A Canadian naturalistic study of a community-based cohort treated for bipolar disorder.

BACKGROUND: Bipolar illness is associated with significant psychosocial morbidity and health resource utilization. Second generation antipsychotics, used alone or in combination with mood stabilizers are effective in treating acute mania in community settings. This study was designed to compare the change in clinical parameters and resource utilization at one month in a group of patients who required treatment intervention for exacerbation of mania. The clinical response at one year was also evaluated. METHODS: 496 patients were enrolled at 75 psychiatric practices across Canada. The Olanzapine cohort (n = 287) included patients who had olanzapine added to their medication regimen or the dose of olanzapine increased. The Other cohort (n = 209) had a medication other than olanzapine added or the dose adjusted. Changes from baseline in the Young Mania Rating Scale (YMRS), Montgomery Asberg Depression Rating Scale, Beck Anxiety Inventory and SF-12 Health Survey were compared at one month using ANCOVA. Categorical variables at one month for health resource utilization, employment status, abuse/dependency, and the number of suicide attempts were compared using Fisher's Exact test. Patients were followed for one year and a subgroup was evaluated. RESULTS: At one month, patients in the Olanzapine cohort recorded a mean reduction in the YMRS of 11.5, significantly greater than the mean reduction in the Other cohort of 9.7 (ANCOVA P = 0.002). The Olanzapine cohort was significantly improved compared to the Other cohort on the scales for depression and anxiety and did not experience the deterioration in physical functioning seen in the Other cohort. No significant differences were detected in health-related quality-of-life measures, employment status, drug abuse/dependency, number of suicide attempts, mental functioning, emergency room visits or inpatient psychiatric hospitalizations. In a subgroup treated for 12 months with a single second generation antipsychotic, improvements in illness severity measures were maintained with no evidence of significant differences among the antipsychotics. CONCLUSIONS: Patients with bipolar disorder requiring treatment intervention for exacerbation of mania in the community setting responded to olanzapine at one month. In a subset analysis, second generation antipsychotic treatment continued to be beneficial in reducing bipolar symptoms at one year.

Early drotrecogin alpha (activated) administration in severe sepsis is associated with lower mortality: a retrospective analysis of the Canadian ENHANCE cohort.

INTRODUCTION: Early multimodal treatment of severe sepsis, including the use of drotrecogin alfa (activated) (DrotAA) when indicated, is considered essential for optimum outcome. However, predicting which infected patients will progress to severe sepsis and the need for aggressive intervention continues to be problematic. We therefore wished to explore whether there were any potential early markers that might predict improved survival in response to early use of DrotAA in patients with severe sepsis. In particular, in the dynamic setting of severe sepsis, we postulated that changes in markers reflecting evolving rather than baseline clinical status might guide therapy. METHODS: Data on a cohort of 305 Canadian patients from the open label ENHANCE trial of DrotAA in severe sepsis was retrospectively analyzed to search for potential clinical predictors of outcome in severe sepsis. Patients received a 96-hour infusion of DrotAA and were followed for 28 days. The association between time to treatment and mortality within subgroups defined by dynamic changes in various potential markers was explored. RESULTS: Mortality at 28 days was 22.6% and the variables of age, time to treatment, and early changes in serum creatinine and platelet count were identified by logistic regression as independent predictors of mortality. Across all age ranges, 28-day mortality was lower when DrotAA was administered within 24 hours of first sepsis-induced organ dysfunction compared to administration after 24 hours for both subgroups of patients defined by changes in platelet count and creatinine within the first day. CONCLUSIONS: These findings suggest that when indicated, treatment with DrotAA should be initiated as soon as possible, regardless of age. TRIAL REGISTRATION: Previous trial registration number: NCT00568893.

A Canadian observational study of the optimal method of transition from postmenopausal hormone therapy to raloxifene.

OBJECTIVE: To determine the optimal method of transition from postmenopausal hormone therapy (HT) to raloxifene (RLX) therapy in order to minimize hot flashes and night sweats. METHODS: Postmenopausal women in Canada who had discontinued HT (estrogen with or without progestogen) in the preceding nine months and who were starting RLX were followed for approximately nine months in this observational study. The method of transition from HT to RLX therapy (method and duration of tapering HT, duration of washout) and the frequency and severity of hot flashes during the transition and RLX treatment periods were recorded. RESULTS: There were 373 women who participated in this study. Most women (86.3%) had a washout period between HT and RLX, and 55.2% had tapered their HT in some fashion. After beginning RLX, women who had had a washout duration of more than one week were found to be more likely to have an improvement in the severity of hot flashes (odds ratio [OR] = 6.3), and in the frequency of hot flashes (OR = 4.6), than women with a shorter washout or no washout period at all. The method of tapering of HT did not seem to affect either the severity or the frequency of hot flashes once on RLX. Women who had undergone a tapering period of more than one week's duration were more likely (OR = 2.6) to experience an improvement in the frequency (but not the severity) of hot flashes on RLX. CONCLUSION: Women who had a washout period following HT had better amelioration of hot flashes on RLX therapy.

Atomoxetine and neuropsychological function in children with attention-deficit/hyperactivity disorder: results of a pilot study.

This pilot longitudinal study using measures from parents and teachers evaluated the effects of flexible doses of atomoxetine (ATX) on neuropsychological and functional outcomes in 21 children with attention-deficit/hyperactivity disorder (ADHD) (mean age, 8.0 +/- 1.3 years; inattentive subtype, 71.4%; combined subtype, 28.6%). Among 16 children completing 6 months of ATX treatment, neuropsychological function measured by the NEPSY instrument found significant improvement from baseline in the memory and learning domain (p = 0.01); this change was also seen in an age- and sex-matched healthy control group (p = 0.011). The patient group showed significant improvement on the Test of Everyday Attention (TEA-Ch) and parent and teacher versions of the Behavior Rating Inventory of Executive Function (BRIEF), which assess attentional and executive processes, respectively. Functional improvement was also observed on the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) and parent and teacher versions of the ADHD Rating Scale (ADHDRS-IV), and the investigator-rated Clinical Global Impressions-Severity (CGI-S) scale evidenced reductions in ADHD symptoms. These findings suggest that potential benefits of ATX treatment may extend beyond reduction of core ADHD symptoms to amelioration of some neuropsychological and functional deficits.

Frequency of painful physical symptoms with major depressive disorder in asia: relationship with disease severity and quality of life.

OBJECTIVE: Patients with major depressive disorder (MDD) frequently report concomitant painful physical symptoms, which may negatively impact diagnosis and treatment. The purpose of this study was to estimate the frequency of painful physical symptoms in Asian patients treated for an acute episode of MDD and to describe the associated demographics, clinical status, treatment patterns, and socioeconomic burden. METHOD: This multicountry, observational study enrolled 909 patients with MDD (DSM-IV-TR or ICD-10 criteria) in the psychiatric care setting from June 14, 2006, to February 15, 2007. Patients were classified as positive for painful physical symptoms (PPS+) if they achieved a mean score >or= 2 on the modified Somatic Symptom Inventory. The Clinical Global Impressions-Severity of Illness scale (CGI-S) and 17-item Hamilton Rating Scale for Depression (HAM-D(17)) determined depression severity, and the EuroQoL Questionnaire-5 dimensions (EQ-5D) assessed subjective well-being. RESULTS: Overall, 51.8% of patients were classified as PPS+. PPS+ patients were more likely to be female (72.2% vs. 65.1%, p = .022), had relatively more medical comorbidity (29.7% vs. 21.0% with >or= 1 comorbidity, p = .003), were more significantly depressed (CGI-S mean [SE] score = 4.84 [0.03] vs. 4.63 [0.04], p < .001; HAM-D(17) mean [SE] score = 24.80 [0.26] vs. 22.39 [0.27], p < .001), and reported a lower quality of life (EQ-5D health state mean [SE] score = 42.96 [0.92] vs. 52.92 [0.95], p < .001) than PPS- patients. PPS+ and PPS- patients did not differ markedly, however, in terms of MDD medications prescribed or MDD-related disability at work. CONCLUSION: Painful physical symptoms are experienced by approximately half of patients with MDD in Asia and are associated with poor clinical status and perceived quality of life.