Abstract
Introduction
Up to 80% of children have been affected by otitis media with effusion (OME) by the age of 4 years, but prevalence declines beyond 6 years of age. Non-purulent middle-ear infections can occur in children or adults after upper respiratory tract infection or acute otitis media. Half or more of cases resolve within 3 months and 95% within 1 year, but complications such as tympanic membrane perforation, tympanosclerosis, otorrhoea, and cholesteatoma can occur.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent otitis media with effusion in children? What are the effects of pharmacological, mechanical, and surgical interventions to treat otitis media with effusion in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found one systematic review and one RCT that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: adenoidectomy, antibiotics, antihistamines, autoinflation, bottle feeding, decongestants, exposure to other children, intranasal corticosteroids, mucolytics, oral corticosteroids, passive smoking, and ventilation tubes.
Key Points
Otitis media with effusion (OME, glue ear) usually presents with concerns about the child's behaviour, performance at school, or language development.
Children usually only have mild hearing impairment and few other symptoms.
Up to 80% of children have been affected by the age of 4 years, but prevalence declines beyond 6 years of age.
Non-purulent middle-ear infections can occur in children or adults after upper respiratory tract infection or acute otitis media.
Half or more of cases resolve within 3 months and 95% within 1 year, but complications such as tympanic membrane perforation, tympanosclerosis, otorrhoea, and cholesteatoma can occur.
Risk of OME is increased with passive smoking, bottle feeding, low socioeconomic group, and exposure to many other children.
However, there is no evidence to show whether interventions to modify these risk factors reduce the risk of OME.
Autoinflation with purpose-manufactured devices may improve effusions over 2 weeks to 3 months, but long-term efficacy is unknown.
We don't know whether non-purpose-manufactured devices are effective in treating otitis media with effusion. Children may find autoinflation difficult.
Oral antibiotics, antihistamines plus oral decongestants, or mucolytics may be of no benefit in OME, and can cause adverse effects.
Antibiotics can cause adverse effects in up to one third of children with OME.
Antihistamines can cause behavioural changes, seizures, and blood pressure variability.
Oral corticosteroids are unlikely to improve symptoms in OME, and can cause growth retardation.
Intranasal corticosteroids are unlikely to be of benefit in children with bilateral otitis media with effusion.
Ventilation tubes may improve short-term outcomes, but the clinical effect size is small. They may also increase the risk of tympanic membrane abnormalities.
Ventilation tubes improve hearing for the first 2 years, but have no longer-term benefit, and may not improve cognition or language development.
Adenoidectomy may improve hearing when performed with tympanostomy, but the clinical relevance of the improvements is unclear.
Combination treatment with ventilation tubes plus adenoidectomy may be more effective than adenoidectomy alone.
About this condition
Definition
Otitis media with effusion (OME) or "glue ear", is serous or mucoid, but not mucopurulent, fluid in the middle ear. Children usually present with hearing impairment and speech problems. By contrast with those with acute otitis media (see review on acute otitis media), children with OME do not suffer from acute ear pain, fever, or malaise. Hearing impairment is usually mild and often identified when parents express concern regarding their child's behaviour, performance at school, or language development.
Incidence/ Prevalence
OME is commonly seen in paediatric practice, and accounts for 25% to 35% of all cases of otitis media. One study in the UK found that, at any time, 5% of children aged 5 years had persistent (at least 3 months) bilateral hearing impairment associated with OME. The prevalence declines considerably beyond 6 years of age. Studies in the USA and Europe have estimated that about 50% to 80% of children aged 4 years have been affected by OME at some time. One study in the USA estimated that, between the ages of 2 months and 2 years, 91% of young children will have one episode of middle-ear effusion, and 52% will have bilateral involvement. OME is the most common reason for referral for surgery in children in the UK. The number of general practitioner consultations for OME increased from 15.2 per 1000 (2–10 year olds) per year to 16.7 per 1000 per year between 1991 and 2001. Middle-ear effusions also occur infrequently in adults after upper respiratory tract infection or after air travel, and may persist for weeks or months after an episode of acute otitis media.
Aetiology/ Risk factors
Contributory factors include upper respiratory tract infection and narrow upper respiratory airways. Case-control studies have identified risk factors, including age 6 years or younger, day care centre attendance, large number of siblings, low socioeconomic group, frequent upper respiratory tract infection, bottle feeding, and household smoking. These factors may be associated with about twice the risk of developing OME.
Prognosis
Data from one prospective study of children aged 2 to 4 years showed that 50% of OME cases resolved within 3 months and 95% within 1 year. In 5% of preschool children, OME (identified by tympanometric screening) persisted for at least 1 year. One cohort study of 3-year-olds found that 65% of OME cases cleared spontaneously within 3 months. Most children aged 6 years or older will not have further problems. The disease is ultimately self-limiting in most cases. However, one large cohort study (534 children) found that middle-ear disease increased reported hearing difficulty at 5 years of age (OR 1.44, 95% CI 1.18 to 1.76) and was associated with delayed language development in children up to 10 years of age. Hearing impairment is the most common complication of OME. Most children with OME have fluctuating or persistent hearing deficits with mild to moderate degrees of hearing loss, averaging 27 decibels. The type of hearing impairment is usually conductive, but it may be sensorineural, or both. The sensorineural type is usually permanent. Tympanic membrane perforation, tympanosclerosis, otorrhoea, and cholesteatoma occur more frequently among children with OME than among those without OME.
Aims of intervention
To improve hearing and wellbeing; to avoid poor behavioural, speech, and educational development; to prevent recurrent earache and otitis media, with minimal adverse effects.
Outcomes
Symptom improvement: hearing impairment, assessed by audiometry or tympanometry (although the positive predictive value of these tests has been reported to be as low as 49%); and resolution of effusion (both speed and completeness) assessed by otoscopy, tympanometry, or global clinical assessment. Developmental and behavioural outcomes: language and speech development. Adverse effects of treatment. Hearing losses as small as 15 decibels may have disabling consequences in children, and so changes of this magnitude are likely to be clinically significant. Patient-centred outcomes in children with OME (e.g., disability or quality of life) need further development and evaluation. Adequate follow-up for a single episode of OME is about 1 to 3 months, but relapses are common and so follow-up for quality-of-life outcomes should ideally be for at least 3 months.
Methods
Clinical Evidence search and appraisal March 2010. The following databases were used to identify studies for this systematic review: Medline 1966 to March 2010, Embase 1980 to March 2010, and The Cochrane Database of Systematic Reviews 2010, February (online version; 1966 to February 2010). When editing this review we used The Cochrane Database of Systematic Reviews 2010, issue 1. An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Otitis media with effusion in children.
| Important outcomes | Adverse effects, Developmental and behavioural outcomes, Symptom improvement | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of pharmacological, mechanical, and surgical interventions to treat otitis media with effusion in children? | |||||||||
| 3 (at least 279) | Symptom improvement | Autoinflation using purpose-manufactured devices versus no treatment | 4 | –3 | –1 | –2 | 0 | Very low | Quality points deducted for incomplete reporting of results, randomising by children but analysing by ear, and lack of blinding. Consistency point deducted for inconsistent results at different time points or by outcome. Directness points deducted for use of composite outcomes and inclusion of co-intervention (myringotomy) |
| 8 (1292) | Symptom improvement | Antibiotics versus placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for short follow-up. Directness point deducted for unclear definition of outcome |
| 5 (418) | Symptom improvement | Antibiotics plus oral corticosteroids versus antibiotics alone | 4 | –1 | –1 | –1 | +1 | Low | Quality point deducted for short follow-up. Consistency point deducted for heterogeneity between RCTs. Directness point deducted for uncertainty about generalisability of results. Effect-size point added for OR <0.5 |
| 3 (108) | Symptom improvement | Oral corticosteroids versus placebo | 4 | –2 | 0 | –1 | +1 | Low | Quality points deducted for sparse data and short follow-up. Directness point deducted for narrow population. Effect-size point added for OR <0.5 |
| 2 (262) | Symptom improvement | Intranasal corticosteroids versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results in one RCT |
| 1 (59) | Symptom improvement | Intranasal corticosteroids plus oral antibiotics versus placebo plus oral antibiotics | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for narrow population |
| 18 (at least 1737) | Symptom improvement | Antihistamines plus oral decongestants versus placebo | 4 | 0 | 0 | 0 | 0 | High | |
| 5 (972) | Adverse effects | Antihistamines plus oral decongestants versus placebo | 4 | 0 | 0 | –1 | +1 | High | Directness point deducted for adverse effects not specified. Effect-size point added for OR >2 |
| 9 (583) | Symptom improvement | Mucolytics versus placebo or no treatment | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and unclear outcome measurement |
| 5 (at least 125) | Symptom improvement | Autoinflation using non-purpose-manufactured devices versus no treatment | 4 | –3 | 0 | –1 | 0 | Very low | Quality points deducted for inclusion of unpublished data, incomplete reporting of results, randomising by children but analysing by ear, and lack of blinding. Directness point deducted for unclear outcome |
| 3 (225) | Symptom improvement | Adenoidectomy versus no treatment | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for incomplete reporting of results and randomising by ears rather than children. Consistency point deducted for conflicting results |
| at least 5 (At least 5) | Symptom improvement | Ventilation tubes versus no ventilation tube/watchful waiting | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for randomising by ears and inclusion of myringotomy in control group. Consistency point deducted for heterogeneity between RCTs |
| At least 3 (At least 559) | Developmental and behavioural outcomes | Ventilation tubes versus no ventilation tube/watchful waiting | 4 | –3 | –1 | 0 | 0 | Very low | Quality points deducted for incomplete reporting of results, inclusion of myringotomy in control group, and for unclear validity of outcomes used. Consistency point deducted for heterogeneity between RCTs |
| At least 4 (at least 610) | Adverse effects | Ventilation tubes versus no ventilation tube/watchful waiting | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for inclusion of myringotomy in control group. Directness point deducted for unclear clinical relevance |
| 3 (not reported) | Symptom improvement | Ventilation tube plus adenoidectomy versus no treatment | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results and incomplete reporting of included population. Directness point deducted for uncertainty of benefit, as the effectiveness is not known and there are no statistical analyses, with a range being reported instead |
| At least 7 (at least 751 ears) | Symptom improvement | Ventilation tube plus adenoidectomy versus adenoidectomy alone | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for analysing by ears rather than children. Consistency point deducted for inconsistent results at different endpoints |
| 4 (398) | Symptom improvement | Ventilation tube plus adenoidectomy versus ventilation tube alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for uncertainty over comparison in review and for analysing by ears rather than children for one outcome (hearing) |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
- Low-quality evidence
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.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Acute otitis media
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
References
- 1.Eden A, Fireman P, Stool SE. Otitis media with effusion: sorting out the options. Patient Care 2000;29:32–56. [Google Scholar]
- 2.Williamson IG, Dunleavey J, Bain J, et al. The natural history of otitis media with effusion: a three year study of the incidence and prevalence of abnormal tympanograms in four SW Hampshire infant and first schools. J Laryngol Otol 1994;108:930–934. [DOI] [PubMed] [Google Scholar]
- 3.Casselbrant ML, Brostoff LM, Cantekin EI, et al. Otitis media with effusion in preschool children. Laryngoscope 1985;95:428–436. [DOI] [PubMed] [Google Scholar]
- 4.Zielhuis GA, Rach GH, Van den Broek P. The occurrence of otitis media with effusion in Dutch pre-school children. Clin Otolaryngol 1990;15:147–153. [DOI] [PubMed] [Google Scholar]
- 5.Paradise JL, Rockette HE, Colborn DK, et al. Otitis media in 2253 Pittsburgh area infants: prevalence and risk factors during the first two years of life. Pediatrics 1997;99:318–333. [DOI] [PubMed] [Google Scholar]
- 6.University of York. Centre for Reviews and Dissemination. 1992. The treatment of persistent glue ear in children. Effect Health Care 1(4). Search date 1992. [Google Scholar]
- 7.Williamson I, Benge S, Mullee M, Little P. Consultations for middle ear disease, antibiotic prescribing and risk factors for re-attendance: a case linked cohort study. Br J Gen Pract 2006;56:170–175. [PMC free article] [PubMed] [Google Scholar]
- 8.Teele D, Klein J, Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study. J Infect Dis 1989;160:83–94. [DOI] [PubMed] [Google Scholar]
- 9.Haggard M, Hughes E. Objectives, values and methods of screening children's hearing: a review of the literature. London: HMSO, 1991. [Google Scholar]
- 10.Zeilhuis GA, Rach GH, Broek PV. Screening for otitis media with effusion in pre-school children. Lancet 1989;1:311–314. [DOI] [PubMed] [Google Scholar]
- 11.Fiellau-Nikolajsen M. Tympanometry in three year old children: prevalence and spontaneous course of MEE. Ann Otol Rhinol Laryngol 1980;89(suppl 68):233–237. [DOI] [PubMed] [Google Scholar]
- 12.Bennett KE, Haggard MP. Behaviour and cognitive outcomes in middle ear disease. Arch Dis Child 1999;80:28–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Lim DJ. Recent advances in otitis media. Ann Otol Rhinol Laryngol Suppl 2002;199:1–124. [Google Scholar]
- 14.Stool SE, Berg SO, Berman S, et al. Otitis media with effusion in young children: clinical practice guideline number 12. AHCPR Publication 94-0622. Rockville, Maryland: Agency for Health Care Policy and Research, Public Health Service, United States Department of Health and Human Services, July 1994. Search date 1992. [Google Scholar]
- 15.Reidpath DD, Glasziou PP, Del Mar C. Systematic review of autoinflation for treatment of glue ear in children. BMJ 1999;318:1177–1178. Search date not reported. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Perera R, Haynes J, Glasziou P, et al. Autoinflation for hearing loss associated with otitis media with effusion. In: The Cochrane Library, Issue 1, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006. [DOI] [PubMed] [Google Scholar]
- 17.Blanshard JD, Maw AR, Bawden R. Conservative treatment of otitis media with effusion by autoinflation of the middle ear. Clin Otolaryngol 1993;18:188–192. [DOI] [PubMed] [Google Scholar]
- 18.Stangerup SE, Sederberg-Olsen J, Balle V. Autoinflation as a treatment of secretory otitis media: a randomized controlled study. Arch Otolaryngol Head Neck Surg 1992;118:149–152. [DOI] [PubMed] [Google Scholar]
- 19.Arick DS, Silman S. Nonsurgical home treatment of middle ear effusion and associated hearing loss in children. Part I: clinical trial. Ear Nose Throat J 2005;84:567–8, 570. [PubMed] [Google Scholar]
- 20.Cantekin EI, McGuire TW. Antibiotics are not effective for otitis media with effusion: reanalysis of meta-analysis. Otorhinolaryngol Nova 1998;8:214–222. Search date 1997; primary sources RCTs in refereed journals and proceedings published between 1980 and 1997 in English language publications. [Google Scholar]
- 21.Thomas CL, Simpson S, Butler CC, et al. Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children. In: The Cochrane Library, Issue 1, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006. [DOI] [PubMed] [Google Scholar]
- 22.Computerised clinical information system. Denver, Colorado: Micromedex, June 1993. [Google Scholar]
- 23.Little P, Gould C, Williamson I, et al. Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ 1997;315:350–352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Wise R, Hart T, Cars O, et al. Antimicrobial resistance is a major threat to public health [Editorial]. BMJ 1998;317:609–610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Cheng K, Ashby D, Smyth R. Oral steroids for cystic fibrosis. In: The Cochrane Library, Issue 1, 2010. Chichester, UK: John Wiley & Sons, Ltd. 10796717 [Google Scholar]
- 26.Williamson I, Benge S, Barton S, et al. Topical intranasal corticosteroids in 4-11 year old children with persistent bilateral otitis media with effusion in primary care: double blind randomised placebo controlled trial. BMJ 2009;339:b4984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Shapiro GG, Bierman CW, Furukawa CT, et al. Treatment of persistent eustachian tube dysfunction with aerosolized nasal dexamethasone phosphate versus placebo. Ann Allergy 1982;49:81–85. [PubMed] [Google Scholar]
- 28.Tracy TM, Demain JG, Hoffman KM, et al. Intranasal beclomethasone as an adjunct to treatment of chronic middle ear effusion. Ann Allergy Asthma Immunol 1998;80:198–206. [DOI] [PubMed] [Google Scholar]
- 29.Griffin GH, Flynn C, Bailey RE, et al. Antihistamines and/or decongestants for otitis media with effusion (OME) in children. In: The Cochrane Library, Issue 1, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006. 17054169 [Google Scholar]
- 30.Graf P. Rhinitis medicamentosa: aspects of pathophysiology and treatment. Eur J Allergy Clin Immunol 1997;52(suppl 40):28–34. [DOI] [PubMed] [Google Scholar]
- 31.Pignataro O, Pignataro LD, Gallus G, et al. Otitis media with effusion and S-carboxymethylcysteine and/or its lysine salt: a critical overview. Int J Pediatr Otorhinolaryngol 1996;35:231–241. Search date 1993; primary sources Medline, Embase, and Biosis. [DOI] [PubMed] [Google Scholar]
- 32.Van der Merwe J, Wagenfeld DJ. The negative effects of mucolytics in otitis media with effusion. S Afr Med J 1987;72:625–626. [PubMed] [Google Scholar]
- 33.Stewart IA, Guy AM, Allison RS, et al. Bromhexine in the treatment of otitis media with effusion. Clin Otolaryngol 1985;10:145–149. [DOI] [PubMed] [Google Scholar]
- 34.Roydhouse N. Bromhexine for otitis media with effusion. N Z Med J 1981;94:373–375. [PubMed] [Google Scholar]
- 35.van den Aardweg Maaike TA, Schilder Anne GM, Herkert Ellen, et al. Adenoidectomy for otitis media in children. In: The Cochrane Library, Issue 1, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2009. [DOI] [PubMed] [Google Scholar]
- 36.Maw R, Bawden R. Spontaneous resolution of severe chronic glue ear in children and the effect of adenoidectomy, tonsillectomy, and insertion of ventilation tubes. BMJ 1993;306:756–760. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Wilks J, Maw R, Peters TJ, et al. Randomised controlled trial of early surgery versus watchful waiting for glue ear: the effect on behavioural problems in pre-school children. Clin Otol 2000;25:209–214. [DOI] [PubMed] [Google Scholar]
- 38.Lous J,Burton MJ, Felding JU, Ovesen T, Rovers MM, Williamson I. Grommets (ventilation tubes) for hearing loss associated with otitis media with effusion in children. In: The Cochrane Library, Issue 1, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2003. [DOI] [PubMed] [Google Scholar]
- 39.Carbonell R, Ruiz-Garcia V. Ventilation tubes after surgery with otitis media with effusion or acute otitis media and swimming. Systematic review and meta-analysis. Int J Pediatr Otorhinolaryngol 2002;66:281–289. Search date 2001; primary sources Medline, Embase, Cochrane library databases, and hand searches. [DOI] [PubMed] [Google Scholar]
- 40.Maw AR. Development of tympanosclerosis in children with otitis media with effusion and ventilation tubes. J Laryngol Otol 1991;105:614–617. [DOI] [PubMed] [Google Scholar]
- 41.Roydhouse N. Adenoidectomy for otitis media with mucoid effusion. Ann Otol Rhinol Laryngol 1980;(suppl 89):312–315. [DOI] [PubMed] [Google Scholar]