Prevalence of current suicidal thoughts and lifetime suicide attempts in individuals with cancer and other chronic diseases in Germany: Evidence for differential associations from a representative community cohort.

BACKGROUND: Research indicates an elevated risk for suicidal thoughts and behaviors (STBs) among individuals with cancer, but community-based studies on the prevalence of STBs in comparison to the general population and other chronic diseases are lacking. METHODS: Data was drawn from the representative population-based, prospective Gutenberg Health Study (GHS). Participants (N = 12,382; age: M = 59.5, SD = 10.8; 48.9 % women) completed highly standardized medical assessments and validated questionnaires such as the PHQ-9. In addition to prevalence estimates (stratified by STBs and gender), logistic regression models were calculated (controlling for confounders). RESULTS: The sample included 1910 individuals with cancer, 8.2 % of whom reported current suicidal thoughts and 2.0 % reported lifetime suicide attempts. There was neither a significant association between a cancer diagnosis and suicidal thoughts (p = .077) nor suicide attempts (p = .17) in models adjusting for age, gender, and income. Other chronic diseases were linked to suicidal thoughts and attempts only in men. LIMITATIONS: Although the investigation of the two kinds of STB are a strength of the study, the items' different time frames complicate comparisons. In addition, the cross-sectional design limits the ability to understand observed relationships and to identify periods of risk. CONCLUSION: This study expands the evidence base regarding the vulnerability to STBs in individuals with cancer, including long-term survivors. It highlights their heterogeneity, differential risk factors underlying suicidal thoughts and attempts, and the relevance of other (contextual) factors shaping an individual's susceptibility to suicidal crises.

A powerful safety net: Social support moderates the association of quality of life deficits with suicidal ideation in long-term childhood cancer survivors.

OBJECTIVES: Cancer survivors are at risk for suicidality. We aimed to expand the knowledge about protective factors and their interplay with risk factors by testing social support as a modifier of the association of Quality of Life (QoL) deficits with suicidal ideation. RESEARCH APPROACH: We surveyed N = 633 childhood cancer survivors (CCS) using validated questionnaires (EORTC Core Quality of Life questionnaire QLQ-C30, Patient Health Questionnaire PHQ-9). The interaction of QoL and social support was investigated using multiple linear regression analysis. FINDINGS: CCS reporting suicide attempts and current suicidal ideation (SI) had lower QoL. CCS with SI reported less social support. QoL and social support were independently associated with SI and interacted: among CCS with less social support, low QoL was more strongly associated with SI. CONCLUSION: The results highlight the need for interdisciplinary survivorship care, and to focus on risk and protective factors to strengthen suicide prevention.

Estimated Annual Healthcare Costs After Acute Pulmonary Embolism: Results From a Prospective Multicentre Cohort Study.

OBJECTIVE: Patients surviving acute pulmonary embolism (PE) necessitate long-term treatment and follow-up. However, the chronic economic impact of PE on European healthcare systems remains to be determined. METHODS AND RESULTS: We calculated the direct cost of illness during the first year after discharge for the index PE, analyzing data from a multicentre prospective cohort study in Germany. Main and accompanying readmission diagnoses were used to calculate DRG-based hospital reimbursements; anticoagulation costs were estimated from the exact treatment duration and each drug's unique national identifier; and outpatient post-PE care costs from guidelines-recommended algorithms and national reimbursement catalogues. Of 1017 patients enrolled at 17 centres, 958 (94%) completed ≥ 3-month follow-up; of those, 24% were rehospitalized (0.34 [95% CI 0.30-0.39] readmissions per PE survivor). Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis of 837 patients with complete 12-month follow-up) cancer, but not recurrent PE, were independent cost predictors by hurdle gamma regression accounting for zero readmissions. Estimated rehospitalization cost was €1138 (95% CI 896-1420) per patient. Anticoagulation duration was 329 (IQR 142-365) days, with estimated average per-patient costs of €1050 (median 972; IQR 458-1197); costs of scheduled ambulatory follow-up visits amounted to €181. Total estimated direct per-patient costs during the first year after PE ranged from €2369 (primary analysis) to €2542 (sensitivity analysis). CONCLUSIONS: By estimating per-patient costs and identifying cost drivers of post-PE care, our study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved cardiovascular prevention. (Trial registration number: DRKS00005939).

Obesity-related inflammatory protein signature in cardiovascular clinical outcomes: results from the Gutenberg Health Study.

OBJECTIVE: The objective of this study was to investigate whether an obesity-related inflammatory protein signature (OIPS) is associated with adverse cardiovascular events. METHODS: The Olink Target 96 Inflammation panel was performed in 6662 participants from the population-based Gutenberg Health Study (GHS). The OIPS was selected by a logistic regression model, and its association with cardiovascular outcomes was evaluated by Cox regression analysis. The GHS-derived OIPS was externally validated in the MyoVasc study. RESULTS: The identified OIPS entailed 21 proteins involved in chemokine activity, tumor necrosis factor (TNF) receptor binding, and growth factor receptor binding. The signature revealed a novel positive association of axis inhibition protein 1 with obesity. The OIPS was associated with increased risk of all-cause and cardiac deaths, major adverse cardiovascular events, and incident coronary artery disease, independent of clinical covariates and established risk instruments. A BMI-stratified analysis confirmed the association of OIPS with increased death in those with obesity and overweight and with increased risk for coronary artery disease in those with obesity. The association of OIPS with increased risk of all-cause and cardiac deaths was validated in the MyoVasc cohort. CONCLUSIONS: The OIPS showed a significant association with adverse clinical outcomes, particularly in those with overweight and obesity, and represents a promising tool for identifying patients at higher risk for worse cardiovascular outcomes.

Role of inflammatory signaling pathways involving the CD40-CD40L-TRAF cascade in diabetes and hypertension-insights from animal and human studies.

CD40L-CD40-TRAF signaling plays a role in atherosclerosis progression and affects the pathogenesis of coronary heart disease (CHD). We tested the hypothesis that CD40L-CD40-TRAF signaling is a potential therapeutic target in hyperlipidemia, diabetes, and hypertension. In mouse models of hyperlipidemia plus diabetes (db/db mice) or hypertension (1 mg/kg/d angiotensin-II for 7 days), TRAF6 inhibitor treatment (2.5 mg/kg/d for 7 or 14 days) normalized markers of oxidative stress and inflammation. As diabetes and hypertension are important comorbidities aggravating CHD, we explored whether the CD40L-CD40-TRAF signaling cascade and their associated inflammatory pathways are expressed in CHD patients suffering from comorbidities. Therefore, we analyzed vascular bypass material (aorta or internal mammary artery) and plasma from patients with CHD with diabetes and/or hypertension. Our Olink targeted plasma proteomic analysis using the IMMUNO-ONCOLOGY panel revealed a pattern of step-wise increase for 13/92 markers of low-grade inflammation with significant changes. CD40L or CD40 significantly correlated with 38 or 56 other inflammatory targets. In addition, specific gene clusters that correlate with the comorbidities were identified in isolated aortic mRNA of CHD patients through RNA-sequencing. These signaling clusters comprised CD40L-CD40-TRAF, immune system, hemostasis, muscle contraction, metabolism of lipids, developmental biology, and apoptosis. Finally, immunological analysis revealed key markers correlated with comorbidities in CHD patients, such as CD40L, NOX2, CD68, and 3-nitrotyrosine. These data indicate that comorbidities increase inflammatory pathways in CHD, and targeting these pathways will be beneficial in reducing cardiovascular events in CHD patients with comorbidities.

Change of Intraocular Pressure Over 5 Years and its Relationship to Cardiovascular Parameters: Results From the Gutenberg Health Study.

Purpose: To investigate the longitudinal change in intraocular pressure (IOP) over 5 years and its relationship with cardiovascular parameters in a population-based sample in Germany. Methods: The Gutenberg Health Study is a prospective, observational, single-center cohort study. The sample was equally stratified for sex, residence, and age decade. IOP was measured with noncontact tonometry at baseline and at 5-year follow-up. Cardiovascular parameters, including body mass index (BMI), systolic blood pressure, and diabetes status, were assessed. Participants without IOP measurement at one time point, who were taking IOP-lowering medications, or who had ophthalmic surgery during the 5-year follow-up interval were excluded, as well as those with glaucoma diagnosis. Univariable and multivariable linear regression analyses were conducted. Results: This analysis included 9633 participants (48.9% female). The mean IOP increased from 14.04 ± 2.78 mmHg at baseline to 14.77 ± 2.92 mmHg at 5-year follow-up (P < 0.001). In multivariable linear regression analyses, an increase in BMI was associated with an increase in IOP over time (P < 0.001), whereas a higher baseline BMI was associated with a lower IOP change (P < 0.001). Higher age and male sex were associated with higher IOP change (P < 0.001). A change in systolic blood pressure was associated with IOP change, whereas baseline systolic blood pressure and diabetes status were not associated. Conclusions: This population-based study found a relationship between IOP change over 5 years and BMI and systolic blood pressure change, respectively. These findings suggest the importance of monitoring cardiovascular risk factors in IOP management.

Age standardization and time-of-day performance for the Oldenburg Sentence Test (OLSA): results from the population-based Gutenberg Health Study.

PURPOSE: The Oldenburg Sentence Test (OLSA) is a German matrix test designed to determine speech recognition thresholds (SRT). It is widely used for hearing-aids and cochlear implant fitting, but an age-adjusted standard is still lacking. In addition, knowing that the ability to concentrate is an important factor in OLSA performance, we hypothesized that OLSA performance would depend on the time of day it was administered. The aim of this study was to propose an age standardization for the OLSA and to determine its diurnal performance. METHODS: The Gutenberg Health Study is an ongoing population-based study and designed as a single-centre observational, prospective cohort study. Participants were interviewed about common otologic symptoms and tested with pure-tone audiometry and OLSA. Two groups-subjects with and without hearing loss-were established. The OLSA was performed in two runs. The SRT was evaluated for each participant. Results were characterized by age in 5-year cohorts, gender and speech recognition threshold (SRT). A time stamp with an hourly interval was also implemented. RESULTS: The mean OLSA SRT was - 6.9 ± 1.0 dB (group 1 male) and - 7.1 ± 0.8 dB (group 1 female) showing an inverse relationship with age in the whole cohort, whereas a linear increase was observed in those without hearing loss. OLSA-SRT values increased more in males than in females with increasing age. No statistical significance was found for the diurnal performance. CONCLUSIONS: A study with 2900 evaluable Oldenburg Sentence Tests is a novelty and representative for the population of Mainz and its surroundings. We postulate an age- and gender-standardized scale for the evaluation of the OLSA. In fact, with an intergroup standard deviation (of about 1.5 dB) compared to the age dependence of 0.7 dB/10 years, this age normalization should be considered as clinically relevant.

Autoantibodies against the chemokine receptor 3 predict cardiovascular risk.

BACKGROUND AND AIMS: Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear. METHODS: Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation. RESULTS: The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model. CONCLUSIONS: In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis.

Development and Phenotype of Heart Failure in Long-Term Survivors of Childhood Cancer: The CVSS Study.

Background The CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study aimed to investigate the prevalence of different stages of heart failure (HF) in childhood cancer survivors (CCSs) compared with the general population. Methods and Results A total of 1002 CCSs (age range, 23-48 years) diagnosed with neoplasia before an age of 15 years underwent a comprehensive cardiovascular screening. An age- and sex-matched sample from the population-based GHS (Gutenberg Health Study) served as a comparison group. Although prevalence of HF was significantly higher in CCSs, prevalence of different HF stages varied strongly by specific tumor history. Compared with the population, the prevalence ratio was 2.6 (95% CI, 2.4-2.8) for HF stage A and 4.6 (95% CI, 4.1-5.1) for the composite of HF stage B to D in an age- and sex-adjusted Poisson regression model. Multivariable linear regression, adjusting for tumor entities, age, sex, and cardiovascular risk factors, revealed a lower left ventricular ejection fraction in patients with history of bone tumors (ß, -4.30 [95% CI, -5.70 to -2.80]), soft tissue sarcoma (ß, -1.60 [95% CI, -2.90 to -0.30]), and renal tumors (ß, -1.60 [95% CI, -2.80 to -0.29]) compared with the population. The same model for the diastolic marker, ratio of the peak early diastolic filling velocity/lateral mitral annular early diastolic velocity, showed an association only with cardiovascular risk factors but not with tumor entities. Conclusions The prevalence of HF stage A to D was significantly higher among long-term CCSs compared with the population and varied strongly by tumor entity. Systolic dysfunction was primarily associated with tumor entities, whereas diastolic dysfunction was associated with a higher burden of cardiovascular risk factors in CCSs.

Quality of life after pediatric cancer: comparison of long-term childhood cancer survivors' quality of life with a representative general population sample and associations with physical health and risk indicators.

BACKGROUND: This study aimed to compare the quality of life (QoL) reported by childhood cancer survivors (CCS) drawn from a cohort of the German Childhood Cancer Registry with a representative general population sample and, within CCS, to test associations between QoL and health behavior, health risk factors, and physical illness. METHODS: CCS (N = 633, age at diagnosis M = 6.34 (SD = 4.38), age at medical assessment M = 34.92 (SD = 5.70)) and a general population sample (age-aligned; N = 975) filled out the EORTC QLQ-C30. Comparisons were performed using General linear models (GLMs) (fixed effects: sex/gender, group (CCS vs. general population); covariates: age, education level). CCS underwent an extensive medical assessment (mean time from diagnosis to assessment was 28.07 (SD = 3.21) years) including an objective diagnosis of health risk factors and physical illnesses (e.g., diabetes and cardiovascular disease). Within CCS, we tested associations between QoL and sociodemographic characteristics, health behavior, health risk factors, and physical illness. RESULTS: CCS, especially female CCS, reported both worse functional QoL and higher symptom burden than the general population. Among CCS, better total QoL was related to younger age, higher level of education, being married, and engaging in active sports. Both health risk factors (dyslipidemia and physical inactivity) and manifest physical illnesses (cardiovascular disease) were associated with lower total QoL. CONCLUSIONS: In all domains, long-term CCS reported worse QoL than the comparison sample. The negative associations with risk factors and physical illnesses indicate an urgent need for long-term surveillance and health promotion.

Clinical profile and outcome of isolated pulmonary embolism: a systematic review and meta-analysis.

Background: Isolated pulmonary embolism (PE) appears to be associated with a specific clinical profile and sequelae compared to deep vein thrombosis (DVT)-associated PE. The objective of this study was to identify clinical characteristics that discriminate both phenotypes, and to characterize their differences in clinical outcome. Methods: We performed a systematic review and meta-analysis of studies comparing PE phenotypes. A systematic search of the electronic databases PubMed and CENTRAL was conducted, from inception until January 27, 2023. Exclusion criteria were irrelevant content, inability to retrieve the article, language other than English or German, the article comprising a review or case study/series, and inappropriate study design. Data on risk factors, clinical characteristics and clinical endpoints were pooled using random-effects meta-analyses. Findings: Fifty studies with 435,768 PE patients were included. In low risk of bias studies, 30% [95% CI 19-42%, I 2 = 97%] of PE were isolated. The Factor V Leiden [OR: 0.47, 95% CI 0.37-0.58, I 2 = 0%] and prothrombin G20210A mutations [OR: 0.55, 95% CI 0.41-0.75, I 2 = 0%] were significantly less prevalent among patients with isolated PE. Female sex [OR: 1.30, 95% CI 1.17-1.45, I 2 = 79%], recent invasive surgery [OR: 1.31, 95% CI 1.23-1.41, I 2 = 65%], a history of myocardial infarction [OR: 2.07, 95% CI 1.85-2.32, I 2 = 0%], left-sided heart failure [OR: 1.70, 95% CI 1.37-2.10, I 2 = 76%], peripheral artery disease [OR: 1.36, 95% CI 1.31-1.42, I 2 = 0%] and diabetes mellitus [OR: 1.23, 95% CI 1.21-1.25, I 2 = 0%] were significantly more frequently represented among isolated PE patients. In a synthesis of clinical outcome data, the risk of recurrent VTE in isolated PE was half that of DVT-associated PE [RR: 0.55, 95% CI 0.44-0.69, I 2 = 0%], while the risk of arterial thrombosis was nearly 3-fold higher [RR: 2.93, 95% CI 1.43-6.02, I 2 = 0%]. Interpretation: Our findings suggest that isolated PE appears to be a specific entity that may signal a long-term risk of arterial thrombosis. Randomised controlled trials are necessary to establish whether alternative treatment regimens are beneficial for this patient subgroup. Funding: None.

DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide and considered one of the most environmentally driven diseases. The role of DNA methylation in response to the individual exposure for the development and progression of CVD is still poorly understood and a synthesis of the evidence is lacking. RESULTS: A systematic review of articles examining measurements of DNA cytosine methylation in CVD was conducted in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The search yielded 5,563 articles from PubMed and CENTRAL databases. From 99 studies with a total of 87,827 individuals eligible for analysis, a database was created combining all CpG-, gene- and study-related information. It contains 74,580 unique CpG sites, of which 1452 CpG sites were mentioned in ≥ 2, and 441 CpG sites in ≥ 3 publications. Two sites were referenced in ≥ 6 publications: cg01656216 (near ZNF438) related to vascular disease and epigenetic age, and cg03636183 (near F2RL3) related to coronary heart disease, myocardial infarction, smoking and air pollution. Of 19,127 mapped genes, 5,807 were reported in ≥ 2 studies. Most frequently reported were TEAD1 (TEA Domain Transcription Factor 1) and PTPRN2 (Protein Tyrosine Phosphatase Receptor Type N2) in association with outcomes ranging from vascular to cardiac disease. Gene set enrichment analysis of 4,532 overlapping genes revealed enrichment for Gene Ontology molecular function "DNA-binding transcription activator activity" (q = 1.65 × 10-11) and biological processes "skeletal system development" (q = 1.89 × 10-23). Gene enrichment demonstrated that general CVD-related terms are shared, while "heart" and "vasculature" specific genes have more disease-specific terms as PR interval for "heart" or platelet distribution width for "vasculature." STRING analysis revealed significant protein-protein interactions between the products of the differentially methylated genes (p = 0.003) suggesting that dysregulation of the protein interaction network could contribute to CVD. Overlaps with curated gene sets from the Molecular Signatures Database showed enrichment of genes in hemostasis (p = 2.9 × 10-6) and atherosclerosis (p = 4.9 × 10-4). CONCLUSION: This review highlights the current state of knowledge on significant relationship between DNA methylation and CVD in humans. An open-access database has been compiled of reported CpG methylation sites, genes and pathways that may play an important role in this relationship.

The association of depressive symptoms and body weight change in midlife - Results from the Gutenberg Health Study in Germany.

BACKGROUND: The present study aimed to investigate how depressive symptoms affect bodyweight change (gain and loss), and how this association is intertwined with other psychosocial and biomedical factors in the adult general population. METHODS: In a population-based, prospective, observational single-center cohort study in the Rhine-Main-Region, Germany (Gutenberg Health Study GHS) with N = 12,220 participants, we analyzed baseline and five year follow-up data with logistic regressions separately for bodyweight gain and loss (vs. stable bodyweight). RESULTS: Overall, 19.8 % of participants gained bodyweight of at least 5 %. More female participants were affected than male participants (23.3 % vs. 16.6 %). Regarding weight loss, overall, 12.4 % lost >5 % of bodyweight; participants were more often female than male (13.0 % vs. 11.8 %). Depressive symptoms at baseline were associated with weight gain (OR = 1.03, 95 % CI = 1.02-1.05). In models controlling for psychosocial and biomedical factors, female gender, younger age, lower socioeconomic status and smoking cessation were associated with weight gain. In weight loss, there was no overall significant effect of depressive symptoms (OR = 1.01 [0.99; 1.03]). Weight loss was associated with female gender, diabetes, less physical activity, and higher BMI at baseline. Only in women, smoking and cancer were associated with weight loss. LIMITATIONS: Depressive symptoms were assessed via self-report. Voluntary weight loss cannot be determined. CONCLUSIONS: Significant weight change frequently occurs in middle to old adulthood resulting from a complex interplay of psychosocial and biomedical factors. Associations with age, gender, somatic illness and health behavior (e.g. smoking cessation) provide important information for the prevention of unfavorable weight change.

Exploring phenotypes of deep vein thrombosis in relation to clinical outcomes beyond recurrence.

BACKGROUND: Deep vein thrombosis (DVT) is a multifactorial disease with several outcomes, but current classifications solely stratify it based on recurrence risk. OBJECTIVES: We aimed to identify DVT phenotypes and assess their relation to recurrent venous thromboembolism (VTE), postthrombotic syndrome, arterial events, and cancer. PATIENTS/METHODS: Hierarchical clustering was performed on a DVT cohort with a follow-up of up to 5 years using 23 baseline characteristics. Phenotypes were summarized by discriminative characteristics. Hazard ratios (HRs) were calculated using Cox regression; the recurrence risk was adjusted for the anticoagulant therapy duration. The study was carried out in accordance with the Declaration of Helsinki and approved by the medical ethics committee. RESULTS: In total, 825 patients were clustered into 4 phenotypes: 1. women using estrogen therapy (n = 112); 2. patients with a cardiovascular risk profile (n = 268); 3. patients with previous VTE (n = 128); and 4. patients without discriminant characteristics (n = 317). Overall, the risks of recurrence, postthrombotic syndrome, arterial events, and cancer were low in phenotype 1 (reference), intermediate in phenotype 4 (HR: 4.6, 1.2, 2.2, 1.8), and high in phenotypes 2 (HR: 6.1, 1.6, 4.5, 2.9) and 3 (HR: 5.7, 2.5, 2.3, 3.7). CONCLUSIONS: This study identified 4 distinct phenotypes among patients with DVT that are not only associated with the increasing recurrence risk but also with outcomes beyond recurrence. Our results thereby highlight the limitations of current risk stratifications that stratify based on the predictors of the recurrence risk only. Overall, risks were lowest in women using estrogen therapy and highest in patients with a cardiovascular risk profile. These findings might inform a more personalized approach to clinical management.

Posttraumatic growth after childhood cancer: Psychometric evaluation of a five-item short form and associations with mental health.

OBJECTIVE: Research has described positive psychological outcomes after severe illness, including posttraumatic growth. The aim of the present research was to evaluate a short scale assessing posttraumatic growth within a sample of cancer survivors to provide an efficient instrument for research and care settings. METHODS: Using data of a registry-based sample of N = 633 childhood cancer survivors (CCS) more than 25 years after diagnosis, we conducted an investigation of a five-item short form of the established Posttraumatic Growth Inventory (PTGI), the PPR-5 (PPR stands for "Posttraumatische Persönliche Reifung", the German expression for posttraumatic growth). We performed a confirmatory factor analysis, tested the PPR-5's internal consistency, and investigated associations with cancer-related, sociodemographic, and mental health variables (assessed using psychometrically tested screening instruments) using group comparisons and correlation analyses within a cross-sectional design. RESULTS: Findings supported a unidimensional structure of the PPR-5. It also showed good reliability (ω = 0.81). CCS especially endorsed Relating to others and Personal strength. The PPR-5's sum score was negatively associated with current depression, anxiety, and sleep disorder symptoms, intake of antidepressants, and lifetime diagnoses of depression and anxiety disorders. It showed positive associations with resilient coping, higher age at diagnosis, partnership, and parenthood. CONCLUSION: The PPR-5 allows for a brief assessment of posttraumatic growth. As it indicates aspects that support positive psychological adaptation to life as a (cancer) survivor, it could inform research and practice (e.g., as a screening measure, or in psychotherapy/counseling settings).

Five-year change in refractive error and its risk factors: results from the Gutenberg Health Study.

BACKGROUND/AIMS: To examine the 5-year change in refractive error in phakic eyes and its risk factors in the general population. METHODS: The Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants from Germany aged 35-74 years at baseline examination (2007-2012). After 5 years, a follow-up examination was carried out (83% participation). 5-year change of spherical equivalent (SE) was computed as difference between follow-up and baseline objective refraction. Linear and logistic regression analysis were conducted analysing potential risk factors. Only phakic eyes at follow-up examination were included. RESULTS: Right eyes of 10 175 subjects were included. An age-related shift of refractive error was identified, namely -0.12 D for age 35-44 years, 0.25 D for age 45-54 years, 0.25 D for age 55-64 years and 0.12 D for age 65-74 years during the 5-year follow-up. Smokers had a hyperopic shift (OR=1.31; p<0.001), while baseline SE (OR=0.89 per dioptre; p<0.001) and female sex (OR=1.49; p<0.001) were linked with a myopic shift. Education, occupation and other cardiovascular parameters were not associated with change in refractive error. CONCLUSIONS: The GHS demonstrates a parabolic shift in refractive error with a myopic shift at age 35-44 years, followed by a hyperopic shift at age 45-64 years which decreases at higher age. Smoking is associated with a hyperopic shift whereas female sex and myopic baseline SE is associated with a myopic shift. Educational level and occupation were not linked to a change in refractive error at age 35-74 years.

Depressive symptoms predict the incidence of common chronic diseases in women and men in a representative community sample.

BACKGROUND: Depression, the most frequent and harmful mental disorder, has been associated with specific somatic diseases as the leading cause of death. The purposes of this prospective study were to predict incident chronic diseases based on baseline depressive symptoms and to test sex-dependent effects. METHODS: In a representative German community sample of over 12 000 participants, baseline depressive symptoms (assessed using the Patient Health Questionnaire-9) were tested as a predictor of new onset of cardiovascular disease (CVD), chronic obstructive lung disease, diabetes, cancer, and migraine at 5-year follow-up. To study disease incidence, we created subsamples for each chronic disease by excluding participants who already had the respective disease at baseline. Potential confounders were included in logistic regression models and sex-specific analyses were performed. RESULTS: Controlling for demographic characteristics and loneliness, in men and women, baseline depressive symptoms were predictive of CVD, chronic obstructive lung disease, diabetes, and migraine, but not of cancer. When we additionally adjusted for metabolic and lifestyle risk factors, there was an 8% increase of chronic obstructive lung disease and migraine per point of depressive symptoms. There was a trend for CVD (4%; p = 0.053). Sex-sensitive analyses revealed trends for the relevance of depressive symptoms for CVD in men (p = 0.065), and for diabetes in women (p = 0.077). CONCLUSIONS: These findings underscore the need to implement screening for depression in the treatment of major somatic illnesses. At the same time, depressed patients should be screened for metabolic and lifestyle risk factors and for somatic diseases and offered lifestyle interventions.

Chronic cigarette smoking is associated with increased arterial stiffness in men and women: evidence from a large population-based cohort.

BACKGROUND: Cigarette smoking is a threat to global human health and a leading cause of the cardiovascular disease (CVD) morbidity and mortality. Importantly, sex-specific differences in smoking-induced arterial stiffness, an early key event in the development of atherosclerotic CVD, remain still elusive. Thus, this study sought out to investigate sex-specific associations between smoking and measures of arterial stiffness. METHODS AND RESULTS: Overall, 15,010 participants (7584 men and 7426 women aged 35-74 years) of the Gutenberg Health Study were examined at baseline during 2007-2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a standardized computer-assisted interview. Arterial stiffness and wave reflection were determined by stiffness index (SI) and augmentation index (AI). In the total sample, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Median cumulative smoking exposure was 22.0 pack-years in current male smokers and 16.0 in current female smokers. In general, multivariable linear regression models adjusted for a comprehensive set of confounders revealed that smoking status, pack-years of smoking, and years since quitting smoking were dose-dependently associated with markers of arterial stiffness. In sex-specific analyses, these associations were overall more pronounced in men and SI was stronger related to the male sex, whereas differences between men and women in the case of AI appeared to be less substantial. DISCUSSION: The present results indicate that chronic smoking is strongly and dose-dependently associated with increased arterial stiffness in a large population-based cohort regardless of sex but with a stronger association in men.

Determinants of mammography screening participation-a cross-sectional analysis of the German population-based Gutenberg Health Study (GHS).

PURPOSE: We investigated the association between social inequality and participation in a mammography screening program (MSP). Since the German government offers mammography screening free of charge, any effect of social inequality on participation should be due to educational status and not due to the financial burden. METHODS: The 'Gutenberg Health Study' is a cohort study in the Rhine-Main-region, Germany. A health check-up was performed, and questions about medical history, health behavior, including secondary prevention such as use of mammography, and social status are included. Two indicators of social inequality (equivalence income and educational status), an interaction term of these two, and different covariables were used to explore an association in different logistic regression models. RESULTS: A total of 4,681 women meeting the inclusion criteria were included. Only 6.2% never participated in the MSP. A higher income was associated with higher chances of ever participating in a mammography screening (odds ratios (OR): 1.67 per €1000; 95%CI:1.26-2.25, model 3, adjusted for age, education and an interaction term of income and education). Compared to women with a low educational status, the odds ratios for ever participating in the MSP was lower for the intermediate educational status group (OR = 0.64, 95%CI:0.45-0.91) and for the high educational status group (0.53, 95%CI:0.37-0.76). Results persisted also after controlling for relevant confounders. CONCLUSIONS: Despite the absence of financial barriers for participation in the MSP, socioeconomic inequalities still influence participation. It would be interesting to examine whether the educational effect is due to an informed decision.

Distribution of Pupil Size and Associated Factors: Results from the Population-Based Gutenberg Health Study.

Results: 18,335 eyes of 9,559 participants aged 40 to 80 years were included in the analysis. Median pupil diameter was 4.19 mm in right eyes and 4.12 mm in left eyes. A smaller pupil was associated with older age, hyperopic refractive error, previous cataract surgery, diabetes, obesity, and ACE inhibitor intake, whereas wider pupil was associated with female gender, arterial hypertension, intake of tricyclic antidepressants, and intake of SNRI and tetracyclic antidepressants. Socioeconomic status and smoking were not associated with pupil size. Conclusion: Individuals of older age, after cataract surgery, under therapy with ACE inhibitors and with diabetes have a smaller pupil. This should be taken into account when planning nonmydriatic fundus photography-based screening programs, for instance, for diabetic retinopathy.