Nedocromil sodium is a pyranoquinoline dicarboxylic acid derivative, formulated in a metered-dose inhaler. Because nedocromil sodium has in vitro and in vivo anti-inflammatory properties, it was evaluated in a group of steroid-dependent patients with asthma to observe how well it might be tolerated and for evidence of any beneficial effects. In a double-blind, group-comparative study, 127 patients received nedocromil sodium and 61 received placebo, administered as two puffs of 2 mg, four times per day, for 12 weeks. Ten patients developed adverse reactions, seven receiving active drug and three patients receiving placebo. Two patients of each group withdrew because of worsening asthma. Despite selecting patients whose asthma was stable, when they were receiving established therapeutic regimens that included steroids and bronchodilators, it was found that diary-card symptom scores, morning and evening peak expiratory flow rate values, and inhaled beta-agonist usage all demonstrated slight but significant benefit with addition of nedocromil sodium. It is concluded that the inhaled, anti-inflammatory agent, nedocromil sodium, may be added to asthma-treatment regimens with the reasonable expectation of further modest symptomatic benefit.
Loracarbef, which is the first agent of the carbacephem class of beta-lactam antibiotics to be developed, provides good activity against a broad spectrum of bacteria. A single-blinded, randomized, parallel clinical trial in 10 centers in the United States compared the efficacy and safety of loracarbef with that of amoxicillin/clavulanate potassium in the treatment of acute bacterial maxillary sinusitis. A 7-10-day regimen of loracarbef (400 mg twice daily) was as effective as amoxicillin/clavulanate (500/125 mg three times a day) and resulted in somewhat fewer side effects. The results of a European trial in Sweden, Finland, and Iceland showed that loracarbef was clinically more effective than doxycycline in the treatment of acute bacterial maxillary sinusitis.
Early complex treatment of a critical brain traumas should be aimed not only at men's life and personality saving, but also at their performance' rehabilitation. Complicity and to some degree individual nature of a critical trauma pathogenesis depend on the associative active methods of surgery interference and conservative pharmacotherapy. The article deals with well-practiced means and methods of symptomatic pharmacotherapy at the early and later stages of the brain traumas with vestibular and hearing system injures and with theoretical and clinical base for modern "quick-action adaptogens" usage in addition to psychoneurocorrectors.
To investigate the value of combined treatment with allopurinol and 5-aminosalicylic (5-ASA) based drugs as maintenance treatment for ulcerative colitis (UC).
199 patients with UC in remission but with active disease during the preceding 3 years were included. Allopurinol 100 mg twice daily or placebo was added to the 5-ASA based maintenance treatment. Clinical and endoscopic follow up was performed after 1, 6 and 12 months.
Intention-to-treat analysis after 6 and 12 months showed similar results in both groups. A log-rank test showed that 77% in the allopurinol compared to 59% in the placebo group were still in remission after 6 months (P=0.0083) and 62% and 53% after 12 months, respectively (P=0.0936). This was mainly due to a higher than expected number of relapses during the first 3 months in the placebo group. After the first 3 months, the rate of relapse in each group was similar.
It appears possible that allopurinol in combination with 5-ASA is better than 5-ASA alone for a 6-month, but not a 12-month period. This has to be verified in further dose-ranging studies.
The Alpha-Tocopherol, Beta-Carotene (ATBC) Lung Cancer Prevention Study was a randomized, double-blind, placebo-controlled, 2 x 2 factorial design, primary prevention trial testing the hypothesis that alpha-tocopherol (50 mg/day) and beta-carotene (20 mg/day) supplements reduce the incidence of lung cancer and possibly other cancers. Total and disease-specific mortality and incidence of various diseases and symptoms were monitored for safety. Between 1985 and 1993, 29,133 eligible male smokers aged 50 to 69 years at entry were randomized to receive daily active supplements or placebo capsules for 5 to 8 years (median 6.1 years), accumulating 169,751 follow-up years. This report describes the study design, methods, and protocol as well as the baseline characteristics and capsule compliance of the participants. The ATBC Study is the largest lung cancer chemoprevention trial conducted to date.
Comment In: Ann Epidemiol. 1994 Jan;4(1):758205274
A prospective cost-effectiveness analysis undertaken as part of the CAESAR (Canada, Australia, Europe, South Africa) placebo-controlled clinical trial showed that the addition of lamivudine to zidovudine-containing regimens for 1 year reduced progression of HIV infection to AIDS or death, as well as significantly reducing the number of hospitalisations, outpatient visits and the requirement for medications for HIV-related illness and adverse events. Data from all 1840 patients included in the 'intent-to-treat' population of the CAESAR trial were used for the present analysis. A Canadian third-party payer perspective was adopted, and all costs were adjusted to 1997 prices.
The savings associated with reduced healthcare resource use in the CAESAR study were estimated to be 1123 Canadian dollars ($Can) per patient, over the year. These savings partly offset the cost of lamivudine. The analysis showed that the addition of lamivudine to zidovudine-containing regimens resulted in an incremental cost-effectiveness ratio of $Can 14,225 [95% confidence interval (CI): $Can4383 to $Can29,577] for progression to AIDS/death avoided and of $Can5631 (95%CI: $Can2010 to $Can12,929) for HIV-related illness avoided.
Our findings indicate that treatments that slow the progression of HIV infection to AIDS or death have the potential to facilitate healthcare savings, which partly offset the drug acquisition costs. The results also demonstrate that it is possible to undertake economic evaluations in parallel with a major clinical end-point study.
A recurring epidemic of asthma exacerbations in children occurs annually in September in North America when school resumes after summer vacation.
Our goal was to determine whether montelukast, added to usual asthma therapy, would reduce days with worse asthma symptoms and unscheduled physician visits of children during the September epidemic.
A total of 194 asthmatic children aged 2 to 14 years, stratified according to age group (2-5, 6-9, and 10-14 years) and gender, participated in a double-blind, randomized, placebo-controlled trial of the addition of montelukast to usual asthma therapy between September 1 and October 15, 2005.
Children randomly assigned to receive montelukast experienced a 53% reduction in days with worse asthma symptoms compared with placebo (3.9% vs 8.3%) and a 78% reduction in unscheduled physician visits for asthma (4 [montelukast] vs 18 [placebo] visits). The benefit of montelukast was seen both in those using and not using regular inhaled corticosteroids and among those reporting and not reporting colds during the trial. There were differences in efficacy according to age and gender. Boys aged 2 to 5 years showed greater benefit from montelukast (0.4% vs 8.8% days with worse asthma symptoms) than did older boys, whereas among girls the treatment effect was most evident in 10- to 14-year-olds (4.6% [montelukast] vs 17.0% [placebo]), with nonsignificant effects in younger girls.
Montelukast added to usual treatment reduced the risk of worsened asthma symptoms and unscheduled physician visits during the predictable annual September asthma epidemic. Treatment-effect differences observed between age and gender groups require additional investigation.
Baseline characteristics in the Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial: a hypertensive population at high cardiovascular risk.
ACCOMPLISH is the first trial designed to compare the effects on major fatal and non-fatal cardiovascular endpoints of two forms of antihypertensive combination therapy: benazepril plus hydrochlorothiazide and amlodipine plus benazepril in hypertensive patients at high cardiovascular risk. Enrollment for this trial is now complete and this report describes the clinical characteristics of the study cohort. Patients with hypertension and a previous history of cardiovascular events, strokes or diabetes mellitus were randomized to double-blind treatment with either of the two combination regimens. The data in this report detail the clinical history and demographic characteristics in patients immediately prior to randomization to study drugs. A total of 11,454 patients were randomized. Mean age (+/-SD) was 68.4+/-6.9 years, 60% were men, and 1360 (12%) were African American. Mean body mass index (BMI) was 31.0+/-6.3 kg/m(2). At study entry, 46% of patients had a history of acute coronary syndromes, coronary artery bypass grafts or percutaneous coronary interventions; 13% had a history of stroke. A history of diabetes mellitus was reported in 6928 (60%) of patients. Mean blood pressure at baseline (on prior hypertension therapy) was 145.4/80.0 mmHg; only 38% of patients had a BP less than 140/90 mmHg. Overall, 97% of patients had received previous antihypertensive treatment (74% on at least two drugs); 53% were on oral diabetes therapy or insulin, 68% on anti-lipid therapy and 63% on anti-platelet agents. In summary, the ACCOMPLISH trial has recruited hypertensive patients at high risk of cardiovascular morbidity and mortality. It is noteworthy that the mean BMI of 31 in this cohort is clearly above the accepted diagnostic criterion of obesity and that 60% of patients are diabetic, possibly reflecting secular trends in clinical disease.