Tonsillectomy versus tonsillotomy for obstructive sleep-disordered breathing in children.

BACKGROUND: Obstructive sleep-disordered breathing (oSDB) is a condition encompassing breathing problems when asleep due to upper airway obstruction. In children, hypertrophy of the tonsils and/or adenoids is thought to be the commonest cause. As such, (adeno)tonsillectomy has long been the treatment of choice. A rise in partial removal of the tonsils over the last decade is due to the hypothesis that tonsillotomy is associated with lower postoperative morbidity and fewer complications. OBJECTIVES: To assess whether partial removal of the tonsils (intracapsular tonsillotomy) is as effective as total removal of the tonsils (extracapsular tonsillectomy) in relieving signs and symptoms of oSDB in children, and has lower postoperative morbidity and fewer complications. SEARCH METHODS: We searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 22 July 2019. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effectiveness of (adeno)tonsillectomy with (adeno)tonsillotomy in children aged 2 to 16 years with oSDB. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and assessed the certainty of the evidence for our pre-defined outcomes using GRADE. Our primary outcomes were disease-specific quality of life, peri-operative blood loss and the proportion of children requiring postoperative medical intervention (with or without hospitalisation). Secondary outcomes included postoperative pain, return to normal activity, recurrence of oSDB symptoms as a result of tonsil regrowth and reoperation rates. MAIN RESULTS: We included 22 studies (1984 children), with predominantly unclear or high risk of bias. Three studies used polysomnography as part of their inclusion criteria. Follow-up duration ranged from six days to six years. Although 19 studies reported on some of our outcomes, we could only pool the results from a few due both to the variety of outcomes and the measurement instruments used, and an absence of combinable data. Disease-specific quality of life Four studies (540 children; 484 (90%) analysed) reported this outcome; data could not be pooled due to the different outcome measurement instruments used. It is very uncertain whether there is any difference in disease-specific quality of life between the two surgical procedures in the short (0 to 6 months; 3 studies, 410 children), medium (7 to 13 months; 2 studies, 117 children) and long term (13 to 24 months; 1 study, 67 children) (very low-certainty evidence). Peri-operative blood loss We are uncertain whether tonsillotomy reduces peri-operative blood loss by a clinically meaningful amount (mean difference (MD) 14.06 mL, 95% CI 1.91 to 26.21 mL; 8 studies, 610 children; very low-certainty evidence). In sensitivity analysis (restricted to three studies with low risk of bias) there was no evidence of a difference between the groups. Postoperative complications requiring medical intervention (with or without hospitalisation) The risk of postoperative complications in the first week after surgery was probably lower in children who underwent tonsillotomy (4.9% versus 2.6%, risk ratio (RR) 1.75, 95% CI 1.06 to 2.91; 16 studies, 1416 children; moderate-certainty evidence). Postoperative pain Eleven studies (1017 children) reported this outcome. Pain was measured using various scales and scored by either children, parents, clinicians or study personnel. When considering postoperative pain there was little or no difference between tonsillectomy and tonsillotomy at 24 hours (10-point scale) (MD 1.09, 95% CI 0.88 to 1.29; 4 studies, 368 children); at two to three days (MD 0.93, 95% CI -0.14 to 2.00; 3 studies, 301 children); or at four to seven days (MD 1.07, 95% CI -0.40 to 2.53; 4 studies, 370 children) (all very low-certainty evidence). In sensitivity analysis (restricted to studies with low risk of bias), we found no evidence of a difference in mean pain scores between groups. Return to normal activity Tonsillotomy probably results in a faster return to normal activity. Children who underwent tonsillotomy were able to return to normal activity four days earlier (MD 3.84 days, 95% CI 0.23 to 7.44; 3 studies, 248 children; moderate-certainty evidence). Recurrence of oSDB and reoperation rates We are uncertain whether there is a difference between the groups in the short (RR 0.26, 95% CI 0.03 to 2.22; 3 studies, 186 children), medium (RR 0.35, 95% CI 0.04 to 3.23; 4 studies, 206 children) or long term (RR 0.21 95% CI 0.01 to 4.13; 1 study, 65 children) (all very low-certainty evidence). AUTHORS' CONCLUSIONS: For children with oSDB selected for tonsil surgery, tonsillotomy probably results in a faster return to normal activity (four days) and in a slight reduction in postoperative complications requiring medical intervention in the first week after surgery. This should be balanced against the clinical effectiveness of one operation over the other. However, this is not possible to determine in this review as data on the long-term effects of the two operations on oSDB symptoms, quality of life, oSDB recurrence and need for reoperation are limited and the evidence is of very low quality leading to a high degree of uncertainty about the results. More robust data from high-quality cohort studies, which may be more appropriate for detecting differences in less common events in the long term, are required to inform guidance on which tonsil surgery technique is best for children with oSDB requiring surgery.

Tonsillectomy or adenotonsillectomy versus non-surgical management for obstructive sleep-disordered breathing in children.

BACKGROUND: Obstructive sleep-disordered breathing (oSDB) is a condition that encompasses breathing problems when asleep, due to an obstruction of the upper airways, ranging in severity from simple snoring to obstructive sleep apnoea syndrome (OSAS). It affects both children and adults. In children, hypertrophy of the tonsils and adenoid tissue is thought to be the commonest cause of oSDB. As such, tonsillectomy - with or without adenoidectomy - is considered an appropriate first-line treatment for most cases of paediatric oSDB. OBJECTIVES: To assess the benefits and harms of tonsillectomy with or without adenoidectomy compared with non-surgical management of children with oSDB. SEARCH METHODS: We searched the Cochrane Register of Studies Online, PubMed, EMBASE, CINAHL, Web of Science, Clinicaltrials.gov, ICTRP and additional sources for published and unpublished trials. The date of the search was 5 March 2015. SELECTION CRITERIA: Randomised controlled trials comparing the effectiveness and safety of (adeno)tonsillectomy with non-surgical management in children with oSDB aged 2 to 16 years. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Three trials (562 children) met our inclusion criteria. Two were at moderate to high risk of bias and one at low risk of bias. We did not pool the results because of substantial clinical heterogeneity. They evaluated three different groups of children: those diagnosed with mild to moderate OSAS by polysomnography (PSG) (453 children aged five to nine years; low risk of bias; CHAT trial), those with a clinical diagnosis of oSDB but with negative PSG recordings (29 children aged two to 14 years; moderate to high risk of bias; Goldstein) and children with Down syndrome or mucopolysaccharidosis (MPS) diagnosed with mild to moderate OSAS by PSG (80 children aged six to 12 years; moderate to high risk of bias; Sudarsan). Moreover, the trials included two different comparisons: adenotonsillectomy versus no surgery (CHAT trial and Goldstein) or versus continuous positive airway pressure (CPAP) (Sudarsan). Disease-specific quality of life and/or symptom score (using a validated instrument): first primary outcomeIn the largest trial with lowest risk of bias (CHAT trial), at seven months, mean scores for those instruments measuring disease-specific quality of life and/or symptoms were lower (that is, better quality of life or fewer symptoms) in children receiving adenotonsillectomy than in those managed by watchful waiting:- OSA-18 questionnaire (scale 18 to 126): 31.8 versus 49.5 (mean difference (MD) -17.7, 95% confidence interval (CI) -21.2 to -14.2);- PSQ-SRBD questionnaire (scale 0 to 1): 0.2 versus 0.5 (MD -0.3, 95% CI -0.31 to -0.26);- Modified Epworth Sleepiness Scale (scale 0 to 24): 5.1 versus 7.1 (MD -2.0, 95% CI -2.9 to -1.1).No data on this primary outcome were reported in the Goldstein trial.In the Sudarsan trial, the mean OSA-18 score at 12 months did not significantly differ between the adenotonsillectomy and CPAP groups. The mean modified Epworth Sleepiness Scale scores did not differ at six months, but were lower in the surgery group at 12 months: 5.5 versus 7.9 (MD -2.4, 95% CI -3.1 to -1.7). Adverse events: second primary outcomeIn the CHAT trial, 15 children experienced a serious adverse event: 6/194 (3%) in the adenotonsillectomy group and 9/203 (4%) in the control group (RD -1%, 95% CI -5% to 2%).No major complications were reported in the Goldstein trial.In the Sudarsan trial, 2/37 (5%) developed a secondary haemorrhage after adenotonsillectomy, while 1/36 (3%) developed a rash on the nasal dorsum secondary to the CPAP mask (RD -3%, 95% CI -6% to 12%). Secondary outcomesIn the CHAT trial, at seven months, mean scores for generic caregiver-rated quality of life were higher in children receiving adenotonsillectomy than in those managed by watchful waiting. No data on this outcome were reported by Sudarsan and Goldstein.In the CHAT trial, at seven months, more children in the surgery group had normalisation of respiratory events during sleep as measured by PSG than those allocated to watchful waiting: 153/194 (79%) versus 93/203 (46%) (RD 33%, 95% CI 24% to 42%). In the Goldstein trial, at six months, PSG recordings were similar between groups and in the Sudarsan trial resolution of OSAS (Apnoea/Hypopnoea Index score below 1) did not significantly differ between the adenotonsillectomy and CPAP groups.In the CHAT trial, at seven months, neurocognitive performance and attention and executive function had not improved with surgery: scores were similar in both groups. In the CHAT trial, at seven months, mean scores for caregiver-reported ratings of behaviour were lower (that is, better behaviour) in children receiving adenotonsillectomy than in those managed by watchful waiting, however, teacher-reported ratings of behaviour did not significantly differ.No data on these outcomes were reported by Goldstein and Sudarsan. AUTHORS' CONCLUSIONS: In otherwise healthy children, without a syndrome, of older age (five to nine years), and diagnosed with mild to moderate OSAS by PSG, there is moderate quality evidence that adenotonsillectomy provides benefit in terms of quality of life, symptoms and behaviour as rated by caregivers and high quality evidence that this procedure is beneficial in terms of PSG parameters. At the same time, high quality evidence indicates no benefit in terms of objective measures of attention and neurocognitive performance compared with watchful waiting. Furthermore, PSG recordings of almost half of the children managed non-surgically had normalised by seven months, indicating that physicians and parents should carefully weigh the benefits and risks of adenotonsillectomy against watchful waiting in these children. This is a condition that may recover spontaneously over time.For non-syndromic children classified as having oSDB on purely clinical grounds but with negative PSG recordings, the evidence on the effects of adenotonsillectomy is of very low quality and is inconclusive.Low-quality evidence suggests that adenotonsillectomy and CPAP may be equally effective in children with Down syndrome or MPS diagnosed with mild to moderate OSAS by PSG.We are unable to present data on the benefits of adenotonsillectomy in children with oSDB aged under five, despite this being a population in whom this procedure is often performed for this purpose.

A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss.

Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met.

Observational retrospective study calculating health service costs of patients receiving surgery for chronic rhinosinusitis in England, using linked patient-level primary and secondary care electronic data.

OBJECTIVES: Chronic rhinosinusitis (CRS) symptoms are experienced by an estimated 11% of UK adults, and symptoms have major impacts on quality of life. Data from UK and elsewhere suggest high economic burden of CRS, but detailed cost information and economic analyses regarding surgical pathway are lacking. This paper estimates healthcare costs for patients receiving surgery for CRS in England. DESIGN: Observational retrospective study examining cost of healthcare of patients receiving CRS surgery. SETTING: Linked electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England. PARTICIPANTS: A phenotyping algorithm using medical ontology terms identified 'definite' CRS cases who received CRS surgery. Patients were registered with a general practice in England. Data covered the period 1997-2016. A cohort of 13 462 patients had received surgery for CRS, with 9056 (67%) having confirmed nasal polyps. OUTCOME MEASURES: Information was extracted on numbers and types of primary care prescriptions and consultations, and inpatient and outpatient hospital investigations and procedures. Resource use was costed using published sources. RESULTS: Total National Health Service costs in CRS surgery patients were £2173 over 1 year including surgery. Total costs per person-quarter were £1983 in the quarter containing surgery, mostly comprising surgical inpatient care costs (£1902), and around £60 per person-quarter in the 2 years before and after surgery, of which half were outpatient costs. Outpatient and primary care costs were low compared with the peak in inpatient costs at surgery. The highest outpatient expenditure was on CT scans, peaking in the quarter preceding surgery. CONCLUSIONS: We present the first study of costs to the English healthcare system for patients receiving surgery for CRS. The total aggregate costs provide a further impetus for trials to evaluate the relative benefit of surgical intervention.

Maximising recruitment to a randomised controlled trial for chronic rhinosinusitis using qualitative research methods: the MACRO conversation study.

BACKGROUND: Randomised controlled trials (RCTs) are considered the 'gold standard' of medical evidence; however, recruitment can be challenging. The MACRO trial is a NIHR-funded RCT for chronic rhinosinusitis (CRS) addressing the challenge of comparing surgery, antibiotics and placebo. The embedded MACRO conversation study (MCS) used qualitative research techniques pioneered by the University of Bristol QuinteT team to explore recruitment issues during the pilot phase, to maximise recruitment in the main trial. METHODS: Setting: Five outpatient Ear Nose and Throat (ENT) departments recruiting for the pilot phase of the MACRO trial (ISRCTN Number: 36962030, prospectively registered 17 October 2018). We conducted a thematic analysis of telephone interviews with 18 recruiters and 19 patients and 61 audio-recordings of recruitment conversations. We reviewed screening and recruitment data and mapped patient pathways at participating sites. We presented preliminary findings to individual site teams. Group discussions enabled further exploration of issues, evolving strategies and potential solutions. Findings were reported back to the funder and used together with recruitment data to justify progression to the main trial. RESULTS: Recruitment in the MACRO pilot trial began slowly but accelerated in time to progress successfully to the main trial. Research nurse involvement was pivotal to successful recruitment. Engaging the wider network of clinical colleagues emerged as an important factor, ensuring the patient pathway through primary and secondary care did not inadvertently affect trial eligibility. The most common reason for patients declining participation was treatment preference. Good patient-clinician relationships engendered trust and supported patient decision-making. Overall, trial involvement appeared clearly presented by recruiters, possibly influenced by pre-trial training. The weakest area of understanding for patients appeared to be trial medications. A clear presentation of medical and surgical treatment options, together with checking patient understanding, had the potential to allay patient concerns. CONCLUSION: The MACRO conversation study contributed to the learning process of optimising recruitment by helping to identify and address recruitment issues. Although some issues were trial-specific, others have applicability to many clinical trial situations. Using qualitative research techniques to identify/explore barriers and facilitators to recruitment may be valuable during the pilot phase of many RCTs including those with complex designs.

Prognostic factors for outcomes of idiopathic sudden sensorineural hearing loss: protocol for the SeaSHeL national prospective cohort study.

INTRODUCTION: The mainstay of treatment for idiopathic sudden sensorineural hearing loss (SSNHL) includes oral steroids, intratympanic steroid injections or a combination of both. The National Institute for Health and Care Excellence, in their recent hearing loss guidelines, highlighted the paucity of evidence assessing the comparative effectiveness of these treatments; and the National Institute for Health Research (NIHR) Health Technology Assessment Programme has since released a commissioned call for a trial to identify the most effective route of administration of steroids as a first-line treatment for idiopathic SSNHL. For such trials to be run effectively, reliable information is needed on patients with SSNHL: where they present, numbers, demographics, treatment pathways, as well as outcomes. This study will collect these data in a nationwide cohort study of patients presenting with SSNHL across 97 National Health Service (NHS) trusts. The study will be delivered through ear, nose and throat (ENT) trainee networks, the NIHR Clinical Research Network (CRN) Audiology Champions and the NIHR CRN. Importantly, this study will also provide a dataset to develop a prognostic model to predict recovery for patients with idiopathic SSNHL. The study objectives are to: (1) map the patient pathway and identify the characteristics of adult patients presenting to NHS ENT and hearing services with SSNHL, (2) develop a prognostic model to predict recovery for patients with idiopathic SSNHL and (3) establish the impact of idiopathic SSNHL on patients' quality of life (QoL). METHODS AND ANALYSIS: Study design: national multicentre prospective cohort study across 97 NHS trusts. INCLUSION CRITERIA: adult patients presenting to NHS ENT and hearing services with SSNHL. OUTCOMES: change in auditory function; change in QoL score. ANALYSIS: multivariable prognostic model, using prespecified candidate predictors. Mean change in QoL scores will be calculated from initial presentation to follow-up. ETHICS AND DISSEMINATION: Health Research Authority and NHS Research Ethics Committee approved the study. Publication will be on behalf of study sites and collaborators. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04108598).

Voice Outcome Measures for Adult Patients With Unilateral Vocal Fold Paralysis: A Systematic Review.

OBJECTIVES: Unilateral vocal fold paralysis (UVFP) typically results in marked changes in voice quality and performance and has a significant impact on quality of life. Treatment approaches generally aim to restore glottal closure for phonation and improve vocal function. There are a wide range of voice outcome measures that are available to measure the treatment effect. Careful selection of voice outcome measures is required to ensure that they are adequate for purpose and are psychometrically sound to detect the treatment effect. This article aims to critically evaluate the literature for voice outcome measures that are used for patients with UVFP. STUDY DESIGN: Systematic review. METHODS: Nine databases were searched for UVFP treatment studies published since 2003 (n = 2,484 articles). These articles and their references were screened using inclusion/exclusion criteria, including population characteristics, treatment, voice outcomes, and study findings. Data from the included articles was extracted and appraised with respect to multidimensionality, timing, selection rationale, validity, reliability, and responsiveness to change of the voice outcome measures. RESULTS: A total of 29 studies met the inclusion criteria for the systematic review. These studies showed considerable variability in the rationale, selection, and application of voice outcome measures for reporting the treatment effect for patients with UVFP. CONCLUSION: There is currently a significant disparity in the selection and use of voice outcome measures for patients with UVFP. A set of principles around selection rationale, validity, reliability, and responsiveness to change is proposed to enhance the judicious selection of voice outcome measures for this patient group. Laryngoscope, 129:187-197, 2019.

Local Delivery of Therapeutics to the Inner Ear: The State of the Science.

Background: Advances in the understanding of the genetic and molecular etiologies of inner ear disorders have enabled the identification of therapeutic targets and innovative delivery approaches to the inner ear. As this field grows, the need for knowledge about effective delivery of therapeutics to the inner ear has become a priority. This review maps all clinical and pre-clinical research published in English in the field to date, to guide both researchers and clinicians about local drug delivery methods in the context of novel therapeutics. Methods: A systematic search was conducted using customized strategies in Cochrane, pubmed and EMBASE databases from inception to 30/09/2018. Two researchers undertook study selection and data extraction independently. Results: Our search returned 12,200 articles, of which 837 articles met the inclusion criteria. 679 were original research and 158 were reviews. There has been a steady increase in the numbers of publications related to inner ear therapeutics delivery over the last three decades, with a sharp rise over the last 2 years. The intra-tympanic route accounts for over 70% of published articles. Less than one third of published research directly assesses delivery efficacy, with most papers using clinical efficacy as a surrogate marker. Conclusion: Research into local therapeutic delivery to the inner ear has undergone a recent surge, improving our understanding of how novel therapeutics can be delivered. Direct assessment of delivery efficacy is challenging, especially in humans, and progress in this area is key to understanding how to make decisions about delivery of novel hearing therapeutics.

Chronic rhinosinusitis: a qualitative study of patient views and experiences of current management in primary and secondary care.

OBJECTIVES: To explore patient views and perspectives of current management of chronic rhinosinusitis (CRS) in primary and secondary care. DESIGN: Semistructured qualitative telephone interviews as part of the MACRO programme (Defining best Management for Adults with Chronic RhinOsinusitis). SETTING: Primary care and secondary care ear, nose and throat outpatient clinics in the UK. PARTICIPANTS: Twenty-five patients consented to in-depth telephone interviews. Transcribed recordings were managed using NVivo software and analysed using inductive thematic analysis. RESULTS: CRS has a significant impact on patients' quality of life, affecting their ability to work effectively, their social interactions and daily living. Patients seek help when symptoms become unmanageable, but can become frustrated with the primary care system with difficulties obtaining an appointment, and lack of continuity of care. Patients perceive that general practitioners can be dismissive of CRS symptoms, and patients often prioritise other concerns when they consult. Health system barriers and poor communication can result in delays in accessing appropriate treatment and referral. Adherence to intranasal steroids is a problem and patients are uncertain about correct technique. Nasal irrigation can be time-consuming and difficult for patients to use. Secondary care consultations can appear rushed, and patients would like specialists to take a more 'holistic' approach to their management. Surgery is often considered a temporary solution, appropriate when medical options have been explored. CONCLUSIONS: Patients are frustrated with the management of their CRS, and poor communication can result in delays in receiving appropriate treatment and timely referral. Patients seek better understanding of their condition and guidance to support treatments decisions in light of uncertainties around the different medical and surgical options. Better coordinated care between general practice and specialist settings and consistency of advice has the potential to increase patient satisfaction and improve outcomes.

Early phase trials of novel hearing therapeutics: Avenues and opportunities.

Novel hearing therapeutics are rapidly progressing along the innovation pathway and into the clinical trial domain. Because these trials are new to the hearing community, they come with challenges in terms of trial design, regulation and delivery. In this paper, we address the key scientific and operational issues and outline the opportunities for interdisciplinary and international collaboration these trials offer. Vital to the future successful implementation of these therapeutics is to evaluate their potential for adoption into healthcare systems, including consideration of their health economic value. This requires early engagement with all stakeholder groups along the hearing innovation pathway.

Hearing Protection, Restoration, and Regeneration: An Overview of Emerging Therapeutics for Inner Ear and Central Hearing Disorders.

OBJECTIVE: To provide an overview of biotechnology and pharmaceutical companies active in the field of inner ear and central hearing disorders and their therapeutic approaches. METHODS: Scientific and grey literature was searched using broad search terms to identify companies and their hearing-related therapeutic approaches. For each approach its lead indication, product, therapeutic modality, target, mechanism of action and current phase of clinical development was collated. RESULTS: A total of 43 biotechnology and pharmaceutical companies have been identified that are developing therapeutics for inner ear and central hearing disorders. Their therapeutics include drug-, cell- and gene-based approaches to prevent hearing loss or its progression, restore hearing, and regenerate the inner ear. Their therapeutic targets and specific mechanisms of action are wide-ranging, reflecting the complexity of the hearing pathways and the diversity of mechanisms underlying inner ear disorders. While none of the novel products under investigation have yet made it to the clinical market, and a large proportion are still at preclinical phase, many therapeutics have already entered clinical testing with more expected to do so in the next few years. CONCLUSION: A wide range of novel therapeutics targeting different hearing, balance and tinnitus pathways, and patient populations are approaching the clinical domain. It is important that clinicians involved in the care of patients with hearing loss prepare for what may become a radically different approach to the management of hearing disorders, and develop a true understanding of the new therapies' mechanisms of action, applications, and indications.

Clarithromycin and endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps: study protocol for the MACRO randomised controlled trial.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common source of ill health; 11% of UK adults reported CRS symptoms in a worldwide population study. Guidelines are conflicting regarding whether antibiotics should be included in primary medical management, reflecting the lack of evidence in systematic reviews. Insufficient evidence to inform the role of surgery contributes to a fivefold variation in UK intervention rates. The objective of this trial is to establish the comparative effectiveness of endoscopic sinus surgery (ESS) or a prolonged course of antibiotics (clarithromycin) in adult patients with CRS in terms of symptomatic improvement and costs to the National Health Service compared with standard medical care (intranasal medication) at 6 months. METHODS/DESIGN: A three-arm parallel-group trial will be conducted with patients who remain symptomatic after receiving appropriate medical therapy (either in primary or secondary care). They will be randomised to receive: (1) intranasal medication plus ESS, (2) intranasal medication plus clarithromycin (250 mg) or (3) intranasal medication plus a placebo. Intranasal medication (current standard medical care) is defined as a spray or drops of intranasal corticosteroids and saline irrigations. The primary outcome measure is the SNOT-22 questionnaire, which assesses disease-specific health-related quality of life. The study sample size is 600. Principal analyses will be according to the randomised groups irrespective of compliance. The trial will be conducted in at least 16 secondary or tertiary care centres with an internal pilot at six sites for 6 months. DISCUSSION: The potential cardiovascular side effects of macrolide antibiotics have been recently highlighted. The effectiveness of antibiotics will be established through this trial, which may help to reduce unnecessary usage and potential morbidity. If ESS is shown to be clinically effective and cost-effective, the trial may encourage earlier intervention. In contrast, if it is shown to be ineffective, then there should be a significant reduction in surgery rates. The trial results will feed into the other components of the MACRO research programme to establish best practice for the management of adults with CRS and design the ideal patient pathway across primary and secondary care. TRIAL REGISTRATION: ISRCTN36962030 . Registered on 17 October 2018.

Expert panel process to optimise the design of a randomised controlled trial in chronic rhinosinusitis (the MACRO programme).

BACKGROUND: MACRO (Defining best Management for Adults with Chronic RhinOsinusitis) is an NIHR-funded programme of work designed to establish best practice for adults with chronic rhinosinusitis (CRS). The 7-year programme comprises three consecutive workstreams, designed to explore NHS care pathways through analysis of primary and secondary data sources, and to undertake a randomised controlled trial to evaluate a longer-term course of macrolide antibiotics and endoscopic sinus surgery for patients with CRS. A number of outstanding elements still required clarification at the funding stage. This paper reports an expert panel review process designed to agree and finalise the MACRO trial design, ensuring relevance to patients and clinicians whilst maximising trial recruitment and retention. METHODS: An expert panel, consisting of the MACRO Programme Management Group, independent advisors, and patient contributors, was convened to review current evidence and the mixed-method data collected as part of the programme, and reach agreement on MACRO trial design. Specifically, agreement was sought for selection of macrolide antibiotic, use of orally administered steroids, inclusion of CRS phenotypes (with/without nasal polyps), and overall trial design. RESULTS: A 12-week course of clarithromycin was agreed as the main trial comparator due to its increasing use as a first- and second-line treatment for patients with CRS, and the perceived need to establish its role in CRS management. Orally administered steroids will be used as a rescue medication during the trial, rather than routinely either pre or post trial randomisation, to limit any potential effects on surgical outcomes and better reflect current UK prescribing habits. Both CRS phenotypes will be included in a single trial to ensure that the MACRO trial is both pragmatic and generalisable to primary care. A modified, three-arm trial design was agreed after intense discussions and further exploratory work. Inclusion criteria were amended to ensure that the patients recruited would be considered eligible for the treatment offered in the trial due to having already received appropriate medical therapy as deemed suitable by their ENT surgeon. A proposed 6-week run-in period prior to randomisation was removed due to the new criteria prior to randomisation. CONCLUSION: The expert panel review process resulted in agreement on key elements and an optimal design for the MACRO trial, considered most likely to be successful in terms of both recruitment potential and ability to establish best management of patients with CRS.

Management strategies for chronic rhinosinusitis: a qualitative study of GP and ENT specialist views of current practice in the UK.

OBJECTIVES: To explore general practitioner (GP) and ears, nose and throat (ENT) specialist perspectives of current treatment strategies for chronic rhinosinusitis (CRS) and care pathways through primary and secondary care. DESIGN: Semi-structured qualitative telephone interviews as part of the MACRO programme (Defining best Management for Adults with Chronic Rhinosinusitis) SETTING: Primary care and secondary care ENT outpatient clinics in the UK. PARTICIPANTS: Twelve GPs and 9 ENT specialists consented to in-depth telephone interviews. Transcribed recordings were managed using NVivo software and analysed using inductive thematic analysis. MAIN OUTCOME MEASURES: Healthcare professional views of management options and care pathways for CRS. RESULTS: GPs describe themselves as confident in recognising CRS, with the exception of assessing nasal polyps. In contrast, specialists report common missed diagnoses (eg, allergy; chronic headache) when patients are referred to ENT clinics, and attribute this to the limited ENT training of GPs. Steroid nasal sprays provide the foundation of treatment in primary care, although local prescribing restrictions can affect treatment choice and poor adherence is perceived to be the causes of inadequate symptom control. Symptom severity, poor response to medical treatment and patient pressure drive referral, although there is uncertainty about optimal timing. Treatment decisions in secondary care are based on disease severity, polyp status, prior medical treatment and patient choice, but there is major uncertainty about the place of longer courses of antibiotics and the use of oral steroids. Surgery is regarded as an important treatment option for patients with severe symptoms or with nasal polyps, although timing of surgery remains unclear, and the uncertainty about net long-term benefits of surgery makes balancing of benefits and risks more difficult. CONCLUSIONS: Clinicians are uncertain about best management of patients with CRS in both primary and secondary care and practice is varied. An integrated care pathway for CRS is needed to improve patient management and timely referral.

Unilateral Vocal Fold Paralysis: A Systematic Review of Speech-Language Pathology Management.

OBJECTIVES: Dysphonia due to unilateral vocal fold paralysis (UVFP) can be characterized by hoarseness and weakness, resulting in a significant impact on patients' activity and participation. Voice therapy provided by a speech-language pathologist is designed to maximize vocal function and improve quality of life. The purpose of this paper is to systematically review literature surrounding the effectiveness of speech-language pathology intervention for the management of UVFP in adults. STUDY DESIGN: This is a systematic review. METHODS: Electronic databases were searched using a range of key terms including dysphonia, vocal fold paralysis, and speech-language pathology. Eligible articles were extracted and reviewed by the authors for risk of bias, methodology, treatment efficacy, and clinical outcomes. RESULTS: Of the 3311 articles identified, 12 met the inclusion criteria: seven case series and five comparative studies. All 12 studies subjectively reported positive effects following the implementation of voice therapy for UVFP; however, the heterogeneity of participant characteristics, voice therapy, and voice outcome resulted in a low level of evidence. CONCLUSIONS: There is presently a lack of methodological rigor and clinical efficacy in the speech-language pathology management of dysphonia arising from UVFP in adults. Reasons for this reduced efficacy can be attributed to the following: (1) no standardized speech-language pathology intervention; (2) no consistency of assessment battery; (3) the variable etiology and clinical presentation of UVFP; and (4) inconsistent timing, frequency, and intensity of treatment. Further research is required to develop the evidence for the management of UVFP incorporating controlled treatment protocols and more rigorous clinical methodology.

Research Into Childhood Obstructive Sleep-Disordered Breathing: A Systematic Review.

BACKGROUND: Despite recent clinical guideline development, the best pathway of care for children with symptoms of obstructive sleep-disordered breathing (oSDB) is still debated. This systematic review aims to map the research in childhood oSDB that has been conducted so far to support further guideline development, identify evidence gaps, and guide future research. METHODS: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library from inception to November 26, 2015. All publications on childhood oSDB were included, irrespective of type and language. The annual number of publications in the field of oSDB was counted over all years; for those published since January 1, 2011 (ie, the date of the latest literature search of the American Academy of Pediatrics guideline), total and annual numbers of publications across main research themes and methodologies were calculated. RESULTS: Of the 7,637 unique records retrieved, 5,871 publications were eligible for inclusion. There was an increase in annual publications since 2000, with 46% published since 2011. Most publications (61%) focused on individual treatment modalities, incidence, or prognosis. Few publications (2.7%) focused on health service delivery, outcomes, and health economics. Observational studies composed 78.5% of publications, 2.4% were randomized controlled trials, and 0.4% used a qualitative approach as their main methodology. CONCLUSIONS: A recent surge in research activity into childhood oSDB has improved the knowledge base for this condition; however, the lack of health services, health economics, and outcomes research impacts the applicability of evidence informing current guidance and leaves important questions for future research. REGISTRATION: PROSPERO: registration number CRD42015029291.

Does laryngeal reinnervation or type I thyroplasty give better voice results for patients with unilateral vocal fold paralysis (VOCALIST): study protocol for a feasibility randomised controlled trial.

INTRODUCTION: A functioning voice is essential for normal human communication. A good voice requires two moving vocal folds; if one fold is paralysed (unilateral vocal fold paralysis (UVFP)) people suffer from a breathy, weak voice that tires easily and is unable to function normally. UVFP can also result in choking and breathlessness. Current treatment for adults with UVFP is speech therapy to stimulate recovery of vocal fold (VF) motion or function and/or injection of the paralysed VF with a material to move it into a more favourable position for the functioning VF to close against. When these therapies are unsuccessful, or only provide temporary relief, surgery is offered. Two available surgical techniques are: (1) surgical medialisation; placing an implant near the paralysed VF to move it to the middle (thyroplasty) and/or repositioning the cartilage (arytenoid adduction) or (2) restoring the nerve supply to the VF (laryngeal reinnervation). Currently there is limited evidence to determine which surgery should be offered to adults with UVFP. METHODS AND ANALYSIS: A feasibility study to test the practicality of running a multicentre, randomised clinical trial of surgery for UVFP, including: (1) a qualitative study to understand the recruitment process and how it operates in clinical centres and (2) a small randomised trial of 30 participants recruited at 3 UK sites comparing non-selective laryngeal reinnervation to type I thyroplasty. Participants will be followed up for 12 months. The primary outcome focuses on recruitment and retention, with secondary outcomes covering voice, swallowing and quality of life. ETHICS AND DISSEMINATION: Ethical approval was received from National Research Ethics Service-Committee Bromley (reference 11/LO/0583). In addition to dissemination of results through presentation and publication of peer-reviewed articles, results will be shared with key clinician and patient groups required to develop the future large-scale randomised controlled trial. TRIAL REGISTRATION NUMBER: ISRCTN90201732; 16 December 2015.