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1.
J Pediatr ; : 114120, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815740

RESUMO

OBJECTIVE: To characterize patterns in the geospatial distribution of pre- and post-natally diagnosed congenital heart disease (CHD) across six surgical centers. STUDY DESIGN: A retrospective , multicenter case series from the Fetal Heart Society identified patients at six centers from 2012 through 2016 with prenatally (PrND) or postnatally (PoND) diagnosed hypoplastic left heart syndrome (HLHS) or d-transposition of the great arteries (TGA). Geospatial analysis for clustering was done by the average nearest neighbor (ANN) tool or optimized hot spot tool, depending on spatial unit and data type. Both point location and county case rate per 10,000 live births were assessed for geographic clustering or dispersion. RESULTS: Of the 453 CHD cases, 26% were PoND (n =117), and 74% were PrND (n=336). PrND cases, in all but one center, displayed significant geographic clustering by ANN. Conversely, PoND cases tended towards geographic dispersion. Dispersion of PoND HLHS occurred in two centers (ANN =1.59, p <0.001; and 1.47, p = 0.016), and PoND TGA occurred in two centers (ANN = 1.22, p < 0.05; and ANN =1.73, p<0.001). Hot spot analysis of all CHD cases (TGA and HLHS combined) revealed clustering near areas of high population density and the tertiary surgical center. Hot spot analysis of county-level case rate, accounting for population density, found variable clustering patterns. CONCLUSION: Geographic dispersion among postnatally detected CHD highlights the need for a wider reach of prenatal cardiac diagnosis tailored to the specific needs of a community. Geospatial analysis can support centers in improving the equitable delivery of prenatal care.

2.
J Cardiovasc Dev Dis ; 11(5)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38786977

RESUMO

Recent literature has established a strong foundation examining the associations between socioeconomic/demographic characteristics and outcomes for congenital heart disease. These associations are found beginning in fetal life and influence rates of prenatal detection, access to timely and appropriate delivery room and neonatal interventions, and surgical and other early childhood outcomes. This review takes a broad look at the existing literature and identifies gaps in the current body of research, particularly as it pertains to disparities in the prenatal detection of congenital heart disease within the United States. It also proposes further research and interventions to address these health disparities.

3.
bioRxiv ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37090523

RESUMO

Interferon-stimulated gene-15 (ISG15) is an interferon-induced protein with two ubiquitin-like (Ubl) domains linked by a short peptide chain, and the conjugated protein of the ISGylation system. Similar to ubiquitin and other Ubls, ISG15 is ligated to its target proteins with a series of E1, E2, and E3 enzymes known as Uba7, Ube2L6/UbcH8, and HERC5, respectively. Ube2L6/UbcH8 plays a literal central role in ISGylation, underscoring it as an important drug target for boosting innate antiviral immunity. Depending on the type of conjugated protein and the ultimate target protein, E2 enzymes have been shown to function as monomers, dimers, or both. UbcH8 has been crystalized in both monomeric and dimeric forms, but the functional state is unclear. Here, we used a combined approach of small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) spectroscopy to characterize UbcH8's oligomeric state in solution. SAXS revealed a dimeric UbcH8 structure that could be dissociated when fused with an N-terminal glutathione S-transferase molecule. NMR spectroscopy validated the presence of a concentration-dependent monomer-dimer equilibrium and suggested a backside dimerization interface. Chemical shift perturbation and peak intensity analysis further suggest dimer-induced conformational dynamics at ISG15 and E3 interfaces - providing hypotheses for the protein's functional mechanisms. Our study highlights the power of combining NMR and SAXS techniques in providing structural information about proteins in solution.

4.
J Cereb Blood Flow Metab ; 44(4): 556-572, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37944245

RESUMO

Hypoglycemia increases the risk related to stroke and neurodegenerative diseases, however, the underlying mechanisms are unclear. For the first time, we studied the effect of a single episode (acute) of severe (ASH) and mild (AMH) hypoglycemia on mouse brain microvascular proteome. After four-hour fasting, insulin was administered (i.p) to lower mean blood glucose in mice and induce ∼30 minutes of ASH (∼30 mg/dL) or AMH (∼75 mg/dL), whereas a similar volume of saline was given to control mice (∼130 mg/dL). Blood glucose was allowed to recover over 60 minutes either spontaneously or by 20% dextrose administration (i.p). Twenty-four hours later, the brain microvessels (BMVs) were isolated, and tandem mass tag (TMT)-based quantitative proteomics was performed using liquid chromatography-mass spectrometry (LC/MS). When compared to control, ASH significantly downregulated 13 proteins (p ≤ 0.05) whereas 23 proteins showed a strong trend toward decrease (p ≤ 0.10). When compared to AMH, ASH significantly induced the expression of 35 proteins with 13 proteins showing an increasing trend. AMH downregulated only 3 proteins. ASH-induced downregulated proteins are involved in actin cytoskeleton maintenance needed for cell shape and migration which are critical for blood-brain barrier maintenance and angiogenesis. In contrast, ASH-induced upregulated proteins are RNA-binding proteins involved in RNA splicing, transport, and stability. Thus, ASH alters BMV proteomics to impair cytoskeletal integrity and RNA processing which are critical for cerebrovascular function.


Assuntos
Hipoglicemia , Proteoma , Camundongos , Animais , Proteoma/metabolismo , Glicemia , Espectrometria de Massas em Tandem/métodos , Encéfalo/metabolismo
5.
Birth Defects Res ; 115(16): 1556-1565, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37589320

RESUMO

BACKGROUND: Congenital heart disease (CHD) is the most common birth defect, influenced by maternal health, environmental conditions, and genetics. Maternal health and nutrition, particularly maternal diabetes, is a modifiable risk factor for development of CHD in the fetus. However, the importance of food access during pregnancy on the development of CHD remains unknown. The objective of this study was to investigate the association between maternal neighborhood characteristics, particularly food access, and occurrence of prenatally diagnosed CHD. METHODS: A retrospective case series studied maternal-fetal dyads with prenatally diagnosed CHD between 2019 and 2021 in Washington, DC. Moran's I of maternal addresses evaluated geographic clustering of disease. Negative binomial regression assessed association between census tract demographics and population-adjusted CHD rate. RESULTS: A total of 307 dyads were analyzed. Global Moran's I showed significant CHD clustering (p-value = .004). However, degree of clustering was not clinically meaningful. After adjusting for neighborhood socioeconomic status, residing in food deserts was not a predictor for CHD. However, neighborhoods with a higher percentage of households receiving Supplemental Nutrition Assistance Program (SNAP) benefits were associated with higher rates of conotruncal heart defects (Incident Rate Ratio [IRR] = 1.04, CI = 1.01-1.08) and aggregate CHD (IRR = 1.03, CI = 1.01-1.05). CONCLUSIONS: Neighborhood location and food access were not associated with CHD. However, increased enrollment in SNAP was associated with higher rates of CHD. The association between CHD and SNAP benefits warrants further exploration. Understanding food access and maternal nutrition may illuminate disparities in the burden of CHD.


Assuntos
Cardiopatias Congênitas , Feminino , Gravidez , Humanos , Estudos Retrospectivos , Fatores de Risco , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/etiologia , Cardiopatias Congênitas/diagnóstico , Características de Residência , Feto
6.
BMC Geriatr ; 23(1): 338, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37259070

RESUMO

BACKGROUND: When there are safety concerns, healthcare professionals (HCPs) may disregard older adults' wishes to return or remain at home. A paradigm shift is needed for HCPs to move from labelling older adults as living at risk to helping them live with risk. The Living with Risk: Decision Support Tool (LwR:DST) was developed to support older adults and HCPs with difficult decision-making regarding living with risk. The study objectives were to: (1) validate, and (2) pilot-test the LwR:DST in hospital and community settings. METHODS: The study was conducted across Canada during the pandemic. The LwR:DST's content was validated with quantitative and qualitative data by: (1) 71 HCPs from hospital and community settings using the Delphi method, and (2) 17 older adults and caregivers using focus groups. HCPs provided feedback on the LwR:DST's content, format and instruction manual while older adults provided feedback on the LwR:DST's communication step. The revised LwR:DST was pilot-tested by 14 HCPs in one hospital and one community setting, and 17 older adults and caregivers described their experience of HCPs using this approach with them. Descriptive and thematic analysis were performed. RESULTS: The LwR:DST underwent two iterations incorporating qualitative and quantitative data provided by HCPs, older adults and caregivers. The quantitative Delphi method data validated the content and the process of the LwR:DST, while the qualitative data provided practical improvements. The pilot-testing results suggest that using the LwR:DST broadens HCPs' clinical thinking, structures their decision-making, improves their communication and increases their competence and comfort with risk assessment and management. Our findings also suggest that the LwR:DST improves older adults' healthcare experience by feeling heard, understood and involved. CONCLUSIONS: This revised LwR:DST should help HCPs systematically identify frail older adults' risks when they remain at or return home and find acceptable ways to mitigate these risks. The LwR:DST induces a paradigm shift by acknowledging that risks are inherent in everyday living and that risk-taking has positive and negative consequences. The challenges involved in integrating the LwR:DST into practice, i.e., when, how and with whom to use it, will be addressed in future research.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Humanos , Idoso , Cuidadores , Pessoal de Saúde , Canadá , Grupos Focais , Pesquisa Qualitativa
7.
J Am Soc Echocardiogr ; 36(7): 724-732, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36906047

RESUMO

INTRODUCTION: A novel technology utilizing artificial intelligence (AI) to provide real-time image-acquisition guidance, enabling novices to obtain diagnostic echocardiographic images, holds promise to expand the reach of echo screening for rheumatic heart disease (RHD). We evaluated the ability of nonexperts to obtain diagnostic-quality images in patients with RHD using AI guidance with color Doppler. METHODS: Novice providers without prior ultrasound experience underwent a 1-day training curriculum to complete a 7-view screening protocol using AI guidance in Kampala, Uganda. All trainees then scanned 8 to 10 volunteer patients using AI guidance, half RHD and half normal. The same patients were scanned by 2 expert sonographers without the use of AI guidance. Images were evaluated by expert blinded cardiologists to assess (1) diagnostic quality to determine presence/absence of RHD and (2) valvular function and (3) to assign an American College of Emergency Physicians score of 1 to 5 for each view. RESULTS: Thirty-six novice participants scanned a total of 50 patients, resulting in a total of 462 echocardiogram studies, 362 obtained by nonexperts using AI guidance and 100 obtained by expert sonographers without AI guidance. Novice images enabled diagnostic interpretation in >90% of studies for presence/absence of RHD, abnormal MV morphology, and mitral regurgitation (vs 99% by experts, P ≤ .001). Images were less diagnostic for aortic valve disease (79% for aortic regurgitation, 50% for aortic stenosis, vs 99% and 91% by experts, P < .001). The American College of Emergency Physicians scores of nonexpert images were highest in the parasternal long-axis images (mean, 3.45; 81% ≥ 3) compared with lower scores for apical 4-chamber (mean, 3.20; 74% ≥ 3) and apical 5-chamber images (mean, 2.43; 38% ≥ 3). CONCLUSIONS: Artificial intelligence guidance with color Doppler is feasible to enable RHD screening by nonexperts, performing significantly better for assessment of the mitral than aortic valve. Further refinement is needed to optimize acquisition of color Doppler apical views.


Assuntos
Insuficiência da Valva Mitral , Cardiopatia Reumática , Humanos , Cardiopatia Reumática/diagnóstico por imagem , Inteligência Artificial , Uganda , Programas de Rastreamento/métodos
8.
AMA J Ethics ; 24(9): E822-829, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36170413

RESUMO

This commentary on a case offers a historical perspective on how home health work became separate from other sites and means of professional caregiving, exacerbating poor continuity of care in the US health care system. Categorizing home health work as domestic work continues to racialize and marginalize workers. Poor public policy responding to market pressures to keep home health work cheap also perpetuates home health workers' classification as independent contractors, their lack of training, and low wages. This commentary suggests an alternative model for the future of home health work in the United States.


Assuntos
Serviços de Assistência Domiciliar , Visitadores Domiciliares , Atenção à Saúde , Pessoal de Saúde , Mão de Obra em Saúde , Humanos , Organizações , Estados Unidos
10.
Gait Posture ; 96: 29-34, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35567894

RESUMO

BACKGROUND: The sagittal plane alignment of ankle-foot orthoses (AFO) and AFO footwear combinations (AFO-FC) has been shown to influence gait outcomes. As such, clinicians often target a particular alignment during the fabricating and fitting of an AFO to maximize outcomes. RESEARCH QUESTION: How does the alignment of an AFO change during the fabrication and fitting process with respect to the intended, benchmark sagittal plane alignment identified by the consulting orthotist? STUDY DESIGN: Prospective METHODS: The assessment of AFO alignment was performed using a convenience sample of 125 custom molded AFOs from 68 individuals fabricated at our center (57 bilateral AFOs, 11 unilateral AFOs). The alignment of each AFO was measured at 5 distinct steps during the fabrication and fitting process using a recently validated method to measure AFO neutral angle using differential inclinometers. RESULTS: Prior to fabrication, the intended, benchmark alignment set by the consulting orthotist was 90 degrees for 92% of AFOs, was between 1 and 7 degrees of dorsiflexion for 7% of AFOs and was 5 degrees of plantarflexion for 1% of AFOs. Repeated measures ANOVA showed that AFO alignment changed between all fabrication and fitting steps. Overall, paired t-tests confirmed that AFO alignment was consistently 2-5 degrees more dorsiflexed than the benchmark alignment. Prior to fitting shoes, 55% of fabricated AFOs measured more than 2 degrees from the benchmark alignment. After fitting shoes, nearly 87% of AFO-FCs were more than 2 degrees from the benchmark alignment. SIGNIFICANCE: The finding of systematic dorsiflexion bias and changes in AFO alignment throughout the fabrication and fitting process indicates the need to improve AFO fabrication precision. The neutral angle measurement methodology - using differential inclinometers - provides a means to improve this precision by enabling orthotists to precisely quantify and make appropriate adjustments to AFO alignment throughout the entire fabrication and fitting process.


Assuntos
Órtoses do Pé , Tornozelo , Articulação do Tornozelo , Fenômenos Biomecânicos , Marcha , Humanos , Amplitude de Movimento Articular
11.
J Pediatr ; 240: 117-121, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480916

RESUMO

OBJECTIVE: To determine presence of spatial clustering or dispersion of pre and postnatally detected hypoplastic left heart syndrome (HLHS) and d-transposition of the great arteries (TGA) cases. STUDY DESIGN: This retrospective study examined all patients with a prenatal or postnatal diagnosis of HLHS or TGA who had an initial visit or hospitalization at our tertiary care center over a 5-year period from 2012 to 2016 (n = 105). Using geographic information systems software, the nearest neighbor ratio (NNR) tool was used to determine whether statistically significant clustering or dispersion occurred. RESULTS: Geographic clustering was observed among prenatally diagnosed pooled cases of HLHS and TGA and all total cases (NNR = 0.73 and 0.66, respectively), but not postnatally detected cases (NNR = 1.08). Notably, there was significant dispersion of postnatally detected TGA cases (NNR = 1.22) There was no pattern for prenatally detected TGA or HLHS when analyzed individually. CONCLUSIONS: The spatial distribution of HLHS and TGA is not random; these conditions occur in geographic clusters. Clustering of all patients in the study population and dispersion of postnatal diagnosis of TGA represent opportunities for improved delivery of fetal cardiac care.


Assuntos
Síndrome do Coração Esquerdo Hipoplásico/epidemiologia , Transposição dos Grandes Vasos/epidemiologia , District of Columbia/epidemiologia , Feminino , Humanos , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico , Recém-Nascido , Masculino , Maryland/epidemiologia , Gravidez , Diagnóstico Pré-Natal , Estudos Retrospectivos , Transposição dos Grandes Vasos/diagnóstico , Virginia/epidemiologia
12.
Cureus ; 13(8): e16908, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34513481

RESUMO

The rise of the digital revolution has disrupted entire industries and job markets, leading individuals to either upgrade or transfer their skills in order to continue within their designated fields or transition to new workplace contexts. Employers expect their employees to apply their knowledge to real-world settings, analyze and solve problems, connect choices to actions, and innovate and create. Moreover, the COVID-19 pandemic has exacerbated changes to the educational landscape by forcing online and remote contexts; physical distancing and other preventive measures have necessitated a shift towards increasing the use of disruptive digital technologies- extended reality (e.g., virtual and augmented reality), gaming, and additive manufacturing-in simulation delivery. Yet Canada's economic and demographic data suggests that many new graduates struggle to transition from school to working life. The confluence of these factors has led to a need for both individuals and higher education institutions to upgrade and adapt to new digital techniques and modalities. As these needs grow, simulation-based education (SBE) techniques and technologies-already an integral part of training for some professions, including nursing, medicine, and various other health professions-are increasingly being used in digital contexts. In this editorial, we provide our perspective of the socio-technological movement associated with health-professions education (HPE) within the SBE context and examine the application and implementation of micro-credentialing within this field. We also discuss the various levels of expertise that learners may acquire. From this vantage point, we address how SBE can complement the assessment of competencies that learners must demonstrate to attain micro-credentials and explore micro-credentialing's advantages for, and use in, HPE.

13.
J Am Heart Assoc ; 10(16): e020992, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34348475

RESUMO

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty-two US pediatric institutions participated in a 10-year review (2008-2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract-based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community deprivation were obtained. Data for 947 cases showed median age at diagnosis of 9 years; 51% and 56% identified as male and non-White, respectively. Most (89%) had health insurance and were first diagnosed in the United States (82%). Only 13% reported travel to an endemic region before diagnosis. Although 96% of patients were prescribed secondary prophylaxis, only 58% were prescribed intramuscular benzathine penicillin G. Higher deprivation was associated with increasing disease severity (odds ratio, 1.25; 95% CI, 1.08-1.46). Conclusions The majority of recent US cases of ARF and RHD are endemic rather than the result of foreign exposure. Children who live in more deprived communities are at risk for more severe disease. This study demonstrates a need to improve guideline-based treatment for ARF/RHD with respect to secondary prophylaxis and to increase research efforts to better understand ARF and RHD in the United States.


Assuntos
Cardiopatia Reumática/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Febre Reumática/diagnóstico , Febre Reumática/epidemiologia , Febre Reumática/terapia , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/terapia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Classe Social , Determinantes Sociais da Saúde , Fatores de Tempo , Viagem , Estados Unidos
14.
Gait Posture ; 90: 86-91, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34418869

RESUMO

BACKGROUND: Changes in gait due to an ankle foot orthosis (AFO) have been shown to be impacted by the sagittal plane alignment of the AFO, but there is variability in practice and lack of consensus as to how this alignment should be measured. The neutral angle is a measure of AFO alignment that has the potential to be used by various specialties that prescribe, provide, and analyze AFOs. Currently, a lack of validated measurement methods prevents the neutral angle from being used in various clinical settings. Two experimental neutral angle measurement methods are proposed to address this shortcoming: a portable low-cost method for use during AFO fabrication and fitting, and a laboratory-based method for use during dynamic three-dimensional gait analysis (3DGA). RESEARCH QUESTION: What is the concurrent validity of the two experimental neutral angle measurement methods against the gold standard? METHODS: The gold standard neutral angle measurement (NAGOLD) was prospectively collected during a static 3DGA trial for 19 pediatric AFOs from 10 individuals. While NAGOLD was being collected, the neutral angle was simultaneously measured using digital differential inclinometers (NAINCL). Within the same 3DGA session, the neutral angle was also measured during the swing phase of gait (NASWING). The NAINCL and NASWING measurements were compared to NAGOLD using repeated measures ANOVA, ICC, and bootstrapped errors-in-variables regressions. RESULTS: Repeated measures ANOVA indicated no differences between measurement methods (p = 0.43) and ICC analysis indicated good absolute agreement (ICC(A-1) = 0.85). Mean absolute deviations between the NAINCL and NASWING with NAGOLD measurements were 2.4 ° and 1.9 °, with standard deviations of 2.9 ° and 2.7 °, respectively. Maximum observed differences were less than 7 °. The NAINCL and NASWING methods explained 74 % and 81 % of the variance in NAGOLD, respectively. SIGNIFICANCE: The concurrent validity of two new neutral angle measurement methods provides alternative means to assess AFO alignment in the clinic.


Assuntos
Órtoses do Pé , Tornozelo , Articulação do Tornozelo , Fenômenos Biomecânicos , Criança , Marcha , Humanos
15.
ACS Omega ; 6(24): 16253, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34179670

RESUMO

[This corrects the article DOI: 10.1021/acsomega.0c05591.].

16.
Pediatr Ann ; 50(3): e121-e127, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34038649

RESUMO

Fetal echocardiography is now commonly used to assess fetuses for congenital heart disease. To care for their patients, it is important for the pediatrician to understand the utility of the test, the benefits, and the limitations of the results. This review outlines the indications, components, and limitations of fetal echocardiography with a focus on the care that the pediatrician provides to newborns and their families. An understanding of the fetal cardiac examination can assist the pediatrician in caring for patients with either normal or abnormal test results. The need for and timing of postnatal cardiology follow-up, and guidance on referral for fetal echocardiogram for future pregnancies are all critical roles that the pediatrician can play. Most importantly, an understanding of the limitations, including difficult-to-diagnose lesions, allows the pediatrician to maintain a high level of suspicion for cardiac defects regardless of fetal echocardiography findings. [Pediatr Ann. 2021;50(3):e121-e127.].


Assuntos
Cardiologia , Ecocardiografia/métodos , Cardiopatias Congênitas/diagnóstico por imagem , Ultrassonografia Pré-Natal , Feminino , Humanos , Recém-Nascido , Pediatras , Pediatria , Gravidez
17.
ACS Omega ; 6(4): 3186-3193, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33553934

RESUMO

Rare diseases impact hundreds of millions of individuals worldwide. However, few therapies exist to treat the rare disease population because financial resources are limited, the number of patients affected is low, bioactivity data is often nonexistent, and very few animal models exist to support preclinical development efforts. Sialidosis is an ultrarare lysosomal storage disorder in which mutations in the NEU1 gene result in the deficiency of the lysosomal enzyme sialidase-1. This enzyme catalyzes the removal of sialic acid moieties from glycoproteins and glycolipids. Therefore, the defective or deficient protein leads to the buildup of sialylated glycoproteins as well as several characteristic symptoms of sialidosis including visual impairment, ataxia, hepatomegaly, dysostosis multiplex, and developmental delay. In this study, we used a bibliometric tool to generate links between lysosomal storage disease (LSD) targets and existing bioactivity data that could be curated in order to build machine learning models and screen compounds in silico. We focused on sialidase as an example, and we used the data curated from the literature to build a Bayesian model which was then used to score compound libraries and rank these molecules for in vitro testing. Two compounds were identified from in vitro testing using microscale thermophoresis, namely sulfameter (K d 2.15 ± 1.02 µM) and mexenone (K d 8.88 ± 4.02 µM), which validated our approach to identifying new molecules binding to this protein, which could represent possible drug candidates that can be evaluated further as potential chaperones for this ultrarare lysosomal disease for which there is currently no treatment. Combining bibliometric and machine learning approaches has the ability to assist in curating small molecule data and model building, respectively, for rare disease drug discovery. This approach also has the capability to identify new compounds that are potential drug candidates.

18.
JMIR Form Res ; 5(2): e22406, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533720

RESUMO

BACKGROUND: As virtual reality (VR) technologies become increasingly accessible and affordable, clinicians are eager to try VR therapy as a novel means to manage behavioral and psychological symptoms of dementia, which are exacerbated during acute care hospitalization, with the goal of reducing the use of antipsychotics, sedatives, and physical restraints associated with negative adverse effects, increased length of stay, and caregiver burden. To date, no evaluations of immersive VR therapy have been reported for patients with dementia in acute care hospitals. OBJECTIVE: This study aimed to determine the feasibility (acceptance, comfort, and safety) of using immersive VR therapy for people living with dementia (mild, moderate, and advanced) during acute care hospitalization and explore its potential to manage behavioral and psychological symptoms of dementia. METHODS: A prospective, longitudinal pilot study was conducted at a community teaching hospital in Toronto. The study was nonrandomized and unblinded. A total of 10 patients aged >65 years (mean 86.5, SD 5.7) diagnosed with dementia participated in one or more research coordinator-facilitated sessions of viewing immersive 360° VR footage of nature scenes displayed on a Samsung Gear VR head-mounted display. This mixed-methods study included review of patient charts, standardized observations during the intervention, and pre- and postintervention semistructured interviews about the VR experience. RESULTS: All recruited participants (N=10) completed the study. Of the 10 participants, 7 (70%) displayed enjoyment or relaxation during the VR session, which averaged 6 minutes per view, and 1 (10%) experienced dizziness. No interference between the VR equipment and hearing aids or medical devices was reported. CONCLUSIONS: It is feasible to expose older people with dementia of various degrees admitted to an acute care hospital to immersive VR therapy. VR therapy was found to be acceptable to and comfortable by most participants. This pilot study provides the basis for conducting the first randomized controlled trial to evaluate the impact of VR therapy on managing behavioral and psychological symptoms of dementia in acute care hospitals.

19.
Telemed J E Health ; 27(11): 1235-1240, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33513044

RESUMO

Background: This study aims to describe one center's experience in expanding a fetal telecardiology program through collaborative work with maternal fetal medicine (MFM) clinics with the goal of safely reaching mothers during the COVID-19 pandemic. We sought to define the extent of fetal telehealth conversion at a large fetal cardiac care center and evaluate the diagnostic accuracy for studies performed. Methods: At our center, fetal telemedicine expanded from one MFM site before the pandemic to four additional sites by May 2020. A retrospective review of fetal telecardiology visits between March 15 and July 15, 2020, was performed. The chart was reviewed for confirmation of diagnosis postnatally. Results: With pandemic onset, there was a large increase in the number of telemedicine visits with a total of 122 mothers seen between five MFM clinics. Fourteen mothers (11.5%) had abnormal fetal echocardiograms requiring additional follow-up, and seven mothers (5.8%) had a fetal echocardiogram suspicious for a critical congenital heart disease (CCHD). All the fetal echocardiograms suspicious for CCHD were confirmed on postnatal echocardiogram. To our knowledge, none of the normal fetal echocardiograms were found to have congenital heart disease postnatally. Conclusions: In response to the COVID-19 pandemic, we rapidly transitioned to fetal telecardiology using a variety of formats. This has reduced potential infectious exposure for pregnant mothers and minimized contact between physicians without compromising diagnostic accuracy. In our experience, the expansion of a telemedicine program requires strong initial infrastructure, prior relationships with MFM providers, and appropriate training among obstetric sonographers.


Assuntos
COVID-19 , Pandemias , Feminino , Humanos , Gravidez , Cuidado Pré-Natal , Estudos Retrospectivos , SARS-CoV-2
20.
Pilot Feasibility Stud ; 6(1): 166, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33292729

RESUMO

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are difficult to manage, particularly in acute care settings. As virtual reality (VR) technology becomes increasingly accessible and affordable, there is growing interest among clinicians to evaluate VR therapy in hospitalized patients, as an alternative to administering antipsychotics/sedatives or using physical restraints associated with negative side effects. OBJECTIVES: Validate and refine the proposed research protocol for a randomized controlled trial (RCT) that evaluates the impact of VR therapy on managing BPSD in acute care hospitals. Special attention was given to ascertain the processes of introducing non-pharmacological interventions in acute care hospitals. METHODS: Ten patients 65 years or older (mean = 87) previously diagnosed with dementia, admitted to an acute care hospital, were recruited over 3-month period into a prospective longitudinal pilot study. The intervention consisted of viewing 20-min of immersive 360° VR using a head-mounted display. Baseline and outcomes data were collected from the hospital electronic medical records, pre/post mood-state questionnaires, Neuropsychiatric Inventory (NPI) score, and standardized qualitative observations. Comprehensive process data and workflow were documented, including timestamps for each study task and detailed notes on personnel requirements and challenges encountered. RESULTS: Of 516 patients admitted during the study, 67 met the inclusion/exclusion criteria. In total, 234 calls were initiated to substitute decision makers (SDM) of the 67 patients for the consenting process. Nearly half (45.6%) of SDMs declined participation, and 40% could not be reached in time before patients being discharged, resulting in 57 eligible patients not being enrolled. Ten consented participants were enrolled and completed the study. The initial VR session averaged 53.6 min, largely due to the administration of NPI (mean = 19.5 min). Only four participants were able to respond reliably to questions. Seven participants opted for additional VR therapy sessions; of those providing feedback regarding the VR content, they wanted more varied scenery (animals, fields of flowers, holiday themes). Few sessions (4/18) encountered technical difficulties. CONCLUSION: The pilot was instrumental in identifying issues and providing recommendations for the RCT. Screening, inclusion criteria, consenting, data collection, and interaction with SDMs and hospital staff were all processes requiring changes and optimizations. Overall, patients with dementia appear to tolerate immersive VR, and with suggested protocol alterations, it is feasible to evaluate this non-pharmacological intervention in acute care hospitals.

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