Self-Reported and Actual Beta-Blocker Prescribing for Heart Failure Patients: Physician Predictors

Beta-blockers reduce mortality among patients with systolic heart failure (HF), yet primary care provider prescription rates remain low.To examine the association between primary care physician characteristics and both self-reported and actual prescription of beta-blockers among patients with systolic HF.Cross-sectional survey with supplementary retrospective chart review.Primary care providers at three New York City Veterans Affairs medical centers.Main outcomes were: 1) self-reported prescribing of beta-blockers, and 2) actual prescribing of beta-blockers among HF patients. Physician HF practice patterns and confidence levels, as well as socio-demographic and clinical characteristics, were also assessed.Sixty-nine of 101 physicians (68%) completed the survey examining self-reported prescribing of beta-blockers. Physicians who served as inpatient ward attendings self-reported significantly higher rates of beta-blocker prescribing among their HF patients when compared with physicians who did not attend (78% vs. 58%; p = 0.002), as did physicians who were very confident in managing HF patients when compared with physicians who were not (82% vs. 68%; p = 0.009). Fifty-one of these 69 surveyed physicians (74%) were successfully matched to 287 HF patients for whom beta-blocker prescribing data was available. Physicians with greater self-reported rates of prescribing beta-blockers were significantly more likely to actually prescribe beta-blockers (p = 0.02); however, no other physician characteristics were significantly associated with actual prescribing of beta-blockers among HF patients.Physician teaching responsibilities and confidence levels were associated with self-reported beta-blocker prescribing among their HF patients. Educational efforts focused on improving confidence levels in HF care and increasing exposure to teaching may improve beta-blocker presciption in HF patients managed in primary care

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Complications of sulcus placement of single-piece acrylic intraocular lenses Recommendations for backup IOL implantation following posterior capsule rupture SPECIAL REPORT

for the ASCRS Cataract Clinical Committee PURPOSE: To describe complications arising from sulcus placement of single-piece acrylic (SPA) intraocular lenses (IOLs), evaluate IOL options for eyes that lack adequate capsule support, and examine the appropriateness of various IOL designs for sulcus placement. SETTING: University and private anterior segment surgery practices. METHODS: RESULTS: Complications of sulcus SPA IOLs included pigment dispersion, iris transillumination defects, dysphotopsia, elevated intraocular pressure, intraocular hemorrhage, and cystoid macular edema. Two patients in the series of 30 patients experienced 1 complication; 8 experienced 2 complications; 13 experienced 3 complications; 4 experienced 4 complications; and 2 experienced 5 complications. Twenty-eight eyes (93%) required surgical intervention; IOL exchange was performed in 25 (83%). Postoperatively, the mean CDVA improved, with most eyes attaining 20/20. CONCLUSIONS: Intraocular lenses designed solely for the capsular bag should not be placed in the ciliary sulcus. Backup IOLs in appropriate powers, sizes, and designs should be available for every cataract procedure. The development, investigation, and supply of IOLs specifically designed for placement in eyes that lack adequate capsule support represent clinically important endeavors for ophthalmology and the ophthalmic industry. J Cataract Refract Surg 2009; 35:1445-1458 Q 2009 ASCRS and ESCRS Single-piece acrylic (SPA) intraocular lenses (IOLs) currently account for approximately one half of the IOLs implanted concurrent with cataract surgery in the United States (Alcon, Inc.; data on file). Given the large annual volume of cataract surgery performed worldwide, a significant number of SPA IOLs may be inadvertently or intentionally placed in the ciliary sulcus; eg, following posterior capsule rupture. This raises the question of whether this strategy is appropriate and the larger issues of which IOL designs are suitable as backup IOLs in the absence of secure capsular bag support. The growing popularity of accommodating, multifocal, toric, and aspheric monofocal IOLs raises additional concerns about whether these IOLs are appropriate for placement in the ciliary sulcus. Finally, the debate continues over whether an anterior chamber IOL (AC IOL) or a sutured posterior chamber IOL (PC IOL) is the best long-term option in the absence of adequate capsule support. To help answer these questions, members of the American Society of Cataract and Refractive Surgery (ASCRS) Cataract Clinical Committee conducted a retrospective survey of patients referred for complications associated with SPA IOLs implanted in the ciliary sulcus. We also reviewed the literature with respect to recommendations for backup IOL design and placement

Matched Cohort Study of Convalescent COVID-19 Plasma Treatment in Severely or Life Threateningly Ill COVID-19 Patients.

BACKGROUND: The utility of convalescent coronavirus disease 2019 (COVID-19) plasma (CCP) in the current pandemic is not well defined. We sought to evaluate the safety and efficacy of CCP in severely or life threateningly ill COVID-19 patients when matched with a contemporaneous cohort. METHODS: Patients with severe or life-threatening COVID-19 were treated with CCP according to Food and Drug Administration criteria, prioritization by an interdisciplinary team, and based on CCP availability. Individual-level matched controls (1:1) were identified from patients admitted during the prior month when no CCP was available. The safety outcome was freedom from adverse transfusion reaction, and the efficacy outcome was a composite of death or worsening O RESULTS: Study patients (n = 94, 47 matched pairs) were 62% male with a mean age of 58, and 98% (90/94) were minorities (53% Hispanic, 45% Black, non-Hispanic) in our inner-city population. Seven-day composite and mortality outcomes suggested a nonsignificant benefit in CCP-treated patients (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.23-2.12; CONCLUSIONS: In this short-term matched cohort study, transfusion with CCP was safe and showed a nonsignificant association with study outcomes. Randomized and larger trials to identify appropriate timing and dosing of CCP in COVID-19 are warranted. TRIAL REGISTRATION:  ClinicalTrials.gov Identifier: NCT04420988

Evidence for a non-antioxidant, dose-dependent role of alpha-lipoic acid in caspase-3 and ERK2 activation in endothelial cells

Endothelial cell apoptosis contributes to atherosclerosis and may be exacerbated by oxidative stress. Results from clinical trials using antioxidant supplementation are equivocal and could be enhanced by antioxidants with additional non-antioxidant properties such as a-lipoic acid and alpha-tocopherol. The aim of this study was to investigate the effects of these antioxidants on cytoprotective pathways and endothelial apoptosis. Endothelial cells were incubated with alpha-lipoic acid and alpha-tocopherol, alone or in combination, prior to incubation with H2O2 or staurosporine. alpha-lipoic acid pre-treatment alone increased caspase-3 activity in a dose-dependent manner. Both H2O2 and staurosporine increased DNA fragmentation and caspase-3 activity and pre-treatment of cells with a-lipoic acid and/or a-tocopherol failed to prevent stress-induced apoptosis. Neither antioxidant treatments nor apoptotic inducers alone altered expressions of BcI-2, Bax, HSP70 or pERK1/2 or pJNK. alpha-lipoic decreased pERK2 in staurosporine-treated cells in a dose-dependent manner. These findings indicate that pre-incubation with alpha-lipoic acid and alpha-tocopherol, alone or in combination, does not protect against oxidative- or non-oxidative-induced apoptosis in endothelial cells. Moreover, we have demonstrated a non-antioxidant, dose-dependent role of alpha-lipoic acid in caspase-3 and ERK2 activation. These data provide an insight and indicate caution in the use of high doses of alpha-lipoic acid as an antioxidant

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