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Background Anaphylaxis is a serious allergic reaction that may cause death; however, the actual risk of death is unclear. Objective To estimate the case fatality rate (CFR) among hospitalizations or emergency department (ED) presentations for anaphylaxis and the mortality rate associated with anaphylaxis for the general population. Methods This was a population-based epidemiologic study using 3 national databases: Nationwide Inpatient Sample (NIS, 1999-2009), Nationwide Emergency Department Sample (NEDS, 2006-2009), and Multiple Cause of Death Data (MCDD, 1999-2009). Sources for these databases are hospital, ED discharge records and death certificates, respectively. Results CFRs were between 0.25% and 0.33% among hospitalizations or ED presentations with anaphylaxis as the principal diagnosis (NIS+NEDS, 2006-2009). These rates represent 63 to 99 deaths per year in the United States, approximately 77% of which occurred in hospitalized patients. Rate of anaphylaxis hospitalizations rose from 21.0 to 25.1 per million population between 1999 and 2009 (annual percent change 2.23%; 95% CI: 1.52%–2.94%), contrasting with a declining CFR among hospitalizations (annual percent change –2.35%; 95% CI: –4.98% to 0.34%). Overall mortality rates ranged from 0.63 to 0.76 per million population (186 to 225 deaths per year, MCDD), and appeared stable in the last decade (annual percent change: –0.31%; 95% CI, –1.54% to 0.93%). Conclusion From 2006 to 2009, the overwhelming majority of hospitalizations or ED presentations for anaphylaxis did not result in death, with an average CFR of 0.3%. Anaphylaxis-related hospitalizations rose steadily in the last decade (1999-2009), but this increase was offset by the declining CFR among those hospitalized; both inpatient and overall mortality rates associated with anaphylaxis appeared stable and were well under 1 per million population. Although anaphylactic reactions are potentially life threatening, the probability of dying is actually very low. With the prevalence of anaphylaxis on the rise, practitioners need to stay vigilant and follow the treatment guidelines to further reduce anaphylaxis-related deaths.

The optical density of the human crystalline lens progressively increases with age, the greatest increase in the visible spectrum being at short wavelengths. This produces a gradual shift in the spectral distribution of the light reaching the retina, yet color appearance remains relatively stable across the life span, implying that the visual system adapts to compensate for changes in spectral sensitivity. We explored properties of this adaptive renormalization by measuring changes in color appearance following cataract surgery. When the lens is removed, cataract patients often report a large perceptual shift in color appearance that can last for months. This change in color appearance was quantified for four cataract patients (63-84 years) by determining the chromaticity of stimuli that appeared achromatic before surgery, and at various intervals after surgery for up to 1 year. Stimuli were presented on a calibrated CRT as 9.5-deg spots, with 3-s duration and 3-s interstimulus intervals (ISIs). Chromaticity was adjusted by the subjects in CIE L * a * b * color space with luminance fixed at 32 cd0m 2 , on a dark background. We also estimated the optical density of the cataractous lens by comparing absolute scotopic thresholds from 410 nm to 600 nm before and after surgery. The results demonstrated that immediately following surgery there is a large increase in the short-wave light reaching the retina, mainly below 500 nm. The achromatic settings generally showed an initial large shift in the "yellow" direction after surgery that gradually (but never fully) returned to the original achromatic point before surgery. The shifts in the achromatic point occur over a number of months and appear to occur independently of the fellow eye.

Objective To determine if there is a difference in the risk of endophthalmitis after an intravitreal steroid injection compared to an anti-vascular endothelial growth factor agent (anti-VEGF) injection Design Retrospective cohort study Participants 75,249 beneficiaries in a large national US medical claims database representing 406,380 intravitreal injections Methods Data were searched for all intravitreal injections (CPT 67028) performed between 2003 and 2012. Cohorts were created based on injections using anti-VEGF agents (bevacizumab, ranibizumab, aflibercept and pegaptanib) and intraocular steroids (triamcinolone and dexamethasone). Endophthalmitis was defined as having a new endophthalmitis diagnosis (ICD9 360.0×) and either a “tap-and-inject” procedure (CPT67015, 67025), a vitrectomy (67036) or an intravitreal antibiotic injection on the same day, between 1 and 14 days post-injection. Exclusion occurred for any history of endophthalmitis, <6 months in the plan or <1 month follow up. The main outcome measure was the odds of endophthalmitis using logistic regression while controlling for injection-associated diagnosis, age, race and gender. Results 387,714 anti-VEGF injections and 18,666 steroid intravitreal injections were performed and were followed by 73 (rate=0.019% or 1/5283 anti-VEGF injections) and 24 (rate= 0.13% or 1/778 steroid injections) cases of endophthalmitis respectively. After controlling for diagnosis, age, race and gender, the odds ratio for endophthalmitis occurring was 6.92 (95% CI: 3.54–13.52, p<0.001) times higher post-steroid injection compared to anti-VEGF injections. Conclusions The rate of endophthalmitis post-intravitreal steroid injection in a national cohort was 0.13% (1/778 injections). This rate conferred a significantly increased odds ratio of 6.92 for endophthalmitis compared to anti-VEGF agents.

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IMPORTANCE Current draft guidelines set forth by the US Food and Drug Administration for compounded or repackaged medications would greatly limit the availability and use of bevacizumab by ophthalmologists across the country. Little evidence beyond highly publicized case reports exists for or against the need for additional regulation of compounded bevacizumab.OBJECTIVE To determine whether the distribution of bevacizumab through compounding pharmacies increases the risk for endophthalmitis compared with the distribution of single-use vials of ranibizumab from the manufacturer. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study using medical claims data from ambulatory care centers across the United States that were submitted to a large, national US insurer. Cohorts were created using information on 530 382 intravitreal injections administered from January 1, 2005, through December 31, 2012. Any individual from this data set who received an intravitreal injection of bevacizumab or ranibizumab (n=383 810) and had at least 6 months of data before and 1 month after the injection was eligible. After exclusions (any previous diagnosis of endophthalmitis, multiple injected drugs given on the index day, or intraocular surgery within 15 days of the injection or between the injection and a diagnosis of endophthalmitis), our analysis involved 383 810 intravitreal injections given to 58 612 patients. Data collection and analysis occurred from February 16 through April 7, 2015. MAIN OUTCOMES AND MEASURESThe odds of developing endophthalmitis after an intravitreal injection of bevacizumab compared with ranibizumab. RESULTSIn total, 296 565 injections of bevacizumab were given to 51 116 patients and 87 245 injections of ranibizumab were given to 7496 patients. We found 71 cases of endophthalmitis (49 in the bevacizumab cohort and 22 in the ranibizumab cohort) for an endophthalmitis rate of 0.017% (95% CI, 0.012%-0.021%; 1 case per 6061 injections) for bevacizumab and 0.025% (95% CI, 0.015%-0.036%; 1 case per 3968 injections) for ranibizumab. After controlling for age, race, sex, injection-related diagnosis, and year of injection, we found no significant association with development of endophthalmitis after a bevacizumab injection compared with ranibizumab (odds ratio, 0.66 [95% CI, 0.39-1.09]; P = .11). CONCLUSIONS AND RELEVANCEThe results of this study suggest bevacizumab as currently used across the United States does not increase the risk for endophthalmitis; therefore, additional regulations on the use of repackaged bevacizumab may be unnecessary.

Summary We identified three zebrafish mutants with defects in biliary development. One of these mutants, pekin (pn), also demonstrated generalized hypopigmentation and other defects, including disruption of retinal cell layers, lack of zymogen granules in the pancreas, and dilated Golgi in intestinal epithelial cells. Bile duct cells in pn demonstrated an accumulation of electron dense bodies. We determined that the causative defect in pn was a splice site mutation in the atp6ap2 gene that leads to an inframe stop codon. atp6ap2 encodes a subunit of the vacuolar H+-ATPase (V-H+-ATPase), which modulates pH in intracellular compartments. The Atp6ap2 subunit has also been shown to function as an intracellular renin receptor that stimulates fibrogenesis. Here we show that mutants and morphants involving other V-H+-ATPase subunits also demonstrated developmental biliary defects, but did not demonstrate the inhibition of fibrogenic genes observed in pn. The defects in pn are reminiscent of those we and others have observed in class C VPS (vacuolar protein sorting) family mutants and morphants, and we report here that knockdown of atp6ap2 and vps33b had an additive negative effect on biliary development. Our findings suggest that pathways important in modulating intracompartmental pH lead to defects in digestive organ development, and support previous studies demonstrating the importance of intracellular sorting pathways in biliary development.