Generating Survival Times to Simulate Cox Proportional Hazards Models

This paper discusses techniques to generate survival times for simulation studies regarding Cox proportional hazards models. In linear regression models, the response variable is directly connected with the considered covariates, the regression coefficients and the simulated random errors. Thus, the response variable can be generated from the regression function, once the regression coefficients and the error distribution are specified. However, in the Cox model, which is formulated via the hazard function, the effect of the covariates have to be translated from the hazards to the survival times, because the usual software packages for estimation of Cox models require the individual survival time data. A general formula describing the relation between the hazard and the corresponding survival time of the Cox model is derived. It is shown how the exponential, the Weibull and the Gompertz distribution can be used to generate appropriate survival times for simulation studies. Additionally, the general relation between hazard and survival time can be used to develop own distributions for special situations and to handle flexibly parameterized proportional hazards models. The use of other distributions than the exponential distribution only is indispensable to investigate the characteristics of the Cox proportional hazards model, especially in non-standard situations, where the partial likelihood depends on the baseline hazard

Bias of Maximum-Likelihood estimates in logistic and Cox regression models: A comparative simulation study

Parameter estimates of logistic and Cox regression models are biased for finite samples. In a simulation study we investigated for both models the behaviour of the bias in relation to sample size and further parameters. In the case of a dichotomous explanatory variable x the magnitude of the bias is strongly influenced by the baseline risk defined by the constants of the models and the risk resulting for the high risk group. To conduct a direct comparison of the bias of the two models analyses were based on the same simulated data. Overall, the bias of the two models appear to be similar, however, the Cox model has less bias in situations where the baseline risk is high

Decreasing sperm quality: a global problem?

<p>Abstract</p> <p>Background</p> <p>Carlsen and coworkers (1992) reviewed 61 heterogeneous observational studies on semen quality published between 1938 and 1990. This review indicates that mean sperm density decreased significantly between 1940 and 1990. An extended meta-analysis with 101 studies confirmed a decline in sperm density for the period from 1934 to 1996 (2000). The key message of the meta-analyses is that sperm counts have decreased globally by about 50% over the past decades. This assessment has been questioned.</p> <p>Discussion</p> <p>A major methodological problem of the meta-analysis is the use of data collected in different countries, at different times, on different populations and with different methods of semen analysis. Furthermore, the results of studies concerning semen analysis are frequently biased e.g. by selection criteria of volunteers. In most studies on human semen characteristics the populations under study are insufficiently defined and the study participants are not a representative population sample. The incidence of testicular cancer has increased in Caucasian men worldwide. The investigation of common risk factors for male reproductive disorders requires well designed epidemiological studies and the collection of individual data.</p> <p>Summary</p> <p>Former meta-analyses of sperm count data show a global downward trend. This conclusion should be interpreted with caution. The included studies are of great heterogeneity due to geographical and/or ethnical variation, different study designs and different methodological standards. Population-based prospective studies are needed to investigate secular trends in male reproductive disorders.</p

The Generalized Estimating Equations in the Past Ten Years: An Overview and A Biomedical Application

The Generalized Estimating Equations (GEE) proposed by Liang and Zeger (1986) have found considerable attention in the last years and several extensions have been proposed. This paper will give a more intuitive description how GEE have been developed during the last years. Additionally we will describe the advantages and disadvantages of the different parametrisations that have been proposed in the literature. We will also give a brief review of the literature available on this topic. [ Published in: Biometrical Journal 40 (2), 115-139

Familial Associations of Lipid Profiles: A Generalised Estimating Equations Approach

Elevated plasma levels of apolipoproteins A1 (apoA1) and B (apoB) are important protective factors and risk factors, respectively, for atherosclerosis and coronary heart disease. It is well known that both apoA1 and apoB reveal strong familial aggregation. Our goal was to investigate whether exogenous variables influence these associations. We used marginal regression models for the mean and association structure (Generalised Estimating Equations 2; GEE2) to analyse data from 1435 family members within 469 families of different sizes included in the Donolo-Tel Aviv Three-Generation Offspring Study. The usual robust variance matrix was approximated by extensions of jackknife estimators of variance to GEE2 models. Upon use of this approach estimation of standard errors in models with quite complex correlation structures was possible. All analyses were easily carried out using a menu-driven stand-alone software tool for marginal regression modelling. We demonstrate that a variety of hypotheses can be tested using Wald statistics by modelling regression matrices for the association structure. We show that correlation for apoB between parent-offspring pairs increased with decreasing age difference and that pairs with individuals of the same gender had more similar apoA1 levels than individuals of different gender. Associations between different relative pairs did not all agree with those expected from differences in kinship coefficients. The analysis using GEE2 models revealed structures that would not have been detected by other models and should therefore be used in addition to traditional approaches of analysing family data. GEE2 should be considered a standard method for the investigation of familial aggregation. [ Published in: Statistics in Medicine 19, Issue 24, 3345-3357

Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study

<p>Abstract</p> <p>Aim</p> <p>To investigate the cancer risk among residents of Rhineland-Palatinate winegrowing communities in an ecological study.</p> <p>Methods</p> <p>On the basis of the Rhineland-Palatinate cancer-registry, we calculated age-adjusted incidence rate ratios for communities with a medium area under wine cultivation (>5 to 20 percent) and a large area under wine cultivation (>20 percent) in comparison with communities with a small area under wine cultivation (>0 to 5 percent). In a side analysis, standardized cancer incidence ratios (SIR) were computed separately for winegrowing communities with small, medium and large area under wine cultivation using estimated German incidence rates as reference.</p> <p>Results</p> <p>A statistically significant positive association with the extent of viniculture can be observed for non-melanoma skin cancer in both males and females, and additionally for prostate cancer, bladder cancer, and non-Hodgkin lymphoma in males, but not in females. Lung cancer risk is significantly reduced in communities with a large area under cultivation. In the side-analysis, elevated SIR for endocrine-related tumors of the breast, testis, prostate, and endometrium were observed.</p> <p>Conclusion</p> <p>This study points to a potentially increased risk of skin cancer, bladder cancer, and endocrine-mediated tumors in Rhineland-Palatinate winegrowing communities. However, due to the explorative ecologic study design and the problem of multiple testing, these findings are not conclusve for a causal relationship.</p

Influence of operative strategy for the aortic arch in DeBakey type I aortic dissection: Analysis of the German Registry for Acute Aortic Dissection Type A

ObjectivePatients treated with an extensive approach including total aortic arch replacement for acute aortic dissection type A may have a favorable long-term prognosis by treating the residual false lumen. Our goal was to analyze the operative strategy for treatment of type I DeBakey aortic dissection from the German Registry for Acute Aortic Dissection Type A (GERAADA) data.MethodsA total of 658 patients with type I DeBakey aortic dissection and entry only in the ascending aorta were identified in the GERAADA. Patients in group A underwent replacement of the ascending aorta with hemiarch replacement. Patients in group B received extensive treatment with total arch replacement or conventional or frozen elephant trunk.ResultsA total of 518 patients in group A and 140 patients in group B were treated. There was an overall 30-day mortality of 20.2% (n = 133). Group A had a slightly lower rate of mortality with 18.7% (n = 97) compared with 25.7% for group B (n = 36), but with no statistical significant difference (P = .067). The onset of new neurologic deficit (13.6% in group vs 12.5% in group B, P = .78) and new malperfusion deficit (8.4% in group A vs 10.7% in group B, P = .53) showed no statistical difference.ConclusionsOn analysis of the GERAADA data, it seems that a more aggressive approach of aortic arch treatment can be applied without higher perioperative risk even in the onset of acute aortic dissection type A. Long-term follow-up data analysis will be necessary to offer the optimal surgical strategy for different patient groups

Strengthening health data on a rare and heterogeneous disease: sarcoma incidence and histological subtypes in Germany

Background: The population-based incidence of sarcoma and its histological subtypes in Germany is unknown. Up-to-date information on a disease with an incidence comparable to other cancer entities is of high public health relevance. The aim of this study was to determine this incidence and to detect significant changes in incidence trends using data from German epidemiological cancer registries. Methods: Pooled data from the German Centre for Cancer Registry Data with a primary diagnosis occurring in 2013 were used. To date, this is the latest data on cancer incidence available for Germany. All German cancer registries with sufficient completeness were included (10 out of 11), covering a population of 70.0 million people, representing 87% of the German population. All malignant sarcomas according to the RARECARE Project and the WHO classification 2002 were considered for analysis and, above all, gastrointestinal stromal tumours (GIST) of uncertain behaviour. Sensitivity analysis was performed excluding certain histologies. Results: The analysis included 3404 cases in men and 3442 cases in women diagnosed in 2013. The age adjusted sarcoma incidence (European standard) was 7.4 (men) and 6.6 (women) per 100,000 inhabitants. About 70% of sarcomas were soft tissue sarcomas, about 22% GIST, and about 9% bone sarcomas. The most common histological subtypes besides GIST were fibrosarcomas (14%) and liposarcomas (12%) in men and complex mixed and stromal neoplasms (22%), non-uterine leiomysarcomas (10%) and fibrosarcomas (9%) in women. Considering the trend for the years of diagnosis 2004 to 2013, there was a significant increase in incidence for GIST while the incidence of soft tissue sarcomas (only men) as well as of bone sarcoma stayed constant over time. As to soft tissue sarcoma in women, the incidence stayed constant up to the year 2009 and significantly decreased afterwards. Conclusion: This study is the first detailed analysis of a German-wide population-based sarcoma incidence showing results comparable to the incidence detected in the RARECARE Project

The ophthalmic branch of the Gutenberg Health Study: study design, cohort profile and self-reported diseases

This paper describes the study design, methodology, cohort profile and self-reported diseases in the ophthalmological branch of the Gutenberg Health Study (GHS).The GHS is an ongoing, prospective, interdisciplinary, single-center, population-based cohort study in Germany. The main goals of the ophthalmological section are to assess the prevalence and incidence of ocular diseases and to explore risk factors, genetic determinants and associations with systemic diseases and conditions. The eye examination at baseline included a medical history, self-reported eye diseases, visual acuity, refractive errors, intraocular pressure, visual field, pachymetry, keratometry, fundus photography and tear sampling. The 5-year follow-up visit additionally encompassed optical coherence tomography, anterior segment imaging and optical biometry. The general examination included anthropometry; blood pressure measurement; carotid artery ultrasound; electrocardiogram; echocardiography; spirometry; cognitive tests; questionnaires; assessment of mental conditions; and DNA, RNA, blood and urine sampling.Of 15,010 participants (aged 35-74 years at the time of inclusion), ocular data are available for 14,700 subjects (97.9%). The mean visual acuity (standard deviation), mean spherical equivalent, median decimal visual acuity, and mean intraocular pressure were 0.08 (0.17) logMar, -0.42 (2.43) diopters, 0.9 and 14.24 (2.79) mm Hg, respectively. The frequencies of self-reported strabismus, glaucoma, surgery for retinal detachment and retinal vascular occlusions were 2.7%, 2.3%, 0.2% and 0.4%, respectively.The GHS is the most extensive dataset of ophthalmic diseases and conditions and their risk factors in Germany and one of the largest cohorts worldwide. This dataset will provide new insight in the epidemiology of ophthalmic diseases and related medical specialties

Chronic health conditions and school performance in first graders : a prospective cohort study

Objective Children with chronic health conditions may perform poorer at school. Associations may be confounded by numerous social factors. We aimed to estimate the effects of a chronic health condition on overall school performance in first graders with an emphasis on rigorous adjustment for potential confounders. Methods A population-based cohort study was performed in the area of Mainz-Bingen (Germany). In 2015 all preschoolers were approached and the presence of a chronic health condition was assessed by parental questionnaires and preschool health examination data. The identification of a chronic health condition was based on special health care needs and presence of a doctor’s diagnosis out of 24 school-relevant diseases. At the end of the first school year, overall school performance was assessed by teachers and rated on a 5-item scale ranging from -10 to 10. Results Of 3683 children approached, 2003 were enrolled. Overall school performance was available for 1462 children (51% boys). Of these, 52% suffered from a chronic health condition. Compared to children without a chronic health condition, children with special health care needs (15%) performed worse at school (adjusted mean difference: -0.95, 95% CI: [-1.55; -0.35], P = 0.002). Children with a doctor’s diagnosis but without special health care needs (37%) did not perform worse at school. The effect was further analysed considering the extent of special health care needed. Conclusions Chronic health conditions affect overall school performance early in primary school. To identify academically at-risk children, a chronic health condition identification based on special health care needs may be used