Chris M. Kozma

Primary Focal Hyperhidrosis: Disease Characteristics and Functional Impairment

Background: There are few published data on the clinical characteristics of hyperhidrosis. Objective: To describe the functional impairment caused by primary focal hyperhidrosis. Methods: Patients with hyperhidrosis (n = 345) were enrolled at the Department of Dermatology, University of Würzburg. Controls (n = 154) were a convenience sample of subjects without hyperhidrosis. Hyperhidrosis characteristics, health-related quality of life and functional impairment were assessed. Results: Patients with axillary hyperhidrosis reported a later age at onset and a higher prevalence of a family history of hyperhidrosis than patients with palmar hyperhidrosis. Sixty-three percent of patients reported occupational impairment related to hyperhidrosis. Hyperhidrosis patients reported emotional and physical impairment, with a greater proportion of the axillary group reporting impairment. More than 50% of patients reported moderate to extreme impairment in personal relationships and in social situations. Conclusion: Primary focal hyperhidrosis is a serious medical condition, affecting work productivity, daily activities, emotional well-being and personal relationships.

Risperidone treatment in elderly patients with dementia: relative risk of cerebrovascular events versus other antipsychotics

BACKGROUND The possibility that low-dose antipsychotic treatment is associated with increased risk of cerebrovascular events (CVEs) in elderly patients with dementia has been raised. The objective was to determine whether risperidone is associated with an increased risk of CVEs relative to other commonly considered alternative treatments. METHODS An analysis of Medicaid data from 1999 to 2002, representing approximately 8 million enrollees from multiple states, was conducted. The primary outcome was the incidence of acute inpatient admission for a CVE within 3 months following initiation of treatment with atypical antipsychotics (risperidone, olanzapine, quetiapine, or ziprasidone), haloperidol, or benzo-diazepines. RESULTS Descriptive analyses found similar rates of incident CVEs across evaluated agents. Multivariate analyses found no differences in comparisons of risperidone with olanzapine or quetiapine. Risperidone and other antipsychotics as a group were also not associated with a higher odds ratio (OR) of incident CVE than either haloperidol or benzodiazepines. With risperidone as the reference group: olanzapine, OR = 1.05, 95% CI 0.63-1.73; quetiapine, OR = 0.66, 95% CI 0.23-1.87; haloperidol, OR = 1.91, 95% CI 1.02-3.60; benzodiazepines, OR = 1.97, 95% CI 1.30-2.98. With benzodiazepines as the reference group, the OR of incident CVE for all antipsychotics as a class was 0.49, 95%CI 0.35-0.69. CONCLUSIONS This study found no significant difference in the incidence of CVEs between patients taking risperidone and those taking other atypical antipsychotics. Risperidone and all atypical antipsychotics were not associated with higher risk than two common treatment alternatives (haloperidol and benzodiazepines). These findings do not support the conclusion that risperidone is associated with a higher risk of CVE than other available treatment alternatives. The data also suggest that patient characteristics other than antipsychotic use are more significant predictors of CVEs. Given the relatively low rates of incident CVEs, a larger sample of patients with groups closely balanced on a wide spectrum of potential risk factors could provide a more precise assessment of risk.

Effect of Organization-Level Variables on Differential Employee Participation in 10 Federal Worksite Health Promotion Programs

Guided by a conceptual model, the authors used both qualitative data (e.g., individual interviews, focus groups) and quantitative data from an employee survey (N = 3,388) m 10 federal agencies to investigate whether organization context and implementation process affected participation in worksite health promotion and disease prevention (HPDP) activities among demographic subgroups. Overall, employees on average participated in fewer than two agency-supported health-related activities per year (17% in fitness, 40% inhealth risk assessment activities). Employees participated more where coworkers endorsed such programs. Minority employees and employees in lower level positions were more likely to participate in fitness activities when organizations had a more comprehensive program structure, engaged in more marketing strategies, gave time off to employees to participate, or had on-site facilities. Management support for the program was related to participation by employees who were male, white, and had upper level positions. The data supported the proposed model; also confirmed was two predicted relationships between model constructs, which provided a better understanding of differential participation by employee groups.

Chronic Anemia and Fatigue in Elderly Patients: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Exploratory Study with Epoetin Alfa

OBJECTIVES: To evaluate the effect of epoetin alfa treatment on hemoglobin (Hb), fatigue, quality of life (QOL), and mobility in elderly patients with chronic anemia.

Risperidone and Falls in Ambulatory Nursing Home Residents With Dementia and Psychosis or Agitation: Secondary Analysis of a Double-Blind, Placebo-Controlled Trial

OBJECTIVE Authors evaluated the association between use/dosage of risperidone (RIS) and falls in a residential-care dementia population. METHODS Authors performed secondary analysis of data from ambulatory patients in a randomized, double-blind, placebo-controlled, 12-week trial of three RIS dosages (0.5 mg/day, 1 mg/day, 2 mg/day). Outcomes included number of fallers, rate of falls, and time until the first fall after randomization. Additional analyses evaluated wandering as a potential moderating or mediating variable. RESULTS The ambulatory sample included 537 subjects. Of those, 22.3% on placebo, 18.0% on RIS 0.5 mg/day, 12.7% on 1 mg/day, and 27.3% on 2 mg/day, respectively, fell during the trial. The difference between the RIS 1 mg/day group and placebo was significant, with a significantly lower hazard ratio in the RIS 1-mg/day group than placebo. Wandering was associated with an increased risk of falls. Among 205 patients with the highest levels of wandering at baseline, RIS 1 mg/day was associated with approximately a 70% reduction in risk for falls versus placebo condition. However, in those with the lowest levels of wandering at baseline, RIS 2 mg/day may have increased the risk of falls. CONCLUSIONS Evaluating the benefits versus risks of risperidone in patients with dementia is complex and must consider multiple outcomes as a function of dose. At 1 mg/day, RIS was associated with decreased falls, especially in patients who exhibit wandering. However, at 2 mg/day, it may increase the risk of falls in ambulatory individuals with low levels of wandering.

Development and Validation of a Patient Satisfaction and Preference Questionnaire for Inhalation Devices

IntroductionThe Patient Satisfaction and Preference Questionnaire (PASAPQ) is a multi-item measure of respiratory inhalation device satisfaction and preference designed to be easily understood and administered to patients with asthma and COPD. This study assessed its validity, reliability and responsiveness and explored the between-group difference in PASAPQ scores that is meaningful.MethodsThe field test version was developed using literature, focus groups and expert opinion. Item reduction followed. The assessment of the validity, reliability and responsiveness of the PASAPQ utilized data from two clinical studies comparing devices delivering the same medication, and was performed with pre-specified criteria. A minimally important difference (MID) was estimated using both anchor- and distribution-based approaches.ResultsTwo factors of the PASAPQ, ‘performance’ and ‘convenience’, were consistent across studies. Missing and out-of-range data were minimal (<1%) and respondents used a full range of response options. All items correlated most highly with their hypothesized scale and all exceeded the minimum correlation criteria of 0.40. Cronbach’s alfa was high (0.87–0.94), providing support for internal reliability for the PASAPQ. Correlations of the overall satisfaction item with the performance domain ranged from 0.78 to 0.91, the convenience domain ranged from 0.54 to 0.71, and the total score ranged from 0.78 to 0.90. These moderate-to-strong correlations provide substantial support for the validity of the PASAPQ domains and total score. Discriminate validity was assessed by calculating PASAPQ scores for patients’ ratings of the device that they preferred compared with the other, non-preferred device. The preferred device was rated higher on all satisfaction measures, supporting the ability of the PASAPQ to discriminate between preferred and non-preferred devices. Although a difference of 3 or 4 points may be sufficient to observe a small effect difference between groups, most of the MID estimates were in the 8–10 point range.Discussion and conclusionOur analyses across asthma, COPD and patients with mixed respiratory disease (with features of both COPD and asthma), study designs and data sets lead us to conclude that the PASAPQ is a practical, valid, reliable and responsive instrument for measuring respiratory device satisfaction. Furthermore, a difference in satisfaction scores between treatment groups of 10 points is, conservatively, a difference that is meaningful to patients.

Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium

BackgroundBecause wide variations in mental health care utilization exist throughout the world, determining long-term effectiveness of psychotropic medications in a real-world setting would be beneficial to physicians and patients. The purpose of this analysis was to describe the effectiveness of injectable risperidone long-acting therapy (RLAT) for schizophrenia across countries.MethodsThis was a pragmatic analysis of data from two prospective observational studies conducted in the US (Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation [SOURCE]; ClinicalTrials.gov registration number for the SOURCE study: NCT00246194) and Spain, Australia, and Belgium (electronic Schizophrenia Treatment Adherence Registry [eSTAR]). Two separate analyses were performed to assess clinical improvement during the study and estimate psychiatric hospitalization rates before and after RLAT initiation. Clinical improvement was evaluated using the Clinical Global Impressions-Severity (CGI-S) and Global Assessment of Functioning (GAF) scales, and change from baseline was evaluated using paired t tests. Psychiatric hospitalization rates were analyzed using incidence densities, and the bootstrap resampling method was used to examine differences between the pre-baseline and post-baseline periods.ResultsThe initial sample comprised 3,069 patients (US, n = 532; Spain, n = 1,345; Australia, n = 784; and Belgium, n = 408). In all, 24 months of study participation, completed by 39.3% (n = 209), 62.7% (n = 843), 45.8% (n = 359), and 64.2% (n = 262) of patients from the US, Spain, Australia, and Belgium, respectively, were included in the clinical analysis. Improvements compared with baseline were observed on both clinical assessments across countries (P < 0.001 at all post-baseline visits). The mean improvement was approximately 1 point on the CGI-S and 15 points on the GAF. A total of 435 (81.8%), 1,339 (99.6%), 734 (93.6%), and 393 (96.3%) patients from the US, Spain, Australia, and Belgium, respectively, had ≥1 post-baseline visit and were included in the analysis of psychiatric hospitalization rates. Hospitalization rates decreased significantly in all countries regardless of hospitalization status at RLAT initiation (P < 0.0001) and decreased significantly in the US and Spain (P < 0.0001) when the analysis was limited to outpatients only.ConclusionsRLAT in patients with schizophrenia was associated with improvements in clinical and functional outcomes and decreased hospitalization rates in the US, Spain, Australia, and Belgium, despite differences in health care delivery systems.

Medication possession ratio: implications of using fixed and variable observation periods in assessing adherence with disease-modifying drugs in patients with multiple sclerosis

Background The purpose of this study was to compare two methods of adherence calculation using administrative data for patients with multiple sclerosis (MS) who are prescribed disease-modifying drugs. Methods Pharmacy-billed disease-modifying drug prescription claims were selected from the 2007–2008 LifeLink™ Health Plan Claims Database. The index date was the first disease-modifying drug prescription claim. Two cohorts were created: all patients with a disease-modifying drug claim in 2007 and a subset with continuous eligibility for 12 months post-index. Adherence was calculated across all disease-modifying drugs for 12 months post-index. Medication possession ratios (MPRs) with variable (start to end of therapy) and fixed (365 days) duration denominators were calculated. Variable MPR was calculated by summing days supply from the first to the last prescription (inclusive) divided by time between the last prescription date plus days supply and the first prescription date. Variable MPR was evaluated for all patients and the continuously eligible cohort. Fixed MPR used the same numerator but divided by 365 days of follow-up and evaluated only for the continuously eligible cohort. Results There were 3405 patients with MS and a disease-modifying drug claim in 2007 and 2145 in the continuously eligible cohort. Means for variable MPR ranged from 87.5% ± 16.6% for the continuously eligible cohort to 90.5% ± 16.0% for the 2007 cohort. The comparable value for fixed MPR was 78.0% ± 28.2% for the continuously eligible cohort. Fixed MPR gave a consistently lower rate of adherence than variable MPR at an 80% adherence threshold. Conclusion Different adherence measures can yield different outcomes, especially when using different eligibility criteria. These results demonstrate the importance of full disclosure of methods used for calculations and specification of the study population.

Risk of diabetic ketoacidosis after exposure to risperidone or olanzapine.

AbstractBackground: Atypical antipsychotics have been associated with metabolic abnormalities including impaired glucose metabolism, exacerbation of existing diabetes mellitus and new-onset type 2 diabetes. Not all atypical antipsychotic agents appear to have the same propensity to cause these complications. Objective: To assess diabetic ketoacidosis risk in patients receiving risperidone or olanzapine. Methods: California Medicaid data were evaluated for the presence of a diabetic ketoacidosis hospital claim (9th Edition of the International Classification of Diseases code 2501x) for patients receiving an atypical antipsychotic agent between July 1997 and September 2000. Initial prescription claims were identified for risperidone, olanzapine, clozapine, quetiapine and multiple atypical medications; however, the final analysis was restricted to risperidone and olanzapine owing to sample size challenges in the clozapine and quetiapine groups. Cases were specified if a claim occurred within 45 days after antipsychotic dispensation. Potential confounding variables and duration of antipsychotic exposure were included. Results: Initial users of risperidone (n = 51 330; 31 diabetic ketoacidosis) and olanzapine (n = 51 302; 55 diabetic ketoacidosis) were identified between July 1997 and September 2000. The adjusted risk of diabetic ketoacidosis for olanzapine versus risperidone was 1.62 (p = 0.033). The risk of diabetic ketoacidosis was associated with a longer duration of drug exposure. A progressive and statistically significant divergence in risk was observed between the two treatment groups after the first 30 days of therapy. For risperidone patients, diabetic ketoacidosis risk stabilised after the first 90 days; for olanzapine patients, diabetic ketoacidosis risk continued to increase until 360 days (study duration). For exposures of >30 days, >90 days and >180 days, diabetic ketoacidosis risk was 1.7 (p = 0.026), 2.4 (p = 0.004) and 3.5 (p = 0.001) times greater for olanzapine than risperidone. Treatment group, age, African American race and the presence of schizophrenia or diabetes were significant predictors of diabetic ketoacidosis. Conclusion: The risk of diabetic ketoacidosis appears to be greater for patients exposed to olanzapine compared with risperidone after adjusting for confounding factors. This risk appears to increase with longer duration of exposure to olanzapine.

Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52-week open-label extension (OLE)

Abstract Background: Schizophrenia affects ∼1.1% of the United States population, resulting in substantial direct, indirect and societal costs. Objective: To evaluate hospitalization rates associated with use of paliperidone palmitate (PP). Methods: Data were from a variable-duration double-blind (DB), randomized, relapse-prevention comparison (NCT00111189) of PP vs. placebo (Pbo), followed by a 1-year open-label extension (OLE). Between-phase change in schizophrenia-related hospitalizations was evaluated using data from an investigator-completed questionnaire. Change in hospitalizations using patients before enrollment who participated in the OLE phase was also analyzed. Poisson regression was used to evaluate changes in incidence density within exposure category and by schizophrenia duration. Results: A total of 160 patients in the PP-PP group and 153 in the Pbo-PP group from the DB to the OLE phase were included. Mean age (standard deviation [SD]), gender, and duration of schizophrenia were similar at the start of the DB phase (Pbo: 38.5 years [10.6], 51.0% male, 68.0% ≥5 years’ duration; PP: 37.3 years [11.4] (p = 0.342); 51.9% male (p = 0.874); 70.0% ≥5 years’ duration (p = 0.698), respectively. From the DB to the end of the OLE phase, the number of hospitalizations per person-year for patients treated during the DB phase with Pbo significantly declined from 0.27 to 0.06 (78% reduction; p = 0.005). A statistically nonsignificant difference was observed for PP patients treated during the DB phase with PP (0.11–0.04; 63.6% reduction; p = 0.076), compared with the OLE phase. Change from before enrollment to the end of the OLE phase (n = 381) produced similar results (0.35–0.04; 88.6% reduction; p < 0.001). Patients who enroll in a clinical trial may be different from the general population and this may affect the generalizability of results. Conclusion: From the double-blind to the open-label phase and from prior to the trial until the end of the open-label phase, hospitalizations significantly decreased for patients with schizophrenia treated with PP.