Brief intervention to reduce fatigue impact in patients with inflammatory arthritis: design and outcomes of a single-arm feasibility study.

OBJECTIVES: Patients with inflammatory arthritis report that fatigue is challenging to manage. We developed a manualised, one-to-one, cognitive-behavioural intervention, delivered by rheumatology health professionals (RHPs). The Fatigue - Reducing its Effects through individualised support Episodes in Inflammatory Arthritis (FREE-IA) study tested the feasibility of RHP training, intervention delivery and outcome collection ahead of a potential trial of clinical and cost-effectiveness. METHODS: In this single-arm feasibility study, eligible patients were ≥18 years, had a clinician-confirmed diagnosis of an inflammatory arthritis and scored ≥6/10 on the Bristol Rheumatoid Arthritis Fatigue (BRAF) Numerical Rating Scale (NRS) Fatigue Effect. Following training, RHPs delivered two to four sessions to participants. Baseline data were collected before the first session (T0) and outcomes at 6 weeks (T1) and 6 months (T2). The proposed primary outcome was fatigue impact (BRAF NRS Fatigue Effect). Secondary outcomes included fatigue severity and coping, disease impact and disability, and measures of therapeutic mechanism (self-efficacy and confidence to manage health). RESULTS: Eight RHPs at five hospitals delivered 113 sessions to 46 participants. Of a potential 138 primary and secondary outcome responses at T0, T1 and T2, there were 13 (9.4%) and 27 (19.6%) missing primary and secondary outcome responses, respectively. Results indicated improvements in all measures except disability, at either T1 or T2, or both. CONCLUSIONS: This study showed it was feasible to deliver the intervention, including training RHPs, and recruit and follow-up participants with high retention. While there was no control group, observed within-group improvements suggest potential promise of the intervention and support for a definitive trial to test effectiveness.

Urinary Volatile Organic Compound Testing in Fast-Track Patients with Suspected Colorectal Cancer.

Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. A prospective, multi-center, observational feasibility study was performed across three sites. Patients referred to NHS fast-track pathways for potential CRC provided a urine sample that underwent Gas Chromatography-Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS), and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. 558 patients participated with 23 (4%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity = 0.878, specificity = 0.882, AUROC = 0.896) but it is labour intensive. Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified suggesting VOC analysis may have future utility as a triage tool.

The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial.

STUDY OBJECTIVE: Epistaxis is a common emergency department (ED) presentation and, if simple first aid measures fail, can lead to a need for anterior nasal packing. Tranexamic acid is an agent that contributes to blood clot stability. The aim of this study is to investigate the effectiveness of topical intranasal tranexamic acid in adult patients presenting to the ED with persistent epistaxis, and whether it reduces the need for anterior nasal packing. METHODS: From May 5, 2017, to March 31, 2019, a double-blind, placebo-controlled, multicenter, 1:1, randomized controlled trial was conducted across 26 EDs in the United Kingdom. Participants with spontaneous epistaxis, persisting after simple first aid and the application of a topical vasoconstrictor, were randomly allocated to receive topical tranexamic acid or placebo. The primary outcome was the need for anterior nasal packing of any kind during the index ED attendance. Secondary outcome measures included hospital admission, need for blood transfusion, recurrent epistaxis, and any thrombotic events requiring any hospital reattendance within 1 week. RESULTS: The study sample consisted of 496 participants with spontaneous epistaxis, persisting after simple first aid and application of a topical vasoconstrictor. In total, 211 participants (42.5%) received anterior nasal packing during the index ED attendance, including 111 of 254 (43.7%) in the tranexamic acid group versus 100 of 242 (41.3%) in the placebo group. The difference was not statistically significant (odds ratio 1.107; 95% confidence interval 0.769 to 1.594; P=.59). Furthermore, there were no statistically significant differences between tranexamic acid and placebo for any of the secondary outcome measures. CONCLUSION: In patients presenting to an ED with atraumatic epistaxis that is uncontrolled with simple first aid measures, topical tranexamic acid applied in the bleeding nostril on a cotton wool dental roll is no more effective than placebo at controlling bleeding and reducing the need for anterior nasal packing.

Evaluation of pre-hospital use of a valsalva assist device in the emergency treatment of supraventricular tachycardia [EVADE]: a randomised controlled feasibility trial.

BACKGROUND: The valsalva manoeuvre is an internationally recommended initial treatment for supraventricular tachycardia (SVT). The pre-hospital use of a valsalva assist device, to help deliver this manoeuvre, could improve cardioversion rates and reduce the need for patients to attend hospital. METHODS: We conducted a randomised controlled feasibility trial comparing ambulance clinician use of a valsalva assist device versus standard care to treat adult patients presenting to an ambulance service in the south west of England. Eligible consenting participants were randomised 1:1 to device or standard care with trial procedures mirroring a proposed definitive trial.Feasibility was assessed upon ambulance clinician and participant recruitment rates and feedback, data completeness and potential future primary outcome rates. RESULTS: Over a 6 months period (1 July to 31 December 2018), 276 (23%) of 1183 eligible ambulance clinicians were trained and they recruited 34 participants; approximately 10% of patients presenting with suspected SVT during that time. Seventeen participants were randomised to each arm and all underwent their allocated valsalva strain method. All trial data and 63/68 (93%) of pre and post-valsalva ECGs were available. Seven (21%) participants had ineligible initial rhythms on retrospective expert ECG review. Valsalva assist device use was associated with cardioversion and non-conveyance in 4 (24%) and 2 (12%) participants respectively. No participants assigned to standard care were cardioverted and all were conveyed. Participant feedback highlighted the challenges of retaining trial information during an SVT attack. CONCLUSIONS: The trial achieved efficient clinician training, randomisation and data collection, and there was an encouraging effect signal associated with device use. However, trial design changes should be considered to address the relatively small proportion of eligible patients recruited and challenges identified with consent and confirmation of cardioversion as a primary outcome. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (NCT03514628) on 2 May 2018.

SAFE, a new therapeutic intervention for families of children with autism: a randomised controlled feasibility trial.

OBJECTIVES: To establish the feasibility of a definitive randomised controlled trial of Systemic Autism-related Family Enabling (SAFE), an intervention for families of children with autism. DESIGN: A randomised, controlled, multicentred feasibility study. SETTING: Participants were identified from three National Health Service (NHS) diagnosing centres in Plymouth and Cornwall and a community pathway. PARTICIPANTS: 34 families of a child with a diagnosis of autism severity level 1 or 2 between 3 and 16 years. Four families were lost to follow-up. INTERVENTIONS: SAFE is a manualised five-session family therapy-based intervention delivered over 16 weeks and designed for families of children with autism. SAFE involves families attending five 3-hour sessions led by systemic practitioners. PRIMARY AND SECONDARY OUTCOME MEASURES: The proposed primary outcome measure was the Systemic CORE 15 (SCORE-15). Proposed secondary outcome measures: Patient Health Questionnaire-Somatic Anxiety Depressive Symptoms, the Coding of Attachment-Related Parenting for use with children with Autism, the Child Behaviour Checklist (CBCL), the Reflective Functioning Questionnaire (RFQ) and the Caregiving Helplessness Questionnaire. Outcome measures were collected at baseline and 24 weeks post randomisation. RESULTS: All primary caregivers retained in the study completed the SCORE-15 at both time points. 34 of the target of 36 families were recruited and 88% of families were retained. Training for therapists was effective. Feedback revealed willingness to undergo randomisation. There was 100% attendance at appropriate sessions for core family members. The SCORE-15 showed reduction in scores for families receiving SAFE compared with controls suggesting positive change. Qualitative data also revealed that families found the study acceptable and families receiving SAFE experienced positive change. Feedback indicated that the SCORE-15 should be retained as a primary measure in a future trial, but secondary measures should be reduced. CONCLUSIONS: This study indicates that a larger trial of SAFE is feasible. Findings suggest that SAFE can address current gaps in recommended care, can be confidently delivered by NHS staff and has potential as a beneficial treatment. TRIAL REGISTRATION NUMBERS: ISCTRN83964946 and IRAS213527.

A self-management programme to reduce falls and improve safe mobility in people with secondary progressive MS: the BRiMS feasibility RCT.

BACKGROUND: Balance, mobility impairments and falls are common problems for people with multiple sclerosis (MS). Our ongoing research has led to the development of Balance Right in MS (BRiMS), a 13-week home- and group-based exercise and education programme intended to improve balance and encourage safer mobility. OBJECTIVE: This feasibility trial aimed to obtain the necessary data and operational experience to finalise the planning of a future definitive multicentre randomised controlled trial. DESIGN: Randomised controlled feasibility trial. Participants were block randomised 1 : 1. Researcher-blinded assessments were scheduled at baseline and at 15 and 27 weeks post randomisation. As is appropriate in a feasibility trial, statistical analyses were descriptive rather than involving formal/inferential comparisons. The qualitative elements utilised template analysis as the chosen analytical framework. SETTING: Four sites across the UK. PARTICIPANTS: Eligibility criteria included having a diagnosis of secondary progressive MS, an Expanded Disability Status Scale (EDSS) score of between ≥ 4.0 and ≤ 7.0 points and a self-report of two or more falls in the preceding 6 months. INTERVENTIONS: Intervention - manualised 13-week education and exercise programme (BRiMS) plus usual care. Comparator - usual care alone. MAIN OUTCOME MEASURES: Trial feasibility, proposed outcomes for the definitive trial (including impact of MS, mobility, quality of life and falls), feasibility of the BRiMS programme (via process evaluation) and economic data. RESULTS: A total of 56 participants (mean age 59.7 years, standard deviation 9.7 years; 66% female; median EDSS score of 6.0 points, interquartile range 6.0-6.5 points) were recruited in 5 months; 30 were block randomised to the intervention group. The demographic and clinical data were broadly comparable at baseline; however, the intervention group scored worse on the majority of baseline outcome measures. Eleven participants (19.6%) withdrew or were lost to follow-up. Worsening of MS-related symptoms unrelated to the trial was the most common reason (n = 5) for withdrawal. Potential primary and secondary outcomes and economic data had completion rates of > 98% for all those assessed. However, the overall return rate for the patient-reported falls diary was 62%. After adjusting for baseline score, the differences between the groups (intervention compared with usual care) at week 27 for the potential primary outcomes were MS Walking Scale (12-item) version 2 -7.7 [95% confidence interval (CI) -17.2 to 1.8], MS Impact Scale (29-item) version 2 (MSIS-29vs2) physical 0.6 (95% CI -7.8 to 9) and MSIS-29vs2 psychological -0.4 (95% CI -9.9 to 9) (negative score indicates improvement). After the removal of one outlier, a total of 715 falls were self-reported over the 27-week trial period, with substantial variation between individuals (range 0-93 falls). Of these 715 falls, 101 (14%) were reported as injurious. Qualitative feedback indicated that trial processes and participant burden were acceptable, and participants highlighted physical and behavioural changes that they perceived to result from undertaking BRiMS. Engagement varied, influenced by a range of condition- and context-related factors. Suggestions to improve the utility and accessibility of BRiMS were highlighted. CONCLUSIONS: The results suggest that the trial procedures are feasible and acceptable, and retention, programme engagement and outcome completion rates were sufficient to satisfy the a priori progression criteria. Challenges were experienced in some areas of data collection, such as completion of daily diaries. FUTURE WORK: Further development of BRiMS is required to address logistical issues and enhance user-satisfaction and adherence. Following this, a definitive trial to assess the clinical effectiveness and cost-effectiveness of the BRiMS intervention is warranted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13587999. 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. 23, No. 27. See the NIHR Journals Library website for further project information.

People with secondary progressive multiple sclerosis (SPMS) often have problems with walking and balance, which lead them to fall. Undertaking exercise and learning about falls prevention could help reduce injury risk and improve mobility. We developed a mobility, balance and falls programme called Balance Right in MS (BRiMS). Before testing its effectiveness in a large-scale trial, we needed to conduct a small-scale version of the trial. We asked people with SPMS who had balance and mobility problems to be assigned by chance to undertake the BRiMS programme plus their usual care, or to continue with usual care only. Questionnaires were used to ask people about their mobility, falls and quality of life, and we measured their balance and activity levels. We interviewed participants about BRiMS and being in the trial, and collected information about costs. Fifty-six people entered the trial from three areas of the south-west and from Ayrshire. At completion of the study we were able to review 44 people. The key measures were completed by 98% of those we assessed, but only around half (62%) of the diaries detailing falls were returned. As this was a feasibility trial, the numbers were too small for us to look at differences between the groups. Participants liked the BRiMS programme; some did a lot of exercise and learning activities, but most did not manage the amount we asked them to do. People reported feeling a little overwhelmed by the educational content of BRiMS, and that this should be reduced in future. They told us that they felt that their balance had improved and that they fell less frequently after the BRiMS programme. Our assessment of the trial methods we used showed that it would be possible to conduct a full-scale trial using this design, but that we need to adapt the BRiMS programme further to make it more user-friendly.

SAFE, a new therapeutic intervention for families of children with autism: study protocol for a feasibility randomised controlled trial.

INTRODUCTION: Incidence of autistic traits, mental health problems, stress and poor coping is high among family members of children with autism. These problems are coupled with challenging behaviour among children with autism. Current treatment for these families is disjointed and costly. The need for whole family support is supported by the National Institute for Health and Care Excellence recommendations, developments regarding children's service provision, research and requests by families of children with autism. Despite evidence that family therapies can provide benefits to these families, efficacy has not been subject to a randomised controlled trial. Systemic Autism-related Family Enabling (SAFE) is a new family therapy intervention designed specifically for families of children with autism. We aim to establish the feasibility of running a fully powered randomised controlled trial to evaluate SAFE. METHODS AND ANALYSIS: Families of children with autism aged 3-16 years will be invited to participate. Consenting participants will be randomised 2:1 to either SAFE+support as usual or support as usual alone. The proposed primary outcome measure for the main trial will be the Systemic CORE 15. Participants will also complete proposed secondary outcome measures, indexing changes in child behaviour, child-parent attachment, anxiety and depression. Generic health economic outcome measures (EuroQol 5 dimensions and Child Health Utility 9 Dimensions) will also provide data on the feasibility of cost-effectiveness analysis. Questionnaires will be completed at baseline and 32 weeks post-allocation. Data on ability to identify, recruit, randomise, retain and collect data from families, acceptability of outcome measures, adherence of therapists and families to the intervention, appropriateness of resource use questionnaires and effectiveness of training will be collected for feasibility analysis. Qualitative data will also explore acceptability of SAFE and reasons for declining and withdrawing from the study. ETHICS AND DISSEMINATION: The current trial protocol received ethical approval from the South West-Exeter Research Ethics Committee (Ref: 17/SW/0192). The findings of the trial will be disseminated in collaboration with our Family Consultation Group and other partners. Findings will be shared locally, nationally and internationally through events, conferences and published papers. TRIAL REGISTRATION NUMBER: ISCTRN83964946 (Pre-results) IRAS 213527.

Novel use of tranexamic acid to reduce the need for Nasal Packing in Epistaxis (NoPac) randomised controlled trial: research protocol.

INTRODUCTION: Patients presenting to emergency departments (EDs) with epistaxis uncontrolled by subsequent simple first aid measures or application of topical vasoconstrictors will typically undergo anterior nasal packing. Packing is effective, but can be extremely painful and unpleasant and patients usually need hospital admission. Tranexamic acid (TXA) is a cheap, safe, readily available antifibrinolytic agent known to be beneficial in a variety of clinical settings where uncontrolled bleeding may be a problem. Anecdotal evidence suggests that topical TXA may be of value in persistent epistaxis; however, further evaluation is required. METHODS AND ANALYSIS: This is a multicentre, double-blind, parallel group, randomised, controlled trial comparing the use of topical intranasal TXA with indistinguishable placebo in adults presenting to UK EDs with persistent atraumatic epistaxis. Follow-up is at 1 week by structured telephone review. The primary outcome measure is the subsequent need for anterior nasal packing in the ED. Key secondary outcomes include the need for hospital admission, blood transfusion and/or further treatment for epistaxis during the index ED attendance. Recruiting 450 patients will provide 90% power to demonstrate an absolute reduction in packing rate from 95% to 85%. An improvement of this magnitude would be of significant benefit to patients and healthcare providers and justify a change to standard practice. Given the low cost of TXA and its short administration time, a full economic evaluation is not being undertaken. ETHICS AND DISSEMINATION: The study has been approved by the South West-Bristol Research Ethics Committee (reference 17/SW/0010). We aim to publish the findings in a high impact, international peer-reviewed journal. Results will also be shared with the Hereditary Haemorrhagic Telangiectasia foundation and telangiectasia UK for dissemination through appropriate related forums. TRIAL REGISTRATION NUMBER: ISRCTN34153772 and EudraCT No: 2016-001530-10.

Testing of a novel Valsalva Assist Device with supine and modified positions in healthy volunteers.

BACKGROUND: The Valsalva manoeuvre (VM) is used to treat supraventricular tachycardia (SVT) by inducing a vagal response (drop in HR). There is debate as to the best position in which to carry out the VM and how the strain should be delivered in practice. We aimed to compare vagal responses induced with supine and modified VMs using strains delivered with a standardised manometer or novel Valsalva Assist Device (VAD), a simple device to provide resistance to exhalation. METHODS: We conducted a repeated measures randomised trial of four VMs (two supine VM and two modified VMs), in healthy adult volunteers, with strains delivered using an adapted sphygmomanometer (manometer) or a VAD. Changes in HR, pressure and duration of strain and adverse events were monitored and compared between the techniques and devices. The trial was approved by the University of Exeter Medical School Research ethics committee. RESULTS: 75 healthy participants aged 19-55 years were recruited over a 4-month period. A mixed-effects linear regression showed the modified VM resulted in a 3.8 beats per min (bpm) greater drop in HR compared with the supine VM (p=0.002, 95% CI 2.2 to 5.4). VM strains produced by the VAD were of a similar pressure but of slightly shorter duration and resulted in a 1.9 bpm smaller drop in HR compared with the manometer (p=0.01, 95% CI 0.4 to 3.4). There were no differences in adverse events. CONCLUSIONS: Modified VM was associated with a greater drop in HR than a supine VM with no increase in adverse events in healthy volunteers. The VAD can be used to safely generate the recommended VM strain pressure, but produced a smaller drop in HR compared with a manometer and requires modification to enable the recommended strain duration to be achieved consistently. TRIAL REGISTRATION NUMBER: NCT03298880.

Trial of intraoperative cell salvage versus transfusion in ovarian cancer (TIC TOC): protocol for a randomised controlled feasibility study.

INTRODUCTION: Ovarian cancer is the leading cause of death from gynaecological cancer, with more than 7000 new cases registered in the UK in 2014. In patients suitable for surgery, the National Institute of Health and Care Excellence guidance for treatment recommends surgical resection of all macroscopic tumour, followed by chemotherapy. The surgical procedure can be extensive and associated with substantial blood loss which is conventionally replaced with a donor blood transfusion. While often necessary and lifesaving, the use of donor blood is associated with increased risks of complications and adverse surgical outcomes. Intraoperative cell salvage (ICS) is a blood conservation strategy in which red cells collected from blood lost during surgery are returned to the patient thus minimising the use of donor blood. This is the protocol for a feasibility randomised controlled trial with an embedded qualitative study and feasibility economic evaluation. If feasible, a later definitive trial will test the effectiveness and cost-effectiveness of ICS reinfusion versus donor blood transfusion in ovarian cancer surgery. METHODS AND ANALYSIS: Sixty adult women scheduled for primary or interval ovarian cancer surgery at participating UK National Health Service Trusts will be recruited and individually randomised in a 1:1 ratio to receive ICS reinfusion or donor blood (as required) during surgery. Participants will be followed up by telephone at 30 days postoperatively for adverse events monitoring and by postal questionnaire at 6 weeks and 3 monthly thereafter, to capture quality of life and resource use data. Qualitative interviews will capture participants' and clinicians' experiences of the study. ETHICS AND DISSEMINATION: This study has been granted ethical approval by the South West-Exeter Research Ethics Committee (ref: 16/SW/0256). Results will be disseminated via peer-reviewed publications and will inform the design of a larger trial. TRIAL REGISTRATION NUMBER: ISRCTN19517317.

Chewing gum vs. ibuprofen in the management of orthodontic pain, a multi-centre randomised controlled trial - the effect of anxiety.

OBJECTIVES: Pain is a common side effect of orthodontic treatment. An objective of this study, part of a large previously reported RCT on pain and analgesic use, was to determine the effect of anxiety on perceived pain and use of analgesia. METHODS: 1000 patients aged 11-17 years, undergoing upper and lower fixed appliance treatment in nine hospital departments were recruited into this two-arm parallel design randomised controlled trial. One arm was given sugar-free chewing gum and the other arm ibuprofen for pain relief. Neither the clinicians nor patients were blinded to assignment. In addition to recording pain experience and analgesic use for 3 days following appliance placement and first archwire change, each patient recorded their level of anxiety immediately following the fitting of the appliance and the first archwire change. RESULTS: 419 chewing gum group (84%) and 407 ibuprofen group (83%) questionnaires were returned following appliance placement, and 343 chewing gum group (70%) and 341 ibuprofen group (71%) questionnaires were returned following the first archwire change. The mean anxiety scores following fitting of the appliance and first archwire change were 2.7 (SD 2.1) and 1.6 (SD 1.8), respectively. There were weak but significant positive associations between anxiety scores and pain scores. Multi-level modelling produced a coefficient for anxiety of 0.23 (95% CI 0.17-0.28) for appliance placement, suggesting a small rise (0.23) on the 11-point pain scale for a one-point increase on the corresponding anxiety scale. Following archwire change, the corresponding coefficient was 0.32 (0.24-0.39). For ibuprofen use, again simple analyses suggested a relationship with anxiety. Multi-level logistic modelling produced an odds ratio for ibuprofen use of 1.11 (95% CI 1.07-1.15) at appliance placement and 1.21 (1.10-1.33) at the first archwire change. There was a 10-20% increase in the odds of using ibuprofen for each one-point increase on the anxiety scale. No such relationship was found between anxiety and chewing gum use. There were no adverse effects or harms reported during the trial. Approvals were granted by the Research Ethics Committee (08/H0106/139), R&D and MHRA (Eudract 2008-005522-36) and the trial was registered on the ISRCTN (79884739) and NIHR (6631) portfolios. Support was provided by the British Orthodontic Society Foundation. CONCLUSIONS: There was a weak positive correlation between anxiety reported and pain experienced following both the initial fitting of the fixed appliances and at the subsequent archwire change. Patients that were more anxious tended to take more ibuprofen for their pain relief.

Comparative assessment of chewing gum and ibuprofen in the management of orthodontic pain with fixed appliances: A pragmatic multicenter randomized controlled trial.

INTRODUCTION: The aim of this randomized trial was to investigate the effect of the use of a sugar-free chewing gum vs ibuprofen on reported pain in orthodontic patients. METHODS: This was a 2-arm parallel design randomized controlled trial in 9 sites in the southwest of England. Patients about to undergo orthodontic treatment with maxillary and mandibular fixed appliances were recruited and randomly allocated to an experimental chewing gum group or a control ibuprofen group. Eligibility criteria included patients undergoing fixed maxillary and mandibular appliance therapy, aged 11 to 17 years, and able to use ibuprofen and chewing gum. The primary outcome measure was pain experienced after appliance placement using a mean of 3 recordings on a scale of 0 to 10. Secondary outcome measures were pain experienced in the subsequent 3 days, pain after the first archwire change, ibuprofen use, and appliance breakages. Pain scores were recorded with a questionnaire and posted to a collection center by each patient. Randomization was by means of a central telephone service and comprised computer-generated random numbers used to generate a sequential allocation list, with permuted blocks of variable size (2 and 4) and stratified by center. Neither the clinicians nor the patients were blinded to the intervention. Patients in the control group were permitted to use ibuprofen only, and patients in the experimental group were allowed to use ibuprofen if they did not get sufficient analgesia from the chewing gum. Data were analyzed using the principle of intention to treat with multilevel modeling to reflect the structured nature of the data (scores within patient within site). RESULTS: One thousand patients were recruited and randomized in a ratio of 1:1 to the chewing gum and ibuprofen (control) groups. The male-to-female ratios were similar in the groups. The pain questionnaire response rates were good at approximately 84% and 83% after appliance placement (chewing gum group, 419; ibuprofen group, 407) and 70% and 71% after the first archwire change (chewing gum group, 343; ibuprofen group, 341). The primary outcomes were similar for the 2 groups: mean pain scores, 4.31 in the chewing gum group and 4.17 in the ibuprofen group; difference, 0.14 (95% CI, -0.13 to 0.41). There was a suggestion that the relative pain scores for the 2 groups changed over time, with the chewing gum group experiencing slightly more pain on the day of bond-up and less on the subsequent 3 days; however, the differences had no clinical importance. There were no significant differences for the period after archwire change. The reported use of ibuprofen was less in the chewing gum group than in the ibuprofen group; after appliance placement, the mean numbers of occasions that ibuprofen was used were 2.1 in the chewing gum group and 3.0 in the ibuprofen group (adjusted difference, -0.96 [95% CI, -0.75 to -1.17; P <0.001]); after archwire change, the figures were 0.8 and 1.5 occasions (difference, -0.65 [-0.44 to -0.86; P <0.001]). After appliance placement and the first archwire change, there was no clinically or statistically significant difference in appliance breakages between the chewing gum and ibuprofen groups after either bond-up (7% and 8.8%, respectively) or the first archwire change (4.2% and 5.5%, respectively). No adverse events were reported. CONCLUSIONS: The use of a sugar-free chewing gum may reduce the level of ibuprofen usage but has no clinically or statistically significant effect on bond failures. REGISTRATION: International Standard Randomised Controlled Trial Number (79884739) and National Institute of Health Research (6631) portfolios. FUNDING: This research was supported by an award by the British Orthodontic Society Foundation.

Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial.

BACKGROUND: The Valsalva manoeuvre is an internationally recommended treatment for supraventricular tachycardia, but cardioversion is rare in practice (5-20%), necessitating the use of other treatments including adenosine, which patients often find unpleasant. We assessed whether a postural modification to the Valsalva manoeuvre could improve its effectiveness. METHODS: We did a randomised controlled, parallel-group trial at emergency departments in England. We randomly allocated adults presenting with supraventricular tachycardia (excluding atrial fibrillation and flutter) in a 1:1 ratio to undergo a modified Valsalva manoeuvre (done semi-recumbent with supine repositioning and passive leg raise immediately after the Valsalva strain), or a standard semi-recumbent Valsalva manoeuvre. A 40 mm Hg pressure, 15 s standardised strain was used in both groups. Randomisation, stratified by centre, was done centrally and independently, with allocation with serially numbered, opaque, sealed, tamper-evident envelopes. Patients and treating clinicians were not masked to allocation. The primary outcome was return to sinus rhythm at 1 min after intervention, determined by the treating clinician and electrocardiogram and confirmed by an investigator masked to treatment allocation. This study is registered with Current Controlled Trials (ISRCTN67937027). FINDINGS: We enrolled 433 participants between Jan 11, 2013, and Dec 29, 2014. Excluding second attendance by five participants, 214 participants in each group were included in the intention-to-treat analysis. 37 (17%) of 214 participants assigned to standard Valsalva manoeuvre achieved sinus rhythm compared with 93 (43%) of 214 in the modified Valsalva manoeuvre group (adjusted odds ratio 3·7 (95% CI 2·3-5·8; p<0·0001). We recorded no serious adverse events. INTERPRETATION: In patients with supraventricular tachycardia, a modified Valsalva manoeuvre with leg elevation and supine positioning at the end of the strain should be considered as a routine first treatment, and can be taught to patients. FUNDING: National Institute for Health Research.

PAin SoluTions In the Emergency Setting (PASTIES)--patient controlled analgesia versus routine care in emergency department patients with non-traumatic abdominal pain: randomised trial.

OBJECTIVE: To determine whether patient controlled analgesia (PCA) is better than routine care in providing effective analgesia for patients presenting to emergency departments with moderate to severe non-traumatic abdominal pain. DESIGN: Pragmatic, multicentre, parallel group, randomised controlled trial SETTING: Five English hospitals. PARTICIPANTS: 200 adults (66% (n=130) female), aged 18 to 75 years, who presented to the emergency department requiring intravenous opioid analgesia for the treatment of moderate to severe non-traumatic abdominal pain and were expected to be admitted to hospital for at least 12 hours. INTERVENTIONS: Patient controlled analgesia or nurse titrated analgesia (treatment as usual). MAIN OUTCOME MEASURES: The primary outcome was total pain experienced over the 12 hour study period, derived by standardised area under the curve (scaled from 0 to 100) of each participant's hourly pain scores, captured using a visual analogue scale. Pre-specified secondary outcomes included total morphine use, percentage of study period in moderate or severe pain, percentage of study period asleep, length of hospital stay, and satisfaction with pain management. RESULTS: 196 participants were included in the primary analyses (99 allocated to PCA and 97 to treatment as usual). Mean total pain experienced was 35.3 (SD 25.8) in the PCA group compared with 47.3 (24.7) in the treatment as usual group. The adjusted between group difference was 6.3 (95% confidence interval 0.7 to 11.9). Participants in the PCA group received significantly more morphine (mean 36.1 (SD 22.4) v 23.6 (13.1) mg; mean difference 12.3 (95% confidence interval 7.2 to 17.4) mg), spent less of the study period in moderate or severe pain (32.6% v 46.9%; mean difference 14.5% (5.6% to 23.5%)), and were more likely to be perfectly or very satisfied with the management of their pain (83% (73/88) v 66% (57/87); adjusted odds ratio 2.56 (1.25 to 5.23)) in comparison with participants in the treatment as usual group. CONCLUSIONS: Significant reductions in pain can be achieved by PCA compared with treatment as usual in patients presenting to the emergency department with non-traumatic abdominal pain. Trial registration European Clinical Trials Database EudraCT2011-000194-31; Current Controlled Trials ISRCTN25343280.

PAin SoluTions In the Emergency Setting (PASTIES)--patient controlled analgesia versus routine care in emergency department patients with pain from traumatic injuries: randomised trial.

OBJECTIVE: To determine whether patient controlled analgesia (PCA) is better than routine care in patients presenting to emergency departments with moderate to severe pain from traumatic injuries. DESIGN: Pragmatic, multicentre, parallel group, randomised controlled trial. SETTING: Five English hospitals. PARTICIPANTS: 200 adults (71% (n = 142) male), aged 18 to 75 years, who presented to the emergency department requiring intravenous opioid analgesia for the treatment of moderate to severe pain from traumatic injuries and were expected to be admitted to hospital for at least 12 hours. INTERVENTIONS: PCA (n = 99) or nurse titrated analgesia (treatment as usual; n = 101). MAIN OUTCOME MEASURES: The primary outcome was total pain experienced over the 12 hour study period, derived by standardised area under the curve (scaled from 0 to 100) of each participant's hourly pain scores, captured using a visual analogue scale. Pre-specified secondary outcomes included total morphine use, percentage of study period in moderate/severe pain, percentage of study period asleep, length of hospital stay, and satisfaction with pain management. RESULTS: 200 participants were included in the primary analyses. Mean total pain experienced was 47.2 (SD 21.9) for the treatment as usual group and 44.0 (24.0) for the PCA group. Adjusted analyses indicated slightly (but not statistically significantly) lower total pain experienced in the PCA group than in the routine care group (mean difference 2.7, 95% confidence interval -2.4 to 7.8). Participants allocated to PCA used more morphine in total than did participants in the treatment as usual group (mean 44.3 (23.2) v 27.2 (18.2) mg; mean difference 17.0, 11.3 to 22.7). PCA participants spent, on average, less time in moderate/severe pain (36.2% (31.0) v 44.1% (31.6)), but the difference was not statistically significant. A higher proportion of PCA participants reported being perfectly or very satisfied compared with the treatment as usual group (86% (78/91) v 76% (74/98)), but this was also not statistically significant. CONCLUSIONS: PCA provided no statistically significant reduction in pain compared with routine care for emergency department patients with traumatic injuries. Trial registration European Clinical Trials Database EudraCT2011-000194-31; Current Controlled Trials ISRCTN25343280.

Comparative assessment of alignment efficiency and space closure of active and passive self-ligating vs conventional appliances in adolescents: a single-center randomized controlled trial.

INTRODUCTION: The aim of this study was to compare the time to initial alignment and extraction space closure using conventional brackets and active and passive self-ligating brackets. METHODS: One hundred adolescent patients 11 to 18 years of age undergoing maxillary and mandibular fixed appliance therapy after the extraction of 4 premolars were randomized with stratification of 2 age ranges (11-14 and 15-18 years) and 3 maxillomandibular plane angles (high, medium, and low) with an allocation ratio of 1:2:2. Restrictions were applied using a block size of 10. Allocation was to 1 of 3 treatment groups: conventional brackets, active self-ligating, or passive self-ligating brackets. All subjects were treated with the same archwire sequence and space-closing mechanics in a district general hospital setting. The trial was a 3-arm parallel design. Labial-segment alignment and space closure were measured on study models taken every 12 weeks throughout treatment. All measurements were made by 1 operator who was blinded to bracket type. The patients and other operators were not blinded to bracket type during treatment. RESULTS: Ninety-eight patients were followed to completion of treatment (conventional, n = 20; active self-ligating brackets, n = 37; passive self-ligating brackets, n = 41). The data were analyzed using linear mixed models and demonstrated a significant effect of bracket type on the time to initial alignment (P = 0.001), which was shorter with the conventional brackets than either of the self-ligating brackets. Sidak's adjustment showed no significant difference in effect size (the difference in average response in millimeters) between the active and passive self-ligating brackets (the results are presented as effect size, 95% confidence intervals, probabilities, and intraclass correlation coefficients) (-0.42 [-1.32, 0.48], 0.600, 0.15), but the conventional bracket was significantly different from both of these (-1.98 [-3.19, -0.76], 0.001, 0.15; and -1.56 [-2.79, -0.32], 0.001, 0.15). There was no statistically significant difference between any of the 3 bracket types with respect to space closure. Space-closure times were shorter in the mandible, except for the Damon 3MX bracket (Ormco, Orange, Calif), where active and total space-closure times were shorter in the maxilla. No adverse events were recorded in the trial. CONCLUSIONS: Time to initial alignment was significantly shorter for the conventional bracket than for either the active or passive self-ligating brackets. There was no statistically significant difference in passive, active, or total space-closure times among the 3 brackets under investigation.

Randomised Evaluation of modified Valsalva Effectiveness in Re-entrant Tachycardias (REVERT) study.

INTRODUCTION: The Valsalva manoeuvre (VM) is a recommended first-line physical treatment for patients with re-entrant supraventricular tachycardia (SVT), but is often ineffective in standard practice. A failed VM is typically followed by treatment with intravenous adenosine, which patients often find unpleasant. VM effectiveness might be improved by a modification to posture which exaggerates the manoeuvre's vagal response and reduces the need for further emergency treatment. METHODS AND ANALYSIS: This is a multicentre randomised controlled clinical trial in 10 UK emergency departments (EDs). It compares a standard VM with a modified VM incorporating leg elevation and a supine posture after a standardised strain in stable adult patients presenting to the ED with SVT. The primary outcome measure is return to sinus rhythm on a 12-lead ECG. Secondary outcome measures include the need for treatment with adenosine or other antiarrhythmic treatments and the time patients spend in the ED. We plan to recruit approximately 372 patients, with 80% power to demonstrate an absolute improvement in cardioversion rate of 12%. An improvement of this magnitude through the use of a modified VM would be of significant benefit to patients and healthcare providers, and justify a change to standard practice. ETHICS AND DISSEMINATION: The study has been approved by the South West-Exeter Research Ethics Committee (REC reference 12/SW/0281). The trial will be published in an international peer reviewed journal. Study findings will be sent to the European and International resuscitation councils to inform future revisions of arrhythmia management guidelines. RESULTS: The trial will also be disseminated at international conferences and to patients through the Arrhythmia Alliance, a patient support charity. REGISTRATION: The study is registered with Current Controlled Trials (ISRCTN67937027) and has been adopted by the National Institute for Health Research (NIHR) Clinical Research Network.

PAin SoluTions In the Emergency Setting (PASTIES); a protocol for two open-label randomised trials of patient-controlled analgesia (PCA) versus routine care in the emergency department.

INTRODUCTION: Pain is the commonest reason that patients present to an emergency department (ED), but it is often not treated effectively. Patient controlled analgesia (PCA) is used in other hospital settings but there is little evidence to support its use in emergency patients. We describe two randomised trials aiming to compare PCA to nurse titrated analgesia (routine care) in adult patients who present to the ED requiring intravenous opioid analgesia for the treatment of moderate to severe pain and are subsequently admitted to hospital. METHODS AND ANALYSIS: Two prospective multi-centre open-label randomised trials of PCA versus routine care in emergency department patients who require intravenous opioid analgesia followed by admission to hospital; one trial involving patients with traumatic musculoskeletal injuries and the second involving patients with non-traumatic abdominal pain. In each trial, 200 participants will be randomised to receive either routine care or PCA, and followed for the first 12 h of their hospital stay. The primary outcome measure is hourly pain score recorded by the participant using a visual analogue scale (VAS) over the 12 h study period, with the primary statistical analyses based on the area under the curve of these pain scores. Secondary outcomes include total opioid use, side effects, time spent asleep, patient satisfaction, length of hospital stay and incremental cost effectiveness ratio. ETHICS AND DISSEMINATION: The study is approved by the South Central-Southampton A Research Ethics Committee (REC reference 11/SC/0151). Data collection will be completed by August 2013, with statistical analyses starting after all final data queries are resolved. Dissemination plans include presentations at local, national and international scientific meetings held by relevant Colleges and societies. Publications should be ready for submission during 2014. A lay summary of the results will be available to study participants on request, and disseminated via a publically accessible website. REGISTRATION DETAILS: The study is registered with the European Clinical Trials Database (EudraCT Number: 2011-000194-31) and is on the ISCRTN register (ISRCTN25343280).