Table 3.

Summary of findings: Alternating versus single agent for fever in children

Alternating versus single agent for fever in children
Patient or population: children with fever Intervention: alternating versus single agent
Outcomes	Timepoint	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
		Assumed risk	Corresponding risk
		Single agent	Alternating regimen
Mean Temperature	1 hour	The mean temperature in the control group was 37.6 °C	The mean temperature in the intervention groups was 0 °C higher (0.28 °C lower to 0.28 °C higher)	‐	40 (1 study)	⊕⊝⊝⊝ very low1,2,3,4	Children in the alternating regimen group received a second dose of antipyretic at 3‐4 hours
	4 hours	The mean temperature in the control groups ranged from 37.5 °C to 38.0 °C	The mean temperature in the intervention groups was 0.60 °C lower (0.94 °C to 0.26 °C lower)	‐	78 (2 studies)	⊕⊕⊝⊝ low5,6,7
	6 hours	The mean temperature in the control group was 38.5 °C	The mean temperature in the intervention groups was 1.60°C lower (2.27 °C to 0.93 °C lower)	‐	40 (1 study)	⊕⊝⊝⊝ very low1,3,4
Proportion febrile	1 hour	20 per 100	20 per 100 (6 to 69)	RR 1 (0.29 to 3.45)	40 (1 study)	⊕⊝⊝⊝ very low1,2,3,4	Children in the alternating regimen group received a second dose of antipyretic at 3‐4 hours
	4 hours	30 per 100	2 per 100 (0 to 39)	RR 0.08 (0.00 to 1.29)	40 (1 study)	⊕⊝⊝⊝ very low1,3,4
	6 hours	45 per 100	11 per 100 (5 to 25)	RR 0.25 (0.11 to 0.55)	109 (2 studies)	⊕⊕⊝⊝ low8,6,7
*The basis for the assumed risk (eg the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate.

¹ This single study compared a single dose of ibuprofen with ibuprofen plus paracetamol 3 hours later. ² At this time point both treatment arms had received the same medication so differences would not be expected. ³ Downgraded by 1 for risk of bias: this study was at unclear risk of selection bias as allocation concealment was not described. ⁴ Downgraded by 2 for very serious imprecision due to the very small sample size. ⁵Paul 2010 compared ibuprofen at baseline plus paracetamol at 3 hours in the intervention group. Kramer 2008 compared paracetamol at baseline plus ibuprofen at 3 hours in the intervention group. ⁶ Downgraded by 1 for serious risk of bias: both studies are at unclear risk of selection bias as allocation concealment was not described. ⁷ Downgraded by 1 for imprecision due to the small sample size. ⁸Paul 2010 compared ibuprofen at baseline plus paracetamol at 3 hours in the intervention group. Nabulsi 2006 compared ibuprofen at baseline plus paracetamol at 4 hours in the intervention group.