Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Tonsillectomy is regularly performed in adults with acute tonsillitis, but with scarce evidence. A reduction in tonsillectomies has coincided with an increase in acute adult hospitalisation for tonsillitis complications. We aimed to assess the clinical effectiveness and cost-effectiveness of conservative management versus tonsillectomy in patients with recurrent acute tonsillitis. METHODS: This pragmatic multicentre, open-label, randomised controlled trial was conducted in 27 hospitals in the UK. Participants were adults aged 16 years or older who were newly referred to secondary care otolaryngology clinics with recurrent acute tonsillitis. Patients were randomly assigned (1:1) to receive tonsillectomy or conservative management using random permuted blocks of variable length. Stratification by recruiting centre and baseline symptom severity was assessed using the Tonsil Outcome Inventory-14 score (categories defined as mild 0-35, moderate 36-48, or severe 49-70). Participants in the tonsillectomy group received elective surgery to dissect the palatine tonsils within 8 weeks after random assignment and those in the conservative management group received standard non-surgical care during 24 months. The primary outcome was the number of sore throat days collected during 24 months after random assignment, reported once per week with a text message. The primary analysis was done in the intention-to-treat (ITT) population. This study is registered with the ISRCTN registry, 55284102. FINDINGS: Between May 11, 2015, and April 30, 2018, 4165 participants with recurrent acute tonsillitis were assessed for eligibility and 3712 were excluded. 453 eligible participants were randomly assigned (233 in the immediate tonsillectomy group vs 220 in the conservative management group). 429 (95%) patients were included in the primary ITT analysis (224 vs 205). The median age of participants was 23 years (IQR 19-30), with 355 (78%) females and 97 (21%) males. Most participants were White (407 [90%]). Participants in the immediate tonsillectomy group had fewer days of sore throat during 24 months than those in the conservative management group (median 23 days [IQR 11-46] vs 30 days [14-65]). After adjustment for site and baseline severity, the incident rate ratio of total sore throat days in the immediate tonsillectomy group (n=224) compared with the conservative management group (n=205) was 0·53 (95% CI 0·43 to 0·65; <0·0001). 191 adverse events in 90 (39%) of 231 participants were deemed related to tonsillectomy. The most common adverse event was bleeding (54 events in 44 [19%] participants). No deaths occurred during the study. INTERPRETATION: Compared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. FUNDING: National Institute for Health Research.

Screening for silent aspiration in hyperacute stroke: A feasibility study of clinical swallowing examination and cough reflex testing.

BACKGROUND: Silent aspiration (SA) is common post-stroke and associated with increased risk of pneumonia, length of stay and healthcare costs. Clinical swallow examinations (CSEs) are unreliable measures of SA. There is no consensus on the clinical components that best detect SA. Cough reflex testing (CRT) is an alternative/adjunct whose SA detection accuracy also lacks consensus. AIMS: To investigate the feasibility of CSE versus CRT against gold standard flexible endoscopic evaluation of swallowing (FEES) for SA identification and to estimate its prevalence in a hyperacute stroke setting. METHODS & PROCEDURES: A single-arm preliminary, prospective, feasibility study of patients less than 72 h post-stroke, over a 31-day period on a hyperacute stroke unit: the Royal Victoria Infirmary, Newcastle-upon-Tyne, UK. Ethical approval for the study was obtained. The study tested the feasibility and acceptability of introducing CRT and developing a standardized CSE. Consent/assent was obtained for all participants. Patients unfit for study were excluded. OUTCOMES & RESULTS: A total of 62% of patients less than 72 h post-stroke (n = 61) were eligible. A total of 75% of those approached (n = 30) consented. A total of 23 patients completed all tests. The principal barrier was anxiety regarding FEES. Mean test time for CRT = 6 min; CSE = 8 min; FEES = 17 min. Patients rated CRT and FEES on average as moderately uncomfortable. A total of 30% (n = 7) of participants who received FEES presented with SA. CONCLUSIONS & IMPLICATIONS: CRT, CSE and FEES are feasible in 58% of hyperacute stroke patients in this setting. FEES anxiety is the main recruitment barrier and is not always well tolerated. Results support further work to establish optimum methods and differential sensitivity/specificity of CRT and CSE in hyperacute stroke for SA identification. WHAT THIS PAPER ADDS: What is already known on this subject SA significantly increases the risk of pneumonia in the early days post-stroke. CSEs are unreliable for identification of SA risk in this population. CRT is gaining popularity as a potential tool to identify stroke patients at risk of SA, though there are questions regarding the efficacy of the clinical protocol currently being used in the UK. What this study adds to existing knowledge This study demonstrates that it is practical and feasible to carry out a larger scale study in this setting to compare CSE and CRT including a consideration of an approach combining both methods for clinical identification of SA versus FEES. Preliminary findings suggest that CSE may have higher levels of sensitivity than CRT for SA identification. What are the potential or actual clinical implications of this work? The results of this study suggest that further work is needed to establish the optimum methods and differential sensitivity/specificity of clinical tools for SA detection in hyperacute stroke.

The utility of a symptom model to predict the risk of oesophageal cancer.

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

The expense of sending cerebrospinal fluid for analysis on all lumbar punctures in pediatric acute lymphoblastic leukemia patients.

BACKGROUND: Central nervous system (CNS) relapse in pediatric acute lymphoblastic leukemia (ALL) patients is uncommon. The cerebrospinal fluid (CSF) of patients with ALL is routinely sampled at each intrathecal chemotherapy treatment to screen for CNS relapse. The analysis of CSF is both time consuming and resource intensive and must be completed approximately 20 times per patient throughout treatment. Our objective was to examine the expense of routine screening on all CSF samples for CNS relapse in ALL patients, and to identify if CNS relapse can be detected clinically. METHODS: We identified all patients diagnosed with ALL at the Children's Hospital of Eastern Ontario (CHEO) between January 2001 and June 2021. We collected the total number of CSF samples in these patients and the number of CSF samples positive for CNS relapse. An in-depth chart review on the patients who relapsed in the CNS was completed to identify symptoms at relapse. RESULTS: Over the study period, 351 patients were diagnosed with ALL and underwent a total of 6515 lumbar punctures (LPs), each of which examined the CSF. The cost of CSF sample analysis is $14.32 (Canadian dollars [CDN]); thus, the total cost for the study sample was $93,294.80 (CDN). There were 14 CNS relapses and although symptoms including headache, vomiting, and fatigue were common, two patients were asymptomatic at relapse. CONCLUSIONS: Given the marginal cost of routine CSF screening and the lack of specific and sensitive symptoms for CNS relapse, we conclude that the routine practice of sending all CSF samples for analysis of CNS relapse in ALL patients is relatively inexpensive and beneficial.

Improving patient care pathways in otitis externa.

INTRODUCTION: Referrals for otitis externa (OE) have dramatically increased but the reasons for this remain unclear. We aim to characterize management of patients both pre- and post-referral to identify areas of improvement at the primary-secondary care interface. METHODS: Questionnaire study from consultant-led research clinic specifically set up to prospectively analyse OE referrals at a tertiary referral centre for Otolaryngology. RESULTS: Sixty-two patients were included; 63% female, median age 57 years. One was excluded (clinically not OE). Most patients had multiple primary care visits before referral (average 4 GP; 2 practice nurse). Sixty per cent had received oral antibiotics (16% multiple classes). Eighteen per cent had never had ear drops. Thirty-nine per cent were not advised to keep ears dry. Twenty-one per cent had dermatitis; 13% contact allergy, 30% systemic allergy, 5% diabetes. Less than 10% had narrow canals. Thirty-six per cent had active discharge but <7% needed a wick. Approximately 75% appear suitable for community aural care clinics. CONCLUSIONS: OE occurs most commonly in female patients, often with associated risk factors. Patients often consult primary care several times prior to referral. Lifestyle advice and ototopical drops are frequently overlooked; instead, often inappropriately treated with oral antibiotics. Most ears were anatomically normal, and community aural care clinics may have a role in more timely and accessible treatment.

Psychometric Properties of the MDADI-A Preliminary Study of Whether Less is Truly More?

The MD Anderson Dysphagia Inventory (MDADI) is a 20-item dysphagia-specific QOL questionnaire with four subscales: global, emotional, functional, and physical. It is widely used in clinical practice and in research; however, its psychometric properties have been under-researched. We aim to evaluate the organisation of the MDADI subscales and identify any redundant items. The MDADI is a routinely collected outcome measure at two centres in northeast England. Questionnaires completed at three months following treatment were extracted from these existing databases. Factor analysis was carried out with the aim of reducing redundancy among the set of questionnaire items. Cases with missing values were excluded. A total of 196 complete patient questionnaires were used in factor analysis. A one-factor model accounted for around 50% of the total variance in item responses. The top five endorsed items (abbreviated by the questionnaire item keywords: Excluded, Irritate, Esteem, Social, and Why) in this one factor appeared in three (emotional, functional, and physical) of the four supposed MDADI subscales, i.e. global, emotional, functional, and physical. Our results suggest an overlap of three MDADI subscales across the top five endorsed items. The content of the top five questions all appear related to the psychosocial aspects of swallowing. This implies some redundancy of the items in the original subscales of the questionnaire. Using the most endorsed items, it appears feasible to abbreviate the 20-item MDADI questionnaire to a 5-item "MiniDADI" questionnaire, which is likely to have greater utility in routine clinical practice outside of research settings.

Swab-yourself Trial With Economic Monitoring and Testing for Infections Collectively (SYSTEMATIC): Part 1. A Diagnostic Accuracy and Cost-effectiveness Study Comparing Clinician-taken vs Self-taken Rectal and Pharyngeal Samples for the Diagnosis of Gonorrhea and Chlamydia.

BACKGROUND: Urogenital testing misses extragenital Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). Extragenital self-sampling is frequently undertaken despite no robust randomized, controlled trial evidence of efficacy. We compared clinician-taken rectal and pharyngeal samples with self-taken samples for diagnostic accuracy and cost in men who have sex with men (MSM) and in females. METHODS: This was a prospective convenience sample from a UK sexual health clinic. We randomized the order of clinician- and self-taken samples from the pharynx and rectum, plus first catch urine (MSM) and vulvovaginal swabs (females), for NG/CT detection. RESULTS: Of 1793 participants (1284 females, 509 MSM), 116 had NG detected (75 urogenital, 83 rectum, 72 pharynx); 9.4% infected females and 67.3% MSM were urogenital-negative. A total of 276 had CT detected (217 urogenital, 249 rectum, 63 pharynx); 13.1% infected females and 71.8% MSM were urogenital-negative. Sexual history did not identify those with rectal infections. There was no difference in diagnostic accuracy between clinician- and self-taken samples from the rectum or pharynx. Clinicians took swabs more quickly than participants, so costs were lower. However, in asymptomatic people, nonqualified clinicians would oversee self-swabbing making these costs lower. CONCLUSIONS: There was no difference in the diagnostic accuracy of clinician-taken compared with self-taken extragenital samples. Sexual history did not identify those with rectal infections, so individuals should have extragenital clinician- or self-taken samples. Clinician-taken swabs cost less than self-taken swabs; however, in asymptomatic people or those who perform home testing, the costs would be lower than for clinician-taken swabs. CLINICAL TRIALS REGISTRATION: NCT02371109.

Swab-Yourself Trial With Economic Monitoring and Testing for Infections Collectively (SYSTEMATIC): Part 2. A Diagnostic Accuracy and Cost-effectiveness Study Comparing Rectal, Pharyngeal, and Urogenital Samples Analyzed Individually, Versus as a Pooled Specimen, for the Diagnosis of Gonorrhea and Chlamydia.

BACKGROUND: Sexual history does not accurately identify those with extragenital Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT), so universal extragenital sampling is recommended. Nucleic acid amplification tests (NAATs) are expensive. If urogenital, plus rectal and pharyngeal, samples are analyzed, the diagnostic cost is trebled. Pooling samples into 1 NAAT container would cost the same as urogenital samples alone. We compared clinician triple samples analyzed individually with self-taken pooled samples for diagnostic accuracy, and cost, in men who have sex with men (MSM) and females. METHODS: This was a prospective, convenience sample in United Kingdom sexual health clinic. Randomized order of clinician and self-samples from pharynx, rectum, plus first-catch urine (FCU) in MSM and vulvovaginal swabs (VVS) in females, for NG and CT detection. RESULTS: Of 1793 participants (1284 females, 509 MSM), 116 had NG detected (75 urogenital, 83 rectum, 72 pharynx); 276 had CT detected (217 urogenital, 249 rectum, 63 pharynx). There was no difference in sensitivities between clinician triple samples and self-pooled specimens for NG (99.1% and 98.3%), but clinician samples analyzed individually identified 3% more chlamydia infections than pooled (99.3% and 96.0%; P = .027). However, pooled specimens identified more infections than VVS/FCU alone. Pooled specimens missed 2 NG and 11 CT infections, whereas VVS/FCU missed 41 NG and 58 CT infections. Self-taken pooled specimens were the most cost-effective. CONCLUSIONS: FCU/VVS testing alone missed many infections. Self-taken pooled samples were as sensitive as clinician triple samples for identifying NG, but clinician samples analyzed individually identified 3% more CT infections than pooled. The extragenital sampling was achievable at no additional diagnostic cost to the FCU/VVS. CLINICAL TRIALS REGISTRATION: NCT02371109.

Utility of Whole Genome Sequencing in Assessing and Enhancing Partner Notification of Neisseria gonorrhoeae Infection.

BACKGROUND: Gonorrhea is a sexually transmitted infection of global concern. We investigated whole-genome sequencing (WGS) as a tool to measure and enhance partner notification (PN) in gonorrhea management. METHODS: Between May and November 2018, all N. gonorrhoeae isolated from patients attending Leeds Sexual Health, United Kingdom, underwent WGS. Reports listing sequences within 20 single-nucleotide polymorphisms (SNPs) of study isolates within a database containing select isolates from April 1, 2016, to November 15, 2018, were issued to clinicians. The proportion of cases with a potential transmission partner identified by PN was determined from patient and PN data. The WGS reports were reviewed to identify additional cases within 6 SNPs or less and verified for PN concordance. RESULTS: Three hundred eighty isolates from 377 cases were successfully sequenced; 292 had traceable/contactable partners and 69 (18%) had a potential transmission partner identified by PN. Concordant PN and WGS links were identified in 47 partner pairs. Of 308 cases with no transmission partner by PN, 185 (60%) had a case within 6 SNPs or less; examination of these cases' PN data identified 7 partner pairs with previously unrecognized PN link, giving a total of 54 pairs; all had 4 or less SNP differences. The WGS clusters confirmed gaps in partner finding, at individual and group levels. Despite the clinic providing sexual health services to the whole city, 35 cases with multiple partners had no genetically related case, suggesting multiple undiagnosed infections. CONCLUSIONS: Whole-genome sequencing could improve gonorrhea PN and control by identifying new links and clusters with significant gaps in partner finding.

The acid test: Proton pump inhibitors in persistent throat symptoms: A systematic review of systematic reviews.

INTRODUCTION: Proton pump inhibitors (PPIs) have evolved to become a frequent treatment option for patients with persistent throat symptoms. The evidence for their use in this context is, however, conflicting. This review assesses the quality of the published systematic reviews and meta-analyses evaluating PPIs in persistent throat symptoms. METHODS: Following a literature search, systematic review were evaluated using the Reporting of Bias in Systematic Reviews (ROBIS) tool and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Outcome measures were analysed using the "checklist to operationalize measurement characteristics of patient-reported outcome measures." RESULTS: 10 systematic reviews were assessed. All but one were at high risk of bias. No review met the PRISMA checklist criteria. No identified PROM met the checklist requirements for validation. Significant methodological concerns include inappropriate selection of studies for inclusion, poor selection of outcome measures, a lack of appropriate bias assessments and inconsistent reporting of reviews. CONCLUSION: The quality of evidence concerning the role of PPIs in persistent throat symptoms gives serious cause for concern. Collectively, nine studies at high risk of bias have been cited 714 times. Systematic reviews typically attract these high numbers of citations and, if their premises and conclusions do not withstand scrutiny, they are open to widespread misinterpretation, perpetuation of misunderstanding and negative clinical impact.

The immunotherapeutic role of indoleamine 2,3-dioxygenase in head and neck squamous cell carcinoma: A systematic review.

BACKGROUND: Novel cancer immunotherapy seeks to harness the body's own immune system and tip the balance in favour of antitumour activity. The intracellular enzyme indoleamine 2,3-dioxygenase (IDO) is a critical regulator of the tumour microenvironment (TME) via tryptophan metabolism. The potential immunotherapeutic role of IDO in head and neck squamous cell carcinoma (HNSCC) requires further exploration. We aim to assess the evidence on IDO in HNSCC. METHODS: A systematic review of literature and clinical trials databases. RESULTS: We included 40 studies: seven involved cell lines: eight assessed tumour immunohistochemistry: ten measured IDO gene transcription: 15 reported on clinical trials. Increased cell line IDO expression was postulated to adversely affect tumour metabolism and apoptosis. Immunohistochemical IDO expression correlated with worse survival. Gene transcription studies associated IDO with positive PD-L1 and human papillomavirus (HPV) status. Phase I/II clinical trials showed (a) overall response (34%-55%) and disease control rates (62%-70%) for IDO1 inhibitor in combination with a PD-1 inhibitor, (b) similar safety profiles when both are used in combination therapy compared to each as monotherapies and (c) IDO gene expression as a predictive biomarker for response to PD-L1 therapy. CONCLUSIONS: IDO expression is increased in the TME of HNSCC, which correlates with poor prognosis. However, the exact mechanism of IDO-driven immune modulation in the TME is an enigma. Future translational studies should map IDO activity during HNSCC treatment and elucidate its precise role in the TME, such research will underpin the development of clinical trials establishing the efficacy of IDO inhibitors in HNSCC.

Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial.

BACKGROUND: Gonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimicrobial resistance is emerging. The objective of this study was to assess the effectiveness of gentamicin as an alternative to ceftriaxone (both combined with azithromycin) for treatment of gonorrhoea. METHODS: G-ToG was a multicentre, parallel-group, pragmatic, randomised, non-inferiority trial comparing treatment with gentamicin to treatment with ceftriaxone for patients with gonorrhoea. The patients, treating physician, and assessing physician were masked to treatment but the treating nurse was not. The trial took place at 14 sexual health clinics in England. Adults aged 16-70 years were eligible for participation if they had a diagnosis of uncomplicated genital, pharyngeal, or rectal gonorrhoea. Participants were randomly assigned to receive a single intramuscular dose of either gentamicin 240 mg (gentamicin group) or ceftriaxone 500 mg (ceftriaxone group). All participants also received a single 1 g dose of oral azithromycin. Randomisation (1:1) was stratified by clinic and performed using a secure web-based system. The primary outcome was clearance of Neisseria gonorrhoeae at all initially infected sites, defined as a negative nucleic acid amplification test 2 weeks post treatment. Primary outcome analyses included only participants who had follow-up data, irrespective of the baseline visit N gonorrhoeae test result. The margin used to establish non-inferiority was a lower confidence limit of 5% for the risk difference. This trial is registered with ISRCTN, number ISRCTN51783227. FINDINGS: Of 1762 patients assessed, we enrolled 720 participants between Oct 7, 2014, and Nov 14, 2016, and randomly assigned 358 to gentamicin and 362 to ceftriaxone. Primary outcome data were available for 306 (85%) of 362 participants allocated to ceftriaxone and 292 (82%) of 358 participants allocated to gentamicin. At 2 weeks after treatment, infection had cleared for 299 (98%) of 306 participants in the ceftriaxone group compared with 267 (91%) of 292 participants in the gentamicin group (adjusted risk difference -6·4%, 95% CI -10·4% to -2·4%). Of the 328 participants who had a genital infection, 151 (98%) of 154 in the ceftriaxone group and 163 (94%) of 174 in the gentamicin group had clearance at follow-up (adjusted risk difference -4·4%, -8·7 to 0). For participants with a pharyngeal infection, a greater proportion receiving ceftriaxone had clearance at follow-up (108 [96%] in the ceftriaxone group compared with 82 [80%] in the gentamicin group; adjusted risk difference -15·3%, -24·0 to -6·5). Similarly, a greater proportion of participants with rectal infection in the ceftriaxone group had clearance (134 [98%] in the ceftriaxone group compared with 107 [90%] in the gentamicin group; adjusted risk difference -7·8%, -13·6 to -2·0). Thus, we did not find that a single dose of gentamicin 240 mg was non-inferior to a single dose of ceftriaxone 500 mg for the treatment of gonorrhoea, when both drugs were combined with a 1 g dose of oral azithromycin. The side-effect profiles were similar between groups, although severity of pain at the injection site was higher for gentamicin (mean visual analogue pain score 36 of 100 in the gentamicin group vs 21 of 100 in the ceftriaxone group). INTERPRETATION: Gentamicin is not appropriate as first-line treatment for gonorrhoea but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbour a ceftriaxone-resistant isolate. Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhoea. FUNDING: UK National Institute for Health Research.

Evaluating a young-onset dementia service from two sides of the coin: staff and service user perspectives.

BACKGROUND: People with young-onset dementia (YOD) can often struggle getting the right treatment. This is because of their frequently different characteristics and needs compared to people with late-onset dementia. The aim of this project was to assess a memory service for its adaptation to the needs and wishes of people with YOD and their carers. METHODS: This project evaluated a memory service in the North West of England by performing two focus groups with clinical staff and six semi-structured interviews with people with YOD and carers. The focus groups took place on site and lasted one hour each. People with YOD and their carers were identified via the memory clinics caseload and via the local Alzheimer's Society charity organisation. Both focus groups and interviews were audio-recorded and transcribed, and data were analysed using thematic analysis. The public (a person living with YOD and his carer) were involved from the design stages of the project through to the analysis and dissemination. RESULTS: Eleven members of staff with different clinical backgrounds participated in the focus groups and six interviews were held with people with YOD and their carers. Both indicated that whilst the diagnostic process is relatively well conducted at the service, the post-diagnostic service has many gaps. These include limited post-diagnostic support by the service, better enabling peer support, as well as providing meaningful activities, as some activities provided might be more suitable to older adults with dementia. CONCLUSIONS: Post-diagnostic services and support for people with YOD and their carers need to be improved. The next step will be to implement the findings from this service evaluation in practice and improve service satisfaction and relevance to people with YOD.

Just Google it! Impact of media coverage of an outbreak of high-level azithromycin-resistant Neisseria gonorrhoeae on online searches, and attendances, testing and diagnoses at sexual health clinics in England between 2015 and 2016: an interrupted time series analysis using surveillance data.

OBJECTIVES: To determine if media coverage of an outbreak of high-level azithromycin-resistant Neisseria gonorrhoeae (HL-AziR) impacted online search interest or was temporally associated with health-seeking behaviours in several English cities. METHODS: A descriptive analysis of outbreak-related online media articles and relative search interest (RSI) using Google and an interrupted time series analysis using routine surveillance data from sexual health clinics (SHCs) in England (GUMCAD STI surveillance system). The main outcomes were adjusted incidence rate ratios (IRRs) of weekly attendances, gonorrhoea tests and diagnoses of gonorrhoea or 'any STI' in selected cities after media coverage of the outbreak in 2015 and 2016. RESULTS: RSI for outbreak-related terms peaked during media coverage in September 2015 with smaller peaks coinciding with subsequent coverage. The greatest increase in RSI was in Leeds, which coincided with a 63% rise (n=1932; IRR 1.26, 95% CI 1.12 to 1.43) in SHC attendances by women. There was only a 7% (n=1358; IRR 1.01, 95% CI 0.91 to 1.11) increase in attendances by men. Modest increases in outcomes occurred in four other cities with a high RSI. There was no evidence of increases in outcomes in cities, other than Leeds, after subsequent media coverage of the outbreak. CONCLUSIONS: National and local media coverage of the HL-AziR outbreak coincided with peak RSI for related terms, and a transient increase in attendances, gonorrhoea tests and diagnoses of gonorrhoea or 'any STI' in some cities with a high RSI. Our analysis demonstrates the potential for media coverage to influence health-seeking behaviours during high-profile STI outbreaks.

Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family.

The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease.

Excess Mucin Impairs Subglottic Epithelial Host Defense in Mechanically Ventilated Patients.

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

Is Scottish Intercollegiate Guidelines Network guidance for GP management of tonsillitis suitable? A qualitative study.

Background: The Scottish Intercollegiate Guidelines Network (SIGN) developed guidelines for the management of sore throat and indications for tonsillectomy in 1999 to address concerns of unnecessary surgery. Emergency admissions to hospital for tonsillitis have since increased. Adults experience an average of 27 episodes of tonsillitis before undergoing tonsillectomy. We wished to explore the appropriateness of the guidance and/or its implementation in primary care. Aim: To explore the attitudes of GPs to the referral criteria they use when managing adults presenting with acute tonsillitis. Design: Secondary analysis of qualitative data from the NAtional Trial of Tonsillectomy IN Adults (NATTINA) feasibility and process evaluation. Participants and Setting: Twenty-one GPs from practices throughout the UK. Method: In-depth interviews with GPs concerning both the feasibility and process evaluation phases of NATTINA. Analysis was conducted using the framework method. Results: GPs felt it was rarely necessary to refer patients. They were aware of guidelines and would refer if requested by a patient who fulfilled the guidelines criteria and/or who were missing considerable amounts of work. Conclusion: The introduction of the guidelines appears to coincide with what some may have hoped to be a desired effect of reducing adult sore throat referrals and subsequent tonsillectomies by increasing the number of episodes a patient must suffer before the referral threshold is met. GPs may find equipoise for tonsillectomy referral challenging as many patients express a strong preference for surgery. We believe this paper reinforces GP professionalism and patient-centred consultations, and challenges the role of clinical guidelines.

Inducible laryngeal obstruction: an official joint European Respiratory Society and European Laryngological Society statement.

Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenclature and variable approaches to assessment and management. A task force of the European Respiratory Society (ERS) and European Laryngological Society (ELS) was thus set up to address this, and to identify research priorities.A literature search identified relevant articles published until June 2016, using all identifiable terms for ILO, although including only articles using laryngoscopy. In total, 172 out of 252 articles met the inclusion criteria, summarised in sections on diagnostic approach, aetiology, comorbidities, epidemiology and treatment. The consensus taxonomy published by ERS, ELS and the American College of Chest Physicians (ACCP) in 2015 is used throughout this statement.We highlight the high prevalence of ILO and the clinical impact for those affected. Despite recent advances, most aspects of this condition unfortunately remain incompletely understood, precluding firm guidance. Specifically, validated diagnostic and treatment algorithms are yet to be established, and no randomised control studies were identified in this search; hence we also make recommendations for future research.