Non-Surgical Respiratory Management in Relation to Feeding and Growth in Patients with Robin Sequence; a Prospective Longitudinal Study.

OBJECTIVE: To reflect upon our non-surgical respiratory management by evaluating clinical outcomes regarding airway, feeding, and growth during the first year of life in patients with Robin Sequence. DESIGN: Prospective study. SETTING: Sophia Children's Hospital, Rotterdam, the Netherlands. PATIENTS/ PARTICIPANTS: 36 patients with Robin Sequence who were treated between 2011 and 2021. INTERVENTIONS: Positional therapy and respiratory support. MAIN OUTCOME MEASURE(S): Data on respiratory outcomes included polysomnography characteristics and capillary blood gas values. Feeding outcomes were based on the requirement of additional tube feeding. Outcomes on growth were expressed as standard-deviation-scores (SDS) for weight-for-age (WFA) and height-for-age (HFA). RESULTS: Twenty patients were treated with positional therapy (PT), whilst the other 16 patients required respiratory support. Twenty-two patients presented with non-isolated Robin Sequence (RS). During the first year of life, obstructive apnea hypopnea index decreased, oxygen levels enhanced, and capillary blood gas values improved. Eighty-six percent (31/36) experienced feeding difficulties, which completely resolved in 71% (22/31) during their first year of life. From start treatment, to stop treatment, to the age of 1 year, the SDS WFA worsened from -0.40 to -0.33 to -1.03, respectively. CONCLUSIONS: Non-surgical respiratory treatment resulted in an improvement of respiratory outcomes to near normal during the first year of life in patients with RS. These patients often experience feeding difficulties and endure impaired weight gain up to 1 year of age, despite near normalization of breathing. The high prevalence of feeding difficulties and impaired weight for age indicate the urgency for early recognition and adequate treatment to support optimal growth.

De novo TRPV4 Leu619Pro variant causes a new channelopathy characterised by giant cell lesions of the jaws and skull, skeletal abnormalities and polyneuropathy.

BACKGROUND: Pathogenic germline variants in Transient Receptor Potential Vanilloid 4 Cation Channel (TRPV4) lead to channelopathies, which are phenotypically diverse and heterogeneous disorders grossly divided in neuromuscular disorders and skeletal dysplasia. We recently reported in sporadic giant cell lesions of the jaws (GCLJs) novel, somatic, heterozygous, gain-of-function mutations in TRPV4, at Met713. METHODS: Here we report two unrelated women with a de novo germline p.Leu619Pro TRPV4 variant and an overlapping systemic disorder affecting all organs individually described in TRPV4 channelopathies. RESULTS: From an early age, both patients had several lesions of the nervous system including progressive polyneuropathy, and multiple aggressive giant cell-rich lesions of the jaws and craniofacial/skull bones, and other skeletal lesions. One patient had a relatively milder disease phenotype possibly due to postzygotic somatic mosaicism. Indeed, the TRPV4 p.Leu619Pro variant was present at a lower frequency (variant allele frequency (VAF)=21.6%) than expected for a heterozygous variant as seen in the other proband, and showed variable regional frequency in the GCLJ (VAF ranging from 42% to 10%). In silico structural analysis suggests that the gain-of-function p.Leu619Pro alters the ion channel activity leading to constitutive ion leakage. CONCLUSION: Our findings define a novel polysystemic syndrome due to germline TRPV4 p.Leu619Pro and further extend the spectrum of TRPV4 channelopathies. They further highlight the convergence of TRPV4 mutations on different organ systems leading to complex phenotypes which are further mitigated by possible post-zygotic mosaicism. Treatment of this disorder is challenging, and surgical intervention of the GCLJ worsens the lesions, suggesting the future use of MEK inhibitors and TRPV4 antagonists as therapeutic modalities for unmet clinical needs.

Mandibular distraction to correct severe non-isolated mandibular hypoplasia: The role of drug-induced sleep endoscopy (DISE) in decision making.

OBJECTIVES: In patients with mandibular hypoplasia, mandibular distraction osteogenesis (MDO) aims to relieve tongue-based airway obstruction. Drug-induced sleep endoscopy (DISE) provides a dynamic assessment of the upper airway and visualizes anatomical site and cause of airway obstruction. The aim of this study was to evaluate the effect of MDO on tongue-based airway obstruction found by DISE within a non-isolated patient population with severe upper airway obstruction (UAO). Furthermore, we aimed to assess the additional value of DISE in clinical decision making by correlating DISE findings to functional airway outcomes after MDO. METHODS: Findings on DISE in children who underwent MDO were retrospectively gathered and evaluated. According to DISE findings, severity of tongue-based obstruction was scored using a 4-step classification similar to the one that is used by Bravo et al.. Intubation conditions were scored according to the Cormack Lehane score (CLS). Pre-and postoperative DISE findings were compared and correlated with functional airway outcomes following MDO. RESULTS: In 19 out of 28 MDO procedures, both a pre-and postoperative DISE was available. Tongue-based obstruction scores improved in 13 procedures, which correlated to a functional improvement in seven. Postoperative tongue-based obstruction differed significantly between patients with successful MDO and patients treated unsuccessfully (2.00 ((Interquartile range (IQR) 1.00-2.00) vs. 3.00 (IQR 2.00-4.00), p = 0.028), whereas this difference was not significant for the CLS (1.00 (IQR 1.00-1.50) vs. 2.00 (IQR 1.00-4.00), p = 0.066). If no improvement of tongue-based obstruction was seen, MDO is very unlikely to be successful on the functional airway. CONCLUSIONS: DISE provides information on the site and nature of airway obstruction and can visualize the effect of MDO on the severity of tongue-based airway obstruction. Therefore, it can be of additional value in understanding the differences in functional airway outcomes after MDO and aids in deciding appropriate and targeted treatment. Hence, standardized use of DISE, in addition to the clinical assessment of mandibular position and a polysomnography, during MDO management is highly recommended.

Evaluation of the OSA treatment protocol in syndromic craniosynostosis during the first 6 years of life.

INTRODUCTION: Obstructive sleep apnea (OSA) is frequently present in patients with syndromic craniosynostosis. The aim of this study is to determine the long-term effectiveness of our OSA treatment protocol in our tertiary center in a cohort of children with syndromic craniosynostosis. METHODS: Children with syndromic craniosynostosis born between January 2005 and December 2013 were eligible for inclusion (n = 114). Data from ambulatory and inhospital polysomnographies were used. The obstructive-apnea/hypopnea index was used for OSA classification. RESULTS: Polysomnographies were performed in 83 patients. Mild OSA was diagnosed in 19, moderate in six, and severe in seven children. Of the 32 patients with OSA, 12 patients (37.5%) initially received expectant care of which OSA resolved spontaneously in nine without recurrence. Twenty patients were surgically treated. Adenotonsillectomy (ATE) had a 90% success rate with no OSA recurrence. Monobloc surgery was performed in four patients with mild OSA, although not OSA-indicated. Monobloc was performed for moderate or severe OSA in six patients, in four patients in combination with ATE and with mandibular distraction in one. Monobloc surgery for moderate or severe OSA had a 100% success rate in treating OSA and decannulation. CONCLUSION: Expectant care is often sufficient to resolve mild OSA in patients with syndromic craniosynostosis, and should also be considered in patients with moderate OSA with close follow-up. ATE has an important role in the OSA treatment protocol. Monobloc surgery, combined with mandibular distraction on indication, is effective in resolving moderate to severe OSA with a stable long-term result.

Swallowing problems in children with a tracheostomy.

Children with a tracheostomy often present with swallowing disorders. Assessing the impact the presence of the tracheostomy tube has on swallowing function next to the underlying pathology can be very challenging. This article gives an overview of normal swallowing physiology and development, swallowing difficulties as encountered in various airway pathologies and addresses the mechanism by which the tracheostomy tube impacts swallowing. We discuss methods of investigating swallowing disorders and offer tools for management in everyday practice.

Structure and Function of the Vocal Cords after Airway Reconstruction on Magnetic Resonance Imaging.

OBJECTIVES/HYPOTHESIS: Dysphonia is a common problem at long-term follow-up after airway surgery for laryngotracheal stenosis (LTS) with major impact on quality of life. Dysphonia after LTS can be caused by scar tissue from initial stenosis along with anatomical alterations after surgery. There is need for a modality to noninvasively image structure and function of the reconstructed upper airways including the vocal cords to assess voice outcome and possible treatment after LTS. Our objective was to correlate vocal cord structure and function of patients after airway reconstruction for LTS on static and dynamic magnetic resonance imaging (MRI) to voice outcome. STUDY DESIGN: Prospective cohort study. METHODS: Voice outcome was assessed by voice questionnaires ((pediatric) Voice Handicap Index (p)VHI)) and the Dysphonia Severity Index (DSI). Postsurgical anatomy, airway lumen, and vocal cord thickness and movement on multiplanar static high-resolution MRI and dynamic acquisitions during phonation was correlated to voice outcome. RESULTS: Forty-eight patients (age 14.4 (range 7.5-30.7) years) and 11 healthy volunteers (15.9 (8.2-28.8) years) were included. Static MRI demonstrated vocal cord thickening in 80.9% of patients, correlated to a decrease in DSI (expected odds 0.75 [C.I. 0.58-0.96] P = .02). Dynamic MRI showed impaired vocal cord adduction during phonation in 61.7% of patients, associated with a lower DSI score (0.65 [C.I. 0.48-0.88] P = .006). CONCLUSIONS: In LTS patients, after airway reconstruction MRI can safely provide excellent structural and functional detail of the vocal cords correlating to DSI, with further usefulness expected from technical refinements. We therefore suggest MRI as a tool for extensive imaging during LTS follow-up. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2402-E2408, 2021.

MRI of the upper airways in children and young adults: the MUSIC study.

RATIONALE: Paediatric laryngotracheal stenosis (LTS) is often successfully corrected with open airway surgery. However, respiratory and vocal sequelae frequently remain. Clinical care and surgical interventions could be improved with better understanding of these sequelae. OBJECTIVE: The objective of this cross-sectional study was to develop an upper airway MRI protocol to obtain information on anatomical and functional sequelae post-LTS repair. METHODS: Forty-eight patients (age 14.4 (range 7.5-30.7) years) and 11 healthy volunteers (15.9 (8.2-28.8) years) were included. Spirometry and static and dynamic upper airway MRI (3.0 T, 30 min protocol) were conducted. Analysis included assessment of postoperative anatomy and airway lumen measurements during static and dynamic (inspiration and phonation) acquisitions. MAIN RESULTS: Good image quality without artefacts was achieved for static and dynamic images in the majority of MRIs. MRI showed vocal cord thickening in 80.9% of patients and compared with volunteers, a significant decrease in vocal cord lumen area (22.0 (IQR 17.7-30.3) mm2 vs 35.1 (21.2-54.7) mm2, p=0.03) but not cricoid lumen area (62.3±27.0 mm2 vs 66.2±34.8 mm2, p=0.70). Furthermore, 53.2% of patients had an A-frame deformation at site of previous tracheal cannula, showing lumen collapse during inspiration. Dynamic imaging showed incomplete vocal cord abduction during inspiration in 42.6% and incomplete adduction during phonation in 61.7% of patients. CONCLUSIONS: Static and dynamic MRI is an excellent modality to non-invasively image anatomy, tissue characteristics and vocal cord dynamics of the upper airways. MRI-derived knowledge on postsurgical LTS sequelae might be used to improve surgery.

IVORY Guidelines (Instructional Videos in Otorhinolaryngology by YO-IFOS): A Consensus on Surgical Videos in Ear, Nose, and Throat.

OBJECTIVES/HYPOTHESIS: Otolaryngology instructional videos available online are often of poor quality. The objective of this article was to establish international consensus recommendations for the production of educational surgical videos in otolaryngology. STUDY DESIGN: DELPHI survey. METHODS: Twenty-seven international respondents participated in this study from 12 countries. Consensus was reached after three rounds of questionnaires following the Delphi methodology. The proposals having reached the 80% agreement threshold in the third round were retained. RESULTS: The main recommendations are as follows: 1) Ethics: patients must be anonymized and unrecognizable (apart from plastic surgery if necessary). A signed authorization must be obtained if the person is recognizable. 2) Technical aspects: videos should be edited and in high-definition (HD) quality if possible. Narration or subtitles and didactic illustrations are recommended. 3) Case presentation: name of pathology and procedure must be specified; the case should be presented with relevant workup. 4) Surgery: surgical procedures should be divided into several distinct stages and include tips and pitfalls. Pathology should be shown if relevant. Key points should be detailed at the end of the procedure. 5) Organ-specific: type of approach and bilateral audiometry should be specified in otology. Coronal plane computed tomography scans should be shown in endonasal surgery. It is recommended to show pre- and postoperative videos in voice surgery and preoperative drawings and photos of scars in plastic surgery, as well as the ventilation method in airway surgery. CONCLUSIONS: International recommendations have been determined to assist in the creation and standardization of educational surgical videos in otolaryngology and head and neck surgery. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E732-E737, 2021.

Swallowing problems in children with a tracheostomy tube.

INTRODUCTION: Swallowing problems in children with a tracheostomy tube seem to be a common problem, although exact prevalence is not known. The aim of this study is to identify the prevalence and type of swallowing problems in children with a tracheostomy tube. METHODS: We retrospectively included 44 children having a tracheostomy tube at Erasmus MC-Sophia Children's hospital. Assessment by a specialized speech and language therapist, the Modified Evans Blue Dye test, Video Fluoroscopic Swallowing Study and a Fiber-optic Endoscopic Evaluation of Swallowing were reviewed with regard to the different phases of swallowing, in particular signs of aspiration. RESULTS: In our cohort, 31 (70%) children with a tracheostomy tube presented with problems in the oral and/or the pharyngeal phase of swallowing. Overall 19 (43%) children aspirated. CONCLUSIONS: The majority of children with a tracheostomy tube have swallowing problems in the different swallowing phases with a high risk for aspiration.

Pharmacokinetics and safety of tobramycin nebulization with the I-neb and PARI-LC Plus in children with cystic fibrosis: A randomized, crossover study.

AIMS: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I-neb device to the standard PARI-LC Plus nebulizer in children with cystic fibrosis. METHODS: A randomized, open-label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I-neb (75 mg) and PARI-LC Plus (300 mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM-1 and NAG) were measured. Patient and nebulizer satisfaction were assessed. RESULTS: Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG/creatinine ratios at visit 2 for both nebulizers suggest TIS-induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I-neb. CONCLUSIONS: Nebulization of 75 mg TIS with the I-neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI-LC Plus and was well tolerated and preferred over the PARI-LC Plus. Long-term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.

Magnetic resonance imaging of the larynx in the pediatric population: A systematic review.

BACKGROUND: Magnetic Resonance Imaging (MRI) techniques to image the larynx have evolved rapidly into a promising and safe imaging modality, without need for sedation or ionizing radiation. MRI is therefore of great interest to image pediatric laryngeal diseases. Our aim was to review MRI developments relevant for the pediatric larynx and to discuss future imaging options. METHODS: A systematic search was conducted to identify all morphological and diagnostic studies in which MRI was used to image the pediatric larynx, laryngeal disease, or vocal cords. RESULTS: Fourteen articles were included: three studies on anatomical imaging of the larynx, two studies on Diffusion Weighted Imaging, four studies on vocal cord imaging and five studies on the effect of anaesthesiology on the pediatric larynx. MRI has been used for pediatric laryngeal imaging since 1991. MRI provides excellent soft tissue contrast and good visualization of vascular diseases such as haemangiomas. However, visualization of cartilaginous structures, with varying ossification during childhood, and tissue differentiation remain challenging. The latter has been partly overcome with diffusion weighted imaging (DWI), differentiating between benign and malignant masses with excellent sensitivity (94-94.4%) and specificity (91.2-100%). Vocal cord imaging evolved from static images focused on vocal tract growth to dynamic images able to detect abnormal vocal cord movement. CONCLUSION: MRI is promising to evaluate the pediatric larynx, but studies using MRI as diagnostic imaging modality are scarce. New static and dynamic MR imaging techniques could be implemented in the pediatric population. Further research on imaging of pediatric laryngeal diseases should be conducted.

Reference Values for Central Airway Dimensions on CT Images of Children and Adolescents.

OBJECTIVE: The purpose of this study was to acquire normative data on central airway dimensions on chest CT scans in the pediatric population. MATERIALS AND METHODS: Chest CT findings reported as normal by a radiologist were collected retrospectively at 10 international centers. An experienced and independent thoracic radiologist reevaluated all CT scans for image quality and for normal findings. Semiautomated image analysis was performed to measure dimensions of the trachea and right and left main bronchi at inspiration. Intrathoracic tracheal length was measured from carina to thorax inlet. Cross-sectional area and short and long axes were measured perpendicular to the longitudinal airway axis starting from the carina every centimeter upward for the trachea and every 0.5 cm downward for the main bronchi. The effects on airway diameters of age, sex, intrathoracic tracheal length, and distance from the carina were investigated by use of mixed-effects models analysis. RESULTS: Among 1160 CT scans collected, 388 were evaluated as normal by the independent radiologist with sufficient image quality and adequate inspiratory volume level. Central airways were successfully semiautomatically analyzed in 294 of 388 CT studies. Age, sex, intrathoracic tracheal length, and distance from carina were all significant predictors in the models for tracheal and right and left main bronchial diameters (p < 0.001). The central airway dimensions increased with age up to 20 years, and dimensions were larger in male than in female adolescents. CONCLUSION: Normative data were determined for the central airways of children and adolescents. Central airway dimensions depended on distance from the carina and on intrathoracic tracheal length.

Reliability and validity of the Dutch pediatric Voice Handicap Index.

INTRODUCTION: The pediatric voice handicap index (pVHI) has been developed to provide a better insight into the parents' perception of their child's voice related quality of life. The purpose of the present study was to validate the Dutch pVHI by evaluating its internal consistency and reliability. Furthermore, we determined the optimal cut-off point for a normal pVHI score. METHODS: All items of the English pVHI were translated into Dutch. Parents of children in our dysphonic and control group were asked to fill out the questionnaire. For the test re-test analysis we used a different study group who filled out the pVHI twice as part of a large follow up study. Internal consistency was analyzed through Cronbach's α coefficient. The test-retest reliability was assessed by determining Pearson's correlation coefficient. Mann-Whitney test was used to compare the scores of the questionnaire of the control group with the dysphonic group. By calculating receiver operating characteristic (ROC) curves, sensitivity and specificity we were able to set a cut-off point. RESULTS: We obtained data from 122 asymptomatic children and from 79 dysphonic children. The scores of the questionnaire significantly differed between both groups. The internal consistency showed an overall Cronbach α coefficient of 0.96 and an excellent test-retest reliability of the total pVHI questionnaire with a Pearson's correlation coefficient of 0.90. A cut-off point for the total pVHI questionnaire was set at 7 points with a specificity of 85% and sensitivity of 100%. A cut-off point for the VAS score was set at 13 with a specificity of 93% and sensitivity of 97%. CONCLUSIONS: The Dutch pVHI is a valid and reliable tool for the assessment of children with voice problems. By setting a cut-off point for the score of the total pVHI questionnaire of 7 points and the VAS score of 13, the pVHI might be used as a screening tool to assess dysphonic complaints and the pVHI might be a useful and complementary tool to identify children with dysphonia.

Voice outcome and voice-related quality of life after surgery for pediatric laryngotracheal stenosis.

OBJECTIVES: To evaluate the long-term outcome of voice quality and voice-related quality of life after open airway surgery for pediatric laryngotracheal stenosis. STUDY DESIGN: Prospective cohort study. METHODS: Children under the age of 18 years at time of follow-up and with a history of open airway surgery for acquired laryngotracheal stenosis were included in this analysis. To assess voice-related quality of life, the pediatric voice handicap (pVHI) index was completed by the patients' parents. The dysphonia severity index (DSI) was used as an objective measurement for voice quality. RESULTS: Fifty-five parents completed the pVHI, and 38 children completed the DSI. This showed high pVHI values and low total DSI scores, indicating significant voice disturbance. After multivariate analysis, the presence of comorbidities and glottic involvement of the stenosis are associated with poor long-term voice-related quality of life. CONCLUSION: Significant voice disturbance is common after surgery for pediatric laryngotracheal stenosis. Glottic involvement of the stenosis and comorbidities is associated with poor voice-related quality of life. Evaluation of pre- and postoperative voice quality and voice-related quality of life is advised for children treated for laryngotracheal stenosis. LEVEL OF EVIDENCE: 2B. Laryngoscope, 127:1707-1711, 2017.

Reliability of the reflux finding score for infants in flexible versus rigid laryngoscopy.

OBJECTIVES: The Reflux Finding Score for Infants (RFS-I) was developed to assess signs of laryngopharyngeal reflux (LPR) in infants. With flexible laryngoscopy, moderate inter- and highly variable intraobserver reliability was found. We hypothesized that the use of rigid laryngoscopy would increase reliability and therefore evaluated the reliability of the RFS-I for flexible versus rigid laryngoscopy in infants. METHODS: We established a set of videos of consecutively performed flexible and rigid laryngoscopies in infants. The RFS-I was scored twice by 4 otorhinolaryngologists, 2 otorhinolaryngology fellows, and 2 inexperienced observers. Cohen's and Fleiss' kappas (k) were calculated for categorical data and the intraclass correlation coefficient (ICC) was calculated for ordinal data. RESULTS: The study set consisted of laryngoscopic videos of 30 infants (median age 7.5 (0-19.8) months). Overall interobserver reliability of the RFS-I was moderate for both flexible (ICC = 0.60, 95% CI 0.44-0.76) and rigid (ICC = 0.42, 95% CI 0.26-0.62) laryngoscopy. There were no significant differences in reliability of overall RFS-I scores and individual RFS-I items for flexible versus rigid laryngoscopy. Intraobserver reliability of the total RFS-I score ranged from fair to excellent for both flexible (ICC = 0.33-0.93) and rigid (ICC = 0.39-0.86) laryngoscopies. Comparing RFS-I results for flexible versus rigid laryngoscopy per observer, reliability ranged from no to substantial (k = -0.16-0.63, mean k = 0.22), with an observed agreement of 0.08-0.35. CONCLUSION: Reliability of the RFS-I was moderate and did not differ between flexible and rigid laryngoscopies. The RFS-I is not suitable to detect signs or to guide treatment of LPR in infants, neither with flexible nor with rigid laryngoscopy.

Long-term functional airway assessment after open airway surgery for laryngotracheal stenosis.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to evaluate our patient-reported and objective long-term outcomes of patients treated for laryngotracheal stenosis. STUDY DESIGN: Prospective cohort study. METHODS: Sixty-five patients were evaluated after a median follow-up of 7 years after surgery. Follow-up measurements consisted of pulmonary function testing, Bruce treadmill test, and Child Health Questionnaires (CHQ). RESULTS: Pulmonary function tests were available in 43 patients, and 30/43 had abnormal forced expiratory volume in 1 second/forced inspiratory volume in 1 second (FIV1), 25/43 had abnormal FIV1/maximum vital capacity, and 24/43 had abnormal peak expiratory flow. One-third of patients had reduced exercise tolerance. CHQ revealed significant positive correlations with pulmonary function results and exercise tolerance. Multivariate analysis showed that glottic involvement of the stenosis and the presence of comorbidities at time of surgery are the only factors for poor long-term functional outcome. CONCLUSIONS: The majority of patients show deficits in pulmonary function and exercise tolerance related to lower scores of quality of life. Glottic involvement of the stenosis and the presence of comorbidities are the only significant factors for poor functional outcome. Long-term multidisciplinary follow up is mandatory after surgery for laryngotracheal stenosis. LEVEL OF EVIDENCE: 2B.

Positive pressure therapy for Ménière's disease or syndrome.

BACKGROUND: Ménière's disease is an incapacitating disease in which recurrent attacks of vertigo are accompanied by hearing loss, tinnitus and/or aural fullness, all of which are discontinuous and variable in intensity. A number of different therapies have been identified for patients with this disease, ranging from dietary measures (e.g. a low-salt diet) and medication (e.g. betahistine (Serc®), diuretics) to extensive surgery (e.g. endolymphatic sac surgery). The Meniett® low-pressure pulse generator (Medtronic ENT, 1999) is a device that is designed to generate a computer-controlled sequence of low-pressure (micro-pressure) pulses, which are thought to be transmitted to the vestibular system of the inner ear. The pressure pulse passes via a tympanostomy tube (grommet) to the middle ear, and hence to the inner ear via the round and/or oval window. The hypothesis is that these low-pressure pulses reduce endolymphatic hydrops. OBJECTIVES: To assess the effects of positive pressure therapy (e.g. the Meniett device) on the symptoms of Ménière's disease or syndrome. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 6 June 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing positive pressure therapy (using the Meniett or a similar device) with placebo in patients with Ménière's disease. The primary outcome was control of vertigo; secondary outcomes were loss or gain of hearing, severity of tinnitus, perception of aural fullness, functional level, complications or adverse effects, and sick days. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, assessed risk of bias and extracted data. We contacted authors for additional data. Where possible, we pooled study results using a fixed-effect, mean difference (MD) meta-analysis and tested for statistical heterogeneity using both the Chi² test and I² statistic. This was only possible for the secondary outcomes loss or gain of hearing and sick days. We presented results using forest plots with 95% confidence intervals (Cl). MAIN RESULTS: We included five randomised clinical trials with 265 participants. All trials were prospective, double-blind, placebo-controlled randomised controlled trials on the effects of positive pressure therapy on vertigo complaints in Ménière's disease. Overall, the risk of bias varied: three out of five studies were at low risk, one was at unclear risk and one was at high risk of bias. Control of vertigo For the primary outcome, control of vertigo, it was not possible to pool data due to heterogeneity in the measurement of the outcome measures. In most studies, no significant difference was found between the positive pressure therapy group and the placebo group in vertigo scores or vertigo days. Only one study, at low risk of bias, showed a significant difference in one measure of vertigo control in favour of positive pressure therapy. In this study, the mean visual analogue scale (VAS) score for vertigo after eight weeks of treatment was 25.5 in the positive pressure therapy group and 46.6 in the placebo group (mean difference (MD) -21.10, 95% CI -35.47 to -6.73; scale not stated - presumed to be 0 to 100). Secondary outcomes For the secondary outcomes, we carried out two pooled analyses. We found statistically significant results for loss or gain of hearing . Hearing was 7.38 decibels better in the placebo group compared to the positive pressure therapy group (MD) (95% CI 2.51 to 12.25; two studies, 123 participants). The severity of tinnitus and perception of aural fullness were either not measured or inadequate data were provided in the included studies. For the secondary outcome functional level , it was not possible to perform a pooled analysis. One included study showed less functional impairment in the positive pressure group than the placebo group (AAO-HNS criteria, one- to six-point scale: MD -1.10, 95% CI -1.81 to -0.39, 40 participants); another study did not show any significant results. In addition to the predefined secondary outcome measures, we included sick days as an additional outcome measure, as two studies used this outcome measure and it is a complementary measurement of impairment due to Ménière's disease. We did not find a statistically significant difference in sick days. No complications or adverse effects were noted by any study. AUTHORS' CONCLUSIONS: There is no evidence, from five included studies, to show that positive pressure therapy is effective for the symptoms of Ménière's disease. There is some moderate quality evidence, from two studies, that hearing levels are worse in patients who use this therapy. The positive pressure therapy device itself is minimally invasive. However, in order to use it, a tympanostomy tube (grommet) needs to be inserted, with the associated risks. These include the risks of anaesthesia, the general risks of any surgery and the specific risks of otorrhoea and tympanosclerosis associated with the insertion of a tympanostomy tube. Notwithstanding these comments, no complications or adverse effects were noted in any of the included studies.

Intratympanic gentamicin treatment for Ménière's disease: a randomized, double-blind, placebo-controlled trial on dose efficacy - results of a prematurely ended study.

BACKGROUND: Gentamicin is used as a therapeutic agent for Ménière's disease because of its vestibulotoxicity causing chemo-ablation of the vestibular sensory epithelia. Its use has increased in recent years. However, there is still no consensus about the dose regimen of gentamicin in the treatment of Ménière's disease. In this study two different dose regimen treatment protocols are compared in a placebo controlled study design. The primary objective is to quantify the treatment effect on dizziness, the secondary objective is hearing evaluation. METHODS: We performed a randomized, double-blind, placebo-controlled study in adults with unilateral Ménière's disease according to the AAO-HNS guidelines resistant to conservative medication. Three groups received four injections, administered weekly (four intratympanic injections with 40 mg/mL gentamicin solution, two injections gentamicin solution and two injections of placebo in random order, or four injections with placebo). Outcome measures were the score on the Dizziness Handicap Inventory and pure tone audiometry (PTA). Intended follow-up was 2 years. RESULTS: During follow-up one patient exceeded the accepted amount of hearing loss. Further, enrollment was very slow (until 12 months between two patients) and new insights showed an apparent benefit of intratympanic gentamicin treatment (ITG). Therefore we performed an unscheduled interim analysis which showed that PTA threshold shifts reached the stopping criteria in two more patients. Because of this, this study was ended. Of the three patients with the significant PTA threshold shift two were enrolled in the gentamicin group. CONCLUSION: No conclusions can be drawn concerning doses regimens. Now that new publications have shown that ITG treatment can be an effective and safe treatment, a placebo-controlled randomized controlled trial may not pass the ethical committee because of these recent reports in literature. Still, a dose regimen study (without placebo) on ITG treatment needs to be performed. TRIAL REGISTRATION: This trial was registered in The University Medical Center Utrecht/ Gelre hospital Apeldoorn. Protocol ID: 07/343, EudraCT number 2006-005913-37.

Development of the reflux finding score for infants and its observer agreement.

OBJECTIVE: It is hypothesized that laryngeal edema is caused by laryngopharyngeal reflux (LPR) (ie, gastroesophageal reflux extending into the larynx and pharynx). The validated reflux finding score (RFS) assesses LPR disease in adults. We, therefore, aimed to develop an adapted RFS for infants (RFS-I) and assess its observer agreement. STUDY DESIGN: Visibility of laryngeal anatomic landmarks was assessed by determining observer agreement. The RFS-I was developed based on the RFS, the found observer agreement, and expert opinion. An educational tutorial was developed which was presented to 3 pediatric otorhinolaryngologists, 2 otorhinolaryngologists, and 2 gastroenterology fellows. They then scored videos of flexible laryngoscopy procedures of infants who were either diagnosed with or specifically without laryngeal edema. RESULTS: In total, 52 infants were included with a median age of 19.5 (0-70) weeks, with 12 and 40 infants, respectively, for the assessment of the laryngeal anatomic landmarks and the assessment of the RFS-I. Overall interobserver agreement of the RFS-I was moderate (intraclass correlation coefficient = 0.45). Intraobserver agreement ranged from moderate to excellent agreement (intraclass correlation coefficient = 0.50-0.87). CONCLUSION: A standardized scoring instrument was developed for the diagnosis of LPR disease using flexible laryngoscopy. Using this tool, only moderate interobserver agreement was reached with a highly variable intraobserver agreement. Because a valid scoring system for flexible laryngoscopy is lacking up until now, the RFS-I and flexible laryngoscopy should not be used solely to clinically assess LPR related findings of the larynx, nor to guide treatment.

Case report: traumatic displacement of a cochlear implant magnet.

OBJECTIVES: To date, over 200 000 cochlear implants (CIs) have been implanted worldwide and the incidence is still increasing. We present a case of traumatic displacement of CI magnet to raise awareness about this complication and to highlight the need for vigilance during surgery as well as for proper counseling. METHODS: The clinical presentation of a 1.5-year-old boy with a traumatic displacement of a CI magnet was presented and the literature was reviewed for this rare complication. RESULTS: After minor head injury, the sound processor could no longer connect to the CI. X-ray imaging demonstrated displacement of the CI magnet. During revision surgery, the magnet was replaced by a new magnet in the silicon holding cap. Intraoperative impedance measurements were normal and the CI was successfully activated 4 weeks postoperatively. CONCLUSIONS: Clinicians and patients should be aware of the risk of displacement of the CI magnet after (minor) head injury. Young boys tend to have a higher risk for this complication.