COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients.

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

Effect of eyedrops and applanation tonometry on optical biometry.

PURPOSE: To determine whether eyedrops (phenylephrine, tropicamide, and fluorescein-proparacaine) and Goldmann applanation tonometry (GAT) have an effect on optical biometry measurements for preoperative cataract surgery workup. SETTING: George Washington University, Washington, DC. DESIGN: Nonrandomized controlled trial. METHODS: Participants older than 18 years with no contraindications to eyedrops or tonometry were recruited. Optical biometry measurements were obtained on a single eye using the Lenstar LS900. One drop each of phenylephrine, tropicamide, and fluorescein-proparacaine was applied to the same eye, and measurements were repeated. GAT was performed, and measurements were repeated. For controls, the contralateral eye was also measured at each interval. RESULTS: There was no statistically significant difference in mean predicted postoperative refraction (PPOR) keratometry (K) 1, K2, or axis postdrops and post-GAT 62 eyes (n = 62). After drops were applied, mean central corneal thickness increased from 540 to 542 µm (P = .0002), mean anterior chamber depth (ACD) increased from 3.68 to 3.70 mm (P < .0001), and lens thickness (LT) decreased from 3.66 to 3.65 (P = .001). After GAT, ACD increased to 3.76 mm (P < .0001), and LT increased to 3.60 mm (P < .0001). There was no statistically significant difference in PPOR or other parameters for the control eyes (n = 5). CONCLUSIONS: GAT and phenylephrine, tropicamide, and fluorescein-proparacaine drops did not affect the primary outcome of PPOR. This suggests that cataract surgery candidates do not need to return for a separate preoperative visit for optical biometry.

Methicillin-Resistant Staphylococcus aureus Keratitis: Initial Treatment, Risk Factors, Clinical Features, and Treatment Outcomes.

PURPOSE: To analyze the clinical characteristics, management choices, and outcomes of cases of methicillin-resistant Staphylococcus aureus (MRSA) keratitis. DESIGN: Retrospective interventional case series. METHODS: Fifty-two culture-proven (52 eyes) cases of MRSA keratitis diagnosed and treated at the University of Pittsburgh Medical Center were identified and reviewed. RESULTS: The mean age was 66.6 ± 19.2 years with a median follow-up time of 147 days. The most prevalent risk factors included a history of ocular surgery (62.5%), topical corticosteroid use (35.4%), and dry eye syndrome (37.5%). There was a high burden of systemic disease (95.8%). The average presenting logarithm of minimal angle of resolution visual acuity was 1.7 ± 0.8 and the average final logarithm of minimal angle of resolution visual acuity was 1.2 + 1.0. Initial antibiotic treatment varied, with 20.8% receiving moxifloxacin alone, 20.8% receiving fortified cefazolin and fortified tobramycin together, and 12.5% receiving fortified vancomycin and fortified tobramycin, although other antibiotics were used during treatment if warranted. Surgical management was often required as 17.3% of eyes perforated: 13.5% required tarsorrhaphy, 5.8% required penetrating keratoplasty, and 1 eye was enucleated. When patients treated with fourth-generation fluoroquinolones were compared with those treated with fortified vancomycin, no difference in final visual acuity, treatment duration, or need for surgery was found. CONCLUSION: MRSA causes fulminant keratitis often requiring surgical management with poor visual acuity outcomes. Poor ocular surface, topical corticosteroid use, previous ocular surgery, and/or a high burden of systemic disease were identified as common risk factors. Patients treated with fluoroquinolones in our study had comparable outcomes to those treated with fortified vancomycin; however, those treated with fortified vancomycin tended to have more severe ulcers at presentation.

Pterygium: new insights.

Pterygia are common conjunctival degenerations with well-documented risk factors but an unclear pathogenesis. Better understanding of the pathogenesis of pterygium could lead to improved surgical outcomes and decreased postoperative recurrence. Currently, pterygium excision with conjunctival autograft remains the preferred surgical technique to decrease pterygium recurrence. Many adjuvant therapies have been used in pterygium surgery to varying degrees of success. Topical cyclosporine, an immunosuppressive medication, in conjunction with conjunctival autograft was found to be most successful in decreasing pterygium recurrence according to a recent meta-analysis. Other adjuvant therapies such as mitomycin-C (MMC), 5-fluorouracil (5-FU), and beta-irradiation have also been used, though usage of these may cause multiple adverse effects. Recent research indicates that interactions between mouse double minute 2 (MDM2) and p53 could play a role in the occurrence of pterygium. Nutlin, an MDM2 antagonist, was found to have significantly less toxicity in conjunctival cells when compared with MMC on laboratory analysis of pterygium samples.

Improving multidisciplinary severe sepsis management using the Sepsis Six .

Each year in the UK, it is estimated that more than 100,000 people are admitted to hospital with sepsis and around 37,000 people will die as a result of the condition. We present an audit, re-audit and the implications these have had on the management of severe sepsis using the Sepsis Six, ultimately through actively promoting teamwork to initiate the protocol. This led to a significant improvement in management, decreasing admissions to the intensive care unit (ITU), length of stay in hospital and the number of patient deaths.The initial audit and re-audit were done over 2-month periods. All clerking notes of patients with a medical consultant diagnosis of 'sepsis' on post-take ward round were analysed and further screened for presence of severe sepsis according to national guidelines.There was significant improvement from only 1% of patients being appropriately managed (according to the existing guidelines) to 67% of eligible subjects adhering to the protocol (p<0.0001). Initially, 19% were admitted to the ITU (6% died), improving to 7% on re-audit (with no deaths). Length of hospital stay reduced from 10 to 7 days (p<0.0001).There was a complete change in the management of severe sepsis with trust-wide updated protocols, resulting in a decrease in hospital morbidity and mortality.

A low concentration of ethanol impairs learning but not motor and sensory behavior in Drosophila larvae.

Drosophila melanogaster has proven to be a useful model system for the genetic analysis of ethanol-associated behaviors. However, past studies have focused on the response of the adult fly to large, and often sedating, doses of ethanol. The pharmacological effects of low and moderate quantities of ethanol have remained understudied. In this study, we tested the acute effects of low doses of ethanol (∼7 mM internal concentration) on Drosophila larvae. While ethanol did not affect locomotion or the response to an odorant, we observed that ethanol impaired associative olfactory learning when the heat shock unconditioned stimulus (US) intensity was low but not when the heat shock US intensity was high. We determined that the reduction in learning at low US intensity was not a result of ethanol anesthesia since ethanol-treated larvae responded to the heat shock in the same manner as untreated animals. Instead, low doses of ethanol likely impair the neuronal plasticity that underlies olfactory associative learning. This impairment in learning was reversible indicating that exposure to low doses of ethanol does not leave any long lasting behavioral or physiological effects.