Implications of Seizure-Cluster Treatment on Healthcare Utilization: Use of Approved Rescue Medications

Figures & data

Figure 1 PRISMA diagram for literature search via PubMed. Adapted from Page MJ, McKenzie, JE, Bossuyt, PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;n71.¹⁷

Abbreviations: ARS, acute repetitive seizures; IV, intravenous; SC, seizure cluster.

Table 1 Summary of Data from the Included Seizure-Cluster Studies

	Diazepam Rectal Gel (N=149 Enrolled; n=149 Treated)	Midazolam Nasal Spray (N=175 Enrolled; n=161 Treated)	Diazepam Nasal Spray (N=175 Enrolled; n=163 Treated)
Age range, y	2–76 2–5, n=33 6–11, n=39 12–76, n=77	12–62 <18, n=8 18–64, n=153 Mean, 32.9; median, 31.0	6–65 6–11, n=45 12–65, n=118 Mean, 23.1; median, 18.0
Duration of treatment	Range, 2 mo–2.5 y 48% >2 y	Median, 16.8 mo <6 mo: 12% ≥6–<12 mo: 22% ≥12 mo: 66%	Median, 15.1 mo <6 mo: 5.5% ≥6–<12 mo: 12.9% ≥12 mo: 81.6%
Seizure clusters treated (mean number of clusters per treated person with epilepsy)	1578 (10.6^a) Median: 8 per person,^b or ~5.3 per person per year^c,d	1998 (12.4^a) ~8.9 per person per year^c	3853 (23.6%^a) ~18.8 per person per year^c
Doses per mo	Median, 0.4^b Monthly range, 0.03–4.3	Doses not available Median treated clusters, 5.9/y (range, 0.5–50.4/y)	Mean, 2.3 Monthly range, 1–10

Notes: ^aCalculated as number of seizure clusters divided by the number of treated participants in the study; ^bFor the 125 participants with at least 2 treatments, 24 received a single treatment during the study; ^cCalculated as total number of ([seizures / treated participants] / median months duration) × 12 months; ^dCalculated using an approximate median 24 months duration.

Figure 2 Seizure episodes treated with only one dose for control at 6, 12, and 24 hours. ^aIn the midazolam study, an additional 28 doses were administered more than 6 hours after the first dose.

Table 2 Number of Doses Used per Seizure Episode at 6, 12, and 24 Hours

Doses	Diazepam Rectal Gel^a	Midazolam Nasal Spray^b	Diazepam Nasal Spray
0–6 hours
First doses	Not reported	1998	3853
Second doses		769	224
Doses per seizure episode^c		1.38	1.06
0–12 hours
First doses	1578	Not reported	3853
Second doses	363^a		318
Doses per seizure episode^c	1.23		1.08
0–24 hours
First doses	Not reported	Not reported	3853
Second doses			485
Doses per seizure episode^c			1.13

Notes: ^aIn the diazepam rectal gel study, second doses were not provided for all participants per protocol and all doses were assumed to be first doses; however, a second dose may have been appropriate for 363 seizures owing to lack of efficacy. ^bIn the midazolam study, an additional 28 doses were administered more than 6 hours after the first dose. ^cCalculated as (first doses + second doses) / first doses.

Page MJ, McKenzie, JE, Bossuyt, PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;n71. doi:10.1136/bmj.n71

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