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Biomedical subjects

Susanne Rosthøj

Publications and source records attributed to Susanne Rosthøj.

6 recordsLinked to original sources

Estimation of optimal dynamic anticoagulation regimes from observational data: a regret-based approach.

A complication of long-term anticoagulation is that the optimal dose level varies not only between patients but over time within patients, in response to short-term changes in lifestyle. Consequently, doseage needs to be adaptive but there are as yet no accepted decision rules. Since anticoagulant use is increasing worldwide there is a need for more objective and routine procedures. In this paper, we describe an analysis of observational longitudinal anticoagulant data, aimed at determining an optimal reactive dose-changing strategy. We use the regret parameterization approach advocated by Murphy (J. R. Stat. Soc. Ser. B 2003; 65:331-366). Practical problems encountered in the implementation of the approach are discussed and illustrated.

Algorithms↗

Sudden cardiovascular death following myocardial infarction: the importance of left ventricular systolic dysfunction and congestive heart failure.

BACKGROUND: To study the prognostic information of congestive heart failure (CHF) and left ventricular systolic dysfunction regarding sudden and non-sudden cardiovascular death (SCD and non-SCD) in patients with acute myocardial infarction (MI), as this may indicate the potential benefit of implantable defibrillators. METHODS: Data from consecutive patients with acute MI screened in 1990-92 for the TRAndolapril Cardiac Evaluation (TRACE) study were entered into a registry. A total of 5502 patients were alive 30 days after the MI and were followed for up to 4 years with respect to cause of death. SCD was defined as cardiovascular death within 1 h of onset of symptoms. An echocardiography was performed 1-6 days after the admission and evaluated centrally using the wall motion index (WMI). RESULTS: Half of the patients had CHF and 17% of the patients had WMI < or =1.0 (corresponding to an ejection fraction < or =0.30). During follow-up 431 patients died from SCD and 606 from non-SCD. The risk ratios for SCD and non-SCD associated with WMI < or =1.0 were 3.17 and 2.95, transient CHF 2.01 and 1.46, and permanent CHF 3.71 and 4.42, respectively. No risk factor was a specific marker of SCD or non-SCD. The 3-year probability of SCD was 7.9% for patients with transient CHF, 13.3% for permanent CHF, and 15.5% for WMI < or =1.0. CONCLUSIONS: CHF and low WMI identify a relevant proportion of patients with MI who are at high absolute risk of SCD. This study indicates the relevance of defibrillators in consecutive post-MI patients with left ventricular dysfunction or clinical signs of heart failure.

Aged↗

Explained variation and predictive accuracy in general parametric statistical models: the role of model misspecification.

When studying a regression model measures of explained variation are used to assess the degree to which the covariates determine the outcome of interest. Measures of predictive accuracy are used to assess the accuracy of the predictions based on the covariates and the regression model. We give a detailed and general introduction to the two measures and the estimation procedures. The framework we set up allows for a study of the effect of misspecification on the quantities estimated. We also introduce a generalization to survival analysis.

Female↗

SAS macros for estimation of the cumulative incidence functions based on a Cox regression model for competing risks survival data.

When considering competing risks survival data, the cause specific hazard functions are often modelled by the proportional hazards Cox regression model. First, we present how to estimate the parameters in this model when some of the covariates are allowed to have exactly the same effect on several causes of failure. In many cases, the focus is not on the parameter estimates, but rather on the probability of observing a failure from a specific cause for individuals with specified covariate values. These probabilities, the cumulative incidences, are not simple functions of the parameters and they are, so far, not provided by the standard statistical software packages. We present two SAS macros: a SAS macro named CumInc for estimation of the cumulative incidences and a SAS macro named CumIncV for estimation of the cumulative incidences and the variances of the estimated cumulative incidences. The use of the macros is demonstrated through an example.

Proportional Hazards Models↗

Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia.

PURPOSE: Thioguanine nucleotides (TGNs) mediate the cytotoxicity of mercaptopurine (MP). Methylated MP metabolites (formed by thiopurine methyltransferase [TPMT]) and methotrexate (MTX) polyglutamates can inhibit de novo purine synthesis. We explored whether dose adjustment of MP and MTX by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E-MTX (pharmacology group), or by WBC only (control group). RESULTS: After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P =.00003), high WBC at diagnosis (P =.03), pharmacology arm (6.6 times increased relapse hazard for girls), high TPMT activity (P =.002), and high average neutrophil counts during maintenance therapy (P =.0009), with a significant interaction between sex and randomization group (P =.0007). For girls, the relapse risk was 5% in the control group and 19% in the pharmacology group (P =.001) because of an increased relapse hazard during the first year after cessation of therapy. TPMT activity was the most significant predictor of relapses among girls in the pharmacology arm (P <.0001). Overall, the TPMT activity was higher for patients who relapsed after cessation of therapy compared with those who stayed in remission (girls 19.5 v 17.4 U/mL, P =.03; boys 19.3 v 18.0 U/mL, P =.04). CONCLUSION: Adding pharmacologically guided treatment intensification to dose adjustments by blood counts may not be warranted for girls, whereas new approaches to optimize maintenance therapy are needed for boys.

Administration, Oral↗

Competing risks as a multi-state model.

This paper deals with the competing risks model as a special case of a multi-state model. The properties of the model are reviewed and contrasted to the so-called latent failure time approach. The relation between the competing risks model and right-censoring is discussed and regression analysis of the cumulative incidence function briefly reviewed. Two real data examples are presented and a guide to the practitioner is given.

Animals↗