A hierarchical frailty model applied to two-generation melanoma data

We present a hierarchical frailty model based on distributions derived from non-negative Lévy processes. The model may be applied to data with several levels of dependence, such as family data or other general clusters, and is an alternative to additive frailty models. We present several parametric examples of the model, and properties such as expected values, variance and covariance. The model is applied to a case-cohort sample of age at onset for melanoma from the Swedish Multi-Generation Register, organized in nuclear families of parents and one or two children. We compare the genetic component of the total frailty variance to the common environmental term, and estimate the effect of birth cohort and gender. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Heterogeneity in multistage carcinogenesis and mixture modeling

Carcinogenesis is commonly described as a multistage process, in which stem cells are transformed into cancer cells via a series of mutations. In this article, we consider extensions of the multistage carcinogenesis model by mixture modeling. This approach allows us to describe population heterogeneity in a biologically meaningful way. We focus on finite mixture models, for which we prove identifiability. These models are applied to human lung cancer data from several birth cohorts. Maximum likelihood estimation does not perform well in this application due to the heavy censoring in our data. We thus use analytic graduation instead. Very good fits are achieved for models that combine a small high risk group with a large group that is quasi immune

Matched Ascertainment of Informative Families for Complex Genetic Modelling

Family data are used extensively in quantitative genetic studies to disentangle the genetic and environmental contributions to various diseases. Many family studies based their analysis on population-based registers containing a large number of individuals composed of small family units. For binary trait analyses, exact marginal likelihood is a common approach, but, due to the computational demand of the enormous data sets, it allows only a limited number of effects in the model. This makes it particularly difficult to perform joint estimation of variance components for a binary trait and the potential confounders. We have developed a data-reduction method of ascertaining informative families from population-based family registers. We propose a scheme where the ascertained families match the full cohort with respect to some relevant statistics, such as the risk to relatives of an affected individual. The ascertainment-adjusted analysis, which we implement using a pseudo-likelihood approach, is shown to be efficient relative to the analysis of the whole cohort and robust to mis-specification of the random effect distribution

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Risk adjustment of health-care performance measures in a multinational register-based study: A pragmatic approach to a complicated topic

Objectives: Health-care performance comparisons across countries are gaining popularity. In such comparisons, the risk adjustment methodology plays a key role for meaningful comparisons. However, comparisons may be complicated by the fact that not all participating countries are allowed to share their data across borders, meaning that only simple methods are easily used for the risk adjustment. In this study, we develop a pragmatic approach using patient-level register data from Finland, Hungary, Italy, Norway, and Sweden. Methods: Data on acute myocardial infarction patients were gathered from health-care registers in several countries. In addition to unadjusted estimates, we studied the effects of adjusting for age, gender, and a number of comorbidities. The stability of estimates for 90-day mortality and length of stay of the first hospital episode following diagnosis of acute myocardial infarction is studied graphically, using different choices of reference data. Logistic regression models are used for mortality, and negative binomial models are used for length of stay. Results: Results from the sensitivity analysis show that the various models of risk adjustment give similar results for the countries, with some exceptions for Hungary and Italy. Based on the results, in Finland and Hungary, the 90-day mortality after acute myocardial infarction is higher than in Italy, Norway, and Sweden. Conclusion: Health-care registers give encouraging possibilities to performance measurement and enable the comparison of entire patient populations between countries. Risk adjustment methodology is affected by the availability of data, and thus, the building of risk adjustment methodology must be transparent, especially when doing multinational comparative research. In that case, even basic methods of risk adjustment may still be valuable

Performance comparison of hip fracture pathways in two capital cities: Associations with level and change of integration.

Finland and Norway have health care systems that have a varying degree of vertical integration. In Finland the financial responsibility for all patient treatment is placed at the municipal level, while in Norway the responsibility for patients is divided between the municipalities (primary and long-term care) and state-owned hospitals. From 2012, the Norwegian system became more vertically integrated following the introduction of the Coordination Reform. The aim of the paper is to analyse the associations between different modes of integration and performance indicators. The data included operated hip fracture patients from the years 2009– 2014 residing in the cities of Oslo and Helsinki. Data from routinely collected national registers, also including data from primary health and long-term-care services, were linked. Performance indicators were compared at baseline (before the Coordination Reform, i.e., 2009–2011), and trends were described and analysed by difference-in-difference methods. The baseline study indicated that hip fracture patients in Oslo, compared with those in Helsinki, had longer stays in acute hospitals. They used less institutional care outside of hospitals as well as more GP services and fewer other outpatient services. Mortality was lower, and the probability of being discharged to home within 90 days from the index day was higher. After the Coordination Reform, the length of stay in hospital was shorter and the length of the first institutional episode in Oslo was longer than before the Reform, demonstrating that the shorter hospital stays were more than compensated for by longer stays in long-term-care institutions. The number of patients institutionalised 90 days from the index day increased and the number of patients discharged to home within 90 days from the index day decreased in Oslo after the Reform while the opposite trends were observed in Helsinki. After the Reform, the performance differences between the two regions had decreased