Burden of hyperphagia and obesity in Bardet-Biedl syndrome: a multicountry survey.

BACKGROUND: Signs and symptoms of Bardet-Biedl syndrome (BBS) occur during early childhood, progress over time, and place substantial, multifaceted burden on patients and their caregivers. Hyperphagia may be a contributing factor to early-onset obesity in BBS; however, there are limited insights into its impacts on patients and caregivers. We quantified disease burden as it relates to the physical and emotional impacts of hyperphagia in BBS. METHODS: The CAREgiver Burden in BBS (CARE-BBS) study was a multicountry, cross-sectional survey of adult caregivers of patients with BBS who have had hyperphagia and obesity. The survey consisted of questionnaires including Symptoms of Hyperphagia, Impacts of Hyperphagia, Impact of Weight on Quality of Life (IWQOL)-Kids Parent Proxy, and Patient-Reported Outcome Measurement Information System (PROMIS) v1.0-Global Health 7. In addition, clinical characteristics, medical history, and weight management questions were included. Outcomes were scored and summarized descriptively in aggregate and by country, age, and obesity severity according to weight class. RESULTS: There were 242 caregivers of patients with BBS who completed the survey. Caregivers observed hyperphagic behaviors throughout the day, with negotiating for food (90%) and waking up and asking or looking for food during the night (88%) being the most frequent. Hyperphagia had at least a moderate negative impact on most patients' mood/emotions (56%), sleep (54%), school (57%), leisure (62%), and familial relationships (51%). Hyperphagia affected concentration at school (78%), and symptoms of BBS contributed to patients missing ≥ 1 day of school a week (82%). Responses from the IWQOL-Kids Parent Proxy suggested obesity most greatly negatively affected physical comfort (mean [standard deviation (SD)], 41.7 [17.2]), body esteem (41.0 [17.8]), and social life (41.7 [18.0]). On the PROMIS questionnaire, mean (SD) global health score for pediatric patients with BBS and overweight or obesity (36.8 [10.6]) was lower than the general population (mean, 50). CONCLUSIONS: Evidence from this study suggests that hyperphagia and obesity may have broad negative impacts on the lives of patients with BBS, including physical health, emotional well-being, school performance, and personal relationships. Therapies that target hyperphagia may alleviate the extensive clinical and nonclinical impacts experienced by patients with BBS and their caregivers.

Caregiver burden in Bardet-Biedl syndrome: findings from the CARE-BBS study.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare, genetically heterogeneous obesity syndrome associated with hyperphagia. Given the early onset of BBS symptoms in childhood and multifaceted complications, this study aimed to quantify the caregiver burden associated with BBS. METHODS: A cross-sectional, multi-country survey of caregivers from the United States (US), United Kingdom (UK), Canada, and Germany was designed to quantify the extent of caregiver burden associated with obesity and hyperphagia symptoms (i.e., uncontrollable hunger) among patients with BBS. RESULTS: A total of 242 caregivers across the four countries met the inclusion criteria and completed the survey. The mean (standard deviation [SD]) age of the caregivers was 41.9 (6.7) years, and the mean (SD) age of individuals with BBS in their care was 12.0 (3.7) years. Hyperphagia contributed to a BBS diagnosis in 230 of 242 individuals (95.0%). On average, caregivers used eight different weight management approaches for those in their care and expressed a strong desire for more effective weight management methods. Based on the Impacts of Hyperphagia: Caregiver version, patients' hyperphagia had a moderate-to-severe impact on caregiver mood (56.6%), sleep (46.6%), and relationships (48.0%). Caregivers reported experiencing a high level of personal strain (mean [SD], 17.1 [2.9]) and family impact (mean [SD] score, 26.0 [3.8]) due to BBS, as measured by the Revised Impact on Family Scale. Among caregivers in the workforce, there also was high impairment in total work productivity (mean [SD], 60.9% [21.4%]) due to caring for patients with BBS according to the Work Productivity and Activity Impairment. More than half (53%) of the caregivers reported spending over 5,000 out-of-pocket in local currency for medical expenses for the patient with BBS in their care. CONCLUSIONS: Obesity and hyperphagia have negative impacts on the lives of caregivers of patients with BBS. The burden is demonstrated to be multifaceted, with various components that may interact with and confound each other, including intensive weight management efforts, productivity loses, impaired family dynamics and out-of-pocket medical expenses.

Development and validation of a novel patient-reported outcome measure in people with episodic migraine and chronic migraine: The Activity Impairment in Migraine Diary.

OBJECTIVE: To evaluate the content validity and psychometric properties of the Activity Impairment in Migraine Diary (AIM-D). BACKGROUND: Measuring treatment effects on migraine impairment requires a psychometrically sound patient-reported outcome (PRO) measure developed consistent with U.S. Food and Drug Administration guidance. METHODS: The AIM-D was created from concepts that emerged during qualitative interviews with five clinicians experienced in treating migraine and concept elicitation (CE) interviews with 40 adults with episodic migraine (EM) or chronic migraine (CM). The initial version was refined based on three waves of cognitive interviews with 38 adults with EM or CM and input from a panel of clinical and measurement experts. The AIM-D was psychometrically evaluated using data from 316 adults with EM or CM who participated in a 13-week prospective observational study. Study participants completed PRO assessments including the AIM-D and a daily headache diary. Exploratory and confirmatory factor analysis were used to determine the factor structure. The reliability, validity, and responsiveness of the AIM-D were assessed. Additional PRO measures including the Patient Global Impression - Severity (PGI-S), Migraine Specific Quality of Life Questionnaire, Version 2.1 Role Function-Restrictive domain, and Headache Impact Test were used for psychometric evaluation of the AIM-D. RESULTS: Based on CE interviews with adults with migraine and input from an expert panel, activity impairment was identified as the target in the preliminary conceptual framework, which had two domains: performance of daily activities (PDAs) and physical impairment (PI). Revision of the draft AIM-D through multiple rounds of cognitive interviews and expert panel meetings resulted in a content valid 11-item version. Exploratory factor analysis supported both one- and two-domain structures for the AIM-D, which were further supported by confirmatory factor analysis (factor loadings all >0.90). The AIM-D domains (PDA and PI) and total score showed high internal consistency reliability (Cronbach's alpha 0.95-0.97), acceptable test-retest reliability for weekly average scores (intraclass correlation coefficient >0.60 for participants with no change in PGI-S between baseline and week 2), and good convergent and known-groups validity. There was evidence of responsiveness based on changes in PGI-S score and monthly migraine days. CONCLUSION: The AIM-D is a content valid and psychometrically sound measure designed to evaluate activity impairment and is suitable for use in clinical trials of preventive treatments for EM or CM.

The Vulvodynia Experience Questionnaire: Qualitative Development of a New Patient-Reported Outcome Measure for Vulvodynia.

INTRODUCTION: Vulvodynia is defined as vulvar pain of at least 3 months duration without a clear identifiable cause. There are currently no validated questionnaires that assess the experience of women with localized vulvodynia of the vestibule (vestibulodynia, previously known as vulvar vestibulitis) that meet the requirements of the Food and Drug Administration's Patient Reported Outcome (PRO) Guidance. AIM: To develop a new content-valid PRO assessment in accordance with the Food and Drug Administration's PRO guidance to assess the symptoms and impacts of localized vulvodynia. MATERIAL AND METHODS: Participants were recruited for concept elicitation interviews (ie, interviews with open-ended questions with the goal of eliciting volunteered data about the symptoms and impacts of vulvodynia). Participants were identified as having localized vulvodynia by clinicians who were experts in treating vulvar disorders. Eligibility was confirmed by the recruiting clinician, and informed consent was obtained; participants were then scheduled for in-person interviews. 25 participants were interviewed from United States (US). After concept elicitation interviews, the draft Vulvodynia Experience Questionnaire (VEQ) was developed based on the results. Cognitive interviews were conducted with 20 participants from US sites to assess the content validity of the VEQ (eg, interpretation and clarity of the items, relevance of concepts). The VEQ was further revised after cognitive interviews. All interviews were conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and analyzed using a qualitative data analysis software program. RESULTS: 17 unique symptoms and 32 unique impacts were reported during concept elicitation interviews. Pain (n = 25, 100%) and burning (n = 24, 96%) were the most frequently reported symptoms of localized vulvodynia, and negative impact on emotional well-being (n = 25, 100%) was the most frequently reported impact. After analysis, item generation, and cognitive interviews, the resulting VEQ v2.0 contains 3 parts (part 1, pain; part 2, associated symptoms; part 3, impacts) with a total of 25 items that measure the most frequently reported symptoms and impacts of localized vulvodynia. STRENGTH AND LIMITATIONS: The VEQ is a multidimensional assessment of the core symptoms and impacts of localized vulvodynia that, after additional psychometric testing including the ability to detect change, may be used in clinical trials to characterize the benefits of novel treatments. The VEQ requires additional testing to establish its cultural relevance and linguistic validity in other countries. CONCLUSION: The VEQ is a novel method of collecting information on localized vulvodynia symptoms and impacts that may be suitable for use in clinical trials after psychometric testing. Goldstein AT, Diez PMQ, Kapanadze S, et al. The Vulvodynia Experience Questionnaire: Qualitative Development of a New Patient-Reported Outcome Measure for Vulvodynia. J Sex Med 2020;17:2055-2066.

Evaluation and Validation of the Modified Reflux Symptom Questionnaire-Electronic Diary in Patients With Persistent Gastroesophageal Reflux Disease.

OBJECTIVES: This study aimed to examine the validity of the modified Reflux Symptom Questionnaire-electronic Diary (mRESQ-eD) through patient input and psychometric testing of the questionnaire to support use in clinical trials in patients with persistent gastroesophageal reflux disease (GERD) and in accordance with Food and Drug Administration guidance on patient-reported outcome instruments. METHODS: Cognitive interviews were conducted with patients (n = 30) to evaluate the interpretability and content validity of draft mRESQ-eD items. Patient data from a phase 2b clinical study (ClinicalTrials.gov identifier: NCT02637557) on persistent GERD served to aid in the construction of weekly scores for heartburn severity, regurgitation severity, and total GERD severity. These scores' psychometric properties were also evaluated. RESULTS: Minor modifications were made to the draft mRESQ-eD based on patient feedback to improve interpretability and clarity of the instrument. Psychometric analysis suggested that an 8-item version of the mRESQ-eD was best suited to the clinical data. The internal consistency was found to be high (Coefficient ω = 0.95). Retest reliability and convergent validity were strong for a heartburn weekly severity score, regurgitation weekly severity score, and total GERD severity score. DISCUSSION: The final 8-item mRESQ-eD is a reliable and valid instrument with good psychometric properties for use in clinical trials in patients with persistent GERD. The mRESQ-eD may be considered for inclusion in clinical trials for persistent GERD and potentially positioned, in consultation with Food and Drug Administration, as endpoints to characterize treatment benefit.