A multinational investigation of the impact of subcutaneous sumatriptan. I: Design, methods and clinical findings

This report describes the design, methods and clinical results of a prospective sequential multinational (5 countries) study conducted to evaluate the effects of subcutaneous sumatriptan on health-related quality of life, workplace productivity, clinical parameters and patient satisfaction. Adult patients with moderate to severe migraine initially received customary therapy for migraine episodes for 12 weeks, followed by 24 weeks' treatment with self-administered subcutaneous sumatriptan 6 mg. Demographic, baseline, health-related quality of life and patient satisfaction rating data were collected during visits to the clinic. Data relating to migraine symptoms, migraine therapy, work productivity and non-work activity time were collected on diary cards filled out by the patients. 749 patients were recruited to the study and 637 received at least 1 dose of sumatriptan. Overall, 75.5% of migraines were successfully treated within 2 hours with sumatriptan compared with 31.9% with customary therapy; 36% of patients reported complete relief at 2 hours with sumatriptan treatment compared with 1% of patients receiving customary therapy. 69% of patients successfully treated 70% of their migraines with sumatriptan within 2 hours, compared with 12% of patients with customary therapy. No serious adverse events were reported; 50% of patients reported an adverse event during the 12-week customary therapy phase and 89% of patients during the 24-week sumatriptan phase. These clinical results, which are consistent with those reported in randomised blinded studies of subcutaneous sumatriptan, suggest that relief of migraine symptoms occurs more often, and in less time, in patients receiving subcutaneous sumatriptan rather than customary therapy as their primary medication.     

Increasing physician involvement In cholesterol-lowering practices: The role of knowledge,attitudes and perceptions

The study evaluated a multifaceted educational intervention systematically designed to increase physician involvement in cholesterol-lowering practices. We hypothesized that knowledge, perceptions and behaviours would be enhanced in participating physicians, compared with controls. Method: Fifty-one family physicians were assigned randomly to three groups; the two experimental groups attended a training workshop, received physician and patient education materials and ongoing consultant support. One experimental group also received a “cuing” intervention. The control group received no interventions. Outcome measures included knowledge and attitude scores, self-efficacy perceptions, and physician dietary counselling behaviour. Measures were taken at pretest, 6 weeks and 15 months later. Results: Intervention group physicians achieved significantly higher knowledge scores than the control group at the six-week test; the differences disappeared at 15 months. Attitudes, self-reported practices and overall self-efficacy scores were similar across groups. Within group variation was highly significant. Physician dietary counselling scores were significantly higher in the intervention groups (p = 0.0001). Some associations were seen among knowledge, attitude, self-efficacy and dietary counselling scores. Conclusion: Physician behaviour change in cholesterol reduction may not depend entirely upon knowledge, attitudes and perceptions. This revised version was published online in June 2006 with corrections to the Cover Date.     

Effects of reciprocal treatment with estrogen and estrogen plus parathyroid hormone on bone structure and strength in ovariectomized rats.

Intermittent administration of PTH has been found to be an effective anabolic agent in cancellous bone. We have reported previously that combined treatment with PTH and estrogen in estrogen-deficient rats was beneficial in correcting established osteopenia. To determine if the beneficial effects of PTH therapy can be preserved by estrogen alone and whether PTH therapy can be effective in treating osteopenic subjects stabilized with estrogen, we have undertaken a "crossover" study in the rat model of estrogen-deficiency induced osteopenia. Six-month-old female rats were ovariectomized and after 5 wk treated for 8 wk with vehicle, 30 micrograms/kg per day of rPTH(1-34) plus 15 micrograms/kg per day of 17 beta-estradiol or 17 beta-estradiol alone. One group from each treatment regimen was then sacrificed and for an additional 8 weeks the remaining rats were (a) maintained on their previous treatment; (b) "crossed over" to their reciprocal treatment; or (c) administered vehicle only. At the end of this second 8-wk treatment period all rats were sacrificed. Bone mineral density of the distal femur, histomorphometric measurements of the proximal tibia and mechanical testing of the distal femur and selected vertebral bodies were performed. Our results demonstrated that (a) the gains in bone mass, trabecular connectivity and mechanical strength induced by PTH can be maintained by estrogen alone, but are reversed when both agents are withdrawn; and (b) rats with established osteopenia, maintained on estrogen treatment alone, can derive the full beneficial effects from the addition of PTH to the treatment at a later date. These data indicate that combined and/or sequential use of antiresorptive and anabolic agents may be a promising approach to the treatment of osteoporosis.     

Same-sex attraction, drug injection and binge drinking among Australian adolescents

OBJECTIVE: To document the prevalence of same-sex attraction among students in years 10 and 12 in Australian Government high schools and to assess the association between same-sex attraction, binge drinking and drug injection. METHOD: Cross-section survey by anonymous, self-administered questionnaire of 3,387 students in Years 10 and 12 of the Government school system in Australia. RESULTS: Approximately 6% of respondents reported being currently attracted to members of their own sex. Being attracted to members of the same-sex was associated with more frequent binge drinking among boys and girls, and a three- to four-fold increase in the likelihood of reporting injecting drug use both over the lifetime and within the previous 12 months. CONCLUSIONS: Adolescents attracted to members of the same-sex report engaging in elevated levels of health-limiting behaviours. There is an urgent need for further research to document the reasons for this. It is recommended that health promotion activities directed at moderating young people's drug and alcohol practices explicitly acknowledge the over-representation of same-sex attracted young people in their target audience.     

Mild traumatic brain injury from motor vehicle accidents: factors associated with return to work

OBJECTIVES: To describe return to work (RTW) for motor vehicle accident (MVA) survivors with mild traumatic brain injury (MTBI) and to examine relationships between RTW and injury severity, cognitive impairment, social interaction, discharge disposition, and sociodemographics. DESIGN: Inception cohort assessed within 1 month of injury and at follow-up 6 to 9 months (mean = 7.4) after injury, for comparisons on outcome of RTW. SETTING: Tertiary care center in Toronto (time 1); at home for follow-up. PARTICIPANTS: Fifty patients with MTBI resulting from MVA who were consecutively admitted during a 20-month period ending April 1994. Thirteen of 63 eligible patients refused consent or were lost to follow-up. Mean age was 31; 62% were men. Eligibility criteria: (1) patients had been working; (2) they had no history of head injury, neurologic disease, or psychiatric illness requiring hospitalization; and (3) they had no catastrophic impairment from accident. MAIN OUTCOME MEASURE: Return to work (at premorbid or modified level). RESULTS: Of the 42% who returned to work, 12% resumed their premorbid level of employment and 30% returned to modified work. There were significant differences (p<.05) between the groups in level of social interaction, premorbid occupation, and discharge disposition. On one test of cognitive functioning the difference was at p = .06. CONCLUSION: Social interaction, jobs with greater decision-making latitude, and discharge home were positively related to RTW for this population. Cognitive impairment within the first month was not a reliable indicator of RTW potential.     

'Outside-in' signalling mechanisms underlying CD11b/CD18-mediated NADPH oxidase activation in human adherent blood eosinophils

1 Incubation of human eosinophils in BSA-coated tissue culture plates resulted in time-dependent adhesion and attendant activation of the NADPH oxidase that were both inhibited (by >85%) by blocking antibodies raised against CD11b and CD18. 2 SB 203580, an inhibitor of p38 mitogen-activated protein (MAP) kinase, did not influence adhesion but inhibited superoxide anion generation (pIC50=-6.57). 3 PP1, an inhibitor of the src-family of protein tyrosine kinases, inhibited adhesion and CD11b/CD18-mediated superoxide anion generation with similar potencies (pEC50s=-5.53 and -5.99 respectively) suggesting that inhibition of the NADPH oxidase was a direct consequence of blocking adhesion. 4 The protein kinase C (PKC) inhibitors Ro-31 8220 (broad spectrum inhibitor), GF 109203X (inhibitor of conventional and novel isoforms) and G? 6976 (inhibitor of conventional isoforms) suppressed adhesion-dependent NADPH oxidase activation (pIC50s=-6.61, -6.05 and -4.89 respectively) without affecting adhesion. Based upon the selectivity of these drugs PKCdelta and PKCepsilon are implicated in the suppression of oxidant production. 5 Wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PtdIns 3-kinase), abolished superoxide anion production in adherent eosinophils (pEC50=-9.06). Similarly, CD11b/CD18-dependent adhesion was suppressed with the same potency (pEC50=-9.29) although the maximum effect did not exceed 50% implying that wortmannin also had an affect on those processes that govern adhesion-driven oxidase activation. 6 PD 098059 and piceatannol, inhibitors of MAP kinase kinase-1 and the syk tyrosine kinase respectively, had no effect on CD11b/CD18-mediated adhesion or NADPH oxidase activation. 7 The results of this study demonstrate that human eosinophils adhere to BSA-coated plastic by a CD11b/CD18-dependent mechanism, which is responsible for activation of the NADPH oxidase. Although the signalling pathway(s) utilized by CD11b/CD18 is still to be elucidated, the data presented herein implicate p38 MAP kinase, novel PKCs and PtdIns 3-kinase.     

Thoracic Aortic Aneurysms: Role of Echocardiography

This article describes the evolving role of echocardiography for the detection and evaluation of thoracic aortic aneurysms. A brief summary of the clinical, anatomical, and pathological features of the etiologic categories of thoracic aneurysms is presented. The advantages and limitations of echocardiography and its comparison with other techniques (computed tomographic scanning, magnetic resonance imaging, and aortography) are discussed.