OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine.

OBJECTIVE: To assess the effects of treatment with onabotulinumtoxinA (Botox, Allergan, Inc., Irvine, CA) on health-related quality of life (HRQoL) and headache impact in adults with chronic migraine (CM). METHODS: The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program (PREEMPT 1 and 2) included a 24-week, double-blind phase (2 12-week cycles) followed by a 32-week, open-label phase (3 cycles). Thirty-one injections of 5U each (155 U of onabotulinumtoxinA or placebo) were administered to fixed sites. An additional 40 U could be administered "following the pain." Prespecified analysis of headache impact (Headache Impact Test [HIT]-6) and HRQoL (Migraine-Specific Quality of Life Questionnaire v2.1 [MSQ]) assessments were performed. Because the studies were similar in design and did not notably differ in outcome, pooled results are presented here. RESULTS: A total of 1,384 subjects were included in the pooled analyses (onabotulinumtoxinA, n = 688; placebo, n = 696). Baseline mean total HIT-6 and MSQ v2.1 scores were comparable between groups; 93.1% were severely impacted based on HIT-6 scores ≥60. At 24 weeks, in comparison with placebo, onabotulinumtoxinA treatment significantly reduced HIT-6 scores and the proportion of patients with HIT-6 scores in the severe range at all timepoints including week 24 (p < 0.001). OnabotulinumtoxinA treatment significantly improved all domains of the MSQ v2.1 at 24 weeks (p < 0.001). CONCLUSIONS: Treatment of CM with onabotulinumtoxinA is associated with significant and clinically meaningful reductions in headache impact and improvements in HRQoL. CLASSIFICATION OF EVIDENCE: This study provides Class 1A evidence that onabotulinumtoxinA treatment reduces headache impact and improves HRQoL.

Par complex in cancer: a regulator of normal cell polarity joins the dark side.

In the past 20 years, the discovery and characterization of the molecular machinery that controls cellular polarization have enabled us to achieve a better understanding of many biological processes. Spatial asymmetry or establishment of cell polarity during embryogenesis, epithelial morphogenesis, neuronal differentiation, and migration of fibroblasts and T cells are thought to rely on a small number of evolutionarily conserved proteins and pathways. Correct polarization is crucial for normal cell physiology and tissue homeostasis, and is lost in cancer. Thus, cell polarity signaling is likely to have an important function in tumor progression. Recent findings have identified a regulator of cell polarity, the Par complex, as an important signaling node in tumorigenesis. In normal cell types, the Par complex is part of the molecular machinery that regulates cell polarity and maintains normal cell homeostasis. As such, the polarity regulators are proposed to have a tumor suppressor function, consistent with the loss of polarity genes associated with hyperproliferation in Drosophila melanogaster. However, recent studies showing that some members of this complex also display pro-oncogenic activities suggest a more complex regulation of the polarity machinery during cellular transformation. Here, we examine the existing data about the different functions of the Par complex. We discuss how spatial restriction, binding partners and substrate specificity determine the signaling properties of Par complex proteins. A better understanding of these processes will very likely shed some light on how the Par complex can switch from a normal polarity regulation function to promotion of transformation downstream of oncogenes.

Nonqualified benefit programs help recruit and retain physicians.

Healthcare reform, mergers, and managed care are leading many physician employees to reconsider their association with hospitals and other healthcare facilities. Healthcare organizations can no longer rely on traditional retirement benefit packages and qualified plans to attract or keep these physicians. Changes in tax legislation have made nonqualified retirement plans an important factor in recruiting and retaining physicians. This article examines nonqualified retirement plans and how they can be used by healthcare organizations to supplement qualified plans benefits. While the article focuses on physicians, nonqualified plans also can be used to supplement benefits and secure the financial future of other high-salaried healthcare professionals.

Initial encounters between people with a mild mental handicap and psychiatrists: an investigation of a method of evaluating interview skills.

This study reports the results of an initial study into the ability of psychiatrists to interview people with a mild mental handicap who are accompanied by a caregiver. Initial interviews by 12 psychiatrists of different ages (30-57 years) and differing levels of experience with this client group were recorded on video tape. Three of the recordings were used to train four judges who were familiar with examining clinical interactions, though not between doctors and patients. The judges used a specially designed rating scale. The remaining nine interviews were evaluated independently by the four judges. There was a correlation of 0.65 (Kendall's coefficient of concordance, W) for the judges' evaluations using the rating scale for the nine interviewers. However, there was greater agreement between judges as to who were the best and worst interviewers (W = 0.86). Some of the aspects of the interviews which contributed to the variability in the judgments are discussed.