection. Methods: Perioperative data were acquired from 194,319 noncardiac surgical operations at 123 Veterans Affairs Medical Centers between October 1, 1991, and August 31, 1995. Current Procedural Terminology code-based analysis was undertaken for major pulmonary resections (lobectomy and pneumonectomy). Preoperative, intraoperative, and outcome variables were collected. The 30-day mortality and morbidity models were developed by means of multivariable stepwise logistic regression with the preoperative and intraoperative variables used as independent predictors of outcome. Results: A total of 3516 patients (mean age 64 ± 9 years) underwent either lobectomy (n = 2949) or pneumonectomy (n = 567). Thirty-day mortality was 4.0% for lobectomy (119/2949) and 11.5% for pneumonectomy (65/567). The preoperative predictors of 30-day mortality were albumin, do not resuscitate status, transfusion of more than 4 units, age, disseminated cancer, impaired sensorium, prothrombin time more than 12 seconds, type of operation, and dyspnea. When the intraoperative variables were considered, intraoperative blood loss was added to the preoperative model. In the presence of these intraoperative variables in the model, do not resuscitate status and prothrombin time more than 12 seconds were only marginally significant. Thirty-day morbidity, defined as the presence of 1 or more of the 21 predefined complications, was 23.8% for lobectomy (703/2949) and 25.7% for pneumonectomy (146/567). In multivariable models, independent preoperative predictors (P < .05) of 30-day morbidity were age, weight loss greater than 10% in the 6 months before surgery, history of chronic obstructive pulmonary disease, transfusion of more than 4 units, albumin, hemiplegia, smoking, and dyspnea. When intraoperative variables were added to the preoperative model, the duration of operation time and intraoperative transfusions were included in the model and albumin became marginally significant. Conclusions: This analysis identifies independent patient risk factors that are associated with 30-day mortality and morbidity for patients undergoing a major pulmonary resection. This series provides an initial risk-adjustment model for major pulmonary resections. Future refinements will allow comparative assessment of surgical outcomes and quality of care at many institutions. (J Thorac Cardiovasc Surg 1999;117:969-79)

The effectiveness of perioperative β-blockade in patients undergoing noncardiac surgery remains controversial.To determine the associations of early perioperative exposure to β-blockers with 30-day postoperative outcome in patients undergoing noncardiac surgery.A retrospective cohort analysis evaluating exposure to β-blockers on the day of or following major noncardiac surgery among a population-based sample of 136,745 patients who were 1:1 matched on propensity scores (37,805 matched pairs) treated at 104 VA medical centers from January 2005 through August 2010.All cause 30-day mortality and cardiac morbidity (cardiac arrest or Q-wave myocardial infarction).Overall 55,138 patients (40.3%) were exposed to β-blockers. Exposure was higher in the 66.7% of 13,863 patients undergoing vascular surgery (95% CI, 65.9%-67.5%) than in the 37.4% of 122,882 patients undergoing nonvascular surgery (95% CI, 37.1%-37.6%; P.001). Exposure increased as Revised Cardiac Risk Index factors increased, with 25.3% (95% CI, 24.9%-25.6%) of those with no risk vs 71.3% (95% CI, 69.5%-73.2%) of those with 4 risk factors or more exposed to β-blockers (P.001). Death occurred among 1.1% (95% CI, 1.1%-1.2%) and cardiac morbidity occurred among 0.9% (95% CI, 0.8%-0.9%) of patients. In the propensity matched cohort, exposure was associated with lower mortality (relative risk [RR], 0.73; 95% CI, 0.65-0.83; P.001; number need to treat [NNT], 241; 95% CI, 173-397). When stratified by cumulative numbers of Revised Cardiac Risk Index factors, β-blocker exposure was associated with significantly lower mortality among patients with 2 factors (RR, 0.63 [95% CI, 0.50-0.80]; P.001; NNT, 105 [95% CI, 69-212]), 3 factors (RR, 0.54 [95% CI, 0.39-0.73]; P.001; NNT, 41 [95% CI, 28-80]), or 4 factors or more (RR, 0.40 [95% CI, 0.25-0.73]; P.001; NNT, 18 [95% CI, 12-34]). This association was limited to patients undergoing nonvascular surgery. β-Blocker exposure was also associated with a lower rate of nonfatal Q-wave infarction or cardiac arrest (RR, 0.67 [95% CI, 0.57-0.79]; P.001; NNT, 339 [95% CI, 240-582]), again limited to patients undergoing nonvascular surgery.Among propensity-matched patients undergoing noncardiac, nonvascular surgery, perioperative β-blocker exposure was associated with lower rates of 30-day all-cause mortality in patients with 2 or more Revised Cardiac Risk Index factors. Our findings support use of a cumulative number of Revised Cardiac Risk Index predictors in decision making regarding institution and continuation of perioperative β-blockade. A multicenter randomized trial involving patients at a low to intermediate risk by these factors would be of interest to validate these observational findings.

The efficacy of statins in reducing perioperative cardiovascular and other organ system complications in patients undergoing noncardiac surgery remains controversial. Owing to a paucity of randomized clinical trials, analyses of large databases may facilitate informed hypothesis generation and more efficient trial design.To evaluate associations of early perioperative statin use with outcomes in a national cohort of veterans undergoing noncardiac surgery.This retrospective, observational cohort analysis included 180 478 veterans undergoing elective or emergent noncardiac surgery (including vascular, general, neurosurgery, orthopedic, thoracic, urologic, and otolaryngologic) who were admitted within 7 days of surgery and sampled by the Veterans Affairs Surgical Quality Improvement Program (VASQIP). Patients were admitted to Department of Veterans Affairs hospitals and underwent 30-day postoperative follow-up. Data were collected from October 1, 2005, to September 30, 2010, and analyzed from November 28, 2013, to October 31, 2016.Statin use on the day of or the day after surgery.All-cause 30-day mortality (primary outcome) and standardized 30-day cardiovascular and noncardiovascular outcomes captured by VASQIP. Use of statins and other perioperative cardiovascular medications was ascertained from the Veterans Affairs Pharmacy Benefits Management research database.A total of 180 478 eligible patients (95.6% men and 4.4% women; mean [SD] age, 63.8 [11.6] years) underwent analysis, and 96 486 were included in the propensity score-matched cohort (96.3% men; 3.7% women; mean [SD] age, 65.9 [10.6] years). At the time of hospital admission, 37.8% of patients had an active outpatient prescription for a statin, of whom 80.8% were prescribed simvastatin and 59.5% used moderate-intensity dosing. Exposure to a statin on the day of or the day after surgery based on an inpatient prescription was noted in 31.5% of the cohort. Among 48 243 propensity score-matched pairs of early perioperative statin-exposed and nonexposed patients, 30-day all-cause mortality was significantly reduced in exposed patients (relative risk, 0.82; 95% CI, 0.75-0.89; P .001; number needed to treat, 244; 95% CI, 170-432). Of the secondary outcomes, a significant association with reduced risk of any complication was noted (relative risk, 0.82; 95% CI, 0.79-0.86; P .001; number needed to treat, 67; 95% CI, 55-87); all were significant except for the central nervous system and thrombosis categories, with the greatest risk reduction (relative risk, 0.73; 95% CI, 0.64-0.83) for cardiac complications.Early perioperative exposure to a statin was associated with a significant reduction in all-cause perioperative mortality and several cardiovascular and noncardiovascular complications. However, the potential for selection biases in these results must be considered.

Objective To determine long-term effects on substance use and substance use disorder (SUD), up to 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA; n=436); to test whether medication at follow-up, cumulative psychostimulant treatment over time, or both relate to substance use/SUD; and to compare substance use/SUD in the ADHD sample to the non-ADHD childhood classmate comparison group (n = 261). Method Mixed-effects regression models with planned contrasts were used for all tests except the important cumulative stimulant treatment question, for which propensity score matching analysis was used. Results The originally randomized treatment groups did not differ significantly on substance use/SUD by the 8-year follow-up or earlier (mean age=17 years). Neither medication at follow-up (mostly stimulants) nor cumulative stimulant treatment was associated with adolescent substance use/SUD. Substance use at all time points, including use of two or more substances and SUD, were each greater in the ADHD than in the non-ADHD samples, regardless of sex. Conclusions Medication for ADHD did not protect from, or contribute to, visible risk of substance use or SUD by adolescence, whether analyzed as randomized treatment assignment in childhood, as medication at follow-up, or as cumulative stimulant treatment over an 8-year follow-up from childhood. These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication. Clinical trial registration information—Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); http://clinical trials.gov/; NCT00000388.

Objectives: Our objective was to compare long-term outcomes of deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) for patients with Parkinson disease (PD) in a multicenter randomized controlled trial. Methods: Patients randomly assigned to GPi (n = 89) or STN DBS (n = 70) were followed for 36 months. The primary outcome was motor function on stimulation/off medication using the Unified Parkinson9s Disease Rating Scale motor subscale. Secondary outcomes included quality of life and neurocognitive function. Results: Motor function improved between baseline and 36 months for GPi (41.1 to 27.1; 95% confidence interval [CI] −16.4 to −10.8; p p p = 0.59). Health-related quality of life improved at 6 months on all subscales (all p values significant), but improvement diminished over time. Mattis Dementia Rating Scale scores declined faster for STN than GPi patients ( p = 0.01); other neurocognitive measures showed gradual decline overall. Conclusions: The beneficial effect of DBS on motor function was stable and comparable by target over 36 months. Slight declines in quality of life following initial gains and gradual decline in neurocognitive function likely reflect underlying disease progression and highlight the importance of nonmotor symptoms in determining quality of life. Classification of Evidence: This study provides Class III evidence that improvement of motor symptoms of PD by DBS remains stable over 3 years and does not differ by surgical target. Neurology ® 2012;79:55–65

Laparoscopic repair of ventral incisional hernias has not been proved to be safer than open mesh repair.Prospective randomized trial conducted between February 1, 2004, to January 31, 2007.Four Veterans Affairs medical centers.One hundred sixty-two patients with ventral incisional hernias.Standardized laparoscopic or open repair.Overall complication rates at 8 weeks and the odds of complications, adjusted for study site, body mass index, and hernia type.Of the 162 randomized patients, 146 underwent surgery (73 open and 73 laparoscopic repairs). Complications were less common in the laparoscopic group (23 patients [31.5%]) compared with the open repair group (35 patients [47.9%]; adjusted odds ratio [AOR], 0.45; 95% confidence interval [CI], 0.22-0.91; P = .03). Surgical site infection through 8 weeks was less common in the laparoscopic group (5.6% vs 23.3%; AOR, 0.2; 95% CI, 0.1-0.6). The mean worst pain score in the laparoscopic group was 15.2 mm lower on a visual analog scale at 52 weeks (95% CI, 1.0-29.3; P = .04). Time to resume work activities was shorter for the laparoscopic group than for the open repair group (median, 23.0 days vs 28.5 days), with an adjusted hazard ratio of 0.54 (95% CI, 0.28-1.04; P = .06). Overall recurrence at 2 years was 12.5% in the laparoscopic group and 8.2% in the open repair group (AOR, 1.6; 95% CI, 0.5-4.7; adjusted P = .44).Laparoscopic repair was associated with fewer, albeit more severe, complications and improved some patient-centered outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00240188.

Objective To determine the influence of the preoperative placement of a left ventricular assist device on survival after heart transplantation. Design Prospective cohort study. Setting Organ sharing database with patient level data on heart transplants in the United States. Participants 2786 adults aged 18 or older in status 1A or 1B (highest priority for heart transplantation with either some form of ventricular assist device, intravenous inotrope, or life expectancy of less than seven days), based on the United Network for Organ Sharing Registry, 1996-2004. Main outcome measure Survival after heart transplantation in patients who did and did not receive a left ventricular assist device. Results The left ventricular assist device was not associated with decreased survival, even after the data were stratified by propensity score (the odds of being a treated patient). Inspection of the strata showed no difference in survival between patients who received the device and those who did not. The hazard ratios in strata 1 to 5 were 0.69, 1.37, 1.55, 0.75, and 1.19, respectively, and none was statistically significant. Conclusion Overall, survival after heart transplantation in patients who received a left ventricular assist device before transplantation was comparable to those who did not receive the device.

Objective: To determine the influence of the type of left ventricular assisted device (LVAD) as predictor of survival, hospitalizations due to infection, and rejection following heart transplantation and to delineate any further predictors of such outcomes. Methods: Patients who received a left ventricular assist device (HeartMate [Thoratec Corp., Pleasanton, CA, USA] or Novacor [World Heart Corporation, Ottawa, Canada]) as a bridge to heart transplantation between October 1991 and June 2004 using the United Network for Organ Sharing (UNOS) Thoracic Registry database were evaluated. Comparison of survival curves between HeartMate and Novacor was performed using Kaplan–Meier survival method and Cox proportional hazard model adjusting for patient demographics and co-morbidities. Infection and rejection rates between the two devices were analyzed using multivariable logistic regression model. Results: The UNOS database provided 1255 patients with HeartMate and 154 patients with Novacor between 1991 and 2004. Unadjusted one- and five-year survivals for HeartMate and Novacor were 0.84 and 0.80 and 0.72 and 0.56, respectively, following heart transplantation. Adjusting for patient demographics and co-morbidities, no statistical significant difference in one-year survival was observed between those who received HeartMate and Novacor (HR = 1.49, p = 0.127). At five years, however, the HeartMate group had higher survival than Novacor (HR = 1.53, p = 0.043). All-time posttransplant hospitalizations due to infection and rejection were similar between HeartMate and Novacor recipients after adjusting for patient case mix. Conclusion: Controlling for patient case mix, there was no survival difference at one year between those who received Novacor versus HeartMate LVAD. At five years, a Novacor bridge to transplant patient on average had statistically significantly lower survival than HeartMate recipients. No difference in infection and rejection were observed.

Objectives To determine any long-term effects, 6 and 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA; N = 436); to test whether attention-deficit/hyperactivity disorder (ADHD) symptom trajectory through 3 years predicts outcome in subsequent years; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers (local normative comparison group; N = 261). Method Mixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent, teacher, and youth report. Results In nearly every analysis, the originally randomized treatment groups did not differ significantly on repeated measures or newly analyzed variables (e.g., grades earned in school, arrests, psychiatric hospitalizations, other clinically relevant outcomes). Medication use decreased by 62% after the 14-month controlled trial, but adjusting for this did not change the results. ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes. The MTA participants fared worse than the local normative comparison group on 91% of the variables tested. Conclusions Type or intensity of 14 months of treatment for ADHD in childhood (at age 7.0–9.9 years) does not predict functioning 6 to 8 years later. Rather, early ADHD symptom trajectory regardless of treatment type is prognostic. This finding implies that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best long-term prognosis. As a group, however, despite initial symptom improvement during treatment that is largely maintained after treatment, children with combined-type ADHD exhibit significant impairment in adolescence. Innovative treatment approaches targeting specific areas of adolescent impairment are needed.

Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy.Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (70 years vsor = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stageor = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006.Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists.The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events.Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P.001). Motor function improved significantly (P.001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P.001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P.001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events.clinicaltrials.gov Identifier: NCT00056563.

To evaluate the hypothesis of stimulant medication effect on physical growth in the follow-up phase of the Multimodal Treatment Study of Children With ADHD.Naturalistic subgroups were established based on patterns of treatment with stimulant medication at baseline, 14-, 24-, and 36-month assessments: not medicated (n = 65), newly medicated (n = 88), consistently medicated (n = 70), and inconsistently medicated (n = 147). Analysis of variance was used to evaluate effects of subgroup and assessment time on measures of relative size (z scores) obtained from growth norms.The subgroup x assessment time interaction was significant for z height (p.005) and z weight (p.0001), due primarily to divergence of the newly medicated and the not medicated subgroups. These initially stimulant-naïve subgroups had z scores significantly0 at baseline. The newly medicated subgroup showed decreases in relative size that reached asymptotes by the 36-month assessment, when this group showed average growth of 2.0 cm and 2.7 kg less than the not medicated subgroup, which showed slight increases in relative size.Stimulant-naïve school-age children with Combined type attention-deficit/hyperactivity disorder were, as a group, larger than expected from norms before treatment but show stimulant-related decreases in growth rates after initiation of treatment, which appeared to reach asymptotes within 3 years without evidence of growth rebound.

To evaluate risk of new-onset type 2 diabetes associated with use of selected antipsychotic agents, the authors conducted a new-user cohort study in a national sample of US Veterans Health Administration patients with schizophrenia (and no preexisting diabetes). The authors studied 15,767 patients who initiated use of olanzapine, risperidone, quetiapine, or haloperidol in 1999–2001 after at least 3 months with no antipsychotic prescriptions. Patients were followed for just over 1 year. New-onset diabetes was identified through diagnostic codes and prescriptions for diabetes medication. In Cox proportional hazards regression adjusting for potential confounders, with patients initiating haloperidol use designated the reference group, diabetes risk was increased equally with new use of olanzapine (hazard ratio (HR) ¼ 1.64, 95% confidence interval (CI): 1.22, 2.19), risperidone (HR ¼ 1.60, 95% CI: 1.19, 2.14), or quetiapine (HR ¼ 1.67, 95% CI: 1.01, 2.76). Diabetes risks were higher in patients under age 50 years. When data were reanalyzed with prevalent-user cohorts and matched case-control designs, results were similar, with slightly less elevated risk estimates. Assuming that the observed associations are causal, approximately one third of new cases of diabetes may be attributed to use of olanzapine, risperidone, and quetiapine in patients taking these medications. Prescribers should be mindful of diabetes risks when treating patients with schizophrenia. antipsychotic agents; case-control studies; cohort studies; diabetes mellitus; pharmacoepidemiology; schizophrenia; veterans

To examine, in the Veterans Health Administration (VHA), the relation between surgical volume and outcome in eight commonly performed operations of intermediate complexity.In multihospital health care systems such as VHA, consideration is often given to closing low-volume surgical services, with the assumption that better surgical outcomes are achieved in hospitals with larger surgical volumes. Literature data to support this assumption in intermediate-complexity operations are either limited or controversial.The VHA National Surgical Quality Improvement Program data on nonruptured abdominal aortic aneurysmectomy, vascular infrainguinal reconstruction, carotid endarterectomy (CEA), lung lobectomy/pneumonectomy, open and laparoscopic cholecystectomy, partial colectomy, and total hip arthroplasty were used. Pearson correlation, analysis of variance, mixed effects hierarchical logistic regression, and automatic interaction detection analysis were used to assess the association of annual procedure/specialty volume with risk-adjusted 30-day death (and stroke in CEA).Eight major surgical procedures (68,631 operations) were analyzed. No statistically significant associations between procedure or specialty volume and 30-day mortality rate (or 30-day stroke rate in CEA) were found.In VHA hospitals, the procedure and surgical specialty volume in eight prevalent operations of intermediate complexity are not associated with risk-adjusted 30-day mortality rate from these operations, or with the risk-adjusted 30-day stroke rate from CEA. Volume of surgery in these operations should not be used as a surrogate for quality of surgical care.

Background Approximately 30 000 people die annually by suicide in the United States. Although 60% of suicides occur during a mood disorder, mostly untreated, little is known about the relationship between antidepressant medication use and the rate of suicide in the United States. Objective To examine the association between antidepressant medication prescription and suicide rate by analyzing associations at the county level across the United States. Design Analysis of National Vital Statistics from the Centers for Disease Control and Prevention. Setting All US counties. Participants All US individuals who committed suicide between 1996 and 1998. Main Outcome Measures National county-level suicide rate data are broken down by age, sex, income, and race for the period of 1996 to 1998. National county-level antidepressant prescription data are expressed as number of pills prescribed. The primary outcome measure is the suicide rate in each county expressed as the number of suicides for a given population size. Results The overall relationship between antidepressant medication prescription and suicide rate was not significant. Within individual classes of antidepressants, prescriptions for selective serotonin reuptake inhibitors (SSRIs) and other new-generation non-SSRI antidepressants (eg, nefazodone hydrochloride, mirtazapine, bupropion hydrochloride, and venlafaxine hydrochloride) are associated with lower suicide rates (both within and between counties). A positive association between tricyclic antidepressant (TCA) prescription and suicide rate was observed. Results are adjusted for age, sex, race, income, and county-to-county variability in suicide rates. Higher suicide rates in rural areas are associated with fewer antidepressant prescriptions, lower income, and relatively more prescriptions for TCAs. Conclusions The aggregate nature of these observational data preclude a direct causal interpretation of the results. A high number of TCA prescriptions may be a marker for those counties with more limited access to quality mental health care and inadequate treatment and detection of depression, which in turn lead to increased suicide rates. By contrast, increases in prescriptions for SSRIs and other new-generation non-SSRIs are associated with lower suicide rates both between and within counties over time and may reflect antidepressant efficacy, compliance, a better quality of mental health care, and low toxicity in the event of a suicide attempt by overdose.

To improve the precision and reliability of estimates of the association between preoperative serum albumin concentration and surgical outcomes.Prospective observational study. Patients were followed up for 30 days postoperatively. Multiple logistic regression models were developed to evaluate serum albumin level as a predictor of operative mortality and morbidity in relation to 61 other preoperative patient risk variables.Forty-four tertiary care Veterans Affairs (VA) medical centers.A total of 54215 major noncardiac surgery cases from the National VA Surgical Risk Study.Thirty-day operative mortality and morbidity.A decrease in serum albumin from concentrations greater than 46 g/L to less than 21 g/L was associated with an exponential increase in mortality rates from less than 1% to 29% and in morbidity rates from 10% to 65%. In the regression models, albumin level was the strongest predictor of mortality and morbidity for surgery as a whole and within several subspecialties selected for further analysis. Albumin level was a better predictor of some types of morbidity, particularly sepsis and major infections, than other types.Serum albumin concentration is a better predictor of surgical outcomes than many other preoperative patient characteristics. It is a relatively low-cost test that should be used more frequently as a prognostic tool to detect malnutrition and risk of adverse surgical outcomes, particularly in populations in whom comorbid conditions are relatively frequent.