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Hospitalization Is an Underutilized Opportunity to Vaccinate for Influenza

      Influenza is a common viral cause of acute respiratory tract infections with substantial morbidity and mortality. In the 2017 to 2018 season, influenza resulted in an estimated 49 million illnesses, 960,000 hospitalizations, and 79,000 influenza-associated deaths.
      • Rolfes M.A.
      • Flannery B.
      • Chung J.
      • et al.
      Effects of influenza vaccination in the United States during the 2017-2018 influenza season.
      Although the Advisory Committee on Immunization Practices recommends annual influenza vaccination for all individuals 6 months and older without a contraindication, vaccination rates remain low.
      Estimates of influenza vaccination coverage among adults—United States, 2017–18 flu season.
      Unfortunately, influenza vaccination rates declined by 6% in 2017 to 2018 to only 37% in those 18 years and older. Influenza vaccine effectiveness (ie, how well the influenza vaccine worked in preventing influenza-like outpatient illness) in 2017 to 2018 was less than optimal at 38% (95% CI, 31%-43%).
      • Rolfes M.A.
      • Flannery B.
      • Chung J.
      • et al.
      Effects of influenza vaccination in the United States during the 2017-2018 influenza season.
      It is important to remember that influenza vaccine has 0% vaccine effectiveness when it is not administered. Despite less than optimal vaccine effectiveness in 2017 to 2018, influenza vaccination in the United States in 2017 to 2018 still prevented an estimated 7.1 million illnesses, 3.7 million medical visits, 109,000 hospitalizations, and 8000 deaths. In addition, even when influenza vaccination “fails” and a patient is hospitalized with influenza, data suggest that influenza vaccination can still protect against severe outcomes such as intensive care unit admission and death in some seasons.
      • Arriola C.
      • Garg S.
      • Anderson E.J.
      • et al.
      Influenza vaccination modifies disease severity among community-dwelling adults hospitalized with influenza.
      The Joint Commission

      The Joint Commission. Specifications manual for national hospital inpatient quality measures, http://www.jointcommission.org/specifications_manual_for_national_hospital_inpatient_quality_measures.aspx. Accessed April 4, 2018, 2018.

      has considered influenza vaccination a metric of quality care for patients admitted to hospitals from October to March. Reasons cited by physicians for not vaccinating during inpatient hospitalization have included that the patient may not be sufficiently stable and that the acute care setting is not appropriate for vaccination.
      • Bloom H.G.
      • Wheeler D.A.
      • Linn J.
      A managed care organization’s attempt to increase influenza and pneumococcal immunizations for older adults in an acute care setting.
      Yet studies have shown that strategies to improve inpatient flu vaccination are feasible and can improve influenza vaccination rates up to 78%.
      • Rees S.
      • Stevens L.
      • Drayton J.
      • Engledow N.
      • Sanders J.
      Improving inpatient pneumococcal and influenza vaccination rates.
      Despite recommendations for inpatient influenza vaccine administration, until recently we have known very little about the immune response to influenza vaccination and the safety of inpatient influenza vaccination. Concern exists that the immune response to influenza vaccination in those hospitalized could be blunted because of age, admitting condition, or other comorbidities. A small prospective study compared the immune response to influenza vaccination in 51 inpatient high-risk adults (≥65 years of age or 18-64 years of age with a diagnosis of congestive heart failure, cardiomyopathy, diabetes mellitus, chronic obstructive pulmonary disease, liver disease, asthma, or kidney disease) with the response observed in 177 adults vaccinated in an ambulatory setting.
      • Berry B.B.
      • Ehlert D.A.
      • Battiola R.J.
      • Sedmak G.
      Influenza vaccination is safe and immunogenic when administered to hospitalized patients.
      They found similar rates of seroconversion and 4-fold or greater increase in antibody titers to at least 1 influenza strain. We recently published data on serological responses to influenza vaccination in 95 hospitalized adults enrolled in the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community study.
      • Pratt C.Q.
      • Zhu Y.
      • Grijalva C.G.
      • et al.
      Serological response to influenza vaccination among adults hospitalized with community-acquired pneumonia.
      Factors associated with non-seroconversion included diabetes mellitus, previous receipt of seasonal influenza vaccine, detection of a bacterial pathogen, and baseline seropositivity to influenza B (Yamagata lineage).
      • Pratt C.Q.
      • Zhu Y.
      • Grijalva C.G.
      • et al.
      Serological response to influenza vaccination among adults hospitalized with community-acquired pneumonia.
      Despite these limitations, almost 70% of patients had a 4-fold or greater increase in antibody titers to at least 1 influenza strain and seropositive titers (≥1:40) were achieved in more than 50% against influenza A strains and about 75% against influenza B. Thus, data suggest that inpatient adults vaccinated against influenza can achieve a seropositive titer and most develop a 4-fold or greater increase in antibody titers to 1 or more influenza strain.
      Although limited data from the same prospective study of high-risk inpatient adults found that 12% of hospitalized patients had injection site soreness,
      • Berry B.B.
      • Ehlert D.A.
      • Battiola R.J.
      • Sedmak G.
      Influenza vaccination is safe and immunogenic when administered to hospitalized patients.
      extensive safety data supporting inpatient influenza vaccination were lacking. Tartof et al
      • Tartof S.Y.
      • Qian L.
      • Rieg G.K.
      • et al.
      Safety of seasonal influenza vaccination in hospitalized surgical patients: a cohort study.
      previously published data from a retrospective cohort study using the Kaiser Permanente Southern California (KPSC) health care system and found no difference in inpatient or emergency department visits, postdischarge fever, or need for evaluation of infection in those surgical patients who received influenza vaccine before hospital discharge compared with those who did not.
      In this issue of Mayo Clinic Proceedings, Tartof et al
      • Tartof S.
      • Qian L.
      • Liu A.
      • et al.
      Safety of influenza vaccination administered during hospitalization.
      expand their previous findings by evaluating data from 3 influenza seasons from KPSC including all hospitalized patients 6 months and older (influenza vaccination eligible) without a contraindication to influenza vaccination. The study evaluated several outcomes of interest (fever, clinical laboratory evaluations for infection, outpatient and emergency department visits, and hospital readmissions) within 7 days after hospital discharge in patients vaccinated during hospitalization compared with those who did not receive influenza vaccination or received influenza vaccination at other times. Tartof et al used propensity score analyses with inverse probability of treatment weighting to account for potential biases due to observed confounders that existed between these groups at baseline.
      This study had several salient findings. First, after adjustment, there was no overall increase in fever (relative risk [RR], 0.80; 95% CI, 0.68-0.93), clinical evaluation for infection (RR, 0.95; 95% CI, 0.92-0.98), outpatient visits (RR, 0.97; 95% CI, 0.95-0.99), or risk of readmission (RR, 0.88%; 95% CI, 0.83-0.95) within 7 days of discharge in comparison to those who were not vaccinated during hospitalization, although some differences existed in subgroups. Second, the rates of influenza immunization in hospitalized patients remain low despite current recommendations. Finally, among those who were not vaccinated at hospital discharge, only 26% ultimately received influenza vaccination in the remainder of the influenza season.
      • Tartof S.
      • Qian L.
      • Liu A.
      • et al.
      Safety of influenza vaccination administered during hospitalization.
      These data provide clear support for the safety and necessity of vaccinating patients before hospital discharge.
      These influenza vaccination data after hospital discharge are critical real-world data and represent a “best-case” scenario because KPSC is known to be heavily focused on prevention strategies (eg, influenza vaccination). Because of fragmentation of care, achieving the 26% rate of influenza vaccination after hospital discharge observed in this study will not be possible in many other health care systems. The recent data on influenza vaccine safety and immunogenicity and the poor rate of influenza immunization after hospital discharge should spur us on to ensure influenza vaccine administration before hospital discharge.
      Despite the important reassurance that this study provides about influenza vaccination safety in hospitalized patients, many questions remain. These questions include uncertainty as to why it is so difficult to administer influenza vaccination after hospitalization (eg, vaccine refusal, lack of health care encounters); whether these safety data also apply for high-dose and adjuvanted influenza vaccination; whether influenza vaccination during hospitalization prevents subsequent influenza-like illness, laboratory-confirmed influenza illness, and influenza-related rehospitalization; and whether these safety data also apply to hospitalized children (children were included but comprised <5% of all hospital admissions
      • Tartof S.
      • Qian L.
      • Liu A.
      • et al.
      Safety of influenza vaccination administered during hospitalization.
      ).
      Annual influenza vaccination remains an effective strategy to protect against influenza and its associated complications. After more than half a century of routine use, there are still many unanswered questions about influenza vaccination, and better influenza vaccines are urgently needed. Because most hospitalized patients who do not receive influenza vaccination before hospital discharge remain influenza unvaccinated, improving influenza vaccination before hospital discharge is an important and underutilized tool for preventing the substantial mortality and morbidity of influenza.

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        • et al.
        Effects of influenza vaccination in the United States during the 2017-2018 influenza season.
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        • et al.
        Influenza vaccination modifies disease severity among community-dwelling adults hospitalized with influenza.
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      2. The Joint Commission. Specifications manual for national hospital inpatient quality measures, http://www.jointcommission.org/specifications_manual_for_national_hospital_inpatient_quality_measures.aspx. Accessed April 4, 2018, 2018.

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