Cost-benefit of influenza vaccination in preventing sudden cardiac arrest amongst Australian adults.

OBJECTIVE: The objective of the study was to estimate the economic cost benefit of funding influenza vaccination to all Australian adults 50-64 years and predict its effect on sudden cardiac arrest (SCA) deaths and hospitalisation. METHODS: We combined SCA hospitalisation data from the Australian Institute of Health and Welfare (AIHW) with survival, vaccination, and cost parameters from published literature to create a model estimating the cost benefit of universally funded influenza vaccinations to prevent SCA deaths and hospitalisation. Costs were considered from a government perspective and included cost of vaccines and GP consultations, whilst averted deaths were estimated through the age-adjusted value of a statistical life. RESULTS: The target policy was estimated to prevent 278 SCA hospitalisations and 1269 SCA deaths. This would result in cost-savings of almost $4 billion annually, with an incremental benefit-cost ratio (BCR) of 59.94. The majority of savings were associate with averted deaths. When a sensitivity analysis was performed by altering statistical life year values and reducing life years left, the cost-saving remained significant with a minimum BCR of 29.97 derived. CONCLUSIONS: Reducing SCA through extended vaccination including adults 50-64 years is likely to be a cost beneficial policy from a governmental perspective. SCA deaths account for a significant economic loss due to the high mortality rate, which was far greater than the costs saved through averted hospitalisations. More accurate parameters are needed to improve the reliability of these estimate; however, this model can be used as a basis for further research into the economic impact of SCA.

Estimated health and economic impact of using high-dose influenza vaccine on respiratory and circulatory plus respiratory hospitalizations of older adults in Australia.

Background: Standard dose influenza vaccine provides moderate protection from infection, but with lower effectiveness among the elderly. High dose and adjuvanted vaccines (HD-TIV and aTIV) were developed to address this. This study aims to estimate the incremental health and economic impact of using HD-TIV (high dose trivalent vaccine) instead of aTIV (adjuvanted trivalent vaccine) on respiratory and circulatory plus respiratory hospitalizations of older people (≥65 years) in Australia. Methods: This is a modelling study comparing predicted hospitalization outcomes in people receiving HD-TIV or aTIV during an average influenza season in Australia. Hospitalization records of Australian adults ≥65 years of age from 01 April to 30 November during 15 influenza seasons (2002-2017 excluding 2009, which was a pandemic) were extracted from the Australian Institute of Health and Welfare [AIHW] and used to calculate hospitalisation rates during an average season. Relative vaccine effectiveness data for aTIV and HD-TIV were used to estimate morbidity burden related to influenza. Results: Between 2002 and 2017, the average respiratory hospitalization rate among older people during influenza season (April-November) was 3,445/100,000 population-seasons, with an average cost of AU$ 7,175 per admission. The average circulatory plus respiratory hospitalization rate among older Australian people during that time was 10,393/100,000 population-seasons, with an average cost of AU$ 7829 per admission. For older Australians, HD-TIV may avert an additional 6,315-9,410 respiratory admissions each year, with an incremental healthcare cost saving of AU$ 15.9-38.2 million per year compared to aTIV. Similar results were also noted for circulatory plus respiratory hospitalizations. Conclusions: From the modelled estimations, HD-TIV was associated with less economic burden and fewer respiratory, and circulatory plus respiratory hospitalizations than aTIV for older Australians.

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.

Effect of statin use on the risk of influenza and influenza vaccine effectiveness.

BACKGROUND: Some studies have shown that statins reduce the efficacy of influenza vaccine. The aim was to examine the impact of statins on influenza and influenza vaccine effectiveness (VE). METHODS: This study was a post-hoc analysis of subjects in a prospective case-control study of influenza and acute myocardial infarction, where data on influenza infection, vaccination and statin use was collected. Study participants, aged ≥40 years were recruited from tertiary hospitals in Sydney from 2008 to 2010. Univariate and logistic regression analysis was performed. RESULTS: Of total 559 participants, 276 (49.4%) had been vaccinated and 196 (35.1%) were taking statins. The rate of laboratory confirmed influenza was significantly higher in unvaccinated statin users (adjusted odds ratio (AOR), 2.44; 95% CI: 1.06-5.62) compared to unvaccinated non-users. The VE was 98% overall, and not significantly different between statin users (92.4%) and non-statin users (100%). In adjusted analysis of all subjects, vaccination was significantly protective (AOR, 0.02; 95% CI: 0.01-0.15), and statins remained significantly associated with influenza risk (AOR, 2.47; 95% CI: 1.08-5.64). CONCLUSION: There was no significant difference in influenza VE by statin use, and vaccine was highly effective in both statin users and non-users. There was a significantly higher risk of influenza among statin users, independent of vaccination. Statins may increase the risk of influenza through immunomodulatory mechanisms, or this may be confounded by other risk factors for influenza. It is important that people on statins should be vaccinated against influenza.

Estimated hospitalisations attributable to seasonal and pandemic influenza in Australia: 2001- 2013.

BACKGROUND: Influenza continues to cause seasonal epidemics and pandemics in humans. The burden of influenza is underestimated by traditional laboratory-based surveillance, and modelled estimates are required for influenza-attributable morbidity and mortality. We aimed to estimate the influenza-attributable hospitalisation in Australia, by influenza type. METHODS: A generalised-additive regression model was used to estimate type- and age-specific influenza-attributable hospitalisation rates per 100,000 population by principal diagnosis in Australia, from 2001 through 2013. Weekly counts of laboratory-confirmed influenza notifications and by type, influenza A and B were used as covariates in the model. Main principal diagnosis categories of interest were influenza and pneumonia and respiratory admissions. A smoothing spline was used to control for unmeasured time varying factors. Results for 2009, in which the pandemic influenza A(H1N1)pdm09 virus circulated, were not included in annual averages and are reported separately. RESULTS: During the study period, the estimated annual average, all-age, annual respiratory hospitalisation rates attributable to seasonal influenza type A, B and total influenza were 45.4 (95% CI: 34.9, 55.9), 32.6 (95% CI: 22.8, 42.4), and 76.9 (95% CI: 73.6, 80.2) per 100,000 population, respectively. During 2009, the estimated total pandemic influenza-attributable, all-age, respiratory hospitalisation rate was 56.1 (95% CI: 47.4, 64.9) per 100,000. Older adults (≥85 years of age) experienced the highest influenza-attributable hospitalisation rates for both seasonal and 2009 pandemic influenza. Collinearity between influenza A and B time series in some years limited the ability of the model to resolve differences in influenza attribution between the two virus types. CONCLUSION: Both seasonal and pandemic influenza caused considerable morbidity in Australia during the years studied, particularly among older adults. The pandemic hospitalisation rate in 2009 was lower than the average overall annual rate for seasonal influenza, but young to middle aged adults experience a hospitalisation rate similar to that of severe seasonal influenza.

Inter-seasonality of influenza in Australia.

BACKGROUND: It appears inter-seasonal influenza notifications have been increasing in summer months in Australia. This study aims to determine changes in inter-seasonal influenza activity in Australia over time. METHODS: Routine influenza surveillance data and hospitalisations data were analysed to study the epidemiology of inter-seasonal influenza and to examine the impact of inter-seasonal influenza on morbidity in Australia at a national level. To adjust for changes in testing over time, we calculated a ratio of summer-to-winter notifications for each year in the study. A P-value of <0.05 was used for statistical significance. RESULTS: Nationally, 18 933 notifications were reported during summer months from December to February 2005-2016. There have been increasing summer notifications over time, which corresponded to similarly increased notifications in winter. A significant upward trend was observed for rate of notification during summer period over these years, P < 0.01. However, the ratio of summer-to-winter notifications demonstrated that while notifications have increased, the ratio has not increased markedly over the years and did not show a significant trend. No seasonal trend in rates of hospitalisation for influenza and pneumonia, respiratory and circulatory diagnosis was observed over the studied years. CONCLUSION: This study provides a clearer understanding of the epidemiology and burden of inter-seasonal influenza and trends over time in Australia. The ratio of summer-to-winter notifications remains relatively constant and is supported by reasonably constant hospitalisation rates over the years.

Epidemiology of influenza B in Australia: 2001-2014 influenza seasons.

BACKGROUND: Influenza B is characterised by two antigenic lineages: B/Victoria and B/Yamagata. These lineages circulate together with influenza A during influenza seasons, with varying incidence from year to year and by geographic region. OBJECTIVE: To determine the epidemiology of influenza B relative to influenza A in Australia. METHODS: Laboratory-confirmed influenza notifications between 2001 and 2014 in Australia were obtained from the Australian National Notifiable Diseases Surveillance System. RESULTS: A total of 278 485 laboratory-confirmed influenza cases were notified during the study period, comprising influenza A (82.2%), B (17.1%) and 'other and untyped' (0.7%). The proportion of notifications that were influenza B was highest in five- to nine-year-olds (27.5%) and lowest in persons aged 85 years and over (11.5%). Of all B notifications with lineage determined, 77.1% were B/Victoria and 22.9% were B/Yamagata infections. Mismatches between the dominant B lineage in a season and the trivalent vaccine B lineage occurred in over one-third of seasons during the study years. In general, influenza B notifications peaked later than influenza A notifications. CONCLUSION: The proportion of circulating influenza B in Australia during 2001-2014 was slightly lower than the global average and was dominated by B/Victoria. Compared with influenza A, influenza B infection was more common among older children and young adults and less common in the very elderly. Influenza B lineage mismatch with the trivalent vaccine occurred about one-third of the time.

Influenza vaccine as a coronary intervention for prevention of myocardial infarction.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Influenza is one of the leading infectious causes of morbidity and mortality globally, and evidence is accumulating that it can precipitate acute myocardial infarction (AMI). This is thought to be due to a range of factors including inflammatory release of cytokines, disruption of atherosclerotic plaques and thrombogenesis, which may acutely occlude a coronary artery. There is a large body of observational and clinical trial evidence that shows that influenza vaccine protects against AMI. Estimates of the efficacy of influenza vaccine in preventing AMI range from 15% to 45%. This is a similar range of efficacy compared with the accepted routine coronary prevention measures such as smoking cessation (32-43%), statins (19-30%) and antihypertensive therapy (17-25%). Influenza vaccine should be considered as an integral part of CVD management and prevention. While it is recommended in many guidelines for patients with CVD, rates of vaccination in risk groups aged <65 years are very low, in the range of 30%. The incorporation of vaccination into routine CVD prevention in patient care requires a clinical practice paradigm change.

Immunogenicity and safety of inactivated quadrivalent influenza vaccine in adults: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: A quadrivalent influenza vaccine (QIV) includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata). The presence of both B lineages eliminate potential B lineage mismatch of trivalent influenza vaccine (TIV) with the circulating strain. METHODS: Electronic database searches of Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Scopus and Web of Science were conducted for articles published until June 30, 2015 inclusive. Articles were limited to randomised controlled trials (RCTs) in adults using inactivated intramuscular vaccine and published in English language only. Summary estimates of immunogenicity (by seroprotection and seroconversion rates) and adverse events outcomes were compared between QIV and TIV, using a risk ratio (RR). Studies were pooled using inverse variance weights with a random effect model and the I(2) statistic was used to estimate heterogeneity. RESULTS: A total of five RCTs were included in the meta-analysis. For immunogenicity outcomes, QIV had similar efficacy for the three common strains; A/H1N1, A/H3N2 and the B lineage included in the TIV. QIV also showed superior efficacy for the B lineage not included in the TIV; pooled seroprotection RR of 1.14 (95%CI: 1.03-1.25, p=0.008) and seroconversion RR of 1.78 (95%CI: 1.24-2.55, p=0.002) for B/Victoria, and pooled seroprotection RR of 1.12 (95%CI: 1.02-1.22, p=0.01) and seroconversion RR of 2.11 (95%CI: 1.51-2.95, p<0.001) for B/Yamagata, respectively. No significant differences were found between QIV and TIV for aggregated local and systemic adverse events within 7days post-vaccination. There were no vaccine-related serious adverse events reported for either QIV or TIV. Compared to TIV, injection-site pain was more common for QIV, with a pooled RR of 1.18 (95%CI: 1.03-1.35, p=0.02). CONCLUSION: In adults, inactivated QIV was as immunogenic as seasonal TIV, with equivalent efficacy against the shared three strains included in TIV, and a superior immunogenicity against the non-TIV B lineage.

A randomized clinical trial of the immunogenicity of 7-valent pneumococcal conjugate vaccine compared to 23-valent polysaccharide vaccine in frail, hospitalized elderly.

BACKGROUND: Elderly people do not mount strong immune responses to vaccines. We compared 23-valent capsular polysaccharide (23vPPV) alone versus 7-valent conjugate (PCV7) vaccine followed by 23vPPV 6 months later in hospitalized elderly. METHODS: Participants were randomized to receive 23vPPV or PCV7-23vPPV. Antibodies against serotypes 3, 4, 6A, 6B, 9V, 14, 18C, 19A, 19F, 23F were measured by enzyme-linked immunosorbent (ELISA) and opsonophagocytic (OPA) assays at baseline, 6 months and 12 months. RESULTS: Of 312 recruited, between 40% and 72% of subjects had undetectable OPA titres at baseline. After one dose, PCV7 recipients had significantly higher responses to serotypes 9V (both assays) and 23F (OPA only), and 23vPPV recipients had significantly higher responses to serotype 3 (ELISA), 19F and 19A (OPA only). In subjects with undetectable OPA titres at baseline, a proportionately greater rise in OPA titre (P<0.01) was seen for all serotypes after both vaccines. The GMT ratio of OPA was significantly higher at 12 months in the PCV7-23vPPV group for serotypes 6A, 9V, 18C and 23F. OPA titre levels for these serotypes increased moderately after 6 months, whereas immunity waned in the 23vPPV only arm. CONCLUSION: We did not show overwhelming benefit of one vaccine over the other. Low baseline immunity does not preclude a robust immune response, reiterating the importance of vaccinating the frail elderly. A schedule of PCV7-23vPPV prevents waning of antibody, suggesting that both vaccines could be useful in the elderly. Follow up studies are needed to determine persistence of immunity. TRIAL REGISTRATION: The Australian Clinical Trials Registry ACTRN12607000387426.

Decrease in breast cancer incidence following a rapid fall in use of hormone replacement therapy in Australia.

OBJECTIVE: To determine if the recent rapid fall in use of hormone replacement therapy (HRT) in Australia has been followed by a reduction in breast cancer incidence among women aged 50 years or older, but not among younger women. DESIGN AND SETTING: Analysis of trends in annual prescribing of HRT, using Pharmaceutical Benefits Scheme data, and in annual age-standardised breast cancer incidence rates in Australian women for the period 1996-2003. RESULTS: In Australia, prescribing of HRT increased from 1996 to 2001, but dropped by 40% from 2001 to 2003. Age-standardised breast cancer incidence rates in women aged > or = 50 years also increased to 2001 but declined thereafter. The incidence rates in this age group were lower by 6.7% (95% CI, 3.9%-9.3%; P < 0.001) in 2003 compared with 2001, equivalent to 600 (95% CI, 350-830) fewer breast cancers (out of about 9000 incident breast cancers annually for women this age). There was no significant change in breast cancer incidence for women aged < 50 years. CONCLUSIONS: While other factors may have contributed to a recent reduction in breast cancer incidence among Australian women aged > or = 50 years, the available evidence suggests that much of the decrease is due to the recent fall in use of HRT. This is consistent with other evidence that the HRT-associated increase in risk of breast cancer is reversible after ceasing use of HRT.