Trials and errors.
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Clinical Trials as Topic↗
Biomedical subjects
P Knipschild
Publications and source records attributed to P Knipschild.
Searching for alternatives: loser pays.
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Clinical Trials as Topic↗
Oral contraceptive use and the occurrence of gallstone disease--a case-control study.
BACKGROUND: We evaluated the hypothesized transient effect of oral contraceptive use on the occurrence of gallstone disease in a case-control study. METHODS: The study comprised 82 acute cases, and 249 general population controls, 28 elective cases, and 106 radiodiagnosis controls. Risk-period-specific rate ratios were estimated by logistic regression analysis. RESULTS: During the first 5 years after any year of oral contraceptive use (0- to 5-year risk period) the rate ratio was 1.6 (90% confidence interval, 0.83-2.95), and for the 6- to 10- and 11- to 20-year risk periods, 1.2 (0.67-2.13) and 1.1 (0.69-1.65), respectively. Further evaluation showed substantial confounding by other risk factors. After these were controlled for, the rate ratios were 1.1, 1.8, and 1.0 for the respective risk periods. When oral contraceptive use had been started recently (within 5 years before diagnosis) the rate ratio was 4.8 (0.79-29.7); recent oral contraceptive use was not associated with gallstone disease if preceded by 6 or more years of oral contraceptive use (rate ratio 0.8 (0.15-4.55)). CONCLUSIONS: The results are consistent with a transient effect of oral contraceptive use that does not accumulate beyond 10 years of use. However, the substantial confounding effect in our study raises the question whether the present and previously reported estimates of the effect may be biased by confounding.
Adult↗
Control of confounding requires specification of risk periods.
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Case-Control Studies↗
Oral contraceptives and the risk of gallbladder disease: a meta-analysis.
OBJECTIVES: This study was designed to assess the risk of gallbladder disease due to oral contraceptive use by conducting a thorough literature review. METHODS: Controlled epidemiologic studies published through March 1992 were systematically searched and evaluated. Of 25 studies (27 publications), 9 could stand the test of critical appraisal with respect to validity. Restriction to these studies was judged to circumvent publication bias at the same time. RESULTS: Oral contraceptive use is associated with a slightly and transiently increased rate of gallbladder disease. The results of six selected studies in which asymptomatic women were screened for gallstones were strikingly similar. Pooling of these results yielded an odds ratio, for ever vs never oral contraceptive use, of 1.36. A dose-effect relationship was indicated, suggesting that modern low-dose oral contraceptives are safer than older formulas, but an effect cannot be excluded. CONCLUSIONS: Considering the large efforts already devoted to this exposure-disease relationship, the probably weak effect, and the rapidly changing formulas of oral contraceptives, the authors suggest that the safety of new oral contraceptives be evaluated by studying bile saturation and biliary function rather than by waiting for gallbladder disease to develop.
Adolescent↗
The comprehensiveness of Medline and Embase computer searches. Searches for controlled trials of homoeopathy, ascorbic acid for common cold and ginkgo biloba for cerebral insufficiency and intermittent claudication.
OBJECTIVE: To assess the comprehensiveness of Medline and Embase computer searches for controlled trials. DESIGN: Comparison of articles found after an exhaustive search of the literature with the yield of a Medline or Embase search. This was performed for controlled clinical trials on the efficacy of three interventions: homoeopathy, ascorbic acid for common cold, and ginkgo biloba for intermittent claudication and cerebral insufficiency. The number of controlled trials found by exhaustive search of the literature was 107, 61 and 45, respectively. RESULTS: For homoeopathy, ascorbic acid and ginkgo the proportion of all trials found by Medline was 17%, 36% and 31% respectively and for Embase 13%, 25% and 58% respectively. After checking of the references in the Medline articles 44%, 79% and 76% of all trials were identified. After checking of the references in the Embase articles 42%, 72% and 93% of all trials were identified. About 20% of the articles was not correctly indexed. Of the best trials 68%, 91% and 83% could be found with Medline and 55%, 82% and 92% of the best trials were identified through Embase. CONCLUSIONS: For the topics mentioned, Medline and Embase searches are sufficient to get an impression of the evidence from controlled trials, but only if references in the articles are followed for further evidence. If one wants to get a more complete picture, additional search strategies make sense. Of course, this picture may be different for other topics.
Abstracting and Indexing↗
Is gallstone disease caused by obesity or by dieting?
The effects of dieting and obesity on the risk of acute gallstone disease were evaluated in a case-control study in Maastricht, The Netherlands, during 1983-1986. The study comprised 151 cases with acutely symptomatic gallstone disease and 451 population controls. The effects of dieting and obesity as measured by body mass index (weight (kg)/height (m)2) were disentangled in a multivariate logistic regression analysis. Both dieting and body mass index were positively associated with the rate of gallstone disease. The association with dieting largely disappeared when initial body mass index was controlled for (rate ratio = 1.4, 95% confidence interval 0.8-2.4). Conversely, controlling for dieting did not affect the association between body mass index and gallstone disease. Analysis by risk period (year 1 and 2-5, 6-10, and 11-15 years prior to interview) did not show consistent risk period-specific effects when initial body mass index was controlled for. The authors conclude that dieting does not account for the association between obesity and gallstone disease. In obese persons, dieting does not increase the risk of acute gallstone disease over the long term.
Adult↗
Ginkgo biloba for cerebral insufficiency.
1. By means of a critical review we tried to establish whether there is evidence from controlled trials in humans on the efficacy of Ginkgo biloba extracts in cerebral insufficiency. 2. The methodological quality of 40 trials on Ginkgo and cerebral insufficiency was assessed using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. A comparison of the quality was made with trials of co-dergocrine, which is registered for the same indication. 3. There were eight well performed trials out of a total of 40. Shortcomings were limited numbers of patients included, and incomplete description of randomization procedures, patient characteristics, effect measurement and data presentation. In no trial was double-blindness checked. Virtually all trials reported positive results, in most trials the dosage was 120 mg Ginkgo extract a day, given for at least 4-6 weeks. For the best trials, there were no marked differences in the quality of the evidence of the efficacy of Ginkgo in cerebral insufficiency compared with co-dergocrine. The results of the review may be complicated by a combination of publication bias and other biases, because there were no negative results reported in many trials of low methodological quality. 4. Positive results have been reported for Ginkgo biloba extracts in the treatment of cerebral insufficiency. The clinical evidence is similar to that of a registered product which is prescribed for the same indication. However, further studies should be conducted for a more detailed assessment of the efficacy.
Cerebrovascular Disorders↗
Health-care professionals' views of the effectiveness of pressure ulcer treatments. A survey among nursing-home physicians, dermatologists and nursing staff in The Netherlands.
In a survey, 237 nursing-home physicians, 113 dermatologists, and 164 supervisory nurses in nursing homes rated 30 treatments for stage III pressure ulcers by scoring their effectiveness. On average, there seems to be a fair degree of consensus between these groups of health-care workers about the effectiveness of most treatments. The most notable exceptions are ultraviolet light, ultrasound, and laser therapy and myocutaneous flap operations. Here, the dermatologists disagree with both nursing-home physicians and nurses. However, within all specialties there is disagreement about the efficacy of ultraviolet light, ultrasound, and laser therapy and the topical application of zinc oxide, betadine iodine, sodium hypochlorite and a few others.
Attitude of Health Personnel↗
Review articles and publication bias.
Publication bias occurs if the results from studies which have not been published are different from the published ones. From a Bayesian viewpoint, it also concerns non-publication of studies with similar results as the published ones because the strength of the evidence will be influenced. Publication bias complicates the interpretation of reviews and meta-analyses. If favourable results are published more often there will be an overestimation of the effects of a treatment. There have been several attempts to assess the magnitude of publication bias. Unpublished trials could be identified by means of a survey among researchers, and the results could subsequently be compared with the outcomes of published trials. Also, the results from published trials could be compared with trials from a registry. Furthermore, the results from registered but unpublished trials could be compared with those of registered and subsequently published trials. Studies addressing publication bias have shown that it is a serious problem which complicates the interpretation of reviews. In assessments of publication bias other factors must be taken into account. These include the mode of publication: refereed journals, other journals, books, etc. Differences could also be related to the quality of trials. Finally, the source of funding may influence both the results and subsequent publication. Publication bias can only be avoided by registration of all trials before data collection is started; several of such registries have already been installed. Perhaps, if more of such registries exist, reviewers could only use registered trials for their main conclusions. All other information could then be considered sensitive to publication bias.
Meta-Analysis as Topic↗
Physiotherapy exercises and back pain.
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Back Pain↗
Pregnancy and gallstone disease: an empiric demonstration of the importance of specification of risk periods.
This paper discusses the importance of specification of risk periods in research of the effect of pregnancy on the occurrence of gallstone disease. The authors present data from a case-control study, started in 1983 in Maastricht, The Netherlands. The study comprised 100 acute gallstone cases and 305 general population controls and 41 elective cases and 122 elective radiodiagnosis controls. In a conventional analysis, the rate ratio for one or more pregnancies ever (vs. never) was 1.2 (90% confidence interval 1.02-1.36). In an analysis that discerned several subsequent risk periods, an effect was found only for the risk period up to 5 years after pregnancy (rate ratio, 2.4; 90% confidence interval 1.12-4.96). Beyond this risk period no effect was noted. The results suggest that pregnancy increases the rate of gallstone formation only transiently. Six reasons for specifying risk periods in nonexperimental etiologic studies are discussed. The authors contend that ignoring of risk periods explains part of the variation in the findings of earlier studies on pregnancy and the risk of gallstone disease.
Adult↗
Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans.
Fifty-three controlled trials of the effects of niacin, vitamin B6, and multivitamins on mental functions are reviewed. The results are interpreted with emphasis on the methodological quality of the trials. It turns out that virtually all trials show serious short-comings: in the number of participants, the presentation of baseline characteristics and outcomes, and the description of changes in concomitant treatments. Only in autistic children are some positive results are found with very high dosages of vitamin B6 combined with magnesium, but further evidence is needed before more definitive conclusions can be drawn. For many other indications (hyperactive children, children with Down's syndrome, IQ changes in healthy schoolchildren, schizophrenia, psychological functions in healthy adults and geriatric patients) there is no adequate support from controlled trials in favor of vitamin supplementation.
Adult↗
Trials of homeopathy.
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Clinical Trials as Topic↗
Clinical trials of homoeopathy.
OBJECTIVE: To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN: Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING: Controlled trials published world wide. MAIN OUTCOME MEASURES: Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS: In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS: At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials.
Clinical Trials as Topic↗
Does alcohol protect against the formation of gallstones? A demonstration of protopathic bias.
Previous studies have found an inverse relation between alcohol use and clinical gallstone disease, suggestive of a protective effect of alcohol use. However, such an inverse relation may (at least partly) be explained by a reduction of alcohol use because of symptoms related to clinical gallstone disease (protopathic bias). We empirically evaluated the consequences of different designs for the avoidance of such bias in a series of case-control studies. A first study deliberately used a design that is commonly seen in the literature. Cases of clinical gallstone disease, referred to hospital because of symptoms, were contrasted with general population controls. The results suggested an inverse relation between alcohol use and gallstones. Next, three alternative case-control studies were performed using designs that safeguard against protopathic bias. In none of these studies was an association between alcohol use and gallstones found. This demonstrates the probable existence of protopathic bias in case-control studies on alcohol use and gallstones. It is argued that earlier non-experimental studies on this topic were susceptible to such bias. This has most likely led to an overestimation of the protective effect.
Adult↗
The qualification period.
For randomized trials that do not require prompt onset of therapy, a pre-admission preparation, called the qualification period, can deal with certain customary difficulties in design, analysis, and ethics. For the patients' baseline state, the qualification period can be used to "wash out" effects of previous treatment, to verify admission criteria, and to identify or stratify suitable prognostic indicators. For treatment, the qualification period can be used to test and adjust therapeutic dosages, to exclude placebo responders, and to confirm early responsiveness to long-term active therapy. For intention-to-treat analyses, the qualification period can allow special stratifications for patients who are therapeutically difficult to regulate or who comply imperfectly. By offering the cited improvements as well as a brief "pilot exposure" for each patient, the qualification period can also enhance the "informed consent" and general ethics of a trial.
Clinical Trials as Topic↗