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A J de Craen

Publications and source records attributed to A J de Craen.

At least 19 recordsLinked to original sources
PubMed2001

Alternative medicine: a "mirror image" for scientific reasoning in conventional medicine.

A reflection on the scientific behavior of adherents of conventional medicine toward one form of alternative medicine-homeopathy-teaches us that physicians do reject seemingly solid evidence because it is not compatible with theory. Further reflection, however, shows that physicians do the same within conventional medical science: Sometimes they discard a theory because of new facts, but at other times they cling to a theory despite the facts. This essay highlights the seeming contradiction and discusses whether it still permits the building of rational medical science. We propose that rational science is compatible with physicians' behavior, provided that physicians acknowledge the subjective element in the evaluation of science, as exemplified in the crossword analogy by the philosopher Haack. This type of thinking fits very well with the Bayesian approach to decision making that has been advocated for decades in clinical medicine. It does not lead to complete and uncontrollable subjectivity because discernment between rivaling explanations is still possible through argument and counterargument.

Bayes Theorem↗
PubMed2001

Impact of experimentally-induced expectancy on the analgesic efficacy of tramadol in chronic pain patients: a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial.

Variations in treatment effects between drug trials are usually attributed to different patient characteristics, variations in outcome assessment, and random error. We have previously hypothesized that part of the variation in treatment effects between drug trials might be caused by differences in nonspecific factors. In a randomized clinical trial, we aimed to investigate whether experimentally induced expectancy can modify the analgesic effect of tramadol relative to placebo in chronic pain patients. In a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial, chronic pain patients attending a chronic pain outpatient clinic were randomized to receive a single oral dose of 50 mg tramadol or placebo, and they were further randomized to receive positive or neutral information, verbally expressed by the physician, regarding the expected analgesic effect of the drug. Pain intensity was measured using a 10 centimeter visual analogue scale at baseline, and 0.5, 1, 2, 4, 6, and 8 hours after baseline. The one-hour pain intensity difference, calculated as the sum of pain intensity differences between baseline and 0.5 and 1 hour, was taken as main outcome measure. The one-hour sum of pain intensity differences of 28 patients treated after positive expectation and randomized to tramadol was 1.4 cm, while in 27 patients randomized to placebo, it was 0.8 cm. This corresponds with an analgesic effect of tramadol relative to placebo of 0.6 cm (95% confidence interval [CI], -0.5 cm to 1.8 cm). The 28 patients in the neutral expectancy group who were randomized to tramadol reported a 1.4 cm decrease on the sum of pain intensity differences, while 28 patients in the placebo group reported a 0.9 cm decrease. This corresponds with an analgesic effect of tramadol relative to placebo of 0.5 cm (95% CI, -0.9 cm to 1.8 cm). The 0.1 cm difference (0.6 cm - 0.5 cm) in analgesic effect between positive and neutral expectancy group was not statistically significant (95% CI, -0.7 cm to 1.0 cm). This trial did not discern a significant difference in the analgesic effect of tramadol between a positive and neutral expectancy group. This means that the phenomenon either does not exist, or we had an inappropriate model to demonstrate it. Regardless, this study demonstrates the type of quality trial that should be done to find out which non-specific factors, such as information regarding the expected effect, can modify treatment effects.

Adult↗
PubMed2001

Forearm blood flow measurements using computerized R-wave triggered strain-gauge venous occlusion plethysmography: unilateral vs. bilateral measurements.

The human forearm is a well established model to study local vascular reactivity in humans in vivo, using strain-gauge venous occlusion plethysmography to measure blood flow and changes in blood flow in the forearm. To reduce the intra-individual variability of the forearm blood flow (FBF), it has been advocated that simultaneous measurements of contralateral forearm blood flow is obligatory. Therefore, the use of the calculated forearm ratio (FR) is recommended instead of using the actual FBF. In the present study we compared the intra-individual variability of forearm blood flow measurements and the forearm ratio, by using computerized R-wave triggered strain-gauge venous occlusion plethysmography, to test if bilateral expression of measurements is better than unilateral. Results were obtained in eight volunteers. Intra-arterial infused sodium nitroprusside induced a dose dependent increase in forearm blood flow and a dose dependent increase in the calculated forearm ratio. Intra-arterial infused norepinephrine induced a dose dependent decrease in forearm blood flow and a dose dependent decrease in the calculated forearm ratio. The differences between the variation coefficients of the forearm blood flow measurements and the calculated forearm ratio were different. These results support our hypothesis that by using a computerized, R-wave triggered system for unilateral forearm blood flow measurement is a more reliable outcome than the calculated forearm ratio derived from bilateral measurements.

Adult↗
PubMed2001

Disability in the oldest old: "can do" or "do do"?

OBJECTIVE: To investigate the discrepancies between outcomes for competence (can do) and actual performance (do do) in activities of daily living (ADLs). DESIGN: Baseline measurements of a population-based follow-up study. SETTING: Leiden 85-Plus Study, the Netherlands. PARTICIPANTS: Five hundred and ninety-nine persons, age 85. The response rate was 86%. MEASUREMENTS: Face-to-face interviews. Measurements of competence and actual performance were based on the Groningen Activity Restriction Scale. Help received was assessed for several domains. Prevalence rates for disability were assessed according to the concepts of both competence and actual performance. Analysis was performed separately for basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs). RESULTS: Seventy-seven percent of the oldest old were competent to perform all the BADLs and performed them regularly. Fifteen percent were not competent to perform certain BADLs independently but performed them regularly with help from others. The prevalence of disability defined as inability in one or more BADLs was 22% for women and 10% for men. The prevalence of disability defined as inactivity in one or more BADLs was 16% for women and 17% for men. Only 5% of the oldest old were competent to perform all IADLs and performed them regularly. In spite of being competent, 70% did not perform certain IADLs regularly. The prevalence of disability defined as inability in one or more IADLs was 64% for women and 55% for men. The prevalence of disability defined as inactivity in one or more IADLs was 92% for women and 98% for men. CONCLUSION: The structural discrepancies between the outcomes of competence and actual performance have important consequences when estimating disability in old people. Promoting actual performance in IADLs may reduce disability.

Activities of Daily Living↗
PubMed2001

Cognitive function in the oldest old: women perform better than men.

OBJECTIVE: Limited formal education is associated with poor cognitive function. This could explain sex differences in cognitive function in the oldest old. Whether limited formal education explains differences in cognitive function between elderly women and men was explored. METHODS: The Leiden 85-plus Study is a population based study investigating all 85 year old inhabitants of Leiden with an overall response rate of 87%. A sample of 599 participants were visited at their place of residence. The mini mental state examination was completed by all participants. Cognitive speed and memory were determined with four neuropsychological tests in participants with a mini mental state examination score higher than 18 points. RESULTS: The proportion of women with limited formal education was significantly higher than that of men (70% v 53%, p=0.001), but women had better scores for cognitive speed and memory than men (p<0.05). After adjustment for differences in limited formal education and the presence of depressive symptoms, the odds ratio for women to have a higher cognitive speed than men was 1.7 (95% CI; 1.0 to 2.6), and for them to have a better memory the odds ratio was 1.8 (95%CI; 1.2 to 2.7). CONCLUSION: Women have a better cognitive function than men, despite their lower level of formal education. Limited formal education alone, therefore, cannot explain the differences in cognitive function in women and men. These findings support the alternative hypothesis that biological differences, such as atherosclerosis, between women and men account for the sex differences in cognitive decline.

Aged↗
PubMed2000

['Informed consent' and prerandomization].

The usual procedure in randomised controlled trials is to obtain informed consent first, after which participants can be randomised. The reversal of the order, first randomisation and then informed consent, is called pre-randomisation (Zelen design). In the Netherlands, there is discussion as to whether pre-randomisation should be allowed in medical research. Full informed consent regarding the design of the investigation may lead to unwanted loss of distinction between the experimental and control groups, thus reducing the internal validity of the investigation. A possible solution could be to include, in the informed consent procedure, the statement that certain information has been withheld because revealing it now would make the investigation useless, but that it will be revealed to all participants afterwards and that the study design was approved by the medical ethics committee. In this way, the advantage of the enhanced internal validity of the pre-randomisation design is retained while simultaneously keeping intact the sequence of first informed consent and then randomisation.

Humans↗
PubMed2000

[Roaming through methodology. XVII. The placebo effect].

The placebo effect is well known, but there are many misconceptions. One of these misconceptions is that one-third of patients respond to placebos. This misunderstanding is probably due to methodologically poor research conducted in the 1950s. Another error is that the effect in the placebo arm of a clinical trial is often confused with the placebo effect. The belief in the placebo effect is enormous, but the quantity and quality of data to substantiate this belief are very limited. Investigating the placebo effect is methodologically difficult, not easy to get financed and considered unrewarding.

Clinical Trials as Topic↗
PubMed2000

Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos.

We carried out a meta-analysis of 22 trials to determine the comparative placebo effect of (a) subcutaneous vs. oral and (b) in-hospital vs. at-home administration in the treatment of migraine. The headache relief rates were combined from the placebo arms of these randomised clinical trials assessing the value of sumatriptan in acute treatment of migraine. The main outcome measure was the proportion of patients reclassified from severe or moderate headache severity to no or mild headache severity 2 h after the beginning of treatment. In the oral regimen 222 of 865 patients (25.7%) reported no or mild headache severity after 2 h, compared to 279 of 862 patients (32.4%) of those receiving subcutaneous placebo (6.7% difference; 95% CI 2.4-11.0%). Adjusting for treatment setting and severity of headache at baseline did not change the observed difference. After placebo treatment at home 285 of 1,054 patients (27.0%) reported no or mild headache severity after 2 h, compared to 216 of 673 patients (32.1%) among those receiving placebo in hospital (5.1 % difference; 95% CI 0.6-9.5%). When adjusted for route of administration and severity of headache at baseline, the difference in relief rates between home and hospital setting disappeared. These findings indicate that subcutaneous administration enhances the placebo effect of acute treatment of migraine. Future trials of antimigraine drugs assessing the relative efficacy of various routes of administration should use a double-dummy technique. The interpreting of placebo-controlled trial results must therefore consider that the effect in the drug arm of the trial depends in part on the route of administration.

Administration, Oral↗
PubMed2000

Why use placebos in clinical trials? A narrative review of the methodological literature.

Researchers have a number of different options for their choice of control or comparison intervention in randomized trials. We surveyed the methodological literature looking for reasons why a researcher might choose to administer a placebo (i.e., a mimic intervention) to control subjects. Two implicit assumptions were that the issue of placebo is pertinent only to drug trials and that the nonplacebo effect of a treatment is the "real" or "true" effect. Explicit reasons given in the literature for the use of placebos were facilitating blinding and controlling for the placebo effect. The importance of the latter was often inadequately argued. Reasons to avoid placebos in controlled trials, other than ethics and feasibility, are that placebos do not inform real decisions, and may interfere with accurate estimation of effect size and with nonspecific aspects of treatment. Placebo-controlled trials have high internal validity but may be difficult to apply to clinical practice; the situation is reversed for trials without placebo control.

Double-Blind Method↗
PubMed2000

Clinical outcome after standardized versus dosimetric radioiodine treatment of hyperthyroidism: an equivalence study.

The aim of this study was to investigate the equivalence in outcome of standardized versus uptake-adjusted dosing of radioactive iodine (131I) for hyperthyroidism. We performed a 1-year follow-up study of two patient cohorts: 326 patients referred for 131I treatment of hyperthyroidism in Graves' disease (GD; n=216) or toxic multinodular goitre (TMG; n=110) in the period June 1995 to January 1998. Of these patients 128 were treated according to a standardized regimen, based on palpated thyroid volume and diagnosis, and 198 with a 131I uptake-adjusted dosimetric method. The incidence of hypothyroidism, euthyroidism or recurrence of disease was recorded. In Graves' disease hypothyroid outcome in the standardized versus adjusted method was 40.7% vs 44.6% (95% CI difference, -17.4 to +9.5%); it was 67.4% vs 70.8% (95% CI difference -15.9 to +9.3%) for all non-euthyroid outcomes. In TMG, due to wide confidence interval ranges a conclusion of equivalence could be made only for recurrence of hyperthyroidism (mean -3.2%, 95% CI, -13.8 to +7.5%). A simplified dosage method for 131I treatment of hyperthyroidism, which omits 131I uptake adjustment, may improve procedure efficiency and patient convenience, and leads to an equivalent outcome in GD and probable equivalent outcome in TMG.

Adult↗
PubMed1999

[The practice of systematic reviews. I. Introduction].

A systematic review of the results of randomized, controlled trials employs explicit, systematic methods to produce unbiased and precise estimates of the effect of a treatment on outcomes of clinical importance. The results of such systematic reviews are of importance in that they inform providers and consumers about the effect of treatments and identify priorities for new research. The Cochrane Collaboration is a systematic programme to try to harness this valuable information. An overview of the actual status of systematic reviews of health care interventions is given and a miniseries of papers on systematic reviews is introduced.

Clinical Trials as Topic↗
PubMed1999

A systematic review of Helicobacter pylori eradication therapy--the impact of antimicrobial resistance on eradication rates.

BACKGROUND: We systematically reviewed all available data in the literature to determine the overall eradication rates of currently advised Helicobacter pylori eradication regimens and to resolve conflicting evidence on the impact of antimicrobial resistance on the eradication rates. METHODS: A comprehensive search of all published trials on H. pylori eradication therapy was carried out via an electronic database search, hand-searching and checking reference lists of pharmaceutical companies and other reviews. Full papers and abstracts in the English language which study currently advised eradication regimes were included. RESULTS: 770 study-arms were analysed. Mean eradication rates for bismuth based triple, proton pump inhibitor triple, quadruple and ranitidine bismuth citrate combination therapies vary from 65 to 92%. In case of nitroimidazole resistance, a drop in efficacy of up to 50% was found for bismuth-based triple and proton pump inhibitor-based triple therapies. For quadruple therapy, a significant difference in efficacy was found in the equal-effects analysis; however, this could not be confirmed in the random-effects analysis. In case of clarithromycin resistance, a mean drop in efficacy of 56% was found for one- and two-week clarithromycin containing proton pump inhibitor-triple therapies and of 58% for two-week ranitidine bismuth citrate combined with clarithromycin therapies. For ranitidine bismuth citrate combined with clarithromycin and nitroimidazole, no difference in efficacy was found in case of nitroimidazole or clarithromycin resistance, but data are still scarce. CONCLUSIONS: The cure rate with most regimens dropped significantly, in case of nitroimidazole-resistant strains, compared to nitroimidazole-susceptible strains. In case of clarithromycin resistance, the efficacy of most regimens is also decreased; however, data are still scarce. These data should allow physicians to make a better choice of an appropriate therapy for their patients.

Anti-Bacterial Agents↗
PubMed1999

Placebo effect in the treatment of duodenal ulcer.

AIMS: To assess whether frequency of placebo administration is associated with duodenal ulcer healing. METHODS: A systematic literature review of randomized clinical trials was undertaken. 79 of 80 trials that met the inclusion criteria. The pooled 4 week placebo healing rate of all duodenal ulcer trials that employed a four times a day regimen was compared with the rate obtained from trials with a twice a day regimen. RESULTS: The pooled 4 week healing rate of the 51 trials with a four times a day regimen was 44. 2% (805 of 1821 patients) compared with 36.2% (545 of 1504 patients) in the 28 trials with a twice a day regimen (difference, 8.0% [equal effects model]; 95% confidence interval, 4.6% to 11.3%). Depending on the statistical analysis, the rate difference ranged from 6.0% (multivariable random effects model) to 8.0% (equal effects model). A number of sensitivity analyses showed comparable differences between the two regimens. Most of these sensitivity analyses were not significant, probably because a number of trials were excluded resulting in a loss of power. CONCLUSIONS: We found a relation between frequency of placebo administration and healing of duodenal ulcer. We realize that the comparison was based on nonrandomized data. However, we speculate that the difference between regimens was induced by the difference in frequency of placebo administration. A better knowledge of various placebo effects is required in order to make clinically relevant assessments of treatment effects derived from placebo-controlled trials.

Duodenal Ulcer↗
PubMed1999

Helicobacter pylori eradication therapy in The Netherlands.

BACKGROUND: Helicobacter pylori cure rates vary in different geographical regions because of differences in hosts as well as in H. pylori strains. OBJECTIVE: To review systematically all available data in the literature to determine H. pylori eradication rates in The Netherlands. METHODS: A search of all published trials on H. pylori eradication therapy performed in The Netherlands was conducted via electronic database search, hand-searching of abstracts from scientific meetings and checking reference lists of pharmaceutical companies. Full papers and abstracts were included. Data on anti-H. pylori therapies were pooled based on duration and combination of drugs. Only triple and quadruple eradication regimens were studied. Dual therapies were excluded, except for ranitidine bismuth citrate-based dual therapies. RESULTS: We analysed 38 study arms, involving 2197 patients. Twenty different pooled regimens were studied with a mean intention-to-treat eradication rate of 83% (range 35-96%). There were no significant differences in the percentage of patients that stopped treatment due to adverse events between the groups. In these pooled regimens only bismuth combined with tetracycline and metronidazole for 1 or 2 weeks was significantly lower in efficacy in metronidazole-resistant strains than in metronidazole-sensitive strains. The prevalence of metronidazole-resistant strains in The Netherlands showed large regional differences (7-50%). CONCLUSIONS: A therapy should be tested in a defined population before becoming standard. Several eradication regimens studied in The Netherlands yield acceptable cure rates of 80% or more on an intention-to-treat basis. We advise taking the local prevalence of metronidazole resistance into account when choosing a first-line eradication regimen.

Antacids↗
PubMed1999

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia.

AIM: To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin/eosin (H/E) slides, MIB 1 slides, and the combined use of H/E and MIB 1 slides. METHODS: 10 slides were stained with H/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six observers first scored the H/E slides separately from the MIB 1 slides and second the combined H/E and MIB 1 slides. RESULTS: Unweighted group kappa for MIB 1 was 0.62 and the weighted group kappa was 0.91. This was significantly better than the unweighted group kappa for H/E slides (0.47, p = 0.023) as well as the weighted group kappa for H/E slides (0.82, p = 0.014). There was no improvement by the combined use of H/E and MIB 1 slides. VIN 2 is far less confused with VIN 3 in the combined use of H/E and MIB 1 slides (9%) than in H/E slides (38%) (p = 0.007). There is a tendency to grade VIN in a two tailed grading system rather than a three tailed grading system, which became more apparent with the combined use of H/E and MIB 1 slides. CONCLUSIONS: The interobserver variation with sole use of MIB 1 is better than with the use of H/E stain in VIN. The use of MIB 1 in grading VIN diminishes confusion between VIN 2 and VIN 3 fourfold. A two tailed grading system for VIN seems already to work in daily practice.

Antibodies, Monoclonal↗