bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robot-assisted radical cystectomy with intracorporeal urinary diversion versus open radical cystectomy (iROC): protocol for a randomised controlled trial with internal feasibility study
Authors: Catto James W F , Khetrapal Pramit , Ambler Gareth , Sarpong Rachael , Khan Muhammad Shamim , Tan Melanie , Feber Andrew , Dixon Simon , Goodwin Louise , Williams Norman R , McGrath John , Rowe Edward , Koupparis Anthony , Brew-Graves Chris , Kelly John D 
Published: May 2020

IntroductionBladder cancer (BC) is a common malignancy and one of the most expensive to manage. Radical cystectomy (RC) with pelvic lymphadenectomy is a gold standard treatment for high-risk BC. Reductions in morbidity and mortality from RC may be achieved through robot-assisted RC (RARC). Prospective comparisons between open RC (ORC) and RARC have been limited by sample size, use of extracorporeal reconstruction and use of outcomes important for ORC. Conversely, while RARC is gaining in popularity, there is little evidence to suggest it is superior to ORC. We are undertaking a prospective randomised controlled trial (RCT) to compare RARC with intracorporeal reconstruction (iRARC) and ORC using multimodal outcomes to explore qualitative and quantitative recovery after surgery.Methods and analysisiROC is a multicentre prospective RCT in English National Health Service (NHS) cancer centres. We will randomise 320 patients undergoing RC to either iRARC or ORC. Treatment allocation will occur after trial entry and consent. The primary outcome is days alive and out of hospital within the first 90 days from surgery. Secondary outcomes will measure functional recovery (activity trackers, chair-to-stand tests and health related quality of life (HRQOL) questionnaires), morbidity (complications and readmissions), cost-effectiveness (using EuroQol-5 Domain-5 levels (EQ-5D-5L) and unit costs) and surgeon fatigue. Patients will be analysed according to intention to treat. The primary outcome will be transformed and analysed using regression. All statistical assumptions will be investigated. Secondary outcomes will be analysed using appropriate regression methods. An internal feasibility study of the first 30 patients will evaluate recruitment rates, acceptance of randomised treatment choice, compliance outcome collection and to revise our sample size.Ethics and disseminationThe study has ethical approval (REC reference 16/NE/0418). Findings will be made available to patients, clinicians, funders and the NHS through peer-reviewed publications, social media and patient support groups.Trial registration numbersISRCTN13680280andNCT03049410.
Cognitive-behavioural therapy (CBT) for renal fatigue (BReF): a feasibility randomised-controlled trial of CBT for the management of fatigue in haemodialysis (HD) patients
Authors: Picariello Federica , Moss-Morris Rona , Macdougall Iain C , Norton Sam , Da Silva-Gane Maria , Farrington Ken , Clayton Hope , Chilcot Joseph 
Published: May 2020

IntroductionFatigue is one of the most common and disabling symptoms in end-stage kidney disease, particularly among in-centre haemodialysis patients. This two-arm parallel group feasibility randomised controlled trial will determine whether a fully powered efficacy trial is achievable by examining the feasibility of recruitment, acceptability and potential benefits of a cognitive-behavioural therapy (CBT)-based intervention for fatigue among in-centre haemodialysis patients.MethodsWe aim to recruit 40 adult patients undergoing in-centre haemodialysis at secondary care outpatient dialysis units, who meet clinical levels of fatigue. Patients will be randomised individually (using a 1:1 ratio) to either a 4–6 weeks’ CBT-based intervention (intervention arm) or to a waiting-list control (control arm). The primary feasibility outcomes include descriptive data on numbers within each recruiting centre meeting eligibility criteria, rates of recruitment, numbers retained postrandomisation and treatment adherence. To assess the potential benefits of the cognitive-behavioural therapy for renal fatigue intervention, secondary self-report outcomes include measures of fatigue severity (Chalder Fatigue Questionnaire), fatigue-related functional impairment (Work and Social Adjustment Scale), sleep quality (Pittsburgh Sleep Quality Index), depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7). Changes in fatigue perceptions (Brief Illness Perception Questionnaire), cognitive and behavioural responses to fatigue (Cognitive and Behavioural Responses to Symptoms Questionnaire), sleep hygiene behaviours (Sleep Hygiene Index) and physical activity (International Physical Activity Questionnaire–short form) will also be explored. These self-report measures will be collected at baseline and 3 months postrandomisation. Nested qualitative interviews will be conducted postintervention to explore the acceptability of the intervention and identify any areas in need of improvement. The statistician and assessor will be blinded to treatment allocation.Ethics and disseminationA National Health Service (NHS) Research Ethics Committee approved the study. Any amendments to the protocol will be submitted to the NHS Committee and study sponsor.Trial registration numberISRCTN91238019;Pre-results.
Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study
Authors: Liu Hanning , Xu Zhengxi , Sun Cheng , Chen Qianlong , Bao Ning , Chen Wen , Zhou Zhou , Wang Xiaoqi , Zheng Zhe 
Published: May 2020

ObjectiveAs a marker of in vivo thromboxane generation, high-level urinary thromboxane metabolites (TXA-M) increase the occurrence of cardiovascular events in high-risk patients. To investigate whether perioperative urinary TXA-M level is associated with major adverse cardiac and cerebrovascular events (MACCE) after coronary artery bypass graft (CABG) surgery, we designed a nested case-control study.DesignObservational, nested case-control study.SettingSingle-centre outcomes research in Fuwai Hospital, Beijing, China.ParticipantsOne thousand six hundred and seventy Chinese patients undergoing CABG surgery from September 2011 to October 2013.MethodsWe obtained urinary samples from 1670 Chinese patients undergoing CABG 1 hour before surgery (pre-CABG), and 6 hours (post-CABG 6 hours) and 24 hours after surgery (post-CABG 24 hours). Patients were followed up for 1 year, and we observed 56 patients had MACCE. For each patient with MACCE, we matched three control subjects. Perioperative urinary TXA-M of the three time spots was detected in these 224 patients.ResultsPost-CABG 24 hours TXA-M is significantly higher than that of patients without MACCE (11 101vs8849 pg/mg creatine, P=0.007). In addition, patients in the intermediate tertile and upper tertile of post-CABG 24 hours urinary TXA-M have a 2.2 times higher (HR 2.22, 95% CI 1.04 to 4.71, P=0.038) and a 2.8 times higher (HR 2.81, 95% CI 1.35 to 5.85, P=0.006) risk of 1 year MACCE than those in the lower tertile, respectively.ConclusionsIn conclusion, post-CABG 24 hours urinary TXA-M elevation is associated with an increase of 1 year adverse events after CABG, indicating that the induction of cyclo-oxygenase-2 by surgery-related inflammatory stimuli or platelet turnover may be responsible for the high levels of post-CABG urinary TXA-M.Trial registration numberNCT01573143.
Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study
Authors: Jitsumura Maki , Cunningham Andrew Laurence , Hitchings Matthew David , Islam Saiful , Davies Angharad P , Row Paula E , Riddell Andrew D , Kinross James , Wilkinson Tom S , Jenkins G J , Williams John G , Harris Dean Anthony 
Published: May 2020

BackgroundThe interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response.Methods and analysisThis single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-naïve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40 cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study.Ethics and disseminationThe trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University’s Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared with trial participants.Trial registration numberISRCTN58082603; Pre-results.
Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS): protocol and study rationale for a randomised, double-blind, placebo-controlled, phase I/II clinical trial
Authors: Zhao Tian Xiao , Kostapanos Michalis , Griffiths Charmaine , Arbon Emma L , Hubsch Annette , Kaloyirou Fotini , Helmy Joanna , Hoole Stephen P , Rudd James H F , Wood Graham , Burling Keith , Bond Simon , Cheriyan Joseph , Mallat Ziad 
Published: May 2020

IntroductionInflammation and dysregulated immune responses play a crucial role in atherosclerosis, underlying ischaemic heart disease (IHD) and acute coronary syndromes (ACSs). Immune responses are also major determinants of the postischaemic injury in myocardial infarction. Regulatory T cells (CD4+CD25+FOXP3+; Treg) induce immune tolerance and preserve immune homeostasis. Recent in vivo studies suggested that low-dose interleukin-2 (IL-2) can increase Treg cell numbers. Aldesleukin is a human recombinant form of IL-2 that has been used therapeutically in several autoimmune diseases. However, its safety and efficacy is unknown in the setting of coronary artery disease.Method and analysisLow-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes is a single-centre, first-in-class, dose-escalation, two-part clinical trial. Patients with stable IHD (part A) and ACS (part B) will be randomised to receive either IL-2 (aldesleukin; dose range 0.3–3×106IU) or placebo once daily, given subcutaneously, for five consecutive days. Part A will have five dose levels with five patients in each group. Group 1 will receive a dose of 0.3×106IU, while the dose for the remaining four groups will be determined on completion of the preceding group. Part B will have four dose levels with eight patients in each group. The dose of the first group will be based on part A. Doses for each of the subsequent three groups will similarly be determined after completion of the previous group. The primary endpoint is safety and tolerability of aldesleukin and to determine the dose that increases mean circulating Treg levels by at least 75%.Ethics and disseminationThe study received a favourable opinion by the Greater Manchester Central Research Ethics Committee, UK (17/NW/0012). The results of this study will be reported through peer-reviewed journals, conference presentations and an internal organisational report.Trial registration numberNCT03113773; Pre-results.
Proinsulin in the identification and risk stratification of gestational diabetes mellitus: study protocol for a prospective, longitudinal cohort study
Authors: Peter Rajesh , Bright Dominic , Cheung Wai-Yee , Luzio Stephen D , Dunseath Gareth J 
Published: May 2020

IntroductionGestational diabetes mellitus (GDM) is a common metabolic disorder occurring in up to 10% of pregnancies in the western world. Most women with GDM are asymptomatic; therefore, it is important to screen, diagnose and manage the condition as it is associated with an increased risk of maternal and perinatal complications. Diagnosis of GDM is made in the late second trimester or early third trimester because accurate diagnosis or risk stratification in the first trimester is still lacking. An increase in serum proinsulin may be seen earlier in pregnancy and before a change in glycaemic control can be identified. This study will aim to establish if fasting proinsulin concentrations at 16–18 weeks gestation will help to identify or risk stratify high-risk pregnant women with GDM.Methods and analysisThis is a prospective, longitudinal cohort study. Two oral glucose tolerance tests will be carried out at 16–18 and 24–28 weeks gestation in 200 pregnant women with at least one risk factor for GDM (body mass index>30 kg/m2, previous macrosomic baby (>4.5 kg), previous gestational diabetes, first degree relative with type 2 diabetes mellitus) recruited from antenatal clinics. Blood samples will be taken fasting and at 30 min, 1 and 2 hours following the 75 g glucose load. In addition, a fasting blood sample will be taken 6-weeks post delivery. All samples will be analysed for glucose, insulin, C peptide and proinsulin. Recruitment began in November 2017. Optimal cut-off points for proinsulin to diagnose gestational diabetes according to National Institute for Health and Care Excellence (2015) criteria will be established by the receiver operating characteristic plot and sensitivity and specificity will be calculated to assess the diagnostic accuracy of proinsulin at 16–18 weeks gestation.Ethics and disseminationThis study received ethical approval from the Wales Research Ethics Committee (Panel 6) (Ref. 17/WA/0194). Data will be presented at international conferences and published in peer-reviewed journals.Trial registration numberISRCTN16416602; Pre-results.
Efficacy of a standardised acupuncture approach for women with bothersome menopausal symptoms: a pragmatic randomised study in primary care (the ACOM study)
Authors: Lund Kamma Sundgaard , Siersma Volkert , Brodersen John , Waldorff Frans Boch 
Published: May 2020

ObjectiveTo investigate the efficacy of a standardised brief acupuncture approach for women with moderate-to-severe menopausal symptoms.DesignRandomised and controlled, with 1:1 allocation to the intervention group or the control group. The assessor and the statistician were blinded.SettingNine Danish primary care practices.Participants70 women with moderate-to-severe menopausal symptoms and nine general practitioners with accredited education in acupuncture.InterventionThe acupuncture style was western medical with a standardised approach in the predefined acupuncture points CV-3, CV-4, LR-8, SP-6 and SP-9. The intervention group received one treatment for five consecutive weeks. The control group was offered treatment after 6 weeks.Main outcome measuresOutcomes were the differences between the randomisation groups in changes to mean scores using the scales in the MenoScores Questionnaire, measured from baseline to week 6. The primary outcome was the hot flushes scale; the secondary outcomes were the other scales in the questionnaire. All analyses were based on intention-to-treat analysis.Results36 participants received the intervention, and 34 participants were in the control group. Four participants dropped out before week 6. The acupuncture intervention significantly decreased hot flushes: Δ −1.6 (95% CI [−2.3 to −0.8]; p<0.0001), day-and-night sweats: Δ −1.2 (95% CI [−2.0 to −0.4]; p=0.0056), general sweating: Δ −0.9(95% CI [−1.6 to −0.2]; p=0.0086), menopausal-specific sleeping problems: Δ −1.8 (95% CI [−2.7 to −1.0]; p<0.0001), emotional symptoms: Δ −3.4 (95% CI [−5.3 to −1.4]; p=0.0008), physical symptoms: Δ −1.7 (95% CI [−3 to −0.4]; p=0.010) and skin and hair symptoms: Δ −1.5 (95% CI [−2.5 to −0.6]; p=0.0021) compared with the control group at the 6-week follow-up. The pattern of decrease in hot flushes, emotional symptoms, skin and hair symptoms was already apparent 3 weeks into the study. Mild potential adverse effects were reported by four participants, but no severe adverse effects were reported.ConclusionsThe standardised and brief acupuncture treatment produced a fast and clinically relevant reduction in moderate-to-severe menopausal symptoms during the six-week intervention. No severe adverse effects were reported.Trial registration numberNCT02746497; Results.
ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for an interventional randomised controlled trial
Authors: China Louise , Skene Simon S , Bennett Kate , Shabir Zainib , Hamilton Roseanna , Bevan Scott , Chandler Torsten , Maini Alexander A , Becares Natalia , Gilroy Derek , Forrest Ewan H , O’Brien Alastair 
Published: May 2020

IntroductionCirculating prostaglandin E2levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds to and inactivates this immune-suppressive lipid mediator. Human albumin solution (HAS) could thus be repurposed as an immune-restorative drug in these patients.This is a phase III randomised controlled trial (RCT) to verify whether targeting a serum albumin level of ≥35 g/L in hospitalised patients with decompensated cirrhosis using repeated intravenous infusions of 20% HAS will reduce incidence of infection, renal dysfunction and mortality for the treatment period (maximum 14 days or discharge if <14 days) compared with standard medical care.Methods and analysisAlbumin To prevenT Infection in chronic liveR failurE stage 2 is a multicentre, open-label, interventional RCT. Patients with decompensated cirrhosis admitted to the hospital with a serum albumin of <30 g/L are eligible, subject to exclusion criteria. Patients randomised to intravenous HAS will have this administered, according to serum albumin levels, for up to 14 days or discharge. The infusion protocol aims to increase serum albumin to near-normal levels.The composite primary endpoint is: new infection, renal dysfunction or mortality within the trial treatment period. Secondary endpoints include mortality at up to 6 months, incidence of other organ failures, cost-effectiveness and quality of life outcomes and time to liver transplant. The trial will recruit 866 patients at more than 30 sites across the UK.EthicsanddisseminationResearch ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001–0001). The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the National Institute for Health Research (ISRCTN14174793). This manuscript refers to version 6.0 of the protocol. Results will be disseminated through peer-reviewed journals and international conferences. Recruitment of the first participant occurred on 25 January 2016.
General practitioners and emergency departments (GPED)—efficient models of care: a mixed-methods study protocol
Authors: Morton Katherine , Voss Sarah , Adamson Joy , Baxter Helen , Bloor Karen , Brandling Janet , Cowlishaw Sean , Doran Tim , Gibson Andrew , Gutacker Nils , Liu Dan , Purdy Sarah , Roy Paul , Salisbury Christopher , Scantlebury Arabella , Vaittinen Anu , Watson Rose , Benger Jonathan Richard 
Published: May 2020

IntroductionPressure continues to grow on emergency departments in the UK and throughout the world, with declining performance and adverse effects on patient outcome, safety and experience. One proposed solution is to locate general practitioners to work in or alongside the emergency department (GPED). Several GPED models have been introduced, however, evidence of effectiveness is weak. This study aims to evaluate the impact of GPED on patient care, the primary care and acute hospital team and the wider urgent care system.Methods and analysisThe study will be divided into three work packages (WPs). WP-A; Mapping and Taxonomy: mapping, description and classification of current models of GPED in all emergency departments in England and interviews with key informants to examine the hypotheses that underpin GPED. WP-B; Quantitative Analysis of National Data: measurement of the effectiveness, costs and consequences of the GPED models identified in WP-A, compared with a no-GPED model, using retrospective analysis of Hospital Episode Statistics Data. WP-C; Case Studies: detailed case studies of different GPED models using a mixture of qualitative and quantitative methods including: non-participant observation of clinical care, semistructured interviews with staff, patients and carers; workforce surveys with emergency department staff and analysis of available local routinely collected hospital data. Prospective case study sites will be identified by completing telephone interviews with sites awarded capital funding by the UK government to implement GPED initiatives. The study has a strong patient and public involvement group that has contributed to study design and materials, and which will be closely involved in data interpretation and dissemination.Ethics and disseminationThe study has been approved by the National Health Service East Midlands—Leicester South Research Ethics Committee: 17/EM/0312. The results of the study will be disseminated through peer-reviewed journals, conferences and a planned programme of knowledge mobilisation.Trial registration numberISRCTN51780222.