International consensus (ICON) on management of otitis media with effusion in children.

Otitis media with effusion (OME) is a common childhood disease defined as the presence of liquid in the middle ear without signs or symptoms of acute ear infection. Children can be impacted mainly with hearing impairment and/or co-occurring recurrent acute otitis media (AOM) thus requiring treatment. Although many meta-analyses and national guidelines have been issued, management remains difficult to standardize, and use of surgical and medical treatments continue to vary. We convened an international consensus conference as part of the 2017 International Federation of Oto-rhino-laryngological Societies Congress, to identify best practices in OME management. Overall, regional differences were minor and consensual management was obtained on several important issues. At initial assessment, although a thorough medical examination is necessary to seek reflux, allergy or nasal obstruction symptoms; an age-appropriate auditory test is the only assessment required in children without abnormal history. Non-surgical treatments poorly address the underlying problem of an age-dependent dysfunctional Eustachian tube; auto-inflation seems to be the only beneficial, low-risk and low-cost non-surgical therapy. There was a clear international recommendation against using steroids, antibiotics, decongestants or antihistamines to treat OME, because of side-effects, cost issues and no convincing evidence of long-term effectiveness. Decisions to insert tympanostomy ventilation tubes should be based on an auditory test but also take into account the child's context and overall hearing difficulties. Tubes significantly improve hearing and reduce the number of recurrent AOM with effusion while in place. Adjuvant adenoidectomy should be considered in children over four years of age, and in those with significant nasal obstruction or infection.

Addiction potential of phentermine prescribed during long-term treatment of obesity.

OBJECTIVE: To investigate if phentermine treatment induces phentermine abuse, psychological dependence (addiction) or phentermine drug craving in overweight, obese and weight loss maintenance patients. To investigate whether amphetamine-like withdrawal occurs after abrupt cessation of long-term phentermine treatment. DESIGN: Clinical intervention trial with interruption of phentermine treatment in long-term patients. SUBJECTS: 269 obese, overweight or formerly obese subjects (age: 20-88 years, BMI: 21-74 kg m(-2)) treated with phentermine long-term (LTP, N=117), 1.1-21.1 years, or short-term (ATP, N=152), 4-22 days, with phentermine doses of 18.75-112.5 (LTP) and 15-93.75 (ATP) mg per day. MEASUREMENTS: Module K of the Mini International Neuropsychiatric Interview modified for phentermine (MINI-SUD), Severity of Dependence Scale (SDS), 45-item Cocaine Craving Questionnaire-NOW (CCQ-NOW) modified for phentermine (PCQ-NOW), and Amphetamine Withdrawal Questionnaire (AWQ) modified for phentermine (PWQ). RESULTS: MINI-SUD interviews were negative for phentermine abuse or psychological dependence in all LTP patients. SDS examination scores were low for all LTP and ATP patients, indicating they were not psychologically dependent upon phentermine. PCQ-NOW scores were low for all LTP and ATP patients, indicating neither short-term nor long-term phentermine treatment had induced phentermine craving. Other than an increase in hunger or eating, amphetamine-like withdrawal symptoms did not occur upon abrupt phentermine cessation as measured by sequential PWQ scores. CONCLUSIONS: Phentermine abuse or psychological dependence (addiction) does not occur in patients treated with phentermine for obesity. Phentermine treatment does not induce phentermine drug craving, a hallmark sign of addiction. Amphetamine-like withdrawal does not occur upon abrupt treatment cessation even at doses much higher than commonly recommended and after treatment durations of up to 21 years.

Selecting infants with OM that need referral and further assessment: creating a case-finding instrument.

OBJECTIVE: In the Netherlands, many children are surgically treated for OM. Recent publications question the need for surgical treatment in common uncomplicated OM, although there is certainly a subgroup of infants that do need further assessment and possible treatment. The present study explores the possibility of using known and presumed risk factors for OM as an instrument for selecting and routing an infant with OM to further care. METHODS: Two questionnaires were used. A questionnaire embracing a wide range of OM-related factors was sent to 6531 children aged nine months that were routinely invited for the hearing screen at nine months. In a second stage, a structured history questionnaire regarding ear and/or hearing problems, subsequent referral and/or treatment, was sent to all parents of children at age 21 months, responding to the first questionnaire. Univariate analysis was performed for identification of potential predictors for surgical treatment of OM for the whole sample as well as for 4 different subsets. Multivariable regression analysis with stepwise backward deletion was applied to arrive at a model for optimal prediction of tube insertion. A ROC (receiver operating characteristic) curve and the accompanying sensitivity and specificity values were analyzed to determine cut off values. RESULTS: Univariate analysis found 10 items predicting surgical treatment for OM. Multivariable regression analysis resulted in a model with a ROC curve having an area of 0.801 and estimated coefficients for risk factors which were used to calculate a OM-score for each case. CONCLUSION: The developed scoring sheet, e.g., to be used in combination with physical examinations and/or tympanometry looks promising as a predictor for those children that might benefit from further assessment and eventually surgically treatment for OM.

The 14-item Paediatric Throat Disorders Outcome Test: a valid, sensitive, reliable, parent-reported outcome measure for paediatric throat disorders.

OBJECTIVES: We modified and abbreviated a pre-existing research questionnaire, the Tonsil and Adenoid Health Status Instrument, to make it suitable for rapid completion as a disease-specific, health-related quality of life research tool for children with tonsil and adenoid disease in the UK. We determined the main psychometric properties of the resulting 14-item Paediatric Throat Disorders Outcome Test. DESIGN, SETTING AND PARTICIPANTS: Pre- and post-operative questionnaires were completed by the parents of children with throat disorders referred to two large hospitals. We included children with recurrent tonsillitis and with obstructive sleep apnoea. A separate cohort of healthy children of comparable age range was also studied. MAIN OUTCOME MEASURES: The test's internal consistency and responsiveness were analysed and its construct validity documented via known-group differences. RESULTS: A total of 126 completed questionnaires were received from the hospital referral group. The children's mean age was 6.5 years (range one to 16). The 40 unaffected children were well matched in age to the study population (mean 6.1 years, range two to 15). Cronbach's alpha coefficient for the pre-operative assessment total score was 0.84. The test-retest reliability coefficient for the total score was 0.98, indicating very high reproducibility. The 14-item Paediatric Throat Disorders Outcome Test discriminated well between children known to suffer with throat problems and a group of healthy controls (p < 0.0001; t = 24.016). Six months after surgical intervention, parentally reported questionnaire scores had improved (i.e. were lower) (p < 0.0001; t = 7.01). The standard effect size (i.e. change in mean divided by baseline standard deviation) for children for whom post-operative questionnaires were completed was 1.53; this is very large. CONCLUSIONS: The 14-item Paediatric Throat Disorders Outcome Test is an appropriate, disease-specific, parent-reported outcome measure for children with throat disorders, for which we have demonstrated internal consistency, reliability, responsiveness to change and two forms of construct validity.

Grommets in otitis media with effusion: an individual patient data meta-analysis.

AIMS: To identify subgroups of children with otitis media with effusion (OME) that might benefit more than others from treatment with ventilation tubes. METHODS: An individual patient data (IPD) meta-analysis on seven randomised controlled trials (n = 1234 children in all), focusing on interactions between treatment and baseline characteristics--hearing level (HL), history of acute otitis media, common colds, attending day-care, gender, age, socioeconomic status, siblings, season, passive smoking, and history of breast feeding. Outcome measures that could be studied were mean time spent with effusion (n = 557), mean hearing levels (n = 557 in studies that randomised children, and n = 180 in studies that randomised ears), and language development (n = 381). RESULTS: In the trials that treated both ears the only significant interaction was between day-care and surgery, occurring where mean hearing level was the outcome measure. None of the other baseline variables showed an interaction effect with treatment that would justify subgrouping. In the trials that treated only one ear, the baseline hearing level showed a significant but not pervasive interaction with treatment-that is, only with a cut-off of 25 dB HL. CONCLUSIONS: The effects of conventional ventilation tubes in children studied so far are small and limited in duration. Observation (watchful waiting) therefore seems to be an adequate management strategy for most children with OME. Ventilation tubes might be used in young children that grow up in an environment with a high infection load (for example, children attending day-care), or in older children with a hearing level of 25 dB HL or greater in both ears persisting for at least 12 weeks.

Can meaningful effective connectivities be obtained between auditory cortical regions?

Structural equation modeling (SEM) of neuroimaging data can be evaluated both for the goodness of fit of the model and for the strength of path coefficients (as an index of effective connectivity). SEM of auditory fMRI data is made difficult by the necessary sparse temporal sampling of the time series (to avoid contamination of auditory activation by the response to scanner noise) and by the paucity of well-defined anatomical information to constrain the functional model. We used SEM (i.e., a model incorporating latent variables) to investigate how well fMRI data in four adjacent cortical fields can be described as an auditory network. Seven of the 14 models (2 hemispheres x (6 subjects and 1 group)) produced a plausible description of the measured data. Since the auditory model to be tested is not fully validated by anatomical data, our approach requires that goodness of fit be confirmed to ensure generalizability of connectivity patterns. For good-fitting models, connectivity patterns varied significantly across subjects and were not replicable across stimulus conditions. SEM of central auditory function therefore appears to be highly sensitive to the voxel-selection procedure and/or the sampling of the time series.

Generalisability of clinical trials in otitis media with effusion.

OBJECTIVE: The impact of a randomised controlled trial (RCT) upon practice depends on its external validity (generalisability). This paper summarises and illustrates a framework for judging and augmenting external validity, emphasising its application to treatment trials in otitis media with effusion (OME) so as to permit stronger inferences in the future. METHODS: The external validity of two surgical trials in the field of OME (TARGET, UK and KNOOP-3, the Netherlands) has been examined within a framework emphasising effect modification, in four specific ways: (1) comparison of the demographic characteristics of the trial population with the domain population; (2) studying the distributions on possible effect modifiers (i.e. variables conditioning the benefit from intervention); (3) studying whether effect modification occurs in the analyses; and (4) comparing outcome measures between the randomised and the eligible but non-randomised children. RESULTS: For neither KNOOP-3 and TARGET were large discrepancies found between randomised and non-randomised children for any of the demographic variables. Differences in distributions along possible effect modifiers were found, but the overlaps were large enough for it still to be possible to study whether these factors indeed modified the outcome. Results for the randomised and non-randomised but eligible patients were similar. The results of both trials therefore appear to be generalisable to their domain populations. CONCLUSIONS: A superficial contrast in the results (KNOOP null, TARGET positive) does not amount to a contradiction, because of differences in the clinical question appropriate to the respective age and populations defined. Attention to quality of design and external validity of randomised controlled trials should achieve higher applicability.

Improving referrals for glue ear from primary care: are multiple interventions better than one alone?

OBJECTIVES: To evaluate the effect of a risk factor checklist and training video for general practitioners in reducing inter-practice variation and improving the appropriateness of referrals (assessed by their positive predictive value or PPV) of patients with suspected otitis media with effusion (OME or 'glue ear') to secondary care. METHODS: Fifty general practices (177 practitioners) from the NHS Trent region and the West of Scotland were cluster-randomised either to a control group (n = 12) or to one of three intervention groups (training video (n = 16), checklist (n = 11), or both (n = 11)). Data on all paediatric ear, nose and throat (ENT) referrals and diagnostic results at ENT clinics were collected for a one-year period pre- and post-intervention. Referral rates for OME and for closely related conditions were calculated for children aged 0-15 years, based on each practice's list size. PPV was defined as the proportion of referrals resulting in bilateral hearing loss > or = 20 dB at the ENT outpatient department. RESULTS: There was a significant improvement in the PPV, adjusted for patients' waiting time between general practitioner (GP) referral and being seen at the ENT department. The improvement in PPV pre- and post-intervention was 15% (95% confidence interval, CI: -12.1% to 41.7%) for the practices receiving both interventions, compared with a degradation of 20% pre- and post-intervention (95% CI: -32.9% to -6.4%) for practices receiving only one intervention and a degradation of 34% for those receiving no intervention. CONCLUSIONS: Disseminating a risk factor checklist and training video on glue ear to GPs using a multi-channel approach can improve the quality of referrals to ENT.

Behaviour and developmental effects of otitis media with effusion into the teens.

OBJECTIVE: To examine whether behavioural or cognitive sequelae of otitis media with effusion (OME) continue into late childhood and the early teens (11-18 years). SETTING: Data from a large multipurpose birth cohort study: the Dunedin multidisciplinary health and development study. PARTICIPANTS: Around 1000 children from the study. The main independent variable of interest was otological status of the child up to age 9. MAIN OUTCOME MEASURES: Parent and teacher rated behaviour problems, including antisocial, neurotic, hyperactive, and inattentive behaviours, and tests of academic achievement including intelligence quotient (IQ), reading, and spelling were available in a high proportion of the cohort at ages 11 to 18 years. RESULTS: After adjustments for covariates such as socioeconomic status, hyperactive and inattentive behaviour problems were evident as late as 15 years, and lower IQ associated with OME remained significant to 13 years. The largest effects were observed for deficits in reading ability between 11 and 18 years. CONCLUSIONS: No previous study considering behaviour problems as an outcome has followed children long enough to determine whether some of the early sequelae of OME are still present in the early to late teens. Some developmental sequelae of OME, particularly deficits in reading ability, can persist into late childhood and the early teens.

Functional magnetic resonance imaging measurements of sound-level encoding in the absence of background scanner noise.

Effects of sound level on auditory cortical activation are seen in neuroimaging data. However, factors such as the cortical response to the intense ambient scanner noise and to the bandwidth of the acoustic stimuli will both confound precise quantification and interpretation of such sound-level effects. The present study used temporally "sparse" imaging to reduce effects of scanner noise. To achieve control for stimulus bandwidth, three schemes were compared for sound-level matching across bandwidth: component level, root-mean-square power and loudness. The calculation of the loudness match was based on the model reported by Moore and Glasberg [Acta Acust. 82, 335-345 (1996)]. Ten normally hearing volunteers were scanned using functional magnetic resonance imaging (tMRI) while listening to a 300-Hz tone presented at six different sound levels between 66 and 91 dB SPL and a harmonic-complex tone (F0= 186 Hz) presented at 65 and 85 dB SPL. This range of sound levels encompassed all three bases of sound-level matching. Activation in the superior temporal gyrus, induced by each of the eight tone conditions relative to a quiet baseline condition, was quantified as to extent and magnitude. Sound level had a small, but significant, effect on the extent of activation for the pure tone, but not for the harmonic-complex tone, while it had a significant effect on the response magnitude for both types of stimulus. Response magnitude increased linearly as a function of sound level for the full range of levels for the pure tone. The harmonic-complex tone produced greater activation than the pure tone, irrespective of the matching scheme for sound level, indicating that bandwidth had a greater effect on the pattern of auditory activation than sound level. Nevertheless, when the data were collapsed across stimulus class, extent and magnitude were significantly correlated with the loudness scale (measured in phons), but not with the intensity scale (measured in SPL). We therefore recommend the loudness formula as the most appropriate basis of matching sound level to control for loudness effects when cortical responses to other stimulus attributes, such as stimulus class, are the principal concern.

Modulation and task effects in auditory processing measured using fMRI.

Active listening has been reported to elicit a different sensory response from passive listening and is generally observed as an increase in the magnitude of activation. Sensory activation differences may therefore be masked by the effect of attention. The present study measured activation induced by static and modulated tones, while controlling attention by using target-discrimination and passive listening tasks. The factorial design enabled us to determine whether the stimulus-induced activation in auditory cortex was independent of the information-processing demands of the task. Contrasted against a silent baseline, listening to the tones induced widespread activation in the temporal cortex, including Heschl's gyrus (HG), planum temporale, superior temporal gyrus (STG), and superior temporal sulcus. No additional auditory areas were recruited in the response to modulated tones compared to static tones, but there was an increase in the response in the STG, anterior to HG. Relative to passive listening, the active task increased the response in the STG, posterior to HG. The active task also recruited regions in the frontal and parietal cortex and subcortical areas. These findings indicate that preferential responses to the changing spectro-temporal properties of the stimuli and to the target-discrimination task involve distinct, non-overlapping areas of the secondary auditory cortex. Thus, in the present study, differences in sensory activation were not masked by the effects of attention.

Behaviour and cognitive outcomes from middle ear disease.

OBJECTIVES: To resolve controversies over associations between a history of middle ear disease and psychosocial or cognitive/educational outcomes. DESIGN: Multipurpose longitudinal birth cohort study. Original cohort comprised all UK births between 5 and 11 April 1970; data were available for approximately 12,000 children at 5 years old and 9000 children at 10 years old. METHODS: For 5 year old children, parent reported data were available on health, social, and behavioural factors, including data on two validated markers of middle ear disease. Cognitive tests were administered at 5 and 10 years of age, and behavioural problems rated at 10 years by the child's teacher. RESULTS: After adjustment for social background and maternal malaise, the developmental sequelae of middle ear disease remained significant even at 10 years. The largest effects were observed in behaviour problems and language test data at age 5, but effect sizes were modest overall. IMPLICATIONS: These results provide an epidemiological basis for policies that aim to minimise the sequelae of middle ear disease by awareness in parents and preschool teachers, early referral, and intervention for more serious or persistent cases.

"Sparse" temporal sampling in auditory fMRI.

The use of functional magnetic resonance imaging (fMRI) to explore central auditory function may be compromised by the intense bursts of stray acoustic noise produced by the scanner whenever the magnetic resonance signal is read out. We present results evaluating the use of one method to reduce the effect of the scanner noise: "sparse" temporal sampling. Using this technique, single volumes of brain images are acquired at the end of stimulus and baseline conditions. To optimize detection of the activation, images are taken near to the maxima and minima of the hemodynamic response during the experimental cycle. Thus, the effective auditory stimulus for the activation is not masked by the scanner noise. In experiment 1, the course of the hemodynamic response to auditory stimulation was mapped during continuous task performance. The mean peak of the response was at 10.5 sec after stimulus onset, with little further change until stimulus offset. In experiment 2, sparse imaging was used to acquire activation images. Despite the fewer samples with sparse imaging, this method successfully delimited broadly the same regions of activation as conventional continuous imaging. However, the mean percentage MR signal change within the region of interest was greater using sparse imaging. Auditory experiments that use continuous imaging methods may measure activation that is a result of an interaction between the stimulus and task factors (e.g., attentive effort) induced by the intense background noise. We suggest that sparse imaging is advantageous in auditory experiments as it ensures that the obtained activation depends on the stimulus alone.

Alternatives in screening at school entry: comparison of the childhood middle ear disease and hearing questionnaire (CMEDHQ) and the pure tone sweep test.

Some health authorities in the UK are discontinuing hearing screening at school entry, mainly because the pure tone sweep test is under-specific (i.e. fails too many children) and thus leads to unnecessary and costly, but unproductive, follow-up assessment. A screening method with different properties such as a questionnaire could be a more cost-effective method of mass screening children. The MRC Institute of Hearing Research has developed and evaluated through several stages such a screening questionnaire (the Childhood Middle Ear Disease and Hearing Questionnaire (CMEDHQ), containing 11 scored questions under two broad headings: history and presentation of the disease, and consultation/treatment history. In a service-based evaluation, 2860 mainstream reception-year school children from two consecutive years, attending schools in south west Cumbria in the North-West Regional Health Authority received the sweep test and the CMEDHQ. (Although predominantly designed to detect middle ear problems, the questionnaire also has some potential to detect permanent hearing loss; thus providing a useful backstop for detection of permanent losses either missed or not present in earlier infancy.) The screening CMEDHQ obtained a very high response rate (90%). Follow-up included 235 control cases as well as all pure tone sweep test failures. Analysis, by use of a definition of cases conservative with respect to the sensitivity of the questionnaire, showed that the CMEDHQ has better specificity, but slightly lower sensitivity, than the pure tone sweep test for composite system decision (where 'case' = treated at ENT; 'non-case' = pass at whatever stage was reached before discharge). Follow-up indicated that the limited method available for assessing sensitivity might give an over-favourable view of the pure tone sweep test. Possible improvement of questionnaire sensitivity by further refinements is under examination. The findings show that it is worth conducting a fully parallel multi-district cost-effectiveness comparison of the pure tone sweep test versus the CMEDHQ.