Best Evidence Topics

Randomised control trial

Paul IM. Beiler J. McMonagle A. Shaffer ML. Duda L. Berlin CM Jr.
Effect of Honey, Dextromethorphan, and No Treatment on Nocturnal Cough and Sleep Quality for Coughing Children and Their Parents
Archives of Pediatrics & Adolescent Medicine
December 2007; Vol 161 (12), 1140-6
  • Submitted by:Beth Heppermann - Emergency Medicine Resident
  • Institution:Grand Rapids Medical Education & Research/Michigan State University
  • Date submitted:6th February 2009
Before CA, i rated this paper: 6/10
1 Objectives and hypotheses
1.1 Are the objectives of the study clearly stated?
  Yes. To compare the effects of a single nocturnal dose of buckwheat honey or honey-flavored dextromethorphan with no treatment on nocturnal cough and sleep difficulty associated with childhood upper respiratory tract infections.
2 Design
2.1 Is the study design suitable for the objectives
  Yes. A survey was administered to parents on 2 consecutive days, first on the day of presentation when no
medication had been given the prior evening and then the next day when honey, honey-flavored DM, or no treatment had been given prior to bedtime.
2.2 Who / what was studied?
  105 Children aged 2-18 years with URIs, nocturnal symptoms and illness duration of 7 days or less.
2.3 Was this the right sample to answer the objectives?
2.4 Is the study large enough to achieve its objectives? Have sample size estimates been performed?
  Yes. The prospectively estimated sample size necessary to detect a 1-point difference between any 2 treatment groups with 80% power was 35 subjects per treatment group for a total sample size of 105 subjects with alpha =.05.
2.5 Were all subjects accounted for?
  Yes. One hundred thirty children with URIs were enrolled and 105 (81%) completed the single-night study.
2.6 Were all appropriate outcomes considered?
  Yes. Cough frequency, cough severity, bothersome nature of cough, and child and parent sleep quality.
2.7 Has ethical approval been obtained if appropriate?
  not mentioned
2.8 Were the patients randomised between treatments?
  Yes, each child was randomly assigned in a partially doubleblinded fashion.
2.9 How was randomisation carried out?
  The randomization sequence was constructed by a statistician not affiliated with the study and was then used by the study coordinators to assign treatment groups.
2.10 Are the outcomes clinically relevant?
3 Measurement and observation
3.1 Is it clear what was measured, how it was measured and what the outcomes were?
  Yes. Subjective parental assessments of their child’s cough and sleep difficulty on the previous night were assessed through previously validated questions using a 7-point Likert scale (Figure 1). A second survey asking the same questions as those answered at enrollment was then administered via telephone interview the following day to the same parent by trained study coordinators, who were blinded to the treatment group, to assess symptom severity for the night when DM, honey, or no treatment was given.
3.2 Are the measurements valid?
  Investigators at the Massachusetts General Hospital recently validated this survey with 120 caregivers of children aged 1 to 18 years and found it to be reliable for assessing changes in cough frequency and severity over time.
3.3 Are the measurements reliable?
3.4 Are the measurements reproducible?
3.5 Were the patients and the investigators blinded?
  Partially double blinded. The syringes used for all of the 3 treatment groups were opaque and were placed in brown paper bags to avoid investigator unblinding. Although the no-treatment group was not blinded to their treatment arm, the honey and DM groups remained blinded. A compounding pharmacy prepared the DM to approximate the consistency, texture, flavor, smell, and sweetness of honey.
4 Presentation of results
4.1 Are the basic data adequately described?
  Yes, the average score for each outcome was reported before treatment and after treatment and the differences were calculated.
4.2 Were groups comparable at baseline?
  Yes. See Table 1
4.3 Are the results presented clearly, objectively and in sufficient detail to enable readers to make their own judgement?
  Yes. See Figure 2
4.4 Are the results internally consistent, i.e. do the numbers add up properly?
4.5 Were side effects reported?
  Yes. The combination of mild reactions that include hyperactivity, nervousness, and insomnia occurred in 5 patients treated with honey, 2 patients in the DM group, and no patients in the no-treatment arm (P=.04). In the honey group, the parent of 1 patient reported drowsiness and the parents of 2 patients reported stomachache, nausea, or vomiting, but these adverse events were not significant when examined separately from a statistical perspective (drowsiness, P=.65; stomachache, nausea, vomiting, P=.21).
5 Analysis
5.1 Are the data suitable for analysis?
5.2 Are the methods appropriate to the data?
5.3 Are any statistics correctly performed and interpreted?
  Yes. In pairwise comparisons, honey was significantly superior to no treatment for our a priori primary outcome of cough frequency (P=.01) as well as the combined symptom score (P=.04), with marginally significant superiority for child sleep (P=.09) and the bothersome nature of the cough (P=.08). Nonsignificant outcomes included cough severity (P=.18) and parent sleep (P=.17). In contrast, DM was not significantly better than no treatment for any study outcome. Similarly, pairwise comparison of honey with DM revealed no statistically significant differences.
6 Discussion
6.1 Are the results discussed in relation to existing knowledge on the subject and study objectives?
  yes. These findings complement the results of their previous study that found no difference between DM, diphenhydramine, or placebo for children with URIs.
6.2 Is the discussion biased?
  No, the authors discuss both positives and negatives of their study.
7 Interpretation
7.1 Are the authors' conclusions justified by the data?
7.2 What level of evidence has this paper presented? (using CEBM levels)
7.3 Does this paper help me answer my problem?
  Yes, it provides an alternative remedy for cough associated with URIs, especially in light of the fact that DM is no longer supported by the American Academy of Pediatrics or the American College of Chest Physicians.
After CA, i rated this paper: 8/10
8 Implementation
8.1 Can any necessary change be implemented in practice?
  Yes, honey is relatively inexpensive and readily available at most stores and can therefore be recommended to parents of children with cough associated with URI.
8.2 What aids to implementation exist?
  Honey is widely available and inexpensive.
8.3 What barriers to implementation exist?
  This treatment is not commonly used in the US and would therefore require parental education as well as education of physicians and other care providers.