A globally implemented unified phylogenetic classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. We formulated global consensus of HRSV classification on the basis of the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality curated dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to GenBank and GISAID (https://www.gisaid.org) public sequence databases through March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B and provided guidelines for defining prospective lineages. Our classification demonstrated robustness in its applicability to both complete and partial genomes. We envision that this unified HRSV classification proposal will strengthen HRSV molecular epidemiology on a global scale.

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BACKGROUND: Respiratory syncytial virus (RSV) infection imposes substantial health burden and disproportionally affects young infants, elderly, and immunocompromised hosts. RSV harbors key surface glycoproteins F and G, both crucial for viral infection and evolution.
METHODS: In this study, we examined the genetic characteaistics of 179 RSV isolates collected between 2017 and 2021 in Taiwan. G ectodomain and whole F gene were sequenced and aligned with available references from GenBank.
RESULTS: RSV ON1 and BA9 were two predominant genotypes throughout the study period. Genetic variations of G protein accumulated over time. New ON1 strains containing E257K and K204R-V225A-T238I-Y280H in combination emerged in 2019 and contributed to a local endemic in 2020. RSV-B strain with A131T and T137I substitution in G protein emerged in 2018. On the other hand, F protein of both RSV genotypes was generally conserved but some feature changes should be noted: RSV-B in Taiwan harbored 100% of I206M and Q209R in site Ø, and L172Q and S173L in site V. These amino acid changes do not affect the susceptibility of Nirsevimab but imply no effectiveness of Suptavumab.
CONCLUSIONS: RSV continuously evolves in Taiwan and accumulated signature genetic changes over time. Vigilant RSV genomic surveillance is important to monitor the viral evolution in the upcoming future of new RSV vaccines and prophylaxis.

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UNASSIGNED: Our cost of illness study aimed to provide an estimate of the burden related to systemic lupus erythematosus (SLE) in the Mexican context.
UNASSIGNED: Our model was used to simulate the resource utilization and economic consequences over a period of 5 years for patients with SLE in Mexico. The model simulated four health states-three phenotypes of SLE, including mild, moderate, and severe states, and death. Clinical parameters were retrieved from the literature. Resource utilization in our model represents the most common practice in the Mexican healthcare system. These include disease management, transient events (e.g. infections, flares, and complications due to SLE-related organ damage), and indirect costs. Direct non-medical costs were not considered. One-way sensitivity analysis was performed.
UNASSIGNED: The number of targeted Mexican SLE patients was 57,754. The numbers of SLE patients diagnosed with mild, moderate, and severe phenotypes were 8,230, 44,291, and 5,233, respectively. Disease management costs, including the treatment of each phenotype and disease follow-up, were MXN 4 billion ($ 415 million); the costs of transient events (infections, flares, and consequences of SLE-related organ damage) were MXN 5 billion ($ 478 million). Productivity loss costs among adult employed Mexican patients with SLE were estimated at MXN 17 billion ($ 1.6 billion). The total SLE cost in Mexico over 5 years from the payer and societal perspectives is estimated at MXN 9 billion ($ 893 million) and 26 billion ($ 2.5 billion), respectively. Over 5 years, the costs per patient per year from the payer and societal perspectives were MXN 32,131($ 3,095) and MXN 91,661($ 8,830), respectively.
UNASSIGNED: The findings pointed out the substantial economic burden associated with SLE, including the costs of disease progression and SLE transient events, such as flare-ups, infections, and organ damage, in addition to productivity loss due to work capacity impairment.

We tested the effect of statins on C-reactive protein (CRP) and apolipoprotein E (APOE)\'s associations with dementia severity.
A total of 1725 participants of the Alzheimer\'s Disease Neuroimaging Initiative (ADNI) were assigned from 12-month follow-up data into the following groups: (1) ε4 (-)/statin (-), (2) ε4 (-)/statin (+), (3) ε4 (+)/statin (-), and (4) ε4 (+)/statin (+). Dementia severity was assessed by a δ homolog: \"dHABS.\" A mediation model was stratified on statin use and moderation effects tested by a chi-square difference.
Plasma CRP level decreased with ε4 allelic dose. Statins had no effect on the dHABS d-score in non-carriers but were associated with better scores in carriers. Treated carriers did not have more severe dementia than non-carriers. Statin use moderated the mutual adjusted effects of APOE and CRP. CRP was not a mediator of APOE\'s effect.
Statins may provide a protective effect on the dementia severity of ε4 carriers.
δ is a dementia-specific phenotype related to general intelligence \"g\" and is assessed via a \"d-score.\" Apolipoprotein E (APOE) and plasma C-reactive protein (CRP) are independently associated with δ. Plasma CRP decreases with ε4 allelic dose. Statins were associated with better (less demented) d-scores in ε4 carriers but had no effect in non-ε4 carriers. Treated ε4 carriers did not have more severe dementia than non-carriers. Statin use moderated the effects of APOE and CRP on δ. CRP was not a mediator of APOE\'s effect on δ.

Meta-analytic structural equation modeling was used to estimate the relative contributions of general cognitive ability or g (defined by executive functions, short-term memory, and intelligence) and basic domain-specific mathematical abilities to performance in more complex mathematics domains. The domain-specific abilities included mathematics fluency (e.g., speed of retrieving basic facts), computational skills (i.e., accuracy at solving multi-step arithmetic, algebra, or geometry problems), and word problems (i.e., mathematics problems presented in narrative form). The core analysis included 448 independent samples and 431,344 participants and revealed that g predicted performance in all three mathematics domains. Mathematics fluency contributed to the prediction of computational skills, and both mathematics fluency and computational skills predicted word problem performance, controlling g. The relative contribution of g was consistently larger than basic domain-specific abilities, although the latter may be underestimated. The patterns were similar across younger and older individuals, individuals with and without a disability (e.g., learning disability), concurrent and longitudinal assessments, and family socioeconomic status, and have implications for fostering mathematical development.

UNASSIGNED: This study aimed to evaluate the value and affordability of insulin glargine 300 U/mL (Gla-300) in a budget impact model from a United States (U.S.) payer perspective by leveraging recent real-world evidence (RWE) studies and incorporating the recent insulin price caps where applicable.
UNASSIGNED: An economic model for a hypothetical one million U.S. health-plan population was developed to assess the budgetary impact of therapeutic interchanges in either direction between the two long- and longer-acting basal insulins (BIs) for patients with type 2 diabetes over a three-year model horizon. The utilization of long-acting BIs, longer-acting BIs, biosimilar BIs, and insulin degludec (IDeg-100) were informed by IQVIA data and internal forecasting at Sanofi. The DELIVER-2 and DELIVER-naïve studies provided healthcare resource utilization (HCRU) parameters. In the model base case, 24% of patients switched from long-acting BIs to insulin glargine biosimilars, IDeg-100, and other longer-acting BIs (Gla-300) by projected year 3.
UNASSIGNED: The base case total costs were $10,145 per patient per year (PPPY) in year 3 for the cumulative population. When all patients switched to Gla-300, the total costs in year 3 were $8,799, reflecting a net savings of -$660 PPPY compared to the budget increase of $686 PPPY in the base case. However, the longer-acting to long-acting BIs reversal scenario demonstrated a budgetary decrease of $676 PPPY over the model horizon. The reduction in incremental PPPY cost of $93 was observed using net drug costs rather than wholesale acquisition costs (WAC).
UNASSIGNED: The market shares for years 1-3 were based on expectations supported by the clinicians\' expert opinions and were not obtained from real-world data.
UNASSIGNED: The economic value of increased utilization of Gla-300 was driven by the reduction in HCRU, costs and market shares assumptions. Budgetary reductions were achieved by switching patients from long-acting BIs to Gla-300.
Type 2 Diabetes (T2D) is a chronic and debilitating condition that can lead to severe macro or microvascular complications. To mitigate these complications, it is crucial to effectively manage blood glucose levels. When other treatments prove ineffective in achieving adequate glucose control, insulin-based therapy becomes necessary. However, insulin-based treatments often come with the risk of hypoglycemic episodes, which can lead to increased utilization of healthcare resources (HCRU) and have a negative impact on costs.This study aimed to assess the budgetary impact of higher market shares of longer-acting basal insulins (specifically insulin glargine Gla-300) compared to long-acting basal insulins, insulin glargine biosimilars, and insulin degludec (IDeg) in the treatment of T2D. The perspective taken was that of a U.S. payer, taking into account the recent insulin price caps where applicable.The economic benefit of increased utilization of Gla-300 was driven by reductions in HCRU, costs, and market share assumptions. This resulted in a budgetary increase of $686 per patient per year (PPPY). In an alternative scenario where all patients transitioned to Gla-300, it led to a net savings of $660 PPPY.These findings provide valuable insights for decision-makers and healthcare professionals when making choices related to formulary placement and treatment utilization.

The construct validity of group factor models of personality, which are typically derived from factor analysis of questionnaire items, relies on the ability of each factor to predict meaningful and differentiated real-world outcomes. In a sample of 481 participants, we used the Big Five Aspect Scales (BFAS) personality questionnaire, two laboratory-measured reaction time (RT) tasks, and a short-form test of cognitive ability (ICAR-16) to test the hypothesis that the Intellect and Openness aspects of Big Five Openness to Experience differentially correlate with reaction time moments. We found that higher scores on the Intellect aspect significantly correlate with faster and less variable response times, while no such association is observed for the Openness aspect. Further, we found that this advantage lies solely in the decisional, but not perceptual, stage of information processing; no other Big Five aspect showed a similar pattern of results. In sum, these findings represent the largest and most comprehensive study to date on personality factors and reaction time, and the first to demonstrate a mechanistic validation of BFAS Intellect through a differential pattern of associations with RT and Big Five personality aspects.