Adult-onset hearing loss and incident cognitive impairment and dementia - A systematic review and meta-analysis of cohort studies.

BACKGROUND: We comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the evidence for dose-response, risk for various dementia subtypes, and other moderators. Previous meta-analyses were less comprehensive. METHODS: We included cohort studies with participants without dementia and with hearing assessments at baseline, minimum 2 years follow-up and incident cognitive outcomes. We used random-effect models and subgroup and meta-regression on moderator analyses. RESULTS: We identified fifty studies (N=1,548,754). Hearing loss (yes/no) was associated with incident dementia risk (HR=1.35 [95% CI = 1.26 - 1.45), mild cognitive impairment (MCI HR=1.29 [95% CI = 1.11 - 1.50]), cognitive decline not specified as MCI or dementia (HR=1.29 [95% CI = 1.17 - 1.42]), and Alzheimer's disease dementia (ADD, HR=1.56 [95% CI = 1.30 - 1.87]), but not with vascular dementia (HR, 1.30 [95% CI = 0.83 - 2.05]). Each 10-decibel worsening of hearing was associated with a 16% increase in dementia risk (95% CI = 1.07 - 1.27). The effect of hearing loss did not vary across potential moderators. CONCLUSIONS: Cohort studies consistently support that adult-onset hearing loss increases the risk of incident cognitive decline, dementia, MCI, and ADD.

A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss.

Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met.

Preparing for Otoferlin gene therapy trials: A survey of NHS Paediatric Audiology and Cochlear Implant services on diagnosis and management of Auditory Neuropathy Spectrum Disorder.

OBJECTIVES: Gene therapy for monogenic hearing loss is on the horizon. The first trials in patients with Auditory Neuropathy Spectrum Disorder (ANSD) due to pathogenic variants in the Otoferlin (OTOF) gene will open this year. In the UK, the new NHS Genomic Medicine Service (GMS) offers genetic testing in each child diagnosed with congenital or early onset sensorineural hearing loss. This survey study aims to map preexisting clinical pathways for the diagnosis and management of children with ANSD and identify opportunities for improvement in early identification of OTOF- related ANSD. METHODS: A Google form with 24 questions in English covering the ANSD clinical pathway was developed with clinicians involved in the diagnosis and management ANSD. The survey was disseminated via email to all Lead clinicians of NHS Tertiary Paediatric Audiology and Cochlear Implant Services within the UK. RESULTS: Data was received from 27 (34 %) NHS Tertiary Paediatric Audiology Services and 8 (n = 57 %) Paediatric Cochlear Implant Services. Services follow existing national guidance and provide multidisciplinary care with structured patient pathways for referral, diagnosis, and management of children with ANSD and multidisciplinary input throughout. Clinicians are aware of the genetic causes of ANSD and new processes for genetic testing, but do not uniformly refer children with ANSD for testing for OTOF pathogenic variants. As such, they had difficulty estimating numbers of children with OTOF pathogenic variants under their care. CONCLUSION: Those results highlight the urgency of implementing hearing gene panel sequencing for all children with ANSD to provide opportunities for early diagnosis and candidacy for OTOF gene therapy trials.

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.

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.

Cataloging Existing Hearing Loss Cohort Data to Guide the Development of Precision Medicine for Sensorineural Hearing Loss: A Systematic Review of Hearing Repositories.

Recent breakthroughs in our understanding of sensorineural hearing loss etiology have encouraged the identification of novel hearing therapeutics, paving the way for precision hearing medicine. Critical to this field is the curation of health resources on hearing data. A systematic review of the literature was conducted to map existing (inter)national and regional datasets that include hearing data to inform the development of future hearing repositories. Systematic literature review was performed adhering to Preferred Reporting Items for Systematic Review and MetaAnalysis recommendations. Databases, including those from gray literature, were searched to identify publications reporting on phenotypic and/ or genotypic hearing data in May 2019. The databases reviewed were Medline, PubMed, Embase databases, and Google Scholar. Publications on local datasets were excluded. All hearing datasets identified in the screening process were noted. For each dataset, geography, context, objective, period of time run, numbers and demographics of participants, genomic data, hearing measures and instruments used were extracted and cataloged. One hundred and eighty-eight datasets were identified, containing hearing data on populations ranging from 100 to 1.39 million individuals, and all extracted data have been cataloged. This searchable resource has been made accessible online. This unique catalog provides an overview of existing datasets that contain valuable information on hearing. This can be used to inform the development of national and international patient data repositories for hearing loss and guide strategic collaboration between key stakeholder groups, pivotal to the delivery and development of sensorineural hearing loss precision diagnostics and treatments.

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.

Mapping Two Decades of Paediatric Down Syndrome Research Literature.

Background: While research has led to significant advancements in the health and life expectancy of children with Down Syndrome (DS), there remains a significant burden of disease and health inequity. Further research, focused on areas of greatest need, is imperative to address this. An understanding of what research has been undertaken, and any existing gaps, helps to guide future academic efforts. Methods: We utilised an epistemological approach to summarise two decades of paediatric DS literature. Publications were categorised according to the country of origin, methodology, primary health themes and subcategory research themes. Results: Across 5,800 paediatric DS publications we demonstrate a general increase in the number of publications in this field between 2000 and 2014, with a trending decline thereafter. The majority of publications were affiliated with Institutions based in Western countries. The majority of studies utilised a cross-sectional methodology (33.3%), while relatively few were interventional (5.6%), qualitative (2.7%) or mixed-method studies (1.6%). Most publications focused on development & cognition (13.1%), neurology (9.9%) and oncology (9.8%), with fewer focusing on genitourinary health (0.9%), growth (0.9%), mortality (0.9%) and child protection (0.2%). Conclusion: These findings highlight areas of relative paucity within the paediatric DS literature which may warrant increased academic attention.

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.

Managing comorbid cognitive impairment and hearing loss in older adults: a UK survey of audiology and memory services.

BACKGROUND: midlife hearing loss is a potentially modifiable risk factor for dementia. Addressing comorbid hearing loss and cognitive impairment in services for older adults may offer opportunities to reduce dementia risk. OBJECTIVE: to explore current practice and views amongst UK professionals regarding hearing assessment and care in memory clinics and cognitive assessment and care in hearing aid clinics. METHODS: national survey study. Between July 2021 and March 2022, we distributed the online survey link via email and via QR codes at conferences to professionals working in National Health Service (NHS) memory services and audiologists working in NHS and private adult audiology services. We present descriptive statistics. RESULTS: 135 professionals working in NHS memory services and 156 audiologists (68% NHS, 32% private sector) responded. Of those working in memory services, 79% estimate that >25% of their patients have significant hearing difficulties; 98% think it useful to ask about hearing difficulties and 91% do so; 56% think it useful to perform a hearing test in clinic but only 4% do so. Of audiologists, 36% estimate that >25% of their older adult patients have significant memory problems; 90% think it useful to perform cognitive assessments, but only 4% do so. Main barriers cited are lack of training, time and resources. CONCLUSIONS: although professionals working in memory and audiology services felt addressing this comorbidity would be useful, current practice varies and does not generally address it. These results inform future research into operational solutions to integrating memory and audiology services.

Effectiveness of analgesic ear drops as add-on treatment to oral analgesics in children with acute otitis media: study protocol of the OPTIMA pragmatic randomised controlled trial.

INTRODUCTION: Ear pain is the most prominent symptom of childhood acute otitis media (AOM). To control the pain and reduce reliance on antibiotics, evidence of effectiveness for alternative interventions is urgently needed. This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM. METHODS AND ANALYSIS: This is a pragmatic, two-arm, individually randomised, open, superiority trial with cost-effectiveness analysis and nested mixed-methods process evaluation in general practices in the Netherlands. We aim to recruit 300 children aged 1-6 years with a general practitioner (GP) diagnosis of AOM and ear pain. Children will be randomly allocated (ratio 1:1) to either (1) lidocaine hydrochloride 5 mg/g ear drops (Otalgan) one to two drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics); or (2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0-10) over the first 3 days. Secondary outcomes include proportion of children consuming antibiotics, oral analgesic use and overall symptom burden in the first 7 days; number of days with ear pain, number of GP reconsultations and subsequent antibiotic prescribing, adverse events, complications of AOM and cost-effectiveness during 4-week follow-up; generic and disease-specific quality of life at 4 weeks; parents' and GPs' views and experiences with treatment acceptability, usability and satisfaction. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee Utrecht, the Netherlands, has approved the protocol (21-447/G-D). All parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings. TRIAL REGISTRATION: The Netherlands Trial Register: NL9500; date of registration: 28 May 2021. At the time of publication of the study protocol paper, we were unable to make any amendments to the trial registration record in the Netherlands Trial Register. The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors guidelines. The trial was therefore reregistered in ClinicalTrials.gov (NCT05651633; date of registration: 15 December 2022). This second registration is for modification purposes only and the Netherlands Trial Register record (NL9500) should be regarded as the primary trial registration.

[Acute ear discharge, a reason for consultation]. / Een acuut loopoor.

It is often thought that acute ear discharge as a presenting symptom of acute otitis media (AOM) means that the infection is petering out. However, children with AOM presenting with ear discharge due to a spontaneous perforation of the eardrum (AOMd) have a poorer prognosis (i.e. higher rates of ear pain and/or fever at 3-7 days) than those without ear discharge. In this article we emphasize the importance of physical examination and early treatment of children and adults who present with acute ear discharge.

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.

COVID-VU - ENT-UK national survey of flexible nasendoscopy in the upper aerodigestive tract amidst the COVID-19 pandemic.

BACKGROUND: Flexible nasendoscopy (FNE) is an invaluable multi-disciplinary tool for upper aerodigestive tract (UADT) examination. During the COVID-19 pandemic concerns were raised that FNE had the potential of generating aerosols resulting in human cross-contamination when performed on SARS-COV2 carriers. In the UK, and other European countries, national guidelines were issued restricting FNE to essential cases. We surveyed ENT-UK members and Royal College of Speech and Language Therapists (RCSLT) members to determine the impact of the COVID-19 pandemic (first peak) on FNE practice in the UK. METHODS: An observational internet-based survey constructed in accordance to the CHERRIES checklist and setup in SurveyMonkey of FNE practice amongst UK-based ENT surgeons and speech and language therapists in community clinics, the outpatient department, inpatient wards, ICU, emergency department and operating theatres (through the NHS and private sector) prior to, during and following the first COVID-19 wave in the UK. RESULTS: 314 responses collected (24% response rate), 82% from ENT clinicians, 17% from SLTs and 1% from other allied healthcare professionals. Overall, there has been a large reduction in the volume and indications for FNE during the first peak of the COVID-19 pandemic with limited recovery by mid-August 2020. Cancer and airway assessments were impacted less. A wide range of FNE protocols influenced by local factors are reported, varying in endoscope preference, Personal Protective Equipment (PPE) and sterilization methods. Where dedicated Aerosol Generating Procedure (AGP) rooms were unavailable, clinicians resorted to window opening and variable room "down-time" between patients. Endoscope preference reflected availability and user familiarity, ENT trainees favoring the use of single-use video endoscopes. CONCLUSION: Despite national guidance, local practice of FNE remains interrupted and highly variable in the UK. A collaborative inter-disciplinary approach is required to re-introduce FNE safely in volume across healthcare settings, re-establishing timely endoscopic diagnosis and pre-pandemic levels of patient care.

Early Health Economic Modeling of Novel Therapeutics in Age-Related Hearing Loss.

Background: Health systems face challenges to accelerate access to innovations that add value and avoid those unlikely to do so. This is very timely to the field of age-related sensorineural hearing loss (ARHL), where a significant unmet market need has been identified and sizeable investments made to promote the development of novel hearing therapeutics (NT). This study aims to apply health economic modeling to inform the development of cost-effective NT. Methods: We developed a decision-analytic model to assess the potential costs and effects of using regenerative NT in patients ≥50 with ARHL. This was compared to the current standard of care including hearing aids and cochlear implants. Input data was collected from systematic literature searches and expert opinion. A UK NHS healthcare perspective was adopted. Three different but related analyses were performed using probabilistic modeling: (1) headroom analysis, (2) scenario analyses, and (3) threshold analyses. Results: The headroom analysis shows an incremental net monetary benefit (iNMB) of £20,017[£11,299-£28,737] compared to the standard of care due to quality-adjusted life-years (QALY) gains and cost savings. Higher therapeutic efficacy and access for patients with all degrees of hearing loss yields higher iNMBs. Threshold analyses shows that the ceiling price of the therapeutic increases with more severe degrees of hearing loss. Conclusion: NT for ARHL are potentially cost-effective under current willingness-to-pay (WTP) thresholds with considerable room for improvement in the current standard of care pathway. Our model can be used to help decision makers decide which therapeutics represent value for money and are worth commissioning, thereby paving the way for urgently needed NT.

Observational retrospective study calculating health service costs of patients receiving surgery for chronic rhinosinusitis in England, using linked patient-level primary and secondary care electronic data.

OBJECTIVES: Chronic rhinosinusitis (CRS) symptoms are experienced by an estimated 11% of UK adults, and symptoms have major impacts on quality of life. Data from UK and elsewhere suggest high economic burden of CRS, but detailed cost information and economic analyses regarding surgical pathway are lacking. This paper estimates healthcare costs for patients receiving surgery for CRS in England. DESIGN: Observational retrospective study examining cost of healthcare of patients receiving CRS surgery. SETTING: Linked electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England. PARTICIPANTS: A phenotyping algorithm using medical ontology terms identified 'definite' CRS cases who received CRS surgery. Patients were registered with a general practice in England. Data covered the period 1997-2016. A cohort of 13 462 patients had received surgery for CRS, with 9056 (67%) having confirmed nasal polyps. OUTCOME MEASURES: Information was extracted on numbers and types of primary care prescriptions and consultations, and inpatient and outpatient hospital investigations and procedures. Resource use was costed using published sources. RESULTS: Total National Health Service costs in CRS surgery patients were £2173 over 1 year including surgery. Total costs per person-quarter were £1983 in the quarter containing surgery, mostly comprising surgical inpatient care costs (£1902), and around £60 per person-quarter in the 2 years before and after surgery, of which half were outpatient costs. Outpatient and primary care costs were low compared with the peak in inpatient costs at surgery. The highest outpatient expenditure was on CT scans, peaking in the quarter preceding surgery. CONCLUSIONS: We present the first study of costs to the English healthcare system for patients receiving surgery for CRS. The total aggregate costs provide a further impetus for trials to evaluate the relative benefit of surgical intervention.

Topical or oral antibiotics for children with acute otitis media presenting with ear discharge: study protocol of a randomised controlled non-inferiority trial.

BACKGROUND: Around 15%-20% of children with acute otitis media present with ear discharge due to a spontaneous tear or perforation of the eardrum (AOMd). Current guidance recommends clinicians to consider oral antibiotics as first-line treatment in this condition. The opening in the eardrum however should allow topical antibiotics to enter the middle ear directly. Local administration of antibiotics does not expose children to systemic side effects and may put less selective resistance pressure on bacteria. Evidence on the effectiveness of this approach in children with AOMd is lacking. METHODS AND ANALYSIS: A primary care-based, open, individually randomised, controlled, non-inferiority trial. The trial aims to recruit 350 children aged 6 months to 12 years with AOMd and ear pain and/or fever. Participants will be randomised to 7 days of hydrocortisone-bacitracin-colistin eardrops five drops three times daily or amoxicillin oral suspension 50 mg/kg body weight per day, divided over three doses. Parents will keep a daily diary of AOM symptoms, adverse events and complications for 2 weeks. In addition, they will record AOM recurrences, healthcare utilisation and societal costs for 3 months. The primary outcome is the proportion of children without ear pain and fever at day 3. Secondary outcomes include ear pain and fever intensity/severity; days with ear discharge; eardrum perforation at 2 weeks; adverse events during first 2 weeks; costs; and cost effectiveness at 2 weeks and 3 months. The primary analyses will be intention-to-treat and per-protocol analyses will be conducted as well. ETHICS AND DISSEMINATION: The medical research ethics committee Utrecht, The Netherlands has given ethical approval (17-400/G-M). Parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings. TRIAL REGISTRATION NUMBER: The Netherlands National Trial Register; NTR6723. Date of registration: 27 November 2017.

A Strong Decline in the Incidence of Childhood Otitis Media During the COVID-19 Pandemic in the Netherlands.

Introduction: Recent reports have highlighted the impact of the COVID-19 pandemic on the incidence of infectious disease illnesses and antibiotic use. This study investigates the effect of the pandemic on childhood incidence of otitis media (OM) and associated antibiotic prescribing in a large primary care-based cohort in the Netherlands. Material and Methods: Retrospective observational cohort study using routine health care data from the Julius General Practitioners' Network (JGPN). All children aged 0-12 registered in 62 practices before the COVID-19 pandemic (1 March 2019 - 29 February 2020) and/or during the pandemic (1 March 2020 - 28 February 2021) were included. Data on acute otitis media (AOM), otitis media with effusion (OME), ear discharge episodes and associated antibiotic prescriptions were extracted. Incidence rates per 1,000 child years (IR), incidence rate ratios (IRR) and incidence rate differences (IRD) were compared between the two study periods. Results: OM episodes declined considerably during the COVID-19 pandemic: IR pre-COVID-19 vs COVID-19 for AOM 73.7 vs 27.1 [IRR 0.37]; for OME 9.6 vs 4.1 [IRR 0.43]; and for ear discharge 12.6 vs 5.8 [IRR 0.46]. The absolute number of AOM episodes in which oral antibiotics were prescribed declined accordingly (IRD pre-COVID-19 vs COVID-19: -22.4 per 1,000 child years), but the proportion of AOM episodes with antibiotic prescription was similar in both periods (47% vs 46%, respectively). Discussion: GP consultation for AOM, OME and ear discharge declined by 63%, 57% and 54% respectively in the Netherlands during the COVID-19 pandemic. Similar antibiotic prescription rates before and during the pandemic indicate that the case-mix presenting to primary care did not considerably change. Our data therefore suggest a true decline as a consequence of infection control measures introduced during the pandemic.