To the Editor
Anaphylaxis is a life-threatening systemic reaction that may be induced by allergens such as drugs, insect stings, and food1,2. Rapid administration of adrenaline is important to prevent fatalities1, but it sometimes takes too long to arrive at a medical institution in an emergency. Adrenaline auto-injectors (AAIs) can be used by non-healthcare professionals. However, patients and their caregivers often cannot use AAIs correctly because of insufficient practice even if they have experienced anaphylaxis3. Therefore, physicians must have their patients practice AAI use at home.
The aim of the present study was to evaluate the sustained effect of education for patients or caregivers on practical performance in administering AAI with a diary that was filled out on practice days to maintain motivation for practicing AAI use.
Eligible participants included patients or their caregivers who were prescribed the EpiPen (Mylan Specialty LP, Basking Ridge, NJ) as an AAI for an allergy (including food allergy or insect stings). This study was conducted at the Department of Pediatrics, Kochi Medical School Hospital (KMS) and Kochi Prefectural Hata Kenmin Hospital (HK). Participants were asked for their informed consent for inclusion in this study at both hospitals. Between October 2017 and August 2018, 102 patients with their caregivers were invited to join this study. Exclusion criteria were as follows: 1. caregiver did not give consent; 2. siblings had already participated in this study; and 3. patients moved from our hospital.
Their caregivers or patients were asked about their age, history of anaphylaxis of patients and other family members, experience using an AAI, and history of AAI prescriptions to patients or their family. In addition, the number of prescriptions was also determined.
Patients were provided with an AAI diary. In the diary, patients or caregiver filled out the practice days for one year. At recruitment, patients who had already been prescribed an AAI were asked to demonstrate how to use the device using the EpiPen trainer without an opportunity to read the instructions. Their skill was checked for the following items: a) how to hold the AAI, b) removing the blue cap, c) selecting the mid-anterolateral thigh as the correct site of injection, d) holding firmly in place for 5 seconds, and e) massaging after injection.
All participants were subsequently instructed on how to correctly use the AAI by a medical doctor. They were given material with pictures about the five points above. Participants were told to practice with the EpiPen trainer at home. After one year, the AAI diaries were collected, the practice days were confirmed, and participants were asked to demonstrate its use without reading the instructions. Participants were assessed by a single investigator at each institution prior to and around one year later.
Statistical analysis was conducted using IBM SPSS Statistics 23.0 (IBM Corporation, Armonk, NY, USA). Frequencies are reported as numbers and percentages. Continuous data are presented as medians with interquartile range (IQR). Significance was evaluated using chi-squared tests or Fisher’s exact test. The conventional cut-off of p<0.05 was used to determine significance.Considering past prescriptions, a total sample size of 120 was calculated (n=100, KMS; n=20, HK). This study was approved by the Ethics Review Boards of KMS and HK.
A total of 102 patients participated in the study. The flowchart of the study is presented in Fig. 1. Baseline characteristics of the patients are presented in Table 1. The patients had a median age of 7.5 (5-10) years, 74% of patients had a history of anaphylaxis, and 5% of patients had used an AAI at least once. The prescription history was as follows: 1st prescription 19.6%, 2nd prescription 15.7%, 3rdprescription 14.7%, and more than the 3rdprescription 50.0%. Overall, 3.9% of participants had another family member who had an AAI. The percentage with a family history of anaphylaxis was 16.7%. Ninety-three participants were the caregivers of the patients; their median age was 38 (34-42) years. The final study population comprised 97 participants (sum of patients and their caregivers for subjects).
The pass rate at baseline is presented in Table 2. Because patients who were prescribed an AAI for the first time (n=20) were excluded, 82 subjects were assessed at baseline. The pass rate was 46.3%. When the categories of holding for 5 seconds and massaging were excluded, the pass rate was 68.3%. The pass rate increased significantly as the number of prescriptions increased. A history of anaphylaxis was not associated with AAI skill, with the results for each individual skill as follows: a) p=0.551, b) p=0.163, c) p=1.000, d) p=0.566, and e) p=1.000.
The pass rate after one year of using the AAI diary is presented in Table 3. The pass rate increased obviously to 83.5%. Without the categories of holding for 5 seconds and massaging, the pass rate was 88.7%. A history of anaphylaxis was not associated with AAI skill, with the results for each individual skill as follows: a) p=0.130, b) p=0.309, c) p=0.669, d) p=0.669, and e) p=1.000. In addition, there was no significant difference between the 1st prescription and more than the 2nd prescription.
The present data showed that the AAI diary helped participants maintain their skill for using an AAI. This is clinically important, because patients or their caregivers must use an AAI correctly when the patients have severe anaphylaxis. Aisha et al. reported that it was necessary to identify and design interventions targeting areas of poor technique that were identified when using an AAI, and those interventions should be acceptable, understandable, and cost-effective3. In the present study, the pass rate for AAI skill was very low at baseline, even though allergy specialists trained the patients or the caregivers at the time of prescription.
Although we thought that it might be better that such education be given by pharmacists, a previous study showed that pharmacists in the Netherlands had considerable gaps in knowledge about food allergy and instruction on how to use an AAI, and none of them demonstrated correct AAI use4. We also suppose that some Japanese pharmacists are unable to use an AAI correctly. Therefore, research about this problem is also necessary.
Participants’ period of maintaining skill one year after training by a specialist was assessed. Another study with pre-school teachers showed that the number of auto-injector administrations without any drug-related problems increased directly after the education session and decreased 4-12 weeks afterwards. After 4-12 weeks, the effect of the education was decreased5. This study showed that the participants forgot the proper use of the AAI within 3 months after the 1st educational session. This result is consistent with that of the present study.
Some adrenaline auto-injector devices have been approved by several countries, but the EpiPen is the only device that approved for use in Japan. Another study showed that the percentage of correct use of an AAI differed among devices6,7. A device with audible voice instructions was thought to be very useful, but all devices do not have the same function, and audible voice instructions require time for listening. We are also able to use an application with a mobile phone for the EpiPen. In any case, it is important to be able to use the AAI unexpectedly. Even though there are several opinions about the holding time of the device in place3, the present data showed the same result without keeping the device for 5 minutes on the leg.
The day of assessment was not exactly one year among the participants (e.g., earlier than one year or later than one year), and the subjects also might train in AAI use on the day when their AAI skill was assessed. Hence, even with just possession of the diary, the pass rate might increase because the motivation to acquire the skill might be higher. To the best of our knowledge, this is the first study
Taku Oishi, MD1), Kouhei Hagino, MD2), Hajime Kuroiwa, PhD3), and Mikiya Fujieda, MD, PhD1)
1) Department of Pediatrics, Kochi Medical School, Kochi University
Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan
2) Department of Pediatrics, Kochi Prefectural Hata Kenmin Hospital
3-1 Yoshina, Yamana-cho, Sukumo, Kochi 788-0785, Japan
3) Integrated Center for Advanced Medical Technologies, Kochi Medical School
Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan