UNASSIGNED: Coronary heart disease (CHD) is a common and frequent disease with a long and incurable course, and the quality of life of patients is severely reduced. This study was to develop and validate a quality of life scale for patients with CHD based on the Chinese context.
UNASSIGNED: The scale QLICD-CHD (V2.0) was developed based on the QLICD-CHD (V1.0), using a programmed decision procedures. Based on the data measuring QoL 3 times before and after treatments from 189 patients with CHD, the psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness employing correlation analysis, multi-trait scaling analysis, structural equation modeling, t-test and also G-study and D-study of generalizability theory analysis. The SF-36 scale was used as the criterion to evaluate the criterion-related validity. Paired t tests were conducted to evaluate the responsiveness on each domain/facet as well as the total of the scale, with Standardized Response Mean (SRM) being calculated.
UNASSIGNED: The QLICD-CHD (V2.0) has been developed with 42 items in 4 domains. The Cronbach\'s α of the general module, the specific module and the total scale were 0.91, 0.92 and 0.91 respectively. The overall score and the test-retest reliability coefficients in all domains are higher than 0.60, except for the specific module. Correlation and factor analysis confirmed good construct validity and criterion-related validity. After treatments, the overall score and score of all domains have statistically significant changes (P<0.01). The SRM of domain-level score ranges from 0.27 to 0.50. Generalizability Theory further confirm the reliability of the scale through more accurate variance component studies.
UNASSIGNED: The QLICD-CHD (V2.0) could be used as a useful instrument in assessing QoL for patients with CHD, with good psychometric properties.

UNASSIGNED: The International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) is a knee-specific patient-reported outcome (PRO) measure that is commonly used to evaluate patients with various knee disorders. The Thai version of the IKDC-SKF (Thai IKDC-SKF) was shown to have good validity and reliability; nonetheless, no data regarding its responsiveness are available.
UNASSIGNED: To evaluate the responsiveness of the Thai IKDC-SKF for assessing patients with anterior cruciate ligament (ACL) injury and determine the minimal clinically important difference (MCID) for this PRO measure.
UNASSIGNED: Cohort study (diagnosis); Level of evidence, 3.
UNASSIGNED: This prospective study included ACL-injured patients who were scheduled for ACL reconstruction (ACLR) at a single institution. The patients completed the Thai IKDC-SKF at the baseline and the 6-month postoperative follow-up. The global rating of change scale was an anchor question that evaluated patients\' overall perception of a clinical change compared with their preoperative condition. The effect size and standardized response mean were calculated. The MCID was identified with an anchor-based approach by plotting a receiver operating characteristic curve and calculating the value that maximized the Youden index.
UNASSIGNED: Of 59 enrolled patients, 53 patients (89.8%) completed the preoperative and 6-month postoperative Thai IKDC-SKF. The mean (±SD) age of the participants was 32.3 ± 10.3 years, and 86.8% were men. The mean Thai IKDC-SKF score improved significantly from preoperatively to the 6-month follow-up (from 56.3 ± 14.9 to 70.8 ± 14.1, respectively; P < .001), with an effect size of 0.975 and a standardized response mean of 0.977. A receiver operating characteristic curve was generated to determine the ability of the Thai IKDC-SKF to distinguish between improved patients and unimproved patients, and the area under the curve was 0.80 (95% CI, 0.68-0.92), which was considered excellent. The MCID was 15.5, which yielded a sensitivity and specificity of 0.55 and 1, respectively.
UNASSIGNED: This study confirmed the responsiveness of the Thai IKDC-SKF for detecting a clinical change in ACL-injured patients after ACLR. The identified MCID of 15.5 can be used to calculate the significant clinical change and sample size in future studies.

Quality of life (QOL) in patients with Chronic obstructive pulmonary disease (COPD) is a major global concern in respiratory care with the specific instruments used rarely being developed using a modular approach. This paper is aimed to develop the COPD scale of the system of QOL Instruments for Chronic Diseases (QLICD-COPD) by the modular approach based on Classical Test Theory and Generalizability Theory (GT). 114 inpatients with COPD were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, and also GT analysis. The Results showed that Multi-trait scaling analysis, correlation and factor analyses confirmed good construct validity and criterion-related validity with almost all correlation coefficients or factor loadings being above 0.40. The internal consistency α and test-retest reliability coefficients (Pearson r and Intra-class correlations ICC) for all domains except for the social domain were larger than 0.70, ranging between 0.70-0.86 with r = 0.85 for the overall. The overall score and scores for physical and the specific domains had statistically significant changes after treatments with moderate effect size SRM (standardized response mean) ranging from 0.32 to 0.44. All G-coefficients and index of dependability were all greater than 0.80 exception of social domain (0.546 and 0.500 respectively), confirming the reliability of the scale further. It concluded that the QLICD-COPD has good validity, reliability, and moderate responsiveness, and can be used as the QOL instrument for patients with COPD.

OBJECTIVE: To compare the responsiveness of the Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) to the 36-Item Short Form Survey Physical Component Score (SF36-PCS) in orthopaedic trauma patients from pre-injury to one year recovery.
METHODS: Prospective cohort study at a Level 1 trauma centre.
METHODS: Patients over the age of 18 with orthopaedic trauma injuries to the pelvis, lower extremity or upper extremity between 2017 and 2018.
METHODS: The PROMIS-PF and SF36-PCS assessments were conducted at baseline, 3 months, 6 months and 12 months. Responsiveness of each measure was assessed between time points by calculating the standardized response mean (SRM), the proportions of patients exceeding minimal clinically important difference (MCID), and the floor and ceiling effects.
RESULTS: Sixty-eight patients with completed assessments at every timepoint were included: mean age 44.7 years, 39 were male and mean Injury Severity Score (ISS) was 7.4 (range: 4-16). Mean time of completion for the SF-36 at all the time points was 5.6 min vs 1.7 min for the PROMIS-PF (p<0.01). The SRM was comparable between measures at all the time points. Although a greater proportion of patients achieved MCID for SF36-PCS between all the time points, this only approached statistical significance between the 6- and 12-month assessments (47.1% vs 33.8%; p = 0.15). There was a significant ceiling effect demonstrated with the PROMIS-PF at baseline and 12-month assessments, with 34 (50.0%) patients and 7 (10.3%) patients achieving the maximum scores at each time point, respectively.
CONCLUSIONS: PROMIS-PF has a more favourable responder burden based on lower time to completion and comparable responsiveness to the SF-36 PCS. However, there are limitations in responsiveness with the PROMIS-PF in patients who are higher functioning as demonstrated by the ceiling effects in patients at baseline pre-injury and at 12 months post-injury timepoints.

Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations in MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form of CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies of CMT2A have described the phenotypic spectrum of the disease, but longitudinal natural history studies are lacking. In this large multicentre prospective cohort study of 196 patients with dominant and autosomal recessive CMT2A, we present an in-depth genotype-phenotype study of the baseline characteristics of patients with CMT2A and longitudinal data (1-2 years) to describe the natural history. A childhood onset of autosomal dominant CMT2A is the most predictive marker of significant disease severity and is independent of the disease duration. When compared to adult onset autosomal dominant CMT2A, it is associated with significantly higher rates of use of ankle-foot orthoses, full-time use of wheelchair, dexterity difficulties and also has significantly higher CMT Examination Score (CMTESv2) and CMT Neuropathy Score (CMTNSv2) at initial assessment. Analysis of longitudinal data using the CMTESv2 and its Rasch-weighted counterpart, CMTESv2-R, show that over 1 year, the CMTESv2 increases significantly in autosomal dominant CMT2A (mean change 0.84 ± 2.42; two-tailed paired t-test P = 0.039). Furthermore, over 2 years both the CMTESv2 (mean change 0.97 ± 1.77; two-tailed paired t-test P = 0.003) and the CMTESv2-R (mean change 1.21 ± 2.52; two-tailed paired t-test P = 0.009) increase significantly with respective standardized response means of 0.55 and 0.48. In the paediatric CMT2A population (autosomal dominant and autosomal recessive CMT2A grouped together), the CMT Pediatric Scale increases significantly both over 1 year (mean change 2.24 ± 3.09; two-tailed paired t-test P = 0.009) and over 2 years (mean change 4.00 ± 3.79; two-tailed paired t-test P = 0.031) with respective standardized response means of 0.72 and 1.06. This cross-sectional and longitudinal study of the largest CMT2A cohort reported to date provides guidance for variant interpretation, informs prognosis and also provides natural history data that will guide clinical trial design.

BACKGROUND: Quality of life (QOL) for patients with Peptic ulcer disease (PUD) is of interest worldwide and disease-specific instruments are needed for clinical research and practice. This paper focus on the development and validation of the PUD scale under the system of quality of life instruments for chronic diseases (QLICD-PU) by the modular approach and both classical test theory and Generalizability Theory.
METHODS: The QLICD-PU is developed based on programmatic decision-making procedures, including multiple nominal and focus group discussions, in-depth interviews, and quantitative statistical procedures. Based on the data of 153 PUD inpatients, correlation analysis, factor analysis, t-test, and Generalizability Theory analysis (including generalizability study and decision study, ie. G-study and D-study) were used to assess the validity, reliability, and responsiveness of the scale.
RESULTS: When the popular scale health survey short form (SF-36) was used as the standard, correlation and factor analysis confirmed good construct validity and criterion-related validity of QLICD-PU. Except for the social domain (0.62), the internal consistency α of all domains is higher than 0.70. The overall score and the test-retest reliability coefficients (Pearson r and intra-class correlation ICC) in all domains are higher than 0.80 (0.77 in the social domain). After treatments, the overall score and scores of all domains have statistically significant changes (P < 0.01), except for social impact and sexual function scores. The SRM (Standardized response mean) of domain-level scores ranges from 0.34 to 1.03. The G coefficient and reliability index (Ф coefficient) further confirm the reliability of the scale through more accurate variance components and decision-making information about changes in the number of items.
CONCLUSIONS: The QLICD-PU can be used as a useful measurement to assess the quality of life of PUD patients with good psychometric characteristics and multiple advantages.

An important challenge in rare disease clinical trials is to demonstrate a clinically meaningful and statistically significant response to treatment. Selecting the most appropriate and sensitive efficacy endpoints for a treatment trial is part art and part science. The types of endpoints should align with the stage of development (e.g., proof of concept vs. confirmation of clinical efficacy). The patient characteristics and disease stage should reflect the treatment goal of improving disease manifestations or preventing disease progression. For rare diseases, regulatory approval requires demonstration of clinical benefit, defined as how a patient, feels, functions, or survives, in at least one adequate and well-controlled pivotal study conducted according to Good Clinical Practice. In some cases, full regulatory approval can occur using a validated surrogate biomarker, while accelerated, or provisional, approval can occur using a biomarker that is likely to predict clinical benefit. Rare disease studies are small by necessity and require the use of endpoints with large effect sizes to demonstrate statistical significance. Understanding the quantitative factors that determine effect size and its impact on powering the study with an adequate sample size is key to the successful choice of endpoints. Interpreting the clinical meaningfulness of an observed change in an efficacy endpoint can be justified by statistical methods, regulatory precedence, and clinical context. Heterogeneous diseases that affect multiple organ systems may be better accommodated by endpoints that assess mean change across multiple endpoints within the same patient rather than mean change in an individual endpoint across all patients.

This research was designed to develop a nasopharyngeal cancer (NPC) scale based on quality of life (QOL) instruments for cancer patients (QLICP-NA). This scale was developed by using a modular approach and was evaluated by classical test and generalizability theories.
Programmed decision procedures and theories on instrument development were applied to create QLICP-NA V2.0. A total of 121 NPC inpatients were assessed using QLICP-NA V2.0 to measure their QOL data from hospital admission until discharge. Scale validity, reliability, and responsiveness were evaluated by correlation, factor, parallel, multi-trait scaling, and t test analyses, as well as by generalizability (G) and decision (D) studies of the generalizability theory.
Results of multi-trait scaling, correlation, factor, and parallel analyses indicated that QLICP-NA V2.0 exhibited good construct validity. The significant difference of QOL between the treated and untreated NPC patients indicated a good clinical validity of the questionnaire. The internal consistency (α) and test-retest reliability coefficients (intra-class correlations) of each domain, as well as the overall scale, were all >0.70. Ceiling effects were not found in all domains and most facets, except for common side effects (24.8 %) in the domain of common symptoms and side effects, tumor early symptoms (27.3 %) and therapeutic side effects (23.2 %) in specific domain, whereas floor effects did not exist in each domain/facet. The overall changes in the physical and social domains were significantly different between pre- and post-treatments with a moderate effective size (standard response mean) ranging from 0.21 to 0.27 (p < 0.05), but these changes were not obvious in the other domains, as well as in the overall scale. Scale reliability was further confirmed by G coefficients and index of dependability, with more exact variance components based on generalizability theory.
QLICP-NA V2.0 exhibited reasonable degrees of validity, reliability, and responsiveness. However, this scale must be further improved before it can be used as a practical instrument to evaluate the QOL of NPC patients in China.

To identify the most sensitive scale for use in clinical trials on multiple system atrophy (MSA), a short and sensitive scale is needed for MSA clinical trials. Potential candidates are the Unified MSA Rating Scale (UMSARS), Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), MSA Health-Related Quality of Life scale (MSA-QoL), and Scales for Outcomes in Parkinson\'s Disease-Autonomic questionnaire (SCOPA-AUT). We enrolled patients with MSA from eight hospitals in Hokkaido, Japan. Board-certified neurologists assessed each patient at 6-month intervals and scored them on the UMSARS, SARA, BBS, MSA-QoL, and SCOPA-AUT. Score changes were evaluated using the standardized response mean (SRM). The correlation between disease duration and each score was examined. The first evaluation was conducted on 85 patients (60 patients with MSA cerebellar ataxia dominant subtype [MSA-C] and 25 patients with MSA Parkinsonism-dominant subtype [MSA-P]). Sixty-nine patients were examined after 6 months and 63 patients after 12 months. The UMSARS Part 4 had the largest SRM after 6 months and the SARA after 12 months. SRMs for MSA-P, the shorter duration group, and the early-onset group were larger than were those for MSA-C, the longer duration group, and the late-onset group. SRMs for items regarding skilled hand activities, walking, and standing were relatively large. Our study indicates that the UMSARS (parts 2 and 4), SARA, and BBS are sensitive scales for evaluating MSA progression over 12 months. Items with large SRMs effectively evaluated short-term changes.

This study aimed to develop and validate the Simplified Chinese Version of the Quality of Life Questionnaire for Hepatocellular Carcinoma (the QLQ-HCC18). It was developed by the strict translation procedure of EORTC guidelines, and the psychometrics were evaluated on a sample of 114 patients. The internal consistency Cronbach\'s α were greater than 0.60 for all domains (exception of Jaundice 0.38), and all test-retest reliability coefficients were greater than 0.80. Four out of eight domains had statistically significant changes with effect size standardized response mean (SRM) ranging from 0.31 to 0.73. The Simplified Chinese version of QLQ-HCC18 demonstrates good validity, reliability, and responsiveness.