ABSTRACT
The emergence and establishment of SARS-CoV-2 variants of interest (VOI) and variants of concern (VOC) highlight the importance of genomic surveillance. We propose a statistical learning strategy (SLS) for identifying and spatiotemporally tracking potentially relevant Spike protein mutations. We analyzed 167,893 Spike protein sequences from US COVID-19 cases (excluding 21,391 sequences from VOI/VOC strains) deposited at GISAID from January 19, 2020 to March 15, 2021. Alignment against the reference Spike protein sequence led to the identification of viral residue variants (VRVs), i.e., residues harboring a substitution compared to the reference strain. Next, generalized additive models were applied to model VRV temporal dynamics, to identify VRVs with significant and substantial dynamics (false discovery rate q-value <0.01; maximum VRV proportion > 10% on at least one day). Unsupervised learning was then applied to hierarchically organize VRVs by spatiotemporal patterns and identify VRV-haplotypes. Finally, homology modelling was performed to gain insight into potential impact of VRVs on Spike protein structure. We identified 90 VRVs, 71 of which have not previously been observed in a VOI/VOC, and 35 of which have emerged recently and are durably present. Our analysis identifies 17 VRVs [~]91 days earlier than their first corresponding VOI/VOC publication. Unsupervised learning revealed eight VRV-haplotypes of 4 VRVs or more, suggesting two emerging strains (B1.1.222 and B.1.234). Structural modeling supported potential functional impact of the D1118H and L452R mutations. The SLS approach equally monitors all Spike residues over time, independently of existing phylogenic classifications, and is complementary to existing genomic surveillance methods.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the cost-effectiveness of combining Chinese medicine (CM) with Western medicine (WM) for ischemic stroke patients.</p><p><b>METHODS</b>Hospitalization summary reports between 2006 and 2010 from eight hospitals in Beijing were used to analyze the length of stay (LOS), cost per stay (CPS), and outcomes at discharge.</p><p><b>RESULTS</b>Among 12,009 patients (female, 36.44%; mean age, 69.98±13.06 years old), a substantial number of patients were treated by the WM_Chinese patent medicine (CPM)_Chinese herbal medicine (CHM) (38.90%); followed by the WM_CPM (32.55%), the WM (24.26%), and the WM_CHM (4.15%). With adjustment for confounding variables, LOS of the WM_CPM_CHM group was about 10 days longer than that of the WM group, and about 6 days longer than that of the WM_CPM group or the WM_CHM group (P<0.01); CPS of the WM_CPM_CHM group was United States dollar (USD) 1,288 more than that of the WM group, and about USD 600 more than that of the WM_CPM group or the WM_CHM group (P<0.01). Compared with the WM group, odd ratio (OR) of recovered and improved outcome of the WM_CPM_CHM group was the highest [OR: 12.76, 95% confidence intervals (CI): 9.23, 17.64, P<0.01], OR of death outcome of the WM_CPM_CHM group was the lowest (OR: 0.08, 95% CI: 0.05, 0.12, P<0.01). There was no significant difference between LOS, CPS and OR of the WM_CPM group and those of the WM_CHM group (P>0.05). Cost/effectiveness and incremental cost-effectiveness ratio of the WM_CPM_CHM group were robustly higher than those of the WM group.</p><p><b>CONCLUSION</b>Compared with WM alone, supplementing CPM and CHM to WM provides significant health benefits of improving the chance of recovered and improved outcome, and reducing the death rate, at an expense of longer LOS and higher CPS.</p>
