Biomedical subjects

Per Kragh Andersen

Publications and source records attributed to Per Kragh Andersen.

8 recordsLinked to original sources

PubMed2003

Does pregnancy induce the shedding of premalignant ovarian cells?

BACKGROUND: High parity is associated with reduced risk of ovarian cancer. One hypothesis is that pregnancy is associated with clearance of a fraction of the genetically modified (premalignant) cells from the ovaries. METHODS: We evaluated this hypothesis using a model that estimates the cell clearance fraction at first and second pregnancy according to age at pregnancy. The model was fitted using reproductive history data from a cohort of 1.5 million Danish women born between 1935 and 1978 and followed for 28.7 million person-years. During this follow-up period, 2,035 developed invasive ovarian cancer. RESULTS: We found the model to have a satisfactory fit despite the very few parameters involved. The model estimated similar cell clearance fractions for the first and second pregnancy and decreasing clearance with later age at pregnancy. CONCLUSION: The relation of pregnancy history to risk of ovarian cancer can be well described by a cell clearance model that allows the cell clearance fraction to decrease with age at pregnancy.

Adult↗

PubMed2002

Adjustment for misclassification in studies of familial aggregation of disease using routine register data.

This paper discusses the misclassification that occurs when relying solely on routine register data in family studies of disease clustering. A register study of familial aggregation of schizophrenia is used as an example. The familial aggregation is studied using a regression model for the disease in the child including the disease status of the parents as a risk factor. If all the information is found in the routine registers then the disease status of the parents is only known from the time when the register started and if this information is used unquestioningly the parents who have had the disease before this time are misclassified as disease-free. Two methods are presented to adjust for this misclassification: regression calibration and an EM-type algorithm. These methods are used in the schizophrenia example where the large effect of having a schizophrenic mother hardly shows any signs of bias due to misclassification. The methods are also studied in simulations showing that the misclassification problem increases with the disease frequency.

Adolescent↗

PubMed2002

Updating of covariates and choice of time origin in survival analysis: problems with vaguely defined disease states.

This paper discusses survival analysis based on updated covariates with focus on proportional hazard regression in situations where some disease states may be vaguely defined. Analyses of a trial in liver cirrhosis are used to motivate the discussion. We use problems caused by inclusion of recordings from unscheduled follow-ups to illustrate the importance of appropriate coding of covariates and describe how such problems may be approached using appropriately 'lagged' covariates. The choice of time origin is discussed with emphasis on situations where disease initiation is difficult to define. Simulations are used to assess the effect of an erroneously specified time origin. It is argued that age or calendar time may frequently be sensible time variables.

Cohort Studies↗

PubMed2002

Fever in pregnancy and risk of fetal death: a cohort study.

BACKGROUND: Hyperthermia acts as a teratogen in some animals where it can induce resorption of the fetus and fetal death. Fever during pregnancy, especially in the period of embryogenesis, is also suspected as being a risk factor for fetal death in human beings. We did a large cohort study in Denmark to investigate this possibility. METHODS: We interviewed 24040 women who were recruited in the first half of pregnancy to the Danish National Birth Cohort Study, and obtained information on the number of fever incidents during the first 16 weeks of pregnancy. For each fever episode, the highest measured body temperature, duration of incident, and gestational age were recorded. Outcomes of pregnancies were identified through linkage with the Civil Registration System and the National Discharge Registry. Cox's regression with time-dependent variables was used to estimate the relative risk of fetal death, taking delayed entry into account. FINDINGS: 1145 pregnancies resulted in a miscarriage or stillbirth (4.8%). During the first 16 pregnancy weeks 18.5% of the women experienced at least one episode of fever. However, we found no association between fever in pregnancy and fetal death before or after adjustment for known risk factors of fetal death (relative risk 0.95 [95% CI 0.80-1.13]). This finding was consistent irrespective of measured maximum temperature, duration and number of fever incidents, or the gestational time of the fever incident, and was observed for fetal death in all three trimesters of pregnancy. INTERPRETATION: We found no evidence that fever in the first 16 weeks of pregnancy is associated with the risk of fetal death in clinically recognised pregnancies.

Abortion, Spontaneous↗

PubMed2002

Case-control study of genetic and environmental influences on premature death of adult adoptees.

Genetic and environmental influence on risk of premature death in adulthood was investigated by estimating the associations in total and cause-specific mortality of adult Danish adoptees and their biological and adoptive parents. Among all 14,427 nonfamilial adoptions formally granted in Denmark during the period 1923 through 1947, we identified 976 case families in which the adoptee died before a fixed date. As control families, we selected 976 families where the adoptees were alive on that date, and matched to the case adoptees with regard to gender and year and month of birth. The data were viewed as a cohort of case parents and a cohort of control parents, and lifetime distributions in the two cohorts were compared using a Cox regression, stratified with regard to the matching variables: gender and year of birth. In the main analyses, the sample was restricted with regard to birth year of the adoptees, and age of transfer to the adoptive parents, and age at death was restricted to the same range for parents and offspring (25-64 years) in order to consider a symmetric lifetime distribution. This reduces the sample to 459 case families and 738 control families. Various truncations, restrictions, and stratifications were used in order to examine the robustness of the results. The results showed a higher mortality among biological parents who had children dying in the age range 25 through 64 years, and this was significant for death from natural causes, infectious causes, vascular causes, and from all causes combined. There were no significant effects for the adoptive parents. This study supports that there are moderate genetic influences on the risk of dying prematurely in adulthood, and only a small, if any, effect of the family environment.

Adoption↗

PubMed2002

Cohabitation and marital status as predictors of mortality--an eight year follow-up study.

In a follow-up study of 1265 women and men aged 50, 60 and 70 years, we analysed how mortality was associated with cohabitation status (living alone/not living alone), living with/without a partner, and marital status respectively. Data originate from a longitudinal questionnaire study of a random sample of people born in 1920, 1930 and 1940 with baseline in 1990. Survival time for all individuals were established during the next 8 years until May 1998. Multivariate Cox analysis stratified by age and gender showed that individuals living alone experienced a significantly increased mortality compared to individuals living with somebody HR = 1.42(1.04-1.95) adjusted for functional ability, self-rated health, having children, smoking, diet and physical activity. Similar analyses were performed for the variable living with/without a partner HR = 1.38(1.01-1.88) and marital status HR = 1.25(0.93-1.69), adjusted for the same covariates. Inclusion of the health behaviour variables--smoking, diet and physical activity--one by one to a model with functional ability, self-rated health and one of the three determinants (cohabitation status, living with/without partner, marital status) showed no effect on the association with mortality. Hereby, we found no evidence of an indirect effect of health behaviours on the association between living arrangements and mortality. In contrast to many previous studies, we found no significant gender and age differences in the association between living arrangement and mortality. We suggest that in future studies of social relations and mortality, cohabitation status is considered to replace marital status as this variable may account for more of the variation in mortality.

Activities of Daily Living↗

PubMed2002

Multi-state models for event history analysis.

An introduction to event history analysis via multi-state models in given. Examples include the two-state model for survival analysis, the competing risks and illness-death models, and models for bone marrow transplantation. Statistical model specification via transition intensities and likelihood inference is introduced. Consequences of observational patterns are discussed, and a real example concerning mortality and bleeding episodes in a liver cirrhosis trial is discussed.

Biometry↗

PubMed2002

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↗