Publications by authors named "Margaretha Casselbrant"

58 Publications

Prevalence of chronic ear disease among HIV+ children in Sub-Saharan Africa.

Int J Pediatr Otorhinolaryngol 2017 Dec 19;103:133-136. Epub 2017 Oct 19.

Department of Otolaryngology-Head & Neck Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; Department of Pediatrics, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA. Electronic address:

Objectives: To determine the prevalence of chronic ear disease in HIV+, highly active anti-retroviral therapy (HAART)-treated children and compare this to the prevalence in healthy children of similar age living in a similar setting.

Introduction: From previous clinical work in Ethiopia, we suspected that chronic middle ear disease was common both in the general pediatric population and especially among children with HIV/AIDS. Few studies have examined the prevalence of chronic ear disease in HIV + children, particularly in those treated with HAART.

Methods: Full examination of the head and neck was performed by otolaryngologists. This including cleaning of cerumen, otoscopy and microscopic otoscopy when needed. Patient's medical records were reviewed. Presence or absence of tympanic membrane (TM) perforation (unilateral or bilateral), tympanosclerosis, TM atrophy, otorrhea and/or cholesteatoma was documented.

Results: 112 HIV+ and 162 healthy (HIVU) children were included. Prevalence of TM perforations was 17% in the HIV + infected versus 3% in the HIVU (Fisher's-Exact-Test; OR: 7.2, 95% CI 2.5-20, p-value <0.0001). Presence of unilateral TM perforations was 12% in the HIV + population and 2% in the HIVU population (Fisher's-Exact-Test; OR: 6.8, 95% CI 2.0-22, p-value 0.002). The presence of bilateral perforations was 4% in the HIV + population and 1% in the HIVU population (Fisher's-Exact-Test; OR: 6.8, 95% CI 1.1-42, p-value 0.088). In the HIV + cohort, 2% were diagnosed with cholesteatoma compared to 0% in the HIVU population (95% CI HIV+ 0.002-0.06; HIVU 0.0-0.02) and 8% of HIV + subjects had active middle ear discharge, compared to 0% in the HIVU population (95% CI HIV+ 0.04-0.1; HIVU 0.0-0.02). Neither tympanosclerosis nor tympanic membrane atrophy was more frequent in the HIV + population compared to the HIVU population. Persistent or recurrent TM perforation was not more frequent in children with prior tympanoplasty in the HIV + population compared to the HIVU population.

Conclusion: TM perforations are significantly more common in HAART-treated HIV + children than in healthy, age-matched HIVU population. Otorrhea and cholesteatoma were found only in the HIV + cohort.
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http://dx.doi.org/10.1016/j.ijporl.2017.10.024DOI Listing
December 2017

Prevalence of hearing-loss among HAART-treated children in the Horn of Africa.

Int J Pediatr Otorhinolaryngol 2017 Jul 2;98:166-170. Epub 2017 May 2.

Departments of Otolaryngology-Head & Neck Surgery and Pediatrics, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA. Electronic address:

Objectives: The prevalence of hearing loss (HL) in children infected with HIV/AIDS is not well studied. Even fewer studies focus on stable HIV-infected children treated with high-effective antiretroviral therapy (HAART). We aim to compare the prevalence of ear disease and HL in HAART-treated, HIV + children in Addis Ababa, Ethiopia with a well, similarly-aged elementary school population with unknown HIV status (HIVU).

Methods: Children underwent standard head and neck examination and cerumen removal by board certified otolaryngologists. Next, certified audiologists performed hearing screening with pure-tone audiometry using a circumaural headset but without an ambient noise reducing environment. Children failing audiometric screening underwent full behavioral audiometry including air and bone testing. The primary outcome parameter was HL > 25 dB with the audiologist accounting for background noise. A second endpoint was PTA >40 dB (500, 1000, 2000 Hz) without assessment of background noise.

Results: 107 HIV+ and 147 HIVU children met inclusion criteria. In the HIV + cohort 17.8% had evidence of TM perforations and 8.4% had otorrhea. In the HIVU group 2.7% had a TM perforation and 0% had otorrhea. Hearing was significantly worse in HIV + children. (Audiologist determination: 38.3% HL HIV+, 12.2% HIVU, Fisher's-Exact-Test OR: 4.5, 95% CI 2.4-8.3, p-value <0.0001; Worse-hearing-ear PTA > 40 dB: 19.6% HL HIV+, 6.1% HIVU, OR: 3.7, 95% CI 1.7-8.4, p-value <0.001).

Conclusions: Chronic OM, conductive and mixed hearing losses are significantly more common in HAART-treated HIV + children than in well, similarly-aged controls. Rates of SNHL are similar.
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http://dx.doi.org/10.1016/j.ijporl.2017.04.050DOI Listing
July 2017

Panel 7: Otitis Media: Treatment and Complications.

Otolaryngol Head Neck Surg 2017 04;156(4_suppl):S88-S105

5 Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh of UPMC, Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Objective We aimed to summarize key articles published between 2011 and 2015 on the treatment of (recurrent) acute otitis media, otitis media with effusion, tympanostomy tube otorrhea, chronic suppurative otitis media and complications of otitis media, and their implications for clinical practice. Data Sources PubMed, Ovid Medline, the Cochrane Library, and Clinical Evidence (BMJ Publishing). Review Methods All types of articles related to otitis media treatment and complications between June 2011 and March 2015 were identified. A total of 1122 potential related articles were reviewed by the panel members; 118 relevant articles were ultimately included in this summary. Conclusions Recent literature and guidelines emphasize accurate diagnosis of acute otitis media and optimal management of ear pain. Watchful waiting is optional in mild to moderate acute otitis media; antibiotics do shorten symptoms and duration of middle ear effusion. The additive benefit of adenoidectomy to tympanostomy tubes in recurrent acute otitis media and otitis media with effusion is controversial and age dependent. Topical antibiotic is the treatment of choice in acute tube otorrhea. Symptomatic hearing loss due to persistent otitis media with effusion is best treated with tympanostomy tubes. Novel molecular and biomaterial treatments as adjuvants to surgical closure of eardrum perforations seem promising. There is insufficient evidence to support the use of complementary and alternative treatments. Implications for Practice Emphasis on accurate diagnosis of otitis media, in its various forms, is important to reduce overdiagnosis, overtreatment, and antibiotic resistance. Children at risk for otitis media and its complications deserve special attention.
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http://dx.doi.org/10.1177/0194599816633697DOI Listing
April 2017

Otitis media.

Nat Rev Dis Primers 2016 09 8;2:16063. Epub 2016 Sep 8.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Otitis media (OM) or middle ear inflammation is a spectrum of diseases, including acute otitis media (AOM), otitis media with effusion (OME; 'glue ear') and chronic suppurative otitis media (CSOM). OM is among the most common diseases in young children worldwide. Although OM may resolve spontaneously without complications, it can be associated with hearing loss and life-long sequelae. In developing countries, CSOM is a leading cause of hearing loss. OM can be of bacterial or viral origin; during 'colds', viruses can ascend through the Eustachian tube to the middle ear and pave the way for bacterial otopathogens that reside in the nasopharynx. Diagnosis depends on typical signs and symptoms, such as acute ear pain and bulging of the tympanic membrane (eardrum) for AOM and hearing loss for OME; diagnostic modalities include (pneumatic) otoscopy, tympanometry and audiometry. Symptomatic management of ear pain and fever is the mainstay of AOM treatment, reserving antibiotics for children with severe, persistent or recurrent infections. Management of OME largely consists of watchful waiting, with ventilation (tympanostomy) tubes primarily for children with chronic effusions and hearing loss, developmental delays or learning difficulties. The role of hearing aids to alleviate symptoms of hearing loss in the management of OME needs further study. Insertion of ventilation tubes and adenoidectomy are common operations for recurrent AOM to prevent recurrences, but their effectiveness is still debated. Despite reports of a decline in the incidence of OM over the past decade, attributed to the implementation of clinical guidelines that promote accurate diagnosis and judicious use of antibiotics and to pneumococcal conjugate vaccination, OM continues to be a leading cause for medical consultation, antibiotic prescription and surgery in high-income countries.
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http://dx.doi.org/10.1038/nrdp.2016.63DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097351PMC
September 2016

Information on co-morbidities collected by history is useful for assigning Otitis Media risk to children.

Int J Pediatr Otorhinolaryngol 2016 Jun 11;85:136-40. Epub 2016 Apr 11.

University of Pittsburgh School of Medicine, Department of Otolaryngology, Pittsburgh, PA, USA.

Objectives: Determine if a 2-Step multivariate analysis of historical symptom/sign data for comorbid diseases can abstract high-level constructs useful in assigning a child's "risk" for different Otitis Media expressions.

Methods: Seventeen items related to the symptom/sign expression of hypothesized Otitis Media comorbidities were collected by history on 141 3-year-old children. Using established criteria, the children were assigned to 1 of 3 groups: Control (no significant past Otitis Media, n=45), Chronic Otitis Media with Effusion (n=45) and Recurrent Acute Otitis Media (n=51). Principal Component Analysis was used to identify factors representing the non-redundant shared information among related items and Discriminant Analysis operating on those factors was used to estimate the best predictor equation for pairwise group assignments.

Results: Six multivariate factors representing the assignable comorbidities of frequent colds, nasal allergy, gastroesophageal disease (specific and general), nasal congestion and asthma were identified and explained 81% of the variance in the 17 items. Discriminant Analysis showed that, for the Control-Chronic Otitis Media with Effusion comparison, a combination of 3 factors and, for the Control-Recurrent Acute Otitis Media comparison, a combination of 2 factors had assignment accuracies of 74% and 68%, respectively. For the contrast between the two disease expressions, a 2-factor combination had an assignment accuracy of 61%.

Conclusion: These results show that this analytic methodology can abstract high-level constructs, comorbidities, from low-level data, symptom/sign scores, support a linkage between certain comorbidities and Otitis Media risk and suggest that specific comorbidity combinations contain information relevant to assigning the risk for different Otitis Media expressions.
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http://dx.doi.org/10.1016/j.ijporl.2016.03.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890165PMC
June 2016

Meniere's disease.

Nat Rev Dis Primers 2016 05 12;2:16028. Epub 2016 May 12.

Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.

Meniere's disease (MD) is a disorder of the inner ear that causes vertigo attacks, fluctuating hearing loss, tinnitus and aural fullness. The aetiology of MD is multifactorial. A characteristic sign of MD is endolymphatic hydrops (EH), a disorder in which excessive endolymph accumulates in the inner ear and causes damage to the ganglion cells. In most patients, the clinical symptoms of MD present after considerable accumulation of endolymph has occurred. However, some patients develop symptoms in the early stages of EH. The reason for the variability in the symptomatology is unknown and the relationship between EH and the clinical symptoms of MD requires further study. The diagnosis of MD is based on clinical symptoms but can be complemented with functional inner ear tests, including audiometry, vestibular-evoked myogenic potential testing, caloric testing, electrocochleography or head impulse tests. MRI has been optimized to directly visualize EH in the cochlea, vestibule and semicircular canals, and its use is shifting from the research setting to the clinic. The management of MD is mainly aimed at the relief of acute attacks of vertigo and the prevention of recurrent attacks. Therapeutic options are based on empirical evidence and include the management of risk factors and a conservative approach as the first line of treatment. When medical treatment is unable to suppress vertigo attacks, intratympanic gentamicin therapy or endolymphatic sac decompression surgery is usually considered. This Primer covers the pathophysiology, symptomatology, diagnosis, management, quality of life and prevention of MD.
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http://dx.doi.org/10.1038/nrdp.2016.28DOI Listing
May 2016

Craniofacial shape in children with and without a positive otitis media history.

Int J Pediatr Otorhinolaryngol 2016 May 5;84:110-5. Epub 2016 Mar 5.

Department of Otolaryngology, University of Pittsburgh School of Medicine, United States.

Objectives: Past studies using traditional morphometric approaches have reported a handful of differences in craniofacial dimensions between individuals with and without otitis media (OM). In this study, a geometric morphometry (GM) approach was used to determine if craniofacial shape is different among children with no history of OM and a history of recurrent acute OM (RAOM) at two different ages.

Methods: Nineteen standard landmarks were identified on lateral cephalometric radiographs from 79 children (41 Control, 38 RAOM) at 4 years and 52 children (27 Control, 25 RAOM) at 6 years of age. Following Procrustes superimposition of the landmark coordinate data, comparisons of group differences in overall size and shape were performed. Discriminant function analysis and principal component analysis were used to determine which, if any, aspects of shape variation distinguished RAOM from Control groups.

Results: At 4 years of age, craniofacial size and shape were significantly different between RAOM and Control groups (p<0.05). Shape differences were evident in the relative positions of the mandible, cranial base, external acoustic meatus, sphenoid and palate. Those shape differences were not found in the 6-year old group.

Conclusions: At 4 years of age, the RAOM and Control groups have distinct craniofacial morphologies, but by 6 years of age these differences have largely disappeared. This is consistent with the clinical observation that excess RAOM risk resolves around 6 years of age and the hypothesis that this resolution is partially a result of age-related craniofacial changes.
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http://dx.doi.org/10.1016/j.ijporl.2016.02.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839180PMC
May 2016

Eustachian Tube Function in 6-Year-Old Children with and without a History of Middle Ear Disease.

Otolaryngol Head Neck Surg 2016 Mar 1;154(3):502-7. Epub 2015 Dec 1.

Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Objective: To test the hypothesis that eustachian tube opening efficiency, measured as the fractional gradient equilibrated (FGE), is lower in 6-year-old children with no middle ear disease but a well-documented history of recurrent acute otitis media, as compared with children with a negative disease history (control).

Study Design: Cross-sectional study.

Setting: Tertiary care pediatric hospital.

Subjects And Methods: Bilateral eustachian tube function was evaluated in 44 healthy 6-year-old children (19 boys, 29 white). None had middle ear disease at the time of testing, but 23 had a history of recurrent acute otitis media. Twenty-one had no significant past otitis media. Eustachian tube function was measured with a pressure chamber protocol that established negative middle ear gauge pressures (referenced to the chamber pressure) and recorded that pressure before and after a swallow. FGE was calculated as the change in middle ear gauge pressure with swallowing divided by the preswallow pressure. Between-group comparisons of the preswallow pressures and FGEs were made with a 2-tailed Student's t test.

Results: FGE was independent of the preswallow middle ear gauge pressure. For the 39 and 44 evaluable ears in the control and recurrent acute otitis media groups, the mean preswallow pressures were -194 daPa (95% confidence interval [95% CI] = -211 to -177) versus -203 (95% CI = -216 to -190; P > .40), and FGEs were 0.32 (95% CI = 0.21-0.43) vs 0.16 (95% CI = 0.08-0.24; P = .016), respectively.

Conclusion: In children with past recurrent acute otitis media, residual eustachian tube opening inefficiency is maintained after they have "outgrown" their middle ear disease.
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http://dx.doi.org/10.1177/0194599815620149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769931PMC
March 2016

Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus.

PLoS One 2015 15;10(7):e0132551. Epub 2015 Jul 15.

Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.

Background: Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts.

Methods: We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls.

Results: In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNFα secretion in myeloid dendritic cells.

Conclusions: The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132551PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503307PMC
May 2016

Intratemporal and intracranial complications of acute otitis media in a pediatric population.

Int J Pediatr Otorhinolaryngol 2014 Dec 6;78(12):2161-4. Epub 2014 Oct 6.

Children's Hospital of Pittsburgh of UPMC, Department of Otolaryngology, 4401 Penn Ave., Pittsburgh, PA 15224, United States. Electronic address:

Objective: To review all cases intratemporal and intracranial complications of acute otitis media (AOM) in infants and children from 1998 to 2013.

Methods: Retrospective chart review of 109 consecutive patients admitted for complications of AOM during a 15-year period at a tertiary-care children's hospital. The main outcomes are: (1) complications of AOM, (2) bacteriology, (3) management strategies.

Results: In our population, complications included mastoiditis (86.1%), subperiosteal abscess (38%), facial nerve palsy (16.7%), sigmoid sinus thrombosis (8.3%) and epidural abscess (7.4%). Other complications included post-auricular cellulitis, otic hydrocephalus and elevated intracranial pressure, internal jugular thrombosis, cranial nerve VI palsy and Gradenigo's syndrome, labyrinthine fistula, sensorineural hearing loss, and cerebellar infarct. Sixty-one patients (56%) received antibiotics prior to presentation. Cultures revealed Streptococcus pneumoniae in 36 patients (33.3%), other bacteria in 30 patients (27.8%), and "no growth" in 33 patients (30.5%). Nine patients (8.3%) did not undergo culture. Of the patients with S. pneumoniae, 20 cultures (55%) were found to be multidrug-resistant. Eleven patients (10.2%) were treated non-surgically, 31 (31%) were treated with myringotomy and intravenous antibiotics. Forty patients (97.5%) presenting with subperiosteal abscess required mastoid surgery. Thirteen of 18 (72.2%) patients with facial paralysis had full recovery. Eight of 10 (80%) patients with epidural abscess empyema required mastoid surgery and incision and drainage of the abscess.

Conclusion: Complications of AOM are uncommon, yet continue to have potentially serious consequences. The bacteriology in this population reveals an increasing trend of multi-drug resistant S. pneumoniae as the causative organism.
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http://dx.doi.org/10.1016/j.ijporl.2014.09.032DOI Listing
December 2014

Eustachian tube function in young children without a history of otitis media evaluated using a pressure chamber protocol.

Acta Otolaryngol 2014 Jun;134(6):579-87

Department of Otolaryngology, Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine , Pittsburgh, PA , USA.

Conclusions: Protocol limitations were identified and accounted for in the analysis. Percent gradient equilibrated (PGE) was affected by driving gradient direction in a similar manner to other efficiency measures. A finer resolution of possible age-related changes in eustachian tube opening efficiency is expected with the application of more sophisticated statistical models to the complete dataset at study end.

Objective: To report the results of an interim analysis for an ongoing study designed to characterize the age-related changes in eustachian tube opening efficiency measured using a pressure chamber protocol in children without a history of middle ear disease.

Methods: To date, 41 children aged 3 years without a history of otitis media have been enrolled in a longitudinal study of the age-related changes in eustachian tube function and evaluated at yearly intervals between 3 and 7 years of age. Eustachian tube opening efficiency, the percent of the applied pressure gradient equilibrated by swallowing, was measured by repeat tympanometry during a pressure chamber protocol. Data (120 tests) were analyzed using an ANOVA with variance partitioned by age (3 through 6 years), gradient direction (positive/negative), and ear (left/right).

Results: PGE was higher for left ears and positive driving gradients, but was not different among age groups.
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http://dx.doi.org/10.3109/00016489.2014.882017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380175PMC
June 2014

The forced-response test does not discriminate ears with different otitis media expressions.

Laryngoscope 2014 Nov 11;124(11):2619-23. Epub 2014 Aug 11.

Department of Otolaryngology, Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.

Objectives/hypothesis: Test the hypothesis that the eustachian tube (ET) function measured using standard manometric test methods is different between groups of ears with tympanostomy tubes inserted for recurrent acute otitis media (RAOM) and for chronic otitis media with effusion (COME).

Study Design: A cross-sectional study of ET function in populations of young children with different otitis media expressions.

Methods: The results for forced-response testing of ET function were compared using a general linear model between 37 ears of 26 children and 34 ears of 26 children, aged 3 and 4 years, with ventilation tubes inserted for COME and RAOM, respectively.

Results: There were no significant between-group differences in either the active measure of ET opening function, dilatory efficiency, or in the passive measures reflecting the magnitude of the forces that tend to hold the ET lumen closed, the opening and closing pressures, and passive trans-ET conductance.

Conclusions: The results do not support the hypothesis that ET closing forces are less in ears with RAOM when compared to ears with COME, and from the results of earlier studies, ears without disease. Both groups were characterized by a low ET opening efficiency (referenced to ears of adults with no disease history). Because both disease expressions present the same pattern of ET dysfunction, other factors are required to explain why a subset of ears with that type of dysfunction develop RAOM, as opposed to the default expression of COME.

Level Of Evidence: 2b
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http://dx.doi.org/10.1002/lary.24647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136992PMC
November 2014

In reference to What is the role of tympanostomy tubes in the treatment of recurrent acute otitis media?

Laryngoscope 2013 Dec 19;123(12):E127. Epub 2013 Sep 19.

Department of Pediatric Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1002/lary.24142DOI Listing
December 2013

A genome-wide association study of chronic otitis media with effusion and recurrent otitis media identifies a novel susceptibility locus on chromosome 2.

J Assoc Res Otolaryngol 2013 Dec 23;14(6):791-800. Epub 2013 Aug 23.

Center for Public Health Genomics, University of Virginia, P.O. Box 800717, Charlottesville, VA, USA.

Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with the most significant associations. Replication genotyping in an independent family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with P < 10(-4) and 12 imputed SNPs with P < 10(-4) on chromosome 15 (near the strongest signal). We replicated the association of rs10497394 (GWAS discovery P = 1.30 × 10(-5)) on chromosome 2 in the independent otitis media population (P = 4.7 × 10(-5); meta-analysis P = 1.52 × 10(-8)). Three additional SNPs had replication P values < 0.10. Two were on chromosome 15q26.1 including rs1110060, the strongest association with COME/ROM in the primary GWAS (P = 3.4 ×10(-7)) in KIF7 intron 7 (P = 0.072), and rs10775247, a non-synonymous SNP in TICRR exon 2 (P = 0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P = 0.045). We have performed the first GWAS of COME/ROM and have identified a SNP rs10497394 on chromosome 2 is significantly associated with COME/ROM susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7 and SP3. The genomic and functional significance of this newly identified locus in COME/ROM pathogenesis requires additional investigation.
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http://dx.doi.org/10.1007/s10162-013-0411-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825021PMC
December 2013

Sensitivity and specificity of eustachian tube function tests in adults.

JAMA Otolaryngol Head Neck Surg 2013 Jul;139(7):719-27

Division of Pediatric Otolaryngology, Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Importance: The study demonstrates the utility of eustachian tube (ET) function (ETF) test results for accurately assigning ears to disease state.

Objectives: To determine if ETF tests can identify ears with physician-diagnosed ET dysfunction (ETD) in a mixed population at high sensitivity and specificity and to define the interrelatedness of ETF test parameters.

Design, Setting, And Participants: Through use of the forced-response, inflation-deflation, Valsalva, and sniffing tests, ETF was evaluated in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2). Data were analyzed using logistic regression including each parameter independently and then a step-down discriminant analysis including all ETF test parameters to predict group assignment. Factor analysis operating over all parameters was used to explore relatedness.

Exposures: ETF testing.

Main Outcomes And Measures: ETF parameters for the forced response, inflation-deflation, Valsalva, and sniffing tests measured in 15 control ears of adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes inserted for ETD (group 2).

Results: The discriminant analysis identified 4 ETF test parameters (Valsalva, ET opening pressure, dilatory efficiency, and percentage of positive pressure equilibrated) that together correctly assigned ears to group 2 at a sensitivity of 95% and a specificity of 83%. Individual parameters representing the efficiency of ET opening during swallowing showed moderately accurate assignments of ears to their respective groups. Three factors captured approximately 98% of the variance among parameters: the first had negative loadings of the ETF structural parameters; the second had positive loadings of the muscle-assisted ET opening parameters; and the third had negative loadings of the muscle-assisted ET opening parameters and positive loadings of the structural parameters.

Conclusions And Relevance: These results show that ETF tests can correctly assign individual ears to physician-diagnosed ETD with high sensitivity and specificity and that ETF test parameters can be grouped into structural-functional categories.
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http://dx.doi.org/10.1001/jamaoto.2013.3559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792585PMC
July 2013

Childhood socioeconomic status, telomere length, and susceptibility to upper respiratory infection.

Brain Behav Immun 2013 Nov 8;34:31-8. Epub 2013 Jul 8.

Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213, USA. Electronic address:

Low socioeconomic status (SES) during childhood and adolescence has been found to predict greater susceptibility to common cold viruses in adults. Here, we test whether low childhood SES is associated with shorter leukocyte telomere length in adulthood, and whether telomere length mediates the association between childhood SES and susceptibility to acute upper respiratory disease in adulthood. At baseline, 196 healthy volunteers reported whether they currently owned their home and, for each year of their childhood, whether their parents owned the family home. Volunteers also had blood drawn for assessment of specific antibody to the challenge virus, and for CD8+ CD28- T-lymphocyte telomere length (in a subset, n=135). They were subsequently quarantined in a hotel, exposed to a virus (rhinovirus [RV] 39) that causes a common cold and followed for infection and illness (clinical cold) over five post-exposure days. Lower childhood SES as measured by fewer years of parental home ownership was associated with shorter adult CD8+ CD28- telomere length and with an increased probability of developing infection and clinical illness when exposed to a common cold virus in adulthood. These associations were independent of adult SES, age, sex, race, body mass, neuroticism, and childhood family characteristics. Associations with infections and colds were also independent of pre-challenge viral-specific antibody and season. Further analyses do not support mediating roles for smoking, alcohol consumption or physical activity but suggest that CD8+ CD28- cell telomere length may act as a partial mediator of the associations between childhood SES and infection and childhood SES and colds.
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http://dx.doi.org/10.1016/j.bbi.2013.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795973PMC
November 2013

Eustachian tube function as a predictor of the recurrence of middle ear effusion in children.

Laryngoscope 2013 Sep 10;123(9):2285-90. Epub 2013 Apr 10.

Department of Otolaryngology, Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A.

Objectives/hypothesis: In children with ventilation tubes (VTs) inserted for chronic otitis media with effusion (COME), the authors sought to determine whether any parameter of Eustachian tube (ET) function measured by the forced response test (FRT) predicts disease recurrence after the VT becomes nonfunctional.

Study Design: Prospective study of those factors that predict disease recurrence in children with VTs inserted for COME.

Methods: Forty-nine subjects (73 ears; 28 male, 34 white, aged 5.3 ± 1.2 years) with COME had VTs inserted and were evaluable for disease status after the VT(s) became nonfunctional. The FRT was done when the VTs were patent, and results for the last test before the VT became nonfunctional were used in the analysis. After each VT became nonfunctional, the children were followed for disease recurrence over a 12-month period. Logistic regression was used to determine whether the ET opening pressure, closing pressure, and/or dilatory efficiency predicted disease recurrence. That model was expanded to include age, sex, race, history of adenoidectomy, previous VTs, and duration of VT patency as potential predictive factors.

Results: Twenty-nine (40%) ears had recurrence of significant disease within 12 months after the VT became nonfunctional. For the complete logistic regression model, male gender (P = .03), nonwhite race (P = .02), shorter period of VT patency (P = .01), and low dilatory efficiency (P = .01) were significant predictors of disease recurrence.

Conclusions: A measure of active ET function, dilatory efficiency, but not measures of passive function predicted disease recurrence within the 12 months after the VT became nonfunctional in children with COME.
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http://dx.doi.org/10.1002/lary.24021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711968PMC
September 2013

Panel 8: Complications and sequelae.

Otolaryngol Head Neck Surg 2013 Apr;148(4 Suppl):E122-43

Department of Otolaryngology, Loma Linda University, Loma Linda, California 92354, USA.

Background And Objectives: Although serious complications of otitis media (OM) such as brain abscess are rare, sequelae of OM such as tympanic membrane perforation and atelectatic tympanic membrane are quite common. Inner ear sequelae can cause hearing loss and speech and language problems. The objectives of this article are to provide a state-of-the-art review on recent articles on complications and sequelae of OM in different anatomic locations, from the tympanic membrane to intracranial sites, as well as hearing loss and speech and language development.

Data Sources: Primarily PubMed supplemented by Ovid MEDLINE and the Cochrane Database.

Review Methods: All types of articles related to OM complications and sequelae published in English between January 2007 and June 2011 were identified. A total of 127 relevant quality articles are summarized and included in this report.

Results: Key findings are summarized based on the following major anatomic locations and categories: tympanic membrane; cholesteatoma; ossicular problems; mucosal sequelae; inner ear sequelae; speech and language development; extracranial areas, including mastoiditis and facial nerve paralysis; intracranial complications; and future research goals. New information and insights were gained to prevent complications and sequelae.

Conclusion And Implications For Practice: Over the past 4 years, progress has been made in advancing the knowledge on the complications and sequelae of OM, which can be used to prevent and treat them effectively. Areas of potential future research have been identified and outlined.
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http://dx.doi.org/10.1177/0194599812467425DOI Listing
April 2013

Panel 1: Epidemiology, natural history, and risk factors.

Otolaryngol Head Neck Surg 2013 Apr;148(4 Suppl):E1-E25

Epidemiology and Statistics Program, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, Maryland 20892, USA.

Background: The First International Symposium on Recent Advances in Otitis Media (OM) with Effusion was held in Columbus, Ohio, in 1975. The symposium has been organized in the United States every 4 years since, followed by a research conference to (a) assess major research accomplishments, (b) identify important research questions and opportunities, (c) develop consensus on definitions and terminology, and (d) establish priorities with short- and long-term research goals. One of the principal areas reviewed quadrennially is Epidemiology, Natural History, and Risk Factors.

Objective: To provide a review of recent literature on the epidemiology, natural history, and risk factors for OM.

Data Sources And Review Methods: A search of OM articles in English published July 2007 to June 2011 was conducted using PubMed and related databases. Those with findings judged of importance for epidemiology, public health, and/or statistical methods were reviewed.

Results: The literature has continued to expand, increasing understanding of the worldwide burden of OM in childhood, complications from treatment failures, and comorbidities. Novel risk factors, including genetic factors, have been examined for OM susceptibility. Population-based studies in Canada, the United States, and other countries confirmed reductions in OM prevalence. Although most studies concentrated on acute OM (AOM) or OM with effusion (OME), a few examined severe chronic suppurative OM (CSOM), a major public health problem in developing countries and for certain indigenous populations around the world.

Conclusions And Implications For Practice: Recent publications have reinforced earlier epidemiological findings, while extending our knowledge in human population groups with high burden of OM.
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http://dx.doi.org/10.1177/0194599812460984DOI Listing
April 2013

Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults.

JAMA 2013 Feb;309(7):699-705

Department of Psychology, Carnegie Mellon University, 5000 Forbes Ave, Pittsburgh, PA 15213, USA.

Importance: Although leukocyte telomere length is associated with mortality and many chronic diseases thought to be manifestations of age-related functional decline, it is not known whether it relates to acute disease in younger healthy populations.

Objective: To determine whether shorter telomeres in leukocytes, especially CD8CD28- T cells, are associated with decreased resistance to upper respiratory infection and clinical illness in young to midlife adults.

Design, Setting, And Participants: Between 2008 and 2011, telomere length was assessed in peripheral blood mononuclear cells (PBMCs) and T-cell subsets (CD4, CD8CD28+, CD8CD28-) from 152 healthy 18- to 55-year-old residents of Pittsburgh, Pennsylvania. Participants were subsequently quarantined (single rooms), administered nasal drops containing a common cold virus (rhinovirus 39), and monitored for 5 days for development of infection and clinical illness.

Main Outcome Measures: Infection (virus shedding or 4-fold increase in virus-specific antibody titer) and clinical illness (verified infection plus objective signs of illness).

Results: Rates of infections and clinical illness were 69% (n = 105) and 22% (n = 33), respectively. Shorter telomeres were associated with greater odds of infection, independent of prechallenge virus-specific antibody, demographics, contraceptive use, season, and body mass index (PBMC: odds ratio [OR] per 1-SD decrease in telomere length, 1.71 [95% CI, 1.08-2.72]; n = 128 [shortest tertile 77% infected; middle, 66%; longest, 57%]; CD4: OR, 1.76 [95% CI, 1.15-2.70]; n = 146 [shortest tertile 80% infected; middle, 71%; longest, 54%]; CD8CD28+: OR, 1.93 [95% CI, 1.21-3.09], n = 132 [shortest tertile 84% infected; middle, 64%; longest, 58%]; CD8CD28-: OR, 2.02 [95% CI, 1.29-3.16]; n = 144 [shortest tertile 77% infected; middle, 75%; longest, 50%]). CD8CD28- was the only cell population in which shorter telomeres were associated with greater risk of clinical illness (OR, 1.69 [95% CI, 1.01-2.84]; n = 144 [shortest tertile, 26%; middle, 22%; longest, 13%]). The association between CD8CD28- telomere length and infection increased with age (CD8CD28- telomere length × age interaction, b = 0.09 [95% CI, 0.02-0.16], P = .01, n = 144).

Conclusion And Relevance: In this preliminary study among a cohort of healthy 18- to 55-year-olds, shorter CD8CD28- T-cell telomere length was associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness.
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http://dx.doi.org/10.1001/jama.2013.613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786437PMC
February 2013

The Cephalic Index is not different among groups of children aged 36-48 months with chronic otitis media with effusion, recurrent acute otitis media and controls.

Int J Pediatr Otorhinolaryngol 2013 Mar 30;77(3):334-7. Epub 2012 Dec 30.

Department of Otolaryngology, Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Objectives: The Cephalic Index, an anthropometric measure of head shape, was reported to be different between individuals with and without signs of past or concurrent otitis media (OM). In this study, we compared the Cephalic Index and other measures of head shape among groups of children aged 36-48 months with a documented history of chronic OM with effusion (COME), recurrent acute OM (RAOM) and CONTROLS (few to no OM episodes) to test that hypothesis.

Methods: In 41 CONTROL, 36 COME and 42 RAOM children, Maximum Head Width, Maximum Head Length and Head Circumference were measured and the Cephalic Index (Head Width/Head Length×100) was calculated. The four measures were compared among the three groups using a General Linear Model that included group, sex and race as factors and age as a covariate.

Results: There were no differences among groups in the Cephalic Index or Head Length. Head Width was significantly smaller in the RAOM when compared to the CONTROL group and Head Circumference was significantly smaller in the RAOM and COME groups when compared to the CONTROL group. For all measures, the distribution of values showed significant overlap among groups.

Conclusions: These results do not support the hypothesis that the Cephalic Index is different between young children with and without OM, but did document differences in Head Width and Circumference among groups. However, the large overlap in each measure for the three groups suggests that none capture sufficient information on Eustachian tube anatomy to predict disease presentation.
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http://dx.doi.org/10.1016/j.ijporl.2012.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570633PMC
March 2013

Reproducibility of the forced response test in children with chronic otitis media with effusion.

Otol Neurotol 2013 Jan;34(1):16-21

Department of Otolaryngology, Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.

Hypothesis: Eustachian tube function is stable over time in children with ventilation tubes for chronic otitis media with effusion.

Background: Clinical studies report that Eustachian tube function tests in patients with a persistent tympanic membrane perforation predict the success of myringoplasty, and those in patients with ventilation tubes for chronic otitis media predict disease recurrence after the tubes become nonfunctional. In those studies, Eustachian tube function was usually tested only once, which presumes a semi-stable basal level of function for greatest diagnostic and prognostic usefulness. We investigated the stability of repeated measurements of Eustachian tube function using the forced response test.

Methods: Thirty-nine children aged 36 to 83 months with bilateral ventilation tubes for chronic otitis media with effusion were evaluated using the forced response test 3 times at 3- to 4-month intervals. The variability across test sessions in the Eustachian tube opening pressure, closing pressure, and dilatory efficiency was estimated using regression/correlation analyses.

Results: For all test parameters, the between-session and between-ear correlation coefficients were significant, but the shared variance in the parameters among test sessions and between ears at the same test session was relatively low. The average slope for each parameter as a function of the time with a ventilation tube was zero.

Conclusion: The low between-test shared variance for the test parameters raises questions as to whether a single forced response test captures sufficient information to accurately diagnose the cause of any dysfunction or to predict with high specificity and sensitivity future disease experience or surgical results.
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http://dx.doi.org/10.1097/MAO.0b013e31827853f4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523714PMC
January 2013

Treatment of acute otitis media in young children.

Curr Allergy Asthma Rep 2012 Dec;12(6):559-63

University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Faculty Pavilion, Pittsburgh, PA 15224, USA.

Although acute otitis media (AOM) is one of the most common pediatric problems, the debate over treatment, especially in young children, continues. The 2004 Guideline on treatment of AOM stated that observation without antimicrobial therapy was an option for selected children 6-24 months of age with AOM. Two recent randomized trials sought to determine the necessity of antimicrobial treatment in young children; both studies found modest, statistically significant, positive effects of treatment. However, these studies provoked a flurry of discussion in the literature and the issue remains unsettled. That prevention is preferable to treatment is not controversial. Eliminating or modifying risk factors and use of vaccines, both bacterial and viral, may help decrease the number of AOM episodes. The discussion on treatment of AOM in young children must also take into account side effects of treatment and effect of treatment on possible long-lasting sequelae of AOM, such as developmental outcomes.
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http://dx.doi.org/10.1007/s11882-012-0309-9DOI Listing
December 2012

The otolaryngologic manifestations in children with eosinophilic esophagitis.

Int J Pediatr Otorhinolaryngol 2012 Jan 16;76(1):116-9. Epub 2011 Nov 16.

Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, United States.

Objectives: (1) To describe the incidence of eosinophilic esophagitis (EoE) in the population of patients undergoing esophagoscopy with biopsy by a pediatric otolaryngology service. (2) To elucidate the demographics, presenting symptoms, and endoscopic findings in children with EoE.

Design: Case series.

Patients/methods: The reports of esophageal biopsy specimens taken over 5 years in 2429 patients were reviewed. Ninety-two patients who received their initial diagnosis of EoE by the pediatric otolaryngology service with specimens showing 15 or greater eosinophils per high power field (HPF) were included.

Interventions: The demographic data, history, presenting symptoms, and endoscopic findings were reviewed retrospectively for the patients.

Main Outcome Measure: The percentage of children diagnosed with EoE of all children undergoing esophageal biopsy.

Results: A total of 92 children were diagnosed with EoE (3.8% of total children biopsied). The mean age at biopsy was 4.4 years, much lower than previously reported in the literature (approximately 8 years); 73% were boys and 27% girls. The main presenting symptom was cough (46%) followed by hoarseness, throat clearing, burping/vomiting, and abdominal pain. Forty three percent had a history of asthma and 17% a history of GERD. Half of patients had esophageal edema, a third were normal, and only a quarter had mucosal furrowing on endoscopic examination.

Conclusions: EoE is increasingly diagnosed as a clinical entity with a distinct symptom profile and etiology. Increased understanding of EoE and its predisposing factors requires a multidisciplinary approach to diagnosis and management involving the pediatric otolaryngologist.
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http://dx.doi.org/10.1016/j.ijporl.2011.10.015DOI Listing
January 2012

Evaluation of 15 functional candidate genes for association with chronic otitis media with effusion and/or recurrent otitis media (COME/ROM).

PLoS One 2011 16;6(8):e22297. Epub 2011 Aug 16.

Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America.

DNA sequence variants in genes involved in the innate immune response and secondary response to infection may confer susceptibility to chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). We evaluated single nucleotide polymorphisms (SNPs) in 15 functional candidate genes. A total of 99 SNPs were successfully genotyped on the Sequenom platform in 142 families (618 subjects) from the Minnesota COME/ROM Family Study. Data were analyzed for association with COME/ROM using the Generalized Disequilibrium Test (GDT). Sex and age at exam were adjusted as covariates, relatedness was accounted for, and genotype differences from all phenotypically discordant relative pairs were utilized to measure the evidence of association between COME/ROM and each SNP. SNP rs2735733 in the region of the mucin 5, subtypes A/C gene (MUC5AC) exhibited nominal evidence for association with COME/ROM (P = 0.002). Two additional SNPs from this region had P values<0.05. Other variants exhibiting associations with COME/ROM at P<0.05 included the SCN1B SNP rs8100085 (P = 0.013), SFTPD SNP rs1051246 (P = 0.039) and TLR4 SNP rs2770146 (P = 0.038). However, none of these associations replicated in an independent sample of COME/ROM families. The candidate gene variants examined do not appear to make a major contribution to COME/ROM susceptibility, despite a priori evidence from functional or animal model studies for a role in COME/ROM pathology.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022297PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156706PMC
February 2012

A pilot study of the ability of the forced response test to discriminate between 3-year-old children with chronic otitis media with effusion or with recurrent acute otitis media.

Acta Otolaryngol 2011 Nov 17;131(11):1150-4. Epub 2011 Aug 17.

Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

Conclusions: When used to test 3-year-old children within 3 months of tympanostomy tube placement for recurrent acute otitis media (rAOM) or chronic otitis media with effusion (cOME) the forced response test (FRT) showed relatively minor differences in the active and passive functions of the eustachian tube. While the sample size was small, the high variability in all test parameters suggests that the FRT alone is not capable of distinguishing between children with different expressions of otitis media.

Objective: The FRT was designed to measure the passive and active properties of the eustachian tube. We evaluated the ability of that test to discriminate groups of children with rAOM or cOME.

Methods: Twenty-two ears (15 children) with a confirmed history of rAOM and 24 ears (17 children) with a confirmed history of cOME were tested at 3 years of age within 3 months of ventilation tube placement. The parameters of the FRT were compared between these groups using a two-tailed Student's t test and the frequencies of ears evidencing eustachian tube dilation with swallowing were compared between groups using a χ(2) test.

Results: Passive resistance and one measure of active function were significantly higher in the rAOM group. The frequency of tubal dilation was not significantly different between groups. There were no differences in any of the FRT measures between cOME ears that did and did not have acute otitis media by history.
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http://dx.doi.org/10.3109/00016489.2011.603137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663051PMC
November 2011

Tympanostomy tube placement and vestibular function in children.

Otolaryngol Head Neck Surg 2011 Oct 15;145(4):666-72. Epub 2011 Jun 15.

Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224, USA.

Objective: To determine the effect of bilateral myringotomy with tube placement (BMT) on balance in children 4 to 7 years old.

Study Design: Case-control study.

Setting: Tertiary-care academic hospital.

Subjects And Methods: Children with otitis media with effusion (OME) who were scheduled for BMT underwent rotational chair testing (RCT) and computerized dynamic posturography (CDP) preoperatively and at 1, 3, and 6 months postoperatively. Control children without a significant history of middle ear disease were tested at the same intervals. Analysis of covariance was performed to evaluate the effect of BMT on RCT and CDP outcomes with age as a covariate.

Results: Seventy-two cases and 56 controls were enrolled. Mean (SD) age was 69 (12) months for cases and 72 (15) months for controls. No difference was seen between groups on RCT outcomes or sensory organization test (SOT) scores. Higher sway velocity during CDP was observed in the OME group both preoperatively and 1 month postoperatively. This difference was not statistically significant. There was no difference between groups 3 months postoperatively. At 6 months, the BMT group had a statistically significant decrease in sway velocity compared with the control group.

Conclusion: No difference was observed between children with OME and controls in RCT or SOT scores. Gradual improvement in sway velocity was observed after BMT. At the final time point, the groups did significantly differ in speed of sway, although the preoperative baseline difference failed to reach statistical significance. The authors suggest that physicians continue to inquire about balance development in patients with OME.
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http://dx.doi.org/10.1177/0194599811412038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856627PMC
October 2011

Perioperative incidence and management of hyponatremia in vWD patients undergoing adenotonsillectomy.

Laryngoscope 2011 Jul 6;121(7):1399-403. Epub 2011 Jun 6.

Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.

Objectives/hypothesis: To analyze the incidence and severity of hyponatremia in patients receiving synthetic desmopressin (DDAVP) in the perioperative setting of oropharyngeal surgery in the treatment of von Willebrand disease and to propose a standardized protocol for perioperative fluid resuscitation and postoperative sodium monitoring after DDAVP administration.

Study Design: Retrospective medical record review.

Methods: A retrospective medical record review in an academic pediatric medical center was conducted. From October 1, 2002, to February 1, 2009, all patients undergoing adenotonsillectomy and receiving DDAVP preoperatively for the treatment of von Willebrand disease were identified. A total of 76 patients were identified by initial database review; 63 patients were included in the study, and 13 patients were excluded secondary to incomplete data. DDAVP dose and timing, perioperative fluid volume and composition, and postoperative sodium levels were collected. Extreme adverse events related to hyponatremia were recorded.

Results: Forty-seven of 63 (74.6%) patients developed some degree of hyponatremia after DDAVP administration, and six of 63 (9.5%) patients developed extreme hyponatremia, with the degree of hyponatremia related to the volume of perioperative fluid resuscitation. The sodium nadir occurred within 9 to 20 hours after DDAVP administration. No serious adverse events related to hyponatremia were recorded during the study period.

Conclusions: The incidence of hyponatremia in children receiving DDAVP for prophylaxis of intraoperative bleeding following oropharyngeal surgery is high. The degree of hyponatremia is related to the perioperative fluid volume administered. A protocol for DDAVP administration, perioperative fluid resuscitation, and postoperative sodium monitoring that aims to reduce the incidence of hyponatremia in this population is proposed.
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http://dx.doi.org/10.1002/lary.21735DOI Listing
July 2011

Reply to Letter to the Editor.

Int J Pediatr Otorhinolaryngol 2010 Aug 10;74(8):971. Epub 2010 Apr 10.

Children's Hospital of Pittsburgh of UPMC, Department of Otolaryngology, 4401 Penn Ave. Pittsburgh, PA 15224, United States.

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http://dx.doi.org/10.1016/j.ijporl.2010.03.011DOI Listing
August 2010

Post-tonsillectomy bleeding in children with von Willebrand disease: a single-institution experience.

Otolaryngol Head Neck Surg 2010 May;142(5):715-21

Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Objectives: 1) Compare rates of post-tonsillectomy bleeding in pediatric patients with and without von Willebrand disease (vWD). 2) Identify factors that may increase the risk for post-tonsillectomy bleeding in children with and without vWD.

Study Design: Historical cohort study.

Setting: Tertiary care, university-based pediatric hospital.

Subjects And Methods: Medical records were examined for 99 patients with vWD and 99 patients without vWD younger than 18 years who underwent tonsillectomy with or without adenoidectomy from August 1997 to October 2005. Subjects were matched for age, year of surgery, type of surgery, and indication for surgery.

Results: Post-tonsillectomy hemorrhage occurred in eight of 99 (8%) vWD patients and in six of 99 (6%) non-vWD patients (P = 0.58, odds ratio 1.36, 95% CI 0.45-4.08). A two-sample test of proportions demonstrated lower and upper limits of -0.051 and 0.092. Four of eight children with vWD and two of six non-vWD patients required surgical intervention for control of bleeding. Ninety-three of 99 vWD patients received desmopressin acetate (DDAVP) preoperatively. In patients with vWD who responded to DDAVP challenge, there was no increased likelihood of post-tonsillectomy bleeding compared with non-vWD patients. No significant difference in the number of bleeding events was noted on the basis of demographics, preoperative laboratories, or use of aminocaproic acid.

Conclusion: Children with vWD undergoing tonsillectomy have a postoperative bleeding rate similar to that of a matched group. However, the sample size was not sufficient to eliminate the possibility of a clinically important difference between the two groups.
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http://dx.doi.org/10.1016/j.otohns.2010.01.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275349PMC
May 2010