Psychometric evaluation of the Dysphagia Symptom Questionnaire for adults and adolescents with eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus leading to symptoms of esophageal dysfunction; dysphagia is the most common symptom experienced by adults and adolescents. Objective: We sought to perform a psychometric evaluation of the Dysphagia Symptom Questionnaire (DSQ), a patient-reported outcome measure for patients with EoE. Methods: Using baseline and week 24 data from the randomized, interventional, multinational phase 3 R668-EE-1774 trial (NCT03633617), the measurement properties of the DSQ-including reliability, construct and known-groups validity, responsiveness, and interpretation of change-were evaluated. Results: The analysis population comprised 239 patients with EoE (age [mean ± SD], 28.1 ± 13.14 years; 63.6% male; 90.4% White). Intraclass correlation coefficients of 0.92 and 0.97 exceeded the acceptable reliability threshold (≥0.70). Construct validity correlations with EoE symptom and impact measures were moderate at baseline (|r| = 0.44-0.55) and week 24 (|r| = 0.55-0.69), and the DSQ biweekly total score discriminated among groups defined by disease severity. Analyses exploring interpretation of change from baseline on the DSQ biweekly total score indicated thresholds for within-patient improvement ranging from 9 to 23 points; a within-patient improvement from baseline of 13 points or greater could be considered clinically meaningful. Conclusions: This analysis confirmed that the DSQ has acceptable distributional properties, test-retest reliability, construct validity, and ability to detect change. Therefore, the DSQ is a valid and reliable measure to assess the patient-reported symptom of dysphagia among adult and adolescent patients with EoE in the context of a clinical trial setting.

Validation of NASH-CHECK: a novel patient-reported outcome measure for nonalcoholic steatohepatitis.

BACKGROUND: Standardized measures for evaluating patients' experiences with nonalcoholic steatohepatitis (NASH) and their perceived changes with treatment in clinical trials have been limited. To meet this need, a patient-reported outcome (PRO) measure, NASH-CHECK, was developed to evaluate symptoms and health-related quality of life for patients with NASH. The objective of this study was to conduct a quantitative evaluation of the psychometric properties of NASH-CHECK. METHODS: The study used data from a phase 2, randomized controlled trial of adult patients with NASH (NCT02855164). Analyses were conducted to determine the optimal scoring of NASH-CHECK and to evaluate reliability, construct validity, and ability to detect change in NASH-CHECK scale scores. RESULTS: Data were available for 253 patients with NASH (61% female; mean [standard deviation] age = 53 [12] years). Following initial item-level analyses, including correlations and exploratory factor analysis, three items were removed from the measure. Confirmatory factor analysis supported the formation of four multi-item scales (Cognitive Symptoms, Activity Limitations, Social Impact, and Emotional Impact) and five single-item scales (Abdominal Pain, Abdominal Bloating, Fatigue, Sleep, and Itchy Skin). Psychometric analyses of the final NASH-CHECK scales provided support for their internal reliability, test-retest reliability, construct validity, and ability to detect change. CONCLUSION: The results support NASH-CHECK as a reliable, valid, and responsive measure to assess patients' perspectives of symptoms and the health-related quality of life impact of NASH in clinical trials and in routine practice.

Content Validation of Patient-Reported Sleep Measures and Development of a Conceptual Model of Sleep Disturbance in Patients with Moderate-to-Severe, Uncontrolled Asthma.

Purpose: Sleep disturbance is common in patients with asthma and can lead to subsequent impacts on health-related quality of life (HRQOL). Fit-for-purpose patient-reported outcome measures (PROMs) assessing asthma-related sleep disturbance and next-day HRQOL impact (next-day impact) are needed to evaluate disease burden and treatment effects. Patients and Methods: Adults (18-65 years) from three US clinics were recruited for semistructured interviews. Concept elicitation (CE) identified how asthma affects participants' sleep and how asthma-related sleep disturbances impact their daily lives, which informed conceptual model development. Cognitive debriefing (CD) of the Asthma Sleep Disturbance Questionnaire (ASDQ), Sleep Diary, and Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment Short Form 8a (PROMIS SRI SF8a) was completed to assess each measure's content validity. Results: Twelve individuals participated in two interview rounds (6 individuals per round). Participants most frequently reported asthma-related nighttime awakening and decreased sleep quality and duration. Negative impacts of a poor night's sleep due to asthma symptoms included feeling tired/fatigue/lack of energy and subsequent negative impacts on physical functioning, emotions and mood, mental functioning, work or volunteerism, and social functioning. Across both rounds of CD interviews, participants generally found the Sleep Diary and PROMIS SRI SF8a items relevant and easy to complete with no modifications. The ASDQ was modified for clarity and consistency. Conclusion: As described in the conceptual model, asthma affects multiple aspects of sleep that can cause next-day fatigue and other subsequent negative HRQOL impacts. This study demonstrates that the ASDQ, Sleep Diary, and PROMIS SRI SF8a items are comprehensive, relevant, and appropriate for patients with moderate-to-severe, uncontrolled asthma. Evaluation of psychometric properties for the ASDQ, Sleep Diary, and PROMIS SRI SF8a based on clinical trial data in patients with moderate-to-severe, uncontrolled asthma will further support their use.

Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis.

INTRODUCTION: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6-11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. METHODS: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6-11 years with severe AD. These included test-retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. RESULTS: The Worst Itch Scale consisted of two items asking about 'worst itching' experienced 'last night' and 'today'. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. CONCLUSIONS: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6-11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3-4-point change in the Worst Itch Scale score. TRIAL REGISTRATION: NCT03345914. Video: How can we reliably assess itch intensity in children 6-11 years with severe atopic dermatitis in clinical trial settings?

Development and content validation of a self-completed, electronic Pediatric Asthma Symptom Diary.

BACKGROUND: Childhood asthma is an important unmet need. To date, patient-reported outcome measures (PROMs) for children with asthma have used a combination of caregiver or proxy-reported and self-reported measures. No comprehensive measure is available to assess the severity and impact of daytime and nighttime asthma symptoms and rescue medication use for self-completion by children aged 6-11 years. This study aimed to develop a novel, interactive, electronic Pediatric Asthma Symptom Diary (ePASD) measuring self-reported key symptom severity and proximal impacts of asthma in young children with varying reading ability and disease severity, consistent with US Food and Drug Administration (FDA) PRO guidance and the International Society for Health Economics and Outcomes Research (ISPOR) good research practices. METHODS: A targeted literature review and clinician interviews were undertaken to characterize symptoms and impacts experienced by children with mild-to-severe asthma. Concept elicitation interviews (CEIs) were conducted with 44 children and their caregivers (30 US; 14 UK). Following item and digital application development, the ePASD was assessed for relevance, understanding, and interpretability through cognitive debriefing interviews (CDIs) with 21 US children. Face validity/translatability assessments were also performed. RESULTS: Key measurement concepts included cough, wheeze, difficulty breathing, chest tightness/discomfort, nighttime awakening, and daytime activity limitations. Concept saturation was reached during CEIs for primary asthma-related daytime and nighttime symptoms and core impacts. Most CDI participants found the ePASD items clear, understandable, and comprehensive. Standardized training is anticipated to facilitate reliable child self-report. CONCLUSION: The ePASD, a novel PROM for children aged 6-11 years with asthma, uses an innovative multimedia approach and has been developed in accordance with FDA PRO guidance and ISPOR good research practices, directly capturing the child's self-reported asthma symptoms, impacts on daily activities and nighttime awakening, and rescue medication use.

Development of Sinonasal Outcome Test (SNOT-22) Domains in Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVES/HYPOTHESIS: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nasal polyps (CRSwNP). STUDY DESIGN: Validation of SNOT-22 domain structure, using data from 3 randomized, placebo-controlled, double-blinded, multicenter clinical trials of dupilumab in adults with moderate-to-severe CRSwNP. METHODS: Preliminary dimensional structure was derived by exploratory factor analyses of SNOT-22 data from a phase 2 trial (NCT01920893) of dupilumab for the treatment of CRSwNP. Data from 2 phase 3 clinical trials (NCT02912468 and NCT02898454) were then used for confirmatory factor analysis, and evaluated for reliability, construct validity, and responsiveness. In all three trials, the SNOT-22 was administered electronically on a tablet and trial participants were required to answer all items. RESULTS: Factor analysis supported five domains: Nasal, Ear/Facial, Sleep, Function, and Emotion. Correlations between domains were moderate to high, ranging from 0.53 (Nasal-Emotion) to 0.88 (Function-Sleep). Construct validity was mostly supported; relationships with other measures were almost always in the intended direction and magnitude. Internal consistency reliability also confirmed questionnaire structure with strong Cronbach's alpha values (all >0.80). Moderate-to-high correlations were observed between change in SNOT-22 domain scores and other study patient-reported outcome measures, along with large effect-size estimates (≥0.7), demonstrating responsiveness of the Nasal, Sleep, and Function domains. Emotion and Ear/Facial domains had small-to-moderate effect sizes. CONCLUSIONS: Psychometric analyses support the validity, reliability, and responsiveness of five domains of SNOT-22 (Nasal, Ear/Facial, Sleep, Function, and Emotion) for assessing symptoms and impact on HRQoL in patients with CRSwNP. Laryngoscope, 132:933-941, 2022.

Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis.

OBJECTIVES/HYPOTHESIS: Clinical trials of biologics to treat chronic rhinosinusitis with nasal polyposis (CRSwNP) have evaluated objective outcomes (e.g., University of Pennsylvania Smell Identification Test [UPSIT], nasal polyps score [NPS], and computed tomography Lund-Mackay score [CT-LMK]) and patient-reported symptoms (e.g., nasal congestion/obstruction [NC], loss of smell [LoS], and total symptom score [TSS]). We estimated anchor-based thresholds for clinically meaningful change in objective and patient-reported outcomes in patients with CRSwNP using data from LIBERTY NP SINUS-24 and SINUS-52 trials (NCT02912468; NCT02898454). METHODS: Target patient-reported outcomes were NC, LoS, and TSS; target objective outcomes were UPSIT, NPS, and CT-LMK. Anchor measures were the 22-item sinonasal outcome test (SNOT-22) rhinologic symptoms domain and total score and rhinosinusitis visual analog scale (VAS). The appropriateness of each anchor measure was evaluated by reviewing correlations between change in anchor measures and target outcomes and descriptive scores on target outcomes by levels of change in the anchor measure. Established thresholds for anchor measures (3.8 points for SNOT-22 rhinologic symptoms, 8.9 points for SNOT-22 total, 1-category improvement for rhinosinusitis VAS) were used to estimate clinically meaningful score changes for each target outcome. RESULTS: Based on correlations between change in anchor measures and target outcomes, SNOT-22 rhinologic symptoms domain was deemed the most appropriate anchor measure. Using this anchor measure, thresholds for clinically meaningful within-patient change were NC: 1 point; LoS: 1 point; TSS: 3 points; UPSIT: 8 points; NPS: 1 point; and CT-LMK: 5 points. CONCLUSION: These thresholds support interpretation of efficacy results for target outcomes in CRSwNP trials. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:265-271, 2022.

Definition of Clinically Meaningful Within-Patient Changes in POEM and CDLQI in Children 6 to 11 Years of Age with Severe Atopic Dermatitis.

INTRODUCTION: The Patient-Oriented Eczema Measure (POEM) assesses patient-reported severity of atopic dermatitis (AD) symptoms, whereas the Children's Dermatology Life Quality Index (CDLQI) measures how AD affects health-related quality of life (HRQoL) in children. Although the POEM and CDLQI have established thresholds for clinically meaningful within-patient change in adolescents (aged 12-17 years), there are no defined within-patient responder thresholds for clinically meaningful change in children aged 6-11 years. METHODS: Data from the LIBERTY AD PEDS phase 3 randomized, double-blind, placebo-controlled trial of dupilumab in children aged 6-11 years with severe AD were used to define the threshold for within-patient meaningful change in POEM and CDLQI scores. Anchor-based methods were applied to estimate mean change in POEM and CDLQI scores from baseline to week 16, with anchors of a 1-point improvement in the Patient Global Impression of Disease (PGID) scale and an improvement in score of ''A little better'' on the Patient Global Impression of Change (PGIC) scale. The distribution-based methods, a one-half standard deviation (SD) at baseline and a standard error mean (SEM) were also used. RESULTS: The mean POEM change scores associated with the anchors were a change of - 8.40 with the PGID anchor and - 6.30 with the PGIC anchor. Distribution-based estimates for POEM were one-half SD at baseline of 2.76, with a SEM of 3.32. Mean CDLQI change scores corresponding to the PGID and PGIC anchors were - 7.30 and - 6.80, respectively, while distribution-based estimates for CDLQI were a one-half SD at baseline of 3.69, with a SEM of 3.52. CONCLUSIONS: In children with severe AD, an appropriate minimum threshold of clinically meaningful within-patient change was estimated as 6 points for both the POEM and CDLQI scores. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03345914. What is the clinically meaningful within-person change in Patient-Oriented Eczema Measure and Children's Dermatology Life Quality Index scores in children 6 to 11 years old with severe atopic dermatitis? (MP4 289443 KB).

Development of the impact of weight on daily activities questionnaire: A patient-reported outcome measure.

While patient-reported outcome measures are available to evaluate health-related quality of life and functioning in obesity, existing measures do not evaluate the impact of excess weight and weight loss on the ability to perform regularly occurring daily activities. Three iterative sets of qualitative interviews were conducted in two countries (United States, n = 23; United Kingdom, n = 23) with individuals with body mass index ≥30 kg/m2 to inform development of the Impact of Weight on Daily Activities Questionnaire (IWDAQ) for use in clinical trials to evaluate daily activity limitations associated with excess weight. Candidate concepts were selected based on the literature, expert opinion, and previously conducted qualitative research, after which the draft IWDAQ was developed and tested. Interviews included a brief concept elicitation phase, followed by cognitive debriefing during which the IWDAQ was refined based upon participants' feedback. The IWDAQ uses a novel, adaptive questionnaire design, such that clinical trial participants choose the three IWDAQ activities they would most like to improve with weight loss and rate the degree of limitation in each of these activities at baseline. By allowing individuals participating in trials to identify and monitor changes in the activities they most want to see improve with weight loss, the 19-item IWDAQ has the potential to detect the benefits of weight-loss treatment that individuals with obesity value most.

Treatment Mode Preferences in Rheumatoid Arthritis: Moving Toward Shared Decision-Making.

PURPOSE: Current knowledge of the reasons for patients' preference for rheumatoid arthritis (RA) treatment modes is limited. This study was designed to identify preferences for four treatment modes, and to obtain in-depth information on the reasons for these preferences. PATIENTS AND METHODS: In this multi-national, cross-sectional, qualitative study, in-depth interviews were conducted with adult patients with RA in the United States, France, Germany, Italy, Spain, Switzerland, the United Kingdom, and Brazil. Patients' strength of preference was evaluated using a 100-point allocation task (0-100; 100=strongest) across four treatment modes: oral, self-injection, clinic-injection, and infusion. Qualitative descriptive analysis methods were used to identify, characterize, and summarize patterns found in the interview data relating to reasons for these preferences. RESULTS: 100 patients were interviewed (female, 75.0%; mean age, 53.9 years; mean 11.6 years since diagnosis). Among the four treatment modes, oral administration was allocated the highest mean (standard deviation) preference points (47.3 [33.1]) and was ranked first choice by the greatest percentage of patients (57.0%), followed by self-injection (29.7 [27.7]; 29.0%), infusion (15.4 [24.6]; 16.0%), and clinic-injection (7.5 [14.1]; 2.0%). Overall, 56.0% of patients had a "strong" first-choice preference (ie, point allocation ≥70); most of these patients chose oral (62.5%) vs self-injection (23.2%), infusion (10.7%), or clinic-injection (3.6%). Speed and/or ease of administration were the most commonly reported reasons for patients choosing oral (52.6%) or self-injection (55.2%). The most common reasons for patients not choosing oral or self-injection were not wanting to take another pill (37.2%) and avoiding pain due to needles (46.5%), respectively. CONCLUSION: These data report factors important to patients regarding preferences for RA treatment modes. Patients may benefit from discussions with their healthcare professionals and/or patient support groups, regarding RA treatment modes, to facilitate shared decision-making.

Responder Threshold for Patient-Oriented Eczema Measure (POEM) and Children's Dermatology Life Quality Index (CDLQI) in Adolescents with Atopic Dermatitis.

INTRODUCTION: The Patient-Oriented Eczema Measure (POEM) assesses patient-reported frequency of atopic dermatitis (AD) symptoms, while the Children's Dermatology Life Quality Index (CDLQI) measures the impact of skin disease on health-related quality of life (HRQoL) in children. There is currently no threshold for clinically meaningful within-person change in POEM or CDLQI scores in adolescents. Here we empirically derive within-person thresholds of meaningful within-person change in POEM and CDLQI scores in adolescents with moderate-to-severe AD. METHODS: Data were used from a phase 3, randomized, double-blind, placebo-controlled trial of dupilumab in adolescents (aged ≥ 12 to < 18 years) with moderate-to-severe AD. Anchor-based methods were employed using the mean change in POEM and CDLQI scores from baseline to week 16 linked with a 1-point improvement in Patient Global Assessment of Disease (PGAD), a score of "a little better" on the Patient Global Assessment of Treatment effect (PGAT), a 50-74% improvement from baseline in the Eczema Area and Severity Index (EASI-50-74), and a 1-point improvement in Investigator's Global Assessment (IGA) score. RESULTS: A mean change of - 7.8 and - 5.6 in the POEM score was associated with PGAD and PGAT anchors, respectively. EASI-50-74 was associated with a mean change in POEM score of - 8.2, while the IGA anchor was associated with a mean change of - 7.9 in POEM score. The mean changes in CDLQI score associated with PGAD and PGAT anchors were - 6.4 and - 6.6, respectively, while CDLQI mean scores changed by - 8.3 and - 8.0 for the EASI and IGA anchors, respectively. CONCLUSION: In adolescents (aged ≥ 12 to < 18 years) with moderate-to-severe AD, a within-person change of 6-8 points in POEM and CDLQI scores, independently, can be considered a reasonable responder threshold for clinically meaningful change in each of the two scales, respectively. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03054428. FUNDING: Sanofi and Regeneron Pharmaceuticals, Inc.

A descriptive follow-up interview study assessing patient-centred outcomes: Salford Lung Study in Asthma (SLS Asthma).

The Salford Lung Study in Asthma (SLS Asthma) was a multicentre, randomised, controlled, open-label trial that assessed initiating once-daily, single-inhaler fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg or 200 µg/25 µg versus continuing usual care. A subgroup (n = 400) from SLS Asthma was enrolled in this exploratory, interview-based follow-up study. Quantitative and qualitative data were collected via questionnaires. The primary objective was to capture patient-centred outcomes (symptom experience, quality of life [QoL], disease management behaviours) and patient experience. Secondary objectives were to assess the correlation of patient-reported outcomes with pre-defined variables from SLS Asthma (Asthma Control Test [ACT] score). The follow-up sample was representative of the SLS Asthma population; half reported asthma improvement during the study. Breathlessness was the most likely symptom to improve (47.8% of patients reported improvement). Most patients reported 'no change' in overall QoL (57.5%) and daily life domains (functioning 66.3%, activities 68.3%, relationships 86.8%, psychological 68.5%). Functioning was reported as the most frequently improved domain (29.8% of patients). Perceived improvement in asthma control (42.5%) and confidence (37.3%) was frequent. ACT responders (defined as patients achieving an ACT score ≥20 and/or an increase of ≥3 in ACT score from baseline at Week 52) were more likely to report asthma improvement (88.7% of patients reporting 'a lot' of improvement) than non-responders. Patients' asthma experiences generally improved during SLS Asthma. Clinical improvements were often associated with perceived improvement by patients, particularly among ACT responders.

Follow-up interviews from The Salford Lung Study (COPD) and analyses per treatment and exacerbations.

The Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD) was a 12-month, Phase III, open-label, randomised study comparing the effectiveness and safety of initiating once-daily fluticasone furoate 100 µg/vilanterol 25 µg (FF/VI) with continuing usual care (UC). Follow-up interviews were conducted among a subset of 400 patients who completed SLS COPD to further understand patients' experiences with treatment outcomes and the impact of COPD, and potential risk factors associated with higher rates of exacerbations during SLS COPD. Another objective was to explore how such patient-centred outcomes differed by randomised treatment. Patients' perceived control over COPD and effects on quality of life (QoL) were similar between treatment groups at the time of the follow-up interview, but more patients in the FF/VI group compared with UC reported perceived improvements in COPD control and QoL during the study. Of patients who experienced ≥2 exacerbations during SLS COPD, a greater percentage were women, were unemployed or homemakers, or were on long-term sick leave. Having ≥2 exacerbations also appeared to be associated with smoking, seeing a hospital specialist, a feeling of having no/little control over COPD, perceived worsening of feelings of control and reduced overall QoL since the start of the study, being aware of impending exacerbation occurrence and a more severe last exacerbation. Initiation of FF/VI was associated with a greater perceived improvement in patients' control of their COPD and QoL throughout SLS COPD than continuation of UC. Suggestions that smoking status and feelings of control are potentially related to exacerbation require further investigation.

Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers.

BACKGROUND AND METHODS: Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A. Neurological involvement results in severe disability and premature death, but understanding of the natural history of the disease remains limited. In this study, 32 caregivers of patients with MLD in the USA (16 with late-infantile MLD; 16 with juvenile MLD) were interviewed about their experiences of the disease. Qualitative analysis of the interview transcripts was performed to gain insights into symptom onset, the diagnostic process and disease progression, with a focus on the differences between late-infantile and juvenile MLD. RESULTS: The mean ages of patients at interview were 7.6 years and 20.7 years for individuals with late-infantile and juvenile MLD, respectively. Patients with late-infantile MLD had a mean age of 1.5 years at symptom onset and 2.6 years at diagnosis. The most common initial symptoms in this group related to problems with gross motor function (12/16 patients); 11 patients never learned to walk independently. For patients with juvenile MLD, the mean ages at symptom onset and diagnosis were 8.7 years and 11.6 years, respectively. Cognitive or social/behavioural problems were the most common first reported symptoms in this group (9/16 and 7/16 patients, respectively); these were generally followed by deterioration in motor function. The rate of functional decline was more rapid in patients with late-infantile MLD than those with juvenile MLD; the mean time from first symptom to first functional loss was 1 year versus 6.1 years, respectively. Nine patients with juvenile MLD and three with late-infantile MLD had undergone a haematopoietic stem cell transplant; outcomes following transplant were variable. CONCLUSIONS: Our data highlight clear overall differences in symptom profiles and disease progression between late-infantile and juvenile MLD, but also indicate some degree of interindividual variability within each subtype. These findings are broadly consistent with previously published descriptions of MLD and enhance our knowledge of the natural history of the disease, which ultimately should help to improve patient care and aid assessments of the effectiveness of disease-related interventions in the future.

Health-related quality of life in alcohol dependence: Similar cross-cultural impact beyond specific drinking habits.

This study explores sociocultural differences in alcohol-related impact on quality of life between France and United Kingdom. We included 38 alcohol-dependent patients in France and United Kingdom in 10 focus groups. We used a text-mining approach. Three classes of each corpus regarded identical themes across the countries: (a) core impact on quality of life, (b) drinking habits, (c) sources of help. Core impact was similar between the two countries. Main differences were in drinking habits and referral to sources of help. Despite differences in drinking habits, the domains of life impacted by alcohol were non-country specific.

Is the EQ-5D fit for purpose in asthma? Acceptability and content validity from the patient perspective.

BACKGROUND: The increasing emphasis on patient-reported outcomes in health care decision making has prompted greater rigor in the evidence to support the instruments used. Acceptability and content validity are important properties of any measure to ensure it assesses the relevant aspects of the target concept. The purpose of this study was to evaluate the acceptability and content validity of the EQ-5D 5-Level (EQ-5D-5L) to assess the impact of asthma on patients' lives. METHODS: Qualitative interviews were conducted with 40 adults with asthma in the United Kingdom. The first 25 interviews used cognitive-debriefing methods to assess the relevance and acceptability of the EQ-5D-5L and two asthma-specific measures for comparison: an asthma-specific, preference-based measure (the Asthma Quality of Life Utility Index-5 Dimensions) and an Asthma Symptom Diary. The final 15 interviews combined concept elicitation to identify patient-perceived asthma impact, and cognitive debriefing to assess relevance and acceptability of the EQ-5D-5L and the Asthma Symptom Diary. Cognitive-debriefing feedback on the content of the measures was collated and summarized descriptively. The concept-elicitation data were analyzed thematically. RESULTS: Participants were aged 20 to 57 years and 62.5% were female. Although some participants expressed positive opinions on aspects of the EQ-5D-5L, only the usual activities dimension was consistently considered relevant to participants' asthma experiences. The mobility and self-care dimensions prompted strong negative reactions from some participants. Variations in interpretation of the mobility dimension and difficulties with multiple concepts in the pain/discomfort and anxiety/depression dimensions also were noted. Concepts reported by participants as missing included environmental triggers, asthma symptoms, emotions, and sleep. The EQ-5D-5L was the least preferred measure to describe the impact of asthma on participants' lives. Participants reported shortness of breath and impact on activities as especially salient issues. CONCLUSIONS: The content of the EQ-5D-5L was poorly aligned with the patient-perceived impact of asthma, and the measure failed to meet basic standards for acceptability and content validity as a measure to assess the impact of asthma from the patient perspective. The shortcomings identified raise concerns regarding the appropriateness of the EQ-5D in asthma and further evaluation is warranted.

Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD): follow-up interviews on patient-centred outcomes.

This study investigated patient perceptions, experiences and management of COPD throughout the SLS COPD study. Follow-up interviews were conducted with 400 patients who completed SLS COPD; a mixed-methods approach was used to collect quantitative and qualitative information. Structured interviews using closed-ended questions were conducted with 360 patients, detailing aspects of background/lifestyle information and COPD. Extended interviews containing open-ended questions on perceptions of COPD and quality of life (QoL) in addition to the closed-ended questions were completed by 40 further patients. Participants also completed the Adherence Starts with Knowledge-12 (ASK-12) and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Quantitative data were analysed descriptively; qualitative data were analysed using qualitative description. The participants (n = 400) were reasonably representative of the SLS COPD population; mean age was 66.2 years. Breathlessness was the most commonly recalled symptom of/associated with COPD (88.5% of patients) and was the symptom that changed the most (improved, 26.8%/worsened, 20.9%) throughout the study. Participants' daily functioning and activities were most affected by symptoms of/associated with COPD, followed by relationships and psychological issues. 66.5% of participants experienced exacerbations, 60.5% of whom reported self-management as their first treatment strategy (taking antibiotics, resting and/or corticosteroids). Qualitative analysis revealed COPD symptoms, breathlessness in particular, to have a significant impact on mobility and in turn QoL. In conclusion, breathlessness was cited in these interviews as the COPD symptom with the greatest impact on participants' daily functioning, activities and self-care. The findings provided significant additional knowledge to the SLS COPD study findings.

Quantifying the relative importance to patients of avoiding symptoms and outcomes of heart failure.

OBJECTIVE: To evaluate heart failure (HF) patients' disease knowledge and preferences for avoiding different disease outcomes. METHODS: An online survey was administered to 400 individuals with a self-reported diagnosis of HF to elicit relative importance weights (RIWs) for avoiding 11 potential HF symptoms and outcomes using best-worst scaling. The survey also included questions about individuals' HF knowledge, and demographic and disease-experience characteristics. Differences in RIWs among sub-groups, defined by HF knowledge, caregiver support, age, recent hospitalization or emergency room visit for HF, health-related quality-of-life, and cardiac device experience were examined. RESULTS: Relative to limitations in usual activities (RIW 1.00), respondents preferred avoiding severe, infrequent cardiovascular events (e.g. stroke [RIW 8.51], heart transplant [RIW 7.84], or heart attack [RIW 5.3]) most, followed by difficulty breathing (RIW 2.55), inability to enjoy life (RIW 1.84), cardiac device implantation (RIW 1.74), and atrial fibrillation (RIW 1.57). Patients preferred avoiding swelling (RIW 0.47) and fatigue (RIW 0.58) least. RIWs for avoiding severe, infrequent events were higher among those with high disease knowledge, those without caregivers, and those without a recent hospitalization or emergency room visit. CONCLUSIONS: Patients' preferences for avoiding HF outcomes vary across outcomes and by individuals' knowledge, caregiver status, and age. Healthcare providers should solicit and incorporate insights about patients' knowledge of HF and their preferences for avoiding HF outcomes into HF education and management planning efforts.

Early patient experiences with montelukast orally disintegrating tablets in Japan: a cross-sectional survey of treatment satisfaction in patients with asthma and/or allergic rhinitis.

OBJECTIVE: Orally disintegrating tablets (ODTs) offer a valuable treatment option, particularly when swallowing solid tablets with water is difficult or inconvenient. Montelukast is an effective treatment for asthma and allergic rhinitis (AR), and an ODT formulation became available in Japan in 2015. This study investigated levels of satisfaction with this new formulation among adults with asthma and/or AR in Japan. METHODS: Patients aged 20 years or older who were refilling a prescription for montelukast ODT in pharmacies across Japan completed questions on satisfaction with key features of montelukast ODT and the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Study variables were analyzed descriptively. Factors associated with TSQM-9 global satisfaction and convenience domain scores were examined using analysis of covariance. RESULTS: Of the 201 patients who participated, 89.6% reported overall satisfaction with montelukast ODT. Overall satisfaction was highest in patients with AR only (94.7% satisfied) or with asthma and AR (90.2% satisfied), and in patients with treatment duration <4 weeks (98.5% satisfied). Mean TSQM-9 global satisfaction and convenience domain scores were 58.9 and 66.7, respectively; scores were higher for patients with both asthma and AR and for those with longer disease duration. Overall ease of taking and dissolving speed were most closely associated with TSQM-9 global satisfaction scores, and ability to take without water and taste were most closely associated with TSQM-9 convenience scores. LIMITATIONS: The generalizability of the findings was limited by the convenience sample and the descriptive, single-arm study design. The study was limited to adults with asthma and/or AR. CONCLUSION: Montelukast ODT may be an acceptable dosage formulation for adults with mild-to-moderate asthma and/or AR in Japan. Satisfaction was high, particularly with respect to tablet size, dissolving speed, taste, and ease of taking.

Treatment satisfaction in cystic fibrosis: early patient experience with tobramycin inhalation powder.

BACKGROUND: This study assessed treatment satisfaction of cystic fibrosis (CF) patients in a routine clinical setting for tobramycin inhalation powder (TIP), the first dry powder-inhaled antibiotic for Pseudomonas aeruginosa infection. METHODS: CF patients aged 6 years or older treated with at least one cycle of TIP completed a web survey on experience with TIP, including the Treatment Satisfaction Questionnaire for Medication (TSQM). Regression analysis determined the factors associated with TSQM global satisfaction. RESULTS: Eighty patients (mean age ± standard deviation: 24.4±9.4 years; 57.5% female; mean forced expiratory volume in 1 second ± standard deviation: 67.1%±27.3% predicted) completed the survey. The majority expressed satisfaction with TIP's administration time (100%), time to clean (97.1%), portability (97.1%), and ease of use (94.3%). Effectiveness was significantly associated with TSQM global satisfaction (regression R-squared: 0.54). CONCLUSION: Patient preferences for TIP were based on administration time and ease of use. Global satisfaction was related to greater patient-perceived effectiveness.