Showing papers by "Peter C Gøtzsche published in 1998"

House dust mite control measures in the management of asthma: meta-analysis

Abstract: Objective To determine whether patients with asthma who are sensitive to mites benefit from measures designed to reduce their exposure to house dust mite antigen in the home. Design Meta-analysis of randomised trials that investigated the effects on asthma patients of chemical or physical measures to control mites, or both, in comparison with an untreated control group. All trials in any language were eligible for inclusion. Subjects Patients with bronchial asthma as diagnosed by a doctor and sensitisation to mites as determined by skin prick testing, bronchial provocation testing, or serum assays for specific IgE antibodies. Main outcome measures Number of patients whose allergic symptoms improved, improvement in asthma symptoms, improvement in peak expiratory flow rate. Outcomes measured on different scales were combined using the standardised effect size method (the difference in effect was divided by the standard deviation of the measurements). Results 23 studies were included in the meta-analysis; 6 studies used chemical methods to reduce exposure to mites, 13 used physical methods, and 4 used a combination. Altogether, 41/113 patients exposed to treatment interventions improved compared with 38/117 in the control groups (odds ratio 1.20, 95% confidence interval 0.66 to 2.18). The standardised mean difference for improvement in asthma symptoms was −0.06 (95% confidence interval −0.54 to 0.41). For peak flow rate measured in the morning the standardised mean difference was −0.03 (−0.25 to 0.19). As measured in the original units this difference between the treatment and the control group corresponds to −3 l/min (95% confidence interval −25 l/min to 19 l/min). The results were similar in the subgroups of trials that reported successful reduction in exposure to mites or had long follow up times. Conclusion Current chemical and physical methods aimed at reducing exposure to allergens from house dust mites seem to be ineffective and cannot be recommended as prophylactic treatment for asthma patients sensitive to mites.

Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis

Abstract: Objective: To determine whether short term, oral low dose prednisolone (⩽15 mg daily) is superior to placebo and non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis. Design: Meta-analysis of randomised trials of oral corticosteroids compared with placebo or a non-steroidal anti-inflammatory drug. Setting: Trials conducted anywhere in the world. Subjects: Patients with rheumatoid arthritis. Main outcome measures: Joint tenderness, pain, and grip strength. Outcomes measured on different scales were combined by using the standardised effect size (difference in effect divided by SD of the measurements). Results: Ten studies were included in the meta-analysis. Prednisolone had a marked effect over placebo on joint tenderness (standardised effect size 1.31; 95% confidence interval 0.78 to 1.83), pain (1.75; 0.87 to 2.64), and grip strength (0.41; 0.13 to 0.69). Measured in the original units the differences were 12 (6 to 18) tender joints and 22 mm Hg (5 mm Hg to 40 mm Hg) for grip strength. Prednisolone also had a greater effect than non-steroidal anti-inflammatory drugs on joint tenderness (0.63; 0.11 to 1.16) and pain (1.25; 0.26 to 2.24), whereas the difference in grip strength was not significant (0.31; −0.02 to 0.64). Measured in the original units the differences were 9 (5 to 12) tender joints and 12 mm Hg (−6 mm Hg to 31 mm Hg). The risk of adverse effects during moderate and long term use seemed acceptable. Conclusion: Prednisolone in low doses (⩽15 mg daily) may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means. Key messages Prednisolone in low doses—that is, no more than 15 mg daily—is highly effective in patients with rheumatoid arthritis The risk of adverse effects is acceptable in short, moderate, or long term use Oral low dose prednisolone may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means Further short term placebo controlled trials to study the clinical effect of prednisolone or other oral corticosteroids are no longer necessary

The controlled clinical trial turns 100 years: Fibiger's trial of serum treatment of diphtheria

Abstract: The British Medical Research Council's trial of streptomycin for pulmonary tuberculosis, published in 1948,1 has been proposed as the first randomised trial in which random numbers were used and allocation of patients was effectively concealed. Before 1948 several randomised trials had been reported,2 but the method of randomisation was either not stated3 or was open to selection bias—for example, randomisation with use of a deck of cards.4 The earliest of these trials was published in 1898.5 It investigated the effect of serum treatment on diphtheria and was conducted by the Danish Nobel laureate, Johannes Fibiger. It was the first clinical trial in which random allocation was used and emphasised as a pivotal methodological principle. This pioneering improvement in methodology, combined with a large number of patients and rigorous planning, conduct, and reporting, makes the trial a milestone in the history of clinical trials. Fibiger's trial was published in Danish and its method of randomisation has often been quoted incorrectly. We have translated central passages into English (available on the BMJ website at www.bmj.com) and discussed its methodological merit. ### Summary points A large randomised clinical trial was performed as early as 1898 Random allocation was emphasised as a central methodological principle Patients were allocated to serum or no serum according to day of admittance, which created two comparable groups The planning, conduct, and reporting of the trial was of high quality The efficacy of serum treatment on diphtheria was shown The trial was the first properly conducted controlled clinical trial Johannes A G Fibiger (1867-1928) was born in Silkeborg, Denmark (figure). After receiving his medical degree in 1890 from the University of Copenhagen he visited Robert Koch and Emil von Behring in Germany. In 1895 Fibiger was awarded a doctoral degree for a thesis on diphtheria from the …

The sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson's disease: A meta-analysis

Abstract: The association between the sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of Parkinson's disease was examined in a meta-analysis of case-control studies. The odds ratio was calculated for the risk of Parkinson's disease among poor metabolisers compared with extensive metabolisers. Twenty-one studies were identified of which six were excluded because they were not reported as full papers (n = 3), used incomplete genotype analysis (n = 2) or used Parkinson patients as both control individuals and cases (n = 1). The overall odds ratio was 1.48 (95% confidence interval 1.10-1.99). The odds ratio was 1.05 (95% confidence interval 0.63-1.77) in studies discriminating extensive and poor metabolisers by phenotyping (n = 8) and 1.67 (95% confidence interval 1.11-2.50) in studies using genotyping (n = 7). This difference was caused by a single large study using genotyping. We conclude that there is no convincing evidence of an association between the debrisoquine/sparteine polymorphism and Parkinson's disease. However, it could prove worthwhile to perform another large study using genotyping.

Neuropsychiatric manifestations after mefloquine therapy for Plasmodium falciparum malaria: comparing a retrospective and a prospective study

Abstract: Mefloquine is widely used for the treatment of patients with chloroquine-resistant Plasmodium falciparum malaria. A 1987 report of possible mefloquine-induced toxic encephalopathy prompted an investigation by the manufacturer and the World Health Organization (WHO) of adverse psychiatric events associated with use of this antimalarial. Interim guidelines were issued by WHO in 1989 and a more systematic surveillance was initiated. Subsequent studies identified neuropsychiatric side effects in 1/159-1/1217 treated individuals. The authors of this paper launched a 3-year prospective study (1990-93) of 54 malaria patients treated with mefloquine at a medical center in Copenhagen Denmark and compared its results with those of their earlier (1982-88) retrospective study of 81 malaria patients treated at the same facility. No cases of adverse neurologic or neuropsychiatric sequelae were recorded in the retrospective study which did not specifically probe about such effects. In the prospective study which did include questions on this outcome 15 patients (28%) had one or more mild or moderate neuropsychiatric complaint (e.g. hallucinations nightmares depression anxiety sleeplessness and mania). Non-neuropsychiatric adverse reactions occurred in 78 patients (96%) in the retrospective study and 44 (81%) in the prospective study. These findings point out that studies conducted under virtually the same conditions may produce discrepant results depending on what is probed.

Intermittent low dose prednisolone is safe in rheumatoid arthritis.

Abstract: EDITOR—In our meta-analysis we concluded that doses of prednisolone of ≤15 mg daily may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means.1 An accompanying editorial by Dennison and Cooper warned that doubts about the safety of this treatment remained.2 They also mentioned a number of side effects reported in a narrative review by Caldwell and Furst which we also cited in our meta-analysis (reference number 57). They complained that we had not subjected our …