Cognitive impairment and liver fibrosis in non-alcoholic fatty liver disease.

Background: Data regarding the prevalence and phenotype of cognitive impairment in non-alcoholic fatty liver disease (NAFLD) are limited. Objective: We assessed the prevalence and nature of cognitive deficits in people with NAFLD and assessed whether liver fibrosis, an important determinant of outcomes in NAFLD, is associated with worse cognitive performance. Methods: We performed a prospective cross-sectional study. Patients with NAFLD underwent liver fibrosis assessment with transient elastography and the following assessments: Cognitive Change Index, Eight-Item Informant Interview to Differentiate Aging and Dementia Questionnaire (AD8), Montreal Cognitive Assessment (MoCA), EncephalApp minimal hepatic encephalopathy test and a limited National Institutes of Health Toolbox battery (Flanker Inhibitory Control and Attention Test, Pattern Comparison Test and Auditory Verbal Learning Test). We used multiple linear regression models to examine the association between liver fibrosis and cognitive measures while adjusting for relevant covariates. Results: We included 69 participants with mean age 50.4 years (SD 14.4); 62% were women. The median liver stiffness was 5.0 kilopascals (IQR 4.0-6.9), and 25% had liver fibrosis (≥7.0 kilopascals). Cognitive deficits were common in people with NAFLD; 41% had subjective cognitive impairment, 13% had an AD8 >2, 32% had MoCA <26 and 12% had encephalopathy detected on the EncephalApp test. In adjusted models, people with liver fibrosis had modestly worse performance only on the Flanker Inhibitory Control and Attention Task (ß=-0.3; 95% CI -0.6 to -0.1). Conclusion: Cognitive deficits are common in people with NAFLD, among whom liver fibrosis was modestly associated with worse inhibitory control and attention.

A Technique of Deep Brain Stimulation of the Globus Pallidus Interna for Dystonia Under General Anesthesia With Sevoflurane.

Background Globus pallidus interna (GPi) deep brain stimulation (DBS) is an established surgical procedure that confers a benefit in medication refractory dystonia. Patients with generalized dystonia require general anesthesia (GA) for the surgery as their movements may hinder the surgical procedure. General anesthetics tend to dampen the microelectrode recordings (MERs) from the GPi. Methods We describe our experience with a series of consecutive patients with dystonia who underwent bilateral GPi DBS using standard DBS and MER under GA using sevoflurane as the maintenance general anesthetic drug. All patients had Medtronic 3,387 leads implanted and connected to an RC battery. Patients underwent sequential programming of the DBS after the surgery. Results The mean age of the 13 patients who underwent DBS of the GPi for dystonia was 46.5 years with a range from 29 to 71 years. Every patient in our case series received various doses of (1.37% to 2.11%) inhaled sevoflurane for anesthesia maintenance. Sevoflurane provided adequate anesthesia and allowed accurate MERs from the GPi. No adverse effects were encountered. On follow-up and sequential DBS programming, patients had significant improvements in dystonia attesting to the accuracy of the electrode placements. Conclusions We report our experience using sevoflurane for maintenance of GA for bilateral GPi DBS for dystonia. The main benefits identified have been adequate anesthesia and reduction of dystonia-related movements to allow the performance of the DBS surgery. The MER signals from the GPi were not suppressed by sevoflurane. This allowed accurate mapping and placement of the DBS implants in the GPi.

Barriers to receipt of novel oral oncolytics: A single-institution quality improvement investigation.

INTRODUCTION: Novel oral oncolytic agents have become the standard of care and first-line therapies for many malignancies. However, issues impacting access to these drugs are not well explored. As part of a quality improvement project in a large tertiary academic institution, we aim to identify potential barriers that delay treatment for patients who are prescribed novel oral oncolytics. METHODS: This was a retrospective review of adults who were newly prescribed a novel oral oncolytic for Food and Drug Administration-approved indications at a single tertiary care center. Patients were identified via electronic prescription data (e-Scribe). Demographics, insurance information, and prescription dates were extracted from the electronic medical record and pharmacy claims data. Statistical analyses were performed to determine whether time-to-receipt was associated with insurance category, pharmacy transfers, cost assistance, and drug prescribed. RESULTS: Of the 270 successfully filled prescriptions, the mean time-to-receipt was 7.3 ± 10.3 days (range: 0-109 days). Patients with Medicare experienced longer time-to-receipt (9.1 ± 13.1 days) compared to patients with commercial insurance (4.4 ± 3.3). Uninsured patients experienced the longest time-to-receipt (15.7 ± 7.8 days) overall. Pharmacy transfers and cost assistance programs were also significantly associated with longer time-to-receipt. Ten prescriptions remained unfilled 90 days after the study period and were considered abandoned. CONCLUSION: Insurance has a significant effect on the time-to-receipt of newly prescribed novel oral oncolytics. Pharmacy transfers and applying for cost assistance are also associated with longer wait times for patients. Our retrospective analysis identifies areas of improvement for future interventions to reduce wait times for patients receiving novel oral oncolytics.

Use of Six-Minute Walk Test to Measure Functional Capacity After Liver Transplantation.

BACKGROUND: Functional impairment is common in people with chronic liver disease (CLD), and improvement is expected following liver transplantation (LT). The Six-Minute Walk Test (6MWT) is an objective measure of functional performance. OBJECTIVE: The aims of this study were: (1) to evaluate the feasibility of 6MWT performance after LT, (2) to compare post-LT 6MWT performance over time between patients with and without CLD, (3) to determine when post-LT 6MWT performance approaches expected values, and (4) to investigate predictors of poor 6MWT performance. METHODS: The 6MWT was performed by 162 consecutive ambulatory participants (50 healthy controls, 62 with CLD, 50 with LT). Sex, age, and body mass index were used to predict expected 6MWT performance. Chi-square testing, analysis of variance, and Pearson coefficients compared percentage of predicted 6-minute walk distance (%6MWD) across groups. Multivariable mixed models assessed predictors of improvement. RESULTS: The participants' mean age was 53.5 years (SD=13.0), 39.5% were female, and 39.1% were nonwhite. At 1-month post-LT, only 52% of all LT recipients met the inclusion criteria for 6MWT performance. Mean %6MWD values for female participants improved from 49.8 (SD=22.2) at 1 month post-LT to 90.6 (SD=12.8) at 1 year post-LT (P<.0001), which did not differ statistically from the CLD group (X̅=95.9, SD=15.6) or the control group (X̅=95.6, SD=18.0) (P=.58). However, at 1-year post-LT, mean %6MWD values for male participants (X̅=80.4, SD=19.5) remained worse than for both the CLD group (X̅=93.3, SD=13.7) and the control group (X̅=91.9, SD=14.3) (P=.03). Six-Minute Walk Test performance was directly correlated with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) physical component score (r=.51, P<.01) and was inversely correlated with nonalcoholic steatohepatitis (r=-.52, P<.01) and diabetes (r=-.48, P<.05). In multivariate analysis adjusted for age and sex, hepatitis C independently predicted 6MWT improvement (estimated ß=69.8, standard error=27.6, P=.01). LIMITATIONS: A significant proportion of patients evaluated for enrollment were excluded due to level of illness early after LT (n=99, 47.4%). Thus, sampling bias occurred in this study toward patients without significant postoperative complications. CONCLUSIONS: The 6MWT is a simple test of physical functioning but may be difficult to apply in LT recipients. The 6MWT performance improved following LT but was lower than expected, suggesting a low level of fitness up to 1 year following LT.