Assessing time-by-covariate interactions in relative survival models using restrictive cubic spline functions.

BACKGROUND: The Cox model is widely used in the evaluation of prognostic factors in clinical research. However, in population-based studies, which assess long-term survival of unselected populations, relative-survival models are often considered more appropriate. In both approaches, the validity of proportional hazards hypothesis should be evaluated. METHODS: We propose a new method in which restricted cubic spline functions are employed to model time-by-covariate interactions in relative survival analyses. The method allows investigation of the shape of possible dependence of the covariate effect on time without having to specify a particular functional form. Restricted cubic spline functions allow graphing of such time-by-covariate interactions, to test formally the proportional hazards assumption, and also to test the linearity of the time-by-covariate interaction. RESULTS: Application of our new method to assess mortality in colon cancer provides strong evidence against the proportional hazards hypothesis, which is rejected for all prognostic factors. The results corroborate previous analyses of similar data-sets, suggesting the importance of both modelling of non-proportional hazards and relative survival approach. We also demonstrate the advantages of using restricted cubic spline functions for modelling non-proportional hazards in relative-survival analysis. The results provide new insights in the estimated impact of older age and of period of diagnosis. DISCUSSION: Using restricted cubic splines in a relative survival model allows the representation of both simple and complex patterns of changes in relative risks over time, with a single parsimonious model without a priori assumptions about the functional form of these changes.

Modelling time-dependent hazard ratios in relative survival: application to colon cancer.

The Cox model is widely used in the evaluation of prognostic factors in clinical research. In population-based studies, however, which assess long-term survival of unselected populations, relative survival models are often considered more appropriate. In both approaches, the validity of proportional hazard hypothesis should be evaluated. To explore the validity of the proportional hazard assumption in a population-based study of colon cancer, to propose non-proportional hazard relative survival models and to evaluate their utility. The use of a piecewise proportional hazard relative survival model in colon cancer has shown that the effects of most clinical prognostic factors such as age, period of diagnosis and stage are non-proportional. The non-proportional hazard relative survival models developed in this article have been found to be efficient tools for better understanding the time-dependent aspect of prognostic factors.

Stroke patterns in cardio-embolic infarction in a population-based study.

The study demonstrates that clinical-radiological causes and outcome of cardio-embolic infarcts in a population-based study correspond to a well-identified stroke pattern. Cardio-embolic infarcts was diagnosed in 882 cases (37.9%) of 2,330 consecutive first-ever stroke patients included in a prospective population-based stroke registry over a 14-year period (1985-1997). Thirty-three criteria out of 98 were introduced into a monovariate analysis and the significant variable were introduced into a multivariate analysis to identify significant criteria to define stroke patterns in cardio-embolic infarction. Cardiac sources of embolus included atrial arrhythmia, valvular heart disease (19%), and cardiac failure (18%). Patients with cardio-embolic infarction showed a significantly higher rate of female predominance (p < 0.001), history of ischemic heart disease (p < 0.001), acute stroke onset (p < 0.05), headache (p < 0.05), previous treatment by anti-platelets and anti-K-vitamin (p < 0.001), Wernicke aphasia (p < 0.001), severe deficit (p < 0.001) and death (p < 0.001). After a logistic procedure, female gender and ischemic heart disease were the two independent risk factors associated with cardio-embolic stroke. Cardio-embolic stroke is a specific subtype of stroke with its own clinical, radiological, etiological and prognostic characteristics. In the acute stage, it is necessary to identify quickly this type of stroke because of severe prognosis and appropriate treatment.

Interval cancers in a community-based programme of colorectal cancer screening with faecal occult blood test.

Interval cancers represent the major limitation of screening for colorectal cancer with the faecal occult blood test. The aim of this study was to describe the characteristics of interval cancers and the sensitivity of the screening programme in a well-defined French population. During five screening rounds, 398 cancers were diagnosed in those of the population having performed at least one screening test; 57.8% of them were interval cancers. The proportion of interval cancers was higher among cancers of the rectal ampulla (72.2%) than among cancers of other sites (52.9%) (P < 0.001). The proportion of TNM stage I and II were higher among screen-detected cancers (73.8%) than among interval cancers (57.4%). The overall sensitivity of the screening programme was 62.9% within 1 year, and 48.7% within 2 years. An improvement in the sensitivity of the faecal occult blood test for colorectal cancer screening is needed, without an unacceptable loss of specificity.

Modeling of high-cost patient distribution within renal failure diagnosis related group.

Modeling by mixed-distribution was proposed in order to analyze heterogeneity of costs and length of stays within Diagnosis Related Groups (DRGs). A mixed-distribution model based on Weibull distributions was applied to 791 discharge abstracts of French DRG no. 450 (Health Care Financing Administration 3 DRG no. 316 "Renal failure") from a national database. Three subgroups of cost and length of stay were identified. Except for age, clinical criteria significantly linked with the long-stay subgroup were the same as those associated with the high-cost subgroup: acute renal failure, intensive care, infectious complications, and vascular investigations. The identification of factors associated with high costs, based on the proposed model, will allow physicians to understand more accurately how their choice of specific procedures influences hospital costs.

[Health care pattern of the initial course of treatment of breast cancer in the French Department of Côte-d'Or from 1982 to 1992]. / Filières de soins du traitement initial du cancer du sein en Côte-d'Or de 1982 à 1992.

PURPOSE: The aim of this study was to describe the implication of the different health care structures in the treatment of breast cancer. METHODS: In Côte-d'Or, from 1982 to 1992, there were 2432 cases of breast cancer. Surgery came first as treatment for 93% of the patients, radiotherapy came second (77%). The department is subdivided in several geographic areas (ZPIU):--Dijon, equipped with university hospital (UH) and with private hospitals (PH),--cities with general hospitals (GH)--and areas without hospitals. Demographic, geographic and clinical variables were studied in order to explain the patient distribution between the various hospitals. RESULTS: 52% of the cases were operated in PH, 37% in UH and 11% in GH. The main users of the GH were women who lived nearby. Age over 75 was associated with a treatment in GH. Women with clinical signs of severity were twice as often operated in UH rather than PH. Post-operative radiotherapy was done in 95% of the cases in the same structure where surgery was done. CONCLUSION: No matter how popular university and private hospitals were in our regional capital, general hospitals played a proximity role.