A randomized, double-blind, placebo-controlled study of venlafaxine XR in out-patients with tension-type headache.

The aim of this study was to evaluate in a double-blind, randomized, placebo-controlled study the safety and efficacy of venlafaxine extended release (XR) in the prophylactic treatment of out-patients with tension-type headache (TTH) and no current depression or anxiety disorders. Sixty neurology and headache clinic out-patients meeting the International Headache Society diagnostic criteria for TTH were treated with venlafaxine XR (150 mg/day, n = 34) or placebo (n = 26) for 12 weeks. The primary efficacy variable was the decline in number of days with headache. At end-point, the venlafaxine XR group had a significantly greater decrease in the number of days with headache compared with placebo (P = 0.05). Differences with regard to secondary efficacy variables where not significant. The number needed to treat for responders (>or=50% reduction in days with headache) was 3.48. Six patients in the venlafaxine XR group interrupted therapy due to adverse events, while no patients in the placebo group did so for the same reason. The number needed to harm was 5.58. This study provides preliminary evidence for the efficacy and safety of venlafaxine XR 150 mg/day in reducing the number of days with TTH.

Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder. A double-blind, randomized, placebo controlled study.

The primary endpoints in this study were the remission rates [final Hamilton Rating Scale for Anxiety (HAM-A) total score < or =7] and reduction from baseline in the HAM-A total score in patients with generalized anxiety disorder (GAD) and no associated depression. Patients with GAD (DSM-IV and HAM-A total score >18) were randomly assigned to treatment with venlafaxine XR or placebo for 8 weeks. A 1-week placebo run-in period preceded the double-blind phase. Patients with a >20% drop in their total HAM-A score during the run-in period, were excluded from the double-blind phase. All patients started therapy with 75 mg/day venlafaxine XR or matched placebo. Patients with less than 30% decrease in their HAM-A total score at the end of the second week, doubled their dose. Patients on the 150 mg/day dose underwent a 1-week taper period. Of the 24 patients in the venlafaxine XR group, 62.5% achieved remission versus 9.1% in the placebo group (P=0.0006). The mean decrease from baseline in HAM-A total score was 19.2 points for the venlafaxine XR group and 10.8 points for the placebo group (P<0.001). Eleven placebo-treated patients and seven venlafaxine XR treated patients doubled their dose at the end of the second week of double-blind treatment. No patient interrupted therapy because of side-effects. No changes in systolic or diastolic blood pressure were observed. Venlafaxine XR 75-150 mg/day was well tolerated. The remission rates achieved with venlafaxine 75-150 mg/day in non-depressed GAD patients were high with good tolerability.

Bacterial susceptibilities to piperacillin/tazobactam in a tertiary care hospital: 5-year review.

Several factors influence the speed of development of antibacterial resistance, among which is the amount of antibiotic consumption. During the 3-year period 1998-2000, the consumption of piperacillin/tazobactam (pip/tazo) increased by 85% in our hospital. Five years ago we conducted a comparative in vitro study to evaluate susceptibilities of microorganisms to pip/tazo. The objective of the present study was to re-evaluate in vitro susceptibilities to pip/tazo, compared to other beta-lactams, and the potential impact its increased consumption might have on its susceptibility patterns. The study was performed between November 2000 and April 2001. As in 1996, of the beta-lactams studied, pip/tazo and imipenem had the highest susceptibility rates against selected pathogens (>90% susceptibility rates). P. aeruginosa susceptibilities to both imipenem and pip/tazo were high (97% for both). P. aeruginosa susceptibilities to cefepime were lower. Despite its increased use, pip/tazo retained its initially observed high susceptibility rates for the study pathogens.

Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia.

This was a 6-week, double-blind, randomized trial of the efficacy and tolerability of venlafaxine and fluoxetine in 109 patients with major depression and melancholia. Hospitalized and day care patients with DSM-IV major depression and melancholia and a baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of > or = 25 were eligible. The doses were venlafaxine 75 mg/day or fluoxetine 20 mg/day from days 1-4, venlafaxine 150 mg/day or fluoxetine 40 mg/day from days 5-10, and venlafaxine 225 mg/day or fluoxetine 60 mg/day from days 11-42. The intention-to-treat analyses included 55 patients on venlafaxine and 54 on fluoxetine. At the final evaluation, 70% of patients with venlafaxine and 66% with fluoxetine had > or = 50% reduction in the MADRS score, and 70% with venlafaxine and 62% with fluoxetine had a Clinical Global Impression (CGI) score of 1 or 2. A CGI improvement score of 1 was observed in 51% of patients with venlafaxine and 32% with fluoxetine (P = 0.018). A final Hamilton Depression Rating Scale (HAM-D) score < 7 was attained in 41% of venlafaxine-treated and 36% of fluoxetine-treated patients. Overall, 22% of patients in each group discontinued therapy, but only 5% on venlafaxine and 9% on fluoxetine discontinued for adverse events. Nausea was reported in 5.5% of venlafaxine-treated patients and 14.8% of fluoxetine-treated patients. Venlafaxine was effective and well tolerated for treating inpatients with major depression and melancholia. Based on remission criteria (HAM-D < 7 or CGI of 1), venlafaxine was superior to fluoxetine.

Comparative in vitro evaluation of piperacillin/tazobactam in a tertiary care hospital.

Bacterial resistance is usually a serious problem in tertiary care hospitals. The aim of this in vitro study was to evaluate the beta-lactamase inhibitor combination piperacillin/tazobactam in a hospital environment with high bacterial resistance rates and compare it with other beta-lactam agents. Three hundred and sixty-two isolates from various clinical materials were studied during the period March-August 1996. Material for culture was collected from patients of all the wards of our hospital, with the majority being from the Intensive Care Unit (45%). Pathogenic Gram-positive and Gram-negative bacteria with high resistance rates and beta-lactamase production were studied (staphylococci, enterococci, Enterobacteriaceae, Pseudomonas). Significant bacterial resistance rates were identified for ceftazidime (50% for Klebsiellae, 60% for Enterobacter spp, 60% for Proteus spp, 33% for Pseudomonas spp, 75% for Acinetobacter spp) and ciprofloxacin (33% for both Klebsiellae and Enterobacter spp, 67% for Pseudomonas spp, 50% Acinetobacter spp). Fifty percent of Enterococcus isolates were resistance to ciprofloxacin but all of them were susceptible to piperacillin/tazobactam, amoxicillin/clavulanate and imipenem. The antibacterial activity of piperacillin/tazobactam (susceptibility rates 83 to 100% for Enterobacteriaceae, 83% for Pseudomonas spp and 75% for Acinetobacter spp) was higher than that of ceftazidime, piperacillin and ciprofloxacin. Imipenem, being mostly a reserve product, showed higher activity against Acinetobacter, Klebsiella and Enterobacter species.

In vitro comparative assessment of beta-lactamase inhibitors and their penicillin combinations against selected enterobacteria.

A comparative in vitro assessment of the inhibitory activity of clavulanate, sulbactam and tazobactam against the most frequent beta-lactamases found in enterobacteria isolated in Greek hospitals, has been performed. Tazobactam and clavulanate were potent inhibitors of TEM-1, SHV-1, SHV-2 and SHV-5 while sulbactam was less effective. In addition, tazobactam exerted a moderate inhibitory activity against AmpC-type beta-lactamases. In contrast with clavulanate, tazobactam could not cause significant induction of chromosomal cephalosporinases. Potentiation of the activity of penicillins (amoxycillin, ampicillin, ticarcillin and piperacillin), when combined with the inhibitors, has also been evaluated using a sample of recently isolated enterobacteria with beta-lactamase-mediated resistance. The results showed that the most effective among the commercially available combinations, is piperacillin/tazobactam followed by ticarcillin/clavulanate.

Intravesical mitoxantrone for superficial bladder tumors.

Thirty-five patients (33 males, median age 58) with stage T alpha (21 patients) or T1, grade 1 (17 patients) or grade 2 superficial bladder carcinoma, were treated with transurethral resection (TUR) followed by intravesical prophylactic therapy with 10 mg mitoxantrone administered weekly for 6 weeks and then monthly for 10 months. Twenty-five patients were newly diagnosed and 10 had relapsed after previous therapy. Diagnosis was confirmed with cytology and biopsy. The aim of the study was to evaluate the prophylactic effect (relapse rate, disease free interval) and toxicity of intravesical mitoxantrone in superficial bladder carcinoma. Relapses were established with biopsy. After a mean period of 12 months follow-up (median 8.3 months), 63% of patients in the whole group, 72% in the newly diagnosed group and 40% in the group of previously relapsed patients remained relapse free. These rates compare very favorably with the most effective prophylactic agents available. At the end of the follow-up period the median disease-free survival for the whole group was not reached. Therapy was well tolerated with no systemic toxicity and 14 patients reporting grade 1-2 local toxicity. In no patient was treatment discontinued due to toxicity. Mitoxantrone is an effective and safe agent for the post-TUR adjuvant intravesical therapy.

Effect of minocycline on the sperm count and activity in infertile men with high pus cell count in their seminal fluid.

Twenty-five infertile males with 5 or more pus cells per 1000 x field in their seminal fluid were randomly assigned to treatment with minocycline 200 mg daily for one (Group A) or two (Group B) weeks. At the end of the treatment period a statistically significant reduction of pus cells, and a statistically significant increase in the sperm count and the motile sperm were observed (Wilcoxon matched-pairs signed-ranks test, p < 0.01). No statistically significant differences were observed between the two groups (Mann Whitney U test). No toxicity was reported. In conclusion, minocycline improves the seminal indices, in infertile males with high pus cell count in their seminal fluid.

Piperacillin alone vs triple antibiotic combination in gynecological infections.

Forty hospitalized adult patients with gynecological infections were randomly assigned to treatment either with piperacillin alone (22 patients) or with the combination of gentamicin, clindamycin and penicillin G (18 patients). The aim of the study was to investigate the possibility of replacing a triple combination therapy with a single-agent broad spectrum antibiotic. Penicillin G was added for the coverage of enterococci. The median duration of treatment was 8 days for both groups. The daily dose for the administered drugs was 12g for piperacillin, 4mg/kg for gentamicin, 1.8g for clindamycin and 20 million units for penicillin G. The cure-improvement rate in the single agent therapy group was 90.9% and in the combination therapy group 94.4%. These differences were not statistically significant. No side effects were reported. It is concluded that single agent piperacillin is as effective as the combination therapy used in this study for the treatment of hospitalized gynecological infections.

In vitro synergistic activities of aminoglycosides and new beta-lactams against multiresistant Pseudomonas aeruginosa.

The in vitro interactions between amikacin, netilmicin, tobramycin, gentamicin, and various antipseudomonal beta-lactams were studied by the agar dilution checkerboard technique against 30 Pseudomonas aeruginosa strains resistant to all tested antibiotics. Amikacin produced more frequent synergy both at the total and clinically applicable level. Among the beta-lactams, clinically relevant synergistic interactions were obtained in the following order: ceftazidime and ceftriaxone greater than moxalactam greater than aztreonam greater than cefotaxime greater than azlocillin greater than cefoperazone greater than cefsulodin greater than carbenicillin.

Ketoconazole compared with griseofulvin in dermatophytoses: a randomized, double-blind trial.

50 patients with drug-resistant and/or extensive superficial mycoses and positive cultures for dermatophytes, were randomly assigned to treatment either with 200 mg ketoconazole (26 patients, mean age 31 years) or 500 mg griseofulvin (24 patients, mean age 32.5 years) daily, administered in identical capsules. Patients were evaluated before and during treatment, clinically, by direct microscopy and cultures in double-blind conditions. The maximum duration of treatment was 6 weeks. 26/26 patients in the ketoconazole group and 22/24 patients in the griseofulvin group had negative cultures after 2.5 and 3 weeks (median values) respectively. Clinical symptoms responded rapidly and completely to both treatments. Therapeutic results were statistically significant in both groups. 1 patient in each group relapsed during the next 3 months after the end of the treatment. No unwanted effects were reported. Although both treatments were effective, therapeutic results were slightly better and appeared earlier with ketoconazole.

Once weekly administration of levamisole in rheumatoid arthritis.

The therapeutic as well as the unwanted effects, in rheumatoid arthritis patients, of once weekly administration of 150 mg levamisole were compared, under double-blind conditions, with 3 50-mg daily doses of levamisole for 3 consecutive days weekly and placebo. The applied minimization method was used to assign patients to treatment groups so that all groups were comparable at the start of the trial. All patients were evaluated monthly, for 26 weeks. Three patients on the levamisole 3-day-weekly dosage interrupted their treatment because of side-effects. Except for the unwanted effects, the differences in the therapeutic efficacy in the 2 levamisole groups were not statistically significant. Twenty-one patients (3 in the levamisole once weekly administration group and 18 in the placebo group) interrupted their treatment because of inefficacy. Placebo was statistically less effective than the active drug. It is concluded that once weekly is as effective as 3-day-weekly administration of levamisole, but has fewer side-effects.

Double-blind evaluation of miconazole tampons, compared with clotrimazole vaginal tablets, in vaginal candidiasis.

Fifty-one patients with vaginal candidiasis and positive cultures in Nickerson medium were treated either with two miconazole tampons daily for five days (26 patients, median age 28 years) or with one clotrimazole vaginal tablet daily for six days (25 patients, median age 36 years) in a randomized double-blind trial. Seven days after the end of the treatment, 24 (92%) patients in the miconazole group and 19 (76%) in the clotrimazole group had negative cultures. One month after the end of the treatment, the relapse rate was significantly (P less than 0.05) higher in the clotrimazole group. Symptoms subsided rapidly in both groups. No unwanted effects were reported.

Double-blind evaluation of domperidone in acute vomiting and dyspeptic disorders.

The anti-emetic effects of domperidone were evaluated under double-blind conditions in twenty-four patients with acute vomiting randomly assigned to treatment either with 10 mg i.m. domperidone (six female, five males) or with placebo (seven females, six males). The therapeutic results were better with domperidone and the differences from placebo were statistically significant (p less than 0.02). In a second randomized, crossover, double-blind trial, domperidone (10 mg t.i.d.) evaluated according to a nine-symptom rating scale, in eighteen dyspeptic patients, proved significantly more effective than placebo. The duration of treatment was 6 weeks and the drugs were crossed-over after 3 weeks. The difference between the two groups was most marked during the second phase of the trial. No side-effects were reported.

Mobilization of refractory chronic schizophrenics with haloperidol.

Adequate high doses of haloperidol have been administered to 24 chronic, refractory to standard antipsychotic treatment, schizophrenics (16 male, 8 female, mean age 32.9 years) to investigate the possibility of mobilizing and releasing these patients from the hospital. Treatment was started with 20 mg haloperidol and optimal doses were determined for each patient. The median daily optimal dose at the end of the trial was 100mg. All patients were followed up for 16 weeks. Evaluating criteria were the BPRS, the Discharge Readiness Questionnaire, a side-effect rating scale, a CGI scale and the number of patients able to leave the hospital. 3 patients were evaluated as able to leave the hospital. 87.4% of the patients were subjectively evaluated as improved. High doses of haloperidol did not correlate with a higher incidence of unwanted effects. On the contrary antiparkinson treatment was discontinued or decreased in 14 patients. It is concluded that nonresponsive chronic schizophrenics can profit from adequate high doses of haloperidol.

Double-blind therapeutic evaluation of fluspirilene compared with fluphenazine decanoate in chronic schizophrenics.

Fifty chronic schizophrenics were randomly assigned to a 16-week treatment either with fluspirilene or with fluphenazine decanoate. The aim of the study was to compare the antipsychotic action and the side effects of the two neuroleptics. Fluphenazine decanoate caused more side effects and the difference between the two groups was statistically significant in the items tremor, severe extrapyramidal effects and parkinsonism. More patients in the fluspirilene group (nine patients) compared with only three in the fluphenazine decanoate group remained free of side effects during the whole trial. Judged from the BPRS fluspirilene proved an equally potent neuroleptic with fluphenazine decanoate although statistically significant improvement has been obtained in more items of the scale in the fluspirilene group. The improvement in the NOSIE-30 was much more clear in the fluspirilene group. Although Clinical Global Impressions of the investigators and the nursing personnel favored fluspirilene, the differences between the two groups were not statistically significant.