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Purpose Acne vulgaris is a ubiquitous condition in men and women starting in adolescence. It is often persistent and refractory to multiple treatment methods. Although multiple medications may be used on- or off-label for treatment, many adverse effects and risks exist with these treatments, and there has not been an agent with a novel mechanism of action introduced in 40 years. Clascoterone is a recently approved topical acne medication with the first novel mechanism of action since isotretinoin. The purpose of this article was to review the clinical data regarding the safety and efficacy of topical clascoterone for the treatment of acne vulgaris in male and female subjects aged >12 years. Methods A literature search of PubMed, EMBASE, and MEDLINE was conducted for clinical trials published between January 2014 and March 2021 in the English language using the key words Winlevi, clascoterone, and acne vulgaris. Articles were selected if they were related to the approval by the US Food and Drug Administration of clascoterone or provided novel data regarding this drug entity. Findings Two Phase III randomized controlled trials (NCT02608450 and NCT02608476) were ultimately selected, as these trials provided pivotal information to the US Food and Drug Administration for the approval of topical clascoterone. Implications The findings of this review show that topical clascoterone is likely an effective and safe option for the treatment of acne vulgaris. It offers efficacy rates similar to those of current medications through a novel mechanism of action. Its place in therapy remains unclear, but it might be placed ahead of other androgen receptor antagonists such as spironolactone due to its avoidance of systemic side effects.

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 The purpose of this article is to review the available trials that led to the Food and Drug Administration (FDA) approval of berotralstat, an oral kallikrein inhibitor, for the prevention of hereditary angioedema (HAE) attacks. Data Sources PubMed and ClincalTrials.gov were searched using key term berotralstat to identify phase III clinical trials related to the FDA approval of berotralstat from April 2018 to May 2021. Study Selection and Data Extraction Trials selected were those that influenced the FDA approval of berotralstat or provided novel information regarding the safety and efficacy of this therapy in the treatment of HAE. Data Synthesis Both APeX-2 and ApeX-J found clinically significant benefit with berotralstat 150 mg daily for reduction in HAE attacks when compared with placebo (1.31 vs 2.35, P < 0.001, and 1.11 vs 2.18, P < 0.001, attacks in the APeX-2 and APeX-J trials, respectively). APeX-2 also showed a statistically significant benefit for berotralstat 110 mg daily (1.65 vs 2.35 attacks [1.65 attacks, P = 0.024]). Relevance to Patient Care and Clinical Practice An advantage berotralstat has over the other approved therapies is that it is administered orally, which may garner patient preference because of ease of administration. Berotralstat has also shown a potential benefit in reducing the need for standard-of-care treatment for HAE attacks, which has not been studied with alternative agents. Conclusions Berotralstat 150 mg daily has been proven safe and effective in clinical studies and appears to be a viable oral alternative to parenteral medications currently used in HAE prophylaxis.

Paediatric tracheostomy is most commonly performed in children on the paediatric intensive care unit (PICU) to facilitate long-term ventilation. We sought to identify trends in UK tracheostomy practice in PICUs. Data were analysed from 250 261 admissions, including 4409 children tracheostomised between 2003 and 2017. The incidence of tracheostomy in 2017 was approximately half that in 2003 (incidence rate ratio=0.48, 95% CI 0.40 to 0.57). The percentage of patients tracheostomised during a PICU admission, as a proportion of all admissions, was 2.44% (n=319) in 2003 and reduced to 0.97% (n=180) in 2017. Nevertheless, we identified great variability in practice between different PICUs with tracheostomy rates between 0.0% and 4.0% of all admissions. Risk-adjusted PICU mortality was comparable between tracheostomised children and all admissions to PICU.

Objective: To review the safety and efficacy of brexanolone for the treatment of moderate to severe postpartum depression (PPD). Data Sources: A literature search through PubMed was conducted (January 2012 to July 2019) using the keyword brexanolone for clinical trials published in the English language. Study Selection and Data Extraction: Articles were selected if they were related to the Food and Drug Administration (FDA) approval of brexanolone or provided novel clinical information regarding this drug entity. Data Synthesis: The findings of the review show that brexanolone administered via IV infusion is both an effective and a fairly safe option for the treatment of PPD. Relevance to Patient Care and Clinical Practice: There are several antidepressants currently used to treat PPD; however, this is the first with FDA approval for this indication. The rapid onset of action of brexanolone may offer a quicker relief of these symptoms and may possibly lead to improved quality of life for both the mother and the child. Conclusion and Relevance: The recent FDA approval of brexanolone may offer an effective treatment of moderate to severe PPD and has been shown to rapidly decrease depression symptoms.

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.

Purpose This article discusses the pharmacology of bempedoic acid, the trials that led to United States Food and Drug Administration (FDA) approval of its use, and the overall safety and efficacy of this therapy in heterozygous familial hypercholesterolemia, established atherosclerotic cardiovascular disease (ASCVD), and hyperlipidemia. Methods A database search of PubMed and ClinicalTrials.gov was conducted for articles published between January 2012 to September 2020 and containing the key words bempedoic acid, ezetimibe, Nexletol and Nexlizet. Trials from the CLEAR series were selected, as they played a pivotal role in the establishment of FDA approval, along with additional trials published after FDA approval, which provided novel evidence on the use of bempedoic acid in the treatment of hypercholesterolemia. Publications that were not randomized, controlled trials were not included in this review. Only randomized controlled trials in which ezetimibe was used in conjunction with bempedoic acid were included in this review as they were relevant to the new FDA approval of bempedoic acid. Findings The findings of the present review show that bempedoic acid is both an effective and well-tolerated option for the treatment of hypercholesterolemia when used without ezetimibe in addition to standard therapy. It also appears that the combination with ezetimibe increases the cholesterol-lowering effect more than either agent alone when added to standard therapy. Implications Hypercholesteremia continues to be a major contributing factor leading to ASCVD. Bempedoic acid is an additional treatment option, along with both statins and diet and exercise, for reducing cholesterol levels and ASCVD events. With the new FDA approval, bempedoic acid may offer an effective therapy for reducing low-density lipoprotein cholesterol in patients at high risk for cardiovascular events due to established ASCVD or heterozygous familial hypercholesterolemia.

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.

This chapter is a focus on the rise and consolidation of psychiatric power and its control of individuals and populations who have become problematised and classified as mentally ill and madness throughout a long and enduring history of the present. For example, Michel Foucault describes how the patient and madness are socially constructed through disciplinarian techniques, such as the ‘medical gaze’ – the use and abuse of surveillance to control societal ills and give credibility to medical institutions and professional power the truthful arbiter of labelling mental illness. The key aim of Foucault’s point here has been “to create a history of the different modes by which, in our culture human beings are made subjects”. The history of how people are classified as subjects as having a medical disorder or mental illness is about revealing how psychiatry became embedded in the occidental culture in particular to have the legitimacy and power to define people as problems of scientific knowledge sanctioned by its truth claims that were rarely contested.

BackgroundMastoiditis is the most common intra-temporal complication of acute otitis media. Despite potentially lethal sequelae, optimal management remains poorly defined.MethodA retrospective case review was conducted of children diagnosed with mastoiditis at a tertiary referral centre, in North East England, between 2010 and 2017.ResultsFifty-one cases were identified, 49 without cholesteatoma. Median patient age was 42 months (2 months to 18 years) and median hospital stay was 4 days (range, 0–27 days). There was no incidence trend over time. Imaging was conducted in 15 out of 49 cases. Surgery was performed in 29 out of 49 cases, most commonly mastoidectomy with (9 out of 29) or without (9 out of 29) grommets. Complications included sigmoid sinus thrombosis (3 out of 49) and extradural abscess (2 out of 51), amongst others; no fatalities occurred.ConclusionA detailed contemporary description of paediatric mastoiditis presentation and management is presented. The findings broadly mirror those published by other UK centres, but suggest a higher rate of identified disease complications and surgical interventions.

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.

Purpose There are roughly 30 million Americans diagnosed with diabetes mellitus (DM), with nearly 95% of these cases being type 2 (T2)-DM. The American Diabetes Association continues to recommend metformin as the first-line initial treatment of T2DM, in combination with lifestyle modifications; yet, many require multiple therapies to achieve adequate glycemic control. In patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, adding a glucagon-like peptide 1 receptor agonist is a preferred treatment option; however, many patients are apprehensive about injecting medications. Semaglutide is the first oral option in this life-saving medication class. The purpose of this article was to review the pharmacology, clinical trials, safety profile, along with recommended dosing and costs, of oral semaglutide used for managing patients with T2DM. Methods A search through the PubMed, MEDLINE and Cochrane libraries was conducted for literature published from January 2017 through December 2020, using the key word semaglutide. Articles were selected if they were related to the approval of oral semaglutide or provided novel clinical information regarding this drug entity in its oral dosage formulation. Findings Three Phase II studies of the pharmacokinetic properties and Phase III trials from the PIONEER series were ultimately selected, as these trials were thought to provide pivotal information to the US Food and Drug Administration for the approval of oral semaglutide. Implications On review of the literature, it appeared that semaglutide is a viable option in treating T2DM. The use of this medication has been associated with glycosylated hemoglobin lowering similar to that with the injectable medication in its same class. Semaglutide was also showed some potential in preventing cardiovascular events as well as increasing weight loss.

Objective: The purpose of this article is to review the available clinical trial data that led to the Food and Drug Administration (FDA) approval of solriamfetol as well as its role in clinical practice. Data Sources: A MEDLINE/PubMed search was conducted (January 2000 to February 2020) using the keyword solriamfetol to discover appropriate clinical trials. Study Selection and Data Extraction: Articles were included that were published in the English language and related to the FDA approval of solriamfetol or provided novel information regarding this drug entity. Data Synthesis: The findings of the review show that solriamfetol may be a safe and effective option for the treatment of excessive sleepiness (ES) related to narcolepsy and obstructive sleep apnea (OSA). Relevance to Patient Care and Clinical Practice: Solriamfetol is distinguished from other stimulants in that it has lower binding affinity to dopamine and norepinephrine transporters and does not have the monoamine-releasing effects of amphetamines at usual therapeutic doses. Because of solriamfetol’s unique mechanism of action, there may be a reduction in abuse potential compared with the other currently FDA-approved options. Conclusions: In clinical trials, solriamfetol has shown dose-dependent improvement in wakefulness over placebo and adds another option for clinicians when treating ES in narcolepsy and OSA.

The aim of this report was to review the recent literature related to the assessment and management of obstructive sleep apnea (OSA) in children under the age of 2 years. Adenotonsillectomy (AT) indications are changing, with a greater proportion of younger children undergoing AT for OSA. Medical therapies may be an alternative to AT in mild-moderate OSA cases; however, further research is needed. Coblation® intracapsular tonsillectomy may confer benefits in reduced post-operative pain and hemorrhage. Recent concerns regarding the safety of general anesthesia in young children are an important area for further investigation. There is a paucity of literature related to OSA in children younger than 2 years. Recent large-scale trials have actively excluded children from this age group and there are no planned studies of this specific population. These children represent a distinct population with differing etiologies, presentations, investigations, and management consideration.

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

Introduction: Benign paroxysmal positional vertigo (BPPV) is the most common cause of dizziness in the elderly. This has been identified as a risk factor in falls. Falls are the leading cause of disability and the leading cause of death from injury among people over 75 in the UK. Methods: We assessed the effect of BPPV treatment on falls in an elderly population by retrospectively reviewing one unit’s experience of BPPV management over an 8-year period from June 2008 to June 2016. We specifically assessed patients who were referred for the primary reason of falls and were aged over 65 years. These patients were evaluated and treated with particle repositioning maneuvers if their positional tests were positive. The frequency of falls prior to their visit and at 6-month clinic follow-up were reviewed. Results: The total number of falls in the cohort reduced significantly ( P < .0001) after the procedure, from 128 to 46 falls (64% reduction). Associated comorbidities were also evaluated in this group. Conclusion: A prompt and effective treatment of BPPV is prudent to prevent devastating falls in older people in our communities.

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.

BackgroundMastoiditis is an otological emergency, and cross-sectional imaging has a role in the diagnosis of complications and surgical planning. Advances in imaging technology are becoming increasingly sophisticated and, by the same token, the ability to accurately interpret findings is essential.MethodsThis paper reviews common and rare complications of mastoiditis using case-led examples. A radiologist-derived systematic checklist is proposed, to assist the ENT surgeon with interpreting cross-sectional imaging in emergency mastoiditis cases when the opinion of a head and neck radiologist may be difficult to obtain.ResultsA 16-point checklist (the ‘mastoid 16’) was used on a case-led basis to review the radiological features of both common and rare complications of mastoiditis; this is complemented with imaging examples.ConclusionAcute mastoiditis has a range of serious complications that may be amenable to treatment, once diagnosed using appropriate imaging. The proposed checklist provides a systematic approach to identifying complications of mastoiditis.

Objective: The purpose of this article is to review the available clinical trial data for andexanet alfa and its role in clinical practice. Data Sources: A MEDLINE/PubMed search was conducted (January 2000 to January 2019) using the keyword andexanet alfa for clinical trials. References of identified articles were searched by hand for additional citations. Study Selection and Data Extraction: We included English-language articles related to the Food and Drug Administration (FDA) approval of andexanet alfa or provided novel information regarding this drug entity. Data Synthesis: The findings of the review show that andexanet alfa may be a safe and effective option for the reversal of apixaban and rivaroxaban. Relevance to Patient Care and Clinical Practice: With the approval of this reversal agent, patients and providers can feel safer when using apixaban and rivaroxaban, which in turn may increase the use of these anticoagulant agents. Conclusions: The new FDA approval of andexanet alfa will allow safer use of oral anticoagulants and will likely further the use of direct oral anticoagulants for anticoagulant needs. Reversing enoxaparin-/edoxaban-induced bleeding with this agent should be limited because there is no FDA approval owing to the fact that only phase II trial data available.

Objective of review Acute otitis media (AOM) is the largest cause of antimicrobial prescriptions amongst children in developed countries. Excessive and inappropriate prescribing is known to drive antimicrobial resistance, but less is known of antimicrobial resistance in AOM-associated bacteria. Type of review & search strategy We conducted a systematic review and meta-analysis of bacterial prevalence and antimicrobial resistance in studies of paediatric AOM identified from Ovid Medline, Embase and the Cochrane library. Results From 48 unique studies, 15,871 samples were included. Only 0.67 (CI 0.63–0.71) of all ear samples grew a bacterial pathogen. The most common bacterial causes of AOM in children were Streptococcus pneumoniae 0.30 (CI 0.27–0.32), Haemophilus influenza 0.23 (CI 0.20–0.26), and Moraxella catarrhalis 0.05 (CI 0.04–0.06). Resistance patterns varied amongst organisms and antimicrobial agents. The pooled proportion of bacterial culture-positive episodes of AOM that could be effectively treated with amoxicillin was 0.85 (CI 0.76–0.94), erythromycin was 0.64 (0.48–0.78) and amoxicillin-clavulanate was 0.95 (CI 0.85–0.98). Conclusion We have demonstrated the bacteriology and antimicrobial resistance patterns of AOM. Of samples which grew bacteria, on average approximately 15% of isolates demonstrated resistance to amoxicillin; a typical first-line agent. Greater understanding of local bacteriology and resistance patterns is needed to enable improved antimicrobial stewardship.

Objective Paediatric solid organ transplantation is an increasingly successful treatment. Improved survival is paralleled by increased secondary complications of immunosuppression, including post-transplant lymphoproliferative disease (PTLD). PTLD frequently presents in Waldeyer's lymphatic ring. Adenotonsillar hypertrophy (ATH) is common in children, however in children after transplant, ATH may indicate PTLD. We review the literature on ATH and the role of adenotonsillectomy in children after transplantation. Methods A comprehensive literature search was performed on the 26 th September 2017 of Ovid Medline (1996–September 2017), Embase (1996–2017) and EBM reviews (Cochrane database of systematic reviews 2005–September 20 th 2017). Results were limited to English language publications within the last 20 years. Abstracts were screened for relevance to PTLD and ATH in the paediatric solid organ transplantation population. Screening of the bibliographies identified further articles. Results 85 unique articles were screened to yield 18 relevant publications. 10 were retrospective studies and 8 were prospective studies. Conclusion In children, we report a PTLD incidence of up to 15%, with up to 63% of cases presenting in the head and neck. Histological examination of adenotonsillectomy specimens found PTLD in a mean 5.7% (range 0–39%). We found a lack of prospective studies into this topic and further high quality research is needed. Clinical assessment of ATH in children after transplantation and when to perform a diagnostic adenotonsillectomy remains challenging. Children with ATH warrant prompt further investigation and support from colleagues in transplantation and oncology is required.

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:This study aimed to compare the efficacy of diode laser, coblation and cold dissection tonsillectomy in paediatric patients.Methods:A total of 120 patients aged 10–15 years with recurrent tonsillitis were recruited. Participants were prospectively randomised to diode laser, coblation or cold dissection tonsillectomy. Operative time and blood loss were recorded. Pain was recorded on a Wong–Baker FACES®pain scale.Results:The operative time (10 ± 0.99 minutes), blood loss (20 ± 0.85 ml) and pain were significantly lower with coblation tonsillectomy than with cold dissection tonsillectomy (20 ± 1.0 minutes and 30 ± 1.0 ml;p= 0.0001) and diode laser tonsillectomy (15 ± 0.83 minutes and 25 ± 0.83 ml;p= 0.0001). Diode laser tonsillectomy had a shorter operative time (p= 0.0001) and less blood loss (p= 0.001) compared with cold dissection tonsillectomy. However, at post-operative day seven, the diode laser tonsillectomy group had significantly higher pain scores compared with the cold dissection (p= 0.042) and coblation (p= 0.04) tonsillectomy groups.Conclusion:Both coblation and diode laser tonsillectomy are associated with significantly reduced blood loss and shorter operative times compared with cold dissection tonsillectomy. However, we advocate coblation tonsillectomy because of the lower post-operative pain scores compared with diode laser and cold dissection tonsillectomy.

Background:Olfactory dysfunction is a common condition that may in some cases require imaging to investigate a potential underlying cause.Objectives:This review describes the anatomy of normal olfaction and illustrates the pathological substrates of olfactory dysfunction amenable to imaging.

Student musicians are at risk for noise-induced hearing loss (NIHL) as they develop skills and perform during instructional activities. Studies using longitudinal dosimeter data show that pedagogical procedures and instructor behaviors are highly predictive of NIHL risk, thus implying the need for innovative approaches to increase instructor competency in managing instructional activities without interfering with artistic and academic freedom. Ambient information systems, an emerging trend in human-computer interaction that infuses psychological behavioral theories into technologies, can help construct informative risk-regulating systems. The purpose of this study was to determine the effects of introducing an ambient information system into the ensemble setting. The system used two ambient displays and a counterbalanced within-subjects treatment study design with six jazz ensemble instructors to determine if the system could induce a behavior change that alters trends in measures resulting from dosimeter data. This study assessed efficacy using time series analysis to determine changes in eight statistical measures of behavior over a 9-wk period. Analysis showed that the system was effective, as all instructors showed changes in a combination of measures. This study is in an important step in developing non-interfering technology to reduce NIHL among academic musicians.

Objectives/Hypothesis The association between extraesophageal reflux (EER) and symptoms of gastroesophageal reflux disease (GERD) is inadequately understood. We used the Comprehensive Reflux Symptom Scale (CReSS) to evaluate EER and reflux-symptom prevalence in gastroenterology and otolaryngology outpatients and symptom awareness among UK gastroenterologists. Study Design Cross-sectional cohort survey. Methods Six hundred thirty-nine participants were surveyed: 103 controls, 359 patients undergoing esophagogastroduodenoscopy (EGD), and 177 otolaryngology clinic patients with throat symptoms. Participants completed the CReSS questionnaire. The study was undertaken in the Endoscopy Unit and the Department of Otolaryngology–Head and Neck Surgery, Newcastle upon Tyne Hospitals, Newcastle-upon-Tyne, United Kingdom. Registered members of the British Gastroenterology Society were asked to rate how frequently reflux patients might complain of each CReSS item. Results The median CReSS total in volunteers (4) was significantly lower (P 15% of ENT patients and 28% of EGD patients. Three major, robust CReSS factors: esophageal, pharyngeal, and upper airway emerged. Of 259 gastroenterologists, >20% scored 8 of the 34 symptoms as never being reported by reflux patients. Conclusions Endorsement of each EER CReSS item by 28% to 58% of patients with endoscopic evidence of GERD supports the Montreal consensus on an EER-GERD continuum. Gastroenterologists vary considerably in their appreciation of EER symptom relevance. The advantages of CReSS include standardized, comprehensive capture of patient experience; discriminant validity of ENT and GERD patients from volunteers; and discrete esophageal, pharyngeal, and upper airway subscales. Level of Evidence 4 Laryngoscope, 125:424–430, 2015

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.

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.

Objective:To investigate throat-related quality of life in peritonsillar abscess sufferers.Method:The adult tonsil outcome inventory questionnaire, which is a validated throat-related quality of life tool, was administered to individuals who had recently suffered a peritonsillar abscess and to control subjects.Results:The mean inventory score was significantly higher (reflecting poorer throat-related quality of life) in peritonsillar abscess sufferers (n = 55, mean score 25.8 out of 100) than in age- and gender-matched controls (n = 55, mean score 8.7) (p Conclusion:Peritonsillar abscess had a significant impact on throat-related quality of life. In many, peritonsillar abscess represented an acute episode on a background of chronic throat problems. For optimal management, notably the place and timing of tonsillectomy, this impact should be taken into account. The adult tonsil outcome inventory is an ideal tool for use in clinical practice.

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.

Background Type 2 diabetes, dyslipidemia, and obesity continue to be common disorders that many clinicians and patients struggle to control. There are likely numerous reasons for poor control of these diseases, including medication efficacy and adverse effects, access to medications and health care, poor adherence, and lack of lifestyle changes by patients. Several new and emerging medications may help resolve these issues. Objective The goal of this article is to review new and emerging medications for type 2 diabetes mellitus, dyslipidemia, and obesity. Methods The Food and Drug Administration drug approval list for 2011 and 2012 was searched to identify newly approved drugs for type 2 diabetes, dyslipidemia, and obesity. New drug entities or existing drug entities with a new indication were included. To identify emerging therapies, we performed targeted searches on clinicaltrials.gov using the listed disease states and Phase III studies. PubMed was searched with these drug names to identify clinical trials for inclusion in this review. Preclinical trials and non–English-language publications were excluded, as were trials not evaluating the efficacy of these agents. The websites goodRx.com and rxpriceverify.com were used to identify pricing. Results For type 2 diabetes, exenatide extended-release causes fewer adverse effects and better efficacy than the daily exenatide formulation. The new sodium-glucose cotransporter 2 inhibitor drug class has a unique mechanism of action, hemoglobin A 1c reductions near 1%, and seemingly few adverse effects. With respect to dyslipidemia, icosapent ethyl effectively lowers triglyceride levels by ∼20% to 45% (depending on baseline triglyceride level), with little effect on LDL-C. For treatment of obesity, lorcaserin is a novel anorexic agent that results in an ∼5.5-kg mean weight loss, and phentermine-topiramate controlled-release reduces weight by ∼12.2 kg. Conclusion Although these agents certainly add to our armamentarium, none appear to offer significant advantages over currently available options. High costs will likely prevent these novel agents from being used as first-line agents in most patients. Further studies will help to more clearly define their roles in therapy.

Objectives/Hypothesis: A literature review regarding the use of laryngopharyngeal mucosal signs in diagnosing laryngopharyngeal reflux (LPR). Study Design: Literature review. Methods: A search of MEDLINE in February 2012 using the terms laryngopharyngeal reflux, laryngitis, mucosa, appearances, and signs (English language only). Results: One or more laryngopharyngeal mucosal signs associated with LPR were identified in 64% to 93% of healthy volunteers (3% >5 signs) and in 17% to 85% of gastroesophageal reflux disease sufferers (Reflux Finding Score [RFS] >7 in 24%). Reinke's edema, pseudosulcus, ventricular obliteration, vocal cord nodules, and granulomas have in some, but not all studies, been shown to be more prevalent in those with pH-proven pharyngeal reflux. Pseudosulcus, interarytenoid thickening, and Reinke's edema were more prevalent in those symptomatic of LPR than those not. The use of multiple mucosal signs may improve detection of reflux sufferers from asymptomatic controls. The RFS has a sensitivity and specificity of 87.8% and 37.5%, respectively, for picking up pH-proven pharyngeal reflux individuals. Inter- and intrarater reliability for identifying signs is fair to good in most studies. Conclusions: The limited evidence for each mucosal finding should be considered in making the diagnosis of LPR. Further quality research in to mucosal findings in LPR is needed.

Extended-interval monitoring of warfarin has been proposed to reduce follow-up burden and improve patient satisfaction. We aimed to make an initial assessment of anticoagulation satisfaction before and after an extended-interval warfarin monitoring intervention. We conducted a translational prospective single-arm pilot study of extended-interval warfarin monitoring in five pharmacist-managed anticoagulation clinics. Patients meeting CHEST guideline criteria for extended-interval warfarin monitoring began progressive extended-interval follow-up (6, 8, and 12 weeks thereafter). The Duke Anticoagulation Satisfaction Scale (DASS) was administered at baseline and at end-of-study or study removal (in patients no longer appropriate for extended interval follow-up). Forty-six patients had evaluable pre- and post-intervention DASS survey data. Mean age of patients was 66.5 years, 74 % were non-Hispanic whites, and 48 % were men. Patients completed a mean ± SD of 34 ± 22 weeks of follow-up. Mean ± SD total DASS score at baseline was 45.2 ± 14.2 versus 49.1 ± 14.9 at end-of-study (mean change, +3.9 [95 % CI −0.6–8.4; p = 0.09]), indicating no benefit—and trending toward decrement—to anticoagulation satisfaction. Change in anticoagulation satisfaction varied substantially following extended-interval monitoring, with no evidence of improved satisfaction. Plausible reasons for patients not preferring extended-interval monitoring include increased anxiety and disengagement from self-management activities, both potentially related to less frequent feedback and reassurance during extended interval-monitoring. Additional research is needed to identify who is likely to benefit most from extended-interval monitoring. Anticoagulation satisfaction should be considered with clinical factors and shared-decision making when implementing extended-interval warfarin monitoring.

Background:Despite the patient numbers and scope of ENT surgery, it is under-represented in most undergraduate medical curricula.Method:An online questionnaire was e-mailed, at National Health Service trust level, to 3544 newly qualified doctors from 30 UK medical schools. Undergraduate ENT exposure, confidence and educational value were measured on a Likert scale.Results:We received 444 eligible responses. The mean undergraduate ENT exposure was 3.4 days of pre-clinical teaching plus 5.0 days of ENT departmental experience. However, 15.8 per cent of respondents reported no formal departmental ENT experience, and 65.8 per cent would have liked further undergraduate experience. Teaching modalities with a lower perceived educational value were generally offered more frequently than those with a higher perceived educational value. Graduates felt significantly less confident with ENT history-taking, examination and management, compared with their cardiology clinical competencies (p Conclusion:These results highlight the lack of UK ENT undergraduate education, and the significant effect this has on junior doctors’ clinical confidence. In addition, commonly used teaching methods may not be optimally effective.

Clin. Otolaryngol. 2011, 36, 45–50 Objectives: To generate consensus amongst faculty members regarding follow-up practice for well-defined clinical scenarios using a Delphi exercise and to identify whether disseminating the consensus guidelines changed follow-up practice. Study Design: Generation of consensus using a Delphi exercise and an audit of follow-up practice before and after dissemination of the resultant guidelines. Setting: The department of Otorhinolaryngology-Head and Neck Surgery at the Freeman Hospital, Newcastle upon Tyne, UK. Participants and methods: Panel members for this exercise included 11 consultants and two associate specialists and one co-ordinator. We identified clinical scenarios where ≥80% agreement existed that routine follow-up appointments should not be made and subsequently disseminated guidelines widely to all medical staff. The follow-up rates for the scenarios where consensus existed regarding follow-up practice were audited from clinic letters before and after the guidelines were disseminated. Main outcome measures: Agreement on scenarios where routine follow-up appointments should not be made was assessed using a Likert scale (1–5). Results: Of 13 faculty members, 12 responded to rounds one and two, and 11 responded to round three. The Delphi exercise identified 18 clinical scenarios where there was ≥80% agreement on patients not routinely being followed up. Comparison of the follow-up practice prior to and after the Delphi exercise identified a reduction in follow-up for all 18 scenarios of 48%. Conclusion: Consensus regarding routine follow-up can be reached by using the Delphi process in ENT practice. This can translate into a real change in clinical practice. Furthermore, this process could be applied for consensus building in other related areas.

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.

Background:FloSeal, a locally applied haemostatic agent, has been shown to be effective in a variety of clinical situations. This study investigated its potential benefits in the management of epistaxis.Methods:The outcomes of a series of patients with epistaxis presenting to one ENT unit, over a two-month period, were compared. Patients were either treated with FloSeal or traditional epistaxis management techniques. Success of FloSeal was classed as complete haemostasis after its application, without the need for further interventions and no readmission with epistaxis within 7 days.Results:Our study comprised 101 adults, with a mean age of 70 years (range, 22–98 years). The overall success rate for FloSeal was 14 per cent (5 out of 36 cases). It was successful in 66 per cent of anterior epistaxis cases (2 out of 3) and in only 9 per cent of posterior epistaxis cases (3 out of 33). There was a significantly higher failure rate of FloSeal compared with nasal packing in posterior epistaxis (p < 0.001).Conclusion:Our findings suggest that FloSeal has a limited role in the management of epistaxis.

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 …

Background:Isolated olfactory dysfunction is a common complaint; the vast majority of cases are benign and untreatable. A common dilemma is whether to image the olfactory tract of affected patients.Methods:A case review of 100 consecutive patients who underwent magnetic resonance imaging for the primary complaint of olfactory dysfunction was performed. Patients with a diagnosis of chronic rhinosinusitis, with or without nasal polyps, were excluded.Results:Magnetic resonance imaging abnormalities that were considered clinically relevant to the presentation of olfactory dysfunction were found in only seven patients (7 per cent). Of these, only one patient (1 per cent) had an abnormality found that altered their clinical management. A comparison of the findings for children (less than 16 years old,n = 5) with those for adults (equal to or more than 16 years old,n = 95) revealed that 4 per cent of adults scanned had olfactory-related pathology diagnosed, as opposed to 60 per cent of children.Conclusion:Cross-sectional imaging may not be necessary in most patients with olfactory dysfunction. Imaging adds little to the patient history and clinical examination findings.

Objectives We aimed to assess self-report and perceptual voice outcomes in patients undergoing local anaesthetic injection laryngoplasty in our outpatient clinic. Design Prospective case series. Setting Department of Otolaryngology-Head and Neck Surgery, Freeman Hospital, Newcastle-upon-Tyne, UK. Participants Sixty-eight patients underwent local anaesthetic injection laryngoplasty in the outpatient clinic over the 2-year study period. Main outcome measure Voice Performance Questionnaire (patient-rated), and perceptual voice analysis (observer-rated) Grade, Roughness, Breathiness, Aesthenia and Strain scores were recorded before and 2 weeks after injection laryngoplasty. Results Fifty-seven patients had sufficient pre- and post-procedure data to be included in the analysis. These included 32 men and 25 women, age range 26–97 years. Of the remaining patients, they were excluded due to failed procedure (n = 3), too unwell to proceed (n = 1), died before follow-up was complete (n = 3) and incomplete data (n = 4). The median Voice Performance Questionnaire score improved from 42 to 21; (P

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.

Objective: The incidence of quinsy is rising in the UK for reasons which are unclear. There were >7000 hospital diagnosed episodes last year in England alone. Some suggest a link to the decline in elective tonsillectomy. Our aim was to compare chronic throat symptoms in quinsy patients and controls.Method: The validated 16-item Tonsillectomy Outcome Inventory (TOI-16) was used to compare the impact of throat symptoms over the previous 6 months in 119 controls (no quinsy history) and 55 contactable (by telephone) quinsy patients (34M, 21F), who had an average experience of 1.4 (range 0-4) quinsies. Analysis was in SPSS.Results: The TOI-16 Cronbach’s α = .92, indicating high internal consistency. The mean 6-month overall throat impact scores in quinsy patients (21.0) were significantly greater than that in volunteers (10.9 P < .05). The post-quinsy interval had only modest effect on the overall mean score. Younger people had higher scores in both groups. On item-by-item analysis, quinsy patients recorded si...

Objective: Diagnosis and management of EER remains controversial. We have validated a reliable Comprehensive Reflux Symptom Scale (CReSS) incorporating 34 possible symptoms of EER and gastroesophageal reflux disease (GERD). We aimed to compare CReSS in healthy volunteers, throat clinic attenders, and a heterogeneous group referred for upper gastrointestinal (GI) endoscopy.Method: The CReSS was administered to 532 participants: 103 healthy volunteers, mean age 55 years, 39% male, 15% smokers; 175 throat clinic attenders, mean age 56 years, 37% male, 11% smokers; and 254 attenders for GI endoscopy, mean age 58 years, 41% male, 14% smokers. Regular recent antacid use was recorded.Results: The mean CReSS total was 6.5 (SD 8.14) in volunteers, significantly lower (P < .001) than in throat 32.19 (SD 22.37) or GI patients 39.67 (SD 26.14). CReSS totals were independent of age. All items were endorsed by at least 17% of throat patients, 30% of GI patients. The top symptoms in throat patients were throat clearing,...

A young woman presented with prominence of the dorsum of her nose since childhood. She had become increasingly self-conscious of her appearance but was otherwise fit and well. She denied symptoms of nasal obstruction, epistaxis or discharge but described an intermittent ache related to the lump. There was no history of seizures, meningitis or cerebral abscess. Examination revealed a firm midline dorsal hump (figures 1 and 2). The rest of the examination …