Hyponatremia, hypernatremia and impairment of functional, psychological and sexual domains.

OBJECTIVE: To determine the influence of serum sodium on physical, psychologic and sexual function. METHODS: This is a cross-sectional survey on 3340 community-dwelling men aged 40-79 years from a prospective cohort study in eight European countries, the European Male Ageing Study (EMAS). Participants filled-out the Short Form-36 (SF-36), the Physical Activity Scale for the Elderly (PASE), and the EMAS sexual function questionnaire. For all the analyses, serum sodium corrected for glycaemia ([Na+]G) was used. RESULTS: The relationship between [Na+]G and SF-36 physical function score (F = 3.99; p = 0.01), SF-36 mental health score (F = 7.69; p < 0.001), and PASE score (F = 14.95; p < 0.001) were best described by a quadratic equation, with worse scores for [Na+]G in either the lowest or the highest ends of the range. After dividing the sample into [Na+]G < 136 mmol/L (n = 81), 136-147 mmol/L (n = 3223) and > 147 mmol/L (n = 36), linear regression analyses with linear spline functions adjusted for confounders did not confirm these relationships. Similarly, erectile dysfunction and [Na+]G, were in a quadratic relationship (F = 9.00; p < 0.001). After adjusting for confounders, the linear regression with spline functions denoted a significantly worsened erectile function for increases in serum [Na+]G > 147 mmol/L (B = 0.15 [0.04;0.26], p < 0.01) but no relationship with [Na+]G < 136 mmol/L. Likewise, the relationship of [Na+]G with concerns about sexual dysfunction was confirmed only for men with serum [Na+]G > 147 mmol/L. CONCLUSIONS: This is the first study supporting an association between [Na+]G and sexual function. A worsening of erection and concerns about sexual function were observed for the highest values of [Na+]G, independently of other relevant factors.

Highly Variable Paracetamol Pharmacokinetics After Multiple Oral Dosing in Frail Older People: A Population Pharmacokinetic Analysis.

INTRODUCTION: Paracetamol pharmacokinetics (PK) is highly variable in older fit adults after intravenous administration. Frailty and oral administration likely result in additional variability. The aim was to determine oral paracetamol PK and variability in geriatric inpatients. METHODS: A population PK analysis, using NONMEM 7.2, was performed on 245 paracetamol samples in 40 geriatric inpatients (median age 87 [range 80-95] years, bodyweight 66.4 [49.3-110] kg, 92.5% frail [Edmonton Frail Scale]). All subjects received paracetamol 1000 mg as tablet (72.5%) or granulate (27.5%) three times daily. Simulations of dosing regimens (1000 mg every 6 hours [q6h] or q8h) were performed to determine target attainment, using mean steady-state concentration (Css-mean) of 10 mg/L as target. RESULTS: A one-compartment model with first order absorption and lag time best described the data. The inter-individual variability was high, with absorption rate constant containing the highest variability. The inter-individual variability could not be explained by covariates. Simulations of 1000 mg q6h and q8h resulted in a Css-mean of 10.8 [25-75th percentiles 8.2-12.7] and 8.13 [6.3-9.6] mg/L, respectively, for the average geriatric inpatient. The majority of the population remained off-target (22.2% [q6h] and 52.2% [q8h] <8 mg/L; 31.3 [q6h] and 7.6% [q8h] >12 mg/L). CONCLUSION: A population of average geriatric inpatients achieved target Css-mean with paracetamol 1000 mg q6h, while q8h resulted in underexposure for the majority of them. Due to high unexplained variability, a relevant proportion remained either above or below the target concentration of 10 mg/L. Research focusing on PK, efficacy and safety is needed to recommend dosing regimens.

Association of orthogeriatric care models with evaluation and treatment of osteoporosis: a systematic review and meta-analysis.

This systematic review and meta-analysis found low-quality evidence that orthogeriatric care is positively associated with diagnosis of osteoporosis, prescription of calcium and vitamin D supplements and bisphosphonates in older hip fracture patients. Evidence on fall and fracture prevention was scarce and inconclusive. Orthogeriatrics may reduce the treatment gap following hip fractures. INTRODUCTION: Hip fracture patients are at imminent risk of additional fractures and falls. Orthogeriatric care might reduce the osteoporosis treatment gap and improve outcomes in these patients. However, the optimal orthogeriatric care model (geriatric liaison service, co-management, or geriatrician-led care) remains unclear. PURPOSE: To summarize the association of different orthogeriatric care models for older hip fracture patients, compared to usual orthopaedic care, with fall prevention measures, diagnosis and treatment of osteoporosis and future falls and fractures. METHODS: Two independent reviewers retrieved randomized controlled trials (RCTs) or controlled observational studies. Random effects meta-analysis was applied (PROSPERO ID: 165914). RESULTS: One RCT and twelve controlled observational studies were included, encompassing 20,078 participants (68% women, median ages between 75 and 85 years). Orthogeriatric care was associated with higher odds of diagnosing osteoporosis (odds ratio [OR] 11.36; 95% confidence interval [CI] 7.26-17.77), initiation of calcium and vitamin D supplements (OR 41.44; 95% CI 7.07-242.91) and discharge on anti-osteoporosis medication (OR 7.06; 95% CI 2.87-17.34). However, there was substantial heterogeneity in these findings. Evidence on fall prevention and subsequent fractures was scarce and inconclusive. Almost all studies were at high risk of bias. Evidence was insufficient to compare different care models directly against each other. CONCLUSIONS: Low-quality evidence suggests that orthogeriatric care is associated with higher rates of diagnosing osteoporosis, initiation of calcium and vitamin D supplements and anti-osteoporosis medication. Whether orthogeriatric care prevents subsequent falls and fractures in older hip fracture patients remains unclear.

Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis.

AIMS: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about 1 year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration. METHODS: The diagnostic performances of serum NfL were based on a cohort of 149 serum samples of patients with ALS, 19 serum samples of patients with a disease mimicking ALS and 82 serum samples of disease control patients. The serum NfL levels were correlated with the number of regions (thoracic, bulbar, upper limb and lower limb) displaying upper and/or lower motor neuron degeneration. The prognostic performances of serum NfL were investigated based on a Cox regression analysis. RESULTS: The associated predictive values and likelihood ratio to discriminate patients with ALS and ALS mimics were established. Serum NfL was associated with motor neuron degeneration driven by upper motor neuron (UMN) degeneration and was independently associated with survival in patients with ALS. CONCLUSIONS: Altogether, these findings suggest that elevated serum NfL levels in ALS are driven by UMN degeneration and the disease progression rate and are independently associated with survival at time of diagnosis.

[The development of clinical practice algorithms for the appropriate use of psychotropic drugs in older persons with high risk of falls]. / Ontwikkeling van algoritmes voor oordeelkundig gebruik van psychofarmaca bij ouderen met verhoogd valrisico.

Psychotropic drugs (hypno-sedatives, antidepressants and antipsychotics) are commonly used in the older population. On the long term, psychotropic drug use in older persons is associated with several negative functional outcomes such as an increased risk of falls. Gradual withdrawal of psychotropic drugs in older persons is feasible and leads to a significant reduction of falls. Both withdrawal of psychotropic drugs as well as the initiation of appropriate treatment with psychotropic drugs requires knowledge, consultation and cooperation between disciplines and a mentality change among healthcare professionals. In order to inform and support healthcare professionals, the Centre of Expertise for Fall and Fracture Prevention Flanders developed three clinical practice algorithms for the appropriate use of psychotropic drugs in older persons with high risk of falls and a fact sheet with background information.

Ergotamine-induced pleural and pericardial effusion successfully treated with colchicine.

A 83-year-old woman was admitted to hospital with chest pain, fever, dry cough and palpitations. Chest X-ray revealed a pleural effusion, assumed to be caused by cardiac failure and respiratory infection. Despite treatment with antibiotics and diuretics, the pleural effusion increased on chest X-ray and there were signs of pleural and pericardial effusion on computed tomography (CT) scan. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was not successful. Meanwhile patients' long-term use of ergotamine for migraine was revealed, which is associated with pleuropulmonary and cardiac fibrotic reactions. Tentative treatment with colchicine was successful, with complete resolution of pleural fluid, fever, cough and inflammatory parameters. This case highlights the importance of establishing an ergot alkaloid use registry in unexplained pleuropericardial effusions and supports the use of colchicine as a potential therapeutic approach.

[The attitudes and perceptions of older persons towards the automatic monitoring of the activities of daily living using contactless sensors: a systematic literature review]. / Hoe denken ouderen over automatische contactloze monitoring? Een systematische literatuurstudie.

INTRODUCTION: Technologies for contactless monitoring are increasingly used in order to contribute to qualitative and cost-effective care for older persons. The purpose of this systematic literature review is to explore the attitudes and perceptions of older persons towards the use of systems for contactless monitoring. METHODOLOGY: Relevant studies were identified through an extensive search strategy in Medline, Embase and Cinahl for studies published between January 1990 and August 19 2012; using a reference list offered by a group of experts in this field of research and through the exploration of the reference lists of all relevant studies. RESULTS: Nine studies with a qualitative study design and one study with a combined study design were included in this literature review. Various aspects of the attitudes, perceptions and needs of older persons as potential or actual end-users of contactless monitoring are discussed in five themes. This refers to the perceptions of older persons on the potential usefulness of contactless monitoring, the communication of information obtained through monitoring, several concerns when contactless monitoring is used and the participation and involvement of the person who is monitored. All these facets can influence the willingness of older people to accept these monitoring systems. CONCLUSIONS: This review can offer technology developers and care providers useful information to promote acceptance and successful integration of systems for contactless monitoring into daily practice by ensuring that they meet the needs, concerns and wishes of older persons as their end-users. Further exploration of the attitudes and perceptions of older people towards contactless monitoring through qualitative and quantitative research with a good methodological quality is required.

Musculoskeletal frailty: a geriatric syndrome at the core of fracture occurrence in older age.

A progressive decline in physiologic reserves inevitably occurs with ageing. Frailty results from reaching a threshold of decline across multiple organ systems. By consequence, frail elderly experience an excess vulnerability to stressors and are at high risk for functional deficits and comorbid disorders, possibly leading to institutionalization, hospitalization and death. The phenotype of frailty is referred to as the frailty syndrome and is widely recognized in geriatric medical practice. Although frailty affects both musculoskeletal and nonmusculoskeletal systems, sarcopenia, which is defined as age-related loss of muscle mass and strength, constitutes one of the main determinants of fracture risk in older age and one of the main components of the clinical frailty syndrome. As a result, operational definitions of frailty and therapeutic strategies in older patients tend to focus on the consequences of sarcopenia.

Cognitive aging and Alzheimer's disease.

Cognitive aging and clinically probable Alzheimer's disease can be discriminated by means of clinical and neuropsychological testing, and structural and functional imaging techniques. Research at the level of cognitive brain systems and at the molecular level provides exciting new insights into the relation between aging and neurodegeneration. The advances at the clinical and at the basic research levels are necessary if we wish to meet the formidable challenge that the increasing prevalence of Alzheimer's disease poses to the medical community.

Implication of APP secretases in notch signaling.

Signaling via notch receptors and their ligands is an evolutionary ancient and highly conserved mechanism governing cell-fate decisions throughout the animal kingdom. Upon ligand binding, notch receptors are subject to a two-step proteolysis essential for signal transduction. First, the ectodomain is removed by an enzyme cleaving near the outer-membrane surface ("site2"). Consecutively, the notch intracellular domain is liberated by a second protease cutting within the transmembrane sequence ("site3"). The intracellular domain is then transferred to the nucleus to act as a transcriptional coactivator. The proteases involved in notch receptor activation are shared with other proteins undergoing regulated intramembrane proteolysis, with intriguing parallels to APP. Specifically, site3 cleavage of Notch, as well as gamma-secretase processing of APP depend both critically on presenilins 1 and 2. Moreover, ADAM 10 and ADAM 17, the proteases proposed to perform site2 cleavage, are also the most probable candidate alpha-secretases to cleave APP. While the biological significance of APP processing remains to be further elucidated, interference with notch signaling has been shown to have severe consequences both in small animal models as well as in humans. Thus, a growing number of long known genetic syndromes like Alagille syndrome or Fallot's tetralogy can be caused by mutations of genes relevant for the notch signaling pathway. Likewise, the anticipated interference of gamma-secretase inhibitors with site3 cleavage may turn out to be a major obstacle for this therapeutic approach to Alzheimer's disease.