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Background  A wide range of methods have been used for estimating influenza‐associated deaths in temperate countries. Direct comparisons of estimates produced by using different models with US mortality data have not been published. Objective  Compare estimates of US influenza‐associated deaths made by using four models and summarize strengths and weaknesses of each model. Methods  US mortality data from the 1972–1973 through 2002–2003 respiratory seasons and World Health Organization influenza surveillance data were used to estimate influenza‐associated respiratory and circulatory deaths. Four models were used: (i) rate‐difference (using peri‐season or summer‐season baselines), (ii) Serfling least squares cyclical regression, (iii) Serfling–Poisson regression, (iv) and autoregressive integrated moving average models. Results  Annual estimates of influenza‐associated deaths made using each model were similar and positively correlated, except for estimates from the summer‐season rate‐difference model, which were consistently higher. From the 1976/1977 through the 2002/2003 seasons the, the Poisson regression models estimated that an annual average of 25 470 [95% confidence interval (CI) 19 781–31 159] influenza‐associated respiratory and circulatory deaths [9·9 deaths per 100 000 (95% CI 7·9–11·9)], while peri‐season rate‐difference models using a 15% threshold estimated an annual average of 22 454 (95% CI 16 189–28 719) deaths [8·6 deaths per 100 000 (95% CI 6·4–10·9)]. Conclusions  Estimates of influenza‐associated mortality were of similar magnitude. Poisson regression models permit the estimation of deaths associated with influenza A and B, but require robust viral surveillance data. By contrast, simple peri‐season rate‐difference models may prove useful for estimating mortality in countries with sparse viral surveillance data or complex influenza seasonality.

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ContextThe goal of influenza vaccination programs is to reduce influenza-associated disease outcomes. Therefore, estimating the reduced burden of influenza as a result of vaccination over time and by age group would allow for a clear understanding of the value of influenza vaccines in the US, and of areas where improvements could lead to greatest benefits.ObjectiveTo estimate the direct effect of influenza vaccination in the US in terms of averted number of cases, medically-attended cases, and hospitalizations over six recent influenza seasons.DesignUsing existing surveillance data, we present a method for assessing the impact of influenza vaccination where impact is defined as either the number of averted outcomes or as the prevented disease fraction (the number of cases estimated to have been averted relative to the number of cases that would have occurred in the absence of vaccination).ResultsWe estimated that during our 6-year study period, the number of influenza illnesses averted by vaccination ranged from a low of approximately 1.1 million (95% confidence interval (CI) 0.6–1.7 million) during the 2006–2007 season to a high of 5 million (CI 2.9–8.6 million) during the 2010–2011 season while the number of averted hospitalizations ranged from a low of 7,700 (CI 3,700–14,100) in 2009–2010 to a high of 40,400 (CI 20,800–73,000) in 2010–2011. Prevented fractions varied across age groups and over time. The highest prevented fraction in the study period was observed in 2010–2011, reflecting the post-pandemic expansion of vaccination coverage.ConclusionsInfluenza vaccination programs in the US produce a substantial health benefit in terms of averted cases, clinic visits and hospitalizations. Our results underscore the potential for additional disease prevention through increased vaccination coverage, particularly among nonelderly adults, and increased vaccine effectiveness, particularly among the elderly.

Cys/CySS and GSH/GSSG redox states in human plasma undergo diurnal variation with an increased magnitude of variation in Cys/CySS redox state in older persons. This variation could alter sensitivity to oxidative stress over a course of hours.

Most estimates of US deaths associated with influenza circulation have been similar despite the use of different approaches. However, a recently published estimate suggested that previous estimates substantially overestimated deaths associated with influenza, and concluded that substantial numbers of deaths during a future pandemic could be prevented because of improvements in medical care. We reviewed the data sources and methods used to estimate influenza-associated deaths. We suggest that discrepancies between the recent estimate and previous estimates of the number of influenza-associated deaths are attributable primarily to the use of different outcomes and methods. We also believe that secondary bacterial infections will likely result in substantial morbidity and mortality during a future influenza pandemic, despite medical progress.

Hepatic cytochrome P450 (P450) enzyme activities and gene expression can be profoundly altered in disease states. In general the levels of affected hepatic P450 enzymes are depressed by diseases, causing potential and documented impairment of drug clearance and clinical drug toxicity. However, modulation of P450s is enzyme selective and this selectivity differs among different diseases. This review will concentrate on regulation of P450s in diabetes, obesity and infectious and inflammatory disease, conditions that affect millions of people worldwide every day.

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