Two randomized controlled trials of SB742457 in mild-to-moderate Alzheimer's disease.

BACKGROUND: Two previous studies of SB742457, a 5-hydroxytryptamine (5-HT6) receptor antagonist, suggested the efficacy of improvements in cognition and global outcome in Alzheimer's disease (AD). METHODS: Two randomized, placebo-controlled trials investigated SB742457 15 and 35 mg daily in subjects with mild-to-moderate AD (Mini-Mental Health State Examination [MMSE] 10-26). Study 1 (n = 576) investigated SB742457 and donepezil (5-10 mg daily) as monotherapy for 6 months. Study 2 (n = 684) investigated SB742457 in subjects who were maintained on donepezil. Coprimary endpoints at 24 weeks assessed cognition (AD Assessment Scale-Cognitive Subscale [ADAS-Cog]) and global outcome (Study 1: Clinician Interview-Based Impression of Change Plus Caregiver Input [CIBIC+]; Study 2: Clinical Dementia Rating-Sum of Boxes [CDR-SB]). Safety was assessed throughout. RESULTS: Both studies failed to achieve formal statistical significance for their primary objectives. Study 1: SB742457 monotherapy was not statistically significantly different from placebo on any endpoint. Donepezil improved CIBIC+ but not ADAS-Cog. Study 2: SB742457 35 mg showed statistically significant differences relative to placebo for ADAS-cog (weeks 12, 24, and 48, but not week 36), ADCS-ADL (weeks 12-36, but not week 48), and CDR-SB (week 12 only). CONCLUSION: Neither study met the overall criteria for success, but as an adjunct to donepezil, SB742457 was associated with sustained improvements for up to 48 weeks in cognition and ADL, compared with donepezil alone.Clinical Trial Registration: Clinicaltrials.gov: Study 1 NCT00708552; Study 2 NCT00710684.

Is the ASVAB ST composite score a reliable predictor of first-attempt graduation for the U.S. Army operating room specialist course?

The U.S. Army Operating Room Specialist (68D) Course provides first class medical technician training to U.S. Army enlisted soldiers of the Army Medical Command. With a failure rate of approximately 12% over a 2-year period, this study was commissioned to determine whether the Armed Services Vocational Aptitude Battery (ASVAB) skilled technical (ST) Score served as a reliable predictor for successful first-attempt completion of the 68D course. A sample size of 373 was analyzed via a multivariate binary logistic regression model with 6 distinct independent variables. This study found that the ASVAB ST score, gender, and rank were predictors to first-attempt successful completion of the 68D training program. Specifically, students with an ST score 10 points higher than their peers were 5 times more likely to graduate. In addition, females were 2.5 times more likely to succeed than males and Army Privates (E2) were 3.2 times more likely than Privates (El). Specialists, Corporals (E4), Sergeants (E5), and Staff Sergeants (E6) combined, were 34 times more likely to succeed than Els. Although further study may be warranted, increasing the minimum ST score requirement in the admission guidelines and/or specific preventive assistance for lower-ranked students may decrease the first-attempt failure rate.

Interruptions and pediatric patient safety.

This study explored interruptions in pediatric nurses' work and the systems issues related to interruptions in nursing work environments. A total of 5,325 interruptions were observed in this study, providing information on sources, types, and causes of interruptions. The nursing work being performed when interrupted and the outcomes of these interruptions are described.

Restless legs syndrome in women: a review.

Restless legs syndrome (RLS) is a neurological disorder with significant negative impact on sleep and quality of life, yet data suggest that it is frequently underdiagnosed. The clinical features, diagnosis, epidemiology, pathophysiology, and treatment options for RLS are reviewed and discussed, with particular emphasis on RLS in women. RLS is characterized by unpleasant sensations causing an urge to move the legs. RLS symptoms are exacerbated by rest, relieved by movement, and worse at night than during the day. The motor and sensory symptoms of RLS can have a negative impact on patients' sleep, resulting in a reduction in daytime functioning and overall quality of life. The prevalence of RLS is reported to increase with age and to be up to almost twice as high in women as in men. The explanation for this is unknown, although there is evidence that parity may be a factor. Diagnosis of RLS is made using four essential criteria based on the patient's report of sensorimotor symptoms. Several large, double-blind, placebo-controlled studies have demonstrated that dopamine agonists, such as ropinirole and pramipexole, are an efficacious first-line therapy for the treatment of RLS symptoms. As RLS is more prevalent in women, professionals working in the field of women's health need to be aware of this condition, its differential diagnosis, and the treatment options available. Accurate diagnosis is essential to facilitate appropriate management and treatment. Dopamine agonists have been shown to be an effective therapy for patients with moderate to severe symptoms of RLS.

Seeds of change: using peacemaking circles to build a village for every child.

Roca, Inc., a grassroots human development and community organization, has adopted the peacemaking circle as a tool in its relationship building with youth, communities, and formal systems. Circles are a method of communication derived from aboriginal and native traditions. In Massachusetts, the Department of Social Services and the Department of Youth Services are exploring the application of the circle in programming with youth and families. By providing a consistent structure for open, democratic communication, peacemaking circles enhance the formation of positive relationships in families, communities, and systems. The outcome is a stronger community with greater unity across truly diverse participants. This article presents the theory and practice of peacemaking circles, the lessons and challenges of implementing circles in formal organizations, and the potential of the circle to support a strengths-based and community-based approach to child welfare.

Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression.

BACKGROUND: This was the first controlled continuation phase study (up to 1-year total treatment) to evaluate the safety and efficacy of bupropion SR for decreasing the risk for relapse of depression in patients who responded to bupropion SR. METHODS: Patients with recurrent major depression were treated with bupropion SR 300 mg/day during an 8-week open-label phase. Responders (based on Clinical Global Impressions Scale for Improvement of Illness scores) entered a randomized, double-blind phase where they received bupropion SR 300 mg/day or placebo for up to 44 weeks. After randomization, relapse was defined as the point at which the investigator intervened by withdrawing the patient from the study to treat depression. RESULTS: Four hundred twenty-three patients were randomized. A statistically significant difference in favor of bupropion SR over placebo was seen in the time to treatment intervention for depression when survival curves were compared (log-rank test, p =.003). Statistically significant separation between bupropion SR and placebo began at double-blind week 12 (p <.05). Adverse events in bupropion SR-treated patients accounted for 9% and 4% of discontinuations from the open-label and double-blind phases, respectively. CONCLUSIONS: Bupropion SR was shown to be effective and well tolerated in decreasing the risk for relapse of depression for up to 44 weeks.

Prevalence of sexual dysfunction among newer antidepressants.

BACKGROUND: Sexual dysfunction commonly occurs during antidepressant treatment. However, the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature. The objectives of this study were (1) to estimate the prevalence of sexual dysfunction among patients taking newer antidepressants (bupropion immediate release [IR], bupropion sustained release [SR], citalopram, fluoxetine, mirtazapine, nefazodone, paroxetine, sertraline, venlafaxine, and venlafaxine extended release [XR]) and (2) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction. METHOD: This cross-sectional, observational study was conducted in 1101 U.S. primary care clinics. Adult outpatients (4534 women and 1763 men) receiving antidepressant monotherapy were enrolled. The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Questionnaire. RESULTS: In the overall population, bupropion IR (22%) and SR (25%) and nefazodone (28%) were associated with the lowest risk for sexual dysfunction, whereas selective serotonin reuptake inhibitor (SSRI) antidepressants, mirtazapine, and venlafaxine XR were associated with higher rates (36%-43%). In a prospectively defined subpopulation unlikely to have predisposing factors for sexual dysfunction, the prevalence of sexual dysfunction ranged from 7% to 30%, with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR. Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction. CONCLUSION: Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a validated rating scale. Overall, SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone. Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians, greater recognition and education are imperative when prescribing antidepressant treatment.

Effect on body weight of bupropion sustained-release in patients with major depression treated for 52 weeks.

BACKGROUND: Short-term studies have demonstrated a modest weight-reducing to weight-neutral effect among patients receiving bupropion sustained-release (SR) for the treatment of depression. OBJECTIVE: This study was conducted to evaluate the long-term effects of bupropion SR on body weight in patients with depression. METHODS: This analysis was conducted within a long-term relapse-prevention study in patients with major depression. Those whose depression had responded to open-label treatment with bupropion SR were randomized to 44 weeks of double-blind treatment with bupropion SR 300 mg/d or placebo. Patients were categorized by body mass index (BMI) as follows: BMI < 22, BMI 22 to 26, BMI > or = 27, and BMI > or = 30. RESULTS: Four hundred twenty-three patients were enrolled in the double-blind phase of the study, 210 receiving bupropion SR and 213 receiving placebo. At the end of the open-label phase, the following mean weight losses were seen in the 4 BMI groups: BMI < 22, 0.5 kg; BMI 22 to 26, 1.1 kg; and BMI > or = 27 and BMI > or = 30, 1.8 kg each. At the end of double-blind treatment, mean change-from-baseline weights were as follows: BMI < 22, -0.1 kg; BMI 22 to 26, -0.6 kg; BMI > or = 27, -1.4 kg; and BMI > or = 30, -2.4 kg. The rate of change in body weight during the double-blind phase was statistically significant compared with baseline BMI (P < 0.001, analysis of covariance). CONCLUSIONS: Modest mean weight losses that increased with increasing baseline body weight were observed with long-term bupropion SR treatment. The findings of this analysis suggest that bupropion SR may be an appropriate therapeutic option in normal-weight or overweight patients with depression who are concerned about weight gain.