The practice nurse for a large health centre who is responsible for running the self-referral asthma clinic for children and young adults stops you (the GP) during the lunch break. She has just seen a 2 year old child in the morning clinic with a barking cough and, from the description his mother gives, what sounds like inspiratory stridor during the previous night. She arranged for the child to be reviewed in your evening surgery. She poses the question, in children with mild to moderate croup, does nebulised budesonide decrease the risk of hospital admission compared with placebo? During her lunch break, she has a look for articles on the use of nebulised budesonide in croup on Medline (using Winspirs).

She presents you with her search strategy and a research article and asks whether you are going to give the child nebulised budesonide. By the time you see the child that evening, he has a barking cough, mild inspiratory stridor and a hoarse voice.

Decide:

• Will you give the child nebulised budesonide?
• Should you change local practice policy?

Search strategy for Croup – type in:

1. Explode CROUP/ all subheadings
2. BUDESONIDE
3. CLINICAL TRIAL IN PT*
4. #1 and #2 and #3

You find the article: Klassen, T.P. Feldman, M.E. Watters, L.K. et al. Nebulized budesonide for children with mild to moderate croup. NEJM 1994; 331(5):285-289.

Read the article and decide:

• Is the evidence from this randomised trial valid?
• If valid, is this evidence important?
• If valid and important, can you apply this evidence in caring for your patient?

Completed Therapy Worksheet for Child Health

Clinical Question

In children of mild to moderate group does nebulized budesonide or placebo reduce the risk of hospital admission?

Are the results of this single preventive or therapeutic trial valid?

Was the assignment of patients to treatments randomised? And was the randomisation list concealed?

Yes, and randomisation performed by pharmacy as concealed.

Were all patients who entered the trial accounted for at its conclusion? And were they analysed in the groups to which they were randomised?

Yes.

Were patients and clinicians kept “blind” to which treatment was being received?

Yes. Both budesonide and placebo were given in opaque chambers.

Were the groups similar at the start of the trial?

Yes – more or less. Slightly longer duration of cough and higher temperature in experimental group.

Are the valid results of this randomised trial important?

Sample calculations:

Occurrence of childhood asthma		Relative Risk Reduction (RRR)	Absolute Risk Reduction (ARR)	Number Needed to Treat (NNT)
Usual Insulin Control Event Rate (EER)	Intensive Insulin Experimental Event Rate (CER)	(CER EER) / CER	CER – EER	1 / ARR
2.8%	9.6%	(9.6% – 2.8%) / 9.6% = 71%	9.6% – 2.8% = 6.8%	1 / 6.8% = 15pts

begin{align}
text{95% Confidence Interval ($CI$) on an $NNT$} \
&= 1 / text{(limits on the $CI$ of its $ARR$)} \
&=pm1.96 sqrt{frac{mathit{CER}times(1- mathit{CER})}{text{# of control pts.}} + frac{mathit{EER}times(1-mathit{EER})}{ text{# of exper pts.}}}
\
&=pm1.96 sqrt{frac{(0.96times0.904)}{730}+frac{0.028times0.972}{711}}= pm2.4% \
&=pm2.4%
end{align}

Your calculations:

Risk of hospital admission one week later		Relative Risk Reduction (RRR)	Absolute Risk Reduction (ARR)	Number Needed to Treat (NNT)
EER	CER	(CER – EER) / CER	CER – EER	1 / ARR
1/27 = 0.4	7/27 = 0.26	0.85	0.22	5

Can you apply this valid, important evidence about a treatment in caring for your patient?

Do these results apply to your patient?

Is your patient so different from those in the trial that its results can’t help you?

No. Patient in the scenario has a croup score 2-3, similar to patients in the trial. Assume baseline risk of hospital admission – 5%

How great would the potential benefit of therapy actually be for your individual patient?

1. Method 1: f
   $$
   1.1. text{ Risk of the outcome in your patient, relative to patients in the trial. expressed as a decimal: } 0.2 \\
   1.2.~mathit{NNT}/f = 5/0.2 = 25 \\
   1.3. text{ $NNT$ for patients like yours} = 25$$
2. Method 2:
   $$ 1 / (mathit{PEER}times mathit{RRR})\\
   2.1. text{ Your patient’s expected event rate if they received the control treatment: $PEER$}: 5%\\
   2.2.~ 1 / (mathit{PEER}timesmathit{RRR}) = 1/0.05times0.85 = 24\\
   2.3. text{ $NNT$ for patients like yours} = 24$$
3. Method 3:
   $$ 1/mathit{PEER}-(mathit{PEER}times text{Relative Risk})\\
   3.1. text{ Your patient’s expected event rate if they received the control treatment: $PEER$}: 5%\\
   3.2. text{ Relative Risk}=mathit{EER}/mathit{CER}= 0.15\\
   3.3.~1/mathit{PEER}-(mathit{PEER}times mathit{RR}) = 24$$

Are your patient’s values and satisfied by the regimen and its preferences consequences?

Do your patient and you have a clear assessment of their values and preferences?

Consider inconvenience and cost of nebuliser versus hospital admissions saved.

Are they met by this regimen and its consequences?

Yes, probably.

Additional Notes

The study includes a mix of mild to moderate croup. In primary care, mild cases will predominate and the treatment effect may differ. Caution in applying these results to primary care.

Croup – Nebulized Budesonide reduces hospital admission in children with mild to moderate croup

Clinical Bottom Line

Nebulized budesonide compared with placebo reduces hospital admission and improves symptoms in children with mild to moderate croup.

Citation

Klassen, T.P. Feldman, M.E. Watters, L.K. et al. Nebulized budesonide for children with mild to moderate croup. NEJM 1994; 331(5):285-289.

Clinical Question

In children with mild to moderate croup does nebulized budesonide compared with placebo reduce the risk of hospital admission?

Search Terms

‘explode CROUP/all subheadings’ and ‘BUDESONIDE‘ and ‘CLINICAL TRIAL IN PT‘

The Study

1. Randomised, controlled trial of children with croup score of 2-7 (out of possible 17) seen in A&E department.
2. Randomisation was concealed and children, parents and clinicians were blind to treatment.
3. They performed an intention to treat analysis.
4. Control group (N = 27; 27 analysed) : 4 ml nebulized normal saline.
5. Experimental group(N = 27; 27 analysed) : 4 ml nebulized budesonide (2 mg).

The Evidence

Admission one week later

EER	CER	ARR (95% CI)	NNT (95% CI)
1/27 = 0.4	7/27 = 0.26	0.22 (0.042 to 0.402)	5 (2 to 24)

Mean 2 point reduction in croup score in treatment group (p<0.05).

Comments

• The small number of patients studied produces wide confidence intervals.
• Watch for more recent studies on this topic.