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Biomedical subjects

B C Michel

Publications and source records attributed to B C Michel.

17 recordsLinked to original sources
PubMed1999

Redundancy of single diagnostic test evaluation.

Diagnostic research and diagnostic practice frequently do not cohere. Studies commonly evaluate whether a single test discriminates between disease presence and absence, whereas in practice a test is always judged in the context of other information. This study illustrates drawbacks of single-test evaluation and discusses principles of diagnostic research. We used data on 140 patients suspected of pulmonary embolism who had an inconclusive ventilation-perfusion lung scan. We evaluated three tests: partial pressure of oxygen in arterial blood (PaO2), x-ray film of the thorax, and leg ultrasound. On the basis of single-test evaluations, ultrasound was most informative. Given a prior probability of 0.27, it had a much better combination of positive and negative predictive value (0.71 and 0.21, respectively) relative to thorax x-ray (0.33 and 0.11) and PaO2 (0.35 and 0.27). The combination of positive and negative likelihood ratio was also more promising for ultrasound (7.3 and 0.7) than for thorax x-ray (1.3 and 0.3) and PaO2 (1.3 and 0.9). As the tests are always performed after the history and physical, we judged their added value using multivariable logistic modeling with receiver operating characteristic (ROC) analyses. The ROC areas of the model, including history and physical, with additional PaO2, thorax x-ray, or ultrasound, were 0.75, 0.77, 0.81, and 0.81, respectively, which indicated similar added value of thorax x-ray and ultrasound. Application of the models to patient subgroups also yielded added predictive value for thorax x-ray film. Thus, the results of single-test evaluations may be very misleading. As no diagnosis is based on one test, single-test evaluations have limited value in diagnostic research and only have relevance in the context of screening and the initial phase of test development. Diagnostic research should always apply an approach of constructing, extending, and validating diagnostic models in agreement with routine clinical work-up using logistic regression analyses.

Analysis of Variance↗
PubMed1998

Sample size calculation in economic evaluations.

A simulation method is presented for sample size calculation in economic evaluations. As input the method requires: the expected difference and variance of costs and effects, their correlation, the significance level (alpha) and the power of the testing method and the maximum acceptable ratio of incremental effectiveness to incremental costs. The method is illustrated with data from two trials. The first compares primary coronary angioplasty with streptokinase in the treatment of acute myocardial infarction, in the second trial, lansoprazole is compared with omeprazole in the treatment of reflux oesophagitis. These case studies show how the various parameters influence the sample size. Given the large number of parameters that have to be specified in advance, the lack of knowledge about costs and their standard deviation, and the difficulty of specifying the maximum acceptable ratio of incremental effectiveness to incremental costs, the conclusion of the study is that from a technical point of view it is possible to perform a sample size calculation for an economic evaluation, but one should wonder how useful it is.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

The role of a decision rule in symptomatic pulmonary embolism patients with a non-high probability ventilation-perfusion scan.

BACKGROUND: In order to improve the use of information contained in the medical history and physical examination in patients with suspected pulmonary embolism and a non-high probability ventilation-perfusion scan, we assessed whether a simple, quantitative decision rule could be derived for the diagnosis or exclusion of pulmonary embolism. METHODS: In 140 consecutive symptomatic patients with a non-high probability ventilation-perfusion scan and an interpretable pulmonary angiogram, various clinical and lung scan items were collected prospectively and analyzed by multivariate stepwise logistic regression analysis to identify the most informative combination of items. RESULTS: The prevalence of proven pulmonary embolism in the patient population was 27.1%. A decision rule containing the presence of wheezing, previous deep venous thrombosis, recently developed or worsened cough, body temperature above 37 degrees C and multiple defects on the perfusion scan was constructed. For the rule the area under the Receiver Operating Characteristic curve was larger than that of the prior probability of pulmonary embolism as assessed by the physician at presentation (0.76 versus 0.59; p = 0.0097). At the cut-off point with the maximal positive predictive value 2% of the patients scored positive, at the cut-off point with the maximal negative predictive value pulmonary embolism could be excluded in 16% of the patients. CONCLUSIONS: We derived a simple decision rule containing 5 easily interpretable variables for the patient population specified. The optimal use of the rule appears to be in the exclusion of pulmonary embolism. Prospective validation of this rule is indicated to confirm its clinical utility.

Adult↗
PubMed1996

[Costs of diagnosis and treatment for pulmonary embolism lower due to application of consensus strategy].

OBJECTIVE: To compare the costs of diagnosis and treatment of patients clinically suspected of pulmonary embolism, before and after the adoption of the Dutch consensus for the diagnosis of pulmonary embolism. DESIGN: Study of the records, followed by a prospective study with a follow-up lasting 6 months. SETTING: Academic Medical Centre and Slotervaart Hospital, Amsterdam, the Netherlands. METHOD: Data were collected on 120 patients from the preconsensus period and on 452 patients examined according to the consensus strategy. This established the average patterns of medical consumption of patients before and after adoption of consensus. The mean costs per patient were then estimated. RESULTS: Diagnosis and treatment of a patient according to the consensus strategy on the basis of our estimates were considerably less expensive than non-protocolled diagnosis and treatment (Dfl. 4,413 as against Dfl. 5,115 per patient). This difference mainly resulted from shorter hospital stays owing to more rapid completion of the diagnosis. Considering the large number of annual hospital admissions in the Netherlands in connection with this diagnosis, savings of up to Dfl. 26 million would appear possible if the consensus were followed nationwide. CONCLUSION: Considerable amounts are involved in the diagnosis and treatment of pulmonary embolism in the Netherlands. Accordingly, further research into possibilities to make these more efficient would appear advisable.

Clinical Protocols↗
PubMed1996

The role of plasma D-dimers concentration in the exclusion of pulmonary embolism.

OBJECTIVE: To determine the role of four ELISA D-dimer assays in the exclusion of pulmonary embolism. DESIGN: Blinded comparison using pulmonary angiography and/or lung scintigraphy as a reference method. SETTING: A secondary and tertiary referral centre. PATIENTS AND METHODS: Consecutive patients with suspected pulmonary embolism underwent lung scintigraphy, followed by angiography if a non-diagnostic result was obtained. Comorbid conditions resulting in elevated plasma D-dimer levels were defined a priori. Cut-off levels for 100% sensitivity was determined. A decision-analytic model was used to determine effectiveness and costs in the management pulmonary embolism. MAIN OUTCOME MEASURES: The exclusion efficacy of the various assays at a sensitivity of 100% and cost-effectiveness. RESULTS: A total of 179 patients were included (78 inpatients and 101 outpatients; 74 patients had comorbid conditions). Pulmonary embolism could be adequately excluded in between 8% and 18% of all patients, an in between 3% and 7% and 11% and 27% of inpatients and outpatients, respectively, depending on the assay used. D-dimer assays could exclude pulmonary embolism in <5% of patients with comorbid conditions, whereas this increased to 14-32% in outpatients without comorbid conditions. A cost-effectiveness analysis showed a cost reduction of 10% at a specificity of 30%, largely due to a 28% decrease in angiography requirements. Furthermore, for every 2% decrease to sensitivity, one per 1000 evaluated patients would die as a result of inadequately treated pulmonary embolism. CONCLUSION: D-dimer ELISA assays may have a role in the exclusion of pulmonary embolism in symptomatic outpatients, where the application may reduce angiography by 30% and costs by 10%.

Adult↗
PubMed1996

Economic aspects of treatment with captopril for patients with asymptomatic left ventricular dysfunction in The Netherlands.

OBJECTIVE: To estimate the costs and effects of preventive treatment with captopril compared with the current treatment policy in patients with asymptomatic left ventricular dysfunction after a myocardial infarction. METHODS: Estimates of effects are based on the results of the SAVE trial. Costs are estimated on the basis of current treatment patterns in four Dutch hospitals. All knowledge is incorporated in a mathematical model extrapolating the SAVE results to 20 years. RESULTS AND CONCLUSIONS: Captopril treatment is expected to increase survival at certain costs. The average additional costs per patient are estimated at DF1 2,491 in 4 years and at DF1 8,723 in 20 years of treatment. Costs per additional survivor after 4 years are estimated at DF1 69,126. After extrapolation of the results of the SAVE trial to 20 years, costs per life-year gained can be estimated at DF1 15,799. From univariate sensitivity analysis it appears that the results are highly sensitive for the costs of treatment with captopril and the occurrence and prevention of clinical heart failure. Varying all estimates randomly between upper and lower limits-in 5,000 simulations-an estimate of costs per life-year gained of DF1 15,729 is made for 20 years of treatment, with 95% of all estimates between DF10 and DF1 50, 000. On a national level, undiscounted costs are expected to increase up to approximately DF1 42 million annually during the first 40 years after introduction of the preventative strategy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Simulation models in the planning of health care facilities: an application in the case of neonatal extracorporeal membrane oxygenation.

OBJECTIVES: To investigate whether modelling techniques can be used in the planning of health care facilities for patients requiring neonatal extracorporeal membrane oxygenation (ECMO). METHODS: In a micro-simulation model the number of patients that will have to be referred to facilities abroad is estimated for any number of neonatal ECMO patients presenting annually for treatment in The Netherlands, and any number of ECMO facilities. The inputs to the model consist of the number of ECMO facilities, the number of patients presenting annually, the duration of treatment and the date on which patients present for ECMO treatment. The model is estimated on data from The Netherlands for 1992, during which 29 patients were treated in three facilities. Several future scenarios are modelled, principally one in which a potential increase to 56 patients per year is foreseen. RESULTS: The model indicates that, if such an increase takes place, no additional ECMO facilities will be necessary in The Netherlands if between three and four referrals annually to centres outside the region (or abroad) are considered acceptable and feasible. In that situation, it is expected that on 22 occasions each year two patients will be treated simultaneously, for a total of 81 days. On ten occasions, all three facilities will be occupied at the same time, for 21 days in total. On 199 days, at least one of the facilities will be occupied. CONCLUSION: The current study shows that the acceptability and feasibility of patient referrals to ECMO centres abroad is an important issue which health care planners will have to consider. The study also shows that modelling techniques can provide information that is useful to policy-makers in the planning of health care facilities.

Computer Simulation↗
PubMed1996

The cost effectiveness of diclofenac plus misoprostol compared with diclofenac monotherapy in patients with rheumatoid arthritis.

The objective of our study was to estimate the cost effectiveness of treatment with a fixed-dose combination of diclofenac and misoprostol compared with diclofenac monotherapy in the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers in rheumatoid arthritis (RA) patients. A model was used to incorporate estimates of costs, incidence of ulcers and their complications, death rates and the efficacy of misoprostol. The costs per ulcer-free period gained and costs per additional survivor were calculated. Cost effectiveness was calculated for the treatment of all RA patients, and of risk groups only. All costs were measured in 1995 Netherlands guilders (NLG; exchange rate at the time of the study: NLG1 = $US0.60). The analysis showed that if 100 RA patients receive 3 months of treatment with diclofenac plus misoprostol, instead of diclofenac alone, this will lead to overall additional costs of NLG773, while 0.82 symptomatic ulcers and 0.019 deaths will be prevented. If misoprostol is given only to patients at high risk for NSAID-induced ulcer, cost savings will occur instead of additional costs. Univariate sensitivity analysis showed that the outcomes are sensitive to changes in: (i) the percentage of ulcers treated in the ambulatory setting; (ii) the price difference between diclofenac and the fixed-dose diclofenac-misoprostol combination; (iii) the percentage of ulcers with complications; and (iv) the efficacy of misoprostol. In conclusion, it can be stated that treatment with diclofenac-misoprostol is cost saving in RA patients at high risk for NSAID-induced ulcers. For RA patients in general, the cost-effectiveness of this intervention compares favourably with that of other prophylactic treatments.

Age Factors↗
PubMed1995

Societal perspective on the burden of migraine in The Netherlands.

This study presents a comprehensive overview of the societal burden of migraine in The Netherlands. We assessed the direct and indirect costs of this disease, and the health status of patients with migraine. We developed the 'illness and labour' (I&L) questionnaire to collect data on the effect of illness on labour performance. 846 migraine patients and 834 controls were selected from the general population. Participants completed an I&L questionnaire as well as generic health status questionnaires. The direct costs of migraine amounted to 134 million Netherlands guilders (NLG) [$US1 = NLG1.68, October 1994]. Conservative calculations of the costs of absence from work and reduced productivity at work were NLG264 and NLG277 million per year, respectively. Our study did not indicate that migraine caused household productivity losses. The baseline estimate of the total societal costs of migraine in The Netherlands was NLG675 million per year. The assessment of health status showed considerable impairment of psychological and social functioning in migraine patients.

Absenteeism↗
PubMed1994

[Is the use of helicopters with a trauma team in severely injured accident victims in The Netherlands cost effective? A modelling approach].

OBJECTIVE: The assessment of the cost-effectiveness of helicopter medical crews for patients with major trauma in the Dutch situation. DESIGN: A modelling approach, combining available information with plausible assumptions. SETTING: Institute for Medical Technology Assessment, Rotterdam. METHODS: First, a baseline scenario was developed, implementing information that was available in the literature and a few assumptions. The sensitivity of the cost-effectiveness for the various assumptions was evaluated in alternative scenarios. END-POINTS. The relation between the costs per life year gained and the expected increase in the number of patients surviving an accident is established for the separate scenarios. RESULTS: In the baseline scenario the number of victims with a trauma score < or = 12 is estimated at 4500 per year, it is assumed that victims who die at the scene of the accident are unsalvageable and that hospital treatment costs Dfl. 27,000.--per patient. As a result costs per life year saved are only under Dfl. 50,000.--when more than 29 patients per year (9.23% gain in survival) are additionally saved. Sensitivity analysis shows that the cost-effectiveness depends highly on the expected gain in survival and on the estimate of the costs of hospital treatment. Both variables are surrounded with a lot of uncertainty. CONCLUSIONS: Relying on the information that is available at this moment, no definite conclusions can be drawn on the cost-effectiveness of this facility, because too many essential data are missing. Empirical research is necessary.

Aircraft↗
PubMed1994

Assessing the benefits of transplant services.

This chapter presents some methods for the assessment of transplant benefits, using the example of liver transplantation. An independent assessment of the benefits of medical technology is especially important for evaluation of the balance between the costs and benefits involved. To enable comparison with other health-care facilities, benefits are defined in terms of a combination of life-years gained and quality of life. The number of life-years gained can be calculated by comparing the survival expected with and without transplantation. Survival with transplantation is estimated on the basis of observed survival, acknowledging that the probability of survival may have changed over time, owing to changes in therapy and selection criteria. To estimate survival without transplantation, several techniques are available. Prognostic models, correcting for stage of disease, are often used. Pitfalls in the use of these models are discussed. The number of life-years gained can be corrected for quality of life by weighing survival with and without transplantation with an index representing quality of life. A method for the calculation of such an index is given. Finally, some cost estimates are presented and the results are discussed.

Cost-Benefit Analysis↗
PubMed1993

[Cost-effectiveness analysis of long-term liver transplantation; the liver transplantation program of Groningen 1979-1991].

A medical technology assessment of the liver transplantation programme of Groningen University Hospital, which was commissioned by the Dutch National Health Insurance Board, is discussed. The results of all 152 liver transplantations performed between 1979 and November 1990 were analysed. The main objective of the study was to evaluate the long-term effects of liver transplantation. Five years after transplantation 59% of the adult patients were still alive. The survival probability depended greatly on the primary liver disease. Mortality and morbidity occurred mainly within the first year after transplantation. Thereafter the prospects for the patients were excellent, with regard to both the probability of survival and the quality of life. The costs of liver transplantation could be calculated only for patients with primary biliary cirrhosis and other forms of biliary cirrhosis, not caused by hepatitis B infection or alcohol abuse. For these patients the costs of a liver transplantation were estimated at HFl. 263,000--(with a 10% margin), 10 years of follow-up included and corrected for the costs that would have been made for the treatment of the liver disease. For this population of patients a liver transplantation costs between Hfl. 64,000--and Hfl. 79,000--per life year gained, 10 years of follow-up included. Costs of cyclosporin still take up a major part of the costs. The need for liver transplantation in the Netherlands was estimated at between 35 and 126 transplantations per year, depending on indications, contraindications, referral policy and the percentage of retransplantations.

Adolescent↗
PubMed1987

Inability of recombinant interferon-gamma to activate the antibacterial activity of mouse peritoneal macrophages against Listeria monocytogenes and Salmonella typhimurium.

The effect of recombinant murine interferon-gamma (rIFN-gamma) as single stimulus for the activation of antibacterial activity of macrophages was investigated on the basis of the rate of intracellular killing of Listeria monocytogenes and Salmonella typhimurium by normal and rIFN gamma-activated peritoneal macrophages of CBA and C57BL/10 mice, which differ in natural resistance to infection by these bacteria. Eighteen hours after i.p. injection of 10 to 1 X 10(4) U rIFN-gamma, resident and exudate peritoneal macrophages which had phagocytosed L. monocytogenes or S. typhimurium in vivo, killed both species in vitro just as efficiently as did resident macrophages of normal mice. Similar results were obtained after 18 hr of in vitro incubation of resident or exudate peritoneal macrophages with 0.1 to 1 X 10(4) U/ml rIFN-gamma. Consistent with the in vitro findings, two i.v. injections of 5 X 10(4) U rIFN-gamma did not affect the rate of in vivo proliferation of L. monocytogenes or S. typhimurium in the spleens of mice during the first 2 days after i.v. injection of the bacteria. Compared with the effect on the controls, two i.p. injections of 5 X 10(2) to 5 X 10(4) U rIFN-gamma did not decrease the numbers of viable S. typhimurium in either the peritoneal cell suspension or the spleen 24 hr after i.p. injection of the bacteria. Checking the state of activation of rIFN-gamma-activated macrophages on the basis of two commonly used criteria for macrophage activation showed that rIFN-gamma-activated macrophages inhibited the intracellular replication of Toxoplasma gondii and displayed enhanced O2 consumption and H2O2 release after stimulation with phorbol myristate acetate compared with macrophages from normal CBA and C57BL/10 mice. The present findings show that as single activating stimulus, rIFN-gamma is not capable of activating the antibacterial effector functions of peritoneal macrophages against facultative intracellular pathogens such as L. monocytogenes and S. typhimurium.

Animals↗
PubMed1987

Salmonella-typhimurium-specific difference in rate of intracellular killing by resident peritoneal macrophages from salmonella-resistant CBA and salmonella-susceptible C57BL/10 mice.

The aim of the present study was to determine whether the difference between the rate of intracellular killing of Salmonella typhimurium by macrophages of salmonella-resistant CBA and salmonella-susceptible C57BL/10 mice also holds for other salmonellae and other bacteria species. After in vivo phagocytosis, the initial rate of in vitro intracellular killing of S. typhimurium phagetype 505, S. typhimurium phagetype 510, and S. typhimurium M206 by macrophages of CBA mice amounted always to approximately 1.7 times the value found for macrophages of C57BL/10 mice (p less than 0.001), indicating that the difference in killing efficiency between CBA and C57BL/10 macrophages holds for various strains of S. typhimurium. However, some other salmonella species, i.e., S. dublin and S. heidelberg, as well as E. coli 054 and 02K1+, Listeria monocytogenes EGD and L347, and Staphylococcus aureus were killed equally efficiently by macrophages of both mouse strains. These findings indicate that the difference between the rates of intracellular killing by macrophages of salmonella-resistant CBA and salmonella-susceptible C57BL/10 does not hold for several other bacteria species and thus might be specific for S. typhimurium. Subsequent experiments showed that the in vivo proliferation of S. typhimurium 510 in the first 2 days after i.v. injection was 2.0-fold to 3.0-fold higher in the spleens and livers of C57BL/10 mice than in those of CBA mice, whereas the in vivo proliferation of S. dublin and S. heidelberg was between 1.0-fold to 1.4-fold higher in the C57BL/10 mice. These findings suggest that the differences between the rate of in vitro intracellular killing of salmonella by CBA and C57BL/10 macrophages are reflected in differences in the rate of in vivo proliferation of these microorganisms in CBA and C57BL/10 mice. To gain insight into the involvement of the oxidative metabolism of CBA and C57BL/10 macrophages in the difference in the rate of intracellular killing of S. typhimurium, the O2 consumption and H2O2 release by resident peritoneal macrophages was determined. The amplitudes of the respiratory burst and the release of H2O2 was identical in macrophages of the two mouse strains after triggering by either preopsonized heat-killed S. typhimurium or phorbol myristic acetate. These findings indicate that the mouse species-associated difference in the intracellular killing of S. typhimurium is not caused by a difference in the oxidative metabolism of CBA and C57BL/10 macrophages.

Animals↗
PubMedDate not supplied

The cost-effectiveness of diagnostic strategies in patients with suspected pulmonary embolism.

The cost-effectiveness of various diagnostic strategies in patients with clinically suspected pulmonary embolism (PE) was analysed using a modelling approach. In 451 consecutive patients with clinically suspected PE data on the performance of diagnostic tests were collected prospectively in two large teaching hospitals in Amsterdam, The Netherlands. The ventilation-perfusion lung scan was used as the primary diagnostic test in all patients. In patients with a non-diagnostic lung scan result the performance of a clinical decision rule, a D-dimer test, and ultrasonography of the leg veins was evaluated with pulmonary angiography as the gold standard. It was estimated that the strategy recommended by a 1992 Dutch consensus meeting costs about Dfl 4400 per patient and that 97.02% of the patients can be expected to survive the first 6 months after the primary PE. The nation-wide annual costs for the diagnosis and treatment of patients by this strategy were estimated at 163 million Dutch Guilders. Subsequently, the costs and effects of alternative strategies were evaluated in a modelling approach, and compared with those of the consensus strategy. One strategy was selected that produces the best results in terms of survival and leads to considerable savings as compared with the consensus strategy. In this strategy subsequently a ventilation-perfusion scan, a clinical decision rule, a D-dimer test, a pulmonary angiography and leg ultrasonography are performed. Patients with a high probability ventilation-perfusion scan, an abnormal angiography or leg ultrasound test are treated, whereas treatment is withheld in patients with a normal ventilation-perfusion scan, a normal clinical decision rule, a negative D-dimer test, a normal angiography, or a normal leg ultrasound test. This strategy will have to prove its value and usefulness in clinical practice in a subsequent prospective validation phase.

Anticoagulants↗
PubMedDate not supplied

Application of treatment thresholds to diagnostic-test evaluation: an alternative to the comparison of areas under receiver operating characteristic curves.

Diagnostic tests are often evaluated by comparison of the areas under receiver operating characteristic (ROC) curves. In this study the authors compared this approach with a more direct method that takes into account consequences of a diagnosis. Data from a prospective study of diagnosis of pulmonary embolism were used for a motivating example. Using multivariable logistic regression analysis, three diagnostic models were built and compared based on their ROC curves. Although model 1 (0.706) and model 2 (0.702) had the same ROC-curve area, they performed differently when risks and benefits of subsequent decisions were considered by applying the treatment probability threshold. Models 1 and 3 (0.611) had substantially different ROC-curve areas but performed similarly taking into account the therapeutic consequences. This demonstrates that comparison of diagnostic tests using the areas under the ROC curves may lead to erroneous conclusions about therapeutic usefulness. To correspond to daily practice, it would be more appropriate to also consider the clinical implications in evaluating diagnostic tests. This is made feasible by explicit definition and application of a treatment threshold.

Decision Support Techniques↗