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BackgroundThe erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation.MethodsAn individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention.ResultsThe analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization.ConclusionThe early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.

BACKGROUND: Shared decision making (SDM) involves patients and doctors contributing as partners to treatment decisions. It is not known whether or to what extent SDM contributes to the welfare arising from a consultation, and how important this contribution is relative to other attributes of a consultation. AIM: To identify patient preferences for SDM relative to other utility bearing attributes of a consultation. DESIGN OF STUDY: In parallel with a randomised trial in training GPs in SDM competencies and risk communication skills, a discrete choice experiment exercise was conducted to assess patients' utilities. SETTING: Twenty general practices in South Wales, UK. METHOD: Five hundred and eighty-four responders from 747 patients attending the randomised trial (response rate = 78%). All patients had one of four conditions (atrial fibrillation, menorrhagia, menopausal symptoms or prostatism) and attended a consultation with a doctor in their own practice. Patients were randomised to attend a consultation either with a doctor who had received no training in the study or risk communication training alone or SDM training alone, or both combined. RESULTS: Five key utility bearing attributes of a consultation were identified. All significantly influenced patient's choice of preferred consultation style (P<0.001). Larger increases in utility were associated with changes on 'doctor listens' attribute, followed by easily understood information, a shared treatment decision, more information and longer consultation. Utilities were influenced by whether the doctor had received risk communication training alone or SDM training alone, or both combined, prior to the consultations. The randomised trial itself had identified that the communication processes of these consultations changed significantly, with greater patient involvement in decision making, after the training interventions. CONCLUSION: Shared treatment decisions were valued less than some other attributes of a consultation. However, patient utilities for such involvement appeared responsive to changes in experiences of consultations. This suggests that SDM may gain greater value among patients once they have experienced it. [ABSTRACT FROM AUTHOR]

Clinical practice frequently generates questions that are not easily answered by randomized trials. On conventional hierarchies of evidence, 'weaker' study designs are often more feasible. Also, much research is not well designed. Yet we still need to make best use of the available evidence. Systematic reviews must therefore address the danger of underestimating the evidence from relevant literature if it includes only that of a certain methodological quality. This would run the risk of missing or distorting the true message that the review is trying to identify. We propose a classification of research which does not reject studies on the basis of design alone, but recognizes the importance of assessing the message or 'signal' within each piece of research. It explicitly introduces judgement into the appraisal and synthesis of evidence, and affords more flexibility in attaching weight to evidence that might otherwise be lost. It includes an assessment of methodological quality, balancing this against the weight of its message, rather than rejecting studies which are below a certain threshold for quality. Fundamentally flawed research will still be rejected, but more commonly papers can still be used, tempering the importance that we attach to their signal by the amount of 'noise' around that signal. The balance of these two elements may be termed the 'signal to noise ratio'. [ABSTRACT FROM AUTHOR]

Background: There is a lack of high quality, child-centred and effective health information to support development of self-care practices and expertise in children with acute and long-term conditions. In type 1 diabetes, clinical guidelines indicate that high-quality, child-centred information underpins achievement of optimal glycaemic control with the aim of minimising acute readmissions and reducing the risk of complications in later life. This paper describes the development of a range of child-centred diabetes information resources and outlines the study design and protocol for a randomized controlled trial to evaluate the information resources in routine practice. The aim of the diabetes information intervention is to improve children and young people's quality of life by increasing self-efficacy in managing their type 1 diabetes.Methods/design: We used published evidence, undertook qualitative research and consulted with children, young people and key stakeholders to design and produce a range of child-centred, age-appropriate children's diabetes diaries, carbohydrate recording sheets, and assembled child-centred, age-appropriate diabetes information packs containing published information in a folder that can be personalized by children and young people with pens and stickers. Resources have been designed for children/young people 6-10; 11-15; and 16-18 years.To evaluate the information resources, we designed a pragmatic randomized controlled trial to assess the effectiveness, cost effectiveness, and implementation in routine practice of individually tailored, age-appropriate diabetes diaries and information packs for children and young people age 6-18 years, compared with currently available standard practice.Children and young people will be stratified by gender, length of time since diagnosis (< 2 years and > 2 years) and age (6-10; 11-15; and 16-18 years). The following data will be collected at baseline, 3 and 6 months: PedsQL (generic, diabetes and parent versions), and EQ-5 D (parent and child); NHS resource use and process data (questionnaire and interview). Baseline and subsequent HbA1c measurements, blood glucose meter use, readings and insulin dose will be taken from routine test results and hand-held records when attending routine 3-4 monthly clinic visits.The primary outcome measure is diabetes self-efficacy and quality-of-life (Diabetes PedsQL). Secondary outcomes include: HbA1c, generic quality of life, routinely collected NHS/child-held data, costs, service use, acceptability and utility.Trial Registration: ISRCTN17551624. [ABSTRACT FROM AUTHOR]

Background and Aims: Alcohol use increases throughout adolescence. Emergency department (ED) attendance is an opportunity for alcohol screening and brief intervention (ASBI), which is effective for adults. This trial evaluated the effectiveness and cost-effectiveness of ASBI compared with screening alone (SA) in high-risk adolescents., Design, Setting and Participants: Multi-centre, three-group, single-blind, individually randomized trial with follow-ups after 6 and 12 months in 10 ED settings in England. From October 2014 to May 2015 we screened 3327 adolescents aged 14 to 18 years, of whom 756 (22.7%) scored at least 3 on the Alcohol Use Disorders Identification Test: consumption (AUDIT-C) and consented to participate in this trial. Mean age was 16.1 years; 50.2% were female and 84.9% were white., Interventions: Interventions were personalized feedback and brief advice (PFBA), personalized feedback plus electronic brief intervention (eBI) and SA., Measures: The primary outcome was the weekly alcohol consumed in standard UK units (8 g ethanol) at 12 months post-randomization, derived from extended AUDIT-C. Economic outcomes included quality of life and service use, from perspectives of both the National Health Service and personal social services (NHS&PSS) and society., Findings: At 12 months, mean weekly consumption was 2.99 [95% confidence interval (CI) = 2.38-3.70] standard units for the SA group, 3.56 (95% CI = 2.90, 4.32) for PFBA and 3.18 (95% CI = 2.50, 3.97) for eBI, showing no significant differences. The PFBA group consumed mean 0.57 (-0.36, 1.70) units more than SA; and eBIs consumed 0.19 (-0.71, 1.30) more. Bayes factors suggested lack of effectiveness explained non-significance. From the NHS&PSS perspective, economic analysis showed that PFBA and eBI were not cost-effective compared with SA: PFBA yielded incremental cost-effectiveness ratio of £6213 (-£736 843, £812 884), with the intervention having 54% probability of being cost-effective compared with SA at the £20 000 WTP threshold., Conclusions: In emergency departments in England, neither personalized feedback and brief advice nor personalized feedback plus electronic brief intervention showed evidence of being effective or cost-effective when compared with screening alone in reducing alcohol consumption among adolescents., (© 2022 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Individuals with low serum vitamin B-12 and high serum folate have higher plasma concentrations of methylmalonic acid (MMA). Whether folic acid (FA) causes an increase in MMA is not known., Objectives: We aimed to determine the impact of FA supplementation on plasma MMA concentration in people with low or marginal serum vitamin B-12., Methods: We conducted a multicenter double-blind placebo-controlled randomized trial of oral FA (5 mg/d for 12 wk) in middle-aged patients treated with antidepressant medication participating in the FoLATED (Folate Augmentation of Treatment-Evaluation for Depression) trial. Participants defined as having "low" serum vitamin B-12 (vitamin B-12 ≥150 and <220 ng/L) or "marginal" serum vitamin B-12 (vitamin B-12 ≥ 220 and <280 ng/L) were included. The primary outcome of this substudy was MMA at week 12. A mixed-effects linear regression was fitted and reported using the adjusted mean difference (aMD)., Results: A total of 177 participants were included (85 randomly assigned to placebo and 92 to FA); the mean ± SD age was 46.2 ± 11.8 y, and 112 (63.3%) were female. The MMA analysis included 135 participants and the aMD was -0.01 (95% CI: -0.06, 0.04; P = 0.71). Serum folate was measured on 166 participants and increased in the supplementation group; the aMD was 21.6 μg/L (95% CI: 8.13, 25.02 μg/L; P < 0.001). A total of 117 participants were assessed for RBC folate, which also increased in the supplementation group; the aMD was 461 μg/L (95% CI: 387, 535 μg/L; P < 0.001)., Conclusions: Supplementation of FA leads to an increase of serum and RBC folate, but does not change plasma MMA concentration in individuals with serum vitamin B-12 between 150 and 280 ng/L. We cannot exclude effects in older people or those with serum vitamin B-12 <150 ng/L. Previously reported associations may arise from effects of impaired vitamin B-12 status on folate metabolism.This trial was registered at www.isrctn.com as ISRCTN37558856., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression., Aims: To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627)., Method: RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated., Results: After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94-9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI -2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI -2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group., Conclusions: The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.

Objective: To estimate the effectiveness of standardised self-management kits for children with type 1 diabetes., Design: Pragmatic trial with randomisation ratio of two intervention: one control. Qualitative process evaluation., Setting: 11 diabetes clinics in England and Wales., Participants: Between February 2010 and August 2011, we validly randomised 308 children aged 6-18 years; 201 received the intervention., Intervention: We designed kits to empower children to achieve glycaemic control, notably by recording blood glucose and titrating insulin. The comparator was usual treatment. OUTCOME MEASURES AT 3 AND 6 MONTHS: Primary: Diabetes Pediatric Quality of Life Inventory (PedsQL). Secondary: HbA1c; General PedsQL; EQ-5D; healthcare resource use., Results: Of the five Diabetes PedsQL dimensions, Worry showed adjusted scores significantly favouring self-management kits at 3 months (mean child-reported difference =+5.87; Standard error[SE]=2.19; 95% confidence interval [CI]) from +1.57 to +10.18; p=0.008); but Treatment Adherence significantly favoured controls at 6 months (mean child-reported difference=-4.68; SE=1.74; 95%CI from -8.10 to -1.25; p=0.008). Intervention children reported significantly worse changes between 3 and 6 months on four of the five Diabetes PedsQL dimensions and on the total score (mean difference=-3.20; SE=1.33; 95% CI from -5.73 to -0.67; p=0.020). There was no evidence of change in HbA1c; only 18% of participants in each group achieved recommended levels at 6 months. No serious adverse reactions attributable to the intervention or its absence were reported.Use of kits was poor. Few children or parents associated blood glucose readings with better glycaemic control. The kits, costing £185, alienated many children and parents., Conclusions: Standardised kits showed no evidence of benefit, inhibited diabetes self-management and increased worry. Future research should study relationships between children and professionals, and seek new methods of helping children and parents to manage diabetes., Trial Registration Number: ISRCTN17551624., Competing Interests: Competing interests: Professor JWG has received payments from Pfizer, Bayer and Ipsen for lectures, development of educational presentations and travel/accommodation to attend scientific meetings and advisory board meetings. His employer (Cardiff University) has also received funding from Novo Nordisk to support the development of patient-support materials used in the Development and Evaluation of a Psychosocial Intervention for Children and Teenagers Experiencing Diabetes (DEPICTED) research study., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: To explore patients' experience of receiving pain relief injection for suspected hip fracture from paramedics at the location of the injury., Design: Qualitative interviews within a feasibility trial about an alternative to routine prehospital pain management for patients with suspected hip fracture., Setting: Patients treated by paramedics in the catchment area of one emergency department in South Wales., Participants: Six patients and one carer of a patient who received fascia iliaca compartment block (FICB)., Intervention: FICB administered to patients with suspected hip fracture by trained paramedics. We randomly allocated eligible patients to FICB-a local anaesthetic injection directly into the hip region-or usual care-most commonly morphine-using audited scratch cards., Outcomes: Acceptability and experience of receiving FICB, assessed through interview data. We audio-recorded, with participants' consent, and conducted thematic analysis of interview transcripts. The analysis team comprised two researchers, one paramedic and one lay member., Results: Patients had little or no memory of being offered, consenting to or receiving FICB. They recalled the reassuring manner and high quality of care received. They accepted FICB without question. Partial or confused memory characterised experience of subsequent hospital care until surgery. They said their priorities when calling for emergency help were to receive effective care. After hospital treatment, they wanted to regain their health and mobility and resume the quality of life they experienced before their injury., Conclusions: This study did not raise any concerns about the acceptability of FICB administered at the scene of injury by paramedics to people with suspected hip fracture. It adds to existing evidence about patient and carer experience of on-scene care for people with suspected hip fracture. Further research is needed to assess safety, effectiveness and cost effectiveness of this health technology in a new setting., Trial Registration Number: ISRCTN60065373., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To estimate the effect of deprivation on the demand for calls to National Health Service Direct Wales (NHSDW) controlling for confounding factors., Design: Study of routine data on over 400 000 calls to NHSDW using multiple regression to analyse the logarithms of ward-specific call rates across Wales by characteristics of call, patient and ward, notably the Welsh Index of Multiple Deprivation., Setting: 810 electoral wards with average population of 3300, defined by 1998 administrative boundaries., Population: All calls to NHSDW between January 2002 and June 2004., Main Outcome Measures: We used ward populations as denominators to calculate the rates of three categories of calls: calls seeking advice, calls seeking information and all calls combined., Results: Confounding variables explained 31% of variation in advice call rates, but only 14% of variation in information call rates and in all call rates (all significant at 0.1% level). However, deprivation was only a statistically significant predictor of information call rates. The proportion of the ward population categorised as 'white' was a highly significant predictor of all three call rates. For advice calls and combined calls, rates decreased highly significantly with the proportion of those who called the service for themselves. Information call rates were higher on weekdays and highest on Mondays, while advice call rates were highest on Sundays., Conclusions: Deprivation had no consistent effect on demand for the service and the relationship needs further exploration. While our data may have underestimated the 'need' of deprived patients, they yield no evidence that policy-makers should seek to improve demand from those patients. However, we found differences in the way callers use advice and information calls. Previously unexplored variables that help to predict ward-specific call rates include: ethnicity, day of the week and whether patients made the calls themselves., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Refractory depression is a major contributor to the economic burden of depression. Radically open dialectical behaviour therapy (RO DBT) is an unevaluated new treatment targeting overcontrolled personality, common in refractory depression, but it is not yet known whether the additional expense of RO DBT is good value for money.AimsTo estimate the cost-effectiveness of RO DBT plus treatment as usual (TAU) compared with TAU alone in people with refractory depression (trial registration: ISRCTN85784627)., Method: We undertook a cost-effectiveness analysis alongside a randomised trial evaluating RO DBT plus TAU versus TAU alone for refractory depression in three UK secondary care centres. Our economic evaluation, 12 months after randomisation, adopted the perspective of the UK National Health Service (NHS) and personal social services. It evaluated cost-effectiveness by comparing the net cost of RO DBT with the net gain in quality-adjusted life-years (QALYs), estimated using the EQ-5D-3L measure of health-related quality of life., Results: The additional cost of RO DBT plus TAU compared with TAU alone was £7048 and was associated with a difference of 0.032 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of £220 250 per QALY. This ICER was well above the National Institute for Health and Care Excellence (NICE) upper threshold of £30 000 per QALY. A cost-effectiveness acceptability curve indicated that RO DBT had a zero probability of being cost-effective compared with TAU at the NICE £30 000 threshold., Conclusions: In its current resource-intensive form, RO DBT is not a cost-effective use of resources in the UK NHS.Declaration of interestR.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from the National Institute for Health Research (NIHR). T.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd, and a grant outside the submitted work from the Medical Research Council. He was co-director of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two directors of Radically Open Ltd. H.O'M. reports personal fees outside the submitted work from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.R. provides RO DBT supervision through her company S C Rushbrook Ltd. I.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M. Stanton reports personal fees outside the submitted work from British Isles DBT Training, Stanton Psychological Services Ltd and Taylor & Francis. M. Swales reports personal fees outside the submitted work from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis. B.W. was co-director of Radically Open Ltd between November 2014 and February 2015.

Background: In managing hip fracture, effective pain relief before admission to hospital is difficult without risking side effects. Although emergency departments routinely use fascia iliaca compartment block (FICB), there has been little evaluation of its use by paramedics before hospital admission. We aimed to assess whether a multi-centre randomised trial to evaluate FICB was feasible., Methods: Volunteer paramedics used scratchcards to allocate patients with hip fracture at random between FICB and pain relief as usual. Primary outcomes were mortality and quality of life. We also measured adverse events, costs, final diagnosis, length of stay in hospital, pain scores and quality of care and collected qualitative data about acceptability to patients in interviews, and paramedics in focus groups. We pre-specified criteria for deciding whether to progress to a fully powered trial based on the recruitment of paramedics and patients, delivery of FICB, retrieval of outcome data, safety, acceptability, and diagnostic accuracy of hip fracture., Results: We effectively met all progression criteria: we recruited 19 paramedics who randomly allocated 71 patients between trial arms between 28 June 2016 and 31 July 2017; 57 (31 experimental arm, 26 usual care arm, 80% overall) retrospectively consented to follow-up. Just over half (17/31) of experimental participants received FICB; all others had contraindications, including nine taking anticoagulants. Four of the 31 participants assigned FICB and six of the 26 assigned usual care died within 6 months of hospital admission. Serious adverse events were also similar: 3/35 experimental versus 4/36 in usual care. Paramedics' recognition of hip fracture had sensitivity of 49/64 (77%) with a positive predictive value of 46/57 (81%). We received quality of life questionnaires for 30 of 49 patients (61%) at 1 month and 12 of 17 (71%) at 6 months. Patient satisfaction was similar: experimental mean 3.4 ( n  = 20) versus 3.5 ( n  = 13) for usual care., Conclusions: RAPID met all progression criteria within reasonable limits. As equipoise remains, we plan to undertake a fully powered multi-centre trial to test clinical and cost effectiveness of paramedic-administered FICB at the scene of hip fracture., Trial Registration: ISRCTN 60065373 sought 5 November 2015., Competing Interests: Competing interestsIan Pallister is Director of Trauma Simulation Ltd., which produced the bespoke mannequin used in training. The other authors declare that they have no competing interests.

Objectives: To explore paramedics' experience of delivering fascia iliaca compartment block ( FICB) to patients with suspected hip fracture at the scene of injury., Design: Focus groups within a randomised controlled trial., Setting: Paramedics based at ambulance stations in the catchment area of one Emergency Department in South Wales, recruited and trained in a feasibility study about an alternative to routine prehospital pain management for patients with suspected hip fracture., Participants: 11 paramedics., Intervention: Paramedic-administered FICB to patients with suspected hip fracture. We randomly allocated eligible patients to FICB, a local anaesthetic injection directly into the hip region-or usual care, most commonly morphine - using audited scratch cards., Outcomes: Paramedics' experiences of administering FICB gathered through thematic analysis of interview transcripts by two researchers, one paramedic and one lay member., Results: Respondents believed that FICB was a suitable intervention for paramedics to deliver. It aligned with routine practice and was within people's capabilities. They said it took up to 10 minutes longer than usual care to prepare and deliver, in part due to nervousness and unfamiliarity with a new procedure. They praised the training provided but said they were anxious about causing harm by injecting into the wrong location. Confidence increased after one paramedic team successfully treated a patient for local anaesthetic toxicity. Reported challenges related to the emergency context: patients often waited many hours for ambulance arrival; moving patients exacerbated their pain; family and neighbours were present as paramedics administered treatment., Conclusions: Paramedics are willing and able to administer FICB to patients with suspected hip fracture before ambulance transport to hospital. Feasibility study findings will inform further research., Trial Registration Number: ISRCTN60065373; Pre results., Competing Interests: Competing interests: IP is Director of Trauma Simulation, which produced the bespoke mannequin used in training. The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The value of qualitative methods within trials is widely recognised, but their full potential is not being realised. There are also issues with the visibility, recognition and reporting of qualitative methods in trials. To identify potential improvements in qualitative research within trials, we need to study trials that have included qualitative methods. We aimed to explore the frequency of reporting qualitative methods in registered trials, the types of trials using qualitative methods and where in the world these trials were conducted., Methods: We included registries if they were searchable using keywords and held summaries of trials rather than listing reports or publications. We searched the included registries from the first available record in 1999 to the end of 2016 for the term 'qualitative'. We included trials only if we could confirm that they used qualitative methods through documented use of qualitative data collection and analysis in the registry summary. We analysed registered trials reporting the use of qualitative methods by: year registered, the country responsible for overseeing governance of the trial and the type of trial intervention (categorised as surgical, medical device, behavioural, drug or other)., Results: We included three registries: ClinicalTrials.gov, the International Standard Randomised Controlled Trial Number Registry (ISRCTN) and the World Health Organisation International Clinical Trials Registry Platform (WHO ICTRP). A total of 615,311 trials appear in these three registries from 1999 until the end of 2016. Numbers differed across registries with the WHO ICTRP the largest (366,753 trials), ClinicalTrials.gov the second largest (233,277) and ISRCTN the smallest (15,301). Of these registered trials, we confirmed that 1492 (0.24%) reported using qualitative methods. The ISRCTN contributed the highest percentage of trials reported as using qualitative methods (3.4%); in contrast, ClinicalTrials.gov reported 0.3% and WHO ICTRP reported 0.03%. The number and percentage of trials reported to use qualitative methods increased over time from 0 (0.0%) in 1999 to 285 (0.38%) in 2016. Trials reported as using qualitative methods originated from 52 countries across the world. Most were in Western higher-income countries: 38% in the United Kingdom and 28% in the United States. Most registered trials reported as using qualitative methods evaluated behavioural (39%) or other interventions with many fewer trials evaluating drugs (5%), medical devices (5%) or surgical interventions (4%)., Conclusion: The reported use of qualitative methods in registered trials has increased over time and worldwide. They are reportedly more frequent in high-income countries and in trials of behavioural and other interventions. Trialists and other stakeholders need to recognise the benefits of using qualitative methods in surgical, device and drug trials, and trials conducted in poorer countries. Moreover, they should seriously consider using qualitative methods in these trials.

Objectives: To develop and undertake initial validation of a patient-reported outcome measure to assess health-related quality of life in patients with breast cancer-related upper limb lymphedema (ULL)., Study Design and Setting: We developed and validated the Upper Limb Lymphedema Quality of Life (ULLQoL) scale in two stages: devising the items and pretesting with patients and clinicians; longitudinal validation to test its psychometric properties-underlying dimensions, internal consistency, test-retest reliability, construct validity, and responsiveness. Patients with ULL were recruited from two outpatient clinics., Results: We derived the ULLQoL scale from a pool of 98 items generated by patients. After further consultation, we produced the draft ULLQoL scale. For validation, 103 patients with ULL completed the draft scale and two generic health measures: SF-36 and ED-5D-3L. Psychometric analysis identified two components, physical and emotional well-being, with good internal consistency and test-retest reliability. Significant correlations with SF-36, EQ-5D-3L, and percentage excess limb volume confirmed construct validity. The ULLQoL scale showed good responsiveness to change reported by lymphedema patients and moderate to large effect sizes., Conclusion: The 14-item ULLQoL scale is a robust ULL-specific measure that is feasible and valid to use in both the clinical and research settings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Incisional hernias are common complications of midline abdominal closure. The 'Hughes Repair' combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. There is evidence to suggest this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared Hughes repair with standard mass closure for the prevention of incisional hernia formation. This paper aims to test the feasibility of running a randomised controlled trial of a comparison of abdominal wall closure methods following midline incisional surgery for colorectal cancer, in preparation to a definitive randomised controlled trial., Design and Setting: A feasibility trial (with 1:1 randomisation) conducted perioperatively during colorectal cancer surgery., Participants: Patients undergoing midline incisional surgery for resection of colorectal cancer., Interventions: Comparison of two suture techniques (Hughes repair or standard mass closure) for the closure of the midline abdominal wound following surgery for colorectal cancer., Primary and Secondary Outcomes: A 30-patient feasibility trial assessed recruitment, randomisation, deliverability and early safety of the surgical techniques used., Results: A total of 30 patients were randomised from 43 patients recruited and consented, over a 5-month period. 14 and 16 patients were randomised to arms A and B, respectively. There was one superficial surgical site infection (SSI) and two organ space SSIs reported in arm A, and two superficial SSIs and one complete wound dehiscence in arm B. There were no suspected unexpected serious adverse reactions reported in either arm. Independent data monitoring committee found no early safety concerns., Conclusions: The feasibility trial found no early safety concerns and demonstrated that the trial was acceptable to patients. Progression to the pilot and main phases of the trial has now commenced following approval by the independent data monitoring committee., Trial Registration Number: ISRCTN 25616490., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Study Objective: We aim to determine clinical and cost-effectiveness of a paramedic protocol for the care of older people who fall., Methods: We undertook a cluster randomized trial in 3 UK ambulance services between March 2011 and June 2012. We included patients aged 65 years or older after an emergency call for a fall, attended by paramedics based at trial stations. Intervention paramedics could refer the patient to a community-based falls service instead of transporting the patient to the emergency department. Control paramedics provided care as usual. The primary outcome was subsequent emergency contacts or death., Results: One hundred five paramedics based at 14 intervention stations attended 3,073 eligible patients; 110 paramedics based at 11 control stations attended 2,841 eligible patients. We analyzed primary outcomes for 2,391 intervention and 2,264 control patients. One third of patients made further emergency contacts or died within 1 month, and two thirds within 6 months, with no difference between groups. Subsequent 999 call rates within 6 months were lower in the intervention arm (0.0125 versus 0.0172; adjusted difference -0.0045; 95% confidence interval -0.0073 to -0.0017). Intervention paramedics referred 8% of patients (204/2,420) to falls services and left fewer patients at the scene without any ongoing care. Intervention patients reported higher satisfaction with interpersonal aspects of care. There were no other differences between groups. Mean intervention cost was $23 per patient, with no difference in overall resource use between groups at 1 or 6 months., Conclusion: A clinical protocol for paramedics reduced emergency ambulance calls for patients attended for a fall safely and at modest cost., (Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The majority of residents in care homes in the United Kingdom are living with dementia or significant memory problems. Caring in this setting can be difficult and stressful for care staff who work long hours, have little opportunity for training, are poorly paid and yet subject to high expectation. This may affect their mental and physical wellbeing, cause high rates of staff turnover and absenteeism, and affect the quality of care they provide. The main objective of this survey was to explore the nature, characteristics and associations of stress in care home staff., Methods: Staff working in a stratified random sample of care homes within Wales completed measures covering: general health and wellbeing (SF-12); stress (Work Stress Inventory); job content (Karasek Job Content); approach to, and experience of, working with people living with dementia (Approaches to Dementia Questionnaire; and Experience of Working with Dementia Patients); and Productivity and Health Status (SPS-6). Multiple linear regressions explored the effects of home and staff characteristics on carers., Results: 212 staff from 72 care homes completed questionnaires. Staff from nursing homes experienced more work stress than those from residential homes (difference 0.30; 95% confidence interval (CI) from 0.10 to 0.51; P  < 0.01), and were more likely to report that their health reduced their ability to work (difference -4.77; CI -7.80 to -1.73; P  < 0.01). Psychological demands on nurses were higher than on other staff (difference = 1.57; CI 0.03 to 3.10; P  < 0.05). A positive approach to dementia was more evident in those trained in dementia care (difference 8.54; CI 2.31 to 14.76; P  < 0.01), and in staff working in local authority homes than in the private sector (difference 7.75; CI 2.56 to 12.94; P  < 0.01)., Conclusions: Our study highlights the importance of dementia training in care homes, with a particular need in the private sector. An effective intervention to reduce stress in health and social care staff is required, especially in nursing and larger care homes, and for nursing staff., Trial Registration: ISRCTN registry: ISRCTN80487202. Registered 24 July 2013.

Background: Emergency calls are frequently made to ambulance services for older people who have fallen, but ambulance crews often leave patients at the scene without any ongoing care. We evaluated a new clinical protocol which allowed paramedics to assess older people who had fallen and, if appropriate, refer them to community-based falls services., Objectives: To compare outcomes, processes and costs of care between intervention and control groups; and to understand factors which facilitate or hinder use., Design: Cluster randomised controlled trial., Participants: Participating paramedics at three ambulance services in England and Wales were based at stations randomised to intervention or control arms. Participants were aged 65 years and over, attended by a study paramedic for a fall-related emergency service call, and resident in the trial catchment areas., Interventions: Intervention paramedics received a clinical protocol with referral pathway, training and support to change practice. Control paramedics continued practice as normal., Outcomes: The primary outcome comprised subsequent emergency health-care contacts (emergency admissions, emergency department attendances, emergency service calls) or death at 1 month and 6 months. Secondary outcomes included pathway of care, ambulance service operational indicators, self-reported outcomes and costs of care. Those assessing outcomes remained blinded to group allocation., Results: Across sites, 3073 eligible patients attended by 105 paramedics from 14 ambulance stations were randomly allocated to the intervention group, and 2841 eligible patients attended by 110 paramedics from 11 stations were randomly allocated to the control group. After excluding dissenting and unmatched patients, 2391 intervention group patients and 2264 control group patients were included in primary outcome analyses. We did not find an effect on our overall primary outcome at 1 month or 6 months. However, further emergency service calls were reduced at both 1 month and 6 months; a smaller proportion of patients had made further emergency service calls at 1 month (18.5% vs. 21.8%) and the rate per patient-day at risk at 6 months was lower in the intervention group (0.013 vs. 0.017). Rate of conveyance to emergency department at index incident was similar between groups. Eight per cent of trial eligible patients in the intervention arm were referred to falls services by attending paramedics, compared with 1% in the control arm. The proportion of patients left at scene without further care was lower in the intervention group than in the control group (22.6% vs. 30.3%). We found no differences in duration of episode of care or job cycle. No adverse events were reported. Mean cost of the intervention was £17.30 per patient. There were no significant differences in mean resource utilisation, utilities at 1 month or 6 months or quality-adjusted life-years. In total, 58 patients, 25 paramedics and 31 stakeholders participated in focus groups or interviews. Patients were very satisfied with assessments carried out by paramedics. Paramedics reported that the intervention had increased their confidence to leave patients at home, but barriers to referral included patients' social situations and autonomy., Conclusions: Findings indicate that this new pathway may be introduced by ambulance services at modest cost, without risk of harm and with some reductions in further emergency calls. However, we did not find evidence of improved health outcomes or reductions in overall NHS emergency workload. Further research is necessary to understand issues in implementation, the costs and benefits of e-trials and the performance of the modified Falls Efficacy Scale., Trial Registration: Current Controlled Trials ISRCTN60481756 and PROSPERO CRD42013006418., 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. 21, No. 13. See the NIHR Journals Library website for further project information.

Background: Adequate pain relief at the point of injury and during transport to hospital is a major challenge in all acute traumas, especially for those with hip fractures, whose injuries are difficult to immobilise and whose long-term outcomes may be adversely affected by administration of opiate analgesics. Fascia iliaca compartment block (FICB) is a procedure routinely undertaken by doctors and nurses in the emergency department for patients with hip fracture but not yet evaluated for use by paramedics at the scene of emergency calls. In this feasibility study, we aim to test whether FICB administered by paramedics at the scene of participants' hip fractures is feasible, safe and acceptable. This will enable us to decide whether to proceed to a fully powered, multi-centre pragmatic randomised trial to evaluate whether the procedure is effective for patients and worthwhile for the NHS., Methods/design: In this study, we propose to recruit ten paramedics in an urban area of South Wales. We will train them to carry out FICB when they attend patients with hip fracture. We will randomly allocate eligible patients to FICB or usual care using audited scratch cards. We will follow up participants to assess measurability of key outcomes including quality of life, pain scores, adverse events, length of stay in hospital, acceptability to patients and compliance of paramedics. We will assess whether the findings meet specified feasibility criteria and, if so, plan a full trial., Discussion: This study will enable us to recommend whether to undertake a definitive trial of FICB by paramedics for hip fracture., Trial Registration: ISRCTN60065373.

Background: Trials increasingly experience problems in recruiting participants. Understanding the causes of poor recruitment is critical to developing solutions. We interviewed people who had declined a trial of an innovative psychological therapy for depression (REFRAMED) about their response to the trial invitation, in order to understand their decision and identify ways to improve recruitment., Methods: Of 214 people who declined the trial, 35 (16 %) gave permission to be contacted about a qualitative study to explore their decision. Analysis of transcripts of semi-structured interviews was informed by grounded theory., Results: We interviewed 20 informants: 14 women and six men, aged 18 to 77 years. Many interviewees had prior experience of research participation and positive views of the trial. Interviewees' decision making resembled a four-stage sequential process; in each stage they either decided not to participate in the trial or progressed to the next stage. In stage 1, interviewees assessed the invitation in the context of their experiences and attitudes; we term those who opted out at this stage 'prior decliners' as they had an established position of declining trials. In stage 2, interviewees assessed their own eligibility; those who judged themselves ineligible and opted out at this stage are termed 'self-excluders'. In stage 3, interviewees assessed their need for the trial therapy and potential to benefit; we term those who decided they did not need the trial therapy and opted out at this stage 'treatment decliners'. In stage 4, interviewees deliberated the benefits and costs of trial participation; those who opted out after judging that disadvantages outweighed advantages are termed 'trial decliners'. Across all stages, most individuals declined because they judged themselves ineligible or not in need of the trial therapy. While 'prior decliners' are unlikely to respond to any trial recruitment initiative, the factors leading others to decline are amenable to amelioration as they do not arise from a rejection of trials or a personal stance., Conclusions: To improve recruitment in similar trials, the most successful interventions are likely to address patients' assessments of their eligibility and their potential to benefit from the trial treatment, rather than reducing trial burden., Trial Registration: International Standard Randomised Controlled Trial Number: ISRCTN85784627 . Registration date 10 August 2011.

Objectives: To develop a tool for the accurate reporting and aggregation of findings from each of the multiple methods used in a complex evaluation in an unbiased way., Study Design and Setting: We developed a Method for Aggregating The Reporting of Interventions in Complex Studies (MATRICS) within a gastroenterology study [Evaluating New Innovations in (the delivery and organisation of) Gastrointestinal (GI) endoscopy services by the NHS Modernisation Agency (ENIGMA)]. We subsequently tested it on a different gastroenterology trial [Multi-Institutional Nurse Endoscopy Trial (MINuET)]. We created three layers to define the effects, methods, and findings from ENIGMA. We assigned numbers to each effect in layer 1 and letters to each method in layer 2. We used an alphanumeric code based on layers 1 and 2 to every finding in layer 3 to link the aims, methods, and findings. We illustrated analogous findings by assigning more than one alphanumeric code to a finding. We also showed that more than one effect or method could report the same finding. We presented contradictory findings by listing them in adjacent rows of the MATRICS., Results: MATRICS was useful for the effective synthesis and presentation of findings of the multiple methods from ENIGMA. We subsequently successfully tested it by applying it to the MINuET trial., Conclusion: MATRICS is effective for synthesizing the findings of complex, multiple-method studies., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: Patient satisfaction is a key indicator of the quality of gastrointestinal (GI) endoscopy. The aim of this study was to develop and validate a specific patient satisfaction questionnaire for patients undergoing GI endoscopy--the Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ)., Patients and Methods: We developed and validated the GESQ within the context of a national multi-institution nurse endoscopy trial, based in secondary care, in three stages: (1) item generation with a panel of patients and professionals following a detailed literature review to identify the most relevant items from existing scales; (2) development and piloting of a draft questionnaire on a sample of patients referred for GI endoscopy; and (3) testing of the questionnaire within a large multicenter pragmatic randomized trial. We undertook psychometric analysis of the questionnaire to identify the underlying dimensions and assessed the questionnaire for reliability and validity., Results: The final version of the GESQ contains 21 items. Principal components analysis revealed four subscales with high internal consistency: skills and hospital (seven items; Cronbach's alpha 0.83), pain and discomfort during and after endoscopy (four items; Cronbach's alpha 0.84), information before endoscopy (five items; Cronbach's alpha 0.80), and information after endoscopy (five items; Cronbach's alpha 0.76)., Conclusions: The four identified subscales are clinically relevant and correspond to domains of patient satisfaction identified in previous studies. Our development and validation of the GESQ confirmed that it is a valid, reliable, interpretable, and acceptable tool to measure satisfaction in patients who have undergone a GI endoscopy., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: To develop and validate a gastrointestinal (GI) symptom rating questionnaire for patients with luminal GI symptoms including where no diagnosis has been made., Study Design and Setting: We developed and validated the Gastrointestinal Symptom Rating Questionnaire (GSRQ) in three stages: (1) item generation to identify the relevant items for scale inclusion; (2) development and piloting on patients with a known GI disorder; and (3) testing in a sample of trial patients. We examined the underlying dimensions of the scale, internal consistency, validity, reproducibility, and responsiveness., Results: We identified four interpretable factors on the GSRQ. The GSRQ had good internal consistency (corrected item-subscale correlations between 0.4 and 0.8) and Cronbach's alpha greater than 0.7 for each subscale. Construct validity was demonstrated by modest but significant correlations with the Short Form 36 and the EQ5D index value. We demonstrated good reproducibility with intraclass correlations for test-retest scores between 0.71 and 0.77, and significant responsiveness ratios for all subscales in patients who had improved, and in two of the subscales in patients who had deteriorated., Conclusion: The GSRQ could be a useful tool to monitor quality of life in various luminal GI conditions and where a formal diagnosis has not been made., (Copyright © 2015 Elsevier Inc. All rights reserved.)

It has been suggested that giving cell-salvaged blood through a leucocyte depletion filter can cause hypotension due to bradykinin released when factor XII and platelets are activated by the negatively charged surface of the filter. We measured the concentration of bradykinin and cysteinyl leukotrienes in cell-salvaged blood sampled before and after passage through a negatively charged leucodepletion filter in 24 consecutive patients with gynaecological or bowel cancer undergoing elective surgery with cell salvage. In no case was an increase in bradykinin concentration observed after passage through the filter; in 23 patients the post-filtration bradykinin concentration was zero (p = 0.007). The change in the concentration of cysteinyl leukotrienes detected during passage across the filter was not statistically significant (p = 0.1). Our findings do not support the suggestion that either bradykinin or cysteinyl leukotrienes are generated in cell-salvaged blood during passage through leucodepletion filters., (© 2015 The Association of Anaesthetists of Great Britain and Ireland.)

Background: Group cognitive stimulation therapy programmes can benefit cognition and quality of life for people with dementia. Evidence for home-based, carer-led cognitive stimulation interventions is limited., Objectives: To evaluate the clinical effectiveness and cost-effectiveness of carer-delivered individual cognitive stimulation therapy (iCST) for people with dementia and their family carers, compared with treatment as usual (TAU)., Design: A multicentre, single-blind, randomised controlled trial assessing clinical effectiveness and cost-effectiveness. Assessments were at baseline, 13 weeks and 26 weeks (primary end point)., Setting: Participants were recruited through Memory Clinics and Community Mental Health Teams for older people., Participants: A total of 356 caregiving dyads were recruited and 273 completed the trial., Intervention: iCST consisted of structured cognitive stimulation sessions for people with dementia, completed up to three times weekly over 25 weeks. Family carers were supported to deliver the sessions at home., Main Outcome Measures: Primary outcomes for the person with dementia were cognition and quality of life. Secondary outcomes included behavioural and psychological symptoms, activities of daily living, depressive symptoms and relationship quality. The primary outcome for the family carers was mental/physical health (Short Form questionnaire-12 items). Health-related quality of life (European Quality of Life-5 Dimensions), mood symptoms, resilience and relationship quality comprised the secondary outcomes. Costs were estimated from health and social care and societal perspectives., Results: There were no differences in any of the primary outcomes for people with dementia between intervention and TAU [cognition: mean difference -0.55, 95% confidence interval (CI) -2.00 to 0.90; p-value = 0.45; self-reported quality of life: mean difference -0.02, 95% CI -1.22 to 0.82; p-value = 0.97 at the 6-month follow-up]. iCST did not improve mental/physical health for carers. People with dementia in the iCST group experienced better relationship quality with their carer, but there was no evidence that iCST improved their activities of daily living, depression or behavioural and psychological symptoms. iCST seemed to improve health-related quality of life for carers but did not benefit carers' resilience or their relationship quality with their relative. Carers conducting more sessions had fewer depressive symptoms. Qualitative data suggested that people with dementia and their carers experienced better communication owing to iCST. Adjusted mean costs were not significantly different between the groups. From the societal perspective, both health gains and cost savings were observed., Conclusions: iCST did not improve cognition or quality of life for people with dementia, or carers' physical and mental health. Costs of the intervention were offset by some reductions in social care and other services. Although there was some evidence of improvement in terms of the caregiving relationship and carers' health-related quality of life, iCST does not appear to deliver clinical benefits for cognition and quality of life for people with dementia. Most people received fewer than the recommended number of iCST sessions. Further research is needed to ascertain the clinical effectiveness of carer-led cognitive stimulation interventions for people with dementia., Trial Registration: Current Controlled Trials ISRCTN65945963., Funding: This project was funded by the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme and will be published in full in Health Technology Assessment; Vol. 19, No. 64. See the NIHR Journals Library website for further information.

Introduction: Only 30-40% of depressed patients treated with medication achieve full remission. Studies that change medication or augment it by psychotherapy achieve only limited benefits, in part because current treatments are not designed for chronic and complex patients. Previous trials have excluded high-risk patients and those with comorbid personality disorder. Radically Open Dialectical Behaviour Therapy (RO-DBT) is a novel, transdiagnostic treatment for disorders of emotional over-control. The REFRAMED trial aims to evaluate the effectiveness and cost-effectiveness of RO-DBT for patients with treatment-resistant depression., Methods and Analysis: REFRAMED is a multicentre randomised controlled trial, comparing 7 months of individual and group RO-DBT treatment with treatment as usual (TAU). Our primary outcome measure is depressive symptoms 12 months after randomisation. We shall estimate the cost-effectiveness of RO-DBT by cost per quality-adjusted life year. Causal analyses will explore the mechanisms by which RO-DBT is effective., Ethics and Dissemination: The National Research Ethics Service (NRES) Committee South Central - Southampton A first granted ethical approval on 20 June 2011, reference number 11/SC/0146., Trial Registration Number: ISRCTN85784627., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To develop, validate and apply a generic clinical severity index applicable to all adult patients with inflammatory bowel disease (IBD)., Design: A review of the literature and an expert focus group consultation were carried out in order to draw out relevant items from existing literature. The new index was called the IBD Index (IBDEX). Standard psychometric analysis was carried out. The construct validity was assessed against biochemical markers, clinical and endoscopic indices. The new index was completed again within 6 weeks to check responsiveness and reproducibility., Results: IBDEX was used to assess 255 adult patients with IBD (125 with Crohn's disease and 130 with ulcerative colitis), and 64 patients were re-evaluated within 6 weeks. It had good internal consistency (Cronbach's α=0.79) and correlated very well with the Harvey Bradshaw Index (r=0.94), the Simple Clinical Colitis Activity Index (r=0.92), the Mayo Clinic Index (r=0.87) and the Simple Endoscopic Score (r=0.76), all with p values <0.05. IBDEX had a moderate but positive correlation with C reactive protein (r=0.51) and erythrocyte sedimentation rate (r=0.36) p values both <0.05. The test-retest reliability was good (intraclass correlation coefficient 0.97) and responsiveness ratio was 2.27., Conclusions: IBDEX is the first properly validated Clinical Disease Severity Index in IBD. Our results showed that it is valid, reliable and reproducible and has the potential to be used in clinical practice.