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.     

HETEROGENEITY OF SYSTEMIC LUPUS ERYTHEMATOSUS ELUCIDATED BY CLUSTER ANALYSIS

For 75 patients with systemic lupus erythematosus (SLE), 39 laboratory and clinical characteristics, including HLA-A, B, C and DR typing, were analysed using a cluster analysis technique. Three groups were identified. Group I (46 patients) was characterized by infrequently severe disease, good response to therapy and infrequent multisystem involvement. Group I1 (24 patients) was characterized by a severe course of disease (although the tendency to remit after therapy was not unusual), and, frequently, renal involvement and pericarditis. Group 111 (5 patients) was characterized by more severe renal disease. Of the 75 patients studied, 38.7% possessed HLA-DR3, compared to 17.4% of controls. Group I patients did not differ from controls but 80% of Group II patients and 4/5 Group III patients had DR3. Cluster analysis identifies subsets of SLE patients who show marked differences in disease course and severity, correlated with possession of the HLA B8, DR3 phenotype.     

In situ fluorescence hybridization of Y translations: cytogenetic analysis using probes Y190 and Y431

Two moderately repetitive DNA probes (Y190 and Y431) and a fluorescent in situ hybridization technique, using a biotin, avidin, anti-avidin system, were employed to investigate a group of patients with Y chromosome abnormalities. In normal male subjects, a bright fluorescent spot could be detected in cells in interphase and on the short arm of the Y chromosome in metaphase spreads. Translocations of DNA fragments of the short arm of the Y chromosome to autosomes 10, 13 and 15 were observed in five patients. In a 45,XX male subject the translocation involved one of the X chromosomes. With this in situ hybridization procedure, bright fluorescent spots were also noticed in uncultured amniotic cells and chorionic cellular elements from male fetuses, thus allowing a rapid and reproducible approach to prenatal fetal sexing.     

Obtaining pharmacoeconomic data in health care organizations

The article illustrates the process and techniques of obtaining or collecting pharmacoeconomic data in various health care organizations, focusing on hospitals, physicians' offices, and pharmacies as the research settings. The role that pharmacoeconomic data have in the decision-making process as well as the perspective of the decision maker are also discussed. The three primary components needed to conduct a complete pharmacoeconomic analysis (clinical outcomes, humanistic outcomes, and economic outcomes) are described in relation to the health care organization. The strengths, weaknesses, advantages, and disadvantages of such data are discussed. Various databases that are accessible within each organization are also outlined.     

Multivariate analysis of health status scores: chronic airway disorders and the MOS SF-36

Multivariate analysis of variance (MANOVA) with follow-up canonical discriminant analysis may be used to interpret differences in health-related quality of life measured by the Medical Outcome Study Short Form 36 (MOS SF-36). Due to the moderate correlations between the 8 health dimensions of the SF-36, MANOVA is theoretically a more appropriate method than traditional univariate approaches for detecting group differences on the SF-36. Additionally, canonical discriminant analysis presents a novel approach to understanding the relationship between health dimensions of the SF-36 and model-independent variables. Results from the MANOVA and canonical discriminant analysis provide evidence of the sensitivity of the SF-36 in cross-sectional, self-reported data. Significant differences in health status (alpha less than or equal to 0.05) were found for the variables of age, and primary physician visits, and between levels of disease severity, type of breathing problem, whether patients had seen a specialist or not, use of emergency room, the comorbid states of depression and arthritis, and income. No significant differences in health status were reported between males and females or racial groups.     

Comparing dihydroergotamine mesylate and sumatriptan in the management of acute migraine. A retrospective cost-efficacy analysis

The annual cost of managing migraine totals billions of US dollars. This retrospective economic analysis of a clinical trial comparing subcutaneous dihydroergotamine mesylate (DHE) with subcutaneous sumatriptan in the treatment of acute migraine is appropriate because, although each product has been shown to be efficacious, the acquisition cost of sumatriptan is over 3 times that of DHE. Total costs in each treatment group were calculated and applied independently to 11 clinical trial efficacy measures. Three of the efficacy measures showed no statistically significant difference between treatment arms, leading to a decision to use the less expensive DHE. In 4 of the efficacy measures. DHE was the obvious choice because it is more efficacious and less expensive. For the final 4 efficacy measures, where sumatriptan is more efficacious and more expensive, incremental cost-efficacy ratios were calculated to determine the additional expenditure required to achieve outcomes associated with quick relief. Depending on the efficacy variable chosen and the assumptions used in the model, the incremental cost-efficacy ratios ranged from $US4000 to $US6700 per year (1993 dollars) for each additional patient who is successfully treated with sumatriptan compared with DHE. Therefore, in a population of 100 migraineurs, an additional 13 to 22 patients would achieve these short term benefits of sumatriptan, although it would cost an additional $US88 395 annually, given the assumptions made. Because each product has unique advantages, we conclude that the more cost-efficacious product is dependent on the outcome of interest and the amount that the patient or provider is willing to pay to achieve that outcome.     

Natural antibodies to oxidation‐specific epitopes: innate immune response and venous thromboembolic disease

Essentials

• Natural antibodies to oxidation‐specific epitopes have antithrombotic properties.
• We evaluated the relation between natural IgM and IgG antibodies and the venous thrombosis risk.
• Risk of recurrent thrombosis was higher in patients with low natural IgM antibody levels.
• The protective effect of high IgM levels suggests a role of innate immune response in thrombosis.

Summary

Background and objectives

Natural antibodies to oxidation‐specific epitopes protect from atherothrombotic events. Whether mechanisms of innate immunity are relevant in the pathogenesis of venous thromboembolism (VTE) is unknown.

Patients/Methods

We measured plasma levels of immunoglobulin M (IgM) antibodies to oxidized low‐density lipoproteins (OxLDL) and phosphocholine (PC) by enzyme linked immune assay in 663 patients with unprovoked VTE, who were prospectively followed after discontinuation of anticoagulation for a median of 8.8 years. The study endpoint was recurrent VTE.

Results

IgM antibody levels to OxLDL and PC were higher in patients without compared to those with recurrent VTE (n = 174, 26.2%). For each doubling of OxLDL‐IgM or PC‐IgM the hazard ratio (HR) of recurrence was 0.88 (95% confidence interval [CI], 0.77–1.01) and 0.82 (95% CI, 0.71–0.94), respectively. After 5 years the probability of recurrence in patients with PC‐IgM levels in the highest tertile (> 19.6 RLU/100 ms) was 13.0% (95% CI, 8.1–17.6%), compared with 21.1% (95% CI, 14.9–26.9%) in the middle tertile and 20.6% (95% CI, 14.7–26.0%) in the lowest tertile. The corresponding HR was 0.56 (0.39–0.82) for PC‐IgM levels in the highest compared with the lowest tertile. Neither immunoglobulin G IgG antibody levels to OxLDL nor those to PC were associated with risk of VTE.

Conclusion

Levels of natural IgM antibodies to oxidation‐specific epitopes are inversely related to the risk of VTE.     

S6K1 controls pancreatic β cell size independently of intrauterine growth restriction

Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance. Here we found that S6K1 deficiency in mice also leads to decreased β cell growth, intrauterine growth restriction (IUGR), and impaired placental development. IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic β cell growth and the onset of T2DM later in life. However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore β cell size or insulin levels in S6K1^–/– embryos, suggesting that loss of S6K1 leads to an intrinsic β cell lesion. Consistent with this hypothesis, reexpression of S6K1 in β cells of S6K1^–/– mice restored embryonic β cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR. Together, these data suggest that a nutrient-mediated reduction in intrinsic β cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced β cell growth and eventual development of T2DM later in life.