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1.
Ophthalmologica ; : 1-9, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38723611

RESUMO

INTRODUCTION: This study aimed to investigate the incidence of and risk factors for epiretinal membrane (ERM) formation following primary rhegmatogenous retinal detachment (RRD) repair. METHODS: This comparative, retrospective, single-center cohort study included eyes with primary RRD treated between 2011 and 2023 at Massachusetts Eye and Ear, Boston, Massachusetts, with pars plana vitrectomy (PPV), scleral buckle (SB), PPV+SB, or pneumatic retinopexy (PnR). Demographic, clinical, and surgical parameters were collected from medical records. The primary outcome was the risk of ERM formation, while the secondary outcome was the risk of ERM requiring surgery. Univariable and multivariable Cox regression were performed, and a hazard ratio (HR) and 95% confidence interval (95% CI) were reported. RESULTS: Overall, 394 eyes were included. The mean age was 58.49 ± 12.8 years, and most patients were male. There was a significantly lower risk of ERM formation following SB compared to PPV in the univariable analysis (HR = 0.2, 95% CI = 0.08-0.60, p = 0.003); however, there was no significant association between treatment modality and ERM formation on multivariable Cox regression controlling for confounding factors (p = 0.24). ERM formation was found more commonly in patients who were older (HR = 1.0 per 1 year increase in age, 95% CI = 1.01-1.04, p = 0.001), those with worse baseline visual acuity (HR = 1.3, 95% CI = 1.09-1.71, p = 0.008), and those with macula-off RRDs (HR = 2.1, 95% CI = 1.41-3.32, p < 0.001). CONCLUSION: Surgical modality does not have a significant impact on the risk of ERM following retinal detachment repair. However, age, baseline visual acuity, and macular status are important predictors of ERM formation after RRD repair.

2.
BMC Palliat Care ; 23(1): 169, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003449

RESUMO

BACKGROUND: Despite the availability of guidance for the provision of good end-of-life care, there are significant variations across the UK in its delivery. This study sought to identify the influences on end-of-life treatment and care planning across several areas where deficiencies in evidence-based practice have been identified, and to develop consensus among healthcare providers and users for recommendations on how to address these deficits. METHODS: An online survey (106 responses), qualitative interviews (55 participants) and a consensus-building exercise (475 participants in the initial round) were undertaken. Participants included people approaching the end of life, people important to them, and health and care practitioners who help people plan for the end of life or provide end-of-life care. Recruitment was via online methods, including social media and online newsletters of relevant charities and professional organisations. Thematic analysis using the framework method was used to analyse qualitative data. Synthesis of qualitative and quantitative data led to the development of statements regarding recommendations for advancing implementation of good practice. A two-stage consensus-building exercise asked respondents first to rate these statements and then to rate and rank further sub-recommendations in three areas. RESULTS: Results from the consensus building exercise confirmed that end-of-life care planning conversations are to be welcomed and encouraged, and that the priority should be to have the conversation (which could be initiated by a range of professionals, or people planning end-of-life care themselves), rather than to wait for an ideal time to have it. Further rounds identified specific components of a standardised record of end-of-life treatment and care preferences that should be prioritised, specific health and care staff that should be empowered through training in advanced communication, and aspects of communication most important to include in training for healthcare professionals. CONCLUSIONS: Our study has identified opportunities for action to improve end-of-life treatment and care by combining multiple stakeholder perspectives and building consensus among them: the resulting recommendations have sufficient granularity to be implemented and evaluated. They are of relevance to policy makers, those who train healthcare professionals, and those looking after patients approaching the end of life.


Assuntos
Consenso , Pesquisa Qualitativa , Assistência Terminal , Humanos , Assistência Terminal/métodos , Assistência Terminal/normas , Reino Unido , Inquéritos e Questionários , Masculino , Feminino , Pessoa de Meia-Idade , Planejamento Antecipado de Cuidados/normas , Adulto , Idoso
3.
Graefes Arch Clin Exp Ophthalmol ; 261(12): 3635-3641, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37266703

RESUMO

PURPOSE: Small choroidal melanocytic lesions have a low rate of metastasis and can be reasonably managed with surveillance until they demonstrate evidence of growth or clinical risk factors for melanoma. However, even choroidal nevi are not stationary, with many exhibiting slow growth over time. We sought to quantify the growth rates of indeterminate choroidal lesions that were initially observed prior to a clinical diagnosis of melanoma. METHODS: A single-center retrospective study was performed of patients diagnosed with choroidal melanoma based upon clinical characteristics who were initially followed for indeterminate lesions over at least 6 months. Subjects were included if they had a minimum of two B-scan ultrasound measurements prior to the visit at which melanoma was diagnosed. Demographic and tumor characteristics were collected from the medical record. Growth rates were calculated as the change in lesion thickness in mm per month and were recorded at 6-month intervals; ultrasound measurements less than 1 month apart were excluded. The characteristics of indeterminate lesions with faster versus slower growth rates prior to melanoma diagnosis were compared. RESULTS: Fifty-four patients met inclusion criteria. The mean age at melanoma diagnosis was 67.4 years, and 53.7% were female. Subjects had a median of four B-scan ultrasound measurements prior to melanoma diagnosis (range 2-19) and were followed for a median of 40.6 months (range 9.9-138.0 months). The mean lesion thickness was 1.4 mm (range 0.5-2.2 mm) at presentation, and increased to 2.3 mm (range 1.5-5.7 mm) at melanoma diagnosis. The mean growth rate did not exceed 0.021 mm/month (95% CI: 0.004-0.039; equivalent to 0.25 mm/year) for indeterminate lesions, but increased to 0.057 mm/month (95% CI: 0.043-0.071 mm/month; equivalent to 0.68 mm/year) at the time of melanoma diagnosis. Rapidly growing lesions had a greater tumor thickness and shorter duration of observation at the time of melanoma diagnosis. CONCLUSION: For most indeterminate choroidal lesions eventually diagnosed as melanoma, the lesion thickness was relatively stable for a period of time, then rose significantly between the penultimate visit and the final visit. These findings confirm the recommendation for continued monitoring of suspicious choroidal lesions, as the growth rate may accelerate just prior to melanoma diagnosis. Lesions with a mean growth rate of up to 0.25 mm/year were observed, whereas lesions clinically determined to have transformed into melanoma demonstrated a mean growth rate of 0.68 mm/year. These values provide a baseline for future studies and potential therapies directed at stabilizing or reducing the growth of indeterminate choroidal lesions or small choroidal melanomas. Limitations of this study include its retrospective nature and reliance on clinical diagnostic criteria.


Assuntos
Neoplasias da Coroide , Melanoma , Neoplasias Cutâneas , Humanos , Feminino , Masculino , Estudos Retrospectivos , Melanoma/diagnóstico , Melanoma/patologia , Corioide/patologia , Neoplasias da Coroide/diagnóstico , Neoplasias Cutâneas/diagnóstico
4.
Retina ; 43(4): 600-605, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729639

RESUMO

PURPOSE: To determine the incidence of and identify risk factors for redetachment in eyes that underwent rhegmatogenous retinal detachment (RRD) repair after infectious endophthalmitis. METHODS: Retrospective chart review of patients who had RRD surgery following a diagnosis of endophthalmitis from 2008 to 2021 at a tertiary referral center. Demographic and clinical characteristics as well as operative details were collected. Subjects with prior RRD, trauma, keratoprosthesis, or less than 3 months of postoperative follow-up were excluded. Univariate logistic regression analyses were performed. RESULTS: Thirty-four eyes of 34 patients were included. Most subjects were male with a mean age of 60.1 years. Exogenous (58.8%) was more common than endogenous (41.2%) sources of endophthalmitis. Seventeen of 34 eyes (50.0%) experienced redetachment. Significant risk factors were infection with virulent organisms, hypotony, and postoperative proliferative vitreoretinopathy. Initial management with vitreous tap or vitrectomy, exogenous versus endogenous source, and surgical procedure were not associated with recurrent RRD. At the final follow-up, 32 of 34 eyes (91.2%) were attached, although more than one third of these had silicone oil. CONCLUSION: Redetachment occurred in half of eyes that underwent surgical repair of RRD after endophthalmitis. Early vitrectomy, with or without prior vitreous tap, was not associated with a higher risk of redetachment and improved the likelihood of a positive culture result. Culture data can aid in risk stratification because organism virulence was a risk factor for recurrent RRD. Although visual outcomes were generally poor, most retinas remained attached at the final visit.


Assuntos
Doenças da Córnea , Endoftalmite , Descolamento Retiniano , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Descolamento Retiniano/diagnóstico , Estudos Retrospectivos , Córnea , Doenças da Córnea/cirurgia , Próteses e Implantes/efeitos adversos , Vitrectomia/métodos , Endoftalmite/cirurgia , Endoftalmite/complicações , Seguimentos
5.
Nature ; 531(7594): 323-8, 2016 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-26958831

RESUMO

The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.


Assuntos
Catarata/terapia , Cristalino/citologia , Cristalino/fisiologia , Recuperação de Função Fisiológica , Regeneração/fisiologia , Células-Tronco/citologia , Visão Ocular/fisiologia , Animais , Catarata/congênito , Catarata/patologia , Catarata/fisiopatologia , Extração de Catarata , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Proteínas do Olho/metabolismo , Proteínas de Homeodomínio/metabolismo , Homeostase , Humanos , Macaca , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Células-Tronco/metabolismo
6.
BMC Palliat Care ; 21(1): 211, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36447187

RESUMO

BACKGROUND: Resources for healthcare professionals, patients and those important to them relating to planning and coordinating treatment and care at the end of life are abundant, and can be difficult to navigate. However, they have not been systematically collated or catalogued in terms of their purpose, scope or intended audience. AIM: To collate, categorise and characterise advance care planning and end-of-life treatment and care (EoLT + C) resources directed towards healthcare professionals, patients and their families. METHODS: Rapid review and thematic synthesis of resources available in the United Kingdom. Google searches and reviews of websites belonging to selected organisations that develop and publish materials relating to EoLT + C, and advance care planning were used. Materials were included if they were intended for those over 18 living in the UK and pertained to five domains of EoLT + C: identifying those approaching end of life; accessing EoLT + C services; conducting important conversations about EoLT + C and preferences; advance care planning, including recording of preferences and plans; and ensuring that plans and preferences are accessed and used by health and social care services. RESULTS: 246 resources directed at healthcare professionals, patients and their families were identified, collated, catalogued and made internationally available for clinicians, researchers, patients and the public. 61 were classified as interactive, providing decision support in EoLT + C that went beyond simply providing information. Of these, there was notable content overlap among tools for identifying patients in their last year of life. There was variation in the development of tools across all domains of end-of-life care by geography and patient group. Few interactive resources integrated seamlessly with a digital interface or healthcare provider workflows. Incentives for the adoption of best-practice appeared rare. CONCLUSIONS: We present a repeatable and scalable approach to the cataloguing and characterisation of palliative care resources. The identified resources will be of benefit not only to those in the UK but to those in other countries, developing or evaluating their own resources for aiding professionals and patients to plan and deliver excellent treatment and care at the end of life.


Assuntos
Planejamento Antecipado de Cuidados , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Humanos , Morte , Cuidados Paliativos
7.
Nature ; 523(7562): 607-11, 2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-26200341

RESUMO

The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.


Assuntos
Catarata/tratamento farmacológico , Catarata/metabolismo , Lanosterol/farmacologia , Lanosterol/uso terapêutico , Agregados Proteicos/efeitos dos fármacos , Agregação Patológica de Proteínas/tratamento farmacológico , Adulto , Sequência de Aminoácidos , Amiloide/química , Amiloide/efeitos dos fármacos , Amiloide/metabolismo , Amiloide/ultraestrutura , Animais , Sequência de Bases , Catarata/congênito , Catarata/genética , Catarata/patologia , Linhagem Celular , Criança , Cristalinas/química , Cristalinas/genética , Cristalinas/metabolismo , Cristalinas/ultraestrutura , Cães , Feminino , Humanos , Lanosterol/administração & dosagem , Cristalino/efeitos dos fármacos , Cristalino/metabolismo , Cristalino/patologia , Masculino , Modelos Moleculares , Dados de Sequência Molecular , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Proteínas Mutantes/ultraestrutura , Linhagem , Agregação Patológica de Proteínas/patologia
8.
Graefes Arch Clin Exp Ophthalmol ; 258(3): 663-667, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31823061

RESUMO

PURPOSE: Anecdotal reports of refractive changes in pregnancy are familiar to optometrists and ophthalmologists. Refractive stability during pregnancy has implications in both prescribing of refractive correction and candidacy for refractive surgery. This study aims to examine refractive status in a nationally representative sample of US pregnant women. METHODS: The National Health and Nutrition Examination Survey (NHANES) is a weighted, stratified, cross-sectional survey of the US population conducted every 2 years. During 2005-2006 and 2007-2008, the exam included multiple ophthalmic tests including refraction, keratometry, and lensometry. Female participants aged 20-44 years with available vision examination data were included in the study. Subjects were excluded if best obtainable visual acuity was worse than 20/40 or there was prior history of cataract or refractive surgery. The primary outcome was defined as refractive change stratified by trimester of pregnancy. RESULTS: 301 pregnant women were matched with 301 nonpregnant controls based on age, ethnicity, and education. There was no difference in refractive error between pregnant women and matched nonpregnant controls (all p > 0.99). For the refractive change analysis, a subgroup of 60 pregnant subjects with glasses at presentation was matched to 60 nonpregnant controls. Multivariate regression showed a significant increase in refractive change versus prior to glasses prescription by trimester of pregnancy (p = 0.02), though this change was not in a specific direction (i.e., no significant shift toward either myopia or hyperopia). CONCLUSIONS: Pregnant women have greater refractive difference from prior spectacle prescription later in pregnancy, but the direction of this change is variable and not significant. This finding may reflect a longer time to last glasses prescription later in pregnancy, given concerns that refractive error fluctuates in pregnancy. Additional longitudinal studies are needed to better characterize the effects of pregnancy on refractive status.


Assuntos
Inquéritos Nutricionais/métodos , Complicações na Gravidez/epidemiologia , Refração Ocular/fisiologia , Erros de Refração/epidemiologia , Acuidade Visual , Adulto , Estudos Transversais , Feminino , Humanos , Morbidade/tendências , Gravidez , Complicações na Gravidez/fisiopatologia , Prevalência , Erros de Refração/fisiopatologia , Estados Unidos/epidemiologia
9.
Orbit ; 38(6): 492-494, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30628515

RESUMO

A 5-year-old otherwise healthy girl presented to the oculoplastic service with a painless superotemporal subconjunctival mass in the left eye. Visual acuity was within normal limits, and there was no evidence of proptosis or orbital enlargement. Excision was performed to remove the anterior portion of the mass for alleviation of symptoms. On histopathological analysis, the mass was comprised of fibroadipose tissue consistent with dermolipoma and contained a hard nodule found to be a calcified tooth. In the periocular region, odontogenic choristoma (tooth) is a rare lesion, and has been reported to occur within teratomas, dermoid cysts, and displaced oral embryonic epithelium. We describe an unusual case of a tooth occurring within a sporadic dermolipoma. The clinical presentation, examination, management, and histopathology are reviewed.


Assuntos
Coristoma/patologia , Doenças da Túnica Conjuntiva/patologia , Lipoma/patologia , Neoplasias Cutâneas/patologia , Dente , Pré-Escolar , Coristoma/cirurgia , Doenças da Túnica Conjuntiva/cirurgia , Feminino , Humanos , Lipoma/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Neoplasias Cutâneas/cirurgia
10.
Med Care ; 56(1): 19-24, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087980

RESUMO

OBJECTIVE: The intensive and varied services required by high-need patients have inspired a number of new care delivery models; however, evidence of their effectiveness is mixed. This study evaluated whether augmenting a patient-centered medical home (PCMH) with intensive outpatient management enhances high-need patients' care processes. RESEARCH DESIGN: Retrospective analysis using differences-in-differences and χ tests. SUBJECTS: Of 545 high-need patients receiving PCMH care, 140 were previously randomly selected for the intensive outpatient management program; the remaining received usual care. MEASURES: We evaluated program effects on care continuity (proportion of primary care visits with assigned primary care physician); access (proportion of telephone visits out of all primary care encounters, missed appointment rate); care coordination (rate of follow-up after hospital discharge, new telehealth enrollment); and patient engagement (rates of online personal health record registration, advance directive completion). RESULTS: Compared with patients receiving usual care, patients enrolled in intensive management experienced a 5.9% increase in proportion of primary care visits with an assigned primary care physician (P<0.001) and a 17.9% increase in proportion of telephone-based visits (P<0.001). Patients in the program had 7.5% higher rates of telehealth referral (P=0.01), 17.2% higher rates of advance directive completion (P<0.01), and 9.3% higher rates of personal health record registration (P=0.02). There was no effect on missed appointments or posthospital discharge visit rates. CONCLUSIONS: Augmenting a PCMH with intensive outpatient management may have positive effects on primary care processes related to continuity, access, coordination, and patient engagement.


Assuntos
Assistência ao Convalescente/métodos , Assistência Ambulatorial/estatística & dados numéricos , Pacientes Ambulatoriais/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos
12.
Health Care Manage Rev ; 43(3): 238-248, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29533272

RESUMO

BACKGROUND: New models of patient-centered primary care such as the patient-centered medical home (PCMH) depend on high levels of interdisciplinary primary care team functioning to achieve improved outcomes. A few studies have qualitatively assessed barriers and facilitators to optimal team functioning; however, we know of no prior study that assesses PCMH team functioning in relationship to patient health outcomes. PURPOSE: The aim of the study was to assess the relationships between primary care team functioning, patients' use of acute care, and mortality. METHODOLOGY/APPROACH: Retrospective longitudinal cohort analysis of patient outcomes measured at two time points (2012 and 2013) after PCMH implementation began in Veterans Health Administration practices. Multilevel models examined practice-level measures of team functioning in relationship to patient outcomes (all-cause and ambulatory care-sensitive condition-related hospitalizations, emergency department visits, and mortality). We controlled for practice-level factors likely to affect team functioning, including leadership support, provider and staff burnout, and staffing sufficiency, as well as for individual patient characteristics. We also tested the model among a subgroup of vulnerable patients (homeless, mentally ill, or with dementia). RESULTS: In adjusted analyses, higher team functioning was associated with lower mortality (OR = 0.92, p = .04) among all patients and with fewer all-cause admissions (incidence rate ratio [IRR] = 0.90, p < 0.01), ambulatory care-sensitive condition-related admissions (IRR = 0.91, p = .04), and emergency department visits (IRR = 0.91, p = .03) in the vulnerable patient subgroup. CONCLUSION: These early findings give support for the importance of team functioning within PCMH models for achieving improved patient outcomes. PRACTICE IMPLICATIONS: A focus on team functioning is important especially in the early implementation of team-based primary care models.


Assuntos
Atenção à Saúde , Ciência da Implementação , Equipe de Assistência ao Paciente/organização & administração , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/organização & administração , Idoso , Estudos de Coortes , Feminino , Humanos , Liderança , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Retrospectivos , Estados Unidos , United States Department of Veterans Affairs
13.
Proc Natl Acad Sci U S A ; 111(30): 11181-6, 2014 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-25024200

RESUMO

Acute glaucoma is a sight-threatening condition characterized by a sudden and substantial rise in intraocular pressure (IOP) and consequent retinal ganglion cell (RGC) death. Angle closure glaucoma, a common cause of glaucoma in Asia that affects tens of millions of people worldwide, often presents acutely with loss of vision, pain, and high IOP. Even when medical and surgical treatment is available, acute angle closure glaucoma can cause permanent and irreversible loss of vision. Toll-like receptor 4 (TLR4) signaling has been previously implicated in the pathogenesis of IOP-induced RGC death, although the underlying mechanisms are largely unknown. In the present study, we used an acute IOP elevation/glaucoma model to investigate the underlying mechanism of RGC death. We found that TLR4 leads to increased caspase-8 expression; this elevation increases IL-1ß expression and RGC death via a caspase-1-dependent pathway involving Nod-like receptor family, pyrin domain containing 1 (NLRP1)/NLRP3 inflammasomes and a caspase-1-independent pathway. We show that inhibition of caspase-8 activation significantly attenuates RGC death by down-regulating the activation of NLRP1 and NLRP3, thus demonstrating the pivotal role of caspase-8 in the TLR4-mediated activation of inflammasomes. These findings demonstrate collectively a critical role of caspase-8 in transducing TLR4-mediated IL-1ß production and RGC death and highlight signal transduction in a caspase-1-dependent NLRP1/NLRP3 inflammasome pathway and a caspase-1-independent pathway in acute glaucoma. These results provide new insight into the pathogenesis of glaucoma and point to a treatment strategy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Transporte/metabolismo , Caspase 8/metabolismo , Proteínas do Olho/metabolismo , Glaucoma/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Doença Aguda , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas de Transporte/genética , Caspase 1/genética , Caspase 1/metabolismo , Caspase 8/genética , Modelos Animais de Doenças , Ativação Enzimática/genética , Proteínas do Olho/genética , Glaucoma/genética , Humanos , Inflamassomos/genética , Interleucina-1beta/genética , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
14.
Proc Natl Acad Sci U S A ; 111(20): 7415-20, 2014 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-24799683

RESUMO

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.


Assuntos
Aneuploidia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 18 , Análise Custo-Benefício , Síndrome de Down/diagnóstico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Humanos , Cariotipagem , Masculino , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Semicondutores , Sensibilidade e Especificidade , Trissomia/diagnóstico , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18
15.
Health Care Manage Rev ; 42(4): 282-291, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28885989

RESUMO

BACKGROUND: To be successful, accountable care organizations (ACOs) must effectively manage patient care. Health information technology (HIT) can support care delivery by providing various degrees of coordination. Few studies have examined the role of HIT functionalities or the role of different levels of coordination enabled by HIT on care management processes. PURPOSES: We examine HIT functionalities in ACOs, categorized by the level of coordination they enable in terms of information and work flow, to determine which specific HIT functionalities and levels of coordination are most strongly associated with care management processes. METHODOLOGY/APPROACH: Retrospective cross-sectional analysis was done using 2012 data from the National Survey of Accountable Care Organizations. HIT functionalities are categorized into coordination levels: information capture, the lowest level, which coordinates through standardization; information provision, which supports unidirectional activities; and information exchange, which reflects the highest level of coordination allowing for bidirectional exchange. The Care Management Process index (CMP index) includes 13 questions about the extent to which care is planned, monitored, and supported by providers and patients. Multiple regressions adjusting for organizational and ACO contractual factors are used to assess relationships between HIT functionalities and the CMP index. FINDINGS: HIT functionality coordinating the most complex interdependences (information exchange) was associated with a 0.41 standard deviation change in the CMP index (ß = .41, p < .001), but the associations for information capture (ß = -.01, p = .97) and information provision (ß = .15, p = .48) functionalities were not significant. IMPLICATIONS: The current study has shed some light on the relationship between HIT and care management processes by specifying the coordination roles that HIT may play and, in particular, the importance of information exchange functionalities. Although these represent early findings, further research can help policy makers and clinical leaders understand how to prioritize HIT development given resource constraints.


Assuntos
Organizações de Assistência Responsáveis/organização & administração , Informática Médica/organização & administração , Administração dos Cuidados ao Paciente , Estudos Transversais , Atenção à Saúde/métodos , Atenção à Saúde/organização & administração , Humanos , Medicare , Propriedade , Estudos Retrospectivos , Estados Unidos
16.
Mol Pharm ; 13(9): 2877-80, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-26836112

RESUMO

Vision impairment and blindness create a significant impact on quality of life and loss of productivity. Health care expenditures for vision problems, including direct medical costs and indirect costs for support services and loss of productivity, amount to $139 billion annually. It is projected that by 2020, five million people will have visual impairment due to age related macular degeneration and diabetic macular edema. VEGF inhibitor therapy has been shown to be a cost-effective treatment for age related macular degeneration and diabetic macular edema that has reduced the incidence of vision loss and can reduce the associated economic and societal cost.


Assuntos
Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Bevacizumab/economia , Bevacizumab/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/fisiopatologia , Custos de Cuidados de Saúde , Humanos , Degeneração Macular/tratamento farmacológico , Degeneração Macular/fisiopatologia , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Qualidade de Vida , Acuidade Visual/efeitos dos fármacos
17.
Mol Pharm ; 13(9): 2881-90, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27089240

RESUMO

The wet form of age-related macular degeneration (AMD) is a leading cause of blindness among elderly Americans and is characterized by abnormal vessel growth, termed choroidal neovascularization (CNV). Integrin α5ß1 is a transmembrane receptor that binds matrix macromolecules and proteinases to stimulate angiogenesis. We recently demonstrated that integrin α5ß1 plays a critical role in the development of choroidal neovascularization. In this study, we determined the role and underlying mechanisms of integrin α5ß1 in angiogenesis in human choroidal endothelial cells and evaluated the antiangiogenic effects of delivering a combination therapy of ATN-161, an integrin α5ß1 inhibitor, and an anti-VEGF monoclonal antibody to rats with laser-induced CNV. Vascular endothelial growth factor (VEGF) is a signaling protein that stimulates vasculogenesis and angiogenesis through a pathway that is distinct from the integrin α5ß1 signaling pathway. Our results indicate that fibronectin binds to integrin α5ß1 and synergizes VEGF-induced angiogenesis via two independent signaling pathways, FN/integrin α5ß1/FAK/ERK1/2 and FN/integrin α5ß1/FAK/AKT. Integrin α5 knockdown by shRNA inhibits endothelial cell migration, tube formation, and proliferation, while ATN-161 only partially decreases integrin α5 function. Treatment with ATN-161 combined with anti-VEGF antibody showed joint effects in attenuating angiogenesis. In summary, our results provide the first evidence for the mechanisms by which integrin α5ß1 is involved in ocular pathological neovascularization in vivo, suggesting that dual inhibition of integrin α5ß1 and VEGF may be a promising novel therapeutic strategy for CNV in wet AMD.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Integrina alfa5beta1/metabolismo , Degeneração Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Anticorpos Monoclonais/imunologia , Western Blotting , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neovascularização de Coroide/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Fibronectinas/metabolismo , Imunofluorescência , Masculino , Ligação Proteica , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Health Care Manage Rev ; 41(2): 88-100, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25978003

RESUMO

BACKGROUND: The accountable care organization (ACO) is a new type of health care organization incentivized to improve quality of care, improve population health, and reduce the cost of care. An ACO's success in meeting these objectives depends greatly upon its ability to improve patient care management. Numerous studies have found relational coordination to be positively associated with key measures of organizational performance in health care organizations, including quality and efficiency. PURPOSE: The purpose of this paper is twofold: (a) identify the extent to which ACO leaders are aware of the dimensions of relational coordination, and (b) identify the ways these leaders believe the dimensions influenced care management practices in their organization. METHODOLOGY/APPROACH: We performed content analysis of interviews with managerial and clinical leaders from a diverse group of 11 ACOs to assess awareness of relational coordination and identify the ways that dimensions of relational coordination were perceived to influence development of care management practices. FINDINGS: ACO leaders mentioned four relational coordination dimensions: shared goals, frequency of communication, timeliness of communication, and problem solving communication. Three dimensions - shared knowledge of team members' tasks, mutual respect, and accuracy of communication - were not mentioned. Our analysis identified numerous ways leaders believed the four mentioned dimensions contributed to the development of care management, including contributions to standardization of care, patient engagement, coordination of care, and care planning. DISCUSSION: We propose two hypotheses for future research on relational coordination and care management. PRACTICE IMPLICATIONS: If relational coordination is to have a beneficial influence on ACO performance, organizational leaders must become more aware of relational coordination and its various dimensions and become cognizant of relational coordination's influence on care management in their ACO. We suggest a number of means by which ACO leaders could become more aware of relational coordination and its potential effects.


Assuntos
Organizações de Assistência Responsáveis/organização & administração , Administração dos Cuidados ao Paciente/métodos , Comunicação , Humanos , Entrevistas como Assunto , Liderança , Objetivos Organizacionais , Equipe de Assistência ao Paciente
20.
J Biol Chem ; 289(10): 6362-6371, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24407289

RESUMO

Cell transplantation is a potential therapeutic strategy for retinal degenerative diseases involving the loss of photoreceptors. However, it faces challenges to clinical translation due to safety concerns and a limited supply of cells. Human retinal progenitor cells (hRPCs) from fetal neural retina are expandable in vitro and maintain an undifferentiated state. This study aimed to investigate the therapeutic potential of hRPCs transplanted into a Royal College of Surgeons (RCS) rat model of retinal degeneration. At 12 weeks, optokinetic response showed that hRPC-grafted eyes had significantly superior visual acuity compared with vehicle-treated eyes. Histological evaluation of outer nuclear layer (ONL) characteristics such as ONL thickness, spread distance, and cell count demonstrated a significantly greater preservation of the ONL in hRPC-treated eyes compared with both vehicle-treated and control eyes. The transplanted hRPCs arrested visual decline over time in the RCS rat and rescued retinal morphology, demonstrating their potential as a therapy for retinal diseases. We suggest that the preservation of visual acuity was likely achieved through host photoreceptor rescue. We found that hRPC transplantation into the subretinal space of RCS rats was well tolerated, with no adverse effects such as tumor formation noted at 12 weeks after treatment.


Assuntos
Células-Tronco Embrionárias/transplante , Epitélio Pigmentado Ocular/transplante , Retina , Degeneração Retiniana/cirurgia , Transplante de Células-Tronco , Animais , Separação Celular , Células Cultivadas , Modelos Animais de Doenças , Feto/citologia , Humanos , Ratos , Retina/citologia , Retina/embriologia , Retina/fisiologia , Degeneração Retiniana/fisiopatologia , Acuidade Visual
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