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.

Is the early identification and referral of suspected head and neck cancers by community pharmacists feasible? A qualitative interview study exploring the views of patients in North East England.

INTRODUCTION: Head and neck cancer (HNC) is the eighth most common cancer in the United Kingdom. Survival rates improve when the cancer is diagnosed at an early stage, highlighting a key need to identify at-risk patients. This study aimed to explore opportunistic HNC identification and referral by community pharmacists (CPs) using a symptom-based risk assessment calculator, from the perspective of patients with a diagnosis of HNC. METHODS: Purposive sampling was used to recruit patients from the HNC pathway in three large teaching hospitals in Northern England. Qualitative methodology was used to collect data through an iterative series of semistructured telephone interviews. Framework analysis was utilised to identify key themes. RESULTS: Four main themes were constructed through the analytic process: (1) HNC presentation and seeking help; (2) the role of the CP; (3) public perception of HNC and (4) the role of a symptom-based risk calculator. Participants agreed that CPs could play a role in the identification and referral of suspected HNCs, but there were concerns about access as patients frequently only encounter the medicine counter assistant when they visit the pharmacy. HNC symptoms are frequently attributed to common or minor conditions initially and therefore considered not urgent, leading to delays in seeking help. While there is public promotion for some cancers, there is little known about HNC. Early presentation of HNC can be quite variable, therefore raising awareness would help. The use of a symptom-based risk calculator was considered beneficial if it enabled earlier referral and diagnosis. Participants suggested that it would also be useful if the public were made aware of it and could self-assess their symptoms. CONCLUSION: In principle, CPs could play a role in the identification and referral of HNC, but there was uncertainty as to how the intervention would work. Future research is needed to develop an intervention that would facilitate earlier identification and referral of HNC while not disrupting CP work and that would promote HNC and the risk calculator more widely. PATIENT OR PUBLIC CONTRIBUTION: Patient and public involvement and engagement (PPIE) was integrated throughout the project. Initially, the proposal was discussed during a Cancer Head and Neck Group Experience (CHANGE) PPIE meeting. CHANGE was set up to support HNC research in 2018. The group is composed of seven members (four female, three male) with an age range of 50-71 years, who were diagnosed at Sunderland Royal Hospital. A patient representative from the University of Sunderland PPIE group and a trustee of the Northern HNC Charity were recruited as co-applicants. They attended project management group meetings and reviewed patient-facing documentation.

Bucket handle meniscus tears in low-resource settings can be successfully treated with a cost-effective technique.

PURPOSE: In regions of the world where resources can limit medical care (limited-resource settings, LRS), most meniscal tears are often treated with meniscectomy. A simple, low-cost option for meniscal repair has been developed. We sought to evaluate patient reported outcomes (PROMs) and clinical failure rates of bucket handle meniscus tears (BHTs) treated with meniscal repair in a LRS. METHODS: We prospectively enrolled patients over 18 who were treated for BHT with meniscal repair in a LRS. Meniscal repair was primarily accomplished using an outside-in technique. Pre-injury and final follow-up PROMs were recorded. Clinical failure was defined as the need for re-operation or symptoms that prevented the patient from returning to recreational activities or work responsibilities. RESULTS: Nineteen patients with a mean age of 25.4 years were eligible. Two patients sustained a clinical failure (10.5%). At mean follow-up of 40.6 months, there was significant improvement in all PROMs from baseline. Subgroup analysis revealed no significant difference in the failure group compared to the success group in number of knots used, pre-injury Tegner score, number of devices used, suture type, or technique. CONCLUSION: Bucket-handle meniscal tears can be repaired using a low-cost technique resulting in satisfactory healing rates and excellent outcomes.

Quality of life following treatment for T1a glottic cancer with surgery or radiotherapy: outcomes from the Head and Neck 5000 cohort.

OBJECTIVES: To investigate the quality of life in patients treated with either RT or surgery alone for T1a glottic carcinoma. DESIGN: This prospective cohort study aims to assess generic- and disease-specific patient-reported QoL in patients treated with either surgery or RT for T1a glottic carcinoma. SETTINGS: Multicentre, secondary care specialist head and neck units in the UK. PARTICIPANTS: Participants were recruited as part of the multicentre, prospective Head and Neck 5000 cohort between 2011 and 2014. MAIN OUTCOME MEASURES: Baseline demographic data were collected. All participants completed the EORTC QLQ C30 and EORTC QLQ H&N35 questionnaires at baseline, 4 months, 12 months and after 36 months. RESULTS: One hundred and twenty three participants received radiotherapy only (n = 68) or surgery only (n = 55). Overall QoL scores were similar between both groups. The median (IQR) EORTC QLQ C30 summary scores at 12 months were 89.3 (79.1, 95.7) and 92.6 (74.4, 97.9) for the radiotherapy and surgery groups respectively. The equivalent summary scores for the EORTC QLQ H&N35 were 91.9 (83.8, 94.9) and 90.4 (85.5, 94.9). There was a modest difference in some QoL subscales between the groups, but no differences existed beyond 4 months. CONCLUSIONS: Patient-reported QoL is similar following either radiotherapy or surgery for T1a glottic carcinoma. These data support current guidance recommended TLM for this disease.

Survival outcomes for patients with nasopharyngeal carcinoma in non-endemic region in the UK treated with intensity modulated based radiotherapy 65 Gy in 30 fractions ± weekly cisplatin chemotherapy.

Background: Nasopharyngeal carcinoma (NPC) is rare in the UK. The aim of the current study was to investigate survival outcomes for patients with NPC treated with (chemo)radiotherapy using 65 Gy in 30 fractions in a non-endemic region. Materials and methods: All consecutive 62 patients with histology proven non-metastatic nasopharyngeal carcinoma diagnosed between January 2009 to June 2019 were included in this retrospective analysis. Results: Median age was 59 years (range:19-81). The majority of patients had stage III disease (66.1%). Induction chemotherapy was given in 21% of patients and 82.3% of patients received concomitant systemic therapy. All patients were treated with 65 Gy in 30 fractions. There was disease recurrence in 17.4% patients. The 5-year disease-free, disease-specific and overall survival were 81.9%, 79.2% and 76.4%, respectively. On univariate analysis, disease recurrence was associated with N-stage (p = 0.047) and overall stage group (p = 0.023). Conclusion: To the best of authors' knowledge, this is the first report of the use of 65 Gy in 30 fractions of radiotherapy ± weekly cisplatin chemotherapy in NPC in a real-world setting. Our results are comparable to that from other non-endemic regions of the world using different dose fractionation of (chemo)radiotherapy. Future randomised control trials are warranted to compare various dose fractionations in these settings.

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.

Primary transoral robotic surgery +/- adjuvant therapy for oropharyngeal squamous cell carcinoma-A large observational single-centre series from the United Kingdom.

OBJECTIVES: To analyse the oncological outcomes following primary Transoral Robotic Surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC). DESIGN: Observational case series. SETTING: Tertiary centre; first TORS practice to commence in the UK. PARTICIPANTS: All consecutive patients undergoing primary TORS with curative intent, with or without adjuvant treatment. MAIN OUTCOME MEASURES: Descriptive analysis of patient and tumour pathology variables. Survival outcomes: Overall, Disease-Specific, Progression-Free and Locoregional control. RESULTS: The cohort comprised of 120 patients undergoing TORS with minimum 12-month follow-up data and the following characteristics: mean age 58 years, 91 males (76%), 78 tonsil (65%) and 34 base of tongue primaries (28%), 89% HPV-related OPSCC. The surgical pathology revealed 14 (12%) with positive margins, 19 (16%) had close margins <2mm and 31% with extranodal extension. The treatment was as follows: 39 (33%) treated with TORS alone, 50 (42%) received adjuvant radiotherapy and 31 (26%) received adjuvant radiotherapy with chemotherapy. There were 15 recurrences. Estimated survival for all patients at 3 years (95% CI): overall 85% (78-92), disease-specific 90% (85-96), progression-free 86% (79-92) and locoregional control 90% (84-96). The equivalent survival figures for the HPV-related cases alone were as follows: overall 88% (82-94), disease-specific 93% (87-98), progression-free 88% (81-95) and locoregional control 92% (87-98). CONCLUSIONS: Whilst TORS has become a common practice in the management of OPSCC in the UK, these are the first reported oncological outcomes. For selected patients, TORS with or without adjuvant therapy is an appropriate treatment modality.

Molecular phylogeny and evolution of world Tachinidae (Diptera).

We reconstructed phylogenetic relationships within the diverse parasitoid fly family Tachinidae using four nuclear loci (7800 bp) and including an exceptionally large sample of more than 500 taxa from around the world. The position of the earthworm-parasitizing Polleniinae (Calliphoridae s.l.) as sister to Tachinidae is strongly supported. Our analyses recovered each of the four tachinid subfamilies and most recognized tribes, with some important exceptions in the Dexiinae and Tachininae. Most notably, the tachinine tribes Macquartiini and Myiophasiini form a clade sister to all other Tachinidae, and a clade of Palpostomatini is reconstructed as sister to Dexiinae + Phasiinae. Although most nodes are well-supported, relationships within several lineages that appear to have undergone rapid episodes of diversification (basal Dexiinae and Tachininae, Blondeliini) were poorly resolved. Reconstructions of host use evolution are equivocal, but generally support the hypothesis that the ancestral host of tachinids was a beetle and that subsequent host shifts to caterpillars may coincide with accelerated diversification. Evolutionary reconstructions of reproductive strategy using alternative methods were incongruent, however it is most likely that ancestral tachinids possessed unincubated, thick shelled eggs from which incubated eggs evolved repeatedly, potentially expanding available host niches. These results provide a broad foundation for understanding the phylogeny and evolution of this important family of parasitoid insects. We hope it will serve as a framework to be used in concert with morphology and other sources of evidence to revise the higher taxonomic classification of Tachinidae and further explore their evolutionary history and diversification.

Robotic lateral oropharyngectomy following diagnostic tonsillectomy is oncologically safe in patients with high risk human papillomavirus related squamous cell cancer.

PURPOSE: Diagnostic tonsillectomy is rarely an oncologic operation owing to close or positive margins. The standard of care is for further treatment to the primary site, typically with adjuvant radiotherapy. METHODS: 14 patients with close or positive margins following a diagnostic tonsillectomy underwent transoral robotic surgery (TORS) and lateral oropharyngectomy; five patients with the longest follow-up had their excision specimens examined with a step serial sectioning technique (SSS). RESULTS: Conventional histopathological examination of the TORS resection specimens did not demonstrate residual carcinoma in 13 patients, confirmed by examination using SSS in 5 patients. There were no post-operative complications or long-term functional deficit. Seven patients received surgery alone with 100% overall and disease specific survival, respectively (median follow-up 27.5 months; range 5.2-50.4). CONCLUSIONS: This prospective study suggests that TORS lateral oropharyngectomy alone is an oncologically safe treatment when close or positive margins are identified on diagnostic tonsillectomy in HPV-positive SCC.

Explosive radiation or uninformative genes? Origin and early diversification of tachinid flies (Diptera: Tachinidae).

Molecular phylogenetic studies at all taxonomic levels often infer rapid radiation events based on short, poorly resolved internodes. While such rapid episodes of diversification are an important and widespread evolutionary phenomenon, much of this poor phylogenetic resolution may be attributed to the continuing widespread use of "traditional" markers (mitochondrial, ribosomal, and some nuclear protein-coding genes) that are often poorly suited to resolve difficult, higher-level phylogenetic problems. Here we reconstruct phylogenetic relationships among a representative set of taxa of the parasitoid fly family Tachinidae and related outgroups of the superfamily Oestroidea. The Tachinidae are one of the most species rich, yet evolutionarily recent families of Diptera, providing an ideal case study for examining the differential performance of loci in resolving phylogenetic relationships and the benefits of adding more loci to phylogenetic analyses. We assess the phylogenetic utility of nine genes including both traditional genes (e.g., CO1 mtDNA, 28S rDNA) and nuclear protein-coding genes newly developed for phylogenetic analysis. Our phylogenetic findings, based on a limited set of taxa, include: a close relationship between Tachinidae and the calliphorid subfamily Polleninae, monophyly of Tachinidae and the subfamilies Exoristinae and Dexiinae, subfamily groupings of Dexiinae+Phasiinae and Tachininae+Exoristinae, and robust phylogenetic placement of the somewhat enigmatic genera Strongygaster, Euthera, and Ceracia. In contrast to poor resolution and phylogenetic incongruence of "traditional genes," we find that a more selective set of highly informative genes is able to more precisely identify regions of the phylogeny that experienced rapid radiation of lineages, while more accurately depicting their phylogenetic context. Although much expanded taxon sampling is necessary to effectively assess the monophyly of and relationships among major tachinid lineages and their relatives, we show that a small number of well-chosen nuclear protein-coding genes can successfully resolve even difficult phylogenetic problems.

A new Loewia Egger (Diptera: Tachinidae) from Turkey, with taxonomic and nomenclatural remarks on congeners.

The new species Loewia papei sp. nov. from southern Anatolia (Turkey) is described, illustrated and compared with congeners. A brief diagnosis of Loewia Egger is provided and the systematics of the genus are discussed. Loewia nudigena Mesnil, 1972 is fixed as the type species of Fortisia Rondani, 1861 (junior synonym of Loewia). A full list of previously known valid species of Loewia is provided along with information on primary types, type repositories (where known), and type localities. A lectotype is designated for Thrychogena brevifrons Rondani, 1856 (= Loewia brevifrons (Rondani, 1856)).

Novel method to plan and design services. Using software to optimise the head and neck cancer patient's commute to hospital.

Travelling for hospital appointments represents a significant burden to patients. We have developed a computer programme that accurately evaluates patient commutes between their home and treatment hospital in public and private transport. This has been applied to a cohort of Head and Neck Cancer (HNC) patients to plan the locations of satellite hospitals and assess their impact on patients' commutes. Patients diagnosed with HNC were identified from our hospital's database between December 2019 and January 2022. Using Python, commuting distances from patients' postcodes to our tertiary referral hospital were calculated. These commutes incorporated routes along defined roads, traffic data, and were calculated using public and private transport. Patient commutes from their postcodes to four satellite hospitals were also calculated. We identified their closest hospital and compared that journey to the patients' journey to our tertiary centre. We included 709 patients in our analysis. Patients would have a significantly shorter journey distance and time in both public and private transport if satellite hospitals were used for appointments alongside our tertiary centre. Average travel times would reduce by 10 minutes in private and 25 minutes in public transport. Furthermore, 70% of patients required ≥2 forms of public transport to get to our hospital. This would drop to 44.1% of patients if satellite hospitals were included in our service. Our programme would allow the most accessible sites to be identified for establishing outreach clinics at appropriate satellite hospitals, therefore improving patient access to healthcare.