High MERS-CoV seropositivity associated with camel herd profile, husbandry practices and household socio-demographic characteristics in Northern Kenya.

Despite high exposure to Middle East respiratory syndrome coronavirus (MERS-CoV), the predictors for seropositivity in the context of husbandry practices for camels in Eastern Africa are not well understood. We conducted a cross-sectional survey to describe the camel herd profile and determine the factors associated with MERS-CoV seropositivity in Northern Kenya. We enrolled 29 camel-owning households and administered questionnaires to collect herd and household data. Serum samples collected from 493 randomly selected camels were tested for anti-MERS-CoV antibodies using a microneutralisation assay, and regression analysis used to correlate herd and household characteristics with camel seropositivity. Households reared camels (median = 23 camels and IQR 16-56), and at least one other livestock species in two distinct herds; a home herd kept near homesteads, and a range/fora herd that resided far from the homestead. The overall MERS-CoV IgG seropositivity was 76.3%, with no statistically significant difference between home and fora herds. Significant predictors for seropositivity (P ⩽ 0.05) included camels 6-10 years old (aOR 2.3, 95% CI 1.0-5.2), herds with ⩾25 camels (aOR 2.0, 95% CI 1.2-3.4) and camels from Gabra community (aOR 2.3, 95% CI 1.2-4.2). These results suggest high levels of virus transmission among camels, with potential for human infection.

Rhinosinusitis, symptomatology & absence of polyposis in children with primary ciliary dyskinesia.

INTRODUCTION: Primary Ciliary Dyskinesia (PCD) describes a group of inherited disorders which result in functional ciliary defects leading to mucous stasis. Clinical manifestations include otitis media with effusion and chronic rhinosinusitis. Nasal polyposis has previously been thought to be linked to PCD, and current theories of 'polypogenesis' suggest that early and severe polyp formation could be expected among sufferers of this condition. METHODS: Cross-sectional observational review of all children attending the multi-disciplinary clinic at a national tertiary-referral centre for PCD across a 3-month period. Careful examination was undertaken, and the SNOT-20 questionnaire administered. RESULTS: Thirty patients were included. No nasal polyps were found, despite children clearly suffering rhinosinusitis and being debilitated by their symptoms. The rhinologically orientated questions of the SNOT-20 produced the most positive responses; however some other questions were found not to be useful in a paediatric population. CONCLUSIONS: Nasal polyps do not occur in children with PCD, despite the presence of rhinosinusitis. Given that many current theories of polyp pathogenesis hinge on prolongation of proinflammatory stimuli, further investigations are needed into why this should not occur in the situation of chronic mucous stasis which is the hallmark of PCD.

Identification of predictors and development of a screening protocol for cerebello-pontine lesions in patients presenting with audio-vestibular dysfunction.

OBJECTIVES: Magnetic resonance imaging (MRI) scanning in the investigation of cerebellopontine angle lesions represents a finite resource, the use of which needs to be carefully rationalised. Our aim was to identify predictive factors that can distinguish between patients with and without cerebellopontine angle lesions, and develop a screening protocol which could be useful in the clinical setting as an aid to clinical judgment. DESIGN: Case-control study. SETTING: Secondary care. PARTICIPANTS: Audio-vestibular features were collated on 136 patients (M : F 1.39 : 1) and 288 controls (M : F 1 : 1.1). INTERVENTION: Diagnostic by analysis of symptoms and audiometric data using logistic regression, receiver-operator characteristic curves and backwards elimination. MAIN OUTCOME MEASURES: Development of a predictive algorithm comprising those factors which are most strongly predictive of the presence of a cerebellopontine angle lesion. RESULTS: Positive predictors of a cerebellopontine angle lesion include the interaural threshold difference at 1 (P = 0.044) and 4 kHz (P = 0.034). The threshold in the better hearing ear at 0.25 kHz exerts a negative predictive (i.e. protective) effect (P = 0.005). The presence of tinnitus does not appear to influence the outcome on logistic regression. Although vertigo does exert an influence on the overall model, its impact is highly equivocal. CONCLUSIONS: We have identified audiometric factors which exert a positive and negative predictive influence on the presence of a cerebellopontine angle lesion, and audiovestibular symptoms which appear to exert little effect on the model. Our predictive equation represents a user-friendly standardised method of risk-stratification of patients within a general otolaryngology clinic.

Out-patient management of patients with a peritonsillar abscess.

In the United Kingdom, patients with a peritonsillar abscess are usually managed as inpatients. However, studies in other countries have shown successful management of these patients as outpatients. We designed an evidence based protocol for the management of patients with a peritonsillar abscess. Diagnosis was by aspiration of pus. Initial treatment was with analgesia, 1.2 g co-amoxiclav and 4 mg dexamethasone intravenously. Data were collected prospectively over 11 months on the management of all patients who had been confirmed by aspiration of pus to have a peritonsillar abscess. Four of the 46 patients (9%) treated as per the protocol required admission, two immediately and two later on. Of the 44 patients initially treated as outpatients, 41 said they were happy to have been treated as outpatients and not admitted to hospital (93%). Patients with a peritonsillar abscess can be managed successfully as outpatients with a high degree of patient satisfaction.

The compliance, true positive and false negative rates of the Charing Cross protocol for magnetic resonance imaging screening for cerebellopontine angle lesions.

OBJECTIVES: To assess the effectiveness and determine the compliance to a local protocol for requesting magnetic resonance imaging scans to screen for the presence of cerebellopontine angle lesions. METHODS: A combined retrospective study of all patients who had magnetic resonance imaging scans requested six months prior to and one year following introduction of the protocol and assessment of the true positive and false negative rate of the protocol by assessment of its sensitivity in cases referred from outside the department. RESULTS: Comparison of the number of scans in each period showed a reduction in annualised rate of 142 to 46. The incidence of positive scans was the same in both periods, increasing the true positive rate from 1.4 to 4.3 per cent. The false negative rate was 1.1 per cent. CONCLUSIONS: The Charing Cross protocol has a good compliance rate within the department, has reduced the cost of screening for cerebellopontine angle lesions and has an acceptable true positive and false negative rate.

Screening patients with sensorineural hearing loss for vestibular schwannoma using a Bayesian classifier.

OBJECTIVES: Selecting patients with asymmetrical sensorineural hearing loss for further investigation continues to pose clinical and medicolegal challenges, given the disparity between the number of symptomatic patients, and the low incidence of vestibular schwannoma as the underlying cause. We developed and validated a diagnostic model using a generalisation of neural networks, for detecting vestibular schwannomas from clinical and audiological data, and compared its performance with six previously published clinical and audiological decision-support screening protocols. DESIGN: Probabilistic complex data classification using a neural network generalization. SETTINGS: Tertiary referral lateral skull base and a computational neuroscience unit. PARTICIPANTS: Clinical and audiometric details of 129 patients with, and as many age and sex-matched patients without vestibular schwannomas, as determined with magnetic resonance imaging. MAIN OUTCOME MEASURES: The ability to diagnose a patient as having or not having vestibular schwannoma. RESULTS: A Gaussian Process Ordinal Regression Classifier was trained and cross-validated to classify cases as 'with' or 'without' vestibular schwannoma, and its diagnostic performance was assessed using receiver operator characteristic plots. It proved possible to pre-select sensitivity and specificity, with an area under the curve of 0.8025. At 95% sensitivity, the trained system had a specificity of 56%, 30% better than audiological protocols with closest sensitivities. The sensitivities of previously-published audiological protocols ranged between 82-97%, and their specificities ranged between 15-61%. DISCUSSION: The Gaussian Process ORdinal Regression Classifier increased the flexibility and specificity of the screening process for vestibular schwannoma when applied to a sample of matched patients with and without this condition. If applied prospectively, it could reduce the number of 'normal' magnetic resonance (MR) scans by as much as 30% without reducing detection sensitivity. Performance can be further improed through incorporating additional data domains. Current findings need to be reproduced using a larger dataset.

The modified 'Parent's Kiss' for the removal of paediatric nasal foreign bodies.

Paediatric nasal foreign bodies is a common clinical problem effecting children mainly 2-8 years of age. Often treated in A & E Departments, with little or no specialised ENT experience or equipment. We present a simple, parent administered technique for removal of paediatric nasal foreign bodies. The technique is safe and effective and is easy to perform on nervous and frightened children.

Thromboprophylaxis in ENT patients: A national survey.

The aim of this survey was to establish whether ENT departments in England follow British Medical Journal guidelines on thromboprophylaxis. A telephone survey of doctors in 80 ENT departments was used to present six clinical scenarios. The participants were asked what their local department routinely did. They were also asked whether they were aware of a local or national thromboprophylaxis policy. For patients undergoing procedures other than major head and neck procedures, compliance was poor and ranged between 7.5% and 37.5%. For laryngectomy, the rate was 82.6%. There was no statistical difference in answers given by doctors of different levels of seniority. Where local thromboprophylaxis guidelines exist, compliance is found to be statistically better. These results suggest that most ENT departments do not follow national or local guidelines on thromboprophylaxis. Greater awareness of existing guidelines is required.

A bifid intra-tympanic facial nerve in association with a normal stapes.

A rare facial nerve anomaly was incidentally discovered whilst performing a tympanoplasty and ossicular reconstruction on a patient with an acquired unilateral conductive hearing loss. The nerve was seen to bifurcate and straddle a normal stapes superstructure as it ran posteriorly through the middle ear, a unique and as yet unreported combination. This case highlights the importance of vigilance regarding facial nerve anatomical variations encountered during middle-ear surgery thus avoiding inadvertent damage. The purported embryological mechanism responsible for such anomalies of the intra-tympanic facial nerve is discussed.

How we do it: ionomeric cement to attach the stapes prosthesis to the long process of the incus.

Keypoints * The successful use of glass-ionomeric cement in primary stapes surgery for attachment of the wire loop of the stapes prosthesis to the long process of the incus is reported. * Early hearing outcomes were similar in patients where cement was used for stapes prosthesis attachment compared with those with standard wire crimping technique. * Use of glass-ionomeric cement to attach the stapes prosthesis to the incus may prevent stapes prosthesis displacement and loosening. * This technique may decrease rates of revision stapes surgery and allow the safe use of magnetic resonance image scanning.

Hearing outcomes in children with primary ciliary dyskinesia--a longitudinal study.

Primary ciliary dyskinesia (PCD) is a congenital abnormality of ciliary structure or function. The otological manifestations of the disease include otitis media with effusion (OME). To date, the severity of hearing loss and natural progression of OME in this select group of patients has not been documented. In this retrospective observational study, we looked at the tympanograms and audiograms of all children with PCD attending the Royal Brompton Hospital multidisciplinary clinic. Our results show an improvement in both hearing thresholds and tympanograms with age (p<0.001). Most cases resolve by the age of 12. This supports the current practice of conservative management in these patients. The problems of persistent otorrhoea and residual tympanic membrane perforation are thereby avoided with the reassurance that hearing loss will spontaneously resolve with time.

Magnetic resonance imaging screening for vestibular schwannoma: analysis of published protocols.

This study seeks to define the most appropriate guidelines for selection of patients for magnetic resonance imaging (MRI) to exclude a vestibular schwannoma. Improved selection may reduce patient anxiety and improve resource utilization. All MRIs of the internal auditory meatus, performed during the year 2000, were reviewed. Audiograms and symptoms were collated for all 'positive' scans and 100 negative scans. Information was analysed using seven published protocols and other defined frequency specific criteria. A diagnosis of vestibular schwannoma was made on 36 scans. Four criteria had a sensitivity of >95 per cent; of these the highest specificity (49 per cent) utilized an interaural difference at two adjacent frequencies of 15.dB in unilateral hearing loss and 20.dB in bilateral asymmetric loss. Applying our best protocol would have reduced the number of scans performed from 392 to 168. The one patient with a vestibular schwannoma who was excluded had trigeminal paraesthesia, an independent indication for investigation.

Glomus jugulare tumour presenting with isolated accessory nerve palsy.

Glomus tumours of the skull base are rare, and most frequently present with symptoms of hearing loss and tinnitus. Diagnosis is often delayed due to the slow growth of the tumour. We describe the previously unreported occurrence of a glomus tumour presenting with a unilateral accessory nerve palsy.

A targeted approach significantly increases the identification rate of patients with undiagnosed haemochromatosis.

OBJECTIVE: To determine the optimal means of identifying patients with undiagnosed haemochromatosis. DESIGN: Case-control study where cases are defined by the presence of specific clinical diagnoses or symptoms. SETTING: Primary care patients were recruited from three Oxfordshire practices and secondary care patients were recruited from those patients attending specialist clinics in Amiens University Hospital. SUBJECTS: A total of 569 patients recruited via hospital clinics and 60 primary care patients (recruited from 4022 consultations) presenting with the following haemochromatosis associated conditions, diabetes, arthralgia/chronic fatigue, osteoporosis or arthropathy were studied. The control group, a total of 991 healthy volunteers, were recruited through a Health Appraisal Centre. Patients and controls were included in the study if they or their family members had not previously been diagnosed with hereditary haemochromatosis. MAIN OUTCOME MEASURES: Serum ferritin concentration, transferrin saturation (Tsat) and presence of HFE mutations, C282Y and H63D. The check-up in controls consisted of a questionnaire, clinical examination, biochemical tests and screening for the presence of the C282Y and H63D mutations. RESULTS: Patient groups presenting with unstable diabetes or chronic fatigue and arthralgia together with a raised serum ferritin concentration showed an enrichment in the haemochromatosis-associated genotype HH/YY, odds ratio (OR) = 40.1, confidence interval (CI) = 8.0-202.1 and OR = 103, CI = 22.9-469.7, respectively. CONCLUSION: Patients presenting to hospital clinics with haemochromatosis associated conditions should be screened biochemically for iron overload. Only those with a serum ferritin >300 microg L-1 or Tsat >40% should subsequently go on to be genotyped for HFE mutations. The patients at greatest risk of having undiagnosed haemochromatosis are those presenting with unstable diabetes, or fatigue and/or arthralgia in the absence of any other explanation.

Guidelines for referral to a regional genetics service: GPs respond by referring more appropriate cases.

OBJECTIVES: The aim of this study was to see whether guidelines on whom to refer to a regional genetics service could improve the appropriateness of referrals to the service. It also aimed to assess whether the genetic clinic assessment of risk agreed with that described in the GP letter. METHODS: Referral guidelines were sent to all Oxfordshire GPs and the subsequent content of the referral letters was analysed. A retrospective assessment of referral letters sent during the 6 months before dissemination was also made. RESULTS: The study showed that post-guidelines, fewer "lower risk" referrals were made and that the description of the risk in the GP letter improved, so that a greater proportion of genetic clinic risks agreed with those described in the GP letter. CONCLUSION: The use of referral guidelines can help GPs to act as gatekeeper for referrals to secondary care.

Multiple signaling cascades are differentially involved in gene induction by double stranded RNA in interferon-alpha-primed cells.

Priming with interfon (IFN)alpha enhanced the ability of the synthetic double-stranded RNA polyriboinosinic acid: polyribocytidilic acid (pI:C), but not interleukin-1 beta, to activate both p38 mitogen-activated kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling cascades. Activation by pI:C in IFN alpha-primed cells was delayed compared to activation with interleukin-1 beta, and this delay was followed by high, sustained activation of p38 MAPK and a modest elevation of ERK activation. Pharmacologic inhibition of either the ERK or the p38 MAPK pathway, using U0126 and SB203580, respectively, reduced interleukin-6 protein induction by at least 70%, and combined inhibition of both pathways fully blocked interleukin-6 protein expression and reduced interleukin-6 mRNA induction by more than 80%. In contrast, induction of double-stranded RNA-activated protein kinase (PKR) mRNA and protein by IFN alpha and/or pI:C was minimally affected by either inhibitor. Induction of interferon-regulatory factor-1 (IRF-1) by pI:C in IFN alpha primed cells was profoundly inhibited by U0126 but not by SB203580. Thus, IFN alpha priming enhances activation of p38 MAPK and ERK pathways by pI:C but not by interleukin-1 beta, thereby enhancing the expression of some, but not all, genes that are induced by pI:C.

Modulation of double-stranded RNA-mediated gene induction by interferon in human umbilical vein endothelial cells.

Endothelial cells respond to double-stranded RNA (dsRNA) with expression of a number of important immunomodulatory and inflammatory response genes, including adhesion molecules, cytokines, and antiviral genes. Considerable differences are seen when genes are induced by dsRNA compared with cytokines. Much higher levels of mRNA for interleukin-6 (IL-6), 2',5'-oligoadenylate synthetase (2',5'-OAS), protein kinase (PKR), and interferon (IFN) regulatory factor-1 (IRF-1) result from incubation with dsRNA than with IL-1beta, tumor necrosis factor-alpha (TNF-alpha), or IFN-alpha, whereas the differences in vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin mRNA expression in response to dsRNA, IL-1beta, and TNF-alpha are relatively minor. IFN-alpha priming enhances responsiveness of some, but not all, genes to dsRNA but not to IL-1beta, but the optimal time for pretreatment varies considerably among different dsRNA-responsive genes. Protein translation is reduced in human umbilical vein endothelial cells (HUVEC) in response to incubation with dsRNA, and this decrease is accentuated if cells are primed with IFN-alpha. Despite this decrease, IFN-alpha priming causes very high levels of IL-6 protein expression in response to dsRNA but not in response to IL-1beta or TNF-alpha. These studies demonstrate that priming with class I IFN can enhance the response to dsRNA through the heightened expression of genes that contribute to both the cellular response to viral infection and the host immunologic response.