Eye care delivery models to improve access to eye care for Indigenous people in high-income countries: protocol for a scoping review.

INTRODUCTION: Globally, there are an estimated 370 million Indigenous people across 90 countries. Indigenous people experience worse health compared with non-Indigenous people, including higher rates of avoidable visual impairment. Countries such as Australia and Canada have service delivery models aimed at improving access to eye care for Indigenous people. We will conduct a scoping review to identify and summarise these service delivery models to improve access to eye care for Indigenous people in high-income countries. METHODS AND ANALYSIS: An information specialist will conduct searches on MEDLINE, Embase and Global Health. All databases will be searched from their inception date with no language limits used. We will search the grey literature via websites of relevant government and service provider agencies. Field experts will be contacted to identify additional articles, and reference lists of relevant articles will be searched. All quantitative and qualitative study designs will be eligible if they describe a model of eye care service delivery aimed at Indigenous populations. Two reviewers will independently screen titles, abstracts and full-text articles; and complete data extraction. For each service delivery model, we will extract data on the context, inputs, outputs, Indigenous engagement and enabling health system functions. Where models were evaluated, we will extract details. We will summarise findings using descriptive statistics and thematic analysis. ETHICS AND DISSEMINATION: Ethical approval is not required, as our review will include published and publicly accessible data. This review is part of a project to improve access to eye care services for Māori in Aotearoa New Zealand. The findings will be useful to policymakers, health service managers and clinicians responsible for eye care services in New Zealand, and other high-income countries with Indigenous populations. We will publish our findings in a peer-reviewed journal and develop an accessible summary of results for website posting and stakeholder meetings

Numerical modelling of the lobes of radio galaxies in cluster environments II : Magnetic field configuration and observability

Copyright The Authors 2014. Published by Oxford University Press on behalf of the Royal Astronomical Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly citedWe describe three-dimensional magnetohydrodynamical modelling of powerful radio galaxies in realistic poor cluster environments. This modelling extends our earlier work on the hydrodynamics of radio galaxies as a function of their cluster environment to consider the magnetic field configuration in the lobes and its observational consequences, using a realistic model for the magnetic field in the intracluster medium, very high density contrast in the lobes and high numerical resolution. We confirm, now with a realistic magnetic field model, that lobes have characteristic trajectories in the radio power/linear size diagram which depend strongly on their environment. We investigate the detailed evolution of polarized emission, showing that the lobes evolve from the initially ordered field configuration imposed by our boundary conditions to one in which the longitudinal field comes to dominate. We obtain simulated observations of polarization whose properties are quantitatively consistent with observations. The highly spatially intermittent magnetic field also reproduces the observation that inverse-Compton emission from lobes is much smoother than synchrotron. Our simulations allow us to study the depolarizing effect of the external medium on the lobes, and so to demonstrate that Faraday depolarization from environments of the type we consider can reproduce the integrated fractional polarization properties of large samples and the observed preferential depolarization of the receding lobe.Peer reviewe

Three-dimensional magnetohydrodynamic simulations of the evolution of magnetic fields in Fanaroff-Riley class II radio sources

Radio observations of Fanaroff-Riley class II sources often show correlations between the synchrotron emission and the linear-polarimetric distributions. Magnetic position vectors seem to align with the projected emission of both the radio jets and the sources' edges. Using statistics we study such relation as well as its unknown time evolution via synthetic polarisation maps of model FR II sources formed in 3D-MHD numerical simulations of bipolar, hypersonic and weakly magnetised jets. The magnetic field is initially random with a Kolmogorov power spectrum, everywhere. We investigate the structure and evolution of magnetic fields in the sources as a function of the power of jets and the observational viewing angle. Our synthetic polarisation maps agree with observations, showing B-field vectors which are predominantly aligned with the jet axis, and show that magnetic fields inside sources are shaped by the jets' backflow. Polarimetry is found to correlate with time, the viewing angle and the jet-to-ambient density contrast. The magnetic structure inside thin elongated sources is more uniform than inside more spherical ones. We see jets increase the magnetic energy in cocoons in proportion to the jet velocity and the cocoon width. Filaments in the synthetic emission maps suggest turbulence develops in evolved sources.Comment: Accepted for publication in the MNRAS. 21 pages, 11 figure

Interventions to promote access to eyecare for non-dominant ethnic groups in high-income countries: a scoping review

Purpose People who are distinct from the dominant ethnic group within a country can experience a variety of barriers to accessing eyecare services. We conducted a scoping review to map published interventions aimed at improving access to eyecare for non-Indigenous, non-dominant ethnic groups residing in high-income countries. Methods We searched MEDLINE, Embase and Global Health for studies that described an intervention to promote access to eyecare for the target population. Two authors independently screened titles and abstracts followed by review of the full text of potentially relevant sources. For included studies, data extraction was carried out independently by two authors. Findings were summarised using a combination of descriptive statistics and thematic analysis. Results We screened 5220 titles/abstracts, of which 82 reports describing 67 studies met the inclusion criteria. Most studies were conducted in the USA (90%), attempted to improve access for Black (48%) or Latinx (28%) communities at-risk for diabetic retinopathy (42%) and glaucoma (18%). Only 30% included the target population in the design of the intervention; those that did tended to be larger, collaborative initiatives, which addressed both patient and provider components of access. Forty-eight studies (72%) evaluated whether an intervention changed an outcome measure. Among these, attendance at a follow-up eye examination after screening was the most common (n=20/48, 42%), and directly supporting patients to overcome barriers to attendance was reported as the most effective approach. Building relationships between patients and providers, running coordinated, longitudinal initiatives and supporting reduction of root causes for inequity (education and economic) were key themes highlighted for success. Conclusion Although research evaluating interventions for non-dominant, non-Indigenous ethnic groups exist, key gaps remain. In particular, the paucity of relevant studies outside the USA needs to be addressed, and target communities need to be involved in the design and implementation of interventions more frequently

Changes in the variability and periodicity of precipitation in Scotland

This paper analyses the temporal and spatial changes in the amount and variability of rainfall in Scotland. The sequential Mann–Kendall test reveals that total annual precipitation has increased across Scotland since the 1970s with increasing trends in variability beginning between the mid-1960s and the mid-1970s. Whilst temporally consistent increasing trends in precipitation totals prevail in the West, many weather stations in the East have experienced subsequent trend turning points in the following two decades, explaining the larger magnitude of the trends in western Scotland in recent decades. Trend analyses on six measures of rainfall variability indicate an increase in rainfall variability during the period 1961–2000, as measured by the intra-annual variance, the winter to summer precipitation ratio and the annual cumulative sum range, with decreasing trends observed in the number of dry days. Periodicities associated with the North Atlantic Oscillation and the Atlantic Multidecadal Oscillation could explain the observed temporal variability of rainfall

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis. RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives. CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.)

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Protocol for evaluation of the cost-effectiveness of ePrescribing systems and candidate prototype for other related health information technologies

Background: This protocol concerns the assessment of cost-effectiveness of hospital health information technology (HIT) in four hospitals. Two of these hospitals are acquiring ePrescribing systems incorporating extensive decision support, while the other two will implement systems incorporating more basic clinical algorithms. Implementation of an ePrescribing system will have diffuse effects over myriad clinical processes, so the protocol has to deal with a large amount of information collected at various ‘levels’ across the system. Methods/Design: The method we propose is use of Bayesian ideas as a philosophical guide. Assessment of cost-effectiveness requires a number of parameters in order to measure incremental cost utility or benefit – the effectiveness of the intervention in reducing frequency of preventable adverse events; utilities for these adverse events; costs of HIT systems; and cost consequences of adverse events averted. There is no single end-point that adequately and unproblematically captures the effectiveness of the intervention; we therefore plan to observe changes in error rates and adverse events in four error categories (death, permanent disability, moderate disability, minimal effect). For each category we will elicit and pool subjective probability densities from experts for reductions in adverse events, resulting from deployment of the intervention in a hospital with extensive decision support. The experts will have been briefed with quantitative and qualitative data from the study and external data sources prior to elicitation. Following this, there will be a process of deliberative dialogues so that experts can “re-calibrate” their subjective probability estimates. The consolidated densities assembled from the repeat elicitation exercise will then be used to populate a health economic model, along with salient utilities. The credible limits from these densities can define thresholds for sensitivity analyses. Discussion: The protocol we present here was designed for evaluation of ePrescribing systems. However, the methodology we propose could be used whenever research cannot provide a direct and unbiased measure of comparative effectiveness