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To assess whether extra-oesophageal symptoms are predictive of oesophageal malignancy.A prospective, single-centre cross-sectional questionnaire study at a tertiary referral unit for oesophageal cancer using the Comprehensive Reflux Symptoms Scale (CReSS) questionnaire tool. Respondents with oesophageal malignancy were compared with historical cohorts undergoing airway examination or upper gastrointestinal endoscopy and found to have benign diagnoses. We developed a model for predicting oesophageal cancer using linear discriminant analysis and logistic regression, assessed by Monte Carlo cross validation.Respondents with oesophageal malignancy (n = 146; mean age 70.5; male: female, 71:29) were compared with those undergoing airway examination (n = 177) and upper gastrointestinal endoscopy (n = 351), found to have benign diagnoses. No single questionnaire item, or group of co-varying items (factors), reliably discriminated oesophageal cancer from other diagnoses. Individual items which suggested higher risk of oesophageal malignancy included dysphagia (area under the curve (AUC) 0.68), low appetite (AUC 0.66), and early satiety (AUC 0.58). Conversely, throat pain (AUC 0.38), bloating (AUC 0.38) and heartburn (AUC 0.37) were inversely related to cancer risk. A forward stepwise regression analysis including a subset of 12 CReSS questionnaire items together with age and sex derived a model predictive of oesophageal malignancy in this cohort (AUC 0.89).We demonstrate a model comprised of 12 questionnaire items and 2 demographic parameters as a potential predictive tool for oesophageal malignancy diagnosis in this study population. Translating this model for predicting oesophageal malignancy in the general population is a valuable topic for future research.

Background Idiopathic subglottic stenosis (iSGS) is a rare fibrotic disease of the proximal airway affecting adult Caucasian women nearly exclusively. Life-threatening ventilatory obstruction occurs secondary to pernicious subglottic mucosal scar. Disease rarity and wide geographic patient distribution has previously limited substantive mechanistic investigation into iSGS pathogenesis. Result By harnessing pathogenic mucosa from an international iSGS patient cohort and single-cell RNA sequencing, we unbiasedly characterize the cell subsets in the proximal airway scar and detail their molecular phenotypes. Results show that the airway epithelium in iSGS patients is depleted of basal progenitor cells, and the residual epithelial cells acquire a mesenchymal phenotype. Observed displacement of bacteria beneath the lamina propria provides functional support for the molecular evidence of epithelial dysfunction. Matched tissue microbiomes support displacement of the native microbiome into the lamina propria of iSGS patients rather than disrupted bacterial community structure. However, animal models confirm that bacteria are necessary for pathologic proximal airway fibrosis and suggest an equally essential role for host adaptive immunity. Human samples from iSGS airway scar demonstrate adaptive immune activation in response to the proximal airway microbiome of both matched iSGS patients and healthy controls. Clinical outcome data from iSGS patients suggests surgical extirpation of airway scar and reconstitution with unaffected tracheal mucosa halts the progressive fibrosis. Conclusion Our data support an iSGS disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. These results refine our understanding of iSGS and implicate shared pathogenic mechanisms with distal airway fibrotic diseases.

Idiopathic subglottic stenosis (iSGS) is a rare fibrotic disease of the proximal airway affecting adult Caucasian women nearly exclusively. Life-threatening ventilatory obstruction occurs secondary to pernicious subglottic mucosal scar. Diverse diseases in divergent organ systems are associated with fibrosis, suggesting common biologic mechanisms. One well characterized pathway is chronic inflammation secondary to pathogen. In the present study, we explored the role of the proximal airway microbiome in iSGS pathogenesis. In human samples, abundant bacteria are detectable in iSGS scar as well as in health subglottic controls or patients that developed subglottic stenosis following endotracheal intubation. Interestingly, the community structure of the iSGS proximal airway microbiome does not appear disrupted. Rather, in iSGS defects in the airway epithelial barrier allow displacement of the native microbiome into the immunoprivileged lamina propria and are associated with adaptive immune activation. Animal models of iSGS confirm both bacteria and an adaptive immune response are necessary for pathologic proximal airway fibrosis. Single cell RNA sequencing of the affected airway in iSGS offers an unbiased characterization of the observed epithelial barrier dysfunction. The airway scar in iSGS patients demonstrates basal cell depletion and epithelial acquisition of a mesenchymal phenotype. The epithelial alterations are associated with the observed microbiome displacement, dysregulated immune activation, and localized fibrosis. These results refine our understanding of iSGS and implicate shared pathogenic mechanisms with distal airway fibrotic diseases.

Objective Coronavirus disease 2019 (COVID-19) is a respiratory infection known as severe respiratory acute syndrome coronavirus 2 (SARS-CoV-2). The purpose of this manuscript is to review information leading to the Food and Drug Administration (FDA) approval of the Pfizer-BioNTech COVID-19 Vaccine. Data Sources A literature search was conducted of PubMed and clinicaltrials.gov (August 2018—October 2021) to identify trials related to the FDA approval of Pfizer-BioNTech COVID-19 Vaccine. Study selection and data extraction Trials included are those the FDA deemed significant and accurate enough to be included in the FDA approval process. Information not recognized by the Centers of Disease Control and Prevention (CDC) nor FDA is omitted to not add to further confusion and misinformation. Data synthesis In persons 16 years or older without evidence of prior SARS-CoV-2 infection, a total of 77 COVID-19 cases (0.39%) in the vaccine group from 7 days onward after the second dose vs 833 (4.1%) in the placebo group (Vaccine efficacy 91.1%; 95% confidence interval [CI]: 88.8-93.1). According the CDC definition of severe infection, there were no severe infections in the vaccine group 7 days and onward after the second dose, compared to 31 (0.15%) in the placebo group (Vaccine efficacy 100%; 95% CI: 87.6-100.0). Relevance to Patient Care and Clinical Practice: Reduction of infection by SARS-COV-2 is a top priority in protecting the health of all people and the official approval of the Pfizer-BioNTech vaccination may improve this goal. Conclusions Data available show a high efficacy rate of preventing SARS -CoV-2 with relatively low rates of ADE after full vaccination with Pfizer-BioNTech COVID-19 vaccine.

BackgroundTracheostomies in children are associated with significant morbidity, poor quality of life, excess healthcare costs and excess mortality. The underlying mechanisms facilitating adverse respiratory outcomes in tracheostomised children are poorly understood. We aimed to characterise airway host defence in tracheostomised children using serial molecular analyses.MethodsTracheal aspirates, tracheal cytology brushings and nasal swabs were prospectively collected from children with a tracheostomy and controls. Transcriptomic, proteomic and metabolomic methods were applied to characterise the impact of tracheostomy on host immune response and the airway microbiome.ResultsChildren followed up serially from the time of tracheostomy up to 3 months postprocedure (n=9) were studied. A further cohort of children with a long-term tracheostomy were also enrolled (n=24). Controls (n=13) comprised children without a tracheostomy undergoing bronchoscopy. Long-term tracheostomy was associated with airway neutrophilic inflammation, superoxide production and evidence of proteolysis when compared with controls. Reduced airway microbial diversity was established pre-tracheostomy and sustained thereafter.ConclusionsLong-term childhood tracheostomy is associated with a inflammatory tracheal phenotype characterised by neutrophilic inflammation and the ongoing presence of potential respiratory pathogens. These findings suggest neutrophil recruitment and activation as potential exploratory targets in seeking to prevent recurrent airway complications in this vulnerable group of patients.

ObjectivesTo explore the experience of caring for children with tracheostomies from the perspectives of parents and health professional caregivers.DesignQualitative semistructured interview study.SettingOne region in England covered by a tertiary care centre that includes urban and remote rural areas and has a high level of deprivation.ParticipantsA purposive sample of health professionals and parents who care for children who have, or have had, tracheostomies and who received care at the tertiary care centre.InterventionInterviews undertaken by telephone or video link.Primary and secondary outcome measuresQualitative reflexive thematic analysis with QSR Nvivo 12.ResultsThis paper outlines key determinants and mediators of the experiences of caregiving and the impact on psychological and physical health and quality of life of parents and their families, confidence of healthcare providers and perceived quality of care. For parents, access to care packages and respite care at home as well as communication and relationships with healthcare providers are key mediators of their experience of caregiving, whereas for health professionals, an essential influence is multidisciplinary team working and support. We also highlight a range of challenges focused on the shared care space, including: a lack of standardisation in access to different support teams, care packages and respite care, irregular training and updates, and differences in health provider expertise and experiences across departments and shift patterns, exacerbated in some settings by limited contact with children with tracheostomies.ConclusionsUnderstanding the experiences of caregiving can help inform measures to support caregivers and improve quality standards. Our findings suggest there is a need to facilitate further standardisation of care and support available for parent caregivers and that this may be transferable to other regions. Potential solutions to be explored could include the development of a paediatric tracheostomy service specification, increasing use of paediatric tracheostomy specialist nurse roles, and addressing the emotional and psychological support needs of caregivers.

Introduction\ud \ud Otitis media is an umbrella term for middle ear inflammation; ranging from acute infection to chronic mucosal disease. It is a leading cause of antimicrobial therapy prescriptions and surgery in children. Despite this, treatments have changed little in over 50 years. Research has been limited by the lack of physiological models of middle ear epithelium.\ud \ud \ud Methods\ud \ud We develop a novel human middle ear epithelial culture using an air-liquid interface (ALI) system; akin to the healthy ventilated middle ear in vivo. We validate this using immunohistochemistry, immunofluorescence, scanning and transmission electron microscopy, and membrane conductance studies. We also utilize this model to perform a pilot challenge of middle ear epithelial cells with SARS-CoV-2.\ud \ud \ud Results\ud \ud We demonstrate that human middle ear epithelial cells cultured at an ALI undergo mucociliary differentiation to produce diverse epithelial subtypes including basal (p63+), goblet (MUC5AC+, MUC5B+), and ciliated (FOXJ1+) cells. Mature ciliagenesis is visualized and tight junction formation is shown with electron microscopy, and confirmed by membrane conductance. Together, these demonstrate this model reflects the complex epithelial cell types which exist in vivo. Following SARS-CoV-2 challenge, human middle ear epithelium shows positive viral uptake, as measured by polymerase chain reaction and immunohistochemistry.\ud \ud \ud Conclusion\ud \ud We describe a novel physiological system to study the human middle ear. This can be utilized for translational research into middle ear diseases. We also demonstrate, for the first time under controlled conditions, that human middle ear epithelium is susceptible to SARS-CoV-2 infection, which has important clinical implications for safe otological surgery.\ud \ud \ud Level of Evidence\ud \ud NA.

Objective Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We evaluate the evidence of a dysregulated immune response in the pathogenesis of OM. Methods A comprehensive systematic review of the literature using search terms [otitis media OR glue ear OR AOM OR OME] OR [middle ear AND (infection OR inflammation)] which were run through Medline and Embase via Ovid, including both human and animal studies. In total, 82 955 studies underwent automated filtering followed by manual screening. One hundred studies were included in the review. Results Most studies were based on in vitro or animal work. Abnormalities in pathogen detection pathways, such as Toll-like receptors, have confirmed roles in OM. The aetiology of OM, its chronic subgroups (chronic OM, persistent OM with effusion) and recurrent acute OM is complex; however, inflammatory signalling mechanisms are frequently implicated. Host epithelium likely plays a crucial role, but the characterisation of human middle ear tissue lags behind that of other anatomical subsites. Conclusions Translational research for OM presently falls far behind its clinical importance. This has likely hindered the development of new diagnostic and treatment modalities. Further work is urgently required; particularly to disentangle the respective immune pathologies in the clinically observed phenotypes and thereby work towards more personalised treatments.

Rationale and objective: Forensic radiology is a relatively unknown subspecialty which is becoming increasingly more important. The field incorporates antemortem and postmortem imaging for the detection and documentation of various pathologies for medicolegal purposes. Postmortem imaging is increasingly used in conjunction with the traditional autopsy in a process called a “virtual” autopsy. Radiography has been a staple of forensic investigations for over a century, first used in 1896. Advanced imaging techniques such as postmortem computed tomography and postmortem magnetic resonance imaging have only recently gained acceptance in the forensic science community. Postmortem computed tomography and postmortem magnetic resonance imaging methods are now widely used in some parts of the world, while other countries including the United States have been slower to adopt these methods into their daily practice. Advanced forensic imaging is increasingly used in the courts where juries have responded positively to such presentation of forensic data. For these reasons, advanced postmortem imaging is becoming a regular part of forensic investigations. The increase in the use of forensic imaging presents a unique opportunity for radiologists to collaborate with pathologists and law enforcement officials. This paper provides an overview of forensic radiology and identifies potential challenges and opportunities.

Background: Idiopathic pseudotumour (IP) is a non-specific, non-neoplastic, inflammatory process without identifiable local or systemic causes. IP in the head and neck region present diagnostic and management issues. Methodology: Retrospective case series and literature review. Results: We describe clinical history, examination, laboratory investigations and image findings of three patients, all males who presented with facial pain and ophthalmoplegia. Scans revealed lesions in the pterygopalatine fossa. The diagnosis of idiopathic pseudotumour was confirmed by histopathology. We discuss their treatment pathways and prognosis. Conclusions: Idiopathic pseudotumours in the head and neck region especially those involving anterior skull base are rare. Understanding their presentation and characteristics might help an unsuspecting otorhinolaryngologist in the diagnosis and treatment of these lesions.

This paper explores the incidence and consequence of public policies in the United Kingdom through the conceptual lens of governmentality (Foucault, 1977). This paper focuses on England and considers the implications of the shift of the inter-relationship between the State, and social care. In many ways, public policy provides three pathways for vulnerable adults. First, as independent self-managing consumers with private means and resources; Second, as people in need of some support to enable them to continue to self manage; Third, as dependent and unable to commit to self-management. Governmentality that derives from the work of Michel Foucault provides an innovative analytical framework through which to view public policy and practice that is largely governed by discourses of personalisation, safeguarding, capability and risk.

This cohort study uses Hospital Episode Statistics admission data to evaluate hospital resource use and associated costs for pediatric tracheostomy.

The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we applied single-cell RNA sequencing and proteomics to a primary cell model of human nasal epithelium differentiated at air-liquid interface. SARS-CoV-2 demonstrated widespread tropism for nasal epithelial cell types. The host response was dominated by type I and III IFNs and interferon-stimulated gene products. This response was notably delayed in onset relative to viral gene expression and compared to other respiratory viruses. Nevertheless, once established, the paracrine IFN response began to impact on SARS-CoV-2 replication. When provided prior to infection, recombinant IFNβ or IFNλ1 induced an efficient antiviral state that potently restricted SARS-CoV-2 viral replication, preserving epithelial barrier integrity. These data suggest that the IFN-I/III response to SARS-CoV-2 initiates in the nasal airway and suggest nasal delivery of recombinant IFNs to be a potential chemoprophylactic strategy.

Children undergoing heart transplant are at higher risk of developing post-transplant lymphoproliferative disorder (PTLD) than other solid organ recipients. The factors driving that risk are unclear. This study investigated risk factors for PTLD in children transplanted at 1 of 2 United Kingdom pediatric cardiac transplantation centers.All children (18 years, n = 200) transplanted at our institution over a 16-year period were analyzed. Freedom from PTLD was assessed using the Kaplan-Meier method and Cox proportional regression.PTLD occurred in 17 of 71 children transplanted for congenital heart disease (CHD) and 18 of 129 transplanted for acquired cardiomyopathy (ACM). The cumulative incidence of all PTLD was 21.1% at 5 years after transplant. Median time from transplant to PTLD was 2.9 years (interquartile range: 0.9-4.6). Negative Epstein-Barr virus (EBV) serostatus pre-transplant (adjusted hazard ratio [HR]: 2.7, 95% CI: 1.3-5.6, p = 0.01) and underlying CHD (adjusted HR: 3.2, 95% CI: 1.4-7.4, p = 0.007) were independently associated with higher risk of PTLD. Age at thymectomy was significantly different between children with CHD and ACM (0.4 vs 5.5 years, p0.01). Median CD4Underlying CHD is an independent risk factor for PTLD and is associated with a younger age at thymectomy. A persistent association with altered T lymphocyte subsets may contribute to the impaired response to primary EBV infection and increase the risk of PTLD.

Shifts in cellular metabolic phenotypes have the potential to cause disease-driving processes in respiratory disease. The respiratory epithelium is particularly susceptible to metabolic shifts in disease, but our understanding of these processes is limited by the incompatibility of the technology required to measure metabolism in real-time with the cell culture platforms used to generate differentiated respiratory epithelial cell types. Thus, to date, our understanding of respiratory epithelial metabolism has been restricted to that of basal epithelial cells in submerged culture, or via indirect end point metabolomics readouts in lung tissue. Here we present a novel methodology using the widely available Seahorse Analyzer platform to monitor real-time changes in the cellular metabolism of fully differentiated primary human airway epithelial cells grown at air-liquid interface (ALI). We show increased glycolytic, but not mitochondrial, ATP production rates in response to physiologically relevant increases in glucose availability. We also show that pharmacological inhibition of lactate dehydrogenase is able to reduce glucose-induced shifts toward aerobic glycolysis. This method is timely given the recent advances in our understanding of new respiratory epithelial subtypes that can only be observed in vitro through culture at ALI and will open new avenues to measure real-time metabolic changes in healthy and diseased respiratory epithelium, and in turn the potential for the development of novel therapeutics targeting metabolic-driven disease phenotypes.

The world is suffering a respiratory pandemic disease caused by a novel coronavirus (2019-nCoV), commonly known as COVID-19 (coronavirus disease 2019). The Food and Drug Administration issued an emergency authorization for chloroquine and hydroxychloroquine as experimental treatments for COVID-19 leading to a shortage of both medications. A literature review conducted in April 2020 shows a lack of high-quality data available, resulting in ambiguous guideline recommendations. Decisions to use either drug should be made with careful consideration of risks versus benefits along with proper monitoring. Because of its higher potency and better safety profile, hydroxychloroquine may be the more reasonable treatment option if treatment is initiated.

Objectives To explore the impact of the COVID-19 pandemic on the experiences of caregivers of children with tracheostomies. Design Qualitative semistructured interviews. Setting All participants were currently, or had previously cared for, a tracheostomised child who had attended a tertiary care centre in the North of England. Health professionals were purposively sampled to include accounts from a range of professions from primary, community, secondary and tertiary care. Participants Carers of children with tracheostomies (n=34), including health professionals (n=17) and parents (n=17). Interventions Interviews were undertaken between July 2020 and February 2021 by telephone or video link. Main outcome measure Qualitative reflexive thematic analysis with QSR NVivo V.12. Results The pandemic has presented an additional and, for some, substantial challenge when caring for tracheostomised children, but this was not always felt to be the most overriding concern. Interviews demonstrated rapid adaptation, normalisation and varying degrees of stoicism and citizenship around constantly changing pandemic-related requirements, rules and regulations. This paper focuses on four key themes: ‘reconceptualising safe care and safe places’; ‘disrupted support and isolation’; ‘relationships, trust and communication’; and ‘coping with uncertainty and shifting boundaries of responsibility’. These are described within the context of the impact on the child, the emotional and physical well-being of carers and the challenges to maintaining the values of family-centred care. Conclusions As we move to the next phase of the pandemic, we need to understand the impact on vulnerable groups so that their needs can be prioritised., For those with complex care needs the challenges of Covid-19 have been heightened. Caregivers of children with tracheostomies describe the pressures placed on trust, communication and relationships and the challenges of delivering family centred care.

This article describes a project-based learning pedagogical approach to learning legal concepts that transforms these concepts into managerial propositions for students, especially for computer information systems and business administration majors. This pedagogy provides opportunities and experiences for students to become sensitive enough to real-world topics that they can posit a question to a legal professional regarding cyber business laws. The hands-on project-based learning method is an engaging and interactive way to learn the information in a group environment, and then it requires the student to demonstrate knowledge at the individual level. The data collected for this study suggests that the project-based learning style is effective for learning legal concepts.

Objective Gastro-oesophageal reflux disease is thought to be a risk factor for head and neck malignancies. Bile acids are one of the principle components of gastric refluxate and have previously been implicated in the development of oesophageal and bowel malignancies. There is clear evidence that bile acids reflux into the laryngopharynx. Despite this, the carcinogenic properties of bile acids in this area are yet to be fully identified. We therefore investigated the potential role of bile acids in pharyngeal malignancy, through the highly conserved process of epithelial–mesenchymal transition (EMT). EMT occurs in invasion and metastasis and is a central process in the development of epithelial carcinoma. Design Translational research study. Methods Human hypopharyngeal squamous carcinoma FaDu cells were challenged with primary (cholic or chenodeoxycholic) and secondary (deoxycholic or lithocholic) bile acids. EMT-relevant proteins TGF-β1 and MMP-9 were measured in the cell culture supernates at 48 h via ELISA. Cell viability was confirmed >95% via CellTiter-Blue assay. Results Significantly greater concentrations of TGF-β1 were measured in the culture supernates of cells treated with cholic acid, deoxycholic acid and chenodeoxycholic acid. MMP-9 levels were increased in deoxycholic acid and lithocolic acid stimulations when compared to control (P < 0.05). Conclusion This is the first demonstration that bile acids induce TGF-β1 and MMP-9 in pharyngeal cells. TGF-β1 is considered a master switch for EMT, while MMP-9 is a part of the EMT proteome which degrades basement membranes. This implies a potential role for bile acids in pharyngeal carcinogenesis through the mechanism of EMT and suggests potential novel therapeutic targets.

There is limited guidance available to clinicians regarding the management of antithrombotic therapy during epistaxis, whilst there has been an increase in the use of anticoagulation and antiplatelet therapy. In addition, the introduction of direct oral anticoagulants (DOACs), such as dabigatran and rivaroxaban, over the last decade has significantly increased the complexity of managing the anticoagulated epistaxis patient. We undertook a systemic literature review investigating potential management strategies for each class of anti-thrombotic therapy during epistaxis. A PubMED and Cochrane Library search was performed on 10/03/16 using, but not limited to, the search terms epistaxis, nosebleed, nose bleeding, nasal haemorrhage, nasal bleeding AND each of the following search terms: antithrombotic, anticoagulant, antiplatelet, aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, apixaban and tranexamic acid. This yielded 3815 results, of which 29 were considered relevant. Other sources such as national and international guidelines related to the management of anti-thrombotics were also utilised. We present the findings related to the management of each class of anti-thrombotic therapy during epistaxis. Overall we found a lack of evidence regarding this topic and further high quality research is needed. This is an area growing in complexity and the support of colleagues in Haematology and Cardiology is increasingly important.

A normally fit and well 3-year-old girl awoke distressed. Her parents identified a long hair protruding from her mouth. She was comforted and given some food and drink. Afterwards they could no longer see the hair and she had no ongoing pain or issues initially. Over the subsequent days, she had

Rationale:\ud Aspiration of infective subglottic secretions causes ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Mechanisms underlying subglottic colonization in critical illness have not been defined, limiting strategies for targeted prevention of VAP.\ud \ud Objectives:\ud To characterize subglottic host defense dysfunction in mechanically ventilated patients in the intensive care unit (ICU). To determine whether subglottic mucin contributes to neutrophil phagocytic impairment and bacterial growth.\ud \ud Methods:\ud Prospective subglottic sampling in mechanically ventilated patients (intubated for four or more days), and newly intubated control patients (intubated for less than 30 minutes). Isolation and culture of primary subglottic epithelial cells from controls. Laboratory analysis of host innate immune defenses.\ud \ud Measurements and Main Results:\ud Twenty-four patients in the ICU and 27 newly intubated control patients were studied. Subglottic ICU samples had significantly reduced microbiological diversity and contained potential respiratory pathogens. The subglottic microenvironment in ICU was characterized by neutrophilic inflammation, significantly increased pro-inflammatory cytokines and neutrophil proteases, and altered physical properties of subglottic secretions, including accumulation of mucins. Subglottic mucin from ICU patients impaired the capacity of neutrophils to phagocytose and kill bacteria. Phagocytic function was reversible upon treatment with a mucolytic agent. Subglottic mucus promoted growth and invasion of bacterial pathogens in a novel air-liquid interface model of primary human subglottic epithelium.\ud \ud Conclusions:\ud Mechanical ventilation in ICU is characterized by substantial mucin secretion and neutrophilic inflammation. Mucin impairs neutrophil dysfunction and promotes bacterial growth. Mucolytic agents reverse mucin-mediated neutrophil dysfunction. Enhanced mucus disruption and removal has potential to augment preventive benefits of subglottic drainage.

Background:Recently, there has been increased emphasis on the development and application of patient-reported outcome measures. This drive to assess the impact of illness or interventions, from the patient's perspective, has resulted in a greater number of available questionnaires. The importance of selecting an appropriate patient-reported outcome measure is specifically emphasised in the paediatric population. The literature on patient-reported outcome measures used in paediatric otolaryngology was reviewed.Methods:A comprehensive literature search was conducted using the databases Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and PsycInfo, using the terms: ‘health assessment questionnaire’, ‘structured questionnaire’, ‘questionnaire’, ‘patient reported outcome measures’, ‘PROM’, ‘quality of life’ or ‘survey’, and ‘children’ or ‘otolaryngology’. The search was limited to English-language articles published between 1996 and 2016.Results:The search yielded 656 articles, of which 63 were considered relevant. This included general paediatric patient-reported outcome measures applied to otolaryngology, and paediatric otolaryngology disease-specific patient-reported outcome measures.Conclusion:A large collection of patient-reported outcome measures are described in the paediatric otolaryngology literature. Greater standardisation of the patient-reported outcome measures used in paediatric otolaryngology would assist in pooling of data and increase the validation of tools used.

Objective Gastroesophageal reflux is thought to be a risk factor for laryngotracheal stenosis. Bile acids are a component of gastric refluxate and have previously been implicated in the development of fibrosis in other airway subsites. There is clear evidence that bile acids reflux into the upper airway. We therefore investigated the potential role of bile acids in the pathophysiology of laryngotracheal fibrosis and stenosis, specifically investigating the highly conserved process of epithelial–mesenchymal transition (EMT). Study Design Translational research study. Methods Human primary tracheal epithelial cells (PTECs) were challenged with the four most common digestive bile acids (cholic, chenodeoxycholic, deoxycholic, and lithocholic). EMT markers transforming growth factor (TGF)‐β1, Matrix metalloproteinase (MMP)‐9, and procollagen proteins were measured in the supernatant at 48 hours via enzyme‐linked immunosorbent assay. Real‐time polymerase chain reaction was also used to measure E‐cadherin and fibronectin expression. Results Significantly greater concentrations of TGF‐β1 and MMP‐9 were measured in the culture supernatants of cells treated with each bile acid at 10 µmol/L. Lithocholic acid and deoxycholic acid induced significantly increased expression of procollagen protein. Upregulation of fibronectin and downregulation of E‐cadherin were observed with all bile acids, except for deoxycholic acid. Conclusion This is the first proof of principle demonstration that physiologically relevant bile acid challenge induces EMT mechanisms in PTECs. This implies a potential role for bile acids in laryngotracheal scarring and airway remodeling of potential translational significance in laryngotracheal stenosis. Level of Evidence NA. Laryngoscope, 128:2029–2033, 2018

With the number of individuals diagnosed with type 2 diabetes on the rise, it has become more important to ensure these patients are effectively treated. The Centers for Disease Control and Prevention estimated that 8.3% of all Americans were diagnosed with diabetes in 2011 and this number will likely continue to rise. With lifestyle interventions, such as proper diet and exercise, continuing to be an essential component of diabetes treatment, more patients are requiring medication therapy to help them reach their therapeutic goals. It is important for the clinician, when determining the treatment strategy for these individuals, to find a balance between reaching treatment goals and limiting the adverse effects of the treatments themselves. Of all the adverse events associated with treatment of diabetes, the risk of hypoglycemia is one that most therapies have in common. This risk is often a limiting factor when attempting to aggressively treat diabetic patients. This manuscript will review how hypoglycemia is defined and categorized, as well as discuss the prevalence of hypoglycemia among the many different treatment options.

Type 2 diabetes and obesity commonly occur together. Obesity contributes to insulin resistance, a main cause of type 2 diabetes. Modest weight loss reduces glucose, lipids, blood pressure, need for medications, and cardiovascular risk. A number of approaches can be used to achieve weight loss, including lifestyle modification, surgery, and medication. Lorcaserin, a novel antiobesity agent, affects central serotonin subtype 2A receptors, resulting in decreased food intake and increased satiety. It has been studied in obese patients with type 2 diabetes and results in an approximately 5.5 kg weight loss, on average, when used for one year. Headache, back pain, nasopharyngitis, and nausea were the most common adverse effects noted with lorcaserin. Hypoglycemia was more common in the lorcaserin groups in the clinical trials, but none of the episodes were categorized as severe. Based on the results of these studies, lorcaserin was approved at a dose of 10 mg twice daily in patients with a body mass index ≥30 kg/m(2) or ≥27 kg/m(2) with at least one weight-related comorbidity, such as hypertension, type 2 diabetes mellitus, or dyslipidemia, in addition to a reduced calorie diet and increased physical activity. Lorcaserin is effective for weight loss in obese patients with and without type 2 diabetes, although its specific role in the management of obesity is unclear at this time. This paper reviews the clinical trials of lorcaserin, its use from the patient perspective, and its potential role in the treatment of obesity.

Anosmia is present in approximately 1% of the population and can have a significant impact on quality of life 1. In contrast to acquired anosmia, congenital anosmia is a relatively rare condition characterized by a complete lack of olfactory perception and the aplasia or hypoplasia of the olfactory bulb. Kallmann syndrome (congenital hypogonadotropic hypogonadism and anosmia) is the best known condition assoicated with congenital anosmia 2,3. Kallmann Syndrome has a prevalence of around 1 in 8000, and is five times more common in men than women 2,3. This article is protected by copyright. All rights reserved.

Institutions, at state and local level, have been perceived as a mechanism of supporting the vulnerable within society. The processes of globalisation within an economic, political and social context have played a fundamental role in institutions. The 'State' that administers institutions has experienced involvement and adjustment by central government's policy of privatisation and deregulation. The aim of this paper is to critically explore the current debates on institutions within British society. We frame the debates within Foucault's notion of 'governmentality', which highlights how government provides governance of 'action at a distance' in order to detract blame from government and its policies and place this blame onto individuals and communities themselves (1978, p. 33).

Summary Aims The 2012 American College of Chest Physician Evidence-Based Management of Anticoagulant Therapy guidelines suggest an international normalized ratio (INR) testing interval of up to 12 weeks, rather than every 4 weeks, for patients with consistently stable INRs while taking vitamin K antagonists. We aimed to examine the feasibility of extended-interval follow-up in a real-world setting. Methods Patients receiving stable warfarin therapy for ≥12 weeks at baseline began extended-interval follow-up with visits occurring at 6 weeks, 14 weeks, and every 12 weeks thereafter to a maximum of 68 weeks or until they were no longer suitable for extended-interval follow-up. A single INR excursion >0.3 from goal was permitted if a reversible precipitating factor was identified and the INR was expected to return to goal without dose adjustment. The primary outcome was the proportion of patients completing all study follow-up visits. Results Of 48 patients enrolled, 47 had evaluable data. The most common indication for anticoagulation was atrial fibrillation/flutter (53.2%). At baseline, mean prior warfarin treatment duration was 6.7 ± 6 years and median number of weeks on a stable regimen was 24 weeks (IQR, 19–37.5). Eleven patients (23%) completed all study follow-up visits, whereas 17 (36%) did not maintain a stable INR past the 14-week follow-up. Conclusion A large proportion of patients with previously stable (≥3 months) INRs were not able to maintain stable INRs during extended-interval follow-up. More research is needed to identify patient characteristics predictive of success with extended-interval follow-up prior to broad implementation.

Type 2 diabetes mellitus continues to be a challenging disease to manage successfully. Beyond the first-line option metformin, there are a number of classes of medications from which to select. This article reviews the new sodium-glucose cotransporter 2 inhibitors canagliflozin and dapagliflozin, including their benefits, adverse effects, and potential place in therapy. Upon review, the use of these medications has led to an A1c reduction between -0.37% and -1.16%. These medications also have been shown to reduce A1c when used with insulin. Some adverse effects were noted when using canagliflozin and dapagliflozin, with the most frequent being urinary tract infections and genital mycotic infections. We review the sodium-glucose cotransporter 2 inhibitors approved by the US Food and Drug Administration and their potential roles in the management of type 2 diabetes mellitus.

What you need to know In many, tonsillitis is self-limiting and of relatively short duration. A subset of patients suffers from recurrent debilitating episodes, with impaired daily functioning and absence from work.1 Adult tonsillitis places a substantial burden on healthcare resources. Costs include primary care consultations, medical treatment, hospital admissions, and treatment of potentially life threatening complications.123 There are three approaches to the management of tonsillitis: conservative (wait and watch), antibiotics, or tonsillectomy. Tonsillectomy provides definitive treatment for recurrent tonsillitis and was performed on more than 17 000 adult patients in England in 2014-2015.4 Currently there is uncertainty around the severity of disease at which it is cost effective to perform tonsillectomy on adults with recurrent tonsillitis, as compared with conservative management. ### Search strategy and study selection We searched Medline, Embase, and the Cochrane Library using the terms “tonsillitis” or “tonsillectomy” or “pharyngitis.” We included studies that involved adults and were published in English between 1996 and February 2017 (table 1⇓). We found Cochrane reviews comparing antibiotics with placebo, and comparing tonsillectomy with watchful waiting. We also found a review of qualitative outcomes in tonsillectomy, two retrospective studies investigating complications of tonsillectomy, a cross-sectional study of the complications of tonsillitis and tonsillectomy rates, and a small cohort study observing economic outcomes pre and post tonsillectomy. View this table: Table 1 Summary of evidence for the treatment of recurrent adult tonsillitis In the UK, Clinical Commissioning …

Objectives To perform a multifactorial exploration of the aetiology of peritonsillar abscess (PTA) in adults, in order to develop greater clinical understanding of the condition and improve management. Design A literature review exploring key pathogens, predisposing host factors and current pathogenic hypotheses. Methods A PubMed search for articles published between January 1980 and January 2012 using the terms 'peritonsillar abscess AND microbiology', 'peritonsillar abscess AND pathophysiology' and 'peritonsillar abscess AND etiology'. Results Major pathogens in PTA are opportunistic microflora. Group A streptococcal PTA infections present differently from polymicrobial PTA. A number of host factors influence the conditions required for the pathogenesis of PTA. Conclusions PTA is clinically distinct from acute tonsillitis and occurs in people with a chronic underlying susceptibility. Targeting host factors, including oral hygiene, antibiotic use and smoking, may prevent PTA. Re-education of clinicians concerning the aetiology of PTA is necessary for appropriate disease management.

Thousands of taxis cruise a metropolitan road network looking for passengers that may be scattered or clustered in highly active locations. Taxicab drivers tend to gravitate to the known clusters, often leading to supply and demand disequilibrium as areas become under or over served. Many cities monitor their taxi fleet's locations using GPS devices and track passenger occupancy through trip meters, thereby producing data streams of taxicab trajectories and passenger activities. This paper presents the Service Disequilibrium Detection (SDD) framework which aims at identifying regions of service disequilibrium using this information. The SDD framework models request wait time and taxicab location uncertainty inherent in the discrete data streams and identifies the disequilibrium regions using two methods: (1) Bayesian spatial scan statistics, and (2) Poisson-based hypothesis testing. We claim the SDD framework can detect emerging disequilibrium and validate this claim using a large Shanghai taxi GPS data set.

Taxicab service plays a vital role in public transportation by offering passengers quick personalized destination service in a semiprivate and secure manner. Taxicabs cruise the road network looking for a fare at designated taxi stands or alongside the streets. However, this service is often inefficient due to a low ratio of live miles (miles with a fare) to cruising miles (miles without a fare). The unpredictable nature of passengers and destinations make efficient systematic routing a challenge. With higher fuel costs and decreasing budgets, pressure mounts on taxicab drivers who directly derive their income from fares and spend anywhere from 35-60 percent of their time cruising the road network for these fares. Therefore, the goal of this paper is to reduce the number of cruising miles while increasing the number of live miles, thus increasing profitability, without systematic routing. This paper presents a simple yet practical method for reducing cruising miles by suggesting profitable locations to taxicab drivers. The concept uses the same principle that a taxicab driver uses: follow your experience. In our approach, historical data serves as experience and a derived Spatio-Temporal Profitability (STP) map guides cruising taxicabs. We claim that the STP map is useful in guiding for better profitability and validate this by showing a positive correlation between the cruising profitability score based on the STP map and the actual profitability of the taxicab drivers. Experiments using a large Shanghai taxi GPS data set demonstrate the effectiveness of the proposed method.