Delirium tremens: a double-blind comparison of diazepam and barbital treatment. Ondansetron is not superior to moderate dose metoclopramide in the prevention of post-operative nausea and vomiting after minor gynaecological surgery. Local anaesthesia in flexible nasendoscopy. A comparison between cocaine and co-phenylcaine. Medical treatment of acute low back pain. Diflunisal compared with indomethacin in acute lumbago. Double blind study on the efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute alcohol withdrawal syndrome. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial. Double-blind comparison of intravenously injected butorphanol and meperidine in parturients.
The effect of diazepam and barbital in the treatment of delirium tremens and other acute conditions related to alcohol abuse was evaluated in a double-blind trial. 91 patients participated in the study, 44 in the diazepam group, 47 in the barbital group. The choice of diazepam rather than chlordiazepoxide was motivated by its major anticonvulsive properties. Barbital was given by the oral route, diazepam as intramuscular injections. Different ways of drug administration to patients with delirium tremens are discussed. It is concluded that the two different ways used in the study probably did not have a noteworthy influence on the results. All patients were excluded who had taken psychoactive drugs before admission. Nevertheless a considerable part of the patients had diazepam, but not barbital, in the blood before treatment was initiated. This may give support to the use of barbital as a "special purpose drug" in the treatment of these conditions. The patients were divided into three diagnostic categories, according to the severity of the clinical condition. No difference between the two drugs tested was found in the milder conditions, but barbital was found superior to diazepam in the treatment of fully developed delirium tremens. Peri-operative nausea and vomiting (PONV), remain a considerable problem. Ondansetron is being promoted currently as the drug of choice for the prevention and treatment of PONV. Experiments to investigate efficacy of ondansetron in PONV have been made with placebo or single doses of other drugs, e.g. metoclopramide, and often with different anaesthetic regimes with different emetic potential. This study investigated the relative benefits, in the prevention of PONV, of ondansetron compared with metoclopramide used at a dose higher than used in previous studies. Ninety-six patients undergoing minor gynaecological surgery were randomized to receive either ondansetron 4 mg or metoclopramide 0.4 mg kg-1. The patients were then assessed in the recovery room, in the day ward prior to discharge and the following day for the occurrence of PONV. Emetic symptoms occurred in similar proportions of patients who received ondansetron and metoclopramide. Nausea scores were similar between the groups in the recovery ward and 24-h follow-ups but there were higher post-operative nausea scores in the ondansetron group in the day ward (P = 0.001). There were no significant side effects due to either drug. We conclude that moderate dose metoclopramide is an effective alternative to ondansetron in the control of PONV. Flexible nasendoscopy is now an integral part of the diagnostic process in Otorhinolaryngology. Topical local anaesthesia is generally recommended and cocaine is usually the drug of choice in view of its concurrent vasoconstrictor action. However, it is expensive, a controlled drug and serious side effects have been reported. Co-phenylcaine forte is a new preparation which also has both local anaesthetic and vasoconstrictor properties. This study compares the efficacy of cocaine and Co-phenylcaine in flexible nasendoscopy and concludes that they provide similar local anaesthesia and vasoconstriction of the nasal mucosa. Co-phenylcaine forte can therefore be used as an alternative to cocaine in flexible nasendoscopy. Diflunisal and indomethacin were compared in patients with acute lumbago in a double-blind prospective clinical trial. The dosage of diflunisal was 500 mg twice daily (d-group) and the dosage of indomethacin 50 mg three times daily (i-group). Out of 133 patients, 66 were in the d-group and 67 in the i-group. They were followed up for a week. In addition to the patient's own daily evaluation of pain and functional disability, control visits were performed by the investigators on days 0, 3 and 7. Both of the test drugs were effective in the dosages used. Patients' pain was decreased, functional disability was improved and patients' subjective evaluation of treatment efficacy was very similar to that of the investigators. There were no differences as to the treatment efficacy, but reports of side-effects were slightly less (p less than 0.05) in the d-group than in the i-group. If patients who had no side-effects were compared, the efficacy of diflunisal was better than indomethacin (p less than 0.05). It can be said that indomethacin was essentially as effective as diflunisal, but at the expense of an increased frequency of side-effects. In the d-group two patients (3%) and in i-group six patients (9%) discontinued the therapy because of side-effects. In acute lumbago rapid relief of pain and other harmful symptoms hastens improvement. For such indications the choice of drug therapy in general practice should be based in particular on considerations of safety and lack of potential side-effects in addition to efficacy. 1. Efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute or Primary Alcohol Withdrawal Syndrome (PAWS) were assessed during a randomized double blind clinical trial, carried out on sixty male alcoholic in-patients. 2. The two drugs were administered four times a day in double dummy conditions, according to a fixed-flexible decreasing dosage schedule (six days basic regimen). 3. Drug efficacy was measured daily throughout the study period using a battery of standard instruments for collecting quantitative clinical, behavioral, psychopathological and laboratory data. Side effects were daily recorded. 4. Tetrabamate was found to be as efficient as chlordiazepoxide in reducing the intensity of the PAWS, improving sleep and vital signs rapidly and alleviating anxiety progressively. 5. Tetrabamate was found particularly beneficial for severe tremor. Psychomotor and mood scores consistently favored tetrabamate, suggesting psychoanaleptic properties of this compound (increased diurnal vigilance). 6. Side effects were minimal with tetrabamate and generally of weak intensity with chlordiazepoxide. 7. The results of this study indicate that tetrabamate may represent a new alternative drug of choice for the therapy of the acute alcohol withdrawal syndrome. Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.
                To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.
                Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication).
                Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not.
                The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events.
                Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data. Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs. One hundred women with moderate-to-very-severe prepartum pain participated in a double-blind study of intravenously injected butorphanol and meperidine that compared the analgesic properties, effect on the process of labor, condition of the newborn and the incidence of side effects associated with the two drugs. Cervical dilation, infant birth weight and Apgar scores were not significantly different between the test groups. The mean fetal heart rate for the butorphanol group was significantly faster than that of the meperidine group. Butorphanol provided significantly more analgesia than meperidine at 30 minutes and one hour after administration, based on pain intensity and pain relief scores. Some side effects, including sedation, dizziness, lightheadedness, nausea, vomiting and pain at the injection site, were reported for both drugs.
The conclusion is that the choice of drug must be made based on consideration of drug-specific side effect properties.