The Association Between C24:0/C16:0 Ceramide Ratio and Cardiorespiratory Fitness is Robust to Effect Modifications by Age and Sex.

Ceramides and cardiorespiratory (CR) fitness are both related to cardiovascular diseases. The associations of three blood plasma ceramides (C16:0, C22:0, and C24:0) with CR fitness in the population-based Study of Health in Pomerania (SHIP-START-1; n = 1,102; mean age 50.3 years, 51.5% women) are investigated. In addition, subgroup analysis according to age (

Low-grade inflammation is associated with a heterogeneous lipoprotein subclass profile in an apparently healthy population sample.

BACKGROUND AND AIMS: Prevention measures for cardiovascular diseases (CVD) have shifted their focus from lipoproteins to the immune system. However, low-grade inflammation and dyslipidemia are tightly entangled. The objective of this study was to assess the relations between a broad panel of inflammatory biomarkers and lipoprotein subclass parameters. METHODS: We utilized data from the population-based Study of Health in Pomerania (SHIP-TREND, n = 403). Plasma concentrations of 37 inflammatory markers were measured by a bead-based assay. Furthermore, we employed nuclear magnetic resonance spectroscopy to measure total cholesterol, total triglycerides, total phospholipids as well as the fractional concentrations of cholesterol, triglycerides, phospholipids, ApoA1, ApoA2 and ApoB in all major lipoprotein subclasses. Associations between inflammatory biomarkers and lipoprotein subclasses were analyzed by adjusted linear regression models. RESULTS: APRIL, BAFF, TWEAK, sCD30, Pentraxin-3, sTNFR1, sTNFR2, Osteocalcin, Chitinase 3-like 1, IFN-alpha2, IFN-gamma, IL-11, IL-12p40, IL-29, IL-32, IL-35, TSLP, MMP1 and MMP2 were related with lipoprotein subclass components, forming two distinct clusters. APRIL had inverse relations to HDL-C (total and subclasses) and HDL Apo-A1 and Apo-A2 content. MMP-2 was inversely related to VLDL-C (total and subclasses), IDL-C as well as LDL5/6-C and VLDL-TG, IDL-TG, total triglycerides as well as LDL5/5-TG and HDL4-TG. Additionally, we identified a cluster of cytokines linked to the Th1-immune response, which were associated with an atherogenic lipoprotein profile. CONCLUSION: Our findings expand the existing knowledge of inflammation-lipoprotein interactions, many of which are suggested to be involved in the pathogeneses of chronic non-communicable diseases. The results of our study support the use of immunomodulatory substances for the treatment and possibly prevention of CVD.

Sphingosine-1-phosphate and vascular disease in the general population.

BACKGROUND AND AIMS: Sphingosine-1-phosphate (S1P) is a sphingolipid which influences the immune and vascular system. The relationship between S1P and vascular disease in the general population is currently unclear. We explored the relation between S1P and vascular markers, (i.e. ankle-brachial index (ABI), carotid intima-media thickness (cIMT), presence of carotid atherosclerotic plaques and brachial artery flow-mediated dilation (FMD). METHODS: S1P was measured by liquid chromatography-tandem mass spectrometry in the population-based Study of Health in Pomerania (SHIP-TREND-0). Subjects with prevalent cancer, severe renal insufficiency, history of myocardial infarction and extreme values for S1P were excluded. Sex stratified linear regression models adjusted for age, smoking and waist-to-hip ratio were used. RESULTS: A total of n = 3643 participants (52% women, median age 51, 25th and 75th percentiles 39 and 63 years) were included. In men, a 1 standard deviation higher S1P concentration was associated with a significantly greater cIMT (ß: 0.0057 95%-confidence interval [CI]: 0.00027-0.0112 mm; p = 0.04) and a lower ABI (ß: -0.0090 95% CI: -0.0153 to -0.0029; p < 0.01). In women, S1P was also positively associated with cIMT (ß: 0.0044 95% CI: 0.0001-0.0086 mm; p = 0.04). CONCLUSIONS: We found that S1P was positively related to a greater cIMT in both sexes and a lower ABI in men. There was no association of S1P with any of the other investigated markers. Future studies are warranted to assess the suitability of S1P as a biomarker for vascular disease.

Association of Cardiopulmonary Exercise Capacity and Adipokines in the General Population.

Adipokines and cardiorespiratory fitness (CRF) are associated with the (patho)physiology of cardiometabolic diseases. Whether CRF and adipokines are related is unclear. We investigated associations of CRF with leptin, adiponectin, chemerin, resistin and vaspin. Data from the population-based Study of Health in Pomerania was used (n=1,479; median age 49 years; 51% women). Cardiopulmonary exercise testing was used to measure CRF. Circulating adipokine concentrations were measured by enzyme-linked immunosorbent assay. The association between CRF and adipokines was assessed using multivariable sex-specific quantile regression models. Higher maximum oxygen uptake was significantly associated with lower leptin (men:-0.11 ng/ml; 95%-confidence interval [CI]:-0.18 to-0.03 ng/ml; p<0.005; women:-0.17 ng/ml; 95%-CI:-0.33 to-0.02 ng/ml; p<0.05) and chemerin (men:-0.26 ng/ml; 95%-CI:-0.52 to-0.01 ng/ml; p<0.05; women:-0.41 ng/ml; 95%-CI:-0.82 to-0.01 ng/ml; p<0.05) as well as higher adiponectin concentrations (men: 0.06 µg/ml; 95%-CI: 0.02 to 0.11 µg/ml; p<0.05; women: 0.03 µg/ml; 95%-CI:-0.05 to 0.10 µg/ml; p=0.48). We found that CRF was inversely associated with leptin and chemerin in both sexes and positively associated with adiponectin only in men.

German version of the outcome expectations for exercise scale-2 : Psychometric properties in geriatric patients after hip or pelvic fractures with fear of falling.

OBJECTIVE: Physical exercise is associated with many health benefits. Especially for older adults it is challenging to achieve an appropriate adherence to exercise programs. The outcome expectations for exercise scale 2 (OEE-2) is a 13-item self-report questionnaire to assess negative and positive exercise outcome expectations in older adults. The aim of this study was to translate the OEE­2 into German and to assess the psychometric properties of this version. METHODS: The OEE­2 was translated from English into German including a forward and backward translation process. Psychometric properties were assessed in 115 patients with hip/pelvic fractures (76% female, mean age 82.5 years) and fear of falling during geriatric inpatient rehabilitation. RESULTS: Principal component analyses could confirm a two-factor solution (positive/negative OEE) that explained 58% of the total variance, with an overall internal reliability of α = 0.89. Cronbach's α for the 9­item positive OEE subscale was 0.89, for the 4­item negative OEE subscale 0.79. The two subscales were correlated with rs = 0.49. Correlations of the OEE total score were highest with the perceived ability to manage falls, prefracture leisure time activities and prior training history (rs = 0.35-0.41). CONCLUSION: These results revealed good internal reliability and construct validity of the German version of the OEE­2. The instrument is valid for measuring physical exercise outcome expectations in older, German-speaking patients with hip or pelvic fractures and fear of falling.

The association between thyroid function biomarkers and attention deficit hyperactivity disorder.

The relation between thyroid function biomarkers and attention deficit hyperactivity disorder (ADHD) in children and adolescents is currently unclear. Cross-sectional data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Baseline) was analyzed to assess the association between thyroid function biomarkers and ADHD in a population-based, nationally representative sample. The study cohort included 11,588 children and adolescents with 572 and 559 having an ADHD diagnosis or symptoms, respectively. ADHD symptoms were assessed through the Inattention/Hyperactivity subscale of the Strength and Difficulties Questionnaire. ADHD diagnosis was determined by a physician or psychologist. Serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations were determined enzymatically. Adjusted regression models were used to relate serum TSH, fT3, and fT4 with risk for ADHD diagnosis or symptoms. In children, a 1 mIU/l higher TSH was related to a 10% lower risk (odds ratio [OR] 0.90; 95% confidence interval [CI] 0.81-1.00) of ADHD diagnosis. We found a significant positive association between fT3 and continuously assessed ADHD symptoms in children (ß 0.08; 95% CI 0.03-0.14). Our results suggest that physical maturity may influence the association between thyroid function biomarkers and risk for ADHD.

Effects of an intervention to reduce fear of falling and increase physical activity during hip and pelvic fracture rehabilitation.

BACKGROUND: fear of falling and reduced fall-related self-efficacy are frequent consequences of falls and associated with poorer rehabilitation outcomes. To address these psychological consequences, geriatric inpatient rehabilitation was augmented with a cognitive behavioural intervention ("Step by Step") and evaluated in a RCT. METHODS: one hundred fifteen hip and pelvic fracture patients (age = 82.5 years, 70% female) admitted to geriatric inpatient rehabilitation were randomly allocated to the intervention or control group. The intervention consisted of eight additional individual sessions during inpatient rehabilitation, one home visit and four telephone calls delivered over 2 months after discharge. Both groups received geriatric inpatient rehabilitation. Primary outcomes were fall-related self-efficacy (short falls efficacy scale-international) and physical activity as measured by daily walking duration (activPAL3™ sensor) after admission to rehabilitation, before discharge and 1-month post-intervention. RESULTS: in covariance analyses, patients in the intervention group showed a significant improvement in fall-related self-efficacy (P = 0.025, d = -0.42), but no difference in total daily walking duration (P = 0.688, d = 0.07) 1-month post-intervention compared to the control condition. Further significant effects in favour of the intervention group were found in the secondary outcomes "perceived ability to manage falls" (P = 0.031, d = 0.41), "physical performance" (short physical performance battery) (P = 0.002, d = 0.58) and a lower "number of falls" (P = 0.029, d = -0.45). CONCLUSIONS: the intervention improved psychological and physical performance measures but did not increase daily walking duration. For the inpatient part of the intervention further research on the required minimum intensity needed to be effective is of interest. Duration and components used to improve physical activity after discharge should be reconsidered.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

Correlates of fear of falling and falls efficacy in geriatric patients recovering from hip/pelvic fracture.

OBJECTIVE: To gain a better understanding about the nature of fear of falling, this study analyzed associations between psychological and physical aspects related to fear of falling and falls efficacy in hip/pelvic fracture patients. DESIGN: Baseline data of a randomized controlled trial. SETTING: Geriatric inpatient rehabilitation hospital. SUBJECTS: In all, 115 geriatric patients with hip/pelvic fracture (mean age: 82.5 years) reporting fear of falling within first week of inpatient rehabilitation. INTERVENTIONS: None. MAIN MEASURES: Falls efficacy (Short Falls Efficacy Scale-International; Perceived Ability to Manage Falls), fear of falling (one-item question), fall-related post-traumatic stress symptoms (six items based on Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria), physical performance (Short Physical Performance Battery) and psychological inflexibility (Acceptance and Action Questionnaire-II) were assessed. RESULTS: Path analyses demonstrated that low falls efficacy (Short Falls Efficacy Scale International) was significantly related to poor physical performance (ß* = -.277, P ⩽ .001), but not to psychological inflexibility and fall-related post-traumatic stress symptoms (P ⩾ .05.). Fear of falling was directly associated with fall-related post-traumatic stress symptoms (ß*= .270, P = .007) and indirectly with psychological inflexibility (ß*= .110, P = .022). Low perceived ability to manage falls was significantly related to previous falls (ß* = -.348, P ⩽ .001), psychological inflexibility (ß* = -.216, P = .022) and female gender (ß* = -.239, P ⩽ .01). CONCLUSION: Falls efficacy and fear of falling constitute distinct constructs. Falls efficacy measured with the Short Falls Efficacy Scale International reflects the appraisal of poor physical performance. Fear of falling measured by the single-item question constitutes a fall-specific psychological construct associated with psychological inflexibility and fall-related post-traumatic stress symptoms.

Sex-Specific Associations of Brain-Derived Neurotrophic Factor and Cardiorespiratory Fitness in the General Population.

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1 mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF.

Global epidemiology of hyperthyroidism and hypothyroidism.

Thyroid hormones are essential for growth, neuronal development, reproduction and regulation of energy metabolism. Hypothyroidism and hyperthyroidism are common conditions with potentially devastating health consequences that affect all populations worldwide. Iodine nutrition is a key determinant of thyroid disease risk; however, other factors, such as ageing, smoking status, genetic susceptibility, ethnicity, endocrine disruptors and the advent of novel therapeutics, including immune checkpoint inhibitors, also influence thyroid disease epidemiology. In the developed world, the prevalence of undiagnosed thyroid disease is likely falling owing to widespread thyroid function testing and relatively low thresholds for treatment initiation. However, continued vigilance against iodine deficiency remains essential in developed countries, particularly in Europe. In this report, we review the global incidence and prevalence of hyperthyroidism and hypothyroidism, highlighting geographical differences and the effect of environmental factors, such as iodine supplementation, on these data. We also highlight the pressing need for detailed epidemiological surveys of thyroid dysfunction and iodine status in developing countries.

Hip and pelvic fracture patients with fear of falling: development and description of the "Step by Step" treatment protocol.

OBJECTIVE: Based on a theoretical framework and sound evidence, this article describes a rehabilitation programme for patients with fear of falling after hip and pelvic fracture. RATIONALE: Based on exercise science principles, current knowledge from fall prevention, emotion regulation, and the Health Action Process Approach we developed a theoretical framework, from which the components of the intervention were derived. Description of the intervention: The intervention consists of 6 components: (1) relaxation, (2) meaningful activities and mobility-based goals, (3) falls related cognitions and emotions, coping with high risk tasks and situations, (4) individual exercise programme, (5) planning and implementing exercises and activities, and (6) fall risks and hazards. The intervention comprises of 8 individual sessions during 3 to 5 weeks of inpatient rehabilitation and 4 telephone calls and 1 home visit over a 2-month post-discharge period. Each session or telephone call takes about 30-60 minutes. It is provided to geriatric hip and pelvic fracture patients with concerns about falling and no cognitive impairment. To ensure completeness of reporting, the Template for Intervention Description and Replication (TIDierR) is used. RESULTS: Fifty-seven patients were assigned to the intervention group. All 46 completers met all pre-defined criteria for an intervention per protocol. CONCLUSION: The programme is feasible to administer. We have completed a randomised controlled trial, which will be submitted in due time (for trial protocol: www.isrctn.org ; ISRCTN79191813).

Problem-solving in caregiver-counselling (PLiP Study): study protocol of a cluster randomized pragmatic trial.

BACKGROUND: Despite the positive evaluation of various caregiver interventions over the past 3 decades, only very few intervention protocols have been translated to delivery in service contexts. The purpose of this study is to train care counsellors of statutory long term care insurances in problem-solving and to evaluate this approach as an additional component in the statutory care counselling in Germany. METHODS: A pragmatic cluster randomized controlled trial in which 38 sites with 58 care counsellors are randomly assigned to provide either routine counselling plus additional problem-solving for caregivers or routine counselling alone. The counsellor training comprises an initial 2-day training, a follow-up day after 4 months, and biweekly supervision contacts with a psychotherapist for 6 months over the phone. The agreed minimum counselling intensity is one initial face-to-face contact including a caregiver assessment and at least one telephone follow-up contact. Caregivers who are positively screened for significant strain in their role are followed up at 3 and 6 months after baseline assessment. Main outcome are caregivers' depressive symptoms. DISCUSSION: While it is unclear if the expected very low amount of additional counselling time is sufficient to yield any additional effects on caregiver depression, it is also unclear if the additional problem-solving component yields to synergies with routine counselling that is based on information and case management. There are different potential individual and organisational barriers to a consistent intervention delivery like gratification for participation, time for extra work or internal motivation to participate. TRIAL REGISTRATION: ( ISRCTN23635523 ).

Costs of informal care in a sample of German geriatric stroke survivors.

Stroke is a leading cause of long-term disability. A large proportion of geriatric stroke survivors receive informal care. The assessment and monetary valuation of informal care should therefore constitute an essential part of any health economic analysis, but it is hardly measured in stroke caregiver studies. The aim of the current research was to estimate the amount of informal care provided by caregivers of stroke survivors aged 60 years and older and to calculate its economic value. Information about caregiving time in activities of daily living (ADL), instrumental activities of daily living (IADL), and supervision during the last 3 months was obtained from 122 caregivers by means of structured interviews. The proxy good method was applied for the monetary valuation of time. About 63 % of the stroke survivors in our sample were moderately cognitively impaired. The results showed that the majority of the main caregivers assisted in ADL and IADL. Supervision was delivered by 45.9 %. The median amount of help in ADL was 13.9, in IADL 22.2, and in supervision 13.9 h/week. The median overall amount of care was 42.8 h/week. Fifty percent were supported by additional persons (2.7 h/week). The mean overall costs of informal care were calculated at 2252 €/month. Our results reveal the high social and economic costs of informal care. The main burden of caregiving appears to be carried by the primary caregiver. Consequently, support and counseling of this group is important. Furthermore, caregiver interventions should be aimed at the mobilization of informal resources.