Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 79
Filtrar
1.
Alzheimers Dement (N Y) ; 10(2): e12467, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38698931

RESUMEN

INTRODUCTION: There are few widely-available, evidence-based options to support quality of life (QOL) for people living with Alzheimer's disease and related dementias. METHODS: We performed a randomized, controlled trial with a Waitlist control group to determine whether an online, livestream, mind-body, group movement program (Moving Together, 1 hour, 2 days/week, 12 weeks) improves QOL in people with cognitive impairment (PWCI) or care partners (CPs) and explore mechanisms of action. The primary outcome for both participants was self-reported QOL. Secondary outcomes and potential mediators included mobility, isolation, well-being, cognitive function, and sleep in PWCI and burden, positive emotions, caregiver self-efficacy, stress management, and sleep in CPs. Blinded assessors collected outcome data at baseline, 12, and 24 weeks. We assessed adverse events including falls through monthly check-in surveys and collected qualitative data through evaluation surveys. Intention-to-treat analyses used linear mixed models to compare mean change over time between groups and calculated standardized effect sizes (ESs). RESULTS: Ninety-seven dyads enrolled (PWCI: age 76 ± 11 years, 43% female, 80% non-Hispanic White; CPs: age 66 ± 12 years, 78% female, 71% non-Hispanic White); 15% withdrew before 12 weeks and 22% before 24 weeks. PWCI self-reported significantly better QOL from baseline to 12 weeks in the Moving Together group compared to the Waitlist group (ES = 0.474, p = 0.048) and CPs self-reported improved ability to manage stress (ES = 0.484, p = 0.021). Improvements in participant self-reported QOL were mediated by improvements in their self-reported well-being and CP-reported ability to manage stress. Results were similar when the Waitlist group participated in the program (QOL ES = 0.663, p = 0.006; stress management ES = 0.742, p = 0.002) and were supported by qualitative data. Exploratory analyses suggested possible fall reduction in PWCI. There were no study-related serious adverse events. DISCUSSION: Online programs such as Moving Together offer a scalable strategy for supporting high QOL for PWCI and helping CPs manage stress. TRIAL REGISTRATION: ClinicalTrials.gov NCT04621448. Highlights: The approval of new medications that slow cognitive decline in people living with Alzheimer's disease and related disorders (ADRD) has raised hope and excitement. However, these medications do not appear to impact quality of life, which is often considered by patients and care partners to be the most important outcome.In this randomized clinical trial, we found that an evidence-based, online, livestream, mind-body, group movement program significantly and meaningfully improves self-rated quality of life in people with ADRD and helps care partners manage stress. Mediation analyses revealed that the key drivers of improvements in participants' quality of life were improvements in their feelings of well-being and care partners' ability to manage stress. Exploratory analyses also suggested a 30% reduction in falls.These results are important because they suggest that an online program, which is available now and can be performed by people from the comfort of home or other location of choice, could be recommended as a complement or alternative to new therapies to help maximize quality of life for people living with ADRD and their care partners.

2.
ACS Synth Biol ; 13(4): 1152-1164, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38467017

RESUMEN

While synthetic biology has advanced complex capabilities such as sensing and molecular synthesis in aqueous solutions, important applications may also be pursued for biological systems in solid materials. Harsh processing conditions used to produce many synthetic materials such as plastics make the incorporation of biological functionality challenging. One technology that shows promise in circumventing these issues is cell-free protein synthesis (CFPS), where core cellular functionality is reconstituted outside the cell. CFPS enables genetic functions to be implemented without the complications of membrane transport or concerns over the cellular viability or release of genetically modified organisms. Here, we demonstrate that dried CFPS reactions have remarkable tolerance to heat and organic solvent exposure during the casting processes for polymer materials. We demonstrate the utility of this observation by creating plastics that have spatially patterned genetic functionality, produce antimicrobials in situ, and perform sensing reactions. The resulting materials unlock the potential to deliver DNA-programmable biofunctionality in a ubiquitous class of synthetic materials.


Asunto(s)
Polímeros , Biosíntesis de Proteínas , Sistema Libre de Células , Biología Sintética/métodos , ADN/genética
3.
Genet Med ; 26(5): 101075, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38251460

RESUMEN

PURPOSE: This study aims to assess the diagnostic utility and provide reporting recommendations for clinical DNA methylation episignature testing based on the cohort of patients tested through the EpiSign Clinical Testing Network. METHODS: The EpiSign assay utilized unsupervised clustering techniques and a support vector machine-based classification algorithm to compare each patient's genome-wide DNA methylation profile with the EpiSign Knowledge Database, yielding the result that was reported. An international working group, representing distinct EpiSign Clinical Testing Network health jurisdictions, collaborated to establish recommendations for interpretation and reporting of episignature testing. RESULTS: Among 2399 cases analyzed, 1667 cases underwent a comprehensive screen of validated episignatures, imprinting, and promoter regions, resulting in 18.7% (312/1667) positive reports. The remaining 732 referrals underwent targeted episignature analysis for assessment of sequence or copy-number variants (CNVs) of uncertain significance or for assessment of clinical diagnoses without confirmed molecular findings, and 32.4% (237/732) were positive. Cases with detailed clinical information were highlighted to describe various utility scenarios for episignature testing. CONCLUSION: Clinical DNA methylation testing including episignatures, imprinting, and promoter analysis provided by an integrated network of clinical laboratories enables test standardization and demonstrates significant diagnostic yield and clinical utility beyond DNA sequence analysis in rare diseases.


Asunto(s)
Metilación de ADN , Pruebas Genéticas , Enfermedades Raras , Humanos , Metilación de ADN/genética , Enfermedades Raras/genética , Enfermedades Raras/diagnóstico , Pruebas Genéticas/normas , Pruebas Genéticas/métodos , Femenino , Regiones Promotoras Genéticas/genética , Masculino , Variaciones en el Número de Copia de ADN/genética , Niño , Adulto , Preescolar , Impresión Genómica/genética
4.
Glob Adv Integr Med Health ; 12: 27536130231202989, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37745819

RESUMEN

Background: Preventing Loss of Independence through Exercise (PLIÉ) is an in-person group mind-body movement program for people across the spectrum of cognitive decline and care partners (CPs). Objective: This study developed and refined an online version called Moving Together and tested feasibility and satisfaction with an online delivery. Methods: In Phase 1, we used qualitative methods to determine which elements of the in-person program were essential to retain for the online version and adaptations that would be needed to support the user experience. In Phase 2, we created a prototype of the online program and iteratively refined it based on user feedback. In Phase 3, we assessed feasibility of online delivery based on class attendance and program completion; we assessed satisfaction and participant-reported outcomes using a post-program evaluation survey with quantitative and qualitative components. Results: Phase 1 findings from 27 participants (14 PLWD, 13 CPs) revealed three key considerations related to online delivery of PLIÉ: technology use, social connection as a primary motivator, and physical safety concerns. Phase 2 iterative testing among 25 participants (14 PLWD, 11 CPs) resulted in key refinements to program delivery and instructional elements; Phase 3 pilot testing included 39 participants (12 PLWD, 15 CPs, 12 MCI) who attended 75 ± 29% of 24 classes; 77% completed the 12-week program, of whom 96% rated it as excellent or good. Participant-reported outcomes included improvements in social connection, emotional well-being, physical function, cognitive function and present-centered body awareness. PLWD or MCI also reported improvements in self-concept, and CPs reported improvements in caregiving self-efficacy. The primary challenges were related to participant navigation of technology. Conclusion: The Moving Together online program is feasible for PLWD or MCI and CPs with participants reporting high satisfaction and positive outcomes across multiple domains. Providing individual technology support is critical for the success of livestreamed, online interventions for dementia.

5.
JAMA Pediatr ; 177(12): 1358-1360, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37747729

RESUMEN

This study evaluates whether implementation of a content expert­developed clinical documentation tool can be beneficial to workflow by reducing time from patient arrival to encounter closure among pediatric patients receiving intestinal rehabilitation.


Asunto(s)
Documentación , Registros Electrónicos de Salud , Humanos , Flujo de Trabajo
6.
J Am Med Inform Assoc ; 30(12): 2021-2027, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37643734

RESUMEN

OBJECTIVE: To describe real-world practices and variation in implementation of the Information Blocking provisions amongst healthcare organizations caring for pediatric patients. MATERIALS AND METHODS: An online survey regarding implementation practices was distributed to representatives from 10 participating US healthcare organizations located in 6 different states. The survey was followed by structured interviews conducted through video conference. Information was gathered about implementation practices at each organization, with a focus on patient and proxy portal access to, and segmentation capabilities of, certain data classes listed in the United States Core Data for Interoperability Version 1. RESULTS: All organizations had implemented the information blocking provisions at their institution. All organizations utilized different portal account types for proxies and users. All organizations reported the capability of sharing labs, medications, problem lists, imaging, and notes with the parent/guardian of the non-adolescent minor user with differences in how sensitive elements within the data classes were protected. Variability existed in how data was shared with the remaining user types. DISCUSSION: Significant variability exists in how organizations have implemented the information blocking rules. Variation in data sharing and data access between institutions can result in privacy breaches and create confusion about completeness of data for patients and families. CONCLUSION: Healthcare organizations have utilized varying strategies to comply with the information blocking provisions of the 21st Century Cures Act. Increased clarity from the Office of the National Coordinator for Health Information Technology on minor, adolescent, and caregiver privacy and improved segmentation capabilities from Electronic Health Record vendors is needed.


Asunto(s)
Registros Electrónicos de Salud , Informática Médica , Humanos , Adolescente , Estados Unidos , Niño , Confidencialidad , Difusión de la Información/métodos , Privacidad
7.
J Pediatr Gastroenterol Nutr ; 77(4): 519-526, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37501225

RESUMEN

OBJECTIVES: Outpatient inflammatory bowel disease (IBD) care shifted from office visits (OVs) to a model with integrated telemedicine during the 2020 COVID-19 pandemic. We describe the impact of this shift on delivery of pediatric IBD care. METHODS: We collected electronic medical record data from office and telemedicine visits for pediatric patients with IBD at a single center from April 2019 to December 2020. We compared visit volume, duration, and test ordering between 2019 and 2020, and between OV and telemedicine, and assessed for differences in telemedicine adoption by sociodemographic factors. RESULTS: Visit volume was maintained between 2019 and 2020. Median overall appointment time was shorter for telemedicine versus OV [46 (interquartile range, IQR 35-72) vs 62 (IQR 51-80) minutes; P < 0.001] with no significant difference in time spent with provider [28 (IQR 21-41) vs OV 30 (IQR 24-39) minutes; P = 0.08]. Accounting for drive time, telemedicine visits were 2.6 times shorter than office visits in 2020 ( P < 0.001). In univariate analyses, there was no difference in telemedicine utilization by race or gender. Variables significantly associated with telemedicine were older age, English as primary language, being non-Hispanic, commercial insurance, living in an area of very high opportunity, and having a longer drive time to the office ( P < 0.05 for all comparisons). In multivariate analyses, visits among patients with commercial insurance were significantly more likely to be conducted via telemedicine ( P = 0.02). Among those with a telemedicine visit, multivariate analyses demonstrated multiracial patients were significantly more likely to have video visits (vs audio-only; P = 0.02), while patients with public insurance, no or missing insurance, and whose primary language was Arabic were significantly less likely to have video visits ( P < 0.05 for all comparisons). CONCLUSIONS: Integrated telemedicine allowed for continued delivery of pediatric IBD care and significantly decreased appointment time. While telemedicine may improve access for those who live further from the office, concerns remain about the introduction of disparities.


Asunto(s)
COVID-19 , Enfermedades Inflamatorias del Intestino , Telemedicina , Humanos , Niño , COVID-19/epidemiología , Pandemias , Atención Ambulatoria , Enfermedades Inflamatorias del Intestino/terapia
8.
Curr Pharm Teach Learn ; 15(8): 754-760, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37507313

RESUMEN

BACKGROUND AND PURPOSE: To assess pharmacy students' understanding of the importance of genetic counseling through a didactic lecture and active in-class learning exercise in a required pharmacogenomics course. EDUCATIONAL ACTIVITY AND SETTING: During the second year, students are enrolled in a two-credit hour pharmacogenomics course which is taught by multiple faculty members from various disciplines. The pharmacy students were taught the clinical importance of genetic results and counseling patients on their individualized reports by a clinical laboratory geneticist and a clinical genetic counselor. After completion of the didactic portion of the class, students practiced genetic counseling skills through role playing with clinical cases involving genetic reports. Students' knowledge of clinical applications of pharmacogenomic data was assessed prior to and following the counseling experience. FINDINGS: A paired sample t-test was chosen to analyze the data to determine if there was a difference in mean scores upon the completion of the lecture. There was a statistically significant mean difference between the total scores for the pretest (mean (M) = 37.89, SD = 6.66) and the total scores for the posttest (M = 48.33, SD = 5.24); t(140) = 17.53, P < .001, α = 0.05. The effect size for this analysis (d = 1.74) surpassed Cohen's determination for large effect (d = 0.8). SUMMARY: The genetic counseling lecture and activity increased the students' overall awareness of the importance of how sensitive genetic information is reported and delivered to patients.


Asunto(s)
Asesoramiento Genético , Estudiantes de Farmacia , Humanos , Curriculum , Evaluación Educacional/métodos , Competencia Clínica
9.
J Pediatr Gastroenterol Nutr ; 77(3): 319-326, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37079871

RESUMEN

OBJECTIVES: The purpose of our study is to compare in-person and telehealth pediatric care ambulatory visits for gastroenterology (GI) at the Nemours Children's Health System in the Delaware Valley (NCH-DV) based on geospatial, demographic, socioeconomic, and digital disparities. METHODS: Characteristics of 26,565 patient encounters from January 2019 to December 2020 were analyzed. U.S. Census Bureau geographic identifiers were assigned to each participant and aligned with the American Community Survey (2015-2019) socioeconomic and digital outcomes. Reported odds ratios (OR) are telehealth encounter/in-person encounter. RESULTS: GI telehealth usage increased 145-fold in 2020 compared to 2019 for NCH-DV. Comparing telehealth to in-person usage in 2020 revealed that GI patients who required a language translator were 2.2-fold less likely to choose telehealth [individual level adjusted OR (I-OR a ) [95% confidence interval, CI], 0.45 [0.30-0.66], P < 0.001]. Individuals of Hispanic ethnicity or non-Hispanic Black or African American race are 1.3-1.4-fold less likely to utilize telehealth than non-Hispanic Whites (I-OR a [95% CI], 0.73 [0.59-0.89], P = 0.002 and 0.76 [0.60-0.95], P = 0.02, respectively). Households in census block groups (BG) that are more likely to utilize telehealth: have broadband access (BG-OR = 2.51 [1.22-5.31], P = 0.014); are above the poverty level (BG-OR = 4.44 [2.00-10.24], P < 0.001); own their own home (BG-OR = 1.79 [1.25-2.60], P = 0.002); and have a bachelor's degree or higher (BG-OR = 6.55 [3.25-13.80], P < 0.001). CONCLUSIONS: Our study is the largest reported pediatric GI telehealth experience in North America that describes racial, ethnic, socioeconomic, and digital inequities. Advocacy and research for pediatric GI focused on telehealth equity and inclusion is urgently needed.


Asunto(s)
Gastroenterología , Disparidades en Atención de Salud , Telemedicina , Niño , Humanos , Etnicidad , Hispánicos o Latinos , Pobreza , Negro o Afroamericano , Blanco
10.
J Pediatr Gastroenterol Nutr ; 76(5): 684-694, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36976575

RESUMEN

Telehealth (TH) broadly encompasses remote activities of clinical care (telemedicine), provider and patient education, and general health services. The use of synchronous video for TH first occurred in 1964 and then catapulted to the forefront in 2020 during the coronavirus disease 2019 public health emergency. Due to the sudden need for increased TH utilization by nearly all health care providers at that time, TH became essential to clinical practice. However, its sustainable future is unclear in part given that best practices for TH in pediatric gastroenterology (GI), hepatology, and nutrition remain undefined and non-standardized. Key areas for review include historical perspective, general and subspeciality usage, health care disparities, quality of care and the provider-patient interaction, logistics and operations, licensure and liability, reimbursement and insurance coverage, research and quality improvement (QI) priorities, and future use of TH in pediatric GI with a call for advocacy. This position paper from the Telehealth Special Interest Group of North American Society of Gastroenterology, Hepatology and Nutrition provides recommendations for pediatric GI-focused TH best practices, reviews areas for research and QI growth, and presents advocacy opportunities.


Asunto(s)
COVID-19 , Gastroenterología , Telemedicina , Niño , Humanos , Gastroenterología/educación , Sociedades , América del Norte , Sociedades Médicas
12.
Transl Psychiatry ; 12(1): 421, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36182950

RESUMEN

CHD8, a major autism gene, functions in chromatin remodelling and has various roles involving several biological pathways. Therefore, unsurprisingly, previous studies have shown that intellectual developmental disorder with autism and macrocephaly (IDDAM), the syndrome caused by pathogenic variants in CHD8, consists of a broad range of phenotypic abnormalities. We collected and reviewed 106 individuals with IDDAM, including 36 individuals not previously published, thus enabling thorough genotype-phenotype analyses, involving the CHD8 mutation spectrum, characterization of the CHD8 DNA methylation episignature, and the systematic analysis of phenotypes collected in Human Phenotype Ontology (HPO). We identified 29 unique nonsense, 25 frameshift, 24 missense, and 12 splice site variants. Furthermore, two unique inframe deletions, one larger deletion (exons 26-28), and one translocation were observed. Methylation analysis was performed for 13 patients, 11 of which showed the previously established episignature for IDDAM (85%) associated with CHD8 haploinsufficiency, one analysis was inconclusive, and one showing a possible gain-of-function signature instead of the expected haploinsufficiency signature was observed. Consistent with previous studies, phenotypical abnormalities affected multiple organ systems. Many neurological abnormalities, like intellectual disability (68%) and hypotonia (29%) were observed, as well as a wide variety of behavioural abnormalities (88%). Most frequently observed behavioural problems included autism spectrum disorder (76%), short attention span (32%), abnormal social behaviour (31%), sleep disturbance (29%) and impaired social interactions (28%). Furthermore, abnormalities in the digestive (53%), musculoskeletal (79%) and genitourinary systems (18%) were noted. Although no significant difference in severity was observed between males and females, individuals with a missense variant were less severely affected. Our study provides an extensive review of all phenotypic abnormalities in patients with IDDAM and provides clinical recommendations, which will be of significant value to individuals with a pathogenic variant in CHD8, their families, and clinicians as it gives a more refined insight into the clinical and molecular spectrum of IDDAM, which is essential for accurate care and counselling.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Discapacidad Intelectual , Megalencefalia , Trastorno del Espectro Autista/genética , Trastorno Autístico/genética , Proteínas de Unión al ADN/genética , Femenino , Estudios de Asociación Genética , Humanos , Discapacidad Intelectual/genética , Masculino , Megalencefalia/genética , Fenotipo , Factores de Transcripción/genética
13.
Am J Med Genet A ; 188(7): 2217-2225, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35384273

RESUMEN

Kabuki syndrome is a Mendelian disorder of the epigenetic machinery characterized by typical dysmorphic features, intellectual disability, and postnatal growth deficiency. Pathogenic variants in the genes encoding the chromatin modifiers KMT2D and KDM6A are responsible for Kabuki syndrome 1 (KS1) and Kabuki syndrome 2 (KS2), respectively. In addition, 11 cases of KS1 caused by mosaic variants in KMT2D have been reported in the literature. Some of these individuals display milder craniofacial and growth phenotypes, and most do not have congenital heart defects. We report the case of an infant with severe hypoplastic left heart syndrome with mitral atresia and aortic atresia (HLHS MA-AA), pulmonary vein stenosis, and atypical facies with a somatic mosaic de novo nonsense variant in KMT2D (c.8200C>T, p.R2734*) identified on trio exome sequencing of peripheral blood and present in 11.2% of sequencing reads. KS was confirmed with EpiSign, a diagnostic genome-wide DNA methylation platform used to identify epigenetic signatures. This case suggests that use of this newly available clinical test can guide the interpretation of low-level mosaic variants identified through sequencing and suggests a new lower limit of mosaicism in whole blood required for a diagnosis of KS.


Asunto(s)
Anomalías Múltiples , Cardiopatías Congénitas , Enfermedades Hematológicas , Enfermedades Vestibulares , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Metilación de ADN/genética , Cara/anomalías , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/genética , Humanos , Mutación , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/genética
14.
Appl Clin Inform ; 13(1): 230-241, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35172372

RESUMEN

BACKGROUND: The rapid, large-scale deployment of new health technologies can introduce challenges to clinicians who are already under stress. The novel coronavirus disease 19 (COVID-19) pandemic transformed health care in the United States to include a telehealth model of care delivery. Clarifying paths through which telehealth technology use is associated with change in provider well-being and interest in sustaining virtual care delivery can inform planning and optimization efforts. OBJECTIVE: This study aimed to characterize provider-reported changes in well-being and daily work associated with the pandemic-accelerated expansion of telehealth and assess the relationship of provider perceptions of telehealth effectiveness, efficiency, and work-life balance with desire for future telehealth. METHODS: A cross-sectional survey study was conducted October through November 2020, 6 months after the outbreak of COVID-19 at three children's hospitals. Factor analysis and structural equation modeling (SEM) were used to examine telehealth factors associated with reported change in well-being and desire for future telehealth. RESULTS: A total of 947 nontrainee physicians, advanced practice providers, and psychologists were surveyed. Of them, 502 (53.0%) providers responded and 467 (49.3%) met inclusion criteria of telehealth use during the study period. Of these, 325 (69.6%) were female, 301 (65.6%) were physicians, and 220 (47.1%) were medical subspecialists. Providers were 4.77 times as likely (95% confidence interval [CI]: 3.29-7.06) to report improved versus worsened well-being associated with telehealth. Also, 95.5% of providers (95% CI: 93.2-97.2%) wish to continue performing telehealth postpandemic. Our model explains 66% of the variance in telehealth-attributed provider well-being and 59% of the variance for future telehealth preference and suggests telehealth resources significantly influence provider-perceived telehealth care effectiveness which in turn significantly influences provider well-being and desire to perform telehealth. CONCLUSION: Telehealth has potential to promote provider well-being; telehealth-related changes in provider well-being are associated with both provider-perceived effectiveness of telemedicine for patients and adequacy of telehealth resources.


Asunto(s)
COVID-19 , Telemedicina , Niño , Estudios Transversales , Femenino , Personal de Salud , Humanos , SARS-CoV-2 , Estados Unidos
15.
Genet Med ; 24(4): 905-914, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35027293

RESUMEN

PURPOSE: Gabriele-de Vries syndrome (GADEVS) is a rare genetic disorder characterized by developmental delay and/or intellectual disability, hypotonia, feeding difficulties, and distinct facial features. To refine the phenotype and to better understand the molecular basis of the syndrome, we analyzed clinical data and performed genome-wide DNA methylation analysis of a series of individuals carrying a YY1 variant. METHODS: Clinical data were collected for 13 individuals not yet reported through an international call for collaboration. DNA was collected for 11 of these individuals and 2 previously reported individuals in an attempt to delineate a specific DNA methylation signature in GADEVS. RESULTS: Phenotype in most individuals overlapped with the previously described features. We described 1 individual with atypical phenotype, heterozygous for a missense variant in a domain usually not involved in individuals with YY1 pathogenic missense variations. We also described a specific peripheral blood DNA methylation profile associated with YY1 variants. CONCLUSION: We reported a distinct DNA methylation episignature in GADEVS. We expanded the clinical profile of GADEVS to include thin/sparse hair and cryptorchidism. We also highlighted the utility of DNA methylation episignature analysis for classification of variants of unknown clinical significance.


Asunto(s)
Discapacidad Intelectual , Trastornos del Neurodesarrollo , Metilación de ADN/genética , Genoma , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Masculino , Trastornos del Neurodesarrollo/genética , Fenotipo , Síndrome
16.
Am J Med Genet A ; 188(5): 1550-1555, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35040536

RESUMEN

Pathogenic variants in KMT2D are typically associated with Kabuki syndrome (KS), a rare multisystem disorder. KS is characterized by facial dysmorphisms, intellectual disability, skeletal and dermatoglyphic differences, and poor growth. Seventy percent of individuals with clinically diagnosed KS have a confirmed pathogenic variant in KMT2D or less commonly KDM6A. The majority of mutations found in KMT2D are de novo nonsense or frameshift, with deletions and duplications rarely reported in the literature. Here, we present the case of near complete deletion of KMT2D in a college student with normal intelligence discovered via exome sequencing and EpiSign methylation testing. This case provides evidence that large deletions in KMT2D are compatible with normal intelligence and presents EpiSign as a method for discovering molecular causes of KS not identified by traditional molecular testing.


Asunto(s)
Anomalías Múltiples , Enfermedades Hematológicas , Enfermedades Vestibulares , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Cara/anomalías , Enfermedades Hematológicas/genética , Humanos , Mutación , Estudiantes , Enfermedades Vestibulares/genética
17.
JIMD Rep ; 62(1): 35-43, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34765396

RESUMEN

HSD10 disease is a rare X-linked mitochondrial disorder caused by pathogenic variants in the HSD17B10 gene. The phenotype results from impaired 17ß-hydroxysteroid dehydrogenase 10 (17ß-HSD10) protein structure and function. HSD10 is a multifunctional protein involved in enzymatic degradation of isoleucine and branched-chain fatty acids, the metabolism of sex hormones and neurosteroids, as well as in regulating mitochondrial RNA maturation. HSD10 disease is characterised by progressive neurologic impairment. Disease onset is varied and includes neonatal-onset, infantile-onset and late-onset in males. Females can also be affected. Our index case is a 45-month-old female, who initially presented at 11 months of age with global developmental delay. She subsequently began to lose previously acquired cognitive and motor skills starting around 29 months of age. Brain MRI showed abnormalities in the basal ganglia indicative of possible mitochondrial disease. Urine organic acid analysis revealed elevations of 2-methyl-3-hydroxybutyric acid and tiglyglycine. HSD17B10 gene sequencing revealed a likely pathogenic variant, NM_001037811.2:c.439C>T (p.Arg147Cys) inherited from her mother, expected to be causative of HSD10 disease. Her X-chromosome inactivation study is consistent with a skewed X-inactivation pattern. We report a female patient with HSD10 disease caused by a missense pathogenic variant, Arg147Cys in the HSD17B10 gene. The patient is the fifth severely affected female with this disease. This case adds to the small number of known affected families with this highly variable disease in the literature. These findings support the possibility of X-inactivation patterns influencing the penetrance of HSD10 disease in females.

18.
Curr Probl Pediatr Adolesc Health Care ; 51(11): 101101, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34776370

RESUMEN

Patient portals are the primary means by which electronic health information (EHI) is shared with patients and families. The use of patient portals increased during the COVID-19 pandemic and may continue to rise with the implementation and enforcement of the 21st Century Cures Act that encourages facilitation of access to EHI and prohibits information blocking. Research on the use of patient portals by adolescents and their families is limited. Potential benefits of portal use to adolescents include increased engagement in their own health care, direct communication with their health care clinicians, and facilitation of transition of care to new clinicians in adulthood. Clinicians need to educate adolescents on the functions available through the portal, appropriate use and expectations for messaging through the portal, and the pros and cons of viewing EHI such as test results independently. Parental proxy access to the adolescent's portal should be carefully and thoughtfully implemented, because it poses a potential breach to confidential care via disclosure of sensitive or protected information. Adolescents who choose to deny their parents proxy access to the portal should be supported in that decision. It is important that all clinicians understand portal functionality and have strategies to optimize use within their practice. This paper provides the reader considerations and tips for portal use within this population.


Asunto(s)
COVID-19 , Portales del Paciente , Adolescente , Adulto , Comunicación , Humanos , Pandemias , SARS-CoV-2 , Adulto Joven
19.
Med Care ; 59(12): 1067-1074, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34593709

RESUMEN

BACKGROUND: The increase in telehealth in response to the coronavirus disease 2019 pandemic highlights the need to understand patients' capacity to utilize this care modality. Patient portals are a tool whose use requires similar resources and skills as those required for telehealth. Patients' capacity to use patient portals may therefore provide insight regarding patients' readiness and capacity to use telehealth. OBJECTIVE: The aim of this study was to examine factors related to patients' capacity to use a patient portal and test the impact of these factors on patients' portal use. RESEARCH DESIGN AND SUBJECTS: Using data from a large-scale pragmatic randomized controlled trial of patient portal use, 1081 hospitalized patients responded to survey items that were then mapped onto the 4 dimensions of the Engagement Capacity Framework: self-efficacy, resources, willingness, and capabilities. MEASURES: The outcome variable was frequency of outpatient portal use. We evaluated associations between Engagement Capacity Framework dimensions and patient portal use, using regression analyses. RESULTS: Patients with fewer resources, fewer capabilities, lower willingness, and lower overall capacity to use patient portals used the portal less; in contrast, those with lower perceived self-efficacy used the portal more. CONCLUSIONS: Our findings highlight differences in patients' capacity to use patient portals, which provide an initial understanding of factors that may influence the use of telehealth and offer important guidance in efforts to support patients' telehealth use. Offering patients training tailored to the use of telehealth tools may be particularly beneficial.


Asunto(s)
Participación del Paciente/psicología , Portales del Paciente , Telemedicina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Participación del Paciente/estadística & datos numéricos , Autoeficacia , Autoevaluación (Psicología) , Encuestas y Cuestionarios , Estados Unidos
20.
J Alzheimers Dis ; 82(4): 1543-1557, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34180414

RESUMEN

BACKGROUND: Preventing Loss of Independence through Exercise (PLIÉ) is a group movement program initially developed for people with mild-to-moderate dementia that integrates principles from several well-established traditions to specifically address the needs of people with cognitive impairment. OBJECTIVE: To investigate whether PLIÉ would benefit cognitive and behavioral outcomes and functional brain connectivity in older adults with milder forms of cognitive impairment. METHODS: Participants (≥55 y) with subjective memory decline (SMD) or mild cognitive impairment (MCI) were assessed with tests of cognitive and physical function, self-report questionnaires, and resting state functional magnetic resonance imaging (rs-fMRI) on a 3 Tesla scanner before and after participating in twice weekly PLIÉ classes for 12 weeks at the San Francisco Veterans Affairs Medical Center. RESULTS: Eighteen participants completed the pre-post intervention pilot trial. We observed significant improvements on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog; effect size 0.34, p = 0.002) and enhanced functional connections between the medial prefrontal cortex (mPFC) and other nodes of the default mode network (DMN) after PLIÉ. Improvements (i.e., lower scores) on ADAS-cog were significantly correlated with enhanced functional connectivity between the mPFC and left lateral parietal cortex (Spearman's ρ= -0.74, p = 0.001) and between the mPFC and right hippocampus (Spearman's ρ= -0.83, p = 0.001). After completing PLIÉ, participants reported significant reductions in feelings of social isolation and improvements in well-being and interoceptive self-regulation. CONCLUSION: These preliminary findings of post-PLIÉ improvements in DMN functional connectivity, cognition, interoceptive self-regulation, well-being and reduced feelings of social isolation warrant larger randomized, controlled trials of PLIÉ in older adults with SMD and MCI.


Asunto(s)
Encéfalo/patología , Disfunción Cognitiva , Terapia por Ejercicio , Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Vida Independiente , Anciano , California , Disfunción Cognitiva/psicología , Disfunción Cognitiva/terapia , Ejercicio Físico/psicología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Terapias Mente-Cuerpo , Pruebas Neuropsicológicas/estadística & datos numéricos , Proyectos Piloto , Autoinforme , Encuestas y Cuestionarios
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...