Article Identification

Article Title: Rabies post-exposure prophylaxis in the emergency department

Authors: Terese Lewis, PharmD; Krysta Baack, PharmD; Leigh Gomez, PharmD; Heather Nichols, MBA; Caitlin Lemmons; Wesley Zeger, DOb

Journal Name: American Journal of Emergency Medicine

Year: 2024

Volume: 78

Issue: 202–205

Type of Study: Retrospective chart review conducted as a quality improvement project

DOI: 10.1016/j.ajem.2024.01.027

Quick Reference Summary

Primary Outcome: The study found a 78.3% rate of appropriate completion of the rabies vaccine series among patients receiving post-exposure prophylaxis (PEP) in the emergency department (ED).

Secondary Findings: Completion rates were higher at Nebraska Medicine Medical Center (82%) compared to Bellevue Medical Center (69%) (p = 0.12), and implementing a dose rounding policy could result in a potential cost savings of $57,928.64 over the study period.

Core Clinical Question

What is the rate of patient compliance in completing the rabies vaccine series following post-exposure prophylaxis (PEP) in emergency department settings at two Nebraska Medicine campuses, and how do different follow-up processes impact this compliance?

Background

Disease Overview:

Rabies is a zoonotic single-stranded RNA lyssavirus causing acute, often fatal infections of the central nervous system (CNS), including encephalomyelitis, encephalitis, and meningoencephalitis.

Prior Data:

Approximately 23,000 people in the United States are estimated to receive PEP yearly.

Previous studies indicated that dose rounding strategies do not significantly affect re-presentation rates to the ED.

Current Standard of Care:

Nebraska Medicine adheres to Advisory Committee on Immunization Practices (ACIP) guidelines, including a 20 units/kg administration of rabies immunoglobulin (RIG) and a structured vaccination series.

Knowledge Gaps Addressed:

Limited data on patient compliance rates for completing the rabies vaccine series.

Impact of different follow-up scheduling processes on vaccine series completion.

Study Rationale:

To evaluate and compare patient compliance between two different follow-up processes at Nebraska Medicine campuses and assess potential cost savings from dose rounding protocols.

Methods Summary

Study Design:

Retrospective chart review as a quality improvement project.

Setting and Time Period:

Nebraska Medicine Medical Center (NMC) and Bellevue Medical Center (BMC) Emergency Departments from July 1, 2019, to June 30, 2022.

Population Characteristics:

Patients >18 years of age receiving RIG and/or rabies vaccine in the ED.

Inclusion/Exclusion Criteria:

Included: Patients >18 years who received RIG and/or rabies vaccine without being admitted.

Excluded: Patients admitted post initial vaccine or RIG administration and those who received initial or follow-up vaccines elsewhere.

Intervention Details:

NMC: Follow-up vaccines scheduled at the outpatient infusion center by the ED pharmacist.

BMC: Follow-up vaccines administered as “Nurse Only” return visits to the ED.

Control/Comparison Group Details:

Comparison between NMC's pharmacist-scheduled follow-ups and BMC's nurse-managed return visits.

Primary and Secondary Outcomes:

Primary: Rate of patient compliance in completing the rabies vaccine series.

Secondary: Differences in compliance between campuses, factors impacting compliance, and potential cost savings from dose rounding.

Statistical Analysis Approach:

Descriptive statistics with 95% confidence intervals.

Fisher's exact test for comparing compliance rates and secondary aims.

Sample Size Calculations:

Not explicitly reported.

Ethics and Funding Information:

No financial support provided relevant to this article.

Declaration of Competing Interest: All authors report no conflicts of interest.

Detailed Results

Participant Flow and Demographics:

• Total Encounters: 723 identified; Unique Patients: 173 after combining rabies series.
• Included Patients: 143 (104 from NMC, 39 from BMC).
• Gender: 53.8% female (77/143).
• Most Common Exposure: Animal bite, predominantly by bats.
• Payor Type: Majority had commercial insurance (69.9%).
• Immune Status: 95.1% immunocompetent.

Primary Outcome Results:

Completion Rate: 78.3% overall.

By Campus:

• NMC: 82%
• BMC: 69%
• Statistical Significance: Not significant (p = 0.12)

Secondary Outcome Results:

Statistically Significant Factors:

• Payor Type: Higher completion in patients with commercial insurance (p = 0.0327)
• Exposure Type: Higher completion in bite and unknown exposures (p = 0.0003)

Dose Rounding Policy Impact:

• 56 fewer vials used
• Potential Cost Savings: $57,928.64
• Statistical Significance: Not specified

Subgroup Analyses:

Higher completion rates in patients with commercial insurance and those exposed via bite or unknown means.

Adverse Events/Safety Data:

Not reported in the study.

Results Tables

Table 1: Baseline Demographics

Characteristic	NMC/Infusion Center (n = 104)	BMC ED (n = 39)	Total (n = 143)	P-value
Gender, F, n (%)	58 (55.8%)	19 (48.7%)	77 (53.8%)	0.4590
Reason for Visit	0.2875
- Animal Bite	45 (43.3%)	22 (56.4%)	67 (46.9%)
- Exposure	34 (32.7%)	10 (25.6%)	44 (30.8%)
- Injection	5 (4.8%)	2 (5.1%)	7 (4.9%)
- Wound Check	2 (1.9%)	2 (5.1%)	4 (2.8%)
- Bite-Other	1 (1.0%)	0 (0.0%)	1 (0.7%)
- Animal Contact	3 (2.9%)	1 (2.6%)	4 (2.8%)
- Immunizations	0 (0.0%)	1 (2.6%)	1 (0.7%)
- Extremity Laceration	1 (1.0%)	0 (0.0%)	1 (0.7%)
- Other	13 (12.5%)	1 (2.6%)	14 (9.8%)
Payor Type, n (%)	0.3598
- Commercial	69 (66.3%)	31 (79.5%)	100 (69.9%)
- Medicaid/Medicare	23 (22.1%)	4 (10.3%)	27 (18.9%)
- Workman's Comp	3 (2.9%)	2 (5.1%)	5 (3.5%)
- Uninsured/Self-Pay	6 (5.8%)	2 (5.1%)	8 (5.6%)
- Other	3 (2.9%)	0 (0.0%)	3 (2.1%)
Immune Status	98 (94.2%) Immunocompetent	38 (97.4%) Immunocompetent	136 (95.1%) Immunocompetent	0.6740
Referral, n (%)	0.4351
- Self	67 (64.4%)	21 (53.8%)	88 (61.5%)
- Urgent Care	4 (3.8%)	1 (2.6%)	5 (3.5%)
- PCP	16 (15.4%)	10 (25.6%)	26 (18.2%)
- Health Department	10 (9.6%)	4 (10.3%)	14 (9.8%)
- Humane Society	7 (6.7%)	2 (5.1%)	9 (6.3%)
- Animal Control	0 (0.0%)	1 (2.6%)	1 (0.7%)
Animal Type, n (%)	0.1783
- Bat	69 (67.0%)	18 (47.5%)	87 (61.7%)
- Cat	13 (12.6%)	8 (21.1%)	21 (14.9%)
- Dog	15 (14.6%)	10 (26.3%)	25 (17.7%)
- Raccoon	5 (4.9%)	2 (5.3%)	7 (5.0%)
- Groundhog	1 (1.0%)	0 (0.0%)	1 (0.7%)
- Unknown/Missing	1 (1.0%)	1 (1.0%)	2 (1.4%)
Exposure Type, n (%)	0.0778
- Bite	52 (50.0%)	26 (66.7%)	78 (54.5%)
- Unknown	48 (46.2%)	10 (25.6%)	58 (40.6%)
- Mucous Membrane	2 (1.9%)	1 (2.6%)	3 (2.1%)
- Scratch	2 (1.9%)	2 (5.1%)	4 (2.8%)
Exposure Risk, n (%)	0.8780
- Low	6 (5.8%)	2 (5.1%)	8 (5.6%)
- Moderate	3 (2.9%)	2 (5.1%)	5 (3.5%)
- High	95 (91.3%)	35 (89.7%)	130 (90.9%)

Table 2: Primary Outcome

Outcome	NMC/Infusion Center (n = 104)	BMC ED (n = 39)	Total (n = 143)	P-value
Primary Outcome
- Completion Rate (%)	82%	69%	78.3%	0.12

Table 3: Secondary Outcomes

Secondary Outcome	NMC/Infusion Center (n = 104)	BMC ED (n = 39)	Total (n = 143)	P-value
Frequency of Completion	85 (81.7%)	27 (69.2%)	-	0.1159
Rates of Completion by Exposure and Payor	-

Table 4: Results Secondary Outcomes Continued

Did Not Appropriately Complete Series (n = 31)	Did Appropriately Complete Series (n = 112)	Total (n = 143)	P-value
Exposure Risk, n (%)	0.4853
- Low	2 (6.5%)	6 (5.4%)	8 (5.6%)
- Moderate	2 (6.5%)	3 (2.7%)	5 (3.5%)
- High	27 (87.1%)	103 (92.0%)	130 (90.9%)
Payor Type, n (%)	0.0327
- Commercial	17 (54.8%)	83 (74.1%)	100 (69.9%)
- Medicaid/Medicare	8 (25.8%)	19 (17.0%)	27 (18.9%)
- Workman's Comp	1 (3.2%)	4 (3.6%)	5 (3.5%)
- Uninsured/Self-Pay	5 (16.1%)	3 (2.7%)	8 (5.6%)
- Other	0 (0.0%)	3 (2.7%)	3 (2.1%)
Exposure Type, n (%)	0.0003
- Bite	27 (87.1%)	51 (45.5%)	78 (54.5%)
- Unknown	4 (12.9%)	54 (48.2%)	58 (40.6%)
- Mucous Membrane	0 (0.0%)	3 (2.7%)	3 (2.1%)
- Scratch	0 (0.0%)	4 (3.6%)	4 (2.8%)

Authors' Conclusions

Primary Conclusions:

• Higher rabies vaccine series completion rates were observed at NMC (82%) compared to BMC (69%), though the difference was not statistically significant.
• Implementing a dose rounding policy could lead to significant cost savings without compromising vaccine series completion.

Interpretation of Results:

• The presence of 24/7 pharmacist coverage at NMC may contribute to higher compliance rates.
• Commercial insurance and specific exposure types (bite, unknown) are associated with better vaccine completion.

Clinical Implications:

• Optimizing follow-up processes, such as enhancing pharmacist involvement, can improve vaccine compliance.
• Dose rounding protocols present a viable strategy for reducing costs in PEP administration.

Future Research Recommendations:

• Prospective studies to confirm the impact of pharmacist coverage on vaccine compliance.
• Exploration of strategies to enhance compliance among patients with non-commercial insurance and varied exposure types.

Critical Analysis

A. Strengths

• Well-Balanced Cohorts: The NMC and BMC patient groups were similar in baseline characteristics, enhancing internal validity.
• Real-World Applicability: Results are directly applicable to emergency department settings, supporting practical implementation.
• Cost Analysis: Inclusion of potential cost savings from dose rounding provides valuable economic insights.

B. Limitations

• Retrospective Design: Potential for charting inaccuracies and missing data due to reliance on electronic medical records.
• Single-Center Design: Limits the generalizability of findings to other institutions with different practices.
• Excluded Data: Potential loss of follow-up data if patients received vaccines outside the studied centers.
• Cost Estimation: May be overestimated due to varying acquisition costs across institutions.

C. Literature Context

Previous Studies and Meta-Analyses:

• Acquisto NM, Uttaro E, Debona D, Minhaj FS. Assessment of rabies immune globulin dose rounding at a university health system. Am J Emerg Med. 2022 Aug;58:141–7.
  • Found no association between dose rounding and ED re-presentation.
• Hwang GS, Rizk E, Bui LN, Iso T, Sartain EI, Tran AT, et al. Adherence to guideline recommendations for human rabies immune globulin patient selection, dosing, timing, first anatomical site of administration in rabies postexposure prophylaxis. Hum Vaccin Immunother. 2020;16(1):51–60.
  • Emphasized the importance of adhering to WHO recommendations to ensure effective PEP.

Contrasting Methodological Quality:

• The current study's retrospective design contrasts with prospective studies that may offer higher internal validity.
• Variability in pharmacist coverage hours between NMC and BMC presents a unique methodological aspect.

Comparisons with Guidelines:

• The study supports ACIP guidelines by demonstrating effective PEP completion rates.
• Aligns with WHO recommendations on RIG administration for effective passive immunity.

This Trial's Contribution:

• Adds evidence on the impact of pharmacist-managed follow-up systems on vaccine compliance.
• Provides a cost-benefit analysis of dose rounding policies in PEP.

Clinical Application

Impact on Practice:

• Findings suggest that enhancing pharmacist involvement in scheduling follow-up vaccines may improve compliance rates.
• Implementing dose rounding protocols can lead to substantial cost savings without negatively impacting vaccine completion.

Applicable Patient Populations/Scenarios:

• Patients receiving PEP in emergency departments, particularly those with commercial insurance and specific types of exposures (bites, unknown).

Implementation Considerations:

• Ensuring 24/7 pharmacist coverage could be pivotal in improving PEP adherence.
• Dose rounding policies should be evaluated for adoption to optimize resource utilization.

How To Use This Info In Practice

Practitioners should consider adopting pharmacist-managed follow-up scheduling and dose rounding protocols to enhance rabies vaccine series completion and achieve cost savings.

Notes for Clarity

• Statistical Significance: Bolded where applicable.
• Confidence Intervals: Provided when available.
• Conflicts of Interest: All authors reported no conflicts.
• Areas of Uncertainty: Recognition of non-significant p-values and potential generalizability issues.
• Funding Sources: No financial support reported relevant to the article.
• Post-Hoc Analyses: Not explicitly flagged; based on provided data, no clear indication.