Can short PROMs support valid factor-based sub-scores? Example of COMQ-12 in chronic otitis media.

PURPOSE: Interpretable factor solutions for questionnaire instruments are typically taken as justification for use of factor-based sub-scores. They can indeed articulate content and construct validities of a total and components but do not guarantee criterion validity for clinical application. Our previous documentation of basic psychometric characteristics for a 12-item patient-reported outcome measure in adult chronic otitis media (COMQ-12) justified next appraising criterion validity of sub-scores. METHODS: On 246 cases at 1st clinic visit, we compared various classes of factor solution, concentrating on the best-fitting 3-factor ones as widely supported. Clinical data offered two independent measures as external criteria: binaural hearing (audiometric thresholds measured via audiometry) for evaluating 'Hearing' sub-score, and oto-microscopic findings for the 'Ear discharge symptoms' sub-score. As criterion for the total, and for semi-generic 'Activities/healthcare' sub-score, the generic Short Form-36 item set offered a widely used multi-item criterion measure. RESULTS: Factor model fit and parsimony again favoured a 3-factor solution for COMQ-12; however insufficient item support and the dominant 1st principal component of variation made sub-scoring problematic. The best solution was bi-factor, from which only the weighted total score met the declared convergent validity standard of r = 0.50. Two of the more specific sub-scores ('Ear discharge symptoms' and 'Hearing') correlated poorly with clinical findings and weighted binaural hearing thresholds. CONCLUSION: The COMQ-12 total is acceptably content-valid for general clinical purposes, but the small item set, reflecting excessive pressure for brevity in clinical application, does not well support three criterion-valid factor-based scores. This distinction should be made explicit, and profile sub-scoring discouraged until good convergent and furthermore divergent criterion validities are shown.

Gains in Quality of Life in Chronic Otitis Media Patients After Surgery, Adjusted for Placebo Bias.

OBJECTIVE: Using a short-form specific questionnaire, we sought to quantify specific and generic benefits of surgery for chronic otitis media (COM) while adjusting for expectancy (placebo) bias. STUDY DESIGN: A prospective observational pretreatment/posttreatment study. SETTING: A national tertiary referral center. PATIENTS: Consecutive adult COM patients were enrolled for 1 year. Of 246 patients, 205 were recommended for surgery, and 167 were operated on the (more) affected ear. INTERVENTIONS: All patients filled out two questionnaires, one specific (Chronic Otitis Media Questionaire-12) and one generic (Short Form-36) at baseline, and then again 6 and 12 months after surgery. MAIN OUTCOME MEASURES: Factor-based scores of questionnaires, standardized response means (SRMs) for treatment effects, with multiple linear regression for implementing bias adjustment. RESULTS: All but one (generic Short Form-36 "mental" scale) of the seven considered measures gave very highly significant ( p < 0.001) improvements. Unadjusted SRMs were large (1.0-2.0 standard deviation units) for audiometry, symptoms of ear discharge, reported hearing, and aggregate specific quality of life, but only moderate for the less specific activity/healthcare. The proposed bias adjustment reduced SRM magnitudes for most measures by about a third, for activity/healthcare and ear discharge by only a tenth to a fifth, and for audiometry not at all. CONCLUSION: Most scores of the specific questionnaire displayed definite placebo-like biases; this demands caution in interpreting improvement after COM surgery. With bias adjustments, credible and worthwhile magnitudes of improvements remained for Chronic Otitis Media Questionnaire-12 total and subscores (0.5-1.09 standard deviation SRM), but not for generic quality of life.

COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study.

Since its first emergence in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic. Whilst often considered a respiratory disease, a large proportion of COVID-19 patients report neurological symptoms, and there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and it is reasonable to expect that many of these may translate into cognitive problems. Indeed, cognitive problems are one of the most commonly reported symptoms in those experiencing "Long COVID"-the chronic illness following COVID-19 infection that affects between 10 and 25% of patients. The COVID and Cognition Study is a part cross-sectional, part longitudinal, study documenting and aiming to understand the cognitive problems in Long COVID. In this first paper from the study, we document the characteristics of our sample of 181 individuals who had experienced COVID-19 infection, and 185 who had not. We explore which factors may be predictive of ongoing symptoms and their severity, as well as conducting an in-depth analysis of symptom profiles. Finally, we explore which factors predict the presence and severity of cognitive symptoms, both throughout the ongoing illness and at the time of testing. The main finding from this first analysis is that that severity of initial illness is a significant predictor of the presence and severity of ongoing symptoms, and that some symptoms during the initial illness-particularly limb weakness-may be more common in those that have more severe ongoing symptoms. Symptom profiles can be well described in terms of 5 or 6 factors, reflecting the variety of this highly heterogenous condition experienced by the individual. Specifically, we found that neurological/psychiatric and fatigue/mixed symptoms during the initial illness, and that neurological, gastrointestinal, and cardiopulmonary/fatigue symptoms during the ongoing illness, predicted experience of cognitive symptoms.

COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are several mechanisms by which the COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those experiencing Long COVID - the chronic illness following the COVID-19 infection that affects between 10 and 25% of patients. However, there is yet little research testing cognition in Long COVID. The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had experienced the COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits. In this second paper from the study, we assess this sample on tests of memory, language, and executive function. We hypothesize that performance on "objective" cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information about the mechanism. We found a consistent pattern of memory deficits in those that had experienced the COVID-19 infection, with deficits increasing with the severity of self-reported ongoing symptoms. Fatigue/Mixed symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance.

Hearing in Adults: A Digital Reprint of the Main Report From the MRC National Study of Hearing.

The 1011-page book, Hearing in Adults, published in 1995, contains the fullest report of the United Kingdom's Medical Research Council National Study of Hearing. It was designed to determine the prevalence and distribution in Great Britain of audiometrically measured hearing loss as a function of age, gender, occupation, and noise exposure. The study's size, quality, and breadth made it unique when it was done in the 1980s. These qualities remain, and its data are still the primary U.K. source for the prevalence of auditory problems. However, only 550 copies were printed, and the book is essentially unobtainable today. We describe here a fully searchable, open-access, digital (PDF) "reprinting" of Hearing in Adults, summarizing the study's design and the book's contents, together with a brief commentary in the light of subsequent developments.

Contrasting Effects of Pressure Compensation on TEOAE and DPOAE in Children With Negative Middle Ear Pressure.

In children with normal cochlear acuity, middle ear fluid often abolishes otoacoustic emissions (OAEs), and negative middle ear pressure (NMEP) reduces them. No convincing evidence of beneficial pressure compensation on distortion product OAE (DPOAE) has yet been presented. Two studies aimed to document effects of NMEP on transient OAE (TEOAE) and DPOAE. In Study 1, TEOAE and DPOAE pass/fail responses were analyzed before and after pressure compensation in 50 consecutive qualifying referrals having NMEP from -100 to -299 daPa. Study 2 concentrated on DPOAE, recording both amplitude (distortion product amplitude) and signal-to-noise ratio (SNR) before and after pressure compensation. Of the 20 participants, 5 had both ears qualifying. An effect of compensation on meeting a pass criterion was present in TEOAE for both left and right ear data in Study 1 but not demonstrable in DPOAE. In Study 2, the distortion product amplitude compensation effect was marginal overall, and depended on recording frequency band. SNR values improved moderately after pressure compensation in the two (overlapping) sets of single-ear data. In the five cases with both ears qualifying, a stronger compensation effect size, over 3 dB, was seen. The absolute dependence of SNR on frequency was also strongly replicated, but in no analysis, the frequency × compensation interaction was significant. Independent of particular frequency range, the data support a limited SNR improvement in 2 to 3 dB for compensation in DPOAE, with slightly larger effects in ears giving SNRs between 0 dB and +6 dB, where pass/fail cutoffs would generally be located.

Psychometric characteristics of the chronic Otitis media questionnaire 12 (COMQ - 12): stability of factor structure and replicability shown by the Serbian version.

BACKGROUND: Recently, demand for and supply of short-form patient-reported outcome measures (PROMs) have risen throughout the world healthcare. Our contribution to meeting that demand has been translating and culturally adapting the Chronic Otitis Media Questionnaire-12 (COMQ-12) for adults into Serbian and enhancing its psychometric base on the relatively large Serbian COM caseload. Chronic otitis media can seriously affect quality of life progressively and in long-term, and it remains the major source of hearing problems in the developing world. METHODS: The translated questionnaire was given twice to 60 adult patients with chronic otitis media of three types (inactive, active mucosal and active squamous disease) and to 60 healthy volunteers. Both patients and volunteers also filled the generic Short-Form 36 questionnaire (SF-36). Conventional statistical procedures were used in strategically driven development of scoring. Additionally, item responses were scaled by linear mapping against the provisional total score. Generalizability, detailed factor interpretation and supportability of scores were criteria, for the best compromise factor solution. RESULTS: Test-retest reliability was very high (0.924 to 0.989, depending on score). The a priori content dimensions of the questionnaire were strongly supported by 3-factor exploratory and confirmatory factor analyses for content validity, separating (i) ear symptoms from (ii) hearing problems, from (iii) daily activity restriction plus healthcare uptake. The 3-factor structure was furthermore highly stable on replication. The very large effect sizes when contrasting patients with healthy volunteers, and active with inactive disease established construct validity for the total score. A strong association with disease activity and a moderate one with generic health-related quality of life (HRQoL), the SF-36, supported construct validity for two of three factors extracted (ear symptoms, and impact on daily activities plus healthcare uptake). CONCLUSIONS: Given the minimal psychometric work to date on COMQ-12, this interim sample with 120 data points adds materially to knowledge of its reliability, several forms of validity and the feasibility of profile sub-scores to supplement total scores. The good psychometric properties shown for COMQ-12 justify both its routine clinical use and acquisition of the necessarily larger sample for generality, score optimisation and the evaluation of responsiveness.

The Chronic Otitis Media Benefit Inventory (COMBI): Development and Validation of a Dynamic Quality of Life Questionnaire for Chronic Ear Disease.

OBJECTIVE: This study introduces a change-oriented short-form health-related quality of life questionnaire suited to symptoms of adult chronic middle ear disease and its consequences, and describes its properties. STUDY DESIGN: Two-centre prospective correlational study primarily for instrument development. SETTING: Two otology secondary care centers in England. PATIENTS: Fifty-two consecutive adult patients with active chronic otitis media undergoing surgery. METHODS: The 12 items for the chronic otitis media benefit inventory (COMBI) were appraised chiefly for internal consistency of resulting score and for factor structure (exploratory factor analysis). RESULTS: The internal consistency of the COMBI was high within our cohort of patients, with a Cronbach's alpha value of 0.907. The three-factor solution from factor analysis explaining 73.6% of the variance was readily interpretable in terms of the intended item content: changes in hearing, ear symptoms, and daily activities plus healthcare uptake. CONCLUSIONS: The COMBI has suitable properties for the dynamic assessment of active chronic otitis media. Initial psychometric appraisal confirms its suitability for early adoption to acquire more comprehensive large-sample information with it and on it, for future refinement and application.

Otitis media.

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.

Precision-scored parental report questions and HL-scaled tympanometry as informative measures of hearing in otitis media 1: Large-sample evidence on determinants and complementarity to pure-tone audiometry.

INTRODUCTION: In otitis media with effusion (OME), hearing loss is a core sign/symptom and basis of concern, with absolute pure-tone threshold sensitivity (in dB HL) by air-conduction providing the default measure of hearing. However several fundamental problems limiting the value of HL measures in otitis media are insufficiently appreciated. To appraise the joint value and implications of multiple hearing measures towards more comprehensive hearing assessment in OM, we examine in two related articles the interrelations and common or diverging determinants of three measures, two of them objective: binaural HL, and ACET (the published quasi-continuous scaling of binaural tympanometry to HL). The third measure is partly subjective: parentally reported hearing difficulties (RHD-4); this is the precision-scored total of the 4 items selected for the OM8-30 general purpose questionnaire for parents in OM. METHODS: The Eurotitis-2 study (Total N=2886) internationally standardises OM8-30 and its OMQ-14 short form. The clinical and parent-response variables acquired cover many issues in diagnosis, symptomatology and impact of OM. Data acquisition was built upon routine clinic practice, enabling us also to document some properties of that practice, such as patterns of missing HL data. To address possible confounding or loss of representativeness from this, we investigated the implications of substituting tympanometry-based ACET for missing HL to give an HL/ACET hybrid. ACET is the mapping of categorical tympanometry to continuous HL. We simulated degrees of artificial missingness of HL up to 35% on the 1430 complete-data cases, using random deletion, with 1000-version bootstrapping. Correlations of this HL/ACET hybrid with pure (100%) HL then documented the degree of correlation retained under dilution of HL by an admixture of ACET; we also documented distribution shapes. For RHD-4, we then probed the determining influences on severity of score as an auditory disability measure, both background ones (from centre, age, sex, socio-economic status, length of history, diagnosis and season) and the two underlying objective hearing measures (HL, ACET). We ran these multiple regressions (GLMs), for representativeness and generality, both on 1430 complete-data cases (i.e. all 3 hearing variables present) and also on supplemented samples according to data required only for particular analyses (N increased by +56% to +68%). A further method of sample supplementation (by up to +96%) used the HL/ACET hybrid. RESULTS: Sex made negligible difference in any analysis. The particular collaborating centre, age, season and diagnosis collectively influenced presence/absence of HL data very strongly. (Area under ROC 0.944). Socio-economic status did not influence HL presence; surprisingly, nor did RHD, ACET or length of history, after control for centre, age, diagnosis and season. Of the inter-correlations between hearing measures, only the one between ACET and RHD was influenced (slightly reduced) by the inclusion of cases without HL data. In the simulated substitutions, Pearson correlation of hybrid HL/ACET with true HL remained above 0.90 for substitution by ACET of up to 30% rate of artificially 'missing' HL. Centre differences were adequately summarised by simple absolute additive differences in mean local case severity. In the determinant models for RHD on the 1430 complete-data cases, HL and the set of background determinants collectively explained broadly similar proportions of RHD's variability, totalling 36.8% explained. On the larger maximum case samples, slightly less absolute variability was explicable than on complete-case data, but relative magnitudes of contribution from individual determinants, both background and hearing measures, remained similar. The expected mean differences in RHD between diagnoses (RAOM, OME, and combined) were found, but the patterns of background and objective measure influences determining RHD did not differ significantly between the diagnoses. CONCLUSIONS: (1) In the Eurotitis-2 database, descriptive differences in various background demographic and clinical measures between cases on whom HL data were obtained versus not, were only of material magnitude for length of history and reported hearing difficulties. Such descriptive differences are not necessarily bases of confounding, so using our framework of 6 background adjuster variables, (particular collaborating centre, age, season, diagnosis, socioeconomic status and length of history) we isolated the determinants of HL data presence. The first four listed strongly predicted HL data presence/absence so are sufficient to control analyses well for any bias or confounding by HL data presence. (2) Diagnoses as OME and combined (OME+RAOM) had higher probability of HL data being present relative to RAOM, indicating that HL acquisition is chiefly seen as confirming and quantifying hearing loss in (suspect) OME, not as ruling it out (e.g. in suspected RAOM). Given this, also using RHD and or ACET as pre-triage to efficiently target capacity and/or reduce costs and opportunity costs of acquiring HL would be rational, but there was no evidence of such precise use of initial hearing-related information to decide on HL acquisition. (3) The full six background variables explained comparable variance in Reported Hearing Difficulties (RHD) to what was explained by ACET, but not quite as much as by HL. Achieving a high percentage explained (32-37% from good models) required both classes of determinant to be entered as predictors. The pattern of background determining influences for RHD was largely stable, with or without objective measures as additional predictors, and on maximum or complete-data cases. Length of history strongly determines RHD for a given concurrent HL. (4) Accepting ACET as substitute where HL was missing in OM cases gave a sample-size enhancement of 17% in Eurotitis-2, with negligible difference in the pattern of determinants. This hybrid measure can be recommended as reasonable next-best when moderate percentages of HL data are missing. (5) The stable pattern of prediction of RHD suggests that our six background determinants provide a very promising low-cost yet comprehensive framework for determination. It hence offers pluripotent statistical adjustment against confounding, applicable to RAOM, OME and combined diagnoses in any analysis using this database. Claims that it thereby offers a sufficient framework for full European standardisation of all the scores from the OM8-30 questionnaire measures await parallel demonstrations for symptom areas other than RHD. As 25% of the variance in RHD severity can be explained by the six adjusters in our framework, none of the six variables should be omitted from acquisition and analytic use in future OM research.

Paracingulate sulcus morphology is associated with hallucinations in the human brain.

Hallucinations are common in psychiatric disorders, and are also experienced by many individuals who are not mentally ill. Here, in 153 participants, we investigate brain structural markers that predict the occurrence of hallucinations by comparing patients with schizophrenia who have experienced hallucinations against patients who have not, matched on a number of demographic and clinical variables. Using both newly validated visual classification techniques and automated, data-driven methods, hallucinations were associated with specific brain morphology differences in the paracingulate sulcus, a fold in the medial prefrontal cortex, with a 1 cm reduction in sulcal length increasing the likelihood of hallucinations by 19.9%, regardless of the sensory modality in which they were experienced. The findings suggest a specific morphological basis for a pervasive feature of typical and atypical human experience.

A causal model for longitudinal randomised trials with time-dependent non-compliance.

In the presence of non-compliance, conventional analysis by intention-to-treat provides an unbiased comparison of treatment policies but typically under-estimates treatment efficacy. With all-or-nothing compliance, efficacy may be specified as the complier-average causal effect (CACE), where compliers are those who receive intervention if and only if randomised to it. We extend the CACE approach to model longitudinal data with time-dependent non-compliance, focusing on the situation in which those randomised to control may receive treatment and allowing treatment effects to vary arbitrarily over time. Defining compliance type to be the time of surgical intervention if randomised to control, so that compliers are patients who would not have received treatment at all if they had been randomised to control, we construct a causal model for the multivariate outcome conditional on compliance type and randomised arm. This model is applied to the trial of alternative regimens for glue ear treatment evaluating surgical interventions in childhood ear disease, where outcomes are measured over five time points, and receipt of surgical intervention in the control arm may occur at any time. We fit the models using Markov chain Monte Carlo methods to obtain estimates of the CACE at successive times after receiving the intervention. In this trial, over a half of those randomised to control eventually receive intervention. We find that surgery is more beneficial than control at 6months, with a small but non-significant beneficial effect at 12months.

Individual differences in behavioral and cardiovascular reactivity to emotive stimuli and their relationship to cognitive flexibility in a primate model of trait anxiety.

High trait anxiety is a risk factor for the development of anxiety disorders. Like the disorders themselves high trait anxiety has marked phenotypic variation at the level of symptomatology and neural circuits, suggesting that there may be different symptoms and distinct neural circuits associated with risk for these disorders. To address these issues, it is essential to develop reliable animal models of trait anxiety in a non-human primate whose brain bears structural and functional similarity to humans. The present study investigated individual variation in responsivity to fearful and anxiety provoking stimuli in the common marmoset monkey. Seven out of 27 animals failed to display discriminative, conditioned cardiovascular and behavioral responses on an auditory fear discrimination task, similar to that seen in high anxious humans and rodents. Their heightened emotionality to a rubber snake was consistent with the hypothesis that they were high in trait-like anxiety. Evidence for phenotypic variation in the high anxiety group was provided by the finding that discrimination failure was predicted early in conditioning by either hyper-vigilant scanning to the cues or a reduction in blood pressure to the context, i.e., test apparatus. Given that high trait anxiety in humans can be associated with altered prefrontal cognitive functioning and previously we implicated the marmoset anterior orbitofrontal (antOFC) and ventrolateral prefrontal cortex (vlPFC) in negative emotion regulation, we also tested the marmosets on two tests of cognitive flexibility differentially dependent on these two regions. While the high anxious group did not differ overall in their perseverative performance, the two distinct phenotypes were differentially correlated with reduced perseverative responding on the OFC- and vlPFC-dependent flexibility tests. Together, this study provides a new model of trait anxiety in marmosets amenable to analysis of phenotypic variation and neural circuitry.

A new health-related quality of life measure for active chronic otitis media (COMQ-12): development and initial validation.

OBJECTIVE: To develop and document for clinical use a new HRQoL questionnaire for the assessment of active chronic otitis media. STUDY DESIGN: Two-center prospective correlational study. SETTING: Two otology referral centers in England. PATIENTS: Fifty consecutive adult patients with a history of active chronic otitis media. RESULTS: Consistency criteria (Cronbach's alpha) and first principle component loadings showed satisfactory scoring with 11 of the original 12 items. A single factor was obtained correlating highly with simple unweighted scoring. CONCLUSION: Sufficient consistency and initial validity information was obtained from patients with a history of active chronic otitis media to justify clinical use of the reduced item set and acquisition of further data to refine scoring.

Young-age gender differences in mathematics mediated by independent control or uncontrollability.

We studied whether the origins of math anxiety can be related to a biologically supported framework of stress induction: (un)controllability perception, here indicated by self-reported independent efforts in mathematics. Math anxiety was tested in 182 children (8- to 11-year-olds). Latent factor modeling was used to test hypotheses on plausible causal processes and mediations within competing models in quasi-experimental contrasts. Uncontrollability perception in mathematics, or (in)dependence of efforts, best fit the data as an antecedent of math anxiety. In addition, the relationship of math anxiety with gender was fully mediated by adaptive perception of control (i.e. controllability). That is, young boys differ from girls in terms of their experience of control in mathematics learning. These differences influence math anxiety. Our findings are consistent with recent suggestions in clinical literature according to which uncontrollability makes women more susceptible to fear and anxiety disorders.

Screening for hearing loss versus parental concern regarding hearing problems: Subsequent referral and treatment for otitis media in the Netherlands.

OBJECTIVE: The present study investigates whether general practitioner (GP) consultation initiated by failing the population hearing screening at age nine months or GP consultation because of parental concern over ear/hearing problems was more important in deciding on referral and/or surgical treatment of otitis media (OM). DESIGN: A questionnaire covering the history between birth and 21 months of age was used to obtain information on referral after failing the hearing screening, GP consultations for ear/hearing problems, and subsequent referral to a specialist and possible surgical treatment at an ENT department. SETTING: The province of Limburg, the Netherlands. SUBJECTS: Healthy infants invited for the hearing screening at age nine months, who responded in an earlier study called PEPPER (Persistent Ear Problems, Providing Evidence for Referral, response rate 58%). MAIN OUTCOME MEASURES: The odds of a child being surgically treated for OM. RESULTS: The response rate for the present questionnaire was 72%. Of all children tested, 3.9% failed the hearing screening and were referred to their GP. Of all 2619 children in this study, 18.6% visited their GP with ear/hearing problems. Children failing the hearing screening without GP consultation for ear/hearing problems were significantly more often treated surgically for OM than children passing the hearing screening but with GP consultation for ear/hearing problems. CONCLUSION: Objectified hearing loss, i.e. failing the hearing screening, was important in the decision for surgical treatment in infants in the Netherlands.

Impact of pneumococcal conjugate vaccination on otitis media: a systematic review.

Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%-9% in randomized trials and 17%-23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3-5 years before 7vCRM introduction (mean change, -15%; range, +14% to -24%) and continued to decline afterward (mean, -19%; range, +7% to -48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM.

Risk factors for failing the hearing screen due to otitis media in Dutch infants.

Hearing loss from otitis media (OM) can affect young children's development. Some children with persistent OM-related hearing loss and associated problems can benefit from treatment, but researchers and clinicians are still unclear on how to identify them best. The present study aims to determine which factors are most related to the hearing loss in OM, as a first step towards an effective case-finding instrument for detecting infants with persistent OM-related hearing loss. The full PEPPER ('Persistent Ear Problems, Providing Evidence for Referral') item pool includes a wide range of risk factors for OM in a single questionnaire, and is easily completed by parents or guardians. The questionnaire was sent to all children invited for the universal hearing screen at age 9 months in Limburg, The Netherlands. Repeatedly failing of the hearing screen was used as outcome marker indicative of OM-related chronic hearing loss. Univariate analyses were conducted to determine statistically significant risk factors predicting 'fail' cases at this hearing screen. Five items were found as individually predictive of hearing screen failure and subsequent referral: 'having severe cold symptoms', 'attending day care with >4 children', 'having siblings', 'severe nasal congestion' and 'male gender'. Suitably worded parental questions document risk factors for OM-related hearing loss in infants, broadly consistent with past general literature on OM risk factors, but more focused. The findings justify further optimising and evaluation of an additive or multiplicative combination of these questions as a means for selecting and routing an infant with diagnosed or suspected OM to further care.

Spatially extended FMRI signal response to stimulus in non-functionally relevant regions of the human brain: preliminary results.

The blood-oxygenation level dependent (BOLD) haemodynamic response function (HDR) in functional magnetic resonance imaging (fMRI) is a delayed and indirect marker of brain activity. In this single case study a small BOLD response synchronised with the stimulus paradigm is found globally, i.e. in all areas outside those of expected activation in a single subject study. The nature of the global response has similar shape properties to the archetypal BOLD HDR, with an early positive signal and a late negative response typical of the negative overshoot. Fitting Poisson curves to these responses showed that voxels were potentially split into two sets: one with dominantly positive signal and the other predominantly negative. A description, quantification and mapping of the global BOLD response is provided along with a 2 × 2 classification table test to demonstrate existence with very high statistical confidence. Potential explanations of the global response are proposed in terms of 1) global HDR balancing; 2) resting state network modulation; and 3) biological systems synchronised with the stimulus cycle. Whilst these widespread and low-level patterns seem unlikely to provide additional information for determining activation in functional neuroimaging studies as conceived in the last 15 years, knowledge of their properties may assist more comprehensive accounts of brain connectivity in the future.