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1.
Proc Natl Acad Sci U S A ; 120(39): e2306732120, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37722059

RESUMO

How do human beings make sense of their relation to the world and realize their ability to effect change? Applying modern concepts and methods of coordination dynamics, we demonstrate that patterns of movement and coordination in 3 to 4-mo-olds may be used to identify states and behavioral phenotypes of emergent agency. By means of a complete coordinative analysis of baby and mobile motion and their interaction, we show that the emergence of agency can take the form of a punctuated self-organizing process, with meaning found both in movement and stillness.


Assuntos
Movimento , Lactente , Humanos , Movimento (Física)
2.
Child Psychiatry Hum Dev ; 54(4): 1152-1166, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35113301

RESUMO

Mindfulness meditation is a means of increasing awareness of the present moment. Mindfulness Mediation Interventions (MMI) positively impact psychological functioning, yet the neurocognitive mechanisms that mediate these effects have been less well-defined. Here, the primary aim was to evaluate whether the effects of a 10-week MMI were mediated by changes in attention and creativity performance, as well as resting-state theta/beta (TB) ratio and alpha power. We also sought to determine whether any of these measures at baseline were predictive of mindfulness success, as rated by the 7-11-year-old participants and their teachers. Reductions in depression from pre-to-post were mediated by reductions in TB ratio and increases in alpha power; however, they were not mediated by attention/creativity changes. Higher baseline attention and creativity scores predicted enhanced mindfulness success post-intervention but notably, follow-up analyses revealed that those scoring lower on these measures were more likely to have reduced depression from pre-to-post.


Assuntos
Transtornos Mentais , Atenção Plena , Humanos , Criança , Atenção , Eletroencefalografia
3.
J Pediatr Psychol ; 47(7): 795-803, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35278071

RESUMO

OBJECTIVE: Both youth self-regulation and quality of parental involvement have been associated with blood glucose levels (HbA1c) of youth with type 1 diabetes mellitus (T1DM). However, it is unclear whether and how youth and parental factors interact in their relation to youth HbA1c. The differential susceptibility hypothesis proposes that youth with high negative affectivity (NA) and low effortful control (EC) may be more susceptible to the deleterious impact of lower quality parenting behaviors but also reap greater benefit from higher quality parenting behaviors. This study investigated whether youth temperament would moderate the link between diabetes-specific parental assistance (e.g., checking blood sugar) or support (e.g., encouraging, praising) and HbA1c among youth with T1DM. METHODS: Primary caregivers of youth with T1DM (N = 101; M age = 12.02, SD = 2.43) completed surveys on diabetes-specific parental involvement and youth temperament. Medical information (i.e., HbA1c) was obtained from chart review. RESULTS: Multiple regression analyses indicated that youth NA and EC significantly interacted with parental assistance, but not support. Specifically, higher parental assistance was associated with higher HbA1c among youth with high NA or high EC. High assistance was only linked to lower HbA1c for youth with low NA. CONCLUSIONS: Results suggest that optimal levels of parental involvement related to better T1DM outcomes depend on youth's NA or EC. Consistent with the goodness-of-fit framework, when parenting approaches match youth's temperament, youth with T1DM may be better able to maintain lower HbA1c. Family interventions for pediatric T1DM management may take into consideration youth temperament.


Assuntos
Diabetes Mellitus Tipo 1 , Adolescente , Criança , Diabetes Mellitus Tipo 1/terapia , Hemoglobinas Glicadas/análise , Humanos , Pais , Temperamento , Resultado do Tratamento
4.
Neuropsychobiology ; 80(2): 158-175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33461198

RESUMO

BACKGROUND: While numerous studies have demonstrated maternal depression's influence on infant brain development, few studies have examined the changes that occur as a consequence of co-occurring experiential factors that affect quality of mother and infant affectionate touch as well as infant temperament and neurophysiological systems. The aim of the study was to examine the interactive effects of maternal depression and breastfeeding on mother and infant affectionate touch and infant temperament and cortical maturation patterns across early development. METHODS: 113 mothers and their infants participated when infants were 1 and 3 months of age. Questionnaires to assess maternal depressive symptoms, feeding, and temperament were completed. Tonic EEG patterns (asymmetry and left and right activity) were collected and the dyads were video-recorded during feeding to assess mother and infant affectionate touch patterns. RESULTS: Data analysis showed that EEG activity and mother-infant affectionate touch differed as a function of mood and feeding method. Notably, only infants of depressed mothers that bottle-fed showed right frontal EEG asymmetry and attenuated change in the left frontal region across 3 months. Breastfeeding positively impacted affectionate touch behaviors and was associated with increased left and decreased right frontal EEG activation even for depressed groups. Furthermore, a model incorporating physiology, maternal depression, touch, temperament, and feeding indicated significant prediction for infant affectionate touch (with breastfeeding and affectively positive temperament demonstrating the strongest prediction). Con-clusion: The findings suggest that breastfeeding and the infant's positive temperament influence mother-infant affectionate touch patterns and result in neuroprotective outcomes for infants, even those exposed to maternal depression within early development.


Assuntos
Afeto/fisiologia , Alimentação com Mamadeira , Aleitamento Materno , Desenvolvimento Infantil/fisiologia , Filho de Pais com Deficiência , Depressão/fisiopatologia , Lobo Frontal/fisiologia , Relações Mãe-Filho , Temperamento/fisiologia , Tato/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
5.
Issues Ment Health Nurs ; 41(7): 637-644, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32243211

RESUMO

Women with perinatal depression have an increased risk for breastfeeding cessation, yet few studies have explored their lived experience. In this qualitative study, semistructured interviews were conducted with a purposeful sample of women (N = 10) who self-reported perinatal depression. Using Giorgi's descriptive phenomenological method of data analysis, five components were found to embody their lived experience of breastfeeding: (a) choosing selflessness, (b) harboring inadequacy, (c) deliberate persevering, (d) discerning meaning, and (e) cherishing intimacy. Findings contribute to understanding the experience of breastfeeding for this population and could provide guidance to improve lactation management and perinatal mental health education for nurses.


Assuntos
Aleitamento Materno/psicologia , Depressão/psicologia , Adulto , Feminino , Humanos , Gravidez , Pesquisa Qualitativa , Inquéritos e Questionários
6.
Am J Public Health ; 109(S1): S48-S55, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30699022

RESUMO

Reducing health disparities requires an understanding of the mechanisms that generate disparities. Life course approaches to health disparities leverage theories that explain how socially patterned physical, environmental, and socioeconomic exposures at different stages of human development shape health within and across generations and can therefore offer substantial insight into the etiology of health disparities. Life course approaches are informed by developmental and structural perspectives. Developmental perspectives emphasize how socially patterned exposures to risk factors during sensitive life stages shift health trajectories, whereas structural perspectives emphasize how social identity and position within socially patterned environments disproportionately allocate risk factors and resources, resulting in altered health trajectories. We conclude that the science of health disparities will be advanced by integrating life course approaches into etiologic and intervention research on health disparities. The following 4 strategies are offered to guide in this process: (1) advance the understanding of multiple exposures and their interactions, (2) integrate life course approaches into the understanding of biological mechanisms, (3) explore transgenerational transmission of health disparities, and (4) integrate life course approaches into health disparities interventions.


Assuntos
Disparidades em Assistência à Saúde , Acontecimentos que Mudam a Vida , Meio Social , Fatores Socioeconômicos , Humanos , Fatores de Risco
7.
Child Psychiatry Hum Dev ; 50(4): 661-667, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30756220

RESUMO

This study examined socio-emotional skills, utilizing a facial emotion recognition (FER) task featuring unfamiliar and familiar faces, in children with autism spectrum disorders (ASD) compared to typically developing (TD) children. Results showed that the TD children were more proficient on the FER overall whereas ASD children recognized familiar expressions more precisely than unfamiliar ones. Further, ASD children did not differ from TD children in recognizing happy expressions but ASD children were less skilled with recognizing negative expressions. Findings suggest that ASD children possess more adept FER abilities than previously thought especially for important social others. Ultimately, a task featuring an array of positive and negative familiar and unfamiliar expressions may provide a more comprehensive assessment of socio-emotional abilities in ASD children.


Assuntos
Inteligência Emocional , Expressão Facial , Reconhecimento Facial , Adolescente , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/psicologia , Criança , Desenvolvimento Infantil , Emoções , Feminino , Felicidade , Humanos , Masculino
8.
Appl Psychophysiol Biofeedback ; 40(4): 269-76, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26159768

RESUMO

Previous studies have examined sex differences in physiological responding, including respiratory sinus arrhythmia (RSA) reactivity in response to changing stimulus conditions involving situation specific or gender related cues, in children and adolescents. The present study examined whether RSA reactivity moderates the relation between aggression and internalizing symptoms and whether there are sex differences in this effect. Participants were 82 adolescents (M age = 12.1 years; 44 girls) from the general middle-school population. Peer nominations assessed aggression and internalizing symptoms, and RSA reactivity (defined as change in RSA from baseline to task) was recorded while participants anticipated and responded to an 85 dB signaled white-noise burst. For girls, internalizing symptoms were associated with aggression only if girls showed low RSA reactivity from baseline to task; there was no effect for boys. This association was absent when girls showed high RSA reactivity. Thus, child sex appears to influence not only levels of physiological responding but also relations of physiological responding to comorbidity of adjustment problems.


Assuntos
Comportamento do Adolescente/fisiologia , Agressão/fisiologia , Comportamento Problema , Arritmia Sinusal Respiratória/fisiologia , Adolescente , Criança , Feminino , Humanos , Masculino , Grupo Associado , Fatores Sexuais
10.
Top Stroke Rehabil ; 21(6): 510-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25467399

RESUMO

BACKGROUND AND OBJECTIVE: Intensive poststroke rehabilitation is critical to maximizing outcomes, improving inpatient flow, and decreasing long-term costs. This regional initiative investigated the impact of improving access to timely intensive home-based stroke rehabilitation follow-up care on hospital length of stay (LOS) and readmission rates. The enhanced service was made available across the region's rural geography to new stroke survivors transitioning home who were unable to access outpatient care. METHODS: All new stroke survivors with ongoing rehabilitation needs being discharged from the hospital and eligible for home care received timely enhanced intensity of home-based rehabilitation services from existing community rehabilitation providers for 2 months after discharge. Five hundred twenty-four stroke survivors received this service over a 3-year period. The service priority rating was increased to reduce wait times to less than 5 days. Collaborative planning across sectors occurred through discharge link meetings. Comparative analysis was used to investigate health system measures before and after service implementation. RESULTS: A 15.7-day decrease in hospital LOS and decreased hospital readmission rates were observed after enhanced service implementation. Functional Independence Measure (FIM) efficiency improved for those discharged from inpatient rehabilitation. Average wait time for community rehabilitation services decreased from 44 days to 4.4 days. The mean total number of community therapy visits more than doubled to an average of 12 per client. CONCLUSION: The provision of timely more intensive home-based rehabilitation services for new stroke survivors transitioning home and unable to access outpatient care was associated with decreased hospital LOS and decreased readmission rates.


Assuntos
Centros Comunitários de Saúde , Avaliação de Resultados em Cuidados de Saúde , Alta do Paciente , Modalidades de Fisioterapia , Centros de Reabilitação , Reabilitação do Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Terapia Ocupacional , Readmissão do Paciente , Encaminhamento e Consulta , Serviço Social , Patologia da Fala e Linguagem , Sobreviventes
11.
Sci Rep ; 14(1): 15580, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971875

RESUMO

A recent experiment probed how purposeful action emerges in early life by manipulating infants' functional connection to an object in the environment (i.e., tethering an infant's foot to a colorful mobile). Vicon motion capture data from multiple infant joints were used here to create Histograms of Joint Displacements (HJDs) to generate pose-based descriptors for 3D infant spatial trajectories. Using HJDs as inputs, machine and deep learning systems were tasked with classifying the experimental state from which snippets of movement data were sampled. The architectures tested included k-Nearest Neighbour (kNN), Linear Discriminant Analysis (LDA), Fully connected network (FCNet), 1D-Convolutional Neural Network (1D-Conv), 1D-Capsule Network (1D-CapsNet), 2D-Conv and 2D-CapsNet. Sliding window scenarios were used for temporal analysis to search for topological changes in infant movement related to functional context. kNN and LDA achieved higher classification accuracy with single joint features, while deep learning approaches, particularly 2D-CapsNet, achieved higher accuracy on full-body features. For each AI architecture tested, measures of foot activity displayed the most distinct and coherent pattern alterations across different experimental stages (reflected in the highest classification accuracy rate), indicating that interaction with the world impacts the infant behaviour most at the site of organism~world connection.


Assuntos
Inteligência Artificial , Humanos , Lactente , Movimento/fisiologia , Feminino , Masculino , Aprendizado Profundo , Conscientização/fisiologia , Redes Neurais de Computação , Meio Ambiente
12.
Am J Prev Med ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971453

RESUMO

INTRODUCTION: Social determinants of health (SDOH) contribute to differences in health outcomes and exacerbate health disparities. This study characterizes the National Institute on Minority Health and Health Disparities' (NIMHD) portfolio of funded grants in SDOH research, identifies gaps, and provides suggestions for future research. METHODS: Using the National Institutes of Health's SDOH Research, Condition, and Disease Categorization, research projects funded from 2019 to 2023 were identified and linked with NIMHD's internal coding system to extract in-depth study characteristics, including sociodemographics of study participants, disease and condition focus, and alignment with strategic priorities. Natural Language Processing methods were used to categorize projects into five Healthy People 2030 SDOH domains. RESULTS: The resulting sample included 675 unique research projects. Most projects included racial and ethnic minority groups (89%), followed by people with lower socioeconomic status (33%), underserved rural communities (16%), and sexual and gender minority groups (13%). Most projects focused on the Etiology of health disparities (61%), followed by Interventions (54%), and Methods and Measurement (39%). Of the Healthy People 2030 domains, Social and Community Context had the greatest representation (61%) whereas Education Access and Quality had the least (6%). Variation in research project characteristics across SDOH domains is also presented. CONCLUSIONS: This study documents characteristics of SDOH research funded by NIMHD and explores how they differ across Healthy People 2030 SDOH domains. Findings highlight how study characteristics and foci align with strategic priorities and suggest opportunities for future research.

13.
Curr Protoc ; 4(3): e977, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38441413

RESUMO

Health disparities are driven by unequal conditions in the environments in which people are born, live, learn, work, play, worship, and age, commonly termed the Social Determinants of Health (SDoH). The availability of recommended measurement protocols for SDoH will enable investigators to consistently collect data for SDoH constructs. The PhenX (consensus measures for Phenotypes and eXposures) Toolkit is a web-based catalog of recommended measurement protocols for use in research studies with human participants. Using standard protocols from the PhenX Toolkit makes it easier to compare and combine studies, potentially increasing the impact of individual studies, and aids in comparability across literature. In 2018, the National Institute on Minority Health and Health Disparities provided support for an initial expert Working Group to identify and recommend established SDoH protocols for inclusion in the PhenX Toolkit. In 2022, a second expert Working Group was convened to build on the work of the first SDoH Working Group and address gaps in the SDoH Toolkit Collections. The SDoH Collections consist of a Core Collection and Individual and Structural Specialty Collections. This article describes a Basic Protocol for using the PhenX Toolkit to select and implement SDoH measurement protocols for use in research studies. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. Basic Protocol: Using the PhenX Toolkit to select and implement SDoH protocols.


Assuntos
Academias e Institutos , Determinantes Sociais da Saúde , Humanos , Consenso , Estudos Epidemiológicos , Empregados do Governo
14.
Res Sq ; 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37503229

RESUMO

Can infant exploration and causal discovery be detected using Artificial Intelligence (AI)? A recent experiment probed how purposeful action emerges in early life by manipulating infants' functional connection to an object in the environment (i.e., tethering one foot to a colorful mobile). Vicon motion capture data from multiple infant joints were used here to create Histograms of Joint Displacements (HJDs) to generate pose-based descriptors for 3D infant spatial trajectories. Using HJDs as inputs, machine and deep learning systems were tasked with classifying the experimental state from which snippets of movement data were sampled. The architectures tested included k-Nearest Neighbour (kNN), Linear Discriminant Analysis (LDA), Fully connected network (FCNet), 1D-Convolutional Neural Network (1D-Conv), 1D-Capsule Network (1D-CapsNet), 2D-Conv and 2D-CapsNet. Sliding window scenarios were used for temporal analysis to search for topological changes in infant movement related to functional context. kNN and LDA achieved higher classification accuracy with single joint features, while deep learning approaches, particularly 2D-CapsNet, achieved higher accuracy on full-body features. For each AI architecture tested, measures of foot activity displayed the most distinct and coherent pattern alterations across different experimental stages (reflected in the highest classification accuracy rate), indicating that interaction with the world impacts the infant behaviour most at the site of organism∼world connection. Pairing theory-driven experimentation with AI tools thus opens a path to developing functionally-relevant assessments of infant behaviour that are likely to be useful in clinical settings.

15.
Front Pharmacol ; 14: 1341746, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38318312

RESUMO

Rett syndrome (RTT) is rare neurodevelopmental disorder caused by mutations in the MECP2 gene that encodes methyl-CpG-binding protein 2 (MeCP2), a DNA-binding protein with roles in epigenetic regulation of gene expression. Functional loss of MeCP2 results in abnormal neuronal maturation and plasticity, characterized by loss of verbal communication and loss of fine and gross motor function, among others. Trofinetide, a synthetic analog of glycine-proline-glutamate, was approved by the US Food and Drug Administration for the treatment of RTT in adult and pediatric patients aged 2 years and older. Here, we present the development of trofinetide from bench research to clinical studies and emphasize how the collaboration between academia, the pharmaceutical industry, and patient advocacy led to the recent approval. The bench-to-bedside development of trofinetide underscores the value of collaboration between these groups in the development and approval of treatments for rare diseases.

16.
Am J Prev Med ; 65(3): 534-542, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36935055

RESUMO

INTRODUCTION: Social determinants are structures and conditions in the biological, physical, built, and social environments that affect health, social and physical functioning, health risk, quality of life, and health outcomes. The adoption of recommended, standard measurement protocols for social determinants of health will advance the science of minority health and health disparities research and provide standard social determinants of health protocols for inclusion in all studies with human participants. METHODS: A PhenX (consensus measures for Phenotypes and eXposures) Working Group of social determinants of health experts was convened from October 2018 to May 2020 and followed a well-established consensus process to identify and recommend social determinants of health measurement protocols. The PhenX Toolkit contains data collection protocols suitable for inclusion in a wide range of research studies. The recommended social determinants of health protocols were shared with the broader scientific community to invite review and feedback before being added to the Toolkit. RESULTS: Nineteen social determinants of health protocols were released in the PhenX Toolkit (https://www.phenxtoolkit.org) in May 2020 to provide measures at the individual and structural levels for built and natural environments, structural racism, economic resources, employment status, occupational health and safety, education, environmental exposures, food environment, health and health care, and sociocultural community context. CONCLUSIONS: Promoting the adoption of well-established social determinants of health protocols can enable consistent data collection and facilitate comparing and combining studies, with the potential to increase their scientific impact.


Assuntos
Qualidade de Vida , Determinantes Sociais da Saúde , Humanos , Fenótipo , Coleta de Dados , Projetos de Pesquisa
17.
Appl Neuropsychol Child ; 11(3): 455-470, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33605177

RESUMO

The study examined the relationship between anxiety, inhibitory control (IC), and resting-state electroencephalography (EEG) in a critical age-range for social and emotional development (8-12-year-olds). The participants were assigned to 4 weeks of either an emotional IC training program, a neutral IC training program, or a waitlisted control, and were tested using cognitive, emotional, and EEG measures. The training was computerized and completed remotely. At baseline, IC accuracy scores were negatively related to both anxiety and depression levels (N = 42). Additionally, increased right lateral frontal alpha asymmetry was predictive of increased anxiety/depression scores. A series of multivariate analyses of covariance and post-hoc tests were conducted to compare effects in the participants that completed the full 16 sessions of training (N = 32). Overall the emotional and neutral training conditions showed similar improvements in IC accuracy, as well as reductions in anxiety compared to the waitlist condition. Minimal neurophysiological changes occurred from pre-to-post; however, lateral frontal asymmetry shifted leftward in the emotional training group. These findings highlight the potential of computerized IC training for mitigating negative emotional functioning in preadolescents. Future research is necessary to determine the long-term effects of IC training and whether longer training intervals facilitate persisting impacts.


Assuntos
Transtornos de Ansiedade , Ansiedade , Depressão , Eletroencefalografia , Humanos , Estudantes
18.
J Dev Behav Pediatr ; 43(9): e598-e604, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35976702

RESUMO

OBJECTIVE: Positive parenting (e.g., parental warmth, mindful parenting) has been posited to promote effective pediatric type 1 diabetes mellitus (T1DM) management. This promotive effect may partly be conferred by fostering child self-regulatory development, such as executive function (EF). However, no research has examined whether better child EF serves as a mechanism underlying associations between positive parenting and child blood glucose levels (HbA1c). Moreover, it is unclear whether mindful parenting offers a unique benefit beyond that of parental warmth-a key pillar of effective parental involvement in T1DM management. METHODS: Primary caregivers of children with T1DM (N = 101; Mage = 12.02) reported on parenting behaviors and child EF. Children's medical information was obtained through chart review. Path analysis was used to examine direct and indirect relations in the cross-sectional data. RESULTS: The path analysis indicated that only parental warmth, not mindful parenting, was significantly associated with lower HbA1c. Both parental warmth and mindful parenting were significantly related to better child EF, but child EF did not mediate the associations between parenting and HbA1c. CONCLUSION: Parental warmth may constitute a key parenting behavior promoting effective pediatric T1DM management. Enhancing parental warmth may be an important target of interventions aiming to improve HbA1c. Although child EF was unrelated to HbA1c in this sample, given positive associations between parental warmth and mindfulness and child EF, longitudinal research is warranted to examine whether these positive parenting behaviors may confer long-term benefits for T1DM self-management through improved EF.


Assuntos
Diabetes Mellitus Tipo 1 , Atenção Plena , Criança , Humanos , Diabetes Mellitus Tipo 1/terapia , Função Executiva , Estudos Transversais , Hemoglobinas Glicadas , Poder Familiar , Pais , Relações Pais-Filho
19.
Contemp Clin Trials ; 114: 106704, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35149233

RESUMO

INTRODUCTION: Rett syndrome (RTT) is a debilitating neurodevelopmental disorder with no approved treatments. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of insulin-like growth factor 1. In a phase 2, placebo-controlled trial in 82 females with RTT aged 5-15 years, a significant (p ≤ 0.042) improvement over placebo was observed with the highest trofinetide dose (200 mg/kg twice daily [BID]) on three measures: Rett Syndrome Behaviour Questionnaire (RSBQ), Clinical Global Impression-Improvement (CGI-I), and RTT-Clinician Domain Specific Concerns-Visual Analog Scale (RTT-DSC-VAS). Trofinetide was well tolerated at all doses (50, 100, and 200 mg/kg BID). A phase 3 trial utilizing disease-specific and novel scales was designed to investigate the efficacy and safety of trofinetide in girls and women with RTT. METHODS: This 12-week, double-blind, randomized, placebo-controlled study (LAVENDER; NCT04181723) will evaluate trofinetide in 187 females, aged 5-20 years, with RTT. Co-primary endpoints are the RSBQ and CGI-I scales. Clinical domains of the CGI-I include communication, ambulation, hand use, seizures, attentiveness, and social (eye contact) and autonomic (breathing) aspects. Secondary endpoints will leverage four novel RTT-specific clinician ratings (derived from the RTT-DSC-VAS) of hand function, ambulation, ability to communicate, and verbal communication, and existing scales, to evaluate other core symptoms of RTT, quality of life and caregiver burden. A 40-week, open-label extension study will follow. DISCUSSION: This study was designed using disease-specific scales optimized to demonstrate changes in core symptoms of RTT and may provide the first phase 3 data demonstrating drug efficacy in individuals with RTT. TRIAL REGISTRATION: Clinicaltrials.govNCT04181723.


Assuntos
Síndrome de Rett , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Glutamatos , Humanos , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Síndrome de Rett/tratamento farmacológico
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