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Chemotherapy of advanced breast cancer: a randomized trial of vincristine, Adriamycin, and cyclophosphamide (VAC) versus cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP).

Fifty-one patients with metastatic breast cancer were randomly allocated to receive either a four drug combination consisting of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP), or a combination of vincristine, Adriamycin, and cyclophosphamide (VAC) with cross-over on relapse. Objective responses were seen in 17 of 26 patients (65%) in the CMFP group and in 14 of 25 patients (56%) in the VAC group, but this difference was not statistically significant. The median duration of response for each group was one year. The estimated median survival was greater for the CMFP group, but this was not significant. Toxicity was more severe with the VAC regimen. It is concluded that there is no therapeutic advantage of the VAC over the CMFP regimen.

Adult↗

Pharmacokinetic comparison of two carbamazepine slow-release formulations.

In a single-blind pharmacokinetic study patients being treated with conventional carbamazepine (CBZ) in a t.i.d. regimen were randomly allocated to identical doses of two CBZ slow-release formulations (Trimonil Retard and Tegretol Retard) administered once daily. Statistical analysis involved the following parameters: AUC, Cmin, Cmax and Fluctuation Index (FI). With regard to Cmin and FI statistically significant differences in favour of Tegretol Retard were observed.

Administration, Oral↗

Single-dose versus six-day therapy with sulfamethizole for asymptomatic bacteriuria during pregnancy. A prospective randomised study.

Single-dose versus conventional six-day therapy with sulfamethizole for asymptomatic urinary tract infection in pregnant women was investigated in a prospective, randomised open study. During a nine-month period 4,274 pregnant women were screened for significant bacteriuria, which was found in 123 (2.9%), of whom only five had symptoms of urinary tract infection. Seventy-nine of the patients had a second urine culture performed, revealing significant counts of the same bacteria in only 41. These 41 patients were randomly allocated to one of the two treatment groups. Control urine cultures one week and 4-6 weeks after start of treatment revealed the same cure rates of approximately 50% in both groups. Single-dose treatment is not inferior to conventional therapy; future study is needed to find the best single-dose regimen.

Bacteriuria↗

A comparison of two types of vacuum drainage after cholecystectomy.

Following cholecystectomy, 50 patients were randomly allocated for suction drainage by small (2.5 mm) Redivac or large calibre (6 mm) Redivac drains. There were 25 patients in each group. Subhepatic collection was detected by ultrasonic examination in 5 patients on the seventh postoperative day. The smaller drain was used in all of these patients. Of these 5 patients, one developed pulmonary infection, a second had internal bleeding requiring laparotomy, while the remaining 3 were asymptomatic. Subhepatic fluid was not detected in any patient who had the larger drain.

Adult↗

Alprazolam and amitriptyline in the treatment of major depressive disorder: a double-blind clinical and sleep EEG study.

This study was designed to compare the antidepressant effects of alprazolam and amitriptyline in a group of 30 inpatients suffering from a severe major endogenous depression, diagnosed by Research Diagnostic Criteria and the Newcastle Rating scale, and to examine the effects of alprazolam and amitriptyline on two biological markers of depression, the dexamethasone suppression test and sleep EEG parameters. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with flexible doses of 4-9 mg of alprazolam and 100-225 mg of amitriptyline. After 4 weeks of treatment the antidepressant effects of amitriptyline significantly exceeded those of alprazolam, as measured on the Hamilton Rating Scale for Depression. There was a high drop-out rate in the alprazolam group because of ineffectiveness of treatment. Alprazolam showed similar effects on sleep parameters as amitriptyline: lengthening of the REM latency and a tendency to shorten stages 3 and 4 and stage REM. These negative clinical results should be interpreted with caution, because of the severity of our selection criteria, and should not be extended to all depressive disorders.

Adult↗

Medium-dose antacids versus cimetidine in the short-term treatment of duodenal ulcer.

Seventy-eight patients with endoscopically proven duodenal ulcer were randomly allocated to be treated with a medium dose of liquid aluminum-magnesium antacid (75 ml in five daily doses) or cimetidine (400 mg twice daily) for 4 weeks in a prospective double-blind, double-dummy study. Healing rates at completion of trial were 66.7% in the cimetidine-treated group and 71.8% in the antacid group (p, ns). Both treatments were equally effective in relieving ulcer symptoms. Among the patient variables considered, only cigarette smoking was found to have a significant negative effect on ulcer healing. These results indicate that medium doses of antacids are as effective as cimetidine in the short-term treatment of duodenal ulcer.

Adult↗

Controlled trial of hypnotherapy in the treatment of severe refractory irritable-bowel syndrome.

30 patients with severe refractory irritable-bowel syndrome were randomly allocated to treatment with either hypnotherapy or psychotherapy and placebo. The psychotherapy patients showed a small but significant improvement in abdominal pain, abdominal distension, and general well-being but not in bowel habit. The hypnotherapy patients showed a dramatic improvement in all features, the difference between the two groups being highly significant. In the hypnotherapy group no relapses were recorded during the 3-month follow-up period, and no substitution symptoms were observed.

Acute Disease↗

Terfenadine once daily in chronic urticaria. A multi-centre double-blind comparison of terfenadine once daily versus twice daily.

The objective of these three double-blind multi-centre studies was to determine whether terfenadine 120 mg once daily has similar efficacy and tolerability as the standard dosage of 60 mg twice daily in the treatment of chronic urticaria. A total of 252 patients were randomly allocated to two parallel groups and treated for 2 weeks with either regimen. Evaluation of efficacy was based on rating scales for investigator and patient, i.e. itch, number of wheals, wheal size and an overall rating of efficacy. A similar improvement was seen in all variables, and there were no statistically significant differences between treatment groups. The power of the studies combined is greater than 80%, i.e. sufficient to state convincingly that treatment effects are not different. Both treatments were also equally well tolerated.

Adult↗

Polyglycolic acid and catgut sutures, with and without oral proteolytic enzymes, in the healing of episiotomies.

Polyglycolic acid (PGA) sutures and traditional catgut were compared in 190 patients undergoing episiotomy. Each group was also randomly allocated to a double blind comparison of therapy with oral proteolytic enzymes (Chymoral) and placebo. The combination of Chymoral and polyglycolic acid sutures was shown to reduce the level of pain, assessed subjectively, and there was a significant reduction in analgesic requirements in the Chymoral/PGA group.

Anti-Inflammatory Agents↗

The efficacy of electroconvulsive therapy in the treatment of schizophrenia. A comparative study.

The efficacy of ECT was investigated in a double-blind trial. Twenty-two patients with schizophrenia received trifluoperazine and were randomly allocated to receive eight real or eight simulated ECTs. In the first eight weeks, the group receiving real ECTs showed significantly more improvement as measured on the Brief Psychiatric Rating Scale. However, the groups showed no significant differences from the twelfth week onwards. The superiority of real ECT was not confirmed at the end of six months.

Clinical Trials as Topic↗

Randomised double-blind placebo-controlled trial of feverfew in migraine prevention.

The use of feverfew (Tanacetum parthenium) for migraine prophylaxis was assessed in a randomised, double-blind, placebo-controlled crossover study. After a one-month single-blind placebo run-in, 72 volunteers were randomly allocated to receive either one capsule of dried feverfew leaves a day or matching placebo for four months and then transferred to the other treatment limb for a further four months. Frequency and severity of attacks were determined from diary cards which were issued every two months; efficacy of each treatment was also assessed by visual analogue scores. 60 patients completed the study and full information was available in 59. Treatment with feverfew was associated with a reduction in the mean number and severity of attacks in each two-month period, and in the degree of vomiting; duration of individual attacks was unaltered. Visual analogue scores also indicated a significant improvement with feverfew. There were no serious side-effects.

Adult↗

Double-blind comparison of two dosage regimens of misoprostol in the treatment of duodenal ulceration.

A multicenter double-blind study was conducted in 416 patients (306 male, 110 female) with active endoscopically proven duodenal ulcers who were randomly allocated to receive the prostaglandin E1 methyl ester analog (Misoprostol/Cytotec), either in a dose of 400 micrograms twice daily (206 patients) or 200 micrograms four times daily (210 patients). No significant difference in the healing rates between the two groups was observed at four or eight weeks. In patients treated twice daily, the ulcer healing rate at four weeks for the intent-to-treat cohort was 124/205 (60.5%) and for the evaluable cohort was 96/136 (69.1%). In patients treated four times daily, the healing rate was 124/207 (59.9%) for the intent-to-treat cohort and 96/148 (64.9%) for the evaluable cohort. Similarly, the healing rates achieved at eight weeks for the twice- and the four-times-daily dosages in the intent-to-treat cohort were 72.2% and 74.4%, respectively, and for the evaluable cohort were 88.0% and 86.6%, respectively. Significantly more patients receiving misoprostol twice daily were free of ulcer pain after four weeks of treatment than were those receiving misoprostol four times daily, namely, 71.4% as compared with 57.9%, respectively (P = 0.003) and for a median period of 21 as compared with 17 days (P = 0.002). Diarrhea was more common in patients receiving the drug twice daily, (15.5%) than in those treated four times daily (5%) (P = 0.001). Diarrhea, three or more stools daily, was often transient and self-limiting and only necessitated withdrawal from the trial in nine (4.4%) of those treated with misoprostol twice daily and in one patient (0.5%) of those treated four times daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

A randomised controlled trial of the effect of the provision of free school milk on the growth of children.

A randomised controlled study was carried out of the effect on growth of the provision of free milk supplements to schoolchildren aged 7 and 8. In selecting children for this study, the aim was to identify those whose socioeconomic circumstances might place them at a disadvantage for growth. Five hundred and eighty-one-children were selected from schools where a high proportion of the pupils received free school meals, and from families with four or more children. The subjects were randomly allocated to receive a third of a pint (190 ml) of free milk daily for six school terms or to a control group. The mean difference in height gain at the end of twenty-one-and-a-half months was 3% or 2.93 mm (P less than 0.05) in favour of the children provided with free milk. The mean difference in weight gain was 130 g (P greater than 0.05) in their favour. The height and weight gain associated with the provision of free mild was very small in the study population, and it is therefore likely that the benefit to growth of providing free milk for the whole unselected population of schoolchildren of these ages would be even smaller.

Animals↗

Termination of second-trimester pregnancy by laminaria and intramuscular injections of 15-methyl PGF2 alpha or 16-phenoxy-omega-17,18,19, 20-tetranor PGE2 methyl sulfonylamide. A randomized study.

The present study included 120 second-trimester patients admitted to the hospital for termination of pregnancy. In all patients, one medium-size laminaria tent was introduced into the cervical canal. The laminaria was withdrawn 12 hours later and the patients randomly allocated to either i.m. injection of 15-methyl PGF2 alpha, 0.25 mg every second hour, or 16-phenoxy-omega-17,18,19,20-tetranor PGE2 methyl sulfonyl-amide, 0.5 mg every fourth hour. Both treatment schedules were equally effective. All patients but 2 (98.3%), one in each group, aborted within 24 hours of prostaglandin treatment. Both methods seem far more effective than other methods at present in use for termination of second-trimester pregnancy. With the E analogue, the frequency of gastro-intestinal side effects was significantly lower than with the F analogue and not more common than following hypertonic saline. The use of laminaria tent was normally uneventful and seemed to reduce the risk of cervical laceration significantly.

Abortion, Induced↗

Comparative study of alginate and non-alginate antacids concurrently administered with H2 antagonists in cases of duodenal ulcer.

In an open comparative study in endoscopically proven cases of duodenal ulcer, concomitant therapy of H2 antagonist was initiated in two randomly allocated, homogenous patient groups, ie, H2 A + RF alginate antacid (Riflux Forte, Sol Pharmaceuticals Ltd) or H2 A + S non-alginate antacid (Siloxogene, Searle Ltd), both Riflux Forte and Siloxogene having similar compositions of antacids. Overall clinical assessment, percentage improvement, assessment of individual clinical symptoms, global assessment and endoscopic assessment all showed that Riflux Forte and Siloxogene together with H2 antagonist are significantly effective in providing a progressive symptomatic relief in duodenal ulcer cases over an evaluable period of eight weeks. Although differences between Riflux Forte and Siloxogene were not statistically significant, a definite trend of more rapid and favourable responses was seen with Riflux Forte, demonstrating the role played by therapy in preventing reflux and stopping the acid pain cycle.

Adolescent↗

Comparative treatment trial of augmentin versus cefaclor for acute otitis media with effusion.

A total of 150 children with acute otitis media were randomly allocated to treatment with amoxicillin-potassium clavulanate (Augmentin) or with cefaclor. Each drug was given in a daily dosage of approximately 40 mg/kg in three divided doses for ten days. Tympanocentesis done before treatment yielded specimens that contained pneumococcus or Haemophilus sp or both in 67% of specimens. Viridans group streptococci were isolated from 10% of specimens and Branhamella catarrhalis from 6%. Patients were scheduled for follow-up examinations at midtreatment, end of therapy, and at 30, 60, and 90 days. Of the 150 children, 130 were evaluable. Five of 60 patients (8%) treated with cefaclor were considered therapeutic failures because of persistent purulent drainage and isolation of the original pathogen or suprainfection. There were no failures among patients treated with Augmentin (P = .019). Rates of relapse, recurrent acute otitis media with effusion, and persistent middle ear effusion were comparable in the two groups of patients. Diaper rash, or loose stools, or both were significantly more common in children treated with Augmentin (34%) than in those taking cefaclor (12%), but in no case was it necessary to discontinue medication because of these mild side effects (P = .002). Cefaclor therapy was discontinued in one patient because of severe abdominal pain and vomiting. In this study, treatment with Augmentin was superior to treatment with cefaclor in the acute phase of acute otitis media with effusion, but Augmentin produced more adverse effects. The rates of persistent middle ear effusion and recurrent acute otitis media with effusion were comparable with the two regimens.

Acute Disease↗

Immune response to hepatitis B vaccine given at different injection sites and by different routes: a controlled randomized study.

Two-hundred-ninety-nine hospital workers were randomly allocated to receive MSD hepatitis B vaccine in different injection sites and by different routes (intramuscularly by gluteal or deltoid injections or subcutaneously in the arm) or Pasteur vaccine subcutaneously. Highest rates of seroconversion and highest mean anti-HB, titres were found in subjects given MSD vaccine by intramuscular injection into the deltoid muscle.

Adult↗

Infant feeding and allergy.

The effect of withholding cows' milk was examined in 487 infants at high risk of allergic disease. Before birth they were randomly allocated either to a control group, most of whom received cows' milk preparations, or to an intervention group, who were offered a soya based substitute. Eczema and wheezing occurred to a similar extent in the two groups during the first year of life, although napkin rash, diarrhoea, and oral thrush were commoner in the intervention group, especially during the first three months. Breast feeding for any length of time was associated with a reduced incidence of wheezing and diarrhoea.

Animals↗