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Background: Central nervous system (CNS) relapse is a devastating and usually fatal complication of aggressive lymphoma. The extent of the disease, the proliferation rate and the sites of extranodal involvement have been discussed as risk factors. We analyzed the patients treated on protocols of the German High-Grade Non-Hodgkin''s Lymphoma Study Group (DSHNHL) between 1990 and 2000, evaluated the rate and prognostic factors for CNS recurrence and developed a risk model trying to identify subsets of patients suitable for future prophylactic strategies.Patients and methods: From 1993 to 2000, 1399 patients [≤60 years with normal lactate dehydrogenase (LDH) and >60 years irrespective of LDH] were randomized to receive six cycles of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-21, CHOP-14 or six cycles of CHOP + etoposide (CHOEP)-21, CHOEP-14 in a 2 × 2 factorial study design in the NHL-B1/B2 studies. From 1990 to 1997, 312 patients ≤60 years with an elevated LDH were randomized to five cycles CHOEP + involved field (IF) radiotherapy or three cycles CHOEP followed by high-dose BCNU, etoposide, cytarabine and melphalan (BEAM) and autologous stem-cell transplantation (NHL-A study).Results: A total number of 1711 patients were initially eligible for this study, of whom 18 patients had to be excluded due to primary CNS involvement. In the remaining 1693 assessable patients, 37 cases of relapse or progression to the CNS (2.2%) were observed. The protocol asked for an intrathecal (i.th.) prophylaxis in patients with lymphoblastic lymphoma only (n = 17), but overall 71 patients (71 of 1693 = 4.2%) received prophylaxis by decision of the treating physicians. Multivariate Cox regression analysis identified increased LDH (P < 0.001) and involvement of more than one extranodal site (P = 0.002) as independent predictors of CNS recurrence in the NHL-B1/B2 study population. Treatment with etoposide also evolved as a prognostic factor because the risk of CNS failure was significantly reduced after CHOEP (P = 0.017). Elderly patients presenting with both an elevated LDH and lymphoma involvement in liver, bladder or adrenals had an up to 15-fold risk of spread of the disease to the CNS.Conclusion: The incidence of CNS relapse in 1693 patients treated for aggressive lymphomas on DSHNHL protocols from 1990 to 2000 was low (2.2%), although CNS prophylaxis was administered to <5% of patients. Thus, a general prophylaxis for all patients is not warranted, the less so since the effectiveness of i.th. prophylaxis itself is judged controversially. Increased LDH and involvement of more than one extranodal site were confirmed as independent risk factors. A cumulative 20% incidence of CNS disease in certain prognostic subgroups of elderly patients may render these candidates for i.th. prophylaxis; however, this approach would imply a potential overtreatment of ∼80% of these patients deemed at high risk. [ABSTRACT FROM AUTHOR]

Background: The addition of etoposide to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone [etoposide to combination chemotherapy with cyclophosphamide, vincristine and prednisone (CHOEP)] improved outcome of young patients with good-prognosis aggressive lymphoma. To improve results further, the maximal dose-escalated version of CHOEP-21 tolerable without stem-cell support (high CHOEP: cyclophosphamide 1400 mg/m2, doxorubicin 65 mg/m2, vincristine 2 mg, etoposide 175 mg/m2 ×3, prednisone 100 mg ×5) was compared with CHOEP-21. Patients and methods: Intention-to-treat analysis of 389 young (18–60 years) patients with good-prognosis (age-adjusted International Prognostic Index = 0, 1) aggressive lymphoma randomized to CHOEP-21 (n = 194) or high CHOEP (n = 195). Results: There was no difference in 3-year event-free (64% versus 67%; P = 0.734) or overall survival (83% versus 87%; P = 0.849). Neither low-risk nor low-intermediate risk patients benefited from high CHOEP. High CHOEP was more toxic than CHOEP-21 (grades 3 and 4 leukocytopenia 100% versus 87.2%, P < 0.001; thrombocytopenia 80.8% versus 9.6%, P < 0.001; infections 35% versus 11%, P < 0.001; therapy-associated deaths 3.1% versus 0%, P = 0.03). Conclusion: Dose-escalated CHOEP-21 does not provide clinical benefit for young patients with good-prognosis aggressive lymphomas. Since differences between chemotherapy regimens are compressed by the addition of rituximab, the results of this trial have bearing on strategies aiming to improve outcome of good-prognosis aggressive lymphomas in the rituximab era. [ABSTRACT FROM AUTHOR]

Purpose: Fractures around the hip are known to be an indicator for fragility and are associated with high mortality and various complications. A special type of fractures around the hip are periprosthetic femur fractures (PPF) after Total Hip Arthroplasty (THA). The aim of this study was to investigate the mortality rate associated with PPF after THA and to identify risk factors that may increase it., Methods: Consecutive patients (N = 158) who were treated for a PPF after THA in our university hospital between 2010 and 2020 were identified and mortality was assessed using the residential registry. Univariate (Kaplan-Meier-Estimator) and multivariate (Cox-Regression) statistical analysis was performed to identify risk factors influencing mortality., Results: One-year-mortality rate was 23.4% and 2-year mortality was 29.2%. Mortality was significantly influenced by age, gender, treatment, type of comorbidity and time of surgery (p < 0.05). Surgical treatment during regular working hours (8 to 18 h) reduced mortality by 53.2% compared to surgery on call (OR: 0.468, 95% CI 0.223, 0.986; p = 0.046). For every year of age, mortality risk increased by 12.9% (OR: 1,129, 95% CI 1.078, 1.182; p < 0.001). The type of fracture according to the Vancouver classification had no influence on mortality (p = 0.179). Plate fixation and conservative treatment were associated with a higher mortality compared to revision arthroplasty (plate: OR 2.8, 95% CI 1.318, 5.998; p = 0.007; conservative: OR 2.5, 95% CI 1.421, 4.507; p = 0.002)., Conclusion: Surgical treatment during regular working hours is associated with lower mortality compared to surgery outside these hours. In this retrospective cohort, time to surgery showed no significant impact on all-cause mortality, and revision arthroplasty was associated with lower mortality than conservative treatment or plate fixation., Level of Evidence: IV (Retrospective cohort study)., (© 2024. The Author(s).)

Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did not assess covariates possibly linked to cognitive performance. We aimed to describe 1) global and domain-specific cognitive performance in adults with PCS, controls with previous SARS-CoV-2 infection and healthy controls, 2) associations of sociodemographics, depressive symptoms, anxiety, fatigue, somatic symptoms and stress with cognitive performance and subjective cognitive decline (SCD), using data of the LIFE-Long-COVID-Study from Leipzig, Germany. Group differences in cognitive performance and associations with sociodemographic and neuropsychiatric covariates were assessed using multivariable regression analyses. Our study included n = 561 adults (M age : 48.8, SD: 12.7; % female: 70.6). Adults with PCS (n = 410) performed worse in tests on episodic memory (b = -1.07, 95 % CI: -1.66, -0.48) and visuospatial abilities (b = -3.92, 95 % CI: -6.01, -1.83) compared to healthy controls (n = 64). No impairments were detected for executive function, verbal fluency, and global cognitive performance. Odds of SCD were not higher in PCS. A previous SARS-CoV-2 infection without PCS (n = 87) was not linked to cognitive impairment. Higher age and higher levels of stress and fatigue were linked to worse performance in several cognitive domains. Routine administration of tests for episodic memory and visuospatial abilities might aid in the identification of individuals at risk for cognitive impairment when reporting symptoms of PCS. Low numbers of participants with severe COVID-19 infections possibly limit generalizability of our findings., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The bejective was to determine health literacy (HL) and care aspects of those affected by Long-COVID., Method: 407 patients with Long-COVID and long-term neuropsychiatric symptoms were interviewed in the LIFE study center. In addition to descriptive analyses, regression models were calculated to examine the relationships between health literacy (HLS-EU-Q16) and various aspects of care (RehaQ-N1)., Results: The results show that 35.8% had problematic and 17.9% had inadequate HL. The majority of subjective needs were unmet and 47.7% of those affected were dissatisfied with the therapy they received., Discussion: Among those affected by Long-COVID, subjective HL is rather reduced. The healthcare system appears to be unprepared for these patients, which is reflected in unmet needs and low treatment satisfaction. This was even more pronounced among those exhibiting lower HL., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme. All rights reserved.)

Background: Mortality of patients with a femoral neck fracture is high, especially within the first year after surgery, but also remains elevated thereafter. The aim of this study was to identify factors potentially associated with long-term mortality in patients homogeneously treated with hemiarthroplasty for femoral neck fracture., Methods: This retrospective cohort study was performed at a single level 1 national trauma center at the university hospital of Leipzig (Saxony, Germany). The study time-window was January 1, 2010 to December 31, 2020. Primary outcome measure was mortality depending on individual patient-related characteristics and perioperative risk factors. Inclusion criteria was a low-energy femoral neck fracture (Garden I-IV) in geriatric patients 60 years of age or older that were primarily treated with bipolar hemiarthroplasty. Date of death or actual residence of patients alive was obtained from the population register of the eastern German state of Saxony, Germany. The outcome was tested using the log-rank test and plotted using Kaplan-Meier curves. Unadjusted and adjusted for other risk factors such as sex and age, hazard ratios were calculated using Cox proportional hazards models and presented with 95% confidence intervals (CI)., Results: The 458 included patients had a median age of 83 (IQR 77-89) years, 346 (75%) were female and 113 (25%) male patients. Mortality rates after 30 days, 1, 5 and 10 years were 13%, 25%, 60% and 80%, respectively. Multivariate regression analysis revealed age (HR = 1.1; p < 0.001), male gender (HR = 1.6; p < 0.001), ASA-Score 3-4 vs. 1-2 (HR = 1.3; p < 0.001), dementia (HR = 1.9; p < 0.001) and a history of malignancy (HR = 1.6; p = 0.002) as independent predictors for a higher long-term mortality risk. Perioperative factors such as preoperative waiting time, early surgical complications, or experience of the surgeon were not associated with a higher overall mortality., Conclusions: In the present study based on data from the population registry from Saxony, Germany the 10-year mortality of older patients above 60 years of age managed with hemiarthroplasty for femoral neck fracture was 80%. Independent risk factors for increased long-term mortality were higher patient age, male gender, severe comorbidity, a history of cancer and in particular dementia. Perioperative factors did not affect long-term mortality., (© 2024. The Author(s).)

Studies show a connection between anxiety and stress, but with little differentiation between different domains of stress. In this article, we utilize a multi-dimensional approach to better understand the relationship between different chronic stress domains and anxiety. This will allow researchers to identify and address those areas of stress that are most relevant with regard to anxiety. We used data from a sub sample of the LIFE-Adult-Study (n = 1085) to analyze the association between nine different areas of chronic stress (Trier Inventory for Chronic Stress, TICS) and anxiety (General Anxiety Disorder 7, GAD-7), controlling for sociodemographic variables, personality, and social support. There was a significant and positive association between Work Overload, Pressure to Perform, Social Tensions, Social Isolation, Chronic Worrying, and anxiety. After including the control variables, only Work Overload and Chronic Worrying remained significant. By focusing on Work Overload and Chronic Worrying researchers, practitioners, and policy makers can help to mitigate anxiety and related health problems in the population in an efficient way.

Introduction: Guidelines increasingly recommend the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) to prevent cardiovascular and cardiorenal endpoints. Both drugs also show beneficial effects in nonalcoholic fatty liver disease (NAFLD). Preexisting GLP-1 RA and SGLT2i therapies are frequently defined as exclusion criterion in clinical studies to avoid confounding effects. We therefore investigated how this might limit recruitment and design of NAFLD studies., Methods: GLP-1 RA and SGLT2i prescriptions were analyzed in NAFLD patients with diabetes mellitus recruited at a tertiary referral center and from the population-based LIFE-Adult-Study. Individuals were stratified according to noninvasive parameters of liver fibrosis based on vibration-controlled transient elastography (VCTE)., Results: 97 individuals were recruited at tertiary care and 473 from the LIFE-Adult-Study. VCTE was available in 97/97 and 147/473 cases.GLP-1 RA or SGLT2i were used in 11.9% of the population-based cohort (LSM < 8 kPa), but in 32.0% with LSM ≥ 8 kPa. In the tertiary clinic, it was 30.9% overall, independent of LSM, and 36.8% in patients with medium and high risk for fibrotic NASH (FAST score > 0.35). At baseline, 3.1% of the patients in tertiary care were taking GLP-1 RA and 4.1% SGLT2i. Four years later, the numbers had increased to 15.5% and 21.6%., Conclusion: GLP-1 RA and SGLT2i are frequently and increasingly prescribed. In candidates for liver biopsy for NASH studies (VCTE ≥ 8 kPa) the use of them exceeds 30%, which needs careful consideration when designing NASH trials., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

While there are studies connecting everyday physical activity (PA) to mental health, they mostly use self-report measures for PA which are biased in multiple ways. Nevertheless, a realistic assessment of everyday PA is important for the development and implementation of low-threshold public health interventions. Therefore, we want to analyze the relationship between objectively measured daily steps and mental health. We included 1451 subjects from a subsample of the population-based LIFE-Adult-Study (2011-2014) with an average age of 55.0 years, 52.1% were female. We analyzed the effects of PA (step count measured via SenseWear Pro 3) on depression (CES-D), anxiety (GAD-7), and quality of sleep (PSQI). The regression analysis showed a significant negative association between low to moderate PA [Incidence rate ratio: 0.87 (0.77; 0.98)] as well as high to very high PA [0.84 (0.74; 0.95)] and depression and no significant associations between PA and anxiety [l-m: 0.98 (0.81; 1.18)/h-vh: 1.00 (0.82; 1.21)] or quality of sleep [l-m: 0.94 (0.84, 1.06)/h-vh: 0.92 (0.82, 1.03)], controlling for sociodemographic variables and personality. Low-threshold interventions that increase daily step count could be a useful approach for the prevention of depression. The use of objective PA measurement for research is highly encouraged.

(1) Background: Several lines of evidence established a link between high-risk (HR) sexual behavior (SB), the persistence of human papillomavirus (HPV) DNA in saliva, and the presence of oncogenic HR-HPV subtypes in oropharyngeal squamous cell carcinoma (OPSCC). A highly influential case-control study by D'Souza et al. comparing OPSCC patients and ENT patients with benign diseases (hospital controls) established HR-SB as a putative etiological risk factor for OPSCC. Aiming to replicate their findings in a nested case-control study of OPSCC patients and propensity score (PS)-matched unaffected controls from a large population-based German cohort study, we here demonstrate discrepant findings regarding HR-SB in OPSCC. (2) Methods: According to the main risk factors for HNSCC (age, sex, tobacco smoking, and alcohol consumption) PS-matched healthy controls invited from the population-based cohort study LIFE and HNSCC (including OPSCC) patients underwent interviews, using AUDIT and Fagerström, as well as questionnaires asking for SB categories as published. Afterwards, by newly calculating PSs for the same four risk factors, we matched each OPSCC patient with two healthy controls and compared responses utilizing chi-squared tests and logistic regression. (3) Results: The HNSCC patients and controls showed significant differences in sex distribution, chronologic age, tobacco-smoking history (pack years), and alcohol dependence (based on AUDIT score). However, PS-matching decreased the differences between OPSCC patients and controls substantially. Despite confirming that OPSCC patients were more likely to self-report their first sexual intercourse before age 18, we found no association between OPSCC and HR-SB, neither for practicing oral-sex, having an increased number of oral- or vaginal-sex partners, nor for having casual sex or having any sexually transmitted disease. (4) Conclusions: Our data, by showing a low prevalence of HR-SB in OPSCC patients, confirm findings from other European studies that differ substantially from North American case-control studies. HR-SB alone may not add excess risk for developing OPSCC.

Introduction: Resilience describes good adaptation to adversity and is a significant factor for well-being in old age. Initial studies indicate a high relevance of social resources. So far, only few studies have investigated resilience patterns in the elderly population. Therefore, the present study aims to investigate sociodemographic and social correlates of resilience in a large population-based sample aged 65 years and older., Methods: Analyses were conducted on n = 2410 people aged 65 years and older from the follow-up survey of the LIFE-Adult-Study. The survey included the variables resilience (Resilience Scale - RS-11), social support (ENRICHD Social Support Inventory - ESSI), and social network (Lubben Social Network Scale - LSNS-6). The association of sociodemographic and social variables with resilience was analyzed using multiple linear regression analysis., Results: The age of 75 years and older was associated with lower resilience compared with the age of 65-74 years. Further, widowed marital status was related to higher resilience. Better social support and a larger social network were significantly associated with higher resilience. No association was found for gender and education., Discussion: The results reveal sociodemographic correlates of resilience in the elderly population that can help identify at-risk groups with lower resilience. Social resources are significant in older age for resilient adaptation and represent a starting point for deriving preventive measures. Social inclusion of older people should be promoted to strengthen resilience in this population and provide favorable conditions for successful aging., (© 2023. The Author(s).)

Backround: Information about the direct comparability of big data of epidemiological cohort studies and the general population still is lacking, especially regarding all-cause mortality rates. The aim of this study was to investigate the overall survival and the influence of several diagnoses in the medical history on survival time, adjusted to common risk factors in a populations-based cohort., Methods: From 10,000 subjects of the population-based cohort LIFE-Adult-Study (Leipzig Research Centre for Civilization Diseases), the medical history and typical risk factors such as age, smoking status and body-mass-index (BMI) were assessed. The survival status was identified from the saxonian population register. Univariate and multivariate analyses were used to determine the influence of the medical history and risk factors on overall survival. To develope an optimal model, the method by Collet [1] was used., Results: The mortality rate of the participants is approximately half the mortality rate expected for the german population. The selection bias in epidemiological studies needs to be considered whenever interpreting results of epidemiological cohort studies. Nevertheless we have shown that several diagnoses proved to have a negative influence on overall survival time even in this relatively healthy cohort. This study showed the significantly increased mortality risk if the following diseases are reported in medical history of the participants in a large population-based cohort study including adults aged 18 and over: diabetes mellitus (HR 1.533, p = 0.002), hypertension (HR 1.447, p = 0.005), liver cirrhosis (HR 4.251, p < 0.001), osteoporosis (HR 2.165, p = 0.011), chronic bronchitis (HR 2.179, p < 0.001), peptic ulcer disease (HR 1.531, p = 0.024) and cancer (HR 1.797, p < 0.001). Surprisingly, asthma has the opposite effect on survival time (HR 0.574, p = 0.024), but we believe this may be due to an overrepresentation of mild to moderate asthma and its management, which includes educating patients about a healthy lifestyle., Conclusion: In the LIFE-Adult-Study, common risk factors and several diseases had relevant effect on overall survival. However, selection bias in epidemiological studies needs to be considered whenever interpreting results of epidemiological cohort studies. Nevertheless it was shown that the general cause-and-effect principles also apply in this relatively healthy cohort., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Zeynalova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Resilience describes a good adaptation to adversity. Strengthening resilience is a promising approach in the prevention of mental health problems. Yet, research on the association of resilience with mental health symptoms in the general population is scarce. The aim of our study is to examine comprehensively the association of resilience with depressive symptoms, anxiety, and perceived stress in a large population-based sample. We analyzed data of n = 3762 participants from the follow-up assessment of the LIFE-Adult-Study, a population-based cohort study in Leipzig. Assessments included resilience (RS-11), depressive symptoms (CES-D), anxiety (GAD-7), and perceived stress (PSQ). The association of resilience with mental health symptoms was examined via multiple linear regression analyses. In our analyses, higher resilience predicted less mental health problems and contributed significantly to the explained variance in mental health outcomes. Women, individuals with previous mental disorders, and those without employment had higher mental health symptoms. Resilience is closely associated with mental health problems in the general population. Vulnerable groups should be targeted with public health measures. Strengthening resilience is a promising approach in the large-scale prevention of mental disorders.

Background: The heartbeat-evoked potential (HEP) is a brain response to each heartbeat, which is thought to reflect cardiac signaling to central autonomic areas and suggested to be a marker of internal body awareness (eg, interoception)., Objectives: Because cardiac communication with central autonomic circuits has been shown to be impaired in patients with atrial fibrillation (AF), we hypothesized that HEPs are attenuated in these patients., Methods: By simultaneous electroencephalography and electrocardiography recordings, HEP was investigated in 56 individuals with persistent AF and 56 control subjects matched for age, sex, and body mass index., Results: HEP in control subjects was characterized by right frontotemporal negativity peaking around 300 to 550 ms after the R-peak, consistent with previous studies. In comparison with control subjects, HEP amplitudes were attenuated, and HEP amplitude differences remained significant when matching the samples for heart frequency, stroke volume (assessed by echocardiography), systolic blood pressure, and the amplitude of the T-wave. Effect sizes for the group differences were medium to large (Cohen's d between 0.6 and 0.9). EEG source analysis on HEP amplitude differences pointed to a neural representation within the right insular cortex, an area known as a hub for central autonomic control., Conclusions: The heartbeat-evoked potential is reduced in AF, particularly in the right insula. We speculate that the attenuated HEP in AF may be a marker of impaired heart-brain interactions. Attenuated interoception might furthermore underlie the frequent occurrence of silent AF., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Resilience is closely related to mental health and well-being. Identifying risk groups with lower resilience and the variables associated with resilience informs preventive approaches. Previous research on resilience patterns in the general population is heterogeneous, and comprehensive large-scale studies are needed. The aim of our study is to examine sociodemographic and social correlates of resilience in a large population-based sample. We examined 4795 participants from the LIFE-Adult-Study. Assessments included resilience (RS-11), social support (ESSI), and social network (LSNS), as well as the sociodemographic variables age, gender, marital status, education, and occupation. The association of resilience with sociodemographic and social correlates was examined using linear regression analyses. Higher resilience was associated with female gender, married marital status, high education, and full-time occupation. Social support and social network were positively associated with resilience. Our results implicate that resilience is related to various sociodemographic variables. Social variables seem to be particularly important for resilience. We identified risk groups with lower resilience, which should be given special attention by public health policies, especially in times of crisis. Reducing loneliness and promoting social connectedness may be promising ways to build resilience in the general population.

Substantial evidence indicates a huge potential for risk reduction of cognitive decline and dementia based on modifiable health and lifestyle factors. To maximize the chances for risk reduction, it is useful to investigate associations of social determinants and lifestyle for brain health. We computed the "LIfestyle for BRAin health" (LIBRA) score for baseline participants of the Leipzig Research Centre for Civilization Diseases (LIFE) Adult Study, a population-based urban cohort in Germany. LIBRA predicts dementia in midlife and early late life populations, comprising 12 modifiable risk factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive inactivity). Associations of social determinants (living situation, marital status, social isolation, education, net equivalence income, occupational status, socioeconomic status/SES, employment) with LIBRA were inspected using age- and sex-adjusted multivariable linear regression analysis. Z-standardization and sampling weights were applied. Participants (n = 6203) were M = 57.4 (SD = 10.6, range 40-79) years old and without dementia, 53.0% were women. Except for marital status, all considered social determinants were significantly associated with LIBRA. Beta coefficients for the association with higher LIBRA scores were most pronounced for low SES (β = 0.80, 95% CI [0.72-0.88]; p < 0.001) and middle SES (β = 0.55, 95% CI [0.47-0.62]; p < 0.001). Social determinants, particularly socioeconomic factors, are associated with lifestyle for brain health, and should thus be addressed in risk reduction strategies for cognitive decline and dementia. A social-ecological public health perspective on risk reduction might be more effective and equitable than focusing on individual lifestyle behaviors alone., (© 2022. The Author(s).)

Background: Research shows a connection between stress and depression, but there is little differentiation between areas of stress, making it difficult to identify and address specific areas in the context of public health measures. We utilized a multi-dimensional approach to chronic stress to better understand the relationship between different areas of stress and depression., Methods: We conducted linear regression analyses and used data from a sub-sample of the LIFE-Adult-Study (N = 1008) to analyze the connection between nine different areas of chronic stress (TICS) and depression (CES-D). In the second analysis, we controlled for sociodemographic variables, personality, physical activity, and social support., Results: There was a significant positive association between the stress domains Excessive Demands from Work, Lack of Social Recognition, Social Isolation, and Chronic Worrying and depression and a significant negative association between Pressure to Perform and depression. After adding control variables, only Pressure to Perform, Social Isolation, and Chronic Worrying remained significant predictors., Conclusions: By focusing on the connections between chronic stress and depression, researchers can help identify the areas that matter most and contribute to the creation of meaningful and efficient interventions. On the basis of our results, measures for the prevention of depression that focus on the reduction of worrying and social isolation are recommended.

Background: PR interval prolongation is a preliminary stage of atrial cardiomyopathy which is considered as an intermediate phenotype for atrial fibrillation (AF). AF is a known risk factor for cerebrovascular adverse outcomes including stroke. Cerebral ischemia is one cause of white matter hyperintensities (WMHs), and cognitive dysfunction., Aim: To analyze the relationship between PR interval and WMHs., Materials and Methods: We performed a cross-sectional analysis with individuals from the LIFE-Adult-Study (a population-based cohort study of randomly selected individuals from Leipzig, Germany) with available brain MRI and ECG. The Fazekas stages were used to quantify WMHs (0 = none; 1 = punctate foci; 2 = beginning confluence; 3 = large confluent areas). Stages 2-3 were defined as advanced WMHs. The PR interval was measured from resting 12-lead ECG. PR duration >200ms was defined as PR interval prolongation. We used a binary logistic regression for statistical analysis. We examined the relationship between MRI and ECG measures and adjusted them for clinical risk factors., Results: We included 2464 individuals (age 59±15 years, 47% women) into analyses. The median PR interval was 160ms (interquartile range 143-179), and 319 (13%) individuals with advanced WMHs, were significantly older, had more cardiovascular comorbidities and risk factors compared to individuals without WMHs (all p<0.005). On univariable analysis, PR interval duration (OR 1.01, 95%CI 1.01-1.02, p≤0.001) and PR interval ≥160 ms (OR 2.1, 95%CI 1.6-2.7, p≤0.001) were associated with advanced WMHs. In multivariable analysis, while PR interval duration was not associated with WMHs in the whole cohort, individuals with PR ≥160ms had higher risk for WMHs., Conclusion: PR interval duration is associated with advanced WMHs beside advanced age, hypertension, and history of stroke. Further research is needed to determine whether changes in PR interval indices are clinically relevant for changes in WMHs., Competing Interests: The authors have declared that no competing interests exist.

Background: Anxiety is a widespread phenomenon, and it is connected to disordered eating and obesity. We want to analyze the connection between anxiety and food addiction (FA) over two points in time to better understand the directionality of the association. Since there are gender differences with regard to anxiety and eating, we are also interested in differences between men and women., Methods: We used data from the population-based LIFE-Adult-Study ( N = 1,474) at time 1 (baseline) and time 2 (first follow-up) to analyze the connections between anxiety (GAD-7) and FA (YFAS) using a multiple group latent cross-lagged panel model with female and male participants as groups. We controlled for age, marital status, socioeconomic status and social support., Results: Anxiety (women: β = 0.50, p ≤ 0.001; men: β = 0.59, p ≤ 0.001) as well as FA (women: β = 0.37, p ≤ 0.001; men: β = 0.58, p ≤ 0.001) exhibited stability over time for both genders. We found a significant association between anxiety at time 1 and FA at time 2 for women (β = 0.25, p ≤ 0.001) but not for men (β = 0.04, p = 0.10), and significant associations between FA at time 1 and anxiety at time 2 for women (β = 0.23, p ≤ 0.001) as well as men (β = 0.21, p ≤ 0.001)., Conclusion: Food addiction longitudinally affects anxiety, independent of gender and other sociodemographic variables. In addition, anxiety affects subsequent FA as well, but only in women. Interventions that address FA could reduce anxiety in men and women, while interventions that mitigate anxiety could help prevent FA in women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hussenoeder, Pabst, Conrad, Löbner, Engel, Zeynalova, Reyes, Glaesmer, Hinz, Witte, Schroeter, Wirkner, Kirsten, Löffler, Villringer and Riedel-Heller.)

Aims: Heart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). It is known that AF impairs the diagnostic accuracy of NT-proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT-proBNP for HF and AF in stable outpatients with cardiovascular risk factors., Methods and Results: Data were obtained from the DIAST-CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population-based cohorts using the same inclusion/exclusion criteria: LIFE-Adult (n = 2869), SHIP (n = 2013), and SHIP-TREND (n = 2408). Serum levels of NT-proBNP were taken once at baseline. The DIAST-CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF (n = 1375) had a median NT-proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF (n = 93), NT-proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group (P < 0.001) and compared with those with only HF [n = 201; 158 (66;363) pg/mL; P < 0.001]. The highest levels of NT-proBNP [868 (213;1397) pg/mL] were measured in patients with concomitant HF and AF (n = 58; P < 0.001 vs. control and vs. HF, P = 1.0 vs. AF). In patients with AF, NT-proBNP levels did not differ between those with HF and preserved ejection fraction (EF) > 50% [n = 38; 603 (175;1070) pg/mL] and those without HF (P = 1.0). Receiver-operating characteristic curves of NT-proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79-0.88]) and for HF with EF < 50% (0.78 [0.72-0.85]; P = 0.18). The AUC for HF with EF > 50% was significantly lower (0.61 [0.56-0.65]) than for AF (P = 0.001). During follow-up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT-proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75-0.83]) than of newly diagnosed HF (0.59 [0.55-0.63]; P < 0.001). Data were validated in three independent population-based cohorts (LIFE-Adult, n = 2869; SHIP, n = 2013; and SHIP-TREND, n = 2408)., Conclusions: In stable outpatients, NT-proBNP is a better marker for prevalent and incident AF than for HF. In AF patients, the diagnostic value of NT-proBNP for HF with EF > 50% is very limited., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Atopic eczema (AE) is known to be associated with depression and anxiety. We aimed at investigating the occurrence of selected psychological comorbidities in patients with AE under treatment in our university dermatological department., Methods: Monocentric prospective examination of adult AE patients using PO-SCORAD (Patient-Oriented Severity Scoring of AD), EASI (Eczema Area and Severity Index), POEM (Patient-Oriented Eczema Measure), DLQI (Dermatologic Life Quality Index), LSNS-6 (Lubben Social Network Scale 6), CES-D (Center for Epidemiologic Studies Depression Scale), HADS-D and -A (Hospital Anxiety and Depression Scale), and GAD-7 (Generalized Anxiety Disorder Scale-7) was carried out. We looked for correlations between AE severity and psychosocial comorbidities. Data were compared with age- and sex-matched controls from nonatopic subjects., Statistics: Mann-Whitney U test and Spearman's rank correlation were used., Results: Eighty-four patients (44 women, median age 35.0 years, range: 19.4-92.8 years) were included. PO-SCORAD was 40.4 [23.4-55.4] (median [interquartile range]), EASI 9.3 [3.4-18.9], POEM 16 [8-24], and DLQI 10 [4-18]. Compared with 161 from the healthy LIFE-Adult cohort controls, our patients with AE had significantly higher scores for HADS, GAD-7, and CES-D (p < 0.001, respectively), but there was no increase in the LSNS score (18 vs. 19; p = 0.067). Within the group of AE patients, there was a significant correlation of the subjective skin severity and the depression and anxiety values: POEM significantly correlated with GAD-7, CES-D, and HADS-A and -D (p < 0.001). PO-SCORAD significantly correlated with GAD-7 and CES-D (p < 0.05). EASI correlated neither with HADS-A or -D nor with CES-D. Patients with suicidal thoughts, plans, or attempts in the last 12 months had significantly more severe AE than those without (POEM 25 [15.3-26] vs. 15 [7-23]; p = 0.013, and PO-SCORAD 51.6 [40.2-63] vs. 20.5 [20.7-52]; p = 0.014)., Conclusion: Patients with AE being currently under treatment in our department had significantly increased scores indicating depression and anxiety. Suicidal tendency was increased in patients with severe AE., Key Message: AE patients may develop depression, anxiety, and suicidal ideation. Patient-oriented scores may help identifying high-risk patients., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background: There are socioeconomic inequalities in dementia risk. Underlying pathways are not well known., Objective: To investigate whether modifiable health and lifestyle factors for brain health mediate the association of socioeconomic status (SES) and cognitive functioning in a population without dementia., Methods: The "LIfestyle for BRAin health" (LIBRA) score was computed for 6,203 baseline participants of the LIFE-Adult-Study. LIBRA predicts dementia in midlife and early late life, based on 12 modifiable factors. Associations of SES (education, net equivalence income, and occupational status) and LIBRA with cognitive functioning (composite score) were investigated using adjusted linear regression models. Bootstrapped structural equation modelling (SEM) was used to investigate whether LIBRA mediated the association of SES and cognitive functioning., Results: Participants were M = 57.4 (SD = 10.6, range: 40-79) years old; 50.3% were female. Both, SES (Wald: F(2)=52.5, p < 0.001) and LIBRA (Wald: F(1)=5.9, p < 0.05) were independently associated with cognitive functioning; there was no interaction (Wald: F(2)=2.9, p = 0.060). Lower SES and higher LIBRA scores indicated lower cognitive functioning. LIBRA partially mediated the association of SES and cognitive functioning (IE: =0.02, 95% CI [0.02, 0.03], p < 0.001). The proportion mediated was 12.7%., Conclusion: Differences in cognitive functioning due to SES can be partially attributed to differences in modifiable health and lifestyle factors; but to a small extent. This suggests that lifestyle interventions could attenuate socioeconomic inequalities in cognitive functioning. However, directly intervening on the social determinants of health may yield greater benefits for dementia risk reduction.

Anxiety is a widespread phenomenon that affects various behaviors. We want to analyze in how far anxiety is connected to eating behaviors since this is one potential pathway to understanding eating-related health outcomes like obesity or eating disorders. We used data from the population-based LIFE-Adult-Study (n = 5019) to analyze the connection between anxiety (GAD-7) and the three dimensions of eating behaviors (FEV)-Cognitive Restraint, Disinhibition, and Hunger-while controlling for sociodemographic variables, smoking, physical activity, personality, and social support. Multivariate regression analyses showed significant positive associations between anxiety and Disinhibition as well as Hunger, but not between anxiety and Cognitive Restraint. Interventions that help individuals to better regulate and cope with anxiety, could be one potential pathway to reducing eating disorders and obesity in the population., (© 2021. The Author(s).)

Brucellosis caused by Brucella abortus and Brucella melitensis is endemic in the Republic of Azerbaijan but a complex mix of fiscal, political and technical constraints has impeded regulatory authority decision making for adoption of a sustainable national control programme. This paper reports a series of epidemiologic studies of the disease in animals and humans which we conducted between 2009 and 2020. A preliminary study and a subsequent larger study using vaccination of all non-pregnant female sheep and goats of breeding age and all females between 3 and 8 months with conjunctival Rev1 vaccine both recorded significant reduction in small ruminant seroprevalences. A case control study of winter pasture flocks found many case and control farmers used raw milk to make dairy products for sale, ate fresh cheese and sold dairy products in unregulated markets. Almost all farmers expressed willingness to pay a portion of the costs associated with elimination of brucellosis from their flocks. A pilot human study in 2009 led to a large study in 2017 which recorded an overall seroprevalence of 8.1% in humans. Persons in farm related occupations were at greater risk than urban persons and males were more likely to be seropositive than females. Risk factors included keeping small ruminants, using raw milk cheese and slaughtering animals whereas having heard education information about brucellosis and vaccinating against brucellosis were protective., (Copyright © 2021 Agricultural Competitiveness 0mprovement Project implemented by the Agency for Agro Credit and Development. Published by Elsevier Ltd.. All rights reserved.)

In elderly patients (pts) with aggressive B cell lymphoma (aNHL), curative treatment often cannot be administered because of comorbidities and tolerability. We analyzed the influence of age in pts > 60 years receiving the R-CHOP-14 regimen within different prospective DSHNHL trials. Of the RICOVER-60 trial and CHOP-R-ESC trials, 1171 aNHL pts were included in this retrospective analysis of age-dependent event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All patients received prophylactic G-CSF, and anti-infective prophylaxis with amphotericin B mouth wash and oral fluorchinolone was optional. In the CHOP-R-ESC trials, prophylaxis was augmented to include mandatory continuous orally administered aciclovir and a pneumocystis prophylaxis with cotrimoxazole as well as oral fluorchinolones during neutropenia. The patient population was separated into 4 age groups (61-65 years, 66-70 years, 71-75 years, and 76-80 years). The results from the RICOVER-60 trial were subsequently confirmed in the following CHOP-R-ESC trials by a multivariate analysis adjusted for IPI factors and gender. Significant differences (p < 0.001) in EFS, PFS, and OS were seen between age groups (RICOVER-60). Hematotoxicity, infections, and TRM increased with age. TRM was significantly elevated in the age group 76-80 years. Therefore, this analysis shows that an age above 75 years defines an especially vulnerable patient population when being treated with chemoimmunotherapy for aNHL. Prophylactic anti-infective drugs are essential and clinically effective in reducing morbidity when treating elderly aNHL pts.

Coronary heart disease, an inflammatory disease, is the leading cause of death globally. White blood cell counts (including monocytes) are easily available biomarkers of systemic inflammation. Monocyte subtypes can be measured by flow cytometry and classified into classical (CD14high, CD16neg), intermediate (CD14high, CD16+) and non-classical (CD14+, CD16high) with distinct functional properties. The goal of this study was to investigate the association of monocyte total count and its subtypes with cardiovascular risk groups defined by the Framingham Risk Score, which is used to estimate the 10-year risk of developing myocardial infarction or predict mortality following coronary heart disease. We also aimed to investigate whether monocyte counts are associated with relevant cardiovascular risk factors not included in the Framingham Risk Score, such as carotid atherosclerotic plaque and intima-media thickness. Our data came from the LIFE-Adult study, a population-based cohort study of 10,000 randomly selected participants in Leipzig, Germany. Data was gathered using self-administered questionnaires and physical examinations. Carotid plaques and intima-media thickness were measured using carotid artery sonography. Monocyte subtypes in blood were determined by 10-color flow cytometry for a total of 690 individuals. In a multivariate regression analysis adjusting for the risk factors BMI, intima-media thickness, presence of carotid plaques and diabetes mellitus, monocyte subtypes and total count were found to be significantly associated with the dichotomized Framingham Risk Score (≥10% versus <10%): Odds ratios [95% confidence interval] for monocyte subtypes: classical: 11.19 [3.79-34.26]; intermediate: 2.27 [1.11-4.71]; non-classical: 4.18 [1.75-10.20]; total: 14.59 [4.61-47.95]. In absence of prospective data, the FRS was used as a surrogate for CHD. Our results indicate that monocyte counts could provide useful predictive value for cardiovascular disease risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Markus Scholz receives funding from Pfizer Inc. for a project not related to this research. The remaining authors have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: White matter lesions (WML) are common structural alterations in the white matter of the brain and their prevalence increases with age. They are associated with cerebral ischaemia and cognitive dysfunction. Patients with heart failure (HF) are at risk for cognitive decline. We hypothesized that the presence and duration of HF are associated with WML., Methods and Results: The LIFE-Adult Study is a population-based study of 10 000 residents of Leipzig, Germany. WML were quantitated in 2490 participants who additionally underwent cerebral MRI using the Fazekas score. Mean age was 64 years, and 46% were female; 2156 (86.6%) subjects had Fazekas score of 0-1, and 334 (13.4%) had Fazekas score of 2-3. Thirty participants had a medical history of HF, 1019 had hypertension, and 51 had a history of stroke. Median left ventricular ejection fraction of the participants with HF was 57% (interquartile ranges 54-62). Age, troponin T, NT-proBNP, body mass index, history of acute myocardial infarction, stroke, HF, and diabetes were positively associated with WML in univariate analysis. On multivariate analysis, age, hypertension, stroke, and HF were independently associated with WML. The odd's ratio for the association of WML (Fazekas 2-3) with HF was 2.8 (95% CI 1.2-6.5; P = 0.019). WML increased with longer duration of HF (P = 0.036 for trend)., Conclusions: In addition to age, hypertension, and stroke, the prevalence and duration of HF are independently associated with WML. This observation sets the stage to investigate the prognostic value of WML in HF and the impact of HF therapies on WML., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: This study investigated utilisation behaviour of the dentist compared to general practitioners (GP) and medical specialists in a German cohort under consideration of risk indicators for irregular dental attendance., Methods: Analysis of the results of the population-based LIFE-Adult-Study (Leipzig, Germany) was performed. A total of 2231 participants of the LIFE-Adult-Study were randomly selected to complete the relevant questionnaire, considering medical attendance behaviour. Associations of self-reported medical conditions, including dentaland medical attendance, sociodemographic factors, as well as self-reported general health status and oral health complaints were determined., Results: Of the 2231 participants who were included in the analysis, 14.2% reported not to have visited the dentist during the preceding 12 months. There could be shown a more selective utilisation behaviour towards medical services in smokers, men, low socioeconomic status and depression. Women were more likely to attend the dentist than men (OR = 1.8, CI = 1.4-2.3). Smoking (OR = 0.7, CI = 0.6-1.0), low socioeconomic status (OR = 0.6, CI = 0.4-0.8) and depression (OR = 0.6, CI = 0.4-0.9) were related to less dental attendance. Additionally, persons who do not visit the dentist regularly showed less attendance of the GP as well as medical specialists (p <0.05). Depression could be shown to be an additional risk factor for unfavourable utilisation behaviour towards the dentist., Conclusions: The results showed differences in dental and medical attendance, depending on different patient-related factors. Focusing attention towards high-risk groups might improve dental as well as medical utilisation behaviour, and therefore health status as well.

Aims: Atrial fibrillation (AF) is a frequent comorbidity in patients with heart failure (HF). HF patients with AF are characterized by high morbidity and increased risk of hospitalizations. We assessed the effects of remote patient management (RPM) in HF patients with AF compared with usual care (UC) in the TIM-HF2 trial., Methods and Results: For this post-hoc analysis, AF status at randomization was assessed in 1537 patients with HF. The primary outcome was the percentage of days lost due to unplanned cardiovascular hospital admissions or death of any cause. Around 966 patients had sinus rhythm (SR) and 571 had AF. The analysis showed a significant interaction between heart rhythm and all-cause mortality (P for interaction = 0.001). AF patients had more days lost due to unplanned cardiovascular hospitalization than SR patients (7.53%, CI 6.01-9.05 vs. 4.90%, CI 3.98-5.82, ratio 1.54, P = 0.004) and higher all-cause mortality (11.9%, CI 9.4-14.9 vs. 8.5%, CI 6.8-10.4, HR 0.66, CI 0.47-0.94, P = 0.029). Patients with AF randomized to RPM had significantly less days lost due to unplanned cardiovascular hospital admissions or all-cause death (5.64%, CI 3.81-7.48) than patients with AF randomized to UC (9.37%, CI 6.98-11.76, ratio 0.60, P = 0.015). No difference was seen in SR patients (UC: 5.25%, CI 3.93-6.58, RPM: 4.55%, CI 3.27-5.83, ratio 0.87, P = 0.452). All-cause mortality in AF patients was reduced with 9.2% (CI 6.1-13.2) in the RPM group compared with 14.5% (CI 10.7-18.1) in the UC group (HR 0.60, CI 0.36-1.00, P = 0.050)., Conclusions: For patients with atrial fibrillation at study entry, RPM was associated with increased days alive out of hospital. Our results identify HF patients with atrial fibrillation as a promising target population for RPM., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Transition from employment to retirement is regarded a crucial event. However, there is mixed evidence on associations between retirement and mental health, especially regarding early retirement. In Germany, cases of early retirement due to ill health-particularly, mental ill health-are increasing. Therefore, we investigated the association between early retirement and depressive symptoms, including information on different types of early retirement., Methods: We analyzed data from 4,808 participants of the population-based LIFE-Adult-Study (age: 40-65 years, 654 retired, 4,154 employed), controlling for sociodemographic information, social network, pre-existing health conditions, and duration of retirement. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Regression analysis using entropy balancing was applied to achieve covariate balance between retired and employed subjects., Results: We found no overall-differences in depressive symptoms between employed and retired persons (men: b = -.52; p = 0.431; women: b = .05; p = .950). When looking at different types of early retirement, ill-health retirement was linked to increased depressive symptoms in women (b = 4.68, 95% CI = 1.71; 7.65), while voluntary retirement was associated with reduced depressive symptoms in men (b= -1.83, 95% CI = -3.22; -.43) even after controlling for covariates. For women, statutory retirement was linked to lower depressive symptomatology (b = -2.00, 95% CI = -3.99; -.02)., Conclusion: Depressive symptomatology among early retirees depends on reason for retirement: For women, ill-health retirement is linked to higher levels of depressive symptoms. Women who retire early due to ill-health constitute a risk group for depressive symptoms that needs specific attention in the health care and social security system., (Copyright © 2020 Zuelke, Roehr, Schroeter, Witte, Hinz, Glaesmer, Engel, Enzenbach, Zachariae, Zeynalova, Loeffler, Villringer and Riedel-Heller.)

Contrast-flow quantitative flow ratio (cQFR) is a new technology for quantitative evaluation of coronary stenosis using computational fluid dynamics based on angiograms. The aim of this study was to assess the sensitivity and specificity of cQFR to detect myocardial ischemia using stress magnetic resonance imaging (MRI) as a reference standard. Patients who received stress MRI and coronary angiography were selected from the hospital database. Relevant ischemia on stress MRI was defined as a perfusion deficit in ≥ 2 of 16 segments. cQFR was quantitated based on 3-dimensional quantitative coronary angiography using QAngio XA3D1.1 software by two blinded and independent investigators. A cQFR of ≤ 0.80 was considered abnormal. Among 87 patients 230 vessels met the criteria for full analysis by cQFR (88%). In vascular territories with a significant perfusion deficit, cQFR was significantly lower compared to areas with normal perfusion (0.72 (0.62-0.78) vs. 0.96 (0.89-0.99); p < 0.001). The sensitivity of cQFR in detecting significant epicardial stenoses of coronary vessels with documented ischemia in stress MRI was 81% (68-90%), the specificity was 88% (82-92%). Diameter stenoses (DS) and area stenoses (AS) in vessels with positive stress MRI were significantly higher than in vessels without ischemia (DS 59.1% (49.4-68.4%) vs. 34.8% (27.1-46.1%) p < 0.001; AS 75.6% (63.0-85.2%) vs. 45.0% (30.8-63.6%), p < 0.001). The analysis reveals a high correlation between coronary stenosis measured by cQFR and ischemic areas detected by stress MRI. The data set the stage to plan randomized studies assessing cQFR measurements with regard to clinical outcomes.

Background: In patients with atrial fibrillation (AF), left atrial (LA) enlargement, and the presence of low-voltage areas (LVAs) indicate an advanced disease stage. NT-proANP is a biomarker, which is significantly higher in both phenotypes. Prediction of LVAs before catheter ablation could impact the prognosis and therapeutical management in AF patients., Objective: The aim of this study was to (a) analyze the predictive value of a novel biomarker-based AF substrate prediction score, and (b) compare it with DR-FLASH and APPLE scores., Methods: Patients undergoing first AF catheter ablation were included. LA volume (LAV) was analyzed prior to ablation using cardiovascular magnetic resonance imaging (CMR). Blood plasma samples from the femoral vein were collected before AF ablation. NT-proANP was analyzed using commercially available assays. LVAs were determined using high-density maps during catheter ablation and defined as <0.5 mV. The novel ANP score (one point for Age ≥ 65 years, NT-proANP > 17 ng/mL, and Persistent AF) was calculated at baseline., Results: The study population included 156 AF patients (64 ± 10 years, 65% males, 61% persistent AF, 28% LVAs). The cut-off ANP score ≥ 2 demonstrated 77% sensitivity and 70% specificity. On logistic regression (odds ratio [OR] 3.469) and receiver operating characteristic (ROC) analysis (area under the curve [AUC] 0.778, P < .001), the ANP score significantly predicted LVAs presence. There were no differences between novel ANP score - which is a new one - is described in the Abstract; with APPLE (AUC 0.718, P = .378) and DR-FLASH (AUC 0.766, P = .856) scores., Conclusions: The novel biomarker-based ANP score demonstrates good prediction of LVAs., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: Atopic eczema (AE) may be associated with several mental health problems. In Germany, existing data from selected patient cohorts may lead to misestimation of the problem., Objectives: We aimed to cross-sectionally determine associations of AE with depression, anxiety, quality of life (QoL) and social interactions in subjects from the population-based LIFE-Adult-Study., Methods: Subjects underwent standardized interviews (medical history) and answered standardized questionnaires [Centre of Epidemiologic studies-Depression scale (CES-D), Generalized Anxiety Disorder (GAD-7), Lubben Social Network Scale (LSNS), Short Form Health Survey (SF-8)]. We compared data from subjects with AE with those from subjects with selected other chronic/disabling diseases (cardiovascular, diabetes, cancer) and adjusted for selected sociodemographic parameters. Multivariate binary logistic regression was used for categorical variables, linear regression for continuous variables., Results: Out of 9104 adults included (57% female, median age 54 years), 372 (4.1%) had a history of AE. Compared with controls, subjects with AE showed higher scores for depressive symptoms (9.3% vs. 6.3%; P < 0.001) and anxiety (8.4% vs. 5.6%, P < 0.001). Odds ratio (OR) was 1.5 [CI 1.0; 2.3] (P = 0.031) for depression, which was comparable to OR in patients with a history of cancer (OR 1.6 [1-2.3], P = 0.001. OR for anxiety in AE was 1.5 [1.0; 2.2], P < 0.049, which was slightly higher than in diabetes mellitus (OR 1.2) and stroke (OR 1.4). Other than in diabetes and/or stroke, we did not find a significant association between AE and social isolation. QoL scores were lower in AE than in controls (mean 46.9 vs. 48.0, P < 0.001 for physical and 50.6 vs. 52.5, P < 0.001 for mental components)., Conclusions: Subjects with AE showed higher values for depression and anxiety as well as lower QoL scores compared to controls. With regard to depression, odds in AE and cancer were hardly different. Medical care of AE patients should therefore include mental health evaluation and treatment if indicated., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Aim: This study explores gender-specific differences in the utilization of health care services in an urban population sample., Method: As part of the LIFE-ADULT-Study, 2244 individuals (19-79 years) filled out a questionnaire about their use of health care services during the past year. Information regarding the frequency of general and specialized practitioners consultation, medical advice from general practitioners and utilization of preventive and health promoting programs were analyzed., Results: Women visited general practitioners or specialists and utilized prevention and health-promotion programs more often than men. No gender differences were found regarding the frequency of receiving medical advice from general practitioners., Conclusions: The results mainly replicate prior findings showing that women utilize health care services more frequently than men. However, these gender differences vary as a function of the indicator employed and should therefore be discussed differentially., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Patients with cardiac complaints but without confirmed diagnosis of coronary heart disease by angiography frequently develop cardiac events in the following years. This follow-up study investigated the frequency of cardiac symptoms and cardiovascular events (CVE) 5 years after initial angiography of patients with nonobstructive coronary artery disease (NobCAD, LIFE Heart study), with the aim to identify gender-specific indicators for CVE. Methods: In 2014/2015, 1462 women and men with NobCAD, defined as no or non-relevant obstructive coronary artery disease were identified among 2660 subjects participating in the observational angiographic LIFE Heart study. Questionnaires of 820 responding patients were analyzed. Results: The median observation time was 55 months. Cardiac symptoms were found in 53.6% of all patients, significantly more often in women than in men (59.4% vs. 48.8%; p  = 0.002). CVE occurred in 46.1% of all participants ( n  = 378/820). Patients with cardiac symptoms had a 2.94 time higher risk for CVE than those without cardiac symptoms ( p  < 0.001). Men with no cardiac symptoms had significantly more CVE ( p  = 0.042) than women. Common risk factors for CVE comprised cardiac symptoms, atrial fibrillation, and age. Sex-specific risk factors comprised body mass index (BMI) ≥25 kg/m 2 for women and anxiety for men. Conclusions: Patients with cardiac symptoms have about three times higher risk for CVE within 5 years than patients without cardiac symptoms. Sex differences exist in patients without symptoms where men were at higher risk for CVE. Atrial fibrillation was the strongest indicator for CVE, whereas anxiety was an indicator only in men and BMI ≥25 kg/m 2 only in women, suggesting sex- and gender-specific phenotypic profiles.

Background: Electro-anatomical remodeling in atrial fibrillation (AF) is associated with disease initiation and progression. Troponin T (TropT) - a specific biomarker for myocardial damage - is associated with AF incidence. However, its association with AF progression is understudied. The aim of the current analysis was to investigate the association between TropT and AF progression phenotypes: persistent AF and left atrial low voltage areas (LVAs)., Methods: Patients undergoing first AF ablation were included into analyses. LVAs were determined using high-density maps and defined as <0.5 mV. Blood samples from femoral vein were collected before catheter ablation. The analysis of TropT serum concentrations was performed using a high-sensitive assay from Roche Diagnostics. Biomarkers, clinical, anthropometric and echocardiographic data were compared with healthy individuals from the epidemiological cohort., Results: The study included 824 healthy individuals without overt cardiovascular disease (54 ± 10 years, 40% males) from epidemiological cohort and 241 AF patients (64 ± 11 years, 59% males, 59% persistent AF, 27% LVAs). Patients with AF had higher TropT levels and larger left atrium (LA), while healthy individuals had better renal function and ejection fraction (all p < 0.001). In clinical cohort, there were significant differences between TropT levels according to AF progression groups: paroxysmal AF without/with LVAs (n = 86/12), persistent AF without/with LVAs (n = 90/53): means 7.3, 12.9, 8.4, 11.3 pg/ml, p < 0.001, respectively. Similar findings were observed for LA and renal function (all p < 0.001). On ROC analysis, TropT significantly predicted LVAs (AUC 0.675, 95%CI 0.598-0.752, p < 0.001) in AF patients., Conclusions: TropT may be useful to differentiate AF progression phenotypes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Schmallenberg virus is an orthobunyavirus that infects ruminants and can cause transient fever, diarrhea, reduced milk production, congenital malformations, and abortions. Following the first suspected cases in Azerbaijan, a surveillance study was launched to determine and follow the situation. Serum samples and fetal tissue were collected starting October 2012 and tested via ELISA and qPCR. A first wave of Schmallenberg virus infections was detected in 2012/2013 in, and was largely limited to, the southern part of the country. In the second and larger wave in 2013/2014, cases were found throughout most of the country. Since then, no major outbreaks have been recorded.

The prediction of arrhythmia recurrences after catheter ablation of atrial fibrillation (AF) remains challenging. The aim of current analysis was to investigate the time-dependent prediction of arrhythmia recurrences after AF catheter ablation during long-term follow-up. The study included 879 patients (61 ± 10 years; 64% males; 39% persistent AF) undergoing first AF catheter ablation. Rhythm outcomes were documented using 7-days Holter monitoring. The APPLE score (Age, Persistent AF, imPaired eGFR, Left atrium (LA), EF) was calculated at baseline, while MB-LATER score (Male gender, Bundle branch block, LA, AF Type, Early Recurrences) 3 months after ablation. The median follow-up time was 37 months [95%CI 35;39]. ERAF and LRAF occurred in 45% and 64%, respectively. On multivariable analysis, ERAF (HR 2.095, 95%CI 1.762-2.490, p < 0.001) was strongly associated with LRAF. The APPLE (HR 1.385, 95%CI 1.276-1.505, p < 0.001) and MB-LATER (HR 1.326, 95%CI 1.239-1.419, p < 0.001) scores significantly predicted LRAF during follow-up. On the ROC analysis, APPLE (AUC 0.640, 95%CI 0.602-0.677, p < 0.001) and MB-LATER (AUC 0.654, 95%CI 0.616-0.691, p < 0.001) demonstrated moderate prediction. Summarizing, ERAF was the strongest predictor for LRAF in time-dependent manner. The APPLE and MB-LATER scores demonstrated moderate prediction of arrhythmia recurrences during long term follow-up.

Background: Cancer patients can feel depression and anxiety any time after a cancer diagnosis. The Generalized Anxiety Disorder Scale (GAD-7) is an instrument for the assessment of anxiety. The main objective of this work was to compare general anxiety levels between cancer survivors and individuals without a history of cancer in a population-based study (LIFE-ADULT) with 10,000 participants., Methods: All participants (18-80 years) completed the GAD-7 and other psychological and medical questionnaires. A score of 10 or greater for GAD-7 (of total 21) indicates a probable generalized anxiety disorder., Results: 954 participants reported a diagnosis of cancer in their medical history. In the multivariate analysis an anxiety disorder was associated with prior cancer diagnosis (OR: 1.8; 95% CI [1.4-2.4]), age -every additional year- (OR: 0.983; [0.976-0.991]), female gender (OR: 1.8; [1.5-2.2]) and low socioeconomic status (OR: 2.0; [1.7-2.5]) all p < 0.001. There were no significant associations between general anxiety and other comorbidities, such as myocardial infarction (OR: 1.0; p = 0.948), stroke (OR: 1.4; p = 0.237) or diabetes (OR: 1.0; p = 0.326). There was also no significant difference in anxiety disorder among cancer survivors regarding the time passed since the initial cancer diagnosis (OR: 1.1; [0.6-1.9], p = 0.804 comparing 5-10 years after a diagnosis of cancer vs. ≤5 years and OR: 0.6; [0.4-1.1], p = 0.107 comparing >10 vs. ≤5 years)., Limitations: This study has a cross-sectional character, therefore, causal conclusions cannot be drawn., Conclusion: Cancer survivors may require screening for anxiety disorders and long-term professional psychosocial support., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: PR interval prolongation is associated with increased risk for atrial fibrillation (AF). Different biomarkers are used to predict AF incidence and its outcomes. The aim of this study was to investigate the association between echocardiographic parameters and blood biomarkers in PR interval groups and AF., Methods: The LIFE-Adult-Study is a population-based cohort study of randomly selected participants from Leipzig, Germany. In this cross-sectional analysis, individuals ≥40 years with available echocardiographic (LA diameter, EF) and laboratory data (creatinine, Troponin, NT-proBNP) were included., Results: The study population comprised 1.429 individuals (median age 56 (IQR 48-66) years, 40% males) with complete ECG, echocardiographic and laboratory data. There were 48 (3.4%) individuals with AF, 177 (12.4%) with short, 138 (9.7%) with prolonged and 1.066 (74.5%) with normal PR interval. Individuals with PR interval prolongation had larger LA diameter, higher Troponin and NT-proBNP levels than individuals with normal PR interval, but lower than AF group (p<0.001). In contrast, eGFR was significantly higher in the group with PR interval prolongation than in AF, but lower than in individuals with normal PR interval (p<0.001). In the multivariate analysis, PR interval prolongation and AF shared similar characteristics, the only parameter different between both groups was NT-proBNP., Conclusions: Individuals with PR interval prolongation and AF showed similarities in echocardiographic parameters, renal function and blood biomarker levels. Longitudinal studies are necessary to prove whether the PR interval prolongation may be considered as preliminary stage for AF., Competing Interests: The authors have declared that no competing interests exist.

Background: Electroanatomic remodeling in atrial fibrillation (AF) leads to disease initiation and perpetuation. Although atrial natriuretic peptide (ANP) is specifically expressed in the atria and is involved in atrial remodeling, B-type natriuretic peptide (BNP) is associated with mortality and cardiovascular events in AF., Objective: The purpose of this study was to investigate the association between N-terminal (NT)-proBNP and NT-proANP levels with 3 AF progression phenotypes: persistent AF, left atrial diameter (LAD) dilation, and left atrial low-voltage areas (LVAs)., Methods: We studied NT-proBNP and NT-proANP in a discovery cohort (n = 51) and replicated the findings in a validation cohort (n = 241) undergoing first AF catheter ablation. Blood plasma samples from femoral vein were collected before catheter ablation. LVAs were determined using high-density maps and defined as <0.5 mV., Results: In our pilot cohort (age 62 ± 10 years; 63% male; 59% persistent AF; 22% LVA), NT-proANP-but not NT-proBNP-levels were significantly higher in LVA patients (14.1 vs 8.6 ng/mL; P = .009) and correlated with LAD (r 2 = 0.362; P = .011). These results were replicated in the validation cohort (age 64 ± 11 years; 59% male; 59% persistent AF; 27% LVA) (12.7 vs 8.8 ng/mL; P = .016) and correlated with LAD (r 2 = 0.180; P = .019). NT-proANP levels increased according to 4 disease progression groups: paroxysmal AF without LVA, persistent AF without LVA, paroxysmal AF with LVA, and persistent AF with LVA (mean 15, 20, 19, and 27 ng/mL, respectively; P = .004)., Conclusion: Natriuretic peptides show different sensitivity for phenotypes of AF progression. The clinical impact of NT-proANP in refining individualized therapy and disease prevention should be addressed in larger studies., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Effective methods to increase awareness of preventable infectious diseases are key components of successful control programmes. Rabies is an example of a disease with significant impact, where public awareness is variable. A recent awareness campaign in a rabies endemic region of Azerbaijan provided a unique opportunity to assess the efficacy of such campaigns. A cluster cross-sectional survey concerning rabies was undertaken following the awareness campaign in 600 households in 38 randomly selected towns, in districts covered by the campaign and matched control regions. This survey demonstrated that the relatively simple awareness campaign was effective at improving knowledge of rabies symptoms and vaccination schedules. Crucially, those in the awareness campaign group were also 1·4 times more likely to report that they had vaccinated their pets, an essential component of human rabies prevention. In addition, low knowledge of appropriate post-exposure treatment and animal sources of rabies provide information useful for future public awareness campaigns in the region and other similar areas.

Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m 2 , females 375 mg/m 2 ) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m 2 dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m 2 was not more toxic than 375 mg/m 2 rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome., (© 2017 John Wiley & Sons Ltd.)

Purpose: To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL)., Patients and Methods: A total of 2,164 patients (18 to 80 years old) with aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High-Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database., Results: The risk model consists of the International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI). In a three-risk group model, the low-risk group (46% of all patients analyzed), the intermediate-risk group (41%), and the high-risk group (12%) showed 2-year rates of CNS disease of 0.6% (CI, 0% to 1.2%), 3.4% (CI, 2.2% to 4.4%), and 10.2% (CI, 6.3% to 14.1%), respectively. Patients from the validation British Columbia Cancer Agency data set showed similar rates of CNS disease for low-risk (0.8%; CI, 0.0% to 1.6%), intermediate-risk (3.9%; CI, 2.3% to 5.5%), and high-risk (12.0%; CI, 7.9% to 16.1%) groups., Conclusion: The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions., (© 2016 by American Society of Clinical Oncology.)

Lumpy skin disease (LSD) is a viral disease of livestock that can cause cutaneous and internal lesions, affecting milk production, hide quality and in some cases death of the infected animal. After an outbreak in neighboring Iran, a working group from the Azerbaijan State Veterinary Control Service was sent to the border rayons (administrative districts) to determine if any cattle in southern Azerbaijan were infected. The Rayonal Veterinary Offices were contacted to look for and report any cases of LSD in their rayons. Animals exhibiting clinical signs consistent with LSD infection were first observed in the rayon of Bilasuvar and more cases were subsequently identified in Jalilabad, Ujar, and Aghdash rayons. Samples were collected from blood, and/or lesions of suspected infected animals and internal organs of cattle that died and were tested at the Republican Veterinary Laboratory in Baku using real-time polymerase chain reaction (PCR). From June to November 2014, 2,762 cattle in Azerbaijan were reported to have clinical signs or gross necropsy lesions consistent with LSD. Of 269 samples tested for LSD virus by real-time PCR, 199 (74%) were positive. A total of 33 cattle died, which was 1.2% of those exhibiting clinical signs of disease. Samples from nodular cutaneous lesions were more frequently positive by PCR and had higher concentrations of virus than blood and pooled internal organ samples. Preventative measures including movement restrictions, vector control and vaccination were put into place to slow the spread of disease. Ongoing surveillance should continue as environmental persistence of the virus may lead to further outbreaks of disease.