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Optogenetic strategies to restore vision in patients blind from end-stage retinal degenerations aim to render remaining retinal neurons light-sensitive. We present an innovative combination of multi-electrode array recordings together with complex pattern-generating light source as a toolset to determine the extent to which neural retinal responses to complex light stimuli can be restored following viral delivery of red-shifted channelrhodopsin in the retinally-degenerate mouse. Our data indicate that retinal output level spatiotemporal response characteristics achieved by optogenetic gene therapy closely parallel those observed for normal mice but equally reveal important limitations, some of which could be mitigated by using bipolar-cell targeted gene-delivery approaches. As clinical trials are commencing, these data provide important new information on the capacity and limitations of channelrhodopsin-based gene therapies. The toolset we established enables comparing optogenetic constructs and stem-cell-based techniques, thereby providing an efficient and sensitive starting point to identify future approaches for vision restoration.
BACKGROUND: GP practices have limited access to medical emergency training and basic life support is often taught out of context as a skills-based event. AIM: To develop and evaluate a whole team integrated simulation-based education, to enhance learning, change behaviours and provide safer care. METHOD: Phase 1: 10 practices piloted a 3-hour programme delivering 40 minutes BLS and AED skills and 2-hour deteriorating patient simulation. Three scenarios where developed: adult chest pain, child anaphylaxis and baby bronchiolitis. An adult simulation patient and relative were used and a child and baby manikin. Two facilitators trained in coaching and debriefing used the 3D debriefing model. Phase 2: 12 new practices undertook identical training derived from Phase 1, with pre- and post-course questionnaires. Teams were scored on: team working, communication, early recognition and systematic approach. The team developed action plans derived from their learning to inform future response. Ten of the 12 practices from Phase 2 received an emergency drill within 6 months of the original session. Three to four members of the whole team integrated training, attended the drill, but were unaware of the nature of the scenario before. Scoring was repeated and action plans were revisited to determine behaviour changes. RESULTS: Every emergency drill demonstrated improved scoring in skills and behaviour. CONCLUSION: A combination of: in situ GP simulation, appropriately qualified facilitators in simulation and debriefing, and action plans developed by the whole team suggests safer care for patients experiencing a medical emergency.
OBJECTIVE: While patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing. METHODS: Baseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Clinician (Neuropsychiatric Inventory; NPI) and carer rated (Cambridge Behavioural Inventory; CBI, Frontal Systems Behaviour Scale; FrSBe) measures were used to quantify symptoms of apathy, and carer burden and psychological wellbeing were determined using the Zarit Burden Interview and Depression, Anxiety and Stress Scale. RESULTS: On the NPI, symptoms of apathy were present in 39% left SD, 56% right SD, 33% PNFA and 43% LPA patients. Multiple regression analysis revealed that 17.9% of the variance in carer burden was uniquely explained by scores on carer rated measures of apathy (CBI, FrSBe), even after accounting for diagnosis, disease duration, and cognitive and language impairment. CONCLUSIONS: Apathy is much more common than current diagnostic criteria for PPA would suggest, though the severity of apathy is similar across patient groups. Increased awareness and routine assessments of apathy symptoms are needed, together with targeted pharmacological and behavioural interventions. Moreover, as apathy substantially contributes to carer burden in PPA, psychoeducation addressing behavioural symptoms may be beneficial.
Teleophthalmology: a strategy for timely diagnosis of sight-threatening diabetic retinopathy in primary care, Concepción, Chile.
AIM: To estimate the prevalence of diabetic retinopathy (DR) in a diabetic population of the public health system. METHODS: This non-experimental, descriptive and cross-sectional study, with no direct control over the variables analysed, was carried out by the Telemedicine Unit of the University of Concepción (TELMED) and the Family Health Centers (CESFAM) of the Health Service Concepción, Chile, among a population of 7382 diabetic patients of the public health system, from October 2014 to June 2015. Two digital images for each patient's eyes were obtained and uploaded to the TELMED tele-ophthalmology platform. The images were remotely evaluated by a retina expert ophthalmologist for diagnosis. Treatment and a referral (if required) were recommended, and an individualised report for each patient was sent to the place of origin. RESULTS: The prevalence of DR in this study was 14.9%. Of these, 48.7% had mild non-proliferative DR (NPDR), 30.8% moderate NPDR, 15.9% severe NPDR, and 4.6% proliferative DR. Of the patients with DR, 17.8% were referred for fluorescein angiography, 4.3% for panretinal photocoagulation, 1.2% for vitrectomy, and 0.4% for cataract surgery. CONCLUSION: The use of telemedicine allowed an increased screening coverage for DR in diabetic patients. The different types of DR were detected in a timely manner, decreasing waiting times due to the lack of specialists in ophthalmology in the public health system.
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BACKGROUND: Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults worldwide. Early detection and treatment are necessary to forestall vision loss from DR. METHODS: A working group of ophthalmic and diabetes experts was established to develop a consensus on the key principles of an effective DR screening program. Recommendations are based on analysis of a structured literature review. RESULTS: The recommendations for implementing an effective DR screening program are: (1) Examination methods must be suitable for the screening region, and DR classification/grading systems must be systematic and uniformly applied. Two-field retinal imaging is sufficient for DR screening and is preferable to seven-field imaging, and referable DR should be well defined and reliably identifiable by qualified screening staff; (2) in many countries/regions, screening can and should take place outside the ophthalmology clinic; (3) screening staff should be accredited and show evidence of ongoing training; (4) screening programs should adhere to relevant national quality assurance standards; (5) studies that use uniform definitions of risk to determine optimum risk-based screening intervals are required; (6) technology infrastructure should be in place to ensure that high-quality images can be stored securely to protect patient information; (7) although screening for diabetic macular edema (DME) in conjunction with DR evaluations may have merit, there is currently insufficient evidence to support implementation of programs solely for DME screening. CONCLUSION: Use of these recommendations may yield more effective DR screening programs that reduce the risk of vision loss worldwide.
Progression from Early/Intermediate to Advanced Forms of Age-Related Macular Degeneration in a Large UK Cohort: Rates and Risk Factors.
PURPOSE: To estimate rates and risk factors for progression to geographic atrophy (GA) or choroidal neovascularization (CNV) among eyes diagnosed with early or intermediate age-related macular degeneration (AMD) in clinical practice. DESIGN: Retrospective cohort analysis of a multicenter electronic medical record (EMR) database from the United Kingdom. PARTICIPANTS: Patients aged 50 years or more with diagnosis of early/intermediate AMD in at least 1 eye (the study eye) and no evidence of CNV or GA in the study eye, from 10 clinical sites using the EMR. METHODS: Anonymized data for 40 543 patients with a diagnosis of early/intermediate AMD were extracted between October 2000 and February 2016 from EMR database records held in the 10 sites. A sample of records randomly selected from each center was used to validate disease definitions. Records were analyzed by subgroup, based on the AMD status of the fellow eye. Multivariate Cox regression models identified other predictors of disease progression. MAIN OUTCOME MEASURES: Progression rate (per 100 person-years) to GA or CNV in study eyes with early/intermediate AMD by fellow eye status and identified risk factors for progression. RESULTS: Study eyes with early/intermediate AMD and a diagnosis of CNV in the fellow eye progressed to CNV fastest (at a rate of 15.2 per 100 person-years), and those with a diagnosis of GA in the fellow eye progressed to GA fastest (11.2 per 100 person-years), compared with the rates per 100 person-years of progression to CNV (3.2-11.9) or GA (2.0-7.8) in the other subgroups. In individuals with bilateral early/intermediate AMD, rates of progression to GA or CNV were 2.0 and 3.2 per 100 person-years, respectively. In the multivariate model, age, female sex, and cardiovascular disease were associated with an increased risk for progression to advanced AMD, whereas diabetes and glaucoma were associated with a decreased rate of progression (hazard ratios, 0.45 and 0.64, respectively). CONCLUSIONS: Progression to GA or CNV was observed frequently in eyes with early/intermediate AMD, with the status of the fellow eye affecting the rate of progression. Novel associations with risk factors were observed and require replication in other cohorts.