Effectiveness of septoplasty compared to medical management in adults with obstruction associated with a deviated nasal septum: the NAIROS RCT.

Background: The indications for septoplasty are practice-based, rather than evidence-based. In addition, internationally accepted guidelines for the management of nasal obstruction associated with nasal septal deviation are lacking. Objective: The objective was to determine the clinical effectiveness and cost-effectiveness of septoplasty, with or without turbinate reduction, compared with medical management, in the management of nasal obstruction associated with a deviated nasal septum. Design: This was a multicentre randomised controlled trial comparing septoplasty, with or without turbinate reduction, with defined medical management; it incorporated a mixed-methods process evaluation and an economic evaluation. Setting: The trial was set in 17 NHS secondary care hospitals in the UK. Participants: A total of 378 eligible participants aged > 18 years were recruited. Interventions: Participants were randomised on a 1: 1 basis and stratified by baseline severity and gender to either (1) septoplasty, with or without turbinate surgery (n = 188) or (2) medical management with intranasal steroid spray and saline spray (n = 190). Main outcome measures: The primary outcome was the Sino-nasal Outcome Test-22 items score at 6 months (patient-reported outcome). The secondary outcomes were as follows: patient-reported outcomes - Nasal Obstruction Symptom Evaluation score at 6 and 12 months, Sino-nasal Outcome Test-22 items subscales at 12 months, Double Ordinal Airway Subjective Scale at 6 and 12 months, the Short Form questionnaire-36 items and costs; objective measurements - peak nasal inspiratory flow and rhinospirometry. The number of adverse events experienced was also recorded. A within-trial economic evaluation from an NHS and Personal Social Services perspective estimated the incremental cost per (1) improvement (of ≥ 9 points) in Sino-nasal Outcome Test-22 items score, (2) adverse event avoided and (3) quality-adjusted life-year gained at 12 months. An economic model estimated the incremental cost per quality-adjusted life-year gained at 24 and 36 months. A mixed-methods process evaluation was undertaken to understand/address recruitment issues and examine the acceptability of trial processes and treatment arms. Results: At the 6-month time point, 307 participants provided primary outcome data (septoplasty, n = 152; medical management, n = 155). An intention-to-treat analysis revealed a greater and more sustained improvement in the primary outcome measure in the surgical arm. The 6-month mean Sino-nasal Outcome Test-22 items scores were -20.0 points lower (better) for participants randomised to septoplasty than for those randomised to medical management [the score for the septoplasty arm was 19.9 and the score for the medical management arm was 39.5 (95% confidence interval -23.6 to -16.4; p < 0.0001)]. This was confirmed by sensitivity analyses and through the analysis of secondary outcomes. Outcomes were statistically significantly related to baseline severity, but not to gender or turbinate reduction. In the surgical and medical management arms, 132 and 95 adverse events occurred, respectively; 14 serious adverse events occurred in the surgical arm and nine in the medical management arm. On average, septoplasty was more costly and more effective in improving Sino-nasal Outcome Test-22 items scores and quality-adjusted life-years than medical management, but incurred a larger number of adverse events. Septoplasty had a 15% probability of being considered cost-effective at 12 months at a £20,000 willingness-to-pay threshold for an additional quality-adjusted life-year. This probability increased to 99% and 100% at 24 and 36 months, respectively. Limitations: COVID-19 had an impact on participant-facing data collection from March 2020. Conclusions: Septoplasty, with or without turbinate reduction, is more effective than medical management with a nasal steroid and saline spray. Baseline severity predicts the degree of improvement in symptoms. Septoplasty has a low probability of cost-effectiveness at 12 months, but may be considered cost-effective at 24 months. Future work should focus on developing a septoplasty patient decision aid. Trial registration: This trial is registered as ISRCTN16168569 and EudraCT 2017-000893-12. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/226/07) and is published in full in Health Technology Assessment; Vol. 28, No. 10. See the NIHR Funding and Awards website for further award information.

Septoplasty is an operation to straighten the septum, which is the partition wall between the nostrils inside the nose. Septoplasty can be used as a treatment for people who have a bent septum and symptoms of a blocked nose, such as difficulty sleeping and exercising. Medical management (a saltwater spray to clear the nose followed by a nose steroid spray) is an alternative treatment to septoplasty. The Nasal AIRway Obstruction Study (NAIROS) aimed to find out whether septoplasty or medical management is a better treatment for people with a bent septum and symptoms of a blocked nose. We recruited 378 patients with at least moderately severe nose symptoms from 17 hospitals in England, Scotland and Wales to take part in the NAIROS. Participants were randomly put into one of two groups: septoplasty or medical management. Participants' nose symptoms were measured both when they joined the study and after 6 months, using a questionnaire called the Sino-nasal Outcome Test-22 items. This questionnaire was chosen because patients reported that it included symptoms that were important to them. Other studies have shown that a 9-point change in the Sino-nasal Outcome Test-22 items score is significant. After 6 months, on average, people in the septoplasty group improved by 25 points, whereas people in the medical management group improved by 5 points. We saw improvement after septoplasty among patients with moderate symptoms, and among those with severe symptoms. Most patients who we spoke to after a septoplasty were happy with their treatment, but some would have liked more information about what to expect after their nose surgery. In the short term, septoplasty is more costly than medical management. However, over the longer term, taking into account all the costs and benefits of treatment, suggests that septoplasty would be considered good value for money for the NHS.

Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis.

INTRODUCTION: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period. METHODS: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period. ETHICS AND DISSEMINATION: Favourable ethical opinion was received from the North East-Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language). TRIAL REGISTRATION NUMBER: ISRCTN15988757.

Acipimox in Mitochondrial Myopathy (AIMM): study protocol for a randomised, double-blinded, placebo-controlled, adaptive design trial of the efficacy of acipimox in adult patients with mitochondrial myopathy.

BACKGROUND: Mitochondrial disease is a heterogenous group of rare, complex neurometabolic disorders. Despite their individual rarity, collectively mitochondrial diseases represent the most common cause of inherited metabolic disorders in the UK; they affect 1 in every 4300 individuals, up to 15,000 adults (and a similar number of children) in the UK. Mitochondrial disease manifests multisystem and isolated organ involvement, commonly affecting those tissues with high energy demands, such as skeletal muscle. Myopathy manifesting as fatigue, muscle weakness and exercise intolerance is common and debilitating in patients with mitochondrial disease. Currently, there are no effective licensed treatments and consequently, there is an urgent clinical need to find an effective drug therapy. AIM: To investigate the efficacy of 12-week treatment with acipimox on the adenosine triphosphate (ATP) content of skeletal muscle in patients with mitochondrial disease and myopathy. METHODS: AIMM is a single-centre, double blind, placebo-controlled, adaptive designed trial, evaluating the efficacy of 12 weeks' administration of acipimox on skeletal muscle ATP content in patients with mitochondrial myopathy. Eligible patients will receive the trial investigational medicinal product (IMP), either acipimox or matched placebo. Participants will also be prescribed low dose aspirin as a non-investigational medical product (nIMP) in order to protect the blinding of the treatment assignment. Eighty to 120 participants will be recruited as required, with an interim analysis for sample size re-estimation and futility assessment being undertaken once the primary outcome for 50 participants has been obtained. Randomisation will be on a 1:1 basis, stratified by Fatigue Impact Scale (FIS) (dichotomised as < 40, ≥ 40). Participants will take part in the trial for up to 20 weeks, from screening visits through to follow-up at 16 weeks post randomisation. The primary outcome of change in ATP content in skeletal muscle and secondary outcomes relating to quality of life, perceived fatigue, disease burden, limb function, balance and walking, skeletal muscle analysis and symptom-limited cardiopulmonary fitness (optional) will be assessed between baseline and 12 weeks. DISCUSSION: The AIMM trial will investigate the effect of acipimox on modulating muscle ATP content and whether it can be repurposed as a new treatment for mitochondrial disease with myopathy. TRIAL REGISTRATION: EudraCT2018-002721-29 . Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019, https://www.isrctn.com/search?q=aimm.

Preoperative behavioural intervention to reduce drinking before elective orthopaedic surgery: the PRE-OP BIRDS feasibility RCT.

BACKGROUND: Heavy alcohol consumption is associated with an increased risk of postoperative complications and extended hospital stay. Alcohol consumption therefore represents a modifiable risk factor for surgical outcomes. Brief behavioural interventions have been shown to be effective in reducing alcohol consumption among increased risk and risky drinkers in other health-care settings and may offer a method of addressing preoperative alcohol consumption. OBJECTIVES: To investigate the feasibility of introducing a screening process to assess adult preoperative drinking levels and to deliver a brief behavioural intervention adapted for the target population group. To conduct a two-arm (brief behavioural intervention plus standard preoperative care vs. standard preoperative care alone), multicentre, pilot randomised controlled trial to assess the feasibility of proceeding to a definitive trial. To conduct focus groups and a national web-based survey to establish current treatment as usual for alcohol screening and intervention in preoperative assessment. DESIGN: A single-centre, qualitative, feasibility study was followed by a multicentre, two-arm (brief behavioural intervention vs. treatment as usual), individually randomised controlled pilot trial with an embedded qualitative process evaluation. Focus groups and a quantitative survey were employed to characterise treatment as usual in preoperative assessment. SETTING: The feasibility study took place at a secondary care hospital in the north-east of England. The pilot trial was conducted at three large secondary care centres in the north-east of England. PARTICIPANTS: Nine health-care professionals and 15 patients (mean age 70.5 years, 86.7% male) participated in the feasibility study. Eleven health-care professionals and 68 patients (mean age 66.2 years, 80.9% male) participated in the pilot randomised trial. An additional 19 health-care professionals were recruited to one of three focus groups, while 62 completed an electronic survey to characterise treatment as usual. INTERVENTIONS: The brief behavioural intervention comprised two sessions. The first session, delivered face to face in the preoperative assessment clinic, involved 5 minutes of structured brief advice followed by 15-20 minutes of behaviour change counselling, including goal-setting, problem-solving and identifying sources of social support. The second session, an optional booster, took place approximately 1 week before surgery and offered the opportunity to assess progress and boost self-efficacy. MAIN OUTCOME MEASURES: Feasibility was assessed using rates of eligibility, recruitment and retention. The progression criteria for a definitive trial were recruitment of ≥ 40% of eligible patients and retention of ≥ 70% at 6-month follow-up. Acceptability was assessed using themes identified in qualitative data. RESULTS: The initial recruitment of eligible patients was low but improved with the optimisation of recruitment processes. The recruitment of eligible participants to the pilot trial (34%) fell short of the progression criteria but was mitigated by very high retention (96%) at the 6-month follow-up. Multimethod analyses identified the methods as acceptable to the patients and professionals involved and offers recommendations of ways to further improve recruitment. CONCLUSIONS: The evidence supports the feasibility of a definitive trial to assess the effectiveness of brief behavioural intervention in reducing preoperative alcohol consumption and for secondary outcomes of surgical complications if recommendations for further improvements are adopted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN36257982. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 12. See the National Institute for Health Research Journals Library website for further project information.

Most patients undergoing knee and hip replacements are over 65 years old. Older patients have an increased risk of complications following surgery. Heavy alcohol consumption in the weeks before surgery increases the risk of complications after surgery, which can extend recovery times. Advice that helps patients reduce their alcohol consumption before surgery may have benefits for recovery. The PRE-OP BIRDS study had two parts: a feasibility study followed by a pilot randomised controlled trial with focus groups and an electronic survey used to characterise usual care in the preoperative assessment clinic. The feasibility study took place at one hospital. It aimed to develop materials that help health-care professionals provide brief advice to patients on how to reduce alcohol consumption before surgery. This brief advice was delivered to eligible patients and the acceptability to staff and patients was assessed in interviews. The pilot trial took place in three hospitals. Patients who agreed to take part were placed, by equal chance, into either a group that received usual care or a group that received usual care plus brief advice about reducing alcohol use. The aim was to count how many people agreed to take part and how many also agreed to complete a follow-up 6 months later. Interviews were carried out with patients and staff to explore their views on the intervention and the trial as a whole. All of this information was collected to help decide if a future larger trial was possible. This work found that the tools used were acceptable to both patients and staff. Although the number of people who agreed to take part was smaller than hoped, almost all of those who took part also completed the 6-month follow-up. Therefore, a future larger trial was found to be possible, but some changes could be made to encourage more people to take part.

Nasal Airway Obstruction Study (NAIROS): a phase III, open-label, mixed-methods, multicentre randomised controlled trial of septoplasty versus medical management of a septal deviation with nasal obstruction.

BACKGROUND: Septoplasty (surgery to straighten a deviation in the nasal septum) is a frequently performed operation worldwide, with approximately 250,000 performed annually in the US and 22,000 in the UK. Most septoplasties aim to improve diurnal and nocturnal nasal obstruction. The evidence base for septoplasty clinical effectiveness is hitherto very limited. AIMS: To establish, and inform guidance for, the best management strategy for individuals with nasal obstruction associated with a deviated septum. METHODS/DESIGN: A multicentre, mixed-methods, open label, randomised controlled trial of septoplasty versus medical management for adults with a deviated septum and a reduced nasal airway. Eligible patients will have septal deflection visible at nasendoscopy and a nasal symptom score ≥ 30 on the NOSE questionnaire. Surgical treatment comprises septoplasty with or without reduction of the inferior nasal turbinate on the anatomically wider side of the nose. Medical management comprises a nasal saline spray followed by a fluorinated steroid spray daily for six months. The recruitment target is 378 patients, recruited from up to 17 sites across Scotland, England and Wales. Randomisation will be on a 1:1 basis, stratified by gender and severity (NOSE score). Participants will be followed up for 12 months post randomisation. The primary outcome measure is the total SNOT-22 score at 6 months. Clinical and economic outcomes will be modelled against baseline severity (NOSE scale) to inform clinical decision-making. The study includes a recruitment enhancement process, and an economic evaluation. DISCUSSION: The NAIROS trial will evaluate the clinical effectiveness and cost-effectiveness of septoplasty versus medical management for adults with a deviated septum and symptoms of nasal blockage. Identifying those individuals most likely to benefit from surgery should enable more efficient and effective clinical decision-making, and avoid unnecessary operations where there is low likelihood of patient benefit. TRIAL REGISTRATION: EudraCT: 2017-000893-12, ISRCTN: 16168569. Registered on 24 March 2017.

Prevalence of symptoms suggestive of extra-oesophageal reflux in a general practice population in the UK.

Unlike gastro-oesophageal reflux, extra-oesophageal reflux (EOR) is not necessarily associated with heartburn. The potential prevalence of EOR in general practice in the UK using the Reflux Symptom Index (RSI) questionnaire was determined. A total of 1152 patients attending a GP surgery for routine conditions completed the RSI questionnaire: 26.5% had an RSI score >10, regarded as a clinically significant score for EOR; 29% of patients with a significant RSI score rated the impact of heartburn in the previous month as zero. Significant numbers of patients presenting to GPs have high RSI scores suggesting significant reflux. Many patients likely to have EOR do not experience classical heartburn. This might explain why some GPs may not attribute common symptoms affecting the throat to gastric reflux.