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

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 (&lt;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).</p

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 (&lt;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).</p

Health inequality implications from a qualitative study of experiences of poverty stigma in Scotland

Rationale: Individuals living in Scotland's most deprived communities experience a higher burden of morbidity and early mortality than those living in more affluent areas. Experiences of poverty-based stigma may be one psychosocial mechanism through which socioeconomic position influences health, although there is little available data on this issue from a Scottish perspective. Objective: The aim of this study was to identify which aspects of poverty stigma are particularly salient to individuals with lived experience of poverty, and may therefore contribute to health inequalities. Methods: Five focus groups were conducted with 39 individuals with experience of living on low incomes in Scotland in order to explore their experiences and perceptions of poverty stigma. Results: Five main themes were identified, reflecting aspects of poverty stigma operating at various structural, public and individual levels: media representations of poverty; negative encounters with social security systems; perceived public attitudes regarding poverty in Scotland; lowered self-esteem and internalisation of negative attitudes, and; emotional responses to stigma. Conclusion: These dimensions of stigma potentially influence public health and health inequalities in Scotland, although future research will be necessary to quantify these and estimate their relationships with health outcomes

Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy

We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a–j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4′,4′-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer

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 β 0.67, CI 0.59-0.75), and prescription of steroids during admission (48hours β 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 β -0.47, CI -0.5- -0.44). COPD (Preoperative β 0.35, CI 0.12-0.58) and delirium (48hours β 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 (β 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.</p

The effect of GLP-1RA exenatide on idiopathic intracranial hypertension:a randomized clinical trial

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure &gt;25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -6.4 ± 2.9 cmCSF (P = 0.030); and 12 weeks -5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signals were noted. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.</p

Blood pressure monitoring in high-risk pregnancy to improve the detection and monitoring of hypertension (the BUMP 1 and 2 trials): protocol for two linked randomised controlled trials.

INTRODUCTION: Self-monitoring of blood pressure (BP) in pregnancy could improve the detection and management of pregnancy hypertension, while also empowering and engaging women in their own care. Two linked trials aim to evaluate whether BP self-monitoring in pregnancy improves the detection of raised BP during higher risk pregnancies (BUMP 1) and whether self-monitoring reduces systolic BP during hypertensive pregnancy (BUMP 2). METHODS AND ANALYSES: Both are multicentre, non-masked, parallel group, randomised controlled trials. Participants will be randomised to self-monitoring with telemonitoring or usual care. BUMP 1 will recruit a minimum of 2262 pregnant women at higher risk of pregnancy hypertension and BUMP 2 will recruit a minimum of 512 pregnant women with either gestational or chronic hypertension. The BUMP 1 primary outcome is the time to the first recording of raised BP by a healthcare professional. The BUMP 2 primary outcome is mean systolic BP between baseline and delivery recorded by healthcare professionals. Other outcomes will include maternal and perinatal outcomes, quality of life and adverse events. An economic evaluation of BP self-monitoring in addition to usual care compared with usual care alone will be assessed across both study populations within trial and with modelling to estimate long-term cost-effectiveness. A linked process evaluation will combine quantitative and qualitative data to examine how BP self-monitoring in pregnancy is implemented and accepted in both daily life and routine clinical practice. ETHICS AND DISSEMINATION: The trials have been approved by a Research Ethics Committee (17/WM/0241) and relevant research authorities. They will be published in peer-reviewed journals and presented at national and international conferences. If shown to be effective, BP self-monitoring would be applicable to a large population of pregnant women. TRIAL REGISTRATION NUMBER: NCT03334149.This work is funded from a National Institute for Health Research (NIHR) Programme grant for applied research (RP-PG- 1209-10051) and an NIHR Professorship awarded to RJM (NIHR-RP- R2- 12-015). RJM and KLT receive funding from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care Oxford at Oxford Health NHS Foundation Trust. JS is a National Institute for Health Research (NIHR) Senior Investigator and supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London (NIHR CLAHRC South London) at King’s College Hospital NHS Foundation Trust. Service support costs will be administered through the NIHR Clinical Research Network