Effect of inhaled corticosteroids on bronchial responsiveness in patients with "corticosteroid naive" mild asthma: a meta-analysis.
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BACKGROUND: Inhaled corticosteroids are the most efficacious anti-inflammatory drugs in asthma. International guidelines also advocate the early introduction of inhaled corticosteroids in corticosteroid naive patients. A study was undertaken to assess the effects of inhaled corticosteroids on bronchial hyperresponsiveness in patients with corticosteroid naive asthma by conventional meta-analysis. METHODS: A Medline search of papers published between January 1966 and June 1998 was performed and 11 papers were selected in which the patients had no history of treatment with inhaled or oral corticosteroids. Bronchial responsiveness to bronchoconstricting agents was considered as the main outcome parameter. Doubling doses (DD) of histamine or methacholine were calculated. RESULTS: The total effect size of inhaled corticosteroids (average daily dose 1000 microg) versus placebo in the 11 studies was +1.16 DD (95% confidence interval (CI) +0.76 to +1.57). When only the eight short term studies (2-8 weeks) were analysed the effect size of the bronchoconstricting agent was +0.91 DD (95% CI +0.65 to +1.16). No relationship was found between the dose of inhaled corticosteroid used and the effect on bronchial responsiveness. CONCLUSION: This meta-analysis in patients with corticosteroid naive asthma indicates that, on average, high doses of inhaled corticosteroids decrease bronchial hyperresponsiveness in 2-8 weeks. It remains unclear whether there is a dose-response relationship between inhaled corticosteroids and effect on bronchial hyperresponsiveness. (+info)
Clinicopathological features of Churg-Strauss syndrome-associated neuropathy.
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We assessed the clinicopathological features of 28 patients with peripheral neuropathy associated with Churg-Strauss syndrome. Initial symptoms attributable to neuropathy were acute painful dysaesthesiae and oedema in the dysaesthetic portion of the distal limbs. Sensory and motor involvement mostly showed a pattern of mononeuritis multiplex in the initial phase, progressing into asymmetrical polyneuropathy, restricted to the limbs. Parallel loss of myelinated and unmyelinated fibres due to axonal degeneration was evident as decreased or absent amplitudes of sensory nerve action potentials and compound muscle action potentials, indicating acute massive axonal loss. Epineurial necrotizing vasculitis was seen in 54% of cases; infiltrates consisted mainly of CD8-positive suppressor/cytotoxic and CD4-positive helper T lymphocytes. Eosinophils were present in infiltrates, but in smaller numbers than lymphocytes. CD20-positive B lymphocytes were seen only occasionally. Deposits of IgG, C3d, IgE and major basic protein were scarce. The mean follow-up period was 4.2 years, with a range of 8 months to 10 years. Fatal outcome was seen only in a single patient, indicating a good survival rate. The patients who responded well to the initial corticosteroid therapy within 4 weeks regained self-controlled functional status in longterm follow-up (modified Rankin score was < or = 2), while those not responding well to the initial corticosteroid therapy led a dependent existence (P < 0.01). In addition the patients with poor functional outcomes had significantly more systemic organ damage caused by vasculitis (P < 0.05). Necrotizing vasculitis mediated by cytotoxic T cells, leading to ischaemic changes, appears to be a major cause of Churg-Strauss syndrome-associated neuropathy. The initial clinical course and the extent of systemic vasculitic lesions may influence the long-term functional prognosis. (+info)
Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell-free systems and inflamed human colorectal biopsies.
(19/7049)
BACKGROUND: The therapeutic efficacy of 5-aminosalicylic acid in inflammatory bowel disease may be related to its antioxidant properties. AIM: To compare in vitro the antioxidant effects of conventional drugs (5-aminosalicylic acid, corticosteroids, metronidazole), with new aminosalicylates (4-aminosalicylic acid, balsalazide) and other potential therapies (ascorbate, N-acetylcysteine, glutathione, verapamil). METHODS: Compounds were assessed for efficacy in reducing the in vitro production of reactive oxygen species by cell-free systems (using xanthine/xanthine oxidase, with or without myeloperoxidase) and by colorectal biopsies from patients with ulcerative colitis using luminol-amplified chemiluminescence. RESULTS: 5-aminosalicylic acid and balsalazide were more potent antioxidants than 4-aminosalicylic acid or N-acetyl-5-aminosalicylic acid in cell-free systems. 5-aminosalicylic acid (20 mM) and balsalazide (20 mM) inhibited rectal biopsy chemiluminescence by 93% and 100%, respectively, compared with only 59% inhibition by 4-aminosalicylic acid (20 mM). Hydrocortisone, metronidazole and verapamil had no significant effect on chemiluminescence in any system. Ascorbate (20 mM) inhibited chemiluminescence by 100% in cell-free systems and by 60% in rectal biopsies. N-acetyl cysteine (10 mM), and both oxidized and reduced glutathione (10 mM), completely inhibited chemiluminescence in cell-free systems, but not with rectal biopsies. CONCLUSIONS: The antioxidant effects of compounds varies between cell-free systems and inflamed colorectal biopsies. The effect of drugs on the chemiluminescence produced by these two assay systems is useful for screening potentially new antioxidant treatments for inflammatory bowel disease. Ascorbate seems worth further study as a novel therapy. (+info)
Pharmacodynamics of vancomycin for the treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.
(20/7049)
With the emergence of beta-lactam antibiotic resistance among strains of Streptococcus pneumoniae, vancomycin has assumed an important role in the treatment of bacterial meningitis. Using the rabbit meningitis model, we evaluated the pharmacokinetics and pharmacodynamics of vancomycin in this setting. Animals were given 80 mg/kg of body weight daily in two or four divided doses to determine the penetration and activity of vancomycin in cerebrospinal fluid (CSF); each regimen was administered with and without dexamethasone. Mean peak (2 h) concentrations in CSF that were four- to eightfold higher than the minimum bactericidal concentration (MBC; 0.5 microgram/ml) for the pathogen were adequate for bacterial clearance. In both groups concentrations in CSF remained higher than the MBC for greater than 80% of the respective dosing intervals, and the penetration of vancomycin into CSF was 20%. Mean concentrations in CSF at 24 to 36 h of therapy were lower than those achieved during the first 12 h, consistent with a decline in the level of antibiotic entry into CSF as inflammation wanes. Rates of bacterial clearance were similar for the two regimens, and for all animals cultures of CSF were sterile by 36 h. The coadministration of dexamethasone significantly reduced the penetration of vancomycin into CSF by 29% and significantly lowered the rate of bacterial clearance during the first 6 h in animals receiving 20-mg/kg doses of vancomycin. For animals receiving 40-mg/kg doses, therapeutic peak concentrations in CSF were obtained even with steroid use, suggesting that the effect of steroids may be circumvented by the use of larger daily doses of vancomycin. (+info)
Impact of an interest in asthma on prescribing costs in general practice.
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OBJECTIVE: To examine the effect on total prescribing costs and prescribing costs for respiratory drugs for practices with at least one general practitioner with a special interest in asthma. DESIGN: Postal questionnaire survey. SETTING: General practitioners in England and Wales. SUBJECTS: 269 members of the General Practitioners in Asthma Group, of whom 103 agreed to participate. MAIN MEASURES: Individual practitioners' and their practices' PACT prescribing costs from the winter quarters of 1989-90 compared with average costs for their family health services authority (FHSA) and a notional national average of all FHSAs combined. RESULTS: The response rate was 57%; the average total prescribing costs for the practices of the 59 respondents were significantly lower than those of their respective FHSAs (mean difference 505 pounds per 1000 patients per quarter (95% confidence interval -934.0 to -76.2, p = 0.022) and lower than the national average. The average prescribing costs for respiratory drugs for the practices were significantly greater than those for their FHSA (195 pounds per 1000 patients per quarter (84.4 to 306.0, p = 0.001) and the national average. Both types of costs varied widely. CONCLUSION: An interest in asthma care in general practice is associated with higher average prescribing costs for respiratory drugs but no increase in overall prescribing costs compared with those for respective FHSAs and national averages. IMPLICATIONS: FHSAs and their medical advisors should not examine high prescribing costs for individual doctors or one therapeutic category but in the context of practice total costs. (+info)
Patterns of anti-inflammatory therapy in the post-guidelines era: a retrospective claims analysis of managed care members.
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Published and widely disseminated guidelines for the care and management of asthma characterize asthma as a chronic, inflammatory disease and propose specific recommendations for therapy with inhaled anti-inflammatory medications. In a retrospective analysis of medical and pharmacy claims data of approximately 28,000 asthmatic members from five managed care settings, the dominant pattern of pharmacologic therapy that emerged was the use of bronchodilators without inhaled anti-inflammatory drug therapy. In addition, a significant proportion of asthmatic patients received no prescription drug therapy for asthma. Less than one third of asthmatic patients received any anti-inflammatory therapy and the majority of these received one or two prescriptions per year. Specialist physicians were two to three times more likely than non-specialists during a study period of 1 year to prescribe an anti-inflammatory medication, and were half as likely to have their asthmatic patients experience an emergency department or hospital event. This database analysis suggests that greater conformity with guidelines and/or access to specialist physician care for asthmatic members will lead to improved patient outcomes. (+info)
Asthma treatment costs using inhaled corticosteroids.
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Asthma is a chronic inflammatory disorder of the airways that affects 10 to 17.5 million people and leads to more than $5 billion in treatment costs in the Unites States annually. This retrospective study is an initial step in understanding the beneficial economic outcomes of inhaled corticosteroid therapy by determining whether differences exist in healthcare utilization expenditures for three inhaled corticosteroids available for use in the United States: (1) beclomethasone dipropionate (Vanceril/Schering and Beclovent/Allan & Hanburys); (2) flunisolide (Aerobid/Forest); and (3) and triamcinolone acetonide (Azmacort/Rhone-Poulenc Rorer). This study was based on an analysis of 4,441 patients with at least one pharmaceutical claim for one of the study drugs, using inpatient, outpatient, and prescription drug claims data obtained from The MEDSTAT Group's MarketScan database for calendar years 1990 through 1993. We tested a null hypothesis for no differences in total asthma treatment costs, when drugs were excluded, using multivariate linear regression modeling controlling for patient demographic and clinical characteristics that might affect the study outcome. We found that, after excluding study drug payments and controlling for other contributing factors, total asthma healthcare expenditures to triamcinolone acetonide (Azmacort) users were higher than those for beclomethasone dipropionate (Vanceril and Beclovent) and flunisolide (Aerobid) users. When study drug costs were included in the expenditure measure, both triamcinolone acetonide (Azmacort) and flunisolide (Aerobid) users had higher expenditures than did beclomethasone dipropionate (Vanceril and Beclovent) users. No significant differences in expenditures were detected between Vanceril and Beclovent patients, a finding consistent with the fact that these drugs are the same type of inhaled corticosteroid. Other factors contributing to differences in total asthma healthcare costs included patient age, patterns of switching among and continuing with study drugs, prestudy asthma utilization or drug proxy severity, and comorbidities of precipitating illnesses. (+info)
The diagnosis, classification, and management of asthma according to severity.
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This activity is designed for primary care and specialist physicians. GOAL: To provide prompt and appropriate treatment for asthma of all levels of severity resulting in improved level of activity and decreased need for urgent care and hospitalization with a possible reduction in the annual decline of lung function, degree of permanent airway damage, and mortality. OBJECTIVES: 1. To provide a framework on the basis of history, physical findings, and laboratory results for the diagnosis of asthma. 2. To improve the ability to classify asthma by degree of severity. 3. To describe an incremental therapeutic approach to asthma by degree of severity. 4. To provide a systematic approach with regard to periodic reevaluation of asthma severity and modification of the treatment plan. (+info)