The objective of this randomised controlled trial was to compare the effects and expense of three approaches to care (1) proactive cardiovascular risk reduction (CaRR) clinic; (2) nurse telephone calls; or (3) usual care for people with cardiovascular risk factors in a Primary Care, Health Service Organisation (HSO) in Ontario, Canada. Subjects included consenting patients with an identified cardiovascular disease (CVD) risk factor identified from the HSO computerised patient information system in 2004. Patients were excluded if they were mentally incompetent, <18 years of age, in a nursing home, or not English speaking. Of 1570 eligible subjects, 523 (33.3%) verbally declined, 145 (9.2%) could not be contacted, and 249 (15.9%) were not needed. The final sample size was 653 (41.6%), 634 completed the follow-up (97%). The Cardiovascular Risk Score, Health and Social Service Utilisation, Montgomery-Asberg Depression Rating, Billings and Moos Indices of Coping, Personal Resource and Self-Efficacy Questionnaires were measured at baseline and 1-year follow-up by clinical examination and telephone interview. Cardiovascular risk scores were reduced in all treatment groups after 1 year. The proportions of subjects showing reduction in risk score greater than or equal to 10% was greatest in the CaRR group (69.2%) compared with Nurse Phone intervention (57.8%) and Usual Care (59.0%) (M-Hchi(2) = 4.33, df = 1, P = 0.037, CaRR-Usual Care). Self-efficacy scores showed the greatest improvements in the CaRR clinic. This effect was achieved with no significant difference in total person per annum costs for direct and indirect health and social service utilisation between all three groups. A CaRR clinic is more effective in reducing CVD risk after 1 year compared with nurse phone intervention and usual care with no additional expense found.

Objective: This study examined differences in children's behavior and expenditures for health and social services used when their parents with dysthymia did or did not respond to antidepressant therapy. Method: Children ages 4 to 16 years of consenting parents enrolled in a treatment trial for dysthymia who did and did not respond to treatment were compared at baseline and 24 months. The responder was a parent with at least a 40% reduction in his or her baseline depressive symptoms using the Montgomery Asberg Depression Rating Scale. Children's behavior was measured using the Child Behavior Checklist, and expenditures for health and social services use was measured in Canadian dollars using the Health and Social Service Utilization Questionnaire. Results: Children of parents with dysthymia who responded to treatment had significantly greater reductions in emotional symptoms at 2-year follow-up than children of nonresponders, along with an economically important (not statistically significant) reduction in expenditures for health and social services use. Conclusions: Reductions in parental symptoms of dysthymia may be associated with reductions in childhood behavioral problems and in expenditures for the child's use of services.

2535 Background: rhIL-18, a potent immunomodulatory cytokine, has demonstrated anti-tumor activity in a variety of preclinical models. Clinical safety and biological activity were examined in a previous study of rhIL-18 administered in a single cycle at IV doses ranging from 3 - 1000 mcg/kg/day for 5 days. The current study examined the effects of administering repeated cycles, and the resulting PK exposure and PD biomarker response data, which are described below. Methods: Three cohorts of 3 patients each were enrolled (6 with melanoma and 3 with metastatic renal cell carcinoma), and received 100, 500, or 1000 mcg/kg doses of rhIL-18 (SB485232) administered as 2h infusions daily for 5 consecutive days every 28 days in repeated cycles (up to 6). Assessments included tolerability, immunogenicity, anti-tumor activity, PK, and biomarkers of immunomodulatory activity. PK and PD measurements were made on Days 1 and 5 of Cycles 1 and 2. Plasma drug concentrations were measured by ELISA. Cytokine/protein biomark...

Background: The burden of comorbid dysthymia and other comorbid psychiatric illnesses in a Canadian primary care setting was measured. Two groups of primary care patients: those who scored positive for comorbid dysthymia versus those who scored negative for any psychiatric disorder were compared. Methods: This was a cross-sectional survey in a Health Service Organization (HSO) in Ontario, Canada. The subjects were patients of the HSO. The main outcome measures were: health status, mood, social adjustment, coping ability, children's psychiatric disorders, child development, family function, and health and social service utilization. Results: Of the 6280 eligible adults who were patients at the HSO, 68.9% consented to be screened for psychiatric disorders; 5.1% screened positive for dysthymia, of which 90% had at least one comorbid psychiatric disorder. The following statistically significant differences were found between people with dysthymia and other comorbid psychiatric disorders versus people without any psychiatric disorder. People with dysthymia were more likely to have worse health status, worry more about their health, and report levels of pain that impaired their function; they had higher MADRS depression scores, lower social role function scores, lower social adjustment scores, and lower coping ability. More children of people with comorbid dysthymia met criteria for one or more childhood psychiatric disorders and there were more families with a parent with dysthymia that were dysfunctional. People with dysthymia used a greater proportion of health and social services, had higher per person annual health care costs (excluding hospital services), and had higher per person annual indirect costs (lost wages). Conclusion: This analysis demonstrated the burden of illness and costs that this disorder imposes on individuals, their families, and society as a whole.

Background: There is little information on the long-term effects and costs of a combination of Sertraline and interpersonal psychotherapy (IPT) for the treatment of dysthymia in primary care. Methods: In a single-blind, randomized clinical trial, 707 adults (18–74 years of age inclusive) with DSM-IV dysthymic disorder, with or without past and/or current major depression, as an acute or chronic episode, in a community-based primary care practice in Ontario, Canada, were randomized to treatment with either Sertraline alone (50–200 mg), or IPT alone (10 sessions), or Sertraline plus IPT combined. In the acute treatment phase (first 6 months) all groups received full active treatment. This was followed by an additional 18-month naturalistic follow-up phase. Subjects were assessed for effectiveness of treatment in reducing depressive symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) at 6 months and twice again during the 18-month follow-up by blind independent observers. Treatment costs and subjects' use of other health and social services were also investigated. Results: At 6 months, 586 subjects completed the MADRS questionnaire. There was a significant difference (P=0.025) in mean MADRS scores: 14.3 (Group I); 14.9 (Group II); 16.8 (Group III), using analysis of covariance. Response (40% improvement) rates were 60.2% for Sertraline alone, 46.6% for IPT alone, and 57.5% for Sertraline augmented by IPT (P=0.02). At 2 years, 525 subjects were retained for follow-up. There was no statistically significant difference between Sertraline alone and Sertraline plus IPT in symptom reduction. However, both were more effective than IPT alone in reducing depressive symptoms (P=0.03). There was a statistically significant difference between groups in costs for use of health and social services. The IPT treatment groups had the lower costs for use of health and social services. Conclusions: Sertraline or Sertraline plus IPT was more effective than IPT alone after 6 months. Over the long term (2 years), all three treatments provide reasonably effective treatment for reducing symptoms of dysthymia, but Sertraline or combining Sertraline with IPT is more effective than IPT alone. Of these two more effective treatments, subjects in the Sertraline plus IPT group had less health and social service costs by $480 per person over 2 years. These findings underscore the effects of combining pharmacotherapy and psychotherapy and the economic value of this more comprehensive treatment of dysthymia in primary care.

The purpose of this naturalistic 2 year randomized trial was to compare the effects and economic consequences of treating dysthymia with sertraline and/or interpersonal psychotherapy (IPT) in primary care. 707 patients with dysthymia were randomized to: Sertraline (N = 229); Sertraline + IPT (N = 247); IPT (N = 231). 525 completed 2 years of follow-up and were assessed using the Montgomery Asberg Depression Rating Scales (MADRS) and the Browne Health Services Utilization Inventory.

Background: Dysthymic disorder is characterised as a chronic state of depressed mood which is not otherwise attributable to physical, psychological or social events. While it can occur alone, there is increasing evidence that the majority of individuals who meet criteria for dysthymic disorder also experience more severe episodic mood disorders throughout their lifetime, and there is also an aggregation of mood disorders within their family members. Patients with dysthymic disorder are most often seen in primary care. Some researchers suggest that the majority of these individuals are never diagnosed or are not diagnosed until a more severe episodic mood disorder develops. The objective of this study was to determine the 12-month prevalence of Axis I psychiatric disorders, and in particular dysthymic disorder, in a primary care Health Service Organization in Ontario, Canada. Methods: Eligible and consenting adults registered with a primary care Health Service Organization were screened using the modified form of the University of Michigan Composite International Diagnostic Interview. Results: Of the 6280 eligible subjects, 4327 (69%) consented to screening. Two hundred and twenty-two (5.1%) subjects screened positive for dysthymic disorder. In addition, 90% of those who screened positive for dysthymic disorder also screened positive for other Axis I disorders including major depressive disorder, panic, simple phobia, and generalized anxiety disorder. Conclusions: There is much potential for the primary care physician to play a pivotal role in the recognition and treatment of dysthymic disorder and associated Axis I disorders. A focus on the family as a unit for care may be especially important given the reported aggregation of dysthymic disorder within families.

The aim of this study was to compare the efficacy, safety, and tolerability of sertraline and clomipramine in the treatment of obsessive-compulsive disorder (OCD). Outpatients with DSM-III-R defined OCD for 1 year or longer and scores of ≥20 on the YaleBrown Obsessive Compulsive Scale (Y-BOCS), ≥7 on the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-OC), ≥4 on the Clinical Global Impression Severity of Illness Scale (CGI-S) and ≤17 on the Hamilton Depression Scale (17 item HAMD) were randomized to sertraline (n = 86) or clomipramine (n = 82) once daily for 16 weeks. Initial daily doses of sertraline and clomipramine were 50 mg. After a minimum of 4 weeks, these doses could be increased by 50 mg increments every 2 weeks to a maximum of 200 mg daily if the response was thought inadequate. Efficacy was assessed at the end of 1, 2, 4, 6, 8, 12 and 16 weeks of therapy using the Y-BOCS, NIMH-OC, CGI-S, CGI Improvement Scale (CGI-I) and Clinical Anxiety Scale (CAS). One hundred sixty-eight patients were randomized and received at least one dose of double-blind medication; 86 received sertraline and 82 clomipramine. Mean final daily doses at final visit were clomipramine 90 mg (efficacy evaluable patients 101 mg, completers 110 mg), and sertraline 129 mg (efficacy evaluable patients 132 mg, completers 136 mg). Mean baseline Y-BOCS, NIMH-OC and CGI-S totals were 27.7, 10.1 and 5.5, respectively, for sertraline and 27.4, 9.9 and 5.5, respectively, for clomipramine. Sertraline demonstrated greater efficacy than clomipramine in the intent-to-treat patient group: mean baseline to final visit changes were 50.8% (Y-BOCS), 41.9% (NIMH-OC) and 37.7% (CGI-S) for sertraline and 42.9% (Y-BOCS), 33.8% (NIMH-OC) and 30.0% (CGI-S) for clomipramine (P < 0.05). The number of patients withdrawing because of adverse events was substantially greater for clomipramine (26%) than sertraline (11%) (P < 0.05). The most frequent adverse events for clomipramine were dry mouth (20%), anxiety (17%), constipation (16%), nausea (15%) and somnolence (11%), and for sertraline, diarrhea (12%) and nausea (12%). In this study, sertraline was more effective than clomipramine in the intent-to-treat analysis. The difference in efficacy between the treatments is almost wholly accounted for by a greater number of clomipramine withdrawals due to the poor patient acceptance of clomipramine. The superior tolerability of sertraline and the lower rate of premature treatment withdrawal relative to clomipramine may offer considerable quality of life and compliance benefits in the long-term management of a chronic disorder such as OCD.

Background: Although it is generally recognized that poverty and depression can coexist among single parents receiving social assistance, there is insufficient research on this topic. The goals of this study therefore were to investigate the prevalence, correlates and health care expenditures associated with depression among sole-support parents receiving social assistance. Methods: Sole-support parents who had applied for social assistance in 2 regions of southwestern Ontario were included in the study. Depression was diagnosed with the 1994 University of Michigan Composite International Diagnostic Interview short forms. Results: The 12-month prevalence rate of depressive disorder among the parents interviewed was 45.4% (345/760). A total of 247 (32.5%) had major depressive disorder alone, 19 (2.5%) had dysthymia, and 79 (10.4%) had both major depressive disorder and dysthymia ("double depression"). Those with major depressive disorder, particularly double depression, had significantly higher rates of coexisting psychiatric disorder than those without depressive disorders. Parents with depression reported higher rates of developmental delay and behaviour problems in their children than parents without depression. Expenditures for health care services were higher for parents with depression and for their children than for parents without depressive disorder and their children. Interpretation: Single parents receiving social assistance have high rates of depression. Such parents with depression also have higher rates of other psychiatric disorders and higher expenditures for health care services, and their children have higher rates of developmental delay and behaviour problems.

OBJECTIVE To evaluate cost and benefits of screening for and treating health and lifestyle risks among community-dwelling elderly. DESIGN Randomized controlled trial. SETTING Primary care. PARTICIPANTS An opportunistic and prompted sample of 619 rostered elderly patients presenting for treatment who screened positive. INTERVENTIONS One third (209) of experimental subjects had screening questionnaires placed in their charts with concerns highlighted for referrals. Two control groups received usual care. MAIN OUTCOME MEASURES Yearly assessments of health service use and multidimensional functional capacity. RESULTS Overall, screening and treatment of functionally active, elderly, middle-class people had no significant beneficial effect. Almost half of the experimental sample was ineligible because of treatment noncompliance. Generally ineligible subjects were older and more severely impaired. Subjects 75 years and older with risk factors showed improvement in daily living activities, and those living alone were found to have improved mental health and social functions (11% and 22%, respectively). CONCLUSIONS Screening and treatment was ineffective in improving total functional capacity of all seniors 65 years and older. Elderly people 75 years and older, however, who were living alone or lonely did benefit from screening and treatment showing an improvement in daily activities, mental health scores, and social functions. This finding has implications for selective preventive health care spending for the elderly. A 2-year follow-up period could be too brief to detect long-term effects of early intervention with younger, middle-class seniors, especially those who are already functionally active.

BACKGROUND:Dysthymic disorder is characterised as a chronic state of depressed mood which is not otherwise attributable to physical, psychological or social events. While it can occur alone, there is increasing evidence that the majority of individuals who meet criteria for dysthymic disorder also experience more severe episodic mood disorders throughout their lifetime, and there is also an aggregation of mood disorders within their family members. Patients with dysthymic disorder are most often seen in primary care. Some researchers suggest that the majority of these individuals are never diagnosed or are not diagnosed until a more severe episodic mood disorder develops. The objective of this study was to determine the 12-month prevalence of Axis I psychiatric disorders, and in particular dysthymic disorder, in a primary care Health Service Organization in Ontario, Canada.METHODS:Eligible and consenting adults registered with a primary care Health Service Organization were screened using the modified form of the University of Michigan Composite International Diagnostic Interview.RESULTS:Of the 6280 eligible subjects, 4327 (69%) consented to screening. Two hundred and twenty-two (5.1%) subjects screened positive for dysthymic disorder. In addition, 90% of those who screened positive for dysthymic disorder also screened positive for other Axis I disorders including major depressive disorder, panic, simple phobia, and generalized anxiety disorder.CONCLUSIONS:There is much potential for the primary care physician to play a pivotal role in the recognition and treatment of dysthymic disorder and associated Axis I disorders. A focus on the family as a unit for care may be especially important given the reported aggregation of dysthymic disorder within families.