Antibiotics for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Antibiotics are sometimes used to treat any bacteria present in the effusion, or associated biofilms. OBJECTIVES: To assess the effects (benefits and harms) of oral antibiotics for otitis media with effusion (OME) in children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished studies to 20 January 2023. SELECTION CRITERIA: We included randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared oral antibiotics with either placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing, 2) otitis media-specific quality of life and 3) anaphylaxis. Secondary outcomes were: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function and 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We identified 19 completed studies that met our inclusion criteria (2581 participants). They assessed a variety of oral antibiotics (including penicillins, cephalosporins, macrolides and trimethoprim), with most studies using a 10- to 14-day treatment course. We had some concerns about the risk of bias in all studies included in this review. Here we report our primary outcomes and main secondary outcome, at the longest reported follow-up time. Antibiotics versus placebo We included 11 studies for this comparison, but none reported all of our outcomes of interest and limited meta-analysis was possible. Hearing One study found that more children may return to normal hearing by two months (resolution of the air-bone gap) after receiving antibiotics as compared with placebo, but the evidence is very uncertain (Peto odds ratio (OR) 9.59, 95% confidence interval (CI) 3.51 to 26.18; 20/49 children who received antibiotics returned to normal hearing versus 0/37 who received placebo; 1 study, 86 participants; very low-certainty evidence). Disease-specific quality of life No studies assessed this outcome. Presence/persistence of OME At 6 to 12 months of follow-up, the use of antibiotics compared with placebo may slightly reduce the number of children with persistent OME, but the confidence intervals were wide, and the evidence is very uncertain (risk ratio (RR) 0.89, 95% CI 0.68 to 1.17; 48% versus 54%; number needed to treat (NNT) 17; 2 studies, 324 participants; very low-certainty evidence). Adverse event: anaphylaxis No studies provided specific data on anaphylaxis. Three of the included studies (448 children) did report adverse events in sufficient detail to assume that no anaphylactic reactions occurred, but the evidence is very uncertain (very low-certainty evidence). Antibiotics versus no treatment We included eight studies for this comparison, but very limited meta-analysis was possible. Hearing One study found that the use of antibiotics compared to no treatment may result in little to no difference in final hearing threshold at three months (mean difference (MD) -5.38 dB HL, 95% CI -9.12 to -1.64; 1 study, 73 participants; low-certainty evidence). The only data identified on the return to normal hearing were reported at 10 days of follow-up, which we considered to be too short to accurately reflect the efficacy of antibiotics. Disease-specific quality of life No studies assessed this outcome. Presence/persistence of OME Antibiotics may reduce the proportion of children who have persistent OME at up to three months of follow-up, when compared with no treatment (RR 0.64, 95% CI 0.50 to 0.80; 6 studies, 542 participants; low-certainty evidence). Adverse event: anaphylaxis No studies provided specific data on anaphylaxis. Two of the included studies (180 children) did report adverse events in sufficient detail to assume that no anaphylactic reactions occurred, but the evidence is very uncertain (very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the use of antibiotics for OME is of low to very low certainty. Although the use of antibiotics compared to no treatment may have a slight beneficial effect on the resolution of OME at up to three months, the overall impact on hearing is very uncertain. The long-term effects of antibiotics are unclear and few of the studies included in this review reported on potential harms. These important endpoints should be considered when weighing up the potential short- and long-term benefits and harms of antibiotic treatment in a condition with a high spontaneous resolution rate.

Adenoidectomy for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to developmental delay, social difficulty and poor quality of life. Management of OME includes watchful waiting, autoinflation, medical and surgical treatment. Adenoidectomy has often been used as a potential treatment for this condition. OBJECTIVES: To assess the benefits and harms of adenoidectomy, either alone or in combination with ventilation tubes (grommets), for OME in children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 January 2023. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared adenoidectomy (alone, or in combination with ventilation tubes) with either no treatment or non-surgical treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes (determined following a multi-stakeholder prioritisation exercise): 1) hearing, 2) otitis media-specific quality of life, 3) haemorrhage. SECONDARY OUTCOMES: 1) persistence of OME, 2) adverse effects, 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial skills, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function, 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We included 10 studies (1785 children). Many of the studies used concomitant interventions for all participants, including insertion of ventilation tubes or myringotomy. All included studies had at least some concerns regarding the risk of bias. We report results for our main outcome measures at the longest available follow-up. We did not identify any data on disease-specific quality of life for any of the comparisons. Further details of additional outcomes and time points are reported in the review. 1) Adenoidectomy (with or without myringotomy) versus no treatment/watchful waiting (three studies) After 12 months there was little difference in the proportion of children whose hearing had returned to normal, but the evidence was very uncertain (adenoidectomy 68%, no treatment 70%; risk ratio (RR) 0.97, 95% confidence interval (CI) 0.65 to 1.46; number needed to treat to benefit (NNTB) 50; 1 study, 42 participants). There is a risk of haemorrhage from adenoidectomy, but the absolute risk appears small (1/251 receiving adenoidectomy compared to 0/229, Peto odds ratio (OR) 6.77, 95% CI 0.13 to 342.54; 1 study, 480 participants; moderate certainty evidence). The risk of persistent OME may be slightly lower after two years in those receiving adenoidectomy (65% versus 73%), but again the difference was small (RR 0.90, 95% CI 0.81 to 1.00; NNTB 13; 3 studies, 354 participants; very low-certainty evidence). 2) Adenoidectomy (with or without myringotomy) versus non-surgical treatment No studies were identified for this comparison. 3) Adenoidectomy and bilateral ventilation tubes versus bilateral ventilation tubes (four studies) There was a slight increase in the proportion of ears with a return to normal hearing after six to nine months (57% adenoidectomy versus 42% without, RR 1.36, 95% CI 0.98 to 1.89; NNTB 7; 1 study, 127 participants (213 ears); very low-certainty evidence). Adenoidectomy may give an increased risk of haemorrhage, but the absolute risk appears small, and the evidence was uncertain (2/416 with adenoidectomy compared to 0/375 in the control group, Peto OR 6.68, 95% CI 0.42 to 107.18; 2 studies, 791 participants). The risk of persistent OME was similar for both groups (82% adenoidectomy and ventilation tubes compared to 85% ventilation tubes alone, RR 0.96, 95% CI 0.86 to 1.07; very low-certainty evidence). 4) Adenoidectomy and unilateral ventilation tube versus unilateral ventilation tube (two studies) Slightly more children returned to normal hearing after adenoidectomy, but the confidence intervals were wide (57% versus 46%, RR 1.24, 95% CI 0.79 to 1.96; NNTB 9; 1 study, 72 participants; very low-certainty evidence). Fewer children may have persistent OME after 12 months, but again the confidence intervals were wide (27.2% compared to 40.5%, RR 0.67, 95% CI 0.35 to 1.29; NNTB 8; 1 study, 74 participants). We did not identify any data on haemorrhage. 5) Adenoidectomy and ventilation tubes versus no treatment/watchful waiting (two studies) We did not identify data on the proportion of children who returned to normal hearing. However, after two years, the mean difference in hearing threshold for those allocated to adenoidectomy was -3.40 dB (95% CI -5.54 to -1.26; 1 study, 211 participants; very low-certainty evidence). There may be a small reduction in the proportion of children with persistent OME after two years, but the evidence was very uncertain (82% compared to 90%, RR 0.91, 95% CI 0.82 to 1.01; NNTB 13; 1 study, 232 participants). We noted that many children in the watchful waiting group had also received surgery by this time point. 6) Adenoidectomy and ventilation tubes versus non-surgical treatment No studies were identified for this comparison. AUTHORS' CONCLUSIONS: When assessed with the GRADE approach, the evidence for adenoidectomy in children with OME is very uncertain. Adenoidectomy may reduce the persistence of OME, although evidence about the effect of this on hearing is unclear. For patients and carers, a return to normal hearing is likely to be important, but few studies measured this outcome. We did not identify any evidence on disease-specific quality of life. There were few data on adverse effects, in particular postoperative bleeding. The risk of haemorrhage appears to be small, but should be considered when choosing a treatment strategy for children with OME. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children.

Autoinflation for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. When persistent, it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and mechanical treatment. Autoinflation is a self-administered technique, which aims to ventilate the middle ear and encourage middle ear fluid clearance by providing a positive pressure of air in the nose and nasopharynx (using a nasal balloon or other handheld device). This positive pressure (sometimes combined with simultaneous swallow) encourages opening of the Eustachian tube and may help ventilate the middle ear. OBJECTIVES: To assess the efficacy (benefits and harms) of autoinflation for the treatment of otitis media with effusion in children. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 January 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared autoinflation with either watchful waiting (no treatment), non-surgical treatment or ventilation tubes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing, 2) OME-specific quality of life and 3) pain and distress. Secondary outcomes were: 1) persistence of OME, 2) other adverse effects (including eardrum perforation), 3) compliance or adherence to treatment, 4) receptive language skills, 5) speech development, 6) cognitive development, 7) psychosocial skills, 8) listening skills, 9) generic health-related quality of life, 10) parental stress, 11) vestibular function and 12) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for each outcome. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We identified 11 completed studies that met our inclusion criteria (1036 participants). The majority of studies included children aged between 3 and 11 years. Most were carried out in Europe or North America, and they were conducted in both hospital and community settings. All compared autoinflation (using a variety of different methods and devices) to no treatment. Most studies required children to carry out autoinflation two to three times per day, for between 2 and 12 weeks. The outcomes were predominantly assessed just after the treatment phase had been completed. Here we report the effects at the longest follow-up for our main outcome measures. Return to normal hearing The evidence was very uncertain regarding the effect of autoinflation on the return to normal hearing. The longest duration of follow-up was 11 weeks. At this time point, the risk ratio was 2.67 in favour of autoinflation (95% confidence interval (CI) 1.73 to 4.12; 85% versus 32%; number needed to treat to benefit (NNTB) 2; 1 study, 94 participants), but the certainty of the evidence was very low. Disease-specific quality of life Autoinflation may result in a moderate improvement in quality of life (related to otitis media) after short-term follow-up. One study assessed quality of life using the Otitis Media Questionnaire-14 (OMQ-14) at three months of follow-up. Results were reported as the number of standard deviations above or below zero difference, with a range from -3 (better) to +3 (worse). The mean difference was -0.42 lower (better) for those who received autoinflation (95% CI -0.62 to -0.22; 1 study, 247 participants; low-certainty evidence; the authors report a change of 0.3 as clinically meaningful). Pain and distress caused by the procedure Autoinflation may result in an increased risk of ear pain, but the evidence was very uncertain. One study assessed this outcome, and identified a risk ratio of 3.50 for otalgia in those who received autoinflation, although the overall occurrence of pain was low (95% CI 0.74 to 16.59; 4.4% versus 1.3%; number needed to treat to harm (NNTH) 32; 1 study, 320 participants; very low-certainty evidence). Persistence of OME The evidence suggests that autoinflation may slightly reduce the persistence of OME at three months. Four studies were included, and the risk ratio for persistence of OME was 0.88 for those receiving autoinflation (95% CI 0.80 to 0.97; 4 studies, 483 participants; absolute reduction of 89 people per 1000 with persistent OME; NNTB 12; low-certainty evidence). AUTHORS' CONCLUSIONS: All the evidence we identified was of low or very low certainty, meaning that we have little confidence in the estimated effects. However, the data suggest that autoinflation may have a beneficial effect on OME-specific quality of life and persistence of OME in the short term, but the effect is uncertain for return to normal hearing and adverse effects. The potential benefits should be weighed against the inconvenience of regularly carrying out autoinflation, and the possible risk of ear pain.

Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is one of the most common childhood infectious diseases. Pain is the key symptom of AOM and central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management. This is an update of a review first published in 2016. OBJECTIVES: Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs as compared with paracetamol in children with AOM. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 5, April 2023; MEDLINE (Ovid, from 1946 to May 2023), Embase (from 1947 to May 2023), CINAHL (from 1981 to May 2023), LILACS (from 1982 to May 2023), and Web of Science Core Collection (from 1955 to May 2023). We searched the WHO ICTRP and ClinicalTrials.gov for completed and ongoing trials (23 May 2023). SELECTION CRITERIA: We included randomised controlled trials comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in non-hospitalised children aged six months to 16 years with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. We extracted and summarised data for the following comparisons: paracetamol versus placebo, NSAIDs versus placebo, NSAIDs versus paracetamol, and NSAIDs plus paracetamol versus paracetamol alone. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We rated the overall certainty of evidence for each outcome of interest using the GRADE approach. MAIN RESULTS: We included four trials (411 children) which were assessed at low to high risk of bias. Paracetamol versus placebo Data from one trial (148 children) informed this comparison. Paracetamol may be more effective than placebo in relieving pain at 48 hours (proportion of children with pain 10% versus 25%, risk ratio (RR) 0.38, 95% confidence interval (CI) 0.17 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 7; low-certainty evidence). The evidence is very uncertain about the effects of paracetamol on fever at 48 hours (RR 1.03, 95% CI 0.07 to 16.12; very low-certainty evidence) and adverse events (RR 1.03, 95% CI 0.21 to 4.93; very low-certainty evidence). No data were available for our other outcomes of interest. NSAIDs versus placebo Data from one trial (146 children) informed this comparison. Ibuprofen may be more effective than placebo in relieving pain at 48 hours (proportion of children with pain 7% versus 25%, RR 0.28, 95% CI 0.11 to 0.70; NNTB 6; low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen on fever at 48 hours (RR 1.06, 95% CI 0.07 to 16.57; very low-certainty evidence) and adverse events (RR 1.76, 95% CI 0.44 to 7.10; very low-certainty evidence). No data were available for our other outcomes of interest. NSAIDs versus paracetamol Data from four trials (411 children) informed this comparison. The evidence is very uncertain about the effect of ibuprofen versus paracetamol in relieving ear pain at 24 hours (RR 0.83, 95% CI 0.59 to 1.18; 2 RCTs, 39 children; very low-certainty evidence); 48 to 72 hours (RR 0.91, 95% CI 0.54 to 1.54; 3 RCTs, 183 children; low-certainty evidence); and four to seven days (RR 0.74, 95% CI 0.17 to 3.23; 2 RCTs, 38 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol on mean pain score at 24 hours (0.29 lower, 95% CI 0.79 lower to 0.20 higher; 3 RCTs, 111 children; very low-certainty evidence); 48 to 72 hours (0.25 lower, 95% CI 0.66 lower to 0.16 higher; 3 RCTs, 108 children; very low-certainty evidence); and four to seven days (0.30 higher, 95% CI 1.78 lower to 2.38 higher; 2 RCTs, 31 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol in resolving fever at 24 hours (RR 0.69, 95% CI 0.24 to 2.00; 2 RCTs, 39 children; very low-certainty evidence); 48 to 72 hours (RR 1.18, 95% CI 0.31 to 4.44; 3 RCTs, 182 children; low-certainty evidence); and four to seven days (RR 2.75, 95% CI 0.12 to 60.70; 2 RCTs, 39 children; very low-certainty evidence). The evidence is very uncertain about the effect of ibuprofen versus paracetamol on adverse events (RR 1.71, 95% CI 0.43 to 6.90; 3 RCTs, 281 children; very low-certainty evidence); reconsultations (RR 1.13, 95% CI 0.92 to 1.40; 1 RCT, 53 children; very low-certainty evidence); and delayed antibiotic prescriptions (RR 1.32, 95% CI 0.74 to 2.35; 1 RCT, 53 children; very low-certainty evidence). No data were available on time to resolution of pain. NSAIDs plus paracetamol versus paracetamol alone Data on the effectiveness of ibuprofen plus paracetamol versus paracetamol alone came from two trials that provided crude subgroup data for 71 children with AOM. The small sample provided imprecise effect estimates, therefore we were unable to draw any firm conclusions (very low-certainty evidence). AUTHORS' CONCLUSIONS: Despite explicit guideline recommendations on the use of analgesics in children with AOM, the current evidence on the effectiveness of paracetamol or NSAIDs, alone or combined, in children with AOM is limited. Paracetamol and ibuprofen as monotherapies may be more effective than placebo in relieving short-term ear pain in children with AOM. The evidence is very uncertain for the effect of ibuprofen versus paracetamol on relieving short-term ear pain in children with AOM, as well as for the effectiveness of ibuprofen plus paracetamol versus paracetamol alone, thereby preventing any firm conclusions. Further research is needed to provide insights into the role of ibuprofen as adjunct to paracetamol, and other analgesics such as anaesthetic eardrops, for children with AOM.

Topical and oral steroids for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. The fluid may cause hearing loss. Although most episodes of OME in children resolve spontaneously within a few months, when persistent it may lead to behavioural problems and a delay in expressive language skills. Management of OME includes watchful waiting, medical, surgical and other treatments, such as autoinflation. Oral or topical steroids are sometimes used to reduce inflammation in the middle ear. OBJECTIVES: To assess the effects (benefits and harms) of topical and oral steroids for OME in children. SEARCH METHODS: We searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished studies on 20 January 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-randomised trials in children aged 6 months to 12 years with unilateral or bilateral OME. We included studies that compared topical or oral steroids with either placebo or watchful waiting (no treatment). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes, determined by a multi-stakeholder prioritisation exercise, were: 1) hearing, 2) OME-specific quality of life and 3) systemic corticosteroid side effects. Secondary outcomes were: 1) presence/persistence of OME, 2) other adverse effects (including local nasal effects), 3) receptive language skills, 4) speech development, 5) cognitive development, 6) psychosocial outcomes, 7) listening skills, 8) generic health-related quality of life, 9) parental stress, 10) vestibular function and 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method to assess hearing, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We included 26 studies in this review (2770 children). Most studies of oral steroids used prednisolone for 7 to 14 days. Studies of topical (nasal) steroids used various preparations (beclomethasone, fluticasone and mometasone) for between two weeks and three months. All studies had at least some concerns regarding risk of bias. Here we report our primary outcomes and main secondary outcome, at the longest reported follow-up. Oral steroids compared to placebo Oral steroids probably result in little or no difference in the proportion of children with normal hearing after 12 months (69.7% of children with steroids, compared to 61.1% of children receiving placebo, risk ratio (RR) 1.14, 95% confidence interval (CI) 0.97 to 1.33; 1 study, 332 participants; moderate-certainty evidence). There is probably little or no difference in OME-related quality of life (mean difference (MD) in OM8-30 score 0.07, 95% CI -0.2 to 0.34; 1 study, 304 participants; moderate-certainty evidence). Oral steroids may reduce the number of children with persistent OME at 6 to 12 months, but the size of the effect was uncertain (absolute risk reduction ranging from 13.3% to 45%, number needed to treat (NNT) of between 3 and 8; low-certainty evidence). The evidence was very uncertain regarding the risk of systemic corticosteroid side effects, and we were unable to conduct any meta-analysis for this outcome. Oral steroids compared to no treatment Oral steroids may result in little or no difference in the persistence of OME after three to nine months (74.5% children receiving steroids versus 73% of those receiving placebo; RR 1.02, 95% CI 0.89 to 1.17; 2 studies, 258 participants; low-certainty evidence). The evidence on adverse effects was very uncertain. We did not identify any evidence on hearing or disease-related quality of life. Topical (intranasal) steroids compared to placebo We did not identify data on the proportion of children who returned to normal hearing. However, the mean change in hearing threshold after two months was -0.3 dB lower (95% CI -6.05 to 5.45; 1 study, 78 participants; very low-certainty evidence). The evidence suggests that nasal steroids make little or no difference to disease-specific quality of life after nine months (OM8-30 score, MD 0.05 higher, 95% CI -0.36 to 0.46; 1 study, 82 participants; low-certainty evidence). The evidence is very uncertain regarding the effect of nasal steroids on persistence of OME at up to one year. Two studies reported this: one showed a potential benefit for nasal steroids, the other showed a benefit with placebo (2 studies, 206 participants). The evidence was also very uncertain regarding the risk of corticosteroid-related side effects, as we were unable to provide a pooled effect estimate. Topical (intranasal) steroids compared to no treatment We did not identify data on the proportion of children who returned to normal hearing. However, the mean difference in final hearing threshold after four weeks was 1.95 dB lower (95% CI -3.85 to -0.05; 1 study, 168 participants; low-certainty evidence). Nasal steroids may reduce the persistence of OME after eight weeks, but the evidence was very uncertain (58.5% of children receiving steroids, compared to 81.3% of children without treatment, RR 0.72, 95% CI 0.57 to 0.91; 2 studies, 134 participants). We did not identify any evidence on disease-related quality of life or adverse effects. AUTHORS' CONCLUSIONS: Overall, oral steroids may have little effect in the treatment of OME, with little improvement in the number of children with normal hearing and no effect on quality of life. There may be a reduction in the proportion of children with persistent disease after 12 months. However, this benefit may be small and must be weighed against the potential for adverse effects associated with oral steroid use. The evidence for nasal steroids was all low- or very low-certainty. It is therefore less clear if nasal steroids have any impact on hearing, quality of life or persistence of OME. Evidence on adverse effects was very limited. OME is likely to resolve spontaneously for most children. The potential benefit of treatment may therefore be small and should be balanced with the risk of adverse effects. Future studies should aim to determine which children are most likely to benefit from treatment, rather than offering interventions to all children.

Ventilation tubes (grommets) for otitis media with effusion (OME) in children.

BACKGROUND: Otitis media with effusion (OME) is an accumulation of fluid in the middle ear cavity, common amongst young children. It may cause hearing loss which, when persistent, may lead to developmental delay, social difficulty and poor quality of life. Management includes watchful waiting, autoinflation, medical and surgical treatment. Insertion of ventilation tubes has often been used as the preferred treatment. OBJECTIVES: To evaluate the effects (benefits and harms) of ventilation tubes (grommets) for OME in children. SEARCH METHODS: We searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science, ClinicalTrials.gov, ICTRP and additional sources for published and unpublished trials on 20 January 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in children (6 months to 12 years) with OME for ≥ 3 months. We included studies that compared ventilation tube (VT) insertion with five comparators: no treatment, watchful waiting (ventilation tubes inserted later, if required), myringotomy, hearing aids and other non-surgical treatments. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were determined following a multi-stakeholder prioritisation exercise and were: 1) hearing; 2) OME-specific quality of life; 3) persistent tympanic membrane perforation (as a severe adverse effect of the surgery). Secondary outcomes were: 1) persistence of OME; 2) other adverse effects (including tympanosclerosis, VT blockage and pain); 3) receptive language skills; 4) speech development; 5) cognitive development; 6) psychosocial skills; 7) listening skills; 8) generic health-related quality of life; 9) parental stress; 10) vestibular function; 11) episodes of acute otitis media. We used GRADE to assess the certainty of evidence for key outcomes. Although we included all measures of hearing assessment, the proportion of children who returned to normal hearing was our preferred method, due to challenges in interpreting the results of mean hearing thresholds. MAIN RESULTS: We included 19 RCTs (2888 children). We considered most of the evidence to be very uncertain, due to wide confidence intervals for the effect estimates, few participants, and a risk of performance and detection bias. Here we report our key outcomes at the longest reported follow-up. There were some limitations to the evidence. No studies investigated the comparison of ventilation tubes versus hearing aids. We did not identify any data on disease-specific quality of life; however, many studies were conducted before the development of specific tools to assess this in otitis media. Short-acting ventilation tubes were used in most studies and thus specific data on the use of long-acting VTs is limited. Finally, we did not identify specific data on the effects of VTs in children at increased risk of OME (e.g. with craniofacial syndromes). Ventilation tubes versus no treatment (four studies) The odds ratio (OR) for a return to normal hearing after 12 months was 1.13 with VTs (95% confidence interval (CI) 0.46 to 2.74; 54% versus 51%; 1 study, 72 participants; very low-certainty evidence). At six months, VTs may lead to a large reduction in persistent OME (risk ratio (RR) 0.30, 95% CI 0.14 to 0.65; 20.4% versus 68.0%; 1 study, 54 participants; low-certainty evidence). The evidence is very uncertain about the chance of persistent tympanic membrane perforation with VTs at 12 months (OR 0.85, 95% CI 0.38 to 1.91; 8.3% versus 9.7%; 1 RCT, 144 participants). Early ventilation tubes versus watchful waiting (six studies) There was little to no difference in the proportion of children whose hearing returned to normal after 8 to 10 years (i.e. by the age of 9 to 13 years) (RR for VTs 0.98, 95% CI 0.94 to 1.03; 93% versus 95%; 1 study, 391 participants; very low-certainty evidence). VTs may also result in little to no difference in the risk of persistent OME after 18 months to 6 years (RR 1.21, 95% CI 0.84 to 1.74; 15% versus 12%; 3 studies, 584 participants; very low-certainty evidence). We were unable to pool data on persistent perforation. One study showed that VTs may increase the risk of perforation after a follow-up duration of 3.75 years (RR 3.65, 95% CI 0.41 to 32.38; 1 study, 391 participants; very low-certainty evidence) but the actual number of children who develop persistent perforation may be low, as demonstrated by another study (1.26%; 1 study, 635 ears; very low-certainty evidence). Ventilation tubes versus non-surgical treatment (one study) One study compared VTs to six months of antibiotics (sulphisoxazole). No data were available on return to normal hearing, but final hearing thresholds were reported. At four months, the mean difference was -5.98 dB HL lower (better) for those receiving VTs, but the evidence is very uncertain (95% CI -9.21 to -2.75; 1 study, 125 participants; very low-certainty evidence). No evidence was identified regarding persistent OME. VTs may result in a low risk of persistent perforation at 18 months of follow-up (no events reported; narrative synthesis of 1 study, 60 participants; low-certainty evidence). Ventilation tubes versus myringotomy (nine studies) We are uncertain whether VTs may slightly increase the likelihood of returning to normal hearing at 6 to 12 months, since the confidence intervals were wide and included the possibility of no effect (RR 1.22, 95% CI 0.59 to 2.53; 74% versus 64%; 2 studies, 132 participants; very low-certainty evidence). After six months, persistent OME may be reduced for those who receive VTs compared to laser myringotomy, but the evidence is very uncertain (OR 0.27, 95% CI 0.19 to 0.38; 1 study, 272 participants; very low-certainty evidence). At six months, the risk of persistent perforation is probably similar with the use of VTs or laser myringotomy (narrative synthesis of 6 studies, 581 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There may be small short- and medium-term improvements in hearing and persistence of OME with VTs, but it is unclear whether these persist after longer follow-up. The RCTs included do not allow us to say when (or how much) VTs improve hearing in any specific child. However, interpretation of the evidence is difficult: many children in the control groups recover spontaneously or receive VTs during follow-up, VTs may block or extrude, and OME may recur. The limited evidence in this review also affects the generalisability/applicability of our findings to situations involving children with underlying conditions (e.g. craniofacial syndromes) or the use of long-acting tubes. Consequently, RCTs may not be the best way to determine whether an intervention is likely to be effective in any individual child. Instead, we must better understand the different OME phenotypes to target interventions to children who will benefit most, and avoid over-treating when spontaneous resolution is likely.

Intratympanic corticosteroids for sudden sensorineural hearing loss.

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is common, and defined as a sudden decrease in sensorineural hearing sensitivity of unknown aetiology. Systemic corticosteroids are widely used, however their value remains unclear. Intratympanic injections of corticosteroids have become increasingly common in the treatment of ISSNHL. OBJECTIVES: To assess the effects of intratympanic corticosteroids in people with ISSNHL. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2021, Issue 9); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials (search date 23 September 2021). SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving people with ISSNHL and follow-up of over a week. Intratympanic corticosteroids were given as primary or secondary treatment (after failure of systemic therapy). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, including GRADE to assess the certainty of the evidence. Our primary outcome was change in hearing threshold with pure tone audiometry. Secondary outcomes included the proportion of people whose hearing improved, final hearing threshold, speech audiometry, frequency-specific hearing changes and adverse effects. MAIN RESULTS: We included 30 studies, comprising 2133 analysed participants. Some studies had more than two treatment arms and were therefore relevant to several comparisons. Studies investigated intratympanic corticosteroids as either primary (initial) therapy or secondary (rescue) therapy after failure of initial treatment. 1. Intratympanic corticosteroids versus systemic corticosteroids as primary therapy We identified 16 studies (1108 participants). Intratympanic therapy may result in little to no improvement in the change in hearing threshold (mean difference (MD) -5.93 dB better, 95% confidence interval (CI) -7.61 to -4.26; 10 studies; 701 participants; low-certainty). We found little to no difference in the proportion of participants whose hearing was improved (risk ratio (RR) 1.04, 95% CI 0.97 to 1.12; 14 studies; 972 participants; moderate-certainty). Intratympanic therapy may result in little to no difference in the final hearing threshold (MD -3.31 dB, 95% CI -6.16 to -0.47; 7 studies; 516 participants; low-certainty). Intratympanic therapy may increase the number of people who experience vertigo or dizziness (RR 2.53, 95% CI 1.41 to 4.54; 1 study; 250 participants; low-certainty) and probably increases the number of people with ear pain (RR 15.68, 95% CI 6.22 to 39.49; 2 studies; 289 participants; moderate-certainty). It also resulted in persistent tympanic membrane perforation (range 0% to 3.9%; 3 studies; 359 participants; very low-certainty), vertigo/dizziness at the time of injection (1% to 21%, 3 studies; 197 participants; very low-certainty) and ear pain at the time of injection (10.5% to 27.1%; 2 studies; 289 participants; low-certainty). 2. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy We identified 10 studies (788 participants). Combined therapy may have a small effect on the change in hearing threshold (MD -8.55 dB better, 95% CI -12.48 to -4.61; 6 studies; 435 participants; low-certainty). The evidence is very uncertain as to whether combined therapy changes the proportion of participants whose hearing is improved (RR 1.27, 95% CI 1.15 to 1.41; 10 studies; 788 participants; very low-certainty). Combined therapy may result in slightly lower (more favourable) final hearing thresholds but the evidence is very uncertain, and it is not clear whether the change would be important to patients (MD -9.11 dB, 95% CI -16.56 to -1.67; 3 studies; 194 participants; very low-certainty). Some adverse effects only occurred in those who received combined therapy. These included persistent tympanic membrane perforation (range 0% to 5.5%; 5 studies; 474 participants; very low-certainty), vertigo or dizziness at the time of injection (range 0% to 8.1%; 4 studies; 341 participants; very low-certainty) and ear pain at the time of injection (13.5%; 1 study; 73 participants; very low-certainty).  3. Intratympanic corticosteroids versus no treatment or placebo as secondary therapy We identified seven studies (279 participants). Intratympanic therapy may have a small effect on the change in hearing threshold (MD -9.07 dB better, 95% CI -11.47 to -6.66; 7 studies; 280 participants; low-certainty). Intratympanic therapy may result in a much higher proportion of participants whose hearing is improved (RR 5.55, 95% CI 2.89 to 10.68; 6 studies; 232 participants; low-certainty). Intratympanic therapy may result in lower (more favourable) final hearing thresholds (MD -11.09 dB, 95% CI -17.46 to -4.72; 5 studies; 203 participants; low-certainty). Some adverse effects only occurred in those who received intratympanic injection. These included persistent tympanic membrane perforation (range 0% to 4.2%; 5 studies; 185 participants; very low-certainty), vertigo or dizziness at the time of injection (range 6.7% to 33%; 3 studies; 128 participants; very low-certainty) and ear pain at the time of injection (0%; 1 study; 44 participants; very low-certainty).  4. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy We identified one study with 76 participants. Change in hearing threshold was not reported. Combined therapy may result in a higher proportion with hearing improvement, but the evidence is very uncertain (RR 2.24, 95% CI 1.10 to 4.55; very low-certainty). Adverse effects were poorly reported with only data for persistent tympanic membrane perforation (rate 8.1%, very low-certainty). AUTHORS' CONCLUSIONS: Most of the evidence in this review is low- or very low-certainty, therefore it is likely that further studies may change our conclusions.   For primary therapy, intratympanic corticosteroids may have little or no effect compared with systemic corticosteroids. There may be a slight benefit from combined treatment when compared with systemic treatment alone, but the evidence is uncertain. For secondary therapy, there is low-certainty evidence that intratympanic corticosteroids, when compared to no treatment or placebo, may result in a much higher proportion of participants whose hearing is improved, but may only have a small effect on the change in hearing threshold. It is very uncertain whether there is additional benefit from combined treatment over systemic steroids alone. Although adverse effects were poorly reported, the different risk profiles of intratympanic treatment (including tympanic membrane perforation, pain and dizziness/vertigo) and systemic treatment (for example, blood glucose problems) should be considered when selecting appropriate treatment.

Systemic antibiotics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a chronic inflammation and infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Systemic antibiotics are a commonly used treatment option for CSOM, which act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be used alone or in addition to other treatments for CSOM. OBJECTIVES: To assess the effects of systemic antibiotics for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials comparing systemic antibiotics (oral, injection) against placebo/no treatment or other systemic antibiotics with at least a one-week follow-up period, involving patients with chronic (at least two weeks) ear discharge of unknown cause or due to CSOM. Other treatments were allowed if both treatment and control arms also received it. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not, measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks); health-related quality of life using a validated instrument; ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: We included 18 studies (2135 participants) with unclear or high risk of bias. 1. Systemic antibiotics versus no treatment/placebo It is very uncertain if there is a difference between systemic (intravenous) antibiotics and placebo in the resolution of ear discharge at between one and two weeks (risk ratio (RR) 8.47, 95% confidence interval (CI) 1.88 to 38.21; 33 participants; 1 study; very low-certainty evidence). The study did not report results for resolution of ear discharge after two weeks. Health-related quality of life was not reported. The evidence is very uncertain for hearing and serious (intracranial) complications. Ear pain and suspected ototoxicity were not reported. 2. Systemic antibiotics versus no treatment/placebo (both study arms received topical antibiotics) Six studies were included of which five presented useable data. There may be little or no difference in the resolution of ear discharge at between one to two weeks for oral ciprofloxacin compared to placebo or no treatment when ciprofloxacin ear drops were used in both intervention arms (RR 1.02, 95% CI 0.93 to 1.12; 390 participants; low-certainty evidence). No results after two weeks were reported. Health-related quality of life was not reported. The evidence is very uncertain for ear pain, serious complications and suspected ototoxicity. 3. Systemic antibiotics versus no treatment/placebo (both study arms received other background treatments) Two studies used topical antibiotics plus steroids as background treatment in both arms. It is very uncertain if there is a difference in resolution of ear discharge between metronidazole and placebo at four weeks (RR 0.91, 95% CI 0.51 to 1.65; 40 participants; 1 study; very low-certainty evidence). This study did not report other outcomes. It is also very uncertain if resolution of ear discharge at six weeks was improved with co-trimoxazole compared to placebo (RR 1.54, 95% CI 1.09 to 2.16; 98 participants; 1 study; very low-certainty evidence). Resolution of ear discharge was not reported at other time points. From the narrative report there was no evidence of a difference between groups for health-related quality of life, hearing or serious complications (very low-certainty evidence). One study (136 participants) used topical antiseptics as background treatment in both arms and found similar resolution of ear discharge between the amoxicillin and no treatment groups at three to four months (RR 1.03, 95% CI 0.75 to 1.41; 136 participants; 1 study; very low-certainty evidence). The narrative report indicated no evidence of differences in hearing or suspected ototoxicity (both very low-certainty evidence). No other outcomes were reported. 4. Different types of systemic antibiotics This is a summary of four comparisons, where different antibiotics were compared to each other. Eight studies compared different types of systemic antibiotics against each other: quinolones against beta-lactams (four studies), lincosamides against nitroimidazoles (one study) and comparisons of different types of beta-lactams (three studies). It was not possible to conclude if there was one class or type of systemic antibiotic that was better in terms of resolution of ear discharge. The studies did not report adverse events well. AUTHORS' CONCLUSIONS: There was a limited amount of evidence available to examine whether systemic antibiotics are effective in achieving resolution of ear discharge for people with CSOM. When used alone (with or without aural toileting), we are very uncertain if systemic antibiotics are more effective than placebo or no treatment. When added to an effective intervention such as topical antibiotics, there seems to be little or no difference in resolution of ear discharge (low-certainty evidence). Data were only available for certain classes of antibiotics and it is very uncertain whether one class of systemic antibiotic may be more effective than another. Adverse effects of systemic antibiotics were poorly reported in the studies included. As we found very sparse evidence for their efficacy, the possibility of adverse events may detract from their use for CSOM.

Topical versus systemic antibiotics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Antibiotics are the most common treatment for CSOM, which act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be administered both topically and systemically, and can be used alone or in addition to other treatments for CSOM such as ear cleaning (aural toileting). OBJECTIVES: To assess the effects of topical versus systemic antibiotics for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The studies compared topical antibiotics against systemic (oral, injection) antibiotics. We separated studies according to whether they compared the same type of antibiotic in both treatment groups, or different types of antibiotics. For each comparison we considered whether there was background treatment for both treatment groups, for example aural toileting (ear cleaning). DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not, measured at between one week and up to two weeks, two weeks up to four weeks, and after four weeks), health-related quality of life using a validated instrument, ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: Six studies (445 participants), all with high risk of bias, were included. All but two studies included patients with confirmed CSOM, where perforation of the ear drum was clearly documented. None of the studies reported results for resolution of ear discharge after four weeks or health-related quality of life. 1. Topical versus systemic administration of the same type of antibiotics (quinolones) Four studies (325 participants) compared topical versus systemic (oral) administration of ciprofloxacin. Three studies reported resolution of ear discharge at one to two weeks and found that the topical administration may slightly increase resolution (risk ratio (RR) 1.48, 95% confidence interval (CI) 1.24 to 1.76; 285 participants; 3 studies; I2 = 0%; low-certainty evidence). In these studies, aural toileting was either not mentioned, or limited to the first visit. Three studies (265 participants) reported that they did not suspect ototoxicity in any participants, but it is unclear how this was measured (very low-certainty evidence). No studies reported the outcomes of ear pain or serious complications. No studies reported results for hearing, despite it being measured in three studies. 2. Topical versus systemic administration of different types of antibiotics (quinolones versus aminoglycosides) One study (60 participants) compared topical ciprofloxacin versus gentamicin injected intramuscularly. No aural toileting was reported. Resolution of ear discharge was not measured at one to two weeks. The study did not report any 'side effects' from which we assumed that no ear pain, suspected ototoxicity or serious complications occurred (very low-certainty evidence). The study stated that "no worsening of the audiometric function related to local or parenteral therapy was observed". 3. Topical versus systemic administration of different types of antibiotics (quinolones versus amoxicillin-clavulanic acid) One study compared topical ofloxacin with amoxicillin-clavulanic acid with all participants receiving suction ear cleaning at the first visit. It is uncertain if there is a difference between the two groups in resolution of ear discharge at one to two weeks due to study limitations and the very small sample size (RR 2.93, 95% CI 1.50 to 5.72; 56 participants; very low-certainty evidence). It is unclear if there is a difference between topical quinolone compared with oral amoxicillin-clavulanic acid with regards to ear pain, hearing or suspected ototoxicity (very low-certainty evidence). No studies reported the outcome of serious complications. AUTHORS' CONCLUSIONS: There was a limited amount of low-quality evidence available, from studies completed over 15 years ago, to examine whether topical or systemic antibiotics are more effective in achieving resolution of ear discharge for people with CSOM. However, amongst this uncertainty there is some evidence to suggest that the topical administration of antibiotics may be more effective than systemic administration of antibiotics in achieving resolution of ear discharge (dry ear). There is limited evidence available regarding different types of antibiotics. It is not possible to determine with any certainty whether or not topical quinolones are better or worse than systemic aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.

Tonsillectomy versus tonsillotomy for obstructive sleep-disordered breathing in children.

BACKGROUND: Obstructive sleep-disordered breathing (oSDB) is a condition encompassing breathing problems when asleep due to upper airway obstruction. In children, hypertrophy of the tonsils and/or adenoids is thought to be the commonest cause. As such, (adeno)tonsillectomy has long been the treatment of choice. A rise in partial removal of the tonsils over the last decade is due to the hypothesis that tonsillotomy is associated with lower postoperative morbidity and fewer complications. OBJECTIVES: To assess whether partial removal of the tonsils (intracapsular tonsillotomy) is as effective as total removal of the tonsils (extracapsular tonsillectomy) in relieving signs and symptoms of oSDB in children, and has lower postoperative morbidity and fewer complications. SEARCH METHODS: We searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 22 July 2019. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effectiveness of (adeno)tonsillectomy with (adeno)tonsillotomy in children aged 2 to 16 years with oSDB. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and assessed the certainty of the evidence for our pre-defined outcomes using GRADE. Our primary outcomes were disease-specific quality of life, peri-operative blood loss and the proportion of children requiring postoperative medical intervention (with or without hospitalisation). Secondary outcomes included postoperative pain, return to normal activity, recurrence of oSDB symptoms as a result of tonsil regrowth and reoperation rates. MAIN RESULTS: We included 22 studies (1984 children), with predominantly unclear or high risk of bias. Three studies used polysomnography as part of their inclusion criteria. Follow-up duration ranged from six days to six years. Although 19 studies reported on some of our outcomes, we could only pool the results from a few due both to the variety of outcomes and the measurement instruments used, and an absence of combinable data. Disease-specific quality of life Four studies (540 children; 484 (90%) analysed) reported this outcome; data could not be pooled due to the different outcome measurement instruments used. It is very uncertain whether there is any difference in disease-specific quality of life between the two surgical procedures in the short (0 to 6 months; 3 studies, 410 children), medium (7 to 13 months; 2 studies, 117 children) and long term (13 to 24 months; 1 study, 67 children) (very low-certainty evidence). Peri-operative blood loss We are uncertain whether tonsillotomy reduces peri-operative blood loss by a clinically meaningful amount (mean difference (MD) 14.06 mL, 95% CI 1.91 to 26.21 mL; 8 studies, 610 children; very low-certainty evidence). In sensitivity analysis (restricted to three studies with low risk of bias) there was no evidence of a difference between the groups. Postoperative complications requiring medical intervention (with or without hospitalisation) The risk of postoperative complications in the first week after surgery was probably lower in children who underwent tonsillotomy (4.9% versus 2.6%, risk ratio (RR) 1.75, 95% CI 1.06 to 2.91; 16 studies, 1416 children; moderate-certainty evidence). Postoperative pain Eleven studies (1017 children) reported this outcome. Pain was measured using various scales and scored by either children, parents, clinicians or study personnel. When considering postoperative pain there was little or no difference between tonsillectomy and tonsillotomy at 24 hours (10-point scale) (MD 1.09, 95% CI 0.88 to 1.29; 4 studies, 368 children); at two to three days (MD 0.93, 95% CI -0.14 to 2.00; 3 studies, 301 children); or at four to seven days (MD 1.07, 95% CI -0.40 to 2.53; 4 studies, 370 children) (all very low-certainty evidence). In sensitivity analysis (restricted to studies with low risk of bias), we found no evidence of a difference in mean pain scores between groups. Return to normal activity Tonsillotomy probably results in a faster return to normal activity. Children who underwent tonsillotomy were able to return to normal activity four days earlier (MD 3.84 days, 95% CI 0.23 to 7.44; 3 studies, 248 children; moderate-certainty evidence). Recurrence of oSDB and reoperation rates We are uncertain whether there is a difference between the groups in the short (RR 0.26, 95% CI 0.03 to 2.22; 3 studies, 186 children), medium (RR 0.35, 95% CI 0.04 to 3.23; 4 studies, 206 children) or long term (RR 0.21 95% CI 0.01 to 4.13; 1 study, 65 children) (all very low-certainty evidence). AUTHORS' CONCLUSIONS: For children with oSDB selected for tonsil surgery, tonsillotomy probably results in a faster return to normal activity (four days) and in a slight reduction in postoperative complications requiring medical intervention in the first week after surgery. This should be balanced against the clinical effectiveness of one operation over the other. However, this is not possible to determine in this review as data on the long-term effects of the two operations on oSDB symptoms, quality of life, oSDB recurrence and need for reoperation are limited and the evidence is of very low quality leading to a high degree of uncertainty about the results. More robust data from high-quality cohort studies, which may be more appropriate for detecting differences in less common events in the long term, are required to inform guidance on which tonsil surgery technique is best for children with oSDB requiring surgery.

Aural toilet (ear cleaning) for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Aural toileting is a term describing a number of processes for manually cleaning the ear. Techniques used may include dry mopping (with cotton wool or tissue paper), suction clearance (typically under a microscope) or irrigation (using manual or automated syringing). Dry mopping may be effective in removing mucopurulent discharge. Compared to irrigation or microsuction it is less effective in removing epithelial debris or thick pus. Aural toileting can be used alone or in addition to other treatments for CSOM, such as antibiotics or topical antiseptics. OBJECTIVES: To assess the effects of aural toilet procedures for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving people (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. We included any aural toileting method as the intervention, at any frequency and for any duration. The comparisons were aural toileting compared with a) placebo or no intervention, and b) any other aural toileting method. We analysed trials in which background treatments were used in both arms (e.g. topical antiseptics or topical antibiotics) separately. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks; health-related quality of life using a validated instrument; and ear pain (otalgia) or discomfort or local irritation. Secondary outcomes were hearing, serious complications, and the adverse events of ear bleeding and dizziness/vertigo/balance problems. MAIN RESULTS: We included three studies with a total of 431 participants (465 ears), reporting on two comparisons. Two studies included only children with CSOM in the community (351 participants) and the other study (80 participants) included children and adults with chronic ear discharge for at least six weeks. None of the included studies reported the outcomes of health-related quality of life, ear pain or the adverse event of ear bleeding. Daily aural toileting (dry mopping) versus no treatment Two studies (351 children; 370 ears) compared daily dry mopping with no treatment. Neither study presented results for resolution of ear discharge at between one and up to two weeks or between two to four weeks. For resolution of ear discharge after four weeks, one study reported the results per person. We are very uncertain whether there is a difference at 16 weeks (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.60 to 1.72; 1 study; 217 participants) because the certainty of the evidence is very low. No results were reported for the adverse events of dizziness, vertigo or balance problems. Only one study reported serious complications, but it was not clear which group these patients were from, or whether the complications occurred pre- or post-treatment. One study reported hearing, but the results were presented by treatment outcome rather than by treatment group so it is not possible to determine whether there is a difference between the two groups. Daily aural toileting versus single aural toileting on top of topical ciprofloxacin One study (80 participants; 95 ears) compared daily aural toileting (suction) with administration of topical antibiotic (ciprofloxacin) ear drops in a clinic, to a single aural toileting (suction) episode followed by daily self-administered topical antibiotic drops, in participants of all ages. We are unsure whether there is a difference in resolution of ear discharge at between one and up to two weeks (RR 1.09, 95% CI 0.91 to 1.30; 1 study; 80 participants) because the certainty of the evidence is very low. There were no results reported for resolution of ear discharge at between two to four weeks. The results for resolution of ear discharge after four weeks were presented by ear, not person, and could not be adjusted to by person. One patient in the group with single aural toileting and self administration of topical antibiotic ear drops reported the adverse event of dizziness, which the authors attributed to the use of cold topical ciprofloxacin. It is very uncertain whether there is a difference between the groups (RR 0.33, 95% CI 0.01 to 7.95; 1 study; 80 participants, very low-certainty). No results were reported for the other adverse events of vertigo or balance problems, or for serious complications. The authors only reported qualitatively that there was no difference between the two groups in hearing results (very low-certainty). AUTHORS' CONCLUSIONS: We are very uncertain whether or not treatment with aural toileting is effective in resolving ear discharge in people with CSOM, due to a lack of data and the poor quality of the available evidence. We also remain uncertain about other outcomes, including adverse events, as these were not well reported. Similarly, we are very uncertain whether daily suction clearance, followed by antibiotic ear drops administered at a clinic, is better than a single episode of suction clearance followed by self-administration of topical antibiotic ear drops.

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

BACKGROUND: Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from the middle ear fluid of children with acute otitis media (AOM). Reducing nasopharyngeal colonisation of this bacterium by PCVs may lead to a decline in AOM. The effects of PCVs deserve ongoing monitoring since studies from the post-PCV era report a shift in causative otopathogens towards non-vaccine serotypes and other bacteria. This updated Cochrane Review was first published in 2002 and updated in 2004, 2009, 2014, and 2019. OBJECTIVES: To assess the effect of PCVs in preventing AOM in children up to 12 years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Web of Science, and two trials registers, ClinicalTrials.gov and WHO ICTRP, to 11 June 2020. SELECTION CRITERIA: Randomised controlled trials of PCV versus placebo or control vaccine. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were frequency of all-cause AOM and adverse effects. Secondary outcomes included frequency of pneumococcal AOM and frequency of recurrent AOM (defined as three or more AOM episodes in six months or four or more in one year). We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 15 publications of 11 trials (60,733 children, range 74 to 37,868 per trial) of 7- to 11-valent PCVs versus control vaccines (meningococcus type C vaccine in three trials, and hepatitis A or B vaccine in eight trials). We included one additional publication of a previously included trial for this 2020 update. We did not find any relevant trials with the newer 13-valent PCV. Most studies were funded by pharmaceutical companies. Overall, risk of bias was low. In seven trials (59,415 children), PCVs were administered in early infancy, whilst four trials (1318 children) included children aged one year and over who were either healthy or had a history of respiratory illness. There was considerable clinical heterogeneity across studies, therefore we reported results from individual studies. PCV administered in early infancy PCV7 The licenced 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) was associated with a 6% (95% confidence interval (CI) -4% to 16%; 1 trial; 1662 children) and 6% (95% CI 4% to 9%; 1 trial; 37,868 children) relative risk reduction (RRR) in low-risk infants (moderate-certainty evidence), but was not associated with a reduction in all-cause AOM in high-risk infants (RRR -5%, 95% CI -25% to 12%). PCV7 with the outer membrane protein complex of Neisseria meningitidis serogroup B as carrier protein (OMPC-PCV7) was not associated with a reduction in all-cause AOM (RRR -1%, 95% CI -12% to 10%; 1 trial; 1666 children; low-certainty evidence). CRM197-PCV7 and OMPC-PCV7 were associated with 20% (95% CI 7% to 31%) and 25% (95% CI 11% to 37%) RRR in pneumococcal AOM, respectively (2 trials; 3328 children; high-certainty evidence), and CRM197-PCV7 with 9% (95% CI -12% to 27%) and 10% (95% CI 7% to 13%) RRR in recurrent AOM (2 trials; 39,530 children; moderate-certainty evidence). PHiD-CV10/11 The effect of a licenced 10-valent PCV conjugated to protein D, a surface lipoprotein of Haemophilus influenzae, (PHiD-CV10) on all-cause AOM in healthy infants varied from 6% (95% CI -6% to 17%; 1 trial; 5095 children) to 15% (95% CI -1% to 28%; 1 trial; 7359 children) RRR (low-certainty evidence). PHiD-CV11 was associated with 34% (95% CI 21% to 44%) RRR in all-cause AOM (1 trial; 4968 children; moderate-certainty evidence). PHiD-CV10 and PHiD-CV11 were associated with 53% (95% CI 16% to 74%) and 52% (95% CI 37% to 63%) RRR in pneumococcal AOM (2 trials; 12,327 children; high-certainty evidence), and PHiD-CV11 with 56% (95% CI -2% to 80%) RRR in recurrent AOM (1 trial; 4968 children; low-certainty evidence). PCV administered at a later age PCV7 We found no evidence of a beneficial effect on all-cause AOM of administering CRM197-PCV7 in children aged 1 to 7 years with a history of respiratory illness or frequent AOM (2 trials; 457 children; moderate-certainty evidence) and CRM197-PCV7 combined with a trivalent influenza vaccine in children aged 18 to 72 months with a history of respiratory tract infections (1 trial; 597 children; moderate-certainty evidence). CRM197-PCV9 In 1 trial including 264 healthy daycare attendees aged 1 to 3 years, CRM197-PCV9 was associated with 17% (95% CI -2% to 33%) RRR in parent-reported all-cause otitis media (very low-certainty evidence). Adverse events Nine trials reported on adverse effects (77,389 children; high-certainty evidence). Mild local reactions and fever were common in both groups, and occurred more frequently in PCV than in control vaccine groups: redness (< 2.5 cm): 5% to 20% versus 0% to 16%; swelling (< 2.5 cm): 5% to 12% versus 0% to 8%; and fever (< 39 °C): 15% to 44% versus 8% to 25%. More severe redness (> 2.5 cm), swelling (> 2.5 cm), and fever (> 39 °C) occurred less frequently (0% to 0.9%, 0.1% to 1.3%, and 0.4% to 2.5%, respectively) in children receiving PCV, and did not differ significantly between PCV and control vaccine groups. Pain or tenderness, or both, was reported more frequently in PCV than in control vaccine groups: 3% to 38% versus 0% to 8%. Serious adverse events judged to be causally related to vaccination were rare and did not differ significantly between groups, and no fatal serious adverse event judged causally related to vaccination was reported. AUTHORS' CONCLUSIONS: Administration of the licenced CRM197-PCV7 and PHiD-CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all-cause AOM is far more uncertain based on low- to moderate-certainty evidence. We found no evidence of a beneficial effect on all-cause AOM of administering PCVs in high-risk infants, after early infancy, and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain and/or tenderness. There was no evidence of a difference in more severe local reactions, fever, or serious adverse events judged to be causally related to vaccination.

Topical antibiotics with steroids for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a chronic inflammation and often polymicrobial infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Topical antibiotics act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be used alone or in addition to other treatments for CSOM, such as steroids, antiseptics or ear cleaning (aural toileting). Antibiotics are commonly prescribed in combined preparations with steroids. OBJECTIVES: To assess the effects of adding a topical steroid to topical antibiotics in the treatment of people with chronic suppurative otitis media (CSOM). SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving participants (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The interventions were any combination of a topical antibiotic agent(s) of any class and a topical corticosteroid (steroid) of any class, applied directly into the ear canal as ear drops, powders or irrigations, or as part of an aural toileting procedure. The two main comparisons were topical antibiotic and steroid compared to a) placebo or no intervention and b) another topical antibiotic. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks and after four weeks; health-related quality of life; ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity. MAIN RESULTS: We included 17 studies addressing 11 treatment comparisons. A total of 1901 participants were included, with one study (40 ears) not reporting the number of participants recruited, which we therefore could not account for. No studies reported health-related quality of life. The main comparisons were: 1. Topical antibiotics with steroids versus placebo or no treatment Three studies (210 participants) compared a topical antibiotic-steroid to saline or no treatment. Resolution of discharge was not reported at between one to two weeks. One study (50 'high-risk' children) reported results at more than four weeks by ear and we could not adjust the results to by person. The study reported that 58% (of 41 ears) resolved with topical antibiotics compared with 50% (of 26 ears) with no treatment, but the evidence is very uncertain. One study (123 participants) noted minor side effects in 16% of participants in both the intervention and placebo groups (very low-certainty evidence). One study (123 participants) reported no change in bone-conduction hearing thresholds and reported no difference in tinnitus or balance problems between groups (very low-certainty evidence). One study (50 participants) reported serious complications, but it was not clear which group these patients were from, or whether the complications occurred pre- or post-treatment. One study (123 participants) reported that no side effects occurred in any participants (very low-certainty evidence). 2. Topical antibiotics with steroids versus topical antibiotics (same antibiotics) only Four studies (475 participants) were included in this comparison. Three studies (340 participants) compared topical antibiotic-steroid combinations to topical antibiotics alone. The evidence suggests little or no difference in resolution of discharge at one to two weeks: 82.7% versus 76.6% (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.96 to 1.21; 335 participants; 3 studies (4 study arms); low-certainty evidence). No results for resolution of discharge after four weeks were reported. One study (110 participants) reported local itchiness but as there was only one episode in each group it is uncertain whether there is a difference (very low-certainty evidence). Three studies (395 participants) investigated suspected ototoxicity but it was not possible to determine whether there were differences between the groups for this outcome (very low-certainty evidence). No study reported serious complications. 3. Topical antibiotics with steroids compared to topical antibiotics alone (different antibiotics) Nine studies (981 participants plus 40 ears) evaluated a range of comparisons of topical non-quinolone antibiotic-steroid combinations versus topical quinolone antibiotics alone. Resolution of discharge may be greater with quinolone topical antibiotics alone at between one to two weeks compared with non-quinolone topical antibiotics with steroids: 82.1% versus 63.2% (RR 0.77, 95% CI 0.71 to 0.84; 7 studies; 903 participants, low-certainty evidence). Results for resolution of ear discharge after four weeks were not reported. One study (52 participants) reported usable data on ear pain, two studies (419 participants) reported hearing outcomes and one study (52 participants) reported balance problems. It was not possible to determine whether there were significant differences between the groups for these outcomes (very low-certainty evidence). Two studies (149 participants) reported no serious complications (very low-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain about the effectiveness of topical antibiotics with steroids in improving the resolution of ear discharge in patients with CSOM because of the limited amount of low-certainty evidence available. Amongst this uncertainty, we found no evidence that the addition of steroids to topical antibiotics affects the resolution of ear discharge. There is also low-certainty evidence that some types of topical antibiotics (without steroids) may be better than topical antibiotic/steroid combinations in improving resolution of discharge. There is also uncertainty about the relative effectiveness of different types of antibiotics; it is not possible to determine with any certainty whether or not quinolones are better or worse than aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.

Topical antibiotics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Topical antibiotics, the most common treatment for CSOM, act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be used alone or in addition to other treatments for CSOM, such as antiseptics or ear cleaning (aural toileting). OBJECTIVES: To assess the effects of topical antibiotics (without steroids) for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 April 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving participants (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The interventions were any single, or combination of, topical antibiotic agent(s) of any class, applied directly into the ear canal as ear drops, powders or irrigations, or as part of an aural toileting procedure. The two main comparisons were topical antibiotic compared to a) placebo or no intervention and b) another topical antibiotic (e.g. topical antibiotic A versus topical antibiotic B). Within each comparison we separated studies where both groups of participants had received topical antibiotic a) alone or with aural toileting and b) on top of background treatment (such as systemic antibiotics). DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks and after four weeks; health-related quality of life using a validated instrument; ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: We included 17 studies with a total of 2198 participants. Twelve studies reported the sample size in terms of participants (not ears); these had a total of 1797 participants. The remaining five studies reported both the number of participants and ears, representing 401 participants, or 510 ears. A: Topical antibiotics versus placebo or no treatment (with aural toilet in both arms and no other background treatment) One small study compared a topical antibiotic (ciprofloxacin) with placebo (saline). All participants received aural toilet. Although ciprofloxacin was better than saline in terms of resolution of discharge at one to two weeks: 84% versus 12% (risk ratio (RR) 6.74, 95% confidence interval (CI) 1.82 to 24.99; 35 participants, very low-certainty evidence), the very low certainty of the evidence means that it is very uncertain whether or not one intervention is better or worse than the other. The study authors reported that "no medical side-effects and worsening of audiological measurements related to this topical medication were detected" (very low-certainty evidence). B: Topical antibiotics versus placebo or no treatment (with use of oral antibiotics in both arms) Four studies compared topical ciprofloxacin to no treatment (three studies; 190 participants) or topical ceftizoxime to no treatment (one study; 248 participants). In each study all participants received the same antibiotic systemically (oral ciprofloxacin, injected ceftizoxime). In at least one study all participants received aural toilet. Useable data were only available from the first three studies; ciprofloxacin was better than no treatment, resolution of discharge occurring in 88.2% versus 60% at one to two weeks (RR 1.47, 95% CI 1.20 to 1.80; 2 studies, 150 participants; low-certainty evidence). None of the studies reported ear pain or discomfort/local irritation. C: Comparisons of different topical antibiotics The certainty of evidence for all outcomes in these comparisons is very low. Quinolones versus aminoglycosides Seven studies compared an aminoglycoside (gentamicin, neomycin or tobramycin) with ciprofloxacin (734 participants) or ofloxacin (214 participants). Whilst resolution of discharge at one to two weeks was higher in the quinolones group the very low certainty of the evidence means that it is very uncertain whether or not one intervention is better or worse than the other (RR 1.95, 95% CI 0.88 to 4.29; 6 studies, 694 participants). One study measured ear pain and reported no difference between the groups. Quinolones versus aminoglycosides/polymyxin B combination ±gramicidin We identified three studies but data on our primary outcome were only available in one study. Comparing ciprofloxacin to a neomycin/polymyxin B/gramicidin combination, for an unknown treatment duration (likely four weeks), ciprofloxacin was better (RR 1.12, 95% CI 1.03 to 1.22, 186 participants). A "few" patients experienced local irritation upon the first instillation of topical treatment (numbers/groups not stated). Others Other studies examined topical gentamicin versus a trimethoprim/sulphacetamide/polymixin B combination (91 participants) and rifampicin versus chloramphenicol (160 participants). Limited data were available and the findings were very uncertain. AUTHORS' CONCLUSIONS: We are uncertain about the effectiveness of topical antibiotics in improving resolution of ear discharge in patients with CSOM because of the limited amount of low-quality evidence available. However, amongst this uncertainty there is some evidence to suggest that the use of topical antibiotics may be effective when compared to placebo, or when used in addition to a systemic antibiotic. There is also uncertainty about the relative effectiveness of different types of antibiotics; it is not possible to determine with any certainty whether or not quinolones are better or worse than aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.

Antimicrobial mouthwashes (gargling) and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to improve patient outcomes and to protect healthcare workers treating them.

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. If the mouth and nose of patients with infection are irrigated with antimicrobial solutions, this may help the patients by killing any coronavirus present at those sites. It may also reduce the risk of the active infection being passed to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves or alterations in the natural microbial flora of the mouth or nose. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to both the patients and the HCWs caring for them. SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020.  SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed RCTs. We therefore planned to include the following types of studies: randomised controlled trials (RCTs); quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies.   We sought studies comparing antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered with any frequency or dosage to suspected/confirmed COVID-19 patients. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) RECOVERY* (www.recoverytrial.net) outcomes in patients (mortality; hospitalisation status; use of ventilation; use of renal dialysis or haemofiltration); 2) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 3) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 4) change in COVID-19 viral load in patients; 5) COVID-19 viral content of aerosol (when present); 6) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 7) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We found no completed studies to include in this review. We identified 16 ongoing studies (including 14 RCTs), which aim to enrol nearly 1250 participants. The interventions included in these trials are ArtemiC (artemisinin, curcumin, frankincense and vitamin C), Citrox (a bioflavonoid), cetylpyridinium chloride, chlorhexidine, chlorine dioxide, essential oils, hydrogen peroxide, hypertonic saline, Kerecis spray (omega 3 viruxide - containing neem oil and St John's wort), neem extract, nitric oxide releasing solution, povidone iodine and saline with baby shampoo.  AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review. This is not surprising given the relatively recent emergence of COVID-19 infection. It is promising that the question posed in this review is being addressed by a number of RCTs and other studies. We are concerned that few of the ongoing studies specifically state that they will evaluate adverse events such as changes in the sense of smell or to the oral and nasal microbiota, and any consequences thereof. Very few interventions have large and dramatic effect sizes. If a positive treatment effect is demonstrated when studies are available for inclusion in this review, it may not be large. In these circumstances in particular it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.

Antimicrobial mouthwashes (gargling) and nasal sprays to protect healthcare workers when undertaking aerosol-generating procedures (AGPs) on patients without suspected or confirmed COVID-19 infection.

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. The risks of transmission of infection are greater when a patient is undergoing an aerosol-generating procedure (AGP). Not all those with COVID-19 infection are symptomatic, or suspected of harbouring the infection. If a patient who is not known to have or suspected of having COVID-19 infection is to undergo an AGP, it would nonetheless be sensible to minimise the risk to those HCWs treating them. If the mouth and nose of an individual undergoing an AGP are irrigated with antimicrobial solutions, this may be a simple and safe method of reducing the risk of any covert infection being passed to HCWs through droplet transmission or direct contact. Alternatively, the use of antimicrobial solutions by the HCW may decrease the chance of them acquiring COVID-19 infection. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves or alterations in the natural microbial flora of the mouth or nose. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to HCWs and/or patients when undertaking AGPs on patients without suspected or confirmed COVID-19 infection. SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020.  SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed RCTs. We therefore planned to include the following types of studies: randomised controlled trials (RCTs); quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies.   We sought studies comparing any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to the patient or HCW before and/or after an AGP. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs or patients; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) COVID-19 viral content of aerosol (when present); 4) change in COVID-19 viral load at site(s) of irrigation; 5) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 6) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We found no completed studies to include in this review.   AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review, nor any ongoing studies. The absence of completed studies is not surprising given the relatively recent emergence of COVID-19 infection. However, we are disappointed that this important clinical question is not being addressed by ongoing studies.

Use of antimicrobial mouthwashes (gargling) and nasal sprays by healthcare workers to protect them when treating patients with suspected or confirmed COVID-19 infection.

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. If the mouth and nose of HCWs are irrigated with antimicrobial solutions, this may help reduce the risk of active infection being passed from infected patients to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves, or alterations in the natural microbial flora of the mouth or nose. Understanding these possible side effects is particularly important when the HCWs are otherwise fit and well. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays used by healthcare workers (HCWs) to protect themselves when treating patients with suspected or confirmed COVID-19 infection. SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020.  SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed randomised controlled trials (RCTs). We therefore planned to include the following types of studies: RCTs; quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies.   We sought studies comparing any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to HCWs, with or without the same intervention being given to the patients with COVID-19. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) viral content of aerosol, when present (if intervention administered to patients); 4) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 5) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We found no completed studies to include in this review. We identified three ongoing studies (including two RCTs), which aim to enrol nearly 700 participants. The interventions included in these trials are povidone iodine, nitric oxide and GLS-1200 oral spray (the constituent of this spray is unclear and may not be antimicrobial in nature).   AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review. This is not surprising given the relatively recent emergence of COVID-19 infection. It is promising that the question posed in this review is being addressed by two RCTs and a non-randomised study. We are concerned that only one of the ongoing studies specifically states that it will evaluate adverse events and it is not clear if this will include changes in the sense of smell or to the oral and nasal microbiota, and any consequences thereof. Very few interventions have large and dramatic effect sizes. If a positive treatment effect is demonstrated when studies are available for inclusion in this review, it may not be large. In these circumstances in particular, where those receiving the intervention are otherwise fit and well, it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.

Antibiotics versus topical antiseptics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Antibiotics and antiseptics kill or inhibit the micro-organisms that may be responsible for the infection. Antibiotics can be applied topically or administered systemically via the oral or injection route. Antiseptics are always directly applied to the ear (topically). OBJECTIVES: To assess the effectiveness of antibiotics versus antiseptics for people with chronic suppurative otitis media (CSOM). SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL; 2019, Issue 4, via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 April 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where ear discharge had continued for more than two weeks. The intervention was any single, or combination of, antibiotic agent, whether applied topically (without steroids) or systemically. The comparison was any single, or combination of, topical antiseptic agent, applied as ear drops, powders or irrigations, or as part of an aural toileting procedure. Two comparisons were topical antiseptics compared to: a) topical antibiotics or b) systemic antibiotics. Within each comparison we separated where both groups of patients had received topical antibiotic a) alone or with aural toilet and b) on top of background treatment (such as systemic antibiotics). DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks; health-related quality of life using a validated instrument; and ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: We identified seven studies (935 participants) across four comparisons with antibiotics compared against acetic acid, aluminium acetate, boric acid and povidone-iodine. None of the included studies reported the outcomes of quality of life or serious complications. A. Topical antiseptic (acetic acid) versus topical antibiotics (quinolones or aminoglycosides) It is very uncertain if there is a difference in resolution of ear discharge with acetic acid compared with aminoglycosides at one to two weeks (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.72 to 1.08; 1 study; 100 participants; very low-certainty evidence). No study reported results for ear discharge after four weeks. It was very uncertain if there was more ear pain, discomfort or local irritation with acetic acid or topical antibiotics due to the low numbers of participants reporting events (RR 0.16, 95% CI 0.02 to 1.34; 2 RCTs; 189 participants; very low-certainty evidence). No differences between groups were reported narratively for hearing (quinolones) or suspected ototoxicity (aminoglycosides) (very low-certainty evidence). B. Topical antiseptic (aluminium acetate) versus topical antibiotics No results for the one study comparing topical antibiotics with aluminium acetate could be used in the review. C. Topical antiseptic (boric acid) versus topical antibiotics (quinolones) One study reported more participants with resolution of ear discharge when using topical antibiotics (quinolones) compared with boric acid ear drops at between one to two weeks (risk ratio (RR) 1.56, 95% confidence interval (CI) 1.27 to 1.92; 1 study; 409 participants; moderate-certainty evidence). This means that one additional person will have resolution of ear discharge for every five people receiving topical antibiotics (compared with boric acid) at two weeks. No study reported results for ear discharge after four weeks. There was a bigger improvement in hearing in the topical antibiotic group compared to the topical antiseptic group (mean difference (MD) 2.79 decibels (dB), 95% CI 0.48 to 5.10; 1 study; 390 participants; low-certainty evidence) but this difference may not be clinically significant. There may be more ear pain, discomfort or irritation with boric acid compared with quinolones (RR 0.56, 95% CI 0.32 to 0.98; 2 studies; 510 participants; low-certainty evidence). Suspected ototoxicity was not reported. D. Topical antiseptic (povidone-iodine) versus topical antibiotics (quinolones) It is uncertain if there is a difference between quinolones and povidone-iodine with respect to resolution of ear discharge at one to two weeks (RR 1.02, 95% CI 0.82 to 1.26; 1 RCT, 39 participants; very low-certainty evidence). The study reported qualitatively that there were no differences between the groups for hearing and no patients developed ototoxic effects (very low-certainty evidence). No results for resolution of ear discharge beyond four weeks, or ear pain, discomfort or irritation, were reported. E. Topical antiseptic (acetic acid) + aural toileting versus topical + systemic antibiotics (quinolones) One study reported that participants receiving topical and oral antibiotics had less resolution of ear discharge compared with acetic acid ear drops and aural toileting (suction clearance every two days) at one month (RR 0.69, 95% CI 0.53 to 0.90; 100 participants). The study did not report results for resolution of ear discharge at between one to two weeks, ear pain, discomfort or irritation, hearing or suspected ototoxicity. AUTHORS' CONCLUSIONS: Treatment of CSOM with topical antibiotics (quinolones) probably results in an increase in resolution of ear discharge compared with boric acid at up to two weeks. There was limited evidence for the efficacy of other topical antibiotics or topical antiseptics and so we are unable to draw conclusions. Adverse events were not well reported.

Topical antiseptics for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Topical antiseptics, one of the possible treatments for CSOM, inhibit the micro-organisms that may be responsible for the infection. Antiseptics can be used alone or in addition to other treatments for CSOM, such as antibiotics or ear cleaning (aural toileting). Antiseptics or their application can cause irritation of the skin of the outer ear, manifesting as discomfort, pain or itching. Some antiseptics (such as alcohol) may have the potential to be toxic to the inner ear (ototoxicity), with a possible increased risk of causing sensorineural hearing loss, dizziness or tinnitus. OBJECTIVES: To assess the effects of topical antiseptics for people with chronic suppurative otitis media. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL; 2019, Issue 4, via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 April 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The interventions were any single, or combination of, topical antiseptic agent of any class, applied directly into the ear canal as ear drops, powders or irrigations, or as part of an aural toileting procedure. Two main comparisons were topical antiseptics compared to: a) placebo or no intervention; and b) another topical antiseptic (e.g. topical antiseptic A versus topical antiseptic B). Within each comparison we separated studies where both groups of patients had received topical antiseptics a) alone or with aural toileting and b) on top of antibiotic treatment. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks; health-related quality of life using a validated instrument; ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. MAIN RESULTS: Five studies were included. It was not possible to calculate the total number of participants as two studies only provided the number of ears included in the study. A. Topical antiseptic (boric acid) versus placebo or no treatment (all patients had aural toileting) Three studies compared topical antiseptics with no treatment, with one study reporting results we could use (254 children; cluster-RCT). This compared the instillation of boric acid in alcohol drops versus no ear drops for one month (both arms used daily dry mopping). We made adjustments to the data to account for the intra-cluster correlation. The very low certainty of the evidence means it is uncertain whether or not treatment with an antiseptic leads to an increase in resolution of ear discharge at both four weeks (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.20 to 3.16; 174 participants) and at three to four months (RR 1.73, 95% CI 1.21 to 2.47; 180 participants). This study narratively described no differences in suspected ototoxicity or hearing outcomes between the arms (very low-certainty evidence). None of the studies reported results for health-related quality of life, adverse effects or serious complications. B. Topical antiseptic A versus topical antiseptic B Two studies compared different antiseptics but only one (93 participants), comparing a single instillation of boric acid powder with daily acetic acid ear drops, provided any information for this comparison. The very low certainty of the evidence means that it is uncertain whether more patients had resolution of ear discharge with boric acid powder compared to acetic acid at four weeks (RR 2.61, 95% CI 1.51 to 4.53; 93 participants), or whether there was a difference between the arms with respect to ear discomfort due to the low number of reported events (RR 0.10, 95% CI 0.01 to 1.81; 93 participants). Narratively, the study reported no difference in hearing outcomes between the groups. None of the included studies reported any of the other primary or secondary outcomes. AUTHORS' CONCLUSIONS: Due to paucity of the evidence and the very low certainty of that which is available the effectiveness and safety profile of antiseptics in the treatment of CSOM is uncertain.

Pneumococcal conjugate vaccines for preventing acute otitis media in children.

BACKGROUND: Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from middle ear fluid of children with acute otitis media (AOM). Reducing nasopharyngeal colonisation of this bacterium by PCVs may lead to a decline in AOM. The effects of PCVs deserve ongoing monitoring since studies from the post-PCV era report a shift in causative otopathogens towards non-vaccine serotypes and other bacteria. This updated Cochrane Review was first published in 2002 and updated in 2004, 2009, and 2014. The review title was changed (to include the population, i.e. children) for this update. OBJECTIVES: To assess the effect of PCVs in preventing AOM in children up to 12 years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Web of Science, and trials registers (ClinicalTrials.gov and WHO ICTRP) to 29 March 2019. SELECTION CRITERIA: Randomised controlled trials of PCV versus placebo or control vaccine. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were frequency of all-cause AOM and adverse effects. Secondary outcomes included frequency of pneumococcal AOM and frequency of recurrent AOM (defined as three or more AOM episodes in six months or four or more in one year). We used GRADE to assess the quality of the evidence. MAIN RESULTS: We included 14 publications of 11 trials (60,733 children, range 74 to 37,868 per trial) of 7- to 11-valent PCVs versus control vaccines (meningococcus type C vaccine in three trials, and hepatitis A or B vaccine in eight trials). We included two additional trials for this update. We did not find any relevant trials with the newer 13-valent PCV. Most studies were funded by pharmaceutical companies. Overall, risk of bias was low. In seven trials (59,415 children) PCVs were administered in early infancy, while four trials (1318 children) included children aged one year and over who were either healthy or had a history of respiratory illness. There was considerable clinical heterogeneity across studies, therefore we did not perform meta-analyses.Adverse eventsNine trials reported on adverse effects (77,389 children; high-quality evidence). Mild local reactions and fever were common in both groups, and occurred more frequently in PCV than in control vaccine groups: redness (< 2.5 cm): 5% to 20% versus 0% to 16%; swelling (< 2.5 cm): 5% to 12% versus 0% to 8%; and fever (< 39 °C): 15% to 44% versus 8% to 25%. More severe redness (> 2.5 cm), swelling (> 2.5 cm), and fever (> 39 °C) occurred less frequently (0% to 0.9%, 0.1% to 1.3%, and 0.4% to 2.5%, respectively in children receiving PCV) and did not differ significantly between PCV and control vaccine groups. Pain or tenderness, or both was reported more frequently in PCV than in control vaccine groups: 3% to 38% versus 0% to 8%. Serious adverse events judged causally related to vaccination were rare and did not differ significantly between groups, and no fatal serious adverse event judged causally related to vaccination was reported.PCV administered in early infancyPCV7The effect of a licenced 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) on all-cause AOM varied from -5% (95% confidence interval (CI) -25% to 12%) relative risk reduction (RRR) in high-risk infants (1 trial; 944 children; moderate-quality evidence) to 6% (95% CI -4% to 16%; 1 trial; 1662 children) and 6% (95% CI 4% to 9%; 1 trial; 37,868 children) RRR in low-risk infants (high-quality evidence). PCV7 with the outer membrane protein complex of Neisseria meningitidis serogroup B as carrier protein (OMPC-PCV7), was not associated with a reduction in all-cause AOM (RRR -1%, 95% CI -12% to 10%; 1 trial; 1666 children; high-quality evidence).CRM197-PCV7 and OMPC-PCV7 were associated with 20% (95% CI 7% to 31%) and 25% (95% CI 11% to 37%) RRR in pneumococcal AOM, respectively (2 trials; 3328 children; high-quality evidence) and CRM197-PCV7 with 9% (95% CI -12% to 27%) to 10% (95% CI 7% to 13%) RRR in recurrent AOM (2 trials; 39,530 children; high-quality evidence).PHiD-CV10/11The effect of a licenced 10-valent PCV conjugated to protein D, a surface lipoprotein of Haemophilus influenzae, (PHiD-CV10) on all-cause AOM varied from 6% (95% CI -6% to 17%; 1 trial; 5095 children) to 15% (95% CI -1% to 28%; 1 trial; 7359 children) RRR in healthy infants (moderate-quality evidence). PHiD-CV11 was associated with 34% (95% CI 21% to 44%) RRR in all-cause AOM (1 trial; 4968 children; high-quality evidence).PHiD-CV10 and PHiD-CV11 were associated with 53% (95% CI 16% to 74%) and 52% (95% CI 37% to 63%) RRR in pneumococcal AOM (2 trials; 12,327 children; high-quality evidence) and PHiD-CV11 with 56% (95% CI -2% to 80%) RRR in recurrent AOM (1 trial; 4968 children; moderate-quality evidence).PCV administered at later agePCV7We found no evidence of a beneficial effect on all-cause AOM of administering CRM197-PCV7 in children aged 1 to 7 years with a history of respiratory illness or frequent AOM (2 trials; 457 children; high-quality evidence) and CRM197-PCV7 combined with a trivalent influenza vaccine in children aged 18 to 72 months with a history of respiratory tract infections (1 trial; 597 children; high-quality evidence).CRM197-PCV9In 1 trial including 264 healthy day-care attendees aged 1 to 3 years, CRM197-PCV9 was associated with 17% (95% CI -2% to 33%) RRR in parent-reported all-cause OM (low-quality evidence). AUTHORS' CONCLUSIONS: Administration of the licenced CRM197-PCV7 and PHiD-CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all-cause AOM is far more uncertain. We found no evidence of a beneficial effect on all-cause AOM of administering PCVs in high-risk infants, after early infancy (i.e. in children one year and above), and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain and/or tenderness. We found no evidence of a difference in more severe local reactions, fever, or serious adverse events judged causally related to vaccination.