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BACKGROUD: The aim of this study was to investigate the associations between fluctuation in blood pressure (BP), ocular perfusion pressure (OPP) and visual field (VF) progression in normal-tension glaucoma (NTG). METHODS: This prospective, longitudinal study included 44 patients with NTG. Only newly diagnosed NTG patients who had not been treated with a glaucoma medication were included. Patients were examined every year for 7 years. Intraocular pressure (IOP), heart rate (HR), systolic BP (SBP), diastolic BP (DBP), ocular perfusion pressure (OPP), and diastolic ocular perfusion pressure (DOPP) were measured at the same time. Ophthalmic examinations, including perimetry, were performed also. Initial VF were compared with follow-up data after 7 years. RESULTS: After 7 years of follow-up, 9 of the 44 patients showed VF progression. The standard deviation (SD) of SBP and OPP were significantly associated with VF progression (P = 0.007, < 0.001, respectively). Multiple regression analysis showed that VF progression was significantly associated with SD of OPP (odds ratio, OR = 2.012, 95% CI = 1.016-3.985; P = 0.045). CONCLUSIONS: Fluctuation in OPP was associated with VF progression in patients with NTG.
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Pressão Sanguínea , Progressão da Doença , Pressão Intraocular , Glaucoma de Baixa Tensão , Campos Visuais , Humanos , Glaucoma de Baixa Tensão/fisiopatologia , Campos Visuais/fisiologia , Masculino , Feminino , Pressão Intraocular/fisiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Pressão Sanguínea/fisiologia , Seguimentos , Idoso , Testes de Campo Visual , AdultoRESUMO
Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been confirmed in glaucoma. We investigated the effects of IOP fluctuation itself on retinal neurodegeneration. Male rats were treated with IOP-lowering eyedrops (brinzolamide and latanoprost) on Mondays and Thursdays (in the irregular instillation group) or daily (in the regular instillation group), and saline was administered daily in the normal control group for 8 weeks. The IOP standard deviation was higher in the irregular instillation group than the regular instillation group or the control group. The degree of oxidative stress, which was analyzed by labeling superoxide, oxidative DNA damage, and nitrotyrosine, was increased in the irregular instillation group. Macroglial activation, expressed by glial fibrillary acidic protein in the optic nerve head and retina, was observed with the irregular instillation of IOP-lowering eyedrops. Microglial activation, as indicated by Iba-1, and the expression of TNF-α did not show a significant difference between the irregular instillation and control groups. Expression of cleaved caspase-3 was upregulated and the number of retinal ganglion cells (RGCs) was decreased in the irregular instillation group. Our findings indicate that IOP fluctuations could be induced by irregular instillation of IOP-lowering eyedrops and this could lead to the degeneration of RGCs, probably through increased oxidative stress and macrogliosis.
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Glaucoma , Pressão Intraocular , Masculino , Animais , Ratos , Retina , Glaucoma/tratamento farmacológico , Células Ganglionares da Retina , Soluções OftálmicasRESUMO
The application of technology in precision medicine (i.e., using data to tailor care for specific groups) and machine learning (modeling data to develop new ways to meet particular needs) plays a vital role in population health. And yet, technology alone cannot resolve the challenges presented by the underlying social determinants of health (SDOH) and the structure of healthcare institutions. Progress requires a partnership of stakeholders to build holistic solutions. Typically, a rigid institutional reliance on a sequential process of hypothesis, study, experimentation, and evaluation drives the development of health programs and policies. While this process works in many cases, the results are not always long-lasting. The roots of many health problems persist in their communities, despite expanded funding and advanced resources. In light of this reality, should healthcare leaders do more of what has been done in the past, or should they explore another way-a new way of thinking-to design collaborative, people-driven programs and policies that can improve and sustain the health of their communities? The response presented here and detailed in our book, Public Health and Health Systems Management: A Population Health Perspective (scheduled for publication in 2025 by Health Administration Press), considers healthcare's complex structure and SDOH and promotes the value of design thinking to address those factors.
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Empatia , Humanos , Determinantes Sociais da Saúde , Atenção à Saúde/organização & administração , Masculino , Feminino , Saúde da População , Melhoria de Qualidade/organização & administração , Comportamento CooperativoRESUMO
This Special Issue provides a wide-ranging update from the front lines of newborn screening (NBS) research and is the result of conversations and collaborations facilitated by the Newborn Screening Translational Research Network (NBSTRN) across the NBS community and their extended networks. For 14 years NBSTRN has accelerated research efforts to advance NBS by creating a research infrastructure available to the NBS community to discover novel technologies to screen, diagnose, and treat newborns.Authors in this Special issues share their innovative and impactful efforts to advance NBS to include additional conditions, populations, genomics, and information sharing.
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Triagem Neonatal , Pesquisa Translacional Biomédica , Recém-Nascido , Humanos , GenômicaRESUMO
This study qualitatively examines the perspectives of doctors and nurses on the implementation of the Advance Care Planning program in Singapore. Findings suggest that a combination of structural and conceptual factors hindered the performance of ACP. Themes on structural factors indicated that low awareness of ACP among senior staff resulted overall lack of buy-in and incorrect implementation of the program due to misconceptions. Conceptual factors pointed to lack of clarity on intended outcomes or roles. Consequently, participants drew meaning through the prism of their profession, resulting in competing expectations and tensions on possible outcomes of the program.
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Planejamento Antecipado de Cuidados , Motivação , Povo Asiático , Humanos , Pesquisa QualitativaRESUMO
Uveitis caused by herpes simplex virus (HSV)-1 is characterized by increased intraocular pressure (IOP) in the presence of anterior chamber inflammation. Despite their clinical significance, the pathogenic changes associated with HSV-1 infection in trabecular meshwork (TM) cells, the key cell type regulating IOP, have not been completely elucidated. In this study, cytokine array analyses showed a significant stepwise increase in monocyte chemoattractant protein (MCP)-1 expression upon HSV-1 infection in TM cells (p < 0.05). HSV-1 infection led to downregulation of fibrogenic molecules (fibronectin, α-smooth muscle actin, connective tissue growth factor and TGF-ß1). Notably, HSV-1 infection caused a significant increase in actin stress fibres, with a twofold increase in active RhoA, which was enhanced by treatment with TGF-ß1 and inhibited by treatment with the Rho-kinase inhibitor, Y-27632. TM cells treated with MCP-1 exhibited a dose-dependent increase in actin stress fibres compared to untreated TM cells. Our study suggests that HSV-1 infection in TM cells increases cell contractile activity rather than fibrotic changes in the extracellular matrix (ECM) components. Taken together, these observations demonstrate the enhanced expression of MCP-1 and TM cell contractile activity upon HSV-1 infection and events with potential implications for the pathobiology of abrupt IOP elevation in HSV-1 anterior uveitis.
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Citocinas/metabolismo , Citoesqueleto/metabolismo , Herpes Simples/metabolismo , Herpes Simples/virologia , Herpesvirus Humano 1/fisiologia , Malha Trabecular/metabolismo , Biomarcadores , Células Cultivadas , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/metabolismo , Transdução de Sinais , Malha Trabecular/patologia , Malha Trabecular/virologia , Uveíte Anterior/metabolismo , Uveíte Anterior/virologia , Replicação Viral , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
OBJECTIVES: A qualitative interpretive-systemic focus group study was conducted to examine the developmental and implementational underpinnings of Asia's first national Advance Care Planning (ACP) programme constituted in Singapore. METHODS: 63 physicians, nurses, medical social workers, and allied health workers who actively rendered ACP were purposively recruited across seven major public hospitals and specialist centers. RESULTS: Framework analysis revealed 19 themes, organized into 5 categories including Life and Death Culture, ACP Coordination, ACP Administration, ACP Outcomes, and Sustainability Shift. These categories and themes formed an Interpretive-Systemic Framework of Sustainable ACP, which reflects the socio-cultural, socio-political, and socio-spiritual contexts that influence ACP provision, highlighting the need to adopt a public health strategy for enhancing societal readiness for end-of-life conversations. SIGNIFICANCE OF RESULTS: The Interpretive-Systemic Framework of Sustainable ACP underscores the importance of health policy, organizational structure, social discourse, and shared meaning in ACP planning and delivery so as to support and empower care decision-making among terminally ill Asian patients and their families facing mortality.
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Planejamento Antecipado de Cuidados , Ásia , Grupos Focais , Pessoal de Saúde , Humanos , Pesquisa Qualitativa , Assistentes SociaisRESUMO
OBJECTIVES: Asia's first national advance care planning (ACP) program was established in Singapore in 2011 to enhance patient autonomy and self-determination in end-of-life (EoL) care decision-making. However, no known study has examined the extent to which ACP in Singapore successfully met its aims. The purpose of the current study was to examine the attitudes of local healthcare professionals on patients' autonomy in decision-making at the EoL since they strongly influence the extent to which patient and family wishes are fulfilled. METHODS: Guided by the Interpretive-Systemic Framework and Proctor's conceptual taxonomy of implementation research outcomes, an interview guide was developed. Inquiries focused on healthcare professionals' attitudes towards ACP, their clinical experiences working with patients and families, and their views on program effectiveness. Sixty-three physicians, nurses, medical social workers, and designated ACP coordinators who were actively engaged in ACP facilitation were recruited from seven major hospitals and specialist centers in Singapore through purposive sampling. Twelve interpretive-systemic focus groups were conducted, recorded, transcribed, and analyzed using a thematic analysis. RESULTS: The extent to which patients in Singapore can exert autonomy in EoL care decision-making is influenced by five themes: (i) collusion over truth-telling to patient, (ii) deferment of autonomy by patients, (iii) negotiating patient self-determination, (iv) relational autonomy as the gold standard and (v) barriers to realization of patient choices. SIGNIFICANCE OF RESULTS: Healthcare practitioners in Asian communities must align themselves with the values and needs of patients and their family and jointly make decisions that are consistent and congruent with the values of patients and their families. Sensitivity towards such cross-cultural practices is key to enhancing ACP awareness, discourse, and acceptability in Asian communities.
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Grupos Focais/métodos , Pessoal de Saúde/psicologia , Participação do Paciente/psicologia , Autonomia Pessoal , Adulto , Planejamento Antecipado de Cuidados/estatística & dados numéricos , Povo Asiático , Atitude do Pessoal de Saúde , Feminino , Grupos Focais/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Participação do Paciente/métodos , Participação do Paciente/estatística & dados numéricos , Pesquisa Qualitativa , Singapura , Assistência Terminal/métodos , Assistência Terminal/psicologia , Assistência Terminal/normasRESUMO
OBJECTIVE: To provide an overview of the current state of research of advance care planning (ACP), highlighting most studied topics, publication time, quality of studies and reported outcomes, and to identify gaps to improve ACP receptivity, utilization, implementation, and outcomes. METHOD: Cochrane methodology for conducting overviews of systematic reviews. Study quality was assessed using a modified version of the Assessing the Methodological Quality of Systematic Reviews tool. The following databases were searched from inception to April 2017: MEDLINE, EBM Reviews, Cochrane Reviews, CINAHL, Global Health, PsycINFO, and EMBASE. Searches were supplemented with gray literature and manual searches. RESULT: Eighty systematic reviews, covering 1,662 single articles, show that ACP-related research focuses on nine main topics: (1) ACP as part of end-of-life or palliative care interventions, (2) care decision-making; (3) communication strategies; (4) factors influencing ACP implementation; (5) ACP for specific patient groups, (6) ACP effectiveness; (7) ACP experiences; (8) ACP cost; and (9) ACP outcome measures. The majority of this research was published since 2014, its quality ranges from moderate to low, and reports on documentation, concordance, preferences, and resource utilization outcomes. SIGNIFICANCE OF RESULTS: Despite the surge of ACP research, there are major knowledge gaps about ACP initiation, timeliness, optimal content, and impact because of the low quality and fragmentation of the available evidence. Research has mostly focused on discrete aspects within ACP instead of using a holistic evaluative approach that takes into account its intricate working mechanisms, the effects of systems and contexts, and the impacts on multilevel stakeholders. Higher quality studies and innovative interventions are needed to develop effective ACP programs and address research gaps.
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PURPOSE: To assess the implementation of evidence-based genomic medicine and its population-level impact on health outcomes and to promote public health genetics interventions, in 2015 the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine formed an action collaborative, the Genomics and Public Health Action Collaborative (GPHAC). This group engaged key stakeholders from public/population health agencies, along with experts in the fields of health disparities, health literacy, implementation science, medical genetics, and patient advocacy. METHODS: In this paper, we present the efforts to identify performance objectives and outcome metrics. Specific attention is placed on measures related to hereditary breast ovarian cancer (HBOC) syndrome and Lynch syndrome (LS), two conditions with existing evidence-based genomic applications that can have immediate impact on morbidity and mortality. RESULTS: Our assessment revealed few existing outcome measures. Therefore, using an implementation research framework, 38 outcome measures were crafted. CONCLUSION: Evidence-based public health requires outcome metrics, yet few exist for genomics. Therefore, we have proposed performance objectives that states might use and provided examples of a few state-level activities already under way, which are designed to collect outcome measures for HBOC and LS.
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Genômica/métodos , Avaliação de Resultados em Cuidados de Saúde/normas , Saúde Pública/métodos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Medicina Baseada em Evidências/métodos , Genômica/normas , Humanos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Prática de Saúde Pública , Resultado do TratamentoRESUMO
OBJECTIVE: We used OCT angiography (OCT-A) to investigate parapapillary choroidal microvasculature dropout (MvD) in glaucomatous eyes with or without disc hemorrhage (DH), and the association with changes in retinal nerve fiber layer (RNFL) thickness. DESIGN: An observational case-control study. PARTICIPANTS: Eighty-two open-angle glaucoma (OAG) eyes with DH and 68 OAG eyes without DH that underwent at least 4 serial OCT examinations were included. METHODS: MvD was defined as complete loss of microvasculature within the choroidal layer of the parapapillary region, as revealed by standardized assessment of OCTA-derived density maps of the vessels of the optic nerve head. The circumferential extent of MvD was measured on OCT-A images. The RNFL thinning rate was calculated using a linear mixed model. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between groups stratified by DH and MvD. MAIN OUTCOME MEASURES: MvD detection rate, the extent of MvD as measured by the MvD angle, and RNFL thinning rate. RESULTS: MvD was found in 38 (46.3%) eyes with DH at the prior DH site, which was found in only 20 (29.4%) eyes without DH, which was significantly different between the 2 groups (P = 0.025). Patients with progressive glaucoma exhibited significantly more MvD than the stable patients in both DH and no-DH groups. There were statistically significant differences between groups subdivided by the presence of DH and MvD as assessed by Kaplan-Meier analysis (log-rank test, P < 0.001). The angle of MvD was significantly greater in eyes with recurrent DH compared with eyes with single DH. Presence of DH, recurrent DH, and presence of MvD were factors associated with progressive RNFL thinning. CONCLUSIONS: We found that MvD was frequent in progressive OAG eyes on the choroidal map of OCT-A, which was more frequently found at the prior DH locations in eyes with DH. This means that observing the presence of MvD using OCT-A may provide a biomarker for glaucoma progression, especially in eyes with DH.
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Doenças da Coroide/diagnóstico , Corioide/irrigação sanguínea , Glaucoma de Ângulo Aberto/diagnóstico , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Hemorragia Retiniana/diagnóstico , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Microvasos , Pessoa de Meia-Idade , Disco Óptico/irrigação sanguínea , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica/métodos , Tonometria Ocular , Testes de Campo Visual , Campos Visuais/fisiologiaRESUMO
PURPOSE: To investigate the relationships between corneal deformation amplitude and posterior pole profiles, including ß-zone parapapillary atrophy (ßPPA), optic disc tilt ratio, torsion degree, and disc-foveal angle, in patients with glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 107 patients with glaucoma. METHODS: Each patient underwent measurement of deformation amplitude with Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany), color optic disc photography, red-free retinal nerve fiber layer photography, axial length measurement, and 24-2 standard automated perimetry. From fundus photographs, the ßPPA area, optic disc tilt ratio, torsion degree, and disc-foveal angle were obtained. Pearson's correlation was used to determine the relationships between deformation amplitude and posterior pole profiles. To determine the factors associated with the posterior pole profiles, univariate and multivariate regression analyses were performed. MAIN OUTCOME MEASURES: Deformation amplitude, ßPPA area, optic disc tilt ratio, torsion degree, and disc-foveal angle. RESULTS: The study included 50 men (46.7%) and 57 women (53.3%). The mean age was 55.38±14.14 years. The mean tilt ratio, torsion degree, and disc-foveal angle were 1.16±0.14, 10.26±7.63°, and 7.60±3.64°, respectively. The mean ßPPA area was 18 211.00±28 725.53 pixels. The ßPPA (r = 0.391, P < 0.001) and tilt ratio (r = 0.408, P < 0.001) had significant relationships with deformation amplitude after adjusting for intraocular pressure (IOP). Torsion degree and disc-foveal angle showed no significant relationship with deformation amplitude. The ßPPA area was associated with deformation amplitude and axial length in both univariate (P = 0.008 and 0.006, respectively) and multivariate (P = 0.035 and <0.001, respectively) regression analyses. The tilt ratio was associated with deformation amplitude in univariate regression analysis (P = 0.002), but not in multivariate regression analysis. Axial length was significantly associated with the tilt ratio in both univariate (P < 0.001) and multivariate (P < 0.001) regression analyses. CONCLUSIONS: Deformation amplitude was associated with PPA area and tilt ratio in patients with glaucoma, although in our data set ßPPA area and tilt ratio were not associated with visual field mean deviation.
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Córnea/fisiologia , Elasticidade/fisiologia , Anormalidades do Olho/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Atrofia Óptica/fisiopatologia , Disco Óptico/anormalidades , Doenças do Nervo Óptico/fisiopatologia , Idoso , Fenômenos Biomecânicos , Estudos Transversais , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Doenças do Nervo Óptico/diagnóstico , Tomografia de Coerência Óptica , Tonometria Ocular , Testes de Campo Visual , Campos VisuaisRESUMO
To inhibit vascular changes in diabetic retinopathy, inhibiting vascular endothelial growth factor (VEGF) has become a mainstay of the treatment of diabetic retinopathy. However, its effects on neuronal cells remain to be elucidated. We aimed to evaluate the effect of VEGF inhibition on neuronal cells in a streptozotocin-induced diabetic rat retina. VEGF inhibition was performed by intravitreal VEGF-A antibody injection. After anti-VEGF treatment, apoptosis in retinal ganglion cells (RGCs) increased, and novel apoptosis in amacrine and bipolar cells of the inner nuclear layer was observed by TUNEL staining. Phosphorylated Akt expression was significantly higher in RGCs but was decreased in neuronal cells of the inner nuclear layer after anti-VEGF treatment by Western blot analysis and immunohistochemical staining. These results demonstrate that VEGF inhibition significantly increased RGC apoptosis and neuronal cell apoptosis in the inner nuclear layer of a diabetic retina, which seems to consist primarily of amacrine and bipolar cells. The phosphorylated Akt pathway, which plays a neuroprotective role via VEGF, was significantly affected by VEGF inhibition in the inner nuclear layer, suggesting that neurotrophic factor deprivation is the main mechanism for neuronal cell death after inhibiting VEGF. The results of this study show that inhibiting VEGF may have detrimental effects on the apoptosis of neuronal cells in the inner layers of the diabetic retina.
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Anticorpos Neutralizantes/farmacologia , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Células Ganglionares da Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/patologia , Masculino , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: The human CAV1-CAV2 locus has been associated with susceptibility to primary open-angle glaucoma in four studies of Caucasian, Chinese, and Pakistani populations, although not in several other studies of non-Korean populations. In this study with Korean participants, the CAV1-CAV2 locus was investigated for associations with susceptibility to primary open-angle glaucoma accompanied by elevated intraocular pressure (IOP), namely, high-tension glaucoma (HTG), as well as with IOP elevation, which is a strong risk factor for glaucoma. METHODS: Two single nucleotide polymorphisms (SNPs) were genotyped in 1,161 Korean participants including 229 patients with HTG and 932 healthy controls and statistically examined for association with HTG susceptibility and IOP. One SNP was rs4236601 G>A, which had been reported in the original study, and the other SNP was rs17588172 T>G, which was perfectly correlated (r2=1) with another reported SNP rs1052990. Expression quantitative trait loci (eQTL) analysis was performed using GENe Expression VARiation (Genevar) data. RESULTS: Both SNPs were associated with HTG susceptibility, but the rs4236601 association disappeared when adjusted for the rs17588172 genotype and not vice versa. The minor allele G of rs17588172 was associated significantly with 1.5-fold increased susceptibility to HTG (p=0.0069) and marginally with IOP elevation (p=0.043) versus the major allele T. This minor allele was also associated with decreased CAV1 and CAV2 mRNA in skin and adipose according to the Genevar eQTL analysis. CONCLUSIONS: The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with IOP elevation, and consequently with increased susceptibility to HTG.
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Caveolina 1/genética , Caveolina 2/genética , Glaucoma/genética , Pressão Intraocular/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Glaucoma de Ângulo Aberto/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , República da Coreia , Fatores de RiscoRESUMO
OBJECTIVES: To identify the factors associated with retinal nerve fiber layer (RNFL) loss in patients with type 2 diabetes. DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-six nonglaucomatous patients with type 2 diabetes without renal impairment (estimated glomerular filtration rate, ≥60 ml/minute per 1.73 m(2)). METHODS: Eyes were divided into 2 groups based on the presence or absence of RNFL defects detected by red-free retinal fundus photography. All participants underwent an eye fundus examination, and the urinary albumin-to-creatinine ratio (ACR) was determined. A cardiovascular autonomic function test was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to the Valsalva maneuver, and standing. Multiple logistic regression analyses were performed to determine potential risk factors related to the presence of RNFL defects in these patients. MAIN OUTCOMES AND MEASURES: The association between RNFL defects and diabetic complications. RESULTS: Among the patients, 43 (44.8%) had localized RNFL defects (group 1), whereas the others (55.2%) did not (group 2). The RNFL defects occurred more frequently on the superior side (75.6% and 71.0% in right and left eyes, respectively) compared with the inferior side (13.8% and 0.0% in right and left eyes, respectively). Patients with RNFL defects (group 1) had significantly higher rates of diabetic retinopathy (60.5%) compared with those without RNFL defects (group 2; 32.1%; P = 0.007). The urinary ACR was significantly higher in patients with RNFL defects than in those without defects (45.3±72.1 µg/mg vs. 15.4±17.3 µg/mg creatinine, respectively; P = 0.015), whereas autonomic function test grading was similar between the groups. The urinary ACR was the only factor related to visual field defect location in both univariate (P = 0.021) and multivariate (P = 0.036) logistic regression analyses after adjusting for age; gender; presence of diabetic retinopathy; diabetes duration; smoking; statin use; and antiplatelet, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker treatment. CONCLUSIONS: Urinary albumin excretion was associated with nerve fiber layer loss in patients with type 2 diabetes. Careful examination of the optic nerve head may be necessary, particularly in patients with type 2 diabetes exhibiting albuminuria.
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Albuminúria/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Neuropatias Diabéticas/diagnóstico , Fibras Nervosas/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/fisiopatologia , Albuminúria/urina , Sistema Nervoso Autônomo/fisiologia , Sistema Cardiovascular/inervação , Creatinina/urina , Estudos Transversais , Diabetes Mellitus Tipo 2/urina , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/urina , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/urina , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Nervo Óptico/fisiopatologia , Doenças do Nervo Óptico/urina , Acuidade VisualRESUMO
Objectives. We developed and implemented an HIV rapid testing-linkage-to-care initiative between federal and local government. Methods. We used mixed methodology; HIV testing data were collected on-site, and qualitative data were collected via telephone. We used postintervention stakeholder and staff interviews to evaluate barriers and facilitators to this initiative. Results. We tested 817 individuals. We identified and confirmed 7 preliminary HIV positive individuals (0.86% seropositivity), 5 of whom were linked to care. Mean testing cost was $48.95 per client; cost per positive result was $5714. Conclusions. This initiative can be used as a template for other health departments and research teams focusing on homelessness and mitigation of the HIV/AIDS epidemic.
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OBJECTIVES: To conduct a comprehensive cost-minimization analysis to comprehend the financial attributes of the first 5 years of an implementation wherein emergency department (ED) registered nurses administered HIV oral rapid tests to patients. METHODS: A health science research implementation team coordinated with ED stakeholders and staff to provide training, implementation guidelines, and support to launch ED registered nurse-administered HIV oral rapid testing. Deidentified quantitative data were gathered from the electronic medical records detailing quarterly HIV rapid test rates in the ED setting spanning the first 5 years. Comprehensive cost analyses were conducted to evaluate the financial impact of this implementation. RESULTS: At 5 years, a total of 2,620 tests were conducted with a quarterly mean of 131 ± 81. Despite quarterly variability in testing rates, regression analysis revealed an average increase of 3.58 tests per quarter. Over the course of this implementation, Veterans Health Administration policy transitioned from written to verbal consent for HIV testing, serving to reduce the time and cost(s) associated with the testing process. CONCLUSIONS: Our data indicated salient health outcome benefits for patients with respect to the potential for earlier detection, and associated long-run cost savings.
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Enfermagem em Emergência/economia , Serviço Hospitalar de Emergência/economia , Infecções por HIV/diagnóstico , Infecções por HIV/economia , Custos Hospitalares , Hospitais de Veteranos/economia , Boca/virologia , Kit de Reagentes para Diagnóstico/economia , Redução de Custos , Análise Custo-Benefício , Infecções por HIV/virologia , Humanos , Modelos Econômicos , Valor Preditivo dos Testes , Avaliação de Programas e Projetos de Saúde , Fatores de TempoRESUMO
Subconjunctival fibrosis at the surgical site determines the outcome of glaucoma surgery. Myofibroblast transformation has a significant role in fibrosis, and vascular endothelial growth factor (VEGF) is reported to trigger myofibroblast transformation by inducing transforming growth factor (TGF)-ß1. In the present study, we used IHC, Western blot analysis, enzyme-linked immunosorbent assay, and electron microscopy to determine the contribution of VEGF to myofibroblast transformation in subconjunctival fibrosis after glaucoma surgery. A rabbit trabeculectomy model was generated, and VEGF stimulation or VEGF inhibition was performed during surgery. VEGF stimulation induced TGF-ß1 expression in a dose-dependent manner. Down-regulation of epithelial markers (E-cadherin and ß-catenin) and up-regulation of mesenchymal marker (α-smooth muscle actin) were observed in the subconjunctival layers after trabeculectomy with VEGF stimulation. Up-regulations of Smad and Snail, which play a central role in myofibroblast transformation, were observed in the conjunctival and subconjunctival layers at the site of trabeculectomy. Electron microscopy revealed changes of the conjunctival epithelial cells, especially the presence of myofilaments and increased rough endoplasmic reticulum in the cytoplasm. Myofibroblast transformation was activated by VEGF stimulation and decreased by VEGF inhibition. These findings suggest that VEGF potentially affected the TGF-ß1/Smad/Snail pathway, thereby triggering myofibroblast transformation. Therapeutic approaches modulating VEGF may control myofibroblast transformation and reduce subconjunctival fibrosis after glaucoma surgery.
Assuntos
Miofibroblastos/efeitos dos fármacos , Trabeculectomia/efeitos adversos , Fator de Crescimento Transformador beta1/biossíntese , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Bevacizumab , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/ultraestrutura , Relação Dose-Resposta a Droga , Células Epiteliais/ultraestrutura , Fibrose , Masculino , Microscopia Eletrônica , Miofibroblastos/metabolismo , Período Pós-Operatório , Coelhos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Smad/biossíntese , Fatores de Transcrição da Família Snail , Fatores de Transcrição/biossíntese , Regulação para Cima/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/fisiologiaRESUMO
OBJECTIVE: To determine whether the ganglion cell-inner plexiform layer (GCIPL) or circumpapillary retinal nerve fiber layer (cpRNFL) is better at distinguishing eyes with early glaucoma from normal eyes on the basis of the the initial location of the visual field (VF) damage. DESIGN: Retrospective, observational study. PARTICIPANTS: Eighty-four patients with early glaucoma and 43 normal subjects were enrolled. The patients with glaucoma were subdivided into 2 groups according to the location of VF damage: (1) an isolated parafoveal scotoma (PFS, N = 42) within 12 points of a central 10 degrees in 1 hemifield or (2) an isolated peripheral nasal step (PNS, N = 42) within the nasal periphery outside 10 degrees of fixation in 1 hemifield. METHODS: All patients underwent macular and optic disc scanning using Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). The GCIPL and cpRNFL thicknesses were compared between groups. Areas under the receiver operating characteristic curves (AUCs) were calculated. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using AUCs. RESULTS: The average and minimum GCIPL of the PFS group were significantly thinner than those of the PNS group, whereas there was no significant difference in the average retinal nerve fiber layer (RNFL) thickness between the 2 groups. The AUCs of the average (0.962) and minimum GCIPL (0.973) thicknesses did not differ from that of the average RNFL thickness (0.972) for discriminating glaucomatous changes between normal and all glaucoma eyes (P =0.566 and 0.974, respectively). In the PFS group, the AUCs of the average (0.988) and minimum GCIPL (0.999) thicknesses were greater than that of the average RNFL thickness (0.961, P =0.307 and 0.125, respectively). However, the AUCs of the average (0.936) and minimum GCIPL (0.947) thicknesses were lower than that of the average RNFL thickness (0.984) in the PNS group (P =0.032 and 0.069, respectively). CONCLUSIONS: The GCIPL parameters were more valuable than the cpRNFL parameters for detecting glaucoma in eyes with parafoveal VF loss, and the cpRNFL parameters were better than the GCIPL parameters for detecting glaucoma in eyes with peripheral VF loss. Clinicians should know that the diagnostic capability of macular GCIPL parameters depends largely on the location of the VF loss.
Assuntos
Glaucoma/diagnóstico , Fibras Nervosas/patologia , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Células Ganglionares da Retina/patologia , Escotoma/diagnóstico , Campos Visuais , Área Sob a Curva , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To compare the initial visual field (VF) defect pattern and the spectral-domain optical coherence tomography (OCT) parameters and investigate the effects of distinct types of optic disc damage on the diagnostic performance of these OCT parameters in early glaucoma. DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 138 control eyes and 160 eyes with early glaucoma were enrolled. The glaucomatous eyes were subdivided into 4 groups according to the type of optic disc damage: focal ischemic (FI) group, myopic (MY) group, senile sclerotic (SS) group, and generalized enlargement (GE) group. METHODS: The values of total deviation (TD) maps were analyzed, and superior-inferior (S-I) differences of TD were calculated. The optic nerve head (ONH) parameters, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using area under the receiver operating characteristic curves (AUCs). RESULTS: The S-I and central S-I difference of the FI group were larger than those of the GE group. The rim area of the SS group was larger than those of the 3 other groups, and the vertical cup-to-disc ratio (CDR) of the GE group was larger than that of the MY group. In addition, the minimum and inferotemporal GCIPL thicknesses of the FI group were smaller than those of the GE group. The AUC of the rim area (0.89) was lower than that of the minimum GCIPL (0.99) in the SS group, and the AUC of the vertical CDR (0.90) was lower than that of the minimum GCIPL (0.99) in the MY group. Furthermore, the AUCs of the minimum GCIPL thicknesses of the FI and MY group were greater than those of the average pRNFL thickness for detecting glaucoma, as opposed to the SS and GE. CONCLUSIONS: The OCT parameters differed among the 4 groups on the basis of the distinct optic disc appearance and initial glaucomatous damage pattern. Clinicians should be aware that the diagnostic capability of OCT parameters could differ according to the type of optic disc damage in early glaucoma.