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Background: Interventions that promote healthy lifestyles are critical for the prevention of Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). However, knowledge of the best practices for implementing AD/ADRD prevention in healthcare settings remains limited. Objective: We aimed to qualitatively identify barriers and facilitators to implementing a clinical trial of a novel lifestyle intervention (My Healthy Brain) in our medical center for older patients with subjective cognitive decline who are at-risk for AD/ADRD. Methods: We conducted focus groups with 26 healthcare professionals (e.g., physicians, psychology, nursing) from 5 clinics that treat older patients (e.g., memory care, psychiatry). Our qualitative analysis integrated two implementation frameworks to systematically capture barriers and facilitators to AD/ADRD prevention (Consolidated Framework for Implementation Science Research) that impact implementation outcomes of acceptability, appropriateness, and feasibility (Proctor's framework). Results: We found widespread support for an RCT of My Healthy Brain and AD/ADRD prevention. Participants identified barriers related to patients (stigma, technological skills), providers (dismissiveness of "worried well," doubting capacity for behavior change), clinics (limited time and resources), and the larger healthcare system (underemphasis on prevention). Implementation strategies guided by Expert Recommendations for Implementing Change (ERIC) included: developing tailored materials, training staff, obtaining buy-in from leadership, addressing stigmatized language and practices, identifying "champions," and integrating with workflows and resources. Conclusions: The results will inform our recruitment, enrollment, and retention procedures to implement the first randomized clinical trial of My Healthy Brain. Our study provides a blueprint for addressing multi-level barriers to the implementation of AD/ADRD prevention for older patients in medical settings.
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Demência , Grupos Focais , Humanos , Demência/prevenção & controle , Masculino , Feminino , Idoso , Pessoal de Saúde/educação , Doença de Alzheimer/prevenção & controle , Estilo de Vida , Disfunção Cognitiva/prevenção & controle , Centros Médicos AcadêmicosRESUMO
PRECIS: After failure of a glaucoma drainage device in children, implantation of a second Ahmed glaucoma valve with mitomycin-C allows a significant reduction of intraocular pressure and number of medications with good medium- and long-term survival. INTRODUCTION: The effectiveness of glaucoma drainage devices (GDD) is limited in time. There is little literature regarding the optimal management strategy after failure of a GDD in pediatric glaucoma. PURPOSE: To report the outcomes of Ahmed glaucoma valve implantation (AGV) with mitomycin-C (MMC) after failure of a GDD in children. METHODS: Retrospective chart review of patients with a history of at least one GDD receiving an AGV implantation with MMC between 2000 and 2019. We defined complete success as an IOP of 5 to 21 mmHg without glaucoma medication and qualified success as a final IOP of 5 to 21 mmHg with one or more glaucoma medication, without loss of vision. RESULTS: Twenty-one patients (22 eyes) met the inclusion criteria. The intraocular pressure and number of medications were significantly reduced. The probability of complete success was 47% [95%CI: 29% - 75%] at 2 years and 34% [95%CI: 18% - 65%] at 4 years. The probability of qualified success was 74% [95%CI: 56% - 97%] at 2 years, and 54% [95%CI: 34% - 84%] at 5 years. Failure happened in 10 eyes after a mean time of 4.3 years ±3.6 [6 mo - 15 y], 5 of which (23%) for severe complication or loss of vision. DISCUSSION: This study of implantation of a second valve with MMC reports a significant decrease of IOP and medications with medium- and long-term success rates close to those reported for a first valve implantation, although with a high risk of complications.
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BACKGROUND: Screening for iron deficiency anemia (IDA) is important in managing pediatric patients with inflammatory bowel disease (IBD). Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous (IV) iron to treat IDA in this population. AIM: To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center. METHODS: A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019. 92 patients met study criteria for IDA, of which 57 received IV iron, 17 received oral iron, and 18 were discharged prior to receiving iron therapy. RESULTS: Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9 (± 0.2) g/dL in mean (± SE) hemoglobin (Hb) concentration by the first ambulatory follow-up, compared to patients who received oral iron 0.8 (± 0.3) g/dL or no iron 0.8 (± 0.3) g/dL (P = 0.03). One out of 57 (1.8%) patients that received IV iron therapy experienced an adverse reaction. CONCLUSION: Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.
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Pediatric neoplastic extraocular soft-tissue lesions in the orbit are uncommon. Early multimodality imaging work-up and recognition of the key imaging features of these lesions allow narrowing of the differential diagnoses in order to direct timely management. In this paper, the authors present a multimodality approach to the imaging work-up of these lesions and highlight the use of ocular ultrasound as a first imaging modality where appropriate. We will discuss vascular neoplasms (congenital hemangioma, infantile hemangioma), optic nerve lesions (meningioma, optic nerve glioma), and other neoplastic lesions (plexiform neurofibroma, teratoma, chloroma, rhabdomyosarcoma, infantile fibrosarcoma, schwannoma).
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Neoplasias Orbitárias , Neoplasias de Tecidos Moles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Diagnóstico Diferencial , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Ultrassonografia/métodosRESUMO
Orbital pathologies can be broadly classified as ocular, extra-ocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In part 1 of this orbital series, the authors will discuss the differential diagnosis and key imaging features of pediatric ocular pathologies. These include congenital and developmental lesions (microphthalmos, anophthalmos, persistent fetal vasculature, coloboma, morning glory disc anomaly, retinopathy of prematurity, Coats disease), optic disc drusen, infective and inflammatory lesions (uveitis, toxocariasis, toxoplasmosis), and ocular neoplasms (retinoblastoma, retinal hamartoma, choroidal melanoma, choroidal nevus). This pictorial review provides a practical approach to the imaging work-up of these anomalies with a focus on ocular US as the first imaging modality and additional use of CT and/or MRI for the evaluation of intracranial abnormalities. The characteristic imaging features of the non-neoplastic mimics of retinoblastoma, such as persistent fetal vasculature and Coats disease, are also highlighted.
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Doenças Orbitárias , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Diagnóstico Diferencial , Diagnóstico por Imagem/métodos , Oftalmopatias/diagnóstico por imagem , Doenças Orbitárias/diagnóstico por imagemRESUMO
Orbital pathologies can be broadly classified as ocular lesions, extraocular soft-tissue pathologies (non-neoplastic and neoplastic), and bony and traumatic lesions. In this paper, we discuss the key imaging features and differential diagnoses of bony and traumatic lesions of the pediatric orbit and globe, emphasizing the role of CT and MRI as the primary imaging modalities. In addition, we highlight the adjunctive role of ocular sonography in the diagnosis of intraocular foreign bodies and discuss the primary role of sonography in the diagnosis of traumatic retinal detachment.
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Órbita , Criança , Pré-Escolar , Humanos , Lactente , Diagnóstico Diferencial , Traumatismos Oculares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Órbita/diagnóstico por imagem , Órbita/lesões , Doenças Orbitárias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodosRESUMO
Orbital pathologies can be broadly classified as ocular, extraocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In this paper, we discuss the key imaging features and differential diagnoses of congenital and developmental lesions (dermoid cyst, dermolipoma), infective and inflammatory pathologies (pre-septal cellulitis, orbital cellulitis, optic neuritis, chalazion, thyroid ophthalmopathy, orbital pseudotumor), and non-neoplastic vascular anomalies (venous malformation, lymphatic malformation, carotid-cavernous fistula), emphasizing the key role of CT and MRI in the imaging work-up. In addition, we highlight the adjunctive role of ocular ultrasound in the diagnosis of dermoid cyst and chalazion, and discuss the primary role of ultrasound in the diagnosis of vascular malformations.
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Doenças Orbitárias , Criança , Pré-Escolar , Humanos , Diagnóstico Diferencial , Diagnóstico por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Doenças Orbitárias/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
Ocular associations in Mowat-Wilson syndrome (MWS) are rare. Those involving the anterior segment are scarce in the literature. We describe a child with genetic confirmation of MWS that presented with acquired onset of unilateral anterior iris adhesions with no known trauma.
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Doença de Hirschsprung , Deficiência Intelectual , Doenças da Íris , Microcefalia , Criança , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Fácies , Doença de Hirschsprung/complicações , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Microcefalia/complicações , Microcefalia/diagnóstico , Microcefalia/genética , Doenças da Íris/diagnóstico , Aderências Teciduais , IrisRESUMO
Inactivating mutations and the duplication of methyl-CpG binding protein 2 (MeCP2), respectively, mediate Rett syndrome (RTT) and MECP2 duplication syndrome. These disorders underscore the conceptual dose-dependent risk posed by MECP2 gene therapy for mosaic RTT patients. Recently, a miRNA-Responsive Autoregulatory Element (miRARE) mitigated the dose-dependent toxicity posed by self-complementary adeno-associated viral vector serotype 9 (AAV9) miniMECP2 gene therapy (scAAV9/miniMECP2-myc) in mice. Here, we report an efficacy assessment for the human-ready version of this regulated gene therapy (TSHA-102) in male Mecp2-/y knockout (KO) mice after intracerebroventricular (ICV) administration at postnatal day 2 (P2) and after intrathecal (IT) administration at P7, P14 (±immunosuppression), and P28 (±immunosuppression). We also report qPCR studies on KO mice treated at P7-P35; protein analyses in KO mice treated at P38; and a survival safety study in female adult Mecp2-/+ mice. In KO mice, TSHA-102 improved respiration, weight, and survival across multiple doses and treatment ages. TSHA-102 significantly improved the front average stance and swing times relative to the front average stride time after P14 administration of the highest dose for that treatment age. Viral genomic DNA and miniMECP2 mRNA were present in the CNS. MiniMeCP2 protein expression was higher in the KO spinal cord compared to the brain. In female mice, TSHA-102 permitted survivals that were similar to those of vehicle-treated controls. In all, these pivotal data helped to support the regulatory approval to initiate a clinical trial for TSHA-102 in RTT patients (clinical trial identifier number NCT05606614).
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Deficiência Intelectual Ligada ao Cromossomo X , MicroRNAs , Síndrome de Rett , Adulto , Humanos , Feminino , Masculino , Animais , Camundongos , Síndrome de Rett/genética , Síndrome de Rett/terapia , Encéfalo , DNA Viral , Terapia Genética , Camundongos KnockoutRESUMO
A 14-year-old boy was referred to the ophthalmology department with a 4-day history of rapid-onset right upper lid pain, swelling and erythema starting 9 hours after his first dose of COVID-19 mRNA vaccination (BNT162b2/Comirnaty, Pfizer-BioNTech). On examination, he had significant right upper lid ptosis, oedema and erythema, with associated limitation of right eye abduction and elevation. He was found to have acute dacryoadenitis with orbital inflammatory disease on clinical and laboratory investigations. He was given tapering oral prednisone and had full resolution of symptoms within 2 weeks. This is the first known case of orbital inflammation after COVID-19 mRNA vaccination. Given the temporal association between the patient's vaccination and symptom onset, we believe it is likely that immunisation prompted the onset of disease.
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COVID-19 , Dacriocistite , Adolescente , Vacina BNT162 , Vacinas contra COVID-19/efeitos adversos , Dacriocistite/etiologia , Humanos , Masculino , RNA Mensageiro , SARS-CoV-2 , VacinaçãoRESUMO
Strabismus is a common condition, affecting 1%-4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification of multiple loci via linkage analyses, no specific genes have been identified from these studies. The current study is based on a seven-generation family with isolated strabismus inherited in an autosomal dominant manner. A total of 13 individuals from a common ancestor have been included for linkage analysis. Among these, nine are affected and four are unaffected. A single linkage signal has been identified at an 8.5 Mb region of chromosome 14q12 with a multipoint LOD (logarithm of the odds) score of 4.69. Disruption of this locus is known to cause FOXG1 syndrome (or congenital Rett syndrome; OMIM #613454 and *164874), in which 84% of affected individuals present with strabismus. With the incorporation of next-generation sequencing and in-depth bioinformatic analyses, a 4 bp non-coding deletion was prioritised as the top candidate for the observed strabismus phenotype. The deletion is predicted to disrupt regulation of FOXG1, which encodes a transcription factor of the Forkhead family. Suggestive of an autoregulation effect, the disrupted sequence matches the consensus FOXG1 and Forkhead family transcription factor binding site and has been observed in previous ChIP-seq studies to be bound by Foxg1 in early mouse brain development. Future study of this specific deletion may shed light on the regulation of FOXG1 expression and may enhance our understanding of the mechanisms contributing to strabismus and FOXG1 syndrome.
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Fatores de Transcrição Forkhead/genética , Proteínas do Tecido Nervoso/genética , Síndrome de Rett/genética , Deleção de Sequência , Estrabismo/genética , Adolescente , Idoso , Idoso de 80 Anos ou mais , Animais , Ligação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Linhagem , Sequenciamento do Exoma , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
PURPOSE: To report the visual outcomes, refractive results, and complications of simple excision for limbal dermoid in the first 8 years of life. METHODS: This retrospective chart review included all children aged 8 years or younger who underwent excision of a grade I or II limbal dermoid without involvement of the visual axis between the years 2000 and 2019. RESULTS: Nineteen patients met the inclusion criteria. Their mean age was 4.2 ± 2.0 years (age range: 9 months to 8 years). The mean change in visual acuity was +1 ± 2.3 lines. The mean astigmatism was 3.20 ± 1.80 diopters (D) preoperatively and 3.50 ± 2.20 D at the last visit; the mean change in the astigmatism power was +0.20 ± 1.20 D (range: -1.50 to +2.75 D). Epithelial healing occurred in a mean of 8 days. No complications such as perforation were encountered. All patients had a good cosmetic outcome. CONCLUSIONS: Reepithelialization led to good cosmetic outcomes after this quick, simple, and uncomplicated procedure. There was no significant change in visual acuity or astigmatism, so amblyopia and astigmatism reduction are poor indications for limbal dermoid excision. Families should be counseled preoperatively that correction of the astigmatism and patching will remain essential in the postoperative management of amblyopia. [J Pediatr Ophthalmol Strabismus. 2021;58(3):196-201.].
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Astigmatismo , Doenças da Córnea , Cisto Dermoide , Neoplasias Oculares , Limbo da Córnea , Astigmatismo/cirurgia , Criança , Pré-Escolar , Doenças da Córnea/cirurgia , Cisto Dermoide/diagnóstico , Cisto Dermoide/cirurgia , Humanos , Lactente , Limbo da Córnea/cirurgia , Estudos RetrospectivosRESUMO
PRECIS: Mitomycin was used with Ahmed valve implantation in 81 eyes of 63 children. After 5 years, probability of intraocular pressure (IOP) control without glaucoma medication was 35±6%; 57% achieved IOP control with topical medications after 10 years. PURPOSE: The purpose of this study was to determine the long-term outcomes of Ahmed glaucoma valve (AGV) implantation with intraoperative application of mitomycin-C (MMC) for the treatment of childhood glaucoma. METHODS: Retrospective review of children undergoing AGV implantation with subtenon application of MMC between 2000 and 2019. We defined surgical success as a final IOP of 5 to 21 mm Hg with no glaucoma medication, no subsequent glaucoma surgery, and no severe complication. Qualified success was defined if the above criteria were met with topical antiglaucoma medication. RESULTS: Eighty-one eyes of 63 patients were included. The probability of complete success was 72±5% (63% to 83%) at 1 year, 58±6% (48% to 70%) at 2 years, and 35±6% (25% to 48%) at 5 years. The probability of qualified success was 92±3% (87% to 98%) at 1 year, 79±5% (70% to 89%) at 5 years, 57±7% (44% to 73%) at 10 years, and 39±9% (24% to 62%) at 14 years. The IOP was reduced by an average of 10.7±9 mm Hg from preoperative visit to the last follow-up, and the number of medications decreased from 3.0±1.4 to 1.5±1.4 after implantation. CONCLUSIONS: A significant proportion of patients achieved long-term IOP control without glaucoma medication. The majority achieved IOP control with additional topical antiglaucoma medications. When compared with existing AGV implantation in childhood literature, the use of MMC appears to lengthen the drop-free (complete success) duration, as well as the long-term IOP control with topical medications.
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Implantes para Drenagem de Glaucoma , Glaucoma , Criança , Seguimentos , Glaucoma/tratamento farmacológico , Glaucoma/cirurgia , Humanos , Pressão Intraocular , Mitomicina , Implantação de Prótese , Estudos Retrospectivos , Resultado do TratamentoRESUMO
MECP2 gene transfer has been shown to extend the survival of Mecp2-/y knockout mice modelling Rett syndrome, an X-linked neurodevelopmental disorder. However, controlling deleterious overexpression of MECP2 remains the critical unmet obstacle towards a safe and effective gene therapy approach for Rett syndrome. A recently developed truncated miniMECP2 gene has also been shown to be therapeutic after AAV9-mediated gene transfer in knockout neonates. We show that AAV9/miniMECP2 has a similar dose-dependent toxicity profile to that of a published second-generation AAV9/MECP2 vector after treatment in adolescent mice. To overcome that toxicity, we developed a risk-driven viral genome design strategy rooted in high-throughput profiling and genome mining to rationally develop a compact, synthetic microRNA target panel (miR-responsive auto-regulatory element, 'miRARE') to minimize the possibility of miniMECP2 transgene overexpression in the context of Rett syndrome gene therapy. The goal of miRARE is to have a built-in inhibitory element responsive to MECP2 overexpression. The data provided herein show that insertion of miRARE into the miniMECP2 gene expression cassette greatly improved the safety of miniMECP2 gene transfer without compromising efficacy. Importantly, this built-in regulation system does not require any additional exogenous drug application, and no miRNAs are expressed from the transgene cassette. Although broad applications of miRARE have yet to be determined, the design of miRARE suggests a potential use in gene therapy approaches for other dose-sensitive genes.
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Terapia Genética/métodos , Proteína 2 de Ligação a Metil-CpG/administração & dosagem , MicroRNAs/administração & dosagem , Engenharia de Proteínas/métodos , Elementos Reguladores de Transcrição , Síndrome de Rett/terapia , Animais , Humanos , Injeções Espinhais , Proteína 2 de Ligação a Metil-CpG/genética , Camundongos , Camundongos Knockout , MicroRNAs/genética , Elementos Reguladores de Transcrição/genética , Síndrome de Rett/genéticaRESUMO
PURPOSE: To evaluate the resection-recession procedure on a single muscle for the management of incomitant strabismus using an alternative calculation. METHODS: The medical records of adult patients undergoing combined adjustable resection-recession surgery on a single rectus muscle at one institution from 2008 to 2019 were reviewed retrospectively. Each patient had a full orthoptic evaluation before and at least 10 weeks after surgery. The main outcome measure was alignment at last follow-up examination in the primary position and eccentric gaze (field of action). RESULTS: A total of 20 procedures in 20 patients were included. The etiology was paretic in 14 cases and restrictive in 6. All rectus muscles were operated. An adjustable suture technique was used in every case, but only 5 required adjustment. The average length of follow-up was 1.7 years (range, 2.4 months to 11.1 years). Postoperative reduction of deviation in eccentric gaze was observed in all patients and averaged 70% (range, 5Δ-48Δ). The technique was particularly helpful for the inferior rectus muscle (85.8% reduction), followed by the medial rectus (66%), lateral rectus (55%), and superior rectus muscles (55%). Three-quarters of the patients became orthotropic in primary position. Good results were noted for both paretic and restrictive etiologies (64%, 83%, resp., reduction in eccentric gaze). Four of 20 patients (20%) were overcorrected in eccentric gaze. One patient required prism to control a small comitant deviation (6Δ). No complications or muscle slippage occurred. CONCLUSIONS: In our study cohort, the resection-recession operation was effective in reducing incomitance when used on any of the four rectus muscles.