Is loneliness associated with cancellation of medical appointments during the COVID-19 pandemic? Evidence from the Hamburg City Health Study (HCHS).

BACKGROUND: The COVID-19 pandemic engendered numerous societal and economic challenges in addition to health-related concerns. Maintenance of healthcare utilization assumed immense significance during this period. However, few studies have examined the association between loneliness and cancelled medical appointments during the COVID-19 pandemic. This study aimed to examine whether medical appointments are less likely to be cancelled with increased loneliness during a pandemic. We analyzed the association between loneliness and both patient- and provider-initiated appointment cancellations. METHODS: Cross-sectional data from the Hamburg City Health Study (HCHS) were collected during April 2020-November 2021. The analytical sample included 1,840 participants with an average age of 55.1 years (standard deviation: 6.5, range 45-76 years). Medical appointments cancelled by individuals-medical appointments in general, and GP, specialist, and dentist appointments-and appointments cancelled by healthcare providers served as outcome measures. Loneliness was quantified using a single item ranging from 0 to 10. Accordingly, we created empirical loneliness tertiles. Covariates were selected based on the Andersen model. Several penalized maximum likelihood logistic regressions were utilized to examine the association between loneliness and cancellation of medical appointments during the COVID-19 pandemic. RESULTS: The penalized maximum likelihood logistic regressions showed that, compared to individuals in the lowest loneliness tertiles, individuals in the other two tertiles reported a higher chance of medical appointments cancellation by individuals, particularly driven by cancelled GP appointments. Except for age and sex, none of the covariates were comparably associated with the outcomes. When appointments cancelled by healthcare providers served as outcomes, only a higher number of chronic conditions was significantly positively associated with it. CONCLUSIONS: Individuals scoring higher in loneliness had a greater chance of cancelling medical (particularly GP) appointments. This may contribute to a potential cascade of loneliness and skipped medical appointments in the future, resulting in adverse health outcomes over the medium-to-long term. Future research should examine whether lonely people are more likely to lack the social motivation to visit the doctor.

Host traits, lifestyle and environment are associated with human skin bacteria.

BACKGROUND: The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin-microbiome interactions are still insufficiently characterized. This contrasts with the broader knowledge about factors influencing gut microbiota. OBJECTIVES: We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two German populations. METHODS: This is a cross-sectional study with 647 participants from two population-based German cohorts, PopGen (n = 294) and KORA FF4 (n = 353), totalling 1794 skin samples. The V1-V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs). RESULTS: We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus. CONCLUSIONS: We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria. Finally, we hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.

Phosphine fumigation - Time dependent changes in the volatile profile of table grapes.

Industrial and agricultural goods are fumigated in transport containers in order to control pest infestations and to avoid the transmission of alien species. Phosphine is increasingly used prior to the export as fumigant for table grapes, fruit cultures and dried fruits to control active table grapevine insect pests. Less knowledge exists for fumigants about the desorption time of toxic gases and factors that affect the composition of the fumigated good. Therefore, red and white table grapes (´Thompson seedless´, ´Scarlotta´ and ´Flame seedless´) were chosen to represent the allowed group of phosphine fumigated foods and were treated with a concentration of 2000 vpm phosphine (PH3) at different temperatures. In the present study, sorption and desorption behavior of PH3 by table grapes and possible changes in their VOC (volatile organic compounds) profiles were investigated. The PH3 concentration was monitored before and after the fumigation process and was determined under the maximum residue level 0.005 ppm after 35 days. The adsorbed amount of PH3 was not influenced by fumigation parameters. For analysis of the influences on the volatile profile after fumigation, a headspace solid-phase micro-extraction coupled to gas chromatography mass spectrometry (HS-SPME-GC/MS) was used. Small differences in volatile profiles of fumigated and subsequently outgassed table grapes compared to non-fumigated table grapes could be observed. A slight influence on the aldehyde group directly after fumigation could be perceived by a decrease of hex-2-en-1-ol and 1- hexanol in PH3-treated table grapes. The concentrations of both compounds increase again after completion of the desorption process. On the other hand terpenes are not significantly influenced by the fumigation process. Overall these changes are likely to affect table grape aroma characteristics directly after a treatment with PH3 and it could be demonstrated that phosphine alters the volatile profile of fumigated table grapes qualitatively and quantitatively.

[Breathing: Ambient Air Pollution and Health - Part III]. / Atmen: Luftschadstoffe und Gesundheit ­ Teil III.

The third part of the DGP statement introduces the current body of knowledge on less studied health outcomes associated with exposure to ambient air pollution: the negative impact on metabolism leading to impaired glucose tolerance and diabetes as well as contribution to the development of neurodegenerative disorders and delayed cognitive function in children. Furthermore, prenatal exposure and adverse effects on mother and child are addressed. Finally, the currently discussed biological mechanisms underlying various health effects associated with exposure to air pollution are described.Differing, but often complementary biological mechanisms create the basis for the diverse health outcomes caused by air pollution. Oxidative stress and a subclinical inflammatory response in the lungs and on a systemic level ("low-grade systemic inflammation") are considered to be key mechanisms. They promote secondary alterations in the body, such as vascular or metabolic processes, and may also result in the currently studied epigenetic phenomena or neuroinflammation. In this context, the health significance of soluble particulate matter and the role of ultrafine particles translocated across biological membranes into blood vessel and transported via the circulation to secondary target organs, such as liver, brain or the fetus, are intensively discussed.Diabetes is one of the leading chronic diseases worldwide, with a prevalence of almost 14 % in Germany. Although lifestyle factors are the main causes, current evidence suggests that long-term exposure to air pollution may additionally increase the risk for type 2 diabetes. Supporting evidence for a causal role of air pollution is provided by studies addressing the regulation of the blood glucose levels in metabolically healthy participants, insulin sensitivity, or pregnancy-related diabetes. Experimental studies provide further support for plausible biological mechanisms. However, prospective studies are needed to gain more evidence, taking multiple lifestyle and environmental factors, such as green space and noise, and an improved individual exposure assessment into account.The aging population has an increased risk of neurodegenerative diseases. First studies point towards a contribution of chronic exposure to air pollution, specifically by particulate matter. Several studies report its association with decreased neurocognitive capacity or an increased prevalence of dementia or Alzheimer's disease in adults. However, the studies are inhomogeneous regarding design, exposure and outcome, leading to inconsistent results. With respect to the influence on neurocognitive development of children, first studies suggest an association between the level of air pollution, e. g. at school, and delayed cognitive development.Even though the evidence for the different biological endpoints during pregnancy is still heterogeneous, the studies generally point towards an adverse impact of air pollution on the maternal and fetal organisms. The strongest evidence exists for low birth weight, with small effect sizes of only some grams, and for a higher incidence of reduced birth weight (< 2500 g). An increased risk for gestational hypertension and preeclampsia underscores the possible impact of exposure to air pollution on the maternal organism. However, the current body of evidence does not yet allow a final conclusion on the influence of intrauterine exposure to air pollution regarding early childhood lung function and development of allergies, particularly in light of the fact that it is hard to distinguish in epidemiological studies between the effects of pre- and postnatal exposure.

[Breathing: Ambient Air Pollution and Health - Part II]. / Atmen: Luftschadstoffe und Gesundheit ­ Teil II.

The second part of the DGP-statement on adverse health effects of ambient air pollution provides an overview of the current ambient air quality in Germany and its development in the past 20 years. Further, effects of air pollution on the cardiovascular system und underlying pathophysiological mechanisms are introduced. Air pollutants form a highly complex and dynamic system of thousands of organic and inorganic components from natural and anthropogenic sources. The pollutants are produced locally or introduced by long-range transport over hundreds of kilometers and are additionally subjected to local meteorological conditions. According to air quality regulations ambient air quality is monitored under uniform standards including immission of particulate matter, up to 2.5 µm (PM2.5) or 10 µm (PM10) in aerodynamic diameter, and of nitrogen dioxide (NO2) or ozone (O3). The clean air measures of recent years led to a continuous decline of air pollution in the past 20 years in Germany. Accordingly, the focus is nowadays directed at population-related health hazards caused by low concentrations of air pollution. Exceeded limits for sulfur dioxide, carbon monoxide, benzene and lead are not detected anymore. Also the number of days with increased ozone concentration declined, although the annual mean concentration is unaltered. Decreasing concentrations of particulate matter and NO2 have been observed, however, about 40 % of the monitoring stations at urban traffic sites still measure values exceeding current limits for NO2. Moreover, the stricter, solely health-based WHO-standards for PM2.5, PM10 and NO2 are still not met so that an optimal protection from air pollution-related health hazards is currently not given for the German population. In recent years, the findings of numerous cross-sectional and longitudinal studies underscored adverse effects of air pollution on the cardiovascular system, especially for particulate matter, although the level of evidence still varies for the different health outcomes. Further, the studies show that cardiovascular health hazards on the population level are of higher relevance than those for the respiratory system. The existing evidence for cardiovascular mortality, hospitalization, ischemic heart diseases, myocardial infarction and stroke can be regarded as strong, while that for heart failure is rather moderate. While the evidence for air pollution-related short-term alteration of the cardiac autonomic balance can be considered as sufficient, long-term effects are still unclear. Likewise, the heterogeneous findings on air pollution-related arrhythmia do currently not allow a distinct conclusion in this regard. A large number of studies support the observation that both, short- and long-term air pollution exposure contribute to increased blood pressure, may impair vascular homeostasis, induce endothelial dysfunction and promote the progression of atherosclerotic lesions. These effects provide reasonable biological explanation for the fatal events associated with exposure to air pollution. Short-term exposure may not pose a significant risk on healthy individuals but may be considered as precursor for fatal events in susceptible populations, while repetitive or long-term exposure may contribute to the development of cardiovascular diseases even in healthy subjects.

[Vascular surgical aspects in abdominal surgery : Results from a tertiary care center over a 10-year time period]. / Gefäßchirurgische Aspekte in der Viszeralchirurgie : Ergebnisse aus einem tertiären Zentrum über einen Zeitraum von 10 Jahren.

AIM: To investigate the perioperative management and outcome of patients undergoing abdominal surgery with additional vascular (comorbid) alterations for internal quality assurance of the clinical results. METHODS: Over a defined study period all consecutive cases of the aforementioned profile were documented and retrospectively analyzed as part of an ongoing prospective monocentric observational study to reflect the daily surgical practice. RESULTS: Over 10 years (from January 1999 to December 2008), a total of 113 cases were registered. Pancreas resection including vascular reconstruction showed the highest percentage (30.1%). Within the target patient groups, similar outcome data were found compared with international reports. An exception was in the case of mesenteric ischemia, where open surgery was more frequently used in comparison to the study situation (included together were patients treated by surgery and interventions). The majority of vascular alterations during the postoperative course and iatrogenic lesions occurred following pancreas resection. In the therapeutic profile there are two particularly important measures, namely open surgery on one hand and image-guided radiology as well as endoscopy on the other hand. The majority of patients with a rare visceral artery aneurysm (considerable potential for rupture or erosion) were more frequently treated with image-guided interventional radiology versus open surgery. This conforms to the current well-established sequential patient (individual), results, and, in particular, risk-adapted staged treatment approach. CONCLUSION: Additional vascular surgical treatment of problematic situations during abdominal surgery or in emergency cases is not daily routine; however, it is a challenging field including a considerable potential for complications (morbidity) and definitely mortality. This requires an experienced surgeon with high expertise, if possible in a center for vascular medicine.

[Liquid biopsy in human non-small-cell lung cancer : Blood-based analysis of ctDNA methylation]. / Liquid Biopsy im nicht-kleinzelligen Lungenkarzinom : Die blutbasierte Analyse der ctDNA-Methylierung.

BACKGROUND: Use of liquid biopsy for minimal invasive follow-up diagnostics of non-small-cell lung carcinomas (NSCLCs). OBJECTIVES: Systematic search for new putative blood-based hypermethylation biomarkers to discriminate NSCLC patients from patients without a malign disease. METHODS: Quantitative analysis of gene promoter DNA methylation of potential biomarkers from cfDNA (plasma) with pyrosequencing. RESULTS: cfDNA hypermethylation in plasma confirmed significant higher methylation frequencies of the candidate gene CFTR of the NSCLC patients compared to the combined control groups and to NSCLC patients after curative therapy of primary NSCLC (post-NSCLC). ROC-analysis of the best discriminatory CpGs of the CFTR promotor (CpG1-2-4) revealed a sensitivity of 52% in NSCLC patients and a specificity of 90% in the post-NSCLC group (AUC: 0.69; p < 0.05). CONCLUSIONS: Promotor hypermethylation of the potential biomarker CFTR shows a discriminatory potential for differentiation of NSCLC patients to patients without a malign disease and should further be investigated.

EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity.

Background: Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients and methods: Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash. Results: A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms. Conclusion: The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

One in two cancer patients is significantly distressed: Prevalence and indicators of distress.

OBJECTIVE: Psychological distress is common in cancer patients, and awareness of its indicators is essential. We aimed to assess the prevalence of psychological distress and to identify problems indicative of high distress. METHODS: We used the distress thermometer (DT) and its 34-item problem list to measure psychological distress in 3724 cancer patients (mean age 58 years; 57% women) across major tumor entities, enrolled in an epidemiological multicenter study. To identify distress-related problems, we conducted monothetic analyses. RESULTS: We found high levels of psychological distress (DT ≥ 5) in 52% of patients. The most prevalent problems were fatigue (56%), sleep problems (51%), and problems getting around (47%). Sadness, fatigue, and sleep problems were most strongly associated with the presence of other problems. High distress was present in 81.4% of patients reporting all 3 of these problems (DT M = 6.4). When analyzing only the subset of physical problems, fatigue, problems getting around, and indigestion showed the strongest association with the remaining problems and 76.3% of patients with all 3 problems were highly distressed (DT M = 6.1). CONCLUSIONS: Our results show a high prevalence of psychological distress in cancer patients, as well as a set of problems that indicate the likely presence of other problems and high distress and can help clinicians identify distressed patients even if no routine distress screening is available.

Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity.

Interactions between the microbiota and distal gut are important for the maintenance of a healthy intestinal barrier; dysbiosis of intestinal microbial communities has emerged as a likely contributor to diseases that arise at the level of the mucosa. Intraepithelial lymphocytes (IELs) are positioned within the epithelial barrier, and in the small intestine they function to maintain epithelial homeostasis. We hypothesized that colon IELs promote epithelial barrier function through the expression of cytokines in response to interactions with commensal bacteria. Profiling of bacterial 16S ribosomal RNA revealed that candidate bacteria in the order Bacteroidales are sufficient to promote IEL presence in the colon that in turn produce interleukin-6 (IL-6) in a MyD88 (myeloid differentiation primary response 88)-dependent manner. IEL-derived IL-6 is functionally important in the maintenance of the epithelial barrier as IL-6-/- mice were noted to have increased paracellular permeability, decreased claudin-1 expression, and a thinner mucus gel layer, all of which were reversed by transfer of IL-6+/+ IELs, leading to protection of mice in response to Citrobacter rodentium infection. Therefore, we conclude that microbiota provide a homeostatic role for epithelial barrier function through regulation of IEL-derived IL-6.

Physical activity, muscular strength, and polypharmacy among older multimorbid persons: Results from the KORA-Age study.

The purpose of this study was to examine whether physical activity (PA) and muscular strength (MS) are related to polypharmacy. Our cross-sectional analysis was based on 711 patients with multimorbidity (MMB), aged 65-94 years, who participated in the KORA-Age study. Participants underwent a face-to-face interview and extensive physical examinations including anthropometric measurements, registration of chronic diseases, determination of health-related behaviors (smoking, alcohol intake, physical activity, etc.), collection of blood samples and measurement of hand-grip strength. PPha was defined as the use of >4 drugs and MMB as having ≥2 of 13 chronic diseases. Prevalence of PPha was 44.6% (n=317), and a significant difference was found in the number of drugs used between participants with and without PPha (7.2±2.1 vs 2.5±1.2, P<.001). Patients in the lower compared to the upper tertile of physical activity had a significantly increased odds to be on PPha (OR: 1.64, 95% CI: 1.05-2.56, P=.031) after controlling for age, gender, BMI, family status, education, alcohol intake, smoking habits, number of diseases, hs-CRP, and telomere length. On the contrary, no significant association between muscular strength and PPha was found (OR: 1.04, 95% CI: 0.66-1.63, P=.873) after multivariable adjustment. Among older persons with MMB, lower levels of physical activity, but not low muscular strength, are associated with higher odds of PPha. Increasing the levels of physical activity appears to be highly recommended in order to potentially reduce the risk of PPha among multimorbid persons aged 65 and older.

Achalasia-an unnecessary long way to diagnosis.

Although achalasia presents with typical symptoms such as dysphagia, regurgitation, weight loss, and atypical chest pain, the time until first diagnosis often takes years and is frustrating for patients and nevertheless associated with high costs for the healthcare system. A total of 563 patients were interviewed with confirmed diagnosis of achalasia regarding their symptoms leading to diagnosis along with past clinical examinations and treatments. Included were patients who had undergone their medical investigations in Germany. Overall, 527 study subjects were included (male 46%, female 54%, mean age at time of interview 51 ± 14.8 years). Dysphagia was present in 86.7%, regurgitation in 82.9%, atypical chest pain in 79%, and weight loss in 58% of patients before diagnosis. On average, it took 25 months (Interquartile Range (IQR) 9-65) until confirmation of correct diagnosis of achalasia. Though, diagnosis was confirmed significantly quicker (35 months IQR 9-89 vs. 20 months IQR 8-53; p < 0.01) in the past 15 years. The majority (72.1%) was transferred to three or more specialists. Almost each patient underwent at least one esophagogastroduodenoscopy (94.2%) and one radiological assessment (89.3%). However, esophageal manometry was performed in 70.4% of patients only. The severity of symptoms was independent with regard to duration until first diagnosis (Eckardt score 7.14 ± 2.64 within 12 months vs. 7.29 ± 2.61 longer than 12 months; P = 0.544). Fifty-five percent of the patients primarily underwent endoscopic dilatation and 37% a surgical myotomy. Endoscopic dilatation was realized significantly faster compared to esophageal myotomy (1 month IQR 0-4 vs. 3 months IQR 1-11; p < 0.001). Although diagnosis of achalasia was significantly faster in the past 15 years, it still takes almost 2 years until the correct diagnosis of achalasia is confirmed. Alarming is the fact that although esophageal manometry is known as the gold standard to differentiate primary motility disorders, only three out of four patients had undergone this diagnostic pathway during their diagnostic work-up. Better education of medical professionals and broader utilization of highly sensitive diagnostic tools, such as high-resolution manometry, are strictly necessary in order to correctly diagnose affected patients and to offer therapy faster.

The risk of being depressed is significantly higher in cancer patients than in the general population: Prevalence and severity of depressive symptoms across major cancer types.

BACKGROUND: Depression is a common co-morbidity of cancer that has a detrimental effect on quality of life, treatment adherence and potentially survival. We conducted an epidemiological multi-center study including a population-based random comparison sample and estimated the prevalence of depressive symptoms by cancer site, thereby identifying cancer patients with the highest prevalence of depression. PATIENTS AND METHODS: We included 4020 adult cancer inpatients and outpatients from five distinct regions across Germany in a proportional stratified random sample based on the nationwide cancer incidence and a comparison group consisting of 5018 participants. Both groups reported depressive symptoms by filling in the Patient Health Questionnaire (PHQ-9). In multivariate analyses adjusted for age and sex, we calculated the odds of being depressed. RESULTS: Out of 5818 eligible patients, 69% participated (51% women, mean age = 58 years). We estimated that one in four cancer patients (24%) is depressed (PHQ-9 ≥ 10). The odds of being depressed among cancer patients were more than five times higher than in the general population (OR, 5.4; 95% CI, 4.6-6.2). Patients with pancreatic (M = 8.0, SD = 5.0), thyroid (M = 7.8, SD = 6.3) and brain tumours (M = 7.6, SD = 4.9) showed the highest prevalence, whereas patients with prostate cancer (M = 4.3, SD = 3.8) and malignant melanoma (M = 5.3, SD = 4.3) had the lowest levels of depressive symptoms. CONCLUSION: Our results help clinicians identify cancer patients in need of psychosocial support when navigating in the growing survivor population.

[A Screening-Tool for Three Dimensions of Work-Related Behavior and Experience Patterns in the Psychosomatic Rehabilitation - A Proposal for a Short-Form of the Occupational Stress and Coping Inventory (AVEM-3D)]. / Ein Verfahren zum Screening dreier Dimensionen arbeitsbezogener Verhaltens- und Erlebensmuster in der psychosomatischen Rehabilitation ­ Vorschlag für eine Kurzform AVEM-3D.

Objectives: The assessment of work pressures is of particular importance in psychosomatic rehabilitation. An established questionnaire is the Occupational Stress and Coping Inventory (German abbr. AVEM), but it is quite long and with regard to scoring time-consuming in routine clinical care. It should therefore be tested, whether a shortened version of the AVEM can be developed, which is able to assess the formerly described three second-order factors of the AVEM, namely Working Commitment, Resilience, and Emotions, sufficiently reliable and valid, and which also may be used for screening of patients with prominent work-related behavior and experience patterns. Methods: Data were collected at admission from consecutive samples of three hospitals of psychosomatic rehabilitation (N = 10,635 patients). The sample was randomly divided in two subsamples (design and validation sample). Using exploratory principal component analyses in the design sample, items with the highest factor loadings for the three new scales were selected and evaluated psychometrically using the validation sample. Possible Cut-off values ought to be derived from distribution patterns of scores in the scales. Relationships with sociodemographic, occupational and diagnosis-related characteristics, as well as with patterns of work-related experiences and behaviors are examined. Results: The three performed principal component analyses explained in the design sample on the respective first factor between 31 % and 34 % of the variance. The selected 20 items were assigned to the 3-factor structure in the validation sample as expected. The three new scales are sufficiently reliable with values of Cronbach's α between 0,84 and 0,88. The naming of the three new scales is based on the names of the secondary factors. Cut-off values for the identification of distinctive patient-reported data are proposed. Conclusion: Main advantages of the proposed shortened version AVEM-3D are that with a considerable smaller number of items the three main dimensions of relevant work-related behavior and experience patterns can be reliably measured. The proposed measure is simple and economic to use and interpret. Based on the present sample we provide means and standard deviations as reference at admission of psychosomatic rehabilitation. As a limitation it should be mentioned that further evaluation of reliability, validity and sensitivity to change restricted to the items of the shortened version is necessary. The practicability and validity of the proposed cut-off values cannot yet be conclusively assessed. Finally, the validity of the AVEM-3D in groups of indications other than psychosomatic patients and in healthy persons remains to be examined.

Handgrip strength is inversely and independently associated with multimorbidity among older women: Results from the KORA-Age study.

BACKGROUND: Data on the association between handgrip strength and multimorbidity (MMB) are missing. AIM: The purpose of this study was to examine if handgrip strength is related to MMB in a large population-based sample of older persons. METHODS: The cross-sectional analysis was based on 1079 older people (aged 65-94years), who participated in the KORA-Age study in the Augsburg region, southern Germany. Participants underwent an interview and extensive examinations, including anthropometric measurements, registration of chronic diseases, determination of health-related behaviors (smoking, alcohol intake and physical activity), collection of blood samples, and muscle strength measurement using hand-grip dynamometry. RESULTS: In men, handgrip strength correlated strongly with the number of co-existing diseases (r=-0.176, p<0.001), and the same pattern was observed for women (r=-0.287, p<0.001). Among women, handgrip strength in the lower tertile compared to the upper tertile was significantly associated with an increased odds of having MMB (OR: 2.57, 95% CI: 1.30-5.07, p=0.007) after controlling for age, BMI, education, alcohol intake, smoking habits, medications number, inflammatory markers, telomere length and levels of physical activity. Contrary, no significant association between handgrip strength and MMB was found among men (OR: 1.32, 95% CI: 0.73-2.40, p=0.362) after multivariable adjustment. CONCLUSION: Lower levels of handgrip strength are associated with a higher odd of MMB among older women even after adjusting for traditional and novel confounders. Increasing the levels of muscular strength in older women seems to be important in order to reduce the risk for the co-occurrence of multiple chronic diseases.

Direct and indirect costs of COPD and its comorbidities: Results from the German COSYCONET study.

BACKGROUND: Reliable up-to-date estimates regarding the economic impact of chronic obstructive pulmonary disease (COPD) are lacking. This study investigates COPD excess healthcare utilization, work absenteeism, and resulting costs within the German COPD cohort COSYCONET. METHODS: Data from 2139 COPD patients in GOLD grade 1-4 from COSYCONET were compared with 1537 lung-healthy control subjects from the population-based KORA platform. Multiple generalized linear models analyzed the association of COPD grades with healthcare utilization, work absence, and costs from a societal perspective while adjusting for sex, age, education, smoking status, body mass index (BMI), and several comorbidities. RESULTS: COPD was significantly associated with excess healthcare utilization, work absence, and premature retirement. Adjusted annual excess cost of COPD in 2012 for GOLD grade 1-4 amounted to €2595 [1770-3678], €3475 [2966-4102], €5955 [5191-6843], and €8924 [7190-10,853] for direct costs, and €8621 [4104-13,857], €9871 [7692-12,777], €16,550 [13,743-20,457], and €27,658 [22,275-35,777] for indirect costs respectively. Comorbidities contributed to the primary effect of COPD on direct costs only. An additional history of cancer or stroke had the largest effect on direct costs, but the effects were smaller than those of COPD grade 3/4. CONCLUSIONS: COPD is associated with substantially higher costs than previously reported.

Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study.

BACKGROUND: Data on the long-term impact of hydrolyzed formulas on allergies are scarce. OBJECTIVE: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence. METHODS: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models. RESULTS: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula. CONCLUSION: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.

Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder.

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.