Establishing UK research priorities in smell and taste disorders: A James Lind alliance priority setting partnership.

OBJECTIVES: To determine the top 10 research priorities in Smell and Taste Disorders (SATD). DESIGN: After steering group was established, an electronic survey was disseminated to determine the list of questions. After removing out-of-scope responses, the remainder were consolidated to create summary questions. A literature search was conducted to remove already answered questions. A second survey was used to determine the top questions that formed the subject of final debate at a workshop attended by clinicians and patients to determine the top 10 priorities. SETTING: A James Lind Alliance Priority Setting Partnership (JLAPSP) was established by FifthSense to identify the top 10 research questions in SATDs in the United Kingdom. PARTICIPANT: All stakeholders in SATDs (patients, healthcare professionals, family, carers, researchers). MAIN OUTCOME MEASURES: Final 10 research priorities. RESULTS: The 665 respondents to the initial survey provided 1698 research questions. Thirteen were out-of-scope and removed; remaining 1685 were then consolidated to form 147 summary questions. Following literature search and discussion with the steering group, 37 questions remained for the second survey, which 235 people responded. The top ten priorities agreed upon in the workshop covered themes of improved understanding of pathophysiologlogy, improving health services, and managing long-term effects of smell/taste disorders. The most important research question agreed was "How can we further our understanding of the mechanism of disease in the nerve pathways that affect smell and taste disorders, including where parosmia and phantosmia exist." CONCLUSION: We report the top 10 research priorities in smell and taste disorders. These priorities will now empower researchers to secure research funding and provide the basis of the FifthSense research hub.

Cholesteatoma and family history: An international survey.

OBJECTIVE: To explore the relative frequency of a family history of cholesteatoma in patients with known cholesteatoma, and whether bilateral disease or earlier diagnosis is more likely in those with a family history. Associations between cleft lip or palate and bilateral disease and age of diagnosis were also explored. DESIGN: An online survey of patients with diagnosed cholesteatoma was conducted between October 2017 and April 2019. PARTICIPANTS: The sample consisted of patients recruited from two UK clinics and self-selected respondents recruited internationally via social media. MAIN OUTCOME MEASURES: Side of cholesteatoma, whether respondents had any family history of cholesteatoma, age of diagnosis and personal or family history of cleft lip or palate were recorded. RESULTS: Of 857 respondents, 89 (10.4%) reported a positive family history of cholesteatoma. Respondents with a family history of cholesteatoma were more likely to have bilateral cholesteatoma (P = .001, odds ratio (OR) 2.15, 95% confidence interval (CI) 1.35-3.43), but there was no difference in the age of diagnosis (P = .23). Those with a history of cleft lip or palate were not more likely to have bilateral disease (P = .051, OR 2.71, CI 1.00-7.38), and there was no difference in age of diagnosis (P = .11). CONCLUSION: The relatively high proportion of respondents that reported a family history of cholesteatoma offers supporting evidence of heritability in cholesteatoma. The use of social media to recruit respondents to this survey means that the results cannot be generalised to other populations with cholesteatoma. Further population-based research is suggested to determine the heritability of cholesteatoma.

How do medical students want to learn ENT? Perspectives from a consensus forum.

OBJECTIVE: The UK Medical Licensing Assessment curriculum represents a consensus on core content, including ENT-related content for newly qualified doctors. No similar consensus exists as to how ENT content should be taught at medical school. METHOD: A virtual consensus forum was held at the 2nd East of England ENT Conference in April 2021. A syllabus of ENT-related items was divided into 'Presentations', 'Conditions' and 'Practical procedures'. Twenty-seven students, 11 foundation doctors and 7 other junior doctors voted via anonymous polling for the best three of nine methods for teaching each syllabus item. RESULTS: For 'Presentations' and 'Conditions', work-based or clinical-based learning and small-group seminars were more popular than other teaching methods. For 'Practical procedures', practical teaching methods were more popular than theoretical methods. CONCLUSION: Students and junior doctors expressed a clear preference for clinical-based teaching and small-group seminars when learning ENT content. E-learning was poorly favoured despite its increasing use.

Outpatient antibiotic prescribing for acute respiratory infections in Vietnamese primary care settings by the WHO AWaRe (Access, Watch and Reserve) classification: An analysis using routinely collected electronic prescription data.

Background: This study aims to investigate patterns of antibiotic prescribing and to determine patient-specific factors associated with the choice of antibiotics by the World Health Organization's Access-Watch-Reserve (WHO AWaRe) class for acute respiratory infections (ARIs) in rural primary care settings in northern Vietnam. Methods: We retrospectively reviewed health records for outpatients who were registered with the Vietnamese Health Insurance Scheme, visited one of 112 commune health centres in 6 rural districts of Nam Dinh province, Vietnam during 2019, and were diagnosed with ARIs. Patient-level prescription data were collected from the electronic patient databases. We used descriptive statistics to investigate patterns of antibiotic prescribing, with the primary outcomes including total antibiotic prescriptions and prescriptions by WHO AWaRe group. We identified patient-specific factors associated with watch-group antibiotic prescribing through multivariable logistic regression analysis. Findings: Among 193,010 outpatient visits for ARIs observed in this study, 187,144 (97.0%) resulted in an antibiotic prescription, of which 172,976 (92.5%) were access-antibiotics, 10,765 (5.6%) were watch-antibiotics, 3366 (1.8%) were not-recommended antibiotics. No patients were treated with reserve-antibiotics. The proportion of watch-antibiotic prescription was highest amongst children under 5-years old (18.1%, compared to 9.5% for 5-17-years, 4.9% for 18-49-years, 4.3% for 50-64-years, and 3.7% for 65-and-above-years). In multivariable logistic regression, children, district, ARI-type, comobid chronic respiratory illness, and follow-up visit were associated with higher likelihood of prescribing watch-group antibiotics. Interpretation: The alarmingly high proportion of antibiotic prescriptions for ARIs in primary care, and the frequent use of watch-antibiotics for children, heighten concerns around antibiotic overuse at the community level. Antimicrobial stewardship interventions and policy attention are needed in primary care settings to tackle the growing threat of antibiotic resistance. Funding: This work was supported through Australian government and UK aid from the UK government funding to FIND (Foundation for Innovative New Diagnostics) grant number FO17-0015, in addition to a Wellcome Trust grant (213920/Z/18/Z), and an Oxford University Clinical Research Unit internal grant from the Wellcome Trust Africa Asia Programme core grant in Vietnam (106680/Z/14/Z).

Digital health: a neglected part of health curricula?

With growing government investment and a thriving consumer market, digital technologies are rapidly transforming our means of healthcare delivery. These innovations offer increased diagnostic accuracy, greater accessibility and reduced costs compared with conventional equivalents. Despite these benefits, implementing digital health poses challenges. Recent surveys of healthcare professionals (HCPs) have revealed marked inequities in digital literacy across the healthcare service, hampering the use of these new technologies in clinical practice. Furthermore, a lack of appropriate training in the associated ethical considerations risks HCPs running into difficulty when it comes to patient rights. In light of this, and with a clear need for dedicated digital health education, we argue that our focus should turn to the foundation setting of any healthcare profession: the undergraduate curriculum.

A systematic review to examine the relationship between objective and patient-reported outcome measures in sinonasal disorders: recommendations for use in research and clinical practice.

BACKGROUND: Common sinonasal disorders include chronic rhinosinusitis (CRS), allergic rhinitis (AR), and a deviated nasal septum (DNS), which often coexist with shared common symptoms including nasal obstruction, olfactory dysfunction, and rhinorrhea. Various objective outcome measures and patient-reported outcome measures (PROMs) are used to assess disease severity; however, there is limited evidence in the literature on the correlation between them. This systematic review aims to examine the relationship between them and provide recommendations. METHODS: A search of MEDLINE and EMBASE identified studies quantifying correlations between objective outcome measures and PROMs for the sinonasal conditions using a narrative synthesis. RESULTS: In total, 59 studies met inclusion criteria. For nasal obstruction, rhinomanometry shows a lack of correlation whereas peak nasal inspiratory flow (PNIF) shows the strongest correlation with PROMs (r > 0.5). The Sniffin' Stick test shows a stronger correlation with PROMs (r > 0.5) than the University of Pennsylvania Smell Identification Test (UPSIT) (r < 0.5). Computed tomography (CT) sinus scores show little evidence of correlation with PROMs and nasal endoscopic ratings (weak correlation, r < 0.5). CONCLUSION: Overall, objective outcome measures and PROMs assessing sinonasal symptoms are poorly correlated, and we recommend that objective outcome measures be used with validated PROMs depending on the setting. PNIF should be used in routine clinical practice for nasal obstruction; rhinomanometry and acoustic rhinometry may be useful in research. The Sniffin' Sticks test is recommended for olfactory dysfunction with UPSIT as an alternative. CT scores should be excluded as a routine CRS outcome measure, and endoscopic scores should be used in combination with PROMs until further research is conducted.

Socioeconomic, comorbidity, lifestyle, and quality of life comparisons between chronic rhinosinusitis phenotypes.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous group of inflammatory sinonasal disorders with key defining symptoms, but traditionally separated into phenotypes by clinical/endoscopic findings. It is not known whether the two phenotypes have differing socioeconomic, comorbidity, and lifestyle differences. This analysis of the Chronic Rhinosinusitis Epidemiology Study (CRES) database sought to analyze any key differences in the socioeconomic variables between those with CRS with nasal polyps (CRSwNPs) and those without nasal polyps (CRSsNPs). We also sought to analyze differences in comorbidities, lifestyle, and quality of life. METHODS: Patients with a confirmed diagnosis of CRS in secondary and tertiary care outpatient settings in the UK were invited to participate in a questionnaire-based case-control study. Variables included demographics, socioeconomic factors, comorbidities, lifestyle factors, and health-related quality of life (HRQoL) (level 3 evidence). RESULTS: A total of 1204 patients' data were analyzed: 553 CRSsNP and 651 CRSwNP participants. The key socioeconomic variables did not demonstrate any notable differences, nor did lifestyle variables other than alcohol consumption being higher in those with CRSwNP (P = .032), but the latter was not significant after adjusting for age and sex. Aside from confirmation of asthma being more common in CRSwNP, it was notable that this group complained less of upper respiratory tract infections (URTIs), and CRSsNP participants showed evidence of worse HRQoL scores in respect of body pain (P = .001). CONCLUSIONS: Patients with CRSwNP experience higher rates of asthma and lower rates of URTIs; patients with CRSsNP have worse body pain scores. Otherwise, there are no demonstrable significant socioeconomic, comorbidity, lifestyle, or quality of life differences between the two phenotypes. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2179-2186, 2021.

Pandoravirus Celtis Illustrates the Microevolution Processes at Work in the Giant Pandoraviridae Genomes.

With genomes of up to 2.7 Mb propagated in µm-long oblong particles and initially predicted to encode more than 2000 proteins, members of the Pandoraviridae family display the most extreme features of the known viral world. The mere existence of such giant viruses raises fundamental questions about their origin and the processes governing their evolution. A previous analysis of six newly available isolates, independently confirmed by a study including three others, established that the Pandoraviridae pan-genome is open, meaning that each new strain exhibits protein-coding genes not previously identified in other family members. With an average increment of about 60 proteins, the gene repertoire shows no sign of reaching a limit and remains largely coding for proteins without recognizable homologs in other viruses or cells (ORFans). To explain these results, we proposed that most new protein-coding genes were created de novo, from pre-existing non-coding regions of the G+C rich pandoravirus genomes. The comparison of the gene content of a new isolate, pandoravirus celtis, closely related (96% identical genome) to the previously described p. quercus is now used to test this hypothesis by studying genomic changes in a microevolution range. Our results confirm that the differences between these two similar gene contents mostly consist of protein-coding genes without known homologs, with statistical signatures close to that of intergenic regions. These newborn proteins are under slight negative selection, perhaps to maintain stable folds and prevent protein aggregation pending the eventual emergence of fitness-increasing functions. Our study also unraveled several insertion events mediated by a transposase of the hAT family, 3 copies of which are found in p. celtis and are presumably active. Members of the Pandoraviridae are presently the first viruses known to encode this type of transposase.

C-reactive protein point of care testing in the management of acute respiratory infections in the Vietnamese primary healthcare setting - a cost benefit analysis.

Aim: We assess the cost-benefit implications of C-reactive protein (CRP) testing in reducing antibiotic prescription for acute respiratory infection in Viet Nam by comparing the incremental costs of CRP testing with the economic costs of antimicrobial resistance averted due to lower antibiotic prescribing. Findings: Patients in the CRP group and the controls incurred similar costs in managing their illness, excluding the costs of the quantitative CRP tests, provided free of charge in the trial context. Assuming a unit cost of $1 per test, the incremental cost of CRP testing was $0.93 per patient. Based on a previous modelling analysis, the 20 percentage point reduction in prescribing observed in the trial implies a societal benefit of $0.82 per patient. With the low levels of adherence to the test results observed in the trial, CRP testing would not be cost-beneficial. The sensitivity analyses showed, however, that with higher adherence to test results their use would be cost-beneficial.

Point-of-care C-reactive protein testing to reduce inappropriate use of antibiotics for non-severe acute respiratory infections in Vietnamese primary health care: a randomised controlled trial.

BACKGROUND: Inappropriate antibiotic use for acute respiratory tract infections is common in primary health care, but distinguishing serious from self-limiting infections is difficult, particularly in low-resource settings. We assessed whether C-reactive protein point-of-care testing can safely reduce antibiotic use in patients with non-severe acute respiratory tract infections in Vietnam. METHOD: We did a multicentre open-label randomised controlled trial in ten primary health-care centres in northern Vietnam. Patients aged 1-65 years with at least one focal and one systemic symptom of acute respiratory tract infection were assigned 1:1 to receive either C-reactive protein point-of-care testing or routine care, following which antibiotic prescribing decisions were made. Patients with severe acute respiratory tract infection were excluded. Enrolled patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone interview was done blind to the intervention. Randomised assignments were concealed from prescribers and patients but not masked as the test result was used to assist treatment decisions. The primary outcome was antibiotic use within 14 days of follow-up. All analyses were prespecified in the protocol and the statistical analysis plan. All analyses were done on the intention-to-treat population and the analysis of the primary endpoint was repeated in the per-protocol population. This trial is registered under number NCT01918579. FINDINGS: Between March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009 adults) were enrolled and randomised. One adult patient withdrew immediately after randomisation. 1017 patients were assigned to receive C-reactive protein point-of-care testing, and 1019 patients were assigned to receive routine care. 115 patients in the C-reactive protein point-of-care group and 72 patients in the routine care group were excluded in the intention-to-treat analysis due to missing primary endpoint. The number of patients who used antibiotics within 14 days was 581 (64%) of 902 patients in the C-reactive protein group versus 738 (78%) of 947 patients in the control group (odds ratio [OR] 0·49, 95% CI 0·40-0·61; p<0·0001). Highly significant differences were seen in both children and adults, with substantial heterogeneity of the intervention effect across the 10 sites (I(2)=84%, 95% CI 66-96). 140 patients in the C-reactive protein group and 137 patients in the routine care group missed the urine test on day 3, 4, or 5. Antibiotic activity in urine on day 3, 4, or 5 was found in 267 (30%) of 877 patients in the C-reactive protein group versus 314 (36%) of 882 patients in the routine treatment group (OR 0·78, 95% CI 0·63-0·95; p=0·015). Time to resolution of symptoms was similar in both groups. Adverse events were rare, with no deaths and a total of 14 hospital admissions (six in the C-reactive protein group and eight in the control group). INTERPRETATION: C-reactive protein point-of-care testing reduced antibiotic use for non-severe acute respiratory tract infection without compromising patients' recovery in primary health care in Vietnam. Health-care providers might have become familiar with the clinical picture of low C-reactive protein, leading to reduction in antibiotic prescribing in both groups, but this would have led to a reduction in observed effect, rather than overestimation. Qualitative analysis is needed to address differences in context in order to implement this strategy to improve rational antibiotic use for patients with acute respiratory infection in low-income and middle-income countries. FUNDING: Wellcome Trust, UK, and Global Antibiotic Resistance Partnership, USA.