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Background: Cutaneous neurofibromas (cNF) are considered one of the highest burdens of neurofibromatosis type 1 (NF1). To date, no medical treatment can cure cNF or prevent their development. In that context, there is an urgent need to prepare and standardize the methodology of future trials targeting cNF., Objectives: The objective was to develop a core outcome domain set suitable for all clinical trials targeting NF1-associated cNF., Methods: The validated approach of this work consisted of a three-phase methodology: (i) generating the domains [systematic literature review (SLR) and qualitative studies]; (ii) agreeing (three-round international e-Delphi consensus process and working groups); and (iii) voting., Results: (i) The SLR and the qualitative studies (three types of focus groups and a French e-survey with 234 participants) resulted in a preliminary list of 31 candidate items and their corresponding definitions. (ii) A total of 229 individuals from 29 countries participated in the first round of the e-Delphi process: 71 patients, relatives or representatives (31.0%), 130 healthcare professionals (HCPs, 56.8%) and 28 researchers, representatives of a drug regulatory authority, industry or pharmaceutical company representatives or journal editors (12.2%). The overall participation rate was 74%. After round 2, five candidate items were excluded. Between rounds 2 and 3, international workshops were held to better understand the disagreements among stakeholders. This phase led to the identification of 19 items as outcome subdomains. (iii) The items were fused to create four outcome domains ('clinical assessment', 'daily life impact', 'patient satisfaction' and 'perception of health') and prioritized. The seven items that did not reach consensus were marked for the research agenda. The final core outcome domain set reached 100% of the votes of the steering committee members., Conclusions: Although numerous outcomes can be explored in studies related to cNF in NF1, the present study offers four outcome domains that should be reported in all trial studies, agreed on by international patients, relatives and representatives of patients; HCPs; researchers, representatives of drug regulatory authorities or pharmaceutical companies and journal editors. The next step will include the development of a set of core outcome measurement instruments to further standardize how these outcomes should be assessed., Competing Interests: Conflicts of interest L.F. is a consultant for Alexion. K.S. is a member of the scientific advisory board of NFlection Therapeutics. S.R.P. is co-founder of NFlection Therapeutics and NF2 Therapeutics, serves on the scientific advisory board of SonALAsense and consults for Akouos. A.J. is a consultant for Alexion. P.W. is a consultant for Alexion, AstraZeneca and Springworks. The other authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cutaneous neurofibromas (cNF) contribute to the impairment of QOL in individuals with neurofibromatosis 1. The cNF-Skindex, validated in a French population, specifically assesses the cNF-related QOL. In this study, we first defined severity strata using an anchoring approach on the basis of patient's burden. In total, 209 patients answered the anchor question and the cNF-Skindex. We tested the agreement among the three strata, generated by all potential couples of cut-off values of the cNF-Skindex and the three strata defined in the anchor question. The cut-off values 12 and 49 provided the highest Kappa value (κ = 0.685, 95% confidence interval = 0.604-0.765). Second, we validated the score and the strata in a United States population using the answers provided by 220 French and 148 United States adults. In the multivariable linear regression analysis, the country of origin was not a factor associated with the score (P = 0.297). The number of cNF along the different severity strata was similar between the French and the United States populations. In conclusion, stratification constitutes a powerful tool to better interpret the cNF-Skindex in daily practice and in clinical trials. This study validates its use in two populations that together constitute a large cohort of patients willing to participate in clinical research., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cutaneous neurofibromas (cNF), present in 95% of individuals with neurofibromatosis 1 (NF1), are considered as one of the greatest medical burden because of physical disfigurement. No specific score evaluates their impact on quality of life (QoL)., Objective: To develop a specific score assessing cNF-related QoL., Methods: Through a multidisciplinary workshop including 10 patients, 3 expert-in-NF1 physicians, 3 health care workers (nurses and psychologist) and 1 methodologist, the French version of the Skindex-16 was modified by adding 3 items. The new cNF-Skindex was validated among patients with NF1 recruited in the ComPaRe online cohort, in France (N = 284). Construct validity was assessed by comparing it with the EQ-5D-5L, its visual analogue scale and the MYMOP2 and by assessing its association with patients' characteristics. Reliability was assessed by a test-retest. An English version of the tool was developed using a back-forward translation., Results: A total of 228 individuals with NF1, with cNF answered the 19-item questionnaire. These items fitted into 3 domains: emotions, symptoms, functioning. One was dropped during analysis because >90% responders were not concerned. The cNF-Skindex significantly correlated with the EQ-5D-5L (N = 193) and MYMOP2 (N = 210) indicating good external validity: rs 0.38 (P < 0.001), and 0.58 (P < 0.001), respectively. Having >50 cNF was the only independent variable associated with the total score cNF-Skindex (β = 15.88, 95%CI 6.96-24.81, P = 0.001), and with the 3 sub-scores: 'functioning' (β = 2.65, 95%CI 0.71-4.59, P = 0.008), 'emotions' (β = 17.03, 95%CI 4.11-29.96, P = 0.010) and 'symptoms' (β = 3.90, 95%CI 1.95-5.85, P < 0.001). Test-retest reliability (N = 133) found an ICC at 0.96 demonstrating good reproducibility., Conclusion: The cNF-Skindex demonstrated excellent psychometric properties. The global and sub-scores were increased with higher number of cNF arguing for its use in further trials aiming to reduce their number or prevent their development. Cross-cultural validation and evaluation of its responsiveness are the next steps., (© 2022 European Academy of Dermatology and Venereology.)

Background: Neurofibromatosis Type 1 (NF1) is a common genetic neurocutaneous disease, with an autosomal dominant inheritance mode. Quality of life has been shown impaired in NF1, due to severe complications, cosmetic features, and uncertainty about the disorder., Methods: This study sought to develop a self-administered questionnaire in French to assess the burden of NF1 (BoN), then translate and linguistically and cross-culturally validate it into American English, standardized methodology applied, as outlined in the report., Results: Based on several discussions with NF1 patients, a 17-item conceptual questionnaire was first produced. Of the 91 NF1 adult patients who responded to the conceptual questionnaire, 65 (64.6% females) were accessible. Subsequent confirmatory analyses generated a 15-item questionnaire grouped into four domains, demonstrating internal consistency (Cronbach's alpha: 091), discriminant validity, and high reliability. The BoN was likewise shown to significantly correlate with other validated questionnaires, such as Dermatology Life Quality Index, Perceived Stress Scale, and SF12 mental score, indicating good external validity., Conclusions: BoN is a specific tool for assessing the burden that NF1 generates on many practical aspects of the patient daily activities, beyond the notion of quality of life". Given the increasing relevance that regulatory authorities attribute to patient-reported outcomes, the BoN questionnaire provides such supplementary information while accounting for the burden of NF1 patients in the broadest sense.

Background: The airways of adult or elderly asthmatics are likely candidates for airway remodeling, resulting in persistent airflow obstruction. This population can provide a good model for cross-sectional evaluation of the effect of asthma duration on airflow., Methods: We evaluated postbronchodilator airflow and lung volumes at baseline and after a short course of oral prednisone in a group of 42 never-smokers with persistent mild or moderate asthma aged 55 years or older. Patients were grouped as having short duration asthma (SDA, <14 years) or long duration asthma (LDA, > or =14 years) according to the median duration of the disease (14 years) of the sample., Results: There were no significant differences in patient characteristics or asthma severity indices between the groups. After a short course of prednisone, forced expiratory volume in 1 second (FEV1) and the ratio of FEV to forced vital capacity (FVC) were significantly higher for the SDA group. Only 3 patients presented persistent airflow limitation (FEV1/FVC% < 75%). An inverse correlation was demonstrated between duration of asthma and postbronchodilator FEV1 (% predicted) (r = -0.43, P = .01) and FEV1/FVC% (r = -0.50, P = .003)., Conclusion: Our data show a close relationship between duration of disease and loss of lung function, supporting the concept of asthma as a slow, progressive disease at least among those patients with a mild-to-moderate severity. Permanent airflow obstruction in mild or moderate asthma is unusual, but can occur in a small number suffering from the disease for years.