Defining performance levels in undergraduate otolaryngology education.

OBJECTIVES: This study seeks the opinions of qualified doctors on what they feel medical students should learn about otolaryngology. It aims to identify both the content deemed relevant and the performance levels for medical students in otolaryngology. METHODS: A national survey developed from a content analysis of undergraduate otolaryngology curricula from the UK was undertaken, accompanied by a review of the literature and input from an expert group. Data were collected from a wide range of doctors. RESULTS: Participants felt that graduating students should be able to: recognise, assess and initiate management for common and life-threatening acute conditions; take an appropriate patient history; and perform an appropriate examination for the majority of otolaryngology clinical conditions but manage only a select few. CONCLUSION: This study reports performance levels for otolaryngology topics at an undergraduate level. Participating doctors felt that a higher level of performance should be expected of students treating life-threatening, acute and common otolaryngology conditions.

Sustainability of Biosimilars in Europe: A Delphi Panel Consensus with Systematic Literature Review.

INTRODUCTION: Biosimilars have the potential to enhance the sustainability of evolving health care systems. A sustainable biosimilars market requires all stakeholders to balance competition and supply chain security. However, there is significant variation in the policies for pricing, procurement, and use of biosimilars in the European Union. A modified Delphi process was conducted to achieve expert consensus on biosimilar market sustainability in Europe. METHODS: The priorities of 11 stakeholders were explored in three stages: a brainstorming stage supported by a systematic literature review (SLR) and key materials identified by the participants; development and review of statements derived during brainstorming; and a facilitated roundtable discussion. RESULTS: Participants argued that a sustainable biosimilar market must deliver tangible and transparent benefits to the health care system, while meeting the needs of all stakeholders. Key drivers of biosimilar market sustainability included: (i) competition is more effective than regulation; (ii) there should be incentives to ensure industry investment in biosimilar development and innovation; (iii) procurement processes must avoid monopolies and minimize market disruption; and (iv) principles for procurement should be defined by all stakeholders. However, findings from the SLR were limited, with significant gaps on the impact of different tender models on supply risks, savings, and sustainability. CONCLUSIONS: A sustainable biosimilar market means that all stakeholders benefit from appropriate and reliable access to biological therapies. Failure to care for biosimilar market sustainability may impoverish biosimilar development and offerings, eventually leading to increased cost for health care systems and patients, with fewer resources for innovation.

Depressed neuromuscular transmission causes weakness in mice lacking BK potassium channels.

Mice lacking functional large-conductance voltage- and Ca2+-activated K+ channels (BK channels) are viable but have motor deficits including ataxia and weakness. The cause of weakness is unknown. In this study, we discovered, in vivo, that skeletal muscle in mice lacking BK channels (BK-/-) was weak in response to nerve stimulation but not to direct muscle stimulation, suggesting a failure of neuromuscular transmission. Voltage-clamp studies of the BK-/- neuromuscular junction (NMJ) revealed a reduction in evoked endplate current amplitude and the frequency of spontaneous vesicle release compared with WT littermates. Responses to 50-Hz stimulation indicated a reduced probability of vesicle release in BK-/- mice, suggestive of lower presynaptic Ca2+ entry. Pharmacological block of BK channels in WT NMJs did not affect NMJ function, surprisingly suggesting that the reduced vesicle release in BK-/- NMJs was not due to loss of BK channel-mediated K+ current. Possible explanations for our data include an effect of BK channels on development of the NMJ, a role for BK channels in regulating presynaptic Ca2+ current or the effectiveness of Ca2+ in triggering release. Consistent with reduced Ca2+ entry or effectiveness of Ca2+ in triggering release, use of 3,4-diaminopyridine to widen action potentials normalized evoked release in BK-/- mice to WT levels. Intraperitoneal application of 3,4-diaminopyridine fully restored in vivo nerve-stimulated muscle force in BK-/- mice. Our work demonstrates that mice lacking BK channels have weakness due to a defect in vesicle release at the NMJ.

Levator Auris Longus Preparation for Examination of Mammalian Neuromuscular Transmission Under Voltage Clamp Conditions.

This protocol describes a technique to record synaptic transmission from the neuromuscular junction under current-clamp and voltage-clamp conditions. An ex vivo preparation of the levator auris longus (LAL) is used because it is a thin muscle that provides easy visualization of the neuromuscular junction for microelectrode impalement at the motor endplate. This method allows for the recording of spontaneous miniature endplate potentials and currents (mEPPs and mEPCs), nerve-evoked endplate potentials and currents (EPPs and EPCs), as well as the membrane properties of the motor endplate. Results obtained from this method include the quantal content (QC), number of vesicle release sites (n), probability of vesicle release (prel), synaptic facilitation and depression, as well as the muscle membrane time constant (τm) and input resistance. Application of this technique to mouse models of human disease can highlight key pathologies in disease states and help identify novel treatment strategies. By fully voltage-clamping a single synapse, this method provides one of the most detailed analyses of synaptic transmission currently available.

An undergraduate Otolaryngology curriculum comparison in the United Kingdom using a curriculum evaluation framework.

OBJECTIVE: To compare undergraduate otolaryngology curricula in the United Kingdom. To develop a tool which would allow undergraduate specialty curricula to be compared. DESIGN: Development of a curriculum evaluation framework (CEF) and survey. SETTING: UK medical schools. PARTICIPANTS: Otolaryngology curricula were requested from all 32 UK medical schools who award a primary medical qualification. Nineteen curricula were received and examined. MAIN OUTCOME MEASURES: Thematic and content analysis of curriculum documents were undertaken. Outcome measures include an examination of curriculum content and methods, type of assessment and alignment of curricula with the General Medical Council's Tomorrow's Doctors document. RESULTS: Learning objectives were listed by 18 of the 19 medical schools who responded. The most commonly included theme was clinical conditions (100%). Psychosocial aspects of otolaryngology was the least covered theme (37%). Examination skills was covered by the majority (74%). Outpatient clinics and theatre attendance were the most commonly utilised teaching methods (47%). Student checklists were the most common form of assessment (32%). Only four medical schools linked their curricula to the GMC's Tomorrow's Doctors document. CONCLUSIONS: The development of a CEF allowed for a systematic comparison of curricula. This study, evaluating otolaryngology curricula, has highlighted the variability of curricula from both a content and methods perspective in the UK. The study provides those involved with curriculum planning an overview of the main themes currently taught in the UK and offers examples of individual topics. It also offers an insight into the way in which otolaryngology is taught in the UK.

ENT manifestations of alkaptonuria: report on a case series.

BACKGROUND: Alkaptonuria is an inborn error of metabolism. It is a multisystem disease with characteristic ENT manifestations. This paper reports, for the first time, the ENT findings in a cohort of alkaptonuria patients. METHOD: Patients attending the National Centre for Alkaptonuria (Royal Liverpool and Broadgreen University Hospitals NHS Trust) underwent a full ENT assessment. RESULTS: Eighteen of the 20 patients (90 per cent) had an ENT sign or symptom. These included discolouration of the pinna, cerumen, nasal septum and pharynx. CONCLUSION: Discolouration of cerumen may occur before 30 years of age and may therefore be an important early clinical sign. Further audiological assessment of patients is needed to clarify if an association exists between alkaptonuria and hearing loss. Alkaptonuria is a condition that could present to the otolaryngologist. Successful early diagnosis and referral to a specialist centre is essential so that patients can be offered disease-modifying therapy.

An unusual cause of nasal airway obstruction in a neonate: trans-sellar, trans-sphenoidal cephalocoele.

INTRODUCTION: Neonates are obligate nasal breathers, and nasal obstruction may have serious implications. We present an extremely rare cause of neonatal nasal obstruction, and its management. CASE REPORT: An eight-day-old neonate was referred for upper airway obstruction. Initial investigations had identified no obvious cause. Rigid airway endoscopy revealed a large, cystic lesion appearing to arise from the roof of the posterior nasal space. Computed tomography and magnetic resonance imaging indicated a basal cephalocoele projecting inferiorly into the oropharynx, with an intracranial connection to the pituitary fossa. Histology showed fibrovascular tissue lined on one aspect by respiratory type epithelium, with mucous glands present. The tissue contained multiple cystic spaces lined by choroid plexus epithelium, with glial tissue present in the walls of the mass. A transpalatal excision of the nasopharyngeal cephalocoele, with closure of the intracranial connection, palatal repair and lumbar drain placement was undertaken. Post-operative recovery was uneventful, with no evidence of cerebrospinal fluid leakage or palatal dysfunction. CONCLUSION: This surgical approach gave excellent access whilst avoiding the obvious morbidity associated with an intracranial approach. Nasal masses should be considered in the differential diagnosis of neonatal respiratory distress due to nasal obstruction.

Potential use of cytokine therapy in poultry.

Newly hatched chickens are highly susceptible to infection during the first 2 weeks of life. The utilisation of cytokines as therapeutic agents in livestock animals, in particular poultry, has become more feasible with the recent cloning of cytokine genes and the progression of new technologies such as live vectors. We have constructed a live recombinant fowlpox virus (FPV) that expresses chicken myelomonocytic growth factor (fp/cMGF). Administration of fp/cMGF to chicks resulted in a marked and sustained increase in the number of circulating blood monocytes as well as an increase in their state of activation, as measured by enhanced phagocytic activity and elevated production of nitric oxide. We have recently cloned the gene for chicken interferon-gamma (ChIFN-gamma). Recombinant ChIFN-gamma was capable of protecting chick fibroblasts from undergoing virus-mediated lysis and induced nitrite secretion from chicken macrophages in vitro. Preliminary vaccination trials have indicated that co-administration of ChIFN-gamma with antigen (sheep red blood cells) resulted in enhanced secondary (IgG) antibody responses and allowed a 10-fold lower dose of antigen to be used. Furthermore, administration of ChIFN-gamma resulted in enhanced weight gain in chicks and improved their resistance to disease challenge. The ability of cytokines to combat infection and enhance vaccine efficacy makes them excellent candidates as a therapeutic agents and adjuvants.