ISOM 2023 Research Panel 5: Interventions- Vaccines and prevention, medical and surgical treatment, and impact of COVID-19 pandemic.

OBJECTIVES: To identify and synthesize key research advances from the literature published between 2019 and 2023 on the advances in preventative measures, and medical and surgical treatment of uncomplicated otitis media (OM) including the impact of the COVID-19 pandemic on OM management. DATA SOURCES: Medline (PubMed), Embase, and the Cochrane Library. REVIEW METHODS: All relevant original articles published in English between June 2019 and February 2023 were identified. Studies related to guideline adherence, impact of treatment on immune response and/or microbiology, tympanoplasty, Eustachian tube balloon dilatation, mastoidectomy procedures, and those focusing on children with Down's syndrome or cleft palate were excluded. MAIN FINDINGS: Of the 9280 unique records screened, 64 were eligible for inclusion; 23 studies related to medical treatment, 20 to vaccines, 13 to surgical treatment, 6 to prevention (excl. vaccines) and 2 to the impact of COVID-19 on OM management. The level of evidence was judged 2 in 11 studies (17.2 %) and 3 or 4 in the remaining 53 studies (82.8 %) mainly due to the observational design, study limitations or low sample sizes. Some important advances in OM management have been made in recent years. Video discharge instructions detailing the identification and management of pain and fever for parents of children with acute otitis media (AOM) was more effective than paper instructions in reducing symptomatology; compared to placebo, levofloxacin solution was more effective for treating chronic suppurative otitis media, whereas AOM recurrences during two years of follow-up did not differ between children with recurrent AOM who received tympanostomy tube (TT) insertion or medical management. Further, novel pneumococcal conjugate vaccines (PCV) schedules for preventing OM in Aboriginal children appeared ineffective, and a protein-based pneumococcal vaccine had no added value over PCV13 for preventing AOM in native American infants. During the COVID-19 pandemic, a decline in OM and TT case volumes and complications was observed. IMPLICATION FOR PRACTICE AND FUTURE RESEARCH: Whether the observed impact of the COVID-19 pandemic on OM management extends to the post-pandemic era is uncertain. Furthermore, the impact of the pandemic on the conduct of urgently needed prospective methodologically rigorous interventional studies aimed at improving OM prevention and treatment remains to be elucidated since the current report consisted of studies predominantly conducted in the pre-pandemic era.

Beyond the polysaccharide and glycoconjugate vaccines for Streptococcus pneumoniae: Does protein/peptide nanovaccines hold promises?

Streptococcus pneumoniae having almost 98 serotypes and being common cause of acute otitis media, pneumonia, bacteremia, meningitis etc., which results in high mortality and morbidity globally. Although vaccines like PCV-13 and PPV-23 are available, some problems like serotype replacement and poor immunogenicity in children, old age and immunocompromised people has been observed. To overcome these drawbacks protein/peptide-based vaccine can be a good strategy as these provides wide serotype coverage. However, immunogenicity of protein subunit vaccines is lower, that issue can be solved by using adjuvants. Recently nanoparticles as an adjuvant for vaccine delivery being used, which has provided not only good immunogenicity but also improved delivery and efficiency of protein-based vaccines. In this review we have discussed the latest advancement of nanoparticles-based protein/peptide vaccine delivery for Streptococcus pneumoniae.

The effect of pneumococcal conjugated vaccines on occurrence of recurrent acute otitis media among infants diagnosed with acute otitis media at an age younger than 2 months.

To examine the impact of pneumococcal conjugate vaccines (PCV) on the occurrence of recurrent acute otitis media (rAOM) among infants diagnosed with an early acute otitis media (AOM) episode. Retrospective cohort study of pediatric patients with a first episode of AOM at an age < 2 months. Data included clinical, demographic, and microbiological findings at the first AOM episode. In addition, a 5-year follow-up after the patient's first episode was completed from the medical records. This information included documentation of rAOM episodes and complications of AOM (hearing loss, speech disturbance, mastoiditis, and tympanic membrane perforation) and of ear-related surgical procedures (ventilation tube placement, adenoidectomies, and mastoid surgery). Two groups were studied: patients diagnosed between 2005 and 2009 (representing the unvaccinated group, group 1) and those diagnosed in 2010-2014 (the vaccinated group, group 2). A total of 170 infants were diagnosed with a first AOM episode at an age < 2 months; 81 of them belonged to group 1 and 89 to group 2. Streptococcus pneumoniae was isolated in the middle-ear fluid in the first AOM episode in 48.1% of the patients in group 1 and in 30.3% in group 2 (P = 0.0316). 49/81 (60.5%) infants in group 1 were diagnosed with rAOM versus 39/80 (43.8%) in group 2 (P = 0.0298). No statistical differences were found between the groups with respect to long-term complications or need for surgery later in life.   Conclusion: Our study showed a significant decrease in the occurrence of rAOM in infants diagnosed with AOM during the first 2 months of life and timely immunized with PCVs following this initial AOM episode. What is Known: • 30% of children experience recurrent AOM (rAOM) at the first year of life. The earlier the age of the first AOM, the greater the risk for future complications. • After the introduction of PCVs, the overall pneumococcal AOM incidence declined. We investigated the future effect of PCVs on rAOM occurrence, when administered after the first AOM episode. What is New: • A retrospective cohort of 170 infants with a first AOM episode at an age <2 months and followed for 5 years, showed a significant decrease (28.0%) of rAOM in immunized infants following the initial AOM episode. • Our findings supplement previous data suggesting that the widespread PCVs use prevents rAOM by preventing early AOM and emphasize the importance of timely administration of the PCVs.

Efficacy of Pneumococcal Vaccine on Otitis Media: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the effect of the pneumococcal vaccine (PCV) toward the surgical management and complications of otitis media. DATA SOURCES: MEDLINE, EMBASE, PubMed, Scopus, and clinicaltrial.gov. REVIEW METHODS: A systematic search was performed using a combination of keywords and standardized terms about PCV and surgical management or complications of otitis media. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies were screened by 3 independent reviewers. Risk of bias assessment, followed by meta-analysis in only randomized-controlled trials was conducted. Vaccine efficacy (VE) and 95% confidence interval (CI) were reported. RESULTS: Of the 2649 abstracts reviewed, 27 studies were included in the qualitative analysis and were categorized into 6 outcomes: tympanostomy tube insertion, otitis media with effusion (OME), mastoiditis, spontaneous tympanic membrane (TM) perforation, recurrent acute otitis media (AOM), and severe AOM. Fifteen studies were included in the meta-analysis to evaluate the rate of tympanostomy tube insertion, OME, and recurrent AOM. PCV was significantly more effective in lowering the rate of tympanostomy tube insertion (VE, 22.2%; 95% CI, 14.6-29.8) and recurrent AOM (VE, 10.06%; 95% CI, 7.46-12.65) when compared with the control group, with no significant difference in reducing the incidence of OME. The qualitative analysis revealed that PCV had efficacy in preventing severe AOM and spontaneous TM perforation but the effect on mastoiditis remained unclear. CONCLUSION: The PCV was effective in reducing the rate of tympanostomy tube insertion and the incidence of recurrent AOM with a nonsignificant effect in preventing OME in children.

Otitis Media Practice During the COVID-19 Pandemic.

The global coronavirus disease-2019 (COVID-19) pandemic has changed the prevalence and management of many pediatric infectious diseases, including acute otitis media (AOM). Coronaviruses are a group of RNA viruses that cause respiratory tract infections in humans. Before the COVID-19 pandemic, coronavirus serotypes OC43, 229E, HKU1, and NL63 were infrequently detected in middle ear fluid (MEF) specimens and nasopharyngeal aspirates in children with AOM during the 1990s and 2000s and were associated with a mild course of the disease. At times when CoV was detected in OM cases, the overall viral load was relatively low. The new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen responsible for the eruption of the COVID-19 global pandemic. Following the pandemic declaration in many countries and by the World Health Organization in March 2020, preventive proactive measures were imposed to limit COVID-19. These included social distancing; lockdowns; closure of workplaces; kindergartens and schools; increased hygiene; use of antiseptics and alcohol-based gels; frequent temperature measurements and wearing masks. These measures were not the only ones taken, as hospitals and clinics tried to minimize treating non-urgent medical referrals such as OM, and elective surgical procedures were canceled, such as ventilating tube insertion (VTI). These changes and regulations altered the way OM is practiced during the COVID-19 pandemic. Advents in technology allowed a vast use of telemedicine technologies for OM, however, the accuracy of AOM diagnosis in those encounters was in doubt, and antibiotic prescription rates were still reported to be high. There was an overall decrease in AOM episodes and admissions rates and with high spontaneous resolution rates of MEF in children, and a reduction in VTI surgeries. Despite an initial fear regarding viral shedding during myringotomy, the procedure was shown to be safe. Special draping techniques for otologic surgery were suggested. Other aspects of OM practice included the presentation of adult patients with AOM who tested positive for SARS-2-CoV and its detection in MEF samples in living patients and in the mucosa of the middle ear and mastoid in post-mortem specimens.

Indirect Impact of Ten-valent Pneumococcal Conjugate Vaccine Program on Reducing Antimicrobial Use and Tympanostomy Tube Placements in Finland.

BACKGROUND: Acute otitis media (AOM) is the most common reason for antimicrobial use, and tympanostomy tube placement (TTP) is the most common reason for surgery requiring general anesthesia in children. Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in Finland in 2010 for infants. We evaluated the indirect impact of PCV10 on these surrogate otitis outcomes in unvaccinated children. METHODS: Using before-after design, unvaccinated children ineligible for National Vaccination Program (born January 2006 to May 2010) were followed-up during 2012-2016 (target cohort, age 1.5-7 years). The target cohort was compared with an age- and season-matched unvaccinated reference cohort (born January 2000 to May 2004) during 2006-2010. Antimicrobial purchase data were obtained from the Social Insurance Institution of Finland benefits register. We assessed the relative reduction by generalized Cox regression for outpatient purchases of antibiotics recommended for treatment of AOM in the Finnish guidelines. Data on all TTP procedures were obtained from national hospital discharge register and Social Insurance Institution benefits register. RESULTS: The rate of outpatient purchases of antimicrobials recommended for AOM was 51 in the unvaccinated reference cohort and 44/100 person-years in the unvaccinated target cohort; relative rate reduction was 14.7% [95% confidence interval: 14.0-15.3] and absolute rate reduction 7/100 person-years. The rates of TTP in the reference and target cohorts were 1.66/100 and 1.61/100 person-years, respectively. The relative rate reduction was 3.6% (0.7-6.5). CONCLUSIONS: Antimicrobial use and TTP procedures reduced in unvaccinated children after PCV10 introduction in infants. These indirect effects contribute to the savings in health care resource use for otitis and may also help in combating antimicrobial resistance.

Unsolved problems and new medical approaches to otitis media.

INTRODUCTION: Otitis media (OM) is a spectrum of infectious and inflammatory diseases that involve the middle ear. It includes acute otitis media (AOM), otitis media with effusion (OME) and chronic suppurative otitis media (CSOM). AREAS COVERED: This manuscript discusses some of the emerging and unsolved problems regarding OM, and some of the newly developed prophylactic and therapeutic medical measures. EXPERT OPINION: In recent years, considerable progress in the knowledge of OM physiopathology has been made. However, although extremely common, diseases included under OM have not been adequately studied, and many areas of development, evolution and possible treatments of these pathologies are not defined. It is necessary that these deficiencies be quickly overcome if we want to reduce the total burden of a group of diseases that still have extremely high medical, social and economic relevance.

A bacterial vaccine polypeptide protective against nontypable Haemophilus influenzae.

Nontypeable strains of Haemophilus influenzae (NTHi) are one of the most common cause of otitis media and the most frequent infection associated with exacerbations of chronic obstructive pulmonary disease; there is currently no vaccine in the U.S. to prevent NTHi. Using bioinformatics and structural vaccinology, we previously identified several NTHi species-conserved and sequence-conserved peptides that mediate passive protection in the rat model of infection. Using these, and similar peptides, we designed Hi Poly 1, a Bacterial Vaccine Polypeptide, comprising 9 unique peptides from 6 different surface proteins. Recombinant Hi Poly 1 was purified by affinity chromatography. Forty chinchillas were immunized three times with 200 µg of Hi Poly 1 with alum adjuvant; similarly, 41 controls were immunized with adjuvant alone. The average Log2 IgG titer among immunized animals was 17.04, and IgG antibodies against each component peptide were detected. In the infant rat model, antisera from immunized chinchillas provided significant passive protection compared to PBS (p = 0.01) and pre-immune sera (p = 0.03). In the established chinchilla model of NTHi otitis media, the vaccinated group cleared infection faster than the control group as indicated by significantly decreased positive findings on video-otoscopy (p < 0.0001) and tympanometry (p = 0.0002) on day 7, and for middle ear fluid obtained by aspiration (p = 0.0001) on day 10 post-infection. Using 12 representative NTHi strains in a Live-Cell ELISA, greater antibody binding to each strain was detected with post Hi Poly 1 than the pre-immune chinchilla antisera. The data from this proof-of-principle study demonstrate the effectiveness of Hi Poly 1 against the NTHi in two relevant preclinical models of bacteremia and otitis media as well as surface antibody binding across the species. The Bacterial Vaccine Polypeptide approach to a vaccine against NTHi also serves as a paradigm for development of similar vaccines to protect against other bacteria.

Updated Guidelines for the Management of Acute Otitis Media in Children by the Italian Society of Pediatrics: Prevention.

BACKGROUND: In recent years, new information has been acquired regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society, therefore, decided to issue an update to the Italian Pediatric Society guidelines published in 2010. METHODS: The search was conducted on Pubmed, and only those studies regarding the pediatric age alone, in English or Italian, published between January 1, 2010 and December 31, 2018, were included. Each study included in the review was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The quality of the systematic reviews was evaluated using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts. RESULTS: The importance of eliminating risk factors (passive smoking, environmental pollution, use of pacifier, obesity, limitation of day-care center attendance) and the promotion of breastfeeding and hygiene practices (nasal lavages) was confirmed. The importance of pneumococcal vaccination in the prevention of AOM was reiterated with regard to the prevention of both the first episode of AOM and recurrences. Grommets can be inserted in selected cases of recurrent AOM that did not respond to all other prevention strategies. Antibiotic prophylaxis is not recommended for the prevention of recurrent AOM, except in certain carefully selected cases. The use of complementary therapies, probiotics, xylitol and vitamin D is not recommended. CONCLUSIONS: The prevention of episodes of AOM requires the elimination of risk factors and pneumococcal and influenza vaccination. The use of other products such as probiotics and vitamin D is not supported by adequate evidence.

Apigetrin treatment attenuates LPS-induced acute otitis media though suppressing inflammation and oxidative stress.

The natural course of otitis media in children is acute and self-limiting. Nevertheless, about 10-20% children could experience recurrent or persistent otitis media. Thus, finding effective candidate to prevent acute otitis media is urgently required. In our study, mouse acute otitis media model was constructed by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Apigetrin (APT) is a flavonoid isolated from various herbal medicines, possessing anti-inflammatory and anti-oxidative bioactivities. However, if APT could attenuate acute otitis media in LPS-induced animal models, little is to be known. Hematoxylin and eosin (H&E) staining suggested that APT treatment reduced LPS-induced higher mucosa thickness. LPS-triggered inflammatory response was also inhibited by APT, as evidenced by the down-regulated neutrophils and macrophages. Additionally, the reduced inflammatory factors, including interleukin-1ß (IL-lß), tumor necrosis factor α (TNF-α), IL-6 and vascular endothelial growth factor (VEGF) were observed in APT-treated mice with acute otitis media. The process was associated with the inhibition of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway, which was proved by the blockage of TLR4, MyD88, p-IKKα, p-IκBα, and p-NF-κB using western blot analysis. Moreover, the production of reactive oxygen species (ROS) caused by LPS was also reduced by APT through promoting anti-oxidants, involving superoxide dismutase (SOD) activity, heme oxygenase-1 (HO-1), NADP(H) quinone oxidoreductase 1 (NQO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions. In contrast, high levels of MDA and kelch-like ECH-associated protein 1 (Keap 1) in LPS-treated mice were down-regulated by APT, which might be associated with the inactivation of NF-κB. In vitro, APT exhibited anti-inflammatory and anti-oxidant effects with little cytotoxicity in LPS-stimulated cells. Together, the data above indicated that APT could ameliorate acute otitis media through inhibiting inflammation and oxidative stress.

Efecto de la lactancia en las infecciones pediátricas frecuentes: estudio de cohorte prospectivo de cinco años / Effect of breastfeeding on common pediatric infections: a 5-year prospective cohort study

Introducción. En los estudios realizados se encontró que la duración de la lactancia tiene un efecto reductor sobre las infecciones frecuentes en los niños durante el período de lactancia. Objetivo. El objetivo de este estudio fue abordar la asociación entre la duración de la lactancia y las enfermedades infecciosas frecuentes en los niños hasta los 5 años de edad para demostrar los efectos protectores de la leche materna. Población y métodos. Se incluyeron 411 lactantes nacidos en Rize, Turquía, entre enero de 2011 y diciembre de 2011. Este estudio de cohorte, prospectivo duró cinco años; en este período, se realizaron 11 entrevistas con cada madre de los lactantes. Se dividió a los lactantes en dos grupos: amamantados durante más y menos de 12 meses, y se estudió la asociación entre la lactancia y las infecciones, como otitis media aguda, gastroenteritis aguda, infección respiratoria aguda e infección urinaria. Resultados. De los 411 nacimientos, se incluyeron 270 lactantes, 193 (71,5%) recibieron lactancia durante más de 12 meses y 77 (28,5%), durante menos de 12 meses. Los lactantes del primer grupo tuvieron menos casos de otitis media aguda y gastroenteritis aguda (n = 77; 28,52%) en comparación con los lactantes amamantados durante menos de 12 meses en el período de cinco años (p < 0,05). Conclusiones. Con este estudio se detectó que la lactancia durante más de 12 meses reduce significativamente las infecciones frecuentes durante la niñez, como la otitis media y la gastroenteritis durante los primeros cinco años de vida.

Introduction.The studies conducted revealed that breastfeeding duration has a reducing effect on common infectious diseases in the children during breastfeeding period. Objective. The aim of the present study was to address the association between breastfeeding duration and common infectious diseases in the children until 5 years of age to show long-term protective effects of the breast milk. Material and methods. The study included 411 infants who were born in Rize (Turkey) between January 2011 and December 2011. The present prospective-cohort study lasted for 5 years and 11 interviews were conducted with each mother of the infants during this period. The infants were divided into two groups as those who were breastfed more and less than 12 months and the association between breastfeeding and infections such as acute otitis media, acute gastroenteritis, acute respiratory tract infections and acute urinary system infections was investigated. Results. Of 270 infants 193 (71.5%) were breastfed longer than 12 months and 77 (28.5%) were breastfed less than 12 months. Infants in the first group had less acute otitis media and acute gastroenteritis (n= 77, 28.52%) when compared with the infants breastfed less than 12 months during 5-year period (p <0.05). Conclusion. The present study detected that breastfeeding duration longer than 12 months significantly reduces the common childhood infections such as otitis media and gastroenteritis during the first 5 years of life.

Panel 6: Vaccines.

Objective To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM bacterial and viral pathogens. Data Sources PubMed database of the National Library of Science. Review Methods We performed literature searches in PubMed for OM pathogens and candidate vaccine antigens, and we restricted the searches to articles in English that were published between July 2011 and June 2015. Panel members reviewed literature in their area of expertise. Conclusions Pneumococcal conjugate vaccines (PCVs) are somewhat effective for the prevention of pneumococcal OM, recurrent OM, OM visits, and tympanostomy tube insertions. Widespread use of PCVs has been associated with shifts in pneumococcal serotypes and bacterial pathogens associated with OM, diminishing PCV effectiveness against AOM. The 10-valent pneumococcal vaccine containing Haemophilus influenzae protein D (PHiD-CV) is effective for pneumococcal OM, but results from studies describing the potential impact on OM due to H influenzae have been inconsistent. Progress in vaccine development for H influenzae, Moraxella catarrhalis, and OM-associated respiratory viruses has been limited. Additional research is needed to extend vaccine protection to additional pneumococcal serotypes and other otopathogens. There are likely to be licensure challenges for protein-based vaccines, and data on correlates of protection for OM vaccine antigens are urgently needed. Implications for Practice OM continues to be a significant health care burden globally. Prevention is preferable to treatment, and vaccine development remains an important goal. As a polymicrobial disease, OM poses significant but not insurmountable challenges for vaccine development.

Protective benefit of predominant breastfeeding against otitis media may be limited to early childhood: results from a prospective birth cohort study.

OBJECTIVES: To examine the long-term effects of predominant breastfeeding on incidence of otitis media. DESIGN: Prospective birth cohort study. SETTING: The West Australian Pregnancy Cohort (Raine) Study recruited 2900 mothers through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia, between 1989 and 1992. PARTICIPANTS: In total, 2237 children participated in a 6-year cohort follow-up, and a subset of 1344 were given ear and hearing assessments. MAIN OUTCOME MEASURES: OM diagnosis at 6 years of age (diagnosed by low-compliance tympanograms, 0-0.1 mmho). This was compared to OM diagnosed at the 3-year cohort follow-up using parent-report measures. Main exposure measures were duration of predominant breastfeeding (defined as the age other milk was introduced) and duration of partial (any) breastfeeding (defined as the age breastfeeding was stopped). RESULTS: There was a significant, independent association between predominant breastfeeding (OR = 1.33 [1.04, 1.69]; P = 0.02) and OM, and breastfeeding duration (OR = 1.35 [1.08, 1.68]; P = 0.01) with OM at 3 years of age. However, at 6 years of age, this relationship was no longer statistically significant (predominant breastfeeding OR = 0.78 [0.48, 1.06]; P = 0.09; duration of breastfeeding, OR = 1.34 [0.81, 2.23]; P = 0.25). CONCLUSIONS: Our findings are in line with a number of epidemiological studies which show a positive association between breastfeeding and OM in early childhood. However, the long-term follow-up of these children revealed that by 6 years of age, there was no significant influence of breastfeeding on presence of OM. These results suggest that the protective effect of predominant breastfeeding for at least 6 months does not extend to school-age children, where other social and environmental factors may be stronger predictors of OM.

Xylitol for preventing acute otitis media in children up to 12 years of age.

BACKGROUND: Acute otitis media (AOM) is the most common bacterial infection among young children in the United States. There are limitations and concerns over its treatment with antibiotics and surgery and so effective preventative measures are attractive. A potential preventative measure is xylitol, a natural sugar substitute that reduces the risk of dental decay. Xylitol can reduce the adherence of Streptococcus pneumoniae (S pneumoniae) and Haemophilus influenzae (H influenzae) to nasopharyngeal cells in vitro. This is an update of a review first published in 2011. OBJECTIVES: To assess the efficacy and safety of xylitol to prevent AOM in children aged up to 12 years. SEARCH METHODS: We searched CENTRAL (to Issue 12, 2015), MEDLINE (1950 to January 2016), Embase (1974 to January 2016), CINAHL (1981 to January 2016), LILACS (1982 to January 2016), Web of Science (2011 to January 2016) and International Pharmaceutical Abstracts (2000 to January 2016). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of children aged 12 years or younger where xylitol supplementation was compared with placebo or no treatment to prevent AOM. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials from search results, assessed and rated study quality and extracted relevant data for inclusion in the review. We contacted trial authors to request missing data. We noted data on any adverse events of xylitol. We extracted data on relevant outcomes and estimated the effect size by calculating risk ratio (RR), risk difference (RD) and associated 95% confidence intervals (CI). MAIN RESULTS: We identified five clinical trials that involved 3405 children for inclusion. For this 2016 update, we identified one new trial for inclusion. This trial was systematically reviewed but due to several sources of heterogeneity, was not included in the meta-analysis. The remaining four trials were of adequate methodological quality. In three RCTs that involved a total of 1826 healthy Finnish children attending daycare, there is moderate quality evidence that xylitol (in any form) can reduce the risk of AOM from 30% to around 22% compared with the control group (RR 0.75, 95% CI 0.65 to 0.88). Among the reasons for dropouts, there were no significant differences in abdominal discomfort and rash between the xylitol and the control groups. Xylitol was not effective in reducing AOM among healthy children during a respiratory infection (RR 1.13, 95% CI 0.83 to 1.53; moderate quality evidence) or among otitis-prone healthy children (RR 0.90, 95% CI 0.67 to 1.21; low-quality evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence showing that the prophylactic administration of xylitol among healthy children attending daycare centres can reduce the occurrence of AOM. There is inconclusive evidence with regard to the efficacy of xylitol in preventing AOM among children with respiratory infection, or among otitis-prone children. The meta-analysis was limited because data came from a small number of studies, and most were from the same research group.

Sulfate-binding protein, CysP, is a candidate vaccine antigen of Moraxella catarrhalis.

Moraxella catarrhalis causes otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). A vaccine to prevent M. catarrhalis infections would have an enormous impact globally in preventing morbidity caused by M. catarrhalis in these populations. Using a genome mining approach we have identified a sulfate binding protein, CysP, of an ATP binding cassette (ABC) transporter system as a novel candidate vaccine antigen. CysP expresses epitopes on the bacterial surface and is highly conserved among strains. Immunization with CysP induces potentially protective immune responses in a murine pulmonary clearance model. In view of these features that indicate CysP is a promising vaccine antigen, we conducted further studies to elucidate its function. These studies demonstrated that CysP binds sulfate and thiosulfate ions, plays a nutritional role for the organism and functions in intracellular survival of M. catarrhalis in human respiratory epithelial cells. The observations that CysP has features of a vaccine antigen and also plays an important role in growth and survival of the organism indicate that CysP is an excellent candidate vaccine antigen to prevent M. catarrhalis otitis media and infections in adults with COPD.

Otologic Concerns for Cleft Lip and Palate Patient.

Understanding eustachian tube physiology and anticipating probable eustachian tube dysfunction is an important component of cleft palate management. This article provides a brief summary of the otologic physiology and issues that may be of concern to cleft palate management. It is of critical importance not only to provide primary closure of the cleft palate, but also to recognize that along with speech, hearing has a critical component to the educational and social success of all individuals.

Policy Options to Promote Smokefree Environments for Children and Adolescents.

Secondhand smoke (SHS) exposure among children is associated with a wide variety of adverse health risks, including: asthma, otitis media, respiratory infections, impaired lung growth and function, decreased exercise tolerance, cognitive impairments, behavior problems, and sudden infant death syndrome. Unfortunately, over 40% of children aged 3-11 years-15.1 million children-are currently exposed to SHS, with nearly 70% of black children in this age group being exposed. Over the past three decades, great strides have been made in establishing smokefree environments for adults, ultimately reducing their SHS exposure. Regulations have been passed at the organizational, local, and state levels that increasingly ban smoking in the workplace and public places. Children's SHS exposure patterns, however, differ from adults' exposures, with greater time spent in the home and other potentially unregulated venues (school, child care, and car). This means that children have been afforded relatively less protection from SHS by these smokefree regulations. It is imperative, therefore, to seek alternative options for promoting smokefree environments for children throughout the United States. This article explores policy options that promote smokefree environments for children and adolescents: comprehensive smokefree/tobacco-free policies covering indoor/outdoor public places, housing, private vehicles, and child care, as well as Clinical Guidelines regarding patient/family interviews on smoking, SHS, cessation, and voluntary smokefree efforts. The policy section highlights the role of child and adolescent health practitioners in promoting these policies with the hope of fostering engagement of these key stakeholders in the policy process. Note, there are a wide range of important policy and regulatory strategies aimed at reducing tobacco initiation and use among children, adolescents, and young adults; while essential in tobacco prevention and control efforts, a discussion of these strategies is beyond the scope of this article.

Severity of pneumococcal versus non-pneumococcal acute otitis media in children.

BACKGROUND: Pneumococcal acute otitis media (AOM) has been previously considered as a more severe disease than that caused by other otopathogens, based on clinical and/or otologic scores. We sought to test this hypothesis in the pneumococcal conjugated vaccine (PCV) era. METHODS: Children <6 years who presented with 'severe' AOM episodes with middle ear fluid (MEF) cultures during 2008-2013 were retrospectively identified. 'Severe' AOM episodes were considered if tympanocentesis was required or if spontaneous otorrhea was present. Data were extracted for demographics, clinical and laboratory tests. Children were categorised according to their PCV status as 'unimmunised' or 'PCV7/PCV13 immunised' and according to their MEF culture results into the 'pneumococcal' or the 'non-pneumococcal' group. Leukocytosis was defined as white blood cells (WBC) count >15 000/µL, and elevated C-reactive protein (CRP) level was considered as >50 mg/L. RESULTS: Of 295 eligible AOM episodes, 106 (36%) were culture positive. Children in the pneumococcal group (65, 61%) had a significantly higher WBC counts and higher CRP levels, were more often <2 years old and were more prone to complicate with acute mastoiditis (AM), compared to children in the non-pneumococcal group, P = 0.03, P = 0.02, P = 0.04 and P = 0.03, respectively. In the pneumococcal group, unimmunised children had higher WBC counts when compared with PCV13-immunised children (P = 0.04), but there were no appreciable differences in CRP levels between unimmunised and PCV7/PCV13-immunised children. CONCLUSION: Pneumococcal AOM is associated with higher leukocytosis and CRP levels than non-pneumococcal AOM. Circulating Streptococcus pneumoniae strains causing 'severe' AOM in PCV13-immunised children yielded lower inflammatory responses when compared with unimmunised children.