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.
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.
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.
The trial was set in 17 NHS secondary care hospitals in the UK.
A total of 378 eligible participants aged > 18 years were recruited.
Participants were randomised on a 1: 1 basis and stratified by baseline severity and gender to either (1) septoplasty, with or without turbinate surgery (
= 188) or (2) medical management with intranasal steroid spray and saline spray (
= 190).
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.
At the 6-month time point, 307 participants provided primary outcome data (septoplasty,
= 152; medical management,
= 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;
< 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.
COVID-19 had an impact on participant-facing data collection from March 2020.
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.
This trial is registered as ISRCTN16168569 and EudraCT 2017-000893-12.
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
; Vol. 28, No. 10. See the NIHR Funding and Awards website for further award information.
Aims
Following a favourable pilot trial using a single bolus of ciclosporin, it has been unclear why 2 large studies (CYCLE and CIRCUS) failed to prevent reperfusion injury and reduce infarct size in ...STEMI (ST elevation myocardial infarction). The purpose of this study was to assess the effect of ciclosporin on myocardial injury, left ventricular remodelling and lymphocyte kinetics in patients with acute STEMI undergoing primary percutaneous coronary intervention.
Methods
In this double‐blind, single centre trial, we randomly assigned 52 acute STEMI patients with an onset of pain of <6 hours and blocked culprit artery to a single bolus of ciclosporin (n = 26) or placebo (n = 26, control group) prior to reperfusion by stent percutaneous coronary intervention. The primary endpoint was infarct size at 12 weeks.
Results
Mean infarct size at 12 weeks was identical in both groups (9.1% standard deviation= 7.0 vs 9.1% standard deviation = 7.0, P = .99; 95% confidence interval for difference: −4.0 to 4.1). CD3 T‐lymphocytes dropped to similar levels at 90 minutes (867 vs 852 cells/μL, control vs ciclosporin) and increased to 1454 vs 1650 cells/μL at 24 hours.
Conclusion
In our pilot trial, a single ciclosporin bolus did not affect infarct size or left ventricular remodelling, matching the results from CYCLE and CIRCUS. Our study suggests that ciclosporin does either not reach ischaemic cardiomyocytes, or requires earlier application during first medical contact. Finally, 1 bolus of ciclosporin is not sufficient to inhibit CD4 T‐lymphocyte proliferation during remodelling. We therefore believe that further studies are warranted.
(Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary percutaneous coronary intervention CAPRI; NCT02390674)
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Abstract
Objective
To assess the clinical effectiveness of septoplasty.
Design
Multicentre, randomised controlled trial.
Setting
17 otolaryngology clinics in the UK’s National Health Service.
...Participants
378 adults (≥18 years, 67% men) newly referred with symptoms of nasal obstruction associated with septal deviation and at least moderate symptoms of nasal obstruction (score >30 on the Nasal Obstruction and Symptom Evaluation (NOSE) scale).
Interventions
Participants were randomised 1:1 to receive either septoplasty (n=188) or defined medical management (n=190, nasal steroid and saline spray for six months), stratified by baseline symptom severity and sex.
Main outcome measures
The primary outcome measure was patient reported score on the Sino-Nasal Outcome Test-22 (SNOT-22) at six months, with 9 points defined as the minimal clinically important difference. Secondary outcomes included quality of life and objective nasal airflow measures.
Results
Mean SNOT-22 scores at six months were 19.9 (95% confidence interval 17.0 to 22.7) in the septoplasty arm (n=152, intention-to-treat population) and 39.5 (36.1 to 42.9) in the medical management arm (n=155); an estimated 20.0 points lower (better) for participants randomised to receive septoplasty (95% confidence interval 16.4 to 23.6, P<0.001, adjusted for baseline continuous SNOT-22 score and the stratification variables sex and baseline NOSE severity categories). Greater improvement in SNOT-22 scores was predicted by higher baseline symptom severity scores. Quality of life outcomes and nasal airflow measures (including peak nasal inspiratory flow and absolute inhalational nasal partitioning ratio) improved more in participants in the septoplasty group. Readmission to hospital with bleeding after septoplasty occurred in seven participants (4% of 174 who had septoplasty), and a further 20 participants (12%) required antibiotics for infections.
Conclusions
Septoplasty is a more effective intervention than a defined medical management regimen with a nasal steroid and saline spray in adults with nasal obstruction associated with a deviated nasal septum.
Trial registration
ISRCTN Registry
ISRCTN16168569
.
IntroductionSkeletal muscle dysfunction is central to both sarcopenia and physical frailty, which are associated with a wide range of adverse outcomes including falls and fractures, longer hospital ...stays, dependency and the need for care. Resistance training may prevent and treat sarcopenia and physical frailty, but not everyone can or wants to exercise. Finding alternatives is critical to alleviate the burden of adverse outcomes associated with sarcopenia and physical frailty. This trial will provide proof-of-concept evidence as to whether metformin can improve physical performance in older people with sarcopenia and physical prefrailty or frailty.Methods and analysisMET-PREVENT is a parallel group, double-blind, placebo-controlled proof-of-concept trial. Trial participants can participate from their own homes, including completing informed consent and screening assessments. Eligible participants with low grip strength or prolonged sit-to-stand time together with slow walk speed will be randomised to either oral metformin hydrochloride 500 mg tablets or matched placebo, taken three times a day for 4 months. The recruitment target is 80 participants from two secondary care hospitals in Newcastle and Gateshead, UK. Local primary care practices will act as participant identification centres. Randomisation will be performed using a web-based minimisation system with a random element, balancing on sex and baseline walk speed. Participants will be followed up for 4 months post-randomisation, with outcomes collected at baseline and 4 months. The primary outcome measure is the four metre walk speed at the 4-month follow-up visit.Ethics and disseminationThe trial has been approved by the Liverpool NHS Research Ethics Committee (20/NW/0470), the Medicines and Healthcare Regulatory Authority (EudraCT 2020-004023-16) and the UK Health Research Authority (IRAS 275219). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community.Trial registration numberISRCTN29932357.
Scalable weight loss maintenance (WLM) interventions for adults with obesity are lacking but vital for the health and economic benefits of weight loss to be fully realised. We examined the ...effectiveness and cost-effectiveness of a low-intensity technology-mediated behavioural intervention to support WLM in adults with obesity after clinically significant weight loss (≥5%) compared to standard lifestyle advice.
The NULevel trial was an open-label randomised controlled superiority trial in 288 adults recruited April 2014 to May 2015 with weight loss of ≥5% within the previous 12 months, from a pre-weight loss BMI of ≥30 kg/m2. Participants were self-selected, and the majority self-certified previous weight loss. We used a web-based randomisation system to assign participants to either standard lifestyle advice via newsletter (control arm) or a technology-mediated low-intensity behavioural WLM programme (intervention arm). The intervention comprised a single face-to-face goal-setting meeting, self-monitoring, and remote feedback on weight, diet, and physical activity via links embedded in short message service (SMS). All participants were provided with wirelessly connected weighing scales, but only participants in the intervention arm were instructed to weigh themselves daily and told that they would receive feedback on their weight. After 12 months, we measured the primary outcome, weight (kilograms), as well as frequency of self-weighing, objective physical activity (via accelerometry), psychological variables, and cost-effectiveness. The study was powered to detect a between-group weight difference of ±2.5 kg at follow-up. Overall, 264 participants (92%) completed the trial. Mean weight gain from baseline to 12 months was 1.8 kg (95% CI 0.5-3.1) in the intervention group (n = 131) and 1.8 kg (95% CI 0.6-3.0) in the control group (n = 133). There was no evidence of an effect on weight at 12 months (difference in adjusted mean weight change from baseline: -0.07 95% CI 1.7 to -1.9, p = 0.9). Intervention participants weighed themselves more frequently than control participants and were more physically active. Intervention participants reported greater satisfaction with weight outcomes, more planning for dietary and physical activity goals and for managing lapses, and greater confidence for healthy eating, weight loss, and WLM. Potential limitations, such as the use of connected weighing study in both trial arms, the absence of a measurement of energy intake, and the recruitment from one region of the United Kingdom, are discussed.
There was no difference in the WLM of participants who received the NULevel intervention compared to participants who received standard lifestyle advice via newsletter. The intervention affected some, but not all, process-related secondary outcomes of the trial.
This trial is registered with the ISRCTN registry (ISRCTN 14657176; registration date 20 March 2014).
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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.
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.
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.
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.
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.
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.
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.
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.
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.
Current Controlled Trials ISRCTN36257982.
This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in
; Vol. 24, No. 12. See the National Institute for Health Research Journals Library website for further project information.
Background
Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for ...nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed.
Objectives
To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women.
Design
This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations.
Participants
Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation.
Interventions
Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment.
Main outcome measures
The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit.
Results
Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron,
n
= 8; ondansetron and dummy metoclopramide,
n
= 8; metoclopramide and ondansetron,
n
= 8; double dummy,
n
= 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported.
Limitations
The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care.
Conclusions
The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy.
Trial registration
Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31.
Funding
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
Health Technology Assessment
; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.
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.
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.
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
journal and to participants and the public (using lay language).
ISRCTN15988757.
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.
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.
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.
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.
EudraCT2018-002721-29 . Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019, https://www.isrctn.com/search?q=aimm.
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