The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

https://cdr.lib.unc.edu/downloads/v692t8920

A global reference for human genetic variation.

Objective To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. Design Collaborative meta-analyses (systematic overviews). Inclusion criteria Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen. Studies reviewed 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. Main outcome measure "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death. Results Overall, among these High risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P <0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000. Conclusions Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation, Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.

/pdf/collaborative-meta-analysis-of-randomised-trials-of-8dyu3duelv.pdf

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

Background Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. Methods We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmunoassays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. Results VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P<0.00...

https://www.nejm.org/doi/pdf/10.1056/NEJM199412013312203

Vascular Endothelial Growth Factor in Ocular Fluid of Patients with Diabetic Retinopathy and Other Retinal Disorders

A global reference for human genetic variation

Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.

Purpose:To investigate the short-term outcomes of 25-gauge pars plana vitrectomy (PPV) in 18 cases of complicated retinal detachment requiring silicone oil tamponade.Methods:In this retrospective noncomparative review, the primary outcome measures included postoperative anatomical status, preoperati

Short-term outcomes of 25-gauge vitrectomy with silicone oil for repair of complicated retinal detachment.

PurposeTo investigate the efficacy of the surgical removal of subfoveal choroidal neovascularization in patients with type 2A idiopathic juxtafoveolar retinal telangiectasis.MethodsTwo patients with bilateral acquired idiopathic juxtafoveolar retinal telangiectasis and a subfoveal choroidal neovascu

Surgical removal of subfoveal neovascularization in idiopathic juxtafoveolar retinal telangiectasis.

• Background: The aim was to describe a pathogenic mechanism for a rhegmatogenous retinal detachment in a 69-year-old man with the morning glory syndrome. • Methods: During vitreous surgery for a retinal detachment, a membrane was removed that covered the optic disc anomaly and produced traction on the peripapillary retina. A retinal hole was found in tissue lying within the optic cup, and the hole was sealed using a autologous plasma —thrombin mixture. Silicone oil was used for retinal tamponade. • Results: A retinal hole in tissue lying within the optic cup provided a fluid pathway between the vitreous cavity and the subretinal space. Following vitrectomy surgery, bubbles of silicone oil passed through the retinal hole into the subretinal space of the macula. • Conclusion: This case demonstrates that a retinal hole in tissue lying within the optic disc anomaly of the morning glory syndrome provides a communication for fluid between the subretinal space and the vitreous cavity, resulting in a rhegmatogenous retinal detachment. Vitreous replacement with silicone oil resulted in the migration of silicone bubbles into the subretinal space.

Communication between the subretinal space and the vitreous cavity in the morning glory syndrome

Objective To assess the comparative effectiveness and cost-effectiveness (cost-utility) of a 0.05% emulsion of topical cyclosporine (Restasis; Allergan Inc, Irvine, California) for the treatment of moderate to severe dry eye syndrome that is unresponsive to conventional therapy. Methods Data from 2 multicenter, randomized, clinical trials and Food and Drug Administration files for topical cyclosporine, 0.05%, emulsion were used in Center for Value-Based Medicine analyses. Analyses included value-based medicine as a comparative effectiveness analysis and average cost-utility analysis using societal and third-party insurer cost perspectives. Main Outcome Measures Outcome measures of comparative effectiveness were quality-adjusted life-year (QALY) gain and percentage of improvement in quality of life, and for cost-effectiveness were cost-utility ratio (CUR) using dollars per QALY. Results Topical cyclosporine, 0.05%, confers a value gain (comparative effectiveness) of 0.0319 QALY per year compared with topical lubricant therapy, a 4.3% improvement in quality of life for the average patient with moderate to severe dry eye syndrome that is unresponsive to conventional lubricant therapy. The societal perspective incremental CUR for cyclosporine over vehicle therapy is $34 953 per QALY and the societal perspective average CUR is $11 199 per QALY. The third-party–insurer incremental CUR is $37 179 per QALY, while the third-party–insurer perspective average CUR is $34 343 per QALY. Conclusions Topical cyclosporine emulsion, 0.05%, confers considerable patient value and is a cost-effective therapy for moderate to severe dry eye syndrome that is unresponsive to conventional therapy.

https://jamanetwork.com/journals/jamaophthalmology/articlepdf/421018/ecs80058_146_152.pdf

Value-Based Medicine, Comparative Effectiveness, and Cost-effectiveness Analysis of Topical Cyclosporine for the Treatment of Dry Eye Syndrome

The cases of 23 patients with untreated cilioretinal artery obstruction were reviewed. Three distinct groups were found: (1) isolated cilioretinal artery obstruction, (2) cilioretinal artery obstruction associated with central retinal venous obstruction, and (3) cilioretinal artery obstruction in conjunction with ischemic optic neuropathy. In the first group 90% of eyes achieved 6/12 or better vision and there was a high incidence of associated atherosclerotic carotid disease. In the second group, 70% of eyes improved to 6/12 or better, while in the last group no eye reached better than 6/120 vision.

Gary C. Brown

Papers

Short-term outcomes of 25-gauge vitrectomy with silicone oil for repair of complicated retinal detachment.

Surgical removal of subfoveal neovascularization in idiopathic juxtafoveolar retinal telangiectasis.

Communication between the subretinal space and the vitreous cavity in the morning glory syndrome

Value-Based Medicine, Comparative Effectiveness, and Cost-effectiveness Analysis of Topical Cyclosporine for the Treatment of Dry Eye Syndrome

Cilioretinal artery obstruction