The thymoprotective function of leptin is indirectly mediated via suppression of obesity

Leptin is an adipokine that regulates metabolism and plays an important role as a neuroendocrine hormone. Leptin mediates these functions via the leptin receptor, and deficiency in either leptin or its receptor leads to obesity in humans and mice. Leptin has far reaching effects on the immune system, as observed in obese mice, which display decreased thymic function and increased inflammatory responses. With expression of the leptin receptor on T cells and supporting thymic epithelium, aberrant signalling through the leptin receptor has been thought to be the direct cause of thymic involution in obese mice. Here, we demonstrate that the absence of leptin receptor on either thymic epithelial cells or T cells does not lead to the loss of thymic function, demonstrating that the thymoprotective effect of leptin is mediated by obesity suppression rather than direct signalling to the cellular components of the thymus.     

Preventable hospitalizations and medicare managed care: a small area analysis

Objective: To examine the association between preventable hospitalization rates and proportions of managed care enrollment at the primary care service area level. Study Design: Multivariate design. Methods: The study used the Healthcare Cost and Utilization Project State Inpatient Data from the Agency for Healthcare Research and Quality for Arizona, Massachusetts, and New York for the years 1995 and 2005 to examine the association between preventable hospitalization rates and proportions of managed care enrollment in 1995 and 2005. The period 1995-2005 was marked by the beginning and end of several legislative and policy initiatives causing changes in elderly hospitalization patterns as well as Medicare managed care enrollment patterns. The study used ordinary least squares regressions, adjusting for heteroscedasticity. A cross-sectional analysis was used to examine the association each year. A pooled sample analysis over years tested the changes in relative contributions of managed care over time. Results: Preventable hospitalization rates were inversely associated with Medicare managed enrollment in both years. This association was, however, found to be weaker in 2005 than in 1995. The decline in contributions of managed care was also statistically significant. Conclusions: Despite increased managed care enrollment, the role of Medicare managed care in explaining declines in preventable hospitalization rates diminished over time. The results could be explained by the growth of private fee-for-service types of managed care plans and the resultant decline in emphasis on care coordination relative to health maintenance organization plans.     

Early treatment of migraine with rizatriptan: a placebo-controlled study

OBJECTIVE: To evaluate the efficacy of rizatriptan when administered early during a migraine attack. BACKGROUND: Several studies indicate that triptans are more efficacious when administered early during a migraine attack, when the pain is still mild. METHODS: One hundred and twelve rizatriptan-na?ve patients aged 20 to 64 years with a history of migraine with or without aura that progressively worsened when left untreated were instructed to treat a total of three migraine attacks with either rizatriptan 10 mg or placebo as early as possible during each attack. Seventy-four patients (68 women and 6 men) were assigned to use the active drug and 38 (35 women and 3 men) to placebo. The primary efficacy endpoint was pain-free response at 2 hours after administration of the study drug. Secondary efficacy measures were pain-free response at 1 hour and sustained pain-free response lasting between 2 and 24 hours. RESULTS: A total of 216 attacks were treated in the rizatriptan group and 109 in the placebo group. Pain-free response at 2 hours after early treatment was noted in 151 (70%) of attacks in the rizatriptan group and in 24 (22%) in the placebo group (P < .01). Pain-free response at 1 hour occurred in 97 (45%) and 9 (8%) attacks, respectively (P < .01). When the attacks were categorized by headache severity at the time of treatment, the pain-free response at 2 hours was higher for mild attacks than for moderate or severe attacks (P < .01). Sustained pain-free response after treatment was significantly higher for attacks treated with rizatriptan (60%) than for those treated with placebo (17%) (P < .001). Adverse events were observed in 62 patients in the rizatriptan group and 15 in the placebo group. Only 1 patient taking rizatriptan discontinued the study because of adverse events, and no serious adverse events were reported. CONCLUSIONS: Rizatriptan is significantly more likely than placebo to produce a pain-free response within 2 hours when the drug is administered early in the migraine attack, when pain is mild rather than moderate or severe.