Analysis of SF-6D Index Data: Is Beta Regression Appropriate?

AbstractBackgroundPreference-weighted index scores of health-related quality of life are commonly skewed to the left and bounded at one. Beta regression is used in various disciplines to address the specific features of bounded outcome variables such as heteroscedasticity, but has rarely been used in the context of health-related quality of life measures. We aimed to examine if beta regression is appropriate for analyzing the relationship between subject characteristics and SF-6D index scores.MethodsWe used data from the population-based German KORA F4 study. Besides classical beta regression, we also fitted extended beta regression models by allowing a regression structure on the precision parameter. Regression coefficients and predictive accuracy of the models were compared to those from a linear regression model with model-based and robust standard errors.ResultsThe beta distribution fitted the empirical distribution of the SF-6D index better than the normal distribution. Extended beta regression performed best in terms of predictive accuracy but confidence intervals of the fit measures suggested that no model was superior to the others. Age had a significant negative effect on the precision parameter indicating higher variation of health utilities in older age groups. The observations reporting perfect health had a high influence on model results.ConclusionsBeta regression, especially with precision covariates is a possible supplement to the methods currently used in the analysis of health utility data. In particular, it accounted for the boundedness and heteroscedasticity of the SF-6D index. A pitfall of the beta regression is that it does not work well in handling one-valued observations

Suicide Mortality in Comparison to Traffic Accidents and Homicides as Causes of Unnatural Death. An Analysis of 14,441 Cases in Germany in the Year 2010

Aim: To assess suicide mortality in comparison to traffic accidents and homicide deaths in Germany in the year 2010 and to compare years of life lost (YLL) due to these unnatural deaths. Methods: Mortality data were provided by the Federal Statistical Office giving death rates (related to 100,000 inhabitants) and proportions (related to 100 deaths of individuals) for suicide, traffic accidents and homicide as well as YLL data. Results: A total of 14,441 unnatural deaths (suicide, traffic accidents, homicide) were reported in 2010 in Germany. Of those, 10,021 subjects (69.4%) committed suicide, 3,942 (27.3%) died in traffic accidents, 478 (3.3%) were murdered. Suicide death rates were by far the highest, with rates for men (18.6) three times higher than for women (6.1). For both sexes, suicide rates increased with age, whereas suicide as a proportion of all causes of death was higher in younger age groups. In both sexes, suicide was the leading cause of YLL (men: 314 YLL, women: 90 YLL). Conclusions: Suicide is the leading cause of unnatural death and YLL. The sex- and age- specific patterns in suicide mortality call for different action plans to target high risk groups

The Outcome of Patients with Melanoma Is Not Associated with the Time Point of Lymphatic Mapping with Respect to Excisional Biopsy of the Primary Tumor

Background: Sentinel lymph node biopsy (SLNB) has become the standard care for melanoma and is an important diagnostic procedure. It has been doubted whether lymphoscintigraphy detects the correct sentinel lymph node (SLN) when excision of the tumor and SLNB are not performed at the same time. This would imply that this sequential approach may have an increased risk of undetected micrometastases resulting in a worse outcome. Objective: The purpose of the present study was to compare the outcome of melanoma patients having received excision of the tumor and SLNB either at the same time or consecutively. Methods: A total of 854 patients with cutaneous melanoma were enrolled in this retrospective study between September 1996 and November 2007. Disease-free (DFS) and overall survivals (OS) were estimated using the Kaplan-Meier product limit method and were analyzed by the log rank test. Results: No statistically significant difference was found regarding DFS, progression rates and OS in patients with primary tumor excision and SLNB at the same time compared with patients with excisional biopsy of primary tumor and SLNB at different times. Conclusion: These data suggest that excisional biopsy of the primary tumor does not prevent the correct SLN mapping in melanoma patients. Copyright (C) 2010 S. Karger AG, Base

Self-assessed quality of care among adults with diagnosed diabetes in Germany

People who have diabetes require regular medical care. The views of patients about the quality of their care are becoming increasingly relevant when it comes to chronic diseases such as diabetes. As part of the nationwide study Disease Knowledge and Information Needs – Diabetes mellitus (2017), data on self-assessed quality of care by people with diagnosed diabetes was collected using the Patient Assessment of Chronic Illness Care – DAWN short form (PACIC-DSF, scale 1 to 5) and analysed for respondents aged 45 years or above. The average score for quality of care was 2.47 and was lower for women than for men (2.33 vs 2.58). The respondents assessed the quality of their care as being worse with rising age and size of the population in their residential area. No significant differences were observed by education group. Overall, people with diabetes in Germany consider the quality of their care to be moderate, which indicates a need for improvement in care

Association between random glucose and all-cause mortality: findings from the mortality follow-up of the German National Health Interview and Examination Survey 1998

Background Random glucose is widely measured in epidemiological studies and in the clinical setting when standardized fasting protocols and oral glucose tolerance testing or HbA1c measuring are not feasible. The relationship between random glucose and all-cause mortality has hardly been studied so far and was examined in the present study. Methods We ascertained mortality status among 5955 persons aged 18–79 years and free of known diabetes when participating in the German National Health Interview and Examination Survey 1998 (mean observation time 11.7 years, 458 deaths). Cox regression was applied to analyze the association of random serum glucose with all-cause mortality taken potential confounders into account. Relative mortality risks were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs) modeling random glucose as categorical or continuous variable. Results Compared to random glucose levels of 4.3 - < 5.3 mmol/L, HRs (95% CIs) were 1.94 (0.85–4.45) for levels < 4.3 mmol/L and 1.16 (0.89–1.50), 1.20 (0.91–1.58), 1.42 (0.88–2.29), 2.02 (1.26–3.25) and 4.71 (2.20–10.10) for levels 5.3 - < 5.8, 5.8 - < 6.8, 6.8 - < 7.8, 7.8 - < 11.1 and ≥ 11.1 mmol/L, adjusted for age, sex, lifestyle, anthropometry and chronic diseases. An additional adjustment for fasting time or HbA1c yielded similar estimates. Modeling continuous random glucose by restricted cubic spline functions revealed comparable findings. Conclusions In the present epidemiological study drawn from the general population, random glucose showed a significant association with all-cause mortality, independent of main potential confounders. Thus, random glucose measures are highly relevant to health risk assessment among people without known diabetes when fasting glucose or HbA1c are difficult to obtain.Peer Reviewe

Gene-Gene Interaction between APOA5 and USF1: Two Candidate Genes for the Metabolic Syndrome

Objective: The metabolic syndrome, a major cluster of risk factors for cardiovascular diseases, shows increasing prevalence worldwide. Several studies have established associations of both apolipoprotein A5 (APOA5) gene variants and upstream stimulatory factor 1 (USF1) gene variants with blood lipid levels and metabolic syndrome. USF1 is a transcription factor for APOA5. Methods: We investigated a possible interaction between these two genes on the risk for the metabolic syndrome, using data from the German population-based KORA survey 4 (1,622 men and women aged 55-74 years). Seven APOA5 single nucleotide polymorphisms (SNPs) were analyzed in combination with six USF1 SNPs, applying logistic regression in an additive model adjusting for age and sex and the definition for metabolic syndrome from the National Cholesterol Education Program's Adult Treatment Panel III (NCEP (AIII)) including medication. Results: The overall prevalence for metabolic syndrome was 41%. Two SNP combinations showed a nominal gene-gene interaction (p values 0.024 and 0.047). The effect of one SNP was modified by the other SNP, with a lower risk for the metabolic syndrome with odds ratios (ORs) between 0.33 (95% CI = 0.13-0.83) and 0.40 (95% CI = 0.15-1.12) when the other SNP was homozygous for the minor allele. Nevertheless, none of the associations remained significant after correction for multiple testing. Conclusion: Thus, there is an indication of an interaction between APOA5 and USF1 on the risk for metabolic syndrome

Utilisation of outpatient medical services by people with diagnosed diabetes during the COVID-19 pandemic in Germany

People with diabetes regularly need outpatient medical care due to their disease and possible concomitant and secondary illnesses. Using data from the nationwide GEDA 2019/2020-EHIS survey conducted from April 2019 to September 2020, the present study examines developments in outpatient utilisation behaviour during the measures put in place to contain the SARS-CoV-2 pandemic. During the observation period, people with diabetes had a significantly higher rate of utilisation of medical services provided by general practitioners (GPs) and specialists than the population as a whole. In the spring of 2020, when the restrictions were put in place, utilisation of specialist medical services by people with diabetes decreased temporarily by 46% compared to the 2019 reference period. In contrast, no relevant decline in the utilisation of medical services provided by GPs was observed, but this could be related to adaptations of care provision through telephone consultations for people with regularly requiring GP office visits. The issue examined here requires further observations in view of the renewed containment measures

Diabetes free life expectancy and years of life lost associated with type 2 diabetes: projected trends in Germany between 2015 and 2040

Background: Type 2 diabetes (T2D) causes substantial disease burden and is projected to affect an increasing number of people in coming decades. This study provides projected estimates of life years free of type 2 diabetes (T2D) and years of life lost (YLL) associated with T2D for Germany in the years 2015 and 2040. Methods: Based on an illness-death model and the associated mathematical relation between prevalence, incidence and mortality, we projected the prevalence of diagnosed T2D using currently available data on the incidence rate of diagnosed T2D and mortality rates of people with and without diagnosed T2D. Projection of prevalence was achieved by integration of a partial differential equation, which governs the illness-death model. These projected parameters were used as input values to calculate life years free of T2D and YLL associated with T2D for the German population aged 40 to 100 years in the years 2015 and 2040, while accounting for different assumptions on future trends in T2D incidence and mortality. Results: Assuming a constant incidence rate, women and men at age 40 years in 2015 will live approximately 38 years and 33 years free of T2D, respectively. Up to the year 2040, these numbers are projected to increase by 1.0 years and 1.3 years. Assuming a decrease in T2D-associated excess mortality of 2% per year, women and men aged 40 years with T2D in 2015 will be expected to lose 1.6 and 2.7 years of life, respectively, compared to a same aged person without T2D. In 2040, these numbers would reduce by approximately 0.9 years and 1.6 years. This translates to 10.8 million and 6.4 million YLL in the German population aged 40–100 years with prevalent T2D in 2015 and 2040, respectively. Conclusions: Given expected trends in mortality and no increase in T2D incidence, the burden due to premature mortality associated with T2D will decrease on the individual as well as on the population level. In addition, the expected lifetime without T2D is likely to increase. However, these trends strongly depend on future improvements of excess mortality associated with T2D and future incidence of T2D, which should motivate increased efforts of primary and tertiary prevention.Peer Reviewe

Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model

Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n= 1522, age 32–72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient = 0.56 standard error (SE) =0.10, p (Bonferroni) = 0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p =0.083) and a significant interaction among women (p =0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β= 0.005, SE= 0.002, p=0.021, n= 131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p= 0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders

Excess mortality in adults with documented diabetes in Germany: routine data analysis of all insurance claims in Germany 2013–2014

Objectives: Little is known about the age-specific excess mortality pattern of people with diagnosed diabetes in Germany. Thus, our goal was to determine the excess mortality in diagnosed diabetes overall and stratified by age and sex based on claims data. Design: Routine data analysis using a claims dataset from all statutory health-insured persons in Germany in 2013, which accounts for about 90% of the population. Participants: We included persons who lived in Germany, were insured at least 360 days, were not self-paying any health services and were aged 30 years or older leading to a total number of 47.3 million insured persons for analyses. Exposure: Diabetes was determined by the International Classification of Diseases-10 codes E10–E14, which were documented in 2013 in at least two-quarters on an outpatient setting or at least once on an inpatient setting. Outcome measures: The vital status in the study population was drawn from the claims dataset for the year 2014. We derived the excess mortality estimated as an age-adjusted mortality rate ratio (MRR) by sex and for age groups using a Poisson model. Main results: We found age-adjusted MRRs (95% CI) for diabetes of 1.52 (1.51 to 1.52) for women and 1.56 (1.56 to 1.56) for men. These figures declined with increasing age and were highest for ages 30–34 years with 6.76 (4.99 to 9.15) for women and 6.87 (5.46 to 8.64) for men, and lowest for age 95 years and older with 1.13 (1.10 to 1.15) for women and 1.11 (1.05 to 1.17) for men. Conclusions: We derived deeply age-stratified figures on excess mortality in diabetes for Germany. Establishing a sustainable analysis of excess mortality is aimed at within the framework of diabetes surveillance.Peer Reviewe