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Background
Observational studies of the relative effectiveness of influenza vaccines are essential for public health decision making. Their estimates, however, are subject to bias due to unmeasured confounders. Instrumental variable (IV) methods can control for observed and unobserved confounders.Methods
We used linked electronic medical record databases in the Veterans Health Administration (VHA) as well as Medicare administrative files to examine the relative vaccine effectiveness (rVE) of high-dose influenza vaccine (HD) versus standard-dose influenza vaccines (SD) in preventing hospitalizations among VHA-enrolled Veterans ≥65?years of age during 5 influenza seasons (2010–2011 through 2014–2015). Using multivariable IV Poisson regression modeling to address unmeasured confounding and bias, we analyzed the data by each season and through longitudinal analysis of all five seasons.Findings
We included 3,638,924 person–influenza seasons of observation where 158,636 (4%) were among HD vaccine recipients and 3,480,288 (96%) were among SD vaccine recipients. Of the 1,728,562 Veterans, 1,702,824 (98.5%) were male and 1,299,412 (75%) were non-Hispanic white. Based on the longitudinal analysis of all five seasons, the IV-adjusted rVE estimate of HD vs. SD was 10% (95% CI, 8–12%) against all-cause hospitalization; 18% (95% CI, 15–21%) against cardiorespiratory-associated hospitalization; and 14% (95% CI, 6–22%) against influenza/pneumonia-associated hospitalization. The findings by season were similar.Interpretation
Our analysis of VHA clinical data collected from approximately 1.7 million Veterans 65?years and older during five seasons demonstrates that high-dose influenza vaccine is more effective than standard-dose influenza vaccines in preventing influenza- or pneumonia-associated hospitalizations, cardiorespiratory hospitalizations, and all-cause hospitalizations. 相似文献The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.
DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.
DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.
Apparent CLint values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CLint values for total metabolism (CYP and CES enzymes) per gram of adult human liver.
Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.
Design: A mixed-methods design, applying the Schwartz and Sprangers response shift (RS) model. RS is a cognitive process wherein, in response to a change in health status, individuals change internal standards, values, or conceptualization of QOL
Setting: Community-dwelling participants who receive medical treatment at a major Midwestern medical system and nearby Veterans’ Affairs hospital.
Participants: A purposive sample of participants with SCI (N?=?40) completed semi-structured interviews and accompanying quantitative measures.
Interventions: Not applicable.
Outcome Measures: Qualitative data were analyzed using content analysis to identify themes. Analysis of variance were performed to detect differences based on themes and QOL, well-being, and demographic and injury characteristics.
Results: Four RS themes were identified, capturing the range of participant perceptions of QOL. The themes ranged from complete RS, indicating active engagement in maintaining QOL, to awareness and comparisons redefining QOL, to a relative lack of RS. Average QOL ratings differed as a function of response shift themes. PROMIS Global Health, Anxiety, and Depression also differed as a function of RS themes.
Conclusion: The RS model contextualizes differences in QOL definitions, appraisals, and adaptations in a way standardized QOL measures alone do not. 相似文献