Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial.

BACKGROUND: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. The use of immediate surgical fixation to manage this type of fracture has increased, despite insufficient evidence of improved outcomes over non-surgical management. The SWIFFT trial compared the clinical effectiveness of surgical fixation with cast immobilisation and early fixation of fractures that fail to unite in adults with scaphoid waist fractures displaced by 2 mm or less. METHODS: This pragmatic, parallel-group, multicentre, open-label, two-arm, randomised superiority trial included adults (aged 16 years or older) who presented to orthopaedic departments of 31 hospitals in England and Wales with a clear bicortical fracture of the scaphoid waist on radiographs. An independent remote randomisation service used a computer-generated allocation sequence with randomly varying block sizes to randomly assign participants (1:1) to receive either early surgical fixation (surgery group) or below-elbow cast immobilisation followed by immediate fixation if non-union of the fracture was confirmed (cast immobilisation group). Randomisation was stratified by whether or not there was displacement of either a step or a gap of 1-2 mm inclusive on any radiographic view. The primary outcome was the total patient-rated wrist evaluation (PRWE) score at 52 weeks after randomisation, and it was analysed on an available case intention-to-treat basis. This trial is registered with the ISRCTN registry, ISRCTN67901257, and is no longer recruiting, but long-term follow-up is ongoing. FINDINGS: Between July 23, 2013, and July 26, 2016, 439 (42%) of 1047 assessed patients (mean age 33 years; 363 [83%] men) were randomly assigned to the surgery group (n=219) or to the cast immobilisation group (n=220). Of these, 408 (93%) participants were included in the primary analysis (203 participants in the surgery group and 205 participants in the cast immobilisation group). 16 participants in the surgery group and 15 participants in the cast immobilisation group were excluded because of either withdrawal, no response, or no follow-up data at 6, 12, 26, or 52 weeks. There was no significant difference in mean PRWE scores at 52 weeks between the surgery group (adjusted mean 11·9 [95% CI 9·2-14·5]) and the cast immobilisation group (14·0 [11·3 to 16·6]; adjusted mean difference -2·1 [95% CI -5·8 to 1·6], p=0·27). More participants in the surgery group (31 [14%] of 219 participants) had a potentially serious complication from surgery than in the cast immobilisation group (three [1%] of 220 participants), but fewer participants in the surgery group (five [2%]) had cast-related complications than in the cast immobilisation group (40 [18%]). The number of participants who had a medical complication was similar between the two groups (four [2%] in the surgery group and five [2%] in the cast immobilisation group). INTERPRETATION: Adult patients with scaphoid waist fractures displaced by 2 mm or less should have initial cast immobilisation, and any suspected non-unions should be confirmed and immediately fixed with surgery. This treatment strategy will help to avoid the risks of surgery and mostly limit the use of surgery to fixing fractures that fail to unite. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Unloading shoes for intermittent claudication: a randomised crossover trial.

BACKGROUND: The purpose of this study was to assess the functional effects and acceptability of rocker-soled shoes that were designed to relatively "unload" the calf muscles during walking in people with calf claudication due to peripheral arterial disease. METHODS: In this randomised AB/BA crossover trial, participants completed two assessment visits up to two weeks apart. At each visit, participants completed walking tests whilst wearing the unloading shoes or visually-similar control shoes. At the end of the second visit, participants were given either the unloading or control shoes to use in their home environment for 2 weeks, with the instruction to wear them for at least 4 h every day. The primary outcome was 6-min walk distance. We also assessed pain-free walking distance and gait biomechanical variables during usual-pace walking, adverse events, and participants' opinions about the shoes. Data for continuous outcomes are presented as mean difference between conditions with corresponding 95% confidence interval. RESULTS: Thirty-four participants (27 males, mean age 68 years, mean ankle-brachial index 0.54) completed both assessment visits. On average, the 6-min walk distance was 11 m greater when participants wore the control shoes (95% CI -5 to 26), whereas mean pain-free walking distance was 7 m greater in the unloading shoes (95% CI -17 to 32). Neither of these differences were statistically significant (p = 0.18 and p = 0.55, respectively). This was despite the unloading shoes reducing peak ankle plantarflexion moment (mean difference 0.2 Nm/kg, 95% CI 0.0 to 0.3) and peak ankle power generation (mean difference 0.6 W/kg, 95% CI 0.2 to 1.0) during pain-free walking. The survey and interview data was mixed, with no clear differences between the unloading and control shoes. CONCLUSIONS: Shoes with modified soles to relatively unload the calf muscles during walking conferred no substantial acute functional benefit over control shoes. TRIAL REGISTRATION: Clinicaltrials.gov, Trial Registration Number: NCT02505503 , First registered 22 July 2015.

Smoking cessation in severe mental ill health: what works? an updated systematic review and meta-analysis.

BACKGROUND: People with severe mental ill health are more likely to smoke than those in the general population. It is therefore important that effective smoking cessation strategies are used to help people with severe mental ill health to stop smoking. This study aims to assess the effectiveness and cost -effectiveness of smoking cessation and reduction strategies in adults with severe mental ill health in both inpatient and outpatient settings. METHODS: This is an update of a previous systematic review. Electronic databases were searched during September 2016 for randomised controlled trials comparing smoking cessation interventions to each other, usual care, or placebo. Data was extracted on biochemically-verified, self-reported smoking cessation (primary outcome), as well as on smoking reduction, body weight, psychiatric symptom, and adverse events (secondary outcomes). RESULTS: We included 26 trials of pharmacological and/or behavioural interventions. Eight trials comparing bupropion to placebo were pooled showing that bupropion improved quit rates significantly in the medium and long term but not the short term (short term RR = 6.42 95% CI 0.82-50.07; medium term RR = 2.93 95% CI 1.61-5.34; long term RR = 3.04 95% CI 1.10-8.42). Five trials comparing varenicline to placebo showed that that the addition of varenicline improved quit rates significantly in the medium term (RR = 4.13 95% CI 1.36-12.53). The results from five trials of specialised smoking cessation programmes were pooled and showed no evidence of benefit in the medium (RR = 1.32 95% CI 0.85-2.06) or long term (RR = 1.33 95% CI 0.85-2.08). There was insufficient data to allowing pooling for all time points for varenicline and trials of specialist smoking cessation programmes. Trials suggest few adverse events although safety data were not always reported. Only one pilot study reported cost effectiveness data. CONCLUSIONS: Bupropion and varenicline, which have been shown to be effective in the general population, also work for people with severe mental ill health and their use in patients with stable psychiatric conditions. Despite good evidence for the effectiveness of smoking cessation interventions for people with severe mental ill health, the percentage of people with severe mental ill health who smoke remains higher than that for the general population.

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol: a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults.

BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013.

Cost-effectiveness of surgery versus cast immobilization for adults with a bicortical fracture of the scaphoid waist : an economic evaluation of the SWIFFT trial.

AIMS: The aim of the Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) was to determine the optimal treatment for adults with a bicortical undisplaced or minimally displaced fracture of the waist of the scaphoid, comparing early surgical fixation with initial cast immobilization, with immediate fixation being offered to patients with nonunion. METHODS: A cost-effectiveness analysis was conducted to assess the relative merits of these forms of treatment. The differences in costs to the healthcare system and quality-adjusted life years (QALYs) of the patients over the one-year follow-up of the trial in the two treatment arms were estimated using regression analysis. RESULTS: Our base case analysis found that patients randomized to early surgical fixation had statistically significantly higher mean costs to the NHS of £1,295 more than for the cast immobilization arm (p < 0.001), primarily due to the cost of surgery. They also had a marginally better quality of life, over the period, of 0.0158 QALYs; however, this was not statistically significant (p = 0.379). The mean combined cost per additional QALY was £81,962, well above the accepted threshold for cost-effectiveness used in the UK and internationally. The probability of early surgery being cost-effective in this setting was only 5.6%. CONCLUSION: Consistent with the clinical findings of SWIFFT, these results indicate that initial cast immobilization of minimally displaced scaphoid fractures, with immediate fixation only offered to patients with nonunion, is the optimal form of treatment, resulting in comparable outcomes with less cost to the healthcare system. Cite this article: Bone Joint J 2021;103-B(7):1277-1283.

An embedded randomised controlled retention trial of personalised text messages compared to non-personalised text messages in an orthopaedic setting.

Background: Several studies have investigated whether personalising trial documentation can aid recruitment and retention. We did a 'study within a trial' (SWAT) evaluating the effectiveness of a personalised text message compared to a non-personalised text message, on the retention rate in a large orthopaedic trial. Methods: The SWAT was embedded in the Knee Replacement Bandaging Study (KReBS) trial. The primary outcome was the proportion of 12-month questionnaires returned. Secondary outcomes were the proportion of questionnaires completed and time to questionnaire return. Binary data were analysed using logistic regression and time to return using Cox proportional hazards regression.  Odds ratios (OR) and hazard ratios (HR) are presented, with associated 95% confidence intervals (CI) and p-values. Results: In total, 1465 participants were included in the SWAT. In the personalised group, 644/723 (89.1%) of participants returned a questionnaire, compared to 654/742 (88.1%) in the non-personalised group. The absolute difference in return rate was 0.9% (95% CI: -2.3% to 4.2%; p=0.57). There was no evidence of a difference between the groups in the likelihood of returning a questionnaire (OR 1.09; 95% CI: 0.79 to 1.51; p=0.61), the likelihood of returning a complete questionnaire (OR 1.11; 95% CI: 0.82 to 1.51; p=0.50) nor in time to return (HR 1.05; 95% CI: 0.94 to 1.17; p=0.40). Conclusion: This SWAT adds to the growing evidence base for whether personalised text messages are effective. Registration: ISRCTN87127065 (20/02/2017); SWAT 35 (01/12/2015).

Frequency of anxiety after stroke: An updated systematic review and meta-analysis of observational studies.

BACKGROUND: Anxiety is a common and distressing problem after stroke. AIMS: To undertake an updated systematic review and meta-analysis of observational studies of anxiety after stroke and integrate the findings with those reported previously. SUMMARY OF REVIEW: Multiple databases were searched in May 2018 and 53 new studies were included following dual independent sifting and data extraction. These were combined with 44 previous studies to form a combined data set of 97 studies, comprising 22,262 participants. Studies using interview methods were of higher quality. Rates of anxiety by interview were 18.7% (95% confidence interval 12.5, 24.9%) and 24.2% (95% confidence interval 21.5, 26.9%) by rating scale. Rates of anxiety did not lower meaningfully up to 24 months after stroke. Eight different anxiety subtypes were also reported. CONCLUSIONS: This review confirms that anxiety occurs in around one in four patients (by rating scale) and one in five patients (by interview). More research on anxiety subtypes is needed for an informed understanding of its effects and the development of interventions.

Surgical fixation compared with cast immobilisation for adults with a bicortical fracture of the scaphoid waist: the SWIFFT RCT.

BACKGROUND: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. Immediate surgical fixation of this fracture has increased. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of surgical fixation with cast treatment and early fixation in adults with scaphoid waist fractures that fail to unite. DESIGN: Multicentre, pragmatic, open-label, parallel two-arm randomised controlled trial with an economic evaluation and a nested qualitative study. SETTING: Orthopaedic departments of 31 hospitals in England and Wales recruited from July 2013, with final follow-up in September 2017. PARTICIPANTS: Adults (aged ≥ 16 years) presenting within 2 weeks of injury with a clear, bicortical fracture of the scaphoid waist on plain radiographs. INTERVENTIONS: Early surgical fixation using Conformité Européenne-marked headless compression screws. Below-elbow cast immobilisation for 6-10 weeks and urgent fixation of confirmed non-union. MAIN OUTCOME MEASURES: The primary outcome and end point was the Patient-Rated Wrist Evaluation total score at 52 weeks, with a clinically relevant difference of 6 points. Secondary outcomes included Patient-Rated Wrist Evaluation pain and function subscales, Short Form questionnaire 12-items, bone union, range of movement, grip strength, complications and return to work. RESULTS: The mean age of 439 participants was 33 years; 363 participants were male (83%) and 269 participants had an undisplaced fracture (61%). The primary analysis was on 408 participants with valid Patient-Rated Wrist Evaluation outcome data for at least one post-randomisation time point (surgery, n = 203 of 219; cast, n = 205 of 220). There was no clinically relevant difference in the Patient-Rated Wrist Evaluation total score at 52 weeks: the mean score in the cast group was 14.0 (95% confidence interval 11.3 to 16.6) and in the surgery group was 11.9 (95% confidence interval 9.2 to 14.5), with an adjusted mean difference of -2.1 in favour of surgery (95% confidence interval -5.8 to 1.6; p = 0.27). The non-union rate was low (surgery group, n = 1; cast group, n = 4). Eight participants in the surgery group had a total of 11 reoperations and one participant in the cast group required a reoperation for non-union. The base-case economic analysis at 52 weeks found that surgery cost £1295 per patient more (95% confidence interval £1084 to £1504) than cast treatment. The base-case analysis of a lifetime-extrapolated model confirmed that the cast treatment pathway was more cost-effective. The nested qualitative study identified patients' desire to have a 'sense of recovering', which surgeons should address at the outset. LIMITATION: There were 17 participants who had initial cast treatment and surgery for confirmed non-union, which in 14 cases was within 6 months from randomisation and in three cases was after 6 months. Three of the four participants in the cast group who had a non-union at 52 weeks were not offered surgery. CONCLUSIONS: Adult patients with an undisplaced or minimally displaced scaphoid waist fracture should have cast immobilisation and suspected non-unions immediately confirmed and urgently fixed. Patients should be followed up at 5 years to investigate the effect of partial union, degenerative arthritis, malunion and screw problems on their quality of life. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67901257. 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. 24, No. 52. See the NIHR Journals Library website for further project information.

Fracture of the scaphoid bone (one of eight small bones in the wrist) is common in young active people. It is caused by a fall on the hand or the hand being suddenly forced backwards. The usual treatment is to rest the wrist in a plaster cast for 6­10 weeks and allow the broken bone to heal. In 1 in 10 cases in which the fracture is treated in a plaster cast, the bone does not heal and an operation is needed. In the operation, the broken bone is held still with a screw. In the last few years, it has become more common to fix the broken bone with a screw in the first few days after injury, instead of resting the wrist in a plaster cast. It is not clear if fixing the bone early with a screw, compared with resting the wrist in a cast, gives better outcomes for patients and if one treatment is better value for money for the NHS. In this study, 439 adult patients agreed either to have surgery to hold the broken scaphoid with a special screw or to have the wrist held still in a plaster cast (with surgery offered after 6 weeks to those who were still not healed). The decision about which treatment to use was made using randomisation, which is similar to tossing a coin. Patients reported their own wrist pain and function at 6, 12, 26 and 52 weeks. Information was also collected on general health, bone healing, grip strength and range of movement, complications from treatment and costs. No important differences were found in patients' wrist pain and function at 52 weeks. The bone did not heal properly in four patients in the surgery group or in nine patients in the plaster cast group at 52 weeks. For one of these patients in the surgery group and four of these patients in the plaster cast group, the bone did not join at all. Eight patients in the surgery group had further surgery following their initial operation to fix their wrist, and one patient in the cast group required repeated surgery because the bone did not join at all. The overall cost of treating with a plaster cast was lower than that of early surgery. Therefore, the findings of the study suggest that a plaster cast should be used initially and that the bone should be immediately fixed with a screw if it does not heal.

Knee Replacement Bandaging Study (KReBS) evaluating the effect of a two-layer compression bandage system on knee function following total knee arthroplasty: study protocol for a randomised controlled trial.

BACKGROUND: Data from a feasibility study suggest that the use of an inelastic, short-stretch compression bandage following total knee arthroplasty is a safe technique that may improve patient-reported health outcomes, and that it is feasible to recruit to a full-scale study. METHODS: We will conduct a randomised controlled trial (RCT) of 2600 adult patients, which has 80% power to detect a 1 point difference in the Oxford Knee Score (a patient self-reported assessment of knee pain and function) at 52 weeks. Short stretch compression bandaging will be compared with standard wool and crepe bandaging following total knee arthroplasty. Recruitment will take place in orthopaedic units across the United Kingdom. Secondary outcomes include the EuroQol 5 Dimensions (EQ-5D)-5 L and EQ-5D-3 L scores, pain, length of hospital stay, and complications. DISCUSSION: The Knee Replacement Bandaging Study (KReBS) is a large study which aims to contribute to the evidence base for informing clinical decisions for the use of compression bandaging following knee arthroplasty. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Register, ISRCTN 87127065 . Registered on 20 February 2017.

Three-curve rocker-soled shoes and gait adaptations to intermittent claudication pain: A randomised crossover trial.

BACKGROUND: Intermittent claudication (IC) is a symptom of peripheral arterial disease where a cramp-like leg pain is exhibited during walking, which affects gait and limits walking distance. Specifically-designed rocker-soled shoes were purported to mechanically unload the calf musculature and increase walking distances until IC pain. RESEARCH QUESTIONS: Do three-curve rocker-soled shoes increase walking distance and what are the biomechanical differences during pain-free walking and IC pain-induced walking, when compared with control shoes? METHODS: Following NHS ethical approval, 31 individuals with claudication (age 69 ± 10 years, stature 1.7 ± 0.9 m, mass 83.2 ± 16.2 kg, ankle-brachial pressure index 0.55 ± 0.14) were randomised in this cross-over trial. Gait parameters whilst walking with rocker-soled shoes were compared with control shoes at three intervals of pain-free walking, at onset of IC pain (initial claudication distance) and when IC intensifies and prevents them walking any further (absolute claudication distance). Two-way repeated measures ANOVA were performed on gait variables. RESULTS: When compared with control shoes, rocker-soled shoes reduced ankle power generation (mean 2.1 vs 1.6 W/kg, respectively; p = 0.006) and altered sagittal kinematics of the hip, knee and ankle. However, this did not translate to a significant increase in initial (138 m vs 146 m, respectively) or absolute (373 m vs 406 m, respectively) claudication distances. In response to IC pain, similar adaptations in temporal-spatial parameters and the sagittal kinematics were observed between the shoe types. SIGNIFICANCE: The three-curved rocker shoes, in their current design, do not augment gait sufficiently to enhance walking distance, when compared with control shoes, and therefore cannot be recommended for the intermittent claudication population. Clinical Reg No. (ClinicalTrials.gov): NCT02505503.

Remote or on-site visits were feasible for the initial setup meetings with hospitals in a multicenter surgical trial: an embedded randomized trial.

OBJECTIVES: To investigate the effects, costs, and feasibility of providing on-site compared with remote meetings to set up hospital sites in a multicenter, surgical randomized controlled trial. STUDY DESIGN AND SETTING: Hospitals were randomized to receive the initial trial setup meetings on-site (i.e., face-to-face) or remotely (i.e., via teleconference). Data were collected on site setup, recruitment, follow-up, and costs for the two methods. The hospital staff experience of trial setup was also surveyed. RESULTS: Thirty-nine sites were randomized and 33 sites set up to recruit (19 on-site and 14 remote). For sites randomized to an on-site meeting compared with remote meeting respectively, the time from first contact to the first recruit was a median of 246 days (interquartile range [IQR] 196-346] vs. 212 days (IQR 154-266), mean recruitment was 10 participants (median 10, IQR 2-17) vs. 11 participants (median 6, IQR 5-23), and participant follow-up at 12 months was 81% vs. 82%. Sites allocated to an initial on-site visit cost on average £289.83 more to setup. CONCLUSION: Remote or on-site visits are feasible for the initial setup meetings with hospitals in a multicenter surgical trial. This embedded trial should be replicated to improve generalizability and increase statistical power using meta-analysis. ISRCTN78899574.

AVURT: aspirin versus placebo for the treatment of venous leg ulcers - a Phase II pilot randomised controlled trial.

BACKGROUND: Venous leg ulcers (VLUs) are the most common cause of leg ulceration, affecting 1 in 100 adults. VLUs may take many months to heal (25% fail to heal). Estimated prevalence is between 1% and 3% of the elderly population. Compression is the mainstay of treatment and few additional therapies exist to improve healing. Two previous trials have indicated that low-dose aspirin, as an adjunct to standard care, may improve healing time, but these trials were insufficiently robust. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. OBJECTIVES: Primary objective - to assess the effects of 300 mg of aspirin (daily) versus placebo on the time to healing of the reference VLU. Secondary objectives - to assess the feasibility of leading into a larger pragmatic Phase III trial and the safety of aspirin in this population. DESIGN: A multicentred, pilot, Phase II randomised double-blind, parallel-group, placebo-controlled efficacy trial. SETTING: Community leg ulcer clinics or services, hospital outpatient clinics, leg ulcer clinics, tissue viability clinics and wound clinics in England, Wales and Scotland. PARTICIPANTS: Patients aged ≥ 18 years with a chronic VLU (i.e. the VLU is > 6 weeks in duration or the patient has a history of VLU) and who are not regularly taking aspirin. INTERVENTIONS: 300 mg of daily oral aspirin versus placebo. All patients were offered care in accordance with Scottish Intercollegiate Guidelines Network (SIGN) guidance with multicomponent compression therapy aiming to deliver 40 mmHg at the ankle when possible. RANDOMISATION: Participants were allocated in a 1 : 1 (aspirin : placebo) ratio by the Research Pharmacy, St George's University Hospitals NHS Foundation Trust, using a randomisation schedule generated in advance by the investigational medicinal product manufacturer. Randomisation was stratified according to ulcer size (≤ 5cm2 or > 5cm2). MAIN OUTCOME MEASURE: The primary outcome was time to healing of the largest eligible ulcer (reference ulcer). FEASIBILITY RESULTS ­ RECRUITMENT: 27 patients were recruited from eight sites over a period of 8 months. The target of 100 patients was not achieved and two sites did not recruit. Barriers to recruitment included a short recruitment window and a large proportion of participants failing to meet the eligibility criteria. RESULTS: The average age of the 27 randomised participants (placebo, n = 13; aspirin, n = 14) was 62 years (standard deviation 13 years), and two-thirds were male (n = 18). Participants had their reference ulcer for a median of 15 months, and the median size of ulcer was 17.1 cm2. There was no evidence of a difference in time to healing of the reference ulcer between groups in an adjusted analysis for log-ulcer area and duration (hazard ratio 0.58, 95% confidence interval 0.18 to 1.85; p = 0.357). One expected, related serious adverse event was recorded for a participant in the aspirin group. LIMITATIONS: The trial under-recruited because many patients did not meet the eligibility criteria. CONCLUSIONS: There was no evidence that aspirin was efficacious in hastening the healing of chronic VLUs. It can be concluded that a larger Phase III (effectiveness) trial would not be feasible. TRIAL REGISTRATION: Clinical Trials.gov NCT02333123; European Clinical Trials Database (EudraCT) 2014-003979-39. 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. 22, No. 55. See the NIHR Journals Library website for further project information.

The Completeness of Intervention Descriptions in Randomised Trials of Supervised Exercise Training in Peripheral Arterial Disease.

Research supports the use of supervised exercise training as a primary therapy for improving the functional status of people with peripheral arterial disease (PAD). Several reviews have focused on reporting the outcomes of exercise interventions, but none have critically examined the quality of intervention reporting. Adequate reporting of the exercise protocols used in randomised controlled trials (RCTs) is central to interpreting study findings and translating effective interventions into practice. The purpose of this review was to evaluate the completeness of intervention descriptions in RCTs of supervised exercise training in people with PAD. A systematic search strategy was used to identify relevant trials published until June 2015. Intervention description completeness in the main trial publication was assessed using the Template for Intervention Description and Replication checklist. Missing intervention details were then sought from additional published material and by emailing authors. Fifty-eight trials were included, reporting on 76 interventions. Within publications, none of the interventions were sufficiently described for all of the items required for replication; this increased to 24 (32%) after contacting authors. Although programme duration, and session frequency and duration were well-reported in publications, complete descriptions of the equipment used, intervention provider, and number of participants per session were missing for three quarters or more of interventions (missing for 75%, 93% and 80% of interventions, respectively). Furthermore, 20%, 24% and 26% of interventions were not sufficiently described for the mode of exercise, intensity of exercise, and tailoring/progression, respectively. Information on intervention adherence/fidelity was also frequently missing: attendance rates were adequately described for 29 (38%) interventions, whereas sufficient detail about the intensity of exercise performed was presented for only 8 (11%) interventions. Important intervention details are commonly missing for supervised exercise programmes in the PAD trial literature. This has implications for the interpretation of outcome data, the investigation of dose-response effects, and the replication of protocols in future studies and clinical practice. Researchers should be mindful of intervention reporting guidelines when attempting to publish information about supervised exercise programmes, regardless of the population being studied.

"Away Days" in multicenter randomized controlled trials: a questionnaire survey of their use and a case study on the effect of one Away Day on patient recruitment.

OBJECTIVE: "Away Days" (trial promotion and training events for trial site personnel) are a well-established method used by trialists to encourage engagement of research sites in the recruitment of patients to multicenter randomized controlled trials (RCTs). We explored the use of Away Days in multicenter RCTs and analyzed the effect on patient recruitment in a case study. METHODS: Members of the United Kingdom Trial Managers' Network were surveyed in June 2013 to investigate their experiences in the design and conduct of Away Days in RCTs. We used data from a multicenter pragmatic surgical trial to explore the effects of an Away Day on the screening and recruitment of patients. RESULTS: A total of 94 people responded to the survey. The majority (78%), who confirmed had organized an Away Day previously, found them to be useful. This is despite their costs. There was no evidence, however, from the analysis of data from a surgical trial that attendance at an Away Day increased the number of patients screened or recruited at participating sites. CONCLUSIONS: Although those responsible for managing RCTs in the UK tend to believe that trial Away Days are beneficial, evidence from a multicenter surgical trial shows no improvement on a key indicator of trial success. This points to the need to carefully consider the aims, design, and conduct of Away Days. Further more rigorous research nested within RCTs would be valuable to evaluate the design and conduct of Away Days.

Social Stories in mainstream schools for children with autism spectrum disorder: a feasibility randomised controlled trial.

OBJECTIVES: To assess the feasibility of recruitment, retention, outcome measures and intervention training/delivery among teachers, parents and children. To calculate a sample size estimation for full trial. DESIGN: A single-centre, unblinded, cluster feasibility randomised controlled trial examining Social Stories delivered within a school environment compared with an attentional control. SETTING: 37 primary schools in York, UK. PARTICIPANTS: 50 participants were recruited and a cluster randomisation approach by school was examined. Participants were randomised into the treatment group (n=23) or a waiting list control group (n=27). OUTCOME MEASURES: Acceptability and feasibility of the trial, intervention and of measurements required to assess outcomes in a definitive trial. RESULTS: An assessment of the questionnaire completion rates indicated teachers would be most appropriate to complete the primary outcome measure. 2 outcome measures: the Social Responsiveness Scale (SRS)-2 and a goal-based measure showed both the highest levels of completion rates (above 80%) at the primary follow-up point (6 weeks postintervention) and captured relevant social and behaviour outcomes. Power calculations were based on these 2 outcome measures leading to a total proposed sample size of 180 participant groups. CONCLUSIONS: Results suggest that a future trial would be feasible to conduct and could inform the policy and practice of using Social Stories in mainstream schools. TRIAL REGISTRATION NUMBER: ISRCTN96286707; Results.

The use of unequal randomisation in clinical trials--An update.

OBJECTIVE: To update a 2005 review of the reasons researchers have given for the use of unequal randomisation in randomised controlled trials (RCTs). MAIN MEASURES: Intervention being tested; type of study; number of participants; randomisation ratio; sample size calculation and reason given for using unequal randomisation. METHODS: Review of trials using unequal randomisation. DATABASES AND SOURCES: Cochrane library, Medline and CINAHL. RESULTS: A total of 86 trials were identified. Of these 82 trials (95%) recruited patients in favour of the experimental group. Various reasons for the use of unequal randomisation were given including: gaining treatment experience; identification of adverse events; ethical; logistic and enhancing recruitment. No trial reported explicitly used it for cost-effectiveness. Most of the papers (i.e. 47, 55%) did not state why they had used unequal randomisation and only 38 trials (44%) appeared to have taken the unequal randomisation into account in their sample size calculation. CONCLUSION: Most studies did not mention the rationale for unequal allocation, and a significant proportion did not appear to account for it in the sample size calculations. Unlike the previous review economic considerations were not stated as a rationale for its use. A number of trials used it to enhance recruitment, although this has not been tested.

Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial.

BACKGROUND: Venous leg ulcers (VLUs) are the commonest cause of leg ulceration, affecting 1 in 100 adults. There is a significant health burden associated with VLUs - it is estimated that the cost of treatment for 1 ulcer is up to £1300 per year in the NHS. The mainstay of treatment is with graduated compression bandaging; however, treatment is often prolonged and up to one quarter of venous leg ulcers do not heal despite standard care. Two previous trials have suggested that low-dose aspirin, as an adjunct to standard care, may hasten healing, but these trials were small and of poor quality. Aspirin is an inexpensive, widely used medication but its safety and efficacy in the treatment of VLUs remains to be established. METHODS/DESIGN: AVURT is a phase II randomised double blind, parallel-group, placebo-controlled efficacy trial. The primary objective is to examine whether aspirin, in addition to standard care, is effective in patients with chronic VLUs (i.e. over 6 weeks in duration or a history of VLU). Secondary objectives include feasibility and safety of aspirin in this population. A target of 100 participants, identified from community leg ulcer clinics and hospital clinics, will be randomised to receive either 300 mg of aspirin once daily or placebo. All participants will receive standard care with compression therapy. The primary outcome will be time to healing of the reference ulcer. Follow-up will occur for a maximum of 27 weeks. The primary analysis will use a Cox proportional hazards model to compare time to healing using the principles of intention-to-treat. Secondary outcomes will include ulcer size, pain evaluation, compliance and adverse events. DISCUSSION: The AVURT trial will investigate the efficacy and safety of aspirin as a treatment for VLU and will inform on the feasibility of proceeding to a larger phase III study. This study will address the paucity of information currently available regarding aspirin therapy to treat VLU. TRIAL REGISTRATION: The study is registered on a public database with clinicaltrials.gov ( NCT02333123 ; registered on 5 November 2014).

Autism Spectrum Social Stories In Schools Trial (ASSSIST): study protocol for a feasibility randomised controlled trial analysing clinical and cost-effectiveness of Social Stories in mainstream schools.

INTRODUCTION: Current evidence suggests that Social Stories can be effective in tackling problem behaviours exhibited by children with autism spectrum disorder. Exploring the meaning of behaviour from a child's perspective allows stories to provide social information that is tailored to their needs. Case reports in children with autism have suggested that these stories can lead to a number of benefits including improvements in social interactions and choice making in educational settings. METHODS AND ANALYSIS: The feasibility of clinical and cost-effectiveness of a Social Stories toolkit will be assessed using a randomised control framework. Participants (n=50) will be randomised to either the Social Stories intervention or a comparator group where they will be read standard stories for an equivalent amount of time. Statistics will be calculated for recruitment rates, follow-up rates and attrition. Economic analysis will determine appropriate measures of generic health and resource use categories for cost-effectiveness analysis. Qualitative analysis will ascertain information on perceptions about the feasibility and acceptability of the intervention. ETHICS AND DISSEMINATION: National Health Service Ethics Approval (NHS; ref 11/YH/0340) for the trial protocol has been obtained along with NHS Research and Development permission from Leeds and York Partnership NHS Foundation Trust. All adverse events will be closely monitored, documented and reported to the study Data Monitoring Ethics Committee. At least one article in a peer reviewed journal will be published and research findings presented at relevant conferences. TRIAL REGISTRATION NUMBER: ISRCTN96286707.

A pilot investigation of the Graduated Recovery Intervention Program (GRIP) for first episode psychosis.

The Graduated Recovery Intervention Program (GRIP) is a new individual cognitive-behavioral therapy program designed to facilitate functional recovery in people who have experienced an initial episode of psychosis. The purposes of this study were to evaluate the feasibility and tolerability of the GRIP intervention, and to compare the effectiveness of GRIP versus treatment as usual (TAU) for improving specific clinical and psychosocial outcomes. Forty-six individuals with first episode psychosis were randomized to GRIP+TAU or TAU alone. Primary outcomes focused on social and role functioning, and quality of life. Secondary outcomes included psychotic symptoms, depression, substance use, social support, attitudes toward medications, well-being, and hospitalizations. The results indicate that GRIP was well-tolerated, as evidenced by good attendance and low drop-out rates, and well-received (based on positive feedback from participants). Although the majority of mixed model analyses were not statistically significant, examination of within-group changes and effect sizes suggests an advantage for GRIP over TAU in improving functional outcomes. These advantages and the fact that the GRIP intervention demonstrated feasibility and tolerability suggest that this intervention is worthy of further investigation.