Influenza Hospitalizations Research Articles

Relative vaccine effectiveness of MF59-adjuvanted vs high-dose trivalent inactivated influenza vaccines for prevention of test-confirmed influenza hospitalizations during the 2017–2020 influenza seasons

ObjectivesThis study evaluated relative vaccine effectiveness (rVE) of MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) vs high-dose trivalent inactivated influenza vaccine (HD-TIV) for prevention of test-confirmed influenza emergency department visits and/or inpatient admissions (“ED/IP”) and for IP admissions alone pooled across the 2017–2020 influenza seasons. Exploratory individual season analyses were also performed. MethodsThis retrospective test-negative design study included United States (US) adults age ≥65 years vaccinated with aTIV or HD-TIV who presented to an ED or IP setting with acute respiratory or febrile illness during the 2017–2020 influenza seasons. Test-positive cases and test-negative controls were grouped by vaccine received. The rVE of aTIV vs HD-TIV was evaluated using a combination of inverse probability of treatment weighting and logistic regression to adjust for potential confounders. ResultsPooled analyses over the three seasons found no significant differences in the rVE of aTIV vs HD-TIV for prevention of test-confirmed influenza ED/IP (−2.5% [−19.6, 12.2]) visits and admissions or IP admissions alone (−1.6% [−22.5, 15.7]). The exploratory individual season analyses also showed no significant differences. ConclusionsEvidence from the 2017–2020 influenza seasons indicates aTIV and HD-TIV are comparable for prevention of test-confirmed influenza ED/IP visits in US adults age ≥65 years.

Cost-Effectiveness of Adjuvanted Quadrivalent Influenza Vaccine for Adults over 65 in France.

In France, influenza accounts for an average of over one million consultations with GPs, 20,000 hospitalizations, and 9000 deaths per year, particularly among the over-65s. This study evaluates the cost-effectiveness of the adjuvanted quadrivalent influenza vaccine (aQIV) compared to standard (SD-QIV) and high-dose (HD-QIV) quadrivalent influenza vaccines for individuals aged 65 and older in France. The age-structured SEIR transmission model, calibrated to simulate a mean influenza season, incorporates a contact matrix to estimate intergroup contact rates. Epidemiological, economic, and utility outcomes are evaluated. Vaccine effectiveness and costs are derived from literature and national insurance data. Quality of life adjustments for influenza attack rates and hospitalizations are applied. Deterministic and probabilistic analyses are also conducted. Compared to SD-QIV, aQIV demonstrates substantial reductions in healthcare utilization and mortality, avoiding 89,485 GP consultations, 2144 hospitalizations, and preventing 1611 deaths. Despite an investment of EUR 110 million, aQIV yields a net saving of EUR 14 million in healthcare spending. Compared to HD-QIV, aQIV saves 62 million euros on vaccination costs. Cost-effectiveness analysis reveals an incremental cost-effectiveness ratio of EUR 7062 per QALY. This study highlights the cost-effectiveness of aQIV versus SD-QIV and HD-QIV, preventing influenza cases, hospitalizations, and deaths.

The relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines in preventing hospitalization and mortality: A meta-analysis of evidence from randomized trials

To summarize current evidence of high-dose influenza vaccine (HD-IV) vs standard-dose (SD-IV) regarding severe clinical outcomes. A prespecified meta-analysis was conducted to assess relative vaccine effectiveness (rVE) of HD-IV vs SD-IV in reducing the rates of (1) pneumonia and influenza (P&I) hospitalization, (2) all hospitalizations, and (3) all-cause death in adults ≥65 years in randomized controlled trials. Pooled effect sizes were estimated using fixed-effects models with the inverse variance method. Five randomized trials were included encompassing 105,685 individuals. HD-IV vs SD-IV reduced P&I hospitalizations (rVE: 23.5%, [95%CI: 12.3 to 33.2]). HD-IV vs SD-IV also reduced rate of all-cause hospitalizations (rVE: 7.3%, [95%CI: 4.5 to 10.0]). No significant differences were observed in death rates (rVE = 1.6% ([95%CI: -2.0 to 5.0]) in HD-IV vs SD-IV. Sensitivity analyses omitting trials with participants sharing the same comorbidity, trials with ≥100 events, and random-effects models provided comparable estimates for all outcomes. HD-IV reduced the incidence of P&I and all-cause hospitalization vs SD-IV in adults ≥65 years in randomized trials, through no significant difference was observed in all-cause death rates. These findings, supported by evidence from several randomized studies, can benefit from replication in a fully powered, individually randomized trial.

Metformin use associated with lower rate of hospitalization for influenza in individuals with diabetes.

To investigate if patients with diabetes taking metformin have better outcomes versus those not taking metformin following an emergency room visit for influenza. Using electronic medical records, we performed a retrospective chart review of all adult patients with a diagnosis of diabetes seen in any Duke University Medical Center-affiliated emergency department for influenza over a 6-year period. We documented patient characteristics and comorbidities, and compared outcomes for patients taking metformin versus patients not taking metformin using both univariable and multivariable analyses. Our primary outcome was hospital admission rate. Secondary outcomes were in-hospital length of stay and in-hospital death. Our cohort included 1023 adult patients with diabetes, of whom 59.9% were female. The mean age was 62.9 years, 58.4% were African American, 36.1% were White, and 81.9% were obese or overweight. Of these patients, 347 (34%) were taking metformin. Patients with diabetes taking metformin were less likely to be hospitalized following an emergency department visit for influenza than patients with diabetes not taking metformin (56.8% vs. 70.1%; p < 0.001). Of those patients admitted, there was no statistically significant difference in length of stay or death. In patients with diabetes, metformin use is associated with lower rate of hospitalization following an emergency department visit for influenza.

The Changing Landscape of Respiratory Viruses Contributing to Hospitalizations in Quebec, Canada: Results From an Active Hospital-Based Surveillance Study.

A comprehensive description of the combined effect of SARS-CoV-2 and respiratory viruses other than SARS-CoV-2 (ORVs) on acute respiratory infection (ARI) hospitalizations is lacking. This study aimed to compare the viral etiology of ARI hospitalizations before the pandemic (8 prepandemic influenza seasons, 2012-13 to 2019-20) and during 3 pandemic years (periods of increased SARS-CoV-2 and ORV circulation in 2020-21, 2021-22, and 2022-23) from an active hospital-based surveillance network in Quebec, Canada. We compared the detection of ORVs and SARS-CoV-2 during 3 pandemic years to that in 8 prepandemic influenza seasons among patients hospitalized with ARI who were tested systematically by the same multiplex polymerase chain reaction (PCR) assay during periods of intense respiratory virus (RV) circulation. The proportions of infections between prepandemic and pandemic years were compared by using appropriate statistical tests. During prepandemic influenza seasons, overall RV detection was 92.7% (1384/1493) (respiratory syncytial virus [RSV]: 721/1493, 48.3%; coinfections: 456/1493, 30.5%) in children (<18 years) and 62.8% (2723/4339) (influenza: 1742/4339, 40.1%; coinfections: 264/4339, 6.1%) in adults. Overall RV detection in children was lower during pandemic years but increased from 58.6% (17/29) in 2020-21 (all ORVs; coinfections: 7/29, 24.1%) to 90.3% (308/341) in 2021-22 (ORVs: 278/341, 82%; SARS-CoV-2: 30/341, 8.8%; coinfections: 110/341, 32.3%) and 88.9% (361/406) in 2022-23 (ORVs: 339/406, 84%; SARS-CoV-2: 22/406, 5.4%; coinfections: 128/406, 31.5%). In adults, overall RV detection was also lower during pandemic years but increased from 43.7% (333/762) in 2020-21 (ORVs: 26/762, 3.4%; SARS-CoV-2: 307/762, 40.3%; coinfections: 7/762, 0.9%) to 57.8% (731/1265) in 2021-22 (ORVs: 179/1265, 14.2%; SARS-CoV-2: 552/1265, 43.6%; coinfections: 42/1265, 3.3%) and 50.1% (746/1488) in 2022-23 (ORVs: 409/1488, 27.5%; SARS-CoV-2: 337/1488, 22.6%; coinfections: 36/1488, 2.4%). No influenza or RSV was detected in 2020-21; however, their detection increased in the 2 subsequent years but did not reach prepandemic levels. Compared to the prepandemic period, the peaks of RSV hospitalization shifted in 2021-22 (16 weeks earlier) and 2022-23 (15 weeks earlier). Moreover, the peaks of influenza hospitalization shifted in 2021-22 (17 weeks later) and 2022-23 (4 weeks earlier). Age distribution was different compared to the prepandemic period, especially during the first pandemic year. Significant shifts in viral etiology, seasonality, and age distribution of ARI hospitalizations occurred during the 3 pandemic years. Changes in age distribution observed in our study may reflect modifications in the landscape of circulating RVs and their contribution to ARI hospitalizations. During the pandemic period, SARS-CoV-2 had a low contribution to pediatric ARI hospitalizations, while it was the main contributor to adult ARI hospitalizations during the first 2 seasons and dropped below ORVs during the third pandemic season. Evolving RVs epidemiology underscores the need for increased scrutiny of ARI hospitalization etiology to inform tailored public health recommendations.

Validation of an automated, end-to-end metagenomic sequencing assay for agnostic detection of respiratory viruses.

Current molecular diagnostics are limited in the number and type of detectable pathogens. Metagenomic next generation sequencing (mNGS) is an emerging, and increasingly feasible, pathogen-agnostic diagnostic approach. Translational barriers prohibit the widespread adoption of this technology in clinical laboratories. We validate an end-to-end mNGS assay for detection of respiratory viruses. Our assay is optimized to reduce turnaround time, lower cost-per-sample, increase throughput, and deploy secure and actionable bioinformatic results. We validated our assay using residual nasopharyngeal swab specimens from Vancouver General Hospital (n = 359), RT-PCR-positive, or negative for Influenza, SARS-CoV-2, and RSV. We quantified sample stability, assay precision, the effect of background nucleic acid levels, and analytical limits of detection. Diagnostic performance metrics were estimated. We report that our mNGS assay is highly precise, semi-quantitative, with analytical limits of detection ranging from 103-104 copies/mL. Our assay is highly specific (100%) and sensitive (61.9% Overall: 86.8%; RT-PCR Ct < 30). Multiplexing capabilities enable processing of up to 55-specimens simultaneously on an Oxford Nanopore GridION device, with results reported within 12-hours. This study outlines the diagnostic performance and feasibility of mNGS for respiratory viral diagnostics, infection control, and public health surveillance. We addressed translational barriers to widespread mNGS adoption.

Summary of the National Advisory Committee on Immunization (NACI) Updated Guidance on Influenza Vaccination During Pregnancy.

Seasonal influenza infection can lead to serious complications and adverse outcomes for pregnant individuals, the developing fetus and infants younger than six months of age. This supplemental statement provides an evidence summary on the safety and effectiveness of influenza vaccination in pregnant individuals, and the benefits and risks to the pregnant person, the developing fetus and infants younger than six months of age. A systematic review was conducted on the effectiveness and safety of influenza vaccination in pregnancy. The National Advisory Committee on Immunization (NACI)'s evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and apply an ethics, equity, feasibility and acceptability lens to develop recommendations. The evidence suggests that influenza vaccination during pregnancy is effective in reducing the risk of laboratory-confirmed influenza infection and hospitalization in both pregnant individuals and their infants up to six months postpartum. The evidence also suggests that influenza vaccination during pregnancy does not increase the risk of non-obstetric serious adverse events in pregnant persons, infant death, spontaneous abortion, stillbirth, preterm birth, small for gestational age, low birth weight and congenital anomalies. Based on this body of evidence, NACI reaffirms the safety and importance of influenza vaccination during pregnancy. NACI recommends that individuals at any stage of pregnancy should receive an age-appropriate inactivated, unadjuvanted or recombinant influenza vaccine each influenza season. Influenza vaccination may be given at the same time as, or at any time before or after administration of another vaccine, including the coronavirus disease 2019 (COVID-19) or pertussis vaccines.

Burden of Neurologic Health Care and Incident Neurologic Diagnoses in the Year After COVID-19 or Influenza Hospitalization.

Following the outbreak of viral infections from the severe acute respiratory syndrome coronavirus 2 virus in 2019 (coronavirus disease 2019 [COVID-19]), reports emerged of long-term neurologic sequelae in survivors. To better understand the burden of neurologic health care and incident neurologic diagnoses in the year after COVID-19 vs influenza, we performed an analysis of patient-level data from a large collection of electronic health records (EMR). We acquired deidentified data from TriNetX, a global health research network providing access to EMR data. We included individuals aged 18 years or older during index event, defined as hospital-based care for COVID-19 (from April 1, 2020, until November 15, 2021) or influenza (from 2016 to 2019). The study outcomes were subsequent health care encounters over the following year for 6 neurologic diagnoses including migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia. We also created a composite of the 6 diagnoses as an incident event, which we call "incident neurologic diagnoses." We performed a 1:1 complete case nearest-neighbor propensity score match on age, sex, race/ethnicity, marital status, US census region patient residence, preindex years of available data, and Elixhauser comorbidity score. We fit time-to-event models and reported hazard ratios for COVID-19 vs influenza infection. After propensity score matching, we had a balanced cohort of 77,272 individuals with COVID-19 and 77,272 individuals with influenza. The mean age was 51.0 ± 19.7 years, 57.7% were female, and 41.5% were White. Compared with patients with influenza, patients with COVID-19 had a lower risk of subsequent care for migraine (HR 0.645, 95% CI 0.604-0.687), epilepsy (HR 0.783, 95% CI 0.727-0.843), neuropathies (HR 0.567, 95% CI 0.532-0.604), movement disorders (HR 0.644, 95% CI 0.598-0.693), stroke (HR 0.904, 95% CI 0.845-0.967), or dementia (HR 0.931, 95% CI 0.870-0.996). Postinfection incident neurologic diagnoses were observed in 2.79% of the COVID-19 cohort vs 4.91% of the influenza cohort (HR 0.618, 95% CI 0.582-0.657). Compared with a matched cohort of adults with a hospitalization or emergency department visit for influenza infection, those with COVID-19 had significantly fewer health care encounters for 6 major neurologic diagnoses over a year of follow-up. Furthermore, we found that COVID-19 infection was associated with a lower risk of an incident neurologic diagnosis in the year after infection.

Number of Influenza Risk Factors Informs an Adult's Increased Potential of Severe Influenza Outcomes: A Multiseason Cohort Study From 2015 to 2020.

While studies have evaluated factors influencing the risk of severe influenza outcomes, there is limited evidence on the additive impact of having multiple influenza risk factors and how this varies by age. Patients ≥18 years of age in the United States were evaluated retrospectively in 5 seasonal cohorts during the 2015-2020 influenza seasons. Patient-level electronic medical records linked to pharmacy and medical claims were used to ascertain covariates and outcomes. Multivariable logistic regression models were fitted for the overall population and by age subgroups to evaluate the association of demographic and clinical characteristics with odds of influenza-related medical encounters (ICD-10 codes J09*-J11*). The logistic regression models included sex, race/ethnicity, geographic region, baseline health care resource use, vaccination status, specific high-risk comorbidities, number of influenza risk factors, body mass index, and smoking status. Odds ratios from each of the 5 seasons were summarized via fixed effect meta-analysis. Season cohort sizes ranged from 887 260 to 3 628 168 adults. Of all patient characteristics evaluated, an individual's cumulative number of high-risk influenza conditions, as defined per the Centers for Disease Control and Prevention, was the most predictive of an increased probability of having an influenza-related medical encounter overall and across age groups. For adults of any age, odds ratios for influenza hospitalization ranged from 1.8 (95% CI, 1.7-2.0) for 1 risk factor to 6.4 (95% CI, 5.8-7.0) for ≥4 risk factors. These results show that a simple measure such as the number of influenza risk factors can be highly informative of an adult's potential for severe influenza outcomes.

Effects of high-dose versus standard-dose quadrivalent influenza vaccine among patients with diabetes: A post-hoc analysis of the DANFLU-1 trial.

High-dose quadrivalent influenza vaccine (QIV-HD) has been shown to be more effective than standard-dose (QIV-SD) in reducing influenza infection, but whether diabetes status affects relative vaccine effectiveness (rVE) is unknown. We aimed to assess rVE on change in glycated haemoglobin [HbA1c (∆HbA1c)], incident diabetes, total all-cause hospitalizations (first + recurrent), and a composite of all-cause mortality and hospitalization for pneumonia or influenza. DANFLU-1 was a pragmatic, open-label trial randomizing adults (65-79 years) 1:1 to QIV-HD or QIV-SD during the 2021/22 influenza season. Cox proportional hazards regression was used to estimate rVE against incident diabetes and the composite endpoint, negative binomial regression to estimate rVE against all-cause hospitalizations, and ANCOVA when assessing rVE against ∆HbA1c. Of the 12 477 participants, 1162 (9.3%) had diabetes at baseline. QIV-HD, compared with QIV-SD, was associated with a reduction in the rate of all-cause hospitalizations irrespective of diabetes [overall: 647 vs. 742 events, incidence rate ratio (IRR): 0.87, 95% CI (0.76-0.99); diabetes: 93 vs. 118 events, IRR: 0.80, 95% CI (0.55-1.15); without diabetes: 554 vs. 624 events, IRR: 0.88, 95% CI (0.76-1.01), pinteraction = 0.62]. Among those with diabetes, QIV-HD was associated with a lower risk of the composite outcome [2 vs. 11 events, HR: 0.18, 95% CI (0.04-0.83)] but had no effect on ∆HbA1c; QIV-HD adjusted mean difference: ∆ + 0.2 mmol/mol, 95% CI (-0.9 to 1.2). QIV-HD did not affect the risk of incident diabetes [HR 1.18, 95% CI (0.94-1.47)]. In this post-hoc analysis, QIV-HD versus QIV-SD was associated with an increased rVE against the composite of all-cause death and hospitalization for pneumonia/influenza, and the all-cause hospitalization rate irrespective of diabetes status.

Impact of influenza related hospitalization in Spain: characteristics and risk factor of mortality during five influenza seasons (2016 to 2021).

Estimating the global influenza burden in terms of hospitalization and death is important for optimizing prevention policies. Identifying risk factors for mortality allows for the design of strategies tailored to groups at the highest risk. This study aims to (a) describe the clinical characteristics of hospitalizations with a diagnosis of influenza over five flu seasons (2016-2017 to 2020-2021), (b) assess the associated morbidity (hospitalization rates and ICU admissions rate), mortality and cost of influenza hospitalizations in different age groups and (c) analyze the risk factors for mortality. This retrospective study included all hospital admissions with a diagnosis of influenza in Spain for five influenza seasons. Data were extracted from the Spanish National Surveillance System for Hospital Data from 1 July 2016 to 30 June 2021. We identified cases coded as having influenza as a primary or secondary diagnosis (International Classification of Diseases, 10th revision, J09-J11). The hospitalization rate was calculated relative to the general population. Independent predictors of mortality were identified using multivariable logistic regression. Over the five seasons, there were 127,160 hospitalizations with a diagnosis of influenza. The mean influenza hospitalization rate varied from 5/100,000 in 2020-2021 (COVID-19 pandemic) to 92.9/100,000 in 2017-2018. The proportion of influenza hospitalizations with ICU admission was 7.4% and was highest in people aged 40-59 years (13.9%). The case fatality rate was 5.8% overall and 9.4% in those aged 80 years or older. Median length of stay was 5 days (and 6 days in the oldest age group). In the multivariable analysis, independent risk factors for mortality were male sex (odds ratio [OR] 1.14, 95% confidence interval [95% CI] 1.08-1.20), age (<5 years: OR 1; 5-19 years: OR 2.02, 95%CI 1.17-3.49; 20-39 years: OR 4.11, 95% CI 2.67-6.32; 40-59 years: OR 8.15, 95% CI 5.60-11.87; 60-79 years: OR 15.10, 95% CI 10.44-21.84; ≥80 years: OR 33.41, 95% CI 23.10-48.34), neurological disorder (OR 1.97, 95% CI 1.83-2.11), heart failure (OR 1.85, 95% CI 1.74-1.96), chronic kidney disease (OR 1.33, 95% CI 1.25-1.41), chronic liver disease (OR 2.95, 95% CI 2.68-3.27), cancer (OR 1.85, 95% CI 1.48-2.24), coinfection with SARS-CoV2 (OR 3.17, 95% CI 2.34-4.28), influenza pneumonia (OR 1.76, 95% CI 1.66-1.86) and admission to intensive care (OR 7.81, 95% CI 7.31-8.36). Influenza entails a major public health burden. People aged over 60-and especially those over 80-show the longest hospital stays. Age is also the most significant risk factor for mortality, along with certain associated comorbidities.

Relative Effectiveness of the MF59®-Adjuvanted Influenza Vaccine Versus High-Dose and Non-Adjuvanted Influenza Vaccines in Preventing Cardiorespiratory Hospitalizations During the 2019-2020 US Influenza Season.

Adults ≥ 65 years of age have suboptimal influenza vaccination responses compared to younger adults due to age-related immunosenescence. Two vaccines were specifically developed to enhance protection: MF59-adjuvanted trivalent influenza vaccine (aIIV3) and high-dose egg-based trivalent influenza vaccine (HD-IIV3e). In a retrospective cohort study conducted using US electronic medical records linked to claims data during the 2019-2020 influenza season, we compared the relative vaccine effectiveness (rVE) of aIIV3 with HD-IIV3e and a standard-dose non-adjuvanted egg-based quadrivalent inactivated influenza vaccine (IIV4e) for the prevention of cardiorespiratory hospitalizations, including influenza hospitalizations. We evaluated outcomes in the "any" diagnosis position and the "admitting" position on the claim. A doubly robust methodology using inverse probability of treatment weighting and logistic regression was used to adjust for covariate imbalance. rVE was calculated as 100 * (1 - ORadjusted). The study included 4,299,594 adults ≥ 65 years of age who received aIIV3, HD-IIV3e, or IIV4e. Overall, aIIV3 was associated with lower proportions of cardiorespiratory hospitalizations with diagnoses in any position compared to HD-IIV3e (rVE = 3.9% [95% CI, 2.7-5.0]) or IIV4e (9.0% [95% CI, 7.7-10.4]). Specifically, aIIV3 was more effective compared with HD-IIV3e and IIV4e in preventing influenza hospitalizations (HD-IIV3e: 9.7% [95% CI, 1.9-17.0]; IIV4e: 25.3% [95% CI, 17.7-32.2]). Consistent trends were observed for admitting diagnoses. Relative to both HD-IIV3e and IIV4e, aIIV3 provided improved protection from cardiorespiratory or influenza hospitalizations.

Estimated Incidence of Hospitalizations and Deaths Attributable to Respiratory Syncytial Virus Infections Among Adults in Germany Between 2015 and 2019.

Respiratory syncytial virus (RSV) burden in adults is underestimated mainly due to unspecific symptoms and limited standard-of-care testing. We estimated the population-based incidence of hospitalization and mortality attributable to RSV among adults with and without risk factors in Germany. Weekly counts of hospitalizations and deaths for respiratory, cardiovascular, and cardiorespiratory diseases were obtained (Statutory Health Insurance database, 2015-2019). A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends, and viral activity while allowing for potential overdispersion. Weekly counts of RSV and influenza hospitalizations in children < 2years and adults ≥ 60years, respectively, were used as viral activity indicators. Models were stratified by age group and risk status (defined as presence of selected comorbidities). Population-based RSV-attributable hospitalization incidence rates were high among adults ≥ 60years: respiratory hospitalizations (236-363 per 100,000 person-years) and cardiorespiratory hospitalizations (584-912 per 100,000 person-years). RSV accounted for 2-3% of all cardiorespiratory hospitalizations in this age group. The increase in cardiorespiratory hospitalization risk associated with underlying risk factors was greater in 18-44year old persons (five to sixfold higher) than in ≥ 75year old persons (two to threefold higher). This is a first model-based study to comprehensively assess adult RSV burden in Germany. Estimated cardiorespiratory RSV hospitalization rates increased with age and were substantially higher in people with risk factors compared to those without risk factors. Our study indicates that RSV, like other respiratory viruses, contributes to both respiratory and cardiovascular hospitalizations. Effective prevention strategies are needed, especially among older adults ≥ 60years and among adults with underlying risk factors.

Impact of obstructive sleep apnea on clinical outcomes of hospitalization due to influenza in children: A propensity score-matched analysis of the US Nationwide Inpatient Sample 2005-2018.

Previous studies have explored the association between obstructive sleep apnea (OSA) and clinical outcomes of influenza in adults, whereas limited research examined this relationship in pediatric populations. This study aimed to evaluate the clinical impact of OSA on the outcomes of pediatric influenza hospitalizations. This was a population-based, retrospective study. Data of children aged 1-19 years hospitalized for influenza infection were extracted from the United States (US) Nationwide Inpatient Sample Database 2005-2018. Univariable and multivariable regression analyses determined associations between OSA, length of stay (LOS), total hospital costs, pneumonia, and life-threatening events. After propensity-score matching, a total of 2100 children were analyzed. The logistic analysis revealed that children with OSA had a significantly increased LOS (β = 2.29 days; 95% confidence interval,CI: 1.01-3.57, p < .001) and total hospital costs (β = 26.06 thousand dollars; 95% CI: 6.62-45.51, p = .009), and higher odds of pneumonia (aged 6-10 years: odds ratio [OR] = 1.52; 95% CI: 1.01-2.27, p = .043; aged ≥ 11 years: OR = 1.83; 95% CI: 1.33-2.53, p < .001). During influenza admissions, children with OSA had longer LOS, higher hospital costs, and an increased risk of pneumonia compared to those without OSA. These findings underscore the importance of recognizing and managing OSA in influenza-related infections among children.

Clinical Outcomes With Electronic Nudges to Increase Influenza Vaccination : A Prespecified Analysis of a Nationwide, Pragmatic, Registry-Based, Randomized Implementation Trial.

In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point. To evaluate the effects of the successful nudging interventions on downstream clinical outcomes. Prespecified exploratory analysis of a nationwide randomized implementation trial. (ClinicalTrials.gov: NCT05542004). The 2022 to 2023 influenza season. 964 870 Danish citizens aged 65 years or older. Usual care or 9 different electronically delivered behavioral nudging letters. Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023. The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care). Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms. In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended. Sanofi.

Excess hospitalizations and in-hospital mortality associated with seasonal influenza in Italy: a 11-year retrospective study

BackgroundInfluenza and flu-like syndromes are difficult to monitor because the symptoms are not specific, laboratory tests are not routinely performed, and diagnosis codes are often lacking or incompletely registered in medical records. This may result in an underestimation of hospital admissions, associated costs, and in-hospital mortality. Therefore, this study aimed to estimate the public health and economic burden of hospitalisations associated with influenza in Italy, at the national and regional levels.MethodsThis 11-year retrospective study included patients admitted to hospitals for influenza or diagnoses associated with influenza (including respiratory and cardiocirculatory conditions) from 2008/09 to 2018/19. Data on hospitalisations were extracted from the Italian Hospital Discharge Records. Information on weekly influenza-like syndrome incidence and weekly average temperature were used to estimate the burden of influenza in terms of hospital admissions in every Italian region and for different age groups by applying a negative binomial model. The model was also applied to estimate in-hospital mortality and the total costs of influenza and influenza-like hospital admissions.ResultsOver the study period, in addition to 3,970 average seasonal admissions coded as influenza, we estimated an average of 21,500 excess hospitalization associated with influenza per season, which corresponds to 36.4 cases per 100,000. Most of the excess hospitalisations concerned older individuals (> 65 years) and children (0–4 years) with 86 and 125 cases per 100,000, respectively. Large variations were observed across regions. Overall, the total estimated hospital burden associated with influenza (including respiratory and cardiocirculatory conditions) was approximately €123 m per year. While the in-hospital mortality for admissions with a primary diagnosis of influenza was very low (~ 150 cases per season), cases increased dramatically for primary diagnoses of influenza and pneumonia (about 9,500 cases per season). The average seasonal in-hospital deaths attributable to influenza were equal to 2,775 cases.ConclusionsOur findings suggest a remarkable underestimation of the burden of influenza, mostly in the older population but not neglectable in younger individuals. Our results may aid the management of current and future flu seasons and should be used for policy making (e.g., vaccine strategies) and operation management choices (e.g., planning and staffing beds during influenza peaks). Overall, the present study supports the need for increased testing for influenza in Italy to tackle the current underestimation of influenza burden.

Population-based Influenza and Respiratory Syncytial Virus Hospitalizations and In-hospital Mortality Rates Among Mexican Children Less Than Five Years of Age.

Population-based information regarding the impact of respiratory syncytial virus (RSV) and influenza on hospital admissions and mortality is scant for many countries. Prospective testing of RSV and influenza virus was undertaken in patients <5 years old admitted to hospital with acute respiratory infection (ARI) between July, 2014 and June, 2015, and mortality rates for children living in 3 municipalities in the state of San Luis Potosí were calculated. During the 12-month study period, 790 children living in these municipalities were admitted with ARI. RSV was detected in 245 (31%) and influenza in 47 (5.9%). History of preterm birth was recorded for 112 children on admission. For children <5 years old, ARI-, RSV- and influenza-associated admission rates were 23.2, 7.2 and 1.4 (per 1000 population), respectively. The corresponding admission rates per 1000 infants <1 year old were 78, 25.2 and 4.4. Preterm infant admission rates were 2 times higher than those of term infants. Six children died; RSV was detected in 4 (66.6%) of the deceased, while no deaths were associated with influenza. ARI and RSV in-hospital mortality rates for children <5 years were 0.18 and 0.12 per 1000 population. ARI and RSV mortality rates in preterm infants were 7 and 14 times higher than in term infants, respectively. RSV was associated with both high admission and in-hospital mortality rates in children <5 years old. Specific interventions, such as active or passive immunization, to prevent RSV infections are required to reduce ARI-associated infant mortality.

Effectiveness of Influenza Vaccination and Early Antiviral Treatment in Reducing Pneumonia Risk in Severe Influenza Cases.

Influenza vaccination may be effective in preventing influenza infection and may reduce the risk of influenza-associated pneumonia. The study aim was to evaluate the effect of influenza vaccination in preventing pneumonia when it failed to prevent influenza hospitalization. This was a case-control study comparing hospitalized cases of influenza with and without pneumonia in patients aged ≥18 years in 16 hospitals in Catalonia over 10 influenza seasons (2010-11 to 2019-20). Data on sociodemographic, virological characteristics, comorbidities, vaccination history, and antiviral treatment were collected and analysed. The crude odds ratio (OR) and adjusted OR (aOR) with the corresponding 95% confidence interval (CI) values were calculated. In total, 5080 patients hospitalized for severe influenza were included, 63.5% (3224/5080) of whom had pneumonia-mostly men (56.8%; 1830/3224) and mostly in the ≥75 age group (39.3%; 1267/3224)-and of whom 14.0% died (451/3224). Virus A and virus B accounted for 78.1% (2518/3224) and 21.9% (705/3224) of influenza types, respectively. Starting antiviral treatment ≤48 h after symptom onset (aOR = 0.69; 95%CI: 0.53-0.90) and a history of seasonal influenza vaccination (aOR = 0.85; 95%CI: 0.72-0.98) were protective factors in developing pneumonia. Adherence to seasonal influenza vaccination and starting antiviral treatment within 48 h of symptom onset can reduce pneumonia risk in severe influenza cases.

Non-COVID-19 hospitalization and mortality during the COVID-19 pandemic in Iran: a longitudinal assessment of 41 million people in 2019-2022.

During a COVID-19 pandemic, it is imperative to investigate the outcomes of all non-COVID-19 diseases. This study determines hospital admissions and mortality rates related to non-COVID-19 diseases during the COVID-19 pandemic among 41 million Iranians. This nationwide retrospective study used data from the Iran Health Insurance Organization. From September 23, 2019, to Feb 19, 2022, there were four study periods: pre-pandemic (Sept 23-Feb 19, 2020), first peak (Mar 20-Apr 19, 2020), first year (Feb 20, 2020-Feb 18, 2021), and the second year (Feb 19, 2021-Feb 19, 2022) following the pandemic. Cause-specific hospital admission and in-hospital mortality are the main outcomes analyzed based on age and sex. Negative binomial regression was used to estimate the monthly adjusted Incidence Rate Ratio (IRR) to compare hospital admission rates in aggregated data. A logistic regression was used to estimate the monthly adjusted in-hospital mortality Odds Ratio (OR) for different pandemic periods. During the study there were 6,522,114 non-COVID-19 hospital admissions and 139,679 deaths. Prior to the COVID-19 outbreak, the standardized hospital admission rate per million person-month was 7115.19, which decreased to 2856.35 during the first peak (IRR 0.40, [0.25-0.64]). In-hospital mortality also increased from 20.20 to 31.99 (OR 2.05, [1.97-2.13]). All age and sex groups had decreased admission rates, except for females at productive ages. Two years after the COVID-19 outbreak, the non-COVID-19 hospital admission rate (IRR 1.25, [1.13-1.40]) and mortality rate (OR 1.05, [1.04-1.07]) increased compared to the rates before the pandemic. The respiratory disease admission rate decreased in the first (IRR 0.23, [0.17-0.31]) and second years (IRR 0.35, [0.26-0.47] compared to the rate before the pandemic. There was a significant reduction in hospitalizations for pneumonia (IRR 0.30, [0.21-0.42]), influenza (IRR 0.04, [0.03-0.06]) and COPD (IRR 0.39, [0.23-0.65]) during the second year. There was a significant and continuous rise in the hematological admission rate during the study, reaching 186.99 per million person-month in the second year, reflecting an IRR of 2.84 [2.42-3.33]compared to the pre-pandemic period. The mortality rates of mental disorders (OR 2.15, [1.65-2.78]) and musculoskeletal (OR 1.48, [1.20-1.82), nervous system (OR 1.42, [1.26-1.60]), metabolic (OR 1.99, [1.80-2.19]) and circulatory diseases (OR 1.35, [1.31-1.39]) increased in the second year compare to pre-pandemic. Myocardial infarction (OR 1.33, [1.19-1.49]), heart failure (OR 1.59, [1.35-1.87]) and stroke (OR 1.35, [1.24-1.47]) showed an increase in mortality rates without changes in hospitalization. In the era of COVID-19, the changes seem to have had a long-term effect on non-COVID-19 diseases. Countries should prepare for similar crises in the future to ensure medical services are not suspended.

Vaccine effectiveness against influenza hospitalisation in adults during the 2022/2023 mixed season of influenza A(H1N1)pdm09, A(H3N2) and B circulation, Europe: VEBIS SARI VE hospital network.

We conducted a multicentre hospital-based test-negative case-control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: -23-36); 20% (95% CI: -4-39) against A(H3N2) and 56% (95% CI: 22-75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.