The Daily Activity Report (DAR) a Novel Measure of Functional Outcome for Serious Mental Illness.

The assessment of real-world functional outcomes in clinical trials for medications targeting negative symptoms and cognitive impairment is extremely important. We tested the psychometric properties of the Daily Activity Report (DAR), a novel assessment of productive daily activity. We administered the DAR and additional assessments of functional outcome, functional capacity, cognition and symptomatology to 50 individuals with schizophrenia at 2 time points, 1 month apart and to 25 healthy controls. The DAR records a person's daily activity for 7 consecutive days based upon phone calls made 3 times a day. A total score and scores in 3 domains; instrumental activities (ie, independent living), social and work or school related activities are generated for the DAR. Inter-item consistency was high 0.89-0.94 for each domain and 0.88 overall. Test-retest reliability across 1 month for the total DAR score was 0.67,P< .0001. The total DAR score as well as scores for social activity and nondomestic work/school differed significantly between control and patient participants (P< .0001). DAR domain scores were associated with negative symptoms and functional outcomes, but the primary score related to these measures was the work/school dimension of the DAR. DAR scores were only weakly and nonsignificantly related to positive symptoms. This study provides preliminary support for the reliability and validity of the DAR using interviewer administration. The development of a patient reported version of the DAR using smart phone technology with automatic scoring is the next step.

Transfusions and patient burden in chemotherapy-induced anaemia in France.

OBJECTIVES: To estimate the patient burden in terms of the time spent on outpatient red blood cell (RBC) transfusions indicated for chemotherapy induced-anaemia (CIA) in patients with cancer in France. METHODS: A retrospective chart review of patients with cancer receiving an outpatient RBC transfusion was conducted at seven treatment centres in France. Total treatment time for one transfusion visit per patient was measured as the elapsed time between pre- and post-transfusion vital sign assessment, including time from transfusion start to stop. Elapsed time from haemoglobin (Hb) level testing to transfusion start and from blood draw for compatibility testing to transfusion start were recorded. In addition, estimated travel time and distance to the transfusion centre, and clinical and demographic information were collected. RESULTS: A total of 103 patients [63.1% men; mean age 66.2 years, standard deviation (SD) 11.9] were enrolled in the study (1 August 2010-31 October 2010). The four most frequent diagnoses were lung cancer (31.1%), urological cancer (15.5%), gynecological cancer (14.6%) and gastrointestinal/colorectal cancer (14.6%). Mean elapsed time between prevital and postvital sign assessment was 4.0 h [95% confidence interval (CI) 1.9-6.1], including a mean of 3.4 h (95% CI 2.5-4.2) for the transfusion itself. Hb level testing (mean pre-transfusion Hb level 8.0 g/dl, SD 0.8) and blood draw for compatibility testing were completed in a mean of 28.8 h (95% CI 1.3-56.2) and 9.4 h (95% CI 0-21.4) prior to transfusion respectively. Patients' one-way mean travel time to the transfusion centre was 32.9 min (95% CI 28.5-37.4) and mean distance travelled was 25.4 km (95% CI 11.6-39.3). CONCLUSION: In France, CIA treatment with RBC transfusion is a time-consuming activity for patients that includes multiple trips to a medical facility, blood testing and the transfusion procedure itself. This burden is important to consider in the context of optimizing proactive monitoring and planning for supportive oncology care.

Synchronization of administrations of chemotherapy and erythropoiesis-stimulating agents and frequency of associated healthcare visits.

PURPOSE: The erythropoiesis-stimulating agents (ESAs), darbepoetin alfa (DA), and epoetin alfa (EA) differ with respect to dosing schedule in chemotherapy-induced anemia. DA can be administered less frequently than EA, which may increase synchronicity between chemotherapy and ESA schedules. This study compared DA and EA with respect to frequency of synchronization and frequencies of total and ESA healthcare visits in current clinical practice. METHODS: A retrospective analysis of ESA utilization during ESA episodes of care was conducted on all cancer patients identified in the SDI health oncology electronic medical records database who underwent chemotherapy and received ESA therapy from July 1, 2007 to March 31, 2010 (n = 6522 DA, n = 3,439 EA). RESULTS: The frequency of synchronization (chemotherapy and ESA therapy on the same day) was higher with DA (67 %) than EA (58 %) (p < 0.001). The odds that an ESA administration was synchronized with chemotherapy were higher with DA compared with EA (odds ratio = 1.46, 95 % CI: 1.37, 1.54). Compared with EA, DA patients had 2.3 fewer visits with an ESA administration (p < 0.001) and 3.0 fewer total visits (p < 0.001). CONCLUSIONS: Compared with patients receiving EA, DA patients were more likely to have an ESA administration on the same healthcare visit as chemotherapy and had fewer visits for any cause or for ESA administration. These results suggest that through greater synchronization of ESA and chemotherapy administrations, DA may reduce patient and practice burden and healthcare utilization.

Staff time and motion assessment for administration of erythropoiesis-stimulating agents: a two-phase pilot study in clinical oncology practices.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are used for the management of anaemia in patients with non-myeloid malignancies where anaemia is due to the effect of concomitant myelosuppressive chemotherapy. Assessing the impact of different ESA dosing regimens on office staff time and projected labour costs is an important component of understanding the potential for optimization of oncology practice efficiencies. OBJECTIVES: A two-phase study was conducted to evaluate staff time and labour costs directly associated with ESA administration in real-world oncology practice settings among cancer patients undergoing chemotherapy. The objective of Phase 1 was to determine the mean staff time required for the process of ESA administration in patients with anaemia due to concomitantly administered chemotherapy. The objective of Phase 2 was to quantify and compare the mean staff time and mean labour costs of ESA administered once weekly (qw) with ESA once every 3 weeks (q3w) over an entire course of chemotherapy. METHODS: Phase 1 was a prospective, cross-sectional time and motion study conducted in six private oncology practices in the US based on nine steps associated with ESA administration. Using findings from Phase 1, Phase 2 was conducted as a retrospective chart review to collect data on the number and types of visits in two private oncology practices for patients receiving a complete course of myelosuppressive chemotherapy. RESULTS: In Phase 1, the mean total time that clinic staff spent on ESA administration was 23.2 min for patient visits that included chemotherapy administration (n(chemo) = 37) and 21.5 min when only ESA was administered (n(ESAonly) = 36). In Phase 2, the mean duration of treatment was significantly longer for q3w than qw (53.84 days for qw vs. 113.38 for q3w, p < 0.0001); thus, analyses were adjusted using analysis of covariance (ANCOVA) for episode duration for between-group comparisons. Following adjustment by ANCOVA, qw darbepoetin alfa (DA) patients (n(qw) = 83) required more staff time for ESA + chemotherapy visits and ESA-only visits than q3w patients (n(q3w) = 118) over a course of chemotherapy. Overall, mean total staff time expended per chemotherapy course was greater for patients receiving qw versus q3w DA. Weekly DA dosing was associated with greater projected mean labour costs ($US38.16 vs. $US31.20 [average for 2007-2010]). CONCLUSIONS: The results from this real-world study demonstrate that oncology practices can attain staff time and labour costs savings through the use of q3w ESA. The degree of savings depends on the individual oncology practice's staffing model and ESA administration processes, including those that allow for optimized synchronization of patient visits for ESA and chemotherapy administration. These findings indicate that additional research using standard ESA administration protocols for longer periods of time with a larger number of oncology practices and patients should be conducted to confirm these findings.

The burden of blood transfusion: a utilization and economic analysis--a pilot study in patients with chemotherapy-induced anemia (CIA).

OBJECTIVE: The objective is to measure the burden of blood transfusion of Packed Red Blood Cells (PRBCs) in patients with chemotherapy-induced anemia (CIA) on the institutional outpatient transfusion center. METHODS: This is a retrospective chart review (starting July 1, 2010, working backwards until 120 evaluable patients are accrued) at a single institutional transfusion center in the US. The mean and standard deviation (SD) were calculated for patient's age, pre-transfusion Hgb level, and other transfusion-related activities. RESULTS: One hundred and twenty records were reviewed. The majority included patients who were female (71%), African American (61%), and had either Medicare (48%) or private insurance (39%). The mean patient age was 59 years and the average pre-transfusion Hgb was 7.9 g/dL. The average patient visit to facility ranged from 213 min for one PRBC unit to 411 minutes for three PRBC units. The mean staff time for patient evaluation was 66 minutes. Actual time for transfusion was ∼100 min for each PRBC unit; 90% of patients received two PRBC units. Staff was engaged in direct patient care for an average of 322 min for two PRBC units. The labor cost of transfusion (in 2011 $US) ranged from $46.13-$49.33 per PRBC unit. The estimated fully loaded bundled cost was $596.49 for transfusion of one unit of PRBC. Limitations of the study include: the site included in this study may not be applicable to all sites in practice and the evaluated patient population was varied, with the exception that all patients were treated for some type of malignancy; and the review of blood bank records for 120 patients was not 120 independent events and, as such, may not have adequately captured actual variability. CONCLUSIONS: This analysis quantifies expense in terms of time for administration of the transfusion, as well as costs associated with outpatient blood transfusions.

Erythropoiesis-Stimulating Agent (ESA) Practice Patterns in Patients With Chemotherapy-Induced Anemia (CIA) Treated at Hospital Oncology Clinics.

OBJECTIVES: To characterize erythropoiesis-stimulating agent (ESA) usage initiated in hospital outpatient oncology centers that employ weekly (QW) and every-3-week (Q3W) ESA dosing regimens; describe the frequency of ESA dosing, transfusions, hemoglobin determinations, and anemia-related visits between these 2 regimens; and compare the rates at which inpatient ESA doses are administered on QW versus Q3W schedules. METHODS: This was a retrospective, observational record review evaluating ESA usage in 641 patients from 8 outpatient oncology clinics throughout the United States. Adult patients who initiated myelosuppressive chemotherapy for a documented solid tumor between August 1, 2007 and June 30, 2009 and received their first 3 consecutive outpatient ESA doses on a QW or Q3W schedule were eligible for study inclusion. During a single course of chemotherapy, ESA administrations were recorded as long as ESA therapy was continued on the initial regimen. ESA doses were captured until termination of ESA therapy, until 9 months had elapsed since the first ESA dose, until the patient was switched to another ESA regimen, or until death. ESA administration during inpatient admissions was also recorded. RESULTS: ESA utilization varied between the dosing groups, with fewer ESA doses administered per follow-up month in patients receiving Q3W versus QW ESA therapy (mean, 1 vs 2 doses). Compared to weekly administration, extended-dose ESA therapy also reduced the number of hemoglobin determinations and anemia-related visits without chemotherapy required per follow-up month. Neither the number of transfusions nor the number of packed red blood cell units administered per follow-up month differed between treatment groups. Compared to weekly ESA therapy, Q3W administration reduced costs associated with ESA prescribing and utilization. CONCLUSION: Extended-dose ESA therapy (Q3W dosing) may improve practice efficiency and may be associated with reduced frequencies of hemoglobin determinations and ESA doses required. Q3W dosing may also reduce inpatient ESA utilization by reducing the number of ESA doses required for previously maintained outpatients.

The Patient Assessment Questionnaire: initial validation of a measure of treatment effectiveness for patients with schizophrenia and schizoaffective disorder.

Investigation of patients' subjective perspective regarding the effectiveness - as opposed to efficacy - of antipsychotic medication has been hampered by a relative shortage of self-report measures of global clinical outcome. This paper presents data supporting the feasibility, inter-item consistency, and construct validity of the Patient Assessment Questionnaire (PAQ)-a self-report measure of psychiatric symptoms, medication side effects and general wellbeing, ultimately intended to assess effectiveness of interventions for schizophrenia-spectrum patients. The original 53-item instrument was developed by a multidisciplinary team which utilized brainstorming sessions for item generation and content analysis, patient focus groups, and expert panel reviews. This instrument and additional validation measures were administered, via Audio Computer-Assisted Self-Interviewing (ACASI), to 300 stable, medicated outpatients diagnosed with schizophrenia or schizoaffective disorder. Item elimination was based on psychometric properties and Item-Response Theory information functions and characteristic curves. Exploratory factor analysis of the resulting 40-item scale yielded a five factor solution. The five subscales (General Distress, Side Effects, Psychotic Symptoms, Cognitive Symptoms, Sleep) showed robust convergent (ß's=0.34-0.75, average ß=0.49) and discriminant validity. The PAQ demonstrates feasibility, reliability, and construct validity as a self-report measure of multiple domains pertinent to effectiveness. Future research needs to establish the PAQ's sensitivity to change.

Utilization and cost in clinical practice of darbepoetin alfa and epoetin alfa for anemia concomitant with chemotherapy.

BACKGROUND: In 2005, the mean weekly dose ratio of epoetin alfa (EA) to darbepoetin alfa (DA) in clinical practice was estimated to be ∼400 to 1. In 2006, a 500-µg dose and new dosing schedule was approved for DA in the United States. In 2007, the warnings and dosing/administration sections were modified for both agents. All of these factors may have changed the way that physicians use EA and DA. Previous studies of the use of erythropoiesis-stimulating agents (ESAs) in patients with anemia concomitant with chemotherapy may thus not reflect current clinical practice. OBJECTIVE: The goal of this study was to examine the use and costs of ESAs in clinical practice in patients with anemia concomitant with chemotherapy. METHODS: Using 2 large US health care claims databases, all adults (aged ≥18 years) were identified who received ESAs in 2008 and had evidence of receipt of chemotherapy ≤42 days before initial ESA receipt (ie, the index date). Episodes of care were defined as beginning on the index date and ending on the date of the last ESA claim that was followed by a ≥42-day gap without any receipt of ESAs, to which was added an assumed duration of clinical benefit (in days) based on the ESA and corresponding dose received. DA- and EA-treated patients were matched using propensity scoring. The mean weekly dose and cost of DA and EA during episodes of care was calculated using all information from relevant claims noted during such episodes. Each database was analyzed separately. RESULTS: In the first database, 475 patients with DA episodes of care were matched to an equal number of patients with EA episodes; in the second database, there were 424 matched pairs. In the first database, the mean (95% CI) weekly dose was 37,444 U (35,942 U-39,001 U) during EA episodes and 110 µg (108 µg-113 µg) during DA episodes; the mean weekly EA/DA dose ratio was 340 to 1. In the second database, the mean (95% CI) weekly dose was 37,047 U (35,944 U-38,175 U) during EA episodes and 121 µg (117 µg-125 µg) during DA episodes; the mean weekly EA/DA dose ratio was 306 to 1. CONCLUSIONS: The mean weekly EA/DA dose ratio during episodes of ESA care has declined in patients with anemia concomitant with chemotherapy, due at least in part to the availability and use of a new dose/dosing schedule for DA without similar changes for EA.

Effect of aripiprazole 2 to 15 mg/d on health-related quality of life in the treatment of irritability associated with autistic disorder in children: a post hoc analysis of two controlled trials.

BACKGROUND: There are limited published data on the impact of treatment on the health-related quality of life (HRQOL) in individuals with autistic disorder. OBJECTIVE: The aim of this study was to evaluate the impact of aripiprazole on HRQOL in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder. METHODS: This post hoc analysis assessed data from two 8-week, double-blind, randomized, placebo-controlled studies that compared the efficacy of aripiprazole (fixed-dose study, 5, 10, and 15 mg/d; flexible-dose study, 2-15 mg/d) with placebo in the treatment of irritability associated with autistic disorder. HRQOL was assessed at baseline and week 8 using 3 Pediatric Quality of Life Inventory (PedsQL™) scales. Clinically relevant improvement in HRQOL was determined using an accepted distribution-based criterion-1 standard error of measurement. RESULTS: In total, 316 patients were randomly assigned to receive treatment with aripiprazole (fixed-dose study, 166; flexible-dose study, 47) or placebo (fixed-dose study, 52; flexible-dose study, 51). Aripiprazole was associated with significantly greater improvement than placebo in PedsQL combined-scales total score (difference, 7.8; 95% CI, 3.8-11.8; P < 0.001) and in 3 PedsQL scale scores (differences [95% CI]: Emotional Functioning, 7.8 [3.4-12.2]; Social Functioning, 6.2 [0.7-11.8]; Cognitive Functioning, 9.3 [3.8-14.9]; all, P < 0.05). Patients who received aripiprazole were significantly more likely than those who received placebo to have a clinically meaningful improvement on the combined-scales total score (odds ratio [OR] = 1.9; 95% CI, 1.0-3.3; P < 0.05), Emotional Functioning scale (OR = 2.2; 95% CI, 1.2-4.0; P < 0.05) and Social Functioning scale (OR = 2.2; 95% CI, 1.2-4.1; P < 0.05), and were significantly less likely to experience deterioration (OR: 0.3, 95% CI: 0.1-0.8; P < 0.05) when "Stable" was used as the reference group. CONCLUSIONS: The findings from the present post hoc analysis suggest that aripiprazole was associated with improved HRQOL, as assessed using 3 PedsQL scales, in pediatric patients with irritability associated with autistic disorder.

Q-TWiST analysis of ixabepilone in combination with capecitabine on quality of life in patients with metastatic breast cancer.

BACKGROUND: Combination therapy with ixabepilone and capecitabine (cape) is approved for use in patients with locally advanced/metastatic breast cancer that is resistant to treatment with anthracyclines or taxanes. The current study evaluated the trade-off between quality and quantity of life using quality-adjusted time without symptoms or toxicity (Q-TWiST) outcomes. METHODS: Within the trial, 752 women were randomly assigned to receive either the combination of ixabepilone and cape (once every 21 days) or cape alone (on days 1-14). The area under the survival curve was partitioned into 3 health states: toxicity (TOX), time without symptoms of disease progression or toxicity, and recurrence (relapse [REL]). The mean time in each health state was weighted by a range of utilities and summed to estimate quality-adjusted survival (QAS). Patient-reported outcomes were also evaluated using the Functional Assessment of Cancer Therapy (FACT)-Breast Symptom Index (FBSI). RESULTS: A statistically significant difference between groups with regard to change from baseline FBSI scores favoring the cape group was observed (P = .0002), but no differences were observed after adjusting for deaths in the analysis. All combinations of utilities for REL and TOX resulted in an observed difference in QAS favoring combination therapy. Differences were found to be statistically significant for comparisons, with higher tolerance for TOX. QAS was found to be greater for the combination therapy group (42.2 weeks vs 38.4 weeks), assuming the base case scenario of utility equal to 0.5 for both TOX and REL (P = .0227). CONCLUSIONS: The Q-TWiST analysis supports a positive benefit-risk ratio for the combination of ixabepilone plus cape in patients with advanced/metastatic breast cancer that is refractory to anthracyclines and taxanes versus cape alone, despite the potential for added toxicities with combination therapy.

Absenteeism and productivity among employees being treated for hepatitis C.

OBJECTIVES: To compare productivity, absence days, and absence costs for treated (HCV-Tx) and untreated (HCV-NoTx) US employees with hepatitis C virus (HCV) infection. STUDY DESIGN: Retrospective database study. METHODS: Employee records from multiple large employers in the United States with data about demographics, jobs, and healthcare use in the Human Capital Management Services database were assessed. HCV subjects were identified by International Classification of Diseases, 9th Revision codes. To test differences between cohorts, t tests and χ2 tests were used. Regression modeling was used to compare absence days, costs,and objectively measured productivity, while controlling for confounding factors. For HCV-Tx employees, the index date was the date of the first treatment with interferon, peginterferon, and/or ribavirin. For HCV-NoTx employees, the index date was the average date by company among HCV-Tx employees. Absence and productivity were measured from each employee's index date to the last date the employee was enrolled in health benefits coverage. RESULTS: A total of 441 HCV-Tx and 1223 HCV-NoTx employees were evaluated. HCV-Tx workers had 0.52 more total monthly absence days and $31.31 in additional monthly absence payments per employee than untreated employees. Treated employees' productivity was lower, with treated subjects processing 11.7% fewer units per hour and 17.4% fewer units per month than untreated employees. CONCLUSIONS: This study quantified the substantial indirect burden of illness associated with use of current HCV treatments. New treatments are needed with improved adverse effect profiles that result in reduced absence from work and improved productivity among HCV-infected persons.

Aripiprazole in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder: results from a 52-week, open-label study.

AIM: To report the long-term efficacy of aripiprazole in the treatment of irritability in children and adolescents (ages 6-17 years) with autistic disorder. METHODS: This was a 52-week, open-label, flexible-dose (2-15 mg/day) study of aripiprazole for the treatment of children and adolescents with irritability associated with autistic disorder. Eligible subjects were enrolled from two 8-week randomized trials or were enrolled as de novo subjects. "Prior aripiprazole" subjects had received treatment with aripiprazole for 8 weeks before entering this study. Evaluation of efficacy, a secondary objective after evaluation of safety and tolerability in this study, was conducted using the caregiver-rated Aberrant Behavior Checklist-Irritability subscale and the clinician-rated Clinical Global Impression-Improvement score. RESULTS: Three hundred thirty subjects received treatment (de novo, n = 86; prior aripiprazole, n = 174; prior placebo, n = 70) and 199 subjects (60.3%) completed 52 weeks of treatment. At their last study visit, 38.2% of subjects were receiving concomitant central nervous system medications (commonly antidepressants, 13.4%; psychostimulants, 11.5%; antiepileptics, 5.9%). At week 52 (observed cases data set), the mean change from baseline in Aberrant Behavior Checklist Irritability subscale scores was -8.0 in de novo subjects and -6.1 in prior placebo subjects; prior aripiprazole subjects maintained symptom improvement that was achieved with treatment in the prior study. At endpoint, the majority of subjects had a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved). CONCLUSION: Aripiprazole reduced symptoms of irritability associated with autistic disorder in pediatric subjects ages 6-17 years who were studied for up to 1 year.

Remission, response without remission, and nonresponse in major depressive disorder: impact on functioning.

Major depressive disorder (MDD) is associated with significant functional impairment. This post-hoc analysis of data from two randomized trials assessed the impact of response status on functioning in MDD. Patients with at least one historical treatment failure followed by an inadequate response after 8 weeks of prospective open-label treatment with escitalopram, fluoxetine, paroxetine-CR, sertraline, or venlafaxine-XR plus single-blind placebo were randomized to 6 weeks of double-blind treatment with adjunctive placebo or adjunctive aripiprazole. At the end of double-blind treatment, patients were defined as: in remission [>or=50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score with MADRS or=50% reduction in MADRS with MADRS >10); or with a nonresponse (all others). Functional status was assessed with the Sheehan Disability Scale. Of the 679 patients, 144 were in remission, 44 had a response without remission, and 491 had a nonresponse. Mean improvements in the Sheehan Disability Scale total and item scores were significantly greater in patients in remission versus those with a response without remission (P<0.02) as well as nonresponse (P<0.001). Structural Equation Modeling found that efficacy (Hamilton Rating Scale for Depression scores) did not significantly correlate with functioning in this study. In conclusion, MDD patients achieving symptomatic remission experience greater functional improvements than those respond without remission. Functioning may be a distinctly different outcome from symptom reduction. Treatments focused on producing high remission rates may improve patient functioning over and above that seen with patients who only achieve response.

Changes in weight and weight-related quality of life in a multicentre, randomized trial of aripiprazole versus standard of care.

BACKGROUND: This is a secondary analysis of clinical trial data collected in 12 European countries. We examined changes in weight and weight-related quality of life among community patients with schizophrenia treated with aripiprazole (ARI) versus standard of care (SOC), consisting of other marketed atypical antipsychotics (olanzapine, quetiapine, and risperidone). METHOD: Five-hundred and fifty-five patients whose clinical symptoms were not optimally controlled and/or experienced tolerability problems with current medication were randomized to ARI (10-30 mg/day) or SOC. Weight and weight-related quality of life (using the IWQOL-Lite) were assessed at baseline, and weeks 8, 18 and 26. Random regression analysis across all time points using all available data was used to compare groups on changes in weight and IWQOL-Lite. Meaningful change from baseline was also assessed. RESULTS: Participants were 59.7% male, with a mean age of 38.5 years (SD 10.9) and mean baseline body mass index of 27.2 (SD 5.1). ARI participants lost an average of 1.7% of baseline weight in comparison to a gain of 2.1% by SOC participants (p<0.0001) at 26 weeks. ARI participants experienced significantly greater increases in physical function, self-esteem, sexual life, and IWQOL-Lite total score. At 26 weeks, 20.7% of ARI participants experienced meaningful improvements in IWQOL-Lite score, versus 13.5% of SOC participants. A clinically meaningful change in weight was also associated with a meaningful change in quality of life (p<0.001). A potential limitation of this study was its funding by a pharmaceutical company. CONCLUSIONS: Compared to standard of care, patients with schizophrenia treated with aripiprazole experienced decreased weight and improved weight-related quality of life over 26 weeks. These changes were both statistically and clinically significant.

Advanced cutaneous malignant melanoma: a systematic review of economic and quality-of-life studies.

OBJECTIVE: Metastatic melanoma (MM), a major concern for health-care providers, is increasing. We systematically reviewed published articles describing the impact of interventions (drugs and screening) on quality of life (QoL) in patients with MM, and articles that measured QoL in MM. METHODS: We searched secondary databases including MEDLINE, Embase, CINAHL, Cochrane, and DARE from inception to 2006 using MESH terms "melanoma" and "metastases." Economic articles were subject to established quality assessment procedures. RESULTS: We found 13 QoL and five economic studies (three cost-effectiveness, two cost-utility; average quality = 83% +/- 7%). No strong evidence was found in this review for cost-effectiveness of interferons in Canada (incremental cost-effectiveness ratio [ICER] = $55,090/quality-adjusted life-year) or temozolomide in the United States (ICER = $36,990/Life-year gained based on nonsignificant efficacy differences). Melanoma screening was not cost-effective in the United States ($150,000-931,000/life-saved) or Germany (no survival benefit). From the 13 QoL studies,eight measured baseline QoL; six studied the same population, generating similar results using different approaches/outcomes. Tools used included GLQ-8, QLQ-C30, QLQ-36, QWB-SA, and SF-36. Baseline scores QoL scores ranged from 0.60 to 0.69. Another five studies (N = 959 patients) were randomized trials analyzing QoL in patients treated with dacarbazine alone, dacarbazine +/- interferon, dacarbazine + fotemustine, interleukin +/- histamine, and temozolomide. Little difference was found in QoL scores between drugs or between baseline and end point. CONCLUSIONS: Cost-effectiveness has not been widely demonstrated for treatment of MM. Only two studies with unimpressive results exist for treatments. Screening was not cost-effective in the United States or Germany. Generally, no significant improvements in QoL were found for any alternative for treating MM. A need exists for effective treatments that improve duration and QoL.

Impact of obesity on health-related quality of life in schizophrenia and bipolar disorder.

OBJECTIVE: Studies have reported that up to 60% of individuals with schizophrenia and 68% of those with bipolar disorder are overweight/obese. This paper explores the health-related quality of life (HRQOL) of individuals with schizophrenia or bipolar disorder as a function of obesity status. METHODS AND PROCEDURES: Two hundred and eleven participants were recruited from four psychiatric programs (outpatient, day treatment, case management, and psychosocial rehabilitation). HRQOL was assessed using both a general measure (Medical Outcomes Study Short-Form-36 (SF-36)) and a weight-related measure (Impact of Weight on Quality of Life-Lite (IWQOL-Lite)). To interpret HRQOL scores obtained by the obese group, we compared scores to those obtained by reference groups from the weight-loss literature. RESULTS: Sixty-three percent of participants with schizophrenia and 68% of those with bipolar disorder were obese. Obese participants were more likely to be women, on mood stabilizers, taking a greater number of psychiatric medications, and to have poorer weight-related and general HRQOL. Weight-related HRQOL in the obese psychiatric sample was more impaired than in outpatient and day treatment samples seeking weight loss but less impaired than in gastric-bypass patients. Several of the physical domains of general HRQOL were more impaired for the obese psychiatric sample than for the outpatient weight-loss sample. However, physical functioning was less impaired for the obese psychiatric sample than for gastric-bypass patients. DISCUSSION: The presence of obesity among individuals with schizophrenia or bipolar disorder is associated with decreased HRQOL. These results have implications for prevention and management of weight gain in individuals with schizophrenia or bipolar disorder.

Treatments for metastatic melanoma: synthesis of evidence from randomized trials.

BACKGROUND: Advanced melanomas (non-resectable Stage-III/IV) are fatal, with few effective treatments. It remains unclear if other drugs offer improvements over the standard, dacarbazine. PURPOSE: We quantified objective response rates (Complete+Partial response) of dacarbazine versus comparators for advanced cutaneous melanoma. METHODS: We retrieved all head-to-head randomized controlled trials involving dacarbazine and other drugs/combinations. Two reviewers searched MEDLINE (1966-Jan 2006), EMBASE (1980-2006), CINAHL (1982-2006) and Cochrane library, then compared results. Differences were resolved through consensus. Rates were combined using random effects meta-analysis. chi2 tested heterogeneity; points from Jadad's method were assessed to examine study quality. RESULTS: We found 48 studies having 111 active treatment arms [24 with dacarbazine monotherapy (n=1390), 75 with dacarbazine combinations (n=4962), and 12 with non-dacarbazine treatments (n=783)] treating 7135 patients. Overall, study quality was poor. Response to dacarbazine monotherapy ranged between 5.3% and 28.0% (average 15.3%), OR=1.31, CI(95%): 1.06-1.61; N=3356. Partial responses comprised 73% of successes. Only adding interferons improved response rates (OR=1.69, CI(95%): 1.07-2.68, N=778) but survival duration was not significantly longer (P=0.32), and trials with larger sample sizes found lower success rates. All other treatments alone or in combination were ineffective P>0.05. CONCLUSIONS: Dacarbazine generally produces poor outcomes. Adding other therapies offers minimal clinical advantages (possibly with interferons). In general, study quality was poor and sample sizes were small. This meta-analysis highlights the unmet need for effective treatment options for advanced melanoma.

The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and safety of aripiprazole versus placebo as adjunctive treatment to standard antidepressant therapy (ADT) in patients with major depressive disorder (MDD) who showed an incomplete response to 1 prospective and 1 to 3 historical courses of ADT within the current episode. METHOD: The study comprised a 7- to 28-day screening phase, an 8-week prospective treatment phase, and a 6-week double-blind treatment phase. Patients with DSM-IV-TR-defined MDD were enrolled between June 16, 2004, and April 27, 2006. During prospective treatment, patients received ADT: escitalopram, fluoxetine, paroxetine controlled-release, sertraline, or venlafaxine extended-release, each with single-blind, adjunctive placebo. Incomplete responders continued ADT and were randomly assigned to double-blind, adjunctive placebo or adjunctive aripiprazole (2-15 mg/day with fluoxetine or paroxetine; 2-20 mg/day with all others). The primary efficacy endpoint was the mean change from end of prospective treatment to end of double-blind treatment (week 14, last observation carried forward) in Montgomery-Asberg Depression Rating Scale (MADRS) total score (analysis of covariance). RESULTS: A total of 178 patients were randomly assigned to adjunctive placebo and 184 to adjunctive aripiprazole. Baseline demographics were similar between groups (mean MADRS total score of 26.0). Mean change in MADRS total score was significantly greater with adjunctive aripiprazole (-8.8) than adjunctive placebo (-5.8; p < .001). Adverse events (AEs) that occurred in > or = 10% of patients with adjunctive placebo or adjunctive aripiprazole were akathisia (4.5% vs. 23.1%), headache (10.8% vs. 6.0%), and restlessness (3.4% vs. 14.3%). Discontinuations due to AEs were low with adjunctive placebo (1.7%) and adjunctive aripiprazole (2.2%); only 1 adjunctive aripiprazole-treated patient discontinued due to akathisia. CONCLUSIONS: In patients with MDD who showed an incomplete response to ADT, adjunctive aripiprazole was efficacious and well tolerated. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00095823.

Risk of diabetes mellitus associated with atypical antipsychotic use among Medicaid patients with bipolar disorder: a nested case-control study.

STUDY OBJECTIVE: To quantify the risk of diabetes mellitus associated with atypical antipsychotics compared with conventional antipsychotics in managed care Medicaid patients with bipolar disorder. DESIGN: Retrospective nested case-control study. DATA SOURCE: Integrated seven-state Medicaid managed care claims database from January 1, 1998-December 31, 2002. PATIENTS: Two hundred eighty-three patients with diabetes (cases) and 1134 controls matched by age, sex, and the index date on which bipolar disorder was diagnosed. MEASUREMENTS AND MAIN RESULTS: Cases were defined as those having an International Classification of Diseases, Ninth Revision diagnosis of diabetes or those receiving treatment with antidiabetic drugs. Both case and control patients had at least a 3-month exposure to either conventional or atypical antipsychotic agents or three filled prescriptions related to treatment for bipolar disorder. Of the 283 cases, 139 (49%) received atypical antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone, and clozapine) and 133 (47%) were prescribed conventional antipsychotics. To compare the risk for new-onset diabetes associated with atypical versus conventional antipsychotics, we conducted a Cox proportional hazard regression, in which we controlled for age; sex; duration of bipolar disorder follow-up; use of lithium, anticonvulsants, antidepressants, and other drugs; and psychiatric and medical comorbidities. Compared with patients receiving conventional antipsychotics, the risk of diabetes was greatest among patients taking risperidone (hazard ratio [HR] 3.8, 95% confidence interval [CI] 2.7-5.3), olanzapine (3.7, 95% CI 2.5-5.3), and quetiapine (2.5, 95% CI 1.4-4.3). The risk for developing diabetes was also associated with weight gain (HR 2.5, 95% CI 1.9-3.4), hypertension (HR 1.6, 95% CI 1.2-2.2), and substance abuse (HR 1.5, 95% CI 1.0-2.2). CONCLUSION: Olanzapine, risperidone, and quetiapine are all associated with development or exacerbation of diabetes mellitus in patients with bipolar disorder. When prescribing therapy for this patient population, metabolic complications such as diabetes, weight gain, and hypertension need to be considered.

Use of effect size to determine optimal dose of duloxetine in major depressive disorder.

OBJECTIVE: At effective doses, patients with major depressive disorder (MDD) treated with duloxetine have been found to experience significant symptom improvement as measured by HAMD(17) total score. In addition, duloxetine-treated patients have significantly higher remission and response rates compared with placebo. The objective of this analysis is to determine the optimal dose of duloxetine in MDD. MATERIALS AND METHODS: Effect size for duloxetine 40mg, 60mg, 80mg, and 120mg per day were estimated using all 6 acute phase III clinical trials in patients with MDD. The tolerability of duloxetine 40mg, 60mg, 80mg, and 120mg were evaluated using pooled data from the 6 studies. The primary efficacy measure in all trials was the HAMD(17) total score, from which were determined the effect size for HAMD(17) change scores, response rates (50% reduction from baseline to endpoint), and remission rates (HAMD(17) total score < or =7). RESULTS: A total of 1619 randomized patients were included in these studies, of which 632 were treated with placebo; 177 with duloxetine 40mg/day; 251 with 60mg/day; 363 with 80mg/day; and 196 with 120mg/day. An evaluation of increments in effect size between doses consistently showed that the most notable gain in effect size for efficacy was the 40-60mg/day dosage range. All dosages from 60 to 120mg were effective. The tolerability assessment indicated duloxetine at 40-120mg/day is well tolerated. Furthermore, the initial doses of 40-80mg/day were found to have comparable tolerability. CONCLUSIONS: The effect size analyses demonstrate that duloxetine 40mg has minimum efficacy, and that duloxetine 60-120mg/day is effective in the treatment of patients with MDD. An initial dose less than 60mg/day might provide better tolerability for some patients diagnosed with MDD.