Developing a core outcome set for clinical trials in olfactory disorders: a COMET initiative.

STATEMENT OF PROBLEM: Evaluating the effectiveness of the management of Olfactory Dysfunction (OD) has been limited by a paucity of high-quality randomised and/or controlled trials. A major barrier is heterogeneity of outcomes in such studies. Core outcome sets (COS) - standardized sets of outcomes that should be measured/reported as determined by consensus-would help overcome this problem and facilitate future meta-analyses and/or systematic reviews (SRs). We set out to develop a COS for interventions for patients with OD. METHODS: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed patients and healthcare practitioners to individually rate the outcomes in terms of importance on a 9-point Likert scale. RESULTS: After 2 rounds of the iterative eDelphi process, the initial outcomes were distilled down to a final COS including subjective questions (visual analogue scores, quantitative and qualitative), quality of life measures, psychophysical testing of smell, baseline psychophysical testing of taste, and presence of side effects along with the investigational medicine/device and patient's symptom log. CONCLUSIONS: Inclusion of these core outcomes in future trials will increase the value of research on clinical interventions for OD. We include recommendations regarding the outcomes that should be measured, although future work will be required to further develop and revalidate existing outcome measures.

Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss.

BACKGROUND: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. METHODS: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. RESULTS: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. CONCLUSIONS: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

The socioeconomic cost of chronic rhinosinusitis study.

INTRODUCTION: Chronic rhinosinusitis (CRS) is highly prevalent, affecting 11% of the population. Studies evaluating the socio-economic impact of CRS are mostly limited to the US population. Currently there is no study that has evaluated the socio-economic costs of CRS in the UK. METHODS: A case-control study of patients with CRS and healthy controls was conducted to investigate the wider socio-economic impact of the disease. Data on demographic and socioeconomic characteristics, out-of-pocket expenditure (OOPE), health resource utilisation, productivity losses and health-related quality of life (HRQoL) via the EQ-5D and SNOT-22 instruments, were collected from questionnaires. RESULTS: A total of 139 CRS participants and 67 control participants completed the questionnaires. The average total OOPE per patient extrapolated to a 12-month period was £304.84. Other important findings include significantly higher reported primary care interactions (4.14 vs. 1.16) as well as secondary care interactions (2.61 vs 0.4) in CRS group as compared to controls over three-months. The average total missed workdays was estimated to be 18.7 per patient per year. The estimated incremental healthcare cost of CRS per year is £16.8 billion or £2.8 billion per million inhabitants. Factors predictive of a higher OOPE include higher household occupancy and income and these accounted for only 9.7% of the total variance in total OOPEs. Other socioeconomic, demographic and HRQoL variables were not found to be predictive factors of OOPE. CONCLUSIONS: This study showed that CRS has a significant wider economic burden beyond the immediate direct healthcare costs. CRS participants had a high level of healthcare service use, OOPE and productivity loss. Results from this study will add to the existing limited data both for the UK and abroad and emphasises the need for effective treatments for these patients to reduce the disease impact.

Comparison of COVID-19 and common cold chemosensory dysfunction.

Anosmia constitutes a prominent symptom of COVID-19. However, anosmia is also a common symptom of acute colds of various origins. In contrast to an acute cold, it appears from several questionnaire-based studies that in the context of COVID-19 infection, anosmia is the main rhinological symptom and is usually not associated with other rhinological symptoms such as rhinorrhoea or nasal obstruction. Until now, no study has directly compared smell and taste function between COVID-19 patients and patients with other causes of upper respiratory tract infection (URTI) using valid and reliable psychophysical tests. In this study, we aimed to objectively assess and compare olfactory and gustatory functions in 10 COVID-19 patients (PCR diagnosed, assessed on average 2 weeks after infection), 10 acute cold (AC) patients (assessed before the COVID-19 outbreak) and 10 healthy controls, matched for age and sex. Smell performance was assessed using the extended "Sniffin' Sticks" test battery (4), while taste function was assessed using "taste strips" (5). Receiver Operating Characteristic (ROC) curves were built to probe olfactory and gustatory scores in terms of their discrimination between COVID-19 and AC patients. Our results suggest that mechanisms of COVID-19 related olfactory dysfunction are different from those seen in an AC and may reflect, at least to some extent, a specific involvement at the level of central nervous system in some COVID-19 patients. In the future, studies to assess the prevalence of persistent anosmia and neuroanatomical changes on MRI correlated to chemosensory function, will be useful to understand these mechanisms.

Anosmia as a presenting symptom of SARS-CoV-2 infection in healthcare workers - A systematic review of the literature, case series, and recommendations for clinical assessment and management.

BACKGROUND: Healthcare workers are at the forefront of the ongoing COVID-19 pandemic and are at high risk for both the contraction and subsequent spread of virus. Understanding the role of anosmia as an early symptom of infection may improve monitoring and management of SARS-CoV2 infection. METHODOLOGY: We conducted a systematic review of the literature of SARS-CoV2 infection/COVID-19 and anosmia to help inform management of anosmia in healthcare works. We report a case series of healthcare workers, who presented with a loss of sense of smell secondary to COVID-19 infection to demonstrate management principles. RT-PCR was used to confirm COVID-19 positivity and psychophysical testing of olfaction was performed using the British version of the University of Pennsylvania Smell Identification Test, UPSIT. RESULTS: The systematic literature search returned 31 articles eligible for inclusion in the study and informed our recommendations for clinical assessment and management. All three healthcare professionals who presented with loss of sense of smell subsequently tested positive for SARS-CoV-2. Psychophysical testing of olfaction using the UPSIT confirmed mild and moderate microsmia in two, respectively, and normosmia at day 17 in one. CONCLUSIONS: Olfactory (± gustatory) dysfunction is indicative of COVID-19 infection and thus has important implications in the context of healthcare workers, or key workers in general, who work in close contact with others if not recognised as suffering from COVID. This leads to a potentially higher likelihood of spreading the virus. In conjunction with our literature review these findings have helped with creating recommendations on the assessment and management of olfactory dysfunction during the ongoing COVID-19 pandemic, both for healthcare workers and patients.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Optimising trial outcomes and patient retention for the MACRO trial for chronic rhinosinusitis.

BACKGROUND: This study aimed to evaluate current subjective and objective outcome assessments for the MACRO (defining best Management for Adults with Chronic RhinOsinusitis) Trial which compares antibiotics, placebo and sinus surgery. This was to identify any redundant assessments and to include patient perspectives to determine acceptability for confirmation in the trial. METHODS: Adults CRS patients meeting the provisional eligibility criteria for the MACRO trial were recruited to this mixed-method study at 2 sites. Correlations between the objective outcome measures and SNOT-22 scores were evaluated. Selected participants took part in a semi-structured telephone interview to explore their experiences and views of undergoing outcome measures. RESULTS: Seventy patients (37% male) were recruited, 36 had CRS without nasal polyps, 34 had CRS with nasal polyps. There was a weak inverse correlation between the SNOT-22 â€Blockage†ratings and Peak Nasal Inspiratory Flow readings, a moderate inverse correlation between the SNOT-22 â€Smell†ratings and Sniffin’ Sticks scores, but no significant correlation between the SNOT-22 and Saccharin test results. The participants’ experience of the trial visit was positive with an acceptable duration of trial visit. Most proposed outcome measures were valued by participants with the exception of the Saccharin test. DISCUSSION: The Sniffin’ Sticks test and PNIF correlate with their respective component SNOT-22 scores but are considered important by patients; PNIF is simple, cheap test to perform. The Saccharin test will be removed as participants did not value it and was not highly rated in parallel work on a core outcome set for CRS.

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records.

BACKGROUND: The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. METHODS: We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). RESULTS: From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. CONCLUSIONS: While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management.

Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records.

BACKGROUND: Macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use. METHODOLOGY: Observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia. RESULTS: Analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular. CONCLUSIONS: Although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.

Exploring the association between ingestion of foods with higher potential salicylate content and symptom exacerbation in chronic rhinosinusitis. Data from the National Chronic Rhinosinusitis Epidemiology Study.

INTRODUCTION: Pharmacological salicylates are known to trigger respiratory exacerbations in patients with Non-Steroidal Exacerbated Respiratory Disease (N-ERD), a specific phenotype of Chronic Rhinosinusitis (CRS) and asthma. The impact of dietary sources of salicylates across subgroups of CRS is not well understood. The hypothesis is that in patients with nasal polyps present, there is likely to be a higher incidence of symptom exacerbation due to dietary salicylates regardless of any known response to pharmacological salicylate. METHODS: The Chronic Rhinosinusitis Epidemiology Study (CRES) was a questionnaire-based case-control study which sought to characterise the UK CRS population in terms of sociological, economic and medical factors. Using specific questions to examine participant responses relating to symptom exacerbation from food groups thought to be high in salicylate content, this analysis of the CRES database sought to compare an estimate of the prevalence of dietary sensitivity due to food with higher potential salicylate content across patients with CRS with (CRSwNPs) and without nasal polyposis (CRSsNPs) and with allergic fungal rhinosinusitis (AFRS). RESULTS: The CRSwNPs group were significantly more likely than controls to report symptom exacerbation due to ingestion of food groups with higher potential dietary salicylate content. The same trend was observed amongst CRSsNPs participants to a lesser degree. Reported response to the individual specific food groups wine, nuts, spicy foods, fruit and vegetables demonstrated that a statistically significant proportion of CRSwNPs and AFRS participants reported sensitivity to wine. CONCLUSIONS: This analysis suggests that there is an association between symptom exacerbation in response to food products with higher potential salicylate content, specifically wine, in CRS patients both with and without nasal polyposis when compared to controls, but especially in the CRSwNPs and AFRS phenotypes. Further studies are needed to detail if this relationship represents a causal relationship to dietary salicylate. The data present the possibility that a wider group of CRS patients may elicit salicylate sensitivity than those with known N-ERD.

EPOS2020: development strategy and goals for the latest European Position Paper on Rhinosinusitis.

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.

Eustachian tube symptoms are frequent in chronic rhinosinusitis and respond well to endoscopic sinus surgery.

BACKGROUND: Symptoms of Eustachian tube (ET) dysfunction are seldom assessed in patients with chronic rhinosinusitis (CRS). The Sino-Nasal Outcome Test (SNOT-22) quality-of-life tool includes two questions that specifically screen for symptoms of ET dysfunction (Ear Fullness; Ear Pain). OBJECTIVE: The purpose of this study was to determine the extent to which these ET symptoms were present in patients with CRS, and whether these symptoms respond to endoscopic sinus surgery (ESS). METHODOLOGY: SNOT-22 data collected prospectively at time of recruitment into IRB-approved clinical trials or case-control studies in CRS was pooled to provide a cross section of the frequency and severity of ET dysfunction. When applicable to the trials, the SNOT-22 was repeated at least 3 months following ESS. RESULTS: Five trials rendering 131 patients were available for assessment. The control group comprised of 251 participants from two case-control studies. Ear Fullness of equal/greather than 1 was reported in 80/131 CRS patients compared to 45/251 control patients. Ear Pain of equal/greather than 1 was reported in 39/131 CRS patients compared to 33/251 control patients. Following ESS, mean Ear Fullness and Ear Pain scores decreased to 1.17 and 0.73, respectively. CONCLUSION: Symptoms suggestive of ET dysfunction are frequent in CRS, and for most patients the symptoms will decrease post-ESS to a level comparable with a non-CRS population. Patients whose ET symptoms do not respond to ESS may represent a target population for emerging therapeutic options for ET dysfunction.

CHronic Rhinosinusitis Outcome MEasures (CHROME), developing a core outcome set for trials of interventions in chronic rhinosinusitis.

STATEMENT OF PROBLEM: Evaluating the effectiveness of treatments in chronic rhinosinusitis (CRS) have been limited by both a paucity of high quality randomised trials, and the heterogeneity of outcomes in those that have been reported. Core outcome sets (COS) are an agreed, standardized set of outcomes that should be measured and reported by future trials as a minimum and will facilitate future meta-analysis of trial results in systematic reviews (SRs). We set out to develop a core outcome set for interventions for adults with CRS. METHOD(S) OF STUDY: A long-list of potential outcomes was identified by a steering group utilising a literature review, thematic analysis of a wide range of stakeholders' views and systematic analysis of currently available Patient Reported Outcome Measures (PROMs). A subsequent e-Delphi process allowed 110 patients and healthcare practitioners to individually rate the outcomes in terms of importance, on a Likert scale. MAIN RESULTS: After 2 rounds of the iterative Delphi process, the 54 initial outcomes were distilled down to a final core-outcome set of 15 items, over 4 domains. PRINCIPAL CONCLUSIONS: The authors hope inclusion of these core outcomes in future trials will increase the value of research on interventions for CRS in adults. It was felt important to make recommendations regarding how these outcomes should be measured, although additional work is now required to further develop and revalidate existing outcome measures.

Health utility reporting in chronic rhinosinusitis patients.

OBJECTIVES: Direct comparison of different diseases allows clinicians and researchers to place the burden of symptoms and impact on quality of life of each condition in context. Generic health-related quality-of-life assessment tools allow such analysis, and limited data are available for British patients with chronic rhinosinusitis. DESIGN: As part of a larger feasibility study, patients underwent baseline assessment using the SNOT-22, SF-12 and EQ-5D-5L tools. Data were analysed using Microsoft Excel and algorithms available for the analysis of the later two tools. We plotted EQ-5D-5L VAS and utility scores and SF-12 MCS and PCS scores separately against SNOT-22 scores and quantified associations using bivariate ordinary least squares regression analysis. SETTING: Patients were prospectively recruited from six UK outpatient clinics. PARTICIPANTS: Adult patients with chronic rhinosinusitis without nasal polyps (CRSsNPs). MAIN OUTCOME MEASURES: Baseline SNOT-22, SF-12 and EQ-5D-5L scores. RESULTS: Fifty-two adults were recruited with a mean age of 55 years, 51% were male. The mean SNOT-22 score was 43.82. Mental and physical component scores of the SF-12 were 46.53 and 46, respectively. Mean index score computed form the EQ-5D-5L was 0.75. Worse (higher) SNOT-22 scores were associated with lower EQ-5D-5L VAS and utility scores and SF-12 MCS and PCS scores. CONCLUSION: The EQ-5D-5L suggests that British CRSsNPs patients are negatively impacted with regards to quality of life. We found the SF-12 to be less sensitive and conclude that the EQ-5D-5L tool is a quick and accessible method for assessing QOL in order it can be compared with other disease states.

The genetics of cholesteatoma. A systematic review using narrative synthesis.

OBJECTIVE: A cholesteatoma is a mass of keratinising epithelium in the middle ear. It is a rare disorder that is associated with significant morbidity, and its causative risk factors are poorly understood; on a global scale, up to a million people are affected by this each year. We have conducted a systematic literature review to identify reports about the heritability of cholesteatoma or any constitutional genetic factors that may be associated with its aetiology. DATA SOURCES: A systematic search of MEDLINE (EBSCO) and two databases of curated genetic research (OMIM and Phenopedia) was conducted. STUDY SELECTION: The participants and populations of interest for this review were people treated for cholesteatoma and their family members. The studies of interest reported evidence of heritability for the trait, or any association with congenital syndromes and particular genetic variants. DATA EXTRACTION: The searches identified 449 unique studies, of which 35 were included in the final narrative synthesis. DATA SYNTHESIS: A narrative synthesis was conducted, and data were tabulated to record characteristics, including study design, genetic data and author conclusions. Most of the studies identified in the literature search, and described here, are case reports and so represent the lowest level of evidence. In a few case reports, congenital and acquired cholesteatomas have been shown to segregate within families in the pattern typical of a monogenic or oligogenic disorder with incomplete penetrance. Evidence from syndromic cases could suggest that genes controlling ear morphology may be risk factors for cholesteatoma formation. CONCLUSIONS: This is the first systematic review about the genetics of cholesteatoma, and we have identified a small body of relevant literature that provides evidence of a heritable component for its aetiology. Cholesteatoma is a complex and heterogeneous clinical phenotype, and it is often associated with chronic otitis media and with some rare congenital syndromes known to affect ear morphology and related pathologies.