The reduced muscle mass and impaired muscle performance that defines sarcopenia in older individuals is associated with increased risk of physical limitation and a variety of chronic diseases. It may also contribute to clinical frailty.A gradual erosion of quality of life (QoL) has been evidenced in these individuals, although much of this research has been done using generic QoL instruments, particularly the SF-36, which may not be ideal in older populations with significant comorbidities. This review and report of an expert meeting, presents the current definitions of these geriatric syndromes (sarcopenia and frailty). It then briefly summarises QoL concepts and specificities in Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts older populations, examines the relevant domains of QoL and what is known concerning QoL decline with these conditions. It calls for a clearer definition of the construct of disability and argues that a disease-specific QoL instrument for sarcopenia/frailty would be an asset for future research and discusses whether there are available and validated components that could be used to this end and whether the psychometric properties of these instruments are sufficiently tested. It calls also for an approach using utility weighting to provide some cost estimates and suggests that a time trade off study could be appropriate.

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This review provides a framework for the development of an operational definition of sarcopenia and of the potential end points that might be adopted in clinical trials among older adults. While the clinical relevance of sarcopenia is widely recognized, there is currently no universally accepted definition of the disorder. The development of interventions to alter the natural history of sarcopenia also requires consensus on the most appropriate end points for determining outcomes of clinical importance which might be utilized in intervention studies. We review current approaches to the definition of sarcopenia and the methods used for the assessment of various aspects of physical function in older people. The potential end points of muscle mass, muscle strength, muscle power, and muscle fatigue, as well as the relationships between them, are explored with reference to the availability and practicality of the available methods for measuring these end points in clinical trials. Based on current evidence, none of the four potential outcomes in question is sufficiently comprehensive to recommend as a uniform single outcome in randomized clinical trials. We propose that sarcopenia may be optimally defined (for the purposes of clinical trial inclusion criteria as well as epidemiological studies) using a combination of measures of muscle mass and physical performance. The choice of outcome measures for clinical trials in sarcopenia is more difficult; co-primary outcomes, tailored to the specific intervention in question, may be the best way forward in this difficult but clinically important area.

Purpose: Nearly all eye drops contain preservatives to decrease contamination. Nonpreservatives such as disodium-ethylene diamine tetra-acetate (EDTA) and phosphate-buffered saline are also regularly added as buffering agents. These components can add to the toxicity of eye drops and cause ocular surface disease. To evaluate the potential toxicity of these common components and their comparative effects on the ocular surface, a tissue culture model utilizing immortalized corneal and conjunctival epithelial cells was utilized. Methods: Immortalized human conjunctival and corneal epithelial cells were grown. At confl uency, medium was replaced with 100 μL of varying concentrations of preservatives: benzalkonium chloride (BAK), methyl paraben (MP), sodium perborate (SP), chlorobutanol (Cbl), and stabilized thimerosal (Thi); varying concentrations of buffer: EDTA; media (viable control); and formalin (dead control). After 1 h, solutions were replaced with 150 μL of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazonium bromide). After 4 h, solutions decanted, 100 μL of acid isopropanol added, and the optical density determined at 572 nm to evaluate cell viability. Results: Conjunctival and corneal cell toxicity was seen with all preservatives. Depending upon concentration, BAK exhibited from 56% to 89% toxicity. In comparison, Cbl exhibited from 50% to 86%, MP from 30% to 76%, SP from 23% to 59%, and Thi from 70% to 95%. EDTA with minimal toxicity (from 6% to 59%) was indistinguishable from SP. Conclusions: Generally, the order of decreasing toxicity at the most commonly used concentrations: Thi (0.0025%) > BAK (0.025%) > Cbl (0.25%) > MP (0.01%) > SP (0.0025%) ≈ EDTA (0.01%). Even at low concentration, these agents will cause some degree of ocular tissue damage.

Purpose: Most eye drops contain preservatives; benzalkonium chloride (BAK) is most common. Recent data demonstrated BAK adding to toxicity. BAK is degraded into hydrogen peroxide (H 2 O 2 ), which in even small amounts is known to be an irritant. Increased toxicity should cause localized infl ammation with increased elaboration of infl ammatory biomarkers. To evaluate the infl ammation BAK causes to the ocular surface, enzyme linked immunosorbant assays (ELISAs) were utilized to quantify the levels of infl ammatory biomarkers in response to BAK and/or H 2 O 2 . Methods: Immortalized human conjunctival and corneal epithelial cells were exposed to: BAK (0.001%-0.1%), hydrogen peroxide (H 2 O 2 ) (0.01%-0.1%), and cell media for 1 h. Cytokine quantifi cation was performed via enzyme-linked immunosorbent assays [ELISAs]). Additional experimentation was performed in which testing solutions were replaced with media after 1 h and the resulting supernatants quantifi ed after 24 h. Results: BAK induced signifi cant amounts of interleukin (IL-) 1 and tumor necrosis factor (TNF), but only moderate amounts of C-reactive protein (CRP), IL-10 and 12, and H 2 O 2 . Lower concentrations of BAK induced proportionally less elaboration. Replacing the test solutions with media and providing 23 h for cytokine elaboration signifi cantly increased TNF, but not IL-1. Lipopolysaccharide (LPS) positive controls induced substantial elaboration/release of both IL-1 and TNF as did in increasing the exposure to the full 24 h. Conclusions: After 1 h of exposure, BAK increased quantities of all biomarkers. The biomarkers in decreasing order of induction/upregulation were: TNF ≥ IL-1 ≥ IL-12 ≥ IL-10 ≥ CRP. Even low concentrations caused some degree of infl ammation. Replacing the testing solution with media and providing 23 h for cytokine elaboration, signifi cantly increased the elaboration/release of TNF, but not IL-1, as compared to the 1-h BAK exposure. Whereas increasing the exposure to the full 24 h by not removing the testing solution at the 1-h time point signifi cantly increased the elaboration/release of both IL-1 and TNF.