Establishing Predictors of Acute Sarcopenia: A Proof-Of-Concept Study Utilising Network Analysis.

Dynamic changes in sarcopenia status following stressor events are defined as acute sarcopenia; it is currently unknown how to stratify risk. Prospective observational study involving elective colorectal surgery, emergency abdominal surgery, and medical patients with infections aged ≥70 years-old. Handgrip strength, muscle quantity (ultrasound Bilateral Anterior Thigh Thickness, BATT, and Bioelectrical Impedance Analysis), and muscle quality (rectus femoris echogenicity) were measured preoperatively in the elective group, and within 48hours, 7days after, and 13weeks after admission/surgery. Serum/plasma samples were collected preoperatively (elective group) and within 48hours of admission/surgery (all groups). LASSO models adjusting for baseline sarcopenia status were performed. Seventy-nine participants were included (mean age 79.1, 39.2% female). Chronic Obstructive Pulmonary Disease (COPD) (48hours ß 0.67, CI 0.59-0.75), and prescription of steroids during admission (48hours ß 1.11, CI 0.98-1.24) were positively associated with sarcopenia at 7days. Delirium was negatively associated with change in BATT to 7days (7days ß -0.47, CI -0.5- -0.44). COPD (Preoperative ß 0.35, CI 0.12-0.58) and delirium (48hours ß 0.13, CI 0.06-0.2) were positively associated with change in echogenicity to 7days in analysis including systemic biomarkers. Participants with sarcopenia at baseline had higher IL-7 concentrations during acute phase of illness (median 8.78pg/mL vs 6.52pg/mL; p=0.014). IL-1b within 48hours of admission/surgery was positively associated with sarcopenia status at 7days (ß 0.24, CI 0.06-0.42). Patients most at risk of acute sarcopenia or reductions in muscle quantity and quality included those prescribed steroids, with COPD or delirium, or with heightened systemic inflammation.

Baseline Nutritional Status and In-Hospital Step Count are Associated with Muscle Quantity, Quality, and Function: Results of an Exploratory Study.

This exploratory study aimed to assess associations of baseline nutritional status and in-hospital step count with muscle quantity, quality, and function. Seventy-nine participants aged ≥70 years (mean age 79.1 years, 44.3% female) were recruited (elective colorectal surgery, emergency abdominal surgery, and general medical patients with infections). Baseline nutrition (Mini Nutritional Assessment) and in-hospital step count (Fitbit Inspire devices) were assessed. Ultrasound quadriceps, bioelectrical impedance analysis, and physical function were assessed at baseline and 7 (±2) days and 13 (±1) weeks post-admission/post-operatively. Baseline nutritional status was associated with baseline rectus femoris ultrasound echogenicity (normal: 58.5, at risk: 68.5, malnourished: 81.2; p = 0.025), bilateral anterior thigh thickness (normal: 5.07 cm, at risk: 4.03 cm, malnourished: 3.05 cm; p = 0.021), and skeletal muscle mass (Sergi equation) (normal: 21.6 kg, at risk: 18.2 kg, malnourished: 12.0 kg; p = 0.007). Step count was associated with baseline patient-reported physical function (<900 37.1, ≥900 44.5; p = 0.010). There was a significant interaction between nutrition, step count, and time for skeletal muscle mass (Janssen equation) (p = 0.022).

Investigating the impact of fluid status on the ultrasound assessment of muscle quantity and quality in the diagnosis of sarcopenia - a multidimensional cross-sectional study.

BACKGROUND: Sarcopenia is a clinical manifestation of adverse ageing, characterised by progressive loss of muscle mass and function. Diagnosis requires assessment of muscle quantity and quality; ultrasound represents an emerging tool for this. However, ultrasound muscle assessment may be impacted by fluid balance. This is particularly important when assessing for acute sarcopenia in hospitalised patients, where fluid disturbance often occurs. The primary aim of this study was to characterise the impact of fluid status on ultrasound muscle assessment, such that this may be accounted for in sarcopenia diagnostics. METHODS: This Multidimensional Cross-sectional study involved 80 participants, who were inpatients at QEHB, a large UK tertiary centre. Fluid status was evaluated clinically and quantified using Bioelectrical Impedance Analysis (BIA). Muscle quantity was measured using Bilateral Anterior Thigh Thickness (BATT) with Rectus Femoris (RF) echogenicity used to assesses muscle adiposity and hence provide an inverse measure of muscle quality. RESULTS: A significant positive correlation was found between fluid status, measured using BIA, and BATT as a measure of muscle quantity, in males (rs = 0.662, p < 0.001) and females (rs = 0.638, p < 0.001). A significant negative correlation was found between fluid status and RF echogenicity (rs=-0.448, p < 0.001). CONCLUSIONS: These findings demonstrate associations between fluid balance and ultrasound assessment of muscle quantity and quality. Given the emerging use of ultrasound muscle assessment in sarcopenia diagnosis, there is a need to account for this in clinical practice. Future research should focus on the development of a corrective equation allowing assessment of muscle quantity and quality which account for changes in fluid status, hence aiding accurate diagnosis of sarcopenia.

Induced frailty and acute sarcopenia are overlapping consequences of hospitalisation in older adults.

Objectives: To determine the effects of hospitalisation upon frailty and sarcopenia. Methods: Prospective cohort study at single UK hospital including adults ≥70 years-old admitted for elective colorectal surgery, emergency abdominal surgery, or acute infections. Serial assessments for frailty (Fried, Frailty Index, Clinical Frailty Scale [CFS]), and sarcopenia (handgrip strength, ultrasound quadriceps and/or bioelectrical impedance analysis, and gait speed and/or Short Physical Performance Battery) were conducted at baseline, 7 days post-admission/post-operatively, and 13 weeks post-admission/post-operatively. Results: Eighty participants were included (mean age 79.2, 38.8% females). Frailty prevalence by all criteria at baseline was higher among medical compared to surgical participants. Median and estimated marginal CFS values and Fried frailty prevalence increased after 7 days, with rates returning towards baseline at 13 weeks. Sarcopenia incidence amongst those who did not have sarcopenia at baseline was 20.0%. However, some participants demonstrated improvements in sarcopenia status, and overall sarcopenia prevalence did not change. There was significant overlap between diagnoses with 37.3% meeting criteria for all four diagnoses at 7 days. Conclusions: Induced frailty and acute sarcopenia are overlapping conditions affecting older adults during hospitalisation. Rates of frailty returned towards baseline at 13 weeks, suggesting that induced frailty is reversible.

Trajectories of muscle quantity, quality and function measurements in hospitalized older adults.

AIM: Acute sarcopenia is defined by the development of incident sarcopenia (low muscle quantity/quality and function) within 6 months of a stressor event. However, outcome measures for clinical trials have not been validated. This study aimed to characterize changes in muscle quantity, quality, strength, and physical function during and after hospitalization. METHODS: Patients aged ≥70 years admitted for elective colorectal surgery, emergency abdominal surgery or acute infections were recruited from a single university hospital. Assessments were carried out at baseline, and within 7 ± 2 days and 13 ± 1 weeks postoperatively or post-admission. RESULTS: A total of 79 participants (mean age 79 years, 39% female) were included. Physical function defined by the Patient-Reported Outcome Measures Information System T-score declined from baseline (42.3, 95% CI 40.2-44.3) to 7 days (36.6, 95% CI 34.5-38.8; P = 0.001), with improvement after 13 weeks (40.5, 95% CI 37.9-43.0). Changes in muscle quantity, quality and function measurements were overall heterogeneous, with few significant changes at the study population level. Change in rectus femoris echogenicity over 13 weeks correlated with changes in handgrip strength (r = 0.53; P < 0.001) and gait speed (r = 0.59; P = 0.003) over the same period. CONCLUSIONS: Patient-Reported Outcome Measures Information System T-score provides a sensitive measure of change in physical function in hospitalized older patients. However, changes in muscle quantity, quality and function measurements were heterogeneous, and not significant at the study population level. Further research should assess for factors that might be predictive of changes within individuals to enable stratified interventions. Geriatr Gerontol Int 2022; 22: 311-318.

The feasibility of conducting acute sarcopenia research in hospitalised older patients: a prospective cohort study.

PURPOSE: To assess feasibility of conducting acute sarcopenia research in complex populations of hospitalised older adults. METHODS: Patients ≥ 70 years old were recruited to three cohorts: elective colorectal surgery, emergency (abdominal) surgery, medical patients with infections. Participants were recruited to the elective cohort in preoperative assessment clinic, and acutely admitted participants from surgical and medical wards at the Queen Elizabeth Hospital Birmingham. Serial measures of muscle quantity (ultrasound quadriceps, bioelectrical impedance analysis), muscle function (hand grip strength, physical performance), and questionnaires (mini-nutritional assessment, physical function) were performed at baseline, within 7 (± 2) days of admission/surgery, and 13 (± 1) weeks post-admission/surgery. Feasibility outcomes were assessed across timepoints including recruitment and drop-out rates, and procedure completion rates. RESULTS: Eighty-one participants were recruited (mean age 79, 38.3% females). Recruitment rates were higher in elective (75%, 24/32) compared to emergency surgery (37.2%, 16/43), and medical participants (45.1%, 41/91; p = 0.003). Drop-out rates varied from 8.3 to 19.5% at 7 days, and 12.5-43.9% at 13 weeks. Age and gender did not differ between patients assessed for eligibility, approached, or recruited. Completion rates were highest for ultrasound quadriceps (98.8%, 80/81 across all groups at baseline). Gait speed completion rates were lower in medical (70.7%, 29/41) compared to elective participants (100%, 24/24) at baseline. CONCLUSION: Higher participation refusal and drop-out rates should be expected for research involving recruitment of participants from the acute setting. Assessment of muscle quantity/quality through ultrasound is recommended in early-stage trials in the acute setting, where completion rates of physical performance testing are expected to be lower.

Memory, attention and fluency deficits in COPD may be a specific form of cognitive impairment.

There is increasing evidence demonstrating an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. We present a narrative review of published studies on the subject and a cross-sectional study investigating domain-specific cognitive impairment in people with COPD compared to people with known Alzheimer's dementia, and controls without known COPD or cognitive impairment. The aim of the study was to compare prevalence and pattern of cognitive impairment between the three groups using the Addenbrooke's Cognitive Examination (ACE)-III tool. A total of 89 participants were recruited (44 with COPD, 17 with Alzheimer's and 28 controls). Patients with COPD had significantly lower total ACE-III scores than controls (p<0.001). When comparing the COPD group to the known Alzheimer's dementia group, overall ACE-III scores were significantly lower in the Alzheimer's dementia group than the COPD group (p=0.019). The domain-specific scores for attention (p<0.004), memory (p<0.004) and fluency (p<0.001) were significantly lower in the Alzheimer's dementia group than the COPD group. Our result suggest that the COPD group were significantly more likely to have cognitive impairment than the healthy control group. This was supported by the results of a narrative review of the published literature. Our results show that the pattern of impairment in the COPD group is different to the pattern of impairment shown in the known Alzheimer's dementia group, with significant differences in the cognitive domains affected. These results are in keeping with the findings of other previously published studies included in the narrative review.

Bilateral Anterior Thigh Thickness: A New Diagnostic Tool for the Identification of Low Muscle Mass?

OBJECTIVES: To develop an ultrasonographic scanning protocol that included an assessment of muscle size [the proposed Bilateral Anterior Thigh Thickness (BATT)] and quality (echogenicity) to support the diagnosis of sarcopenia in a clinical setting. To determine the relationship of BATT and ultrasound echogenicity with physical function parameters of sarcopenia and test the reliability of ultrasound echogenicity measurements. DESIGN: Observational study. SETTING AND PARTICIPANTS: The BATT criteria were determined from a reference population of 113 healthy younger adults and tested in 39 healthy older adults and 31 frail older adults. METHODS: Ultrasonography was used to measure the thickness of rectus femoris and vastus intermedius bilaterally; the thickness measurements were summed to calculate the BATT. Diagnostic criteria for low muscle size were calculated from the reference population. Echogenicity was assessed using freeze-frame images. All individuals underwent anthropological, frailty, and physical performance assessments. RESULTS: The mean (standard deviation) BATTs for the subsamples were as follows: healthy young women (n = 54), 60.6 mm (±11.1); healthy young men (n = 59), 75.8 mm (±10.71); healthy older women (n = 27), 38.4 mm (±7.18); healthy older men (n = 13), 47.5 mm (±10.8); frail older women (n = 17), 29.2 mm (±11.4); and frail older men (n = 14), 27.3 mm (±13.9). The calculated cutoffs for low muscle size in older adults using the BATT criteria were 38.5 mm in women and 54.4 mm in men in this population. The BATT was correlated with grip strength (ρ = 0.750, P < .001 for women; ρ = 0.619, P < .001 for men) and walk speed (ρ = -0.599, P < .001 for women; ρ = -0.324, P = .003 for men). Ultrasound echogenicity increased with age and frailty. Lay sonographers were able to reliably reproduce the same muscle thickness measurements but not the same muscle echogenicity measurements. CONCLUSIONS/IMPLICATIONS: The data support the use of ultrasonography to identify low muscle size in sarcopenia. Ultrasonography provides a pragmatic diagnostic tool that is noninvasive, without radiation exposure, and usable in both community and hospital settings. The proposed BATT criteria could be used to identify low muscle size in clinical practice and research, and in this study have excellent correlation with physical parameters of muscle health. However, this now needs testing in a validation cohort. Ultrasound echogenicity has been demonstrated to be an important surrogate marker of muscle health, but difficulties with reproducibility preclude its widespread clinical use.

Assessing Fluid Resuscitation in Adults with Sepsis Who Are Not Mechanically Ventilated: a Systematic Review of Diagnostic Test Accuracy Studies.

BACKGROUND: Fluid resuscitation is a widely used intervention that is mandated in the management of sepsis. While its use can be life-saving, its overuse is associated with harm. Despite this, the best means of assessing a need for fluid resuscitation in an acute medical setting is unclear. OBJECTIVE: To assess studies of diagnostic tests that identify the need for fluid resuscitation in adults with sepsis, as defined by the presence of fluid responsiveness. DESIGN: Protocol registration was performed in advance (PROSPERO:CRD42017048651). Research database searches were performed alongside additional searches to identify grey literature. Diagnostic test accuracy studies that assessed any fluid assessment tool were identified independently by two authors, before data extraction and quality assessments were performed. PARTICIPANTS: Adults with sepsis, without intensive care organ support, who would be appropriate for admission to an acute medical unit. KEY RESULTS: Of the 26,841 articles that were screened, 14 studies were identified for inclusion, involving a combined total of 594 patients. Five categories of index test were identified: inferior vena cava collapsibility index (IVCCI), haemodynamic change with passive leg raise, haemodynamic change with respiration, haemodynamic change with intravenous fluid administration, and static assessment tools. Due to the high level of clinical heterogeneity affecting all aspects of study design, quantitative analysis was not feasible. There was a lack of consensus on reference tests to determine fluid responsiveness. CONCLUSION: While fluid resuscitation is considered a key part of the management of sepsis, evidence to support fluid assessment in awake adults is lacking. This review has highlighted a number of research recommendations that should be addressed as a matter of urgency if patient harm is to be avoided.

Acetylcholinesterase Activity Measurement and Clinical Features of Delirium.

AIMS: Cholinergic deficiency is commonly implicated in the pathophysiology of delirium. We aimed to investigate the relationship between directly measured serum acetylcholinesterase (AChE) activity and (1) clinical features of delirium and (2) outcomes among older hospital patients with delirium. METHODS: Hospitalised patients with delirium were recruited, and delirium motor subtype, severity and duration of delirium were measured. Serum AChE activity was measured using a colorimetric assay. RESULTS: The mean AChE activity for the whole sample was 2.46 µmol/µL/min (standard deviation 1.75). Higher AChE activity was associated with increased likelihood of hypoactive delirium rather than the hyperactive or mixed subtype (odds ratio 1.98, 95% confidence interval 1.10-3.59). CONCLUSION: Higher AChE activity was associated with hypoactive delirium but did not predict outcomes. Simple enhancement of cholinergic neurotransmission may not be sufficient to treat delirium.

Delirium is not associated with anticholinergic burden or polypharmacy in older patients on admission to an acute hospital: an observational case control study.

BACKGROUND: Older people are commonly prescribed multiple medications, including medications with anticholinergic effects. Polypharmacy and anticholinergic medications may be risk factors for the development of delirium. METHODS: Patients from a medical admission unit who were over 70, with DSM-IV diagnosed delirium and patients without delirium, were investigated. Number of drugs prescribed on admission and anticholinergic burden using two scales (the Anticholinergic Cognitive Burden Scale [ACB] and the Anticholinergic Drug Scale [ADS]) were recorded from electronic prescribing records. The relationship and predictive ability of these were explored. RESULTS: The sample included 125 patients with DSM-IV diagnosed delirium and 122 patients without delirium. The mean age of the sample was 84.0 years. The median number of drugs prescribed was 7: 79.8 % were prescribed ≥5 drugs and 29.0 % ≥10 drugs. The median ACB score was 1 and the median ADS score was 1.5. 73.4 % of patients had an ACB score of ≥1 and 73.0 % had a ADS score ≥1. There was no association between: number of drugs prescribed, rate of polypharmacy, rate of excessive polypharmacy, ACB score and ADS score, and a diagnosis of delirium on admission. Only acetylcholinesterase inhibitor use predicted delirium (OR 3.86, p = 0.04) and the number of drugs prescribed was negatively correlated with age (spearman rho = -0.18, p = 0.006). CONCLUSION: Neither number of drugs prescribed, polypharmacy or anticholinergic burden were associated with delirium on admission, questioning the clinical usefulness of anticholinergic drug scales. Further research is needed to unpick fully the relationship between, drugs, anticholinergic burden, age, and prevalent delirium in older patients and whether there is any role for these scales in clinical practice.