a b s t r a c t

Background: Seasonal influenza is associated with significant healthcare resource utilization. An estimated 490,000 hospitalizations and 34,000 deaths were attributed to influenza during the 2018-2019 season. Despite robust influenza vaccination programs in both the inpatient and outpatient setting, the emergency department (ED) represents a missed opportunity to vaccinate patients at high risk for influenza who do not have access to routine Preventive care. Feasibility and implementation of ED-based influenza vaccination programs have been previously described but have stopped short of describing the predicted health resource impact. The goal of our study was to describe the potential impact of an influenza vaccination program in an urban adult emer- gency department population using historic patient data.

Methods: This was a retrospective study of all encounters within a tertiary care hospital-based ED and three free- standing EDs during influenza season (defined as October 1 - April 30) over a two-years, 2018-2020. Data was obtained from the electronic medical record (EPIC(R)). All ED encounters during the study period were screened for inclusion using ICD 10 codes. Patients with a confirmed positive influenza test and no documented Influenza vaccine for the current season were reviewed for any ED encounter at least 14 days prior to the influenza-positive encounter and during the concurrent influenza season. These ED visits were deemed a missed opportunity to provide vaccination and potentially prevent the influenza-positive encounter. Healthcare resource utilization, including subsequent ED encounters and inpatient admissions, were evaluated for patients with a missed vacci- nation opportunity.

Results: A total of 116,140 ED encounters occurred during the study and were screened for inclusion. Of these, 2115 were influenza-positive encounters, which represented 1963 unique patients. There were 418 patients (21.3%) that had a missed opportunity to be vaccinated during an ED encounter at least 14 days prior to the influenza-positive encounter. Of those with a missed vaccination opportunity, 60 patients (14.4%) had sub- sequent influenza-related encounters, including 69 ED visits and 7 inpatient admissions.

Conclusion: Patients presenting to the ED with influenza frequently had opportunities to be vaccinated during prior ED encounters. An ED-based influenza vaccination program could potentially reduce influenza-related burden on Healthcare resources by preventing future influenza-related ED encounters and hospitalizations.

(C) 2023

1. Background

Influenza has been recognized as a significant cause of morbidity and mortality among the general population, accounting for 13 million med- ical visits, 380,000 hospitalizations, and 28,000 deaths in the 2018-2019 season alone [1]. Moreover, seasonal influenza constitutes a significant

* Corresponding author.

E-mail address: [email protected] (E.L. Simon).

source of healthcare spending, with an estimated Economic burden of

$11.2 billion in 2015 [2].

The Centers for Disease Control (CDC) estimates that national vacci- nation coverage with >=1 dose of the vaccine among adults >=18 years was 45.3% for the 2018-2019 season, which is lower than national coverage goals of 80% annual vaccination for adults aged 18-64 years and 90% for adults over the age of 65 [3].

There continues to be low uptake of the seasonal influenza vaccine in the United States, and multiple reasons have been cited, which

https://doi.org/10.1016/j.ajem.2023.03.019

0735-6757/(C) 2023

include a perceived lack of vaccine efficacy, concerns regarding vaccine side effects, and barriers to vaccine access [4]. Patients also report a lack of convenience, including transportation, time, and cost, as a primary reason they do not receive the seasonal influenza vaccine [4]. Despite the public perception of decreased vaccine efficacy, seasonal influenza vaccines have repeatedly been shown to be efficacious, having recently prevented an estimated 4.4 million influenza illnesses, 58,000 hospital- izations, and 3500 deaths for the 2018-2019 season [5,6]. There is a sig- nificant societal, economic, and ethical incentive to increase seasonal influenza vaccination coverage.

The majority of influenza vaccines are administered within the pri- mary care setting. However, the proportion of Americans with identifi- able primary care providers has fallen over the years [7]. Widening care gaps primarily affect males, racial minorities, low socioeconomic status, and uninsured populations [7]. In many areas, Emergency Departments (EDs) operate as a healthcare “safety net” for underserved populations. EDs increasingly provide not only emergency services but also many primary care services [8].

With over 130 million visits to EDs in the United States annually [9], the ED represents a significant missed opportunity to vaccinate patients for influenza And related complications, especially those who may not have access to routine preventive care [10].

The feasibility and implementation of ED-based influenza vaccination programs have been previously described [10-12]. Influenza vaccination in the ED is supported by the American College of Emergency Physicians and the American Academy of Emergency Medicine [13,14]. These stud- ies have shown improvements in vaccine coverage among ED patients, most willing to be vaccinated, but have stopped short of describing the predicted health resource impact. Therefore, the purpose of this study was to characterize the potential impact of an influenza vaccination program in an urban adult emergency department population using his- torical patient data to determine missed opportunities for vaccination. Specifically, this study aimed to evaluate patients who tested positive for influenza in the ED to determine they had a prior ED encounter within the concurrent influenza season where vaccination could have been administered. This may suggest that their influenza-related encounter may have been prevented if vaccination been previously provided.

1. Methods
   1. Study setting and design

This was a retrospective study of all encounters within a tertiary care hospital-based ED and three freestanding EDs during influenza season (defined as October 1 - April 30) over two years, 2018-2020. The dates were selected to minimize the potential confounding of COVID- 19 infections and preventive measures such as social distancing and masking.

• 1. Study protocol

Data were obtained from the electronic medical record (EMR, EPIC(R)). All ED encounters during the study period where a provider evaluated the patient was screened for inclusion using influenza or re- spiratory infection-related ICD-10 codes. Patients were included if they were confirmed to have a positive influenza test from the index ED encounter. Patients were included more than once if they had

encounter were included to account for time to antibody generation after vaccination. Our healthcare system only utilizes influenza PCR tests which have been shown to have a sensitivity of 98% and specificity of 99% [15]. Influenza vaccination status was queried from the EMR for our health system, which includes vaccinations reported to the Ohio De- partment of Health (ODH). In addition, the most recent influenza vac- cine administration date was obtained to help capture patients who had never been vaccinated in our system compared to patients who had not yet been vaccinated for the current influenza season. Demo- graphic data were obtained for all patients, including age, sex, race, eth- nicity, pregnancy status, insurance or healthcare payer type, and the presence of a medical condition that placed the patient at high risk for complications from influenza. High-risk medical conditions were based on CDC criteria and included pregnancy, chronic pulmonary dis- ease, diabetes, cerebrovascular disease, chronic renal disease, cancer, and human immunodeficiency virus infection. Healthcare resource utilization, which included subsequent ED encounters and inpatient admissions related to influenza, was determined for patients with a missed vaccination opportunity. A subsequent ED or inpatient encounter was deemed influenza-related if the treating ED clinician documented the recent Influenza infection as a contributor. COVID-19 testing was available in mid-February 2020 at the hospital-based ED only. However, testing in influenza-positive patients was completed only for patients with known exposure per institutional protocol.

• 1. Statistical analysis

A convenience sample of all ED encounters between October 1, 2018, to April 30, 2019, and October 1, 2019, to April 30, 2020, was utilized. Descriptive statistics were then used to characterize demographics for patients who met the inclusion criteria for the study. Categorical vari- ables are presented as frequencies and percentages. Comparisons be- tween groups were obtained using Chi-squared tests or Fisher’s exact test. Continuous variables are presented as mean and standard devia- tion, with comparisons performed using t-tests. A significance level of

0.05 was assumed for all tests. Analyses were performed using SAS(R)

Software (Version 9.4, Cary, NC).

1. Results

A total of 116,140 ED encounters occurred during the study and were screened for inclusion. Of these, 2115 were influenza-positive en- counters, which represented 1963 unique patients. Influenza-positive encounters were higher during the 2019-2020 season compared to the 2018-2019 season (Table 1, Fig. 1). In addition, influenza-positive patients were more likely to present to a freestanding ED (n = 1261, 59.6%) than the hospital-based ED (n = 854, 40.4%). The median age was 37 +- 20.9 years; however, nearly 15% of patients were over the age of 65 and thus at higher risk for influenza-related complications (Table 2).

There were 418 patients (21.3%) that had a missed opportunity to be vaccinated during an ED encounter at least 14 days prior to the influenza-positive encounter who did not have a previously docu- mented vaccine in the current influenza season. Missed vaccination opportunities occurred more frequently in young (age 18-64 years)

Table 1

Emergency department encounters.

more than one positive influenza test separated by at least 30 days.

Patients with a confirmed positive influenza test and no documented influenza vaccine for the current season were reviewed for any encoun- ter with a hospital-affiliated ED at least 14 days prior to the influenza- positive encounter and during the concurrent influenza season. These ED visits were deemed a missed opportunity to provide vaccination and potentially prevent the influenza-positive encounter. Only ED encounters that occurred at least 14 days prior to the influenza positive

	HBED	FSED		HBED	FSED		HBED	FSED
All Years	60,423	55,717		854	1261		201	217
2018-2019	30,007	29,351		274	512		76	85
2019-2020	30,416	26,366		580	749		125	132

All encounters Influenza-positive encounters

Missed vaccination opportunities

Fig. 1. Influenza distribution by season.

Table 2 Demographic characteristics.
	All Influenza positive	Missed opportunity	No missed opportunity	p-value
	patients (n = 1963)	patients (n = 418)	(n = 1545)
Age (mean +- SD)	39.3 +- 20.9	40.0 +- 20.5	39.1 +- 21.1	0.4206
Age (years)
< 18, n (%)	275 (14.0)	41 (9.8)	234 (15.2)	0.0204
18-64, n (%)	1421 (72.4)	317 (75.8)	1104 (71.5)
>= 65, n (%)	267 (13.6)	60 (14.4)	207 (13.4)
Sex Male, n (%)	817(41.6)	147 (35.2)	670 (43.4)	0.0026
Race Black	630 (32.1)	185 (44.3)	445 (28.8)	<0.0001
Non-Black	1333 (67.9)	233 (55.7)	1100 (71.2)
Ethnicity Hispanic	22 (1.1)	4 (1.0)	18 (1.2)	0.0367
Not Hispanic	1880 (95.8)	411 (97.9)	1471 (95.2)
Other/Unknown	61 (3.1)	5 (1.2)	56 (3.6)
High Risk Condition
>=1 High Risk Condition	529 (27.0)	157 (37.6)	372 (24.1)	<0.0001
Pregnant	13 (0.7)	13 (3.1)	0 (0.0)	<0.0001
Chronic Pulmonary Disease	314 (16.0)	91 (21.8)	223 (14.4)	0.0003
Diabetes	195 (9.9)	59 (14.1)	136 (8.8)	0.0013
Cerebrovascular Disease	40 (2.0)	15 (3.6)	25 (1.6)	0.0114
Chronic Renal Disease	95 (4.8)	32 (7.6)	63 (4.1)	0.0025
Any Cancer	75 (3.8)	14 (3.3)	61 (4.0)	0.5709
Insurance/Payer Status Medicare	322 (16.4)	88 (21.1)	234 (15.1)	<0.0001
Medicaid	726 (37.0)	208 (49.8)	518 (33.5)
Private Insurance	733 (37.3)	106 (25.4)	627 (40.6)
Self-pay	182 (9.3)	16 (3.8)	166 (10.7)
Influenza Vaccination Any Prior Influenza Vaccine	380 (19.4)	82 (20.0)	298 (19.3)	0.8799
Adequately Immunized Prior	133 (6.8)	0(0.0)	133 (8.6)	<0.0001

Table 3

Healthcare Resource Utilization in Patients with a Missed Vaccination Opportunity.

Inpatient admission at index ED encounter, n (%)	Subsequent healthcare utilization, n (%)	Subsequent ED visits, n	Subsequent inpatient admissions, n
86 (20.5)	60 (14.4)	69	7

female patients who identified as Black race (44.3% vs. 28.8%, p < 0.001) and had at least one High-risk condition (37.6% vs. 24.1%, p < 0.0001). All high-risk conditions were significantly more common in the missed vaccination opportunity group except for any cancer history, with the most prevalent high-risk conditions being chronic pulmonary disease (21.8% vs. 14.4%, p = 0.0003), diabetes (14.1% vs. 8.8%, p = 0.0013),

and chronic renal disease (7.6% vs. 4.1%, p = 0.0025). In addition, patients with a missed opportunity were more likely to be pregnant (3.1% vs. 0.0%, p < 0.001) and have government-sponsored healthcare compared to private insurance or self-pay (p < 0.0001).

Hospital admission at the index ED encounter was required for 86 (20.5%) patients with a missed vaccination opportunity, of which 73 (84.9%) were for patients with government-sponsored healthcare (Medicare [n = 50, 58.1%]; Medicaid [n = 23, 26.7%]). Of those with a missed vaccination opportunity, 60 patients (14.4%) had subsequent influenza-related encounters, including 69 ED visits and 7 inpatient ad- missions (Table 3). All seven subsequent hospitalizations occurred in patients with government-sponsored healthcare, including four with Medicare and three with Medicaid. There was no difference between groups in the number of patients with prior influenza vaccine docu- mented in our system (20.0% vs. 19.3%, p = 0.8799).

1. Discussion

This study demonstrates missed opportunities for influenza vaccina- tion within the ED. >20% of influenza-positive encounters in our institu- tion have a prior ED encounter during which they could have been offered vaccination against influenza. In addition, one in five patients required inpatient admission at the index encounter, and one in seven of these patients required subsequent ED or inpatient encounters for influenza-related complications. These ED encounters and admissions may have been avoided had their influenza vaccine been administered during their ED visit before developing influenza.

ED populations at high risk for influenza-related complications in- clude Patients over the age of 65, those who are uninsured, and those with underlying comorbidities [8,15]. Our historical data demonstrates that patients with missed vaccination opportunities frequently have conditions that place them at higher risk for complications from influ- enza, with 37.6% having at least one high-risk condition. In some urban EDs, over 40% of the ED population meets high-risk criteria, yet most are unvaccinated for influenza [16]. Our data show that pa- tients with high-risk comorbidities are frequently unvaccinated and represent a potential key patient population to target for vaccination campaigns. Previous feasibility studies have shown significant improvements in vaccination distribution to high-risk patients [12,17]. Further, it has been demonstrated that high-risk patients, some of whom are seen repeatedly throughout the year in EDs, rep- resent a targetable population for missed vaccine opportunities [17]. Our study supports this notion; some patients are seen in the ED or admitted to the hospital for influenza-related illness and could have received an influenza vaccine in the ED weeks before their onset of illness.

This study used patient data from three freestanding EDs and one urban hospital-based ED. Of all influenza-positive encounters included, 59.6% of patients presented to a freestanding ED and 52.1% of all identi- fied missed vaccination opportunities took place in a freestanding ED. When considering barriers to influenza vaccination, such as travel to healthcare facilities or geographic locations, our data suggest that implementing ED vaccination programs may be efficacious in reaching patients in hospital-based and freestanding emergency departments.

An ED influenza vaccination program would favorably impact our patient population’s health and mortality, especially in high-risk pa- tients, and would reduce the influenza burden on EDs and hospitals. Prior research has shown that the number needed to treat and prevent influenza for Healthy adults under 65 is 71, and 29 for those 65 and older [18,19]. However, even though the ED represents a prime op- portunity for discussing and administering influenza vaccination to our patients when they are there for something else, it requires addi- tional resources from an already overburdened healthcare system. Successful vaccination campaigns often require ED posters commu- nicating the merits of flu vaccination; public health advertisements recommending vaccination; insurance companies offering discounts for flu vaccination; and buy-in from the hospital and ED staff to vac- cinate patients. Campaigning the Center for Medicare and Medicaid Services for hospital incentives to vaccinate patients is another area of consideration to create a successful vaccination program across the United States.

• 1. Study limitations

This study was limited by its retrospective nature and inherent biases utilizing this study design. Only subjects symptomatic of influenza-like illness and tested for influenza were included. We in- cluded ED and inpatient encounters within our hospital and three free- standing ED facilities. Encounters at facilities outside our health system were not included, which may have underestimated missed vaccination opportunities and subsequent influenza-related healthcare encounters. Only patients who were influenza positive were included. If patients were symptomatic but not tested, or if they did not have any ED ICD- 10 code that was influenza or respiratory illness related, they were not captured by this study. Influenza vaccination status was obtained through the EMR and the ODH, but may not capture patients who re- ceived a vaccination that was not reported to these databases. There was no difference between groups for the number of patients with any prior influenza vaccine documented in our system, suggesting that the observed differences were less likely due to inaccurate or in- complete documentation in the EMR. We assumed patients would have had vaccine efficacy in our study, which may be an overestimation. In our sample, 210 patients (10.3%) who were adequately vaccinated tested positive for influenza later in the season. No interventions in in- fluenza vaccination were studied. We considered a missed opportunity to be any encounter >=14 days prior to the influenza-positive encounter. However, this does not account for patients who would have been ex- posed prior to adequate antibody generation and thus at risk for infec- tion. COVID-19 testing was unavailable at our facilities until February 2020, and testing was restricted according to institutional protocol. Pa- tients who were influenza positive frequently did not have COVID-19 testing performed. Thus, coinfection could not be ruled out and may have contributed to hospitalization rates at index ED encounters or subsequent encounters.

1. Conclusion

Patients presenting to the ED with influenza frequently had opportunities to be vaccinated during prior encounters. Therefore, an ED-based influenza vaccination program could reduce the burden on healthcare resources by preventing future influenza-related ED encoun- ters and hospitalizations.

CRediT authorship contribution statement

Erin L. Simon: Writing - review & editing, Writing - original draft, Supervision, Project administration, Investigation, Conceptualization. Bethany Crouse: Writing - review & editing, Formal analysis, Data curation. Mackenzie Wilson: Writing - original draft. McKinzey Muir: Resources, Data curation. Stephen Sayles: Writing - review & editing. Chris Ramos: Methodology, Formal analysis, Data curation. Michael P. Phelan: Writing - review & editing, Supervision, Conceptualization.

Declaration of Competing Interest

The authors have no conflicts of interest.

References

1. Estimated Flu-Related Illnesses, Medical visits, Hospitalizations, and Deaths in the United States — 2018-2019 Flu Season | CDC. Accessed July 5, 2022. https://www. cdc.gov/flu/about/burden/2018-2019.html; October 4, 2021.
2. Putri WCWS, Muscatello DJ, Stockwell MS, Newall AT. Economic burden of seasonal influenza in the United States. Vaccine. 2018;36(27):3960-6. https://doi.org/10. 1016/j.vaccine.2018.05.057.
3. Flu Vaccination Coverage. United States, 2018-19 Influenza Season | FluVaxView | Seasonal Influenza (Flu) | CDC. Accessed July 5, 2022. https://www.cdc.gov/flu/ fluvaxview/coverage-1819estimates.htm; January 27, 2022.
4. Schmid P, Rauber D, Betsch C, Lidolt G, Denker ML. Barriers of Influenza vaccination intention and behavior - a systematic review of influenza vaccine hesitancy, 2005-2016. PLoS One. 2017;12(1):e0170550. https://doi.org/10.1371/journal.pone. 0170550.
5. CDC. Benefits of Flu Vaccination During 2018-2019 Flu season. Centers for Disease Control and Prevention. Accessed July 5, 2022. https://www.cdc.gov/flu/about/ burden-averted/2018-2019.htm; January 16, 2020.
6. Chung JR, Rolfes MA, Flannery B, et al. Effects of influenza vaccination in the United States during the 2018-2019 influenza season. Clin Infect Dis. 2020;71(8):e368-76. https://doi.org/10.1093/cid/ciz1244.
7. Levine DM, Linder JA, Landon BE. Characteristics of Americans with primary care and changes over time, 2002-2015. JAMA Intern Med. 2020;180(3):463-6. https://doi. org/10.1001/jamainternmed.2019.6282.
8. Trends in the Utilization of Emergency Department Services. 2009-2018. ASPE. https://aspe.hhs.gov/reports/trends-utilization-emergency-department-services- 2009-2018; July 5, 2022.
9. Cairns C, Kang K. National Hospital Ambulatory Medical Care Survey: 2019 emer- gency department summary tables. National Center for Health Statistics (U.S.); 2022. https://doi.org/10.15620/cdc:115748.
10. Slobodkin D, Kitlas J, Zielske P. Opportunities not missed — systematic influenza and pneumococcal immunization in a public inner-city emergency department. Vaccine. 1998;16(19):1795-802. https://doi.org/10.1016/S0264-410X(98)00183-2.
11. Baumer-Mouradian SH, Kleinschmidt A, Servi A, et al. Vaccinating in the emergency department, a novel approach to improve influenza vaccination rates via a quality improvement initiative. Pediatric Quality & Safety. 2020;5(4):e322. https://doi.org/ 10.1097/pq9.0000000000000322.
12. Farrell NM, Lamb M, Baker WE, et al. Operationalizing influenza vaccination in an urban safety-net emergency department. Am J Emerg Med. 2022;52:179-83. https://doi.org/10.1016/j.ajem.2021.12.021.
13. Immunization of Adults and Children in the Emergency Department. Accessed July 5, 2022. https://www.acep.org/patient-care/policy-statements/immunization-of-

adults-and-children-in-the-emergency-department/; 2023.

1. Abraham MK, Perkins J, Vilke GM, Coyne CJ. Influenza in the emergency department: vaccination, diagnosis, and treatment: clinical practice paper approved by American Academy of emergency medicine clinical guidelines committee. J Emerg Med. 2016; 50(3):536-42. https://doi.org/10.1016/j.jemermed.2015.10.013.
2. Maignan M, Viglino D, Hablot M, et al. Diagnostic accuracy of a rapid RT-PCR assay for point-of-care detection of influenza A/B virus at emergency department admis- sion: a prospective evaluation during the 2017/2018 influenza season. PLoS One. 2019;14(5):e0216308. https://doi.org/10.1371/journal.pone.0216308.
3. Hiller KM, Sullivan D. Influenza vaccination in the emergency department: are our patients at risk? J Emerg Med. 2009;37(4):439-43. https://doi.org/10.1016/j. jemermed.2008.08.023.
4. Rimple D, Weiss SJ, Brett M, Ernst AA. An emergency department-based vaccination program: overcoming the barriers for adults at high risk for vaccine-preventable diseases. Acad Emerg Med. 2006;13(9):922-30. https://doi.org/10.1197/j.aem. 2006.04.022.
5. Demicheli V, Jefferson T, Ferroni E, Rivetti A, Di Pietrantonj C. Vaccines for prevent- ing influenza in healthy adults. Cochrane Database Syst Rev. 2018;2(2):CD001269. https://doi.org/10.1002/14651858.CD001269.pub6.
6. Demicheli V, Jefferson T, Di Pietrantonj C, et al. Vaccines for preventing influenza in the elderly. Cochrane Database Syst Rev. 2018;2(2):CD004876. https://doi.org/10. 1002/14651858.CD004876.pub4.