Emergency Medicine

From the Division of Hospital Medicine, University of New Mexico Hospital, Albuquerque (Drs. Bartlett, Pizanis, Angeli, Lacy, and Rogers), Department of Emergency Medicine, University of New Mexico Hospital, Albuquerque (Dr. Scott), and University of New Mexico School of Medicine, Albuquerque (Ms. Baca).

ABSTRACT

Background: Emergency department (ED) crowding is associated with deleterious consequences for patient care and throughput. Admission delays worsen ED crowding. Time to admission (TTA)—the time between an ED admission request and internal medicine (IM) admission orders—can be shortened through implementation of a triage hospitalist role. Limited research is available highlighting the impact of triage hospitalists on throughput, care quality, interprofessional practice, and clinician experience of care.

Methods: A triage hospitalist role was piloted and implemented. Run charts were interpreted using accepted rules for deriving statistically significant conclusions. Statistical analysis was applied to interprofessional practice and clinician experience-of-care survey results.

Results: Following implementation, TTA decreased from 5 hours 19 minutes to 2 hours 8 minutes. Emergency department crowding increased from baseline. The reduction in TTA was associated with decreased time from ED arrival to IM admission request, no change in critical care transfers during the initial 24 hours, and increased admissions to inpatient status. Additionally, decreased TTA was associated with no change in referring hospital transfer rates and no change in hospital medicine length of stay. Interprofessional practice attitudes improved among ED clinicians but not IM clinicians. Clinician experience-of-care results were mixed.

Conclusion: A triage hospitalist role is an effective approach for mitigating admission delays, with no evident adverse clinical consequences. A triage hospitalist alone was incapable of resolving ED crowding issues without a complementary focus on downstream bottlenecks.

Keywords: triage hospitalist, admission delay, quality improvement.

Excess time to admission (TTA), defined as the time between an emergency department (ED) admission request and internal medicine (IM) admission orders, contributes to ED crowding, which is associated with deleterious impacts on patient care and throughput. Prior research has correlated ED crowding with an increase in length of stay (LOS)^1-3 and total inpatient cost,¹ as well as increased inpatient mortality, higher left-without-being-seen rates,⁴ delays in clinically meaningful care,^5,6 and poor patient and clinician satisfaction.^6,7 While various solutions have been proposed to alleviate ED crowding,⁸ excess TTA is one aspect that IM can directly address.

Like many institutions, ours is challenged by ED crowding. Time to admission is a known bottleneck. Underlying factors that contribute to excess TTA include varied admission request volumes in relation to fixed admitting capacity; learner-focused admitting processes; and unreliable strategies for determining whether patients are eligible for ED observation, transfer to an alternative facility, or admission to an alternative primary service.

To address excess TTA, we piloted then implemented a triage hospitalist role, envisioned as responsible for evaluating ED admission requests to IM, making timely determinations of admission appropriateness, and distributing patients to admitting teams. This intervention was selected because of its strengths, including the ability to standardize admission processes, improve the proximity of clinical decision-makers to patient care to reduce delays, and decrease hierarchical imbalances experienced by trainees, and also because the institution expressed a willingness to mitigate its primary weakness (ie, ongoing financial support for sustainability) should it prove successful.

Previously, a triage hospitalist has been defined as “a physician who assesses patients for admission, actively supporting the transition of the patient from the outpatient to the inpatient setting.”⁹ Velásquez et al surveyed 10 academic medical centers and identified significant heterogeneity in the roles and responsibilities of a triage hospitalist.⁹ Limited research addresses the impact of this role on throughput. One report described the volume and source of requests evaluated by a triage hospitalist and the frequency with which the triage hospitalists’ assessment of admission appropriateness aligned with that of the referring clinicians.¹⁰ No prior research is available demonstrating the impact of this role on care quality, interprofessional practice, or clinician experience of care. This article is intended to address these gaps in the literature.

Methods

Setting

The University of New Mexico Hospital has 537 beds and is the only level-1 trauma and academic medical center in the state. On average, approximately 8000 patients register to be seen in the ED per month. Roughly 600 are admitted to IM per month. This study coincided with the COVID-19 pandemic, with low patient volumes in April 2020, overcapacity census starting in May 2020, and markedly high patient volumes in May/June 2020 and November/December 2020. All authors participated in project development, implementation, and analysis.

Preintervention IM Admission Process

When requesting IM admission, ED clinicians (resident, advanced practice provider [APP], or attending) contacted the IM triage person (typically an IM resident physician) by phone or in person. The IM triage person would then assess whether the patient needed critical care consultation (a unique and separate admission pathway), was eligible for ED observation or transfer to an outside hospital, or was clinically appropriate for IM subacute and floor admission. Pending admissions were evaluated in order of severity of illness or based on wait time if severity of illness was equal. Transfers from the intensive care unit (ICU) and referring hospitals were prioritized. Between 7:00 AM and 7:00 PM, patients were typically evaluated by junior team members, with subsequent presentation to an attending, at which time a final admission decision was made. At night, between 7:00 PM and 7:00 AM, 2 IM residents managed triage, admissions, and transfers with an on-call attending physician.

Triage Hospitalist Pilot

Key changes made during the pilot included scheduling an IM attending to serve as triage hospitalist for all IM admission requests from the ED between 7:00 AM and 7:00 PM; requiring that all IM admission requests be initiated by the ED attending and directed to the triage hospitalist; requiring ED attendings to enter into the electronic medical record (EMR) an admission request order (subsequently referred to as ED admission request [EDAR] order); and encouraging bedside handoffs. Eight pilot shifts were completed in November and December 2019.

Measures for Triage Hospitalist Pilot

Data collected included request type (new vs overflow from night) and patient details (name, medical record number). Two time points were recorded: when the EDAR order was entered and when admission orders were entered. Process indicators, including whether the EDAR order was entered and the final triage decision (eg, discharge, IM), were recorded. General feedback was requested at the end of each shift.

Phased Implementation of Triage Hospitalist Role

Triage hospitalist role implementation was approved following the pilot, with additional salary support funded by the institution. A new performance measure (time from admission request to admission order, self-identified goal < 3 hours) was approved by all parties.

In January 2020, the role was scheduled from 7:00 AM to 7:00 PM daily. All hospitalists participated. Based on pilot feedback, IM admission requests could be initiated by an ED attending or an ED APP. In addition to admissions from the ED, the triage hospitalist was tasked with managing ICU, subspecialty, and referring facility transfer requests, as well as staffing some admissions with residents.

In March 2020, to create a single communication pathway while simultaneously hardwiring our measurement strategy, the EDAR order was modified such that it would automatically prompt a 1-way communication to the triage hospitalist using the institution’s secure messaging software. The message included patient name, medical record number, location, ED attending, reason for admission, and consultation priority, as well as 2 questions prompting ED clinicians to reflect on the most common reasons for the triage hospitalist to recommend against IM admission (eligible for admission to other primary service, transfer to alternative hospital).

In July 2020, the triage hospitalist role was scheduled 24 hours a day, 7 days a week, to meet an institutional request. The schedule was divided into a daytime 7:00 AM to 3:00 PM shift, a 3:00 PM to 7:00 PM shift covered by a resident ward team IM attending with additional cross-cover responsibility, and a 7:00 PM to 7:00 AM shift covered by a nocturnist.

Measures for Triage Hospitalist Role

The primary outcome measure was TTA, defined as the time between EDAR (operationalized using EDAR order timestamp) and IM admission decision (operationalized using inpatient bed request order timestamp). Additional outcome measures included the Centers for Medicare & Medicaid Services Electronic Clinical Quality Measure ED-2 (eCQM ED-2), defined as the median time from admit decision to departure from the ED for patients admitted to inpatient status.

Process measures included time between patient arrival to the ED (operationalized using ED registration timestamp) and EDAR and percentage of IM admissions with an EDAR order. Balancing measures included time between bed request order (referred to as the IM admission order) and subsequent admission orders. While the IM admission order prompts an inpatient clinical encounter and inpatient bed assignment, subsequent admission orders are necessary for clinical care. Additional balancing measures included ICU transfer rate within the first 24 hours, referring facility transfer frequency to IM (an indicator of access for patients at outside hospitals), average hospital medicine LOS (operationalized using ED registration timestamp to discharge timestamp), and admission status (inpatient vs observation).

An anonymous preintervention (December 2019) and postintervention (August 2020) survey focusing on interprofessional practice and clinician experience of care was used to obtain feedback from ED and IM attendings, APPs, and trainees. Emergency department clinicians were asked questions pertaining to their IM colleagues and vice versa. A Likert 5-point scale was used to respond.

Data Analysis

The preintervention period was June 1, 2019, to October 31, 2019; the pilot period was November 1, 2019, to December 31, 2019; the staged implementation period was January 1, 2020, to June 30, 2020; and the postintervention period was July 1, 2020, to December 31, 2020. Run charts for outcome, process, and balancing measures were interpreted using rules for deriving statistically significant conclusions.¹¹ Statistical analysis using a t test assuming unequal variances with P < . 05 to indicate statistical significance was applied to experience-of-care results. The study was approved by the Institutional Review Board.

Triage Hospitalist Pilot Time Period

Seventy-four entries were recorded, 56 (75.7%) reflecting new admission requests. Average time between EDAR order and IM admission order was 40 minutes. The EDAR order was entered into the EMR without prompting in 22 (29.7%) cases. In 56 (75.7%) cases, the final triage decision was IM admission. Other dispositions included 3 discharges, 4 transfers, 3 alternative primary service admissions, 1 ED observation, and 7 triage deferrals pending additional workup or stabilization.

Feedback substantiated several benefits, including improved coordination among IM, ED, and consultant clinicians, as well as early admission of seriously ill patients. Feedback also confirmed several expected challenges, including evidence of communication lapses, difficulty with transfer coordinator integration, difficulty hardwiring elements of the verbal and bedside handoff, and perceived high cognitive load for the triage hospitalist. Several unexpected issues included whether ED APPs can request admission independently and how reconsultation is expected to occur if admission is initially deferred.

Triage Hospitalist Implementation Time Period

Time to admission decreased from a baseline pre-pilot average of 5 hours 19 minutes (median, 4 hours 45 minutes) to a postintervention average of 2 hours 8 minutes, with a statistically significant downward shift post intervention (Figure 1).

0523_RFTF_Bartlett_F1.jpg

ED-2 increased from a baseline average of 3 hours 40 minutes (median, 2 hours 39 minutes), with a statistically significant upward shift starting in May 2020 (Figure 2). Time between patient arrival to the ED and EDAR order decreased from a baseline average of 8 hours 47 minutes (median, 8 hours 37 minutes) to a postintervention average of 5 hours 57 minutes, with a statistically significant downward shift post intervention. Percentage of IM admissions with an EDAR order increased from a baseline average of 47% (median, 47%) to 97%, with a statistically significant upward shift starting in January 2020 (Figure 3).

0523_RFTF_Bartlett_F2.jpg

There was no change in observed average time between IM admission order and subsequent admission orders pre and post intervention (16 minutes vs 18 minutes). However, there was a statistically significant shift up to an average of 40 minutes from January through June 2020, which then resolved. The percentage of patients transferred to the ICU within 24 hours of admission to IM did not change (1.1% pre vs 1.4% post intervention). Frequency of patients transferred in from a referring facility also did not change (26/month vs 22/month). Average hospital medicine LOS did not change to a statistically significant degree (6.48 days vs 6.62 days). The percentage of inpatient admissions relative to short stays increased from a baseline of 74.0% (median, 73.6%) to a postintervention average of 82.4%, with a statistically significant shift upward starting March 2020.

0523_RFTF_Bartlett_F3.jpg

Regarding interprofessional practice and clinician experience of care, 122 of 309 preintervention surveys (39.5% response rate) and 98 of 309 postintervention surveys (31.7% response rate) were completed. Pre- and postintervention responses were not linked.

Regarding interprofessional practice, EM residents and EM attendings experienced statistically significant improvements in all interprofessional practice domains (Table 1). Emergency medicine APPs experienced statistically significant improvements post intervention with “I am satisfied with the level of communication with IM hospitalist clinicians” and “Interactions with IM hospitalist clinicians are collaborative” and nonstatistically significant improvement in “Interactions with IM hospitalist clinicians are professional” and “IM hospitalist clinicians treat me with respect.” All EM groups experienced a small but not statistically significant worsening for “Efficiency is more valued than good patient care.” Internal medicine residents experienced statistically significant improvements for “I am satisfied with the level of communication with EM clinicians” and nonstatistically significant improvements for the other 3 domains. Internal medicine attendings experienced nonstatistically significant improvements for “My interactions with ED clinicians are professional,” “EM clinicians treat me with respect,” and “Interactions with EM clinicians are collaborative,” but a nonstatistically significant worsening in “I am satisfied with level of communication with EM clinicians.” Internal medicine residents experienced a nonstatistically significant worsening in “Efficiency is more valued than good patient care,” while IM attendings experienced a nonstatistically significant improvement.

0523_RFTF_Bartlett_T1.jpg

For clinician experience of care, EM residents (P < .001) and attendings (P < .001) experienced statistically significant improvements in “Patients are well informed and involved in the decision to admit,” whereas IM residents and attendings, as well as EM APPs, experienced nonstatistically significant improvements (Table 2). All groups except IM attendings experienced a statistically significant improvement (IM resident P = .011, EM resident P < .001, EM APP P = .001, EM attending P < .001) in “I believe that my patients are evaluated and treated within an appropriate time frame.” Internal medicine attendings felt that this indicator worsened to a nonstatistically significant degree. Post intervention, EM groups experienced a statistically significant worsening in “The process of admitting patients to a UNM IM hospitalist service is difficult,” while IM groups experienced a nonstatistically significant worsening.

0523_RFTF_Bartlett_T2.jpg

Discussion

Implementation of the triage hospitalist role led to a significant reduction in average TTA, from 5 hours 19 minutes to 2 hours 8 minutes. Performance has been sustained at 1 hour 42 minutes on average over the past 6 months. The triage hospitalist was successful at reducing TTA because of their focus on evaluating new admission and transfer requests, deferring other admission responsibilities to on-call admitting teams. Early admission led to no increase in ICU transfers or hospitalist LOS. To ensure that earlier admission reflected improved timeliness of care and that new sources of delay were not being created, we measured the time between IM admission and subsequent admission orders. A statistically significant increase to 40 minutes from January through June 2020 was attributable to the hospitalist acclimating to their new role and the need to standardize workflow. This delay subsequently resolved. An additional benefit of the triage hospitalist was an increase in the proportion of inpatient admissions compared with short stays.

ED-2, an indicator of ED crowding, increased from 3 hours 40 minutes, with a statistically significant upward shift starting May 2020. Increasing ED-2 associated with the triage hospitalist role makes intuitive sense. Patients are admitted 2 hours 40 minutes earlier in their hospital course while downstream bottlenecks preventing patient movement to an inpatient bed remained unchanged. Unfortunately, the COVID-19 pandemic complicates interpretation of ED-2 because the measure reflects institutional capacity to match demand for inpatient beds. Fewer ED registrations and lower hospital medicine census (and resulting inpatient bed availability) in April 2020 during the first COVID-19 surge coincided with an ED-2 nadir of 1 hour 46 minutes. The statistically significant upward shift from May onward reflects ongoing and unprecedented patient volumes. It remains difficult to tease apart the presumed lesser contribution of the triage hospitalist role and presumed larger contribution of high patient volumes on ED-2 increases.

An important complementary change was linkage between the EDAR order and our secure messaging software, creating a single source of admission and transfer requests, prompting early ED clinician consideration of factors that could result in alternative disposition, and ensuring a sustainable data source for TTA. The order did not replace direct communication and included guidance for how triage hospitalists should connect with their ED colleagues. Percentage of IM admissions with the EDAR order increased to 97%. Fallouts are attributed to admissions from non-ED sources (eg, referring facility, endoscopy suite transfers). This communication strategy has been expanded as the primary mechanism of initiating consultation requests between IM and all consulting services.

This intervention was successful from the perspective of ED clinicians. Improvements can be attributed to the simplified admission process, timely patient assessment, a perception that patients are better informed of the decision to admit, and the ability to communicate with the triage hospitalist. Emergency medicine APPs may not have experienced similar improvements due to ongoing perceptions of a hierarchical imbalance. Unfortunately, the small but not statistically significant worsening perspective among ED clinicians that “efficiency is more valued than good patient care” and the statistically significant worsening perspective that “admitting patients to a UNM IM hospitalist service is difficult” may be due to the triage hospitalist responsibility for identifying the roughly 25% of patients who are safe for an alternative disposition.

Internal medicine clinicians experienced no significant changes in attitudes. Underlying causes are likely multifactorial and a focus of ongoing work. Internal medicine residents experienced statistically significant improvements for “I am satisfied with the level of communication with EM clinicians” and nonstatistically significant improvements for the other 3 domains, likely because the intervention enabled them to focus on clinical care rather than the administrative tasks and decision-making complexities inherent to the IM admission process. Internal medicine attendings reported a nonstatistically significant worsening in “I am satisfied with the level of communication with EM clinicians,” which is possibly attributable to challenges connecting with ED attendings after being notified that a new admission is pending. Unfortunately, bedside handoff was not hardwired and is done sporadically. Independent of the data, we believe that the triage hospitalist role has facilitated closer ED-IM relationships by aligning clinical priorities, standardizing processes, improving communication, and reducing sources of hierarchical imbalance and conflict. We expected IM attendings and residents to experience some degree of resolution of the perception that “efficiency is more valued than good patient care” because of the addition of a dedicated triage role. Our data also suggest that IM attendings are less likely to agree that “patients are evaluated and treated within an appropriate time frame.” Both concerns may be linked to the triage hospitalist facing multiple admission and transfer sources with variable arrival rates and variable patient complexity, resulting in high cognitive load and the perception that individual tasks are not completed to the best of their abilities.

To our knowledge, this is the first study assessing the impact of the triage hospitalist role on throughput, clinical care quality, interprofessional practice, and clinician experience of care. In the cross-sectional survey of 10 academic medical centers, 8 had defined triage roles filled by IM attendings, while the remainder had IM attendings supervising trainees.⁹ A complete picture of the prevalence and varying approaches of triage hospitalists models is unknown. Howell et al¹² reported on an approach that reduced admission delays without a resulting increase in mortality or LOS. Our approach differed in several ways, with greater involvement of the triage hospitalist in determining a final admission decision, incorporation of EMR communication, and presence of existing throughput challenges preventing patients from moving seamlessly to an inpatient unit.

Conclusion

We believe this effort was successful for several reasons, including adherence to quality improvement best practices, such as engagement of stakeholders early on, the use of data to inform decision-making, the application of technology to hardwire process, and alignment with institutional priorities. Spread of this intervention will be limited by the financial investment required to start and maintain a triage hospitalist role. A primary limitation of this study is the confounding effect of the COVID-19 pandemic on our analysis. Next steps include identification of clinicians wishing to specialize in triage and expanding triage to include non-IM primary services. Additional research to optimize the triage hospitalist experience of care, as well as to measure improvements in patient-centered outcomes, is necessary.

Corresponding author: Christopher Bartlett, MD, MPH; MSC10 5550, 1 University of New Mexico, Albuquerque, NM 87131; CSBartlett@salud.unm.edu

Disclosures: None reported.

From the Division of Hospital Medicine, University of New Mexico Hospital, Albuquerque (Drs. Bartlett, Pizanis, Angeli, Lacy, and Rogers), Department of Emergency Medicine, University of New Mexico Hospital, Albuquerque (Dr. Scott), and University of New Mexico School of Medicine, Albuquerque (Ms. Baca).

ABSTRACT

Background: Emergency department (ED) crowding is associated with deleterious consequences for patient care and throughput. Admission delays worsen ED crowding. Time to admission (TTA)—the time between an ED admission request and internal medicine (IM) admission orders—can be shortened through implementation of a triage hospitalist role. Limited research is available highlighting the impact of triage hospitalists on throughput, care quality, interprofessional practice, and clinician experience of care.

Methods: A triage hospitalist role was piloted and implemented. Run charts were interpreted using accepted rules for deriving statistically significant conclusions. Statistical analysis was applied to interprofessional practice and clinician experience-of-care survey results.

Results: Following implementation, TTA decreased from 5 hours 19 minutes to 2 hours 8 minutes. Emergency department crowding increased from baseline. The reduction in TTA was associated with decreased time from ED arrival to IM admission request, no change in critical care transfers during the initial 24 hours, and increased admissions to inpatient status. Additionally, decreased TTA was associated with no change in referring hospital transfer rates and no change in hospital medicine length of stay. Interprofessional practice attitudes improved among ED clinicians but not IM clinicians. Clinician experience-of-care results were mixed.

Conclusion: A triage hospitalist role is an effective approach for mitigating admission delays, with no evident adverse clinical consequences. A triage hospitalist alone was incapable of resolving ED crowding issues without a complementary focus on downstream bottlenecks.

Keywords: triage hospitalist, admission delay, quality improvement.

Excess time to admission (TTA), defined as the time between an emergency department (ED) admission request and internal medicine (IM) admission orders, contributes to ED crowding, which is associated with deleterious impacts on patient care and throughput. Prior research has correlated ED crowding with an increase in length of stay (LOS)^1-3 and total inpatient cost,¹ as well as increased inpatient mortality, higher left-without-being-seen rates,⁴ delays in clinically meaningful care,^5,6 and poor patient and clinician satisfaction.^6,7 While various solutions have been proposed to alleviate ED crowding,⁸ excess TTA is one aspect that IM can directly address.

Like many institutions, ours is challenged by ED crowding. Time to admission is a known bottleneck. Underlying factors that contribute to excess TTA include varied admission request volumes in relation to fixed admitting capacity; learner-focused admitting processes; and unreliable strategies for determining whether patients are eligible for ED observation, transfer to an alternative facility, or admission to an alternative primary service.

To address excess TTA, we piloted then implemented a triage hospitalist role, envisioned as responsible for evaluating ED admission requests to IM, making timely determinations of admission appropriateness, and distributing patients to admitting teams. This intervention was selected because of its strengths, including the ability to standardize admission processes, improve the proximity of clinical decision-makers to patient care to reduce delays, and decrease hierarchical imbalances experienced by trainees, and also because the institution expressed a willingness to mitigate its primary weakness (ie, ongoing financial support for sustainability) should it prove successful.

Previously, a triage hospitalist has been defined as “a physician who assesses patients for admission, actively supporting the transition of the patient from the outpatient to the inpatient setting.”⁹ Velásquez et al surveyed 10 academic medical centers and identified significant heterogeneity in the roles and responsibilities of a triage hospitalist.⁹ Limited research addresses the impact of this role on throughput. One report described the volume and source of requests evaluated by a triage hospitalist and the frequency with which the triage hospitalists’ assessment of admission appropriateness aligned with that of the referring clinicians.¹⁰ No prior research is available demonstrating the impact of this role on care quality, interprofessional practice, or clinician experience of care. This article is intended to address these gaps in the literature.

Methods

Setting

The University of New Mexico Hospital has 537 beds and is the only level-1 trauma and academic medical center in the state. On average, approximately 8000 patients register to be seen in the ED per month. Roughly 600 are admitted to IM per month. This study coincided with the COVID-19 pandemic, with low patient volumes in April 2020, overcapacity census starting in May 2020, and markedly high patient volumes in May/June 2020 and November/December 2020. All authors participated in project development, implementation, and analysis.

Preintervention IM Admission Process

When requesting IM admission, ED clinicians (resident, advanced practice provider [APP], or attending) contacted the IM triage person (typically an IM resident physician) by phone or in person. The IM triage person would then assess whether the patient needed critical care consultation (a unique and separate admission pathway), was eligible for ED observation or transfer to an outside hospital, or was clinically appropriate for IM subacute and floor admission. Pending admissions were evaluated in order of severity of illness or based on wait time if severity of illness was equal. Transfers from the intensive care unit (ICU) and referring hospitals were prioritized. Between 7:00 AM and 7:00 PM, patients were typically evaluated by junior team members, with subsequent presentation to an attending, at which time a final admission decision was made. At night, between 7:00 PM and 7:00 AM, 2 IM residents managed triage, admissions, and transfers with an on-call attending physician.

Triage Hospitalist Pilot

Key changes made during the pilot included scheduling an IM attending to serve as triage hospitalist for all IM admission requests from the ED between 7:00 AM and 7:00 PM; requiring that all IM admission requests be initiated by the ED attending and directed to the triage hospitalist; requiring ED attendings to enter into the electronic medical record (EMR) an admission request order (subsequently referred to as ED admission request [EDAR] order); and encouraging bedside handoffs. Eight pilot shifts were completed in November and December 2019.

Measures for Triage Hospitalist Pilot

Data collected included request type (new vs overflow from night) and patient details (name, medical record number). Two time points were recorded: when the EDAR order was entered and when admission orders were entered. Process indicators, including whether the EDAR order was entered and the final triage decision (eg, discharge, IM), were recorded. General feedback was requested at the end of each shift.

Phased Implementation of Triage Hospitalist Role

Triage hospitalist role implementation was approved following the pilot, with additional salary support funded by the institution. A new performance measure (time from admission request to admission order, self-identified goal < 3 hours) was approved by all parties.

In January 2020, the role was scheduled from 7:00 AM to 7:00 PM daily. All hospitalists participated. Based on pilot feedback, IM admission requests could be initiated by an ED attending or an ED APP. In addition to admissions from the ED, the triage hospitalist was tasked with managing ICU, subspecialty, and referring facility transfer requests, as well as staffing some admissions with residents.

In March 2020, to create a single communication pathway while simultaneously hardwiring our measurement strategy, the EDAR order was modified such that it would automatically prompt a 1-way communication to the triage hospitalist using the institution’s secure messaging software. The message included patient name, medical record number, location, ED attending, reason for admission, and consultation priority, as well as 2 questions prompting ED clinicians to reflect on the most common reasons for the triage hospitalist to recommend against IM admission (eligible for admission to other primary service, transfer to alternative hospital).

In July 2020, the triage hospitalist role was scheduled 24 hours a day, 7 days a week, to meet an institutional request. The schedule was divided into a daytime 7:00 AM to 3:00 PM shift, a 3:00 PM to 7:00 PM shift covered by a resident ward team IM attending with additional cross-cover responsibility, and a 7:00 PM to 7:00 AM shift covered by a nocturnist.

Measures for Triage Hospitalist Role

The primary outcome measure was TTA, defined as the time between EDAR (operationalized using EDAR order timestamp) and IM admission decision (operationalized using inpatient bed request order timestamp). Additional outcome measures included the Centers for Medicare & Medicaid Services Electronic Clinical Quality Measure ED-2 (eCQM ED-2), defined as the median time from admit decision to departure from the ED for patients admitted to inpatient status.

Process measures included time between patient arrival to the ED (operationalized using ED registration timestamp) and EDAR and percentage of IM admissions with an EDAR order. Balancing measures included time between bed request order (referred to as the IM admission order) and subsequent admission orders. While the IM admission order prompts an inpatient clinical encounter and inpatient bed assignment, subsequent admission orders are necessary for clinical care. Additional balancing measures included ICU transfer rate within the first 24 hours, referring facility transfer frequency to IM (an indicator of access for patients at outside hospitals), average hospital medicine LOS (operationalized using ED registration timestamp to discharge timestamp), and admission status (inpatient vs observation).

An anonymous preintervention (December 2019) and postintervention (August 2020) survey focusing on interprofessional practice and clinician experience of care was used to obtain feedback from ED and IM attendings, APPs, and trainees. Emergency department clinicians were asked questions pertaining to their IM colleagues and vice versa. A Likert 5-point scale was used to respond.

Data Analysis

The preintervention period was June 1, 2019, to October 31, 2019; the pilot period was November 1, 2019, to December 31, 2019; the staged implementation period was January 1, 2020, to June 30, 2020; and the postintervention period was July 1, 2020, to December 31, 2020. Run charts for outcome, process, and balancing measures were interpreted using rules for deriving statistically significant conclusions.¹¹ Statistical analysis using a t test assuming unequal variances with P < . 05 to indicate statistical significance was applied to experience-of-care results. The study was approved by the Institutional Review Board.

Triage Hospitalist Pilot Time Period

Seventy-four entries were recorded, 56 (75.7%) reflecting new admission requests. Average time between EDAR order and IM admission order was 40 minutes. The EDAR order was entered into the EMR without prompting in 22 (29.7%) cases. In 56 (75.7%) cases, the final triage decision was IM admission. Other dispositions included 3 discharges, 4 transfers, 3 alternative primary service admissions, 1 ED observation, and 7 triage deferrals pending additional workup or stabilization.

Feedback substantiated several benefits, including improved coordination among IM, ED, and consultant clinicians, as well as early admission of seriously ill patients. Feedback also confirmed several expected challenges, including evidence of communication lapses, difficulty with transfer coordinator integration, difficulty hardwiring elements of the verbal and bedside handoff, and perceived high cognitive load for the triage hospitalist. Several unexpected issues included whether ED APPs can request admission independently and how reconsultation is expected to occur if admission is initially deferred.

Triage Hospitalist Implementation Time Period

Time to admission decreased from a baseline pre-pilot average of 5 hours 19 minutes (median, 4 hours 45 minutes) to a postintervention average of 2 hours 8 minutes, with a statistically significant downward shift post intervention (Figure 1).

0523_RFTF_Bartlett_F1.jpg

ED-2 increased from a baseline average of 3 hours 40 minutes (median, 2 hours 39 minutes), with a statistically significant upward shift starting in May 2020 (Figure 2). Time between patient arrival to the ED and EDAR order decreased from a baseline average of 8 hours 47 minutes (median, 8 hours 37 minutes) to a postintervention average of 5 hours 57 minutes, with a statistically significant downward shift post intervention. Percentage of IM admissions with an EDAR order increased from a baseline average of 47% (median, 47%) to 97%, with a statistically significant upward shift starting in January 2020 (Figure 3).

0523_RFTF_Bartlett_F2.jpg

There was no change in observed average time between IM admission order and subsequent admission orders pre and post intervention (16 minutes vs 18 minutes). However, there was a statistically significant shift up to an average of 40 minutes from January through June 2020, which then resolved. The percentage of patients transferred to the ICU within 24 hours of admission to IM did not change (1.1% pre vs 1.4% post intervention). Frequency of patients transferred in from a referring facility also did not change (26/month vs 22/month). Average hospital medicine LOS did not change to a statistically significant degree (6.48 days vs 6.62 days). The percentage of inpatient admissions relative to short stays increased from a baseline of 74.0% (median, 73.6%) to a postintervention average of 82.4%, with a statistically significant shift upward starting March 2020.

0523_RFTF_Bartlett_F3.jpg

Regarding interprofessional practice and clinician experience of care, 122 of 309 preintervention surveys (39.5% response rate) and 98 of 309 postintervention surveys (31.7% response rate) were completed. Pre- and postintervention responses were not linked.

Regarding interprofessional practice, EM residents and EM attendings experienced statistically significant improvements in all interprofessional practice domains (Table 1). Emergency medicine APPs experienced statistically significant improvements post intervention with “I am satisfied with the level of communication with IM hospitalist clinicians” and “Interactions with IM hospitalist clinicians are collaborative” and nonstatistically significant improvement in “Interactions with IM hospitalist clinicians are professional” and “IM hospitalist clinicians treat me with respect.” All EM groups experienced a small but not statistically significant worsening for “Efficiency is more valued than good patient care.” Internal medicine residents experienced statistically significant improvements for “I am satisfied with the level of communication with EM clinicians” and nonstatistically significant improvements for the other 3 domains. Internal medicine attendings experienced nonstatistically significant improvements for “My interactions with ED clinicians are professional,” “EM clinicians treat me with respect,” and “Interactions with EM clinicians are collaborative,” but a nonstatistically significant worsening in “I am satisfied with level of communication with EM clinicians.” Internal medicine residents experienced a nonstatistically significant worsening in “Efficiency is more valued than good patient care,” while IM attendings experienced a nonstatistically significant improvement.

0523_RFTF_Bartlett_T1.jpg

For clinician experience of care, EM residents (P < .001) and attendings (P < .001) experienced statistically significant improvements in “Patients are well informed and involved in the decision to admit,” whereas IM residents and attendings, as well as EM APPs, experienced nonstatistically significant improvements (Table 2). All groups except IM attendings experienced a statistically significant improvement (IM resident P = .011, EM resident P < .001, EM APP P = .001, EM attending P < .001) in “I believe that my patients are evaluated and treated within an appropriate time frame.” Internal medicine attendings felt that this indicator worsened to a nonstatistically significant degree. Post intervention, EM groups experienced a statistically significant worsening in “The process of admitting patients to a UNM IM hospitalist service is difficult,” while IM groups experienced a nonstatistically significant worsening.

0523_RFTF_Bartlett_T2.jpg

Discussion

Implementation of the triage hospitalist role led to a significant reduction in average TTA, from 5 hours 19 minutes to 2 hours 8 minutes. Performance has been sustained at 1 hour 42 minutes on average over the past 6 months. The triage hospitalist was successful at reducing TTA because of their focus on evaluating new admission and transfer requests, deferring other admission responsibilities to on-call admitting teams. Early admission led to no increase in ICU transfers or hospitalist LOS. To ensure that earlier admission reflected improved timeliness of care and that new sources of delay were not being created, we measured the time between IM admission and subsequent admission orders. A statistically significant increase to 40 minutes from January through June 2020 was attributable to the hospitalist acclimating to their new role and the need to standardize workflow. This delay subsequently resolved. An additional benefit of the triage hospitalist was an increase in the proportion of inpatient admissions compared with short stays.

ED-2, an indicator of ED crowding, increased from 3 hours 40 minutes, with a statistically significant upward shift starting May 2020. Increasing ED-2 associated with the triage hospitalist role makes intuitive sense. Patients are admitted 2 hours 40 minutes earlier in their hospital course while downstream bottlenecks preventing patient movement to an inpatient bed remained unchanged. Unfortunately, the COVID-19 pandemic complicates interpretation of ED-2 because the measure reflects institutional capacity to match demand for inpatient beds. Fewer ED registrations and lower hospital medicine census (and resulting inpatient bed availability) in April 2020 during the first COVID-19 surge coincided with an ED-2 nadir of 1 hour 46 minutes. The statistically significant upward shift from May onward reflects ongoing and unprecedented patient volumes. It remains difficult to tease apart the presumed lesser contribution of the triage hospitalist role and presumed larger contribution of high patient volumes on ED-2 increases.

An important complementary change was linkage between the EDAR order and our secure messaging software, creating a single source of admission and transfer requests, prompting early ED clinician consideration of factors that could result in alternative disposition, and ensuring a sustainable data source for TTA. The order did not replace direct communication and included guidance for how triage hospitalists should connect with their ED colleagues. Percentage of IM admissions with the EDAR order increased to 97%. Fallouts are attributed to admissions from non-ED sources (eg, referring facility, endoscopy suite transfers). This communication strategy has been expanded as the primary mechanism of initiating consultation requests between IM and all consulting services.

This intervention was successful from the perspective of ED clinicians. Improvements can be attributed to the simplified admission process, timely patient assessment, a perception that patients are better informed of the decision to admit, and the ability to communicate with the triage hospitalist. Emergency medicine APPs may not have experienced similar improvements due to ongoing perceptions of a hierarchical imbalance. Unfortunately, the small but not statistically significant worsening perspective among ED clinicians that “efficiency is more valued than good patient care” and the statistically significant worsening perspective that “admitting patients to a UNM IM hospitalist service is difficult” may be due to the triage hospitalist responsibility for identifying the roughly 25% of patients who are safe for an alternative disposition.

Internal medicine clinicians experienced no significant changes in attitudes. Underlying causes are likely multifactorial and a focus of ongoing work. Internal medicine residents experienced statistically significant improvements for “I am satisfied with the level of communication with EM clinicians” and nonstatistically significant improvements for the other 3 domains, likely because the intervention enabled them to focus on clinical care rather than the administrative tasks and decision-making complexities inherent to the IM admission process. Internal medicine attendings reported a nonstatistically significant worsening in “I am satisfied with the level of communication with EM clinicians,” which is possibly attributable to challenges connecting with ED attendings after being notified that a new admission is pending. Unfortunately, bedside handoff was not hardwired and is done sporadically. Independent of the data, we believe that the triage hospitalist role has facilitated closer ED-IM relationships by aligning clinical priorities, standardizing processes, improving communication, and reducing sources of hierarchical imbalance and conflict. We expected IM attendings and residents to experience some degree of resolution of the perception that “efficiency is more valued than good patient care” because of the addition of a dedicated triage role. Our data also suggest that IM attendings are less likely to agree that “patients are evaluated and treated within an appropriate time frame.” Both concerns may be linked to the triage hospitalist facing multiple admission and transfer sources with variable arrival rates and variable patient complexity, resulting in high cognitive load and the perception that individual tasks are not completed to the best of their abilities.

To our knowledge, this is the first study assessing the impact of the triage hospitalist role on throughput, clinical care quality, interprofessional practice, and clinician experience of care. In the cross-sectional survey of 10 academic medical centers, 8 had defined triage roles filled by IM attendings, while the remainder had IM attendings supervising trainees.⁹ A complete picture of the prevalence and varying approaches of triage hospitalists models is unknown. Howell et al¹² reported on an approach that reduced admission delays without a resulting increase in mortality or LOS. Our approach differed in several ways, with greater involvement of the triage hospitalist in determining a final admission decision, incorporation of EMR communication, and presence of existing throughput challenges preventing patients from moving seamlessly to an inpatient unit.

Conclusion

We believe this effort was successful for several reasons, including adherence to quality improvement best practices, such as engagement of stakeholders early on, the use of data to inform decision-making, the application of technology to hardwire process, and alignment with institutional priorities. Spread of this intervention will be limited by the financial investment required to start and maintain a triage hospitalist role. A primary limitation of this study is the confounding effect of the COVID-19 pandemic on our analysis. Next steps include identification of clinicians wishing to specialize in triage and expanding triage to include non-IM primary services. Additional research to optimize the triage hospitalist experience of care, as well as to measure improvements in patient-centered outcomes, is necessary.

Corresponding author: Christopher Bartlett, MD, MPH; MSC10 5550, 1 University of New Mexico, Albuquerque, NM 87131; CSBartlett@salud.unm.edu

Disclosures: None reported.

From the Division of Hospital Medicine, University of New Mexico Hospital, Albuquerque (Drs. Bartlett, Pizanis, Angeli, Lacy, and Rogers), Department of Emergency Medicine, University of New Mexico Hospital, Albuquerque (Dr. Scott), and University of New Mexico School of Medicine, Albuquerque (Ms. Baca).

ABSTRACT

Background: Emergency department (ED) crowding is associated with deleterious consequences for patient care and throughput. Admission delays worsen ED crowding. Time to admission (TTA)—the time between an ED admission request and internal medicine (IM) admission orders—can be shortened through implementation of a triage hospitalist role. Limited research is available highlighting the impact of triage hospitalists on throughput, care quality, interprofessional practice, and clinician experience of care.

Methods: A triage hospitalist role was piloted and implemented. Run charts were interpreted using accepted rules for deriving statistically significant conclusions. Statistical analysis was applied to interprofessional practice and clinician experience-of-care survey results.

Results: Following implementation, TTA decreased from 5 hours 19 minutes to 2 hours 8 minutes. Emergency department crowding increased from baseline. The reduction in TTA was associated with decreased time from ED arrival to IM admission request, no change in critical care transfers during the initial 24 hours, and increased admissions to inpatient status. Additionally, decreased TTA was associated with no change in referring hospital transfer rates and no change in hospital medicine length of stay. Interprofessional practice attitudes improved among ED clinicians but not IM clinicians. Clinician experience-of-care results were mixed.

Conclusion: A triage hospitalist role is an effective approach for mitigating admission delays, with no evident adverse clinical consequences. A triage hospitalist alone was incapable of resolving ED crowding issues without a complementary focus on downstream bottlenecks.

Keywords: triage hospitalist, admission delay, quality improvement.

Excess time to admission (TTA), defined as the time between an emergency department (ED) admission request and internal medicine (IM) admission orders, contributes to ED crowding, which is associated with deleterious impacts on patient care and throughput. Prior research has correlated ED crowding with an increase in length of stay (LOS)^1-3 and total inpatient cost,¹ as well as increased inpatient mortality, higher left-without-being-seen rates,⁴ delays in clinically meaningful care,^5,6 and poor patient and clinician satisfaction.^6,7 While various solutions have been proposed to alleviate ED crowding,⁸ excess TTA is one aspect that IM can directly address.

Like many institutions, ours is challenged by ED crowding. Time to admission is a known bottleneck. Underlying factors that contribute to excess TTA include varied admission request volumes in relation to fixed admitting capacity; learner-focused admitting processes; and unreliable strategies for determining whether patients are eligible for ED observation, transfer to an alternative facility, or admission to an alternative primary service.

To address excess TTA, we piloted then implemented a triage hospitalist role, envisioned as responsible for evaluating ED admission requests to IM, making timely determinations of admission appropriateness, and distributing patients to admitting teams. This intervention was selected because of its strengths, including the ability to standardize admission processes, improve the proximity of clinical decision-makers to patient care to reduce delays, and decrease hierarchical imbalances experienced by trainees, and also because the institution expressed a willingness to mitigate its primary weakness (ie, ongoing financial support for sustainability) should it prove successful.

Previously, a triage hospitalist has been defined as “a physician who assesses patients for admission, actively supporting the transition of the patient from the outpatient to the inpatient setting.”⁹ Velásquez et al surveyed 10 academic medical centers and identified significant heterogeneity in the roles and responsibilities of a triage hospitalist.⁹ Limited research addresses the impact of this role on throughput. One report described the volume and source of requests evaluated by a triage hospitalist and the frequency with which the triage hospitalists’ assessment of admission appropriateness aligned with that of the referring clinicians.¹⁰ No prior research is available demonstrating the impact of this role on care quality, interprofessional practice, or clinician experience of care. This article is intended to address these gaps in the literature.

Methods

Setting

The University of New Mexico Hospital has 537 beds and is the only level-1 trauma and academic medical center in the state. On average, approximately 8000 patients register to be seen in the ED per month. Roughly 600 are admitted to IM per month. This study coincided with the COVID-19 pandemic, with low patient volumes in April 2020, overcapacity census starting in May 2020, and markedly high patient volumes in May/June 2020 and November/December 2020. All authors participated in project development, implementation, and analysis.

Preintervention IM Admission Process

When requesting IM admission, ED clinicians (resident, advanced practice provider [APP], or attending) contacted the IM triage person (typically an IM resident physician) by phone or in person. The IM triage person would then assess whether the patient needed critical care consultation (a unique and separate admission pathway), was eligible for ED observation or transfer to an outside hospital, or was clinically appropriate for IM subacute and floor admission. Pending admissions were evaluated in order of severity of illness or based on wait time if severity of illness was equal. Transfers from the intensive care unit (ICU) and referring hospitals were prioritized. Between 7:00 AM and 7:00 PM, patients were typically evaluated by junior team members, with subsequent presentation to an attending, at which time a final admission decision was made. At night, between 7:00 PM and 7:00 AM, 2 IM residents managed triage, admissions, and transfers with an on-call attending physician.

Triage Hospitalist Pilot

Key changes made during the pilot included scheduling an IM attending to serve as triage hospitalist for all IM admission requests from the ED between 7:00 AM and 7:00 PM; requiring that all IM admission requests be initiated by the ED attending and directed to the triage hospitalist; requiring ED attendings to enter into the electronic medical record (EMR) an admission request order (subsequently referred to as ED admission request [EDAR] order); and encouraging bedside handoffs. Eight pilot shifts were completed in November and December 2019.

Measures for Triage Hospitalist Pilot

Data collected included request type (new vs overflow from night) and patient details (name, medical record number). Two time points were recorded: when the EDAR order was entered and when admission orders were entered. Process indicators, including whether the EDAR order was entered and the final triage decision (eg, discharge, IM), were recorded. General feedback was requested at the end of each shift.

Phased Implementation of Triage Hospitalist Role

Triage hospitalist role implementation was approved following the pilot, with additional salary support funded by the institution. A new performance measure (time from admission request to admission order, self-identified goal < 3 hours) was approved by all parties.

In January 2020, the role was scheduled from 7:00 AM to 7:00 PM daily. All hospitalists participated. Based on pilot feedback, IM admission requests could be initiated by an ED attending or an ED APP. In addition to admissions from the ED, the triage hospitalist was tasked with managing ICU, subspecialty, and referring facility transfer requests, as well as staffing some admissions with residents.

In March 2020, to create a single communication pathway while simultaneously hardwiring our measurement strategy, the EDAR order was modified such that it would automatically prompt a 1-way communication to the triage hospitalist using the institution’s secure messaging software. The message included patient name, medical record number, location, ED attending, reason for admission, and consultation priority, as well as 2 questions prompting ED clinicians to reflect on the most common reasons for the triage hospitalist to recommend against IM admission (eligible for admission to other primary service, transfer to alternative hospital).

In July 2020, the triage hospitalist role was scheduled 24 hours a day, 7 days a week, to meet an institutional request. The schedule was divided into a daytime 7:00 AM to 3:00 PM shift, a 3:00 PM to 7:00 PM shift covered by a resident ward team IM attending with additional cross-cover responsibility, and a 7:00 PM to 7:00 AM shift covered by a nocturnist.

Measures for Triage Hospitalist Role

The primary outcome measure was TTA, defined as the time between EDAR (operationalized using EDAR order timestamp) and IM admission decision (operationalized using inpatient bed request order timestamp). Additional outcome measures included the Centers for Medicare & Medicaid Services Electronic Clinical Quality Measure ED-2 (eCQM ED-2), defined as the median time from admit decision to departure from the ED for patients admitted to inpatient status.

Process measures included time between patient arrival to the ED (operationalized using ED registration timestamp) and EDAR and percentage of IM admissions with an EDAR order. Balancing measures included time between bed request order (referred to as the IM admission order) and subsequent admission orders. While the IM admission order prompts an inpatient clinical encounter and inpatient bed assignment, subsequent admission orders are necessary for clinical care. Additional balancing measures included ICU transfer rate within the first 24 hours, referring facility transfer frequency to IM (an indicator of access for patients at outside hospitals), average hospital medicine LOS (operationalized using ED registration timestamp to discharge timestamp), and admission status (inpatient vs observation).

An anonymous preintervention (December 2019) and postintervention (August 2020) survey focusing on interprofessional practice and clinician experience of care was used to obtain feedback from ED and IM attendings, APPs, and trainees. Emergency department clinicians were asked questions pertaining to their IM colleagues and vice versa. A Likert 5-point scale was used to respond.

Data Analysis

The preintervention period was June 1, 2019, to October 31, 2019; the pilot period was November 1, 2019, to December 31, 2019; the staged implementation period was January 1, 2020, to June 30, 2020; and the postintervention period was July 1, 2020, to December 31, 2020. Run charts for outcome, process, and balancing measures were interpreted using rules for deriving statistically significant conclusions.¹¹ Statistical analysis using a t test assuming unequal variances with P < . 05 to indicate statistical significance was applied to experience-of-care results. The study was approved by the Institutional Review Board.

Triage Hospitalist Pilot Time Period

Seventy-four entries were recorded, 56 (75.7%) reflecting new admission requests. Average time between EDAR order and IM admission order was 40 minutes. The EDAR order was entered into the EMR without prompting in 22 (29.7%) cases. In 56 (75.7%) cases, the final triage decision was IM admission. Other dispositions included 3 discharges, 4 transfers, 3 alternative primary service admissions, 1 ED observation, and 7 triage deferrals pending additional workup or stabilization.

Feedback substantiated several benefits, including improved coordination among IM, ED, and consultant clinicians, as well as early admission of seriously ill patients. Feedback also confirmed several expected challenges, including evidence of communication lapses, difficulty with transfer coordinator integration, difficulty hardwiring elements of the verbal and bedside handoff, and perceived high cognitive load for the triage hospitalist. Several unexpected issues included whether ED APPs can request admission independently and how reconsultation is expected to occur if admission is initially deferred.

Triage Hospitalist Implementation Time Period

Time to admission decreased from a baseline pre-pilot average of 5 hours 19 minutes (median, 4 hours 45 minutes) to a postintervention average of 2 hours 8 minutes, with a statistically significant downward shift post intervention (Figure 1).

0523_RFTF_Bartlett_F1.jpg

ED-2 increased from a baseline average of 3 hours 40 minutes (median, 2 hours 39 minutes), with a statistically significant upward shift starting in May 2020 (Figure 2). Time between patient arrival to the ED and EDAR order decreased from a baseline average of 8 hours 47 minutes (median, 8 hours 37 minutes) to a postintervention average of 5 hours 57 minutes, with a statistically significant downward shift post intervention. Percentage of IM admissions with an EDAR order increased from a baseline average of 47% (median, 47%) to 97%, with a statistically significant upward shift starting in January 2020 (Figure 3).

0523_RFTF_Bartlett_F2.jpg

There was no change in observed average time between IM admission order and subsequent admission orders pre and post intervention (16 minutes vs 18 minutes). However, there was a statistically significant shift up to an average of 40 minutes from January through June 2020, which then resolved. The percentage of patients transferred to the ICU within 24 hours of admission to IM did not change (1.1% pre vs 1.4% post intervention). Frequency of patients transferred in from a referring facility also did not change (26/month vs 22/month). Average hospital medicine LOS did not change to a statistically significant degree (6.48 days vs 6.62 days). The percentage of inpatient admissions relative to short stays increased from a baseline of 74.0% (median, 73.6%) to a postintervention average of 82.4%, with a statistically significant shift upward starting March 2020.

0523_RFTF_Bartlett_F3.jpg

Regarding interprofessional practice and clinician experience of care, 122 of 309 preintervention surveys (39.5% response rate) and 98 of 309 postintervention surveys (31.7% response rate) were completed. Pre- and postintervention responses were not linked.

Regarding interprofessional practice, EM residents and EM attendings experienced statistically significant improvements in all interprofessional practice domains (Table 1). Emergency medicine APPs experienced statistically significant improvements post intervention with “I am satisfied with the level of communication with IM hospitalist clinicians” and “Interactions with IM hospitalist clinicians are collaborative” and nonstatistically significant improvement in “Interactions with IM hospitalist clinicians are professional” and “IM hospitalist clinicians treat me with respect.” All EM groups experienced a small but not statistically significant worsening for “Efficiency is more valued than good patient care.” Internal medicine residents experienced statistically significant improvements for “I am satisfied with the level of communication with EM clinicians” and nonstatistically significant improvements for the other 3 domains. Internal medicine attendings experienced nonstatistically significant improvements for “My interactions with ED clinicians are professional,” “EM clinicians treat me with respect,” and “Interactions with EM clinicians are collaborative,” but a nonstatistically significant worsening in “I am satisfied with level of communication with EM clinicians.” Internal medicine residents experienced a nonstatistically significant worsening in “Efficiency is more valued than good patient care,” while IM attendings experienced a nonstatistically significant improvement.

0523_RFTF_Bartlett_T1.jpg

For clinician experience of care, EM residents (P < .001) and attendings (P < .001) experienced statistically significant improvements in “Patients are well informed and involved in the decision to admit,” whereas IM residents and attendings, as well as EM APPs, experienced nonstatistically significant improvements (Table 2). All groups except IM attendings experienced a statistically significant improvement (IM resident P = .011, EM resident P < .001, EM APP P = .001, EM attending P < .001) in “I believe that my patients are evaluated and treated within an appropriate time frame.” Internal medicine attendings felt that this indicator worsened to a nonstatistically significant degree. Post intervention, EM groups experienced a statistically significant worsening in “The process of admitting patients to a UNM IM hospitalist service is difficult,” while IM groups experienced a nonstatistically significant worsening.

0523_RFTF_Bartlett_T2.jpg

Discussion

Implementation of the triage hospitalist role led to a significant reduction in average TTA, from 5 hours 19 minutes to 2 hours 8 minutes. Performance has been sustained at 1 hour 42 minutes on average over the past 6 months. The triage hospitalist was successful at reducing TTA because of their focus on evaluating new admission and transfer requests, deferring other admission responsibilities to on-call admitting teams. Early admission led to no increase in ICU transfers or hospitalist LOS. To ensure that earlier admission reflected improved timeliness of care and that new sources of delay were not being created, we measured the time between IM admission and subsequent admission orders. A statistically significant increase to 40 minutes from January through June 2020 was attributable to the hospitalist acclimating to their new role and the need to standardize workflow. This delay subsequently resolved. An additional benefit of the triage hospitalist was an increase in the proportion of inpatient admissions compared with short stays.

ED-2, an indicator of ED crowding, increased from 3 hours 40 minutes, with a statistically significant upward shift starting May 2020. Increasing ED-2 associated with the triage hospitalist role makes intuitive sense. Patients are admitted 2 hours 40 minutes earlier in their hospital course while downstream bottlenecks preventing patient movement to an inpatient bed remained unchanged. Unfortunately, the COVID-19 pandemic complicates interpretation of ED-2 because the measure reflects institutional capacity to match demand for inpatient beds. Fewer ED registrations and lower hospital medicine census (and resulting inpatient bed availability) in April 2020 during the first COVID-19 surge coincided with an ED-2 nadir of 1 hour 46 minutes. The statistically significant upward shift from May onward reflects ongoing and unprecedented patient volumes. It remains difficult to tease apart the presumed lesser contribution of the triage hospitalist role and presumed larger contribution of high patient volumes on ED-2 increases.

An important complementary change was linkage between the EDAR order and our secure messaging software, creating a single source of admission and transfer requests, prompting early ED clinician consideration of factors that could result in alternative disposition, and ensuring a sustainable data source for TTA. The order did not replace direct communication and included guidance for how triage hospitalists should connect with their ED colleagues. Percentage of IM admissions with the EDAR order increased to 97%. Fallouts are attributed to admissions from non-ED sources (eg, referring facility, endoscopy suite transfers). This communication strategy has been expanded as the primary mechanism of initiating consultation requests between IM and all consulting services.

This intervention was successful from the perspective of ED clinicians. Improvements can be attributed to the simplified admission process, timely patient assessment, a perception that patients are better informed of the decision to admit, and the ability to communicate with the triage hospitalist. Emergency medicine APPs may not have experienced similar improvements due to ongoing perceptions of a hierarchical imbalance. Unfortunately, the small but not statistically significant worsening perspective among ED clinicians that “efficiency is more valued than good patient care” and the statistically significant worsening perspective that “admitting patients to a UNM IM hospitalist service is difficult” may be due to the triage hospitalist responsibility for identifying the roughly 25% of patients who are safe for an alternative disposition.

Internal medicine clinicians experienced no significant changes in attitudes. Underlying causes are likely multifactorial and a focus of ongoing work. Internal medicine residents experienced statistically significant improvements for “I am satisfied with the level of communication with EM clinicians” and nonstatistically significant improvements for the other 3 domains, likely because the intervention enabled them to focus on clinical care rather than the administrative tasks and decision-making complexities inherent to the IM admission process. Internal medicine attendings reported a nonstatistically significant worsening in “I am satisfied with the level of communication with EM clinicians,” which is possibly attributable to challenges connecting with ED attendings after being notified that a new admission is pending. Unfortunately, bedside handoff was not hardwired and is done sporadically. Independent of the data, we believe that the triage hospitalist role has facilitated closer ED-IM relationships by aligning clinical priorities, standardizing processes, improving communication, and reducing sources of hierarchical imbalance and conflict. We expected IM attendings and residents to experience some degree of resolution of the perception that “efficiency is more valued than good patient care” because of the addition of a dedicated triage role. Our data also suggest that IM attendings are less likely to agree that “patients are evaluated and treated within an appropriate time frame.” Both concerns may be linked to the triage hospitalist facing multiple admission and transfer sources with variable arrival rates and variable patient complexity, resulting in high cognitive load and the perception that individual tasks are not completed to the best of their abilities.

To our knowledge, this is the first study assessing the impact of the triage hospitalist role on throughput, clinical care quality, interprofessional practice, and clinician experience of care. In the cross-sectional survey of 10 academic medical centers, 8 had defined triage roles filled by IM attendings, while the remainder had IM attendings supervising trainees.⁹ A complete picture of the prevalence and varying approaches of triage hospitalists models is unknown. Howell et al¹² reported on an approach that reduced admission delays without a resulting increase in mortality or LOS. Our approach differed in several ways, with greater involvement of the triage hospitalist in determining a final admission decision, incorporation of EMR communication, and presence of existing throughput challenges preventing patients from moving seamlessly to an inpatient unit.

Conclusion

We believe this effort was successful for several reasons, including adherence to quality improvement best practices, such as engagement of stakeholders early on, the use of data to inform decision-making, the application of technology to hardwire process, and alignment with institutional priorities. Spread of this intervention will be limited by the financial investment required to start and maintain a triage hospitalist role. A primary limitation of this study is the confounding effect of the COVID-19 pandemic on our analysis. Next steps include identification of clinicians wishing to specialize in triage and expanding triage to include non-IM primary services. Additional research to optimize the triage hospitalist experience of care, as well as to measure improvements in patient-centered outcomes, is necessary.

Corresponding author: Christopher Bartlett, MD, MPH; MSC10 5550, 1 University of New Mexico, Albuquerque, NM 87131; CSBartlett@salud.unm.edu

Disclosures: None reported.

From the Institute for Healthcare Improvement, Boston, MA (Dr. Abid); Continuous Quality Improvement and Patient Safety Department, Armed Forces Hospitals Taif Region, Taif, Saudi Arabia (Dr. Abid); Primary and Secondary Healthcare Department, Government of Punjab, Lahore, Pakistan (Dr. Ahmed); Infection Prevention and Control Department, Armed Forces Hospitals Taif Region, Taif, Saudi Arabia (Dr. Din); Internal Medicine Department, Greater Baltimore Medical Center, Baltimore, MD (Dr. Abid); Department of Anesthesiology and Critical Care, DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX (Dr. Ratnani).

Diagnostic errors are defined by the National Academies of Sciences, Engineering, and Medicine (NASEM) as the failure to either establish an accurate and timely explanation of the patient’s health problem(s) or communicate that explanation to the patient.¹ According to a report by the Institute of Medicine, diagnostic errors account for a substantial number of adverse events in health care, affecting an estimated 12 million Americans each year.¹ Diagnostic errors are a common and serious issue in health care systems, with studies estimating that 5% to 15% of all diagnoses are incorrect.¹ Such errors can result in unnecessary treatments, delays in necessary treatments, and harm to patients. The high prevalence of diagnostic errors in primary care has been identified as a global issue.² While many factors contribute to diagnostic errors, the complex nature of health care systems, the limited processing capacity of human cognition, and deficiencies in interpersonal patient-clinician communication are primary contributors.^3,4

Discussions around the redesign of health care systems to reduce diagnostic errors have been at the forefront of medical research for years.^2,4 To decrease diagnostic errors in health care, a comprehensive strategy is necessary. This strategy should focus on utilizing both human experience (HX) in health care and artificial intelligence (AI) technologies to transform health care systems into proactive, patient-centered, and safer systems, specifically concerning diagnostic errors.¹

Human Experience and Diagnostic Errors

The role of HX in health care cannot be overstated. The HX in health care integrates the sum of all interactions, every encounter among patients, families and care partners, and the health care workforce.⁵ Patients and their families have a unique perspective on their health care experiences that can provide valuable insight into potential diagnostic errors.⁶ The new definition of diagnostic errors introduced in the 2015 NASEM report emphasized the significance of effective communication during the diagnostic procedure.¹ Engaging patients and their families in the diagnostic process can improve communication, improve diagnostic accuracy, and help to identify errors before they cause harm.⁷ However, many patients and families feel that they are not listened to or taken seriously by health care providers, and may not feel comfortable sharing information that they feel is important.⁸ To address this, health care systems can implement programs that encourage patients and families to be more engaged in the diagnostic process, such as shared decision-making, patient portals, and patient and family advisory councils.⁹ Health care systems must prioritize patient-centered care, teamwork, and communication. Patients and their families must be actively engaged in their care, and health care providers must be willing to work collaboratively and listen to patients’ concerns.^6,10

Health care providers also bring their own valuable experiences and expertise to the diagnostic process, as they are often the ones on the front lines of patient care. However, health care providers may not always feel comfortable reporting errors or near misses, and may not have the time or resources to participate in quality improvement initiatives. To address this, health care systems can implement programs that encourage providers to report errors and near misses, such as anonymous reporting systems, just-culture initiatives, and peer review.¹¹ Creating a culture of teamwork and collaboration among health care providers can improve the accuracy of diagnoses and reduce the risk of errors.¹²

A key factor in utilizing HX to reduce diagnostic errors is effective communication. Communication breakdowns among health care providers, patients, and their families are a common contributing factor resulting in diagnostic errors.² Strategies to improve communication include using clear and concise language, involving patients and their families in the decision-making process, and utilizing electronic health records (EHRs) to ensure that all health care providers have access to relevant, accurate, and up-to-date patient information.^4,13,14

Another important aspect of utilizing HX in health care to reduce diagnostic errors is the need to recognize and address cognitive biases that may influence diagnostic decisions.³ Cognitive biases are common in health care and can lead to errors in diagnosis. For example, confirmation bias, which is the tendency to look for information that confirms preexisting beliefs, can lead providers to overlook important diagnostic information.¹⁵ Biases such as anchoring bias, premature closure, and confirmation bias can lead to incorrect diagnoses and can be difficult to recognize and overcome. Addressing cognitive biases requires a commitment to self-reflection and self-awareness among health care providers as well as structured training of health care providers to improve their diagnostic reasoning skills and reduce the risk of cognitive errors.¹⁵ By implementing these strategies around HX in health care, health care systems can become more patient-centered and reduce the likelihood of diagnostic errors (Figure).

0523_Perspectives_F.jpg

Artificial intelligence has the potential to significantly reduce diagnostic errors in health care (Figure), and its role in health care is rapidly expanding. AI technologies such as machine learning (ML) and natural language processing (NLP) have the potential to significantly reduce diagnostic errors by augmenting human cognition and improving access to relevant patient data.^1,16 Machine learning algorithms can analyze large amounts of patient data sets to identify patterns and risk factors and predict patient outcomes, which can aid health care providers in making accurate diagnoses.¹⁷ Artificial intelligence can also help to address some of the communication breakdowns that contribute to diagnostic errors.¹⁸ Natural language processing can improve the accuracy of EHR documentation and reduce the associated clinician burden, making it easier for providers to access relevant patient information and communicate more effectively with each other.¹⁸

In health care, AI can be used to analyze medical images, laboratory results, genomic data, and EHRs to identify potential diagnoses and flag patients who may be at risk for diagnostic errors. One of the primary benefits of AI in health care is its ability to process large amounts of data quickly and accurately.¹⁹ This can be particularly valuable in diagnosing rare or complex conditions. Machine learning algorithms can analyze patient data to identify subtle patterns that may not be apparent to human providers.¹⁶ This can lead to earlier and more accurate diagnoses, which can reduce diagnostic errors and improve patient outcomes.¹⁷ One example of the application of AI in health care is the use of computer-aided detection (CAD) software to analyze medical images. This software can help radiologists detect abnormalities in medical images that may be missed by the human eye, such as early-stage breast cancer.²⁰ Another example is the use of NLP and ML to analyze unstructured data in EHRs, such as physician notes, to identify potential diagnoses and flag patients who may be at risk for diagnostic errors.²¹ A recent study showed that using NLP on EHRs for screening and detecting individuals at risk for psychosis can considerably enhance the prognostic accuracy of psychosis risk calculators.²² This can help identify patients who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes. On the same note, ML-based severe sepsis prediction algorithms have been shown to reduce the average length of stay and in-hospital mortality rate.²³

However, there are also concerns about the use of AI in health care, including the potential for bias and the risk of overreliance on AI. Bias can occur when AI algorithms are trained on data that is not representative of the population being analyzed, leading to inaccurate or unfair results, hence, perpetuating and exacerbating existing biases in health care.²⁴ Over-reliance on AI can occur when health care providers rely too heavily on AI algorithms and fail to consider other important information, such as the lived experience of patients, families, and health care providers. Addressing these concerns will require ongoing efforts to ensure that AI technologies are developed and implemented in an ethical and responsible manner.²⁵

Conclusion

Reducing diagnostic errors is a critical goal for health care systems, and requires a comprehensive approach that utilizes both HX and AI technologies. Engaging patients and their families in the diagnostic process, promoting teamwork and collaboration among health care providers, addressing cognitive biases, and harnessing the power of AI can all contribute to more accurate diagnoses and better patient outcomes. By integrating the lived experience of patients, families, and health care providers with AI technologies, health care systems can be redesigned to become more proactive, safer, and patient-centered in identifying potential health problems and reducing the risk of diagnostic errors, ensuring that patients receive the care they need and deserve.

Corresponding author: Iqbal Ratnani, Department of Anesthesiology and Critical Care, DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin St, Houston, TX 77030; IRatnani@houstonmethodist.org

Disclosures: None reported.

From the Institute for Healthcare Improvement, Boston, MA (Dr. Abid); Continuous Quality Improvement and Patient Safety Department, Armed Forces Hospitals Taif Region, Taif, Saudi Arabia (Dr. Abid); Primary and Secondary Healthcare Department, Government of Punjab, Lahore, Pakistan (Dr. Ahmed); Infection Prevention and Control Department, Armed Forces Hospitals Taif Region, Taif, Saudi Arabia (Dr. Din); Internal Medicine Department, Greater Baltimore Medical Center, Baltimore, MD (Dr. Abid); Department of Anesthesiology and Critical Care, DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX (Dr. Ratnani).

Diagnostic errors are defined by the National Academies of Sciences, Engineering, and Medicine (NASEM) as the failure to either establish an accurate and timely explanation of the patient’s health problem(s) or communicate that explanation to the patient.¹ According to a report by the Institute of Medicine, diagnostic errors account for a substantial number of adverse events in health care, affecting an estimated 12 million Americans each year.¹ Diagnostic errors are a common and serious issue in health care systems, with studies estimating that 5% to 15% of all diagnoses are incorrect.¹ Such errors can result in unnecessary treatments, delays in necessary treatments, and harm to patients. The high prevalence of diagnostic errors in primary care has been identified as a global issue.² While many factors contribute to diagnostic errors, the complex nature of health care systems, the limited processing capacity of human cognition, and deficiencies in interpersonal patient-clinician communication are primary contributors.^3,4

Discussions around the redesign of health care systems to reduce diagnostic errors have been at the forefront of medical research for years.^2,4 To decrease diagnostic errors in health care, a comprehensive strategy is necessary. This strategy should focus on utilizing both human experience (HX) in health care and artificial intelligence (AI) technologies to transform health care systems into proactive, patient-centered, and safer systems, specifically concerning diagnostic errors.¹

Human Experience and Diagnostic Errors

The role of HX in health care cannot be overstated. The HX in health care integrates the sum of all interactions, every encounter among patients, families and care partners, and the health care workforce.⁵ Patients and their families have a unique perspective on their health care experiences that can provide valuable insight into potential diagnostic errors.⁶ The new definition of diagnostic errors introduced in the 2015 NASEM report emphasized the significance of effective communication during the diagnostic procedure.¹ Engaging patients and their families in the diagnostic process can improve communication, improve diagnostic accuracy, and help to identify errors before they cause harm.⁷ However, many patients and families feel that they are not listened to or taken seriously by health care providers, and may not feel comfortable sharing information that they feel is important.⁸ To address this, health care systems can implement programs that encourage patients and families to be more engaged in the diagnostic process, such as shared decision-making, patient portals, and patient and family advisory councils.⁹ Health care systems must prioritize patient-centered care, teamwork, and communication. Patients and their families must be actively engaged in their care, and health care providers must be willing to work collaboratively and listen to patients’ concerns.^6,10

Health care providers also bring their own valuable experiences and expertise to the diagnostic process, as they are often the ones on the front lines of patient care. However, health care providers may not always feel comfortable reporting errors or near misses, and may not have the time or resources to participate in quality improvement initiatives. To address this, health care systems can implement programs that encourage providers to report errors and near misses, such as anonymous reporting systems, just-culture initiatives, and peer review.¹¹ Creating a culture of teamwork and collaboration among health care providers can improve the accuracy of diagnoses and reduce the risk of errors.¹²

A key factor in utilizing HX to reduce diagnostic errors is effective communication. Communication breakdowns among health care providers, patients, and their families are a common contributing factor resulting in diagnostic errors.² Strategies to improve communication include using clear and concise language, involving patients and their families in the decision-making process, and utilizing electronic health records (EHRs) to ensure that all health care providers have access to relevant, accurate, and up-to-date patient information.^4,13,14

Another important aspect of utilizing HX in health care to reduce diagnostic errors is the need to recognize and address cognitive biases that may influence diagnostic decisions.³ Cognitive biases are common in health care and can lead to errors in diagnosis. For example, confirmation bias, which is the tendency to look for information that confirms preexisting beliefs, can lead providers to overlook important diagnostic information.¹⁵ Biases such as anchoring bias, premature closure, and confirmation bias can lead to incorrect diagnoses and can be difficult to recognize and overcome. Addressing cognitive biases requires a commitment to self-reflection and self-awareness among health care providers as well as structured training of health care providers to improve their diagnostic reasoning skills and reduce the risk of cognitive errors.¹⁵ By implementing these strategies around HX in health care, health care systems can become more patient-centered and reduce the likelihood of diagnostic errors (Figure).

0523_Perspectives_F.jpg

Artificial intelligence has the potential to significantly reduce diagnostic errors in health care (Figure), and its role in health care is rapidly expanding. AI technologies such as machine learning (ML) and natural language processing (NLP) have the potential to significantly reduce diagnostic errors by augmenting human cognition and improving access to relevant patient data.^1,16 Machine learning algorithms can analyze large amounts of patient data sets to identify patterns and risk factors and predict patient outcomes, which can aid health care providers in making accurate diagnoses.¹⁷ Artificial intelligence can also help to address some of the communication breakdowns that contribute to diagnostic errors.¹⁸ Natural language processing can improve the accuracy of EHR documentation and reduce the associated clinician burden, making it easier for providers to access relevant patient information and communicate more effectively with each other.¹⁸

In health care, AI can be used to analyze medical images, laboratory results, genomic data, and EHRs to identify potential diagnoses and flag patients who may be at risk for diagnostic errors. One of the primary benefits of AI in health care is its ability to process large amounts of data quickly and accurately.¹⁹ This can be particularly valuable in diagnosing rare or complex conditions. Machine learning algorithms can analyze patient data to identify subtle patterns that may not be apparent to human providers.¹⁶ This can lead to earlier and more accurate diagnoses, which can reduce diagnostic errors and improve patient outcomes.¹⁷ One example of the application of AI in health care is the use of computer-aided detection (CAD) software to analyze medical images. This software can help radiologists detect abnormalities in medical images that may be missed by the human eye, such as early-stage breast cancer.²⁰ Another example is the use of NLP and ML to analyze unstructured data in EHRs, such as physician notes, to identify potential diagnoses and flag patients who may be at risk for diagnostic errors.²¹ A recent study showed that using NLP on EHRs for screening and detecting individuals at risk for psychosis can considerably enhance the prognostic accuracy of psychosis risk calculators.²² This can help identify patients who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes. On the same note, ML-based severe sepsis prediction algorithms have been shown to reduce the average length of stay and in-hospital mortality rate.²³

However, there are also concerns about the use of AI in health care, including the potential for bias and the risk of overreliance on AI. Bias can occur when AI algorithms are trained on data that is not representative of the population being analyzed, leading to inaccurate or unfair results, hence, perpetuating and exacerbating existing biases in health care.²⁴ Over-reliance on AI can occur when health care providers rely too heavily on AI algorithms and fail to consider other important information, such as the lived experience of patients, families, and health care providers. Addressing these concerns will require ongoing efforts to ensure that AI technologies are developed and implemented in an ethical and responsible manner.²⁵

Conclusion

Reducing diagnostic errors is a critical goal for health care systems, and requires a comprehensive approach that utilizes both HX and AI technologies. Engaging patients and their families in the diagnostic process, promoting teamwork and collaboration among health care providers, addressing cognitive biases, and harnessing the power of AI can all contribute to more accurate diagnoses and better patient outcomes. By integrating the lived experience of patients, families, and health care providers with AI technologies, health care systems can be redesigned to become more proactive, safer, and patient-centered in identifying potential health problems and reducing the risk of diagnostic errors, ensuring that patients receive the care they need and deserve.

Corresponding author: Iqbal Ratnani, Department of Anesthesiology and Critical Care, DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin St, Houston, TX 77030; IRatnani@houstonmethodist.org

Disclosures: None reported.

From the Institute for Healthcare Improvement, Boston, MA (Dr. Abid); Continuous Quality Improvement and Patient Safety Department, Armed Forces Hospitals Taif Region, Taif, Saudi Arabia (Dr. Abid); Primary and Secondary Healthcare Department, Government of Punjab, Lahore, Pakistan (Dr. Ahmed); Infection Prevention and Control Department, Armed Forces Hospitals Taif Region, Taif, Saudi Arabia (Dr. Din); Internal Medicine Department, Greater Baltimore Medical Center, Baltimore, MD (Dr. Abid); Department of Anesthesiology and Critical Care, DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX (Dr. Ratnani).

Diagnostic errors are defined by the National Academies of Sciences, Engineering, and Medicine (NASEM) as the failure to either establish an accurate and timely explanation of the patient’s health problem(s) or communicate that explanation to the patient.¹ According to a report by the Institute of Medicine, diagnostic errors account for a substantial number of adverse events in health care, affecting an estimated 12 million Americans each year.¹ Diagnostic errors are a common and serious issue in health care systems, with studies estimating that 5% to 15% of all diagnoses are incorrect.¹ Such errors can result in unnecessary treatments, delays in necessary treatments, and harm to patients. The high prevalence of diagnostic errors in primary care has been identified as a global issue.² While many factors contribute to diagnostic errors, the complex nature of health care systems, the limited processing capacity of human cognition, and deficiencies in interpersonal patient-clinician communication are primary contributors.^3,4

Discussions around the redesign of health care systems to reduce diagnostic errors have been at the forefront of medical research for years.^2,4 To decrease diagnostic errors in health care, a comprehensive strategy is necessary. This strategy should focus on utilizing both human experience (HX) in health care and artificial intelligence (AI) technologies to transform health care systems into proactive, patient-centered, and safer systems, specifically concerning diagnostic errors.¹

Human Experience and Diagnostic Errors

The role of HX in health care cannot be overstated. The HX in health care integrates the sum of all interactions, every encounter among patients, families and care partners, and the health care workforce.⁵ Patients and their families have a unique perspective on their health care experiences that can provide valuable insight into potential diagnostic errors.⁶ The new definition of diagnostic errors introduced in the 2015 NASEM report emphasized the significance of effective communication during the diagnostic procedure.¹ Engaging patients and their families in the diagnostic process can improve communication, improve diagnostic accuracy, and help to identify errors before they cause harm.⁷ However, many patients and families feel that they are not listened to or taken seriously by health care providers, and may not feel comfortable sharing information that they feel is important.⁸ To address this, health care systems can implement programs that encourage patients and families to be more engaged in the diagnostic process, such as shared decision-making, patient portals, and patient and family advisory councils.⁹ Health care systems must prioritize patient-centered care, teamwork, and communication. Patients and their families must be actively engaged in their care, and health care providers must be willing to work collaboratively and listen to patients’ concerns.^6,10

Health care providers also bring their own valuable experiences and expertise to the diagnostic process, as they are often the ones on the front lines of patient care. However, health care providers may not always feel comfortable reporting errors or near misses, and may not have the time or resources to participate in quality improvement initiatives. To address this, health care systems can implement programs that encourage providers to report errors and near misses, such as anonymous reporting systems, just-culture initiatives, and peer review.¹¹ Creating a culture of teamwork and collaboration among health care providers can improve the accuracy of diagnoses and reduce the risk of errors.¹²

A key factor in utilizing HX to reduce diagnostic errors is effective communication. Communication breakdowns among health care providers, patients, and their families are a common contributing factor resulting in diagnostic errors.² Strategies to improve communication include using clear and concise language, involving patients and their families in the decision-making process, and utilizing electronic health records (EHRs) to ensure that all health care providers have access to relevant, accurate, and up-to-date patient information.^4,13,14

Another important aspect of utilizing HX in health care to reduce diagnostic errors is the need to recognize and address cognitive biases that may influence diagnostic decisions.³ Cognitive biases are common in health care and can lead to errors in diagnosis. For example, confirmation bias, which is the tendency to look for information that confirms preexisting beliefs, can lead providers to overlook important diagnostic information.¹⁵ Biases such as anchoring bias, premature closure, and confirmation bias can lead to incorrect diagnoses and can be difficult to recognize and overcome. Addressing cognitive biases requires a commitment to self-reflection and self-awareness among health care providers as well as structured training of health care providers to improve their diagnostic reasoning skills and reduce the risk of cognitive errors.¹⁵ By implementing these strategies around HX in health care, health care systems can become more patient-centered and reduce the likelihood of diagnostic errors (Figure).

0523_Perspectives_F.jpg

Artificial intelligence has the potential to significantly reduce diagnostic errors in health care (Figure), and its role in health care is rapidly expanding. AI technologies such as machine learning (ML) and natural language processing (NLP) have the potential to significantly reduce diagnostic errors by augmenting human cognition and improving access to relevant patient data.^1,16 Machine learning algorithms can analyze large amounts of patient data sets to identify patterns and risk factors and predict patient outcomes, which can aid health care providers in making accurate diagnoses.¹⁷ Artificial intelligence can also help to address some of the communication breakdowns that contribute to diagnostic errors.¹⁸ Natural language processing can improve the accuracy of EHR documentation and reduce the associated clinician burden, making it easier for providers to access relevant patient information and communicate more effectively with each other.¹⁸

In health care, AI can be used to analyze medical images, laboratory results, genomic data, and EHRs to identify potential diagnoses and flag patients who may be at risk for diagnostic errors. One of the primary benefits of AI in health care is its ability to process large amounts of data quickly and accurately.¹⁹ This can be particularly valuable in diagnosing rare or complex conditions. Machine learning algorithms can analyze patient data to identify subtle patterns that may not be apparent to human providers.¹⁶ This can lead to earlier and more accurate diagnoses, which can reduce diagnostic errors and improve patient outcomes.¹⁷ One example of the application of AI in health care is the use of computer-aided detection (CAD) software to analyze medical images. This software can help radiologists detect abnormalities in medical images that may be missed by the human eye, such as early-stage breast cancer.²⁰ Another example is the use of NLP and ML to analyze unstructured data in EHRs, such as physician notes, to identify potential diagnoses and flag patients who may be at risk for diagnostic errors.²¹ A recent study showed that using NLP on EHRs for screening and detecting individuals at risk for psychosis can considerably enhance the prognostic accuracy of psychosis risk calculators.²² This can help identify patients who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes. On the same note, ML-based severe sepsis prediction algorithms have been shown to reduce the average length of stay and in-hospital mortality rate.²³

However, there are also concerns about the use of AI in health care, including the potential for bias and the risk of overreliance on AI. Bias can occur when AI algorithms are trained on data that is not representative of the population being analyzed, leading to inaccurate or unfair results, hence, perpetuating and exacerbating existing biases in health care.²⁴ Over-reliance on AI can occur when health care providers rely too heavily on AI algorithms and fail to consider other important information, such as the lived experience of patients, families, and health care providers. Addressing these concerns will require ongoing efforts to ensure that AI technologies are developed and implemented in an ethical and responsible manner.²⁵

Conclusion

Reducing diagnostic errors is a critical goal for health care systems, and requires a comprehensive approach that utilizes both HX and AI technologies. Engaging patients and their families in the diagnostic process, promoting teamwork and collaboration among health care providers, addressing cognitive biases, and harnessing the power of AI can all contribute to more accurate diagnoses and better patient outcomes. By integrating the lived experience of patients, families, and health care providers with AI technologies, health care systems can be redesigned to become more proactive, safer, and patient-centered in identifying potential health problems and reducing the risk of diagnostic errors, ensuring that patients receive the care they need and deserve.

Corresponding author: Iqbal Ratnani, Department of Anesthesiology and Critical Care, DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin St, Houston, TX 77030; IRatnani@houstonmethodist.org

Disclosures: None reported.

From the University of Missouri School of Medicine, Columbia, MO (Haley Crosby); Department of Clinical Family and Community Medicine, University of Missouri, Columbia, MO (Dr. Pierce); and Department of Medicine, Divisions of Infectious Diseases and Pulmonary, Critical Care and Environmental Medicine, University of Missouri, Columbia, MO, and Divisions of Pulmonary and Critical Care Medicine and Infectious Diseases, University of Maryland Baltimore Washington Medical Center, Glen Burnie, MD (Dr. Regunath).

ABSTRACT

Objective: Multidisciplinary teams (MDTs) improve outcomes for patients with infective endocarditis (IE), but methods of implementation vary. In our academic medical center, we developed an MDT approach guided by a clinical care pathway and assessed outcomes of patients with IE.

Methods: We compared outcomes of patients with IE and indications for surgery between December 2018 and June 2020 with our prior published data for the period January to December 2016. MDT interventions involved recurring conferences with infectious diseases physicians in team meetings and promoting a clinical care pathway to guide providers on steps in management. Primary outcomes were surgery and in-hospital death.

Results: Prior to the intervention, 6 of 21 (28.6%) patients with indications for surgery underwent surgery or were transferred to higher centers for surgery, and 6 (28.6%) patients died. Post intervention, 17 of 31 (54.8%) patients underwent or were transferred for surgery, and 5 (16.1%) died. After adjusting for age and gender, the odds of surgery or transfer for surgery for patients in the postintervention period were 4.88 (95% CI, 1.20-19.79; P = .027) compared with the pre-intervention period. The odds ratio for death among patients in the postintervention period was 0.40 (95% CI, 0.09-1.69; P = .21).

Conclusion: An MDT team approach using a clinical pathway was associated with an increased number of surgeries performed for IE and may lower rates of in-hospital mortality.

Keywords: infective endocarditis, clinical pathway, quality improvement, multidisciplinary team, valve surgery.

Infective endocarditis (IE) is associated with significant morbidity and mortality.¹ Rates of IE due to Staphylococcus aureus are increasing in the United States.² Reported in-hospital mortality from IE ranges from 15% to 20%.³Optimal management of IE requires input from a number of specialties, including infectious diseases (ID), cardiology, cardiothoracic surgery (CTS), oromaxillofacial surgery, radiology (eg, nuclear medicine), and neurology, among others, depending on the site of complications. Guidelines from the United States and Europe recommend incorporating multidisciplinary teams (MDTs) in the management of IE.^1,3-5 These recommendations are based on quasi-experimental before-and-after studies that have consistently demonstrated that MDTs reduce in-hospital and 1-year mortality.^6-11 However, implementation of MDTs can be challenging. Successful MDTs require good team dynamics, unified participation, and seamless communication among team members.

Clinical pathways are defined as “structured, multidisciplinary plans of care used by health services to detail essential steps in the care of patients with a specific clinical problem.”¹² In the modern era, these pathways are often developed and implemented via the electronic health record (EHR) system. Studies of clinical pathways generally demonstrate improvements in patient outcomes, quality of care, or resource utilization.^13,14 Clinical pathways represent 1 possible approach to the implementation of a MDT in the care of patients with IE.¹⁵

In our earlier work, we used quality improvement principles in the design of an MDT approach to IE care at our institution.¹⁶ Despite having indications for surgery, 12 of 21 (57.1%) patients with IE did not undergo surgery, and we identified these missed opportunities for surgery as a leverage point for improvement of outcomes. With input from the various specialties and stakeholders, we developed a clinical pathway (algorithm) for the institutional management of IE that guides next steps in clinical care and their timelines, aiming to reduce by 50% (from 57.1% to 28.6%) the number of patients with IE who do not undergo surgery despite guideline indications for early surgical intervention. In this report, we describe the implementation of this clinical pathway as our MDT approach to the care of patients with IE at our institution.

Methods

The University of Missouri, Columbia, is a tertiary care academic health system with 5 hospitals and more than 60 clinic locations across central Missouri. In the spring of 2018, an MDT was developed, with support from administrative leaders, to improve the care of patients with IE at our institution. The work group prioritized one leverage point to improve IE outcomes, which was improving the number of surgeries performed on those IE patients who had guideline indications for surgery. A clinical pathway was developed around this leverage point (Figure 1). The pathway leveraged the 6 T’s (Table 1) to guide providers through the evaluation and management of IE.¹⁷ The pathway focused on improving adherence to standards of care and reduction in practice variation by defining indications for referrals and diagnostic interventions, helping to reduce delays in consultation and diagnosis. The pathway also clearly outlined the surgical indications and timing for patients with IE and provided the basis for decisions to proceed with surgery.

JCOM0323_Crosby_F1.jpg

Starting in late 2018, in collaboration with cardiology and CTS teams, ID specialists socialized the clinical pathway to inpatient services that cared for patients with IE. Infectious diseases physicians also provided recurring conferences on the effectiveness of MDTs in IE management and participated in heart-valve team case discussions. Finally, in May 2019, an electronic version of the pathway was embedded in the EHR system using a Cerner PowerChart feature known as Care Pathways. The feature presents the user with algorithm questions in the EHR and provides recommendations, relevant orders, timelines, and other decision support in the clinical pathway. The feature is available to all providers in the health system.

JCOM0323_Crosby_T1.jpg

To evaluate the effectiveness of our intervention, we recorded outcomes for patients with IE with surgical indications between December 2018 and June 2020 and compared them with our prior published data from January to December 2016. Cases of IE for the current study period were identified via retrospective chart review. Records from December 2018 to June 2020 were searched using International Statistical Classification of Diseases, Tenth Revision (ICD-10) discharge codes for IE (I33, I33.0, I33.9, I38, I39, M32.11). To select those patients with definitive IE and indications for surgery, the following criteria were applied: age ≥ 18 years; fulfilled modified Duke criteria for definite IE¹⁸; and met ≥ 1 American Heart Association (AHA)/Infection Diseases Society of America criteria for recommendation for surgery. Indications for surgery were ≥ 1 of the following: left-sided endocarditis caused by S aureus, fungal, or highly resistant organism; new heart block; annular or aortic abscess; persistent bacteremia or fever despite 5 days of appropriate antimicrobials; vegetation size ≥ 10 mm and evidence of embolic phenomena; recurrence of prosthetic valve infection; recurrent emboli and persistent vegetation despite antimicrobials; and increase in vegetation size despite antimicrobials.¹⁶

Age was treated as a categorical variable, using the age groups 18 to 44 years, 45 to 64 years, and 65 years and older. Gender was self-reported. Primary outcomes were surgery or transfer to a higher center for surgery and in-hospital death. Secondary outcomes included consults to teams involved in multidisciplinary care of patients with IE, including ID, cardiology, and CTS. Bivariate analyses were performed using Pearson χ² tests. Odds ratios for surgery and death were calculated using a multivariate logistic regression model including age and gender covariates. Statistical significance was defined at α = 0.05, and statistical analysis was performed using Stata/IC v16.1 (StataCorp LLC). Our university institutional review board (IRB) reviewed the project (#2010858-QI) and determined that the project was quality-improvement activity, not human subject research, and therefore did not require additional IRB review.

Results

We identified 21 patients in the pre-intervention period and 31 patients in the postintervention period with definitive IE who had guideline indications for surgery. The postintervention cohort was older and had more male patients; this difference was not statistically significant. No differences were noted between the groups for race, gender, or intravenous (IV) drug use (Table 2). Chi-square tests of independence were performed to assess the relationship between age and our primary outcomes. There was a significant relationship between age and the likelihood of receiving or being transferred for surgery (59.3% vs 50% vs 7.7% for 18-44 y, 45-64 y, and ≥ 65 y, respectively; χ² [2, N = 52] = 9.67; P = .008), but not between age and mortality (14.8% vs 25.0% vs 30.8% for 18-44 y, 45-64 y, and ≥ 65 y, respectively; χ²  = 1.48 [2, N = 52; P = .478]. The electronic version of the clinical pathway was activated and used in only 3 of the 31 patients in the postintervention period. Consultations to ID, cardiology, and CTS teams were compared between the study periods (Table 2). Although more consultations were seen in the postintervention period, differences were not statistically significant.

JCOM0323_Crosby_T2.jpg

The unadjusted primary outcomes are shown in Table 2. More surgeries were performed per guideline indications, and fewer deaths were noted in the postintervention period than in the pre-intervention period, but the differences were not statistically significant (Table 2).

Because the postintervention period had more male patients and older patients, we evaluated the outcomes using a logistic regression model controlling for both age and gender. The odds of surgery or transfer for surgery for patients in the postintervention period were 4.88 (95% CI, 1.20-19.79; P = .027) as compared with the pre-intervention period, and the odds ratio for death among patients in the postintervention period compared with the pre-intervention period was 0.40 (95% CI, 0.09-1.69; P = .21) (Figure 2).

JCOM0323_Crosby_F2.jpg

Discussion

In our study, patients with IE with guideline indications for surgery had significantly higher rates of surgery in the postintervention period than in the pre-intervention period. The implementation of an MDT, recurring educational sessions, and efforts to implement and familiarize team members with the clinical pathway approach are the most likely reasons for this change. The increased rates of surgery in the postintervention period were the likely proximate cause of the 60% reduction in in-hospital mortality. This improvement in mortality, while not statistically significant, is very likely to be clinically significant and helps reinforce the value of the MDT intervention used.

Our findings are consistent with existing and mounting literature on the use of MDTs to improve outcomes for patients with IE, including 2 studies that noted an increased rate of surgery for patients with indications.^8,19 Several other studies in both Europe and North America have found significant decreases in mortality,^6-11,20,21 rates of complications,⁹ time to diagnosis and treatment,¹¹ and length of stay^9,20 for patients with IE managed with an MDT strategy. Although current AHA guidelines for care of patients with IE do suggest an MDT approach, the strategy for this approach is not well established.²² Only 1 study that has implemented a new MDT protocol for care of IE has been conducted in the United States.⁸

While effective MDTs certainly improve outcomes in patients with IE, there are reported differences in implementation of such an approach. With the MDT model as the core, various implementations included regular case conferences,^{10,11,19,21,23} formation of a consulting team,^6,8 or establishment of a new protocol or algorithm for care.^8,9,20 Our approach used a clinical pathway as a basis for improved communication among consulting services, education of learning providers via regular case conferences, and implementation of an electronic clinical care pathway to guide them step by step. Our pathway followed the institutionally standardized algorithm (Figure 1), using what we called the 6 T’s approach (Table 1), that guides providers to evaluate critical cases in a fast track.¹⁷

To the best of our knowledge, ours is the first report of an MDT that used an electronic clinical care pathway embedded within the EHR. The electronic version of our clinical pathway went live for only the second half of the postintervention study period, which is the most likely reason for its limited utilization. It is also possible that educational efforts in the first half of the intervention period were sufficient to familiarize providers with the care pathway such that the electronic version was seldom needed. We are exploring other possible ways of improving electronic pathway utilization, such as improving the feature usability and further systemwide educational efforts.

Our study has other limitations. Quasi-experimental before-and-after comparisons are subject to confounding from concurrent interventions. We had a substantial change in cardiothoracic faculty soon after the commencement of our efforts to form the MDT, and thus cannot rule out differences related to their comfort level in considering or offering surgery. We also cannot rule out a Hawthorne effect, where knowledge of the ongoing quality-improvement project changed provider behavior, making surgery more likely. We did not evaluate rates of right- versus left-sided endocarditis, which have been linked to mortality.²⁴ Our study also was performed across a single academic institution, which may limit its generalizability. Finally, our study may not have been adequately powered to detect differences in mortality due to implementation of the MDT approach.

Conclusion

Our work suggests that an MDT for IE can be successfully designed and implemented with a clinical pathway using quality-improvement tools in centers where subspecialty services are available. Our approach was associated with a higher rate of surgery among patients with guideline indications for surgery and may reduce in-hospital mortality. An electronic clinical care pathway embedded in the EHR is feasible and may have a role in MDT implementation.

These data were also accepted as a poster at IDWeek 2022, Washington, DC. The poster abstract is published in an online supplement of Open Forum Infectious Diseases as an abstract publication.

Corresponding author: Haley Crosby; hwc2pd@health.missouri.edu

Disclosures: None reported.

From the University of Missouri School of Medicine, Columbia, MO (Haley Crosby); Department of Clinical Family and Community Medicine, University of Missouri, Columbia, MO (Dr. Pierce); and Department of Medicine, Divisions of Infectious Diseases and Pulmonary, Critical Care and Environmental Medicine, University of Missouri, Columbia, MO, and Divisions of Pulmonary and Critical Care Medicine and Infectious Diseases, University of Maryland Baltimore Washington Medical Center, Glen Burnie, MD (Dr. Regunath).

ABSTRACT

Objective: Multidisciplinary teams (MDTs) improve outcomes for patients with infective endocarditis (IE), but methods of implementation vary. In our academic medical center, we developed an MDT approach guided by a clinical care pathway and assessed outcomes of patients with IE.

Methods: We compared outcomes of patients with IE and indications for surgery between December 2018 and June 2020 with our prior published data for the period January to December 2016. MDT interventions involved recurring conferences with infectious diseases physicians in team meetings and promoting a clinical care pathway to guide providers on steps in management. Primary outcomes were surgery and in-hospital death.

Results: Prior to the intervention, 6 of 21 (28.6%) patients with indications for surgery underwent surgery or were transferred to higher centers for surgery, and 6 (28.6%) patients died. Post intervention, 17 of 31 (54.8%) patients underwent or were transferred for surgery, and 5 (16.1%) died. After adjusting for age and gender, the odds of surgery or transfer for surgery for patients in the postintervention period were 4.88 (95% CI, 1.20-19.79; P = .027) compared with the pre-intervention period. The odds ratio for death among patients in the postintervention period was 0.40 (95% CI, 0.09-1.69; P = .21).

Conclusion: An MDT team approach using a clinical pathway was associated with an increased number of surgeries performed for IE and may lower rates of in-hospital mortality.

Keywords: infective endocarditis, clinical pathway, quality improvement, multidisciplinary team, valve surgery.

Infective endocarditis (IE) is associated with significant morbidity and mortality.¹ Rates of IE due to Staphylococcus aureus are increasing in the United States.² Reported in-hospital mortality from IE ranges from 15% to 20%.³Optimal management of IE requires input from a number of specialties, including infectious diseases (ID), cardiology, cardiothoracic surgery (CTS), oromaxillofacial surgery, radiology (eg, nuclear medicine), and neurology, among others, depending on the site of complications. Guidelines from the United States and Europe recommend incorporating multidisciplinary teams (MDTs) in the management of IE.^1,3-5 These recommendations are based on quasi-experimental before-and-after studies that have consistently demonstrated that MDTs reduce in-hospital and 1-year mortality.^6-11 However, implementation of MDTs can be challenging. Successful MDTs require good team dynamics, unified participation, and seamless communication among team members.

Clinical pathways are defined as “structured, multidisciplinary plans of care used by health services to detail essential steps in the care of patients with a specific clinical problem.”¹² In the modern era, these pathways are often developed and implemented via the electronic health record (EHR) system. Studies of clinical pathways generally demonstrate improvements in patient outcomes, quality of care, or resource utilization.^13,14 Clinical pathways represent 1 possible approach to the implementation of a MDT in the care of patients with IE.¹⁵

In our earlier work, we used quality improvement principles in the design of an MDT approach to IE care at our institution.¹⁶ Despite having indications for surgery, 12 of 21 (57.1%) patients with IE did not undergo surgery, and we identified these missed opportunities for surgery as a leverage point for improvement of outcomes. With input from the various specialties and stakeholders, we developed a clinical pathway (algorithm) for the institutional management of IE that guides next steps in clinical care and their timelines, aiming to reduce by 50% (from 57.1% to 28.6%) the number of patients with IE who do not undergo surgery despite guideline indications for early surgical intervention. In this report, we describe the implementation of this clinical pathway as our MDT approach to the care of patients with IE at our institution.

Methods

The University of Missouri, Columbia, is a tertiary care academic health system with 5 hospitals and more than 60 clinic locations across central Missouri. In the spring of 2018, an MDT was developed, with support from administrative leaders, to improve the care of patients with IE at our institution. The work group prioritized one leverage point to improve IE outcomes, which was improving the number of surgeries performed on those IE patients who had guideline indications for surgery. A clinical pathway was developed around this leverage point (Figure 1). The pathway leveraged the 6 T’s (Table 1) to guide providers through the evaluation and management of IE.¹⁷ The pathway focused on improving adherence to standards of care and reduction in practice variation by defining indications for referrals and diagnostic interventions, helping to reduce delays in consultation and diagnosis. The pathway also clearly outlined the surgical indications and timing for patients with IE and provided the basis for decisions to proceed with surgery.

JCOM0323_Crosby_F1.jpg

Starting in late 2018, in collaboration with cardiology and CTS teams, ID specialists socialized the clinical pathway to inpatient services that cared for patients with IE. Infectious diseases physicians also provided recurring conferences on the effectiveness of MDTs in IE management and participated in heart-valve team case discussions. Finally, in May 2019, an electronic version of the pathway was embedded in the EHR system using a Cerner PowerChart feature known as Care Pathways. The feature presents the user with algorithm questions in the EHR and provides recommendations, relevant orders, timelines, and other decision support in the clinical pathway. The feature is available to all providers in the health system.

JCOM0323_Crosby_T1.jpg

To evaluate the effectiveness of our intervention, we recorded outcomes for patients with IE with surgical indications between December 2018 and June 2020 and compared them with our prior published data from January to December 2016. Cases of IE for the current study period were identified via retrospective chart review. Records from December 2018 to June 2020 were searched using International Statistical Classification of Diseases, Tenth Revision (ICD-10) discharge codes for IE (I33, I33.0, I33.9, I38, I39, M32.11). To select those patients with definitive IE and indications for surgery, the following criteria were applied: age ≥ 18 years; fulfilled modified Duke criteria for definite IE¹⁸; and met ≥ 1 American Heart Association (AHA)/Infection Diseases Society of America criteria for recommendation for surgery. Indications for surgery were ≥ 1 of the following: left-sided endocarditis caused by S aureus, fungal, or highly resistant organism; new heart block; annular or aortic abscess; persistent bacteremia or fever despite 5 days of appropriate antimicrobials; vegetation size ≥ 10 mm and evidence of embolic phenomena; recurrence of prosthetic valve infection; recurrent emboli and persistent vegetation despite antimicrobials; and increase in vegetation size despite antimicrobials.¹⁶

Age was treated as a categorical variable, using the age groups 18 to 44 years, 45 to 64 years, and 65 years and older. Gender was self-reported. Primary outcomes were surgery or transfer to a higher center for surgery and in-hospital death. Secondary outcomes included consults to teams involved in multidisciplinary care of patients with IE, including ID, cardiology, and CTS. Bivariate analyses were performed using Pearson χ² tests. Odds ratios for surgery and death were calculated using a multivariate logistic regression model including age and gender covariates. Statistical significance was defined at α = 0.05, and statistical analysis was performed using Stata/IC v16.1 (StataCorp LLC). Our university institutional review board (IRB) reviewed the project (#2010858-QI) and determined that the project was quality-improvement activity, not human subject research, and therefore did not require additional IRB review.

Results

We identified 21 patients in the pre-intervention period and 31 patients in the postintervention period with definitive IE who had guideline indications for surgery. The postintervention cohort was older and had more male patients; this difference was not statistically significant. No differences were noted between the groups for race, gender, or intravenous (IV) drug use (Table 2). Chi-square tests of independence were performed to assess the relationship between age and our primary outcomes. There was a significant relationship between age and the likelihood of receiving or being transferred for surgery (59.3% vs 50% vs 7.7% for 18-44 y, 45-64 y, and ≥ 65 y, respectively; χ² [2, N = 52] = 9.67; P = .008), but not between age and mortality (14.8% vs 25.0% vs 30.8% for 18-44 y, 45-64 y, and ≥ 65 y, respectively; χ²  = 1.48 [2, N = 52; P = .478]. The electronic version of the clinical pathway was activated and used in only 3 of the 31 patients in the postintervention period. Consultations to ID, cardiology, and CTS teams were compared between the study periods (Table 2). Although more consultations were seen in the postintervention period, differences were not statistically significant.

JCOM0323_Crosby_T2.jpg

The unadjusted primary outcomes are shown in Table 2. More surgeries were performed per guideline indications, and fewer deaths were noted in the postintervention period than in the pre-intervention period, but the differences were not statistically significant (Table 2).

Because the postintervention period had more male patients and older patients, we evaluated the outcomes using a logistic regression model controlling for both age and gender. The odds of surgery or transfer for surgery for patients in the postintervention period were 4.88 (95% CI, 1.20-19.79; P = .027) as compared with the pre-intervention period, and the odds ratio for death among patients in the postintervention period compared with the pre-intervention period was 0.40 (95% CI, 0.09-1.69; P = .21) (Figure 2).

JCOM0323_Crosby_F2.jpg

Discussion

In our study, patients with IE with guideline indications for surgery had significantly higher rates of surgery in the postintervention period than in the pre-intervention period. The implementation of an MDT, recurring educational sessions, and efforts to implement and familiarize team members with the clinical pathway approach are the most likely reasons for this change. The increased rates of surgery in the postintervention period were the likely proximate cause of the 60% reduction in in-hospital mortality. This improvement in mortality, while not statistically significant, is very likely to be clinically significant and helps reinforce the value of the MDT intervention used.

Our findings are consistent with existing and mounting literature on the use of MDTs to improve outcomes for patients with IE, including 2 studies that noted an increased rate of surgery for patients with indications.^8,19 Several other studies in both Europe and North America have found significant decreases in mortality,^6-11,20,21 rates of complications,⁹ time to diagnosis and treatment,¹¹ and length of stay^9,20 for patients with IE managed with an MDT strategy. Although current AHA guidelines for care of patients with IE do suggest an MDT approach, the strategy for this approach is not well established.²² Only 1 study that has implemented a new MDT protocol for care of IE has been conducted in the United States.⁸

While effective MDTs certainly improve outcomes in patients with IE, there are reported differences in implementation of such an approach. With the MDT model as the core, various implementations included regular case conferences,^{10,11,19,21,23} formation of a consulting team,^6,8 or establishment of a new protocol or algorithm for care.^8,9,20 Our approach used a clinical pathway as a basis for improved communication among consulting services, education of learning providers via regular case conferences, and implementation of an electronic clinical care pathway to guide them step by step. Our pathway followed the institutionally standardized algorithm (Figure 1), using what we called the 6 T’s approach (Table 1), that guides providers to evaluate critical cases in a fast track.¹⁷

To the best of our knowledge, ours is the first report of an MDT that used an electronic clinical care pathway embedded within the EHR. The electronic version of our clinical pathway went live for only the second half of the postintervention study period, which is the most likely reason for its limited utilization. It is also possible that educational efforts in the first half of the intervention period were sufficient to familiarize providers with the care pathway such that the electronic version was seldom needed. We are exploring other possible ways of improving electronic pathway utilization, such as improving the feature usability and further systemwide educational efforts.

Our study has other limitations. Quasi-experimental before-and-after comparisons are subject to confounding from concurrent interventions. We had a substantial change in cardiothoracic faculty soon after the commencement of our efforts to form the MDT, and thus cannot rule out differences related to their comfort level in considering or offering surgery. We also cannot rule out a Hawthorne effect, where knowledge of the ongoing quality-improvement project changed provider behavior, making surgery more likely. We did not evaluate rates of right- versus left-sided endocarditis, which have been linked to mortality.²⁴ Our study also was performed across a single academic institution, which may limit its generalizability. Finally, our study may not have been adequately powered to detect differences in mortality due to implementation of the MDT approach.

Conclusion

Our work suggests that an MDT for IE can be successfully designed and implemented with a clinical pathway using quality-improvement tools in centers where subspecialty services are available. Our approach was associated with a higher rate of surgery among patients with guideline indications for surgery and may reduce in-hospital mortality. An electronic clinical care pathway embedded in the EHR is feasible and may have a role in MDT implementation.

These data were also accepted as a poster at IDWeek 2022, Washington, DC. The poster abstract is published in an online supplement of Open Forum Infectious Diseases as an abstract publication.

Corresponding author: Haley Crosby; hwc2pd@health.missouri.edu

Disclosures: None reported.

From the University of Missouri School of Medicine, Columbia, MO (Haley Crosby); Department of Clinical Family and Community Medicine, University of Missouri, Columbia, MO (Dr. Pierce); and Department of Medicine, Divisions of Infectious Diseases and Pulmonary, Critical Care and Environmental Medicine, University of Missouri, Columbia, MO, and Divisions of Pulmonary and Critical Care Medicine and Infectious Diseases, University of Maryland Baltimore Washington Medical Center, Glen Burnie, MD (Dr. Regunath).

ABSTRACT

Objective: Multidisciplinary teams (MDTs) improve outcomes for patients with infective endocarditis (IE), but methods of implementation vary. In our academic medical center, we developed an MDT approach guided by a clinical care pathway and assessed outcomes of patients with IE.

Methods: We compared outcomes of patients with IE and indications for surgery between December 2018 and June 2020 with our prior published data for the period January to December 2016. MDT interventions involved recurring conferences with infectious diseases physicians in team meetings and promoting a clinical care pathway to guide providers on steps in management. Primary outcomes were surgery and in-hospital death.

Results: Prior to the intervention, 6 of 21 (28.6%) patients with indications for surgery underwent surgery or were transferred to higher centers for surgery, and 6 (28.6%) patients died. Post intervention, 17 of 31 (54.8%) patients underwent or were transferred for surgery, and 5 (16.1%) died. After adjusting for age and gender, the odds of surgery or transfer for surgery for patients in the postintervention period were 4.88 (95% CI, 1.20-19.79; P = .027) compared with the pre-intervention period. The odds ratio for death among patients in the postintervention period was 0.40 (95% CI, 0.09-1.69; P = .21).

Conclusion: An MDT team approach using a clinical pathway was associated with an increased number of surgeries performed for IE and may lower rates of in-hospital mortality.

Keywords: infective endocarditis, clinical pathway, quality improvement, multidisciplinary team, valve surgery.

Infective endocarditis (IE) is associated with significant morbidity and mortality.¹ Rates of IE due to Staphylococcus aureus are increasing in the United States.² Reported in-hospital mortality from IE ranges from 15% to 20%.³Optimal management of IE requires input from a number of specialties, including infectious diseases (ID), cardiology, cardiothoracic surgery (CTS), oromaxillofacial surgery, radiology (eg, nuclear medicine), and neurology, among others, depending on the site of complications. Guidelines from the United States and Europe recommend incorporating multidisciplinary teams (MDTs) in the management of IE.^1,3-5 These recommendations are based on quasi-experimental before-and-after studies that have consistently demonstrated that MDTs reduce in-hospital and 1-year mortality.^6-11 However, implementation of MDTs can be challenging. Successful MDTs require good team dynamics, unified participation, and seamless communication among team members.

Clinical pathways are defined as “structured, multidisciplinary plans of care used by health services to detail essential steps in the care of patients with a specific clinical problem.”¹² In the modern era, these pathways are often developed and implemented via the electronic health record (EHR) system. Studies of clinical pathways generally demonstrate improvements in patient outcomes, quality of care, or resource utilization.^13,14 Clinical pathways represent 1 possible approach to the implementation of a MDT in the care of patients with IE.¹⁵

In our earlier work, we used quality improvement principles in the design of an MDT approach to IE care at our institution.¹⁶ Despite having indications for surgery, 12 of 21 (57.1%) patients with IE did not undergo surgery, and we identified these missed opportunities for surgery as a leverage point for improvement of outcomes. With input from the various specialties and stakeholders, we developed a clinical pathway (algorithm) for the institutional management of IE that guides next steps in clinical care and their timelines, aiming to reduce by 50% (from 57.1% to 28.6%) the number of patients with IE who do not undergo surgery despite guideline indications for early surgical intervention. In this report, we describe the implementation of this clinical pathway as our MDT approach to the care of patients with IE at our institution.

Methods

The University of Missouri, Columbia, is a tertiary care academic health system with 5 hospitals and more than 60 clinic locations across central Missouri. In the spring of 2018, an MDT was developed, with support from administrative leaders, to improve the care of patients with IE at our institution. The work group prioritized one leverage point to improve IE outcomes, which was improving the number of surgeries performed on those IE patients who had guideline indications for surgery. A clinical pathway was developed around this leverage point (Figure 1). The pathway leveraged the 6 T’s (Table 1) to guide providers through the evaluation and management of IE.¹⁷ The pathway focused on improving adherence to standards of care and reduction in practice variation by defining indications for referrals and diagnostic interventions, helping to reduce delays in consultation and diagnosis. The pathway also clearly outlined the surgical indications and timing for patients with IE and provided the basis for decisions to proceed with surgery.

JCOM0323_Crosby_F1.jpg

Starting in late 2018, in collaboration with cardiology and CTS teams, ID specialists socialized the clinical pathway to inpatient services that cared for patients with IE. Infectious diseases physicians also provided recurring conferences on the effectiveness of MDTs in IE management and participated in heart-valve team case discussions. Finally, in May 2019, an electronic version of the pathway was embedded in the EHR system using a Cerner PowerChart feature known as Care Pathways. The feature presents the user with algorithm questions in the EHR and provides recommendations, relevant orders, timelines, and other decision support in the clinical pathway. The feature is available to all providers in the health system.

JCOM0323_Crosby_T1.jpg

To evaluate the effectiveness of our intervention, we recorded outcomes for patients with IE with surgical indications between December 2018 and June 2020 and compared them with our prior published data from January to December 2016. Cases of IE for the current study period were identified via retrospective chart review. Records from December 2018 to June 2020 were searched using International Statistical Classification of Diseases, Tenth Revision (ICD-10) discharge codes for IE (I33, I33.0, I33.9, I38, I39, M32.11). To select those patients with definitive IE and indications for surgery, the following criteria were applied: age ≥ 18 years; fulfilled modified Duke criteria for definite IE¹⁸; and met ≥ 1 American Heart Association (AHA)/Infection Diseases Society of America criteria for recommendation for surgery. Indications for surgery were ≥ 1 of the following: left-sided endocarditis caused by S aureus, fungal, or highly resistant organism; new heart block; annular or aortic abscess; persistent bacteremia or fever despite 5 days of appropriate antimicrobials; vegetation size ≥ 10 mm and evidence of embolic phenomena; recurrence of prosthetic valve infection; recurrent emboli and persistent vegetation despite antimicrobials; and increase in vegetation size despite antimicrobials.¹⁶

Age was treated as a categorical variable, using the age groups 18 to 44 years, 45 to 64 years, and 65 years and older. Gender was self-reported. Primary outcomes were surgery or transfer to a higher center for surgery and in-hospital death. Secondary outcomes included consults to teams involved in multidisciplinary care of patients with IE, including ID, cardiology, and CTS. Bivariate analyses were performed using Pearson χ² tests. Odds ratios for surgery and death were calculated using a multivariate logistic regression model including age and gender covariates. Statistical significance was defined at α = 0.05, and statistical analysis was performed using Stata/IC v16.1 (StataCorp LLC). Our university institutional review board (IRB) reviewed the project (#2010858-QI) and determined that the project was quality-improvement activity, not human subject research, and therefore did not require additional IRB review.

Results

We identified 21 patients in the pre-intervention period and 31 patients in the postintervention period with definitive IE who had guideline indications for surgery. The postintervention cohort was older and had more male patients; this difference was not statistically significant. No differences were noted between the groups for race, gender, or intravenous (IV) drug use (Table 2). Chi-square tests of independence were performed to assess the relationship between age and our primary outcomes. There was a significant relationship between age and the likelihood of receiving or being transferred for surgery (59.3% vs 50% vs 7.7% for 18-44 y, 45-64 y, and ≥ 65 y, respectively; χ² [2, N = 52] = 9.67; P = .008), but not between age and mortality (14.8% vs 25.0% vs 30.8% for 18-44 y, 45-64 y, and ≥ 65 y, respectively; χ²  = 1.48 [2, N = 52; P = .478]. The electronic version of the clinical pathway was activated and used in only 3 of the 31 patients in the postintervention period. Consultations to ID, cardiology, and CTS teams were compared between the study periods (Table 2). Although more consultations were seen in the postintervention period, differences were not statistically significant.

JCOM0323_Crosby_T2.jpg

The unadjusted primary outcomes are shown in Table 2. More surgeries were performed per guideline indications, and fewer deaths were noted in the postintervention period than in the pre-intervention period, but the differences were not statistically significant (Table 2).

Because the postintervention period had more male patients and older patients, we evaluated the outcomes using a logistic regression model controlling for both age and gender. The odds of surgery or transfer for surgery for patients in the postintervention period were 4.88 (95% CI, 1.20-19.79; P = .027) as compared with the pre-intervention period, and the odds ratio for death among patients in the postintervention period compared with the pre-intervention period was 0.40 (95% CI, 0.09-1.69; P = .21) (Figure 2).

JCOM0323_Crosby_F2.jpg

Discussion

In our study, patients with IE with guideline indications for surgery had significantly higher rates of surgery in the postintervention period than in the pre-intervention period. The implementation of an MDT, recurring educational sessions, and efforts to implement and familiarize team members with the clinical pathway approach are the most likely reasons for this change. The increased rates of surgery in the postintervention period were the likely proximate cause of the 60% reduction in in-hospital mortality. This improvement in mortality, while not statistically significant, is very likely to be clinically significant and helps reinforce the value of the MDT intervention used.

Our findings are consistent with existing and mounting literature on the use of MDTs to improve outcomes for patients with IE, including 2 studies that noted an increased rate of surgery for patients with indications.^8,19 Several other studies in both Europe and North America have found significant decreases in mortality,^6-11,20,21 rates of complications,⁹ time to diagnosis and treatment,¹¹ and length of stay^9,20 for patients with IE managed with an MDT strategy. Although current AHA guidelines for care of patients with IE do suggest an MDT approach, the strategy for this approach is not well established.²² Only 1 study that has implemented a new MDT protocol for care of IE has been conducted in the United States.⁸

While effective MDTs certainly improve outcomes in patients with IE, there are reported differences in implementation of such an approach. With the MDT model as the core, various implementations included regular case conferences,^{10,11,19,21,23} formation of a consulting team,^6,8 or establishment of a new protocol or algorithm for care.^8,9,20 Our approach used a clinical pathway as a basis for improved communication among consulting services, education of learning providers via regular case conferences, and implementation of an electronic clinical care pathway to guide them step by step. Our pathway followed the institutionally standardized algorithm (Figure 1), using what we called the 6 T’s approach (Table 1), that guides providers to evaluate critical cases in a fast track.¹⁷

To the best of our knowledge, ours is the first report of an MDT that used an electronic clinical care pathway embedded within the EHR. The electronic version of our clinical pathway went live for only the second half of the postintervention study period, which is the most likely reason for its limited utilization. It is also possible that educational efforts in the first half of the intervention period were sufficient to familiarize providers with the care pathway such that the electronic version was seldom needed. We are exploring other possible ways of improving electronic pathway utilization, such as improving the feature usability and further systemwide educational efforts.

Our study has other limitations. Quasi-experimental before-and-after comparisons are subject to confounding from concurrent interventions. We had a substantial change in cardiothoracic faculty soon after the commencement of our efforts to form the MDT, and thus cannot rule out differences related to their comfort level in considering or offering surgery. We also cannot rule out a Hawthorne effect, where knowledge of the ongoing quality-improvement project changed provider behavior, making surgery more likely. We did not evaluate rates of right- versus left-sided endocarditis, which have been linked to mortality.²⁴ Our study also was performed across a single academic institution, which may limit its generalizability. Finally, our study may not have been adequately powered to detect differences in mortality due to implementation of the MDT approach.

Conclusion

Our work suggests that an MDT for IE can be successfully designed and implemented with a clinical pathway using quality-improvement tools in centers where subspecialty services are available. Our approach was associated with a higher rate of surgery among patients with guideline indications for surgery and may reduce in-hospital mortality. An electronic clinical care pathway embedded in the EHR is feasible and may have a role in MDT implementation.

These data were also accepted as a poster at IDWeek 2022, Washington, DC. The poster abstract is published in an online supplement of Open Forum Infectious Diseases as an abstract publication.

Corresponding author: Haley Crosby; hwc2pd@health.missouri.edu

Disclosures: None reported.

Study 1 Overview (Menon et al)

Objective: To determine whether a 0.25 mg/kg dose of intravenous tenecteplase is noninferior to intravenous alteplase 0.9 mg/kg for patients with acute ischemic stroke eligible for thrombolytic therapy.

Design: Multicenter, parallel-group, open-label randomized controlled trial.

Setting and participants: The trial was conducted at 22 primary and comprehensive stroke centers across Canada. A primary stroke center was defined as a hospital capable of offering intravenous thrombolysis to patients with acute ischemic stroke, while a comprehensive stroke center was able to offer thrombectomy services in addition. The involved centers also participated in Canadian quality improvement registries (either Quality Improvement and Clinical Research [QuiCR] or Optimizing Patient Treatment in Major Ischemic Stroke with EVT [OPTIMISE]) that track patient outcomes. Patients were eligible for inclusion if they were aged 18 years or older, had a diagnosis of acute ischemic stroke, presented within 4.5 hours of symptom onset, and were eligible for thrombolysis according to Canadian guidelines.

Patients were randomized in a 1:1 fashion to either intravenous tenecteplase (0.25 mg/kg single dose, maximum of 25 mg) or intravenous alteplase (0.9 mg/kg total dose to a maximum of 90 mg, delivered as a bolus followed by a continuous infusion). A total of 1600 patients were enrolled, with 816 randomly assigned to the tenecteplase arm and 784 to the alteplase arm; 1577 patients were included in the intention-to-treat (ITT) analysis (n = 806 tenecteplase; n = 771 alteplase). The median age of enrollees was 74 years, and 52.1% of the ITT population were men.

Main outcome measures: In the ITT population, the primary outcome measure was a modified Rankin score (mRS) of 0 or 1 at 90 to 120 days post treatment. Safety outcomes included symptomatic intracerebral hemorrhage, orolingual angioedema, extracranial bleeding that required blood transfusion (all within 24 hours of thrombolytic administration), and all-cause mortality at 90 days. The noninferiority threshold for intravenous tenecteplase was set as the lower 95% CI of the difference between the tenecteplase and alteplase groups in the proportion of patients who met the primary outcome exceeding –5%.

Main results: The primary outcome of mRS of either 0 or 1 at 90 to 120 days of treatment occurred in 296 (36.9%) of the 802 patients assigned to tenecteplase and 266 (34.8%) of the 765 patients assigned to alteplase (unadjusted risk difference, 2.1%; 95% CI, –2.6 to 6.9). The prespecified noninferiority threshold was met. There were no significant differences between the groups in rates of intracerebral hemorrhage at 24 hours or 90-day all-cause mortality.

Conclusion: Intravenous tenecteplase is a reasonable alternative to alteplase for patients eligible for thrombolytic therapy.

Study 2 Overview (Wang et al)

Objective: To determine whether tenecteplase (dose 0.25 mg/kg) is noninferior to alteplase in patients with acute ischemic stroke who are within 4.5 hours of symptom onset and eligible for thrombolytic therapy but either refused or were ineligible for endovascular thrombectomy.

Design: Multicenter, prospective, open-label, randomized, controlled noninferiority trial.

Setting and participants: This trial was conducted at 53 centers across China and included patients 18 years of age or older who were within 4.5 hours of symptom onset and were thrombolytic eligible, had a mRS ≤ 1 at enrollment, and had a National Institutes of Health Stroke Scale score between 5 and 25. Eligible participants were randomized 1:1 to either tenecteplase 0.25 mg/kg (maximum dose 25 mg) or alteplase 0.9 mg/kg (maximum dose 90 mg, administered as a bolus followed by infusion). During the enrollment period (June 12, 2021, to May 29, 2022), a total of 1430 participants were enrolled, and, of those, 716 were randomly assigned to tenecteplase and 714 to alteplase. Six patients assigned to tenecteplase and 7 assigned to alteplase did not receive drugs. At 90 days, 5 in the tenecteplase group and 11 in the alteplase group were lost to follow up.

Main outcome measures: The primary efficacy outcome was a mRS of 0 or 1 at 90 days. The primary safety outcome was intracranial hemorrhage within 36 hours. Safety outcomes included parenchymal hematoma 2, as defined by the European Cooperative Acute Stroke Study III; any intracranial or significant hemorrhage, as defined by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria; and death from all causes at 90 days. Noninferiority for tenecteplase would be declared if the lower 97.5% 1-sided CI for the relative risk (RR) for the primary outcome did not cross 0.937.

Main results: In the modified ITT population, the primary outcome occurred in 439 (62%) of the tenecteplase group and 405 (68%) of the alteplase group (RR, 1.07; 95% CI, 0.98-1.16). This met the prespecified margin for noninferiority. Intracranial hemorrhage within 36 hours was experienced by 15 (2%) patients in the tenecteplase group and 13 (2%) in the alteplase group (RR, 1.18; 95% CI, 0.56-2.50). Death at 90 days occurred in 46 (7%) patients in the tenecteplase group and 35 (5%) in the alteplase group (RR, 1.31; 95% CI, 0.86-2.01).

Conclusion: Tenecteplase was noninferior to alteplase in patients with acute ischemic stroke who met criteria for thrombolysis and either refused or were ineligible for endovascular thrombectomy.

Commentary

Alteplase has been FDA-approved for managing acute ischemic stroke since 1996 and has demonstrated positive effects on functional outcomes. Drawbacks of alteplase therapy, however, include bleeding risk as well as cumbersome administration of a bolus dose followed by a 60-minute infusion. In recent years, the question of whether or not tenecteplase could replace alteplase as the preferred thrombolytic for acute ischemic stroke has garnered much attention. Several features of tenecteplase make it an attractive option, including increased fibrin specificity, a longer half-life, and ease of administration as a single, rapid bolus dose. In phase 2 trials that compared tenecteplase 0.25 mg/kg with alteplase, findings suggested the potential for early neurological improvement as well as improved outcomes at 90 days. While the role of tenecteplase in acute myocardial infarction has been well established due to ease of use and a favorable adverse-effect profile,¹ there is much less evidence from phase 3 randomized controlled clinical trials to secure the role of tenecteplase in acute ischemic stroke.²

Menon et al attempted to close this gap in the literature by conducting a randomized controlled clinical trial (AcT) comparing tenecteplase to alteplase in a Canadian patient population. The trial's patient population mirrors that of real-world data from global registries in terms of age, sex, and baseline stroke severity. In addition, the eligibility window of 4.5 hours from symptom onset as well as the inclusion and exclusion criteria for therapy are common to those utilized in other countries, making the findings generalizable. There were some limitations to the study, however, including the impact of COVID-19 on recruitment efforts as well as limitations of research infrastructure and staffing, which may have limited enrollment efforts at primary stroke centers. Nonetheless, the authors concluded that their results provide evidence that tenecteplase is comparable to alteplase, with similar functional and safety outcomes.

TRACE-2 focused on an Asian patient population and provided follow up to the dose-ranging TRACE-1 phase 2 trial. TRACE-1 showed that tenecteplase 0.25 mg/kg had a similar safety profile to alteplase 0.9 mg/kg in Chinese patients presenting with acute ischemic stroke. TRACE-2 sought to establish noninferiority of tenecteplase and excluded patients who were ineligible for or refused thrombectomy. Interestingly, the tenecteplase arm, as the authors point out, had numerically greater mortality as well as intracranial hemorrhage, but these differences were not statistically significant between the treatment groups at 90 days. The TRACE-2 results parallel those of AcT, and although there were differences in ethnicity between the 2 trials, the authors cite this as evidence that the results are consistent and provide evidence for the role of tenecteplase in the management of acute ischemic stroke. Limitations of this trial include potential bias from its open-label design, as well as exclusion of patients with more severe strokes eligible for thrombectomy, which may limit generalizability to patients with more disabling strokes who could have a higher risk of intracranial hemorrhage.

Application for Clinical Practice and System Implementation

Across the country, many organizations have adopted the off-label use of tenecteplase for managing fibrinolytic-eligible acute ischemic stroke patients. In most cases, the impetus for change is the ease of dosing and administration of tenecteplase compared to alteplase, while the inclusion and exclusion criteria and overall management remain the same. Timely administration of therapy in stroke is critical. This, along with other time constraints in stroke workflows, the weight-based calculation of alteplase doses, and alteplase’s administration method may lead to medication errors when using this agent to treat patients with acute stroke. The rapid, single-dose administration of tenecteplase removes many barriers that hospitals face when patients may need to be treated and then transferred to another site for further care. Without the worry to “drip and ship,” the completion of administration may allow for timely patient transfer and eliminate the need for monitoring of an infusion during transfer. For some organizations, there may be a potential for drug cost-savings as well as improved metrics, such as door-to-needle time, but the overall effects of switching from alteplase to tenecteplase remain to be seen. Currently, tenecteplase is included in stroke guidelines as a “reasonable choice,” though with a low level of evidence.³ However, these 2 studies support the role of tenecteplase in acute ischemic stroke treatment and may provide a foundation for further studies to establish the role of tenecteplase in the acute ischemic stroke population.

Practice Points

• Tenecteplase may be considered as an alternative to alteplase for acute ischemic stroke for patients who meet eligibility criteria for thrombolytics; this recommendation is included in the most recent stroke guidelines, although tenecteplase has not been demonstrated to be superior to alteplase.
• The ease of administration of tenecteplase as a single intravenous bolus dose represents a benefit compared to alteplase; it is an off-label use, however, and further studies are needed to establish the superiority of tenecteplase in terms of functional and safety outcomes.

– Carol Heunisch, PharmD, BCPS, BCCP
Pharmacy Department, NorthShore–Edward-Elmhurst Health, Evanston, IL

Study 1 Overview (Menon et al)

Objective: To determine whether a 0.25 mg/kg dose of intravenous tenecteplase is noninferior to intravenous alteplase 0.9 mg/kg for patients with acute ischemic stroke eligible for thrombolytic therapy.

Design: Multicenter, parallel-group, open-label randomized controlled trial.

Setting and participants: The trial was conducted at 22 primary and comprehensive stroke centers across Canada. A primary stroke center was defined as a hospital capable of offering intravenous thrombolysis to patients with acute ischemic stroke, while a comprehensive stroke center was able to offer thrombectomy services in addition. The involved centers also participated in Canadian quality improvement registries (either Quality Improvement and Clinical Research [QuiCR] or Optimizing Patient Treatment in Major Ischemic Stroke with EVT [OPTIMISE]) that track patient outcomes. Patients were eligible for inclusion if they were aged 18 years or older, had a diagnosis of acute ischemic stroke, presented within 4.5 hours of symptom onset, and were eligible for thrombolysis according to Canadian guidelines.

Patients were randomized in a 1:1 fashion to either intravenous tenecteplase (0.25 mg/kg single dose, maximum of 25 mg) or intravenous alteplase (0.9 mg/kg total dose to a maximum of 90 mg, delivered as a bolus followed by a continuous infusion). A total of 1600 patients were enrolled, with 816 randomly assigned to the tenecteplase arm and 784 to the alteplase arm; 1577 patients were included in the intention-to-treat (ITT) analysis (n = 806 tenecteplase; n = 771 alteplase). The median age of enrollees was 74 years, and 52.1% of the ITT population were men.

Main outcome measures: In the ITT population, the primary outcome measure was a modified Rankin score (mRS) of 0 or 1 at 90 to 120 days post treatment. Safety outcomes included symptomatic intracerebral hemorrhage, orolingual angioedema, extracranial bleeding that required blood transfusion (all within 24 hours of thrombolytic administration), and all-cause mortality at 90 days. The noninferiority threshold for intravenous tenecteplase was set as the lower 95% CI of the difference between the tenecteplase and alteplase groups in the proportion of patients who met the primary outcome exceeding –5%.

Main results: The primary outcome of mRS of either 0 or 1 at 90 to 120 days of treatment occurred in 296 (36.9%) of the 802 patients assigned to tenecteplase and 266 (34.8%) of the 765 patients assigned to alteplase (unadjusted risk difference, 2.1%; 95% CI, –2.6 to 6.9). The prespecified noninferiority threshold was met. There were no significant differences between the groups in rates of intracerebral hemorrhage at 24 hours or 90-day all-cause mortality.

Conclusion: Intravenous tenecteplase is a reasonable alternative to alteplase for patients eligible for thrombolytic therapy.

Study 2 Overview (Wang et al)

Objective: To determine whether tenecteplase (dose 0.25 mg/kg) is noninferior to alteplase in patients with acute ischemic stroke who are within 4.5 hours of symptom onset and eligible for thrombolytic therapy but either refused or were ineligible for endovascular thrombectomy.

Design: Multicenter, prospective, open-label, randomized, controlled noninferiority trial.

Setting and participants: This trial was conducted at 53 centers across China and included patients 18 years of age or older who were within 4.5 hours of symptom onset and were thrombolytic eligible, had a mRS ≤ 1 at enrollment, and had a National Institutes of Health Stroke Scale score between 5 and 25. Eligible participants were randomized 1:1 to either tenecteplase 0.25 mg/kg (maximum dose 25 mg) or alteplase 0.9 mg/kg (maximum dose 90 mg, administered as a bolus followed by infusion). During the enrollment period (June 12, 2021, to May 29, 2022), a total of 1430 participants were enrolled, and, of those, 716 were randomly assigned to tenecteplase and 714 to alteplase. Six patients assigned to tenecteplase and 7 assigned to alteplase did not receive drugs. At 90 days, 5 in the tenecteplase group and 11 in the alteplase group were lost to follow up.

Main outcome measures: The primary efficacy outcome was a mRS of 0 or 1 at 90 days. The primary safety outcome was intracranial hemorrhage within 36 hours. Safety outcomes included parenchymal hematoma 2, as defined by the European Cooperative Acute Stroke Study III; any intracranial or significant hemorrhage, as defined by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria; and death from all causes at 90 days. Noninferiority for tenecteplase would be declared if the lower 97.5% 1-sided CI for the relative risk (RR) for the primary outcome did not cross 0.937.

Main results: In the modified ITT population, the primary outcome occurred in 439 (62%) of the tenecteplase group and 405 (68%) of the alteplase group (RR, 1.07; 95% CI, 0.98-1.16). This met the prespecified margin for noninferiority. Intracranial hemorrhage within 36 hours was experienced by 15 (2%) patients in the tenecteplase group and 13 (2%) in the alteplase group (RR, 1.18; 95% CI, 0.56-2.50). Death at 90 days occurred in 46 (7%) patients in the tenecteplase group and 35 (5%) in the alteplase group (RR, 1.31; 95% CI, 0.86-2.01).

Conclusion: Tenecteplase was noninferior to alteplase in patients with acute ischemic stroke who met criteria for thrombolysis and either refused or were ineligible for endovascular thrombectomy.

Commentary

Alteplase has been FDA-approved for managing acute ischemic stroke since 1996 and has demonstrated positive effects on functional outcomes. Drawbacks of alteplase therapy, however, include bleeding risk as well as cumbersome administration of a bolus dose followed by a 60-minute infusion. In recent years, the question of whether or not tenecteplase could replace alteplase as the preferred thrombolytic for acute ischemic stroke has garnered much attention. Several features of tenecteplase make it an attractive option, including increased fibrin specificity, a longer half-life, and ease of administration as a single, rapid bolus dose. In phase 2 trials that compared tenecteplase 0.25 mg/kg with alteplase, findings suggested the potential for early neurological improvement as well as improved outcomes at 90 days. While the role of tenecteplase in acute myocardial infarction has been well established due to ease of use and a favorable adverse-effect profile,¹ there is much less evidence from phase 3 randomized controlled clinical trials to secure the role of tenecteplase in acute ischemic stroke.²

Menon et al attempted to close this gap in the literature by conducting a randomized controlled clinical trial (AcT) comparing tenecteplase to alteplase in a Canadian patient population. The trial's patient population mirrors that of real-world data from global registries in terms of age, sex, and baseline stroke severity. In addition, the eligibility window of 4.5 hours from symptom onset as well as the inclusion and exclusion criteria for therapy are common to those utilized in other countries, making the findings generalizable. There were some limitations to the study, however, including the impact of COVID-19 on recruitment efforts as well as limitations of research infrastructure and staffing, which may have limited enrollment efforts at primary stroke centers. Nonetheless, the authors concluded that their results provide evidence that tenecteplase is comparable to alteplase, with similar functional and safety outcomes.

TRACE-2 focused on an Asian patient population and provided follow up to the dose-ranging TRACE-1 phase 2 trial. TRACE-1 showed that tenecteplase 0.25 mg/kg had a similar safety profile to alteplase 0.9 mg/kg in Chinese patients presenting with acute ischemic stroke. TRACE-2 sought to establish noninferiority of tenecteplase and excluded patients who were ineligible for or refused thrombectomy. Interestingly, the tenecteplase arm, as the authors point out, had numerically greater mortality as well as intracranial hemorrhage, but these differences were not statistically significant between the treatment groups at 90 days. The TRACE-2 results parallel those of AcT, and although there were differences in ethnicity between the 2 trials, the authors cite this as evidence that the results are consistent and provide evidence for the role of tenecteplase in the management of acute ischemic stroke. Limitations of this trial include potential bias from its open-label design, as well as exclusion of patients with more severe strokes eligible for thrombectomy, which may limit generalizability to patients with more disabling strokes who could have a higher risk of intracranial hemorrhage.

Application for Clinical Practice and System Implementation

Across the country, many organizations have adopted the off-label use of tenecteplase for managing fibrinolytic-eligible acute ischemic stroke patients. In most cases, the impetus for change is the ease of dosing and administration of tenecteplase compared to alteplase, while the inclusion and exclusion criteria and overall management remain the same. Timely administration of therapy in stroke is critical. This, along with other time constraints in stroke workflows, the weight-based calculation of alteplase doses, and alteplase’s administration method may lead to medication errors when using this agent to treat patients with acute stroke. The rapid, single-dose administration of tenecteplase removes many barriers that hospitals face when patients may need to be treated and then transferred to another site for further care. Without the worry to “drip and ship,” the completion of administration may allow for timely patient transfer and eliminate the need for monitoring of an infusion during transfer. For some organizations, there may be a potential for drug cost-savings as well as improved metrics, such as door-to-needle time, but the overall effects of switching from alteplase to tenecteplase remain to be seen. Currently, tenecteplase is included in stroke guidelines as a “reasonable choice,” though with a low level of evidence.³ However, these 2 studies support the role of tenecteplase in acute ischemic stroke treatment and may provide a foundation for further studies to establish the role of tenecteplase in the acute ischemic stroke population.

Practice Points

• Tenecteplase may be considered as an alternative to alteplase for acute ischemic stroke for patients who meet eligibility criteria for thrombolytics; this recommendation is included in the most recent stroke guidelines, although tenecteplase has not been demonstrated to be superior to alteplase.
• The ease of administration of tenecteplase as a single intravenous bolus dose represents a benefit compared to alteplase; it is an off-label use, however, and further studies are needed to establish the superiority of tenecteplase in terms of functional and safety outcomes.

– Carol Heunisch, PharmD, BCPS, BCCP
Pharmacy Department, NorthShore–Edward-Elmhurst Health, Evanston, IL

Study 1 Overview (Menon et al)

Objective: To determine whether a 0.25 mg/kg dose of intravenous tenecteplase is noninferior to intravenous alteplase 0.9 mg/kg for patients with acute ischemic stroke eligible for thrombolytic therapy.

Design: Multicenter, parallel-group, open-label randomized controlled trial.

Setting and participants: The trial was conducted at 22 primary and comprehensive stroke centers across Canada. A primary stroke center was defined as a hospital capable of offering intravenous thrombolysis to patients with acute ischemic stroke, while a comprehensive stroke center was able to offer thrombectomy services in addition. The involved centers also participated in Canadian quality improvement registries (either Quality Improvement and Clinical Research [QuiCR] or Optimizing Patient Treatment in Major Ischemic Stroke with EVT [OPTIMISE]) that track patient outcomes. Patients were eligible for inclusion if they were aged 18 years or older, had a diagnosis of acute ischemic stroke, presented within 4.5 hours of symptom onset, and were eligible for thrombolysis according to Canadian guidelines.

Patients were randomized in a 1:1 fashion to either intravenous tenecteplase (0.25 mg/kg single dose, maximum of 25 mg) or intravenous alteplase (0.9 mg/kg total dose to a maximum of 90 mg, delivered as a bolus followed by a continuous infusion). A total of 1600 patients were enrolled, with 816 randomly assigned to the tenecteplase arm and 784 to the alteplase arm; 1577 patients were included in the intention-to-treat (ITT) analysis (n = 806 tenecteplase; n = 771 alteplase). The median age of enrollees was 74 years, and 52.1% of the ITT population were men.

Main outcome measures: In the ITT population, the primary outcome measure was a modified Rankin score (mRS) of 0 or 1 at 90 to 120 days post treatment. Safety outcomes included symptomatic intracerebral hemorrhage, orolingual angioedema, extracranial bleeding that required blood transfusion (all within 24 hours of thrombolytic administration), and all-cause mortality at 90 days. The noninferiority threshold for intravenous tenecteplase was set as the lower 95% CI of the difference between the tenecteplase and alteplase groups in the proportion of patients who met the primary outcome exceeding –5%.

Main results: The primary outcome of mRS of either 0 or 1 at 90 to 120 days of treatment occurred in 296 (36.9%) of the 802 patients assigned to tenecteplase and 266 (34.8%) of the 765 patients assigned to alteplase (unadjusted risk difference, 2.1%; 95% CI, –2.6 to 6.9). The prespecified noninferiority threshold was met. There were no significant differences between the groups in rates of intracerebral hemorrhage at 24 hours or 90-day all-cause mortality.

Conclusion: Intravenous tenecteplase is a reasonable alternative to alteplase for patients eligible for thrombolytic therapy.

Study 2 Overview (Wang et al)

Objective: To determine whether tenecteplase (dose 0.25 mg/kg) is noninferior to alteplase in patients with acute ischemic stroke who are within 4.5 hours of symptom onset and eligible for thrombolytic therapy but either refused or were ineligible for endovascular thrombectomy.

Design: Multicenter, prospective, open-label, randomized, controlled noninferiority trial.

Setting and participants: This trial was conducted at 53 centers across China and included patients 18 years of age or older who were within 4.5 hours of symptom onset and were thrombolytic eligible, had a mRS ≤ 1 at enrollment, and had a National Institutes of Health Stroke Scale score between 5 and 25. Eligible participants were randomized 1:1 to either tenecteplase 0.25 mg/kg (maximum dose 25 mg) or alteplase 0.9 mg/kg (maximum dose 90 mg, administered as a bolus followed by infusion). During the enrollment period (June 12, 2021, to May 29, 2022), a total of 1430 participants were enrolled, and, of those, 716 were randomly assigned to tenecteplase and 714 to alteplase. Six patients assigned to tenecteplase and 7 assigned to alteplase did not receive drugs. At 90 days, 5 in the tenecteplase group and 11 in the alteplase group were lost to follow up.

Main outcome measures: The primary efficacy outcome was a mRS of 0 or 1 at 90 days. The primary safety outcome was intracranial hemorrhage within 36 hours. Safety outcomes included parenchymal hematoma 2, as defined by the European Cooperative Acute Stroke Study III; any intracranial or significant hemorrhage, as defined by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria; and death from all causes at 90 days. Noninferiority for tenecteplase would be declared if the lower 97.5% 1-sided CI for the relative risk (RR) for the primary outcome did not cross 0.937.

Main results: In the modified ITT population, the primary outcome occurred in 439 (62%) of the tenecteplase group and 405 (68%) of the alteplase group (RR, 1.07; 95% CI, 0.98-1.16). This met the prespecified margin for noninferiority. Intracranial hemorrhage within 36 hours was experienced by 15 (2%) patients in the tenecteplase group and 13 (2%) in the alteplase group (RR, 1.18; 95% CI, 0.56-2.50). Death at 90 days occurred in 46 (7%) patients in the tenecteplase group and 35 (5%) in the alteplase group (RR, 1.31; 95% CI, 0.86-2.01).

Conclusion: Tenecteplase was noninferior to alteplase in patients with acute ischemic stroke who met criteria for thrombolysis and either refused or were ineligible for endovascular thrombectomy.

Commentary

Alteplase has been FDA-approved for managing acute ischemic stroke since 1996 and has demonstrated positive effects on functional outcomes. Drawbacks of alteplase therapy, however, include bleeding risk as well as cumbersome administration of a bolus dose followed by a 60-minute infusion. In recent years, the question of whether or not tenecteplase could replace alteplase as the preferred thrombolytic for acute ischemic stroke has garnered much attention. Several features of tenecteplase make it an attractive option, including increased fibrin specificity, a longer half-life, and ease of administration as a single, rapid bolus dose. In phase 2 trials that compared tenecteplase 0.25 mg/kg with alteplase, findings suggested the potential for early neurological improvement as well as improved outcomes at 90 days. While the role of tenecteplase in acute myocardial infarction has been well established due to ease of use and a favorable adverse-effect profile,¹ there is much less evidence from phase 3 randomized controlled clinical trials to secure the role of tenecteplase in acute ischemic stroke.²

Menon et al attempted to close this gap in the literature by conducting a randomized controlled clinical trial (AcT) comparing tenecteplase to alteplase in a Canadian patient population. The trial's patient population mirrors that of real-world data from global registries in terms of age, sex, and baseline stroke severity. In addition, the eligibility window of 4.5 hours from symptom onset as well as the inclusion and exclusion criteria for therapy are common to those utilized in other countries, making the findings generalizable. There were some limitations to the study, however, including the impact of COVID-19 on recruitment efforts as well as limitations of research infrastructure and staffing, which may have limited enrollment efforts at primary stroke centers. Nonetheless, the authors concluded that their results provide evidence that tenecteplase is comparable to alteplase, with similar functional and safety outcomes.

TRACE-2 focused on an Asian patient population and provided follow up to the dose-ranging TRACE-1 phase 2 trial. TRACE-1 showed that tenecteplase 0.25 mg/kg had a similar safety profile to alteplase 0.9 mg/kg in Chinese patients presenting with acute ischemic stroke. TRACE-2 sought to establish noninferiority of tenecteplase and excluded patients who were ineligible for or refused thrombectomy. Interestingly, the tenecteplase arm, as the authors point out, had numerically greater mortality as well as intracranial hemorrhage, but these differences were not statistically significant between the treatment groups at 90 days. The TRACE-2 results parallel those of AcT, and although there were differences in ethnicity between the 2 trials, the authors cite this as evidence that the results are consistent and provide evidence for the role of tenecteplase in the management of acute ischemic stroke. Limitations of this trial include potential bias from its open-label design, as well as exclusion of patients with more severe strokes eligible for thrombectomy, which may limit generalizability to patients with more disabling strokes who could have a higher risk of intracranial hemorrhage.

Application for Clinical Practice and System Implementation

Across the country, many organizations have adopted the off-label use of tenecteplase for managing fibrinolytic-eligible acute ischemic stroke patients. In most cases, the impetus for change is the ease of dosing and administration of tenecteplase compared to alteplase, while the inclusion and exclusion criteria and overall management remain the same. Timely administration of therapy in stroke is critical. This, along with other time constraints in stroke workflows, the weight-based calculation of alteplase doses, and alteplase’s administration method may lead to medication errors when using this agent to treat patients with acute stroke. The rapid, single-dose administration of tenecteplase removes many barriers that hospitals face when patients may need to be treated and then transferred to another site for further care. Without the worry to “drip and ship,” the completion of administration may allow for timely patient transfer and eliminate the need for monitoring of an infusion during transfer. For some organizations, there may be a potential for drug cost-savings as well as improved metrics, such as door-to-needle time, but the overall effects of switching from alteplase to tenecteplase remain to be seen. Currently, tenecteplase is included in stroke guidelines as a “reasonable choice,” though with a low level of evidence.³ However, these 2 studies support the role of tenecteplase in acute ischemic stroke treatment and may provide a foundation for further studies to establish the role of tenecteplase in the acute ischemic stroke population.

Practice Points

• Tenecteplase may be considered as an alternative to alteplase for acute ischemic stroke for patients who meet eligibility criteria for thrombolytics; this recommendation is included in the most recent stroke guidelines, although tenecteplase has not been demonstrated to be superior to alteplase.
• The ease of administration of tenecteplase as a single intravenous bolus dose represents a benefit compared to alteplase; it is an off-label use, however, and further studies are needed to establish the superiority of tenecteplase in terms of functional and safety outcomes.

– Carol Heunisch, PharmD, BCPS, BCCP
Pharmacy Department, NorthShore–Edward-Elmhurst Health, Evanston, IL

Difficulty in accessing a family physician is associated with a higher risk for unplanned return visits to the emergency department among patients aged 75 years and older, new data indicate.

In a prospective, observational study that included almost 2,000 patients in this age group, 16% of participants attempted to contact their family physicians before their ED visits. Of this group, more than half reported having difficulty seeing their physicians for urgent problems, more than 40% had difficulty speaking with their family physicians by telephone, and more than one-third had difficulty booking appointments for new health problems.

“Difficulty in accessing primary care was associated with a higher rate of return visits to the ED within an elderly population,” write study author Marc Afilalo, MD, director of the ED at Jewish General Hospital in Montreal, and colleagues. “Therefore, community-based programs that target patient education and improved access to primary care are necessary not only for reducing return visits to the ED, but also for continuity of care and patient satisfaction.”

The study was published in Canadian Family Physician.
 

Comorbidities increased risk

Researchers have estimated that half of Canadians aged 75 years or older use emergency services. Data indicate that the number of unplanned return visits to the ED is associated with increased functional decline and death. But the question of how patient access to primary care services affects unplanned ED return visits has received little attention, according to the investigators.

They conducted a multicenter study at three tertiary adult teaching hospitals in Montreal. From 2012 to 2014, they recruited patients aged 75 years and older who had visited the ED and who lived in their own homes or in an autonomous residence.

Investigators collected data through structured interviews, administrative databases, and medical chart reviews. They followed up with participants at 3 months by telephone. The study’s main outcome was return visit to the ED.

The researchers identified 4,577 patients and included 1,998 in their analysis. Of that total, 33% were 85 or older, 34% lived alone, and 91% had a family physician. Within 3 months, 562 patients (28%) had made 894 return visits to the ED.

Among patients aged 85 years or older (relative risk, 0.80), as well as those whose triage score was less severe (RR, 0.83) and those who were admitted during the index ED visit (RR, 0.76), rates of return ED visits were lower. Among patients who had trouble booking appointments with their family doctors to address new problems (RR, 1.19), as well as those who had made ED visits within the previous 6 months (RR, 1.47) or had a higher Charlson comorbidity index score (RR, 1.06 for every 1-unit increase), rates of return visits were higher.

Factors associated with a higher likelihood of return visits were visits to the ED in the previous 6 months (odds ratio, 2.11), increased Charlson comorbidity index score (OR, 1.41 for every 1-unit increase), and having received help from local community services (OR, 3.00).
 

Primary care access

The study suggests that improvements in primary care access are needed to decrease return visits to the ED, Samir Sinha, MD, DPhil, director of geriatrics at Mount Sinai and the University Health Network Hospitals in Toronto, told this news organization. Dr. Sinha was not involved in the study.

“It reminds us of the importance of having a strong primary care system,” he added. “Of this population, 91% had primary care providers. And what the paper demonstrates is that those who are having trouble accessing their primary care providers are more likely to be readmitted to an ED. We can only imagine how much worse the outcomes are for people who don’t have a primary care provider.”

Patients are frequently advised to visit the ED when they contact their primary care providers, said Mark Rosenberg, PhD, professor of geography and planning and the Canada Research Chair in Aging, Health, and Development at Queens University in Kingston, Ont., said in an interview. He noted that primary care is organized as an appointment-based system. Dr. Rosenberg did not participate in the study.

“If I were to call my primary care provider in the middle of the afternoon and say that I have got chest pains, they are going to simply tell me to go to emergency,” said Dr. Rosenberg. “It is not just older people. Many people end up in the ED because they are told to go to the ED.”
 

Associations with age

“The higher your Charlson comorbidity index, the more multiple, complex health issues you’re dealing with,” said Sinha. He added that the data suggest the frailty of the study population.

The association between age 85 years or older and a lower rate of a return ED visits might mean that the patient did not return to independent living after the ED visit, Dr. Rosenberg speculated. “If it’s a serious health problem, you’re more likely to end up going into long-term care at that stage, and you are not going back to living in the community in your home,” he said. “You’re likely going into some sort of transition care or alternative care.”

People aged 85 years or older who are hospitalized are more likely not to survive their index hospital admission, compared with patients who are aged 75-85 years. There would be no possibility that such patients would revisit the ED in the future, said Dr. Sinha.
 

Expanding primary care

The major solution to decreasing reliance on the ED lies in revamping primary health care so that it offers an expanded level of care and 24/7 access, said Dr. Rosenberg.

Providing continuity of care, identifying problems, and managing them in the community before they become urgent or require a hospitalization are priorities for primary care and will help shift away from return visits to the ED, which should be a last resort for patients, said Dr. Sinha.

Moreover, patients must be able to access primary care in various ways, be it a telephone consultation, a video consultation, or a face-to-face consultation, he added. Face-to-face consultations can take place in a provider’s office or even in a patient’s home when warranted, he said. “What we need to make sure of is that all three types of consultations are available, so that people can actually get the most appropriate care at the time they’re calling.”

The study had no external funding. Dr. Afilalo, Dr. Sinha, and Dr. Rosenberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Difficulty in accessing a family physician is associated with a higher risk for unplanned return visits to the emergency department among patients aged 75 years and older, new data indicate.

In a prospective, observational study that included almost 2,000 patients in this age group, 16% of participants attempted to contact their family physicians before their ED visits. Of this group, more than half reported having difficulty seeing their physicians for urgent problems, more than 40% had difficulty speaking with their family physicians by telephone, and more than one-third had difficulty booking appointments for new health problems.

“Difficulty in accessing primary care was associated with a higher rate of return visits to the ED within an elderly population,” write study author Marc Afilalo, MD, director of the ED at Jewish General Hospital in Montreal, and colleagues. “Therefore, community-based programs that target patient education and improved access to primary care are necessary not only for reducing return visits to the ED, but also for continuity of care and patient satisfaction.”

The study was published in Canadian Family Physician.
 

Comorbidities increased risk

Researchers have estimated that half of Canadians aged 75 years or older use emergency services. Data indicate that the number of unplanned return visits to the ED is associated with increased functional decline and death. But the question of how patient access to primary care services affects unplanned ED return visits has received little attention, according to the investigators.

They conducted a multicenter study at three tertiary adult teaching hospitals in Montreal. From 2012 to 2014, they recruited patients aged 75 years and older who had visited the ED and who lived in their own homes or in an autonomous residence.

Investigators collected data through structured interviews, administrative databases, and medical chart reviews. They followed up with participants at 3 months by telephone. The study’s main outcome was return visit to the ED.

The researchers identified 4,577 patients and included 1,998 in their analysis. Of that total, 33% were 85 or older, 34% lived alone, and 91% had a family physician. Within 3 months, 562 patients (28%) had made 894 return visits to the ED.

Among patients aged 85 years or older (relative risk, 0.80), as well as those whose triage score was less severe (RR, 0.83) and those who were admitted during the index ED visit (RR, 0.76), rates of return ED visits were lower. Among patients who had trouble booking appointments with their family doctors to address new problems (RR, 1.19), as well as those who had made ED visits within the previous 6 months (RR, 1.47) or had a higher Charlson comorbidity index score (RR, 1.06 for every 1-unit increase), rates of return visits were higher.

Factors associated with a higher likelihood of return visits were visits to the ED in the previous 6 months (odds ratio, 2.11), increased Charlson comorbidity index score (OR, 1.41 for every 1-unit increase), and having received help from local community services (OR, 3.00).
 

Primary care access

The study suggests that improvements in primary care access are needed to decrease return visits to the ED, Samir Sinha, MD, DPhil, director of geriatrics at Mount Sinai and the University Health Network Hospitals in Toronto, told this news organization. Dr. Sinha was not involved in the study.

“It reminds us of the importance of having a strong primary care system,” he added. “Of this population, 91% had primary care providers. And what the paper demonstrates is that those who are having trouble accessing their primary care providers are more likely to be readmitted to an ED. We can only imagine how much worse the outcomes are for people who don’t have a primary care provider.”

Patients are frequently advised to visit the ED when they contact their primary care providers, said Mark Rosenberg, PhD, professor of geography and planning and the Canada Research Chair in Aging, Health, and Development at Queens University in Kingston, Ont., said in an interview. He noted that primary care is organized as an appointment-based system. Dr. Rosenberg did not participate in the study.

“If I were to call my primary care provider in the middle of the afternoon and say that I have got chest pains, they are going to simply tell me to go to emergency,” said Dr. Rosenberg. “It is not just older people. Many people end up in the ED because they are told to go to the ED.”
 

Associations with age

“The higher your Charlson comorbidity index, the more multiple, complex health issues you’re dealing with,” said Sinha. He added that the data suggest the frailty of the study population.

The association between age 85 years or older and a lower rate of a return ED visits might mean that the patient did not return to independent living after the ED visit, Dr. Rosenberg speculated. “If it’s a serious health problem, you’re more likely to end up going into long-term care at that stage, and you are not going back to living in the community in your home,” he said. “You’re likely going into some sort of transition care or alternative care.”

People aged 85 years or older who are hospitalized are more likely not to survive their index hospital admission, compared with patients who are aged 75-85 years. There would be no possibility that such patients would revisit the ED in the future, said Dr. Sinha.
 

Expanding primary care

The major solution to decreasing reliance on the ED lies in revamping primary health care so that it offers an expanded level of care and 24/7 access, said Dr. Rosenberg.

Providing continuity of care, identifying problems, and managing them in the community before they become urgent or require a hospitalization are priorities for primary care and will help shift away from return visits to the ED, which should be a last resort for patients, said Dr. Sinha.

Moreover, patients must be able to access primary care in various ways, be it a telephone consultation, a video consultation, or a face-to-face consultation, he added. Face-to-face consultations can take place in a provider’s office or even in a patient’s home when warranted, he said. “What we need to make sure of is that all three types of consultations are available, so that people can actually get the most appropriate care at the time they’re calling.”

The study had no external funding. Dr. Afilalo, Dr. Sinha, and Dr. Rosenberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Difficulty in accessing a family physician is associated with a higher risk for unplanned return visits to the emergency department among patients aged 75 years and older, new data indicate.

In a prospective, observational study that included almost 2,000 patients in this age group, 16% of participants attempted to contact their family physicians before their ED visits. Of this group, more than half reported having difficulty seeing their physicians for urgent problems, more than 40% had difficulty speaking with their family physicians by telephone, and more than one-third had difficulty booking appointments for new health problems.

“Difficulty in accessing primary care was associated with a higher rate of return visits to the ED within an elderly population,” write study author Marc Afilalo, MD, director of the ED at Jewish General Hospital in Montreal, and colleagues. “Therefore, community-based programs that target patient education and improved access to primary care are necessary not only for reducing return visits to the ED, but also for continuity of care and patient satisfaction.”

The study was published in Canadian Family Physician.
 

Comorbidities increased risk

Researchers have estimated that half of Canadians aged 75 years or older use emergency services. Data indicate that the number of unplanned return visits to the ED is associated with increased functional decline and death. But the question of how patient access to primary care services affects unplanned ED return visits has received little attention, according to the investigators.

They conducted a multicenter study at three tertiary adult teaching hospitals in Montreal. From 2012 to 2014, they recruited patients aged 75 years and older who had visited the ED and who lived in their own homes or in an autonomous residence.

Investigators collected data through structured interviews, administrative databases, and medical chart reviews. They followed up with participants at 3 months by telephone. The study’s main outcome was return visit to the ED.

The researchers identified 4,577 patients and included 1,998 in their analysis. Of that total, 33% were 85 or older, 34% lived alone, and 91% had a family physician. Within 3 months, 562 patients (28%) had made 894 return visits to the ED.

Among patients aged 85 years or older (relative risk, 0.80), as well as those whose triage score was less severe (RR, 0.83) and those who were admitted during the index ED visit (RR, 0.76), rates of return ED visits were lower. Among patients who had trouble booking appointments with their family doctors to address new problems (RR, 1.19), as well as those who had made ED visits within the previous 6 months (RR, 1.47) or had a higher Charlson comorbidity index score (RR, 1.06 for every 1-unit increase), rates of return visits were higher.

Factors associated with a higher likelihood of return visits were visits to the ED in the previous 6 months (odds ratio, 2.11), increased Charlson comorbidity index score (OR, 1.41 for every 1-unit increase), and having received help from local community services (OR, 3.00).
 

Primary care access

The study suggests that improvements in primary care access are needed to decrease return visits to the ED, Samir Sinha, MD, DPhil, director of geriatrics at Mount Sinai and the University Health Network Hospitals in Toronto, told this news organization. Dr. Sinha was not involved in the study.

“It reminds us of the importance of having a strong primary care system,” he added. “Of this population, 91% had primary care providers. And what the paper demonstrates is that those who are having trouble accessing their primary care providers are more likely to be readmitted to an ED. We can only imagine how much worse the outcomes are for people who don’t have a primary care provider.”

Patients are frequently advised to visit the ED when they contact their primary care providers, said Mark Rosenberg, PhD, professor of geography and planning and the Canada Research Chair in Aging, Health, and Development at Queens University in Kingston, Ont., said in an interview. He noted that primary care is organized as an appointment-based system. Dr. Rosenberg did not participate in the study.

“If I were to call my primary care provider in the middle of the afternoon and say that I have got chest pains, they are going to simply tell me to go to emergency,” said Dr. Rosenberg. “It is not just older people. Many people end up in the ED because they are told to go to the ED.”
 

Associations with age

“The higher your Charlson comorbidity index, the more multiple, complex health issues you’re dealing with,” said Sinha. He added that the data suggest the frailty of the study population.

The association between age 85 years or older and a lower rate of a return ED visits might mean that the patient did not return to independent living after the ED visit, Dr. Rosenberg speculated. “If it’s a serious health problem, you’re more likely to end up going into long-term care at that stage, and you are not going back to living in the community in your home,” he said. “You’re likely going into some sort of transition care or alternative care.”

People aged 85 years or older who are hospitalized are more likely not to survive their index hospital admission, compared with patients who are aged 75-85 years. There would be no possibility that such patients would revisit the ED in the future, said Dr. Sinha.
 

Expanding primary care

The major solution to decreasing reliance on the ED lies in revamping primary health care so that it offers an expanded level of care and 24/7 access, said Dr. Rosenberg.

Providing continuity of care, identifying problems, and managing them in the community before they become urgent or require a hospitalization are priorities for primary care and will help shift away from return visits to the ED, which should be a last resort for patients, said Dr. Sinha.

Moreover, patients must be able to access primary care in various ways, be it a telephone consultation, a video consultation, or a face-to-face consultation, he added. Face-to-face consultations can take place in a provider’s office or even in a patient’s home when warranted, he said. “What we need to make sure of is that all three types of consultations are available, so that people can actually get the most appropriate care at the time they’re calling.”

The study had no external funding. Dr. Afilalo, Dr. Sinha, and Dr. Rosenberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

0722_JCOM_RFTF_Nelson_T1.JPG

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

0722_JCOM_RFTF_Nelson_F1.JPG

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; avery.nelson@uchospitals.edu

Disclosures: None reported.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

0722_JCOM_RFTF_Nelson_T1.JPG

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

0722_JCOM_RFTF_Nelson_F1.JPG

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; avery.nelson@uchospitals.edu

Disclosures: None reported.

From the University of Chicago Medical Center, Chicago, IL.

Abstract

Background: Epistaxis is a common chief complaint addressed by otolaryngologists. A review of the literature showed that there is a deficit in epistaxis education within the nursing community. Conversations with our nursing colleagues confirmed this unmet demand.

Objective: This quality improvement project aimed to increase general epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds among our nursing staff.

Methods: Data were collected through a survey administered before and after our intervention. The survey tested general epistaxis knowledge and assessed comfort and confidence in stopping epistaxis. Our intervention was an educational session covering pertinent epistaxis etiology and management. Quality improvement principles were used to optimize delivery of the intervention.

Results: A total of 51 nurses participated in the project. After participating in the in-service educational session, nurses answered significantly more epistaxis general knowledge questions correctly (mean [SD] difference, 2.07 [1.10] questions; 95% CI, 1.74-2.39; P < .001). There was no statistically significant difference in additional correct questions when stratified by clinical experience or clinical setting (P = .128 and P = 0.446, respectively). Nurses also reported feeling significantly more comfortable and significantly more confident in managing nosebleeds after the in-service (P = .007 and P < 0.001, respectively); 74.46% of nurses had an improvement in comfort level in managing epistaxis and 43.90% of nurses had an improvement in confidence in stopping epistaxis. After we moved the educational session from mid-shift to shift change, the nursing staff reported more satisfaction while maintaining similar improvements in knowledge and confidence.

Conclusion: We were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. Nurses of varying clinical experience and different clinical settings benefitted equally from our intervention.

Keywords: nosebleed; in-service; quality improvement.

Epistaxis, or nosebleed, is estimated to be the chief complaint in 1 in 200 emergency department visits in the United States.¹ Additionally, it represents up to one-third of otolaryngology-related emergency room admissions.² There is no existing literature, to our best knowledge, specifically investigating the incidence of epistaxis after a patient is admitted. Anecdotally, inpatients who develop epistaxis account for an appreciable number of consults to otolaryngology (ENT). Epistaxis is a cross-disciplinary issue, occurring in a range of clinical settings. For example, patients with epistaxis can present to the emergency department or to an outpatient primary care clinic before being referred to ENT. Additionally, inpatients on many different services can develop spontaneous epistaxis due to a variety of environmental and iatrogenic factors, such as dry air, use of nasal cannula, and initiation of anticoagulation. Based on the experience of our ENT providers and discussions with our nursing colleagues, we concluded that there was an interest in epistaxis management training among our nursing workforce.

The presence of unmet demand for epistaxis education among our nursing colleagues was supported by our literature review. A study performed in England surveyed emergency department nurses on first aid measures for management of epistaxis, including ideal head positioning, location of pressure application, and duration of pressure application.³ Overall, only 12% to 14% of the nursing staff answered all 3 questions correctly.³ Additionally, 73% to 78% of the nursing staff felt that their training in epistaxis management was inadequate, and 88% desired further training in epistaxis management.³ If generalized, this study confirms the demand for further epistaxis education among nurses.

In-services have previously been shown to be effective educational tools within the nursing community. A study in Ethiopia that evaluated pain management knowledge and attitudes before and after an in-service found a significant improvement in mean rank score of nurses’ knowledge and attitudes regarding pain management after they participated in the in-service.⁴ Scores on the knowledge survey improved from 41.4% before the intervention to 63.0% post intervention.⁴ A study in Connecticut evaluated nurses’ confidence in discussing suicidal ideation with patients and knowledge surrounding suicide precautions.⁵ After participating in an in-service, nurses were significantly more confident in discussing suicidal ideation with patients; application of appropriate suicide precautions also increased after the in-service.⁵

Our aim was for nurses to have an improvement in overall epistaxis knowledge, perceived comfort level managing nosebleeds, and perceived ability to stop nosebleeds after attending our in-service. Additionally, an overarching priority was to provide high-quality epistaxis education based on the literature and best practice guidelines.

Methods

Setting

This study was carried out at an 811-bed quaternary care center located in Chicago, Illinois. In fiscal year 2021, there were 91 643 emergency department visits and 33 805 hospital admissions. At our flagship hospital, 2658 patients were diagnosed with epistaxis during fiscal year 2021. The emergency department saw 533 patients with epistaxis, with 342 requiring admission and 191 being discharged. Separately, 566 inpatients received a diagnosis of epistaxis during their admission. The remainder of the patients with epistaxis were seen on an outpatient basis.

Data Collection

Data were collected from nurses on 5 different inpatient units. An email with information about the in-service was sent to the nurse managers of the inpatient units. These 5 units were included because the nurse managers responded to the email and facilitated delivery of the in-service. Data collection took place from August to December 2020.

Intervention

A quality improvement team composed of a resident physician champion, nurse educators, and nurse managers was formed. The physician champion was a senior otolaryngology resident who was responsible for designing and administering the pre-test, in-service, and post test. The nurse educators and nurse managers helped coordinate times for the in-service and promoted the in-service for their staff.

Our intervention was an educational in-service, a technique that is commonly used at our institution for nurse education. In-services typically involve delivering a lecture on a clinically relevant topic to a group of nurses on a unit. In developing the in-service, a top priority was to present high-quality evidence-based material. There is an abundance of information in the literature surrounding epistaxis management. The clinical practice guideline published by the American Academy of Otolaryngology lists nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery as first-line treatments for the management of epistaxis.⁶ Nasal packing and nasal cautery tend to be perceived as interventions that require a certain level of expertise and specialized supplies. As such, these interventions are not often performed by floor nurses. In contrast, nasal compression and application of vasoconstrictors require only a few easily accessible supplies, and the risks are relatively minimal. When performing nasal compression, the clinical practice guidelines recommend firm, sustained compression to the lower third of the nose for 5 minutes or longer.⁶ Topical vasoconstrictors are generally underutilized in epistaxis management. In a study looking at a random sample of all US emergency department visits from 1992 to 2001, only 18% of visits used an epistaxis-related medication.² Oxymetazoline hydrochloride is a topical vasoconstrictor that is commonly used as a nasal decongestant. However, its vasoconstrictor properties also make it a useful tool for controlling epistaxis. In a study looking at emergency department visits at the University of Texas Health Science Center, 65% of patients had resolution of nosebleed with application of oxymetazoline hydrochloride as the only intervention, with another 18% experiencing resolution of nosebleed with a combination of oxymetazoline hydrochloride and silver nitrate cautery.⁷ Based on review of the literature, nasal compression and application of vasoconstrictors seemed to be low-resource interventions with minimal morbidity. Therefore, management centered around nasal compression and use of topical vasoconstrictors seemed appropriate for our nursing staff.

The in-service included information about the etiology and management of epistaxis. Particular emphasis was placed on addressing and debunking common misconceptions about nosebleed management. With regards to management, our presentation focused on the use of topical vasoconstrictors and firm pressure to the lower third of the nose for at least 5 minutes. Nasal packing and nasal cautery were presented as procedures that ENT would perform. After the in-service, questions from the nurses were answered as time permitted.

Testing and Outcomes

A pre-test was administered before each in-service. The pre-test components comprised a knowledge survey and a descriptive survey. The general epistaxis knowledge questions on the pre-test included the location of blood vessels most commonly responsible for nosebleeds, the ideal positioning of a patient during a nosebleed, the appropriate location to hold pressure during a nosebleed, and the appropriate duration to hold pressure during a nosebleed. The descriptive survey portion asked nurses to rate whether they felt “very comfortable,” “comfortable,” “uncomfortable,” or “very uncomfortable” managing nosebleeds. It also asked whether nurses thought they would be able to “always,” “usually,” “rarely,” or “never” stop nosebleeds on the floor. We collected demographic information, including gender identity, years of clinical experience, and primary clinical environment.

The post test asked the same questions as the pre-test and was administered immediately after the in-service in order to assess its impact. We also established an ongoing dialogue with our nursing colleagues to obtain feedback on the sessions.

Primary outcomes of interest were the difference in general epistaxis knowledge questions answered correctly between the pre-test and the post test; the difference in comfort level in managing epistaxis before and after the in-service; and the difference in confidence to stop nosebleeds before and after the in-service. A secondary outcome was determining the audience for the in-service. Specifically, we wanted to determine whether there were different outcomes based on clinical setting or years of clinical experience. If nurses in a certain clinical environment or beyond a certain experience level did not show significant improvement from pre-test to post test, we would not target them for the in-service. Another secondary outcome was determining optimal timing for delivery of the in-service. We wanted to determine if there was a nursing preference for delivering the in-service at mid-shift vs shift change.

Analysis

Statistical calculations were performed using Stata 15 (StataCorp LLC). A P value < .05 was considered to be statistically significant. Where applicable, 95% confidence intervals (CI) were calculated. T-test was used to determine whether there was a statistically significant difference between pre-test and post-test epistaxis knowledge question scores. T-test was also used to determine whether there was a statistically significant difference in test scores between nurses receiving the in-service at mid-shift vs shift change. Pearson chi-squared tests were used to determine if there was a statistically significant difference between pre-test and post-test perceptions of epistaxis management, and to investigate outcomes between different subsets of nurses.

SQUIRE 2.0 guidelines were utilized to provide a framework for this project and to structure the manuscript.⁸ This study met criteria for exemption from institutional review board approval.

Results

Fifty-one nurses took part in this project (Table). The majority of participants identified as female (88.24%), and just over half worked on medical floors (52.94%), with most of the remainder working in intensive care (25.49%) and surgical (15.69%) settings. There was a wide range of clinical experience, with 1.96% reporting 0 to 1 years of experience, 29.41% reporting 2 to 5 years, 23.53% reporting 5 to 10 years, 25.49% reporting 10 to 20 years, and 17.65% reporting more than 20 years.

0722_JCOM_RFTF_Nelson_T1.JPG

There were unanswered questions on both the pre-test and post test. There was no consistently unanswered question. Omitted answers on the epistaxis knowledge questions were recorded as an “incorrect” answer. Omitted answers on the perception questions were considered null values and not considered in final analysis.

Primary Measures

General epistaxis knowledge (Figure, part A) improved from the pre-test, where out of 4 questions, the mean (SD) score was 1.74 (1.02) correct questions, to the post-test, where out of 4 questions, the mean score was 3.80 (0.40) correct questions. After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (mean difference, 2.07 [1.10]; 95% CI, 1.74-2.39; P < .001), and 80.43% of them got a perfect score on the epistaxis knowledge questions.

0722_JCOM_RFTF_Nelson_F1.JPG

The second primary measure was the difference in comfort level in managing nosebleed. After participating in the in-service, nurses felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), with 74.46% of nurses having an improved comfort level managing nosebleeds. Before the in-service, 12.76% of nurses felt “very comfortable” in managing nosebleeds vs more than three-quarters (76.59%) after the in-service. Of those who answered that they felt “comfortable” managing nosebleeds on the pre-test, 82.35% improved to feeling “very comfortable” in managing nosebleeds. Before the in-service, 14.89% of nurses felt “uncomfortable” or “very uncomfortable” in managing nosebleeds, and this decreased to 0 post intervention. After the in-service, 100.00% of nurses felt “comfortable” or “very comfortable” in managing nosebleeds.

After receiving the in-service, nurses felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001), with 43.90% of them having an improvement in confidence in stopping epistaxis. Before the in-service, 7.31% of nurses felt that they would “always” be able to stop a nose-bleed, and this increased to 41.46% after the in-service. Of those who answered that they felt that they would “usually” be able to stop a nosebleed on the pre-test, 36.67% changed their answer to state that they would “always” be able to stop a nosebleed on the post test. Before the in-service, 19.51% of nurses felt that they would “rarely” or “never” be able to stop a nosebleed, and this decreased to 2.44% after the in-service.

Secondary Measures

All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. However, to determine whether there was a population who would benefit most from the in-service, we stratified the data by years of clinical experience. There was no statistically significant difference in whether nurses with varying clinical experience learned something new (P = .148): 100% of nurses with 0-1 years of experience, 80.00% of nurses with 2-5 years of experience, 100% of nurses with 5-10 years of experience, 69.23% of nurses with 10-20 years of experience, and 100% of nurses with >20 years of experience “strongly agreed” that they learned something new from this in-service. There was no statistically significant difference on the post test compared to the pre-test in additional correct questions when stratified by clinical experience (P = .128). Second, when we stratified by clinical setting, we did not find a statistically significant difference in whether nurses in different clinical settings learned something new (P = .929): 88.89% of nurses in the medical setting, 87.50% of nurses in the surgical setting, and 84.62% of nurses in the intensive care setting “strongly agreed” that they learned something new from this presentation. On investigating additional questions correct on the post test compared to the pre-test, there was no statistically significant difference in additional correct questions when stratified by clinical setting (P = .446).

Optimal timing of the in-service was another important outcome. Initially, the in-service was administered at mid-shift, with 9 nurses participating at mid-shift, but our nursing colleagues gave unanimous feedback that this was a suboptimal time for delivery of an in-service. We changed the timing of the in-service to shift change; 42 nurses received the in-service at shift-change. There was no statistically significant difference in scores on the epistaxis knowledge questions between these two groups (P = .123). This indicated to us that changing the timing of the delivery resulted in similarly improved outcomes while having the added benefit of being preferred by our nursing colleagues.

Discussion

In undertaking this project, our primary aims were to improve epistaxis knowledge and perceived management in our nursing staff. Among our nursing staff, we were able to significantly increase epistaxis knowledge, improve comfort levels managing epistaxis, and improve confidence in successful epistaxis management. We also found that nurses of varying clinical experience and different clinical settings benefited equally from our intervention. Using quality improvement principles, we optimized our delivery. Our in-service focused on educating nurses to use epistaxis management techniques that were resource-efficient and low risk.

After participating in the in-service, nurses answered significantly more questions about epistaxis general knowledge correctly (Figure, part A; mean difference, 2.07 questions [1.10]; 95% CI, 1.74-2.39; P < .001), felt significantly more comfortable in managing nosebleeds (Figure, part B; P = .007), and felt significantly more confident in stopping nosebleeds (Figure, part C; P < .001). Based on these results, we successfully achieved our primary aims.

Our secondary aim was to determine the audience that would benefit the most from the in-service. All of the nurses who participated either “strongly agreed” or “agreed” that they learned something new from the in-service. There was no statistically significant difference in whether nurses of varying clinical experience learned something new (P = .148) or in additional correct questions when stratified by clinical experience (P =.128). Also, there was no statistically significant difference in whether nurses in different clinical settings learned something new (P = .929) or in additional correct questions when stratified by clinical setting (P = .446). These results indicated to us that all participants learned something new and that there was no specific target audience, but rather that all participants benefitted from our session.

Our nursing colleagues gave us feedback that the timing of the in-service during mid-shift was not ideal. It was difficult to gather nurses mid-shift due to pressing patient-care duties. Nurses also found it difficult to give their full attention at this time. Nurses, nurse educators, and nurse managers suggested that we conduct the in-service at shift change in order to capture a larger population and take advantage of time relatively free of clinical duties. Giving the in-service at a time with relatively fewer clinical responsibilities allowed for a more robust question-and-answer session. It also allowed our nursing colleagues to pay full attention to the in-service. There was no statistically significant difference in epistaxis general knowledge questions answered correctly; this indicates that the quality of the education session did not vary greatly. However, our nursing colleagues strongly preferred the in-service at shift change. By making this modification to our intervention, we were able to optimize our intervention.

The previously mentioned study in England reported that only 12% to 14% of their nursing staff got a perfect score on epistaxis knowledge questions. Prior to our study, there was no literature investigating the impact of an in-service on epistaxis knowledge. After our intervention, 80.43% of our nurses got a perfect score on the epistaxis knowledge questions. We believe that this is a fair comparison because our post-test questions were identical to the survey questions used in the previously mentioned study in England, with the addition of one question.³ Further, the findings of our study are consistent with other studies regarding the positive effect of in-service education on knowledge and attitudes surrounding clinical topics. Similar to the study in Ethiopia investigating nurses’ knowledge surrounding pain management, our study noted a significant improvement in nurses’ knowledge after participating in the in-service.⁴ Also, when comparing our study to the study performed in Connecticut investigating nurses’ confidence surrounding suicide precautions, we found a similar significant improvement in confidence in management after participating in the in-service.⁵

Given our reliance on a survey as a tool to collect information, our study was subject to nonresponse bias. For each main outcome question, there was a handful of nonresponders. While this likely indicated either overlooking a question or deferring to answer due to clinical inexperience or nonapplicable clinical role, it is possible that this may have represented a respondent who did not benefit from the in-service. Another source of possible bias is sampling bias. Attempts were made to capture a wide range of nurses at the in-service. However, if a nurse was not interested in the topic material, whether due to abundant clinical experience or disinterest, it is possible that they may not have attended. Additionally, the cohort was selected purely based on responses from nursing managers to the initial email. It is possible that nonresponding units may have benefitted differently from this in-service.

There were several limitations within our analysis. We did not collect data assessing the long-term retention of epistaxis knowledge and management techniques. It is possible that epistaxis knowledge, comfort in managing nosebleeds, and perceived confidence in stopping nosebleeds decreased back to baseline several months after the in-service. Ideally, we would have been able to collect this data to assess retention of the in-service information. Unfortunately, a significant number of nurses who initially participated in the project became lost to follow-up, making such data collection impossible. Additionally, there was no assessment of actual ability to stop nosebleeds before vs after this in-service. Perceived management of epistaxis vs actual management of epistaxis are 2 vastly different things. However, this data would have been difficult to collect, and it likely would not have been in the best interest of patients, especially before the in-service was administered. As an improvement to this project, we could have assessed how many nosebleeds nurses had seen and successfully stopped after the in-service. As previously mentioned, this was not possible due to losing a significant number of nurses to follow-up. Finally, we did not collect objective data on preference for administration of in-service at mid-shift vs shift change. We relied on subjective data from conversations with our colleagues. By collecting objective data, we could have supported this change to our intervention with data.

The primary challenge to sustainability for this intervention is nursing turnover. With each wave of departing nurses and new nursing hires, the difficulty of ensuring a consistent knowledge base and management standards within our nursing workforce became clearer. After optimizing our intervention, our solution was to provide a hospital-wide in-service, which was recorded and uploaded to an institution-wide in-service library. In this way, a nurse with the desire to learn about epistaxis management could access the material at any point in time. Another solution would have been to appoint champions for epistaxis management within each major department to deliver the epistaxis in-service to new hires and new rotators within the department. However, given the turnover witnessed in our study cohort, this may not be sustainable long term.

Conclusion

Epistaxis is a chief complaint that can present in many different clinical settings and situations. Therefore, the ability to stop epistaxis in a timely and effective fashion is valuable. Our study demonstrated that in-services can improve epistaxis knowledge and improve perceived epistaxis management. Ideally, this intervention will lead to improved patient care. Given that epistaxis is a ubiquitous issue, this study may benefit other institutions who want to improve care for patients with epistaxis.

Next steps for this intervention include utilizing in-services for epistaxis education at other institutions and collecting long-term data within our own institution. Collecting long-term data would allow us to assess the retention of epistaxis knowledge from our in-service.

Acknowledgments: The author thanks the nurse managers, nurse educators, and staff nurses involved in this project, as well as Dr. Louis Portugal for providing mentorship throughout this process and Dr. Dara Adams for assisting with statistical analysis.

Corresponding author: Avery Nelson, MD, University of Chicago Medical Center, 5841 S Maryland Ave, MC 1035, Chicago, IL 60637; avery.nelson@uchospitals.edu

Disclosures: None reported.

From Sharp Memorial Hospital, San Diego, CA (Drs. Poremba, Dehner, Perreiter, Semma, and Mills), Sharp Rees-Stealy Medical Group, San Diego, CA (Dr. Sakoulas), and Collaborative to Halt Antibiotic-Resistant Microbes (CHARM), Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA (Dr. Sakoulas).

Abstract

Objective: To compare the costs of hospitalization of patients with moderate-to-severe COVID-19 who received intravenous immunoglobulin (IVIG) with those of patients of similar comorbidity and illness severity who did not.

Design: Analysis 1 was a case-control study of 10 nonventilated, moderately to severely hypoxic patients with COVID-19 who received IVIG (Privigen [CSL Behring]) matched 1:2 with 20 control patients of similar age, body mass index, degree of hypoxemia, and comorbidities. Analysis 2 consisted of patients enrolled in a previously published, randomized, open-label prospective study of 14 patients with COVID-19 receiving standard of care vs 13 patients who received standard of care plus IVIG (Octagam 10% [Octapharma]).

Setting and participants: Patients with COVID-19 with moderate-to-severe hypoxemia hospitalized at a single site located in San Diego, California.

Measurements: Direct cost of hospitalization.

Results: In the first (case-control) population, mean total direct costs, including IVIG, for the treatment group were $21,982 per IVIG-treated case vs $42,431 per case for matched non-IVIG-receiving controls, representing a net cost reduction of $20,449 (48%) per case. For the second (randomized) group, mean total direct costs, including IVIG, for the treatment group were $28,268 per case vs $62,707 per case for untreated controls, representing a net cost reduction of $34,439 (55%) per case. Of the patients who did not receive IVIG, 24% had hospital costs exceeding $80,000; none of the IVIG-treated patients had costs exceeding this amount (P = .016, Fisher exact test).

Conclusion: If allocated early to the appropriate patient type (moderate-to-severe illness without end-organ comorbidities and age <70 years), IVIG can significantly reduce hospital costs in COVID-19 care. More important, in our study it reduced the demand for scarce critical care resources during the COVID-19 pandemic.

Keywords: IVIG, SARS-CoV-2, cost saving, direct hospital costs.

Intravenous immunoglobulin (IVIG) has been available in most hospitals for 4 decades, with broad therapeutic applications in the treatment of Kawasaki disease and a variety of inflammatory, infectious, autoimmune, and viral diseases, via multifactorial mechanisms of immune modulation.¹ Reports of COVID-19−associated multisystem inflammatory syndrome in adults and children have supported the use of IVIG in treatment.^2,3 Previous studies of IVIG treatment for COVID-19 have produced mixed results. Although retrospective studies have largely been positive,^4-8 prospective clinical trials have been mixed, with some favorable results^9-11 and another, more recent study showing no benefit.¹² However, there is still considerable debate regarding whether some subgroups of patients with COVID-19 may benefit from IVIG; the studies that support this argument, however, have been diluted by broad clinical trials that lack granularity among the heterogeneity of patient characteristics and the timing of IVIG administration.^13,14 One study suggests that patients with COVID-19 who may be particularly poised to benefit from IVIG are those who are younger, have fewer comorbidities, and are treated early.⁸

At our institution, we selectively utilized IVIG to treat patients within 48 hours of rapidly increasing oxygen requirements due to COVID-19, targeting those younger than 70 years, with no previous irreversible end-organ damage, no significant comorbidities (renal failure, heart failure, dementia, active cancer malignancies), and no active treatment for cancer. We analyzed the costs of care of these IVIG (Privigen) recipients and compared them to costs for patients with COVID-19 matched by comorbidities, age, and illness severity who did not receive IVIG. To look for consistency, we examined the cost of care of COVID-19 patients who received IVIG (Octagam) as compared to controls from a previously published pilot trial.¹⁰

Methods

Setting and Treatment

All patients in this study were hospitalized at a single site located in San Diego, California. Treatment patients in both cohorts received IVIG 0.5 g/kg adjusted for body weight daily for 3 consecutive days.

Patient Cohort #1: Retrospective Case-Control Trial

Intravenous immunoglobulin (Privigen 10%, CSL Behring) was utilized off-label to treat moderately to severely ill non-intensive care unit (ICU) patients with COVID-19 requiring ≥3 L of oxygen by nasal cannula who were not mechanically ventilated but were considered at high risk for respiratory failure. Preset exclusion criteria for off-label use of IVIG in the treatment of COVID-19 were age >70 years, active malignancy, organ transplant recipient, renal failure, heart failure, or dementia. Controls were obtained from a list of all admitted patients with COVID-19, matched to cases 2:1 on the basis of age (±10 years), body mass index (±1), gender, comorbidities present at admission (eg, hypertension, diabetes mellitus, lung disease, or history of tobacco use), and maximum oxygen requirements within the first 48 hours of admission. In situations where more than 2 potential matched controls were identified for a patient, the 2 controls closest in age to the treatment patient were selected. One IVIG patient was excluded because only 1 matched-age control could be found. Pregnant patients who otherwise fulfilled the criteria for IVIG administration were also excluded from this analysis.

Patient Cohort #2: Prospective, Randomized, Open-Label Trial

Use of IVIG (Octagam 10%, Octapharma) in COVID-19 was studied in a previously published, prospective, open-label randomized trial.¹⁰ This pilot trial included 16 IVIG-treated patients and 17 control patients, of which 13 and 14 patients, respectively, had hospital cost data available for analysis.¹⁰ Most notably, COVID-19 patients in this study were required to have ≥4 L of oxygen via nasal cannula to maintain arterial oxygen saturationof ≤96%.

Outcomes

Cost data were independently obtained from our finance team, which provided us with the total direct cost and the total pharmaceutical cost associated with each admission. We also compared total length of stay (LOS) and ICU LOS between treatment arms, as these were presumed to be the major drivers of cost difference.

Statistics

Nonparametric comparisons of medians were performed with the Mann-Whitney U test. Comparison of means was done by Student t test. Categorical data were analyzed by Fisher exact test.

This analysis was initiated as an internal quality assessment. It received approval from the Sharp Healthcare Institutional Review Board (research@sharp.com), and was granted a waiver of subject authorization and consent given the retrospective nature of the study.

Results

Case-Control Analysis

A total of 10 hypoxic patients with COVID-19 received Privigen IVIG outside of clinical trial settings. None of the patients was vaccinated against SARS-CoV-2, as hospitalization occurred prior to vaccine availability. In addition, the original SARS-CoV-2 strain was circulating while these patients were hospitalized, preceding subsequent emerging variants. Oxygen requirements within the first 48 hours ranged from 3 L via nasal cannula to requiring bi-level positive pressure airway therapy with 100% oxygen; median age was 56 years and median Charlson comorbidity index was 1. These 10 patients were each matched to 2 control patients hospitalized during a comparable time period and who, based on oxygen requirements, did not receive IVIG. The 20 control patients had a median age of 58.5 years and a Charlson comorbidity index of 1 (Table 1). Rates of comorbidities, such as hypertension, diabetes mellitus, and obesity, were identical in the 2 groups. None of the patients in either group died during the index hospitalization. Fewer control patients received glucocorticoids, which was reflective of lower illness severity/degree of hypoxia in some controls.

0522_JCOM_Sakoulas_t1.JPG

Health care utilization in terms of costs and hospital LOS between the 2 groups are shown in Table 2. The mean total direct hospital cost per case, including IVIG and other drug costs, for the 10 IVIG-treated COVID-19 patients was $21,982 vs $42,431 for the matched controls, a reduction of $20,449 (48%) per case (P = .6187) with IVIG. This difference was heavily driven by 4 control patients (20%) with hospital costs >$80,000, marked by need for ICU transfer, mechanical ventilation during admission, and longer hospital stays. This reduction in progression to mechanical ventilation was consistent with our previously published, open-label, randomized prospective IVIG study, the financial assessment of which is reviewed below. While total direct costs were lower in the treatment arm, the mean drug cost for the treatment arm was $3122 greater than the mean drug cost in the control arm (P = .001622), consistent with the high cost of IVIG therapy (Table 2).

0522_JCOM_Sakoulas_t2.JPG

LOS information was obtained, as this was thought to be a primary driver of direct costs. The average LOS in the IVIG arm was 8.4 days, and the average LOS in the control arm was 13.6 days (P = NS). The average ICU LOS in the IVIG arm was 0 days, while the average ICU LOS in the control arm was 5.3 days (P = .04). As with the differences in cost, the differences in LOS were primarily driven by the 4 outlier cases in our control arm, who each had a LOS >25 days, as well as an ICU LOS >20 days.

Randomized, Open-Label, Patient Cohort Analysis

Patient characteristics, LOS, and rates of mechanical ventilation for the IVIG and control patients were previously published and showed a reduction in mechanical ventilation and hospital LOS with IVIG treatment.¹⁰ In this group of patients, 1 patient treated with IVIG (6%) and 3 patients not treated with IVIG (18%) died. To determine the consistency of these results from the case-control patients with a set of patients obtained from clinical trial randomization, we examined the health care costs of patients from the prior study.¹⁰ As with the case-control group, patients in this portion of the analysis were hospitalized before vaccines were available and prior to any identified variants.

Comparing the hospital cost of the IVIG-treated patients to the control patients from this trial revealed results similar to the matched case-control analysis discussed earlier. Average total direct cost per case, including IVIG, for the IVIG treatment group was $28,268, vs $62,707 per case for non-IVIG controls. This represented a net cost reduction of $34,439 (55%) per case, very similar to that of the prior cohort.

IVIG Reduces Costly Outlier Cases

The case-control and randomized trial groups, yielding a combined 23 IVIG and 34 control patients, showed a median cost per case of $22,578 (range $10,115-$70,929) and $22,645 (range $4723-$279,797) for the IVIG and control groups, respectively. Cases with a cost >$80,000 were 0/23 (0%) vs 8/34 (24%) in the IVIG and control groups, respectively (P = .016, Fisher exact test).

Improving care while simultaneously keeping care costs below reimbursement payment levels received from third-party payers is paramount to the financial survival of health care systems. IVIG appears to do this by reducing the number of patients with COVID-19 who progress to ICU care. We compared the costs of care of our combined case-control and randomized trial cohorts to published data on average reimbursements hospitals receive for COVID-19 care from Medicaid, Medicare, and private insurance (Figure).¹⁵ IVIG demonstrated a reduction in cases where costs exceed reimbursement. Indeed, a comparison of net revenue per case of the case-control group showed significantly higher revenue for the IVIG group compared to controls ($52,704 vs $34,712, P = .0338, Table 2).

0522_JCOM_Sakoulas_f1.JPG

Discussion

As reflected in at least 1 other study,¹⁶ our hospital had been successfully utilizing IVIG in the treatment of viral acute respiratory distress syndrome (ARDS) prior to COVID-19. Therefore, we moved quickly to perform a randomized, open-label pilot study of IVIG (Octagam 10%) in COVID-19, and noted significant clinical benefit that might translate into hospital cost savings.¹⁰ Over the course of the pandemic, evidence has accumulated that IVIG may play an important role in COVID-19 therapeutics, as summarized in a recent review.¹⁷ However, despite promising but inconsistent results, the relatively high acquisition costs of IVIG raised questions as to its pharmacoeconomic value, particularly with such a high volume of COVID-19 patients with hypoxia, in light of limited clinical data.

COVID-19 therapeutics data can be categorized into either high-quality trials showing marginal benefit for some agents or low-quality trials showing greater benefit for other agents, with IVIG studies falling into the latter category.¹⁸ This phenomenon may speak to the pathophysiological heterogeneity of the COVID-19 patient population. High-quality trials enrolling broad patient types lack the granularity to capture and single out relevant patient subsets who would derive maximal therapeutic benefit, with those subsets diluted by other patient types for which no benefit is seen. Meanwhile, the more granular low-quality trials are criticized as underpowered and lacking in translatability to practice.

Positive results from our pilot trial allowed the use of IVIG (Privigen) off-label in hospitalized COVID-19 patients restricted to specific criteria. Patients had to be moderately to severely ill, requiring >3 L of oxygen via nasal cannula; show high risk of clinical deterioration based on respiratory rate and decline in respiratory status; and have underlying comorbidities (such as hypertension, obesity, or diabetes mellitus). However, older patients (>age 70 years) and those with underlying comorbidities marked by organ failure (such as heart failure, renal failure, dementia, or receipt of organ transplant) and active malignancy were excluded, as their clinical outcome in COVID-19 may be considered less modifiable by therapeutics, while simultaneously carrying potentially a higher risk of adverse events from IVIG (volume overload, renal failure). These exclusions are reflected in the overall low Charlson comorbidity index (mean of 1) of the patients in the case-control study arm. As anticipated, we found a net cost reduction: $20,449 (48%) per case among the 10 IVIG-treated patients compared to the 20 matched controls.

We then went back to the patients from the randomized prospective trial and compared costs for the 13 of 16 IVIG patients and 14 of 17 of the control patients for whom data were available. Among untreated controls, we found a net cost reduction of $34,439 (55%) per case. The higher costs seen in the randomized patient cohort compared to the latter case-control group may be due to a combination of the fact that the treated patients had slightly higher comorbidity indices than the case-control group (median Charlson comorbidity index of 2 in both groups) and the fact that they were treated earlier in the pandemic (May/June 2020), as opposed to the case-control group patients, who were treated in November/December 2020.

It was notable that the cost savings across both groups were derived largely from the reduction in the approximately 20% to 25% of control patients who went on to critical illness, including mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and prolonged ICU stays. Indeed, 8 of 34 of the control patients—but none of the 23 IVIG-treated patients—generated hospital costs in excess of $80,000, a difference that was statistically significant even for such a small sample size. Therefore, reducing these very costly outlier events translated into net savings across the board.

In addition to lowering costs, reducing progression to critical illness is extremely important during heavy waves of COVID-19, when the sheer volume of patients results in severe strain due to the relative scarcity of ICU beds, mechanical ventilators, and ECMO. Therefore, reducing the need for these resources would have a vital role that cannot be measured economically.

The major limitations of this study include the small sample size and the potential lack of generalizability of these results to all hospital centers and treating providers. Our group has considerable experience in IVIG utilization in COVID-19 and, as a result, has identified a “sweet spot,” where benefits were seen clinically and economically. However, it remains to be determined whether IVIG will benefit patients with greater illness severity, such as those in the ICU, on mechanical ventilation, or ECMO. Furthermore, while a significant morbidity and mortality burden of COVID-19 rests in extremely elderly patients and those with end-organ comorbidities such as renal failure and heart failure, it is uncertain whether their COVID-19 adverse outcomes can be improved with IVIG or other therapies. We believe such patients may limit the pharmacoeconomic value of IVIG due to their generally poorer prognosis, regardless of intervention. On the other hand, COVID-19 patients who are not that severely ill, with minimal to no hypoxia, generally will do well regardless of therapy. Therefore, IVIG intervention may be an unnecessary treatment expense. Evidence for this was suggested in our pilot trial¹⁰ and supported in a recent meta-analysis of IVIG therapy in COVID-19.¹⁹

Several other therapeutic options with high acquisition costs have seen an increase in use during the COVID-19 pandemic despite relatively lukewarm data. Remdesivir, the first drug found to have a beneficial effect on hospitalized patients with COVID-19, is priced at $3120 for a complete 5-day treatment course in the United States. This was in line with initial pricing models from the Institute for Clinical and Economic Review (ICER) in May 2020, assuming a mortality benefit with remdesivir use. After the SOLIDARITY trial was published, which showed no mortality benefit associated with remdesivir, ICER updated their pricing models in June 2020 and released a statement that the price of remdesivir was too high to align with demonstrated benefits.^20,21 More recent data demonstrate that remdesivir may be beneficial, but only if administered to patients with fewer than 6 days of symptoms.²² However, only a minority of patients present to the hospital early enough in their illness for remdesivir to be beneficial.²²

Tocilizumab, an interleukin-6 inhibitor, saw an increase in use during the pandemic. An 800-mg treatment course for COVID-19 costs $3584. The efficacy of this treatment option came into question after the COVACTA trial failed to show a difference in clinical status or mortality in COVID-19 patients who received tocilizumab vs placebo.^23,24 A more recent study pointed to a survival benefit of tocilizumab in COVID-19, driven by a very large sample size (>4000), yielding statistically significant, but perhaps clinically less significant, effects on survival.²⁵ This latter study points to the extremely large sample sizes required to capture statistically significant benefits of expensive interventions in COVID-19, which our data demonstrate may benefit only a fraction of patients (20%-25% of patients in the case of IVIG). A more granular clinical assessment of these other interventions is needed to be able to capture the patient subtypes where tocilizumab, remdesivir, and other therapies will be cost effective in the treatment of COVID-19 or other virally mediated cases of ARDS.

Conclusion

While IVIG has a high acquisition cost, the drug’s use in hypoxic COVID-19 patients resulted in reduced costs per COVID-19 case of approximately 50% and use of less critical care resources. The difference was consistent between 2 cohorts (randomized trial vs off-label use in prespecified COVID-19 patient types), IVIG products used (Octagam 10% and Privigen), and time period in the pandemic (waves 1 and 2 in May/June 2020 vs wave 3 in November/December 2020), thereby adjusting for potential differences in circulating viral strains. Furthermore, patients from both groups predated SARS-CoV-2 vaccine availability and major circulating viral variants (eg, delta, omicron), thereby eliminating confounding on outcomes posed by these factors. Control patients’ higher costs of care were driven largely by the approximately 25% of patients who required costly hospital critical care resources, a group mitigated by IVIG. When allocated to the appropriate patient type (patients with moderate-to-severe but not critical illness, <age 70 without preexisting comorbidities of end-organ failure or active cancer), IVIG can reduce hospital costs for COVID-19 care. Identification of specific patient populations where IVIG has the most anticipated benefits in viral illness is needed.

Corresponding author: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, 2020 Genesee Avenue, 2nd Floor, San Diego, CA 92123; gsakoulas@health.ucsd.edu

Disclosures: Dr Sakoulas has worked as a consultant for Abbvie, Paratek, and Octapharma, has served as a speaker for Abbvie and Paratek, and has received research funding from Octapharma. The other authors did not report any disclosures.

[embed:render:related:node:255119]

[embed:render:related:node:256742]

From Sharp Memorial Hospital, San Diego, CA (Drs. Poremba, Dehner, Perreiter, Semma, and Mills), Sharp Rees-Stealy Medical Group, San Diego, CA (Dr. Sakoulas), and Collaborative to Halt Antibiotic-Resistant Microbes (CHARM), Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA (Dr. Sakoulas).

Abstract

Objective: To compare the costs of hospitalization of patients with moderate-to-severe COVID-19 who received intravenous immunoglobulin (IVIG) with those of patients of similar comorbidity and illness severity who did not.

Design: Analysis 1 was a case-control study of 10 nonventilated, moderately to severely hypoxic patients with COVID-19 who received IVIG (Privigen [CSL Behring]) matched 1:2 with 20 control patients of similar age, body mass index, degree of hypoxemia, and comorbidities. Analysis 2 consisted of patients enrolled in a previously published, randomized, open-label prospective study of 14 patients with COVID-19 receiving standard of care vs 13 patients who received standard of care plus IVIG (Octagam 10% [Octapharma]).

Setting and participants: Patients with COVID-19 with moderate-to-severe hypoxemia hospitalized at a single site located in San Diego, California.

Measurements: Direct cost of hospitalization.

Results: In the first (case-control) population, mean total direct costs, including IVIG, for the treatment group were $21,982 per IVIG-treated case vs $42,431 per case for matched non-IVIG-receiving controls, representing a net cost reduction of $20,449 (48%) per case. For the second (randomized) group, mean total direct costs, including IVIG, for the treatment group were $28,268 per case vs $62,707 per case for untreated controls, representing a net cost reduction of $34,439 (55%) per case. Of the patients who did not receive IVIG, 24% had hospital costs exceeding $80,000; none of the IVIG-treated patients had costs exceeding this amount (P = .016, Fisher exact test).

Conclusion: If allocated early to the appropriate patient type (moderate-to-severe illness without end-organ comorbidities and age <70 years), IVIG can significantly reduce hospital costs in COVID-19 care. More important, in our study it reduced the demand for scarce critical care resources during the COVID-19 pandemic.

Keywords: IVIG, SARS-CoV-2, cost saving, direct hospital costs.

Intravenous immunoglobulin (IVIG) has been available in most hospitals for 4 decades, with broad therapeutic applications in the treatment of Kawasaki disease and a variety of inflammatory, infectious, autoimmune, and viral diseases, via multifactorial mechanisms of immune modulation.¹ Reports of COVID-19−associated multisystem inflammatory syndrome in adults and children have supported the use of IVIG in treatment.^2,3 Previous studies of IVIG treatment for COVID-19 have produced mixed results. Although retrospective studies have largely been positive,^4-8 prospective clinical trials have been mixed, with some favorable results^9-11 and another, more recent study showing no benefit.¹² However, there is still considerable debate regarding whether some subgroups of patients with COVID-19 may benefit from IVIG; the studies that support this argument, however, have been diluted by broad clinical trials that lack granularity among the heterogeneity of patient characteristics and the timing of IVIG administration.^13,14 One study suggests that patients with COVID-19 who may be particularly poised to benefit from IVIG are those who are younger, have fewer comorbidities, and are treated early.⁸

At our institution, we selectively utilized IVIG to treat patients within 48 hours of rapidly increasing oxygen requirements due to COVID-19, targeting those younger than 70 years, with no previous irreversible end-organ damage, no significant comorbidities (renal failure, heart failure, dementia, active cancer malignancies), and no active treatment for cancer. We analyzed the costs of care of these IVIG (Privigen) recipients and compared them to costs for patients with COVID-19 matched by comorbidities, age, and illness severity who did not receive IVIG. To look for consistency, we examined the cost of care of COVID-19 patients who received IVIG (Octagam) as compared to controls from a previously published pilot trial.¹⁰

Methods

Setting and Treatment

All patients in this study were hospitalized at a single site located in San Diego, California. Treatment patients in both cohorts received IVIG 0.5 g/kg adjusted for body weight daily for 3 consecutive days.

Patient Cohort #1: Retrospective Case-Control Trial

Intravenous immunoglobulin (Privigen 10%, CSL Behring) was utilized off-label to treat moderately to severely ill non-intensive care unit (ICU) patients with COVID-19 requiring ≥3 L of oxygen by nasal cannula who were not mechanically ventilated but were considered at high risk for respiratory failure. Preset exclusion criteria for off-label use of IVIG in the treatment of COVID-19 were age >70 years, active malignancy, organ transplant recipient, renal failure, heart failure, or dementia. Controls were obtained from a list of all admitted patients with COVID-19, matched to cases 2:1 on the basis of age (±10 years), body mass index (±1), gender, comorbidities present at admission (eg, hypertension, diabetes mellitus, lung disease, or history of tobacco use), and maximum oxygen requirements within the first 48 hours of admission. In situations where more than 2 potential matched controls were identified for a patient, the 2 controls closest in age to the treatment patient were selected. One IVIG patient was excluded because only 1 matched-age control could be found. Pregnant patients who otherwise fulfilled the criteria for IVIG administration were also excluded from this analysis.

Patient Cohort #2: Prospective, Randomized, Open-Label Trial

Use of IVIG (Octagam 10%, Octapharma) in COVID-19 was studied in a previously published, prospective, open-label randomized trial.¹⁰ This pilot trial included 16 IVIG-treated patients and 17 control patients, of which 13 and 14 patients, respectively, had hospital cost data available for analysis.¹⁰ Most notably, COVID-19 patients in this study were required to have ≥4 L of oxygen via nasal cannula to maintain arterial oxygen saturationof ≤96%.

Outcomes

Cost data were independently obtained from our finance team, which provided us with the total direct cost and the total pharmaceutical cost associated with each admission. We also compared total length of stay (LOS) and ICU LOS between treatment arms, as these were presumed to be the major drivers of cost difference.

Statistics

Nonparametric comparisons of medians were performed with the Mann-Whitney U test. Comparison of means was done by Student t test. Categorical data were analyzed by Fisher exact test.

This analysis was initiated as an internal quality assessment. It received approval from the Sharp Healthcare Institutional Review Board (research@sharp.com), and was granted a waiver of subject authorization and consent given the retrospective nature of the study.

Results

Case-Control Analysis

A total of 10 hypoxic patients with COVID-19 received Privigen IVIG outside of clinical trial settings. None of the patients was vaccinated against SARS-CoV-2, as hospitalization occurred prior to vaccine availability. In addition, the original SARS-CoV-2 strain was circulating while these patients were hospitalized, preceding subsequent emerging variants. Oxygen requirements within the first 48 hours ranged from 3 L via nasal cannula to requiring bi-level positive pressure airway therapy with 100% oxygen; median age was 56 years and median Charlson comorbidity index was 1. These 10 patients were each matched to 2 control patients hospitalized during a comparable time period and who, based on oxygen requirements, did not receive IVIG. The 20 control patients had a median age of 58.5 years and a Charlson comorbidity index of 1 (Table 1). Rates of comorbidities, such as hypertension, diabetes mellitus, and obesity, were identical in the 2 groups. None of the patients in either group died during the index hospitalization. Fewer control patients received glucocorticoids, which was reflective of lower illness severity/degree of hypoxia in some controls.

0522_JCOM_Sakoulas_t1.JPG

Health care utilization in terms of costs and hospital LOS between the 2 groups are shown in Table 2. The mean total direct hospital cost per case, including IVIG and other drug costs, for the 10 IVIG-treated COVID-19 patients was $21,982 vs $42,431 for the matched controls, a reduction of $20,449 (48%) per case (P = .6187) with IVIG. This difference was heavily driven by 4 control patients (20%) with hospital costs >$80,000, marked by need for ICU transfer, mechanical ventilation during admission, and longer hospital stays. This reduction in progression to mechanical ventilation was consistent with our previously published, open-label, randomized prospective IVIG study, the financial assessment of which is reviewed below. While total direct costs were lower in the treatment arm, the mean drug cost for the treatment arm was $3122 greater than the mean drug cost in the control arm (P = .001622), consistent with the high cost of IVIG therapy (Table 2).

0522_JCOM_Sakoulas_t2.JPG

LOS information was obtained, as this was thought to be a primary driver of direct costs. The average LOS in the IVIG arm was 8.4 days, and the average LOS in the control arm was 13.6 days (P = NS). The average ICU LOS in the IVIG arm was 0 days, while the average ICU LOS in the control arm was 5.3 days (P = .04). As with the differences in cost, the differences in LOS were primarily driven by the 4 outlier cases in our control arm, who each had a LOS >25 days, as well as an ICU LOS >20 days.

Randomized, Open-Label, Patient Cohort Analysis

Patient characteristics, LOS, and rates of mechanical ventilation for the IVIG and control patients were previously published and showed a reduction in mechanical ventilation and hospital LOS with IVIG treatment.¹⁰ In this group of patients, 1 patient treated with IVIG (6%) and 3 patients not treated with IVIG (18%) died. To determine the consistency of these results from the case-control patients with a set of patients obtained from clinical trial randomization, we examined the health care costs of patients from the prior study.¹⁰ As with the case-control group, patients in this portion of the analysis were hospitalized before vaccines were available and prior to any identified variants.

Comparing the hospital cost of the IVIG-treated patients to the control patients from this trial revealed results similar to the matched case-control analysis discussed earlier. Average total direct cost per case, including IVIG, for the IVIG treatment group was $28,268, vs $62,707 per case for non-IVIG controls. This represented a net cost reduction of $34,439 (55%) per case, very similar to that of the prior cohort.

IVIG Reduces Costly Outlier Cases

The case-control and randomized trial groups, yielding a combined 23 IVIG and 34 control patients, showed a median cost per case of $22,578 (range $10,115-$70,929) and $22,645 (range $4723-$279,797) for the IVIG and control groups, respectively. Cases with a cost >$80,000 were 0/23 (0%) vs 8/34 (24%) in the IVIG and control groups, respectively (P = .016, Fisher exact test).

Improving care while simultaneously keeping care costs below reimbursement payment levels received from third-party payers is paramount to the financial survival of health care systems. IVIG appears to do this by reducing the number of patients with COVID-19 who progress to ICU care. We compared the costs of care of our combined case-control and randomized trial cohorts to published data on average reimbursements hospitals receive for COVID-19 care from Medicaid, Medicare, and private insurance (Figure).¹⁵ IVIG demonstrated a reduction in cases where costs exceed reimbursement. Indeed, a comparison of net revenue per case of the case-control group showed significantly higher revenue for the IVIG group compared to controls ($52,704 vs $34,712, P = .0338, Table 2).

0522_JCOM_Sakoulas_f1.JPG

Discussion

As reflected in at least 1 other study,¹⁶ our hospital had been successfully utilizing IVIG in the treatment of viral acute respiratory distress syndrome (ARDS) prior to COVID-19. Therefore, we moved quickly to perform a randomized, open-label pilot study of IVIG (Octagam 10%) in COVID-19, and noted significant clinical benefit that might translate into hospital cost savings.¹⁰ Over the course of the pandemic, evidence has accumulated that IVIG may play an important role in COVID-19 therapeutics, as summarized in a recent review.¹⁷ However, despite promising but inconsistent results, the relatively high acquisition costs of IVIG raised questions as to its pharmacoeconomic value, particularly with such a high volume of COVID-19 patients with hypoxia, in light of limited clinical data.

COVID-19 therapeutics data can be categorized into either high-quality trials showing marginal benefit for some agents or low-quality trials showing greater benefit for other agents, with IVIG studies falling into the latter category.¹⁸ This phenomenon may speak to the pathophysiological heterogeneity of the COVID-19 patient population. High-quality trials enrolling broad patient types lack the granularity to capture and single out relevant patient subsets who would derive maximal therapeutic benefit, with those subsets diluted by other patient types for which no benefit is seen. Meanwhile, the more granular low-quality trials are criticized as underpowered and lacking in translatability to practice.

Positive results from our pilot trial allowed the use of IVIG (Privigen) off-label in hospitalized COVID-19 patients restricted to specific criteria. Patients had to be moderately to severely ill, requiring >3 L of oxygen via nasal cannula; show high risk of clinical deterioration based on respiratory rate and decline in respiratory status; and have underlying comorbidities (such as hypertension, obesity, or diabetes mellitus). However, older patients (>age 70 years) and those with underlying comorbidities marked by organ failure (such as heart failure, renal failure, dementia, or receipt of organ transplant) and active malignancy were excluded, as their clinical outcome in COVID-19 may be considered less modifiable by therapeutics, while simultaneously carrying potentially a higher risk of adverse events from IVIG (volume overload, renal failure). These exclusions are reflected in the overall low Charlson comorbidity index (mean of 1) of the patients in the case-control study arm. As anticipated, we found a net cost reduction: $20,449 (48%) per case among the 10 IVIG-treated patients compared to the 20 matched controls.

We then went back to the patients from the randomized prospective trial and compared costs for the 13 of 16 IVIG patients and 14 of 17 of the control patients for whom data were available. Among untreated controls, we found a net cost reduction of $34,439 (55%) per case. The higher costs seen in the randomized patient cohort compared to the latter case-control group may be due to a combination of the fact that the treated patients had slightly higher comorbidity indices than the case-control group (median Charlson comorbidity index of 2 in both groups) and the fact that they were treated earlier in the pandemic (May/June 2020), as opposed to the case-control group patients, who were treated in November/December 2020.

It was notable that the cost savings across both groups were derived largely from the reduction in the approximately 20% to 25% of control patients who went on to critical illness, including mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and prolonged ICU stays. Indeed, 8 of 34 of the control patients—but none of the 23 IVIG-treated patients—generated hospital costs in excess of $80,000, a difference that was statistically significant even for such a small sample size. Therefore, reducing these very costly outlier events translated into net savings across the board.

In addition to lowering costs, reducing progression to critical illness is extremely important during heavy waves of COVID-19, when the sheer volume of patients results in severe strain due to the relative scarcity of ICU beds, mechanical ventilators, and ECMO. Therefore, reducing the need for these resources would have a vital role that cannot be measured economically.

The major limitations of this study include the small sample size and the potential lack of generalizability of these results to all hospital centers and treating providers. Our group has considerable experience in IVIG utilization in COVID-19 and, as a result, has identified a “sweet spot,” where benefits were seen clinically and economically. However, it remains to be determined whether IVIG will benefit patients with greater illness severity, such as those in the ICU, on mechanical ventilation, or ECMO. Furthermore, while a significant morbidity and mortality burden of COVID-19 rests in extremely elderly patients and those with end-organ comorbidities such as renal failure and heart failure, it is uncertain whether their COVID-19 adverse outcomes can be improved with IVIG or other therapies. We believe such patients may limit the pharmacoeconomic value of IVIG due to their generally poorer prognosis, regardless of intervention. On the other hand, COVID-19 patients who are not that severely ill, with minimal to no hypoxia, generally will do well regardless of therapy. Therefore, IVIG intervention may be an unnecessary treatment expense. Evidence for this was suggested in our pilot trial¹⁰ and supported in a recent meta-analysis of IVIG therapy in COVID-19.¹⁹

Several other therapeutic options with high acquisition costs have seen an increase in use during the COVID-19 pandemic despite relatively lukewarm data. Remdesivir, the first drug found to have a beneficial effect on hospitalized patients with COVID-19, is priced at $3120 for a complete 5-day treatment course in the United States. This was in line with initial pricing models from the Institute for Clinical and Economic Review (ICER) in May 2020, assuming a mortality benefit with remdesivir use. After the SOLIDARITY trial was published, which showed no mortality benefit associated with remdesivir, ICER updated their pricing models in June 2020 and released a statement that the price of remdesivir was too high to align with demonstrated benefits.^20,21 More recent data demonstrate that remdesivir may be beneficial, but only if administered to patients with fewer than 6 days of symptoms.²² However, only a minority of patients present to the hospital early enough in their illness for remdesivir to be beneficial.²²

Tocilizumab, an interleukin-6 inhibitor, saw an increase in use during the pandemic. An 800-mg treatment course for COVID-19 costs $3584. The efficacy of this treatment option came into question after the COVACTA trial failed to show a difference in clinical status or mortality in COVID-19 patients who received tocilizumab vs placebo.^23,24 A more recent study pointed to a survival benefit of tocilizumab in COVID-19, driven by a very large sample size (>4000), yielding statistically significant, but perhaps clinically less significant, effects on survival.²⁵ This latter study points to the extremely large sample sizes required to capture statistically significant benefits of expensive interventions in COVID-19, which our data demonstrate may benefit only a fraction of patients (20%-25% of patients in the case of IVIG). A more granular clinical assessment of these other interventions is needed to be able to capture the patient subtypes where tocilizumab, remdesivir, and other therapies will be cost effective in the treatment of COVID-19 or other virally mediated cases of ARDS.

Conclusion

While IVIG has a high acquisition cost, the drug’s use in hypoxic COVID-19 patients resulted in reduced costs per COVID-19 case of approximately 50% and use of less critical care resources. The difference was consistent between 2 cohorts (randomized trial vs off-label use in prespecified COVID-19 patient types), IVIG products used (Octagam 10% and Privigen), and time period in the pandemic (waves 1 and 2 in May/June 2020 vs wave 3 in November/December 2020), thereby adjusting for potential differences in circulating viral strains. Furthermore, patients from both groups predated SARS-CoV-2 vaccine availability and major circulating viral variants (eg, delta, omicron), thereby eliminating confounding on outcomes posed by these factors. Control patients’ higher costs of care were driven largely by the approximately 25% of patients who required costly hospital critical care resources, a group mitigated by IVIG. When allocated to the appropriate patient type (patients with moderate-to-severe but not critical illness, <age 70 without preexisting comorbidities of end-organ failure or active cancer), IVIG can reduce hospital costs for COVID-19 care. Identification of specific patient populations where IVIG has the most anticipated benefits in viral illness is needed.

Corresponding author: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, 2020 Genesee Avenue, 2nd Floor, San Diego, CA 92123; gsakoulas@health.ucsd.edu

Disclosures: Dr Sakoulas has worked as a consultant for Abbvie, Paratek, and Octapharma, has served as a speaker for Abbvie and Paratek, and has received research funding from Octapharma. The other authors did not report any disclosures.

[embed:render:related:node:255119]

[embed:render:related:node:256742]

From Sharp Memorial Hospital, San Diego, CA (Drs. Poremba, Dehner, Perreiter, Semma, and Mills), Sharp Rees-Stealy Medical Group, San Diego, CA (Dr. Sakoulas), and Collaborative to Halt Antibiotic-Resistant Microbes (CHARM), Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA (Dr. Sakoulas).

Abstract

Objective: To compare the costs of hospitalization of patients with moderate-to-severe COVID-19 who received intravenous immunoglobulin (IVIG) with those of patients of similar comorbidity and illness severity who did not.

Design: Analysis 1 was a case-control study of 10 nonventilated, moderately to severely hypoxic patients with COVID-19 who received IVIG (Privigen [CSL Behring]) matched 1:2 with 20 control patients of similar age, body mass index, degree of hypoxemia, and comorbidities. Analysis 2 consisted of patients enrolled in a previously published, randomized, open-label prospective study of 14 patients with COVID-19 receiving standard of care vs 13 patients who received standard of care plus IVIG (Octagam 10% [Octapharma]).

Setting and participants: Patients with COVID-19 with moderate-to-severe hypoxemia hospitalized at a single site located in San Diego, California.

Measurements: Direct cost of hospitalization.

Results: In the first (case-control) population, mean total direct costs, including IVIG, for the treatment group were $21,982 per IVIG-treated case vs $42,431 per case for matched non-IVIG-receiving controls, representing a net cost reduction of $20,449 (48%) per case. For the second (randomized) group, mean total direct costs, including IVIG, for the treatment group were $28,268 per case vs $62,707 per case for untreated controls, representing a net cost reduction of $34,439 (55%) per case. Of the patients who did not receive IVIG, 24% had hospital costs exceeding $80,000; none of the IVIG-treated patients had costs exceeding this amount (P = .016, Fisher exact test).

Conclusion: If allocated early to the appropriate patient type (moderate-to-severe illness without end-organ comorbidities and age <70 years), IVIG can significantly reduce hospital costs in COVID-19 care. More important, in our study it reduced the demand for scarce critical care resources during the COVID-19 pandemic.

Keywords: IVIG, SARS-CoV-2, cost saving, direct hospital costs.

Intravenous immunoglobulin (IVIG) has been available in most hospitals for 4 decades, with broad therapeutic applications in the treatment of Kawasaki disease and a variety of inflammatory, infectious, autoimmune, and viral diseases, via multifactorial mechanisms of immune modulation.¹ Reports of COVID-19−associated multisystem inflammatory syndrome in adults and children have supported the use of IVIG in treatment.^2,3 Previous studies of IVIG treatment for COVID-19 have produced mixed results. Although retrospective studies have largely been positive,^4-8 prospective clinical trials have been mixed, with some favorable results^9-11 and another, more recent study showing no benefit.¹² However, there is still considerable debate regarding whether some subgroups of patients with COVID-19 may benefit from IVIG; the studies that support this argument, however, have been diluted by broad clinical trials that lack granularity among the heterogeneity of patient characteristics and the timing of IVIG administration.^13,14 One study suggests that patients with COVID-19 who may be particularly poised to benefit from IVIG are those who are younger, have fewer comorbidities, and are treated early.⁸

At our institution, we selectively utilized IVIG to treat patients within 48 hours of rapidly increasing oxygen requirements due to COVID-19, targeting those younger than 70 years, with no previous irreversible end-organ damage, no significant comorbidities (renal failure, heart failure, dementia, active cancer malignancies), and no active treatment for cancer. We analyzed the costs of care of these IVIG (Privigen) recipients and compared them to costs for patients with COVID-19 matched by comorbidities, age, and illness severity who did not receive IVIG. To look for consistency, we examined the cost of care of COVID-19 patients who received IVIG (Octagam) as compared to controls from a previously published pilot trial.¹⁰

Methods

Setting and Treatment

All patients in this study were hospitalized at a single site located in San Diego, California. Treatment patients in both cohorts received IVIG 0.5 g/kg adjusted for body weight daily for 3 consecutive days.

Patient Cohort #1: Retrospective Case-Control Trial

Intravenous immunoglobulin (Privigen 10%, CSL Behring) was utilized off-label to treat moderately to severely ill non-intensive care unit (ICU) patients with COVID-19 requiring ≥3 L of oxygen by nasal cannula who were not mechanically ventilated but were considered at high risk for respiratory failure. Preset exclusion criteria for off-label use of IVIG in the treatment of COVID-19 were age >70 years, active malignancy, organ transplant recipient, renal failure, heart failure, or dementia. Controls were obtained from a list of all admitted patients with COVID-19, matched to cases 2:1 on the basis of age (±10 years), body mass index (±1), gender, comorbidities present at admission (eg, hypertension, diabetes mellitus, lung disease, or history of tobacco use), and maximum oxygen requirements within the first 48 hours of admission. In situations where more than 2 potential matched controls were identified for a patient, the 2 controls closest in age to the treatment patient were selected. One IVIG patient was excluded because only 1 matched-age control could be found. Pregnant patients who otherwise fulfilled the criteria for IVIG administration were also excluded from this analysis.

Patient Cohort #2: Prospective, Randomized, Open-Label Trial

Use of IVIG (Octagam 10%, Octapharma) in COVID-19 was studied in a previously published, prospective, open-label randomized trial.¹⁰ This pilot trial included 16 IVIG-treated patients and 17 control patients, of which 13 and 14 patients, respectively, had hospital cost data available for analysis.¹⁰ Most notably, COVID-19 patients in this study were required to have ≥4 L of oxygen via nasal cannula to maintain arterial oxygen saturationof ≤96%.

Outcomes

Cost data were independently obtained from our finance team, which provided us with the total direct cost and the total pharmaceutical cost associated with each admission. We also compared total length of stay (LOS) and ICU LOS between treatment arms, as these were presumed to be the major drivers of cost difference.

Statistics

Nonparametric comparisons of medians were performed with the Mann-Whitney U test. Comparison of means was done by Student t test. Categorical data were analyzed by Fisher exact test.

This analysis was initiated as an internal quality assessment. It received approval from the Sharp Healthcare Institutional Review Board (research@sharp.com), and was granted a waiver of subject authorization and consent given the retrospective nature of the study.

Results

Case-Control Analysis

A total of 10 hypoxic patients with COVID-19 received Privigen IVIG outside of clinical trial settings. None of the patients was vaccinated against SARS-CoV-2, as hospitalization occurred prior to vaccine availability. In addition, the original SARS-CoV-2 strain was circulating while these patients were hospitalized, preceding subsequent emerging variants. Oxygen requirements within the first 48 hours ranged from 3 L via nasal cannula to requiring bi-level positive pressure airway therapy with 100% oxygen; median age was 56 years and median Charlson comorbidity index was 1. These 10 patients were each matched to 2 control patients hospitalized during a comparable time period and who, based on oxygen requirements, did not receive IVIG. The 20 control patients had a median age of 58.5 years and a Charlson comorbidity index of 1 (Table 1). Rates of comorbidities, such as hypertension, diabetes mellitus, and obesity, were identical in the 2 groups. None of the patients in either group died during the index hospitalization. Fewer control patients received glucocorticoids, which was reflective of lower illness severity/degree of hypoxia in some controls.

0522_JCOM_Sakoulas_t1.JPG

Health care utilization in terms of costs and hospital LOS between the 2 groups are shown in Table 2. The mean total direct hospital cost per case, including IVIG and other drug costs, for the 10 IVIG-treated COVID-19 patients was $21,982 vs $42,431 for the matched controls, a reduction of $20,449 (48%) per case (P = .6187) with IVIG. This difference was heavily driven by 4 control patients (20%) with hospital costs >$80,000, marked by need for ICU transfer, mechanical ventilation during admission, and longer hospital stays. This reduction in progression to mechanical ventilation was consistent with our previously published, open-label, randomized prospective IVIG study, the financial assessment of which is reviewed below. While total direct costs were lower in the treatment arm, the mean drug cost for the treatment arm was $3122 greater than the mean drug cost in the control arm (P = .001622), consistent with the high cost of IVIG therapy (Table 2).

0522_JCOM_Sakoulas_t2.JPG

LOS information was obtained, as this was thought to be a primary driver of direct costs. The average LOS in the IVIG arm was 8.4 days, and the average LOS in the control arm was 13.6 days (P = NS). The average ICU LOS in the IVIG arm was 0 days, while the average ICU LOS in the control arm was 5.3 days (P = .04). As with the differences in cost, the differences in LOS were primarily driven by the 4 outlier cases in our control arm, who each had a LOS >25 days, as well as an ICU LOS >20 days.

Randomized, Open-Label, Patient Cohort Analysis

Patient characteristics, LOS, and rates of mechanical ventilation for the IVIG and control patients were previously published and showed a reduction in mechanical ventilation and hospital LOS with IVIG treatment.¹⁰ In this group of patients, 1 patient treated with IVIG (6%) and 3 patients not treated with IVIG (18%) died. To determine the consistency of these results from the case-control patients with a set of patients obtained from clinical trial randomization, we examined the health care costs of patients from the prior study.¹⁰ As with the case-control group, patients in this portion of the analysis were hospitalized before vaccines were available and prior to any identified variants.

Comparing the hospital cost of the IVIG-treated patients to the control patients from this trial revealed results similar to the matched case-control analysis discussed earlier. Average total direct cost per case, including IVIG, for the IVIG treatment group was $28,268, vs $62,707 per case for non-IVIG controls. This represented a net cost reduction of $34,439 (55%) per case, very similar to that of the prior cohort.

IVIG Reduces Costly Outlier Cases

The case-control and randomized trial groups, yielding a combined 23 IVIG and 34 control patients, showed a median cost per case of $22,578 (range $10,115-$70,929) and $22,645 (range $4723-$279,797) for the IVIG and control groups, respectively. Cases with a cost >$80,000 were 0/23 (0%) vs 8/34 (24%) in the IVIG and control groups, respectively (P = .016, Fisher exact test).

Improving care while simultaneously keeping care costs below reimbursement payment levels received from third-party payers is paramount to the financial survival of health care systems. IVIG appears to do this by reducing the number of patients with COVID-19 who progress to ICU care. We compared the costs of care of our combined case-control and randomized trial cohorts to published data on average reimbursements hospitals receive for COVID-19 care from Medicaid, Medicare, and private insurance (Figure).¹⁵ IVIG demonstrated a reduction in cases where costs exceed reimbursement. Indeed, a comparison of net revenue per case of the case-control group showed significantly higher revenue for the IVIG group compared to controls ($52,704 vs $34,712, P = .0338, Table 2).

0522_JCOM_Sakoulas_f1.JPG

Discussion

As reflected in at least 1 other study,¹⁶ our hospital had been successfully utilizing IVIG in the treatment of viral acute respiratory distress syndrome (ARDS) prior to COVID-19. Therefore, we moved quickly to perform a randomized, open-label pilot study of IVIG (Octagam 10%) in COVID-19, and noted significant clinical benefit that might translate into hospital cost savings.¹⁰ Over the course of the pandemic, evidence has accumulated that IVIG may play an important role in COVID-19 therapeutics, as summarized in a recent review.¹⁷ However, despite promising but inconsistent results, the relatively high acquisition costs of IVIG raised questions as to its pharmacoeconomic value, particularly with such a high volume of COVID-19 patients with hypoxia, in light of limited clinical data.

COVID-19 therapeutics data can be categorized into either high-quality trials showing marginal benefit for some agents or low-quality trials showing greater benefit for other agents, with IVIG studies falling into the latter category.¹⁸ This phenomenon may speak to the pathophysiological heterogeneity of the COVID-19 patient population. High-quality trials enrolling broad patient types lack the granularity to capture and single out relevant patient subsets who would derive maximal therapeutic benefit, with those subsets diluted by other patient types for which no benefit is seen. Meanwhile, the more granular low-quality trials are criticized as underpowered and lacking in translatability to practice.

Positive results from our pilot trial allowed the use of IVIG (Privigen) off-label in hospitalized COVID-19 patients restricted to specific criteria. Patients had to be moderately to severely ill, requiring >3 L of oxygen via nasal cannula; show high risk of clinical deterioration based on respiratory rate and decline in respiratory status; and have underlying comorbidities (such as hypertension, obesity, or diabetes mellitus). However, older patients (>age 70 years) and those with underlying comorbidities marked by organ failure (such as heart failure, renal failure, dementia, or receipt of organ transplant) and active malignancy were excluded, as their clinical outcome in COVID-19 may be considered less modifiable by therapeutics, while simultaneously carrying potentially a higher risk of adverse events from IVIG (volume overload, renal failure). These exclusions are reflected in the overall low Charlson comorbidity index (mean of 1) of the patients in the case-control study arm. As anticipated, we found a net cost reduction: $20,449 (48%) per case among the 10 IVIG-treated patients compared to the 20 matched controls.

We then went back to the patients from the randomized prospective trial and compared costs for the 13 of 16 IVIG patients and 14 of 17 of the control patients for whom data were available. Among untreated controls, we found a net cost reduction of $34,439 (55%) per case. The higher costs seen in the randomized patient cohort compared to the latter case-control group may be due to a combination of the fact that the treated patients had slightly higher comorbidity indices than the case-control group (median Charlson comorbidity index of 2 in both groups) and the fact that they were treated earlier in the pandemic (May/June 2020), as opposed to the case-control group patients, who were treated in November/December 2020.

It was notable that the cost savings across both groups were derived largely from the reduction in the approximately 20% to 25% of control patients who went on to critical illness, including mechanical ventilation, extracorporeal membrane oxygenation (ECMO), and prolonged ICU stays. Indeed, 8 of 34 of the control patients—but none of the 23 IVIG-treated patients—generated hospital costs in excess of $80,000, a difference that was statistically significant even for such a small sample size. Therefore, reducing these very costly outlier events translated into net savings across the board.

In addition to lowering costs, reducing progression to critical illness is extremely important during heavy waves of COVID-19, when the sheer volume of patients results in severe strain due to the relative scarcity of ICU beds, mechanical ventilators, and ECMO. Therefore, reducing the need for these resources would have a vital role that cannot be measured economically.

The major limitations of this study include the small sample size and the potential lack of generalizability of these results to all hospital centers and treating providers. Our group has considerable experience in IVIG utilization in COVID-19 and, as a result, has identified a “sweet spot,” where benefits were seen clinically and economically. However, it remains to be determined whether IVIG will benefit patients with greater illness severity, such as those in the ICU, on mechanical ventilation, or ECMO. Furthermore, while a significant morbidity and mortality burden of COVID-19 rests in extremely elderly patients and those with end-organ comorbidities such as renal failure and heart failure, it is uncertain whether their COVID-19 adverse outcomes can be improved with IVIG or other therapies. We believe such patients may limit the pharmacoeconomic value of IVIG due to their generally poorer prognosis, regardless of intervention. On the other hand, COVID-19 patients who are not that severely ill, with minimal to no hypoxia, generally will do well regardless of therapy. Therefore, IVIG intervention may be an unnecessary treatment expense. Evidence for this was suggested in our pilot trial¹⁰ and supported in a recent meta-analysis of IVIG therapy in COVID-19.¹⁹

Several other therapeutic options with high acquisition costs have seen an increase in use during the COVID-19 pandemic despite relatively lukewarm data. Remdesivir, the first drug found to have a beneficial effect on hospitalized patients with COVID-19, is priced at $3120 for a complete 5-day treatment course in the United States. This was in line with initial pricing models from the Institute for Clinical and Economic Review (ICER) in May 2020, assuming a mortality benefit with remdesivir use. After the SOLIDARITY trial was published, which showed no mortality benefit associated with remdesivir, ICER updated their pricing models in June 2020 and released a statement that the price of remdesivir was too high to align with demonstrated benefits.^20,21 More recent data demonstrate that remdesivir may be beneficial, but only if administered to patients with fewer than 6 days of symptoms.²² However, only a minority of patients present to the hospital early enough in their illness for remdesivir to be beneficial.²²

Tocilizumab, an interleukin-6 inhibitor, saw an increase in use during the pandemic. An 800-mg treatment course for COVID-19 costs $3584. The efficacy of this treatment option came into question after the COVACTA trial failed to show a difference in clinical status or mortality in COVID-19 patients who received tocilizumab vs placebo.^23,24 A more recent study pointed to a survival benefit of tocilizumab in COVID-19, driven by a very large sample size (>4000), yielding statistically significant, but perhaps clinically less significant, effects on survival.²⁵ This latter study points to the extremely large sample sizes required to capture statistically significant benefits of expensive interventions in COVID-19, which our data demonstrate may benefit only a fraction of patients (20%-25% of patients in the case of IVIG). A more granular clinical assessment of these other interventions is needed to be able to capture the patient subtypes where tocilizumab, remdesivir, and other therapies will be cost effective in the treatment of COVID-19 or other virally mediated cases of ARDS.

Conclusion

While IVIG has a high acquisition cost, the drug’s use in hypoxic COVID-19 patients resulted in reduced costs per COVID-19 case of approximately 50% and use of less critical care resources. The difference was consistent between 2 cohorts (randomized trial vs off-label use in prespecified COVID-19 patient types), IVIG products used (Octagam 10% and Privigen), and time period in the pandemic (waves 1 and 2 in May/June 2020 vs wave 3 in November/December 2020), thereby adjusting for potential differences in circulating viral strains. Furthermore, patients from both groups predated SARS-CoV-2 vaccine availability and major circulating viral variants (eg, delta, omicron), thereby eliminating confounding on outcomes posed by these factors. Control patients’ higher costs of care were driven largely by the approximately 25% of patients who required costly hospital critical care resources, a group mitigated by IVIG. When allocated to the appropriate patient type (patients with moderate-to-severe but not critical illness, <age 70 without preexisting comorbidities of end-organ failure or active cancer), IVIG can reduce hospital costs for COVID-19 care. Identification of specific patient populations where IVIG has the most anticipated benefits in viral illness is needed.

Corresponding author: George Sakoulas, MD, Sharp Rees-Stealy Medical Group, 2020 Genesee Avenue, 2nd Floor, San Diego, CA 92123; gsakoulas@health.ucsd.edu

Disclosures: Dr Sakoulas has worked as a consultant for Abbvie, Paratek, and Octapharma, has served as a speaker for Abbvie and Paratek, and has received research funding from Octapharma. The other authors did not report any disclosures.

[embed:render:related:node:255119]

[embed:render:related:node:256742]

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO