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.

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.

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.

Does computer use affect the incidence of distal arm pain? A one-year prospective study using objective measures of computer use.

PURPOSE: To study how objectively recorded mouse and keyboard activity affects distal arm pain among computer workers. METHODS: Computer activities were recorded among 2,146 computer workers. For 52 weeks mouse and keyboard time, sustained activity, speed and micropauses were recorded with a software program installed on the participants' computers. Participants reported weekly pain scores via the software program for elbow, forearm and wrist/hand as well as in a questionnaire at baseline and 1-year follow up. Associations between pain development and computer work were examined for three pain outcomes: acute, prolonged and chronic pain. RESULTS: Mouse time, even at low levels, was associated with acute pain in a similar way for all the examined regions. There were no exposure-response threshold patterns. Keyboard time had no effect. Mouse and keyboard sustained activity, speed and micropauses were not risk factors for acute pain, nor did they modify the effects of mouse or keyboard time. Computer usage parameters were not associated with prolonged or chronic pain. A major limitation of the study was low keyboard times. CONCLUSION: Computer work was not related to the development of prolonged or chronic pain. Mouse time was associated with acute distal arm pain, but the impact was quite small.

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 (TFR(p)), 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 TFR(p) is a distorted indicator of fertility quantum. In addition, we investigated whether such changes in timing explained the observed regional differences in the TFR(p) 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 TFR(p) taking period changes in timing of births into account. Tempo-effects were given by the difference between TFR(p) 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 TFR(p) 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 TFR(p) 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.

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.

Non-parametric estimation and model checking procedures for marginal gap time distributions for recurrent events.

For recurrent events there is evidence that misspecification of the frailty distribution can cause severe bias in estimated regression coefficients (Am. J. Epidemiol 1998; 149:404-411; Statist. Med. 2006; 25:1672-1684). In this paper we adapt a procedure originally suggested in (Biometrika 1999; 86:381-393) for parallel data for checking the gamma frailty to recurrent events. To apply the model checking procedure, a consistent non-parametric estimator for the marginal gap time distributions is needed. This is in general not possible due to induced dependent censoring in the recurrent events setting, however, in (Biometrika 1999; 86:59-70) a non-parametric estimator for the joint gap time distributions based on the principle of inverse probability of censoring weights is suggested. Here, we attempt to apply this estimator in the model checking procedure and the performance of the method is investigated with simulations and applied to Danish registry data. The method is further investigated using the usual Kaplan-Meier estimator and a marginalized estimator for the marginal gap time distributions. We conclude that the procedure only works when the recurrent event is common and when the intra-individual association between gap times is weak.