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Odd O Aalen

Publications and source records attributed to Odd O Aalen.

14 recordsLinked to original sources
PubMed2006

Frailty modelling of colorectal cancer incidence in Norway: indications that individual heterogeneity in risk is related to birth cohort.

Some cancer types level off or decrease in incidence at older age groups, not following the Weibull hazard rate. This stagnation can be explained by the frailty model, which describes the population effect of mixing individuals who are susceptible, with high risk of cancer, with those that are "non-susceptible", with a low risk of cancer even in the oldest age groups. The aim of the study was to apply a frailty model on colorectal cancer incidence data for the Norwegian population aged 40-99 years, diagnosed 1956-2000. The model provided an acceptable fit to the data. The estimated proportion of susceptibles increased from about 5% to about 24% from the first cohort (1851-1855) to the last cohort (1946-1950), in line with the rise in incidence of the disease during this period. According to the frailty modelling, the estimated number of genetic events necessary for a malignant lesion to develop in the colorectum is seven to eight, which accords with the present knowledge regarding colorectal carcinogenesis. The frailty phenomenon may thus be present in this cancer form. The findings indicate that it is possible to model the development of colorectal cancer in the population based on large heterogeneity in risk between individuals, in such a manner that a small group of individuals are susceptible to develop the disease, whereas the remaining majority have a low susceptibility.

Adult↗
PubMed2006

Dynamic path analysis-a new approach to analyzing time-dependent covariates.

In this article we introduce a general approach to dynamic path analysis. This is an extension of classical path analysis to the situation where variables may be time-dependent and where the outcome of main interest is a stochastic process. In particular we will focus on the survival and event history analysis setting where the main outcome is a counting process. Our approach will be especially fruitful for analyzing event history data with internal time-dependent covariates, where an ordinary regression analysis may fail. The approach enables us to describe how the effect of a fixed covariate partly is working directly and partly indirectly through internal time-dependent covariates. For the sequence of times of event, we define a sequence of path analysis models. At each time of an event, ordinary linear regression is used to estimate the relation between the covariates, while the additive hazard model is used for the regression of the counting process on the covariates. The methodology is illustrated using data from a randomized trial on survival for patients with liver cirrhosis.

Aged↗
PubMed2006

[Urine peptide patterns in children with milder types of autism].

BACKGROUND: Autism is a severe developmental disorder. The condition is probably not homogenous. Elevated urine peptides have been found in individuals affected by autism spectrum disorders. This finding may be explained by characteristics of the samples studied. Autistic children without mental retardation (high-functioning autism) or mild mental retardation may represent a more homogenous group among those suffering from autism spectrum disorders. The purpose of this study is to compare urine peptide patterns in this group of patients with healthy controls. This has never been done before. METHOD: Urine from the first miction was frozen immediately in order to inhibit bacterial growth and enzymatic degeneration. Peptides from the urine samples were later analysed by high pressure liquid chromatography (HPLC). RESULTS: No significant differences in urine peptide values were found between the autism spectrum disorders group and the controls. There was an age dependent decrease in peptides, with values decreasing with the age of the child. Three individuals in the autism group (17%) and one in the familiar control group (0.05%) had high levels of urine peptides. No one in the same age non-familiar control group had elevated levels of urine peptides. INTERPRETATION: This study shows that high-functioning autism cannot be identified by the urine peptide pattern.

Adolescent↗
PubMed2006

Dynamic analysis of recurrent event data using the additive hazard model.

We propose a method for analysis of recurrent event data using information on previous occurrences of the event as a time-dependent covariate. The focus is on understanding how to analyze the effect of such a dynamic covariate while at the same time ensuring that the effects of treatment and other fixed covariates are unbiasedly estimated. By applying an additive regression model for the intensity of the recurrent events, concepts like direct, indirect and total effects of the fixed covariates may be defined in an analogous way as for traditional path analysis. Theoretical considerations as well as simulations are presented, and a data set on recurrent bladder tumors is used to illustrate the methodology.

Biometry↗
PubMed2005

Bayesian back-calculation using a multi-state model with application to HIV.

Back-calculation is a method of obtaining estimates of the number of infections of a disease over time. Data on an endpoint of the disease, together with knowledge of the time from infection to endpoint, allows reconstruction of the incidence of infection. The technique has had much success when applied to the HIV epidemic, using incidence of AIDS diagnoses to inform past HIV infections. In recent years, the period from infection to AIDS has changed considerably due to new regimes of anti-viral therapies. This has led to attempts to use incidence of first positive HIV test as an alternative basis for back-calculation. Developing on earlier work, this paper explores the feasibility of a multi-state formulation of the back-calculation method that models the disease and diagnosis processes and uses HIV diagnoses as an endpoint. Estimation is carried out in a Bayesian framework, which naturally allows incorporation of external information to inform the diagnosis probabilities. The idea is illustrated on data from the HIV epidemic in homosexuals in England and Wales.

Bayes Theorem↗
PubMed2005

A distribution for multivariate frailty based on the compound Poisson distribution with random scale.

Frailty models are often used to model heterogeneity in survival analysis. The most common frailty model has an individual intensity which is a product of a random factor and a basic intensity common to all individuals. This paper uses the compound Poisson distribution as the random factor. It allows some individuals to be non-susceptible, which can be useful in many settings. In some diseases, one may suppose that a number of families have an increased susceptibility due to genetic circumstances. Then, it is logical to use a frailty model where the individuals within each family have some shared factor, while individuals between families have different factors. This can be attained by randomizing the Poisson parameter in the compound Poisson distribution. To our knowledge, this is a new distribution. The power variance function distributions are used for the Poisson parameter. The subsequent appearing distributions are studied in some detail, both regarding appearance and various statistical properties. An application to infant mortality data from the Medical Birth Registry of Norway is included, where the model is compared to more traditional shared frailty models.

Humans↗
PubMed2005

Estimating mean sojourn time and screening test sensitivity in breast cancer mammography screening: new results.

OBJECTIVE: To assess if new screening techniques, increased use of hormone replacement therapy, or the transition from breast cancer screening trials to large scale screening programmes may influence the average time in preclinical screening detectable phase (mean sojourn time [MST]) or screening test sensitivity (STS). SETTING: Screening and interval data for 395,188 women participating in the Norwegian Breast Cancer Screening Programme (NBCSP). METHODS: Weighted non-linear least-square regression estimates using a tree step Markov chain model, and a sensitivity analysis of the possible impact by opportunistic screening between ordinary breast cancer screening rounds. RESULTS: MST was estimated to 6.1 (95% confidence interval [CI] 5.1-7.0) years for women aged 50-59 years, and 7.9 (95% CI 6.0-7.9) years for those aged 60-69 years. Correspondingly, STS was estimated to 58% (95% CI 52-64 %) and 73 % (67-78 %), respectively. Simulations revealed that opportunistic screening may give a moderate estimation bias towards higher MST and lower STS. Assuming a probable 21% higher background incidence, due to increased hormone replacement therapy use, MST estimates decreased to 3.9 and 5.0 years for the two age groups, and STS increased to 75 and 85%. CONCLUSIONS: The new estimates indicate that screening detectable phase is longer than that found in previous mammography trials/programmes, but also that the sensitivity of the screening test is lower. Overall, the NBCSP detects more cancer cases than most previous trials/programmes.

Aged↗
PubMed2004

Analysis of testicular cancer data using a frailty model with familial dependence.

Previously published papers have indicated a fairly strong familial dependence intesticular cancer patients. This is particularly evident in brothers. We have applied a frailty model with familial dependence to family data on brothers of testicular cancer patients from the Norwegian Radium Hospital. The model is a two-level frailty, with variation in susceptibility at both the family and the individual level. Specifically, the frailty variable is assumed to be compound Poisson distributed to allow individuals to be non-susceptible. The underlying Poisson parameter is gamma distributed to model how testicular cancer is distributed among families. This is an extension of a previous compound Poisson frailty model developed for individual testicular cancer data, and an alternative to traditional modelling of survival time family data. The likelihood construction and ascertainment problems are looked at in detail. To avoid ascertainment bias, the likelihood is based on the probability of observing the disease status for each brother in a family, given that at least one brother is ascertained. The estimated relative risk for brothers is 7.4. This paper expands on a previous analysis of the data by using a frailty model, which makes it possible to examine how the cancer is distributed among families. The estimated gamma-shaped parameter is 0.151 (95 per cent confidence interval 0.078-0.294), and this indicates that in order to obtain the high relative risks observed for brothers of testicular cancer patients, the distribution of susceptibility has to be strongly skewed among the families. The vast majority of families have a very low risk and a small proportion have a high risk. In addition, a quantity similar to the relative risk is derived to show that the susceptibility is skewly distributed also if the Poisson parameter is Bernoulli or stable distributed. This indicates that the results are valid also if other distributions are used to model familial dependence in the compound Poisson frailty model.

Genetic Predisposition to Disease↗
PubMed2004

Survival models based on the Ornstein-Uhlenbeck process.

When modelling survival data it may be of interest to imagine an underlying process leading up to the event in question. The Ornstein-Uhlenbeck process is a natural model to consider in a biological context because it stabilizes around some equilibrium point. This corresponds to the homeostasis often observed in biology, and also to some extent in the social sciences. First, we study the first-passage time distribution of an Ornstein-Uhlenbeck process, focussing especially on what is termed quasi-stationarity and the various shapes of the hazard rate. Next, we consider a model where the individual hazard rate is a squared function of an Ornstein-Uhlenbeck process. We extend known results on this model. The results on quasi-stationarity are relevant for recent discussions about mortality plateaus. In addition, we point out a connection to models for short-term interest rates in financial modeling.

Humans↗
PubMed2004

Frailty modelling of testicular cancer incidence using Scandinavian data.

The incidence of testicular cancer is highest among young men, and then decreases sharply with age. This points towards a frailty effect, where some men have a much greater risk of testicular cancer than the majority of the male population. Those with the highest risk get cancer, drain the group of individuals at risk, and leave a healthy male population which has approximately zero risk of testicular cancer. This leads to the observed decrease in incidence. We discuss a frailty model, where the frailty is compound-Poisson-distributed. This allows for a non-susceptible group (of zero frailty). The model is successfully applied to incidence data from the Danish and Norwegian registries. It is indicated that there was a decrease in incidence for males born during World War II in both countries. Bootstrap analysis is used to find the degree of variation in the estimates. In the Armitage-Doll multistage model, the estimated number of transitions needed for a cell to become malignant is close to 3 for non-seminomas and 4 for seminomas in both the Danish and Norwegian data. This paper demonstrates that a model including a frailty effect fits the incidence data well and gives interesting results and interpretations, although this is no proof of the effect's truth.

Adolescent↗
PubMed2004

Dynamic analysis of multivariate failure time data.

We present an approach for analyzing internal dependencies in counting processes. This covers the case with repeated events on each of a number of individuals, and more generally, the situation where several processes are observed for each individual. We define dynamic covariates, i.e., covariates depending on the past of the processes. The statistical analysis is performed mainly by the nonparametric additive approach. This yields a method for analyzing multivariate survival data, which is an alternative to the frailty approach. We present cumulative regression plots, statistical tests, residual plots, and a hat matrix plot for studying outliers. A program in R and S-PLUS for analyzing survival data with the additive regression model is available on the web site http://www.med.uio.no/imb/stat/addreg. The program has been developed to fit the counting process framework.

Biometry↗
PubMed2003

Legal access to needles and syringes/needle exchange programmes versus HIV counselling and testing to prevent transmission of HIV among intravenous drug users: a comparative study of Denmark, Norway and Sweden.

BACKGROUND: Countries have adopted different strategies to prevent the transmission of HIV among intravenous drug users. Legal access to needles and syringes/needle exchange programmes as part of such a strategy has been heavily debated. HIV counselling and testing has also been part of prevention strategies. The objective of this study was to discuss the effectiveness of legal access to needles and syringes/ needle exchange programmes versus HIV counselling and testing among intravenous drug users (IDUs) as part of HIV prevention strategies. METHODS: Differences in HIV prevention strategies in Denmark, Norway and Sweden among IDUs are described. Outcome variables of effectiveness were HIV incidence rates over time. These were estimated by back calculation methods from 1980 through 1996, using data from the national HIV and AIDS registers. RESULTS: A comparison of HIV prevention strategies in Denmark, Norway and Sweden suggests that a high level of HIV counselling and testing might be more effective than legal access to needles and syringes/needle exchange programmes. Sweden and Norway, with higher levels of HIV counselling and testing, have had significantly lower incidence rates of HIV among IDUs than Denmark where there was legal access to needles and syringes and a lower level of HIV counselling and testing. In Sweden there was no legal access to drug injection equipment. CONCLUSION: Promotion and accessibility of HIV counselling and testing among intravenous drug users should be considered in countries where such a strategy is not adopted or has low priority.

AIDS Serodiagnosis↗
PubMed2003

Resuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months.

OBJECTIVE: To follow-up children who had been resuscitated at birth with either 21% or 100% oxygen (O2). METHODS: A multicenter study with 10 participating centers recruited 609 infants to the Resair 2 study where resuscitation was performed with either 21% or 100% O2. A follow-up between ages 18 and 24 months was performed. However, during follow-up registration, it was found that 18 infants had been enrolled twice in the original Resair 2 study with different registration numbers, leaving 591 enrolled in the Resair 2 study and 410 enrolled in the 7 centers participating in the follow-up. Of these 410 infants, 79 died (76 in the neonatal and 3 in the postneonatal period). Furthermore, for 8 infants informed consent was not obtained, leaving 323 eligible for follow-up. Of these, 213 infants (66%) were followed-up: 91 (62%) had been resuscitated with 21% O2, and 122 (69%) with 100% O2. At a median age of 22 and 20 months (not significant) in the 21% and 100% groups, respectively, a simple questionnaire was filled out and neurologic assessment was performed in addition to measuring anthropometric data. RESULTS: There were no significant differences in weight, height, or head circumference between the 2 groups. Cerebral palsy developed in 10% and 7%, respectively, in the 2 groups (not significant). In total, 11 cases (12%) in the 21% versus 11 cases (9%) in the 100% O(2) group (odds ratio: 1.39, 95% confidence interval: 0.57-3.36) developed cerebral palsy and/or mental or other delay. Furthermore, it was concluded that 14 (15%) in the 21% group and 12 (10%) in the 100% group were not normal (odds ratio: 1.67, 95% confidence interval: 0.73-3.80). CONCLUSIONS: There were no significant differences in somatic growth or neurologic handicap at an age of 18 to 24 months in infants resuscitated with either 21% or 100% O2 at birth. Based on these data, resuscitation with ambient air seems to be safe, at least in most cases. More studies are needed to settle this issue.

Birth Weight↗