State-Level Masking Mandates and COVID-19 Outcomes in the United States: A Demonstration of the Causal Roadmap.

BACKGROUND: We sought to investigate the effect of public masking mandates in US states on COVID-19 at the national level in Fall 2020. Specifically, we aimed to evaluate how the relative growth of COVID-19 cases and deaths would have differed if all states had issued a mandate to mask in public by 1 September 2020 versus if all states had delayed issuing such a mandate. METHODS: We applied the Causal Roadmap, a formal framework for causal and statistical inference. We defined the outcome as the state-specific relative increase in cumulative cases and in cumulative deaths 21, 30, 45, and 60 days after 1 September. Despite the natural experiment occurring at the state-level, the causal effect of masking policies on COVID-19 outcomes was not identifiable. Nonetheless, we specified the target statistical parameter as the adjusted rate ratio (aRR): the expected outcome with early implementation divided by the expected outcome with delayed implementation, after adjusting for state-level confounders. To minimize strong estimation assumptions, primary analyses used targeted maximum likelihood estimation with Super Learner. RESULTS: After 60 days and at a national level, early implementation was associated with a 9% reduction in new COVID-19 cases (aRR = 0.91 [95% CI = 0.88, 0.95]) and a 16% reduction in new COVID-19 deaths (aRR = 0.84 [95% CI = 0.76, 0.93]). CONCLUSIONS: Although lack of identifiability prohibited causal interpretations, application of the Causal Roadmap facilitated estimation and inference of statistical associations, providing timely answers to pressing questions in the COVID-19 response.

Application of a strain rate gradient microfluidic device to von Willebrand's disease screening.

Von Willebrand's disease (VWD) is the most common inherited bleeding disorder caused by either quantitative or qualitative defects of von Willebrand factor (VWF). Current tests for VWD require relatively large blood volumes, have low throughput, are time-consuming, and do not incorporate the physiologically relevant effects of haemodynamic forces. We developed a microfluidic device incorporating micro-contractions that harnesses well-defined haemodynamic strain gradients to initiate platelet aggregation in citrated whole blood. The microchannel architecture has been specifically designed to allow for continuous real-time imaging of platelet aggregation dynamics. Subjects aged ≥18 years with previously diagnosed VWD or who presented for evaluation of a bleeding disorder, where the possible diagnosis included VWD, were tested. Samples were obtained for device characterization as well as for pathology-based testing. Platelet aggregation in the microfluidic device is independent of platelet amplification loops but dependent on low-level platelet activation, GPIb/IX/V and integrin αIIbß3 engagement. Microfluidic output directly correlates with VWF antigen levels and is able to sensitively detect aggregation defects associated with VWD subtypes. Testing demonstrated a strong correlation with standard clinical laboratory-based tests. Head-to-head comparison with PFA100® demonstrated equivalent, if not improved, sensitivity for screening aggregation defects associated with VWD. This strain rate gradient microfluidic prototype has the potential to be a clinically useful, rapid and high throughput-screening tool for VWD as well as other strain-dependent platelet disorders. In addition, the microfluidic device represents a novel approach to examine the effects of high magnitude/short duration (ms) strain rate gradients on platelet function.

Confocal microscopy of posterior polymorphous endothelial dystrophy.

PURPOSE: To report the in vivo confocal microscopic findings of posterior polymorphous endothelial dystrophy (PPED). METHODS: Four patients with PPED from 2 unrelated families and 2 asymptomatic children of an index patient were included in this observational case series. The eyes of the 6 subjects were examined by confocal light microscopy. RESULTS: Confocal microscopy demonstrated craters, streaks, and cracks over the corneal endothelium surface. Pleomorphism and polymegathism were present in eyes with PPED. Guttae and clusters of abnormal endothelial cells were also identified in corneas of these PPED patients. These findings were absent in eyes without clinical manifestations of PPED. CONCLUSIONS: In vivo confocal microscopy is potentially useful for excluding suspected cases of subclinical PPED. Abnormalities in the Descemet membrane and endothelium were observed.

In vivo confocal microscopy of Thygeson's superficial punctate keratitis.

A 56-year-old Chinese man diagnosed with Thygeson's keratitis by clinical biomicroscopy was examined using a tandem scanning confocal microscope. Among normal superficial epithelial cells, clumps of markedly enlarged epithelial cells were identified. Multiple highly reflective filamentary structures were observed in the deeper layers. Most of these lesions were linear; some demonstrated curled ends and others demonstrated branching lesions with 'sprouts'. No inflammatory cells were evident in the areas of corneal stroma sampled. In vivo confocal microscopy may be helpful in the diagnosis of Thygeson's superficial keratitis. To the best of our knowledge, we report the first in vivo confocal images of focal desquamation of epithelium and intraepithelial hyper-reflective linear lesions in English literature.

Orthokeratology lens-related corneal ulcers in children: a case series.

OBJECTIVE: Orthokeratology is a process by which the corneal curvature is flattened by sequentially fitting rigid gas permeable contact lenses of decreasing central curvature. There has been a resurgence of interest with the recent introduction of reverse geometry lenses. Although promising results have been described in reducing the myopic refractive error, the use of these lenses can be associated with corneal problems, as reported in this case series. DESIGN: Observational case series. PARTICIPANTS: Six children with orthokeratology-related corneal ulcers. METHODS: Consecutive cases of orthokeratology lens (OKL)-related corneal ulcers in children presented to a tertiary referral center (March 1999-June 2001) were reviewed. MAIN OUTCOME MEASURES: Preinfection and postinfection visual acuity, refraction, any organisms identified. RESULTS: Six children between the ages of 9 and 14 years (mean = 12.1) were treated. The male:female ratio was 1:5. All cases were unilateral, with equal numbers of left and right eyes. All children wore the OKL at night for a duration of 8 to 12 hours, with the onset of infection between 3 and 36 months (mean = 16.6) of OKL wear. All of the patients suffered a resultant best-corrected visual acuity loss. Five of the 6 cases were culture positive for Pseudomonas aeruginosa. CONCLUSIONS: In view of the temporary benefits of orthokeratology, together with a known increased risk of infection associated with overnight lens wear, parents of children considering orthokeratology must be informed and warned of the potential for permanent loss of vision. The ophthalmic community should have a heightened awareness of the associated complications.

Orthokeratology lens-related Pseudomonas aeruginosa infectious keratitis.

PURPOSE: To report a case of orthokeratology lens-related Pseudomonas corneal ulcer in an adult. METHODS: Case report. RESULTS: A 37-year-old man presented with a 1-day history of painful red eye. He was a soft contact lens wearer before he started on nocturnal orthokeratology lens wear of 8 to 10 hours per night 9 months ago. Corneal scraping sent for culture revealed a heavy growth of Pseudomonas aeruginosa. The patient was treated with intensive topical fortified tobramycin and ceftazidime drops. The ulcer healed with a residual paraxial corneal scar. Although his best-corrected visual acuity (BCVA) recovered from finger counting (8/200) at presentation to 20/30, he suffered visual loss from a premorbid BSCVA of 20/15. His contrast sensitivity (Vector Vision CSV 1000 test) performance was also worse than his fellow eye. CONCLUSION: Nocturnal orthokeratology lens wear may be associated with an increased risk of infection.