Burden of hereditary transthyretin amyloidosis on quality of life

INTRODUCTION: Hereditary transthyretin (hATTR) amyloidosis is a progressive, degenerative disease, with peripheral neuropathy, cardiomyopathy, and other clinical manifestations. In this study we examine the impact of hATTR amyloidosis on quality of life (QOL). METHODS: Neuropathy-specific QOL, measured with the Norfolk QOL-Diabetic Neuropathy questionnaire, was compared between patients with hATTR amyloidosis and patients with type 2 diabetes, whereas generic QOL, measured with the 36-item Short Form Health Survey version 2 (SF-36v2), was compared between patients with hATTR amyloidosis, the general population, and patients with chronic diseases. RESULTS: Neuropathy-specific QOL for patients with hATTR amyloidosis was nearly equivalent to that of patients with type 2 diabetes with diabetic neuropathy accompanied by a history of ulceration, gangrene, or amputation. Generic QOL was worse than that seen in the general population, with physical functioning worse than that for patients with multiple sclerosis and congestive heart failure. DISCUSSION: Patients with hATTR amyloidosis show significant burden on QOL, particularly in physical functioning. Muscle Nerve 60: 169-175, 201

Inotersen preserves or improves quality of life in hereditary transthyretin amyloidosis

Objective: To examine the impact on quality of life (QOL) of patients with hATTR amyloidosis with polyneuropathy treated with inotersen (Tegsedi™) versus placebo. Methods: Data were from the NEURO-TTR trial (ClinicalTrials.gov Identifier: NCT01737398), a phase 3, multinational, randomized, double-blind, placebo-controlled study of inotersen in patients with hATTR amyloidosis with polyneuropathy. At baseline and week 66, QOL measures-the Norfolk-QOL-Diabetic Neuropathy (DN) questionnaire and SF-36v2® Health Survey (SF-36v2)-were assessed. Treatment differences in mean changes in QOL from baseline to week 66 were tested using mixed-effect models with repeated measures. Responder analyses compared the percentages of patients whose QOL meaningfully improved or worsened from baseline to week 66 in inotersen and placebo arms. Descriptive analysis of item responses examined treatment differences in specific activities and functions at week 66. Results: Statistically significant mean differences between treatment arms were observed for three of five Norfolk-QOL-DN domains and five of eight SF-36v2 domains, with better outcomes for inotersen than placebo in physical functioning, activities of daily living, neuropathic symptoms, pain, role limitations due to health problems, and social functioning. A larger percentage of patients in the inotersen arm than the placebo arm showed preservation or improvement in Norfolk-QOL-DN and SF-36v2 scores from baseline to week 66. Responses at week 66 showed more substantial problems with daily activities and functioning for patients in the placebo arm than in the inotersen arm. Conclusion: Patients with hATTR amyloidosis with polyneuropathy treated with inotersen showed preserved or improved QOL at 66 weeks compared to those who received placebo.This research was funded by Akcea Therapeutics and Ionis Pharmaceuticals, Incinfo:eu-repo/semantics/publishedVersio

Problem Representation in Experts and Novices: Part 2. Underlying Processing Mechanisms

It has been well established that experts and novices focus on different aspects of problems, with novices focusing more on surface features rather than on deep principled features of a problem. What is less clear are the mechanisms that underlie these differences in construal of problem representation. The current study, which uses an `old/new' recognition procedure, examines expert and novice representation of arithmetic equations in which the deep relational properties (i.e., principles of commutativity and associativity) were well known to both groups. Results indicate that both novices and experts encode both surface and principled features in the same serial manner, with surface features preceding principled features for both. At the same time, only for novices and not for experts, surface features compete with deep features, thus requiring additional resources to inhibit this attentional competition

Problem Representation in Experts and Novices: Part 1. Differences in the Content Of Representation

Two experiments examined the content of novice and expert representations for both surface and deep structural elements of arithmetic equations. Experiment 1, which used a forcedchoice categorization task in which surface features of equations (e.g., digits) competed with deep structural principles of mathematics (associativity and commutativity), found that experts were more likely to focus on principles in their judgments than were novices, who focused more often on surface elements. Experiment 2, using a similar task, introduced trials in which only principled elements varied. Novices were able to focus on principled elements in this case, but failed to transfer these representations when surface features were reintroduced