Duke Activity Status Index and Liver Frailty Index predict mortality in ambulatory patients with advanced chronic liver disease: A prospective, observational study.

BACKGROUND: There remains a lack of consensus on how to assess functional exercise capacity and physical frailty in patients with advanced chronic liver disease (CLD) being assessed for liver transplantation (LT). Aim To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD. AIM: To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD. METHODS: We recruited patients from outpatient clinics at University Hospitals Birmingham, UK (2018-2019). We prospectively collated the DASI and LFI to identify the prevalence of, respectively, functional capacity and physical frailty, and to evaluate their accuracy in predicting overall and pre-LT mortality. RESULTS: We studied 307 patients (57% male; median age 54 years; UKELD 52). Median DASI score was 28.7 (IQR 16.2-50.2), mean LFI was 3.82 (SD = 0.72), and 81% were defined either 'pre-frail' or 'frail'. Female sex and hyponatraemia were significant independent predictors of both DASI and LFI. Age and encephalopathy were significant independent predictors of LFI, while BMI significantly predicted DASI. DASI and LFI were significantly related to overall (HR 0.97, p = 0.001 [DASI], HR 2.04, p = 0.001 [LFI]) and pre-LT mortality (HR 0.96, p = 0.02 [DASI], HR 1.94, p = 0.04 [LFI]). CONCLUSIONS: Poor functional exercise capacity and physical frailty are highly prevalent among ambulatory patients with CLD who are being assessed for LT. The DASI and LFI are simple, low-cost tools that predict overall and pre-LT mortality. Implementation of both should be considered in all outpatients with CLD to highlight those who may benefit from targeted nutritional and exercise interventions.

Are physical performance and frailty assessments useful in targeting and improving access to adjuvant therapy in patients undergoing resection for pancreatic cancer?

BACKGROUND: Many patients fail to receive adjuvant chemotherapy following pancreatic cancer surgery. This study implemented a multimodal, multidisciplinary approach to improving recovery after pancreatoduodenectomy (the 'Fast Recovery' programme) and measured its impact on adjuvant chemotherapy uptake and nutritional decline. The predictive accuracies of a bundle of frailty and physical performance assessments, with respect to the recipient of adjuvant chemotherapy, were also evaluated. RESULTS: The N = 44 patients treated after the introduction of the 'Fast Recovery' programme were not found to have a significantly higher adjuvant chemotherapy uptake than the N = 409 treated before the pathway change (80.5 vs. 74.3%, p = 0.452), but did have a significantly lower average weight loss at six weeks post-operatively (mean: 4.3 vs. 6.9 kg, p = 0.013). Of the pre-operative frailty and physical performance assessments tested, the 6-min walk test was found to be the strongest predictor of the receipt of adjuvant chemotherapy (area under the ROC curve: 0.91, p = 0.001); all patients achieving distances ≥ 360 m went on to receive adjuvant chemotherapy, compared to 33% of those walking < 360 m. CONCLUSIONS: The multimodal 'Fast Recovery' programme was not found to significantly improve access to adjuvant chemotherapy, but did appear to have benefits in reducing nutritional decline. Pre-operative assessments were found to be useful in identifying patients at risk of non-receipt of adjuvant therapies, with markers of physical performance appearing to be the best predictors. As such, these markers could be useful in targeting pre- and post-habilitation measures, such as physiotherapy and improved dietetic support.

Home-based exercise in patients with refractory fatigue associated with primary biliary cholangitis: a protocol for the EXerCise Intervention in cholesTatic LivEr Disease (EXCITED) feasibility trial.

INTRODUCTION: Fatigue is the most commonly reported symptom of the liver disease primary biliary cholangitis (PBC). It affects 40%-80% of patients, has no effective treatment and is associated with heightened mortality risk. The pathogenesis is unknown, but muscle bioenergetic abnormalities have been proposed to contribute. Directly observed exercise has been shown to attenuate symptoms in small groups; however, due to the rare nature of the disease, home-based interventions need to be evaluated for feasibility, safety and efficacy. METHODS AND ANALYSIS: This is a phase 1/pilot, single-arm, open-label clinical trial evaluating a novel home-based exercise programme in patients with PBC with severe fatigue. Forty patients with moderate-severe fatigue (PBC40 fatigue domain score >33; other causes of fatigue excluded) will be selected using a convenience sampling method. A 12-week home-based exercise programme, consisting of individualised resistance, aerobic exercises and telephone health calls (first 6 weeks only), will be delivered. Measures of fatigue (PBC40 fatigue domain; fatigue impact scale), quality of life, sleep (Epworth Sleep Score), physical activity, anxiety and depression, aerobic exercise capacity (incremental shuttle walk test; Duke Activity Status Index) and functional capacity (short physical performance battery) will be assessed at baseline and at 6 and 12 weeks following the intervention. ETHICS AND DISSEMINATION: The protocol is approved by the National Research Ethics Service Committee London (IRAS 253115). Recruitment commenced in April 2019 and ended in March 2020. Participant follow-up is due to finish by December 2020. Findings will be disseminated through peer-reviewed publication, conference presentation and social media. TRIAL REGISTRATION NUMBER: NCT04265235.