Additional file 1 of The health-related quality of life, mental health and mental illnesses of patients with inclusion body myositis (IBM): results of a mixed methods systematic review

Additional file 1. Search strategy.pdf. Detailed search terms of the systematic search

Additional file 2 of The health-related quality of life, mental health and mental illnesses of patients with inclusion body myositis (IBM): results of a mixed methods systematic review

Additional file 2. Qualitative evidence profiles.xlsx. Summaries of review findings and ratings of the qualitative studies according to GRADE CERQual

Additional file 3 of The health-related quality of life, mental health and mental illnesses of patients with inclusion body myositis (IBM): results of a mixed methods systematic review

Additional file 3. Overview PROMs for HRQoL assessment IBM.pdf. Overview of applied PROMs for HRQoL assessment in the included quantitative studies

Assessment of face validity of a disease model of nonsense mutation Duchenne muscular dystrophy: a multi-national Delphi panel study

The objective of this study was to assess the face validity of a disease model evaluating the cost-effectiveness of ataluren for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD). This was a Delphi panel study comprising of physicians with first-hand experience of ataluren for the treatment of nmDMD. Consensus was sought for previously unvalidated model data, including patient health status and quality of life measured using the Health Utility Index (HUI), mortality, informal caregiving, and the expected benefit of early ataluren treatment across four states: (1) ambulatory, (2) non-ambulatory, not yet requiring ventilation support, (3) non-ambulatory, night-time ventilation support, and (4) non-ambulatory, full-time ventilation support. Nine experts from five countries participated in the Delphi panel. Consensus was obtained for all questions after three panel rounds (except for two HUI-questions concerning hand function [dexterity]). Consensus HUI-derived utilities for state (1) were 1.0000 for ataluren on top of best supportive care (BSC) and 0.7337 for BSC alone. Corresponding estimates for state (2) were 0.3179 and 0.2672, for state (3) 0.1643 and 0.0913, and for state (4) −0.0732 and −0.1163. Consensus mortality rates for states (1), (2), and (3) were 4%, 13%, and 33%, and life expectancy in state (4) was agreed to be 3 years. Panelists further agreed that two informal caregivers typically provide day-to-day care/support to patients with nmDMD, and that starting treatment with ataluren at 2 versus 5 years of age would be expected to delay loss of ambulation by an additional 2 years, and initiation of night-time and full-time ventilation support by an additional 3 years, respectively. The main limitation concerns the size of the Delphi panel, govern primarily by the rarity of the disease. This study confirms the face validity of key clinical parameters and assumptions underlying the ataluren cost-effectiveness model.</p

Additional file 1 of Areas of improvement in the medical care of SMA: evidence from a nationwide patient registry in Germany

Additional file 1: Questionnaire, English version. Questionnaire, original German version

Table1_Misfolding of fukutin-related protein (FKRP) variants in congenital and limb girdle muscular dystrophies.DOCX

Fukutin-related protein (FKRP, MIM ID 606596) variants cause a range of muscular dystrophies associated with hypo-glycosylation of the matrix receptor, α-dystroglycan. These disorders are almost exclusively caused by homozygous or compound heterozygous missense variants in the FKRP gene that encodes a ribitol phosphotransferase. To understand how seemingly diverse FKRP missense mutations may contribute to disease, we examined the synthesis, intracellular dynamics, and structural consequences of a panel of missense mutations that encompass the disease spectrum. Under non-reducing electrophoresis conditions, wild type FKRP appears to be monomeric whereas disease-causing FKRP mutants migrate as high molecular weight, disulfide-bonded aggregates. These results were recapitulated using cysteine-scanning mutagenesis suggesting that abnormal disulfide bonding may perturb FKRP folding. Using fluorescence recovery after photobleaching, we found that the intracellular mobility of most FKRP mutants in ATP-depleted cells is dramatically reduced but can, in most cases, be rescued with reducing agents. Mass spectrometry showed that wild type and mutant FKRP differentially associate with several endoplasmic reticulum (ER)-resident chaperones. Finally, structural modelling revealed that disease-associated FKRP missense variants affected the local environment of the protein in small but significant ways. These data demonstrate that protein misfolding contributes to the molecular pathophysiology of FKRP-deficient muscular dystrophies and suggest that molecules that rescue this folding defect could be used to treat these disorders.</p

Additional file 3 of A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot–Marie–Tooth type 1A

Additional file 3. Full eligibility criteria

Additional file 1 of A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot–Marie–Tooth type 1A

Additional file 1. Demographic bias analysis

Additional file 2 of A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot–Marie–Tooth type 1A

Additional file 2. Exploratory efficacy endpoints (change from baseline to end of treatment)

Additional file 4 of A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot–Marie–Tooth type 1A

Additional file 4. Sensibility analysis: impact of age and sex on treatment effect