Antipyretic efficacy of alternating therapy depending on the administration interval in children using patient-generated health data: a retrospective observational study (Preprint)

BACKGROUND Caregivers are often advised to give additional antipyretic doses if fever persists or recurs before the next dose time. In previous studies, there is no consistent evidence. In clinical guideline, there is no recommended doses in alternative antipyretics treatment. OBJECTIVE To evaluate more appropriate time intervals for alternative therapy using large-scale patient-generated health data. METHODS Participants were youth (aged 6-144 months) and their caregiver used the Fever Coach mobile application between February 2015 to December 2019. One case was referred to a single record for 72 hours after the first antipyretic record input. Baseline means the temperature record closest to the first antipyretic dose. In total, 138,117 cases with alternative antipyretics were selected for final analysis. Area under the curve (AUC) calculated by the area under the temperature curve from baseline for certain hours was used for efficacy analysis. We counted cases with low body temperature records (<36.0℃) to estimate adverse effects. RESULTS In total 138,117 cases, mean age was 29.58 months, and mean baseline temperature was 38.77℃. The time interval between the first and the second antipyretics was 2-3 h in 44,669 (32.34%), 3-4 h in 48,472 (35.09%), and 4-5 h in 44,976 (32.56%) cases. Within 2 h of the first dose, the 2-3 h interval group continued to have fever >38.0℃. The reduction in body temperature from baseline was -0.33℃, -0.54℃, and -0.62℃ in the 2-3 h, 3-4 h, and 4-5 h interval groups, respectively (P < .001, Effect Size 0.041). Within 6 h, the AUC was -201.59 at 2-3 h interval, -165.62 in 3-4 h interval, and -164.32 in 4-5 h intervals (P < .001, Effect Size 0.014). The area under the curve for alternative therapy with 2-3 h intervals was significantly higher than other interval. The mean body temperature of each hour was drawn and acetaminophen with ibuprofen/dexibuprofen showed the fastest and largest antipyretic effects. Within 12 h, 0.89%, 0.50%, and 0.40% cases had low body temperature (<36.0℃) in the 2-3 h, 3-4 h, and 4-5 h interval groups, respectively (P < .001, Effect Size 0.001). CONCLUSIONS In this study, using large-scale patient-generated health data, antipyretic effects were higher at 2-3h interval in alternating therapy. However, education programs and proper care are needed to avoid overdosing.