Potential deprescribing indications for antidepressants between 2012 and 2019: repeated cross-sectional analysis in two Scottish health boards.

BACKGROUND: Antidepressants have a pivotal role in the treatment of many psychiatric disorders, but there are concerns about long-term use and adverse effects. The objectives of this study were (1) to examine time trends in antidepressant use, (2) to estimate the prevalence of long-term and potential high-risk antidepressant use, and (3) to examine patient characteristics associated with potential deprescribing indications (PDIs) (i.e., simultaneous long-term and potential high-risk antidepressant use). METHODS: Repeated population-based cross-sectional study for all 609,299 people aged ≥ 18 years resident in the Tayside or Fife regions of Scotland. The prevalence of antidepressant use was examined on June 30th (index date) of each year from 2012 to 2019, while the prevalence of long-term and potential high-risk use as well as PDIs was assessed and compared on the same dates in 2012 and 2019. Binary logistic regression modeling was used to examine patient characteristics associated with PDIs. RESULTS: Antidepressant use increased by 27% from 12.0 to 15.3% among adult residents between 2012 and 2019. While the proportion of antidepressants users dispensed ≥ 1 antidepressant for > 2 years increased from 54.3 to 61.9% between 2012 and 2019, the proportion of antidepressant users triggering ≥ 1 indicator of potential high-risk use decreased slightly from 37.9 to 34.7%. In 2019, potential high-risk use most commonly related to indicators targeting fall risk (16.0%), cardiovascular risks (14.1%), insomnia (10.6%), and risk of orthostatic hypotension (8.6%). More than 1 in 4 (25.8%) antidepressant users had PDIs. The main risk factors associated with PDIs included increasing age (65-79, adjusted OR 14.12; 95% CI, 13.15-15.17), increasing number of drugs taken concomitantly (≥ 15 drugs, adjusted OR 7.37; 95% CI, 6.71-8.10), use of tricyclic antidepressants (≥ 50 mg) (adjusted OR 5.49; 95% CI, 5.02-6.01), and concomitant use of ≥ 2 antidepressants (adjusted OR 5.52; 95% CI, 5.20-5.85). CONCLUSIONS: Long-term and potential high-risk use of antidepressants is widespread, and potential deprescribing indications (PDIs) are increasing, suggesting the need for a critical review of their ongoing use by clinicians. If deemed necessary, future deprescribing interventions may use the criteria applied here for identification of patients with PDIs and for evaluating intervention effectiveness.

Deprescribing of antidepressants: development of indicators of high-risk and overprescribing using the RAND/UCLA Appropriateness Method.

BACKGROUND: Antidepressants are first-line medications for many psychiatric disorders. However, their widespread long-term use in some indications (e.g., mild depression and insomnia) is concerning. Particularly in older adults with comorbidities and polypharmacy, who are more susceptible to adverse drug reactions, the risks and benefits of treatment should be regularly reviewed. The aim of this consensus process was to identify explicit criteria of potentially inappropriate antidepressant use (indicators) in order to support primary care clinicians in identifying situations, where deprescribing of antidepressants should be considered. METHODS: We used the RAND/UCLA Appropriateness Method to identify the indicators of high-risk and overprescribing of antidepressants. We combined a structured literature review with a 3-round expert panel, with results discussed in moderated meetings in between rounds. Each of the 282 candidate indicators was scored on a 9-point Likert scale representing the necessity of a critical review of antidepressant continuation (1-3 = not necessary; 4-6 = uncertain; 7-9 = clearly necessary). Experts rated the indicators for the necessity of review, since decisions to deprescribe require considerations of patient risk/benefit balance and preferences. Indicators with a median necessity rating of ≥ 7 without disagreement after 3 rating rounds were accepted. RESULTS: The expert panel comprised 2 general practitioners, 2 clinical pharmacologists, 1 gerontopsychiatrist, 2 psychiatrists, and 3 internists/geriatricians (total N = 10). After 3 assessment rounds, there was consensus for 37 indicators of high-risk and 25 indicators of overprescribing, where critical reviews were felt to be necessary. High-risk prescribing indicators included settings posing risks of drug-drug, drug-disease, and drug-age interactions or the occurrence of adverse drug reactions. Indicators with the highest ratings included those suggesting the possibility of cardiovascular risks (QTc prolongation), delirium, gastrointestinal bleeding, and liver injury in specific patient subgroups with additional risk factors. Overprescribing indicators target patients with long treatment durations for depression, anxiety, and insomnia as well as high doses for pain and insomnia. CONCLUSIONS: Explicit indicators of antidepressant high-risk and overprescribing may be used directly by patients and health care providers, and integrated within clinical decision support tools, in order to improve the overall risk/benefit balance of this commonly prescribed class of prescription drugs.

The somatotroph pituitary gland function in high-aged multimorbid hospitalized patients with IGF-I deficiency.

PURPOSE: It is unclear whether the age-related decline in the somatotropic axis stems from a reduced growth hormone (GH) production in the pituitary gland, or from a peripheral origin akin to an acquired GH resistance. With the help of a GHRH/arginine test, high-aged multimorbid hospitalized patients with IGF-I deficiency are to be tested to determine whether there is primarily a pituitary GH deficiency in the sense of a somatopause. METHODS: Seventeen multimorbid patients (eleven men and six women) with a mean age of 82 years, with IGF-I concentrations below two standard deviations of 30-year-old men and women were identified. Patients suffered from a variety of common age-related stable diseases including coronary artery disease, chronic liver or kidney disease, chronic heart failure as well as acute conditions e.g., urosepsis or endocarditis. To assess the somatotropic axis they underwent a GHRH/arginine test. Results were evaluated using descriptive statistics. RESULTS: In average, the peak concentration of GH after stimulation was 14.8 µg/L with a range from 2.76 to 47.4 µg/L. Taking into account both, gender and BMI (with a mean of 26.5 kg/m²) for each participant, the pituitary gland was adequately stimulated in 16 out of the 17 patients. No patient reported common side effects related to the GHRH/arginine test. CONCLUSION: The somatotroph pituitary gland retains its secretory capacity in the advanced aged. Therefore, age does not seem to be the driving pacemaker for the functional decline of the somatotropic axis within the aged population.

[Update of the S3-guideline on diagnostics, prophylaxis and treatment of osteoporosis]. / Update der S3-Leitlinie Diagnostik, Prophylaxe und Therapie der Osteoporose.

With the aid of a new fracture risk model, the great treatment gap for osteoporosis should be closed. All patients older than 70 years should undergo a diagnostic procedure for osteoporosis. An additional risk threshold (≥ 10% per 3 years for femoral and vertebral fractures) should enable patients with a high risk of fracture to be treated with osteoanabolic agents. The use of osteoanabolic agents makes it necessary to administer antiresorptive drugs afterwards. Due to the low event rate of osteonecrosis of the jaw, the initiation of a specific osteoporosis treatment should not be delayed by prophylactic dental treatment. The adherence to the drug treatment should be improved by an individualized approach on the basis of a cooperation between patients, caregivers, and physicians. A regular assessment of falls, including the timed up and go test should be carried out in patients older than 70 years.

Growth hormone treatment in aged patients with comorbidities: A systematic review.

OBJECTIVE: Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects. DESIGN: A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library. INCLUSION CRITERIA: participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis. RESULTS: The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life. CONCLUSION: Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.

Hypogonadism is frequent in very old men with multimorbidity and is associated with anemia and sarcopenia.

BACKGROUND: Clinical data regarding hypogonadism in very old men with multimorbidity are rare. Hypogonadism can contribute to osteoporosis, anemia and sarcopenia and is therefore a relevant problem for geriatric patients. METHODS: A total of 167 men aged 65-96 years (mean 81 ± 7 years) admitted to an acute geriatric ward were included in a cross-sectional study. Body composition derived from dual-energy X­ray absorptiometry, bone mineral density, handgrip strength, multimorbidity, polypharmacy and laboratory values were obtained from the routine electronic clinical patient file. RESULTS: Hypogonadism was present in 62% (n = 104) of the study participants, of whom 83% showed clinical manifestation of hypogonadism (hypogonadism in combination with anemia, sarcopenia and/or low T­score). The subgroups showed a distribution of 52% primary and 48% secondary hypogonadism. Compared to the eugonadal patients, hypogonadal patients had reduced handgrip strength (p = 0.031) and lower hemoglobin levels (p = 0.043), even after adjustment for age, body mass index and glomerular filtration rate. CONCLUSION: Hypogonadism is common in geriatric patients. If chronic anemia, sarcopenia, or osteoporosis are diagnosed, testosterone levels should be determined in geriatric settings.

Age- and sex-adjusted reference intervals for steroid hormones measured by liquid chromatography-tandem mass spectrometry using a widely available kit.

Objective: Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing. Methods: After validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed. Results: Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples. Conclusions: The reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile. Significance Statement: Quantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.

Quality of life in sarcopenia measured with the SarQoL questionnaire: A meta-analysis of individual patient data.

Age-related sarcopenia, resulting from a gradual loss in skeletal muscle mass and strength, is pivotal to the increased prevalence of functional limitation among the older adult community. The purpose of this meta-analysis of individual patient data is to investigate the difference in health-related quality of life between sarcopenic individuals and those without the condition using the Sarcopenia Quality of Life (SarQoL) questionnaire. A protocol was published on PROSPERO. Multiple databases and the grey literature were searched until March 2023 for studies reporting quality of life assessed with the SarQoL for patients with and without sarcopenia. Two researchers conducted the systematic review independently. A two-stage meta-analysis was performed. First, crude (mean difference) and adjusted (beta coefficient) effect sizes were calculated within each database; then, a random effect meta-analysis was applied to pool them. Heterogeneity was measured using the Q-test and I2 value. Subgroup analyses were performed to investigate the source of potential heterogeneity. The strength of evidence of this association was assessed using GRADE. From the 413 studies identified, 32 were eventually included, of which 10 were unpublished data studies. Sarcopenic participants displayed significantly reduced health-related quality of life compared with non-sarcopenic individuals (mean difference = -12.32; 95 % CI = [-15.27; -9.37]). The model revealed significant heterogeneity. Subgroup analyses revealed a substantial impact of regions, clinical settings, and diagnostic criteria on the difference in health-related quality of life between sarcopenic and non-sarcopenic individuals. The level of evidence was moderate. This meta-analysis of individual patient data suggested that sarcopenia is associated with lower health-related quality of life measured with SarQoL.

11-beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) gene expression in muscle is linked to reduced skeletal muscle index in sarcopenic patients.

BACKGROUND: Glucocorticoids play a significant role in metabolic processes and pathways that impact muscle size, mass, and function. The expression of 11-beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) has been previously described as a major regulator of skeletal muscle function in glucocorticoid-induced muscle atrophy and aging humans. Our study aimed to investigate glucocorticoid metabolism, including the expression of HSD11B1 in skeletal muscle, in patients with sarcopenia. METHODS: Muscle biopsies were taken from the vastus lateralis muscle of thirty-three patients over 60 years of age with hip fractures. Sarcopenia status was assessed according to the criteria of the European Working Group on Sarcopenia in Older People 2. Skeletal muscle mass was measured by bioelectrical impedance analysis. Cortisol and cortisone concentrations were measured in serum. Gene expression analysis of HSD11B1, NR3C1, FBXO32, and TRIM63 in muscle biopsies was performed. Serial cross sections of skeletal muscle were labeled with myosin heavy chain slow (fiber type-1) and fast (fiber type-2) antibodies. RESULTS: The study included 33 patients (21 women) with a mean age of 82.5 ± 6.3 years, 17 patients revealed sarcopenic (n = 16 non-sarcopenic). Serum cortisone concentrations were negatively correlated with muscle mass (ß = - 0.425; p = 0.034) and type-2 fiber diameter (ß = - 0.591; p = 0.003). Gene expression of HSD11B1 (ß = - 0.673; p = 0.008) showed a negative correlation with muscle mass in the sarcopenic group. A significant correlation was found for the non-sarcopenic group for NR3C1 (ß = 0.548; p = 0.028) and muscle mass. CONCLUSION: These findings suggest a pathogenetic role of HSD11B1 in sarcopenic muscle.

[Update of the S3-guideline on diagnostics, prophylaxis and treatment of osteoporosis]. / Update der S3-Leitlinie Diagnostik, Prophylaxe und Therapie der Osteoporose.

With the aid of a new fracture risk model, the great treatment gap for osteoporosis should be closed. All patients older than 70 years should undergo a diagnostic procedure for osteoporosis. An additional risk threshold (≥ 10% per 3 years for femoral and vertebral fractures) should enable patients with a high risk of fracture to be treated with osteoanabolic agents. The use of osteoanabolic agents makes it necessary to administer antiresorptive drugs afterwards. Due to the low event rate of osteonecrosis of the jaw, the initiation of a specific osteoporosis treatment should not be delayed by prophylactic dental treatment. The adherence to the drug treatment should be improved by an individualized approach on the basis of a cooperation between patients, caregivers, and physicians. A regular assessment of falls, including the timed up and go test should be carried out in patients older than 70 years.

Sarcopenic obesity using the ESPEN and EASO consensus statement criteria of 2022 - Results from the German KORA-Age study.

OBJECTIVE: The recent consensus statement of ESPEN and EASO recommends reviewing existing datasets to assess the prevalence of sarcopenic obesity based on the new definition and diagnostic criteria. Therefore, this study aimed to determine the prevalence of sarcopenic obesity in a population-based study and to assess the association of this new definition with clinical traits. METHODS: The KORA (Cooperative Health Research in the Region of Augsburg)-Age baseline examination (2008/2009) comprised 1079 participants aged 65 years and older from southern Germany. Sarcopenic obesity was defined in 998 participants (mean age 75.6 years, 498 women) with complete data according to the 2022 ESPEN and EASO algorithm, which includes reduced handgrip strength, reduced skeletal muscle mass per weight, and elevated fat mass. Body composition was measured using bioelectrical impedance analysis. Associations between sarcopenic obesity and physical activity, disability, multimorbidity, and polypharmacy were assessed using logistic regression analysis. RESULTS: The overall prevalence of sarcopenic obesity was 4.5 % (5.0 % in men, 4.0 % in women). Sarcopenic obesity was associated with disability (2.87 [CI 1.84-4.48]), multimorbidity (≥ 2 comorbidities; 2.59 [CI 1.23-5.46]), polypharmacy (≥ 5 drugs; 1.96 [CI 1.05-3.63]), cognitive impairment (3.03 [CI 1.51-6.06]) and arthritis (2.66 [CI 1.39-5.07]) after adjusting for age, sex and marital status. CONCLUSION: Sarcopenic obesity is prevalent in the older German population and is associated with several clinical traits. Future longitudinal studies are needed to further elucidate whether the observed associations could be causal.

Single and combined use of fall-risk-increasing drugs and fracture risk: a population-based case-control study.

BACKGROUND: while many drug groups are associated with falls in older people, less is known about absolute increases in risk and how these risks vary across different groups of drugs or individuals. METHOD AND DESIGN: we conducted a population based nested case-control study among people aged ≥65 years in the Scottish regions of Tayside and Fife. Cases were individuals hospitalised with a fracture between 2010 and 2020, to whom we matched up to 10 controls. We examined relative and absolute risks of drug groups known as 'Fall-Risk-Increasing Drugs' (FRIDs), alone and in combination, and among younger and older (≥75 years) adults. Adjusting for previous hospitalisations, drug use and laboratory data, we used conditional logistic regression to quantify associations between drug exposures and outcomes. We conducted four sensitivity analyses to test the robustness of our findings. RESULTS: the cohort comprised 246,535 people aged ≥65 years, of whom 18,456 suffered an incident fracture. Fracture risks were significantly increased for most FRIDs examined. Absolute risks were much larger among older vs younger people and both relative and absolute risks increased with the number of FRIDs combined. Overall, the highest absolute increase in risk were found in people aged ≥75 years for selective serotonin reuptake inhibitors (number needed to harm 53), tricyclic antidepressants (NNH 81), antipsychotics (NNH 75) and use of three or more FRIDs (NNH ≤66). CONCLUSION: patients aged ≥75 years prescribed antidepressants or antipsychotics or taking three or more drugs that increase risk of falls may benefit most from deprescribing interventions.

Grip strength values and cut-off points based on over 200,000 adults of the German National Cohort - a comparison to the EWGSOP2 cut-off points.

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP) updated in 2018 the cut-off points for low grip strength to assess sarcopenia based on pooled data from 12 British studies. OBJECTIVE: Comparison of the EWGSOP2 cut-off points for low grip strength to those derived from a large German sample. METHODS: We assessed the grip strength distribution across age and derived low grip strength cut-off points for men and women (peak mean -2.5 × SD) based on 200,389 German National Cohort (NAKO) participants aged 19-75 years. In 1,012 Cooperative Health Research in the Region of Augsburg (KORA)-Age participants aged 65-93 years, we calculated the age-standardised prevalence of low grip strength and time-dependent sensitivity and specificity for all-cause mortality. RESULTS: Grip strength increased in the third and fourth decade of life and declined afterwards. Calculated cut-off points for low grip strength were 29 kg for men and 18 kg for women. In KORA-Age, the age-standardised prevalence of low grip strength was 1.5× higher for NAKO-derived (17.7%) compared to EWGSOP2 (11.7%) cut-off points. NAKO-derived cut-off points yielded a higher sensitivity and lower specificity for all-cause mortality. CONCLUSIONS: Cut-off points for low grip strength from German population-based data were 2 kg higher than the EWGSOP2 cut-off points. Higher cut-off points increase the sensitivity, thereby suggesting an intervention for more patients at risk, while other individuals might receive additional diagnostics/treatment without the urgent need. Research on the effectiveness of intervention in patients with low grip strength defined by different cut-off points is needed.

Sarcopenia: investigation of metabolic changes and its associated mechanisms.

BACKGROUND: Sarcopenia is one of the most predominant musculoskeletal diseases of the elderly, defined as age-related progressive and generalized loss of muscle mass with a simultaneous reduction in muscle strength and/or function. Using metabolomics, we aimed to examine the association between sarcopenia and the plasma metabolic profile of sarcopenic patients, measured using a targeted HPLC-MS/MS platform. METHODS: Plasma samples from 22 (17 men) hip fracture patients undergoing surgery (8 sarcopenic, age 81.4+6.3, and 14 non-sarcopenic, age 78.4±8.1) were analyzed. T test, fold change, orthogonal partial least squares discriminant analysis, and sparse partial least squares discriminant analysis were used for mining significant features. Metabolite set enrichment analysis and mediation analysis by PLSSEM were thereafter performed. RESULTS: Using a univariate analysis for sarcopenia z score, the amino acid citrulline was the only metabolite with a significant group difference after FDR correction. Positive trends were observed between the sarcopenia z score and very long-chain fatty acids as well as dicarboxylic acid carnitines. Multivariate analysis showed citrulline, non-esterified fatty acid 26:2, and decanedioyl carnitine as the top three metabolites according to the variable importance in projection using oPLS-DA and loadings weight by sPLS-DA. Metabolite set enrichment analysis showed carnitine palmitoyltransferase deficiency (II) as the highest condition related to the metabolome. CONCLUSIONS: We observed a difference in the plasma metabolic profile in association with different measures of sarcopenia, which identifies very long-chain fatty acids, Carn.DC and citrulline as key variables associated with the disease severity. These findings point to a potential link between sarcopenia and mitochondrial dysfunction and portraits a number of possible biochemical pathways which might be involved in the disease pathogenesis.

Oral health in patients with neurodegenerative and cerebrovascular disease: a retrospective study.

PURPOSE: This retrospective study investigates oral health and oral care in patients with neurodegenerative and cerebrovascular diseases (CVDs) treated in a dental facility for people with disabilities. METHODS: Oral health indices decayed, missing, and filled teeth (DMFT), periodontal screening index (PSI), treatment spectrum, and oral hygiene were evaluated in 152 patients with multiple sclerosis, Parkinson's disease, dementia, and CVD and 30 controls. Regression analyses identified group differences and influencing factors on DMFT. RESULTS: Patients with neurodegenerative or CVD had a significantly higher DMFT (21.2 ± 5.8 vs. 18.3 ± 5.9), more decayed teeth (4.3 ± 4.8 vs. 1 ± 1.9), fewer filled teeth (7.9 ± 5.5 vs. 11 ± 5.6), and a higher number of surgical (39.5% vs. 20%) treatments but significantly less conservative (49.3% vs. 73.3%) and prosthetic (15.1% vs. 56.7%) treatments than the control group (p< 0.05). The frequency of toothbrushing and the use of an electric toothbrush were related to lower DMFT in patients with neurodegenerative and CVD. Smoking was associated with higher DMFT. CONCLUSIONS: Poor oral health was found in all individuals with disabilities, suggesting that limitations in oral care attributed to aging and neurological disorders negatively affect oral health. Oral rehabilitation of patients with disabilities requires awareness of oral health limitations and early intervention through dental care. Implications for rehabilitationPoor oral health and oral hygiene is common among older people with disabilities.To optimize oral rehabilitation of patients with disabilities, early intervention, individualized treatment plans and an adapted time frame for dental treatment are required.Education of dentists, caregivers, and family members is essential for oral rehabilitation and improvement of oral hygiene in patients with disabilities.

Exploration of mitochondrial defects in sarcopenic hip fracture patients.

Severe cases of age-related loss of muscle function and mass are clinically unique to sarcopenia. Mitochondrial dysfunction has been associated with aging and sarcopenia, but the causal connection in this context is not well eluded. Here we investigated different aspects of mitochondrial respiration in sarcopenia. Open muscle biopsies were taken from a total of 31 hip fracture patients, older than 70 years. Patients were assigned a sarcopenia Z-score based on EWGSOP2 criteria. Primary myoblast cultures were generated from the muscle tissue samples and used for real time metabolic measurement. Muscle and serum samples showed correlation of high Z-scores with reduced mitochondrial complex I activity, increased tricarboxylic acid cycle (TCA) metabolites, reduced vitamin D3 levels, and signs of an altered iron metabolism. Primary myoblast cultures gained from the same muscle biopsies did not show significant mitochondrial defects. We hypothesize that a sum of external consequences, including vitamin D3 deficiency and iron deficiency caused by disturbances in the iron metabolism, result in complex I deficiency, which in turn affects the TCA and contributes to muscle weakness and loss.

Resistance training-induced improvement in physical function is not associated to changes in endocrine somatotropic activity in prefrail older adults.

CONTEXT: Resistance training improves muscle function in prefrail and frail elderly. The role of the somatotropic axis in this physiologic process remains unclear. Insulin-like growth factor I (IGF-I) and its associated proteins Insulin-like growth factor binding protein 3 (IGFBP3) and acid labile subunit (ALS) build a circulating ternary complex that mediates growth hormone (GH) effects on peripheral organs and can serve as a measure of endocrine somatotropic activity. OBJECTIVE: The aim of this study was to assess the association between resistance training-induced changes in physical performance and basal levels of IGF-I, IGFBP-3 and ALS in prefrail older adults. METHODS: 69 prefrail community-dwelling older adults, aged 65 to 94 years, were randomly assigned to a 12-week period of strength or power training or to a control group. The study was registered at clinicaltrials.gov as NCT00783159. Serum concentrations of IGF-I, IGFBP-3 and ALS were measured at rest before and after the intervention. Hormonal differences were examined in relation to changes in physical performance assessed by the Short Physical Performance Battery (SPPB). RESULTS: While resistance training led to significant improvements in SPPB score it did not induce significant differences in somatotropic hormone concentrations. Pre- and post-intervention changes in IGF-I, IGFBP-3, ALS or IGF/IGFBP-3 molar ratio were not related to the intervention mode, even after adjustment for age, sex, nutritional status, as well as SPPB and hormone concentrations at baseline. CONCLUSION: Training-induced improvements in physical performance in prefrail older adults were not associated with significant changes in endocrine somatotropic activity.

Proteomics of the phase angle: Results from the population-based KORA S4 study.

BACKGROUND & AIMS: The phase angle (PhA) measured with bioelectrical impedance analysis is considered to reflect the interrelated components body cell mass and fluid distribution based on technical and physical aspects of the PhA measurement. However, the biomedical meaning of the PhA remains vague. Previous studies mainly assessed associations of the PhA with numerous diseases and health outcomes, but few connected protein markers to the PhA. To broaden our understanding of the biomedical background of the PhA, we aimed to explore a proteomics profile associated with the PhA and related biological factors. METHODS: The study sample encompassed 1484 participants (725 women and 759 men) aged 55-74 years from the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4 study. Proteomics measurements were performed with a proximity extension assay. We employed boosting with stability selection to establish a set of markers that was strongly associated with the PhA from a group of 233 plasma protein markers. We integrated the selected protein markers into a network and enrichment analysis to identify gene ontology (GO) terms significantly overrepresented for the selected PhA protein markers. RESULTS: Boosting with stability selection identified seven protein markers that were strongly and independently associated with the PhA: N-terminal prohormone brain natriuretic peptide (NT-proBNP), insulin-like growth factor-binding protein 2 (IGFBP2), adrenomedullin (ADM), myoglobin (MB), matrix metalloproteinase-9 (MMP9), protein-glutamine gamma-glutamyltransferase 2 (TGM2), and fractalkine (CX3CL1) [beta coefficient per 1 standard deviation increase in normalized protein expression values on a log 2 scale (95% confidence interval): -0.12 (-0.15, -0.08), -0.13 (-0.17, -0.09), -0.14 (-0.18, -0.10), 0.10 (0.07, 0.14), 0.07 (0.04, 0.10), 0.08 (0.05, 0.11), -0.06 (-0.10, -0.03), respectively]. According to the enrichment analysis, this protein profile was significantly overrepresented in the following top five GO terms: positive regulation of cell population proliferation (p-value: 1.32E-04), extracellular space (p-value: 1.34E-04), anatomical structure formation involved in morphogenesis (p-value: 2.92E-04), regulation of multicellular organismal development (p-value: 5.72E-04), and metal ion homeostasis (p-value: 8.86E-04). CONCLUSION: Implementing a proteomics approach, we identified six new protein markers strongly associated with the PhA and confirmed that NT-proBNP is a key PhA marker. The main biological processes that were related to this PhA's protein profile are involved in regulating the amount and growth of cells, reinforcing, from a biomedical perspective, the current technical-based consensus of the PhA to reflect body cell mass.