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Introduction: Appetite loss in older people -anorexia of ageing (AA) - is common. Recognised consequences include under nutrition, sarcopenia, frailty, and increased mortality after discharge from hospital. Identification and management of AA may prevent onset of these health burdens. Whilst appetite can be assessed, this is often not routine. Methods: Cross-sectional data from three studies (carried out 2010-2017), with comparable data collection methods and drawn from the same population, were combined. Participants were over 70 years, admitted to acute wards within a large UK hospital. Appetite was assessed using the simple 4 item Simplified Nutritional Appetite Questionnaire (SNAQ); a score of ≤14/20 defines poor appetite. Correlates of SNAQ scores were evaluated. Results: The dataset included 474 participants (64% female) with mean age 84 (6.5), median Barthel 78 (IQR 53-91), mini-mental state exam (MMSE) 27 (IQR 23-29) and comorbidity index 5 (IQR 4-7). The median GDS for the population was 4 (IQR 4-6). The mean SNAQ score was 13.9 (SD 2.6), and 265 (56%) participants scored ≤14 indicating poor appetite. There was no significant difference between mean SNAQ scores of men and women (P=.26), or those living alone and with others (P=.62). Age, MMSE, comorbidity index, and total number of medications were not related to SNAQ score in continuous analyses but geriatric depression score (GDS-15) was (adjusted coefficient -.248; P<.001); such that lower mood was associated with poorer appetite. Conclusions: These findings highlight the importance of assessing appetite in hospitalised older people, as poor appetite is very common. Appetite can be assessed in hospital using the simple 4 item SNAQ tool. Subclinical low mood, measured by GDS-15, had the strongest association with SNAQ score whilst in hospital. Therefore, for those with poor appetite in hospital, clinicians should have a low threshold to evaluate and treat low mood. [ABSTRACT FROM AUTHOR]

Why Is the Area Important?: A sub-group of rare but serious patient safety incidents, known as 'never events,' is judged to be 'avoidable.' There is growing interest in this concept in international care settings, including UK primary care. However, issues have been raised regarding the well-intentioned coupling of 'preventable harm' with zero tolerance 'never events,' especially around the lack of evidence for such harm ever being totally preventable., What Is Already Known and Gaps in Knowledge?: We consider whether the ideal of reducing preventable harm to 'never' is better for patient safety than, for example, the goal of managing risk materializing into harm to 'as low as reasonably practicable,' which is well-established in other complex socio-technical systems and is demonstrably achievable.We reflect on the 'never event' concept in the primary care context specifically, although the issues and the polarized opinion highlighted are widely applicable. Recent developments to validate primary care 'never event' lists are summarized and alternative safety management strategies considered, e.g. Safety-I and Safety-II., Future Areas for Advancing Research and Practice: Despite their rarity, if there is to be a policy focus on 'never events,' then specialist training for key workforce members is necessary to enable examination of the complex system interactions and design issues, which contribute to such events. The 'never event' term is well intentioned but largely aspirational-however, it is important to question prevailing assumptions about how patient safety can be understood and improved by offering alternative ways of thinking about related complexities., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Laboratory test results management systems are a complex safety issue in primary care settings worldwide. Related failures lead to avoidable patient harm, medicolegal action, patient complaints and additional workload to problem solve identified issues. We aimed to review and learn from 50 clinical negligence cases involving system failures related to the management of test results., Methods: The Medical Protection Society database was searched and a convenience sample of 50 claims identified from a 3-year period covering 2014-2016. A content analysis of documentation was undertaken to quantify and theme data, aided by a Risk Assessment Matrix and the Yorkshire Contributory Factors Framework. Quantitative data were subjected to simple descriptive statistical analysis., Results: 14/50 cases (28%) involved a delay in diagnosis or treatment of a patient with cancer. 15 cases were judged to be 'never events' (30%) and 85 distinct system issues were identified. Just under half of cases involved a failure to notify patients of an abnormal test result (n=24, 48%), while 18 cases (36%) involved a test result not being actioned by a doctor. The most frequently occurring contributory factors (n=30, 60%) were related to local working conditions, for example, unclear professional responsibilities with regards to test result review or follow-up or lack of patient care continuity., Conclusion: This small study highlights why test result management systems fail and contribute to future litigation, providing new insights in this area. Most claims involved avoidable harm to patients and preventable organisational risks. The findings point to the inadequate design of practice systems and the need for proactive strategies to improve the management of test results in order to reduce patient harm., Competing Interests: Competing interests: None declared.

Telomere attrition has been associated with age-related diseases, although causality is unclear and controversial; low-grade systemic inflammation (inflammaging) has also been implicated in age-related pathogenesis. Unpicking the relationship between aging, telomere length (TL), and inflammaging is hence essential to the understanding of aging and management of age-related diseases. This longitudinal study explored whether telomere attrition is a cause or consequence of aging and whether inflammaging explains some of the associations between TL and one marker of aging, grip strength. We studied 253 Hertfordshire Ageing Study participants at baseline and 10-year follow-up (mean age at baseline 67.1 years). Participants completed a health questionnaire and had blood samples collected for immune-endocrine and telomere analysis at both time points. Physical aging was characterized at follow-up using grip strength. Faster telomere attrition was associated with lower grip strength at follow-up (β = 0.98, p = 0.035). This association was completely attenuated when adjusted for inflammaging burden (p = 0.86) over the same period. Similarly, greater inflammaging burden was associated with lower grip strength at follow-up (e.g., interleukin [IL]-1β: β = -2.18, p = 0.001). However, these associations were maintained when adjusted for telomere attrition (IL-1β, p = 0.006). We present evidence that inflammaging may be driving telomere attrition and in part explains the associations that have previously been reported between TL and grip strength. Thus, biomarkers of physical aging, such as inflammaging, may require greater exploration. Further work is now indicated.

Cross-sectional studies show that higher blood concentrations of inflammatory markers tend to be more common in frail older people, but longitudinal evidence that these inflammatory markers are risk factors for frailty is sparse and inconsistent. We investigated the prospective relation between baseline concentrations of the inflammatory markers C-reactive protein (CRP) and fibrinogen and risk of incident frailty in 2,146 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. The relationship between CRP and fibrinogen and risk of incident frailty differed significantly by sex (p for interaction terms <0.05). In age-adjusted logistic regression analyses, for a standard deviation (SD) increase in CRP or fibrinogen, odds ratios (95% confidence intervals) for incident frailty in women were 1.69 (1.32, 2.17) and 1.39 (1.12, 1.72), respectively. Further adjustment for other potential confounding factors attenuated both these estimates. For an SD increase in CRP and fibrinogen, the fully-adjusted odds ratio (95% confidence interval) for incident frailty in women was 1.27 (0.96, 1.69) and 1.31 (1.04, 1.67), respectively. Having a high concentration of both inflammatory markers was more strongly predictive of incident frailty than having a high concentration of either marker alone. In men, there were no significant associations between any of the inflammatory markers and risk of incident frailty. High concentrations of the inflammatory markers CRP and fibrinogen are more strongly predictive of incident frailty in women than in men. Further research is needed to understand the mechanisms underlying this sex difference.

Inflammaging is characterized by the upregulation of the inflammatory response that occurs with advancing age; its roots are strongly embedded in evolutionary theory.Inflammaging is believed to be a consequence of a remodelling of the innate and acquired immune system, resulting in chronic inflammatory cytokine production.Complex interrelated genetic, environmental and age-related factors determine an individual's vulnerability or resilience to inflammaging. These factors include polymorphisms to the promoter regions of cytokines, cytokine receptors and antagonists, age-related decreases in autophagy and increased adiposity. Anti-inflammaging describes the upregulation of the hypothalamic-pituitary axis in response to inflammaging, leading to higher levels of cortisol, which in turn may be detrimental, contributing to less successful ageing and frailty. This may be countered by the adrenal steroid dehydroepiandrosterone, which itself declines with age, leaving certain individuals more vulnerable. Inflammaging and anti-inflammaging have both been linked with a number of age-related outcomes, including chronic morbidity, functional decline and mortality. This important area of research offers unique insights into the ageing process and the potential for screening and targeted interventions.

Background: Age-related hearing loss is a common disabling condition but its causes are not well understood and the role of inflammation as an influencing factor has received little consideration in the literature., Objective: To investigate the association between inflammatory markers and hearing in community-dwelling older men and women., Design: Cross-sectional analysis within a cohort study., Setting: The Hertfordshire Ageing Study., Participants: A total of 343 men and 268 women aged 63-74 years on whom data on audiometric testing, inflammatory markers and covariates were available at follow-up in 1995., Main Outcome Measures: Average hearing threshold level (across 500-4,000 Hz) of the worst hearing ear and audiometric slope in dB/octave from 500 to 4,000 Hz., Results: Older age, smoking, history of noise exposure and male gender (all P < 0.001) were associated with higher mean hearing threshold in the worse ear in univariate analysis. After adjustment for these factors in multiple regression models, four measures of immune or inflammatory status were significantly associated with hearing threshold, namely white blood cell count (r = 0.13, P = 0.001), neutrophil count (r = 0.13, P = 0.002), IL-6 (r = 0.10, P = 0.05) and C-reactive protein (r = 0.11, P = 0.01). None of the inflammatory markers was associated with maximum audiometric slope in adjusted analyses., Conclusions: Markers of inflammatory status were significantly associated with degree of hearing loss in older people. The findings are consistent with the possibility that inflammatory changes occurring with ageing may be involved in age-related hearing loss. Longitudinal data would enable this hypothesis to be explored further.

The facile synthesis of seven new dicationic tripeptide benzyl ester derivatives, with hydrophobic group variations in the C-terminal amino acid component, is described. Moderate to good activity was seen against Gram-positive bacteria in vitro. One cyclohexyl-substituted compound 2c was tested more widely and showed good potency (MIC values ranging from 2-4 μg/mL) against antibiotic-resistant strains of Staphylococcus aureus and Enterococci (VRE, VSE), and against Staphylococcus epidermidis.