Harnessing astaxanthin-loaded diselenium cross-linked apotransferrin nanoparticles for the treatment of secretory otitis media.

Secretory otitis media (SOM) is a clinical condition characterized by the accumulation of fluids and oxidative stress in the middle ear, leading to hearing impairment and infection complications. One potential solution for mitigating oxidative stress associated with SOM is the use of antioxidants such as astaxanthin. However, its effectiveness is limited due to its poor bioavailability and rapid oxidation. Herein, we developed a novel diselenium-crosslinked apotransferrin enriched with astaxanthin (AST@dSe-AFT) nanoparticles to augment the transport of astaxanthin across biological membranes, resulting in increased bioavailability and reduced oxidative stress in SOM. Our research demonstrated that AST@dSe-AFT efficiently accumulated in the middle ear, allowing for controlled delivery of astaxanthin in response to reactive oxygen species and reducing oxidative stress. Additionally, AST@dSe-AFT stimulated macrophages to polarize towards M2 phenotype and neutrophils to polarize towards N2 phenotype, thereby facilitating an anti-inflammatory response and tissue restoration. Importantly, AST@dSe-AFT exhibited no toxicity or adverse effects, suggesting its potential for safety and future clinical translation. Our findings suggested that AST@dSe-AFT represents a promising approach for the treatment of secretory otitis media and other oxidative stress-related disorders.

Is Topical Nasal Steroid Useful for Treatment of Otitis Media with Effusion in Children?

BACKGROUND: Otitis media with effusion is a common and important pediatric clinical problem; it is the leading cause of hearing impairment in children. Medical treatment remains controversial. AIM: To evaluate the usefulness of using topical nasal steroids in the treatment of otitis media with effusion. PATIENTS AND METHODS: Between November 2019 and October 2022, a prospective controlled clinical study was carried out in the department of otolaryngology at Al-Jerrahat Teaching Hospital in Medical City, Baghdad, Iraq. This study comprised 40 patients with bilateral otitis media with effusion (23 males, 17 females). Two groups were created for the patients. Patients in group A (20 patients) were treated with mometasone furoate nasal spray; 1 puff (50 µg) in each nostril daily for 2 weeks, while the 20 patients in group B were treated with saline nasal spray; 1 puff in each nostril daily for 2 weeks. At the end of the first and second weeks of treatment, otoscopic examination was used to monitor the patients. At the end of the second post-treatment week, pure tone audiometry and tympanometry were performed again. Normal otoscopic results, a type A tympanogram, and enhanced pure tone hearing threshold average to be ≤20 dB HL within 0, 5, 1, and 4 KHz were used to characterize resolution of OME. The association between two means was determined using an independent sample t-test, while the association between categorical variables was determined using an X2-test. RESULTS: At the end of 2nd post-treatment week, there was no significant difference regarding improvement of otitis media with effusion regarding otoscopic, audiometric, and tympanometric results in both groups (P-value >0.05). CONCLUSION: Topical nasal steroid is unuseful for the treatment of otitis media with effusion in the short-term.

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.

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.

[Efficacy of bioregulative drugs in the treatment of otitis media with effusion associated with rhinosinusitis and adenoiditis]. / Effektivnost' preparatov bioregulyatsionnoi meditsiny pri lechenii ekssudativnogo srednego otita, sopryazhennogo s rinosinusitom i adenoiditom.

PURPOSE: Improving of otitis media with effusion (OME) with rhinosinusitis (RS) and adenoiditis treatment effectiveness. MATERIALS AND METHODS: The study included 112 patients 12-18 y.o. with otitis media with effusion, who were divided into 2 groups depending on the treatment scheme. The Group I (the main group) patients treatment included Traumeel S and Euphorbium compositum Nasentropfen S in addition to the standard treatment, and the Group II (comparison), children were prescribed standard therapy. Patients of both groups were divided into 3 subgroups depending on the upper respiratory tract inflammation symptoms: A - patients with adenoiditis; B - with rhinosinusitis and C - combination of adenoiditis and rhinosinusitis. The comparison group (groups IIB and IIC) treatment scheme (children with rhinosinusitis) included topical corticosteroids and the main group patients didn't receive corticosteroids. All patients went through complaints and anamnesis collection, routine otorhinolaryngological and instrumental examination before and after treatment. RESULTS: Analysis of treatment results demonstrated high efficacy of multicomponent drugs with low doses of active ingredients in the therapy of patients with OME, regardless of comorbid pathology. Significantly better results were obtained in the patients treated with bioregulatory drugs when comparing the outcomes of OME therapy in combination with adenoiditis (groups IA and IIA). Comparable efficacy results were obtained in the treatment group of patients with OME associated with RS (in groups IB and IIB as well as in groups IC and IIC), where GCS was received in the comparison group. The high efficacy and safety of bioregulatory drugs makes the use of these agents a promising treatment for patients with OME, RS and adenoiditis.

Appropriateness of Diagnosis and Management for Otitis Media With Effusion in Pediatric Urgent Care Clinics.

BACKGROUND: Otitis media with effusion (OME)'s clinical presentation is often confused with acute otitis media (AOM) by clinicians. Despite OME guidelines recommending watchful waiting with no antibiotics, rates of antibiotic use remain elevated. The aim of this study was to determine the clinician diagnosis validity and the rates of antibiotics prescribed among pediatric OME patients evaluated in 3 urgent care clinics within a pediatric health care system. METHODS: We retrospectively reviewed a random sample of encounters for children aged 0 to 18 years with a billing diagnosis of OME in 2019. We recorded clinical symptoms, antibiotic prescribed, and the clinicians' diagnosis. We used the American Academy of Pediatrics guidelines to assign an AOM diagnosis and compared those with the clinicians' final diagnoses using Pearson χ 2 . RESULTS: Of the 912 eligible charts, clinicians' final diagnoses were as follows: AOM for 271 (29.7%) patients, OME for 638 (70.0%) patients, and no ear pathology for 3 (0.3%) patients. Antibiotics were prescribed for 519 (56.9%) patients; of those, only 242 (46.6%) had a final clinician diagnosis of AOM. Antibiotic prescribing rates were higher when a clinician diagnosed AOM compared with OME (89.3% vs 43.2%; P < 0.001). Per American Academy of Pediatrics guidelines, up to 273 (29.9%) patients qualified for an AOM diagnosis, but those were not the same as those diagnosed with AOM by clinicians ( P < 0.001). CONCLUSIONS: When evaluating children with a billing diagnosis of OME, a third fit a diagnosis of AOM. Clinicians commonly misdiagnosed AOM, but also prescribed antibiotics to almost half of those they diagnose with OME.

Improvement of Suspected Eosinophilic Otitis Media with Targeted Biologic Therapy.

OBJECTIVE: To compare the responses of suspected eosinophilic otitis media to treatment with or without a targeted biologic therapy against interleukin-4 (IL-4), IL-5, or IL-13 signaling. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Subjects with type 2 chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and otitis media who underwent treatment between 2005 and 2021. INTERVENTION: Treatment with targeted biologic therapy. MAIN OUTCOME MEASURES: Pre- and posttreatment nasal endoscopy, ear examination, and audiologic evaluation. RESULTS: Four hundred seventy-seven subjects with type 2 CRSwNP were treated between 2005 and 2021. Sixty-two had otitis media with pre- and posttreatment evaluation. Retrospective chart review assessed pre- and posttreatment exam findings, nasal endoscopy, audiometry, and tympanometry. Nineteen subjects received a biologic therapy, whereas 43 did not. Exam, endoscopy, and tympanometry were graded for severity and compared pre- and posttreatment. Subjective ear exam and tympanometry were significantly improved with biologic therapy (control = 0.05, biologic = 0.84, p = 9.3 × 10 -5 ; control = -0.1, biologic = 0.62, p = 0.0002). Conductive hearing loss as assessed by air-bone gaps did not change between groups (control = 1.2 dB better, biologic = 1.2 dB worse, p = 0.32). Nasal endoscopy findings improved with biologic therapy relative to the control group, although not statistically significant (control = 1.04, biologic = 1.36, p = 0.22). CONCLUSIONS: Biologic therapies targeting interleukin-4 (IL-4), IL-5, and IL-13 signaling are potential new treatments for eosinophilic otitis media. This is the largest study demonstrating improvement in subjects with suspected eosinophilic otitis media in response to biologic therapy, and immune modulation represents a novel treatment strategy for this challenging condition. PROFESSIONAL PRACTICE GAP AND EDUCATIONAL NEED: Current treatment strategies for otologic symptoms in eosinophilic disease are not tremendously effective or durable, resulting in a need for improved treatment options. LEARNING OBJECTIVE: To determine if targeted biologic therapy, often used for eosinophilic asthma and type 2 chronic rhinosinusitis with nasal polyposis, improves coexistent suspected eosinophilic otitis media. DESIRED RESULT: Treatment of suspected eosinophilic otitis media with targeted biologic therapy will result in improvement of otologic symptoms with a durable response compared with current treatment options. LEVEL OF EVIDENCE: Level IV. INDICATE IRB OR IACUC: Exempt. HUM00182703.

Refractory tympanostomy tube otorrhea: Outcomes with otowick placement.

OBJECTIVE: To evaluate rates of resolution of and antibiotic use in refractory otorrhea (otorrhea ≥2 weeks with no more than 2 days of otorrhea resolution during the episode) with otowick placement in comparison to medical therapy and tube removals with or without replacements. STUDY DESIGN: Retrospective cohort study of pediatric patients with a history of tympanostomy tube placement and refractory otorrhea between 2017 and 2022. SETTING: Cleveland Clinic Foundation (CCF) pediatric otolaryngology group. METHODS: Demographic data (sex, race, and age at tympanostomy tube placement) were collected. Outcome measures included number of oral and topical antibiotic treatments, duration of otorrhea episode, and resolution of otorrhea at 1 and 3 months follow-up. Wilcoxon rank sum and Kruskal-Wallis tests were used to compare number of antibiotics treatments. An ANOVA test and linear regression model using log-transformed data were used to compare duration of otorrhea. Fisher's exact test was used to compare rates of otorrhea recurrence. RESULTS: 70 patients met inclusion criteria: 37 male (52.9%), 33 female (47.1%), with an average age at tube placement of 29.66 months. There was a statistically significant decrease in total duration of otorrhea (in days) with otowicks (17.29 ± 13.13), compared to patients receiving medical therapy (27.09 ± 22.02) and tube removals and replacements (29.63 ± 19.95) (p = 0.025). There was no significant difference between the follow-up rates of resolution at 1 month (p = 1) and 3 months (p = 0.12). CONCLUSION: Otowick use is associated with shorter duration of otorrhea and can be considered as a first-line treatment for refractory otorrhea. Otowicks and medical therapy alone can reduce need for tube removals and the associated risk of anesthesia.

Application of CNN and ANN in assessment the effect of chemical components of biological nanomaterials in treatment of infection of inner ear and environmental sustainability.

Nanoparticles (NPs) are a promising alternative to antibiotics for targeting microorganisms, especially in the case of difficult-to-treat bacterial illnesses. Antibacterial coatings for medical equipment, materials for infection prevention and healing, bacterial detection systems for medical diagnostics, and antibacterial immunizations are potential applications of nanotechnology. Infections in the ear, which can result in hearing loss, are extremely difficult to cure. The use of nanoparticles to enhance the efficacy of antimicrobial medicines is a potential option. Various types of inorganic, lipid-based, and polymeric nanoparticles have been produced and shown beneficial for the controlled administration of medication. This article focuses on the use of polymeric nanoparticles to treat frequent bacterial diseases in the human body. Using machine learning models such as artificial neural networks (ANNs) and convolutional neural networks (CNNs), this 28-day study evaluates the efficacy of nanoparticle therapy. An innovative application of advanced CNNs, such as Dense Net, for the automatic detection of middle ear infections is reported. Three thousand oto-endoscopic images (OEIs) were categorized as normal, chronic otitis media (COM), and otitis media with effusion (OME). Comparing middle ear effusions to OEIs, CNN models achieved a classification accuracy of 95%, indicating great promise for the automated identification of middle ear infections. The hybrid CNN-ANN model attained an overall accuracy of more than 0.90 percent, with a sensitivity of 95 percent and a specificity of 100 percent in distinguishing earwax from illness, and provided nearly perfect measures of 0.99 percent. Nanoparticles are a promising treatment for difficult-to-treat bacterial diseases, such as ear infections. The application of machine learning models, such as ANNs and CNNs, can improve the efficacy of nanoparticle therapy, especially for the automated detection of middle ear infections. Polymeric nanoparticles, in particular, have shown efficacy in treating common bacterial infections in children, indicating great promise for future treatments.

Resolution of Otitis Media with Effusion in Adults after a Three-Day Course of Treatment with a Manosonic Nebulizer-A Pilot Study.

Background and Objectives: Aerosol drug administration is the primary treatment modality of otitis media with effusion (OME). An automatic manosonic aerosol generator (AMSA) delivers, with an acoustic overpressure, a therapeutic dosage of a drug by inhalation of the aerosol. However, available studies confirming their efficacy, especially in adults, are limited. Therefore, this pilot single-arm trial aimed to analyze changes in adults with OME following AMSA treatment. Materials and Methods: A group of 36 patients (mean age 51.4 years) with OME underwent a three-day treatment with inhaled mucolytic and steroids administered by AMSA. Tympanometry (tympanogram type, volume, compliance, pressure, and gradient) was performed to measure middle ear effusion before and after the intervention. Results: Following the intervention, partial and complete OME remission was observed in, respectively, 29 (81%) and 14 (39%) patients. The tympanogram type of the affected ears differed between baseline and after intervention measurements (p < 0.001). Tympanometry-based normalization, improvement deterioration and no change were observed in, respectively, 34 (68%), 1 (2%) 2 (4%), and 13 (26%) affected ears. Following the intervention, we observed an increase in continuously assessed middle ear volume (∆median 0.19 mL, p = 0.002) and pressure (∆median 142 daPa, p < 0.001), as well as a higher proportion of patients achieving categorical normalization of compliance (16% vs. 54%, p < 0.001) and pressure (28 vs. 64%, p < 0.001). Conclusions: Treatment efficacy was not affected by age, sex, or season of recruitment (all p > 0.05). The results of this pilot study are encouraging, however, the use of AMSA management of OME in adults needs to be verified in future studies.

Acute otitis media in children 6 months to 2 years of age.

QUESTION: Acute otitis media (AOM) is one of the most common findings among children in our family medicine office, and we frequently see this illness during seasons with high rates of upper respiratory tract infections. With more widespread pneumococcal immunization, has the rate of AOM declined? What are the current recommendations for antibiotic treatment? ANSWER: Although rates of the infection have declined over time with better uptake of vaccines against Streptococcus pneumoniae, AOM is still prevalent in the pediatric population and may be associated with serious complications that affect hearing and quality of life. Once a diagnosis has been made (based on a combination of acute onset of symptoms, signs of middle ear inflammation, and effusion), treatment of children 6 months to 2 years of age depends on physical examination findings. Children with perforated tympanic membranes and purulent discharge should receive 10 days of systemic antibiotics. For children with more mild symptoms or early AOM, primary care providers should consider either treatment or watchful waiting.

[SUCCESSFUL TREATMENT FOR OTITIS MEDIA AND SINUSITIS ASSOCIATED WITH EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS USING ANTI-IL-5 RECEPTOR MONOCLONAL ANTIBODY BENRALIZUMAB].

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of ANCA-related vasculitis. Asthma and sinusitis occur first in the course of EGPA, followed by vasculitis symptoms such as fever, weight loss, and peripheral neuropathy. Otitis media with effusion and sensorineural hearing loss occur occasionally in EGPA patients. Here we report a case of a 39-years-old female patient with asthma that developed at age 37 and sinusitis. The patient was diagnosed with EGPA and treatment was started with oral corticosteroids. During the course of treatment, otitis media with effusion and sensorineural hearing loss developed. Benralizumab was administered for severe asthma. After treatment with benralizumab, the symptoms of asthma, otitis media with effusion and sinusitis dramatically improved. This is the first reported case in which benralizumab was used for treating otitis media and sinusitis associated with EGPA. The findings suggest that benralizumab may be effective for otitis media and sinusitis associated with EGPA.

Pharmacotherapy focusing on for the management of otitis media with effusion in children: Systematic review and meta-analysis.

OBJECTIVE: To examine the evidence for treating children with otitis media with effusion with pharmacotherapy. DATA SOURCES: For the systematic review, data were retrieved from PubMed, Cochrane database, and the Japan Medical Abstracts Society Database (1st January 1995 through 31th May 2019). STUDY SELECTION: Articles addressing pharmacotherapy for the management of otitis media with effusion in children were selected in English. DATA EXTRACTION: The database was searched using the keywords "Otitis Media with effusion or secretory otitis media" and the following medical agents: carbocysteine, antihistamines, leukotriene receptor antagonist, and steroid nasal spray. DATA SYNTHESIS: After a critical review of 18 studies, studies addressing steroid nasal spray were eligible for quantitative synthesis. Intranasal steroids for OME showed no benefit with OR 1.155 (95% CI 0.834-1.598) within one month. Conversely, intranasal steroids have effects for OME with OR 1.858 (95% CI 1.240-2.786) for more than one month. CONCLUSIONS: We found evidence of benefit from treatment of OME in children with intranasal steroids and S-carboxymethylcysteine at longer-term follow-up.

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.

Intranasal Surfactant for Acute Otitis Media: A Randomized Trial.

BACKGROUND: Acute otitis media (AOM) is the most frequent reason for children to be prescribed antimicrobial treatment. Surfactants are naturally occurring substances that may restore the eustachian tube's function and potentially enhance resolution of AOM. METHODS: This was a phase 2a, single-center, double-blind, randomized, placebo-controlled, parallel group clinical trial to assess safety, tolerability, and efficacy of 20 mg per day intranasal OP0201 as an adjunct therapy to oral antimicrobial agents for treating AOM in young children. We randomly assigned 103 children aged 6 to 24 months with AOM to receive either OP0201 or placebo twice daily for 10 days. All children received amoxicillin-clavulanate 90/6.4 mg/kg per day in 2 divided doses for 10 days. Participants were managed for up to 1 month. Postrandomization visits occurred between days 4 and 6 (visit 2), days 12 and 14 (visit 3), and days 26 and 30 (visit 4). Primary efficacy endpoints were resolution of a bulging tympanic membrane at visit 2 and resolution of middle-ear effusion at visit 3. RESULTS: No clinically meaningful differences between treatment groups were apparent for primary or secondary endpoints. There were no safety concerns identified. CONCLUSIONS: In young children with AOM, intranasally administered surfactant (OP0201) did not improve clinical outcomes. Further research may be warranted among children with persistent middle-ear effusion.

Effect of Erdosteine on Middle Ear Effusion in Rats by Mediating TLR4 Signaling Pathway.

The study aimed to investigate the effect of erdosteine on middle ear effusion in rats through mediating the Toll-like receptor 4 (TLR4) signaling pathway. Rats were injected with endotoxin to prepare the model of acute secretory otitis media (SOM). Then, they were divided into an acute SOM model group (model group, n = 15) and erdosteine treatment group (18 mg/kg, gavage, treatment group, n = 15). Besides, a normal group (n = 15) was set up. Two weeks later, routine biochemical indicators such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. The inflammatory effusion due to otitis media was scored. The content of myeloperoxidase (MPO), matrix metalloproteinase (MMP), and tumor necrosis factor-beta (TNF-ß) in middle ear lavage fluid was detected via enzyme-linked immunosorbent assay (ELISA). Additionally, histomorphological changes were observed with the help of hematoxylin-eosin (HE) staining, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assays were carried out to measure the expression levels of TLR4 pathway genes and proteins as well as the messenger ribonucleic acid (mRNA) expression levels of key factors for otitis media (mucin 2 (MUC2) and MUC5A). In the model group, the levels of AST, ALP, and glutamic-pyruvic transaminase (GPT) were significantly increased (p < 0.05). Besides, the content of MPO, MMP, and TNF-ß was overtly raised in the model group (p < 0.05), while it was notably lowered in the treatment group (p < 0.05). In the treatment group, the cilia were slightly swollen, and inflammatory cells were fewer. The mRNA levels of MUC2, MUC5A, and pathway genes TLR4 and c-Jun N-terminal kinase (JNK) were elevated in the model group. In addition, the protein assay results revealed that the protein levels of TLR4 and JNK were evidently increased in the model group. Erdosteine can treat the middle ear effusion in rats by repressing the activation of the TLR4 signaling pathway.

[The bacteriological characteristics and drug resistance of the nasopharyngeal region in 311 cases of adenoid hypertrophy with secretory otitis media].

Objective:To analyze the bacteriological distribution and drug resistance of nasopharynx in patients with adenoid hypertrophy complicated with secretory otitis media, and to clarify the distribution of pathogenic bacteria, so as to provide guidance and basis for antibiotic use in clinical treatment. Methods:A retrospective analysis was performed on 311 patients with adenoid hypertrophy and secretory otitis media who underwent surgical treatment in the department of otolaryngology head and neck surgery, Affiliated Hospital of Qingdao University from February 2013 to January 2020. They were divided into 3 groups by age: Group A（0-5 years old）, Group B（6-10 years old）, and Group C（11-16 years old）. The secretions from deep adenoid near the eustachian tube of the affected ear were collected during the surgery for bacterial culture and drug resistance analysis. Results:One hundred and forty-two strains of pathogenic bacteria were isolated and cultured, with a detection rate of 45.66%. Staphylococcus aureus （63 strains）, streptococcus pneumoniae （15 strains） ,streptococcus pyogenes （13 strains） and moraxella cachinella（28 strains）was the main strain.Staphylococcus aureus had high drug resistance rate to penicillin, erythromycin and clindamycin.Streptococcus pneumoniae and Streptococcus pyogenic had high resistance rates to erythromycin,clindamycin and tetracycline. The resistance rate of Moraxella catarrhalis to ampicillin and co-trimoxazole was higher. Conclusion:The main pathogens detected in patients with adenoid hypertrophy complicated with secretory otitis media are staphylococcus aureus, streptococcus pneumoniae, streptococcus pyogenes and moraxella catarrhalis. Drug resistance of different pathogens is quite different. So it is recommended to carry out extensive bacteriological detection, and select antibiotics according to the principle of rational drug use and the results of drug resistance test, so as to achieve good therapeutic effect.