Clinical characterization and mutation spectrum of patients with hypertriglyceridemia in a German outpatient clinic.

BACKGROUND: Severe hypertriglyceridemia (HTG) has predominantly multifactorial causes (MCS). Yet a small subset of patients have the monogenetic form (FCS). It remains a challenge to distinguish patients clinically, since decompensated MCS might mimic FCS´s severity. Aim of the current study was to determine clinical criteria that could sufficiently distinguish both forms as well as to apply the FCS score proposed by Moulin and colleagues. METHODS: We retrospectively studied 72 patients who presented with severe HTG in our clinic during a time span of seven years and received genetic testing. We classified genetic variants (ACMG-criteria), followed by genetic categorization into MCS or FCS. Clinical data were gathered from the medical records and the FCS score was calculated for each patient. RESULTS: Molecular genetic screening revealed eight FCS patients and 64 MCS patients. Altogether, we found 13 pathogenic variants of which four have not been described before. The FCS patients showed a significantly higher median triglyceride level compared to the MCS. The FCS score yielded a sensitivity of 75% and a specificity of 93.7% in our cohort, and significantly differentiated between the FCS and MCS group (p<0.001). CONCLUSIONS: In our cohort we identified several variables that significantly differentiated FCS from MCS. The FCS score performed similar to the original study by Moulin, thereby further validating the discriminatory power of the FCS score in an independent cohort.

Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality.

AIMS: Precision microbiome modulation as a novel treatment strategy is a rapidly evolving and sought goal. The aim of this study is to determine relationships among systemic gut microbial metabolite levels and incident cardiovascular disease risks to identify gut microbial pathways as possible targets for personalized therapeutic interventions. METHODS AND RESULTS: Stable isotope dilution mass spectrometry methods to quantitatively measure aromatic amino acids and their metabolites were used to examine sequential subjects undergoing elective diagnostic cardiac evaluation in two independent cohorts with longitudinal outcome data [US (n = 4000) and EU (n = 833) cohorts]. It was also used in plasma from humans and mice before vs. after a cocktail of poorly absorbed antibiotics to suppress gut microbiota. Multiple aromatic amino acid-derived metabolites that originate, at least in part, from gut bacteria are associated with incident (3-year) major adverse cardiovascular event (MACE) risks (myocardial infarction, stroke, or death) and all-cause mortality independent of traditional risk factors. Key gut microbiota-derived metabolites associated with incident MACE and poorer survival risks include: (i) phenylacetyl glutamine and phenylacetyl glycine (from phenylalanine); (ii) p-cresol (from tyrosine) yielding p-cresol sulfate and p-cresol glucuronide; (iii) 4-OH-phenyllactic acid (from tyrosine) yielding 4-OH-benzoic acid and 4-OH-hippuric acid; (iv) indole (from tryptophan) yielding indole glucuronide and indoxyl sulfate; (v) indole-3-pyruvic acid (from tryptophan) yielding indole-3-lactic acid and indole-3-acetyl-glutamine, and (vi) 5-OH-indole-3-acetic acid (from tryptophan). CONCLUSION: Key gut microbiota-generated metabolites derived from aromatic amino acids independently associated with incident adverse cardiovascular outcomes are identified, and thus will help focus future studies on gut-microbial metabolic outputs relevant to host cardiovascular health.

[COVID-19 vaccination status among nurses and associated factors in long-term care facilities : Results of a cross-sectional survey within the Covid-Heim project]. / COVID-19-Impfstatus von Pflegenden und assoziierte Faktoren in der stationären Langzeitpflege : Ergebnisse einer Querschnittbefragung im Rahmen des Projekts Covid-Heim.

BACKGROUND: Nurses working in long-term care facilities were vaccinated first before residents as a matter of priority to protect the latter. Although the vaccination rate of nursing staff eventually rose due to a facility-based vaccination requirement, studies on associated factors of vaccination status are currently not available for the long-term care setting in Germany. OBJECTIVE: Associated factors of COVID-19 vaccination status among nursing staff in long-term care facilities were explored. METHODS: An online survey was conducted between October 26th 2021 and January 31st 2022. A total of 1546 nurses working in long-term care in Germany responded to questions concerning the Covid-19 vaccination campaign. Logistic regression analyses were performed. RESULTS: In this study 8 out of 10 nurses were vaccinated against COVID-19 (80.6%). Approximately 7 out of 10 nurses thought at least a few times about quitting their job since the pandemic began (71.4%). A positive COVID-19 vaccination status was associated with older age, full-time employment, COVID-19 deaths at the facility and working in northern or western Germany. Frequent thoughts of quitting their job were associated with negative COVID-19 vaccination status. CONCLUSION: The present findings provide evidence on factors associated with the COVID-19 vaccination status of nurses in long-term care facilities in Germany for the first time. Further quantitative as well as qualitative studies are necessary for a more comprehensive understanding of the COVID-19 vaccination decision-making among nurses in long-term care, in order to implement target-oriented future vaccination campaigns in this care setting.

Today's Older Adults Are Cognitively Fitter Than Older Adults Were 20 Years Ago, but When and How They Decline Is No Different Than in the Past.

History-graded increases in older adults' levels of cognitive performance are well documented, but little is known about historical shifts in within-person change: cognitive decline and onset of decline. We combined harmonized perceptual-motor speed data from independent samples recruited in 1990 and 2010 to obtain 2,008 age-matched longitudinal observations (M = 78 years, 50% women) from 228 participants in the Berlin Aging Study (BASE) and 583 participants in the Berlin Aging Study II (BASE-II). We used nonlinear growth models that orthogonalized within- and between-person age effects and controlled for retest effects. At age 78, the later-born BASE-II cohort substantially outperformed the earlier-born BASE cohort (d = 1.20; 25 years of age difference). Age trajectories, however, were parallel, and there was no evidence of cohort differences in the amount or rate of decline and the onset of decline. Cognitive functioning has shifted to higher levels, but cognitive decline in old age appears to proceed similarly as it did two decades ago.

Diabetes type 2 in the Berlin Aging Study II: Cross-sectional and longitudinal data on prevalence, incidence and severity over on average seven years of follow-up.

AIMS: Aim of the current study was to describe the prevalence, incidence, and severity of diabetes mellitus type 2 (T2D) in a cohort of older men and women aged 60 years and above over the course of on average 7 years, since longitudinal data on this topic are scarce for this age group in Germany. METHODS: Baseline data of 1671 participants of the Berlin Aging Study II (BASE-II; 68.8 ± 3.7 years) and follow-up data assessed 7.4 ± 1.5 years later were analysed. The BASE-II is an exploratory, observational study on cross-sectional and longitudinal data of an older population. T2D was diagnosed based on self-report, antidiabetic medication use and laboratory parameters. T2D severity was determined by the diabetes complications severity index (DCSI). Prognostic capacity of laboratory parameters was evaluated. RESULTS: The proportion of participants with T2D increased from 12.9% (37.3% women) at baseline to 17.1% (41.1% women) with 74 incident cases and 22.2% not being aware of the disease at follow-up. The incidence rate is 10.7 new T2D diagnoses per 1000 person-years. More than half of the 41 newly identified incident T2D cases were diagnosed solely by the 2 h-plasma glucose test (OGTT) and diagnosis based on OGTT as the only criterion among incident cases was found more frequently in women (p = 0.028). T2D severity expressed by the DCSI significantly increased from baseline to follow-up (mean DCSI 1.1 ± 1.2 vs. 2.0 ± 1.8; range 0-5 vs. 0-6). Cardiovascular complications had the highest impact (43.2% at baseline and 67.6% at follow-up). CONCLUSIONS: A comprehensive picture of T2D with respect to prevalence, incidence, and severity in older people of the Berlin Aging Study II is provided.

High-Sensitivity Cardiac Troponin T and Cognitive Decline in Older Adults: Results of the Berlin Aging Study II.

INTRODUCTION: There is evidence of an association between markers of cardiac injury and cognition in patients with cardiovascular disease. We hypothesized that levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with cognitive performance and cognitive decline in a population of predominantly healthy older adults. METHODS: We included 1,226 predominantly healthy adults ≥60 years from the Berlin Aging Study II. Participants were recruited from the general population of the Berlin metropolitan area from 2009 to 2014. At baseline, participants underwent measurement of hs-cTnT and cognitive testing using the extended Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) battery. In addition, the Digit Symbol Substitution Test (DSST) was performed at baseline and at follow-up (7.3 ± 1.4 years after the baseline visit). The CERAD test results were summarized into four cognitive domains (processing speed, executive function, visuo-construction, and memory). After summing-up the respective raw scores, we calculated standardized z scores. We performed unadjusted and adjusted linear regression models to assess links between hs-cTnT and cognitive domains. We used linear mixed models to analyze associations between hs-cTnT and cognitive decline according to changes in DSST scores over time. RESULTS: The mean age of study participants at baseline was 68.5 (±3.6) years, 49% were female, and median hs-cTnT levels were 6 ng/L (IQR 4-8 ng/L). We detected no significant association between hs-cTnT and different cognitive domains at baseline after adjustment for age, sex, education, and cardiovascular risk factors. Hs-cTnT was associated with cognitive decline, which remained statistically significant after full adjustment (adjusted beta-coefficient -0.82 (-1.28 to -0.36), p = 0.001). After stratification for sex, the association with hs-cTnT remained statistically significant in men but not in women. CONCLUSION: Higher hs-cTnT levels in older men are associated with cognitive decline measured with the DSST.

[Social participation in nursing homes with Covid-19 protection measures in the second pandemic wave? Linkage of prescriptions and survey]. / Soziale Teilhabe in Pflegeheimen mit Covid-19-Schutzmaßnahmen in der zweiten Pandemiewelle?

Social participation in nursing homes with Covid-19 protection measures in the second pandemic wave? Linkage of prescriptions and survey Abstract: Background: The implementation of protective measures in nursing homes during the Covid-19 pandemic was accompanied with the loss of social participation opportunities in the first Covid-19 wave; this has been inadequately studied for the second Covid wave. Aim: To evaluate the association of protective measures and social participation restrictions for the second Covid-19 wave to develop recommendations for action. Methods: Mixed-methods online surve y of nursing home managers (n = 873) in the second wave. Binary logistic generalized estimating equations were used to evaluate the likelihood of the elimination of social participation services in nursing homes as a function of legal protections. Open-ended responses about maintaining social participation were content analyzed (n = 1042). Results: More than one in two nursing home managers reported prohibited group events (66,6%), and more than one in three prohibited creative activities (42,3%). Visitation restrictions (85,2%) were common in the second wave. The loss of participation services and the protective measures were significantly associated. Qualitative data showed that, for example, the acquisition of mobile shopping stores were opportunities to counteract the social exclusion of the residents. Discussion: The association between the loss of social participation services with the implementation of protective measures was clearly pronounced. Nursing practitioners should focus on enabling social participation whilst guaranteeing protection against infection best possible.

Novel Insights into the Management of Patients with Very High Cardiovascular Risk Eligible for PCSK9 Inhibitor Treatment: Baseline Findings from the PERI-DYS Study.

AIM: The PERI-DYS study aims to characterize two groups of patients with dyslipidaemia at very high CV risk: PCSK9i receivers and patients qualifying for but not receiving PCSK9i. METHODS: This is an observational study by office-based and clinic-based physicians, mainly cardiologists and other internists in Germany, with data extracted from patient charts. CLINICALTRIALS: gov identifier NCT03110432. RESULTS: A total of 1659 patients were enrolled across 70 sites. The majority of patients (91.0%) were reported as having mixed dyslipidaemia or non-familial or heterozygous familial hypercholesterolemia. At enrolment, 794 (47.9%) of patients were PCSK9i receivers (of these 65.9% ongoing, and 34.1% newly treated within 30 days before their baseline visit). Among PCSK9i receivers, the majority had evolocumab 140 mg (n = 632, 38.1% of total). PCSK9i receivers compared to non-receivers were about 2 years younger and had a lower proportion of males. In terms of comorbidities, they had (statistically significantly) more often CAD, and less often PAD, diabetes mellitus, arterial hypertension and chronic renal disease. The calculated untreated median LDL-C was 187 mg/dl (IQR 127; 270) in ongoing PCSK9i receivers, 212 mg/dl (IQR 132; 277) in newly treated PCSK9i receivers, and 179 mg/dl (IQR 129; 257) in non-receivers. Physician-reported statin intolerance was much more common in the two PCSK9i receiver groups as compared to non-receivers (67.3% versus 15.3%). Consequently, patients in the PCSK9i groups received fewer concomitant statins. Mean total cholesterol (143 vs. 172 mg/dl) and LDL-C (69 vs. 99 mg/dl) were considerably lower in ongoing PCSK9i receivers compared to non-receivers. CONCLUSIONS: PCSK9i receivers are characterized by higher baseline LDL-C and a higher portion of statin intolerance compared to those qualified for but not-receiving PCSK9i treatment. On-treatment, LDL-C was lower in PCSK9i receivers. Ongoing follow-up will determine the prognostic importance of these findings.

Muscle Mass and Inflammation in Older Adults: Impact of the Metabolic Syndrome.

BACKGROUND: Inflammatory processes are a cause of accelerated loss of muscle mass. Metabolic syndrome (MetS) is a highly prevalent age-related condition, which may promote and be promoted by inflammation. However, whether inflammation in MetS (metaflammation) is associated with lower muscle mass is still unclear. METHODS: Complete cross-sectional data on body composition, MetS, and the inflammatory markers interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF), and C-reactive protein (CRP) were available for 1,377 BASE-II participants (51.1% women; 68 ± 4 years old). Appendicular lean mass (ALM) was assessed by dual-energy X-ray absorptiometry. Low muscle mass (low ALM-to-BMI ratio [ALMBMI]) was defined according to the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project. Regression models, adjusted for an increasing number of confounders (sex, age, physical activity, morbidities, diabetes mellitus type II, TSH, albumin, HbA1c, smoking habits, alcohol intake, education, and energy intake/day), were used to calculate the association between low ALMBMI and high inflammation (tertile 3) according to MetS. RESULTS: MetS was present in 36.2% of the study population, and 9% had low ALMBMI. In the whole study population, high CRP (odds ratio [OR]: 2.7 [95% CI: 1.6-4.7; p = 0.001]) and high IL-6 (OR: 2.1 [95% CI: 1.2-1.9; p = 0.005]) were associated with low ALMBMI. In contrast, no significant association was found between TNF, IL-10, or IL-1ß with low ALMBMI. When participants were stratified by MetS, results for IL-6 remained significant only in participants with MetS. CONCLUSIONS: Among BASE-II participants, low ALMBMI was associated with inflammation. Low-grade inflammation triggered by disease state, especially in the context of MetS, might favor loss of muscle mass, so a better control of MetS might help to prevent sarcopenia. Intervention studies to test whether strategies to prevent MetS might also prevent loss of muscle mass seem to be promising.

Low-density lipoprotein cholesterol goal attainment in patients with clinical evidence of familial hypercholesterolemia and elevated Lp(a).

BACKGROUND: Although potent lipid-lowering therapies are available, patients commonly fall short of recommended low-density lipoprotein cholesterol (LDL-C) levels. The aim of this study was to examine the relationship between familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] and LDL-C goal attainment, as well as the prevalence and severity of coronary artery disease (CAD). Moreover, we characterized patients failing to meet recommended LDL-C goals. METHODS: We performed a cross-sectional analysis in a cohort of patients undergoing cardiac catheterization. Clinical FH was determined by the Dutch Clinical Lipid Network Score, and Lp(a) ≥ 50 mg/dL (≈ 107 nmol/L) was considered elevated. RESULTS: A total of 838 participants were included. Overall, the prevalence of CAD was 72%, and 62% received lipid-lowering treatment. The prevalence of clinical FH (probable and definite FH) was 4%, and 19% had elevated Lp(a) levels. With 35%, LDL-C goal attainment was generally poor. Among the participants with clinical FH, none reached their LDL-C target. Among patients with elevated Lp(a), LDL-C target achievement was only 28%. The prevalence and severity of CAD were higher in participants with clinical FH (86% prevalence) and elevated Lp(a) (80% prevalence). CONCLUSION: Most participants failed to meet their individual LDL-C goals according to the ESC 2016 and 2019 guidelines. In particular, high-risk patients with clinical FH or elevated Lp(a) rarely met their target for LDL-C. The identification of these patients and more intense treatment approaches are crucial for the improvement of CAD primary and secondary prevention.

Statins Aggravate the Risk of Insulin Resistance in Human Muscle.

Beside their beneficial effects on cardiovascular events, statins are thought to contribute to insulin resistance and type-2 diabetes. It is not known whether these effects are long-term events from statin-treatment or already triggered with the first statin-intake. Skeletal muscle is considered the main site for insulin-stimulated glucose uptake and therefore, a primary target for insulin resistance in the human body. We analyzed localization and expression of proteins related to GLUT4 mediated glucose uptake via AMPKα or AKT in human skeletal muscle tissue from patients with statin-intake >6 months and in primary human myotubes after 96 h statin treatment. The ratio for AMPKα activity significantly increased in human skeletal muscle cells treated with statins for long- and short-term. Furthermore, the insulin-stimulated counterpart, AKT, significantly decreased in activity and protein level, while GSK3ß and mTOR protein expression reduced in statin-treated primary human myotubes, only. However, GLUT4 was normally distributed whereas CAV3 was internalized from plasma membrane around the nucleus in statin-treated primary human myotubes. Statin-treatment activates AMPKα-dependent glucose uptake and remains active after long-term statin treatment. Permanent blocking of its insulin-dependent counterpart AKT activation may lead to metabolic inflexibility and insulin resistance in the long run and may be a direct consequence of statin-treatment.

Psychosocial burden and associated factors among nurses in care homes during the COVID-19 pandemic: findings from a retrospective survey in Germany.

BACKGROUND: Care homes were hit hard by the COVID-19 pandemic. Although high levels of psychosocial burden (i.e., anxiety, depression and stress) during the pandemic have been described for healthcare workers in hospitals, evidence on the psychosocial burden for nurses in care homes during the pandemic is scarce. METHODS: A total of 811 nurses participated in a retrospective online survey between November 2020 and February 2021. Information about the COVID-19 situation (i.e., working demands, COVID-19 cases in their facility, and COVID-19-related burden) of nurses in German care homes during the first wave of the pandemic (March 2020 to June 2020) was gathered. The Stress Scale of the Depression Anxiety and Stress Scales (SDASS-21), the Generalized Anxiety Disorder Scale-2 (GAD-2), the Patients-Health-Questionnaire-2 (PHQ-2), and the Copenhagen Psychosocial Questionnaire (COPSOQ) were used to screen for psychosocial burden. RESULTS: Among nurses, 94.2% stated that working demands since the COVID-19 pandemic increased. Further, 59.1% showed clinically relevant levels of either stress, anxiety, and/or depression. Multiple regression analysis showed significant associations between COVID-19-related burden and qualification (p < .01), dissatisfaction with COVID-19 management of care home manager (p < .05), COVID-19-related anxiety (p < .001), and dementia as a focus of care (p < .05). Stress, depression, and anxiety showed associations with COVID-19 related burden at work (p < .01), COVID-19-related anxiety (p < .001), social support (p < .01), and sense of community (p < .05). Stress was also associated with COVID-19 cases among residents (p < .05), and size of care home (p < .05). CONCLUSION: Short- and long-term strategies (i.e., psychosocial counseling, mandatory team meetings, more highly qualified nurses, additional training) in the work environment of nursing, in crises, but beyond, should be encouraged to reduce the burden on nursing staff in care homes.

[Covid-19 protections and social life limitations in nursing homes - Analysis of prescriptions and survey data]. / Covid-19-Schutzmaßnahmen und Einschränkungen des sozialen Lebens in Pflegeheimen.

Covid-19 protections and social life limitations in nursing homes - Analysis of prescriptions and survey data Abstract. Background: The tension between health protection and restrictions of social life in nursing homes during the pandemic has been little addressed. Aim: The aim of the study was to systematize state-specific regulations and actual prioritizations as well as implementations of the pandemic measures and to relate them to life changes for residents. Methods: In a mixed-methods design, 450 protective measures for nursing homes nationwide were categorized and fed into a survey of nursing home managers (n = 1,260) on the handling of these measures in a protective measures model. The association of protective measures and limitations of social services in nursing homes was analyzed with binary logistic generalized estimation equations. Results: The prescriptions were categorized into five themes. Primary data show that "visitation bans" (98.3 %) and "physical contact reduction" (90.5 %) represented the largest proportion of restrictions. The regulations were variously associated with the "restriction of social services". Thus, across all offers prohibitions and for most offers "contact reductions" were significantly associated, for example that giving up "group opportunities" was almost two times as high when the protective measure "reduction of physical contact" was implemented. "Visit restrictions" on the other hand showed little significant association. Conclusions: The results provide evidence of an association between protective measures and social restrictions in the care homes during the pandemic. However, as these lost exchanges are of high value for the residents, aversive long-term effects must be assumed.

Association of sex-specific differences in lipoprotein(a) concentrations with cardiovascular mortality in individuals with type 2 diabetes mellitus.

BACKGROUND: Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mortality is much higher in women than in men in individuals with type 2 diabetes mellitus. METHODS: We evaluated data from 7443 individuals (3792 women, 50.9%), aged 20 to 81 years, from two independent population-based investigations, SHIP-0 and MONICA/KORA S3. We analyzed the longitudinal sex-specific associations of lipoprotein(a) with cardiovascular mortality in individuals with and without type 2 diabetes mellitus using Cox regression. RESULTS: During a median follow-up of 20.5 years (136,802 person-years), 657 participants (404 men and 253 women) died of cardiovascular causes. Among individuals without type 2 diabetes mellitus, men had a significantly higher risk for cardiovascular mortality compared to women in unadjusted model and after adjustment. On the other hand, in participants with type 2 diabetes mellitus, the risk for cardiovascular mortality was not different between men and women in the unadjusted model and after adjustment for age, body mass index, low-density lipoprotein-cholesterol, fasting status and study sample (SHIP-0, MONICA/KORA S3). Further adjustment for lipoprotein(a) concentrations had no impact on the hazard ratio (HR) for cardiovascular mortality comparing men versus women in individuals without type 2 diabetes mellitus [HR: 1.94; 95% confidence interval (CI) 1.63 to 2.32; p < 0.001]. In individuals with type 2 diabetes mellitus, however, further adjustment for lipoprotein(a) led to an increased risk for cardiovascular mortality in men and a decreased risk in women resulting in a statistically significant difference between men and women (HR: 1.53; 95% CI 1.04 to 2.24; p = 0.029). CONCLUSIONS: Women are described to have a stronger relative increase in cardiovascular mortality than men when comparing individuals with and without type 2 diabetes mellitus. Higher lipoprotein(a) concentrations in women with type 2 diabetes mellitus than in men with type 2 diabetes mellitus might partially explain this finding.

Vitamin D insufficiency is associated with metabolic syndrome independent of insulin resistance and obesity in young adults - The Berlin Aging Study II.

PURPOSE: Age-related changes affect vitamin D absorption and metabolism. Low 25-hydroxyvitamin D concentrations have been reported as risk factor for the development of metabolic syndrome (MetS). However, recent evaluations suggest this association might be explained by obesity or insulin resistance (IR) in subjects with MetS. Our aim was to analyze associations between vitamin D insufficiency and MetS in a young cohort without diabetes and two senior cohorts with and without diabetes. METHODS: Four hundred sixteen young and 1357 older BASE-II participants were analyzed. Type 2 diabetes (T2D) was defined according to European Society of Cardiology (ESC) guidelines, MetS as suggested by International Diabetes Federation/American Heart Association/National Heart, Lung and Blood Institute (IDF/AHA/NHLBI 2009). Vitamin D insufficiency was defined as 25-hydroxyvitamin D concentrations <50 nmol/L. Among other confounders, BMI and IR were taken into account. RESULTS: MetS was prevalent in 7.7% of the young and in 35.6% of the older BASE-II participants and T2D occurred in 12.7% of the older participants. In young subjects without diabetes, vitamin D insufficiency was associated with an independent 3.2-fold increased odds of having MetS (OR: 3.2 CI: 1.0-8.7; p = 0.042). However, in the older participants, this association was lost once BMI was taken into account among those with diabetes, and once IR was taken into account among those without diabetes. CONCLUSION: Independent associations between vitamin D insufficiency and MetS were only found among young subjects without diabetes. In the older adults, BMI annihilated these associations among subjects without diabetes as did HOMA-IR among subjects with diabetes.

Validation of a Laser Ranged Scanner-Based Detection of Spatio-Temporal Gait Parameters Using the aTUG Chair.

This article covers the suitability to measure gait-parameters via a Laser Range Scanner (LRS) that was placed below a chair during the walking phase of the Timed Up&Go Test in a cohort of 92 older adults (mean age 73.5). The results of our study demonstrated a high concordance of gait measurements using a LRS in comparison to the reference GAITRite walkway. Most of aTUG's gait parameters demonstrate a strong correlation coefficient with the GAITRite, indicating high measurement accuracy for the spatial gait parameters. Measurements of velocity had a correlation coefficient of 99%, which can be interpreted as an excellent measurement accuracy. Cadence showed a slightly lower correlation coefficient of 96%, which is still an exceptionally good result, while step length demonstrated a correlation coefficient of 98% per leg and stride length with an accuracy of 99% per leg. In addition to confirming the technical validation of the aTUG regarding its ability to measure gait parameters, we compared results from the GAITRite and the aTUG for several parameters (cadence, velocity, and step length) with results from the Berg Balance Scale (BBS) and the Activities-Specific Balance Confidence-(ABC)-Scale assessments. With confidence coefficients for BBS and velocity, cadence and step length ranging from 0.595 to 0.798 and for ABC ranging from 0.395 to 0.541, both scales demonstrated only a medium-sized correlation. Thus, we found an association of better walking ability (represented by the measured gait parameters) with better balance (BBC) and balance confidence (ABC) overall scores via linear regression. This results from the fact that the BBS incorporates both static and dynamic balance measures and thus, only partly reflects functional requirements for walking. For the ABC score, this effect was even more pronounced. As this is to our best knowledge the first evaluation of the association between gait parameters and these balance scores, we will further investigate this phenomenon and aim to integrate further measures into the aTUG to achieve an increased sensitivity for balance ability.

[Diagnostics and treatment of statin-associated muscle symptoms]. / Diagnostik und Therapie von statinassoziierten Muskelsymptomen.

Statins are among the most frequently prescribed drugs in Germany. Their benefits in lowering cardiovascular risk are beyond dispute. Nevertheless, many patients complain of side effects from statin therapy, including statin-associated muscle symptoms (SAMS) in particular. Despite their relative frequency, it is difficult to objectively diagnose them, as the time until appearance of first symptoms, the nature of the complaints and the severity of muscle problems vary widely. This narrative review summarizes the causes of SAMS as well as new possibilities regarding their diagnosis and therapy.

Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia.

Autosomal-dominant familial hypercholesterolemia (FH) is characterized by increased plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and a substantial risk to develop cardiovascular disease. Causative mutations in three major genes are known: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). We clinically characterized 336 patients suspected to have FH and screened them for disease causing mutations in LDLR, APOB, and PCSK9. We genotyped six single nucleotide polymorphisms (SNPs) to calculate a polygenic risk score for the patients and 1985 controls. The 117 patients had a causative variant in one of the analyzed genes. Most variants were found in the LDLR gene (84.9%) with 11 novel mutations. The mean polygenic risk score was significantly higher in FH mutation negative subjects than in FH mutation positive patients (P < .05) and healthy controls (P < .001), whereas the score of the two latter groups did not differ significantly. However, the score explained only about 3% of the baseline LDL-C variance. We verified the previously described clinical and genetic variability of FH for German hypercholesterolemic patients. Evaluation of a six-SNP polygenic score recently proposed for clinical use suggests that it is not a reliable tool to classify hypercholesterolemic patients.

Patient behaviour in medication management: Findings from a patient usability study that may impact clinical outcomes.

AIMS: Adequate medication management is a key condition to ensuring effective pharmacotherapy. However, it is well acknowledged that older people may encounter difficulties self-administering medicines in a correct manner. METHODS: A mixed method pilot study was performed to investigate medication self-management in older and multimorbid patients with polypharmacy. The pilot study involved medication management tasks followed by semi-structured interviews in 20 patients. The tasks and interviews were based on the patients' individual medication plans, which had been prepared earlier by the pharmacy for each patient on basis of all their prescriptions. RESULTS: The patients' self-reported medication management skills differed from their actual observed medication management performance. In addition, the routines and coping strategies used by the patients to deal with the complexity of their overall medication regimen were not in accordance with the medication plan and the instructions for use on the product labels. Issues were observed on all stages of the medication process that can be considered relevant to patient adherence, especially medication plan recall, product identification, product selection, product handling and product recognition in a multicompartment compliance aid. CONCLUSIONS: The pilot study suggested that medication management issues by older and multimorbid patients remain widely undetermined and unrecognized in primary care. Further investigation and interdisciplinary collaboration will be required to resolve the user problems and ensure adequate patient adherence.

T cell phenotypes associated with insulin resistance: results from the Berlin Aging Study II.

BACKGROUND: Obesity is associated with chronic low-grade inflammation leading to metabolic and cardiovascular diseases, but a subset of obese individuals is considered insulin sensitive (IS). The underlying pathophysiologic mechanisms remain elusive and clinical studies on the relationship between inflammatory markers and metabolically healthy obesity (MHO) are scarce. METHODS: In this cross-sectional analysis, we included a sample of 437 older participants (60-84 years) from the Berlin Aging Study II (BASE-II). Peripheral blood mononuclear cells were isolated, immune cell subsets were analyzed with multiparameter flow cytometry and systemic cytokine levels were measured. Immune cell parameters were correlated with metabolic measures and multiple linear regression analysis was conducted and adjusted for various demographic and clinical factors. RESULTS: We found that frequencies of naïve and memory CD4+ and CD8+ T cells inversely correlated with measures for insulin sensitivity in the older population. Moreover, the percentages of naïve CD4+ and CD8+ T cells were significantly higher, whereas activated T cells and IL-6 levels were lower in IS compared to insulin resistant (IR) obese individuals. The percentages of naïve CD4+ and CD8+ T cells were predictive for impaired insulin sensitivity (ß = 0.16, p = 0.01 and ß = 0.11, p = 0.04), and the association of naïve CD4+ T cells with insulin sensitivity persisted after multivariate adjustment (ß = 0.14, p = 0.02). CONCLUSIONS: These findings support the hypothesis that parameters of systemic inflammation can differentiate IS from IR obese individuals that are at higher risk for cardiometabolic diseases and may have clinical implications with regard to obesity treatment stratification. TRIAL REGISTRATION: DRKS00009277 . Registered 31 August 2015 - Retrospectively registered.