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.

Qualitative evaluation of the Autism Behavior Inventory: use of cognitive interviewing to establish validity of a caregiver report scale for autism spectrum disorder.

PURPOSE: The Autism Behavior Inventory (ABI) is an observer-reported outcome scale measuring core and associated features of autism spectrum disorder (ASD). Extensive scale development (reported elsewhere) took place, in alignment with the Food and Drug Administration's patient-reported outcome guidance, to address the need for instruments to measure change and severity of ASD symptoms. METHODS: Cognitive interviewing was used to confirm understanding and content validity of the scale prior to its use in clinical trials. Respondents were caregivers of individuals with ASD (N = 50). Interviews used a hybrid of the "think-aloud" and verbal probing approach to assess ABI's content validity and participant understanding of the instrument, including: item clarity and relevance; item interpretation; appropriateness of response scales; and clarity of instructions. Audio-recordings of the interviews were transcribed for qualitative data analysis. The scale was revised based on participant feedback and tested in a second round of interviews (round 1 N = 38, round 2 N = 12). RESULTS: In total, 67/70 items reached ≥ 90% understandability across participants. Caregivers were able to select an appropriate response from the options available and reported finding the examples helpful. Based on participant feedback, instructions were simplified, 8 items were removed, and 10 items were reworded. The final revised 62-item scale was presented in round 2, where caregivers reported readily understanding the instructions, response options, and 61/62 items reached ≥ 90% understandability. CONCLUSIONS: Cognitive interviews with caregivers of a diverse sample of individuals with ASD confirm the content validity and relevance of the ABI to assess core and associated symptoms of ASD.

Generation of an iPSC line (AKOSi004-A) from fibroblasts of a female adult NPC1 patient, carrying the compound heterozygous mutation p.Val1023Serfs*15/p.Gly992Arg and of an iPSC line (AKOSi005-A) from a female adult control individual.

Niemann-Pick disease Type C (NPC) is a rare progressive neurodegenerative disorder with an incidence of 1:120,000 caused by mutations in the NPC1 or NPC2 gene leading to a massive cholesterol accumulation. Here, we describe the generation of induced pluripotent stem cells (iPSCs) of an affected female adult individual carrying the NPC1 mutation p.Val1023Serfs*15/p.Gly992Arg and an iPSC line from an unrelated healthy female adult control individual. Human iPSCs were derived from fibroblasts using retroviruses carrying the four reprogramming factors OCT4, SOX2, KLF4 and C-MYC. These lines provide a valuable resource for studying the pathophysiology of NPC and for pharmacological intervention.

Development and Validation Clinician and Patient Reported Photonumeric Scales to Assess Buttocks Cellulite Severity.

BACKGROUND: The Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported PCSS (PR-PCSS) are newly developed tools for assessing cellulite severity. OBJECTIVE: To report on the reliability, validity, and ability to detect a change in cellulite severity on the buttocks of adult women with the CR-PCSS and PR-PCSS. MATERIALS AND METHODS: Content validity of both scales was established through concept elicitation and cognitive interviews. Test-retest reliability was evaluated, and intra-rater (both scales) and inter-rater (CR-PCSS only) reliability were estimated using intraclass correlation coefficients (ICCs) for agreement and consistency. Ability to detect a change was determined using the Subject-Global Aesthetic Improvement Scale (GAIS) or Investigator-GAIS as anchors. RESULTS: For the CR-PCSS (n = 6) at baseline and Day 2, the mean interrater ICCs were ≥0.70 and mean intrarater ICCs (95% confidence interval [CI]) were ≥0.81 (0.72-0.90) for both buttocks. For the PR-PCSS (n = 99) at baseline and Day 14, the mean test-retest reliability ICCs (95% CI) were ≥0.86 (0.79-0.91) for both buttocks. A clinically meaningful change was 1.0 point on the PR-PCSS and 1.0 on the CR-PCSS. CONCLUSION: The CR-PCSS and PR-PCSS reliably assess cellulite severity of the buttocks and can detect a clinically meaningful change after treatment for cellulite.

Illustration of patient-reported outcome challenges and solutions in rare diseases: a systematic review in Cushing's syndrome.

Rare diseases are often not fully understood and efforts put in investigating it from patient perspective are usually met with challenges. We performed a systematic literature review (SLR) for the last 20 years in Cushing's Syndrome (CS) to illustrate Patient-Reported Outcome (PRO) challenges, and show what solutions were found.PROs and other Clinical Outcome Assessment (COA) used with CS patients were reviewed in 36 studies. Two CS-specific Health Related Quality of Life (HRQL) measures were identified (i.e., CushingQoL, Tuebingen CD-25), as well as depression and neurocognitive measures. For CS-specific HRQL measures, the CushingQoL was the most widely used measure due in part to being the first CS-specific HRQL measure developed. With algorithms mapping the CushingQoL to both the SF-6D and EQ-5D, the CushingQoL could be used to facilitate economic modelling studies in the absence of a generic HRQL measure. While the CushingQoL offers only the global scale and two subscales compared to the six subscales of the Tuebingen CD-25, there is not yet adequate statistical validation data available for the Tuebingen CD-25 to suggest it can withstand the scrutiny of review by multiple stakeholders. Results of this review indicate that the inclusion of a measure of depressive symptoms, such as the BDI-II or similar measure, would be reasonable to include given the high level of comorbidity of depression among CS patients. A brief neurocognitive performance outcome, such as Trail Making tasks A and D or Digit Symbol, could help inform the interpretation of HRQL results. Neurocognitive differences may be an unassessed mediator of HRQL outcomes, partly accounting for the persistence of depressive symptoms and HRQL deficits despite treatment. Results suggest that HRQL improvements are possible within this population. These results are limited by small sample sizes and pre/post study design.CS showcases the difficulties encountered in measuring PROs in rare diseases. A solution for this specific case was developed in the form of dedicated PRO instruments, the CushingQOL and the Tuebingen-25. However, some aspects of CS may not be fully answered or not yet validated (e.g., depressive and cognitive symptoms). Further research needs to be done to address them.

When insulin degludec enhances quality of life in patients with type 2 diabetes: a qualitative investigation.

BACKGROUND: Anecdotal reports suggest that insulin degludec (IDeg) may offer unique health-related quality of life (HRQoL) benefits. As the nature of these benefits remain unclear, this study utilized qualitative research methods to investigate and elucidate the experience of "feeling better" after initiating IDeg. METHODS: Twenty adults with type 2 diabetes (T2D) who reported "feeling better" on IDeg for > 3 months participated in 90-min interviews. One focus group and nine telephone interviews were conducted at two sites in the United States (US) and one focus group was conducted in Switzerland. Patients were ≥ 18 years of age, did not take mealtime insulin, and had switched to IDeg from another basal insulin. Discussions were audio-recorded, transcribed and translated (Swiss German). Utilizing grounded theory, transcripts were analyzed by sorting quotes into concepts using thematic analysis. RESULTS: Participants' mean age was 66 years and the average duration of T2D was 17.6 years. Mean duration of IDeg use was 1.45 years. Four major factors were identified as key contributors to patients' sense of "feeling better": 1) reduced sense of diabetes as burdensome and requiring excessive attention; 2) enhanced feelings of adaptability and freedom; 3) heightened sense of security, especially regarding concerns about hypoglycemia; and 4) greater sense of physical well-being (greater energy/less fatigue). Content saturation was achieved. Generally, patients from the US sites were more focused on medical results than Swiss patients, who were more likely to identify IDeg's effect on overall HRQoL. A limitation of the study was that the population was primarily white, > 60 and otherwise healthy (no comorbid physical or mental condition). CONCLUSIONS: A group of patients with T2D, who had switched to IDeg from another basal insulin, reported HRQoL benefits which were attributed to both diabetes-specific improvements (feeling less burdened by day-to-day diabetes demands) and non-specific gains (greater energy). The conclusions may have limited transferability due to the characteristics of the sample population and further research is needed.

Systematic Review: Associations Between Family Functioning and Child Adjustment After Pediatric Cancer Diagnosis: A Meta-Analysis.

Objectives: A systematic review and meta-analysis was conducted to investigate associations between family functioning and child adjustment (patient/siblings) after pediatric cancer diagnosis. Methods: Database searches were performed using Web of Science, Pubmed, Cochrane, PsycInfo, and Embase. After screening 5,563 articles, 35 were identified regarding this topic; 30 contributed data for meta-analyses. Pearson's r correlations were the effect of interest. Omnibus and family functioning domain-specific random-effects meta-analyses were conducted. Data are depicted in forest plots. Results: A statistically significant association was found between family functioning and child adjustment (patient/siblings) after cancer diagnosis (r = 0.19; 95% CI: 0.13­0.24). Greater family cohesion, expressiveness, and support and less family conflict were each associated with better child adjustment outcomes. Conclusions Family functioning is associated with patient and sibling adjustment after pediatric cancer diagnosis. Limitations in the existing literature preclude strong conclusions about the size of these effects and potential moderators.

Socioeconomic status (SES) and childhood acute myeloid leukemia (AML) mortality risk: Analysis of SEER data.

Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3651 pediatric AML patients, aged 0-19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility; F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02-1.12) and 1.05(1.00-1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1 (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3 (high economic/educational disadvantage, high-mobility) and Cluster 6 (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI)=1.19(1.0-1.4) and 1.23 (1.1-1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features.

An Experimental Study of Procedures to Enhance Ratings of Fidelity to an Evidence-Based Family Intervention.

The valid and reliable assessment of fidelity is critical at all stages of intervention research and is particularly germane to interpreting the results of efficacy and implementation trials. Ratings of protocol adherence typically are reliable, but ratings of therapist competence are plagued by low reliability. Because family context and case conceptualization guide the therapist's delivery of interventions, the reliability of fidelity ratings might be improved if the coder is privy to client context in the form of an ecological assessment. We conducted a randomized experiment to test this hypothesis. A subsample of 46 families with 5-year-old children from a multisite randomized trial who participated in the feedback session of the Family Check-Up (FCU) intervention were selected. We randomly assigned FCU feedback sessions to be rated for fidelity to the protocol using the COACH rating system either after the coder reviewed the results of a recent ecological assessment or had not. Inter-rater reliability estimates of fidelity ratings were meaningfully higher for the assessment information condition compared to the no-information condition. Importantly, the reliability of the COACH mean score was found to be statistically significantly higher in the information condition. These findings suggest that the reliability of observational ratings of fidelity, particularly when the competence or quality of delivery is considered, could be improved by providing assessment data to the coders. Our findings might be most applicable to assessment-driven interventions, where assessment data explicitly guides therapist's selection of intervention strategies tailored to the family's context and needs, but they could also apply to other intervention programs and observational coding of context-dependent therapy processes, such as the working alliance.

Family check-up effects across diverse ethnic groups: reducing early-adolescence antisocial behavior by reducing family conflict.

Multicultural responsiveness and adaptation have been a recent area of emphasis in prevention and intervention science. The changing demographics of the United States demand the development of intervention strategies that are acceptable and effective for diverse cultural and ethnic groups. The Family Check-Up (FCU) was developed to be an intervention framework that is flexible and adaptive to diverse cultural groups (Dishion & Stormshak, 2007 ). We empirically evaluated the extent to which the intervention is effective for improving youth adjustment and parent-child interactions for diverse cultural groups. A sample of 1,193 families was drawn from 2 large-scale randomized prevention trials conducted in diverse urban middle schools. We formulated 3 groups on the basis of youth self-identification of ethnicity (European American, African American, Hispanic) and examined group differences in the hypothesized mediating effect of family conflict (FC) on later antisocial behavior (ASB). Path analysis revealed that youths in the intervention condition reported significantly less ASB over a 2-year period (Grades 6-8). Moreover, youth-reported reductions in FC at 12 months were an intervening effect. Ethnicity did not moderate this relationship. Consistent with one of the primary tenets of coercion theory, participation in the FCU acts on ASB through FC across diverse ethnic groups, lending support to the multicultural competence of the model. Limitations of this study are discussed, along with areas for future research.

A Systematic Review of Risk Factors for Intimate Partner Violence.

A systematic review of risk factors for intimate partner violence was conducted. Inclusion criteria included publication in a peer-reviewed journal, a representative community sample or a clinical sample with a control-group comparison, a response rate of at least 50%, use of a physical or sexual violence outcome measure, and control of confounding factors in the analyses. A total of 228 articles were included (170 articles with adult and 58 with adolescent samples). Organized by levels of a dynamic developmental systems perspective, risk factors included: (a) contextual characteristics of partners (demographic, neighborhood, community and school factors), (b) developmental characteristics and behaviors of the partners (e.g., family, peer, psychological/behavioral, and cognitive factors), and (c) relationship influences and interactional patterns. Comparisons to a prior review highlight developments in the field in the past 10 years. Recommendations for intervention and policy along with future directions for intimate partner violence (IPV) risk factor research are presented.

Outness and relationship satisfaction in same-gender couples.

Self-disclosure of sexual orientation, or outness, is a fundamental feature of gay, lesbian, and bisexual (GLB) experience, yet little is known about how outness impacts same-gender relationship satisfaction. Through a qualitative analysis of interviews with 15 same-gender couples, the complexities of navigating a stigmatized identity in a homonegative society emerged, including (a) characteristics of outness, (b) the influence of coupling on an individual's outness, and (c) the impact of outness on same-gender relationship satisfaction. Findings suggest that for GLB persons, outness is a developmental skill, an expression of identity and values, as well as a resilience strategy for managing discrimination and gay-related stress that influences, though does not singularly determine, relationship satisfaction. Implications for clinical practice and future research suggestions are presented.