Table 4.

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

Combined versus single agent for fever in children
Patient or population: children with fever Intervention: combined ibuprofen and paracetamol at baseline Control: a single agent alone at baseline
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	Combined regimen
Mean Temperature	1 hour	The mean temperature in the control groups ranged from 37.6 °C to 37.9 °C	The mean temperature in the intervention groups was 0.27 °C lower (0.45 °C to 0.08 °C lower)	‐	163 (2 studies)	⊕⊝⊝⊝ moderate 1,2,3
	4 hours	The mean temperature in the control groups ranged from 36.5 °C to 37.5 °C	The mean temperature in the intervention groups was 0.7 °C lower (1.05 °C to 0.35 °C lower)	‐	173 (2 studies)	⊕⊝⊝⊝ moderate 4,2,3
	6 hours	The mean temperature in the control group was 38.5 °C	The mean temperature in the intervention groups was 1.30 °C lower (2.01 °C to 0.59 °C lower)	‐	40 (1 study)	⊕⊝⊝⊝ very low5,6,7
Proportion Febrile	1 hour	20 per 100	10 per 100 (2 to 49)	RR 0.5 (0.1 to 2.43)	40 (1 study)	⊕⊝⊝⊝ very low5,6,7
	4 hours	23 per 100	2 per 100 (1 to 10)	RR 0.08 (0.02 to 0.43)	196 (2 studies)	⊕⊝⊝⊝ moderate 4,2,3
	6 hours	50 per 100	5 per 100 (1 to 35)	RR 0.10 (0.01 to 0.71)	40 participants (1 study)	⊕⊝⊝⊝ very low5,6,7
*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 These two studies compared ibuprofen plus paracetamol at baseline with ibuprofen alone (Paul 2010) or ibuprofen or paracetamol alone (Erlewyn‐Lajeunesse 2006). ² No serious indirectness: these studies were conducted in the UK and the USA in children with mild febrile illness. The studies excluded children with signs of severe illness or contra‐indications to the study drugs. ³ Downgraded by 1 for imprecision due to the small sample size of the studies. ⁴ These two studies compared ibuprofen plus paracetamol at baseline with ibuprofen alone (Paul 2010 and Hay 2008). ⁵ This single study was conducted in the USA and compared ibuprofen plus paracetamol at baseline with ibuprofen alone (Paul 2010). ⁶ Downgraded by 1 for risk of selection bias as allocation concealment was not described. ⁷ Downgraded by 2 for very serious imprecision: only one very small study.