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Duration of symptoms of respiratory tract infections in children: systematic review

BMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f7027 (Published 11 December 2013) Cite this as: BMJ 2013;347:f7027

Re: Duration of symptoms of respiratory tract infections in children: systematic review

To the Editor

We read with great interest the paper of Thompson et al. “Duration of symptoms of respiratory tract infections in children: systematic review” (1). We fully agree with the Authors that this kind of data is important to set expectations for parents and physicians. In this paper, the duration of earache was far longer than expected by our clinical experience and the current advice from NICE and CDC. Therefore, we carefully scrutinized the results of earache. For our surprise, we found miscalculations in the results related to our own study (2). We also found inconsistencies in numbers between Tables 1 and 2 (2-7). Further, in Table 1 the Authors have extended the duration of earache to be 1–2 days longer than originally reported in several studies (4-8). Moreover, from three studies (4,5,7) the Authors have included an outcome based on a combination of symptoms as a surrogate outcome of earache. This further prolongs the duration earache because combinations typically include nonspecific symptoms (e.g. irritability, crying, poor appetite) which last longer than earache. Below we describe our observations in detail.

Yours sincerely,

Paula A. Tähtinen, MD, PhD
Aino Ruohola, MD, PhD

Department of Pediatrics and Adolescent Medicine,
Turku University Hospital,
Turku, Finland

TÄHTINEN et al. 2011 (2):

Inconsistencies in numbers between Tables 1 and 2 in the review: No. in sample is 158 and 160, respectively.

Miscalculations: In Table 2, the Authors seem to have visually estimated the numbers from the Kaplan-Meier curve in our Supplement Figure 2. It is of note, though, that the Y-axis in the Kaplan-Meier curve shows an estimate of the cumulative survival rate, and thus it is impossible to determine the number of subjects in the numerator or the denominator based on the curve itself (9). Furthermore, the denominator in our Supplement Figure 2 is 80, not 160. This is because of the high tendency of spontaneous resolution of symptoms, the assessment of treatment effect on symptoms was based on diary recordings of those patients who had the symptom recorded in the diary during the first 48 hours, instead of including all those patients who had the symptom before study entry. In addition, in our analysis 54 children were censored because of the initiation of rescue treatment or withdrawal from the study. Therefore, the numbers provided by the Authors in their Table 2 are incorrect and overestimate the number of children with earache. We provide the correct numbers and proportions of children with earache in Letter Table 1.

BURKE et al. 1991 (3):

Inconsistencies in numbers between Tables 1 and 2 in the review: No. in sample is 113 and 118, respectively.

DAMOISEAUX et al. 2000 (4):

Inconsistencies in numbers between Tables 1 and 2 in the review: No. in sample is 105 and 123, respectively. Proportion of children with earache 72% on day 6 and 72% on day 4, respectively.

Extended duration of earache: In Table 2, the proportion of children with earache is 72% on day 4, which corresponds to the number of children with persistent symptoms in Damoiseaux’s original article. In Table 1, the proportion of children with earache is 72% on day 6.

Surrogate outcome: The Authors have used Damoiseaux´s outcome persistent symptoms (Damoiseaux´s Table 2), i.e. “The primary outcome measure was persistent symptoms at day four, assessed by the doctor and defined as persistent earache, fever (>38oC), crying, or being irritable.”

HOBERMAN et al. 2011 (5):

Inconsistencies in numbers between Tables 1 and 2 in the review: No. in sample is 139 and 147, respectively.

Extended duration of earache: In Table 2, the proportion of children with earache is 47% on day 7. In Table 1, the proportion of children with earache is 47% on day 8.

Surrogate outcome: The Authors, as given in their foot notes, have used Hoberman´s outcome AOM-SOS, “The AOM-SOS scale consists of seven discrete items: tugging of ears, crying, irritability, difficulty sleeping, diminished activity, diminished appetite, and fever.”

LE SAUX et al. 2005 (6):

Inconsistencies in numbers between Tables 1 and 2 in the review: No. in sample is 246 and 254, respectively. Proportion of children with earache on day 3 is 78% and 22%, respectively.

Extended duration of earache: In Table 2, the proportion of children with earache is 22% on day 3, which corresponds to the number of children with earache in Le Saux’s original article. In Table 1, the proportion of children with earache is 78% on day 3.

MYGIND et al. 1981 (8):

Extended duration of earache: In Tables 1 and 2, the number of children with earache is 38% on day 3. However, in the original article, Mygind reports that 62% and 79% of children in placebo and penicillin group, respectively, ”…were quite free from symptoms from and including day 2 (P<0.05)”.

NEUMARK et al. 2007 (7):

Inconsistencies in numbers between Tables 1 and 2 in the review: The proportion of children with earache is 17% on day 8 and 17% on day 7, respectively.

Extended duration of earache: In Table 2, the proportion of children with earache is 17% on day 7, which corresponds to the number of children whose condition was back to normal in Neumark’s original article. In Table 1, the proportion of children with earache is 17% on day 8.

Surrogate outcome: The Authors have used Neumark´s outcome “recovery day” (Neumark´s Figure 1), i.e. the day parents appraised that the condition of their child was back to normal. Comparison between Neumark´s results of earache and that of the Authors is shown in Letter Table 2.

REFERENCES

1.Thompson M, Vodicka TA, Blair PS, Buckley DI, Heneghan C, Hay AD; TARGET Programme Team. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ 2013;347:f7027. doi: 10.1136/bmj.f7027.

2.Tähtinen PA, Laine MK, Huovinen P, Jalava J, Ruuskanen O, Ruohola A. A placebo-controlled trial of antimicrobial treatment for acute otitis media. N Engl J Med 2011;364:116-26.

3.Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children: controlled trial of non-antibiotic treatment in general practice. BMJ 1991;303:558-62.

4.Damoiseaux RA, van Balen FA, Hoes AW, Verheij TJ, de Melker RA. Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ 2000;320:350-4.

5.Hoberman A, Paradise JL, Rockette HE, Shaikh N, Wald ER, Kearney DH, et al. Treatment of acute otitis media in children under 2 years of age. N Engl J Med 2011;364:105-15.

6.Le Saux N, Gaboury I, Baird M, Klassen TP, MacCormick J, Blanchard C, et al. A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age. CMAJ 2005;172:335-41.

7.Neumark T, Mölstad S, Rosen C, Persson LG, Törngren A, Brudin L, et al. Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16. Scand J Prim Health Care 2007;25:166-71.

8.Mygind N, Meistrup-Larsen KI, Thomsen J, Thomsen VF, Josefsson K, Sorensen H. Penicillin in acute otitis media: a double-blind placebo-controlled trial. Clin Otolaryngol Allied Sci 1981;6:5-13.

9.Rich JT, Neely JG, Paniello RC, Voelker CC, Nussenbaum B, Wang EW. A practical guide to understanding Kaplan-Meier curves. Otolaryngol Head Neck Surg 2010;143:331-6.

Competing interests: No competing interests

21 December 2013
Paula A. Tähtinen
Postdoctoral fellow
Ruohola Aino, Clinical lecturer
Department of Pediatrics and Adolescent Medicine, Turku University Hospital
Kiinamyllynkatu 4-8, 20520 Turku, Finland