Reduction In Relative Proportion Research Articles

Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy, December 2021 to January 2022

BackgroundThe SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021.AimTo comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level.MethodsWe analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility.ResultsOmicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9-80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7-3.3 days. As of 17 January 2022, Delta variant represented < 6% of cases. During the Omicron expansion in December 2021, the estimated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduction in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant reproduction numbers' decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022.ConclusionEstimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection.

Population-based cancer predisposition testing as a component of newborn screening: A cost-effectiveness analysis.

10021 Background: The role of population-based newborn genetic testing to identify infants at high risk of childhood-onset cancers has not been studied, despite the availability of cancer surveillance guidelines for early detection in high-risk infants and children. Methods: We developed the Precision Medicine Prevention and Treatment (PreEMPT) Model to estimate the value of targeted population-based newborn genomic sequencing (tNBS) for a select panel of genes associated with early onset pediatric malignancy. Cohorts of US newborns were simulated under tNBS screening vs. usual care, from birth to death. Six pediatric cancer predisposition syndromes were included in the model with mutations in RET, RB1, TP53, DICER1, SUFU or SMARCB1 assigned at birth, using mutation prevalence and disease risks drawn from the published literature, as well as SEER, ClinVar and gnoMAD databases. Newborns with mutations underwent cancer surveillance based on established guidelines for each gene-related pediatric malignancy. Survival benefit was modeled as a reduction in proportion of advanced disease, cancer deaths, and treatment-related late mortality risks. Costs were based on published literature and national databases. Results: In a typical US birth cohort of 4 million newborns, we estimated 1280 cancer cases in the malignancies associated with this gene panel would be detected before age 20 under usual care, resulting in 451 cancer deaths and 490 living with radiation exposure risks. tNBS would prevent 8 cancers (in RET mutation carriers), avert 34 deaths through surveillance, result in 3190 life-years (LY) gained and a 13% relative reduction in proportion of adult survivors at risk for radiation-associated late mortality. Given a sequencing cost of $30 (e.g., $5/gene), the incremental cost-effectiveness ratio (ICER) for tNBS was $230,500 per LY saved; if no additional cost was incurred beyond standard newborn screening, the ICER decreased to $101,100/LY. Conclusions: Population-based genetic testing of newborns can reduce mortality associated with pediatric cancers and could potentially be cost-effective as sequencing costs decline. Further work will include modeling a broader panel of predisposition genes.

Changes in LDL and HDL Subclasses in Normal Pregnancy and Associations with Birth Weight, Birth Length and Head Circumference

Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P < 0.001), due to reduction in relative proportion of LDL I (P < 0.01) and increase of LDL II (P < 0.001) and IIIA (P < 0.05) subclasses. In the same time, HDL size and proportions of HDL 2a particles significantly decreased (P < 0.001), with concomitant increase of HDL 3b and 3c subclasses (P < 0.05). Observed alterations were associated with changes in serum triglyceride levels. Rearrangement in LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.