Validation of the Italian version of the Charcot‐Marie‐Tooth Health Index

The Charcot‐Marie‐Tooth Health Index (CMT‐HI) is a disease‐specific patient‐reported outcome measure measuring overall disease burden in Charcot‐Marie‐Tooth (CMT) patients, designed for natural history studies and clinical trials in English‐speaking affected individuals. We developed and validated its Italian Charcot‐Marie‐Tooth Health Index (I‐CMT‐HI) version. The questionnaire was translated and culturally adapted from source into Italian by two neurologists experienced in CMT and neuromuscular disorders (NMDs). The two translations were reviewed by a panel of seven experts in CMT and NMD. The provisional version was back‐translated into English by a professional translator. The definitive Italian version was developed during a consensus teleconference by the panel and a patient representative from ACMT‐Rete. A series of clinically and genetically characterized CMT patients completed the final questionnaire; 11 participated in a test‐retest reliability assessment of the instrument. The I‐CMT‐HI was administered to 30 CMT patients (13 CMT1A, eight CMTX1, two CMT1B, two CMT1E, two CMT2I, one CMT2A, one CMT2N, one distal Hereditary Motor Neuropathy), with test‐rest in 11:14 females and 16 males, aged (mean ± SD) 48.0 ± 16.4 years (range 18‐81), with CMT Examination Score (CMTES) = 10.0 ± 4.4 (range 2‐18). The I‐CMT‐HI mean total score was 29.4 ± 21.2 (range 0.1‐60.3). The I‐CMT‐HI showed a high test‐retest reliability: intraclass correlation coefficient = 0.95 (95% confidence interval, 0.84‐0.99). No patient had difficulty in completing the questionnaire and none reported any problem with the questions' formulation. The total CMT‐HI score was positively correlated with age and CMTES, with higher disease burden with increasing age and disease severity according to the CMTES. The I‐CMT‐HI is now ready for use in clinical studies in the Italian population.     

Transitioning outcome measures: relationship between the CMTPedS and CMTNSv2 in children,adolescents, and young adults with Charcot‐Marie‐Tooth disease

Long‐term studies of Charcot‐Marie‐Tooth (CMT) disease across the entire lifespan require stable endpoints that measure the same underlying construct (e.g., disability). The aim of this study was to assess the relationship between the CMT Pediatric Scale (CMTPedS) and the adult CMT Neuropathy Score (CMTNSv2) in 203 children, adolescents, and young adults with CMT. There was a moderate curvilinear correlation between the CMTPedS and the CMTNSv2 (Spearman's rho ρ = 0.716, p < 0.0001), although there appears to be a floor effect of the CMTNSv2 in patients with a milder CMT phenotype. Univariate analyses indicate that the relationship between the CMTPedS and CMTNSv2 scores improves with worsening disease severity and advancing age. Although one universal scale throughout life would be ideal, our data supports the transition from the CMTPedS in childhood to the CMTNSv2 in adulthood as a continuum of measuring lifelong disability in patients with CMT.     

Reliability of the Charcot‐Marie‐Tooth functional outcome measure

The CMT‐FOM is a 13‐item clinical outcome assessment (COA) that measures physical ability in adults with Charcot‐Marie‐Tooth disease (CMT). Test‐retest reliability, internal consistency and convergent validity have been established for the CMT‐FOM. This current study sought to establish inter‐rater reliability. Following an in‐person training of six international clinical evaluators we recruited 10 participants with genetically diagnosed CMT1A, (aged 18‐74 years, 6 female). Participants were evaluated using the CMT‐FOM over 2 days. Participants were given at least a 3 hour rest between evaluations, and were assessed twice each day. Following the provision of training by master trainers, all 13 items of the CMT‐FOM exhibited excellent inter‐rater reliability for raw scores (ICC_1,1 0.825‐0.989) and z‐scores (ICC_1,1 0.762‐0.969). Reliability of the CMT‐FOM total score was excellent (ICC_1,1 0.983, 95% CI 0.958‐0.995). The CMT‐FOM is a reliable COA used by clinical evaluators internationally. The next steps are to establish further validation through psychometric evaluation of the CMT‐FOM in the Accelerate Clinical Trials in CMT (ACT‐CMT) study.     

Validation of the parent-proxy pediatric Charcot-Marie-Tooth disease quality of life outcome measure

Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL) in children. We have previously developed and validated the English and Italian versions of the pediatric CMT-specific QOL outcome measure (pCMT-QOL) for children aged 8 to 18. There is currently no parent-proxy CMT QOL outcome measure for use in clinical trials, which could provide complementary information in these children and adolescents. This study describes the validation studies conducted to develop the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old. Development and validation of the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old was iterative, involving identifying relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus-group interviews, and psychometric testing, conducted on parents of children with CMT seen at participating sites from the USA, United Kingdom, and Australia. We utilized previously described methods to develop a working parent-proxy version of the pCMT-QOL measure. From 2010 to 2016, the parent-proxy pCMT-QOL working version was administered to 358 parents of children with CMT aged 8 to 18, seen at the participating study sites of the Inherited Neuropathies Consortium. The resulting data underwent rigorous psychometric analysis, including factor analysis, test-retest reliability, internal consistency, convergent validity, IRT analysis, and longitudinal analysis, to develop the final parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old. The parent-proxy version of the pCMT-QOL outcome measure is a reliable, valid, and sensitive proxy measure of health-related QOL for children aged 8 to 18 with CMT.     

Functional outcome measures for infantile Charcot‐Marie‐Tooth disease: a systematic review

A functional outcome measure for infants (aged 0–3 years) with Charcot‐Marie‐Tooth (CMT) disease is needed for upcoming disease‐modifying trials. A systematic review of outcome measures for infants with neuromuscular disorders was completed to determine if validated measures were available for the CMT infant population. We assessed 20,375 papers and identified seven functional outcome measures for infants with neuromuscular disorders. Six were developed and validated for spinal muscular atrophy (SMA). There were no CMT‐specific outcome measures identified; however, one (motor function measure) assessed a range of neuromuscular disorders including 13 infants and children with CMT. The included studies exhibited “good” face, discriminant, convergent and concurrent validity, and reported excellent intra‐ and inter‐rater reliability. No outcome measure was subjected to item response theory. Studies reported outcome measures comprising of 51 different items assessing six domains of function: reflexive movement, axial movement, limb movement, positioning, gross motor, and fine‐motor skills. Scoring of items ranged from 2‐ to 7‐point rating scales; and none were scaled to normative reference values to account for changes in growth and development. The SMA focus of most items is likely to produce ceiling effects and lack sensitivity and responsiveness for within and between types of CMT in infants. Nevertheless, several items across scales assessing distal strength, gross‐ and fine‐motor function, could be included in the development of a composite functional outcome measure for infants with CMT to assess disease‐modifying interventions.     

Translation and validation of the 15‐item Myasthenia Gravis Quality of life scale in Dutch

Introduction: The 15‐item Myasthenia Gravis Quality of Life (MG‐QOL15) scale has been developed to assess the health‐related quality of life of patients with myasthenia gravis (MG). The aim of this study was to translate the original English version into Dutch and to test the test–retest reliability and construct validity. Methods: Fifty patients with MG were included. Test–retest reliability and internal consistency were assessed using the intraclass correlation coefficient (ICC) and the Cronbach α. Construct validity was assessed by testing 5 predefined hypotheses. Results: A good test–retest reliability was confirmed with an ICC of 0.866. The Cronbach α was 0.93. The predefined hypotheses were confirmed in 80% of cases, which points to good construct validity. Discussion: The Dutch MG‐QOL15 has good test–retest reliability and good construct validity. It can be used for research in a Dutch‐speaking population. It is also suitable for monitoring individual patients in clinical practice. Muscle Nerve 57 : 206–211, 2018     

Psychometrics evaluation of Charcot‐Marie‐Tooth Neuropathy Score (CMTNSv2) second version,using Rasch analysis

Charcot‐Marie‐Tooth Neuropathy Score second version (CMTNSv2) is a validated clinical outcome measure developed for use in clinical trials to monitor disease impairment and progression in affected CMT patients. Currently, all items of CMTNSv2 have identical contribution to the total score. We used Rasch analysis to further explore psychometric properties of CMTNSv2, and in particular, category response functioning, and their weight on the overall disease progression. Weighted category responses represent a more accurate estimate of actual values measuring disease severity and therefore could potentially be used in improving the current version. Copyright © 2014 John Wiley & Sons, Ltd.     

Stigma and discrimination toward mental illness: translation and validation of the Italian version of the attribution questionnaire-27 (AQ-27-I)

Purpose

The aim of this study was to translate the Attribution Questionnaire-27 (AQ-27) to the Italian language (AQ-27-I), and to examine the reliability and validity of this new Italian version.

Methods

The questionnaire was translated using the standard translation/back-translation method. Cronbach’s alpha and intraclass coefficients were used to estimate instrument reliability. Confirmatory factor analysis was conducted to corroborate the original English version factor structure in the new measure, and to establish validity. Path analyses were meant to validate relationships found in the English version among Italian-speaking participants.

Results

The AQ-27-I demonstrated acceptable internal consistency, with a Cronbach’s alpha of 0.82 for the total scale and ranging between 0.52 and 0.91 for the subscales. The test–retest reliability was also satisfactory, with intraclass correlation coefficients of 0.72 for the total scale and ranging between 0.51 and 0.89 for the subscales. Fit indices of the model supported the factor structure and paths.

Conclusions

The AQ-27-I is a reliable measure to assess stigmatizing attitudes in Italian.     

Validation of Serbian version of the disease‐specific myasthenia gravis questionnaire

Basta I, Pekmezovi? T, Padua L, Stojanovi? V, Stevi? Z, Nikoli? A, Peri? S, Lavrni? D. Validation of Serbian version of the disease‐specific myasthenia gravis questionnaire.
Acta Neurol Scand: 2010: 122: 110–114.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Aim – The aim of this study was to validate translated and cross‐cultural adapted Italian version of myasthenia gravis‐specific questionnaire (MGQ) in Serbian MG patients. Materials and Methods – The questionnaire was validated in 140 consecutive MG patients from Belgrade. In each patient association between the total MGQ score and form and severity of the disease was determined. Also, correlation between regional domain scores of MGQ and main clinical findings according to Besinger’s clinical score was analyzed. Results – Patients’ participation in the assessment was satisfactory with excellent internal consistency and reproducibility. Total MGQ score, as well as domain scores, correlated with highly significant inverse relationship with the disease severity and clinical status of patients at the moment of completing the questionnaire. Furthermore, the bulbar domain of the questionnaire appeared more specific and sensitive than clinical history and examination. Conclusion – We concluded that the Serbian version of the MGQ may be useful as a measure of clinical outcome in patients with MG.     

Assisted 6‐minute cycling test: An exploratory study in children

Introduction: The 6‐minute walk test (6MWT) is frequently used as an outcome measure for clinical trials in neuromuscular disease. Because this submaximal endurance test is not feasible for nonambulatory patients, the motor‐assisted 6‐minute cycling test (A6MCT) was developed. Methods: Nineteen children with neuromuscular disorders and children with OXPHOS‐dysfunction performed the a6MCT and the 6MWT to explore feasibility and construct validity. Test–retest reproducibility was evaluated within 3 weeks. Results: The assisted 6‐minute cycling test was feasible in 90% and 78% of the patients with a neuromuscular disorder and OXPHOS‐dysfunction, respectively. The A6MCT for legs correlated with the 6MWT in both patient groups. The assisted 6‐minute cycling showed good reproducibility for both legs and arms. Conclusions: This exploratory study indicates that the assisted 6‐minute cycling test is a promising outcome measure for patients with a neuromuscular disorder and patients with OXPHOS‐dysfunction. Muscle Nerve, 2015. Muscle Nerve 54 : 232–238, 2016     

Myotonic Dystrophy Health Index: Initial evaluation of a disease‐specific outcome measure

Introduction: In preparation for clinical trials we examine the validity, reliability, and patient understanding of the Myotonic Dystrophy Health Index (MDHI). Methods: Initially we partnered with 278 myotonic dystrophy type‐1 (DM1) patients and identified the most relevant questions for the MDHI. Next, we used factor analysis, patient interviews, and test–retest reliability assessments to refine and evaluate the instrument. Lastly, we determined the capability of the MDHI to differentiate between known groups of DM1 participants. Results: Questions in the final MDHI represent 17 areas of DM1 health. The internal consistency was acceptable in all subscales. The MDHI had a high test–retest reliability (ICC = 0.95) and differentiated between DM1 patient groups with different disease severities. Conclusions: Initial evaluation of the MDHI provides evidence that it is valid and reliable as an outcome measure for assessing patient‐reported health. These results suggest that important aspects of DM1 health may be measured effectively using the MDHI. Muscle Nerve 49 : 906–914, 2014     

The Val30Met familial amyloid polyneuropathy specific Rasch‐built overall disability scale (FAP‐RODS©)

Familial amyloid polyneuropathy (FAP) is a chronic debilitating multi‐organic disorder, mainly assessed using ordinal‐based impairment measures. To date, no outcome measure at the activity and participation level has been constructed in FAP. The current study aimed to design an interval activity/participation scale for FAP through Rasch methodology. A preliminary FAP Rasch‐built overall disability scale (pre‐FAP‐RODS) containing 146 activity/participation items was assessed twice (interval: 2–4 week; test‐retest reliability) in 248 patients with Val30Met FAP examined in Porto, Portugal, of which 65.7% have received liver transplantation. An ordinal‐based 24‐item FAP‐symptoms inventory questionnaire (FAP‐SIQ) was also assessed (validity purposes). The pre‐FAP‐RODS and FAP‐SIQ data were subjected to Rasch analyses. The pre‐FAP‐RODS did not meet model's expectations. On the basis of requirements such as misfit statistics, differential item functioning, and local dependency, items were systematically removed until a final 34‐item FAP‐RODS^© was constructed fulfilling all Rasch requirements. Acceptable reliability/validity scores were demonstrated. In conclusion, the 34‐item FAP‐RODS^© is a disease‐specific interval measure suitable for detecting activity and participation restrictions in patients with FAP. The use of the FAP‐RODS^© is recommended for future international clinical trials in patients with Val30Met FAP determining its responsiveness and its cross‐cultural validation. Its expansion to other forms of FAP should also be focus of future clinical studies.     

Italian validation of INQoL,a quality of life questionnaire for adults with muscle diseases

Background and purpose: A quality of life (QoL) questionnaire for neuromuscular diseases was recently constructed and validated in the United Kingdom in a sample of adult patients with a variety of muscle disorders. Preliminary results suggested it could be a more relevant and practical measure of QoL in muscle diseases than generic health measures of QoL. The purpose of our work was: (i) To validate INQoL in Italy on a larger sample of adult patients with muscle diseases (ii) to compare INQoL to SF‐36. Methods: We have translated into Italian and applied language adaptations to the original UK INQoL version. We studied 1092 patients with different muscle disorders and performed (i) test–retest reliability (n = 80); (ii) psychometric (n = 345), known‐group (n = 1092), external criterion (n = 70), and concurrent validity with SF‐36 (n = 183). Results: We have translated and formally validated the Italian version of INQoL confirming and extending results obtained in the United Kingdom. In addition to good results in terms of reliability, known‐group and criterion validity, a comparison with the SF‐36 scales showed a stronger association between INQoL total index and SF‐36 physical (r = ?0.72) than mental (r = ?0.38) summary health indexes. When considering comparable domains of INQoL and SF‐36 with respect to an objective measure of muscle strength assessment (MMRC), regression analysis showed a stronger correlation using INQoL rather than SF‐36 scores. Conclusions: INQoL is recommended to assess QoL in muscle diseases because of its ability to capture physical limitations that are specifically relevant to the muscle condition.     

Determination of the longitudinal validity and minimally important difference of the 8‐item Parkinson's Disease Questionnaire (PDQ‐8)

The aim of our study was to assess the longitudinal validity of the 8‐item Parkinson's Disease Questionnaire (PDQ‐8) in terms of responsiveness and test–retest reliability and to determine the minimally important difference (MID) for PDQ‐8 using the anchor‐based approach in Asians with Parkinson's disease (PD). A consecutive sample of PD patients attending a tertiary neuroscience clinic in Singapore completed the English or Chinese version of PDQ‐8 twice during two different clinic visits. During the second visit, patients were also asked to rate their changes in health in general, PD severity, and overall impact of PD since at the time of their first visit 1 year ago using a 5‐point response scale. A total of 96 patients participated in the study. For patients who reported changed conditions in the second visit, responsiveness measured by Cohen's effect size, standardized response mean, and Guyatt's responsiveness index ranged from 0.21 to 0.68. The intraclass correlation coefficient values calculated using patients reporting no change in health or PD status ranged from 0.64 to 0.76. The mean changed PDQ‐8 summary index score in patients who reported that their health or PD status worsened only “a little bit” ranged from 5.8 to 7.4 points. Our current results show that PDQ‐8 is a longitudinally reliable and responsive measure for assessing the health‐related quality of life in patients with PD. The MID of the PDQ‐8 estimated in the study will further support the use of this instrument in both clinical research and practice. © 2008 Movement Disorder Society     

Innovative quantitative testing of hand function in Charcot‐Marie‐Tooth neuropathy

To describe a new test to quantitatively evaluate hand function in patients affected by Charcot‐Marie‐Tooth neuropathy (CMT). The sensor‐engineered glove test (SEGT) was applied to CMT patients (N: 26) and compared with a cohort of healthy controls (HC, N: 26). CMT patients were further divided into subjects with clinically normal (group 1) or impaired hand (group 2) function. The SEGT parameters evaluated were touch duration, inter‐tapping interval, and movement rate parameters of two different sequences: finger tapping (FT) and index‐medium‐ring‐little (IMRL) performed at self‐paced mode (SPM) and maximum velocity (MV). Hand function and strength were assessed by the 9‐hole peg test (9HPT) and dynamometry. Disability of patients was measured by the CMT neuropathy score. CMT patients had significantly worst performances at SEGT than controls regarding the rate of execution of both FT (at MV) and IMRL sequences (at SPM and MV). The rate parameter at MV in IMRL sequence showed a significant trend of decreasing in its average between HC (n: 26, rate = 3.08 ± 0.52 Hz), group 1 (n: 9, rate = 2.64 ± 0.66 Hz) and group 2 (n: 17, rate = 2.19 ± 0.45 Hz) (p for trend <0.001). No correlations were found with either 9HPT, dynamometry, electrophysiology, and the CMT neuropathy score. The SEGT test is sensitive to show hand dysfunction in CMT patients, with and without clinically impaired hands.     

Construction and validation of the chronic acquired polyneuropathy patient‐reported index (CAP‐PRI): A disease‐specific,health‐related quality‐of‐life instrument

Introduction: Generic health‐related quality‐of‐life (HRQOL) patient‐reported outcome measures have been used in patients with chronic immune‐mediated polyneuropathies. We have created a disease‐specific HRQOL instrument. Methods: The chronic acquired polyneuropathy patient‐reported index (CAP‐PRI) was developed and validated in multiple steps. Items were initially generated through patient and specialist input. The performance of the preliminary 20 items was analyzed via a prospective, 5‐center study involving chronic immune‐mediated polyneuropathy patients. Results: Data analysis suggested modification to a 15‐item scale with 3 response categories rather than 5. The final CAP‐PRI was validated in another prospective, 5‐center study. The CAP‐PRI appeared to be a unidimensional outcome measure that fit the Rasch model in our multicenter cohort. It correlated appropriately with outcome measures commonly used in this patient population. Conclusions: The CAP‐PRI is a simple disease‐specific HRQOL measure that appears to be useful for clinical care and possibly also for clinical trials. Muscle Nerve 54 : 9–17, 2016     

The Reliability and Validity of Kiddie‐Schedule for Affective Disorders and Schizophrenia ‐ Present and Life‐time Version ‐ Persian Version

Background: The validity and reliability of a Persian version of the Kiddie Schedule for Affective Disorders and Schizophrenia‐Present and Lifetime Version (K‐SADS‐PL‐P) was evaluated. Method: The K‐SADS‐PL‐P was administered to 102 inpatients (mean age = 15.3 yrs, SD = 1.81) in a child and adolescent psychiatric ward. The psychometric properties were evaluated in comparison to the results of clinical diagnosis. Results: The K‐SADS‐PL‐P showed good‐to‐excellent concurrent validity in diagnosing current major disorders. Test‐retest reliabilities of most of the current diagnoses were also good to excellent. Conclusion: The Persian version of the K‐SADS‐PL provides reliable and valid youth psychiatric diagnoses.     

Adherence to anti-Parkinson drug therapy in the “REASON” sample of Italian patients with Parkinson’s disease: the linguistic validation of the Italian version of the “Morisky Medical Adherence scale-8 items”

Information about patients’ adherence to therapy represents a primary issue in Parkinson’s disease (PD) management. To perform the linguistic validation of the Italian version of the self-rated 8-Item Morisky Medical Adherence Scale (MMAS-8) and to describe in a sample of Italian patients affected by PD the adherence to anti-Parkinson drug therapy and the association between adherence and some socio-demographic and clinical features. MMAS-8 was translated into Italian language by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators and then by two comprehension tests. The translated version of the MMAS-8 scale was then administered at the baseline visit of the “REASON” study (Italian Study on the Therapy Management in Parkinson’s disease: Motor, Non-Motor, Adherence and Quality Of Life Factors) in a large sample of PD patients. The final version of the MMAS-8 was easily understood. Mean ± SD MMAS-8 score was 6.1 ± 1.2. There were no differences in adherence to therapy in relationship to disease severity, gender, educational level or decision to change therapy. The Italian version of MMAS-8, the key tool of the REASON study to assess the adherence to therapy, has shown to be understandable to patients with PD. Patients enrolled in the REASON study showed medium therapy adherence.     

Facioscapulohumeral muscular dystrophy functional composite outcome measure

Introduction: We developed an evaluator‐administered functional facioscapulohumeral muscular dystrophy composite outcome measure (FSHD‐COM) comprising patient‐identified areas of functional burden for future clinical trials. Methods: We performed a prospective observational study of 41 patients with FSHD at 2 sites. The FSHD‐COM includes functional assessment of the legs, shoulders and arms, trunk, hands, and balance/mobility. We determined the test‐retest reliability and convergent validity compared to established FSHD disease metrics. Results: The FSHD‐COM demonstrated excellent test‐retest reliability (intraclass correlation coefficient [ICC] 0.96; subscale ICC range, 0.90–0.94). Cross‐sectional associations between the FSHD‐COM and disease duration, clinical severity, and strength were moderate to strong (Pearson correlation coefficient range |0.51–0.92|). Discussion: The FSHD‐COM is a disease‐relevant, functional composite outcome measure suitable for future FSHD clinical trials that shows excellent test‐retest reliability and cross‐sectional associations to disease measures. Future directions include determining multisite reliability, sensitivity to change, and the minimal clinically important change in the FSHD‐COM. Muscle Nerve 58 : 72–78, 2018     

Outcome measures for Charcot-Marie-Tooth disease: clinical and neurofunctional assessment in children

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, presenting with symptoms often occurring since childhood, and showing a progressive course. At present, there are no valid and reliable measures for evaluation of impairment and disability in the pediatric population. The aim of this study was to determine the usefulness of outcome measures, commonly used in adult patients, in CMT children. We report the results of a comprehensive evaluation of 21 children affected with CMT type 1A, including clinical examinations, measure of hand and foot muscle strength with a hand-held dynamometer, and the following scales: CMT Neuropathy Score or its clinical component CMT Examination Score, Overall Neuropathy Limitations Scale (ONLS), Walk-12 questionnaire, and nine-hole peg test (9-HPT). Hand grip, three-point pinch, and foot dorsiflexion strength were significantly lower than age/sex equivalent in almost all cases. 9-HPT was significantly abnormal in 62% of patients and CMT Examination Score was <10 points in all cases. ONLS showed presence of minor disability in the upper limbs in 57% and mild abnormalities of gait in 71% of patients. Overall, these scales demonstrated limited potential to measure disability and severity of the disease confirming that it is necessary to identify specific scales for children with CMT.