辉瑞

Economic evaluations of interventions that target or include children require health state utilities (HSUs). Despite the availability of preference-weighted measures for children, methods for valuing child health states and estimating child utilities are not as well established as those for adult HSUs. The objective of this task force was to develop emerging good practice recommendations for valuing child and adolescent health to generate HSUs for use in economic evaluation. This task force identified and described the interrelated methodological choices regarding the valuation of child health to generate HSUs. The task force considered available evidence related to 4 key issues: (1) whose preferences should be sought, (2) whose health is imagined, (3) which method should be used, and (4) the comparability between adult and child utilities. Best practices may vary depending on the modeling context, characteristics of the health states, and the health technology assessment setting in which the HSUs will be used. For any individual study, methods will be informed by empirical evidence, value judgments, and recommendations from healthcare decision makers. Rather than recommending an approach that would apply to every study, this task force presents options to consider when determining the preference elicitation approach to generate utilities for child health states, along with the strengths and limitations of each. Given that child HSUs can affect the outcomes of a cost-utility analysis and subsequent decisions about healthcare resource allocation, this task force recommends that researchers be transparent about methodological choices and their impact on HSUs.

The organic anion transporting polypeptide 1B1 (OATP1B1) plays a critical role in hepatic uptake of a wide range of high- and low-permeability, anionic molecules, particularly those in Extended Clearance Classification System (ECCS) Classes 1 and 3. However, conventional uptake assays using HEK293 cells overexpressing OATP1B1 can yield false-negative results, especially for highly permeable, lipophilic anionic or zwitterionic compounds, where passive diffusion and nonspecific binding may mask transporter-mediated uptake. In this study, we applied the competitive counterflow (CCF) assay to evaluate 58 compounds across different ECCS classes. The assay measures steady-state changes in intracellular [3H]-estradiol-17β-glucuronide retention following exposure to test compounds across multiple concentrations. Several known OATP1B1 substrates, exhibited more than 50

The continual emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the need to update evidence on coronavirus disease 2019 (COVID-19) severity and disease burden, and better understand the impact on prevention, treatment, and healthcare systems. This systematic review aimed to determine relative disease severity, through comparative measures of hospitalization, intensive care unit admission and mortality, between SARS-CoV-2 variants of concern emerging since Omicron was first identified. A protocol was registered a priori (PROSPERO ID: CRD42024619193). Systematic searches of MEDLINE and EMBASE databases were conducted in November 2024 and supplemented by conference searches from 2022–2024. Population, Exposure, Comparisons, Outcomes (PECO) criteria were used to screen publications for inclusion. Critical appraisal tools published in the Joanna Briggs Institute (JBI) Handbook for Evidence Synthesis were used to assess the risk of bias of the primary studies included. The outcomes associated with Omicron variants, identified by sequencing or predominance periods, included hospitalization, admission to intensive care, death, and various composite endpoints. Thirty-two studies fulfilled the eligibility criteria, most reported on relative disease severity for early Omicron BA.5 (n = 23) and XBB (n = 24) variants. Overall, COVID-19 severity appeared largely comparable across the various Omicron subvariants. Among the subset of studies that directly compared various severity outcomes to earlier SARS-CoV-2 variants (n = 7), some reported modest increases or decreases in severity. However, these differences were generally not statistically significant. Five studies stratifying outcomes by the presence of comorbid conditions noted that comorbidities were predictors of significantly worse COVID-19 disease outcomes (p = 0.000–0.027). Overall, this systematic review found the severity of COVID-19 disease to be comparable among Omicron subvariants. As SARS-CoV-2 subvariants continue to emerge, these results highlight the continuing need for vaccination against SARS-CoV-2 infection alongside early antiviral intervention to support short-term management and long-term reduction of COVID-19-associated morbidity and mortality.

The LowCOST-HSQC is a sensitivity-enhanced HSQC version that retains unused proton polarization for subsequent scans in correlations to low natural abundance nuclei like 13C or 15N. Together with fast polarization distribution via isotropic mixing, it allows the acquisition of fast pulsing 2D-experiments. We give a detailed introduction and comparison of three possible INEPT-type transfer elements for the LowCOST approach -- the original LowCOST, the ZIP, and a specific TIG-BIRD element -- and evaluate various variants of the LowCOST-HSQC.