Clinical trial: ulcerative colitis maintenance treatment with 5-ASA: a 1-year, randomized multicentre study comparing MMX with Asacol.

BACKGROUND: 5-ASA-MMX (1.2 g/tablet) is a 5-aminosalicylic acid formulation, designed for once-daily dosing in the treatment of ulcerative colitis. AIM: To evaluate the efficacy and safety of 5-ASA-MMX (2.4 g/day, once daily), compared with Asacol (2.4 g/day, twice daily) in the maintenance of left-sided UC, through a double-blind, double-dummy, parallel-group, randomized, comparator study. METHODS: In all, 331 patients with UC were randomized to receive either 5-ASA-MMX 2.4 g/day, once daily, or Asacol 2.4 g/day, twice daily, for 12 months. All patients were in remission for >or=1 month prior to the trial, with >or=1 documented relapse in the previous year. The co-primary endpoints of this study were the proportion of patients in clinical, and clinical and endoscopic remission following 12 months' treatment. RESULTS: In the intent-to-treat population, excluding those with major protocol deviations, 68.0 and 65.9% patients in the 5-ASA-MMX and Asacol groups, respectively, were in clinical remission (P = 0.69), and 60.9 and 61.7% of patients, respectively, were in clinical and endoscopic remission (P = 0.89). Diary card data revealed statistically significant treatment differences favouring 5-ASA-MMX. Both treatments were similarly tolerated. CONCLUSIONS: Once-daily 5-ASA-MMX is similarly effective with a comparable safety profile to Asacol administered twice daily, for the maintenance treatment of ulcerative colitis.

Quality control of spirometry: a lesson from the BRONCUS trial.

This report describes the quality control programme used within the Bronchitis Randomized on N-acetylcysteine (NAC) Cost-Utility Study, a trial designed to assess the decline in lung function, exacerbation rate, health status, and cost-effectiveness with NAC or a placebo in 523 patients with chronic obstructive pulmonary disease over a 3-yr period. Spirometry was scored from 0 (worst quality) to 6 (best quality). The mean score of 314 spirometries from 243 patients evaluated during the trial was 5.63+/-0.83. Linear regression analysis of the scores of 47 participating centres plotted against the time at which spirometries were performed yielded an intercept of 5.7+/-0.5 and a slope of -0.0001+/-0.001, which suggests that the initial high quality was maintained over time. Retrospective examination of a further 345 postbronchodilator spirometries from 208 patients with a forced expiratory volume at one second exceeding the mean individual value recorded over the study in excess of 20% revealed a slightly lower quality of the start-of-test manoeuvre compared with the 314 spirometries. In conclusion, these findings would suggest that the quality control programme is likely to have helped achieve and maintain long-term spirometry performance in the Bronchitis Randomized on N-acetylcysteine (NAC) Cost-Utility Study trial. Special care should be paid to the spirometries whose forced expiratory volume in one second values exceed the mean value.

The Bronchitis Randomized On NAC Cost-Utility Study (BRONCUS): hypothesis and design. BRONCUS-trial Committee.

Chronic obstructive pulmonary disease (COPD) is an irreversible disorder characterized by airflow obstruction and a progressive decline in forced expiratory volume in one second (FEV1). At present, no treatment except quitting smoking appears to affect the progression of the disease. Oxidative stress has been implicated in its pathogenesis. The Bronchitis Randomized on NAC Cost-Utility Study (BRONCUS) is a phase III, randomized, double-blind, placebo-controlled, parallel group, multicentre study designed to assess the effectiveness of the antioxidant agent N-acetylcysteine (NAC) in altering the decline in FEV1, exacerbation rate, and quality of life in patients with moderate to severe COPD. In addition, cost-utility of the treatment will be estimated. Patients will be followed for 3 yrs and evaluated every 3 months. The necessary sample size to demonstrate an effect on the decline in FEV1 of 20 mL x yr(-1) was estimated to be 478 patients. Five hundred and twenty-three patients with moderate to severe COPD were recruited from 10 European countries from June 1, 1997-December 31, 1999. They were 63+/-8 yrs old and consisted of 243 (46%) current smokers and 280 (54%) exsmokers. Patients had on the average 4.9+/-1.6 exacerbations during the last 2 yrs. Postbronchodilator FEVI averaged 57+/-9% and the reversibility after 400 microg of Salbutamol averaged 4+/-4% predicted. The final results of the trial will be available in about 2 yrs. The study will provide objective data on the effects of N-acetylcysteine on outcome variables in chronic obstructive pulmonary disease.

Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators.

BACKGROUND: Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study. METHODS: Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done. FINDINGS: After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p = 0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients. INTERPRETATION: Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.

Screening study of abdominal aortic aneurysm in a general population: lipid parameters.

The level of blood lipids and apolipoproteins in subjects being screened for abdominal aortic aneurysms have been investigated. As part of an ultrasound screening programme in a population of 65- to 75-year-olds, blood samples were collected from 1460 of 1504 subjects with a normal aorta (97.1%) and 69 of 70 patients with an abdominal aortic aneurysm > 29 mm (99%). Samples were also taken from 22 of 27 patients (81%) with an ectatic aorta (26-29 mm). Total cholesterol, HDL-cholesterol, LDL-cholesterol, Apo-AI and Apo-B levels were significantly higher in women than in men (P < 0.01). Levels of HDL-cholesterol and Apo-AI were significantly lower in patients with an abdominal aortic aneurysm than in normal subjects (P < 0.001). The mean(s.d.) body mass index was 25.1(3.9) in women and 25.5(3.2) in men with aneurysms and not significantly greater than that of normal subjects (25.2(3.61) and 25.2(3.38) respectively).

Screening for abdominal aortic aneurysms and associated risk factors in a general population.

OBJECTIVES: To evaluate the prevalence of abdominal aortic aneurysms (AAA) in a general population and to compare the results with those of similar studies in other countries. DESIGN: Ultrasound screening study and collection of clinical and biochemical data. SETTING: An urban Health Service District in Genoa, Italy. MATERIALS: A general population, aged 65-75 years, invited by personal letter between 1991-1994. RESULTS: 1601 subjects (741 males and 860 females) out of 2734 invited (58.5%) were evaluated. According to the ultrasound findings, 27 patients (1.7%) had an aortic dilatation of 26-29 mm; an AAA of 30-39 mm was found in 37 (2.3%) and an AAA > or = 40 mm in 33 (2.1%). The overall prevalence for AAA was 4.4% (8.8% in males and 0.6% in females respectively). The prevalence of smoking, alcohol consumption, coronary heart disease, chronic obstructive pulmonary disease and arterial disease were significantly higher in patients with AAA (p < 0.01). CONCLUSIONS: Ultrasound screening for AAA is a reliable and useful method and should be focused on men, regardless of concurrent disease.

Gemfibrozil and Mediterranean diet for patients with high plasma levels of lipoprotein [Lp(a)] and cholesterol--pilot study.

Plasma levels of lipoprotein-a [Lp(a)] > 30 mg/dl represent an independent risk factor for cardiovascular diseases with both proatherosclerotic and prothrombotic activity. The results of dietary or pharmacological treatment are not encouraging and are often controversial. We have evaluated a combination of medical treatment with Gemfibrozil (600 mg bid) and a Mediterranean diet for 2 months in 15 patients with both hypercholesterolemia (> 240 mg/dl) and high levels of Lp(a) (> 30 mg/dl). Three patients dropped out within the first 2 weeks, complaining of epigastric pain and burning; the remainder (5 females and 7 males, mean age 70 years) completed the treatment without any side effects. The median values of Lp(a) decreased from 36.5 to 8.4 mg/dl (p < 0.0002) and total cholesterol from 254.5 to 208.0 mg/dl (p < 0.0001). The small number of patients does not permit any definitive conclusion on effectiveness to be drawn, but the results indicate further randomized studies might prove worthwhile.

A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia. A multicentric study from the Italian Co-operative Group GIMEMA.

255 patients with acute non-lymphoid leukaemia (ANLL), observed between October 1984 and June 1987, entered a chemotherapy regimen consisting of induction therapy with cytarabine in combination with idarubicin (IDA/ARA) or daunorubicin (DNR/ARA), followed by consolidation with four courses of IDA + ARA plus 6-thioguanine (6-TG) or DNR + ARA + 6-TG and a 6 month maintenance therapy with 6-TG and ARA. The median age was 62 years (range 55-78 years) and 33 were aged more than 70 years. The treatment groups were comparable for median age, FAB type, performance status and initial blood counts. 249 patients were randomised, 124 to the IDA/ARA arm and 125 to the DNR/ARA arm. Complete remission was achieved in 50 patients (40%) on the IDA/ARA treatment program and 49 patients (39%) on DNR/ARA. No definite differences were found between patients receiving IDA/ARA and those treated with DNR/ARA as far as complete response (CR), overall survival, failure free and relapse free survival are concerned. 74% of the complete responders in the IDA/ARA arm and 51% in the DNR/ARA arm achieved CR after a single course of treatment. Resistant leukaemia was observed in 13.7% of the patients in the IDA/ARA arm and in 31.2% in the DNR/ARA one, whereas hypoplastic death occurred in 29% and 14.4%, respectively. In conclusion, our data failed to show any advantage of idarubicin over daunorubicin even though there is some evidence that IDA, despite the higher toxicity, is more rapid in eradicating leukaemia as proved by the higher CR rate obtained after one course of induction.

Cognitive event-related potentials and reaction time in presenile subjects with initial mild cognitive decline or probable Alzheimer-type dementia.

The so-called contingent negative variation (CNV) is a slow brain potential representing a complex of variously overlapped "endogenous" components of behavior related to different reasonably well-known neurocognitive processes. CNV complex evoked with a standard paradigm (S1-2 sec-S2-motor response) and reaction time (RT) to imperative signal (S2) were recorded and measured in 11 patients with initial presenile idiopathic cognitive decline (PICD), 8 with presenile Alzheimer-type dementia (PAD) and 10 healthy age-matched controls. Significant group differences were obtained for measures of some CNV components, particularly of the late pre-S2 CNV. No significant CNV activity, very prolonged RTs and sometimes characteristic post-imperative negative variation (PINV) were observed in the majority of patients with PAD. These results suggest that CNV complex and RT changes similar to those observed in our patients may constitute a valuable clue for the study of pathophysiological brain functioning in the early stages of presenile idiopathic mental deterioration.

Nicergoline in mild to moderate dementia. A multicenter, double-blind, placebo-controlled study.

In view of some controversies still existing about the real efficacy of ergot derivatives in the management of dementia, a double-blind, randomized, parallel group trial extending up to 6 months was carried out to compare the effects of nicergoline, 60 mg daily, and placebo in 315 patients suffering from mild to moderate dementia. Clinical evaluation was performed by the SCAG scale. The trial, which included a 1-month placebo run-in period, showed that both placebo and nicergoline were associated with some degree of improvement. The effect of nicergoline, however, was significantly greater and more sustained, steadily increasing with time. In particular, the difference between nicergoline and placebo in mean total SCAG score was 5.5 at 3 months (95% confidence interval: 3.6-7.4) and increased to 9.8 at 6 months (95% confidence interval: 7.8-11.8). A comparison of nicergoline versus placebo in the frequencies of changes in each item of the SCAG showed also a significant difference at 6 months, the percent of patients displaying an improvement by at least 2 points ranging from 13.5 (bothersome) to 30.2 (disorientation) in nicergoline group, against 4.1 (self-care) to 14.3 (fatigue) in placebo group. The safety of nicergoline, as judged by hemodynamic changes and drug-related adverse reactions, was quite satisfactory.