BACKGROUND: Evidence is missing on showcasing current practices of degree programs specific to the field of pharmaceutical outcomes research. OBJECTIVES: To measure current practices of pharmacoeconomics and outcomes research PhD programs in the United States and synthesize recommendations for improving the success of programs and prospective students. METHODS: A 23-question online survey instrument was created and distributed to 32 program directors identified in the International Society for Pharmacoeconomics and Outcomes Research educational directory. Descriptive statistics summarized both the program characteristics (including observed and desired number of faculty and students) and training recommendations (traits of program and student success). RESULTS: Of 30 eligible programs that conferred a PhD in pharmacoeconomics, pharmaceutical outcomes research, or a related field, 16 respondents (53%) completed the survey. Seventy-five percent of respondents were located in a school of pharmacy. The average observed number of faculty (7.5) and students (11.5) was lower than the average desired numbers (8.1) and (14.7), respectively. Reputation of faculty research and a collaborative environment with other disciplines were rated highest for a program's success. Faculty's mentoring experience and reputation and student funding opportunities were rated highest for prospective students' success. CONCLUSIONS: Existing and emerging programs as well as prospective students can use these findings to further their chances of success.

OBJECTIVES: To describe nursing compliance with a computer-based pediatric thrombosis risk assessment tool; to generate an estimate of risk factors present in our population; and to explore relationships between risk factors and confirmed thrombotic events. DESIGN: Institutional review board-approved prospective, observational cohort study. SETTING: Pediatric intensive care unit within a tertiary care children's hospital. PATIENTS: All infants and children admitted to the pediatric intensive care unit during a 6-month study period (January 1, 2010-June 30, 2010). MEASUREMENTS AND MAIN RESULTS: Eight hundred admissions were enrolled, representing 742 patients. Thrombosis risk assessment scores were recorded for 707 admissions (88% of total). Mean age = 6.95 ± 6 yrs, mean weight = 28 ± 23 kg, 45% female. A total of 32 thrombi (14 prehospital and 18 in-hospital) were present in the study group. This translated to an overall occurrence rate of 4.3%(1.9% for prehospital and 2.4% for in-hospital). Logistic regression identified that for every 1-point increase in total thrombosis score, the risk of developing a symptomatic thrombus increased by 1.57-fold (95% confidence interval 0.192-5.5) to 2.12-fold (95% confidence interval 0.175-18.34), for prehospital and in-hospital thrombi, respectively (p <.05). The most important risk factors identified for development of any thrombus were thrombophilia (acquired or inherited)(p <.001), presence of a central catheter (p =.01), and age <1 or >14 yrs (p =.052). CONCLUSIONS: Incorporation of a scoring system into the bedside nursing assessment flow sheet was successful and identified children at risk for in-hospital thrombosis. The overall score appears to be most indicative of thrombus risk. These data may serve as a platform for future development of routine screening and possible interventional trials in critically ill children.

BACKGROUND: Antidepressants are the first-line treatment for depression, yet medication-related side effects may be associated with antidepressant discontinuation before reaching a period of exposure believed to result in effectiveness. There is a gap in knowledge of the prevalence of side effects across commonly prescribed antidepressants and the effect of the type of antidepressant on the likelihood of side effects in real-world clinical practice. OBJECTIVE: The aim of this study was to estimate and compare the prevalence of headaches, nausea or vomiting, agitation, sedation, and sexual dysfunction among patients diagnosed with depression who initiated monotherapy across different classes of antidepressants and to estimate the effect of the type of antidepressant on the likelihood of each of the 5 side effects. METHODS: A retrospective cohort of patients aged ≥13 who were newly diagnosed with depression and began antidepressant monotherapy was created using LifeLink managed care claims from 1998 to 2008. Antidepressant groups included selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), bupropion, phenylpiperazine, and tetracyclic antidepressants. Prevalence of headache, nausea or vomiting, agitation, sedation, and sexual dysfunction were compared across antidepressant groups. Propensity-adjusted Cox proportional hazards regression was used to estimate the likelihood of each of the 5 side effects for each antidepressant group compared with SSRIs, adjusted for demographic, clinical, and treatment characteristics. RESULTS: The study cohort included 40,017 patients (3617 adolescents, aged 13-18 years, and 36,400 adults, aged ≥19 years; mean age = 45 years; 67% female) with a new episode of depression who were initiated on antidepressant monotherapy within 30 days of diagnosis (SSRI [66%], bupropion [14%], SNRI [12%], other [8%]). The most common side effects were headache (up to 17/1000 person-months of therapy in adults and adolescents) and nausea (up to 7.2/1000 in adults, 9.3/1000 in adolescents). Relative to adults receiving SSRIs, adults receiving SNRIs had a higher risk of nausea (hazard ratio [HR]= 1.26; 95%CI,1.05-1.51). Adults (HR = 0.78; 95% CI, 0.62-0.96) and adolescents (HR = 0.43; 95% CI, 0.21-0.87) taking bupropion were less likely to experience headaches compared with adults and adolescents, respectively, taking an SSRI. Adolescents receiving a tetracyclic were more likely to experience headaches than adolescents receiving an SSRI (HR = 3.16; 95%CI, 1.13-8.84). CONCLUSIONS: Prevalence and risk of the 5 side effects varied across types of antidepressants for both adults and adolescents. Results from this study were consistent with prior clinical trials, suggesting that variation in side effect profiles exists in a more generalized managed care population.

BACKGROUND: The US Food and Drug Administration has issued warnings about a potential link between leukotriene receptor-modifying agents (LTMA) and suicide. These warnings are based on case reports and there is controversy about the association. While spontaneous reporting of suicide-related events attributed to LTMA has risen dramatically, these data may be biased by the warnings. The objective of this study was to explore the relationship between LTMA and suicide deaths using event data preceding the Food and Drug Administration warnings. METHODS: We conducted a mixed-effects Poisson regression analysis of the association between LTMA prescriptions dispensed and suicide deaths at the county level. Counts of suicide deaths in each US county, stratified by race, age group, gender, and year were obtained from the National Center for Health Statistics for the period January 1, 1999 to December 31, 2006. Counts of LTMA prescriptions dispensed in each US county were obtained from IMS Health Incorporated. The model estimated the overall suicide rate conditional on LTMA use, adjusted for age, gender, race, year, and antidepressant utilization. We also assessed the intracounty and intercounty associations. RESULTS: There were 249,872 suicides in the US between 1999 and 2006, and the annual suicide rate ranged from 11.17 to 11.92 per 100,000 population. There were 118.63, 11.68, and 0.12 million prescriptions dispensed for montelukast, zafirlukast, and zileuton, respectively, between 1999 and 2006. The mean rate of LTMA prescriptions dispensed by county was 42.91 (95% confidence interval [CI] 42.78-43.04), 4.82 (95% CI 4.81-4.84), and 0.05 (95% CI 0.05-0.05) per 1000 for montelukast, zafirlukast, and zileuton, respectively. We found a negative within-county association between the rate of total LTMA prescriptions dispensed and the suicide rate by county (P = 0.0296). This association was primarily driven by montelukast. CONCLUSION: Our results, while subject to certain limitations, provide preliminary evidence that the association between LTMA and suicide could be different (ie, reduced risk) than that which might be anticipated based on previous warnings. Patient-level research is needed to understand more clearly the association between LTMA and suicide.

OBJECTIVES To compare depressed older (≥65) and younger (25-64) adults with regard to antidepressant treatment patterns and to assess factors associated with 180-day nonpersistence. DESIGN Retrospective matched cohort study. SETTING U.S. managed care population. PARTICIPANTS Older and matched younger adults diagnosed with depression and treated with antidepressants. MEASUREMENTS Sociodemographic characteristics, comorbidities, polypharmacy, and characteristics of antidepressant treatment at 180 days were compared between older and younger adults. Analyses were conducted before and after the implementation of Medicare Part D on January 1, 2006, to consider the effect of this policy. RESULTS Few participants received psychotherapy, especially older ones; rates were constant before and after 2006. Before 2006, older adults more frequently received antidepressants at lower (odds ratio (OR)=5.38, 95% confidence interval (CI)=3.57-8.13) or intermediate dose (OR=2.42, 95% CI=1.93-3.02) and had poorer adherence to treatment (P<.001) than younger adults. After 2006, older adults received similar proportions of intermediate or high antidepressant doses as younger adults, but a lower dosage was still more likely to be prescribed (OR=1.87, 95% CI=1.09-3.20) and had higher treatment adherence (P<.001). Medication profile did not significantly affect the risk of nonpersistence, but increased with lower antidepressant dose (P<.001). Whereas nonpersistence was higher in older adults before 2006 (hazard ratio (HR)=1.25, 95% CI=1.22-1.46), the trend reversed after 2006 (HR=0.76, 95% CI=0.66-0.88). CONCLUSION More than half of participants with depression discontinued antidepressant treatment, and psychotherapy was rarely used. Implementation of Medicare Part D was associated with substantial changes in treatment of older adults with depression. The presence of comorbidities or polypharmacy was not associated with nonpersistence in depressed older adults.

The US FDA has issued safety alerts and required manufacturers of leukotriene-modifying agents (LTMAs), including montelukast, zafirlukast and zileuton, to include suicide and neuropsychiatric events as a precaution in the drug label. This paper reviews the existing evidence on the potential association between the LTMAs and suicidal behaviour. We conducted a literature search of MEDLINE, EMBASE and International Pharmaceutical Abstracts from 1995 to 2010 (inclusive) to identify pertinent studies and reports. We also examined data obtained from the FDA adverse event reporting system. To date, there are no well conducted, comparative, observational studies of this association, and the safety alerts are based primarily on case reports. While the FDA safety alerts apply to all three LTMAs, montelukast (known by its trade name Singulair®) is by far the most widely used of these drugs and most of the reports to date regarding suicide pertain to montelukast. From 1998 to 2009 there were 838 suicide-related adverse events associated with leukotrienes reported to the FDA, of which all but five involved montelukast. Nearly all cases were reported in 2008 and 2009 (96.1%) after the FDA warnings. LTMAs are approved for use in asthma and allergic rhinitis, and are effective drugs. Both of these diseases are also associated with suicide, making confirmation of the association more difficult. Given the lack of good evidence, we recommend that a large observational cohort or case-control study be conducted to quantify the association between LTMAs and suicide. Until then, when prescribing LTMAs, clinicians should consider the potential for suicide and monitor patients who may be at elevated risk carefully for suicidal ideation or psychiatric symptoms associated with suicidal behaviour.

A key factor to the successful treatment of HIV is good adherence to antiretroviral therapy (ART). We developed a pharmacist-managed adherence clinic and designed a study to assess the impact of the adherence interventions by measuring the proportion of patients with 95% or greater adherence to ART before and after referral to the program. HIV providers referred patients with adherence problems to a pharmacist-managed adherence clinic. Interventions included scheduled clinic visits with the HIV Clinical Pharmacist and monthly refill reminders from pharmacy staff members over a 6-month period. Those aged 18-75, prescribed an ART regimen for a minimum of 3 months, and who filled their medications exclusively at the clinic pharmacy were eligible for study participation. The Proportion of Days Covered (PDC) served as a surrogate marker of overall adherence. A total of 34 patients were referred to the pharmacy clinic for adherence counseling, of whom 28 enrolled in the study. The proportion of participants with 95% or greater adherence to their ART regimen increased from 7% at baseline to 32% postintervention (p = 0.01). A subanalysis of the PDC revealed an overall increase from a baseline adherence mean of 60% to 81% postintervention (p < 0.0001). There was a notable trend toward an increase in the proportion of participants with an undetectable HIV-1 viral load (58-73%, baseline and postintervention, respectively, p = 0.10), but no statistically significant improvement in CD4 cell count. Clinical pharmacy interventions improved overall adherence to ART regimens in these patients with HIV.

Levetiracetam may be effective in children with acute seizures or status epilepticus. We performed a retrospective chart review of children who received intravenous levetiracetam within 30 minutes of a seizure. Seventy-three patients during a 2-year study period met our inclusion criteria. The mean (+/- S.D.) age and weight of the patients were 5.59 +/- 5.6 years (range, 1 day to 17.8 years) and 23.1 +/- 21 kg (range, 1.97-97 kg), respectively. Patients received a mean (+/- S.D.) levetiracetam dose of 29.4 +/- 13.5 mg/kg. Most children (n = 49, or 67%) received additional antiepileptic drugs to abort their seizure. Overall, the mean (+/- S.D.) total (abortive plus chronic) number of concomitant antiepileptic drugs used by the population was 2.53 +/- 1.7 (1.07 +/- 0.98 as additional abortive therapy, and 1.42 +/- 1.29 as chronic therapy). Most patients received levetiracetam for serial seizures (79%), whereas 12% and 8% manifested a single seizure or status epilepticus, respectively. Clinical effectiveness at 1, 12, 24, 48, and 72 hours after the initial levetiracetam dose constituted the primary study outcome. Eighty-nine percent of patients remained seizure-free at 1 hour. This rate decreased at each evaluation time point. Most patients (71%) were placed on maintenance levetiracetam within 24 hours of their loading dose. The predictive ability of patient and drug regimen variables in outcomes was poor. Only the number of concomitant antiepileptic drugs consistently predicted outcomes. Levetiracetam was well tolerated at the doses studied, and appears most effective in single seizure events.

HASH(0x1b49c760)

OBJECTIVES: To estimate metabolic screening rates, predictors of screening, and incidence of metabolic disturbances in children initiating second-generation antipsychotic (SGA) drug treatment. DESIGN: A retrospective, new-user cohort study (between July 1, 2004, and June 30, 2006) using Medicaid claims data. SETTINGS: California, Missouri, and Oregon. PATIENTS: A total of 5370 children (aged 6-17 years) without diabetes mellitus taking SGA drugs and 15,000 children without diabetes taking albuterol (control) but no SGA drugs. INTERVENTION: Findings 1 year after recommendations from the American Diabetes Association and American Psychiatric Association called for metabolic screening of patients receiving SGA drugs. OUTCOME MEASURES: Serum glucose and lipid testing, 6-month incidence of diabetes, and dyslipidemia disturbances. RESULTS: Glucose screening was performed in 1699 (31.6%[95% confidence interval (CI), 30.4%-32.9%]) SGA-treated children vs 1891 (12.6%[12.1%-13.2%]) control individuals. Lipid testing was performed in 720 (13.4%[95% CI, 12.5%-14.4%]) SGA-treated children vs 458 (3.1%[2.8%-3.3%]) controls. In multivariate logistic regression analysis, children with serious and/or multiple psychiatric diagnoses and those who used health care services more intensively were more likely to receive metabolic screening. The case incidence of glucose and lipid disorders was higher in SGA-treated vs albuterol-treated children (8.9 per 1000 children [95% CI, 6.6%-11.8%] vs 4.9 per 1000 children [3.9%-6.2%]; and 9.7 per 1000 children [95% CI, 7.2%-12.7%] vs 4.6 per 1000 children [95% CI, 3.6%-5.8%], respectively). CONCLUSION: Most children starting treatment with SGA medications in this public sector sample did not receive recommended glucose and lipid screening.