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Biomedical subjects

J C Van Houwelingen

Publications and source records attributed to J C Van Houwelingen.

7 recordsLinked to original sources

Reduced rank proportional hazards model for competing risks.

Competing events concerning individual subjects are of interest in many medical studies. For example, leukemia-free patients surviving a bone marrow transplant are at risk of developing acute or chronic graft-versus-host disease, or they might develop infections. In this situation, competing risks models provide a natural framework to describe the disease. When incorporating covariates influencing the transition intensities, an obvious approach is to use Cox's proportional hazards model for each of the transitions separately. A practical problem then is how to deal with the abundance of regression parameters. Our objective is to describe the competing risks model in fewer parameters, both in order to avoid imprecise estimation in transitions with rare events and in order to facilitate interpretation of these estimates. Suppose that the regression parameters are gathered into a p x K matrix B, with p and K as the number of covariates and transitions, respectively. We propose the use of reduced rank models, where B is required to be of lower rank R, smaller than both p and K. One way to achieve this is to write B = AGamma(intercal) with A and Gamma matrices of dimensions p x R and K x R, respectively. We shall outline an algorithm to obtain estimates and their standard errors in a reduced rank proportional hazards model for competing risks and illustrate the approach on a competing risks model applied to 8966 leukemia patients from the European Group for Blood and Marrow Transplantation.

Biometry↗

Living with Huntington's disease: illness perceptions, coping mechanisms, and spouses' quality of life.

Chronic illness not only affects the life of those suffering from Huntington's disease but also threatens the quality of life (QOL) of their spouses. In this study, we focus on Huntington's disease (HD). The impact of HD on the QOL of spouses has been hardly studied from a behavioral medicine or health psychology perspective. We hypothesize that spouses' illness perceptions and coping mechanisms will contribute significantly to the prediction of their QOL. Illness perceptions, coping mechanisms, and the QOL of 90 spouses of patients with HD were assessed by means of the Illness Perception Questionnaire, the COPE, and the Medical Outcome Study 36-item Short Form Health Survey, respectively. After controlling for demographic and illness-related variables, coping mechanisms explained a significant amount of variance of spouses' role functioning. Given our results, more empirical and longitudinal research is justified on coping mechanisms and illness perceptions of spouses living with Huntington's disease.

Adaptation, Psychological↗

Prognostic models based on literature and individual patient data in logistic regression analysis.

Prognostic models can be developed with multiple regression analysis of a data set containing individual patient data. Often this data set is relatively small, while previously published studies present results for larger numbers of patients. We describe a method to combine univariable regression results from the medical literature with univariable and multivariable results from the data set containing individual patient data. This 'adaptation method' exploits the generally strong correlation between univariable and multivariable regression coefficients. The method is illustrated with several logistic regression models to predict 30-day mortality in patients with acute myocardial infarction. The regression coefficients showed considerably less variability when estimated with the adaptation method, compared to standard maximum likelihood estimates. Also, model performance, as distinguished in calibration and discrimination, improved clearly when compared to models including shrunk or penalized estimates. We conclude that prognostic models may benefit substantially from explicit incorporation of literature data.

Age Factors↗

Can peak expiratory flow measurements reliably identify the presence of airway obstruction and bronchodilator response as assessed by FEV(1) in primary care patients presenting with a persistent cough?

BACKGROUND: In general practice airway obstruction and the bronchodilator response are usually assessed using peak expiratory flow (PEF) measurements. A study was carried out in patients presenting with persistent cough to investigate to what extent PEF measurements are reliable when compared with tests using forced expiratory volume in one second (FEV(1)) as the measure of response. METHODS: Data (questionnaire, physical examination, spirometry, PEF) were collected from 240 patients aged 18-75 years, not previously diagnosed with asthma or chronic obstructive pulmonary disease (COPD), who consulted their general practitioner with cough of at least two weeks duration. The relationship between low PEF (PEF < PEFpred - 1.64RSD) and low FEV(1) (FEV(1) < FEV(1)pred - 1.64RSD) was tested. A positive bronchodilator response after inhaling 400 microg salbutamol was defined as an increase in FEV(1) of > or = 9% predicted and was compared with an absolute increase in PEF with cut off values of 40, 60, and 80 l/min and DeltaPEF % baseline with cut off values of 10%, 15%, and 20%. RESULTS: Forty eight patients (20%) had low FEV(1), 86 (35.8%) had low PEF, and 32 (13.3%) had a positive bronchodilator response. Low PEF had a positive predictive value (PPV) for low FEV(1) of 46.5% and a negative predictive value (NPV) of 95%. DeltaPEF of > or = 10%, > or = 15%, or > or = 20% baseline had PPVs of 36%, 52%, and 67%, respectively, and DeltaPEF of > or = 40, > or = 60, and > or = 80 l/min in absolute terms had PPVs of 39%, 45%, and 57%, respectively, for DeltaFEV(1) > or = 9% predicted; NPVs were high (88-93%). CONCLUSIONS: Although PEF measurements can reliably exclude airway obstruction and bronchodilator response, they are not suitable for use in the assessment of the bronchodilator response in the diagnostic work up of primary care patients with persistent cough. The clinical value of PEF measurements in the diagnosis of reversible obstructive airway disease should therefore be re-evaluated.

Adolescent↗

Value of measuring diurnal peak flow variability in the recognition of asthma: a study in general practice.

In this study we analysed the value of measuring diurnal peak flow variability (DPV) in general practice for diagnosing asthma or chronic obstructive pulmonary disease (COPD). One hundred and eighty-two subjects, aged 18-75 yrs, with undiagnosed asthma or COPD, presenting with a persistent cough recorded a peak flow diary twice daily for 2 weeks. A diagnosis of asthma or COPD was based on the recurrence of airway symptoms in the past year accompanied by spirometric measurements and a provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second. DPV was expressed as amplitude percentage highest of the day. Cut-off values of 15% and 20% (DPV15%, DPV20%) were employed and the number of days that these values were reached, was assessed. The influence of age, sex and pack-years smoking on DPV was analysed by logistic regression. The a priori probability to have asthma (n=69) or COPD (n=12) was 45% (81/182) and increased to >70% with a DPV20% for at least 3, and a DPV15% for at least 4 days. Scoring formulas for asthma (DPV15% (number of days present) + 4 (if female sex)) and for asthma and COPD combined (8x DPV15% (number of days present) + 24 (if female sex) + pack-years smoking) predicted which subjects were at risk for having asthma (or COPD). Simple formulas based on the number of days with diurnal peak flow variability at 15%, female sex and pack-years can predict which patients with persistent cough are likely to have asthma or chronic obstructive pulmonary disease.

Adolescent↗

Predictive value of statistical models.

A review is given of different ways of estimating the error rate of a prediction rule based on a statistical model. A distinction is drawn between apparent, optimum and actual error rates. Moreover it is shown how cross-validation can be used to obtain an adjusted predictor with smaller error rate. A detailed discussion is given for ordinary least squares, logistic regression and Cox regression in survival analysis. Finally, the splitsample approach is discussed and demonstrated on two data sets.

Calibration↗

Multistate modelling of liver transplantation data.

This paper concerns the survival analysis of liver transplant patients when patients with a potentially fatal rejection of the transplanted organ may receive a retransplant. A multistate model, analysing the states 'alive with first graft' and 'alive with second graft' separately, is suggested. Proportional hazards models and logistic regression models are used to evaluate which risk factors related to donor, preservation and recipient, influence the transition intensities. The complete model is used to predict overall survival of a patient and to study the influence of the risk factors on total survival.

Adolescent↗