Yoga for older adults with multimorbidity (the Gentle Years Yoga Trial): study protocol for a randomised controlled trial.

BACKGROUND: Multimorbidity is common in older adults and associated with high levels of illness burden and healthcare expenditure. The evidence base for how to manage older adults with multimorbidity is weak. Yoga might be a useful intervention because it has the potential to improve health-related quality of life, physical functioning, and several medical conditions. The British Wheel of Yoga's Gentle Years Yoga© (GYY) programme was developed specifically for older adults, including those with chronic medical conditions. Data from a pilot trial suggested feasibility of using GYY in this population, but its effectiveness and cost-effectiveness remain uncertain. METHODS: This is a multi-site, individually randomised, superiority trial with an embedded process evaluation and an economic analysis of cost-effectiveness. The trial will compare an experimental strategy of offering a 12-week GYY programme against a control strategy of no offer in community-dwelling adults aged 65 or over who have multimorbidity, defined as having two or more chronic conditions from a predefined list. The primary outcome is health-related quality of life measured using the EQ-5D-5L, the primary endpoint being the overall difference over 12 months. Both groups will continue to be able to access their usual care from primary, secondary, community, and social services. Participants, care providers, and yoga teachers will not be blinded to the allocated intervention. Outcome measures are primarily self-reported. The analysis will follow intention-to-treat principles. DISCUSSION: This pragmatic randomised controlled trial will demonstrate if the GYY programme is an effective, cost-effective, and viable addition to the management of older adults with multimorbidity. TRIAL REGISTRATION: ISRCTN ISRCTN13567538 . Registered on 18 March 2019.

A 2x2 randomised factorial SWAT of the use of a pen and small, financial incentive to improve recruitment in a randomised controlled trial of yoga for older adults with multimorbidity.

Background: Monetary and other incentives may increase recruitment to randomised controlled trials. Methods: This was a 2x2 factorial 'study within a trial' of including a pen and/or £5 with a postal recruitment pack to improve randomisation rate (primary outcome) into the host Gentle Years Yoga trial in older adults with multimorbidity. Secondary outcomes: return, and time to return, of screening form, and the cost per additional participant recruited. Binary data were analysed using logistic regression and time to return data using Cox proportional hazards regression.  Results: 818 potential host trial participants included. Between those sent a pen (n=409) and not sent a pen (n=409), there was no evidence of a difference in the likelihood of being randomised (15 (3.7%) versus 11 (2.7%); OR 1.38, 95% CI 0.63-3.04), in returning a screening form (66 (16.1%) versus 61 (14.9%); OR 1.10, 95% CI 0.75-1.61) nor in time to return the screening form (HR 1.09, 95% CI 0.77-1.55). There was evidence of improved screening return rates (77 (18.8%) versus 50 (12.2%); OR 1.67, 95% CI 1.13-2.45) and time to return screening form (HR 1.56, 95% CI 1.09-2.22) but not randomisation (14 (3.4%) versus 12 (2.9%); OR 1.18, 95% CI 0.54-2.57) in those sent £5 (n=409) compared with those not sent £5 (n=409). No significant interaction effects between the interventions were observed. The cost per additional participant recruited was £32 for the pen and £1000 for the £5 incentive. Conclusion: Including a small, monetary incentive encouraged increased and faster response to the recruitment invitation but did not result in more participants being randomised into the host trial. Since it is relatively costly, we do not recommend this intervention for use to increase recruitment in this population. Pens are cheaper but did not provide evidence of benefit. Further studies may be required.

Baseline testing in cluster randomised controlled trials: should this be done?

BACKGROUND: Comparisons of baseline covariates in randomised controlled trials whilst often undertaken is regarded by many as an exercise in futility. Because of randomisation the null hypothesis is true for baseline comparisons and therefore any differences will occur by chance. However, this is only the case if allocations are not known in advance of recruitment. If this occurs then selection bias at randomisation may be present and it is possible that the statistical testing of covariates may unveil selection bias. In this paper we show that this is particularly the case for cluster randomised trials when post-randomised recruitment often occurs and can lead to selection bias. MAIN TEXT: We take a recently published cluster randomised trial that has suffered from selection bias due to differential recruitment and calculate baseline p values. We show that statistically significant imbalances of p < 0.0001 occurred in 5 of the 10 covariates. In comparison for an individually randomised trial that had no evidence of selection bias only 1 p value of p < 0.05 out of 20 tests was observed. Had baseline p values for the cluster trial been presented to journal editors, reviewers and readers then the results of the trial might have been treated with more caution. CONCLUSION: We argue that the blanket ban of baseline testing as advocated by some may reduce the chance of identifying deficient cluster randomised trials and this opposition should be reconsidered for cluster trials.

United Kingdom Frozen Shoulder Trial (UK FROST), multi-centre, randomised, 12 month, parallel group, superiority study to compare the clinical and cost-effectiveness of Early Structured Physiotherapy versus manipulation under anaesthesia versus arthroscopic capsular release for patients referred to secondary care with a primary frozen shoulder: study protocol for a randomised controlled trial.

BACKGROUND: Frozen shoulder (also known as adhesive capsulitis) occurs when the capsule, or the soft tissue envelope around the ball and socket shoulder joint, becomes scarred and contracted, making the shoulder tight, painful and stiff. It affects around 1 in 12 men and 1 in 10 women of working age. Although this condition can settle with time (typically taking 1 to 3 years), for some people it causes severe symptoms and needs referral to hospital. Our aim is to evaluate the clinical and cost-effectiveness of two invasive and costly surgical interventions that are commonly used in secondary care in the National Health Service (NHS) compared with a non-surgical comparator of Early Structured Physiotherapy. METHODS: We will conduct a randomised controlled trial (RCT) of 500 adult patients with a clinical diagnosis of frozen shoulder, and who have radiographs that exclude other pathology. Early Structured Physiotherapy with an intra-articular steroid injection will be compared with manipulation under anaesthesia with a steroid injection or arthroscopic (keyhole) capsular release followed by manipulation. Both surgical interventions will be followed with a programme of post-procedural physiotherapy. These treatments will be undertaken in NHS hospitals across the United Kingdom. The primary outcome and endpoint will be the Oxford Shoulder Score (a patient self-reported assessment of shoulder function) at 12 months. This will also be measured at baseline, 3 and 6 months after randomisation; and on the day that treatment starts and 6 months later. Secondary outcomes include the Disabilities of Arm Shoulder and Hand (QuickDASH) score, the EQ-5D-5 L score, pain, extent of recovery and complications. We will explore the acceptability of the different treatments to patients and health care professionals using qualitative methods. DISCUSSION: The three treatments being compared are the most frequently used in secondary care in the NHS, but there is uncertainty about which one works best and at what cost. UK FROST is a rigorously designed and adequately powered study to inform clinical decisions for the treatment of this common condition in adults. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Register, ID: ISRCTN48804508 . Registered on 25 July 2014.

An economic evaluation of Alexander Technique lessons or acupuncture sessions for patients with chronic neck pain: A randomized trial (ATLAS).

OBJECTIVES: To assess the cost-effectiveness of acupuncture and usual care, and Alexander Technique lessons and usual care, compared with usual GP care alone for chronic neck pain patients. METHODS: An economic evaluation was undertaken alongside the ATLAS trial, taking both NHS and wider societal viewpoints. Participants were offered up to twelve acupuncture sessions or twenty Alexander lessons (equivalent overall contact time). Costs were in pounds sterling. Effectiveness was measured using the generic EQ-5D to calculate quality adjusted life years (QALYs), as well as using a specific neck pain measure-the Northwick Park Neck Pain Questionnaire (NPQ). RESULTS: In the base case analysis, incremental QALY gains were 0.032 and 0.025 in the acupuncture and Alexander groups, respectively, in comparison to usual GP care, indicating moderate health benefits for both interventions. Incremental costs were £451 for acupuncture and £667 for Alexander, mainly driven by intervention costs. Acupuncture was likely to be cost-effective (ICER = £18,767/QALY bootstrapped 95% CI £4,426 to £74,562) and was robust to most sensitivity analyses. Alexander lessons were not cost-effective at the lower NICE threshold of £20,000/QALY (£25,101/QALY bootstrapped 95% CI -£150,208 to £248,697) but may be at £30,000/QALY, however, there was considerable statistical uncertainty in all tested scenarios. CONCLUSIONS: In comparison with usual care, acupuncture is likely to be cost-effective for chronic neck pain, whereas, largely due to higher intervention costs, Alexander lessons are unlikely to be cost-effective. However, there were high levels of missing data and further research is needed to assess the long-term cost-effectiveness of these interventions.

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.

Text message reminders to improve questionnaire response rates.

OBJECTIVES: To assess whether short message service (SMS) text messages sent as prenotification or postnotification reminders improve questionnaire response rates in randomized controlled trial (RCT) follow-up. STUDY DESIGN AND SETTING: Three "trials within a trial" assessed text message notifications sent before or after receipt of a follow-up questionnaire within an RCT for patients with depression. Consenting patients (n = 523) were randomized to receive a prenotification or no notification at 3 months, prenotification or postnotification at 6 months, and a postnotification or no notification at 12-month follow-up. Unadjusted and adjusted questionnaire return rates and time to return were compared. RESULTS: The two trials comparing prenotification or postnotification with no notification at 3- and 9-month follow-up found no evidence of an effect on questionnaire response rates (3-month response rate: 82.9% vs. 84.7% (difference 1.79%, 95% confidence interval [CI] -4.53% to 8.11%, P = 0.58); 9-month response rate: 77.1% vs. 78.5% (difference = -1.44%, 95% CI -8.56% to 5.67%, P = 0.69). For the trial at 6-month follow-up, there was a statistically significant difference in response rates for postnotification (83.2%) compared with prenotification (75.2%), (difference 7.95%, 95% CI 1.00% to 14.91%, P = 0.02). CONCLUSION: SMS as a prenotification device seems ineffective. For postnotification, the evidence is unclear.

Alexander Technique Lessons or Acupuncture Sessions for Persons With Chronic Neck Pain: A Randomized Trial.

BACKGROUND: Management of chronic neck pain may benefit from additional active self-care-oriented approaches. OBJECTIVE: To evaluate clinical effectiveness of Alexander Technique lessons or acupuncture versus usual care for persons with chronic, nonspecific neck pain. DESIGN: Three-group randomized, controlled trial. (Current Controlled Trials: ISRCTN15186354). SETTING: U.K. primary care. PARTICIPANTS: Persons with neck pain lasting at least 3 months, a score of at least 28% on the Northwick Park Questionnaire (NPQ) for neck pain and associated disability, and no serious underlying pathology. INTERVENTION: 12 acupuncture sessions or 20 one-to-one Alexander lessons (both 600 minutes total) plus usual care versus usual care alone. MEASUREMENTS: NPQ score (primary outcome) at 0, 3, 6, and 12 months (primary end point) and Chronic Pain Self-Efficacy Scale score, quality of life, and adverse events (secondary outcomes). RESULTS: 517 patients were recruited, and the median duration of neck pain was 6 years. Mean attendance was 10 acupuncture sessions and 14 Alexander lessons. Between-group reductions in NPQ score at 12 months versus usual care were 3.92 percentage points for acupuncture (95% CI, 0.97 to 6.87 percentage points) (P = 0.009) and 3.79 percentage points for Alexander lessons (CI, 0.91 to 6.66 percentage points) (P = 0.010). The 12-month reductions in NPQ score from baseline were 32% for acupuncture and 31% for Alexander lessons. Participant self-efficacy improved for both interventions versus usual care at 6 months (P < 0.001) and was significantly associated (P < 0.001) with 12-month NPQ score reductions (acupuncture, 3.34 percentage points [CI, 2.31 to 4.38 percentage points]; Alexander lessons, 3.33 percentage points [CI, 2.22 to 4.44 percentage points]). No reported serious adverse events were considered probably or definitely related to either intervention. LIMITATION: Practitioners belonged to the 2 main U.K.-based professional associations, which may limit generalizability of the findings. CONCLUSION: Acupuncture sessions and Alexander Technique lessons both led to significant reductions in neck pain and associated disability compared with usual care at 12 months. Enhanced self-efficacy may partially explain why longer-term benefits were sustained. PRIMARY FUNDING SOURCE: Arthritis Research UK.

A randomised controlled trial of three or one breathing technique training sessions for breathlessness in people with malignant lung disease.

BACKGROUND: About 90 % of patients with intra-thoracic malignancy experience breathlessness. Breathing training is helpful, but it is unknown whether repeated sessions are needed. The present study aims to test whether three sessions are better than one for breathlessness in this population. METHODS: This is a multi-centre randomised controlled non-blinded parallel arm trial. Participants were allocated to three sessions or single (1:2 ratio) using central computer-generated block randomisation by an independent Trials Unit and stratified for centre. The setting was respiratory, oncology or palliative care clinics at eight UK centres. Inclusion criteria were people with intrathoracic cancer and refractory breathlessness, expected prognosis ≥3 months, and no prior experience of breathing training. The trial intervention was a complex breathlessness intervention (breathing training, anxiety management, relaxation, pacing, and prioritisation) delivered over three hour-long sessions at weekly intervals, or during a single hour-long session. The main primary outcome was worst breathlessness over the previous 24 hours ('worst'), by numerical rating scale (0 = none; 10 = worst imaginable). Our primary analysis was area under the curve (AUC) 'worst' from baseline to 4 weeks. All analyses were by intention to treat. RESULTS: Between April 2011 and October 2013, 156 consenting participants were randomised (52 three; 104 single). Overall, the 'worst' score reduced from 6.81 (SD, 1.89) to 5.84 (2.39). Primary analysis [n = 124 (79 %)], showed no between-arm difference in the AUC: three sessions 22.86 (7.12) vs single session 22.58 (7.10); P value = 0.83); mean difference 0.2, 95 % CIs (-2.31 to 2.97). Complete case analysis showed a non-significant reduction in QALYs with three sessions (mean difference -0.006, 95 % CIs -0.018 to 0.006). Sensitivity analyses found similar results. The probability of the single session being cost-effective (threshold value of £20,000 per QALY) was over 80 %. CONCLUSIONS: There was no evidence that three sessions conferred additional benefits, including cost-effectiveness, over one. A single session of breathing training seems appropriate and minimises patient burden. TRIAL REGISTRATION: Registry: ISRCTN; TRIAL REGISTRATION NUMBER: ISRCTN49387307; http://www.isrctn.com/ISRCTN49387307 ; registration date: 25/01/2011.

Feasibility, acceptability and validity of SMS text messaging for measuring change in depression during a randomised controlled trial.

BACKGROUND: Despite widespread popularity, text messaging has rarely been used for data collection in clinical research. This paper reports on the development, feasibility, acceptability, validity, and discriminant utility of a single item depression rating scale, delivered weekly via an automated SMS system, as part of a large randomised controlled trial. METHODS: 755 depressed patients (BDI-II score ≥20) were recruited from primary care into a randomised trial of acupuncture versus counselling or usual care, and invited to opt into a repeated-measures text messaging sub-study. Two weeks following random allocation, trial participants were sent a weekly text message for 15 weeks. Texts were a single question asking, on a scale from 1 to 9, the extent to which they felt depressed. Feasibility and acceptability of the automated SMS system were evaluated according to cost, ease of implementation, proportion consenting, response rates, and qualitative feedback. Concurrent validity was estimated by correlating SMS responses with the Patient Health Questionnaire (PHQ-9). SMS responses were compared between groups over time to explore treatment effects. RESULTS: 527 (69.8%) trial participants consented to the texting sub-study, of whom 498 (94.5%) responded to at least one message. Participants provided a valid response to an average of 12.5 messages. Invalid responses accounted for 1.1% of texts. The automated SMS system was quick to set-up, inexpensive, and well received. Comparison of PHQ-9 and SMS responses at 3 months demonstrated a moderate to high degree of agreement (Kendall's tau-b = 0.57, p < 0.0001, n = 220). SMS depression scores over the 15 weeks differed significantly between trial arms (p = 0.007), with participants allocated to the acupuncture and counselling arms reporting improved depression outcomes compared to usual GP care alone, which reached statistical significance ten weeks after randomisation. Overall, the single item SMS scale also appeared more responsive to changes in depression, resulting from treatment, than the PHQ-9. CONCLUSIONS: Automated SMS systems offer a feasible and acceptable means of monitoring depression within clinical research. This study provides clear evidence to support the regular use of a simple SMS scale as a sensitive and valid outcome measure of depression within future randomised controlled trials. TRIAL REGISTRATION: Current Controlled Trials - ISRCTN63787732 http://www.controlled-trials.com/ISRCTN63787732/ACUDEP Date of registration: 15/12/2009.

Cost-effectiveness analysis of acupuncture, counselling and usual care in treating patients with depression: the results of the ACUDep trial.

BACKGROUND: New evidence on the clinical effectiveness of acupuncture plus usual care (acupuncture) and counselling plus usual care (counselling) for patients with depression suggests the need to investigate the health-related quality of life and costs of these treatments to understand whether they should be considered a good use of limited health resources. METHODS AND FINDINGS: The cost-effectiveness analyses are based on the Acupuncture, Counselling or Usual care for Depression (ACUDep) trial results. Statistical analyses demonstrate a difference in mean quality adjusted life years (QALYs) and suggest differences in mean costs which are mainly due to the price of the interventions. Probabilistic sensitivity analysis is used to express decision uncertainty. Acupuncture and counselling are found to have higher mean QALYs and costs than usual care. In the base case analysis acupuncture has an incremental cost-effectiveness ratio (ICER) of £4,560 per additional QALY and is cost-effective with a probability of 0.62 at a cost-effectiveness threshold of £20,000 per QALY. Counselling compared with acupuncture is more effective and more costly with an ICER of £71,757 and a probability of being cost-effective of 0.36. A scenario analysis of counselling versus usual care, excluding acupuncture as a comparator, results in an ICER of £7,935 and a probability of 0.91. CONCLUSIONS: Acupuncture is cost-effective compared with counselling or usual care alone, although the ranking of counselling and acupuncture depends on the relative cost of delivering these interventions. For patients in whom acupuncture is unavailable or perhaps inappropriate, counselling has an ICER less than most cost-effectiveness thresholds. However, further research is needed to determine the most cost-effective treatment pathways for depressed patients when the full range of available interventions is considered.

Short message service text messaging was feasible as a tool for data collection in a trial of treatment for irritable bowel syndrome.

OBJECTIVES: To examine the feasibility of collecting data relating to irritable bowel syndrome (IBS), symptoms by short message service (SMS) text and explore the data to assess its usefulness. STUDY DESIGN AND SETTING: In a randomized parallel group design substudy, 59 consenting participants recruited from primary care to a trial of acupuncture for IBS (ISRCTN 08827905) were randomized to receive a one-question SMS message at either 9:30 am or at 6:30 pm for 7 days: "On a scale of 0-9, with 0 being no symptoms and 9 being the worst symptoms you could have, how would you score your IBS symptoms now? Please text back a single number." RESULTS: Of the total messages, 59% (n = 203) were answered within 15 minutes, 73.4% (n = 254) within 1 hour, and 97% (n = 334) within 10 hours. Response rates to evening texts were higher (93.5% vs. 87.6% P = 0.05) and response times shorter though not significantly (median: 0 vs. 5 hours; P = 0.12). There was no difference in mean scores, and morning symptoms varied more. Mean scores correlated significantly with IBS trial primary outcome measure, the IBS symptom severity score, and secondary outcome measures. CONCLUSION: Among IBS trial participants, data collection by SMS is feasible and acceptable, and there is potential for deriving meaningful data from the scores.

Randomized cohort trial was shown to be feasible for evaluating treatments in low back pain.

OBJECTIVE: To investigate the feasibility of conducting a cohort, factorial randomized controlled trial (RCT) in the treatment of patients with low back pain (LBP). STUDY DESIGN AND SETTING: Pragmatic feasibility factorial RCT nested within an observational cohort study in two general practices in York, United Kingdom. RESULTS: Eight hundred forty-five patients aged between 18 and 65 years who had consulted their general practitioner about LBP within the preceding 12 months were mailed an invitation to participate in a cohort trial, with the possibility of later joining a treatment RCT. One hundred twenty-four patients consented to participate in the cohort and treatment trial, and one consented only to the cohort only. Ultimately, 59 patients were randomized into the nested RCT. Outcomes included recruitment, acceptability, and attrition rates as measures of the feasibility of the design and Roland Morris Disability Questionnaire. No statistically significant differences in outcome between treatment groups and usual care were found. CONCLUSIONS: The design was feasible for the evaluation of different back pain treatments. We found zero attrition after randomization and showed that for a remitting relapsing condition, the design allows us to recruit initially ineligible patients from the cohort. Additional statistical analysis using regression discontinuity can also be used with this design.

Clinical and cost-effectiveness of compression hosiery versus compression bandages in treatment of venous leg ulcers (Venous leg Ulcer Study IV, VenUS IV): a randomised controlled trial.

BACKGROUND: Drawbacks exist with the standard treatment (four-layer compression bandages) for venous leg ulcers. We have therefore compared the clinical effectiveness and cost-effectiveness of two-layer compression hosiery with the four-layer bandage for the treatment of such ulcers. METHODS: We undertook this pragmatic, open, randomised controlled trial with two parallel groups in 34 centres in England and Northern Ireland. The centres were community nurse teams or services, family doctor practices, leg ulcer clinics, tissue viability clinics or services, and wound clinics. Participants were aged 18 years or older with a venous leg ulcer and an ankle brachial pressure index of at least 0·8, and were tolerant of high compression. We randomly allocated participants (1:1) to receive two-layer compression hosiery or a four-layer bandage, using a remote randomisation service and prevalidated computer randomisation program. Participants were stratified by ulcer duration and ulcer area with permuted blocks (block sizes four and six). The primary endpoint was time to ulcer healing, with a maximum follow-up of 12 months. Although participants and health-care providers were not masked to treatment allocation, the primary endpoint was measured by masked assessment of photographs. Primary analysis was intention to treat with Cox regression, with adjustment for ulcer area, ulcer duration, physical mobility, and centre. This trial is registered with the ISRCTN register, number ISRCTN49373072. FINDINGS: We randomly allocated 457 participants to the two treatment groups: 230 to two-layer hosiery and 227 to the four-layer bandage, of whom 453 (230 hosiery and 223 bandage) contributed data for analysis. Median time to ulcer healing was 99 days (95% CI 84-126) in the hosiery group and 98 days (85-112) in the bandage group, and the proportion of ulcers healing was much the same in the two groups (70·9% hosiery and 70·4% bandage). More hosiery participants changed their allocated treatment (38·3% hosiery vs 27·0% bandage; p=0·02). 300 participants had 895 adverse events, of which 85 (9·5%) were classed as serious but unrelated to trial treatment. INTERPRETATION: Two-layer compression hosiery is a viable alternative to the four-layer bandage-it is equally as effective at healing venous leg ulcers. However, a higher rate of treatment changes in participants in the hosiery group than in the bandage group suggests that hosiery might not be suitable for all patients. FUNDING: NIHR Health Technology Assessment programme (07/60/26).

Acupuncture and counselling for depression in primary care: a randomised controlled trial.

BACKGROUND: Depression is a significant cause of morbidity. Many patients have communicated an interest in non-pharmacological therapies to their general practitioners. Systematic reviews of acupuncture and counselling for depression in primary care have identified limited evidence. The aim of this study was to evaluate acupuncture versus usual care and counselling versus usual care for patients who continue to experience depression in primary care. METHODS AND FINDINGS: In a randomised controlled trial, 755 patients with depression (Beck Depression Inventory BDI-II score ≥ 20) were recruited from 27 primary care practices in the North of England. Patients were randomised to one of three arms using a ratio of 2.2.1 to acupuncture (302), counselling (302), and usual care alone (151). The primary outcome was the difference in mean Patient Health Questionnaire (PHQ-9) scores at 3 months with secondary analyses over 12 months follow-up. Analysis was by intention-to-treat. PHQ-9 data were available for 614 patients at 3 months and 572 patients at 12 months. Patients attended a mean of ten sessions for acupuncture and nine sessions for counselling. Compared to usual care, there was a statistically significant reduction in mean PHQ-9 depression scores at 3 months for acupuncture (-2.46, 95% CI -3.72 to -1.21) and counselling (-1.73, 95% CI -3.00 to -0.45), and over 12 months for acupuncture (-1.55, 95% CI -2.41 to -0.70) and counselling (-1.50, 95% CI -2.43 to -0.58). Differences between acupuncture and counselling were not significant. In terms of limitations, the trial was not designed to separate out specific from non-specific effects. No serious treatment-related adverse events were reported. CONCLUSIONS: In this randomised controlled trial of acupuncture and counselling for patients presenting with depression, after having consulted their general practitioner in primary care, both interventions were associated with significantly reduced depression at 3 months when compared to usual care alone. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN63787732 Please see later in the article for the Editors' Summary.

Alexander Technique Lessons, Acupuncture Sessions or usual care for patients with chronic neck pain (ATLAS): study protocol for a randomised controlled trial.

BACKGROUND: Chronic neck pain is a common condition in the adult population. More research is needed to evaluate interventions aiming to facilitate beneficial long-term change. We propose to evaluate the effect of Alexander Technique lessons and acupuncture in a rigorously conducted pragmatic trial with an embedded qualitative study. METHODS/DESIGN: We will recruit 500 patients who have been diagnosed with neck pain in primary care, who have continued to experience neck pain for at least three months with 28% minimum cut-off score on the Northwick Park Neck Pain Questionnaire (NPQ). We will exclude patients with serious underlying pathology, prior cervical spine surgery, history of psychosis, rheumatoid arthritis, ankylosing spondylitis, osteoporosis, haemophilia, cancer, HIV or hepatitis, or with alcohol or drug dependency currently or in the last 12 months, or actively pursuing compensation or with pending litigation.The York Trials Unit will randomly allocate participants using a secure computer-based system. We will use block randomisation with allocation to each intervention arm being unambiguously concealed from anyone who might subvert the randomisation process.Participants will be randomised in equal proportions to Alexander Technique lessons, acupuncture or usual care alone. Twenty 30-minute Alexander Technique lessons will be provided by teachers registered with the Society of Teachers of the Alexander Technique and twelve 50-minute sessions of acupuncture will be provided by acupuncturists registered with the British Acupuncture Council. All participants will continue to receive usual GP care.The primary outcome will be the NPQ at 12 months, with the secondary time point at 6 months, and an area-under-curve analysis will include 3, 6 and 12 month time-points. Adverse events will be documented. Potential intervention effect modifiers and mediators to be explored include: self-efficacy, stress management, and the incorporation of practitioner advice about self-care and lifestyle. Qualitative material will be used to address issues of safety, acceptability and factors that impact on longer term outcomes. DISCUSSION: This study will provide robust evidence on whether there are significant clinical benefits to patients, economic benefits demonstrating value for money, and sufficient levels of acceptability and safety. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15186354.

Acupuncture, Counseling, and Usual care for Depression (ACUDep): study protocol for a randomized controlled trial.

BACKGROUND: The evidence on the effect of acupuncture or counseling for depression is not conclusive yet is sufficient to warrant further research. Our aim is to conduct a full-scale RCT to determine the clinical and cost effectiveness of acupuncture and counseling compared to usual care alone. We will explore the experiences and perspectives of patients and practitioners. METHODS/DESIGN: Randomized controlled trial with three parallel arms: acupuncture plus usual care, counseling plus usual care, and usual care alone, in conjunction with a nested qualitative study using in-depth interviews with purposive samples of trial participants. PARTICIPANTS: Patients aged over 18 years diagnosed with depression or mood disorder by their GP and with a score of 20 or above on the Beck Depression Inventory (BDI-II).Randomization: Computer randomization by York Trials Unit to acupuncture, counseling, and usual care alone in proportions of 2:2:1, respectively, with secure allocation concealment. INTERVENTIONS: Patients allocated to acupuncture and counseling groups receive the offer of up to 12 weekly sessions. Both interventions allow flexibility to address patient variation, yet are constrained within defined protocols. Acupuncture is based on traditional Chinese medicine and counseling is non-directive within the humanistic tradition. OUTCOME: The PHQ-9 is the primary outcome measure, collected at baseline, 3, 6, 9, and 12 months. Also measured is BDI-II, SF-36 Bodily pain subscale, and EQ-5D. Texted mood scores are collected weekly over the first 15 weeks. Health-related resource use is collected over 12 months. ANALYSIS: The sample size target was for 640 participants, calculated for an effect size of 0.32 on the PHQ-9 when comparing acupuncture with counseling given 90% power, 5% significance, and 20% loss to follow-up. ANALYSIS of covariance will be used on an intention-to-treat basis. Thematic analysis will be used for qualitative data. We will compare incremental cost-effectiveness of the three treatment options at 12 months. DISCUSSION: Ethical approval was obtained in October 2009. There were six subsequent protocol amendments, the last of which was approved in January 2012. Recruitment of 755 participants took place over 18 months. Data collection will be completed by June 2012. No interim analyses have been conducted. TRIAL REGISTRATION: ISRCTN63787732.

Cost-effectiveness of acupuncture for irritable bowel syndrome: findings from an economic evaluation conducted alongside a pragmatic randomised controlled trial in primary care.

BACKGROUND: There is insufficient evidence to determine whether acupuncture is a cost-effective treatment for irritable bowel syndrome. The objective of this study is to assess the cost-effectiveness of acupuncture as an adjunct to usual care versus usual care alone for the treatment of Irritable Bowel Syndrome (IBS). METHODS: Cost-utility analysis conducted alongside a pragmatic, multicentre, randomised controlled trial. 233 patients with irritable bowel syndrome were randomly allocated to either acupuncture plus usual care, or usual care alone. Cost-effectiveness outcomes are expressed in terms of incremental cost per quality adjusted life year (QALY) at one year after randomisation. Costs were estimated from the UK National Health Service perspective for a time horizon of one year. Cost-utility ratios were estimated based on complete case analysis for the base case analysis, where only patients with available EQ-5D and cost data were included. Sensitivity analyses comprised a multiple imputation approach for missing data and a subgroup analysis for the more severe cases of IBS. RESULTS: The base case analysis showed acupuncture to be marginally more effective than usual care (gain of 0.0035 QALYs, 95% CI: -0.00395 to 0.0465) and more expensive (incremental cost of £218 per patient (95% CI: 55.87 to 492.87) resulting in an incremental cost-effectiveness ratio of approximately £62,500. Sensitivity analysis using multiple imputation for missing data resulted in acupuncture appearing less effective and more costly than usual care, so usual care is dominant. Subgroup analysis selecting the most severe cases of IBS (Symptom Severity Score of over 300) suggested that acupuncture may be a cost-effective treatment option for this group, with a cost-per-QALY of £6,500. CONCLUSIONS: Acupuncture as an adjunct to usual care is not a cost-effective option for the whole IBS population; however it may be cost-effective for those with more severe irritable bowel syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN08827905.

Acupuncture for irritable bowel syndrome: primary care based pragmatic randomised controlled trial.

BACKGROUND: Acupuncture is used by patients as a treatment for irritable bowel syndrome (IBS) but the evidence on effectiveness is limited. The purpose of the study was to evaluate the effectiveness of acupuncture for irritable bowel syndrome in primary care when provided as an adjunct to usual care. DESIGN: A two-arm pragmatic randomised controlled trial. SETTING: Primary care in the United Kingdom. PATIENTS: 233 patients had irritable bowel syndrome with average duration of 13 years and score of at least 100 on the IBS Symptom Severity Score (SSS). INTERVENTIONS: 116 patients were offered 10 weekly individualised acupuncture sessions plus usual care, 117 patients continued with usual care alone. MEASUREMENTS: Primary outcome was the IBS SSS at three months, with outcome data collected every three months to 12 months. RESULTS: There was a statistically significant difference between groups at three months favouring acupuncture with a reduction in IBS Symptom Severity Score of -27.43 (95% CI: -48.66 to -6.21, p=0.012). The number needed to treat for successful treatment (≥50 point reduction in the IBS SSS) was six (95% CI: 3 to 17), based on 49% success in the acupuncture group vs. 31% in the control group, a difference between groups of 18% (95% CI: 6% to 31%). This benefit largely persisted at 6, 9 and 12 months. CONCLUSIONS: Acupuncture for irritable bowel syndrome provided an additional benefit over usual care alone. The magnitude of the effect was sustained over the longer term. Acupuncture should be considered as a treatment option to be offered in primary care alongside other evidenced based treatments. TRIAL REGISTRATION: Current Controlled Trials ISRCTN08827905.

A pragmatic multicentered randomized controlled trial of yoga for chronic low back pain: economic evaluation.

STUDY DESIGN: Multicentered randomized controlled trial with quality of life and resource use data collected. OBJECTIVE: The objective of this study was to evaluate the cost-effectiveness of yoga intervention plus usual care compared with usual care alone for chronic or recurrent low back pain. SUMMARY OF BACKGROUND DATA: Yoga has been shown as an effective intervention for treating chronic or recurrent low back pain. However, there is little evidence on its cost-effectiveness. The data are extracted from a pragmatic, multicentered, randomized controlled trial that has been conducted to evaluate the effectiveness and cost-effectiveness of a 12-week progressive program of yoga plus usual care in patients with chronic or recurrent low back pain. METHODS: With this trial data, a cost-effectiveness analysis during the time period of 12 months from both perspectives of the UK National Health Service and the societal is presented. Main outcome measure is an incremental cost per quality-adjusted life-year (QALY). RESULTS: From the perspective of the U.K. National Health Service, yoga intervention yields an incremental cost-effectiveness ratio of £13,606 per QALY. Given a willingness to pay for an additional QALY of £20,000, the probability of yoga intervention being cost-effective is 72%. From the perspective of the society, yoga intervention is a dominant treatment compared with usual care alone. This result is surrounded by fewer uncertainties-the probability of yoga being cost-effective reaches 95% at a willingness to pay for an additional QALY of £20,000. Sensitive analyses suggest the same results that yoga intervention is likely to be cost-effective in both perspectives. CONCLUSION: On the basis of this trial, 12 weekly group classes of specialized yoga are likely to be a cost-effective intervention for treating patients with chronic or recurrent low back pain.