Determinants of Influenza Mortality Trends: Age-Period-Cohort Analysis of Influenza Mortality in the United States, 1959-2016.

This study examines the roles of age, period, and cohort in influenza mortality trends over the years 1959-2016 in the United States. First, we use Lexis surfaces based on Serfling models to highlight influenza mortality patterns as well as to identify lingering effects of early-life exposure to specific influenza virus subtypes (e.g., H1N1, H3N2). Second, we use age-period-cohort (APC) methods to explore APC linear trends and identify changes in the slope of these trends (contrasts). Our analyses reveal a series of breakpoints where the magnitude and direction of birth cohort trends significantly change, mostly corresponding to years in which important antigenic drifts or shifts took place (i.e., 1947, 1957, 1968, and 1978). Whereas child, youth, and adult influenza mortality appear to be influenced by a combination of cohort- and period-specific factors, reflecting the interaction between the antigenic experience of the population and the evolution of the influenza virus itself, mortality patterns of the elderly appear to be molded by broader cohort factors. The latter would reflect the processes of physiological capital improvement in successive birth cohorts through secular changes in early-life conditions. Antigenic imprinting, cohort morbidity phenotype, and other mechanisms that can generate the observed cohort effects, including the baby boom, are discussed.

Free to die: Economic freedoms and influenza mortality.

Seasonal influenzas are annually responsible for hundreds of thousands of deaths worldwide, often because of insufficient care, which may depend on orientations of economic policy. Yet, the empirical evidence on the relations existing between policies based on different degrees of economic liberalism and flu mortality is still scarce. This paper contributes to filling the gap by proposing an empirical investigation into the effects of various dimensions of liberalism, proxied by the different components of the Fraser Index of Economic Freedom, on deaths from seasonal influenzas in a sample of 38 OECD countries observed from 1970 to 2018. A dynamic panel System-GMM estimator is used to alleviate endogeneity concerns, while alternative models, specifications and subsamples check the robustness of findings. Findings show that: a) not every component of economic freedom has an effect on flu mortality; b) more economic freedom not always means less or more deaths from flu. In particular, stronger protection of property rights and smaller government consumption are associated with higher flu mortality, which is instead lower when people and capital are freer to move. Such results give rise to policy considerations and contribute to inform policymakers about actions that can limit the mortality of a globally widespread disease like flu.

Influenza A subtype H3N2 is associated with an increased risk of hospital dissemination - an observational study over six influenza seasons.

BACKGROUND: Previous studies on hospital-acquired influenza (HAI) have not systematically evaluated the possible impact of different influenza subtypes. HAI has historically been associated with high mortality, but clinical consequences may be less severe in a modern hospital setting. AIMS: To identify and quantify HAI for each season, investigate possible associations with varying influenza subtypes, and to determine HAI-associated mortality. METHODS: All influenza-PCR-positive adult patients (>18 years old) hospitalized in Skåne County during 2013-2019, were prospectively included in the study. Positive influenza samples were subtyped. Medical records of patients with suspected HAI were examined to confirm a nosocomial origin and to determine 30-day mortality. RESULTS: Of 4110 hospitalized patients with a positive influenza PCR, 430 (10.5%) were HAI. Influenza A(H3N2) infections were more often HAI (15.1%) than influenza A(H1N1)pdm09, and influenza B (6.3% and 6.8% respectively, P<0.001). The majority of HAI caused by H3N2 were clustered (73.3 %) and were the cause of all 20 hospital outbreaks consisting of ≥4 affected patients. In contrast, the majority of HAI caused by influenza A(H1N1)pdm09 and influenza B were solitary cases (60% and 63.2%, respectively, P<0.001). Mortality associated with HAI was 9.3% and similar between subtypes. CONCLUSIONS: HAI caused by influenza A(H3N2) was associated with an increased risk of hospital dissemination. Our study is relevant for future seasonal influenza infection control preparedness and shows that subtyping of influenza may help to define relevant infection control measures. Mortality in HAI remains substantial in a modern hospital setting.

Modelling the influenza disease burden in people aged 50-64 and ≥65 years in Australia.

BACKGROUND: Estimation of influenza disease burden is necessary to monitor the impact of intervention programmes. This study aims to estimate the attributable fraction of respiratory and circulatory disease due to influenza among Australian adults 50-64 and ≥65 years of age. METHODS: A semi-parametric generalised-additive model was used to estimate annual and average rate of influenza-attributable hospitalisation and death per 100,000 population under the principal diagnosis of influenza/pneumonia, respiratory, circulatory and myocardial infarction (MI) from 2001 through 2017. RESULTS: Over the study period, seasonal influenza accounted for an estimated annual average respiratory hospitalisation rate of 78.9 (95%CI: 76.3, 81.4) and 287.5 (95%CI: 279.8, 295.3) per 100,000 population in adults aged 50-64 and ≥65 years, respectively. The corresponding respiratory mortality rates were 0.9 (95%CI: 0.7, 1.2) and 18.2 (95%CI: 16.9, 19.4) per 100,000 population. The 2017 season had the highest influenza-attributable respiratory hospitalisations in both age groups, and respiratory complications were estimated approximately 2.5 times higher than the average annual estimate in adults aged ≥65 years in 2017. For mortality, on average, influenza attributed 1,080 circulatory and 361 MI deaths in adults aged ≥65 years per year. Influenza accounted for 1% and 2.8% of total MI deaths in adults aged 50-64 and ≥65 years, respectively. CONCLUSION: Rates of cardiorespiratory morbidity and mortality were high in older adults, whilst the younger age group contributed a lower disease burden. Extension of influenza vaccination programme beyond the targeted population could be an alternative strategy to reduce the burden of influenza.

Trends in Excess Winter Mortality (EWM) from 1900/01 to 2019/20-Evidence for a Complex System of Multiple Long-Term Trends.

Trends in excess winter mortality (EWM) were investigated from the winter of 1900/01 to 2019/20. During the 1918-1919 Spanish flu epidemic a maximum EWM of 100% was observed in both Denmark and the USA, and 131% in Sweden. During the Spanish flu epidemic in the USA 70% of excess winter deaths were coded to influenza. EWM steadily declined from the Spanish flu peak to a minimum around the 1960s to 1980s. This decline was accompanied by a shift in deaths away from the winter and spring, and the EWM calculation shifted from a maximum around April to June in the early 1900s to around March since the late 1960s. EWM has a good correlation with the number of estimated influenza deaths, but in this context influenza pandemics after the Spanish flu only had an EWM equivalent to that for seasonal influenza. This was confirmed for a large sample of world countries for the three pandemics occurring after 1960. Using data from 1980 onward the effect of influenza vaccination on EWM were examined using a large international dataset. No effect of increasing influenza vaccination could be discerned; however, there are multiple competing forces influencing EWM which will obscure any underlying trend, e.g., increasing age at death, multimorbidity, dementia, polypharmacy, diabetes, and obesity-all of which either interfere with vaccine effectiveness or are risk factors for influenza death. After adjusting the trend in EWM in the USA influenza vaccination can be seen to be masking higher winter deaths among a high morbidity US population. Adjusting for the effect of increasing obesity counteracted some of the observed increase in EWM seen in the USA. Winter deaths are clearly the outcome of a complex system of competing long-term trends.

Tail risks and infectious disease: Influenza mortality in the U.S., 1900-2018.

I use extreme values theory and data on influenza mortality from the U.S. for 1900 to 2018 to estimate the tail risks of mortality. I find that the distribution for influenza mortality rates is heavy-tailed, which suggests that the tails of the mortality distribution are more informative than the events of high frequency (i.e., years of low mortality). I also discuss the implications of my estimates for risk management and pandemic planning.

Influenza-associated mortality in Australia, 2010 through 2019: High modelled estimates in 2017.

INTRODUCTION: In Australia, the 2017 and 2019 influenza seasons were severe. High-dose or adjuvanted vaccines were introduced for ≥65 year-olds in 2018. AIM: To compare influenza-associated mortality in 2017 and 2019 with the average for 2010-2019. METHODS: We used time series modelling to obtain estimates of influenza-associated death rates for influenza A(H1N1)pdm09, A(H3N2) and B in Australia, in persons of all ages and <65, 65-74 and ≥75 years. Estimates were made for pneumonia and influenza (P&I, 2010-2018), respiratory (2010-2018), and all-cause outcomes (2010-2019). RESULTS: During 2010 through 2018 (and 2019 for all-cause), influenza was estimated to be associated with an annual average of 2.1 (95% confidence interval (CI) 1.9, 2.4), 4.0 (95% CI 3.4, 4.6), and 11.6 (95% CI 8.4, 15.0) P&I, respiratory and all-cause deaths per 100,000 population, respectively. Influenza A(H1N1)pdm09 was estimated to be associated with less than one quarter of influenza-associated P&I and respiratory deaths, while A(H3N2) and B were each estimated to contribute approximately equally to the remaining influenza-associated deaths. In 2017, the respective rates were 7.8 (95% CI 7.1, 8.4), 12.3 (95% CI 10.9, 13.6) and 26.0 (95% CI 20.8, 32.0) per 100,000. In 2019, the all-cause estimate was 20.8 (95% CI 14.9, 26.7) per 100,000. CONCLUSIONS: Seasonal influenza continues to be associated with substantial mortality in Australia, with at least double the average occurring in 2017. Age-specific monitoring of vaccine effectiveness is needed in Australia to understand higher mortality seasons.

Cold, dry air is associated with influenza and pneumonia mortality in Auckland, New Zealand.

The relationship between weather and influenza and pneumonia mortality was examined retrospectively using daily data from 1980 to 2009 in Auckland, New Zealand, a humid, subtropical location. Mortality events, defined when mortality exceeded 0·95 standard deviation above the mean, followed periods of anomalously cold air (ta.m. = -4·1, P < 0·01; tp.m. = -4·2, P < 0·01) and/or anomalously dry air (ta.m. = -4·1, P < 0·01; tp.m. = -3·8, P < 0·01) by up to 19 days. These results suggest that respiratory infection is enhanced during unusually cold conditions and during conditions with unusually low humidity, even in a subtropical location where humidity is typically high.

Statin treatment and mortality: propensity score-matched analyses of 2007-2008 and 2009-2010 laboratory-confirmed influenza hospitalizations.

Background. Annual influenza epidemics are responsible for substantial morbidity and mortality. The use of immunomodulatory agents such as statins to target host inflammatory responses in influenza virus infection has been suggested as an adjunct treatment, especially during pandemics, when antiviral quantities are limited or vaccine production can be delayed. Methods. We used population-based, influenza hospitalization surveillance data, propensity score-matched analysis, and Cox regression to determine whether there was an association between mortality (within 30 days of a positive influenza test) and statin treatment among hospitalized cohorts from 2 influenza seasons (October 1, 2007 to April 30, 2008 and September 1, 2009 to April 31, 2010). Results. Hazard ratios for death within the 30-day follow-up period were 0.41 (95% confidence interval [CI], .25-.68) for a matched sample from the 2007-2008 season and 0.77 (95% CI, .43-1.36) for a matched sample from the 2009 pandemic. Conclusions. The analysis suggests a protective effect against death from influenza among patients hospitalized in 2007-2008 but not during the pandemic. Sensitivity analysis indicates the findings for 2007-2008 may be influenced by unmeasured confounders. This analysis does not support using statins as an adjunct treatment for preventing death among persons hospitalized for influenza.