Efficacy and tolerability of paliperidone ER and other oral atypical antipsychotics in schizophrenia.

UNLABELLED: Atypical antipsychotics are widely used in the pharmacologic management of schizophrenia. Information to guide evidence-based clinical decision making must be continually updated, particularly as new clinical trial data and new antipsychotic agents become available. OBJECTIVE: This meta-analysis of oral atypical antipsychotics assessed the relative effectiveness and tolerability profile of a recently introduced agent, paliperidone extended-release (ER), to determine its place within the efficacy and tolerability spectrum of the labeled dose ranges of other oral atypical antipsychotics. METHODS: Randomized placebo-controlled studies of risperidone, olanzapine, quetiapine, and aripiprazole were identified via database search (MEDLINE, EMBASE, Cochrane Library, PsycInfo, and Cumulative Index to Nursing & Allied Health Literature). Baseline demographic, efficacy, and safety data were extracted and combined in meta-analysis. Random effects meta-regression assessed potential confounding by patient mean age, gender ratio, and duration of therapy on variability in efficacy and safety. RESULTS: Within the spectrum of efficacy and safety of the class, paliperidone ER demonstrated a novel efficacy-tolerability profile versus the other oral atypical antipsychotics, including lower odds of withdrawal for any reason and less weight gain. Odds of withdrawal due to adverse events were lower with paliperidone ER compared with risperidone and with atypical antipsychotics as a class. Paliperidone ER was associated with lower odds of somnolence and agitation than the atypical class as a whole and with lower odds of weight gain than all of the atypical antipsychotics, including risperidone. The main factor in the observed variability in efficacy results between studies was the antipsychotic, rather than patient-related factors or duration of therapy. CONCLUSIONS: Paliperidone ER is an effective and well-tolerated oral atypical antipsychotic that provides an important new treatment option for patients with schizophrenia. Owing to the heterogeneity within the class, information on individual benefit/risk profiles of antipsychotics is necessary for selecting an appropriate treatment for each patient.

The health status of obese individuals in Canada.

OBJECTIVE: To determine whether there is a clinically relevant difference in the health state utilities of obese and non-obese individuals as measured by the Health Utility Index Mark III. METHODS: Secondary analysis of the population-based, cross-sectional, interviewer-administered National Population Health Survey (NPHS), 1996-1997. A probability sample of house-dwelling Canadians, excluding populations on First Nations Reserves, Canadian Armed Forces Bases, the Yukon and Northwest Territories, and long-term residents of hospitals or residential care facilities. The sub-sample used in this analysis consisted of 38 151 respondents (52.4% male) between the ages of 20 and 64 y, excluding pregnant women. Health Utilities Index-Mark III (HUI3) scores were used to define normal weight (body mass index (BMI) 19-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), obese (BMI 30-34.9 kg/m(2)), and morbidly obese (BMI> or =35 kg/m(2)) individuals. HUI3 scores were age- and gender-standardized. RESULTS: The overall prevalence of obesity (BMI> or =30 kg/m(2)) in this Canadian population was 13.3%. The average difference in HUI3 scores between normal weight and morbidly obese respondents was 0.04 (P<0.001). Statistically significant (P<0.05) differences across BMI categories were found in each of the eight component attributes of the HUI3. The attributes with the most substantial difference between normal and obese patients were cognition, mobility and pain. All demonstrated a > or =2-fold increase in the proportion of individuals in poorer classifications of health when normal weight respondents were compared with the morbidly obese. The magnitude of the decrement in utility ratings associated with obesity was comparable with other chronic non-cardiovascular conditions such as migraine or colitis. CONCLUSION: The results indicate that changes in self-rated health status appear to be due to significant changes across several relevant domain attributes. Obesity has a significant impact on both quality of life and health.

Persistent tuberculosis or specimen contamination?

Cross-contamination during sequential processing of sputum specimens from different patients causes false-positive growth of Mycobacterium tuberculosis in culture. We describe an unusual case of cross-contamination in a 36-year-old man with acquired immunodeficiency syndrome and possible persistent tuberculosis. Culture with 1 of 3 sputum specimens was positive for rifampin-susceptible M tuberculosis. Review of processing revealed that his single culture-positive sputum specimen had followed a sputum specimen from another patient with active pulmonary tuberculosis that was positive in culture for M tuberculosis resistant to rifampin. Molecular strain typing by restriction fragment length polymorphism demonstrated the 2 isolates to be an identical strain of M tuberculosis. Agar proportion susceptibility testing of the rifampin-resistant isolate revealed low numbers of resistant organisms in a range of 1.5% to 3.3%. It was concluded that rifampin-susceptible organisms that constituted approximately 98% of the resistant isolate contaminated sputum from the patient with possible persistent tuberculosis. His culture result was, therefore, considered false positive, not an indication of tuberculosis.

A minimum 5.0 ml of sputum improves the sensitivity of acid-fast smear for Mycobacterium tuberculosis.

Detection of acid-fast bacilli (AFB) by sputum smear supports treatment decisions with pulmonary tuberculosis (TB), but smear sensitivity for Mycobacterium tuberculosis is only approximately 45 to 75%. In an effort to increase sensitivity, smears were prepared using a minimum sputum volume of 5.0 ml. Sensitivity of smears during a 39-mo period (n = 1,849) using >/= 5.0 ml of sputum was 92. 0%, significantly greater (p < 0.001) than a sensitivity of 72.5% in a previous 24-mo period (n = 3,486) when all specimens were processed regardless of volume. All new cases of TB (n = 18) were smear-positive with >/= 5.0 ml of sputum before treatment, and all were receiving antituberculosis drugs at hospital discharge. In contrast, significantly fewer new cases of TB (14 of 26, p = 0.002) were positive before treatment when smears were prepared using sputum of any volume, and significantly fewer of these new TB cases (18 of 26, p = 0.03) were receiving treatment at hospital discharge. The eight cases without treatment were smear-negative. These results indicate that acid-fast smear using >/= 5.0 ml of sputum increases sensitivity for M. tuberculosis and accelerates treatment of TB.

Utility scores for chronic conditions in a community-dwelling population.

OBJECTIVE: The objective of this study was to determine utility scores for various chronic conditions. DESIGN AND SETTING: This study is a descriptive analysis. Health Utilities Index (HUI) scores for 20 chronic conditions were examined from the National Population Health Survey (NPHS) from 1994 to 1995. PATIENTS AND PARTICIPANTS: 17,626 individuals were surveyed (54.3% women). Chronic conditions included: acne (requiring medication), Alzheimer's disease, arthritis/rheumatism, asthma, back problems excluding arthritis, chronic bronchitis or emphysema, cancer, cataracts, diabetes, epilepsy, food allergies, glaucoma, heart disease, high blood pressure, migraine headaches, other allergies, sinusitis, stroke, stomach/intestinal ulcers and urinary incontinence. INTERVENTIONS: Health Utilities Index-Mark III (HUI-Mark III) scores for patients with and without a NPHS-defined chronic condition were collected. Utility scores were examined according to age, gender and comorbidity. MAIN OUTCOME MEASURES AND RESULTS: 42.6% of individuals reported having no NPHS-defined chronic condition. The most commonly reported health conditions were allergies other than food (17.6%) and rheumatism/arthritis (16.5%). The mean HUI-Mark III scores for patients without a health state was 0.933 +/- 0.079. Individuals with Alzheimer's disease (0.580 +/- 0.263), stroke (0.676 +/- 0.230) and urinary incontinence (0.698 +/- 0.230) had the lowest overall HUI-Mark III scores. Utility scores decreased as age and as the number of comorbid conditions increased. CONCLUSIONS: This study provides health economists, researchers and policy-makers with a reference for health utilities of various chronic conditions, different age groups, gender and comorbidities.

Utilization of health care resources by obese Canadians.

BACKGROUND: The prevalence of obesity in Canada has been increasing in recent years. Using data from the National Population Health Survey (NPHS), the authors determined the prevalence of obesity among Canadians, the associated comorbidities and the patterns of resource utilization by obese people. METHODS: The NPHS, a cross-sectional survey conducted in 1994, was administered to 17,626 Canadians 12 years of age or older who were not long-term residents of hospitals or long-term care facilities and were not residing on First Nations reserves or Canadian Armed Forces bases, or in the Yukon and Northwest Territories. For the authors' analysis, the study population consisted of 12,318 Canadians aged 20-64 years who were not pregnant and for whom the body mass index (BMI) had been calculated. The prevalence of comorbidities, health status index scores, self-esteem, self-rated health, restriction of activity, health care resource utilization (physician visits, disability days, admissions to hospital and medication use) were determined for obese people (BMI of 27 or greater) and nonobese people. RESULTS: The NPHS data revealed that 35.2% of men and 25.8% of women in Canada were obese in 1994. Obese respondents were more likely than nonobese respondents to suffer from stress (adjusted odds ratio [OR] 1.20, 95% confidence interval [CI] 1.11-1.31), activity restrictions (adjusted OR 1.39, 95% CI 1.26-1.54) and a number of chronic comorbidities. Obese respondents were also more likely to consult with physicians (adjusted OR 1.32, 95% CI 1.22-1.43), be prescribed a number of medications and to require excess disability days (adjusted OR 1.22, 95% CI 1.08-1.36). INTERPRETATION: Obesity represents a substantial burden on the health of Canadians and on Canada's health care resources.

Quality assessment of economic evaluations published in PharmacoEconomics. The first four years (1992 to 1995).

Our objective was to assess the quality of reporting of original economic research articles in PharmacoEconomics from inception to the end of 1995, in order to identify areas of strength and weakness, and analyse trends over time. Each regular issue of the journal was examined for original economic evaluations. Accepted articles were categorised by study type and by year of publication. A previously developed 13-item quality-scoring checklist was applied. The maximum possible score that an article could be assigned was 4.0. Quality scores were analysed over time and by study type. 54 articles were identified for analysis. Mean overall score (OS) ranged from a minimum of 1.80 to a maximum of 3.75, with a mean OS of 3.01 [standard deviation (SD) = 0.47]. The item with the highest mean score was the 'definition of study aim' (mean OS = 3.46, SD = 0.69). The item with the lowest score was 'ethical problems discussed and identified' (mean OS = 1.44, SD = 0.92). Only 4 items on the checklist had mean scores lower than 3.0. No significant time trend was apparent for OS (R2 = 0.002). Cost-benefit (mean OS = 3.25, SD = 0.85, n = 5), cost-effectiveness (mean OS = 3.11, SD = 0.97, n = 27), and cost-utility (mean OS = 3.29, SD = 0.93, n = 6) analyses had mean scores significantly higher than cost-analysis/cost-of-illness studies (mean OS = 2.51, SD = 1.14, n = 8). The mean OS for cost-minimisation studies was 2.74 (SD = 0.49, n = 8). Despite some weaknesses in particular aspects of economic evaluations published in PharmacoEconomics, we conclude that the journal has offered publications with acceptable overall quality and adequate methodology.

Quality assessment of pharmacoeconomic abstracts of original research articles in selected journals.

OBJECTIVE: To assess and compare the quality of pharmacoeconomic abstracts of cost-minimization analyses, cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses of original research articles in selected medical, pharmacy, and health economics journals. METHODS: MEDLINE was used to identify articles in selected medical, pharmacy, and health economics journals using the MeSH word "economic" and text words "cost" and "pharmacoeconomic"; the journal PharmacoEconomics was searched manually. All retrieved abstracts were evaluated. Original, comparative (at least one drug comparator) research articles (1990-1994) reporting both costs and clinical outcomes were included in the quality analysis. Abstract quality was assessed as a percentage by using a checklist with 29 objective criteria. Group consensus produced interrater reliability greater than 0.8. RESULTS: One thousand two published abstracts labeled with the above key words were identified. Of these, 951 were excluded from quality assessment because they were not original research (18%), were not pharmacoeconomic research (47%), lacked a drug comparator (35%), or did not report a clinical outcome (0.5%). Thus, the quality of 51 (5% of the total) remaining abstracts was assessed. Overall scores were 56% in 1990 and 58% in 1994 (p = 0.094). Medical articles scored highest (61.5%; n = 25), pharmacy articles were next (54.3%; n = 5), and health economics articles were lowest (53.4%; n = 21) (p = 0.091); structured abstracts scored significantly higher (62.5%; n = 20) than unstructured (53.3%; n = 31) (p = 0.003). CONCLUSIONS: Abstract quality was generally poor, with no significant change in quality over time. Medical journals scored highest, probably because they use structured abstracts. Guidelines for structured pharmacoeconomic abstracts may assist in improving quality.

Initial use of a broth microdilution method suitable for in vitro testing of fungal isolates in a clinical microbiology laboratory.

Antifungal susceptibility testing methods currently lack a standardized procedure. Many factors, such as inoculum preparation, inoculum density, medium selection, pH, incubation time and temperature, and endpoint determination, affect results. We developed a workable procedure for fungal susceptibility testing, with a microtiter method based upon modifications of the proposed guidelines from the National Committee for Clinical Laboratory Standards, using two different growth media. For this procedure, the microtiter tray is prepared as a panel of 6 drugs (amphotericin B, flucytosine, fluconazole, ketoconazole, miconazole, and itraconazole) alone and in combination with amphotericin B. Eagle's minimal essential medium and RPMI 1640 are the two growth media. Two separate susceptibility trays are inoculated for each sensitivity test, with one tray incubated at 30 degrees C and the other incubated at 35 degrees C. After 48 h of growth, results for both temperatures and both media are recorded and interpreted. The four test environments (two media each at two temperatures) provided growth for 100 of the first 104 organisms that were submitted for testing. This approach provides a workable methodology for routine antifungal susceptibility testing in a clinical microbiology laboratory setting.