Underutilization of guideline-recommended therapy in patients 80 years and older with peripheral artery diseases.

Background: Ageing is a major cardiovascular risk factor with detrimental changes that culminate in a high atherosclerotic burden. Peripheral artery disease (PAD) is a major manifestation of atherosclerosis with high mortality. Guideline-recommended treatment is essential, however implementation is inadequate. With an ageing society, age-related inequalities are important and have not been elucidated in a high-risk PAD population on a nation-wide scale. We sought to analyse outpatient treatment structures and guideline adherence in treatment of PAD patients older than 80 years. Patients and methods: The study is based on ambulatory claims data comprising 70.1 million statutorily insured patients per year in Germany from 2009 to 2018. We analysed age-related differences in prevalence, pharmacotherapy and specialized outpatient care in PAD patients. Results: Of 17,633,970 PAD patients included, 28% were older than 80 years. PAD prevalence increased between 2008 and 2018 (1.85% vs. 3.14%), with the proportion of older patients increasing by a third (24.4% vs. 31.2%). Octogenarians were undertreated regarding guideline-recommended statin pharmacotherapy compared to younger patients while antiplatelets were prescribed more often (statins 2016: 46.5% vs. 52.4%; antiplatelets 2016 30.6% vs. 29.3%; p<.05). Furthermore, octogenarians received less specialized outpatient care (angiology: 6.4% vs. 9.5%, vascular surgery: 8.1% vs. 11.8%, cardiology: 25.2% vs. 29.2%, p<.05). Conclusions: Our results demonstrate that age-related differences in pharmacotherapy and specialized outpatient care of PAD patients are evident. While overall guideline-recommended outpatient treatment is low, patients 80 years and older are less likely to receive both, leaving age-related health inequalities a challenge of our future.

[Research Data Center on Health - Vision for Further Development from the Research Perspective]. / Forschungsdatenzentrum Gesundheit ­ Vision für eine Weiterentwicklung aus Sicht der Forschung.

The German research data center for health will provide claims data of statutory health insurances. The data center was set up at the medical regulatory body BfArM pursuant to the German data transparency regulation (DaTraV). The data provided by the center will cover about 90% of the German population, supporting research on healthcare issues, including questions of care supply, demand and the (mis-)match of both. These data support the development of recommendations for evidence-based healthcare. The legal framework for the center (including §§ 303a-f of Book V of the Social Security Code and two subsequent ordinances) leaves a considerable degree of freedom when it comes to organisational and procedural aspects of the center's operation. The present paper addresses these degrees of freedom. From the point of view of researchers, ten statements show the potential of the data center and provide ideas for its further and sustainable development.

Gender Differences in Outpatient Peripheral Artery Disease Management in Germany: A Population Based Study 2009-2018.

OBJECTIVE: Peripheral artery disease (PAD) is a major risk factor for morbidity and death. Despite clear guideline recommendations regarding outpatient treatment and pharmacotherapy, implementation is inadequate. Gender differences are becoming increasingly important, especially in patients with atherosclerosis. METHODS: Gender stratified PAD prevalence and differences in treatment by specialised outpatient care and pharmacotherapy were analysed in 70.1 million statutorily insured patients/year in Germany between 2009 and 2018. This was based on claims data according to §295 of the social code (SGB V) and drug prescription data according to §300 SGB V. Diagnosis of PAD was defined according to ICD I70.2-9 coding. Statistical analysis was performed with the chi square test for trend and two way ANOVA. RESULTS: In total, 17 633 970 patients with PAD were identified, of whom 47% were female. Prevalence of PAD in Germany increased between 2009 and 2018 and was higher in male patients. Only a minority of 37.1% presented to a vascular specialist. Interestingly, female patients were both less likely to present to a vascular specialist and to receive guideline recommended pharmacotherapy. Overall prescription rates of statins and antiplatelet drugs increased between 2009 and 2018, however. PAD stages were stratified by intermittent claudication (IC) and chronic limb threatening ischaemia (CLTI). In CLTI even fewer patients received a statin, with the gender gap increasing. CONCLUSION: The results demonstrate gender based differences in pharmacotherapy and specialised outpatient care of patients with PAD. While overall outpatient treatment by vascular specialists and guideline recommended medical therapy of PAD are low, women and patients with CLTI remain undertreated.

[Outpatient pediatric care during the COVID-19 pandemic with special emphasis on screening examinations and immunizations]. / Ambulante kinder- und jugendärztliche Versorgung während der COVID-19-Pandemie unter besonderer Berücksichtigung der Inanspruchnahme von Früherkennung und Impfungen.

BACKGROUND: The COVID-19 pandemic has greatly changed the utilization of ambulatory medical care. Studies indicate that this also includes a decrease in pediatric prevention services. AIM: The aim of the study was to determine how the utilization of pediatric prevention services, in particular screening examinations and immunizations, developed over the course of the first pandemic wave until the end of September 2020 compared with the years 2015 to 2019. MATERIALS AND METHODS: A data analysis based on nationwide statutory medical claims data from the first quarter of 2015 to the third quarter of 2020 was conducted. All treatments of patients aged 0 to 17 years were included and the quarterly case numbers compared on an annual basis. By considering trends and seasonality, preventive and curative treatment cases were modelled as a time series and compared to their expected values. RESULTS AND DISCUSSION: No decreases in the quarterly numbers of screening examinations or immunizations were observed in 2020. In contrast, the number of curative pediatric cases decreased significantly in the second and third quarters of 2020 compared with the same periods of the previous years. Since there was no drop in the number of screening examinations, it should be assumed that the health problems addressed in this framework are detected in a timely manner despite the COVID-19 pandemic. However, since screenings do not cover all age groups, further investigation should be conducted to determine the health consequences of the observed decrease in curative cases.

[Good Practice Data Linkage]. / Gute Praxis Datenlinkage (GPD).

Individual data linkage of different data sources for research purposes is being increasingly used in Germany in recent years. However, generally accepted methodological guidance is missing. The aim of this article is to define such methodological standards for research projects. Another aim is to provide readers with a checklist for critical appraisal of research proposals and articles. Since 2016, an expert panel of members of different German scientific societies have worked together and developed 7 guidelines with a total of 27 practical recommendations. These recommendations include (1) research aims, questions, data sources and resources, (2) infrastructure and data flow, (3) data privacy, (4) ethics, (5) key variables and type of linkage, (6) data validation/quality assurance and (7) long-term use for future research questions. The authors provide a rationale for each recommendation. Future revisions will include any new developments in science and data privacy.

[Quo Vadis Data Linkage in Germany? An Initial Inventory]. / Quo vadis Datenlinkage in Deutschland? Eine erste Bestandsaufnahme.

In recent years, linking different data sources, also called data linkage or record linkage, to address scientific questions, is being increasingly used in Germany. However, there are very few published reports and new projects develop the necessary tools independently of each other. Therefore, a team of researchers joined together to exchange their experiences on data linkage and to give suggestions on how linkage could be done for scientists, reviewers as well as members of data privacy boards and ethics committees. It is the aim of this article to assist future projects that want to link German data on an individual level. In addition to the legal framework conditions (data privacy), also examples of types of data linkage, their fields of application und potential pitfalls as well as the methods of preventing them will be described in an application-oriented fashion.

Trends in the Diagnostic Prevalence of Mental Disorders, 2012-2022­Using Nationwide Outpatient Claims Data for Mental Health Surveillance.

BACKGROUND: Evaluations by the statutory health insurance carriers in Germany have revealed a rising prevalence of diagnoses of mental disorders, at varying levels and to varying extents. For mental health surveillance purposes, we analyzed prevalence trends across health insurance carriers, before and during the COVID-19 pandemic and stratified by diagnosis group, sex and age. METHODS: Nationwide outpatient claims data of all statutorily insured individuals for the years 2012-2022 (Nmin = 68.7 million people, Nmax = 73.7 million people) were used to determine the diagnostic prevalence of mental disorders (ICD-10 F00-F99 and five selected diagnosis groups), with stratification by sex and age. Changes over time in the spectrum of all documented mental disorders are described. RESULTS: Over the period 2012-2022, the percentage of people with outpatient diagnoses of mental disorders rose from 33.4% to 37.9% (a relative increase of 13.4%). In the selected diagnosis groups, the trends ranged from -11.6% to +115.8% and were generally steady over time, though stronger or stagnating trends were seen in some groups from 2020 onward. Diagnostic prevalence rose to a greater extent in male (+18.3%) than in female individuals (+10.8%) over the period 2012-2022. The greatest increases (> +15%) were seen among 11- to 17-year-olds and in 60- to 84-year-olds. The composition of the diagnosis spectrum was more stable in adults than in children and adolescents. CONCLUSION: Trends in diagnostic prevalence differ across mental disorders and population subgroups and have changed in some diagnosis groups since the COVID-19 pandemic. Contextualizing research is needed for a better understanding of these developments.

Spatio-Temporal Trends in the Incidence of Type 2 Diabetes in Germany.

BACKGROUND: There are no data on recent trends in the incidence rate of type 2 diabetes (T2D) in Germany. The aim of this study was to determine the sex-, age-, and region-specific trends in the T2D incidence rate between 2014 and 2019. METHODS: Based on nationwide data from statutorily insured persons in Germany, negative binomial regression models were used to analyze age- and sex-specific trends in the T2D incidence rate. Age- and sex-adjusted trends were calculated for 401 administrative districts using a Bayesian spatio-temporal regression model. RESULTS: During the period concerned, approximately 450 000 new cases of T2D were observed each year among some 63 million persons. Taking all age groups together, the incidence rate decreased in both women and men, from 6.9 (95% confidence interval [6.7; 7.0]) and 8.4 [8.2; 8.6] respectively per 1000 persons in 2014 to 6.1 [5.9; 6.3] and 7.7 [7.5; 8.0] per 1000 persons in 2019. This corresponds to an annual reduction of 2.4% [1.5; 3.2] for women and 1.7% [0.8; 2.5] for men. The incidence rate increased in the age group 20-39 years. The age- and sex-adjusted incidence rate decreased in almost all districts, although regional differences persisted. CONCLUSION: The T2D incidence rate should be closely monitored to see whether the decreasing trend continues. One must not forget that the prevalence can rise despite decreasing incidence. For this reason, the findings do not necessarily mean a decrease in the disease burden of T2D and the associated demand on healthcare resources.

Mental, Neurological, and Somatic Comorbidities and Their Treatment in Persons With Intellectual Disability.

BACKGROUND: Persons with intellectual disability (ID) often suffer from significant comorbidities. As data have been lacking until now, the present report is the first one containing outpatient data on the prevalence of ID in Germany, its comorbidities, and outpatient (drug) treatment. METHODS: This study is based on the nationwide outpatient billing data and drug prescription data of all SHI-insured adults (SHI, statutory health insurance) (age 18-109) who were seen at least once in an outpatient medical practice in 2018. Patients with at least two F70-F79 diagnoses in two quarters were included in the study group (SG) (n = 324 428). A random sample of patients without ID served as the control/comparison group (CG) (n = 648 856). The odds ratios (SG vs. CG) for comorbidities, prescriptions of selected classes of drugs, and involvement of medical specialties were each analyzed by multivariate logistic regression. RESULTS: The prevalence of ID was 0.55%. ID was found to be associated with a variety of comorbidities. The highest odds ratios [OR] were for infantile cerebral palsy (OR: 121.71; 95% confidence interval: [111.67; 132.67]), autism spectrum disorders (OR: 83.85 [75.54; 93.08]), and developmental disabilities (OR: 61.34 [58.86; 63.94]). The most frequently prescribed drug categories (as classified by the anatomic-therapeutic-chemical (ATC) convention) were psychoactive drugs (antipsychotic, anxiolytic, and hypnotic drugs and sedatives) and antiepileptic drugs (OR: 10.40 [10.27; 10.53] and 9.90 [9.75; 10.05], respectively). Both general practitioners (OR: 2.64 [2.59; 2.69]) and medical specialists were consulted by the SG more frequently than by the CG; the type of specialist most commonly consulted was in the neuropsychiatric field, i.e., a neurologist or psychiatrist (OR: 6.85 [6.77; 6.92]). CONCLUSION: A diagnosis of ID frequently appears in outpatient billing data. Future analyses should be devoted to the specific care of people with intellectual disability, who constitute an especially multimorbid and vulnerable patient group.

Income-Related Peripheral Artery Disease Treatment: A Nation-Wide Analysis from 2009-2018.

Economic status has a measurable and significant effect on cardiovascular health. Socioeconomic- and income-related disparities worsen cardiovascular risk factors. Peripheral artery disease (PAD) remains a major risk factor for morbidity and mortality. Not all patients benefit equally from recent advances in outpatient healthcare. The implementation of guideline recommendations regarding treatment is inadequate. Income-related disparities for PAD treatment are unknown. We aimed to analyse income-stratified PAD prevalence, outpatient treatment and pharmacotherapy. Associations of statutory health insurance physicians at the regional level, income-stratified PAD prevalence and differences in outpatient care and pharmacotherapy were analysed in 70.1 million statutorily insured patients/year between 2009 and 2018. Analysis was based on claims data (§295 of the social code (SGB V)) and drug-prescription data (§300 SGB V). The diagnosis of PAD was defined by ICD I70.2-9. Regional income data were derived from the German Census Bureau. PAD prevalence was higher in low-income than in high-income areas. Low-income patients more often presented to angiology outpatient care and more frequently received guideline recommended pharmacotherapy. High-income patients more often presented to outpatient vascular surgery. This was true for statins, antiplatelets, intermittent claudication and critical limb ischemia alike. These data indicate that PAD and income are associated. Regional income is related to insufficiencies in guideline-recommended treatment and contact to vascular specialists. Our results aim to encourage medical professionals to implement PAD guideline recommendations, especially in high-income areas. Further studies on associations between spatial-level income and healthcare in PAD are needed.

Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition.

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23-1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40-2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19-72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.

Peripheral artery disease in Germany (2009-2018): Prevalence, frequency of specialized ambulatory care and use of guideline-recommended therapy - A population-based study.

BACKGROUND: Peripheral artery disease (PAD) patients have high morbidity and mortality rates, demonstrating a need for improved treatment strategies. While underuse and undertreatment have been reported, there is no clear picture of patterns in population-level disease prevalence, prescription of guideline-recommended pharmacotherapy, or frequency of contact with dedicated specialists. We present population-level data on changes in prevalence, care and treatment of PAD from 2009 to 2018 in Germany. METHODS: We analyzed the ambulatory claims data for all statutorily insured patients comprising 70.1 million patients each year and 87% of the German population. Prevalence was assessed by documentation of PAD and stratified by age and sex within the 10-year study timeframe. In addition, current ambulatory care, stratified by vascular specialists (vascular surgeons or angiologists), internists, cardiologists and primary care physicians, were examined. FINDINGS: Prevalence increased from 1·85% in 2009 to 3·14% in 2018, affecting 2·3 million patients in 2018 and more males (55%) than females (45%). A low level of visits to vascular specialists, with 11·1% receiving care from vascular surgeons and 8·1% from angiologists, was shown. Moreover, analysis of guideline-recommended prescriptions revealed increasing, but still insufficient, prescription frequencies among PAD patients between 2009 and 2016, from 42·6% to 56% for statins and from 40·2% to 48·0% for antiplatelets. INTERPRETATION: Our results show that the prevalence of PAD in Germany, as assessed by outpatient PAD documentation, is increasing and PAD patients are underutilizing specialized vascular care; moreover, the prescription frequency of guideline-recommended therapies remains low. There is a clear need to improve the referral and treatment algorithms in the high-risk PAD population. FUNDING: None.

Anthropometric measures and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition.

We examined the associations of measured anthropometric factors, including general and central adiposity and height, with ovarian cancer risk. We also investigated these associations by menopausal status and for specific histological subtypes. Among 226,798 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, there were 611 incident cases of primary, malignant, epithelial ovarian cancer diagnosed during a mean 8.9 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. Compared to women with body mass index (BMI) < 25 kg/m2, obesity (BMI > or = 30 kg/m2) was associated with excess ovarian cancer risk for all women combined (HR = 1.33, 95% CI = 1.05-1.68; p(trend) = 0.02) and postmenopausal women (HR = 1.59, 95% CI = 1.20-2.10; p(trend) = 0.001), but the association was weaker for premenopausal women (HR = 1.16, 95% CI = 0.65-2.06; p(trend) = 0.65). Neither height or weight gain, nor BMI-adjusted measures of fat distribution assessed by waist circumference, waist-hip ratio (WHR) or hip circumference were associated with overall risk. WHR was related to increased risk of mucinous tumors (BMI-adjusted HR per 0.05 unit increment = 1.17, 95% CI = 1.00-1.38). For all women combined, no other significant associations with risk were observed for specific histological subtypes. This large, prospective study provides evidence that obesity is an important modifiable risk factor for epithelial ovarian cancer, particularly among postmenopausal women.

Region-specific nutrient intake patterns exhibit a geographical gradient within and between European countries.

Until recently, the study of nutrient patterns was hampered at an international level by a lack of standardization of both dietary methods and nutrient databases. We aimed to describe the diversity of nutrient patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) study at population level as a starting point for future nutrient pattern analyses and their associations with chronic diseases in multi-center studies. In this cross-sectional study, 36,034 persons aged 35-74 y were administered a single, standardized 24-h dietary recall. Intake of 25 nutrients (excluding intake from dietary supplements) was estimated using a standardized nutrient database. We used a graphic presentation of mean nutrient intakes by region and sex relative to the overall EPIC means to contrast patterns within and between 10 European countries. In Mediterranean regions, including Greece, Italy, and the southern centers of Spain, the nutrient pattern was dominated by relatively high intakes of vitamin E and monounsaturated fatty acids (MUFA), whereas intakes of retinol and vitamin D were relatively low. In contrast, in Nordic countries, including Norway, Sweden, and Denmark, reported intake of these same nutrients resulted in almost the opposite pattern. Population groups in Germany, The Netherlands, and the UK shared a fatty acid pattern of relatively high intakes of PUFA and SFA and relatively low intakes of MUFA, in combination with a relatively high intake of sugar. We confirmed large variability in nutrient intakes across the EPIC study populations and identified 3 main region-specific patterns with a geographical gradient within and between European countries.

Food intake patterns associated with carotid artery atherosclerosis in the Insulin Resistance Atherosclerosis Study.

We aimed to identify food intake patterns that operate via haemostatic and inflammatory pathways on progression of atherosclerosis among 802 middle-aged adults with baseline and 5-year follow-up ultrasound measurements of common (CCA) and internal carotid artery (ICA) intimal medial thickness (IMT). Food intake was ascertained with an FFQ. We derived food patterns using reduced rank regression (RRR) with plasminogen activator inhibitor 1 and fibrinogen as response variables. We explored the impact of various food pattern simplification approaches. We identified a food pattern characterised by higher intakes of less healthful foods (low-fibre bread and cereal, red and processed meat, cottage cheese, tomato foods, regular soft drinks and sweetened beverages) and lower intakes of more healthful foods (wine, rice and pasta, meal replacements and poultry). The pattern was positively associated with mean CCA IMT at follow-up (P = 0.0032), a 1 sd increase corresponding to an increase of 13 mum higher CCA IMT at follow-up, adjusted for demographic and cardiovascular risk factors. With increasing pattern quartile (Q), the percentage change in CCA IMT increased significantly: Q1 0.8 %; Q2 3.2 %; Q3 8.6 %; Q4 7.9 % (P = 0.0045). No clear association with ICA IMT was observed. All simplification methods yielded similar results. The present results support the contention that a pro-inflammatory and pro-thrombotic dietary pattern increases the rate of coronary artery atherosclerosis progression, independent of traditional cardiovascular risk factors. RRR is a promising and robust tool for moving beyond the previous focus on nutrients or foods into research on the health effects of broader dietary patterns.

[Prevalence Rates of Mild Cognitive Impairment and of Dementia in the German Outpatient Health Care Sector 2009-2016]. / Prävalenz von leichten kognitiven Störungen und Demenzen in der ambulanten Routineversorgung in Deutschland 2009­2016.

OBJECTIVE: In Germany, the number of patients with dementia is expected to increase from 1.7 (2017) to more than 3 million people (2050). Preventive and therapeutic measures target at early stages of dementia such as mild cognitive impairment (MCI). Aim of the study is to compare prevalence rates of MCI and dementia over time. METHODS: The study was based on the complete nation-wide outpatient claims data of the panel doctors services according to §â€Š295 SGB V. We identified prevalent patients with MCI (PwMCI) and with dementia (PwD) in the years 2009 to 2016 treated by general practitioners or neuropsychiatric specialists. RESULTS: The number of prevalent PwMCI/PwD increased from 50,760/1,014,381 (2009) to 166,919/1,416,319 (2016) and the corresponding prevalence rates from 0.13 % to 0.42 % (MCI) and from 2.52 % to 3.55 % (dementia), resp. CONCLUSION: Despite the significant prevalence gain, the number of PwMCI identified in outpatient health claims data is much lower than the expected number of 2,8 to 3,7 million people at the population level. Therefore, we anticipate a further increase in the number of PwMCI being treated in the outpatient sector over the coming years.

Good Practice Data Linkage (GPD): A Translation of the German Version.

The data linkage of different data sources for research purposes is being increasingly used in recent years. However, generally accepted methodological guidance is missing. The aim of this article is to provide methodological guidelines and recommendations for research projects that have been consented to across different German research societies. Another aim is to endow readers with a checklist for the critical appraisal of research proposals and articles. This Good Practice Data Linkage (GPD) was already published in German in 2019, but the aspects mentioned can easily be transferred to an international context, especially for other European Union (EU) member states. Therefore, it is now also published in English. Since 2016, an expert panel of members of different German scientific societies have worked together and developed seven guidelines with a total of 27 practical recommendations. These recommendations include (1) the research objectives, research questions, data sources, and resources; (2) the data infrastructure and data flow; (3) data protection; (4) ethics; (5) the key variables and linkage methods; (6) data validation/quality assurance; and (7) the long-term use of data for questions still to be determined. The authors provide a rationale for each recommendation. Future revisions will include new developments in science and updates of data privacy regulations.

A case-control study on fat-to-muscle ratio and risk of breast cancer.

Our objective was to analyze detailed anthropometric characterization for risk of breast cancer in Uruguayan women. The design was a case-control study. The setting was Pereira Rossell Women's Hospital, Montevideo, Uruguay. Subjects were 343 incident breast cancer cases and 1,042 frequency-matched healthy controls who were interviewed on menstrual and reproductive story; and a series of skin folds, circumferences, and diameters were measured to calculate fat and muscle fractions and the derived fat-to-muscle ratio (FMR). Odds ratio (ORs) coefficients were taken as estimates of relative risk derived from unconditional logistic regression. Muscle fraction was negatively associated with risk [OR for highest quartile = 0.23, 95% confidence interval (CI) = 0.15-0.34], fat fraction was positively associated (OR = 3.90, 95% CI = 2.62-5.80), and FMR was positively associated (OR = 4.45, 95% CI = 2.99-6.62). Stratified analyses by body mass index levels also showed risk increases for the highest tertiles of FMR, always displaying significant linear trends. Since increases of risk were found in overweight and in normal weight women, results suggest that fractions and amount of muscle and fat components might be risk factors for breast cancer on the basis of currently existing metabolic and immune interrelationships between adipose and muscular tissue given by glutamine, exercise-derived myokines, and other cytokines produced by these tissues.

Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case-control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.

A statistical test for the equality of differently adjusted incidence rate ratios.

An incidence rate ratio (IRR) is a meaningful effect measure in epidemiology if it is adjusted for all important confounders. For evaluation of the impact of adjustment, adjusted IRRs should be compared with crude IRRs. The aim of this methodological study was to present a statistical approach for testing the equality of adjusted and crude IRRs and to derive a confidence interval for the ratio of the two IRRs. The method can be extended to compare two differently adjusted IRRs and, thus, to evaluate the effect of additional adjustment. The method runs immediately on existing software. To illustrate the application of this approach, the authors studied adjusted IRRs for two risk factors of type 2 diabetes using data from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study from 2005. The statistical method described may be helpful as an additional tool for analyzing epidemiologic cohort data and for interpreting results obtained from Cox regression models with adjustment for different covariates.