Influenza-related Outcomes Research Articles

Cost-effectiveness of high dose versus adjuvanted trivalent influenza vaccines in England and Wales

Aims High dose trivalent influenza vaccine (HD TIV) and adjuvant TIV (aTIV) have been developed specifically for adults aged 65 and older (65+) who are at high risk of life-threatening complications. However, there is a scarcity of evidence comparing the clinical and cost-effectiveness of HD TIV and aTIV. The aim of this study was to determine the cost-effectiveness of HD TIV versus aTIV in the England and Wales 65+ population. Methods A cost-utility analysis was conducted using a decision tree with two influenza related outcomes: Laboratory confirmed cases that could result in GP consultation, and hospitalizations that may result in premature mortality. Due to a lack of comparative evidence, the effectiveness of HD TIV versus aTIV was calculated indirectly, based on relative effectiveness estimates for each vaccine versus a common comparator, standard dose (SD) TIV. The primary analysis included hospitalizations explicitly due to influenza/pneumonia. Cost-effectiveness was established for three scenarios applying differing relative effectiveness estimates for aTIV versus SD TIV. Uncertainty was analysed in one-way deterministic sensitivity analyses. A secondary analysis included hospitalizations due to any respiratory illness. Results The minimum population impact of vaccination with HD TIV rather than aTIV was 13,092 fewer influenza cases, 1,109 fewer influenza related deaths, 4,673 fewer hospitalizations, and 3,245 fewer GP appointments. HD TIV was cost-effective versus aTIV for all three effectiveness scenarios, with incremental cost-effectiveness ratios (ICER) equal to £1,932, £4,181, and £8,767 per quality adjusted life year. Results were consistent across the secondary analysis and deterministic sensitivity analyses. Limitations The analysis was limited by a lack of robust and consistent effectiveness data for aTIV. Conclusion HD TIV is cost-effective versus aTIV in people aged 65+ in England and Wales. Use of HD TIV over aTIV could increase clinical benefits and reduce the public health and economic burden of influenza.

National retrospective cohort study to identify risk factors for in-hospital 30-day lethality in laboratory-confirmed cases of influenza

ObjectiveTo identify factors associated with the risk of death in adolescent and adult inpatients with laboratory-positive (reverse-transcription polymerase chain reaction) influenza in Mexico during consecutive influenza seasons (2018–2020). MethodsA retrospective cohort study used national surveillance system data, enrolling 3.422 individuals. The association between various risk factors and 30-day in-hospital lethality were evaluated through risk ratios (RRs) and 95% confidence intervals (CIs). ResultsThe lethality rate was 18.1%. Flu vaccination history (RR=0.56, 95% CI 0.42–0.78), early antiviral drug administration (≤2 days from symptom onset [reference ≥5 days], RR=0.68, 95% CI 0.58–0.81), and a history of asthma (RR=0.66, 95% CI 0.47–0.95) showed protective effects against influenza-attributable death. Mechanical ventilator support produced the highest increase in death risk (RR=3.31, 95% CI 2.89–3.79). Male sex, older age, AH1N1 subtype, and other chronic diseases were also associated with fatal in-hospital influenza-related outcomes. ConclusionsOur findings highlight the major relevance of promoting immunization in high-risk individuals, together with ensuring early and effective antiviral management in suspected influenza cases.

Impact of COVID-19 infection control measures on influenza-related outcomes in Hong Kong

ABSTRACT Following the announcement of coronavirus disease 2019 (COVID-19) cases in Wuhan on 31 December 2019, government officials in Hong Kong recommended the wearing of face masks as a public infection control measure against the COVID-19 virus and curtail the impact of the concurrent influenza season. The present study evaluated the influenza-related outcomes between the influenza season 2019 and 2020 in Hong Kong as a result of these infection control measures. A Monte Carlo simulation model was designed to estimate the number of influenza cases, clinic visits, hospitalization, deaths, direct medical cost and disability-adjusted life-years (DALYs) for the season 2018–2019 and 2019–2020 in six age groups: 0–5 years, 6–11 years, 12–17 years, 18–49 years, 50–64 years and ≥65 years in Hong Kong. Model inputs were derived from public data and existing literature. The model findings showed significant reduction in influenza-related cases, clinic visits, hospitalization, and deaths in 2020 versus 2019 (p < 0.05). Influenza-related direct costs in all age-groups were significantly reduced by 56%-82% (p < 0.01) in 2020 versus 2019. DALYs were also significantly decreased by 58%-85% (p < 0.01). The direct cost and DALYs avoided in 2020 was the highest among the age group of 0–5 years with a cost-saving of USD593,763 (95%CI 590,730–596,796) per 10,000 population and a DALY reduction of 57.67 (95%CI 57.54–57.83) per 10,000 population. This study illustrated the reduction of all influenza-related outcome measures in Hong Kong as a result of the implementation of public infection control measures against COVID-19.

Summary of the NACI Supplemental Statement on Mammalian Cell Culture-Based Influenza Vaccines.

Mammalian cell culture-based technology is an innovative technique for influenza vaccine manufacturing that may be a valuable alternative to overcome some of the problems and vulnerabilities associated with conventional egg-based influenza vaccine production. Flucelvax® Quad (Seqirus, Inc.) is the first and only mammalian cell culture-based quadrivalent inactivated, subunit influenza vaccine (IIV4-cc) authorized for adult and pediatric use in Canada. The National Advisory Committee on Immunization (NACI) has not previously made a recommendation on cell culture-based influenza vaccines in any population. To review the available evidence for the efficacy, effectiveness, immunogenicity, and safety of IIV4-cc, and to summarize the NACI recommendation regarding the use of Flucelvax Quad in Canada in adults and children. A systematic literature review on the vaccine efficacy, effectiveness, immunogenicity and safety of IIV4-cc in persons four years of age and older was performed. The systematic review's methodology was specified a priori in a written protocol. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and develop a recommendation regarding the use of Flucelvax Quad in adults and children. The proposed recommendation was then considered and approved by NACI in light of the available evidence. Thirteen eligible studies were included in the evidence synthesis. In the four observational studies that assessed vaccine effectiveness of IIV4-cc, there were some data indicating potentially improved protection against influenza compared to conventional egg-based quadrivalent inactivated influenza vaccines (IIV4) or trivalent inactivated influenza vaccine (IIV3), particularly against A(H3N2) virus infection. There was also some evidence that IIV4-cc may be more effective than egg-based trivalent or quadrivalent influenza vaccines against non-laboratory confirmed influenza-related outcomes, but there is insufficient evidence for laboratory-confirmed outcomes. Two randomized controlled trials assessed the immunogenicity and safety of IIV4-cc compared with mammalian cell culture-based trivalent inactivated, subunit influenza vaccine (IIV3-cc). The IIV4-cc was well-tolerated and the reported solicited local and systemic adverse events were generally mild to moderate in intensity, self-limited and did not precipitate sequelae. One clinical review of cases and six peer-reviewed randomized controlled trials (four in adults and two in children) that reported on the safety of IIV3-cc were included in the review. The evidence on immunogenicity and safety was consistent across these studies and showed that there was no significant difference in adults and children four years of age and older who had received IIV3-cc or an egg-based IIV3. NACI concluded that there is fair evidence (Grade B Evidence) that Flucelvax Quad is effective, safe, and has non-inferior immunogenicity to comparable vaccines, based on direct evidence in adults and children nine years of age and older. NACI recommends that Flucelvax Quad may be considered among the IIV4 offered to adults and children nine years of age and older (Discretionary NACI Recommendation).

Estudio de cohorte retrospectivo nacional para identificar los factores de riesgo de letalidad por hospitalización durante 30 días en casos de gripe confirmados por laboratorio

ObjectiveTo identify factors associated with the risk of death in adolescent and adult inpatients with laboratory-positive (reverse-transcription polymerase chain reaction) influenza in Mexico during consecutive influenza seasons (2018-2020). Patients and methodsA retrospective cohort study used national surveillance system data, enrolling 3422 individuals. The association between various risk factors and 30-day in-hospital lethality were evaluated through risk ratios (RR) and 95% confidence intervals (CI). ResultsThe lethality rate was 18.1%. Flu vaccination history (RR = 0.56, 95% CI 0.42-0.78), early antiviral drug administration (≤ two days from symptom onset [reference ≥ 5 days], RR = 0.68, 95% CI 0.58-0.81), and a history of asthma (RR = 0.66, 95% CI 0.47-0.95) showed protective effects against influenza-attributable death. Mechanical ventilator support produced the highest increase in death risk (RR = 3.31, 95% CI 2.89-3.79). Male sex, older age, AH1N1 subtype, and other chronic diseases were also associated with fatal in-hospital influenza-related outcomes. ConclusionsOur findings highlight the major relevance of promoting immunization in high-risk individuals, together with ensuring early and effective antiviral management in suspected influenza cases.

Utility of Rapid Influenza Molecular Testing in an Outpatient Hemodialysis Unit: A Prospective Cohort Study.

Background:Early initiation of antiviral therapy for individuals at risk for severe influenza infection is important for improving patient outcomes. Current guidelines recommend empiric antiviral therapy for patients with end-stage kidney disease presenting with suspected influenza infection. Rapid molecular influenza assays may reduce diagnostic uncertainty and improve patient outcomes by providing faster diagnostics compared to traditional batched polymerase chain reaction (PCR) testing.Objective:To determine the utility of implementing a rapid influenza PCR assay compared to the standard of care in a hemodialysis unit.Design:This is a prospective cohort study.Setting:A hospital-based dialysis unit in a tertiary care hospital.Patients:Adult patients with end-stage kidney disease on intermittent hemodialysis.Measurements:Patient characteristics, influenza PCR swab results, antibiotic prescriptions, antiviral prescriptions, emergency room visits and hospitalizations.Methods:From November 1, 2017 to March 31, 2018, we assigned samples collected from a single center, hemodialysis unit to be processed using a rapid influenza PCR (cobas® Influenza A/B & respiratory syncytial virus assay) or the standard of care (in-house developed multiplex PCR). Samples were assigned to the rapid PCR if the patient received dialysis treatment in the morning dialysis shift, while the remainder were processed as per standard of care. Study outcomes included the time from collection to result of nasopharyngeal swab, prescription of influenza antiviral therapy, time to receiving prescription, and the need for emergency department visit or hospitalization within 2 weeks of presentation.Results:During the study period, 44 patients were assessed (14 with the rapid PCR and 30 with the standard of care assay). Compared to conventional testing, the time to result was shorter using rapid PCR compared to conventional testing (2.3 vs 22.6 hours, P < .0001). Individuals who were tested using the rapid PCR had a tendency to shorter time to receiving antiviral prescriptions (0.7 days vs 2.1 days, P = .11), and fewer emergency department visits (7.1% vs 30%, P = .13) but no difference in hospitalizations (14.3% vs 30%, P = .46) within 2 weeks of testing.Limitations:This is a single center non-randomized study with a relatively small sample size. Patients who were tested using the standard of care assay experienced a delay in the prescription of antiviral therapy which deviates from recommended clinical practice.Conclusions:Rapid influenza molecular testing in the hemodialysis unit was associated with a shorter time to a reportable result and with a tendency to reduced time to prescription of antiviral therapy. Rapid molecular testing should be compared with standard of care (empiric therapy) in terms of economic costs, adverse events, and influenza-related outcomes.

Public health and economic impact of switching from a trivalent to a quadrivalent inactivated influenza vaccine in Mexico

ABSTRACT Most influenza vaccines in Mexico are trivalent, containing two influenza A strains and a single B strain. Quadrivalent influenza vaccines (QIVs) extend protection by including an additional B strain to cover both co-circulating B lineages. Here, we retrospectively estimated how a switch to QIV in Mexico would have impacted influenza-related health outcomes over the 2010/2011 to 2015/2016 influenza seasons, and prospectively estimated the budget impact of using QIV in Mexico’s national immunization program from 2016/2017 to 2020/2021. For the retrospective estimation, we used an age-stratified static model incorporating Mexico-specific input parameters. For the prospective estimation, we used a budget impact model based on retrospective attack rates considering predicted future vaccination coverage. Between 2010/2011 and 2015/2016, a switch to QIV would have prevented 270,596 additional influenza cases, 102,000 general practitioner consultations, 140,062 days of absenteeism, 3,323 hospitalizations, and 312 deaths, saving Mex$214 million (US$10.8 million) in third-party payer costs. In the prospective analysis, a switch to QIV was estimated to prevent an additional 225,497 influenza cases, 85,000 general practitioner consultations, 116,718 days of absenteeism, 2,769 hospitalizations, and 260 deaths, saving Mex$178 million (US$9 million) in third-party payer costs over 5 years. Compared to the trivalent vaccine, the benefit and costs saved with QIV were sensitive to the distribution of influenza A vs. B cases and trivalent vaccine effectiveness against the mismatched B strain. These results suggest switching to QIV in Mexico would benefit healthcare providers and society by preventing influenza cases, morbidity, and deaths, and reducing associated use of medical resources.

94. Pneumonia Severity Scores Poorly Predict Severe Outcomes Among Adults Hospitalized with Influenza

BackgroundInfluenza can lead to severe outcomes among adults hospitalized with influenza, and causes substantial annual morbidity and mortality. We evaluated the performance of validated pneumonia severity indices in predicting severe influenza-associated outcomes.MethodsWe conducted a multicenter study within CDC’s Influenza Hospitalization Surveillance Network (FluSurv-NET) which included adults (≥ 18 years) hospitalized with laboratory-confirmed influenza during the 2017–18 influenza season. Medical charts were abstracted to obtain data on vital signs and laboratory values at admission on a stratified random sample of cases at a subset of hospitals at 11 network sites. Estimates were weighted to reflect the probability of selection. Cases were assigned to low- and high-risk groups based on the CURB-65 (‘Confusion, Urea, Respiratory rate, Blood pressure, Age ≥65’) index (high-risk cutoff = score ≥ 3), and the Pneumonia Severity Index (PSI) (high-risk cutoff = category V). We calculated area under receiver operating characteristic curves (AUROC), sensitivity, and specificity to estimate the performance of each index in predicting severe outcome categories: (1) intensive care unit (ICU) admission, 2) noninvasive mechanical ventilation (NIMV), (3) mechanical ventilation (MV), vasopressors, extracorporeal membrane oxygenation (ECMO) and (4) death.ResultsAmong 27,523 adults hospitalized with influenza, 8665 (31%) were sampled for inclusion in this analysis; median age was 70 years and 92% had ≥ 1 chronic condition. A total of 1,366 (16%) were classified as high-risk by CURB-65 and 1,249 (14%) by PSI. Both indices had low discrimination for severe outcomes; the AUROC for CURB-65 ranged from 0.55 for ICU admission to 0.65 for death, and for PSI ranged from 0.58 for ICU admission to 0.73 for death. Risk status by CURB-65 was less sensitive than PSI in predicting MV, vasopressor, or ECMO usage as well as death (figure). The specificity of CURB-65 and PSI was similar against all outcomes (figure).ConclusionThe CURB-65 and PSI indices performed poorly in predicting severe outcomes other than death; PSI had the best discrimination overall. Alternative approaches are needed to predict severe influenza-related outcomes and optimize clinical care. Disclosures All Authors: No reported Disclosures.

Use of prophylactic antivirals and care home characteristics associated with influenza in care homes with confirmed outbreaks

ObjectivesTo assess the association of antiviral prophylaxis and care home characteristics with the spread and severity of influenza-like illness in care homes with influenza outbreaks in North West England in the 2017/2018 influenza season. Study designThis is a retrospective observational study. MethodsRoutinely collected outbreak surveillance data reported to Public Health England were extracted from health protection electronic records. Data included use of antiviral prophylaxis, influenza-like illness or confirmed influenza, hospital admissions and deaths. Care home characteristics were obtained from the Care Quality Commission website. Single variable analysis and multivariable logistic regression were used to examine associations between care home characteristics, antiviral prophylaxis and influenza-related outcomes. ResultsIn the 109 homes, there were 3498 residents; of whom, 855 (24%) developed an influenza-like illness. Antiviral prophylaxis was given to residents of 67 of the 109 care homes with outbreaks (61%). A significantly higher attack rate was observed among residents of homes given antiviral prophylaxis (27%) than among residents of homes not given antivirals (20%) (P < 0.001). Significantly more deaths occurred in homes for people with learning disabilities and homes that received antiviral prophylaxis (P < 0.001). ConclusionsIn homes given antiviral prophylaxis, there were a higher number of residents with influenza-like illness and deaths. To improve our understanding of the impact of antiviral prophylaxis use in real life, enhanced and timely data collection is needed for identification of temporal associations between exposure and administration of antiviral prophylaxis. Consideration needs also to be given to ensure people with learning disabilities are protected through the seasonal influenza vaccine and timely antiviral prophylaxis when appropriate.

Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccine Among Patients Receiving Maintenance Hemodialysis

Studies of patients on maintenance dialysis therapy suggest that standard-dose influenza vaccine (SDV) may not prevent influenza-related outcomes. Little is known about the comparative effectiveness of SDV versus high-dose influenza vaccine (HDV) in this population. Cohort study using data from the US Renal Data System. 507,552 adults undergoing in-center maintenance hemodialysis between the 2010 to 2011 and 2014 to 2015 influenza seasons. SDV and HDV. All-cause mortality, hospitalization due to influenza or pneumonia, and influenza-like illness during the influenza season. Patients were eligible for inclusion in multiple yearly cohorts; thus, our unit of analysis was the influenza patient-season. To examine the relationship between vaccine dose and effectiveness outcomes, we estimated risk differences and risk ratios using propensity score weighting of Kaplan-Meier functions, accounting for a wide range of patient- and facility-level characteristics. For nonmortality outcomes, we used competing-risk methods to account for the high mortality rate in the dialysis population. Within 225,215 influenza patient-seasons among adults 65 years and older, 97.4% received SDV and 2.6% received HDV. We observed similar risk estimates for HDV and SDV recipients for mortality (risk difference,-0.08%; 95% CI,-0.85% to 0.80%), hospitalization due to influenza or pneumonia (risk difference, 0.15%; 95% CI,-0.69% to 0.93%), and influenza-like illness (risk difference, 0.00%; 95% CI,-1.50% to 1.08%). Our findings were similar among adults younger than 65 years, as well as within other subgroups defined by influenza season, age group, dialysis vintage, month of influenza vaccination, and vaccine valence. Residual confounding and outcome misclassification. The HDV does not appear to provide additional protection beyond the SDV against all-cause mortality or influenza-related outcomes for adults undergoing hemodialysis. The additional cost and side effects associated with HDV should be considered when offering this vaccine. Future studies of HDV and other influenza vaccine strategies are warranted.

Effectiveness of influenza and pneumococcal polysaccharide vaccines against influenza-related outcomes including pneumonia and acute exacerbation of cardiopulmonary diseases: Analysis by dominant viral subtype and vaccine matching.

BackgroundInfluenza and pneumonia are leading causes of morbidity and mortality among the elderly. Although vaccination is a main strategy to prevent these infectious diseases, concerns remain with respect to vaccine effectiveness.MethodsDuring three influenza seasons (2014–2015, 2015–2016 and 2016–2017), we evaluated the effectiveness of the influenza and pneumococcal vaccines against pneumonia and acute exacerbation of cardiopulmonary diseases among the elderly aged ≥65 years with influenza-like illness (ILI). Demographic and clinical data were collected prospectively.ResultsAmong 2,119 enrolled cases, 1,302 (61.4%) and 871 (41.1%) received the influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPV23), respectively. During an A/H3N2-dominant season with poor influenza vaccine effectiveness (2014–2015 season), neither the influenza vaccine nor PPV23 showed significant effectiveness against pneumonia or acute exacerbation of cardiopulmonary diseases. During seasons with good influenza vaccine effectiveness (2015–2016 and 2016–2017 seasons), the influenza vaccine was effective in preventing pneumonia, but PPV23 was not. In particular, the influenza vaccine was effective in preventing acute exacerbation of heart diseases (75.0%) during the A/H1N1-dominant 2015–2016 season.ConclusionThe influenza vaccine was effective in preventing pneumonia only during vaccine-matched seasons with good effectiveness against circulating influenza viruses. In addition, the influenza vaccine was cardio-protective during a vaccine-matched A/H1N1-dominant season.

Economic analysis of pharmacist-administered influenza vaccines in Ontario, Canada.

ObjectiveThe aim of this study was to evaluate the impact of pharmacist administration of influenza vaccine in Ontario on: 1) vaccination-associated costs related to the number of people vaccinated; 2) annual influenza-related outcomes and costs; and 3) change in productivity costs.MethodsUsing available data for Ontario, the total number of vaccinations given by providers in the 2011/12 influenza season (pre) was compared to the 2013/14 influenza season (post). Vaccine costs and provider fees for administration were assigned for both periods. An economic model was created to estimate the impact of the change in influenza vaccination volume on influenza-related outcomes and on the health care costs associated with treating influenza-related outcomes. Productivity costs due to both time off work due to getting vaccinated and influenza illness were considered. One-way sensitivity analysis was used to assess parameter uncertainty.ResultsThe number of vaccinations received by Ontarians increased by 448,000 (3% of the population), with pharmacists vaccinating approximately 765,000 people/year. The increased cost to the Ontario Ministry of Health and Long-term Care was $6.3 million, while the money saved due to reduced influenza-related outcome costs was $763,158. Productivity losses were reduced by $4.5 million and $3.4 million for the time invested to get vaccinated and time off work due to influenza illness, respectively.ConclusionAfter two influenza seasons, following the introduction of pharmacist-administered influenza vaccinations, there was a net immunization increase of almost 450,000, which potentially saved $2.3 million in direct health care costs and lost productivity in the province.

Using Claims and Consumer Wearable Devices Data to Quantify Influenza-Related Outcomes among Type 2 Diabetes Patients—A Large Population Study

Influenza causes substantial morbidity in people with diabetes; annual vaccination is recommended. We conducted a retrospective study of influenza-related outcomes (IRO) among fully insured type 2 diabetics from a large U.S. payer over a 1 year period covering the 2016-17 influenza season. We used bivariate analysis (54,656 diabetics, mean age 54.8 years, s.d. = 10.2) to compare IRO’s inferred from claims data against IRO’s for 113,016 age and gender matched nondiabetics. Diabetics had more influenza events (per ICD-9 and ICD-10 codes, 1.96% vs. 1.37%, p&amp;lt;0.001), and were prescribed more influenza antivirals per 100 ppl (27.1 vs. 22, p&amp;lt;0.001). Within 2-weeks before and 4-weeks after a medical claim for influenza, diabetics with influenza had more observed hyperglycemic events than in a comparable non-influenza period in the same year (3.81% vs. 2.18%, p&amp;lt;0.001), with substantial increases in pneumonia, sepsis and coronary disease (5.5% vs. 0.7%, 5.5% vs. 3.5%, 1.6% vs. 0.3%, p&amp;lt;0.001), and more outpatient antibiotic use per 100 people (54.5 vs. 16.9, p&amp;lt;0.001). 8.2% of type 2 diabetics (vs. 9.1% controls, p&amp;lt;0.001) used commercially available activity and sleep trackers, sharing data through an insurer provided wellness platform. Activity trackers showed that diabetics slept fewer hours compared to controls (6.48 vs. 6.69 hours, p&amp;lt;0.001), and had statistically significant changes in sleep and walking habits in the days around an influenza event as compared to baseline (about 2% more of the night spent restless and 10k fewer steps). This is the first population scale study to use medical claims linked with activity tracking data to quantify the behavioral and clinical effects of influenza in type 2 diabetes. These data highlight the impact of influenza on glycemic control and the daily lives of the Diabetic population, and reinforce the need for annual influenza vaccine, as recommended by the WHO and other global public health bodies. Disclosure S.I. Samson: Employee; Self; Sanofi Pasteur. W. Lee: None. T. Quisel: None. L. Foschini: None. J. Liska: Employee; Self; Sanofi. H.G. Mills: Employee; Self; Sanofi. R.C. Hollingsworth: Employee; Self; Sanofi Pasteur. M.E. Greenberg: Stock/Shareholder; Self; Merck &amp; Co., Inc.. Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi, GlaxoSmithKline plc., Pfizer Inc. A.C. Beal: Employee; Self; Sanofi. Board Member; Self; AcademyHealth.

Statin Use and Risks of Influenza-Related Outcomes Among Older Adults Receiving Standard-Dose or High-Dose Influenza Vaccines Through Medicare During 2010-2015.

Statins are used to reduce cardiovascular disease risk. Recent studies suggest that statin use may be associated with an increased influenza risk among influenza vaccinees. We used Medicare data to evaluate associations between statins and risks of influenza-related encounters among vaccinees. In this retrospective cohort study, we identified Medicare beneficiaries aged > 65 years who received high-dose (HD) or standard-dose (SD) influenza vaccines at pharmacies from 2010-2011 through 2014-2015. Statin users were matched to nonusers by vaccine type, demographics, prior medical encounters, and comorbidities. We used multivariable Poisson models to estimate associations between statin use around the time of vaccination and risk of influenza-related encounters. Study outcomes included influenza-related office visits with a rapid test followed by dispensing of oseltamivir and influenza-related hospitalizations (including emergency room visits) during high influenza circulation periods. The study included 1403651 statin users matched to nonusers. Cohorts were well balanced, with standardized mean differences ≤0.03 for all measured covariates. For statin users compared to nonusers, the adjusted relative risk was 1.086 (95% confidence interval [CI], 1.025-1.150) for influenza-related visits and 1.096 (95% CI, 1.013-1.185) for influenza-related hospitalizations. The risk difference ranged from ‒0.02 to 0.23 for influenza-related visits and from ‒0.04 to 0.13 for hospitalizations, depending on season severity. Results were similar for HD and SD vaccinees and for nonsynthetic and synthetic statin users. Among 2.8 million Medicare beneficiaries, these results suggest that statin use around the time of vaccination does not substantially affect the risk of influenza-related medical encounters among older adults.

A retrospective observational analysis of post-pandemic influenza-related outcomes in the United Kingdom, 2010–2014

ABSTRACTThis study set out to evaluate influenza- and respiratory-related illnesses recorded during primary care physician consultations in England following the H1N1 pandemic in 2009 and to enable the development of a dynamic disease model. Data were obtained from the Clinical Practice Research Datalink of primary care records over four influenza seasons (2010–2014). The primary outcome of the study was incidence of influenza- and respiratory-related diagnoses, calculated per practice and by season and age group. Upper respiratory tract infection diagnoses were most frequently recorded (mean seasonal practice level incidence; 3,762 consultations per 100,000 [SD = 1,989]), and influenza-related diagnoses were least frequently recorded across all seasons, except one. Incidence rates for the under 18 population were higher than those for the general population, in particular for upper respiratory tract infection (range of 8,024–9,950 versus 3,228–4,120, respectively) and otitis media diagnoses (2,668–3,652 versus 782–1,057, respectively). For influenza-related diagnoses, the 65+ age group, the 0 to <2 and 2 to <4 groups had a higher risk (risk ratio = 1.33, 1.12 and 1.16, respectively) than other age groups. This study provides valuable insight into the incidence of influenza- and respiratory-related diagnoses in the primary care setting in England, and suggests a higher burden of disease in young children and the elderly. The study also indicates that some influenza illness is likely to be reported under respiratory-related diagnoses, given the low incidence of influenza-related diagnoses in the study.

The effect of statins on influenza-like illness morbidity and mortality.

The effect of statins on cytokine-mediated inflammatory responses may impact on the prognosis of influenza. We assessed whether statin use decreases the incidence of adverse influenza-related outcomes. Additionally, we used a new-user study design to minimize healthy user bias. We further examined the possibility of non-causal associations by using unrelated outcomes. We used the UK Clinical Practice Research Datalink to identify all patients aged 30 or older diagnosed with influenza-like illness during 1997-2010. Statin users were compared with propensity score-matched patients not receiving statins. The outcome was hospitalization for influenza or pneumonia or death in the 30 days following influenza diagnosis. Logistic regression estimated cumulative incidence ratios. The study cohort included 5181 statin users matched to 5181 non-users. The 30-day incidence of hospitalization or death was 3.5% in statin users and 5.2% in non-users, resulting in a 27% lower incidence with statin use (cumulative incidence ratio: 0.73, 95%CI: 0.59-0.89). New statin users were less protected against our composite outcome. The effect of statins was less pronounced among those with respiratory and cardiac disease. Statin use was shown to be associated with a non-statistically significant risk reduction of motor vehicle accident and burns. The attenuation of the effect of statins with the new-user design, supporting evidence from the assessment of effect modification, and additional sub-analyses evaluating the effect of statins on non-related outcomes suggest that the beneficial effect of statins on influenza-related adverse outcomes may be explained by a healthy user bias. Copyright © 2016 John Wiley & Sons, Ltd.

Early estimation of pandemic influenza Antiviral and Vaccine Effectiveness (EAVE): use of a unique community and laboratory national data-linked cohort study.

After the introduction of any new pandemic influenza, population-level surveillance and rapid assessment of the effectiveness of a new vaccination will be required to ensure that it is targeted to those at increased risk of serious illness or death from influenza. We aimed to build a pandemic influenza reporting platform that will determine, once a new pandemic is under way: the uptake and effectiveness of any new pandemic vaccine or any protective effect conferred by antiviral drugs once available; the clinical attack rate of pandemic influenza; and the existence of protection provided by previous exposure to, and vaccination from, A/H1N1 pandemic or seasonal influenza/identification of susceptible groups. An observational cohort and test-negative study design will be used (post pandemic). A national linkage of patient-level general practice data from 41 Practice Team Information general practices, hospitalisation and death certification, virological swab and serology-linked data. We will study a nationally representative sample of the Scottish population comprising 300,000 patients. Confirmation of influenza using reverse transcription polymerase chain reaction and, in a subset of the population, serology. Future available pandemic influenza vaccination and antivirals will be evaluated. To build a reporting platform tailored towards the evaluation of pandemic influenza vaccination. This system will rapidly measure vaccine effectiveness (VE), adjusting for confounders, estimated by determining laboratory-confirmed influenza; influenza-related morbidity and mortality, including general practice influenza-like illnesses (ILIs); and hospitalisation and death from influenza and pneumonia. Once a validated haemagglutination inhibition assay has been developed (and prior to the introduction of any vaccination), cross-reactivity with previous exposure to A/H1N1 or A/H1N1 vaccination, other pandemic influenza or other seasonal influenza vaccination or exposure will be measured. A new sentinel system, capable of rapidly determining the estimated incidence of pandemic influenza, and pandemic influenza vaccine and antiviral uptake and effectiveness in preventing influenza and influenza-related clinical outcomes, has been created. We have all of the required regulatory approvals to allow rapid activation of the sentinel systems in the event of a pandemic. Of the 41 practices expressing an interest in participating, 40 have completed all of the necessary paperwork to take part in the reporting platform. The data extraction tool has been installed in these practices. Data extraction and deterministic linkage systems have been tested. Four biochemistry laboratories have been recruited, and systems for serology collection and linkage of samples to general practice data have been put in place. The reporting platform has been set up and is ready to be activated in the event of any pandemic of influenza. Building on this infrastructure, there is now the opportunity to extend the network of general practices to allow important subgroup analyses of VE (e.g. for patients with comorbidities, at risk of serious ILI) and to link to other data sources, in particular to test for maternal outcomes in pregnant patients. This study is registered as ISRCTN55398410. The National Institute for Health Research Health Technology Assessment programme.

Clinical presentations and outcomes of influenza infection among hematology/oncology patients from a single cancer center: pandemic and post-pandemic seasons.

Influenza can cause severe infection in hematology/oncology patients. The occurrence of the 2009 pandemic represented an opportunity to study the impact of influenza on such patients in pandemic and post-pandemic seasons. We retrospectively reviewed medical records of hematology/oncology patients who had laboratory-confirmed influenza infection during the 2009 pandemic and the first post-pandemic seasons. We assessed influenza-related outcomes in both seasons with emphasis on the development of pneumonia and mortality. We also analyzed factors associated with poor outcomes. We included 350 patients; 207 were diagnosed in the pandemic and 143 in the post-pandemic seasons. Influenza severity was similar in both seasons with no significant differences in the development of pneumonia or death. Infection with the pH1N1 virus was associated with the development of pneumonia (24.7% vs 14.9%, p = 0.029) but did not affect mortality. A multivariate analysis showed that initiation of antiviral treatment after > 48 h, healthcare acquisition of influenza, and low albumin were independent risk factors for the development of pneumonia (p values 0.022, 0.003, and < 0.0001, respectively). A log-rank test showed increased mortality in patients who received therapy > 48 h after onset of symptoms (p = 0.001). In hematology/oncology patients, influenza was as severe in the post-pandemic as in the pandemic season. Pneumonia developed more commonly in patients infected with pH1N1 virus. Healthcare acquisition of infection and low albumin were associated with the development of pneumonia. Delayed initiation of antiviral treatment was associated with both pneumonia and mortality.

Polymorphisms at Residue 222 of the Hemagglutinin of Pandemic Influenza A(H1N1)pdm09: Association of Quasi-Species to Morbidity and Mortality in Different Risk Categories

The D222G substitution in the hemagglutinin (HA) gene of the pandemic influenza A(H1N1)pdm09 virus has been identified as a potential virulence marker, because this change allows for virus invasion deeper into the respiratory tract. In this study, we analyzed D, G and N polymorphisms at residue 222 by pyrosequencing (PSQ). We initially analyzed 401 samples from Brazilian patients. These were categorized with respect to clinical conditions due to influenza infection (mild, serious or fatal) and sub-stratified by risky factors. The frequency of mixed population of virus, with more than one polymorphism at residue 222, was significantly higher in serious (10.6%) and fatal (46.7%) influenza cases, whereas those who showed mild influenza infections were all infected by D222 wild-type. Mixtures of quasi-species showed a significant association of mortality, especially for those with risk factors, in special pregnant women. These results not only reinforce the association between D222G substitution and influenza A(H1N1)pdm09-associated morbidity and mortality, but also add the perspective that a worse clinical prognosis is most likely correlated with mixtures of quasi-species at this HA residue. Therefore, quasi-species may have a critical and underestimated role in influenza-related clinical outcomes.

Public health impact of including two lineages of influenza B in a quadrivalent seasonal influenza vaccine

The annual trivalent influenza vaccine (TIV) includes viruses representing three influenza strains - one A/H1N1, one A/H3N2, and one B, although two antigenically distinct lineages of influenza B (Victoria and Yamagata) co-circulate annually in the United States. Predicting which lineage of influenza B will predominate during a season is challenging, and cross-protection by immunization against the other lineage is expected to be low. One proposed alternative is to produce a quadrivalent influenza vaccine (QIV) including an influenza B virus from each of the two circulating lineages. We estimated the additional public health benefit of QIV compared with TIV by calculating the expected impact on influenza-related health outcomes (illness, hospitalization, and death) over ten influenza seasons (1999/2000-2008/2009). We included data on the annual incidence of influenza-associated outcomes, virologic circulation, vaccine coverage, and vaccine effectiveness. We also considered annual vaccine production capacity, since available resources would have produced four vaccine viruses instead of three, potentially resulting in fewer doses of QIV. Use of QIV could have reduced annual cases (range: 2200-970,000), hospitalizations (range: 14-8200), and deaths (range: 1-485) in the US. During earlier seasons, adjusting production capacity for a fourth virus in QIV could have resulted in reduced overall influenza vaccine availability and net increases in influenza-associated outcomes. However, in recent seasons, the expected supply of QIV is likely to exceed the doses of vaccine actually administered. The potential net impact of QIV on influenza-associated outcomes is expected to vary between seasons, depending on annual variability in the incidence of influenza caused by the two influenza B lineages, vaccine coverage, and effectiveness. The additional protection provided by including a second lineage of influenza B could result in a modest reduction in influenza-associated outcomes.