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Grommets (ventilation tubes) for recurrent acute otitis media in

children (Review)
Venekamp RP, Mick P, Schilder AGM, Nunez DA
Venekamp RP, Mick P, Schilder AGM, Nunez DA.

Grommets (ventilation tubes) for recurrent acute otitis media in children.
Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No.: CD012017.
DOI: 10.1002/14651858.CD012017.pub2.
www.cochranelibrary.com
Grommets (ventilation tubes) for recurrent acute otitis media in children (Review)
Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews
TABLE OF CONTENTS
HEADER......................................................................................................................................................................................................... 1
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 3
SUMMARY OF FINDINGS.............................................................................................................................................................................. 4
BACKGROUND.............................................................................................................................................................................................. 8
OBJECTIVES.................................................................................................................................................................................................. 9
METHODS..................................................................................................................................................................................................... 9
RESULTS........................................................................................................................................................................................................ 12
Figure 1.................................................................................................................................................................................................. 13
Figure 2.................................................................................................................................................................................................. 14
Figure 3.................................................................................................................................................................................................. 15
Figure 4.................................................................................................................................................................................................. 16
Figure 5.................................................................................................................................................................................................. 17
Figure 6.................................................................................................................................................................................................. 18
DISCUSSION.................................................................................................................................................................................................. 18
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 19
ACKNOWLEDGEMENTS................................................................................................................................................................................ 20
REFERENCES................................................................................................................................................................................................ 21
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 24
DATA AND ANALYSES.................................................................................................................................................................................... 36
Analysis 1.1. Comparison 1 Grommets versus active monitoring, Outcome 1 Proportion of patients who have no AOM 37
recurrences at 6 months post-randomisation....................................................................................................................................
Analysis 1.2. Comparison 1 Grommets versus active monitoring, Outcome 2 Proportion of patients who have no AOM 37
recurrences at 12 months post-randomisation..................................................................................................................................
Analysis 1.3. Comparison 1 Grommets versus active monitoring, Outcome 3 Total number of AOM recurrences at six months 37
post-randomisation...............................................................................................................................................................................
Analysis 2.1. Comparison 2 Grommets versus antibiotic prophylaxis, Outcome 1 Proportion of patients who have no AOM 38
Analysis 2.2. Comparison 2 Grommets versus antibiotic prophylaxis, Outcome 2 Total number of AOM recurrences at six months 38
Analysis 3.1. Comparison 3 Grommets versus placebo medication, Outcome 1 Proportion of patients who have no AOM 39
Analysis 3.2. Comparison 3 Grommets versus placebo medication, Outcome 2 Total number of AOM recurrences at six months 39
ADDITIONAL TABLES.................................................................................................................................................................................... 39
APPENDICES................................................................................................................................................................................................. 41
FEEDBACK..................................................................................................................................................................................................... 44
WHAT'S NEW................................................................................................................................................................................................. 44
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 44
DECLARATIONS OF INTEREST..................................................................................................................................................................... 45
SOURCES OF SUPPORT............................................................................................................................................................................... 45
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 45
NOTES........................................................................................................................................................................................................... 46
INDEX TERMS............................................................................................................................................................................................... 46
Grommets (ventilation tubes) for recurrent acute otitis media in children (Review) i
Informed decisions.
[Intervention Review]
Grommets (ventilation tubes) for recurrent acute otitis media in

children
Roderick P Venekamp1, Paul Mick2, Anne GM Schilder3, Desmond A Nunez2
1Julius Center for Health Sciences and Primary Care & Department of Otorhinolaryngology, University Medical Center Utrecht, Utrecht
University, Utrecht, Netherlands. 2Division of Otolaryngology Head & Neck Surgery, University of British Columbia, Vancouver, Canada.
3evidENT, Ear Institute, Faculty of Brain Sciences, University College London, London, UK
Contact address: Desmond A Nunez, Division of Otolaryngology Head & Neck Surgery, University of British Columbia, Vancouver, BC,
Canada. [email protected].
Editorial group: Cochrane ENT Group.

Publication status and date: Edited (no change to conclusions), comment added to review, published in Issue 6, 2019.
Citation: Venekamp RP, Mick P, Schilder AGM, Nunez DA. Grommets (ventilation tubes) for recurrent acute otitis media in children.
Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No.: CD012017. DOI: 10.1002/14651858.CD012017.pub2.
ABSTRACT
Background
Acute otitis media (AOM) is one of the most common childhood illnesses. While many children experience sporadic AOM episodes, an
important group suffer from recurrent AOM (rAOM), defined as three or more episodes in six months, or four or more in one year. In this
subset of children AOM poses a true burden through frequent episodes of ear pain, general illness, sleepless nights and time lost from
nursery or school. Grommets, also called ventilation or tympanostomy tubes, can be offered for rAOM.
Objectives
To assess the benefits and harms of bilateral grommet insertion with or without concurrent adenoidectomy in children with rAOM.
Search methods
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL; MEDLINE; EMBASE; CINAHL; Web of
Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 4 December 2017.
Selection criteria
Randomised controlled trials (RCTs) comparing bilateral grommet insertion with or without concurrent adenoidectomy and no ear surgery
in children up to age 16 years with rAOM. We planned to apply two main scenarios: grommets as a single surgical intervention and grommets
as concurrent treatment with adenoidectomy (i.e. children in both the intervention and comparator groups underwent adenoidectomy).
The comparators included active monitoring, antibiotic prophylaxis and placebo medication.
Data collection and analysis

We used the standard methodological procedures expected by Cochrane. Primary outcomes were: proportion of children who have no
AOM recurrences at three to six months follow-up (intermediate-term) and persistent tympanic membrane perforation (significant adverse
event). Secondary outcomes were: proportion of children who have no AOM recurrences at six to 12 months follow-up (long-term); total
number of AOM recurrences, disease-specific and generic health-related quality of life, presence of middle ear effusion and other adverse
events at short-term, intermediate-term and long-term follow-up. We used GRADE to assess the quality of the evidence for each outcome;
this is indicated in italics.
Grommets (ventilation tubes) for recurrent acute otitis media in children (Review) 1
Informed decisions.
Main results
Five RCTs (805 children) with unclear or high risk of bias were included. All studies were conducted prior to the introduction of
pneumococcal vaccination in the countries' national immunisation programmes. In none of the trials was adenoidectomy performed
concurrently in both groups.
Grommets versus active monitoring
Grommets were more effective than active monitoring in terms of:
- proportion of children who had no AOM recurrence at six months (one study, 95 children, 46% versus 5%; risk ratio (RR) 9.49, 95%
confidence interval (CI) 2.38 to 37.80, number needed to treat to benefit (NNTB) 3; low-quality evidence);
- proportion of children who had no AOM recurrence at 12 months (one study, 200 children, 48% versus 34%; RR 1.41, 95% CI 1.00 to 1.99,
NNTB 8; low-quality evidence);
- number of AOM recurrences at six months (one study, 95 children, mean number of AOM recurrences per child: 0.67 versus 2.17, mean
difference (MD) -1.50, 95% CI -1.99 to -1.01; low-quality evidence);
- number of AOM recurrences at 12 months (one study, 200 children, one-year AOM incidence rate: 1.15 versus 1.70, incidence rate difference
-0.55, 95% -0.17 to -0.93; low-quality evidence).
Children receiving grommets did not have better disease-specific health-related quality of life (Otitis Media-6 questionnaire) at four (one
study, 85 children) or 12 months (one study, 81 children) than those managed by active monitoring (low-quality evidence).
One study reported no persistent tympanic membrane perforations among 54 children receiving grommets (low-quality evidence).
Grommets versus antibiotic prophylaxis
It is uncertain whether or not grommets are more effective than antibiotic prophylaxis in terms of:
- proportion of children who had no AOM recurrence at six months (two studies, 96 children, 60% versus 35%; RR 1.68, 95% CI 1.07 to 2.65,
I2 = 0%, fixed-effect model, NNTB 5; very low-quality evidence);
- number of AOM recurrences at six months (one study, 43 children, mean number of AOM recurrences per child: 0.86 versus 1.38, MD -0.52,
95% CI -1.37 to 0.33; very low-quality evidence).
Grommets versus placebo medication
Grommets were more effective than placebo medication in terms of:
- proportion of children who had no AOM recurrence at six months (one study, 42 children, 55% versus 15%; RR 3.64, 95% CI 1.20 to 11.04,
NNTB 3; very low-quality evidence);
- number of AOM recurrences at six months (one study, 42 children, mean number of AOM recurrences per child: 0.86 versus 2.0, MD -1.14,
95% CI -2.06 to -0.22; very low-quality evidence).
One study reported persistent tympanic membrane perforations in 3 of 76 children (4%) receiving grommets (low-quality evidence).
Subgroup analysis
There were insufficient data to determine whether presence of middle ear effusion at randomisation, type of grommet or age modified
the effectiveness of grommets.
Authors' conclusions
Current evidence on the effectiveness of grommets in children with rAOM is limited to five RCTs with unclear or high risk of bias, which
were conducted prior to the introduction of pneumococcal vaccination. Low to very low-quality evidence suggests that children receiving
grommets are less likely to have AOM recurrences compared to those managed by active monitoring and placebo medication, but the
magnitude of the effect is modest with around one fewer episode at six months and a less noticeable effect by 12 months. The low to
very low quality of the evidence means that these numbers need to be interpreted with caution since the true effects may be substantially
different. It is uncertain whether or not grommets are more effective than antibiotic prophylaxis. The risk of persistent tympanic membrane
perforation after grommet insertion was low.
Widespread use of pneumococcal vaccination has changed the bacteriology and epidemiology of AOM, and how this might impact the
results of prior trials is unknown. New and high-quality RCTs of grommet insertion in children with rAOM are therefore needed. These
trials should not only focus on the frequency of AOM recurrences, but also collect data on the severity of AOM episodes, antibiotic
Informed decisions.
consumption and adverse effects of both surgery and antibiotics. This is particularly important since grommets may reduce the severity
of AOM recurrences and allow for topical rather than oral antibiotic treatment.
PLAIN LANGUAGE SUMMARY
Grommets for children with recurring acute middle ear infections
Review question
Do children with recurring acute middle ear infections benefit from placement of grommets in both ears (with or without surgical removal
of the adenoids at the same time)?
Background
An acute middle ear infection is one of the most common childhood illnesses. While most children have an occasional episode, some suffer
from recurring ear infections (three or more infections over a period of a six months, or four or more in a year). Such recurring infections
cause considerable distress through frequent ear pain, fever, general illness, sleepless nights and time lost from nursery or school for the
child and from work for their carers. Grommets, also known as ventilation or tympanostomy tubes, can be offered as a treatment. They
are tiny plastic tubes put into the eardrum by an ENT surgeon during a short operation.
Study characteristics
This review includes evidence up to 4 December 2017. We included five randomised controlled trials with a total of 805 children with
recurring acute middle ear infections. All studies were performed before the introduction of vaccination against pneumococcus, a
bacterium that commonly causes ear infections. Surgical removal of the adenoids was not performed in both groups in any of the trials.
Key results
We primarily looked at the difference in the proportion of children who had no further acute middle ear infections at three to six months
follow-up (intermediate-term), and who had a persisting perforation (hole) in the ear drum. We also looked at some other outcomes,
including the proportion of children who had no further episodes of acute middle ear infection.
Grommets versus active monitoring
We found low-quality evidence that fewer children who were treated with grommets had further episodes of ear infection at six and 12
months follow-up than those managed with active monitoring; three and eight children needed to be treated with grommets to benefit
one, respectively. The number of ear infections at six and 12 months follow-up was also lower in the grommets group; the difference was,
however, at best modest with around one fewer episode at six months and a less noticeable effect by 12 months (low to very low-quality
evidence). Children treated with grommets did not have better quality of life at four or 12 months follow-up (low-quality evidence).
Grommets versus antibiotic prophylaxis
It is uncertain whether or not grommets are more effective than antibiotic prophylaxis; we found very low-quality evidence that fewer
children who were treated with grommets had further ear infections at six months than those receiving antibiotic prophylaxis (preventative
antibiotics); five children needed to be treated with grommets to benefit one. The number of ear infections at six months, however, did not
significantly differ between children treated with grommets and those receiving antibiotic prophylaxis (very-low quality evidence).
Grommets versus placebo drugs
We found very low-quality evidence that fewer children who were treated with grommets had further ear infections at six months than
those receiving placebo drugs; three children needed to be treated with grommets to benefit one. The number of ear infections at six
months was also lower in the grommets group; the difference was however at best modest with around one fewer episode (very low-quality
evidence).
Negative effects of grommets were not systematically reported in the studies. Two studies reported on the number of children with a
persistent perforation of the ear drum; this occurred in 0% (0/54) and 4% (3/76) of children receiving grommets, respectively (low-quality
evidence).
Quality of evidence
We judged the quality of the evidence on the benefits and harms of placement of grommets in both ears for children with recurring acute
middle ear infections to be low to very low due to study limitations (risk of bias) and the small to very small sample sizes of included studies
(leading to imprecise effect estimates). This means that the findings of this review should be interpreted with caution since the true effects
of grommets in this group of children may be different than the numbers presented.
SUMMARY OF FINDINGS
Summary of findings for the main comparison. Grommets versus active monitoring for recurrent acute otitis media in children
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Grommets versus active monitoring for recurrent acute otitis media in children
Patients: children with recurrent acute otitis media

Setting: secondary and tertiary care
Intervention: grommets
Better health.
Informed decisions.
Trusted evidence.
Control: active monitoring
Outcomes Anticipated absolute effects* (95% CI) Relative effect № of partici- Quality of the Comments
(95% CI) pants evidence
Risk with active mon- Risk with grommets (studies) (GRADE)
itoring
Proportion of patients who have no Study population RR 9.49 95 ⊕⊕⊝⊝ The NNTB
AOM recurrences at 6 months post- (2.38 to 37.80) (1 RCT) low1 based on the
randomisation 49 per 1000 463 per 1000 study popula-
(116 to 1000) tion risk was 1/
(463-49)* 1000
= 2.41
Significant adverse effect: a tympanic — 0 (0/54) n/a 54 (1 RCT) ⊕⊕⊝⊝ —

membrane perforation persisting for low1
3 months or longer
Proportion of patients who have no Study population RR 1.41 200 ⊕⊕⊝⊝ The NNTB
AOM recurrences at 12 months post- (1.00 to 1.99) (1 RCT) low1 based on the
(479-340)* 1000
= 7.19

Total number of AOM recurrences at 6 89 AOM recurrences 36 AOM recurrences MD -1.50, 95% CI 95 (1 RCT) ⊕⊕⊝⊝ —
months post-randomisation in 41 children; mean in 54 children; mean -1.99 to -1.01 low1
number of AOM recur- number of AOM recur-
rences per child: 2.17 rences per child: 0.67
Total number of AOM recurrences at 119 AOM recurrences 92 AOM recurrences in Incidence rate 200 ⊕⊕⊝⊝ —
12 months post-randomisation in 100 children; inci- 100 children; incidence difference -0.55, (1 RCT) low1
dence rate 1.70 rate 1.15 95% -0.17 to -0.93
4
Disease-specific health-related qual- "no statistically significant differences between treatment groups 85 and 81, re- ⊕⊕⊝⊝ —
ity of life of the child at 4 and 12 were reported at 4 and 12 months for any of the six subdomains of the spectively (1 low1
months post-randomisation using the OM-6 questionnaire" RCT)
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OM-6 questionnaire
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
AOM: acute otitis media; CI: confidence interval;MD: mean difference; n/a: not applicable; NNTB: number needed to treat to benefit; OM-6: Otitis Media-6; RCT: ran-
domised controlled trial; RR: risk ratio
Better health.
Informed decisions.
Trusted evidence.
GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is sub-
stantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1We downgraded the evidence from high to low quality due to study limitations and imprecise effect estimates (only one study with a small sample size).
Summary of findings 2. Grommets versus antibiotic prophylaxis for recurrent acute otitis media in children
Grommets versus antibiotic prophylaxis for recurrent acute otitis media in children

Control: antibiotic prophylaxis
Risk with antibiotic prophy- Risk with grommets (studies) (GRADE)

laxis
Proportion of patients who Study population RR 1.68 96 ⊕⊝⊝⊝ The NNTB

have no AOM recurrences at (1.07 to 2.65) (2 RCTs) very low1 based on the
6 months post-randomisa- 349 per 1000 586 per 1000 study popula-
tion (373 to 924) tion risk was 1/
(586-349)* 1000
= 4.22
Total number of AOM recur- 29 AOM recurrences in 21 19 AOM recurrences in 22 MD -0.52, 95% 43 (1 RCT) ⊕⊝⊝⊝ —
rences at 6 months post- children; mean number of children; mean number of CI -1.37 to 0.33 very low2
randomisation
5
AOM recurrences per child: AOM recurrences per child:
1.38 0.86
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AOM: acute otitis media; CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio

Better health.
Informed decisions.
Trusted evidence.
1We downgraded the evidence from high to very low quality due to study limitations (when we excluded the trial with high risk of bias from the analysis, no statistically significant
difference was observed between groups) and imprecise effect estimates (only two studies with small sample sizes).
2We downgraded the evidence from high to very low quality due to study limitations and imprecise effect estimates (only one study with a very small sample size).
Summary of findings 3. Grommets versus placebo medication for recurrent acute otitis media in children
Grommets versus placebo medication for recurrent acute otitis media in children

Control: placebo medication
Risk with placebo Risk with grommets (studies) (GRADE)
medication

Proportion of patients who have no Study population RR 3.64 42 ⊕⊝⊝⊝ The NNTB
AOM recurrences at 6 months post- (1.20 to 11.04) (1 RCT) very low1 based on the
(546-150)* 1000
= 2.53
Significant adverse effect: a tym- — 4% (3/76) n/a 76 (1 RCT) ⊕⊕⊝⊝ —

panic membrane perforation per- low2
sisting for 3 months or longer
6
Total number of AOM recurrences at 40 AOM recurrences 19 AOM recurrences in 22 MD -1.14, 95% 42 ⊕⊝⊝⊝ —
6 months post-randomisation in 20 children; mean children; mean number CI -2.06 to -0.22 (1 RCT) very low1
number of AOM recur- of AOM recurrences per
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rences per child: 2.0 child: 0.86
AOM: acute otitis media; CI: confidence interval; MD: mean difference; n/a: not applicable; RCT: randomised controlled trial; RR: risk ratio
Better health.
Informed decisions.
Trusted evidence.
1We downgraded the evidence from high to very low quality due to study limitations and imprecise effect estimates (only one study with a very small sample size).
2We downgraded the evidence from high to low quality due to study limitations and imprecise effect estimates (only one study with a small sample size).

7
Informed decisions.
BACKGROUND surgical preference) and the grommet is placed in the incision.

Grommets facilitate middle ear ventilation and provide a route
Description of the condition for drainage of middle ear fluid; they reverse and prevent the
formation of middle ear effusions by providing a surrogate to the
Acute otitis media (AOM) is one of the most common childhood
under-functioning Eustachian tube and so create a less favourable
illnesses; it is defined as the presence of middle ear fluid
environment for viruses and bacteria to cause recurrent middle ear
together with an acute onset of signs and symptoms of middle
infections (Rosenfeld 2013; Schilder 2016).
ear inflammation (Lieberthal 2013). Bulging of the ear drum
or new onset of ear discharge not caused by acute otitis Grommets may also reduce the severity of AOM recurrences,
externa are the cardinal signs of AOM, while ear pain, fever, since they allow for drainage of middle ear fluid that builds up
irritability, and problems feeding and sleeping are among the during an acute infection; as such they may prevent ear pain
typical AOM symptoms (Lieberthal 2013). AOM is one of the most caused by pressure against the tympanic membrane. Finally,
frequent reasons for primary care visits (Ashworth 1995), and grommets allow for topical (local) treatment of AOM recurrences
the prime indication for antibiotic prescription in children in with antibiotic eardrops (van Dongen 2014), thereby avoiding the
more economically developed countries (Finkelstein 2000; Grijalva side effects of systemic antibiotics and potentially reducing the risk
2009; Williamson 2006). In addition to high direct healthcare costs of antimicrobial resistance (Weber 2004).
(Ahmed 2014; Bondy 2000), AOM causes substantial non-healthcare
costs, due to lost days from education or work for parents and the It has been suggested that children suffering from rAOM who have
use of over-the-counter medications (Alsarraf 1999; Niemelä 1999). unilateral or bilateral middle ear effusion at the time of evaluation
for surgery may benefit more from grommets than children who
While many children experience sporadic AOM episodes, an have an aerated middle ear at this time (Rosenfeld 2013).
important group suffer from recurrent AOM (rAOM), defined as
three or more episodes in six months, or four in one year with one Grommets are a temporary treatment. After months or years,
episode in the last six months (Goycoolea 1991; Lieberthal 2013). In depending on the type of grommet, they are extruded into the
this subset of children AOM poses a true burden through frequent external ear canal and the tympanic membrane closes. There
episodes of ear pain, general illness, sleepless nights and time lost are different types of grommets, which are made out of various
from nursery or school. The impact of rAOM on quality of life is materials. Some are so-called short-term grommets that typical
known to equal that of childhood asthma (Brouwer 2005). This stay in place for six to 18 months; others are intermediate/long-
causes families with rAOM to repeatedly seek medical attention term tubes that usually stay in place for a longer period of time.
to relieve the child's symptoms and prevent future episodes.
Importantly, AOM is closely related to otitis media with effusion Complications of grommet insertion include a persisting
(OME, 'glue ear'); children with OME are at risk of AOM recurrences perforation of the tympanic membrane causing a conductive
(Alho 1995), and following an episode of AOM all children have OME hearing loss and the risk of infection, misplacement of the grommet
for some time (Tapiainen 2014). This extends the burden of rAOM in the middle ear, otorrhoea (drainage of middle ear fluid through
to OME and hearing loss-related developmental outcomes (Bennett the tube) and myringosclerosis (calcification or scarring of the
2001). tympanic membrane) that may cause (mild) hearing loss.
The first two years of life represent the period of greatest risk Why it is important to do this review
for the first as well as recurrent episodes of AOM (Schilder 2016;
Recommendations regarding the use of grommets in children
Teele 1989). Age-specific incidence of AOM is highest during the
suffering from rAOM vary within and across countries (CBO Richtlijn
second six months of life, which coincides with the lowest level
2012; Lieberthal 2013; Rosenfeld 2013). Recent US guidelines on the
of serum immunoglobulin (antibody) concentrations. Children
management of AOM (Lieberthal 2013) and on the use of grommets
prone to AOM may have lower age-specific immunoglobulin
(tympanostomy tubes; Rosenfeld 2013) recommend grommets as
levels, which may reflect a generalised poorer antibody response
an optional treatment in children with rAOM. The latter suggests
(Veenhoven 2004). Breastfeeding protects against AOM, whereas
that grommets should not be offered to children with rAOM who
craniofacial malformations like cleft palate and early onset of AOM,
have no middle ear effusion at the time of evaluation for surgery.
a family history of recurrent ear disease, day care attendance, low
In the UK there is guidance on the use of grommets in children
socio-economic status and passive smoking are associated with
with OME (NICE 2008), but national guidance for those with rAOM
increased risk of AOM (Schilder 2016).
is lacking.
Description of the intervention The role of adenoidectomy in reducing rAOM is not fully established
The surgical procedures under consideration in children with rAOM but adenoidectomy as a standalone operation or as an adjunct
are insertion of grommets in both ears (also called ventilation or to grommets may be most beneficial in children below two years
tympanostomy tubes), adenoidectomy, or a combination of the of age (Boonacker 2014; van den Aardweg 2010). Furthermore, it
two. has been suggested that adenoidectomy as an adjunct to primary
grommet insertion might reduce the rate of further AOM episodes
Grommets are tiny plastic tubes that are inserted in the tympanic and the risk of re-insertion of grommets compared to grommet
membrane (eardrum) by an ENT surgeon; in children this usually insertion alone (Mikals 2014).
happens under general anaesthesia as a day-case procedure.
An operating microscope or other magnification is used to The absence of uniform guidance or consensus on the use of
visualise the tympanic membrane where a small incision is made grommets in rAOM contributes to practice variation both within
(myringotomy), middle ear fluid is aspirated (subject to need and and across countries. For example, a pilot study using UK National
Health Service (NHS) Primary Care Trust data showed that in 2012
Informed decisions.
there was a 40- to 60-fold variation in the rate of grommet insertion Types of outcome measures
for rAOM compared to an eight- to nine-fold variation in grommets
We analysed the following outcomes in the review, but we did not
for OME (Bohm 2013, personal communication). Moreover, across
use them as a basis for including or excluding studies.
Western countries the surgical rates for grommets vary from 2 per
1000 children per year in the UK to 20 per 1000 in The Netherlands Primary outcomes
(Schilder 2004).
• Treatment success, defined as the proportion of children
An up-to-date, comprehensive systematic review is therefore who have no AOM recurrences at three to six months post-
urgently needed, summarising the available evidence on the effects randomisation (intermediate-term follow-up).
of grommets with or without concurrent adenoidectomy in children • Significant adverse event: tympanic membrane perforation
with rAOM. persisting for three months or longer. This has been listed as
an important adverse event outcome because a further surgical
OBJECTIVES procedure may ultimately be required to close the perforation if
this persists after extrusion of the grommet.
To assess the benefits and harms of bilateral grommet insertion
with or without concurrent adenoidectomy in children with rAOM. Secondary outcomes
METHODS • Treatment success, defined as the proportion of children
who have no AOM recurrences at six to 12 months post-
Criteria for considering studies for this review randomisation (long-term follow-up).
Types of studies In the short- (up to three months), intermediate- (three to six
Randomised controlled trials (RCTs) irrespective of the months) and long-term (six to 12 months) post-randomisation:
randomisation method and blinding procedure used. We excluded
the second phase of cross-over studies and trials where the patient • Total number of AOM recurrences.
was not the unit of randomisation, i.e. cluster-randomised trials or • Disease-specific health-related quality of life of the child and
trials where 'ears' (right versus left) were randomised. their parents or carers (using any validated instrument; see
Brouwer 2007).
Types of participants • Generic health-related quality of life of the child and parents
Children up to age 16 years with rAOM, defined as three or more (using any validated instrument).
episodes in the previous six months, or four or more in one year • Presence of middle ear effusion.
(Goycoolea 1991; Lieberthal 2013). • Other adverse events: grommet misplaced in middle ear,
postoperative otorrhoea (in the first week after grommet
Types of interventions insertion), myringosclerosis.
Intervention
We discussed and included within our outcomes other adverse
• Bilateral grommet insertion (of any type). effects and complications recorded in RCTs but not listed above.
Comparisons Search methods for identification of studies

The overall comparator was no (ear) surgery. This included the The Cochrane ENT Information Specialist conducted systematic
following comparators: searches for randomised controlled trials and controlled clinical
trials. There were no language, publication year or publication
• active monitoring (grommets versus active monitoring); status restrictions. The date of the search was 4 December 2017.
• antibiotic prophylaxis for a minimum period of three months
(grommets versus antibiotic prophylaxis); Electronic searches
• placebo medication (grommets versus placebo medication). The Information Specialist searched:
We anticipated that both in the intervention and comparator • the Cochrane ENT Trials Register (searched via the Cochrane
groups AOM recurrences would be managed with analgesics and Register of Studies to 4 December 2017);
antibiotics (topical or systemic) either routinely or in selected
• the Cochrane Central Register of Controlled Trials (CENTRAL)
cases.
(searched via the Cochrane Register of Studies to 4 December
We planned to apply two main scenarios depending on whether 2017);
adenoidectomy was performed concurrently: • Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-
Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R)
• grommets as a single surgical intervention: this included studies (1946 to 4 December 2017);
where children in comparator groups received no other surgical • Ovid EMBASE (1974 to 4 December 2017);
intervention; • Ovid CAB Abstracts (1910 to 4 December 2017);
• grommets as concurrent treatment with adenoidectomy: this • EBSCO CINAHL (1982 to 4 December 2017);
included studies where children in both the intervention and
comparator groups underwent adenoidectomy. • LILACS, lilacs.bvsalud.org (searched to 4 December 2017);
• KoreaMed (searched via Google Scholar to 4 December 2017);
Informed decisions.
• IndMed, www.indmed.nic.in (searched to 4 December 2017); • For binary data: numbers of participants experiencing an event
• PakMediNet, www.pakmedinet.com (searched to 4 December and number of patients assessed at the particular time point.
2017); • For ordinal scale data: if the data appeared to be normally
• Web of Knowledge, Web of Science (1945 to 4 December 2017); distributed or if the analysis suggested that parametric tests
• ClinicalTrials.gov (via the Cochrane Register of Studies and were appropriate, we treated those outcome measures as
https://clinicaltrials.gov/ to 4 December 2017); continuous data. Alternatively, if data were available, we
converted them into binary data.
• ICTRP, www.who.int/ictrp (searched to 4 December 2017).
We prespecified the time points of interest for the outcomes in
In searches prior to December 2017, we also searched PubMed as a
this review. While studies reported data at multiple time points,
top-up to Ovid MEDLINE (1946 to November 2015).
we only extracted the longest available data within the time
The Information Specialist modelled subject strategies for points of interest. For example, for 'intermediate-term' follow-up
databases on the search strategy designed for CENTRAL. Where periods, our time point was defined as 'three to six months' post-
appropriate, they were combined with subject strategy adaptations randomisation. If a study reported data at three, four and six
of the highly sensitive search strategy designed by Cochrane for months, we only extracted and analysed the data for the six-month
identifying randomised controlled trials and controlled clinical follow-up.
trials (as described in the Cochrane Handbook for Systematic
Where a study had more than one publication, we retrieved all
Reviews of Interventions Version 5.1.0, Box 6.4.b. (Handbook 2011).
relevant publications to ensure complete data extraction.
Search strategies for major databases including CENTRAL are
provided in Appendix 1. Assessment of risk of bias in included studies
Searching other resources Three review authors (AGMS, RPV and DAN) independently
assessed the risk of bias of the included studies and resolved
We scanned the reference lists of identified publications for
any disagreements by majority opinion. Guided by the Cochrane
additional trials and contacted trial authors where necessary. In
Handbook for Systematic Reviews of Interventions (Handbook 2011),
addition, the Information Specialist searched Ovid MEDLINE to
we took the following items into consideration:
retrieve existing systematic reviews relevant to this systematic
review, so that we could scan their reference lists for additional • random sequence generation (selection bias);
trials, and ran non-systematic searches of Google Scholar to
• allocation concealment (selection bias);
retrieve grey literature and other sources of potential trials.
• blinding of participants and personnel (performance bias);
Data collection and analysis • blinding of outcome assessment (detection bias);
• incomplete outcome data (attrition bias);
Selection of studies
• selective reporting (reporting); and
Three review authors (LL, PTM and RPV) independently screened • other sources of bias.
titles and abstracts obtained from the database searches and
the reference lists of relevant systematic reviews to assess their We presented the results of the 'Risk of bias' assessment in a 'Risk
potential relevance for reviewing the full text. The same review of bias' graph and summary figure.
authors independently reviewed the full text of potentially relevant
articles against the inclusion and exclusion criteria. We resolved Measures of treatment effect
any disagreements by discussion.
We expressed pooled measures of treatment effect for
Data extraction and management dichotomous outcomes as risk ratio (RR) with accompanying 95%
confidence intervals (CI). For the key outcomes presented in the
Three review authors (LL, PTM and RPV) independently extracted 'Summary of findings' table, we also expressed the results as
data from the included studies using standardised data extraction absolute numbers based on the pooled results and compared to the
forms. We extracted the following data from each study: assumed risk. We aimed to calculate the number needed to treat to
benefit (NNTB) using the pooled results.
• Trial characteristics: setting, design, method of data analysis.
• Participants: study population, number of children in each We expressed continuous outcome variables either as a mean
group, participant characteristics such as age and gender. difference (MD) with 95% CIs, if reported on the same scale, or as
• Interventions: type of surgery including pre-operative, intra- a standardised mean difference (SMD) with 95% CIs, if different
operative and postoperative treatment. continuous scales were used.
• Outcomes: primary and secondary outcomes recorded, time Unit of analysis issues
points, adverse effects and complications related to the
intervention and comparators. This review did not use data from phase two of cross-over studies or
• Aspects of methodology relating to risk of bias (see below). from studies where the patient is not the unit of randomisation, i.e.
cluster-randomised trials or studies where 'ears' (right versus left)
We also extracted the following summary statistics for each trial were randomised.
and each outcome:
• For continuous data: mean values, standard deviations and

number of patients for each treatment group.
Informed decisions.
Dealing with missing data Subgroup analysis and investigation of heterogeneity

For continuous outcomes, we aimed to calculate missing statistics, We planned to subgroup studies where most participants (80%
such as standard deviations (SDs), from other available statistics or more) met the criteria stated below to determine whether the
(e.g. P values) according to the methods described in Chapter 7 effect of the intervention was different compared to other patients,
of the Cochrane Handbook for Systematic Reviews of Interventions regardless of whether we observed statistical heterogeneity. We
(Handbook 2011). Apart from imputations for missing SDs, we did planned to present the main analyses of this review in the form of
not conduct other imputations. We extracted and analysed all data forest plots based upon our prime subgroup analysis:
using the available case analysis method.
• presence of middle ear effusion at randomisation or at the time
Assessment of heterogeneity of grommet insertion - yes versus no.
First, we assessed the level of clinical diversity between trials by For this review, effect modifiers included:
reviewing them for potential differences in the types of participants
recruited, interventions used and outcomes measured. We did not • type of grommet (short-term versus intermediate/long-term
pool studies where clinical heterogeneity made it unreasonable length of stay);
to do so. Second, we assessed statistical heterogeneity for each • age (below two years of age versus two years and older).
outcome by visually inspecting the forest plots and by using the
Chi2 test, with a significance level set at P value < 0.10, and We therefore planned to consider these subgroup analyses in the
the I2 statistic, with I2 values over 50% suggesting substantial presence of statistical heterogeneity.
heterogeneity (Higgins 2003).
Sensitivity analysis
Assessment of reporting biases We planned to carry out sensitivity analyses for the following
We assessed reporting bias as within-study (outcome reporting) factors to assess the robustness of the review findings:
and between-study reporting (publication) bias.
• risk of bias of included studies: we excluded from analysis
Outcome reporting bias studies with high risk of bias defined as high risk of allocation
concealment bias and attrition bias (overall loss to follow-up of
We searched the internet, ClinicalTrials.gov (http:// more than 20% or differential follow-up observed, or both).
clinicaltrials.gov/) and the World Health Organization (WHO)
• surgical interventions in comparator groups during follow-
International Clinical Trials Registry Platform (ICTRP) (http://
up as part of protocol: we excluded from analysis studies in
www.who.int/trialsearch) for available study protocols to
which children in the comparator groups underwent surgical
determine whether outcomes reported were pre-defined and
interventions if clinical conditions were met (e.g. paracentesis in
whether all outcomes listed in the study protocol were reported
case of AOM recurrences).
in the trial publications. Where there was insufficient information
to judge the risk of bias, we classified the risk of bias as unclear • occurrence of AOM recurrences between the date of
(Handbook 2011). randomisation and surgery: we excluded from analysis studies
that specifically included AOM recurrences occurring between
Publication bias the date of randomisation and surgery.
We proposed a more formal method of assessing reporting bias, If any of these investigations found a difference in the effect size
i.e. by creating funnel plots, if sufficient trials (10 or more) were or heterogeneity, we reported this in the Effects of interventions
available for an outcome. section.
Data synthesis GRADE and 'Summary of findings'
We conducted all meta-analyses using Review Manager 5.3 We used the GRADE approach to rate the overall quality of evidence
(RevMan 2014). We analysed the available data according to the for each outcome. We judged the quality of evidence as high,
intention-to-treat principle, i.e. by analysing all participants in the moderate, low or very low. We judged evidence from RCTs that
groups to which they were originally randomised. As such, we did not have serious limitations as high quality. However, we
anticipated that some children allocated to the comparator groups downgraded the quality of evidence to moderate, low or very low
received surgery before the end of the trial (i.e. crossed over into based on the following factors:
the surgery group).
• study limitations (risk of bias);
We calculated treatment differences with the Mantel-Haenszel • indirectness of evidence (directness of evidence);
method using a fixed-effect model where no substantial statistical
• imprecision (precision of results);
heterogeneity was present (I2 < 50%). If substantial statistical
heterogeneity was detected but unresolved by sensitivity analysis • inconsistency (consistency of results);
and pre-specified subgroup analyses, we calculated treatment • publication bias (existence of publication bias).
differences using a random-effects (DerSimonian and Laird) model
to provide a more conservative effect estimate. For dichotomous We presented only the top priority outcomes in the 'Summary of
outcomes, we calculated the number needed to treat to benefit findings' tables:
(NNTB) using the results of the meta-analysis (which itself uses risk
ratio) based on the average risk of the control groups in the included
studies ('study population') (Handbook 2011).
Informed decisions.
• treatment success, defined as the proportion of children RESULTS

who have no AOM recurrences at three to six months post-
randomisation; Description of studies
• significant adverse effects: a tympanic membrane perforation Results of the search
persisting for three months or longer;
• treatment success, defined as the proportion of children The searches retrieved a total of 1120 records. Removing duplicates
who have no AOM recurrences at six to 12 months post- left 487 unique articles. After screening titles and abstracts
randomisation; we identified 24 potentially eligible records. We excluded 15
records with reasons (see Characteristics of excluded studies), three
• total number of AOM recurrences at three to six months post-
studies were classified as ongoing (Aabel 2011; Hoberman 2015;
randomisation;
SIUTIT Trial 2015: for details see Characteristics of ongoing studies)
• total number of AOM recurrences at six to 12 months post- and one paper reported additional findings of the Kujala 2012 trial
randomisation; (Kujala 2014) and was therefore included as part of Kujala 2012. This
• disease-specific health-related quality of life; left five studies eligible for inclusion (Casselbrant 1992; El-Sayed
• generic health-related quality of life. 1996; Gebhart 1981; Gonzalez 1986; Kujala 2012). Figure 1 shows the
flow chart of study retrieval and selection.
Informed decisions.
Figure 1. PRISMA flow diagram of search history.
Informed decisions.
Figure 1. (Continued)
Included studies background therapy and the effectiveness of grommets as add-

on therapy to adenoidectomy could therefore not assessed in
For details of the included studies see the Characteristics of
this review. Table 1 provides an overview of interventions and
included studies table.
comparison pairs included in this review. Further details of the
Design specific interventions can be found in the Characteristics of
included studies table.
All five studies were RCTs. Two were two-armed trials, whereas
three trials had a three-armed parallel design. Due to the nature of Outcome measures
the intervention and comparators, all studies were open-label (for
Table 2 summarises whether the included studies did (or did not)
the grommets versus no (ear) surgery comparisons).
report on our pre-specified outcomes. All outcomes were reported
Setting in at least one study, but adverse events were not systematically
assessed in any of the studies.
Studies were conducted in a secondary and/or tertiary care setting
in the USA (three studies), Saudi Arabia (one study) and Finland Funding and conflicts of interest
(one study).
Two studies received non-commercial (governmental) funding.
Participants One study was performed without funding, whereas no details were
provided in one study. Pharmaceutical companies provided the
The number of participants in the included studies ranged from 65 study medications in two studies.
to 300. Participants' ages ranged from 0 to 10 years and 55% to
63% were boys. Children with middle ear effusion at baseline were Excluded studies
excluded in two studies. The proportion of children with OME at
We excluded 15 articles after reviewing the full text. Reasons for
baseline was not reported in two studies and was 29% (18/63) in
exclusion are provided in the Characteristics of excluded studies
one study.
table.
Interventions
Risk of bias in included studies
In the five included studies insertion of grommets in both ears was
compared to active monitoring, antibiotic prophylaxis or placebo Summaries of the 'Risk of bias' assessments of the included studies
medication. None of the studies performed adenoidectomy as are presented in Figure 2 and Figure 3.
Figure 2. 'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages
across all included studies.
Informed decisions.
Figure 3. 'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Allocation (performance bias) is not possible. Blinding of outcome assessment

(detection bias) was not performed in the included studies. As such,
We judged the risk of selection bias due to sequence generation and
we judged both the risk of performance bias and detection bias to
concealment of allocation to be low in one study (20%), high in one
be high in all studies.
study (20%) and unclear in three studies (60%).
Incomplete outcome data
Blinding
We judged the risk of bias for incomplete outcome data to be low
Due to the nature of the studies (comparing surgical and non-
in one study (20%), high in two studies (40%) and unclear in two
surgical interventions), blinding of participants and personnel
studies (40%).
Informed decisions.
Selective reporting See: Summary of findings for the main comparison; Summary of
findings 2; Summary of findings 3. We have reported all available
We judged the risk of outcome reporting bias to be high for Kujala
outcome data for all comparison pairs (those not listed were not
2012. We could not retrieve trial protocols for the remaining four
available).
studies (80%) and therefore we could not determine the risk of
selective outcome reporting bias for these studies. 1. Grommets versus active monitoring
Other potential sources of bias Primary outcomes
We judged the risk of other potential sources of bias to be unclear Treatment success, defined as the proportion of children who
in four studies (80%) and high in one study (20%). have no acute otitis media (AOM) recurrences at six months post-
randomisation (intermediate-term follow-up)
Effects of interventions For this outcome, we could use data from only one study (108
See: Summary of findings for the main comparison Grommets randomised children; 95 (88%) included in analysis) (Gebhart 1981).
versus active monitoring for recurrent acute otitis media in Children receiving grommets were more likely to have no AOM
children; Summary of findings 2 Grommets versus antibiotic recurrences at six months post-randomisation than those managed
prophylaxis for recurrent acute otitis media in children; Summary by active monitoring (46% versus 5%; risk ratio (RR) 9.49, 95%
of findings 3 Grommets versus placebo medication for recurrent confidence interval (CI) 2.38 to 37.80, number needed to treat to
acute otitis media in children benefit (NNTB) 3) (Analysis 1.1; Figure 4).
Figure 4. Forest plot of comparison: 1 Grommets versus active monitoring, outcome: 1.1 Proportion of patients who
have no AOM recurrences at 6 months post-randomisation.
Quality of the evidence Quality of the evidence
The evidence for this outcome was of low quality; we downgraded The evidence for this outcome was of low quality; we downgraded
it from high to low quality due to study limitations and imprecise it from high to low quality due to study limitations and imprecise
effect estimates (only one study with a small sample size). effect estimates (only one study with a relatively small sample size).
Significant adverse event: tympanic membrane perforation persisting Total number of AOM recurrences at six months post-randomisation
for three months or longer
One study reported on this outcome (108 randomised children;
For this outcome, we could use data from only one study (Gebhart 95 (88%) included in analysis) (Gebhart 1981). At six months post-
1981). In this study, no persistent tympanic membrane perforations randomisation, a total of 36 AOM recurrences were observed in
were reported among 54 children receiving grommets. the grommets group (54 children) and 89 in the active monitoring
group (41 children); the mean number of AOM recurrences per child
Quality of the evidence
was 0.67 versus 2.17, respectively (MD -1.50, 95% CI -1.99 to -1.01)
The evidence for this outcome was of low quality; we downgraded (Analysis 1.3).
it from high to low quality due to study limitations and imprecise
effect estimates (only one study with a small sample size).
The evidence for this outcome was of low quality; we downgraded
Secondary outcomes it from high to low quality due to study limitations and imprecise
Treatment success, defined as the proportion of children who have no effect estimates (only one study with a small sample size).
AOM recurrences at 12 months post-randomisation (long-term follow-
up) Total number of AOM recurrences at 12 months post-randomisation
For this outcome, we could use data from only one study (200 One study reported on this outcome (200 randomised children;
randomised children; 200 (100%) included in analysis) (Kujala 200 (100%) included in analysis) (Kujala 2012). At 12 months
2012). Children receiving grommets were more likely to have no post-randomisation, a total of 92 AOM recurrences were observed
AOM recurrences at 12 months post-randomisation than those in the grommets group (100 children) and 119 in the active
managed by active monitoring (48% versus 34%; RR 1.41, 95% CI monitoring group (100 children). The one-year AOM incidence rate
1.00 to 1.99, NNTB 8) (Analysis 1.2). was estimated at 1.15 versus 1.70, respectively (incidence rate
difference -0.55, 95% -0.17 to -0.93).
Informed decisions.
Quality of the evidence randomisation, "no statistically significant differences" between

The evidence for this outcome was of low quality; we downgraded groups were reported for any of the six sub-domains.
it from high to low quality due to study limitations and imprecise Quality of the evidence
effect estimates (only one study with a relatively small sample size).
Disease-specific health-related quality of life of the child at four it from high to low quality due to study limitations and imprecise
months post-randomisation effect estimates (only one study with a small sample size).
One study reported on this outcome for a subset of participating
Other secondary outcomes
children using the OM-6 questionnaire (105 randomised children;
85 (81%) included in analysis) (Kujala 2012). At four months None of the studies reported on generic health-related quality of
post-randomisation, "no statistically significant differences" were life, presence of middle ear effusion or other adverse events.
reported between groups for any of the six sub-domains.
2. Grommets versus antibiotic prophylaxis
Primary outcomes
it from high to low quality due to study limitations and imprecise Treatment success, defined as the proportion of children who have no
effect estimates (only one study with a small sample size). AOM recurrences at six months post-randomisation
For this outcome, we could combine data from two studies

Disease-specific health-related quality of life of the child at 12 months
post-randomisation
(96 children) (Gonzalez 1986; El-Sayed 1996). Children receiving
grommets were more likely to have no AOM recurrences at
One study reported on this outcome for a subset of participating six months post-randomisation than those receiving antibiotic
children using the OM-6 questionnaire (105 randomised children; prophylaxis (60% versus 35%; RR 1.68, 95% CI 1.07 to 2.65, I2 = 0%,
81 (77%) included in analysis) (Kujala 2012). At 12 months post- fixed-effect model, NNTB 5) (Analysis 2.1; Figure 5).
Figure 5. Forest plot of comparison: 2 Grommets versus antibiotic prophylaxis, outcome: 2.1 Proportion of patients
who have no AOM recurrences at 6 months post-randomisation.
When we excluded the study with high risk of bias (El-Sayed 1996), Secondary outcomes
we observed no statistically significant difference between groups
Total number of AOM recurrences at six months post-randomisation
(RR 2.29, 95% CI 0.97 to 5.39). The data did not allow us to perform
any of the planned subgroup analyses and remaining sensitivity One study reported on this outcome (number of randomised
analyses. children unknown; 43 included in analysis) (Gonzalez 1986). At
six months post-randomisation, a total of 19 AOM recurrences
Quality of the evidence were observed in the grommets group (22 children) and 29 in the
The evidence for this outcome was of very low quality; we antibiotic prophylaxis group (21 children); the mean number of
downgraded it from high to very low quality due to study AOM recurrences per child was 0.86 versus 1.38, respectively (MD
limitations (no statistically significant difference between groups -0.52, 95% CI -1.37 to 0.33) (Analysis 2.2).
was observed after exclusion of the trial with high risk of bias)
and imprecise effect estimates (only two studies with small sample
sizes). The evidence for this outcome was of very low quality; we
downgraded it from high to very low quality due to study limitations
Significant adverse event: tympanic membrane perforation and imprecise effect estimates (only one study with a very small
persisting for three months or longer sample size).
For this outcome, we could use data from only one study Other secondary outcomes
(Casselbrant 1992). In this study, a persistent tympanic membrane
perforation was reported in 3 of 76 children (4%) who were None of the studies reported on disease-specific or generic health-
randomised to grommet insertion. related quality of life, presence of middle ear effusion or other
adverse events.
Informed decisions.
3. Grommets versus placebo medication 1986). Children receiving grommets were more likely to have no
AOM recurrences at six months post-randomisation than those
Primary outcomes
receiving placebo medication (55% versus 15%; RR 3.64, 95% CI
Treatment success, defined as the proportion of children who have no 1.20 to 11.04, NNTB 3) (Analysis 3.1; Figure 6).
AOM recurrences at six months post-randomisation
For this outcome, we could use data from only one study (number of
randomised children unknown; 42 included in analysis) (Gonzalez
Figure 6. Forest plot of comparison: 3 Grommets versus placebo medication, outcome: 3.1 Proportion of patients
who have no AOM recurrences at 6 months post-randomisation.
Quality of the evidence Subgroup analyses

The evidence for this outcome was of very low quality; we There were insufficient data to determine whether presence of
downgraded it from high to very low quality due to study limitations middle ear effusion at randomisation, type of grommet or age
and imprecise effect estimates (only one study with a very small modified the effectiveness of grommets.
sample size).
DISCUSSION
Significant adverse event: tympanic membrane perforation persisting
for three months or longer Summary of main results
Only one study reported on the occurrence of persistent tympanic Current evidence on the effectiveness of bilateral grommet
membrane perforation in the grommets group (Casselbrant 1992). insertion in children with recurrent acute otitis media (rAOM) is
The findings are illustrated above (in the grommets versus limited to five RCTs with unclear or high risk of bias, which were
antibiotic prophylaxis comparison). conducted prior to the introduction of pneumococcal vaccination.
Quality of the evidence In none of the studies was adenoidectomy performed concurrently
in both groups.
it from high to low quality due to study limitations and imprecise Low to very low-quality evidence suggests that children receiving
effect estimates (only one study with a small sample size). grommets are less likely to have AOM recurrences at six and
12 months' follow-up compared to those managed by active
Secondary outcomes monitoring and placebo medication, but the magnitude of the
Total number of AOM recurrences at six months post-randomisation effect is modest with around one fewer episode at six months and
a less noticeable effect by 12 months.
One study reported on this outcome (number of randomised
children unknown; 42 included in analysis) (Gonzalez 1986). At Low-quality evidence suggests that disease-specific quality of life is
six months post-randomisation, a total of 19 AOM recurrences similar at four and 12 months in children receiving grommets and
were observed in the grommets group (22 children) and 40 in the those managed by active monitoring.
placebo medication group (20 children); the mean number of AOM
recurrences per child was 0.86 versus 2.0, respectively (MD -1.14, It is uncertain whether or not grommets are more effective than
95% CI -2.06 to -0.22) (Analysis 3.2). antibiotic prophylaxis.
Quality of the evidence The risk of persistent tympanic membrane perforation after
grommet insertion is low (0/54 children in one study and 3/76 in
The evidence for this outcome was of very low quality; we another (low-quality evidence)).
downgraded it from high to very low quality due to study limitations
and imprecise effect estimates (only one study with a very small Overall completeness and applicability of evidence
sample size).
The children participating in the five RCTs included in this review
Other secondary outcomes represent those most commonly encountered in clinical practice,
that is children below six years of age suffering from rAOM.
None of the studies reported on disease-specific or generic health- However, we judged the overall completeness and applicability of
related quality of life, presence of middle ear effusion or other the evidence to be low.
adverse events.
Informed decisions.
All trials were conducted at a time when pneumococcal conjugate 2011) and "may be associated with fewer AOM recurrences" (Steele
vaccination had not yet been introduced to national immunisation 2017).
programmes. Since then pneumococcal vaccination has been
introduced in most countries; this may have changed the Two important clinical practice guidelines were launched in
pathogens causing AOM, its clinical features and the recurrence rate the USA in 2013: one published by the American Academy of
(Coker 2010; Fortanier 2014). How this might impact the results of Pediatrics on the management of AOM (Lieberthal 2013), and one
prior trials is unknown. by the American Academy of Otolaryngology - Head and Neck
Surgery on tympanostomy tubes (Rosenfeld 2013). Both guidelines
None of the studies reported the effect of grommets on the severity recommend grommets as an optional treatment in children with
of AOM recurrences or antibiotic consumption. This is particularly rAOM. The latter suggests that grommets should not be offered to
important since grommets may reduce the severity of AOM children with rAOM who have no middle ear effusion at the time of
recurrences because they allow for drainage of middle ear fluid evaluation for surgery (Rosenfeld 2013).
that builds up during an acute infection; as such they may prevent
ear pain caused by pressure against the tympanic membrane. They In our review, we planned to present the main analyses of the
also allow for topical (local) treatment of AOM recurrences with review in the form of forest plots based on whether middle ear
antibiotic eardrops (van Dongen 2014), and thereby avoid the side effusion was present at randomisation or at the time of surgery. The
effects of systemic antibiotics and potentially reduce the risk of data, however, did not allow us to perform such analysis. Children
antimicrobial resistance (Weber 2004). with middle ear effusion at baseline were excluded in two trials
and presence of OME was only 29% in one study. In this latter
Finally, the included studies did not record adverse events study, results were stratified according to the presence or absence
systematically; nor did they compare effects with costs. A thorough of middle ear effusion at the initial visit (Gonzalez 1986), indicating
evaluation of benefits, harms and cost-effectiveness of grommets that the effect of grommets may be larger in children with rAOM and
versus active monitoring in children with rAOM in the post- concomitant middle ear effusion (no AOM recurrence at six months
pneumococcal conjugate vaccine era is therefore urgently needed. in 8/9 of the grommets group, 1/6 of the antibiotic prophylaxis
group and 1/3 of the placebo medication group) than in those with
Quality of the evidence no middle ear effusion (no AOM recurrence at six months in 4/12 of
the grommets group, 4/15 of the antibiotic prophylaxis group and
The quality of the evidence for the outcomes included in the
2/17 of the placebo medication group). However, we performed this
studies comparing grommets versus active monitoring, antibiotic
analysis post hoc and it was based upon a very small number of
prophylaxis and placebo medication in children with rAOM was very
children.
low to low. Our confidence in the effect estimates is therefore (very)
limited and the findings of this review should be interpreted with We found that the risk of persistent tympanic membrane
caution since the true effects of grommets in this group of children perforation after grommet insertion is low. This is in line with a
may be quite different than the effect estimates presented. previous meta-analysis of tympanostomy tube sequelae, which
indicated that persistent perforation occurred in 2.2% of children
Potential biases in the review process
receiving short-term grommets (Kay 2001).
We closely adhered to the methods and analyses presented in our
protocol, which was developed and published prior to the conduct AUTHORS' CONCLUSIONS
of this review (Lau 2015). We used an extensive search strategy
without language or publication restrictions and reviewed citation Implications for practice
lists of all potentially relevant records; it is therefore unlikely Current evidence on the effectiveness of bilateral grommet
that we have missed relevant studies. The decision, however, to insertion in children with recurrent acute otitis media (rAOM) is
downgrade the quality of evidence according to sample size, i.e. the limited in quantity (five randomised controlled trials (RCTs)) and
determination of 'imprecise effect estimate', was not prespecified, of low to very low quality. The results of the studies included
but based on a post hoc subjective interpretation by the review in this review suggest some benefit of grommets in terms of the
authors. chance of having no further AOM recurrences and reducing the
number of AOM recurrences (around one fewer episode at six
Agreements and disagreements with other studies or months and a less noticeable effect by 12 months) compared to
reviews those managed by active monitoring and placebo medication. It
Several systematic reviews of the effects of grommets in children is uncertain whether or not grommets are more effective than
with rAOM have been published in recent years (Cheong 2012; antibiotic prophylaxis. Our findings suggest that clinicians need to
Damoiseaux 2011; Hellstrom 2011; Lous 2011; Steele 2017). carefully balance the modest potential benefits of grommets in this
Hellstrom concluded in 2011 that "there was insufficient evidence population against the potential harms and the risks of any surgical
to support an effect of grommet insertion for rAOM" (Hellstrom intervention in young children.
2011). Others came to a similar conclusion, i.e. that the "evidence
on the effects of grommet insertion for children with rAOM is Implications for research
(severely) limited" (Damoiseaux 2011; Steele 2017). Widespread use of pneumococcal vaccination has changed the
bacteriology and epidemiology of AOM, and how this might impact
Despite this limitation, Damoiseaux, Lous and Steele the results of prior trials is unknown. New and high-quality RCTs
concluded that grommets seem "to have only a short-term comparing grommets with active monitoring in children with rAOM
benefit" (Damoiseaux 2011), "seems to prevent one attack of AOM are urgently needed.
or keep one child out of three free from AOM in six months" (Lous
Informed decisions.
Children participating in future trials of grommets for rAOM should and systemic, are systematically captured across both treatment
be representative of the populations around the world who are groups. Ideally, future trials will also assess the impact of both
receiving grommets either as a single surgical intervention or in treatment strategies on antimicrobial resistance by collecting stool
combination with adenoidectomy. The type of grommets must samples of participants to detect and quantify the dynamics of
be clearly specified and sample sizes need to be sufficient to the genes in the gut microbiota that confer resistance to the
answer the study question reliably. Preferably, randomisation most commonly used antibiotics. Finally, it is important to capture
should be stratified according to the presence of middle ear health economic data including direct and indirect healthcare costs
effusion at the time of evaluation for surgery to assess whether this to balance the costs of the various treatment strategies against
characteristic modifies the effectiveness of grommets. It is critical benefits in a health economic analysis.
that appropriate outcomes are chosen and it would be ideal if the
choice was consistent across studies. To ensure future trial results ACKNOWLEDGEMENTS
are of maximum value to both professionals and families of children
with rAOM, it is key that all stakeholders involved in the care of We gratefully acknowledge the assistance received from the staff
children with rAOM work together to develop a core set of outcomes at the Cochrane ENT editorial base and thank Samantha Cox for
to be used clinically and across future research into this condition. her support with the search strategy and searches. We would also
These outcomes should likely not only focus on the frequency of like to thank the editors, Dr David Tunkel (peer reviewer) and the
AOM recurrences diagnosed by clinicians in both the short term consumer referee for commenting on the protocol and the full
(three to six months) and the long term (up to two years), but review.
also collect outcomes reported by children and their caregivers
We gratefully thank Loretta Lau for her contribution to the
including validated AOM severity scores such as the AOM Severity
development of this review.
of Symptoms Scale (AOM-SOS) (Shaikh 2009) and the AOM Faces
Scale (AOM‑FS) (Friedman 2006). Furthermore, it is important This project was supported by the National Institute for Health
that adverse effects of grommets, such as the frequency of Research, via Cochrane Infrastructure, Cochrane Programme Grant
persistent tympanic membrane perforations, misplaced grommets or Cochrane Incentive funding to Cochrane ENT. The views and
in the middle ear, postoperative otorrhoea (in the first week opinions expressed therein are those of the authors and do not
after grommet insertion) and myringosclerosis, are consistently necessarily reflect those of the Systematic Reviews Programme,
monitored and that data on antibiotic use, both topical (eardrops) NIHR, NHS or the Department of Health.
Informed decisions.
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General Practice 2006;56(524):170-5. * Indicates the major publication for the study
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Casselbrant 1992
Methods 3-arm, non-blinded (for grommets versus no (ear) surgery comparisons), multicentre, parallel-group
RCT with 2 years of follow-up
Participants Location: USA, Children's Hospital of Pittsburgh Otitis Media Center and 2 private paediatric practices
in Pittsburgh
Setting of recruitment and treatment: secondary and tertiary care
Sample size:
• Number randomised: 86 in intervention, 90 in comparison 1, 88 in comparison 2

• Number completed: 57 in intervention, 40 in comparison 1, 37 in comparison 2
Participant (baseline) characteristics:
• Age: 7 months to 35 months

• Gender: 155 boys (59%), 109 girls (41%)
Inclusion criteria: children aged between 7 months and 35 months with at least 3 AOM episodes in the
previous 6 months or more than 4 in the previous 12 months with the most recent episode having oc-
curred in previous 6 months. At time of entry children were required to be free of OME.
Exclusion criteria: OME at time of entry, asthma, chronic sinusitis or previous tonsillectomy or ade-
noidectomy
Interventions Intervention group: grommets (Teflon® Armstrong type)
Comparator group 1: antibiotic prophylaxis; amoxicillin suspension 20 mg/kg/day once daily for 2
years
Comparator group 2: placebo medication; liquid suspension of similar appearance and taste to antibi-
otic prophylaxis for 2 years
Informed decisions.
Casselbrant 1992 (Continued)

In case of AOM episodes, amoxicillin 40 mg/kg/day divided into 3 daily doses for 10 days was pre-
scribed and tympanocentesis was performed in the antibiotic prophylaxis and placebo medication
groups. If a participant did not improve and if the culture yielded an amoxicillin-resistant organism, a
10-day course of erythromycin and sulfisoxazole or alternative antimicrobial drug was prescribed. In
case of otorrhoea (through a tympanic membrane perforation or grommets), amoxicillin 40 mg/kg/day
and neomycin/polymyxin B/hydrocortisone ear drops were prescribed for 10 days.
Use of additional interventions: participants were randomly allocated to antibiotic prophylaxis or

placebo medication received a nasopharyngeal and middle ear culture (through tympanocentesis) in
case of new AOM or OME episodes
Outcomes Primary outcome: number of AOM episodes in the 2-year postoperative period
Secondary outcomes: proportion of children without AOM recurrences in the 2-year postoperative pe-
riod, proportion of children who had ultimate treatment failure (protocol-defined criteria for a fourth
tympanocentesis within 6 months or a fifth within 12 months; over 180 days with middle ear effusion
in the same ear within 12 months; protocol-defined criteria for a third placement of grommets within
12 months; a suppurative complication; a cholesteatoma; a significant adverse reaction to amoxicillin),
persistent tympanic membrane perforation after grommet insertion, bacteriology of middle ear effu-
sions
Diagnosis of AOM was based on otoscopic signs (erythema or white opacification, fullness or bulging
and decreased mobility of the tympanic membrane), or one or more symptoms (fever, otalgia, irritabili-
ty) in the presence of middle ear effusions or both.
Funding sources Funded by a grant from the National Institute of Deafness and Communication Disorders, National In-
stitute of Health. Amoxicillin and placebo medication were supplied by Beecham Laboratories, Bristol,
TN
Declarations of interest No details provided
Notes Participants lost to follow-up total: 109/243 (45%) (limited to participants with at least 1 follow-up
visit)
Participants lost to follow-up intervention group: 20/77 (26%); 6 treatment failure, 14 loss to fol-
low-up
Participants lost to follow-up comparator group 1: 46/86 (53%); 12 treatment failure, 34 loss to fol-
low-up
Participants lost to follow-up comparator group 2: 43/80 (51%); 11 treatment failure, 32 loss to fol-
low-up
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence genera- Unclear risk Stratified randomisation, but method not described
tion (selection bias)
Allocation concealment Unclear risk Method not described

(selection bias)
Blinding of participants High risk Not blinded

and personnel (perfor-
mance bias)
All outcomes
Blinding of outcome as- High risk Not blinded

sessment (detection bias)
Informed decisions.
Casselbrant 1992 (Continued)

All outcomes
Incomplete outcome data High risk Quote: "The combined attrition rates for the amoxicillin, placebo and tympa-
(attrition bias) nostomy tube groups at the 6-, 12-, 18- and 24-month end points were 21.2%,
All outcomes 28.0%, 35.2% and 38.3%, respectively."
Selective reporting (re- Unclear risk No protocol available; insufficient information to permit a judgement of low or
porting bias) high risk
Other bias Unclear risk Baseline characteristics: balanced
Intention-to-treat analysis: performed
Formal sample size calculations were performed
Co-interventions: different across groups
El-Sayed 1996
Methods 2-arm, non-blinded, single-centre parallel-group RCT with 6 months of follow-up
Participants Location: Saudi Arabia, ENT unit of King Abdel Azir University Hospital, Riyadh
Setting of recruitment and treatment: tertiary care
Sample size:
• Number randomised: ? in intervention, ? in comparison

• Number completed: 31 in intervention, 22 in comparison
• Age: 3 years and below; mean age 20 months

Inclusion criteria: children aged below 3 years with at least 3 AOM episodes diagnosed, documented
and treated by their referring physician in the 6 months prior to referral. Presence or absence of OME
did not preclude inclusion in the study
Exclusion criteria: documented immune deficiency or craniofacial abnormalities such as cleft palate,
Down's syndrome
Interventions Intervention group: grommets (type not described)
Comparator group: antibiotic prophylaxis; sulfamethoxazole-trimethoprim (SMZ-T) 12 mg/kg/day

once daily for 6 months
Oral antibiotics were administered for individual AOM episodes; cefaclor for 10 days
Use of additional interventions: none described
Outcomes Primary outcome: proportion of children who have no AOM recurrences in the 6-month postoperative
period
Secondary outcomes: side effects of medication, number of re-insertions of grommets (data provided
for the treatment group only)
Diagnosis of AOM was based on otoscopy findings and the acute onset of otalgia with or without otor-
rhoea. For those with grommets in place, diagnosis was based upon the presence of otorrhoea.
Informed decisions.
El-Sayed 1996 (Continued)
Funding sources No details provided
Notes Participants lost to follow-up total: 15/68 (22%); 7 non-compliance with medication, 8 loss to fol-
low-up. Insufficient information to calculate the number of excluded children for the grommets and
control groups.
Risk of bias
Random sequence genera- High risk Methods not described; 8/64 children (13%) were placed on a predetermined
tion (selection bias) treatment regime on the basis of the parent's concern
Allocation concealment High risk Methods not described; 8/64 children (13%) were placed on a predetermined
(selection bias) treatment regime

mance bias)
All outcomes

All outcomes
Incomplete outcome data High risk 15/68 children (22%) not included in final analyses; insufficient information
(attrition bias) to calculate the number of excluded children for the grommets and control
All outcomes groups
Did not perform intention-to-treat analysis: children who were non-compliant

with medication were excluded from analyses
Did not perform formal sample size calculations
Co-interventions: similar across groups
Gebhart 1981
Methods 2-arm, non-blinded, single-centre, parallel-group RCT with 6 months of follow-up
Participants Location: USA, general ENT practice
Setting of recruitment and treatment: secondary care
Sample size:
• Number randomised: 58 in intervention, 50 in comparison

• Number completed: 54 in intervention, 41 in comparison
Informed decisions.
Gebhart 1981 (Continued)

• Age: 3 years and below; mean age 20 months
Inclusion criteria: children aged below 3 years with at least 3 AOM episodes diagnosed and treated
by their referring physician in the 6 months prior to referral. Presence or absence of OME, by history or
physical examination, did not preclude inclusion in the study
Exclusion criteria: cleft palate, Down's syndrome, recurrent tonsillitis associated with otitis media
Interventions Intervention group: grommets (Shepard Teflon®)
Comparator group: active monitoring
(Topical) antibiotics were administered for individual AOM episodes; ampicillin (or erythromycin plus a
sulphonamide in case of ampicillin allergy) for 10 days; if drainage was present, and did not clear with
antibiotics, Cortisporin® eardrops were administered
Use of additional interventions: decongestant for URTI or nasal congestion
Outcomes Primary outcome: number of AOM episodes in the 6-month postoperative period
Secondary outcomes: proportion of children without AOM recurrences in the 6-month postoperative
period, grommets-related adverse effects, number of re-insertions of grommets (data provided for the
treatment group only)
Diagnosis of AOM was based on otoscopy findings. For those with grommets in place, diagnosis was
based upon the presence of ear discharge in the external ear canal.
Funding sources This study was supported in part by a grant from the Medical Research Foundation at Riverside
Methodist Hospital and in part by NIH Grant NSO 8854
Notes Participants lost to follow-up total: 13/108 (12%)
Participants lost to follow-up intervention group: 4/58 (7%); inadequate follow-up in 3 children and
parents of 1 child terminated study
Participants lost to follow-up comparator group: 9/50 (18%); inadequate follow-up in 7 children and
parents or the referring physician of 2 children terminated study
Risk of bias
Random sequence genera- Unclear risk Method not described


(selection bias)

mance bias)
All outcomes

All outcomes
Informed decisions.
Gebhart 1981 (Continued)
Incomplete outcome data Unclear risk 13/108 (12%) children not included in final analyses; 4/58 (7%) in grommets
(attrition bias) group and 9/50 (18%) control group; reasons for non-completion are clearly
All outcomes described, but bias due to differential loss to follow-up cannot be excluded
Intention-to-treat analysis was performed
Gonzalez 1986
Methods 3-arm, non-blinded (for grommets versus no (ear) surgery comparisons), multicentre, parallel-group
RCT with 6 months of follow-up
Participants Location: USA, ENT departments of Army Medical Centres
Setting of recruitment and treatment: secondary care
Sample size:
• Number randomised: ? in intervention, ? in comparison 1, ? in comparison 2

• Number completed: 22 in intervention, 21 in comparison 1, 20 in comparison 2
• Age: 6 months to 10 years; mean age 19 months

Inclusion criteria: children aged between 6 months and 10 years with at least 3 AOM episodes in the
previous 6 months or more than 4 in the previous 18 months. Presence or absence of OME did not pre-
clude inclusion in the study.
Exclusion criteria: cleft palate, Down's syndrome, previous grommets or sulphonamide sensitivity
Interventions Intervention group: grommets (0.04 mm Paparella design grommet in majority of children)
Comparator group 1: antibiotic prophylaxis; sulfisoxazole suspension 500 mg twice daily if under 5
years or 1 g twice daily if 5 years and older for 6 months
Comparator group 2: placebo medication; liquid suspension of similar texture and appearance to an-
tibiotic prophylaxis for 6 months
Oral antibiotics for 10 days were administered for individual AOM episodes
Use of additional interventions: postoperative antibiotic drops were initially used in the grommets
group, but were discontinued later in the study
Children in the antibiotic prophylaxis or placebo medication groups who had treatment failure (2 or
more AOM episodes within 3 months) underwent grommet insertion. Children in the grommets group
who had treatment failure were given a course of prophylactic sulfisoxazole. Children with OME that
persisted for longer than 3 months underwent grommet insertion (but were not considered treatment
failures if rAOM was controlled).
Outcomes Primary outcome: number of AOM episodes in the 6-month postoperative period
Informed decisions.
Gonzalez 1986 (Continued)

Secondary outcomes: proportion of children without AOM recurrences in the 6-month postoperative
period, proportion of children who had treatment failure (2 or more AOM episodes within 3 months),
significant complications (no further details provided).
Diagnosis of AOM was defined as the rapid and short onset of signs and symptoms of inflammation in
the middle ear using the following criteria: otalgia (ear tugging in the infant), fever, tympanic mem-
brane erythema or bulging, decreased tympanic membrane mobility, loss of tympanic membrane land-
marks, otorrhoea.
Funding sources Sulfisoxazole and placebo medication were supplied by Hoffman-LaRoche Inc, NJ
No further details provided
Notes Participants lost to follow-up total: unknown; the number of randomised children was not reported
19/41 children (46%) in non-surgical groups underwent grommet insertion during follow-up because of
treatment failure
3/22 children (14%) in the grommets group received sulfisoxazole prophylaxis during follow-up be-
cause of treatment failure
Risk of bias
Random sequence genera- Unclear risk Quote: "children were then randomized into three groups using a list of ran-
tion (selection bias) dom numbers"
Method not described

(selection bias)

mance bias)
All outcomes

All outcomes
Incomplete outcome data Unclear risk Insufficient information to permit a judgement of low or high risk since the
(attrition bias) number of randomised children was not reported
All outcomes
Other bias High risk Baseline characteristics: balanced
Intention-to-treat analysis: unknown
Co-interventions: different across groups
Informed decisions.
Kujala 2012
Methods 3-arm, non-blinded, single-centre, parallel-group RCT with 1 year of follow-up
Participants Location: Finland, ENT department of Oulu University Hospital
Setting of recruitment and treatment: tertiary care
Sample size:
• Number randomised: 100 in intervention, 100 in comparison 1 (and 100 in comparison 2)

• Number completed: 89 in intervention, 91 in comparison 1 (and 96 in comparison 2)
• Age: 10 months to 2 years; mean age 16.0 months

Inclusion criteria: children aged between 10 months and 2 years with at least 3 AOM episodes in the
previous 6 months and residence within 25 miles of participating hospital. At time of entry children
were required to be free of OME.
Exclusion criteria: chronic OME, previous grommets or adenoidectomy, cranial abnormalities, docu-
mented immunological disorders, ongoing prophylaxis for a disease other than AOM
Interventions Intervention group: grommets (Donaldson silicon tubes, TympoVent®, Atos)
Comparator group 1: active monitoring
Comparator group 2: grommets plus adenoidectomy; not relevant for this review (since there is no
"adenoidectomy alone" group) and therefore no further details related to this comparator reported
AOM episodes were treated according to the Finnish guidelines; primary choice of antibiotics: amoxi-
cillin 40 mg/kg/day for 5 days
Use of additional interventions: not described
Outcomes Primary outcomes: treatment failure (2 AOM episodes in 2 months or 3 in 6 months or middle ear effu-
sion for at least 2 months) and time to intervention failure
Secondary outcomes: incidence density of AOM episodes and time to first AOM recurrence.
Diagnosis of AOM was defined as presence of acute upper respiratory symptoms together with middle
ear inflammation and effusion (bulging and/or decreased mobility of the ear drum, air-fluid level) de-
tected by pneumatic otoscopy, tympanometry, otomicroscopy or otorrhoea.
Funding sources Nothing to declare
Declarations of interest Nothing to declare
Notes Participants lost to follow-up total: 20/200 (10%); grommets group: 11/100 (11%), control group:
9/100 (9%), but all randomised children were included in analyses
Risk of bias
Random sequence genera- Low risk Random allocation sequence using permutated blocks with a block size of 3
Informed decisions.
Kujala 2012 (Continued)
Allocation concealment Low risk Treatment allocation as indicated in consecutively numbered, sealed, opaque
(selection bias) envelopes, which were opened sequentially only after written informed con-
sent had been received

mance bias)
All outcomes

All outcomes
Incomplete outcome data Low risk Total number of dropouts: 20/200 (10%). Grommets group: 11/100 (11%), con-
(attrition bias) trol group: 9/100 (9%). All randomised children were included in analyses.
All outcomes
Selective reporting (re- High risk Trial protocol available at ClinicalTrials.gov (NCT00162994)
porting bias)
Primary outcomes as listed at ClinicalTrials.gov (number of acute otitis media
and quality of life issues) differed from those included in manuscript (interven-
tion failure and time to intervention failure).
Definition of intervention failure (2 AOM episodes in 2 months or 3 in 6 months,

or middle ear effusion for at least 2 months as assessed by one of the team's
otolaryngologists) as reported in the manuscript was not prespecified on Clini-
calTrials.gov.
Some of the secondary outcomes as listed on ClinicalTrials.gov (speed of re-

covery of each otitis media, number of days with middle ear effusion, number
of upper respiratory infections, prevention of otitis media caused by pneumo-
coccus) were not reported.
Did perform intention-to-treat analysis
Did perform formal sample size calculations, but these were not prespecified
on ClinicalTrials.gov
AOM: acute otitis media

ENT: ear, nose and throat
GP: general practitioner
OME: otitis media with effusion
rAOM: recurrent acute otitis media
RCT: randomised controlled trial
URTI: upper respiratory tract infection
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Bulman 1984 PARTICIPANTS:
OME not rAOM
Chow 2007 ALLOCATION AND PARTICIPANTS:

Informed decisions.
Study Reason for exclusion

Not a RCT; rAOM and OME
de Beer 2005 ALLOCATION:
Not a RCT
Gates 1985 PARTICIPANTS:
OME not rAOM
Gates 1987 PARTICIPANTS
OME not rAOM
Hammaren-Malmi 2005 PARTICIPANTS AND INTERVENTION:
rAOM and OME; RCT comparing grommets plus adenoidectomy versus grommets alone
Ingels 2005 PARTICIPANTS:
OME not rAOM
Le 1991 PARTICIPANTS AND INTERVENTION:
rAOM and OME; RCT with unilateral grommet insertion and in which contralateral ears were ran-
domised to either myringotomy alone or no surgery
Mandel 1989 PARTICIPANTS:
OME not rAOM
Mandel 1992 PARTICIPANTS:
OME not rAOM
Mattila 2003 INTERVENTION:
RCT comparing grommets plus adenoidectomy versus grommets alone
Qvarnberg 1981 PARTICIPANTS AND INTERVENTION:
Not rAOM; no grommets
Raol 2017 STUDY TYPE:
Not a RCT
Teele 2000 PARTICIPANTS AND INTERVENTION:
Infants at risk of rAOM; no grommets
Weigel 1989 COMPARATOR:
RCT comparing 4 different types of grommets

RCT: randomised controlled trial
Informed decisions.
Characteristics of ongoing studies [ordered by study ID]
Aabel 2011
Trial name or title "The effect of ventilation tubes on recurrent acute otitis media in children 1-6 years"
Methods Allocation: randomised
Design: parallel, open-label
Participants Number: 240
Eligibility criteria: children aged 1 to 6 years with rAOM defined as the occurrence of 3 AOM
episodes in 6 months or 4 episodes in 12 months
Exclusion criteria: previous grommets, previous adenoidectomy or tonsillectomy, plans to move

from district within follow-up time
Interventions Intervention group: grommets (type not described) insertion
AOM recurrences will be treated with antibiotics
Outcomes Primary outcomes: number of AOM recurrences during 1-year follow-up, disease-specific health-
related quality of life (OM-6 and OMO-22) at 3, 6, 9 and 12 months post-randomisation
Secondary outcomes: structural changes in tympanic membrane at 3, 6, 9 and 12 months post-

randomisation, time grommets stay in place, adverse events (chronic otorrhoea, granulation tis-
sue, persistent tympanic membrane perforation)
Starting date Ethical approval obtained on 1 November 2011
Status 24 November 2017 - not yet recruiting
Contact information Peder Aabel, Akershus University Hospital - [email protected]
Magnus von Unge, Akershus University Hospital - [email protected]
Notes ACTRN12611000380998
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336693
Sponsor: Akershus University Hospital
Principal investigators: Peder Aabel and Magnus von Unge, Akershus University Hospital, Norway
Hoberman 2015
Trial name or title Efficacy of tympanostomy tubes for children with recurrent acute otitis media
Design: parallel, open-label
Eligibility criteria: children aged 6 to 35 months with rAOM defined as the occurrence of 3 AOM
episodes in 6 months or 4 episodes in 12 months with at least 1 episode in the preceding 6 months,
and 2 of these AOM episodes have been documented by trained study personnel
Informed decisions.
Hoberman 2015 (Continued)

Exclusion criteria: previous grommets, chronic illness (cystic fibrosis, neoplasm, juvenile dia-
betes, renal or hepatic insufficiency, immune dysfunction, malabsorption, inflammatory bow-
el disease, severe asthma requiring at least 4 courses of oral corticosteroids during the last 12
months), allergy to amoxicillin, congenital anomaly (cleft palate, Down's syndrome), OME for at
least 3 months in addition to rAOM, sensorineural hearing loss
Interventions Intervention group: grommets (Teflon® Armstrong-type) insertion
AOM recurrences will be treated with antibiotic eardrops in the grommets group and with oral an-
tibiotics in the active monitoring group
Outcomes Primary outcome: average number of AOM recurrences during the 2-year follow-up period
Secondary outcomes: severity of AOM recurrences, frequency distribution of AOM recurrences

during the 2-year follow-up period, time to first AOM recurrence, type of AOM recurrences, antibiot-
ic consumption, adverse events (protocol defined diarrhoea, diaper dermatitis, chronic otorrhoea),
antibiotic resistance of nasopharyngeal pathogens, cost-effectiveness
Starting date November 2015 (estimated completion date February 2021)
Contact information Diana Kearney, RN, CCRC - [email protected]
Jennifer Nagg, RN - [email protected]
Notes https://clinicaltrials.gov/ct2/show/NCT02567825
Sponsor and collaborators: University of Pittsburgh, George Washington University, National In-
stitute on Deafness and Other Communication Disorders (NIDCD)
Principal investigators: Alejandro Hoberman, MD - University of Pittsburgh School of Medicine;

Children's Hospital of Pittsburgh of UPMC; Diego Preciado, MD, PhD - George Washington Universi-
ty; Childrens National Medical Center
SIUTIT Trial 2015

Trial name or title SIUTIT Trial
Design: parallel, single-blind (outcome assessor blinded)
Eligibility criteria: children aged 9 to 36 months with at least one Greenland-born parent, B- or C2-
type curve tympanogram at 2 visits 3 to 4 months apart or 3 episodes of AOM in 6 months or 4 in 12
months, American Society of Anaesthesiologists physical status classification class 1 and 2
Exclusion criteria: orofacial cleft, Down's syndrome or known generalised immune deficiency,
American Society of Anaesthesiologists physical status classification class > 2
Interventions Intervention group: grommets (Donaldson-type) insertion
AOM recurrences will be treated according to current practice in Greenland, which includes sys-
temic antibiotic treatment as well as aural toilet and topical antibiotics. Grommet insertion during
the study period is not accepted in the control group.
Informed decisions.
SIUTIT Trial 2015 (Continued)
Outcomes Primary outcome: number of visits to health clinic during the 2-year follow-up period (assessed by
investigating medical records)
Secondary outcomes: number of AOM episodes during the 2-year follow-up period (assessed by
investigating medical records); disease-specific quality of life at baseline, 3 months, 1 year and
2 years follow-up (assessed by OM-6 and Caregiver Impact Questionnaires); number of episodes
where oral or intravenous antibiotics have been administered during the 2-year follow-up period
(assessed by investigating medical records); proportion of children with uni- or bilateral tympan-
ic membrane perforations at 2 years (based on otoscopic images, which will be anonymised and
evaluated by an ENT specialist without knowledge of the intervention), number of ear discharge
episodes during the 2-year follow-up period (assessed by investigating medical records); serious
adverse events
Starting date February 2016 (estimated completion date August 2020)
Contact information Malene N Demant, MD - [email protected]
Notes https://clinicaltrials.gov/ct2/show/NCT02490332
Sponsor and collaborators: Zealand University Hospital; Government of Greenland, Agency for
Health and Prevention; Copenhagen Trial Unit, Center for Clinical Intervention Research
Principal investigator: Malene N Demant, MD - Køge University Hospital
Study director: Preben Homoe, MD PhD - Køge University Hospital

OM-6: Otitis Media-6
Otitis Media Outcome-22
DATA AND ANALYSES
Comparison 1. Grommets versus active monitoring
Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants
1 Proportion of patients who have no AOM re- 1 95 Risk Ratio (M-H, Fixed, 9.49 [2.38, 37.80]
currences at 6 months post-randomisation 95% CI)
2 Proportion of patients who have no AOM re- 1 200 Risk Ratio (M-H, Fixed, 1.41 [1.00, 1.99]
currences at 12 months post-randomisation 95% CI)
3 Total number of AOM recurrences at six 1 95 Mean Difference (IV, -1.5 [-1.99, -1.01]
months post-randomisation Fixed, 95% CI)
Informed decisions.
Analysis 1.1. Comparison 1 Grommets versus active monitoring, Outcome 1

Proportion of patients who have no AOM recurrences at 6 months post-randomisation.
Study or subgroup Grommets Active mon- Risk Ratio Weight Risk Ratio
itoring
n/N n/N M-H, Fixed, 95% CI M-H, Fixed, 95% CI
Gebhart 1981 25/54 2/41 100% 9.49[2.38,37.8]
Total (95% CI) 54 41 100% 9.49[2.38,37.8]

Total events: 25 (Grommets), 2 (Active monitoring)
Heterogeneity: Not applicable
Test for overall effect: Z=3.19(P=0)
Favours active monitoring 0.02 0.1 1 10 50 Favours grommets
Analysis 1.2. Comparison 1 Grommets versus active monitoring, Outcome 2

Study or subgroup Grommets Active mon- Risk Ratio Weight Risk Ratio
itoring
Kujala 2012 48/100 34/100 100% 1.41[1,1.99]
Total (95% CI) 100 100 100% 1.41[1,1.99]

Total events: 48 (Grommets), 34 (Active monitoring)
Test for overall effect: Z=1.98(P=0.05)
Favours active monitoring 0.1 0.2 0.5 1 2 5 10 Favours grommets
Analysis 1.3. Comparison 1 Grommets versus active monitoring, Outcome

3 Total number of AOM recurrences at six months post-randomisation.
Study or subgroup Grommets Active monitoring Mean Difference Weight Mean Difference
N Mean(SD) N Mean(SD) Fixed, 95% CI Fixed, 95% CI
Gebhart 1981 54 0.7 (0.8) 41 2.2 (1.5) 100% -1.5[-1.99,-1.01]
Total *** 54 41 100% -1.5[-1.99,-1.01]

Test for overall effect: Z=6.04(P<0.0001)
Favours grommets -5 -2.5 0 2.5 5 Favours active monitoring
Comparison 2. Grommets versus antibiotic prophylaxis
pants
1 Proportion of patients who have no AOM 2 96 Risk Ratio (M-H, Fixed, 1.68 [1.07, 2.65]
recurrences at 6 months post-randomisa- 95% CI)
tion
Informed decisions.
pants
2 Total number of AOM recurrences at six 1 43 Mean Difference (IV, -0.52 [-1.37, 0.33]
months post-randomisation Fixed, 95% CI)
Analysis 2.1. Comparison 2 Grommets versus antibiotic prophylaxis, Outcome 1

Study or subgroup Grommets Antibiotic Risk Ratio Weight Risk Ratio
prophylaxis
El-Sayed 1996 20/31 10/22 69.57% 1.42[0.84,2.4]
Gonzalez 1986 12/22 5/21 30.43% 2.29[0.97,5.39]
Total (95% CI) 53 43 100% 1.68[1.07,2.65]

Total events: 32 (Grommets), 15 (Antibiotic prophylaxis)
Heterogeneity: Tau2=0; Chi2=0.9, df=1(P=0.34); I2=0%
Favours AB prophylaxis 0.1 0.2 0.5 1 2 5 10 Favours grommets
Analysis 2.2. Comparison 2 Grommets versus antibiotic prophylaxis, Outcome

Study or subgroup Grommets Antibiotic Mean Difference Weight Mean Difference
prophylaxis
Gonzalez 1986 22 0.9 (1.7) 21 1.4 (1.1) 100% -0.52[-1.37,0.33]
Total *** 22 21 100% -0.52[-1.37,0.33]

Favours grommets -5 -2.5 0 2.5 5 Favours AB prophylaxis
Comparison 3. Grommets versus placebo medication
pants
1 Proportion of patients who have no AOM 1 42 Risk Ratio (M-H, Fixed, 3.64 [1.20, 11.04]
recurrences at 6 months post-randomisa- 95% CI)
tion
2 Total number of AOM recurrences at six 1 42 Mean Difference (IV, -1.14 [-2.06,
months post-randomisation Fixed, 95% CI) -0.22]
Informed decisions.
Analysis 3.1. Comparison 3 Grommets versus placebo medication, Outcome 1

Study or subgroup Grommets Placebo Risk Ratio Weight Risk Ratio
Gonzalez 1986 12/22 3/20 100% 3.64[1.2,11.04]
Total (95% CI) 22 20 100% 3.64[1.2,11.04]

Total events: 12 (Grommets), 3 (Placebo)
Favours placebo 0.1 0.2 0.5 1 2 5 10 Favours grommets
Analysis 3.2. Comparison 3 Grommets versus placebo medication, Outcome

Study or subgroup Grommets Placebo Mean Difference Weight Mean Difference
Gonzalez 1986 22 0.9 (1.7) 20 2 (1.4) 100% -1.14[-2.06,-0.22]
Total *** 22 20 100% -1.14[-2.06,-0.22]

Favours grommets -5 -2.5 0 2.5 5 Favours placebo
ADDITIONAL TABLES
Table 1. Interventions and comparison pairs included in this review

Study ID Grommets Grommets plus adenoidecto- Active Placebo Antibiotic Adenoidec-
my monitor- medication prophylaxis tomy
ing
Casselbrant 1992 x x x
El-Sayed 1996 x x
Gebhart 1981 x x
Gonzalez 1986 x x x
Kujala 2012 x x x
Comparison pairs for this review
# Interven- Comparator Number of Study ID

tion trials
1 Grommets Active monitoring 2 Gebhart 1981; Kujala 2012
Informed decisions.
Table 1. Interventions and comparison pairs included in this review (Continued)
2 Grommets Antibiotic prophylaxis 3 Casselbrant 1992; El-Sayed 1996; Gonzalez

1986
3 Grommets Placebo medication 2 Casselbrant 1992; Gonzalez 1986
Table 2. Overview of the outcomes reported in the included studies

Outcomes Casselbrant El-Sayed Gebhart 1981 Gonzalez Kujala 2012
1992 1996 1986
Primary outcomes
Proportion of children who have no AOM re- x x x

currences at 3 to 6 months post-randomisa-
tion
Significant adverse effect: tympanic mem- x x

brane perforation persisting for 3 months or
longer
Secondary outcomes
Proportion of children who have no AOM re- x

currences at 6 to 12 months post-randomi-
sation
Total number of AOM recurrences
< 3 months
3 to 6 months x x
6 to 12 months x
Disease-specific health-related quality of life
< 3 months
3 to 6 months x
6 to 12 months x
Generic health-related quality of life of the

child and parent
< 3 months
3 to 6 months
6 to 12 months
Presence of middle ear effusion
< 3 months
Informed decisions.
Table 2. Overview of the outcomes reported in the included studies (Continued)
3 to 6 months
6 to 12 months
Other adverse effects: ventilation tube x

misplaced in middle ear, otorrhoea with-
in 1 week of ventilation tube placement,
myringosclerosis
APPENDICES
Appendix 1. CENTRAL search strategy
CENTRAL (Cochrane Register of Stud- MEDLINE (Ovid) Embase (Ovid) CINAHL (EBSCO)
ies)
1 MESH DESCRIPTOR Otitis AND CEN- 1 Otitis/ 1 otitis/ S31 S25 AND S30
TRAL:TARGET
2 (otitis or inflamm* or 2 (otitis or inflamm* or infect* or S30 S26 OR S27 OR
2 (otitis or inflamm* or infect* or dis- infect* or disease*).ab,ti. disease).ti,ab. S28 OR S29
ease):AB,EH,KW,KY,MC,MH,TI,TO AND
CENTRAL:TARGET 3 1 or 2 3 1 or 2 S29 TX grommet*
3 #1 OR #2 4 exp Ear, Middle/ 4 exp middle ear/ S28 TX ((tympanos-

tomy or myringoto-
4 MESH DESCRIPTOR Ear, Middle AND 5 (middle adj3 ear).ab,ti. 5 (middle adj3 ear).ti,ab. my or tympanic) n6
CENTRAL:TARGET (tube* or tubulation
6 4 or 5 6 4 or 5
or ventilat*))
5 (middle near ear):AB,EH,KW,KY,M-
7 3 and 6 7 3 and 6
C,MH,TI,TO AND CENTRAL:TARGET S27 TX (middle n3
8 otitis media/ or otitis 8 otitis media/ ear n6 (tube* or
6 #5 OR #4 ventilat* or tubula-
media with effusion/
9 secretory otitis media/ tion))
7 #3 AND #6
9 (middle adj3 ear adj3
effus*).mp. [mp=title, 10 ((otitis adj3 media) or OME).ti,ab. S26 (MH "Middle
8 MESH DESCRIPTOR Otitis Media AND
abstract, original title, Ear Ventilation")
CENTRAL:TARGET 11 (middle adj3 ear adj3 ef-
name of substance word,
fus*).ti,ab. S25 S22 OR S23 OR
9 MESH DESCRIPTOR Otitis Media with Ef- subject heading word,
S24
fusion EXPLODE ALL AND CENTRAL:TAR- keyword heading word, 12 7 or 8 or 9 or 10 or 11
GET protocol supplementary S24 TX (raom or
concept word, rare dis- 13 exp acute disease/ mastoiditis
10 (((otitis near media) or OME)):AB,EH,K- ease supplementary con-
W,KY,MC,MH,TI,TO AND CENTRAL:TARGET cept word, unique identi- 14 (acute or suppurat* or serous or S23 (MH "Mastoidi-
fier] secretory or secretion* or purulen- tis")
11 ((middle near ear near effus*)):AB,E- t).ti,ab.
H,KW,KY,MC,MH,TI,TO AND CEN- 10 ((otitis adj3 media) or S22 S17 AND S21
TRAL:TARGET OME).ab,ti. 15 13 or 14
S21 S18 OR S19 OR
12 #7 OR #8 OR #9 OR #10 OR #11 11 7 or 8 or 9 or 10 16 12 and 15 S20
13 MESH DESCRIPTOR Acute Disease EX- 12 exp Acute Disease/ 17 exp suppurative otitis media/ S20 TX recurrence*
PLODE ALL AND CENTRAL:TARGET or recurrent or
13 (acute or suppurat* 18 (AOM or TYMPANITIS).ti,ab. chronic or persis-
14 (acute or suppurat* or serous or secre- or serous or secretory or tent or persistence
tory or secretion* or purulent):AB,EH,K- 19 16 or 17 or 18
or prone
W,KY,MC,MH,TI,TO AND CENTRAL:TARGET
Informed decisions.
(Continued)
15 #13 OR #14 secretion* or purulen- 20 exp recurrent disease/ S19 (MH "Chronic
t).ab,ti. Disease")
16 #12 AND #15 21 exp chronic disease/
14 12 or 13 S18 (MH "Recur-
17 MESH DESCRIPTOR Otitis Media, 22 exp secondary prevention/ rence")
Suppurative EXPLODE ALL AND CEN- 15 11 and 14
TRAL:TARGET 23 (recurrence* or recurrent or S17 S15 OR S16
16 exp Otitis Media, Sup- chronic or persistent or persistence
18 (AOM or TYMPANITIS):AB,EH,KW,KY,M- purative/ or prone).ti,ab. S16 TX (AOM or
C,MH,TI,TO AND CENTRAL:TARGET TYMPANITIS)
17 (AOM or TYMPA- 24 20 or 21 or 22 or 23
19 #16 OR #17 OR #18 NITIS).ab,ti. S15 S11 AND S14
25 19 and 24
20 MESH DESCRIPTOR Recurrence EX- 18 15 or 16 or 17 S14 S12 OR S13
PLODE ALL AND CENTRAL:TARGET 26 mastoiditis/
19 exp Recurrence/ S13 TX (acute or
21 MESH DESCRIPTOR Chronic Disease 27 (raom or mastoiditis).ti,ab. suppurat* or serous
EXPLODE ALL AND CENTRAL:TARGET 20 exp Chronic Disease/ or secretory or se-
28 25 or 26 or 27
cretion* or puru-
22 MESH DESCRIPTOR Secondary Preven- 21 exp Secondary Pre-
29 exp middle ear ventilation/ lent)
tion EXPLODE ALL AND CENTRAL:TARGET vention/
30 (middle adj3 ear adj6 (tube* or S12 (MH "Acute Dis-
23 (recurrence* or recurrent or chronic or 22 (recurrence* or recur-
ventilat* or tubulation)).ti,ab. ease")
persistent or persistence or prone):AB,E- rent or chronic or per-
H,KW,KY,MC,MH,TI,TO AND CEN- sistent or persistence or S11 S7 OR S8 OR S9
31 ((tympanostomy or myringotomy
TRAL:TARGET prone).ab,ti. OR S10
or tympanic) adj6 (tube* or tubula-
23 19 or 20 or 21 or 22 tion or ventilat*)).ti,ab.
24 #20 OR #21 OR #22 OR #23 S10 TX ((otitis n3
32 "grommet*".ti,ab. media) or OME)
25 #19 AND #24 24 18 and 23
33 29 or 30 or 31 or 32 S9 TX middle n3 ear
26 MESH DESCRIPTOR Mastoiditis EX- 25 Mastoiditis/
n3 effus*
PLODE ALL AND CENTRAL:TARGET 34 28 and 33
26 (raom or mastoidi-
S8 (MH "Otitis Me-
27 (raom or mastoiditis):AB,EH,KW,KY,M- tis).ab,ti.
35 (random* or factorial* or dia with Effusion")
C,MH,TI,TO AND CENTRAL:TARGET placebo* or assign* or allocat* or OR (MH "Otitis Me-
27 24 or 25 or 26
crossover*).tw. dia")
28 #25 OR #26 OR #27
28 exp Middle Ear Venti-
lation/ 36 (control* adj group*).tw. S7 S3 AND S6
29 MESH DESCRIPTOR Middle Ear Ventila-
tion EXPLODE ALL AND CENTRAL:TARGET 37 (trial* and (control* or compara- S6 S4 OR S5
29 (middle adj3 ear adj6
(tube* or ventilat* or tive)).tw.
30 ((middle near ear near (tube* or ven- S5 TX middle n3 ear
tilat* or tubulation))):AB,EH,KW,KY,M- tubulation)).ab,ti.
38 ((blind* or mask*) and (single or
C,MH,TI,TO AND CENTRAL:TARGET double or triple or treble)).tw. S4 (MH "Ear, Mid-
30 ((tympanostomy or
dle")
31 grommet*:AB,EH,KW,KY,MC,MH,TI,TO myringotomy or tympan-
39 (treatment adj arm*).tw.
AND CENTRAL:TARGET ic) adj6 (tube* or tubula- S3 S1 OR S2
tion or ventilat*)).ab,ti. 40 (control* adj group*).tw.
32 (((tympanostomy or myringotomy or S2 TX otitis or in-
tympanic) near (tube* or tubulation or 31 "grommet*".ab,ti. 41 (phase adj (III or three)).tw. flamm* or infect* or
ventilat*))):AB,EH,KW,KY,MC,MH,TI,TO disease
32 28 or 29 or 30 or 31 42 (versus or vs).tw.
AND CENTRAL:TARGET
S1 (MH "Otitis")
33 27 and 32 43 rct.tw.
33 #29 OR #30 OR #31 OR #32
34 randomized con- 44 crossover procedure/
34 #28 AND #33
trolled trial.pt.
45 double blind procedure/
35 controlled clinical tri-
al.pt. 46 single blind procedure/
36 randomized.ab. 47 randomization/
37 placebo.ab. 48 placebo/
38 drug therapy.fs.
Informed decisions.
(Continued)
39 randomly.ab. 49 exp clinical trial/
40 trial.ab. 50 parallel design/
41 groups.ab. 51 Latin square design/
42 34 or 35 or 36 or 37 or 52 35 or 36 or 37 or 38 or 39 or 40 or
38 or 39 or 40 or 41 41 or 42 or 43 or 44 or 45 or 46 or 47
or 48 or 49 or 50 or 51
43 exp animals/ not hu-
mans.sh. 53 exp ANIMAL/ or exp NONHUMAN/
or exp ANIMAL EXPERIMENT/ or exp
44 42 not 43 ANIMAL MODEL/
45 33 and 44 54 exp human/
55 53 not 54
56 52 not 55
57 34 and 56
Cochrane ENT Register LILACS ClinicalTrials.gov ICTRP
1 otitis or inflamm* or infect* or disease ((TW:"middle ear" OR Via the Cochrane Register of Stud- rAOM OR recurren*
TW:"Oído Medio" OR ies AND AOM OR re-
2 middle near ear TW:"Orelha Média" curren* AND otitis
OR TW:tympanostomy 1 grommet OR grommets OR "tym- OR recurren* AND
3 #1 AND #2 panostomy tube" OR "tympanosto-
OR TW:myringotomy tympanitis OR otitis
OR TW:tympanic) AND my tubes" OR "myringotomy tube" AND prone
4 (otitis near media) or OME
(TW:Ventila$ OR TW:tube OR "myringotomy tubes" OR "mid-
5 middle near ear near effus* $ OR TW:tubulation)) OR dle ear tubulation" OR "tympanic
TW:grommet$ membrane ventilation" OR (mid-
6 #3 or #4 or #5 dle AND ear AND ventilation) AND
AND INSEGMENT
7 acute or suppurat* or serous or secreto-
ry or secretion* or purulent Controlled Clinical Trial 2 (nct*):AU AND INSEGMENT
8 #6 AND #7 3 #1 AND #2
9 AOM or TYMPANITIS Via ClinicalTrials.gov
10 #8 or #9 grommet OR grommets OR "tympa-

nostomy tube" OR "tympanostomy
11 recurrence* or recurrent or chronic or tubes" OR "myringotomy tube" OR
persistent or persistence or prone "myringotomy tubes" OR "middle
ear tubulation" OR "tympanic mem-
12 #10 and #11 brane ventilation" OR (middle AND
ear AND ventilation)
13 raom or mastoiditis
Study type: Interventional
14 #12 or #13
15 middle near ear near (tube* or venti-

lat* or tubulation)
16 grommet*
17 (tympanostomy or myringotomy or
tympanic) near (tube* or tubulation or
ventilat*)
18 #15 or #16 or #17
Informed decisions.
(Continued)
19 #14 and #18
FEEDBACK
Comment, 3 February 2019

Summary
I have been looking at your review on grommets as part of a dissemination project of evidence in primary care. I have to disagree with
how you have handled the number of recurrences. It is obvious from your primary meta-analysis that a large number of participants with
grommets did not have any recurrences yet when looking at the number of recurrences you have used the denominator which includes
the children without any. Thus the average number of recurrences per child is misleading. When dealing with data which can occur more
than once to a participant in a time frame you need to analyse this in such a way to deal with the within person variation. The outcome
should be mean number occurrences per person or be measured as a rate ratio and analysed using the GIV method in RevMan (please see
Cochrane handbook on how to meta analyse counts and rates). By analyzing the way you have you have assumed all individuals had a
recurrence and you estimation of this effect has been diluted. If the data has not been provided in a way that allows you to correctly analyse
it then you should leave it as a narrative rather than presenting misleading information. Although this evidence is based on only one study
(therefore deserving the low quality of evidence rating) it is of such high magnitude that I do not believe your summary is accurate. Did you
have a consumer comment on whether they thought this reduction was a meaningful difference to them? Thank you for your attention
to this issue.
Reply
Thank you for your comments. From a methodological point of view you are correct - the number of acute otitis media recurrences reflects
count data and should therefore not be analysed as continuous data; this will be addressed in a future update of the review. For now,
we have decided to leave the review unchanged because 1) this relates to a secondary outcome with low-quality evidence, so it does not
impact/change the conclusions of the review and 2) we do not feel that the current figures warrant immediate action (with the median
number of episodes closely resembling the means presented in the paper).
Contributors
Comment: Vanessa Jordan, University of Auckland
Reply: Roderick P Venekamp, Paul Mick, Anne GM Schilder and Desmond A Nunez, review authors.
WHAT'S NEW
Date Event Description
18 June 2019 Feedback has been incorporated Comment and authors' response added to review.
CONTRIBUTIONS OF AUTHORS
Drafting and final approval of protocol: all authors
Screening search results: PTM and RPV
Extracting data: PTM and RPV
Assessing risk of bias: AGMS, DAN and RPV
Entering data into RevMan: PTM and RPV
Carrying out analysis: PTM and RPV
Interpreting the analysis: all authors
General advice on the review: all authors
Informed decisions.
DECLARATIONS OF INTEREST
Roderick P Venekamp: Roderick Venekamp is an Editor for Cochrane Acute Respiratory Infections and Cochrane ENT, but had no role in
the editorial process for this review.
Paul Mick (PTM): none known.
Anne GM Schilder: Professor Anne Schilder is joint Co-ordinating Editor of Cochrane ENT, but had no role in the editorial process for this
review. Her evidENT team at UCL is supported by her NIHR Research Professorship award with the remit to develop a UK infrastructure and
programme of clinical research in ENT, Hearing and Balance. Her institution has received a grant from GSK for a study on the microbiology
of acute tympanostomy tube otorrhoea.
Desmond A Nunez (DAN): none known.
SOURCES OF SUPPORT
Internal sources
• University of British Columbia, Canada.
External sources
• National Institute for Health Research, UK.
Infrastructure funding for Cochrane ENT
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

This review has been based on a published protocol (Lau 2015). Any differences between the protocol and the review can be found below.
Types of interventions
The Types of interventions section has been rephrased for clarity. In our protocol, this section had read as follows:
Intervention
• Grommet insertion (of any type).
• Adenoidectomy is only allowed as a co-intervention when used in both treatment arms.
Comparator
The comparator will be no surgical treatment: either AOM episode-specific treatment with analgesia +/- antibiotics or antibiotic prophylaxis
for a minimum period of three months. The main comparison pair will be:
• grommet insertion versus AOM episode-specific course of analgesia with or without antibiotics.
Other possible comparison pairs include:
• grommet insertion with concurrent adenoidectomy versus adenoidectomy alone;

• grommet insertion versus antibiotic prophylaxis for a minimum period of three months.
Data collection and analysis

In the protocol, it was stated that two review authors (LL (protocol author) and PTM) would extract data and enter data into RevMan. This
has, however, been performed by three review authors (LL, PTM, RPV).
Subgroup analysis and investigation of heterogeneity

The Subgroup analysis and investigation of heterogeneity section has been rephrased for clarity. In our protocol, this section had read as:
If possible, we will perform pre-planned subgroup analyses even if statistical heterogeneity is not observed. We have planned these
analyses as the factors indicated are suspected to be potential effect modifiers. They include:
• type of surgery (grommets only versus grommets and concurrent adenoidectomy);

• presence of middle ear effusion at randomisation or at the time of surgery (yes versus no)
In addition to the subgroups above, we will conduct the following subgroup analysis in the presence of statistical heterogeneity:
Informed decisions.
• age (below two years of age versus two years and older);
• type of grommet (short-term versus intermediate/long-term).
'Summary of findings' tables

In the final review, we presented outcome data for the "total number of AOM recurrences at six to 12 months post-randomisation" in the
'Summary of findings' table for the comparison grommets versus active monitoring. This outcome was, however, initially not listed in the
'Summary of findings' section of our protocol.
NOTES
This review supersedes the earlier review 'Grommets (ventilation tubes) for recurrent acute otitis media in children' review (McDonald
2008).
INDEX TERMS
Medical Subject Headings (MeSH)

*Middle Ear Ventilation [adverse effects]; Acute Disease; Adenoidectomy; Anti-Bacterial Agents [therapeutic use]; Otitis Media with
Effusion [*therapy]; Quality of Life; Randomized Controlled Trials as Topic; Recurrence; Time Factors
MeSH check words

Adolescent; Child; Child, Preschool; Humans; Infant

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Cochrane

Grommets (ventilation tubes) for recurrent acute otitis media in

Venekamp RP, Mick P, Schilder AGM, Nunez DA

Venekamp RP, Mick P, Schilder AGM, Nunez DA.

Grommets (ventilation tubes) for recurrent acute otitis media in

Roderick P Venekamp1, Paul Mick2, Anne GM Schilder3, Desmond A Nunez2

Editorial group: Cochrane ENT Group.

Data collection and analysis

Grommets versus active monitoring

Grommets were more effective than active monitoring in terms of:

Grommets versus antibiotic prophylaxis

Grommets versus placebo medication

Grommets were more effective than placebo medication in terms of:

PLAIN LANGUAGE SUMMARY

Grommets for children with recurring acute middle ear infections

Grommets versus active monitoring

Grommets versus antibiotic prophylaxis

Grommets versus placebo drugs

Patients: children with recurrent acute otitis media

Significant adverse effect: a tympanic — 0 (0/54) n/a 54 (1 RCT) ⊕⊕⊝⊝ —

Cochrane Database of Systematic Reviews

Patients: children with recurrent acute otitis media

Cochrane Database of Systematic Reviews

Proportion of patients who Study population RR 1.68 96 ⊕⊝⊝⊝ The NNTB

GRADE Working Group grades of evidence

Patients: children with recurrent acute otitis media

Cochrane Database of Systematic Reviews

Significant adverse effect: a tym- — 4% (3/76) n/a 76 (1 RCT) ⊕⊕⊝⊝ —

Cochrane Database of Systematic Reviews

BACKGROUND surgical preference) and the grommet is placed in the incision.

Comparisons Search methods for identification of studies

• For continuous data: mean values, standard deviations and

Dealing with missing data Subgroup analysis and investigation of heterogeneity

• treatment success, defined as the proportion of children RESULTS

Figure 1. PRISMA flow diagram of search history.

Included studies background therapy and the effectiveness of grommets as add-

Allocation (performance bias) is not possible. Blinding of outcome assessment

Quality of the evidence Quality of the evidence

Quality of the evidence randomisation, "no statistically significant differences" between

For this outcome, we could combine data from two studies

Quality of the evidence Subgroup analyses

Mandel 1992 {published data only}

Teele 2000 {published data only} Bohm 2013

Ahmed 2014 Cheong 2012

Ashworth 1995 Finkelstein 2000

Bennett 2001 Fortanier 2014

Database of Systematic Reviews 2014, Issue 4. [DOI: NICE 2008

van Dongen 2014

Characteristics of included studies [ordered by study ID]

Setting of recruitment and treatment: secondary and tertiary care

• Number randomised: 86 in intervention, 90 in comparison 1, 88 in comparison 2

Participant (baseline) characteristics:

• Age: 7 months to 35 months

Interventions Intervention group: grommets (Teflon® Armstrong type)

Casselbrant 1992 (Continued)

Use of additional interventions: participants were randomly allocated to antibiotic prophylaxis or

Declarations of interest No details provided

Bias Authors' judgement Support for judgement

Allocation concealment Unclear risk Method not described

Blinding of participants High risk Not blinded