Double-blind preference and compliance multicentre study in osteoarthritis: once-a-day treatment.

Two-hundred-and-three female patients (mean age: 58 yrs; SD: 8.2 yrs) suffering from osteoarthritis entered this late phase IV multicentre, stratified according to previous therapy (e.g. ketoprofen, naproxen, aspirin, indomethacin or indoprofen), randomized, double-blind, between within-patient trial of 2-week duration. Each patient received either diclofenac SR 100 mg/day (D), piroxicam 20 mg/day (P), or placebo (P1 by oral route. Clinical evaluation (functional class; pain assessment; osteoarthritic condition; joint motility and stiffness) was performed at entry, as well as after the first and the second week. Patient compliance and reported signs and symptoms were recorded after the first week and at the end of the trial. Patient preference, as regards previous therapy, and global evaluation (both by the physicians and the patients) were checked at the end of the trial. The clinical evaluation showed a superiority of D and P over P1. No difference was seen between the two active drugs. Placebo effect was very strong. Global evaluation was significantly in favour of D and P. Patient compliance was extremely good (greater than or equal to 95%). Diclofenac was preferred to naproxen, aspirin and indomethacin, while piroxicam and placebo were preferred only to aspirin. The tolerability of the two active drugs was good and comparable. A significantly lower number of patients complaining of unwanted effects (u.e.) was detected in the placebo group. The number of patients withdrawn for u.e. was similar in the three trial groups.

Effects of chronic administration of the fixed combination slow-release oxprenolol-chlorthalidone on left ventricular hypertrophy in hypertensive patients. Echocardiographic study.

To evaluate the effects of the chronic administration of the fixed combination slow-release, oxprenolol 160 mg and chlorthalidone 20 mg on left ventricular hypertrophy, ten hypertensive out-patients, with left ventricular hypertrophy documented by left ventricular mass index (LVMI) greater than 130 g/m2, were studied. After a two-week placebo period, patients were given the study medication, once daily for six months. Blood pressure and heart rate were measured, 24 h after-dosing, at the end of placebo and thereafter every month. A m-mode echocardiographic examination was performed at the end of the placebo period, after 1 month of active treatment and at the end of the study. In comparison with placebo, the study medication induced a significant reduction (p less than 0.01) of systolic and diastolic blood pressure, 24 h after dosing, after 1 month of treatment (from 181.0 +/- 18.5/108.5 +/- 12.0 to 146.5 +/- 10.8/94.0 +/- 7.7 mmHg), and this reduction was maintained until the end of the study (142.0 +/- 14.0/90.0 +/- 8.2 mmHg). At the 6th month and in comparison with placebo, a significant (p less than 0.01) reduction of left ventricular mass (LVM) and of LVMI was observed (LVM: from 295.9 +/- 113.8 to 221.5 +/- 66.1 g; LVMI: from 158.1 +/- 39.0 to 126.2 +/- 35.8 g/m2. In conclusion, our results confirm the good antihypertensive efficacy of the fixed combination slow-release oxprenolol and chlorthalidone and show that the study medication is able to induce a regression of left ventricular hypertrophy, in hypertensive patients.

A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain.

Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo-controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression.

Factors affecting chronic renal failure progression: results from a multicentre trial. The Northern Italian Cooperative Study Group.

In order to evaluate the prognostic factors concerning the rate of progressive deterioration of renal function, we made an inductive analysis of the behaviour of 456 patients in a multicentre, formal prospective trial aimed at clarifying the possible role of protein restriction in retarding the progression of chronic renal insufficiency (CRI). The main clinical and laboratory findings in patients whose plasma creatinine (PCr) levels doubled in comparison with baseline randomization values or who needed dialysis within 24 months after onset of the study were compared with those of the other patients. In addition, independently of the assigned diet, we tested the main variables that might affect CRI progression (sex, systolic and diastolic blood pressure, change in body weight, hematocrit, calcium-phosphate product, proteinuria, protein catabolic rate, total cholesterol and triglycerides). We used multiple regression analyses and also plotted the mean values of these parameters in each patient against an estimate of the deterioration of chronic renal failure based on the difference between the final and the initial reciprocal of the PCr and the creatinine clearance (CCr) levels. A descriptive analysis of the behaviour of PCr in the three CRI groups and in the four underlying diseases groups was made. PCr levels at entry, underlying disease and proteinuria were prognostic factors for CRI progression. The increase in PCr was 0.0102 mg/dl/month in patients with nephrosclerosis, 0.0203 mg/dl/month in interstitial nephropathy, 0.0360 mg/dl/month in glomerulonephritis and 0.0704 mg/dl/month in polycystic kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Unilateral nephrectomy and progression of renal failure.

Extensive ablation of renal mass in experimental animals leads to progressive glomerulosclerosis and chronic renal failure (CRF). Clinical studies are far from answering the question whether patients with reduced renal mass are at risk of developing progressive CRF. The aim of our study was to examine the morphological and functional aspects of the remnant kidney in a group of patients who underwent unilateral nephrectomy for renal tuberculosis: 313 patients (161 M, 152 F) mean age 57.2 +/- 10.7, were examined after a period ranging from 13.56 to 591.2 months. All patients were on ad libitum diet. Hypertension was found in 34.19% of the patients; SBP was 155.29 +/- 19.9 mmHg and DBP was 92.74 +/- 13.07 mmHg. Estimation of renal size performed by ultrasound scanner gave the following results: length 116.78 +/- 8.99 mm; width 58.24 +/- 7.21 mm; thickness 17.88 +/- 1.96 mm. Kidney function assessed by serum creatinine levels showed a mean level of 1.28 +/- 0.53 mg%. Forty-two patients (13.41%) had serum levels > 1.5 mg% but 18 of them had nonconcomitant systemic or renal involvement. Microalbuminuria determined by RIA assay was found in 50.5% of the patients. In our group of patients renal functional impairment was low and hyperfiltration expressed as microalbuminuria does not appear to be a primary factor in the progression of renal failure.

Effects of two doses of the fixed-combination chlorthalidone and slow-release metoprolol on blood pressure at rest and during exercise: a multicenter study.

To assess the efficacy and tolerability of two doses of chlorthalidone (CHL) and slow-release (SR) metoprolol (MET) given in fixed combination (standard dose: CHL 25 mg and MET 200 mg; lower dose: CHL 12.5 mg and MET 100 mg), a multicenter (5 Centers), double-blind, between-patients study was planned. Seventy-three mild to moderate hypertensive patients, 45 males and 28 females, aged 25-68 years (mean 51.4), at WHO stage I or II, were enrolled into the study. After a 2-week placebo wash-out period, eligible patients were randomly given either of the two drugs for six weeks: 33 were given the standard dose and 40 the lower one. Every 2 weeks, in the morning and 24 h after-dosing lying and standing systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded at rest. At the end of the placebo period and at the end of the study 24 h after-dosing a sub-maximal bicycle ergometer exercise test was performed. In comparison with placebo, both doses induced a significance decrease (p less than 0.01) in lying and standing SBP, DBP and HR, as well as in peak-exercise SBP, HR and pressure-rate product. Furthermore, a significant difference (p less than 0.05) of the higher dose versus the lower one was also observed at the end of the study in the above-mentioned parameters except for SBP at rest and at peak exercise and standing HR at rest.(ABSTRACT TRUNCATED AT 250 WORDS)