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PRIMARY CARE: Kristian Roos, Eva Grahn Håkansson, and Stig Holm Effect of recolonisation with "interfering" streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial BMJ 2001; 322: 210 [Abstract] [Full text]

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Alternatives to antibiotics for otitis media

Wendy McLean   (27 January 2001)

Is it important to properly describe whitdrawals?

Rafael Carbonell-Sanchis   (15 February 2001)

Tampering with Microbial Ecology

Erdem I Cantekin   (18 February 2001)

Alternatives to antibiotics for otitis media 27 January 2001
Wendy McLean, retired Send response to journal: Re: Alternatives to antibiotics for otitis media	There is already a possible way to reduce the use of antibiotics for recurrent otitis media. In 1996 M Uhari et al, writing in the BMJ, reported a trial involving xylitol chewing gum. Other studies have involved xylitol lozenges or syrup and have shown reductions in infection of between 20% (lozenges) and 40% (chewing gum). A xylitol nasal spray is now available (in America and via the internet). Although I have yet to see a proper clinical trial of the spray it is possible that it would be more effective. If the authors wish to demonstrate the advantages of the product which they intend to patent perhaps they should compare it with xylitol.
Is it important to properly describe whitdrawals? 15 February 2001
Rafael Carbonell-Sanchis, Otolaryngologist Hospital de Sagunto, Valencia, Spain Send response to journal: Re: Is it important to properly describe whitdrawals?	Dear Editor: It was with much interest that we read the paper published by Roos K., Grahn E. and Holm S. “Effect of recolonisation with “interfering” alpha streptococi on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial BMJ 2001;322:1-4”. However we would like to make several considerations. Firstly one of the most significant features of the internal validity of clinical trials is the description of whitdrawals (1). Of the 137 eligible participants, we do not know if they were finally randomised or a smaller number was included. The authors do not describe in sufficient detail the study losses and furthermore the number of losses described (20) does not match the difference between the number of patients included (132) and the number of patients included in the efficacy analysis (108). We would also like to point out that for a better interpretation of the results these should have been expressed in terms of relative risk (RR) and number need to treat (NNT). We have calculated the RR and NNT with the authors’ results and have recalculated assuming that the 24 losses (difference between patients included and those with whom the authors conducted the efficacy analysis) are equally distributed between the two branches of the trial. Thus the results presented by the authors would be the following: Risk of acute otitis media + secretory otitis media in Treatment group: (21+10)/53 Risk of acute otitis media + secretory otitis media in Placebo group: (28 + 15)/55 RR = 0.75 ( 0.77- 0.98) NNT 5 ( 3-40) These good results are slightly modified when a sensitivity analysis is conducted Analisis in the worst case: Risk of acute otitis media + secretory otitis media in Treatment group: (21+10+ 12)/(53+12) Risk of acute otitis media + secretory otitis media in Placebo group: (28 + 15)/(55+12) RR = 1.03 ( 0.80- 1.32) Non significant, therefore NNT are not calculated. It is unfortunate that interventions which could mean other forms of treatment are questioned for methodological reasons. References 1. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 1993;270:2598-601. Rafael Carbonell Sanchis MD PhD. Servicio de Otorrinolaringología. Hospital de Sagunto Valencia SPAIN Vicente Ruiz-García MD PhD Unidad de Hospitalización a Domicilio Hospital La Fe Valencia SPAIN Remedios Giner MD PhD Servicio de Medicina Digestiva Hospital Arnau de Vilanova Valencia SPAIN Mª Angeles Rosero Arenas MD PhD Equipo de Atencion Primaria CS Salvador Allende MIR Medicina Familiar y Comunitaria C/ Salvador Allende s/n Valencia SPAIN JA Pérez-Fernandez MD Servicio de Neumología Hospital Arnau de Vilanova Valencia SPAIN Nieves Ramón Bou MD PhD Equipo de Atencion Primaria CS Salvador Allende MIR Medicina Familiar y Comunitaria Valencia SPAIN Miguel Angel García García MD PhD MIR Cuidados Intensivos Hospital La Fe Valencia SPAIN By the critical reading group from La Fe and Arnau de Vilanova Hospitals Mailing address Rafael Carbonell-Sanchis ENT Department. Hospital de Sagunto Avda. Ramón y Cajal s/n 46520 Sagunto Valencia Spain E-mail: carbonell_raf@gva.es
Tampering with Microbial Ecology 18 February 2001
Erdem I Cantekin, Professor of Otolaryngology University of Pittburgh School of Medicine Send response to journal: Re: Tampering with Microbial Ecology	Professor Holt and colleagues have chosen an unusual path by not following the scientific tradition where inquiries are almost always based on building over the existing knowledge base.[1] Before formulating a new hypothesis and testing it, a comprehensive review of the evidence is the standard. Authors, before setting up their experimental protocol, do not bother to provide the current evidence regarding antibiotic therapy for otitis media .[2,3] In their hypothesis testing , they in fact completely ignore that antibiotic prophylaxis for otitis prone children is less effective than placebo treatment. The largest clinical trial (N=194) on the subject has shown that those children who had received placebo prophylaxis had less bouts of acute otitis media then those children who were on antibiotics.[4] Also, antibiotic treatment increases recurrence rates 2 to 6 times. [5] With this missing background material, authors have designed a flawed experiment. They have introduced a strong bias since all children were treated with recurrence causing antibiotics prior to insertion of microbial cocktails in their noses. Treatment of all children with antibiotics makes it impossible to determine the natural history of untreated disease. In other words, this clinical trial had no real control group. A third group who has received neither antibiotics nor bacterial spray is a must before we can advocate alterations of children’s microbial ecology. Moreover, the conclusions are based on a limited data set as well as missing analysis of confounding parameters such as child’s age, prior use of antibiotics, number of prior episodes, the season of the year, etc. This short follow up study (3 months of duration)with it’s basic experimental flaw (no true control group) and the observed marginal benefit of 10 episodes of acute otitis media among the two groups [22/53 (42%) versus12/55(22%)] discredits it’s conclusions and recommendations. I hope the treatment of young children with nasal sprays to alter microbial ecology will not be taken seriously. It is not good science and it is a risky clinical undertaking. References: 1. Roos K, Håkansson EG, Holm S. Effect of recolonisation with "interfering" streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial. BMJ, 2001;322:210. 2. Rand report 2000. Management of Acute Otisis Media. Summary, Evidence Report/Technology Assessment: Number 15, June 2000. Agency for Healthcare Quality and Research, Rockville, MD. http://www.ahrq.gov/clinic/otitisum.htm 3. Cantekin EI. Aggressive and ineffective therapy for otitis media. Otorhinolaryngol Nova 1998;8:136-147. 4. Roark R, Berman S. Continuous twice daily or once daily amoxicillin prophylaxis compared with placebo for children with recurrent acute otitis media. Pediatric Infect Dis J 1997;16:376-381. 5. Cantekin EI, McGuire TW, Griffith TL. Antimicrobial therapy for otitis media with effusion (‘secretory’ otitis media. JAMA 1991;266:3309- 3317. 1991