Investigation of COVID-19 Outbreak among Wildland Firefighters during Wildfire Response,Colorado, USA, 2020

A COVID-19 outbreak occurred among Cameron Peak Fire responders in Colorado, USA, during August 2020–January 2021. The Cameron Peak Fire was the largest recorded wildfire in Colorado history, lasting August–December 2020. At least 6,123 responders were involved, including 1,260 firefighters in 63 crews who mobilized to the fire camps. A total of 79 COVID-19 cases were identified among responders, and 273 close contacts were quarantined. State and local public health investigated the outbreak and coordinated with wildfire management teams to prevent disease spread. We performed whole-genome sequencing and applied social network analysis to visualize clusters and transmission dynamics. Phylogenetic analysis identified 8 lineages among sequenced specimens, implying multiple introductions. Social network analysis identified spread between and within crews. Strategies such as implementing symptom screening and testing of arriving responders, educating responders about overlapping symptoms of smoke inhalation and COVID-19, improving physical distancing of crews, and encouraging vaccinations are recommended.     

Hyperimmunized Chickens Produce Neutralizing Antibodies against SARS-CoV-2

The novel severe acute respiratory syndrome (SARS) coronavirus, SARS-CoV-2, is responsible for the global COVID-19 pandemic. Effective interventions are urgently needed to mitigate the effects of COVID-19 and likely require multiple strategies. Egg-extracted antibody therapies are a low-cost and scalable strategy to protect at-risk individuals from SARS-CoV-2 infection. Commercial laying hens were hyperimmunized against the SARS-CoV-2 S1 protein using three different S1 recombinant proteins and three different doses. Sera and egg yolk were collected at three and six weeks after the second immunization for enzyme-linked immunosorbent assay and plaque-reduction neutralization assay to determine antigen-specific antibody titers and neutralizing antibody titers, respectively. In this study we demonstrate that hens hyperimmunized against the SARS-CoV-2 recombinant S1 and receptor binding domain (RBD) proteins produced neutralizing antibodies against SARS-CoV-2. We further demonstrate that antibody production was dependent on the dose and type of antigen administered. Our data suggests that antibodies purified from the egg yolk of hyperimmunized hens can be used as immunoprophylaxis in humans at risk of exposure to SARS-CoV-2.     

Modeling the Cost-Effectiveness of Adjuvant Osimertinib for Patients with Resected EGFR-mutant Non-Small Cell Lung Cancer

IntroductionThe epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib was recently approved for resected EGFR-mutant stages IB-IIIA non-small cell lung cancer due to improved disease-free survival (DFS) in this population compared with placebo. This study aimed to evaluate the cost-effectiveness (CE) of this strategy.Materials and MethodsWe constructed a Markov model using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of 3 years of adjuvant osimertinib versus placebo over a 10-year time horizon. An overall survival (OS) benefit of 5% was assumed. Costs and utility values were derived from Medicare reimbursement data and literature. A CE threshold of 3 times the gross domestic product per capita was used. Sensitivity analyses were performed.ResultsThe incremental cost-effectiveness ratio for adjuvant osimertinib was $317 119 per QALY-gained versus placebo. Initial costs of osimertinib are higher in years 1-3. Costs due to progressive disease (PD) are higher in the placebo group through the first 6.5 years. Average pre-PD, post-PD, and total costs were $2388, $379 047, and $502 937, respectively, in the placebo group, and $505 775, $255 638, and $800 697, respectively, in the osimertinib group. Sensitivity analysis of OS gains reaches CE with an hazard ratio (HR) of 0.70-0.75 benefit of osimertinib over placebo. A 50% discount to osimertinib drug cost yielded an ICER of $115 419.ConclusionsThree-years of adjuvant osimertinib is CE if one is willing to pay $317 119 more per QALY-gained. Considerable OS benefit over placebo or other economic interventions will be needed to reach CE.     

Advances in Trace Element Supplementation for Parenteral Nutrition

Parenteral nutrition (PN) provides support for patients lacking sufficient intestinal absorption of nutrients. Historically, the need for trace element (TE) supplementation was poorly appreciated, and multi-TE products were not initially subjected to rigorous oversight by the United States Food and Drug Administration (FDA). Subsequently, the American Society for Parenteral and Enteral Nutrition (ASPEN) issued dosage recommendations for PN, which are updated periodically. The FDA has implemented review and approval processes to ensure access to safer and more effective TE products. The development of a multi-TE product meeting ASPEN recommendations and FDA requirements is the result of a partnership between the FDA, industry, and clinicians with expertise in PN. This article examines the rationale for the development of TRALEMENT^® (Trace Elements Injection 4*) and the FDA’s rigorous requirements leading to its review and approval. This combination product contains copper, manganese, selenium, and zinc and is indicated for use in adults and pediatric patients weighing ≥10 kg. Comprehensive management of PN therapy requires consideration of many factors when prescribing, reviewing, preparing, and administering PN, as well as monitoring the nutritional status of patients receiving PN. Understanding patients’ TE requirements and incorporating them into PN is an important part of contemporary PN therapy.     

Divergent Histopathological Networks of Frontotemporal Degeneration Proteinopathy Subytpes

Network analyses inform complex systems such as human brain connectivity, but this approach is seldom applied to gold-standard histopathology. Here, we use two complimentary computational approaches to model microscopic progression of the main subtypes of tauopathy versus TDP-43 proteinopathy in the human brain. Digital histopathology measures were obtained in up to 13 gray matter (GM) and adjacent white matter (WM) cortical brain regions sampled from 53 tauopathy and 66 TDP-43 proteinopathy autopsy patients. First, we constructed a weighted non-directed graph for each group, where nodes are defined as GM and WM regions sampled and edges in the graph are weighted using the group-level Pearson''s correlation coefficient for each pairwise node comparison. Additionally, we performed mediation analyses to test mediation effects of WM pathology between anterior frontotemporal and posterior parietal GM nodes. We find greater correlation (i.e., edges) between GM and WM node pairs in tauopathies compared with TDP-43 proteinopathies. Moreover, WM pathology strongly correlated with a graph metric of pathology spread (i.e., node-strength) in tauopathies (r = 0.60, p < 0.03) but not in TDP-43 proteinopathies (r = 0.03, p = 0.9). Finally, we found mediation effects for WM pathology on the association between anterior and posterior GM pathology in FTLD-Tau but not in FTLD-TDP. These data suggest distinct tau and TDP-43 proteinopathies may have divergent patterns of cellular propagation in GM and WM. More specifically, axonal spread may be more influential in FTLD-Tau progression. Network analyses of digital histopathological measurements can inform models of disease progression of cellular degeneration in the human brain.SIGNIFICANCE STATEMENT In this study, we uniquely perform two complimentary computational approaches to model and contrast microscopic disease progression between common frontotemporal lobar degeneration (FTLD) proteinopathy subtypes with similar clinical syndromes during life. Our models suggest white matter (WM) pathology influences cortical spread of disease in tauopathies that is less evident in TDP-43 proteinopathies. These data support the hypothesis that there are neuropathologic signatures of cellular degeneration within neurocognitive networks for specific protienopathies. These distinctive patterns of cellular pathology can guide future efforts to develop tissue-sensitive imaging and biological markers with diagnostic and prognostic utility for FTLD. Moreover, our novel computational approach can be used in future work to model various neurodegenerative disorders with mixed proteinopathy within the human brain connectome.