Mette Gerster

SAS and R functions to compute pseudo-values for censored data regression

Recently, in a series of papers, a method based on pseudo-values has been proposed for direct regression modeling of the survival function, the restricted mean and cumulative incidence function with right censored data. The models, once the pseudo-values have been computed, can be fit using standard generalized estimating equation software. Here we present SAS macros and R functions to compute these pseudo-values. We illustrate the use of these routines and show how to obtain regression estimates for a study of bone marrow transplant patients.

Breast cancer after bilateral risk-reducing mastectomy

Skytte A‐B, Crüger D, Gerster M, Lænkholm A‐V, Lang C, Brøndum‐Nielsen K, Andersen MK, Sunde L, Kølvraa S, Gerdes A‐M. Breast cancer after bilateral risk‐reducing mastectomy.

Preterm Birth and Birthweight-for-Gestational Age among Immigrant Women in Denmark 1978–2007: A Nationwide Registry Study

BACKGROUND We sought to examine whether age at immigration and length of residence were associated with preterm and small-for-gestational age (SGA) delivery among immigrant women in Denmark. METHODS We included all live singleton deliveries from Danish-born women (1626880) and women from the five largest immigrant groups (68936) from 1978 to 2007. Data from the Danish Medical Birth Registry were linked to: parental country of origin, length of residence and age at immigration. Linear and logistic regression models were used to estimate absolute and relative differences with Danish-born women as the reference group. RESULTS All immigrant groups had an increased risk of SGA delivery with the highest risk among Lebanese-, Somali- and Pakistani-born women: risk differences (RDs) and 95% confidence intervals [CI] per 1000 deliveries of 50.2 [95% CI 43.7, 56.7], 70.1 [95% CI 62.2, 77.9] and 85.7 [95% CI 78.5, 92.9]. Turkish- and Pakistani-born women had increased RDs of 1.8 [95% CI 0.5, 3.1] and 2.2 [95% CI 0.1, 4.2] for very preterm and RDs of 3.5 [95% CI 0.9, 6.1] and 10.2 [95% CI 5.9, 14.5] for moderate preterm delivery. Lebanese-born women had a decreased risk of very preterm delivery, RD of -1.9 [95% CI -3.5, -0.3] and Somali-born women a lower risk of moderate preterm delivery, RD of -7.8 [-12.0, -3.6]. No differences were seen for the remaining groups. The association with length of residence for most immigrant groups was U-shaped, with highest risks among recent and long-term residents. CONCLUSION Immigration was more strongly related to SGA than to preterm delivery. Observed differences in birth outcomes varied by age at immigration and length of residency in Denmark.

Are the educational differences in incidence of cardiovascular disease explained by underlying familial factors? A twin study

To isolate the effect of education from the influence of potential underlying factors, we investigated the association of education with the risk of cardiovascular disease (CVD) and ischemic heart disease (IHD) using twin data to adjust for familial factors shared within twins, including genetic make-up and childhood environment. The study was based on data from the Danish Twin Registry linked to administrative and heath registers in Statistics Denmark. A total of 11,968 monozygotic and 20,464 dizygotic same sexed twins were followed from 1980 to 2009, including more than 8000 events of CVD. Unpaired and intra-pair analyses were compared. In the unpaired analyses, an inverse educational gradient in CVD- and IHD risk was observed. This association was not replicated in the intra-pair analyses that control for shared familial factors exploiting that twins share their intrauterine- and childhood environment and are matched partly or fully on genetic setup. The attenuation of association of education with CVD and IHD in the intra-pair analyses suggests that shared familial factors account for a substantial part of the observed association of education with CVD and IHD in Denmark.

Does the association of education with breast cancer replicate within twin pairs? A register-based study on Danish female twins.

Background:A positive association between socio-economic position and breast cancer has been widely observed, but not hitherto within twin pairs, where shared familial factors were adjusted for.Methods:We used data on education and other factors from the Danish Twin Registry, The Danish Cancer Registry, and official registers on a total of 16 310 twins. Unpaired and intrapair Cox regression analyses were compared.Results:In the unpaired analysis, an educational gradient in breast cancer risk was found. Similar results were seen in the intrapair analyses of all twins, although no longer statistically significant. When intrapair analyses were stratified on zygosity, the effect of education was attenuated in the monozygotic twins.Conclusion:The main findings support an effect of education beyond shared familial factors.

Are low Danish fertility rates explained by changes in timing of births

Aims: The most commonly used indicator of fertility, the period total fertility rate (TFRp), tends to underestimate actual fertility when women delay childbearing. The objective of this study was to examine to which extent fluctuations in Danish fertility rates result from changes in timing of births and, thus, whether the conventional TFRp is a distorted indicator of fertility quantum. In addition, we investigated whether such changes in timing explained the observed regional differences in the TFRp in Denmark. Methods: The study applied age-, period-, county-, and parity-specific data from the Danish Fertility of Women and Couples Dataset, 1980-2001. We evaluated fluctuations in period fertility rates by the tempo-adjusted TFR′ - a proposed variant of the conventional TFRp taking period changes in timing of births into account. Tempo-effects were given by the difference between TFRp and TFR′ , and these period measures were compared to actual cohort fertility. Results: Mean age at childbearing increased with more than 3 years over the period 1980-2001 leading to considerable differences between TFRp and TFR′ . A tempo-effect of up to 0.347 children per woman was observed. Comparisons with actual cohort fertility showed consistency with the TFR′. However, tempo-adjustment did not attenuate observed regional differences. Conclusion: This study indicates that the conventional TFRp consistently underestimates the fertility quantum in periods characterized by changes in timing of births, and that the TFR′ generally provides good indication of actual cohort quantum for the period in question. Considerable tempo-effects were observed within counties; however, differences between regions were not explained by changes in timing of births.

Matched survival data in a co-twin control design

When using the co-twin control design for analysis of event times, one needs a model to address the possible within-pair association. One such model is the shared frailty model in which the random frailty variable creates the desired within-pair association. Standard inference for this model requires independence between the random effect and the covariates. We study how violations of this assumption affect inference for the regression coefficients and conclude that substantial bias may occur. We propose an alternative way of making inference for the regression parameters by using a fixed-effects models for survival in matched pairs. Fitting this model to data generated from the frailty model provides consistent and asymptotically normal estimates of regression coefficients, no matter whether the independence assumption is met.

Are familial factors underlying the association between socioeconomic position and prescription medicine? A register-based study on Danish twins

Objectives Although well established, the association between socioeconomic position and health and health behaviour is not clearly understood, and it has been speculated that familial factors, for example, dispositional factors or exposures in the rearing environment, may be underlying the association. The objective was to compare prescription fillings within twin pairs who are partly or fully genetically identical and share childhood exposures. Design Twin cohort study. Setting Denmark. Participants Data from the Danish Twin Registry were linked to registers in Statistics Denmark and the Danish Registry of Medicinal Product statistics. A total of 8582 monozygotic (MZ) and 15 788 dizygotic same sex (DZSS) twins were included. Outcome measures Number of prescription fillings during follow-up (1995–2005) was analysed according to education and income. Results of unpaired and intrapair analyses were compared. Results An inverse social gradient in filling of prescriptions for all-purpose and system-specific drugs was observed in the unpaired analyses. In the intrapair analyses, associations were attenuated some in DZSS and more in MZ twins. Filling of drugs targeting the nervous system was still strongly associated with income in the intrapair analyses. Conclusions Familial factors seem to account for part of the observed social inequality in filling of prescription medicine.