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BACKGROUND: Falls and fractures are common and morbid for patients with cirrhosis. Bisphosphonates are recommended for the prevention of fractures for people with osteoporosis cirrhosis; however, data supporting effectiveness in cirrhosis are lacking. AIM: We sought to emulate a clinical trial of bisphosphonates in cirrhosis. METHODS: We used national Medicare data (2008-2020) to examine the 5-year risk of fractures in patients who did or did not receive bisphosphonates with a new-user design among people diagnosed with cirrhosis and osteoporosis. We balanced treated and untreated with inverse probability of treatment weighting, evaluated intention-to-treat and as-treated effects, and examined both control exposures (statin use) and outcomes (decompensation) to test causal relationships. RESULTS: There were 253 and 20,888 new users and non-users of bisphosphonates, respectively. The median age was 74 years. The most common bisphosphonate used was alendronate (73.6%). Bisphosphonates significantly reduced fractures overall (27.5% vs. 33.0%, p = 0.0004) in the intention-to-treat analysis, particularly for people <65 years (sHR 0.56) old, men (sHR 0.64) and those with non-alcohol related liver disease (sHR 0.85). Though there were fewer arm (20.7% vs. 26.4%, p < 0.0001) and femur (28.9% vs. 31.2%, p = 0.005), there were more spinal (25.8% vs. 19.0%), rib (40.0% vs. 32.2%) and skull (10.1% vs. 8.7%) fractures. In the as-treated analysis, cumulative bisphosphonate exposure significantly reduced fractures, sHR 0.95 95% CI (0.91, 0.98). Treatment was inconsistent; bisphosphonate users spent 29.9% person-years of follow-up on the drug. CONCLUSION: In a nationally representative cohort of elderly patients with cirrhosis, bisphosphonates reduced fractures overall. Efforts to increase uptake and drug continuation are needed.
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BACKGROUND: Muscle cramps are common among persons with cirrhosis and are associated with poor health-related quality of life (HRQOL). Treatment options are limited. We compared stretching or meditation in a randomized-controlled trial (RCT). PATIENTS: We enrolled 98 patients with a history of >4 muscle cramps in the prior month from 7/22-7/23. We randomized patients 1:1 to stretching versus meditation for 35 days. Our primary outcome was the change in cramp severity measured by the visual analogue scale for cramps (VAS-cramps, scaled 0-10). Secondary outcomes included a patient global impression of change (PGIC), change in sleep quality and global HRQOL measured using the EQ-5D and VAS-global HRQOL. RESULTS: Overall, 48% of patients had cirrhosis, 40% had diabetes, 16% the median age was 63, most were women (67%) and 81% were college educated. Both arms experienced a reduction in cramp severity-a median of 1.44 (.58-2.29) points for stretching and 1.97 (1.01-2.93) points for meditation. These changes were significant changes from baseline (p = .001 for stretching, p < .0001 for meditation) but these changes were equivalent between arms (p = .4). The PGIC was improved: 1.33 (1.02-1.65) for stretching, 1.05 (.70-1.41) for meditation, p-difference .2. Sleep was also improved for both. HRQOL did not change according to the Eq5D; according to the VAS, HRQOL rose for meditation by 6 (.1-11.8) points but not for stretching. More patients recommended stretching than meditation (79.2% vs. 55.3%, p = .02). CONCLUSION: In a randomized trial, stretching and meditation both reduced cramp severity and improved sleep quality and global impression of change. While patients preferred stretching, there was no difference in effect between arms.
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BACKGROUND: Frailty is common in cirrhosis and associated with mortality, hospitalization, and reduced quality of life. Interventions aimed at forestalling frailty are limited by a lack of understanding of underlying physiologic deficits. AIMS: This study's aim was to examine contributions of discrete sensorimotor and neurocognitive capacities to conventional frailty measures of unipedal stance time, chair stands, and grip strength. METHODS: This cross-sectional study enrolled 119 outpatients with cirrhosis (50% female, aged 62.9 ± 7.3 years). Capacities included sensory (lower limb sensation and visual contrast), neurocognitive (Number Connection Tests A and B, simple and recognition reaction time), and muscular (hip/core strength determined by lateral plank time (LPT)). Bivariate analyses and linear regression models were performed to identify significant contributors to each frailty measure. RESULTS: The average performance was 9.8 ± 3.9 chair stands, 12.7 s ±9.9 unipedal stance time, and 60.3 ± 25.6 lb grip strength. In multivariate models, factors explained 40% of variance in unipedal stance and 43% of variance in chair stands. The LPT was most strongly associated with unipedal stance and chair stands. Grip strength was associated with LPT, but did not have physiologic predictors. CONCLUSIONS: Clinically useful measures of frailty in adults with cirrhosis can be explained by disease severity but also deficits in strength and neurocognitive function. Recognition reaction time, a novel measure in cirrhosis, had a significant contribution to frailty. These findings have implications for frailty assessment and suggest that the optimal rehabilitation approach to frailty targets neurocognitive function in addition to strengthening.
