bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open randomised trial of the (Arabin) pessary to prevent preterm birth in twin pregnancy with health economics and acceptability: STOPPIT-2—a study protocol
Authors: Norman Jane E , Norrie John , Maclennan Graeme , Cooper David , Whyte Sonia , Cunningham Burley Sarah , Smith Joel B E , Shennan Andrew , Robson Stephen C , Thornton Steven , Kilby Mark D , Marlow Neil , Stock Sarah J , Bennett Philip R , Denton Jane 
Published: April 2023

IntroductionThe STOPPIT-2 study aims to determine the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix, about which there is current uncertainty. STOPPIT-2 will resolve uncertainty around effectiveness for women with a twin pregnancy and a cervical length of 35 mm or less, define adverse effects, ascertain acceptability and estimate National Health Service costs and savings.MethodsSTOPPIT-2 is a pragmatic multicentre open-label randomised controlled trial. Consenting women with twin pregnancy will have an transvaginal ultrasound scan of their cervical length performed between 18+0 and 20+6 weeks’ gestation by an accredited practitioner: women with a cervical length of ≤35 mm will be eligible for inclusion in the treatment phase of the study. The intervention by the insertion of the Arabin cervical pessary will be compared with standard treatment (no pessary).The primary outcomes are (obstetric) spontaneous onset of labour for the mother leading to delivery before 34 weeks’ gestation and (neonatal) a composite of specific adverse outcomes or death occurring up to the end of the first 4 weeks after the estimated date of delivery to either or both babies.We plan to recruit 500 women in the treatment phase of the study. Assuming a treatment effect of 0.6, and background rates of 35% and 18%, respectively, for each of the primary outcomes, our study has 85% power to detect a difference between the intervention and the control groups.AnalysisData will be analysed on the intention-to-treat principle.EthicsSTOPPIT-2 was approved by the South East Scotland Ethics Committee 02 on 29 August 2014, reference number 14/SS/1031 IRAS ID 159610.DisseminationPeer reviewed journals, presentations at national and international scientific meetings.Trial registration numberNCT98835694andNCT02235181.
TAME trial: a multi-arm phase II randomised trial of four novel interventions for malnutrition enteropathy in Zambia and Zimbabwe - a study protocol
Authors: Kelly Paul , Bell Lauren , Amadi Beatrice , Bwakura-Dangarembizi Mutsa , VanBuskirk Kelley , Chandwe Kanta , Chipunza Miyoba , Ngosa Deophine , Chulu Nivea , Hill Susan , Murch Simon , Playford Raymond , Prendergast Andrew 
Published: April 2023

IntroductionSevere acute malnutrition (SAM) in children in many countries still carries unacceptably high mortality, especially when complicated by secondary infection or metabolic derangements. New therapies are urgently needed and we have identified mucosal healing in the intestine as a potential target for novel treatment approaches.Methods and analysisThe TAME trial (Therapeutic Approaches for Malnutrition Enteropathy) will evaluate four novel treatments in an efficient multi-arm single-blind phase II design. In three hospitals in Zambia and Zimbabwe, 225 children with SAM will be randomised to one of these treatments or to standard care, once their inpatient treatment has reached the point of transition from stabilisation to increased nutritional intake. The four interventions are budesonide, bovine colostrum or N-acetyl glucosamine given orally or via nasogastric tube, or teduglutide given by subcutaneous injection. The primary endpoint will be a composite score of faecal inflammatory markers, and a range of secondary endpoints include clinical and laboratory endpoints. Treatments will be given daily for 14 days, and evaluation of the major endpoints will be at 14 to 18 days, with a final clinical evaluation at 28 days. In a subset of children in Zambia, endoscopic biopsies will be used to evaluate the effect of interventions in detail.Ethics and disseminationThe study has been approved by the University of Zambia Biomedical Research Ethics Committee (006-09-17, dated 9thJuly, 2018), and the Joint Research Ethics Committee of the University of Zimbabwe (24thJuly, 2019). Caregivers will provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings.Trial registration numberNCT03716115.
Is inspiratory muscle training (IMT) an acceptable treatment option for people with chronic obstructive pulmonary disease (COPD) who have declined pulmonary rehabilitation (PR) and can IMT enhance PR uptake? A single-group prepost feasibility study in a home-based setting
Authors: O’Connor Cath , Lawson Rod , Waterhouse Judith , Mills Gary H 
Published: April 2023

ObjectivesThis feasibility study aimed to assess the acceptability of inspiratory muscle training (IMT) in people with chronic obstructive pulmonary disease (COPD) who declined pulmonary rehabilitation (PR) as a potential treatment option or precursor to PR. Objectives were to assess attitudes to IMT, PR and alternatives to PR; factors influencing adherence with IMT and acceptability of outcome measures, research tools and study protocol.DesignA pragmatic, mixed methods, prepost feasibility study was conducted. Recruitment took place over a 4-month period. Participants were followed up for a period of 6 months.SettingsIMT sessions and assessments were conducted in the domiciliary setting.ParticipantsInclusion criteria: people over the age of 35, stable COPD, Medical Research Council Dyspnoea scale of 3 or above, declined PR. Exclusion criteria: history of spontaneous pneumothorax, incomplete recovery from a traumatic pneumothorax, asthma, known recently perforated eardrum, unstable angina, ventricular dysrhythmias, cerebrovascular event or myocardial infarction within the last 2 months. Participants were selected from a purposive sample. Of the 22 potential participants screened, 11 were recruited and interviewed. Ten participants commenced IMT. Seven participants completed the follow-up assessment.InterventionEight weeks of IMT twice a day, 5 days a week with visits once weekly by a physiotherapist. Unsupervised IMT twice a day three times a week until follow-up at 6 months.OutcomesAcceptability of IMT and the study process was explored via semi-structured interviews. Adherence with IMT was assessed by the Powerbreathe K3 device and participant diaries. Uptake of PR was identified.ResultsIMT was found to be acceptable. Adherence was explored. Four people went on to participate in PR.ConclusionsFeasibility was established. A randomised controlled trial is warranted to establish efficacy and cost-effectiveness of IMT in those who decline PR and IMT as an intervention to promote uptake of PR.Trial registration numberNCT01956565; Post-results.
Laparoscopically assisted versus open oesophagectomy for patients with oesophageal cancer—the Randomised Oesophagectomy: Minimally Invasive or Open (ROMIO) study: protocol for a randomised controlled trial (RCT)
Authors: Brierley Rachel C , Gaunt Daisy , Metcalfe Chris , Blazeby Jane M , Blencowe Natalie S , Jepson Marcus , Berrisford Richard G , Avery Kerry N L , Hollingworth William , Rice Caoimhe T , Moure-Fernandez Aida , Wong Newton , Nicklin Joanna , Skilton Anni , Boddy Alex , Byrne James P , Underwood Tim , Vohra Ravi , Catton James A , Pursnani Kish , Melhado Rachel , Alkhaffaf Bilal , Krysztopik Richard , Lamb Peter , Culliford Lucy , Rogers Chris , Howes Benjamin , Chalmers Katy , Cousins Sian , Elliott Jackie , Donovan Jenny , Heys Rachael , Wickens Robin A , Wilkerson Paul , Hollowood Andrew , Streets Christopher , Titcomb Dan , Humphreys Martyn Lee , Wheatley Tim , Sanders Grant , Ariyarathenam Arun , Kelly Jamie , Noble Fergus , Couper Graeme , Skipworth Richard J E , Deans Chris , Ubhi Sukhbir , Williams Robert , Bowrey David , Exon David , Turner Paul , Daya Shetty Vinutha , Chaparala Ram , Akhtar Khurshid , Farooq Naheed , Parsons Simon L , Welch Neil T , Houlihan Rebecca J , Smith Joanne , Schranz Rachel , Rea Nicola , Cooke Jill , Williams Alexandra , Hindmarsh Carolyn , Maitland Sally , Howie Lucy , Barham Christopher Paul 
Published: April 2023

IntroductionSurgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life.Methods and analysisWe will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery.Ethics and disseminationThis study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal.Trial registration numberNCT10386621.
IMPACT study on intervening with a manualised package to achieve treatment adherence in people with tuberculosis: protocol paper for a mixed-methods study, including a pilot randomised controlled trial
Authors: Stagg Helen R , Abubakar Ibrahim , Campbell Colin NJ , Copas Andrew , Darvell Marcia , Horne Robert , Kielmann Karina , Kunst Heinke , Mandelbaum Mike , Pickett Elisha , Story Alistair , Vidal Nicole , Wurie Fatima B , Lipman Marc 
Published: April 2023

IntroductionCompared with the rest of the UK and Western Europe, England has high rates of the infectious disease tuberculosis (TB). TB is curable, although treatment is for at least 6 months and longer when disease is drug resistant. If patients miss too many doses (non-adherence), they may transmit infection for longer and the infecting bacteria may develop resistance to the standard drugs used for treatment. Non-adherence may therefore risk both their health and that of others. Within England, certain population groups are thought to be at higher risk of non-adherence, but the factors contributing to this have been insufficiently determined, as have the best interventions to promote adherence. The objective of this study was to develop a manualised package of interventions for use as part of routine care within National Health Services to address the social and cultural factors that lead to poor adherence to treatment for TB disease.Methods and analysisThis study uses a mixed-methods approach, with six study components. These are (1) scoping reviews of the literature; (2) qualitative research with patients, carers and healthcare professionals; (3) development of the intervention; (4) a pilot randomised controlled trial of the manualised intervention; (5) a process evaluation to examine clinical utility; and (6) a cost analysis.Ethics and disseminationThis study received ethics approval on 24 December 2018 from Camberwell St. Giles Ethics Committee, UK (REC reference 18/LO/1818). Findings will be published and disseminated through peer-reviewed publications and conference presentations, published in an end of study report to our funder (the National Institute for Health Research, UK) and presented to key stakeholders.Trial registration numberNCT95243114Secondary identifying numbersUniversity College London/University College London Hospitals Joint Research Office 17/0726.National Institute for Health Research, UK 16/88/06.
Independent medical evaluation of general practitioners’ follow-up of sick-listed patients: a cross-sectional study in Norway
Authors: Øyeflaten Irene , Maeland Silje , Haukenes Inger 
Published: April 2023

ObjectivesThe study was designed to examine the sufficiency of general practitioners’ (GPs) follow-up of patients on sick leave, assessed by independent medical evaluators.DesignCross-sectional studySettingPrimary health care in the Western part of Norway. The study reuses data from a randomised controlled trial—the Norwegian independent medical evaluation trial (NIME trial).ParticipantsThe intervention group in the NIME trial: Sick-listed workers having undergone an independent medical evaluation by an experienced GP at 6 months of unremitting sick leave (n=937; 57% women). In the current study, the participants were distributed into six exposure groups defined by gender and main sick leave diagnoses (women/musculoskeletal, men/musculoskeletal, women/mental, men/mental, women/all other diagnoses and men/all other diagnoses).Outcome measureThe independent medical evaluators assessment (yes/no) of the sufficiency of the regular GPs follow-up of their sick-listed patients.ResultsEstimates from generalised linear models demonstrate a robust association between men with mental sick leave diagnoses and insufficient follow-up by their regular GP first 6 months of sick leave (adjusted relative risk (RR)=1.8, 95% CI=1.15–1.68). Compared with the reference group, women with musculoskeletal sick leave diagnoses, this was the only significant finding. Men with musculoskeletal diagnoses (adjusted RR=1.4, 95% CI=0.92–2.09); men with other diagnoses (adjusted RR=1.0, 95% CI=0.58–1.73); women with mental diagnoses (adjusted RR=1.2, 95% CI=0.75–1.77) and women with other diagnoses (adjusted RR=1.3, 95% CI=0.58–1.73).ConclusionsAssessment by an independent medical evaluator showed that men with mental sick leave diagnoses may be at risk of insufficient follow-up by their GP. Efforts should be made to clarify unmet needs to initiate relevant actions in healthcare and work life. Avoiding marginalisation in work life is of the utmost importance.Trial registration numberNCT02524392.
Protocol for a multicentre randomised controlled trial to investigate the effect on asthma-related quality of life from breathing retraining in patients with incomplete asthma control attending specialist care in Denmark
Authors: Andreasson Karen Hjerrild , Skou Søren Thorgaard , Ulrik Charlotte Suppli , Madsen Hanne , Sidenius Kirsten , Jacobsen Jannie Søndergaard , Assing Karin Dahl , Rasmussen Kirsten Brændholt , Porsbjerg Celeste , Thomas Mike , Bodtger Uffe 
Published: April 2023

Introduction and aimUncontrolled asthma is a global health challenge with substantial impact on quality of life (QoL) and overall healthcare costs. Unrecognised and/or unmanaged comorbidities often contribute to presence of uncontrolled asthma. Abnormalities in breathing pattern are termed dysfunctional breathing and are not only common in asthma but also lead to asthma-like symptoms and reduced QoL, and, in keeping with this, improvement with breathing normalisation. Evidence-based guidelines recommend breathing retraining interventions as an adjuvant treatment in uncontrolled asthma. Physiotherapy-based breathing pattern modification interventions incorporating relaxation have been shown to improve asthma-related QoL in primary care patients with impaired asthma control. Despite anecdotal reports, effectiveness of breathing retraining in patients referred to secondary care with incomplete asthma control has not been formally assessed in a randomised controlled trial (RCT). We aim to investigate the effect of breathing exercises on asthma-related QoL in patients with incomplete asthma control despite specialist care.Methods and analysisThis two-armed assessor-blinded multicentre RCT will investigate the effect of physiotherapist-delivered breathing retraining on asthma QoL questionnaire (MiniAQLQ) in addition to usual specialist care, recruiting from seven outpatient departments and one specialised clinic representing all regions of Denmark during 2017–2019. We will include 190 consenting adults with incomplete asthma control, defined as Asthma Control Questionnaire 6-item score ≥0.8. Participants will randomly be allocated to either breathing exercise programme in addition to usual care (BrEX +UC) or UC alone. BrEX compiles three physiotherapy sessions and encouragement to perform home exercise daily. Both groups continue usual secondary care management. Primary outcome is between-group difference in MiniAQLQ at 6 months. Secondary outcomes include patient-reported outcome measures, spirometry and accelerometer.Ethics and disseminationEthics Committee, Region Zealand (SJ-552) and Danish Data Protection Agency (REG-55–2016) approved the trial. Results will be reported in peer-reviewed scientific journals.Trial registration numberNCT03127059.
Ascorbic Acid, Corticosteroids and Thiamine in Sepsis (ACTS) protocol and statistical analysis plan: a prospective, multicentre, double-blind, randomised, placebo-controlled clinical trial
Authors: Moskowitz Ari , Yankama Tuyen , Andersen Lars W , Huang David T , Donnino Michael W , Grossestreuer Anne V 
Published: April 2023

IntroductionSeptic shock is a common and highly morbid condition. To date, there is no specific therapy proven to attenuate organ injury in septic shock. Recent studies have suggested a role for the combination of ascorbic acid, corticosteroids and thiamine, although randomised data are lacking.Methods and analysisThe Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis trial is a multi-centre, double-blind, randomised, placebo-controlled clinical trial that aims to determine the impact of ascorbic acid, corticosteroids and thiamine versus placebo on organ injury and mortality in patients with septic shock. Patients are randomised to receive 1500 mg of ascorbic acid, 100 mg of thiamine and 50 mg of hydrocortisone parenterally versus matching placebo every 6 hours for 4 days. Clinical and laboratory data are collected at the time of study enrolment, at 24, 72 and 120 hours. The primary end-point for the trial is change in the Sequential Organ Failure Assessment score between enrolment and 72 hours. Additional key secondary outcomes include the incidence of renal failure and 30-day mortality.Ethics and disseminationThe study was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberThe trial is registered on clinicaltrials.gov (NCT03389555). It was posted on 3 January 2018.
Seasonal malaria vaccination: protocol of a phase 3 trial of seasonal vaccination with the RTS,S/AS01Evaccine, seasonal malaria chemoprevention and the combination of vaccination and chemoprevention
Authors: Chandramohan Daniel , Dicko Alassane , Zongo Issaka , Sagara Issaka , Cairns Matthew , Kuepfer Irene , Diarra Modibo , Tapily Amadou , Issiaka Djibrilla , Sanogo Koualy , Mahamar Almahamoudou , Sompougdou Frederic , Yerbanga Serge , Thera Ismaila , Milligan Paul , Tinto Halidou , Ofori-Anyinam Opokua , Ouedraogo Jean-Bosco , Greenwood B 
Published: April 2023

IntroductionSeasonal malaria chemoprevention (SMC), with sulphadoxine–pyrimethamine plus amodiaquine (SP+AQ) is effective but does not provide complete protection against clinical malaria. The RTS,S/AS01Emalaria vaccine provides a high level of protection shortly after vaccination, but this wanes rapidly. Such a vaccine could be an alternative or additive to SMC. This trial aims to determine whether seasonal vaccination with RTS,S/AS01Evaccine could be an alternative to SMC and whether a combination of the two interventions would provide added benefits.Methods and analysisThis is an individually randomised, double-blind, placebo-controlled trial. 5920 children aged 5–17 months were enrolled in April 2017 in Mali and Burkina Faso. Children in group 1 received three priming doses of RTS,S/AS01Evaccine before the start of the 2017 malaria transmission season and a booster dose at the beginning of two subsequent transmission seasons. In addition, they received SMC SP+AQ placebo on four occasions each year. Children in group 2 received three doses of rabies vaccine in year 1 and hepatitis A vaccine in years 2 and 3 together with four cycles of SMC SP+AQ each year. Children in group 3 received RTS,S/AS01Evaccine and four courses of SMC SP+AQ. Incidence of clinical malaria is determined by case detection at health facilities. Weekly active surveillance for malaria is undertaken in a randomly selected subset of children. The prevalence of malaria is measured in surveys at the end of each transmission season. The primary endpoint is the incidence of clinical malaria confirmed by a positive blood film with a minimum parasite density of 5000 /µL. Primary analysis will be by modified intention to treat defined as children who have received the first dose of the malaria or control vaccine.Ethics and disseminationThe protocol was approved by the national ethics committees of Mali and Burkina Faso and the London School of Hygiene and Tropical Medicine. The results will be presented to all stakeholders and published in open access journals.Trial registration numberNCT03143218
Assessing mental stress on myocardial perfusion and myocardial blood flow in women without obstructive coronary disease: protocol for a mechanistic clinical trial
Authors: Ma Huan , Guo Lan , Fei Hongwen , Yin Han , Wang Haochen , Bai Bingqing , Liu Yuting , Wang Shuxia , Geng Qingshan , Jiang Wei 
Published: April 2023

IntroductionTwo-thirds of women with symptoms of angina have ‘angina with no obstructive coronary artery disease’ (ANOCA). Growing evidence supports the use of coronary artery function testing for the diagnosis of ANOCA. Research into the prevalence of mental stress-induced myocardial ischaemia (MSIMI) among women with ANOCA is lacking. MSIMI is common in clinically stable patients with coronary artery disease. It is not associated coronary stenosis but is a prognostic risk factor. Here, we describe the rationale and protocol for a mechanistic clinical trial to test the following hypotheses: (1) that MSIMI is more common in women with ANOCA women than in age-matched and sex-matched controls, and (2) MSIMI is associated with mental stress-induced myocardial blood flow (MBF) change but not with adenosine vasodilator stress-induced MBF change.Methods and analysisThis is a mechanistic clinical trial. 84 women with confirmed ANOCA and 42 aged-matched healthy women (neither angina symptoms nor coronary stenosis) are to be recruited for mental and adenosine vasodilator stress tests. Positron emission tomography CT with ammonia N-13 will be used to evaluate the myocardial perfusion and MBF changes between stress and rest. MSIMI is defined as a summed difference score (SDS) of ≥3 and adenosine stress-induced myocardial ischaemia is defined as an SDS of ≥4. Other assessments include Reactive Hyperemia Index for microvascular endothelial function, peripheral arterial tonometry or digital vasomotor response, and a series of blood and psychometric tests.Ethics and disseminationThis mechanistic clinical trial was approved by the Ethics Committee of Guangdong Provincial People’s Hospital. Findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberNCT03982901.