Cargando…

Top Caregiver Concerns in Rett syndrome and related disorders: data from the US Natural History Study

OBJECTIVE: Recent advances in the understanding of neurodevelopmental disorders such as Rett syndrome (RTT) has enabled development of novel therapeutic approaches that are currently undergoing clinical evaluation or are proposed to move into clinical development. Clinical trial success depends on o...

Descripción completa

Detalles Bibliográficos
Autores principales: Neul, Jeffrey Lorenz, Benke, Timothy A., Marsh, Eric D., Suter, Bernhard, Silveira, Lori, Fu, Cary, Peters, Sarika U., Percy, Alan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055548/
https://www.ncbi.nlm.nih.gov/pubmed/36993737
http://dx.doi.org/10.21203/rs.3.rs-2566253/v1
_version_ 1785015898038337536
author Neul, Jeffrey Lorenz
Benke, Timothy A.
Marsh, Eric D.
Suter, Bernhard
Silveira, Lori
Fu, Cary
Peters, Sarika U.
Percy, Alan K.
author_facet Neul, Jeffrey Lorenz
Benke, Timothy A.
Marsh, Eric D.
Suter, Bernhard
Silveira, Lori
Fu, Cary
Peters, Sarika U.
Percy, Alan K.
author_sort Neul, Jeffrey Lorenz
collection PubMed
description OBJECTIVE: Recent advances in the understanding of neurodevelopmental disorders such as Rett syndrome (RTT) has enabled development of novel therapeutic approaches that are currently undergoing clinical evaluation or are proposed to move into clinical development. Clinical trial success depends on outcome measures that assess clinical features that are most impactful for affected individuals. To determine the top concerns in RTT and RTT-related disorders we asked caregivers to list the top clinical concerns in order to gain information to guide the development and selection of outcome measures for future clinical trials. METHODS: Caregivers of participants enrolled in the US Natural History Study of RTT and related disorders were asked to identify the top 3 concerning problems impacting the affected participant. We generated a weighted list of top caregiver concerns for each of the diagnostic categories and compared results between the disorders. Further, for Classic RTT, caregiver concerns were analyzed by age, clinical severity, and common RTT-causing mutations in MECP2. RESULTS: The top caregiver concerns for Classic RTT were effective communication, seizures, walking/balance issues, lack of hand use, and constipation. The rank order of the frequency of the top caregiver concerns for Classic RTT varied by age, clinical severity, and specific mutations, consistent with known variation in the frequency of clinical features across these domains. The frequency of caregiver concern for seizures, hand use, and spoken language increased in relation to clinician assessed severity in these clinical domains, showing consistency between clinician assessments and caregiver concerns. Comparison across disorders found commonalities in the top caregiver concerns between Classic RTT, Atypical RTT, MECP2 Duplication Syndrome, CDKL5 Deficiency Disorder, and FOXG1 Syndrome; however, distinct differences in caregiver concerns between these disorders are consistent with the relative prevalence and impact of specific clinical features. CONCLUSION: The top caregiver concerns for individuals with RTT and the RTT-related disorders reflect the impact of the primary clinical symptoms of these disorders. This work is critical in the development of meaningful therapies, as optimal therapy should address these concerns. Further, outcome measures to be utilized in clinical trials should assess these clinical issues identified as most concerning by caregivers.
format Online
Article
Text
id pubmed-10055548
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Journal Experts
record_format MEDLINE/PubMed
spelling pubmed-100555482023-03-30 Top Caregiver Concerns in Rett syndrome and related disorders: data from the US Natural History Study Neul, Jeffrey Lorenz Benke, Timothy A. Marsh, Eric D. Suter, Bernhard Silveira, Lori Fu, Cary Peters, Sarika U. Percy, Alan K. Res Sq Article OBJECTIVE: Recent advances in the understanding of neurodevelopmental disorders such as Rett syndrome (RTT) has enabled development of novel therapeutic approaches that are currently undergoing clinical evaluation or are proposed to move into clinical development. Clinical trial success depends on outcome measures that assess clinical features that are most impactful for affected individuals. To determine the top concerns in RTT and RTT-related disorders we asked caregivers to list the top clinical concerns in order to gain information to guide the development and selection of outcome measures for future clinical trials. METHODS: Caregivers of participants enrolled in the US Natural History Study of RTT and related disorders were asked to identify the top 3 concerning problems impacting the affected participant. We generated a weighted list of top caregiver concerns for each of the diagnostic categories and compared results between the disorders. Further, for Classic RTT, caregiver concerns were analyzed by age, clinical severity, and common RTT-causing mutations in MECP2. RESULTS: The top caregiver concerns for Classic RTT were effective communication, seizures, walking/balance issues, lack of hand use, and constipation. The rank order of the frequency of the top caregiver concerns for Classic RTT varied by age, clinical severity, and specific mutations, consistent with known variation in the frequency of clinical features across these domains. The frequency of caregiver concern for seizures, hand use, and spoken language increased in relation to clinician assessed severity in these clinical domains, showing consistency between clinician assessments and caregiver concerns. Comparison across disorders found commonalities in the top caregiver concerns between Classic RTT, Atypical RTT, MECP2 Duplication Syndrome, CDKL5 Deficiency Disorder, and FOXG1 Syndrome; however, distinct differences in caregiver concerns between these disorders are consistent with the relative prevalence and impact of specific clinical features. CONCLUSION: The top caregiver concerns for individuals with RTT and the RTT-related disorders reflect the impact of the primary clinical symptoms of these disorders. This work is critical in the development of meaningful therapies, as optimal therapy should address these concerns. Further, outcome measures to be utilized in clinical trials should assess these clinical issues identified as most concerning by caregivers. American Journal Experts 2023-03-20 /pmc/articles/PMC10055548/ /pubmed/36993737 http://dx.doi.org/10.21203/rs.3.rs-2566253/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Neul, Jeffrey Lorenz
Benke, Timothy A.
Marsh, Eric D.
Suter, Bernhard
Silveira, Lori
Fu, Cary
Peters, Sarika U.
Percy, Alan K.
Top Caregiver Concerns in Rett syndrome and related disorders: data from the US Natural History Study
title Top Caregiver Concerns in Rett syndrome and related disorders: data from the US Natural History Study
title_full Top Caregiver Concerns in Rett syndrome and related disorders: data from the US Natural History Study
title_fullStr Top Caregiver Concerns in Rett syndrome and related disorders: data from the US Natural History Study
title_full_unstemmed Top Caregiver Concerns in Rett syndrome and related disorders: data from the US Natural History Study
title_short Top Caregiver Concerns in Rett syndrome and related disorders: data from the US Natural History Study
title_sort top caregiver concerns in rett syndrome and related disorders: data from the us natural history study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055548/
https://www.ncbi.nlm.nih.gov/pubmed/36993737
http://dx.doi.org/10.21203/rs.3.rs-2566253/v1
work_keys_str_mv AT neuljeffreylorenz topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy
AT benketimothya topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy
AT marshericd topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy
AT suterbernhard topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy
AT silveiralori topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy
AT fucary topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy
AT peterssarikau topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy
AT percyalank topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy
AT topcaregiverconcernsinrettsyndromeandrelateddisordersdatafromtheusnaturalhistorystudy