bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trial Forge Guidance 3: randomised trials and how to recruit and retain individuals from ethnic minority groups—practical guidance to support better practice
Authors: Dawson Shoba , Banister Katie , Biggs Katie , Cotton Seonaidh , Devane Declan , Gardner Heidi , Gillies Katie , Gopalakrishnan Gosala , Isaacs Talia , Khunti Kamlesh , Nichol Alistair , Parker Adwoa , Russell Amy M. , Shepherd Victoria , Shiely Frances , Shorter Gillian , Starling Bella , Williams Hywel , Willis Andrew , Witham Miles D. , Treweek Shaun 
Published: August 2022

AbstractRandomised trials, especially those intended to directly inform clinical practice and policy, should be designed to reflect all those who could benefit from the intervention under test should it prove effective. This does not always happen. The UK National Institute for Health and Care Research (NIHR) INCLUDE project identified many groups in the UK that are under-served by trials, including ethnic minorities.This guidance document presents four key recommendations for designing and running trials that include the ethnic groups needed by the trial. These are (1) ensure eligibility criteria and recruitment pathway do not limit participation in ways you do not intend, (2) ensure your trial materials are developed with inclusion in mind, (3) ensure staff are culturally competent and (4) build trusting partnerships with community organisations that work with ethnic minority groups. Each recommendation comes with best practice advice, public contributor testimonials, examples of the inclusion problem tackled by the recommendation, or strategies to mitigate the problem, as well as a collection of resources to support implementation of the recommendations.We encourage trial teams to follow the recommendations and, where possible, evaluate the strategies they use to implement them. Finally, while our primary audience is those designing, running and reporting trials, we hope funders, grant reviewers and approvals agencies may also find our guidance useful.
Integration of smoking cessation into standard treatment for patients receiving opioid agonist therapy who are smoking tobacco: protocol for a randomised controlled trial (ATLAS4LAR)
Authors: Druckrey-Fiskaaen Karl Trygve , Furulund Einar , Daltveit Jan Tore , Vold Jørn Henrik , Lid Torgeir Gilje , Madebo Tesfaye , Fadnes Lars Thore ,   for the ATLAS4LAR Study Group, Buljovcic Vibeke Bråthen , Fondenes Trude , Gundersen Per , Carlsen Siv-Elin Leirvåg , Nordbotn Mette Hegland , Pierron Marianne Cook , Sundal Christine , Vold Jørn Henrik , Bergsaker Maren Borsheim , Dahl Eivin , Eielsen Tone Lise , Fiskå Torhild , Holder Eirik , Cruickshank Tine Selmer , Wilk Ewa Joanna 
Published: August 2022

Abstract
Background
About 85% of patients receiving opioid agonist therapy (OAT) for opioid dependence are smoking tobacco. Although smoke-related pulmonary diseases are significant contributors to morbidity and mortality, few smoking cessation interventions are evaluated within this group, and few OAT patients are offered smoking cessation as an integrated part of their addiction treatment. This study protocol describes an integrated smoking cessation intervention aimed at patients receiving OAT and smoking tobacco.

Methods
This is a multicentre, randomised controlled clinical trial that will recruit 266 daily tobacco smoking patients receiving OAT in OAT outpatient clinics in Bergen and Stavanger, Norway. The patients randomised for the intervention arm will be offered smoking cessation therapy consisting of weekly brief behavioural interventions and prescription-free nicotine replacement products. In the control arm, patients will receive standard care without any added interventions related to smoking cessation.
The smoking cessation intervention includes psychoeducational techniques with components from motivational interviewing, and nicotine replacement products such as nicotine lozenges, patches, and chewing gum. The duration of the intervention is 16 weeks, with the option of extending it by a further 8 weeks. The main outcomes are measured at 16 weeks after initiation of the intervention, and sustained effects are evaluated 1 year after intervention initiation.
The primary outcome is smoking cessation verified by carbon monoxide (CO) levels or at least a 50% reduction in the number of cigarettes smoked. Secondary outcomes are changes in psychological well-being, biochemical inflammation markers, changes in physical health, quality of life, and fatigue.

Discussion
Integration of other treatments to standard OAT care improves adherence and completion rates providing another rationale for integrated smoking cessation treatment. Thus, if integrated smoking cessation treatment is superior to standard care, this trial provides important information on further scale-up.

Trial registration
ClinicalTrials.gov NCT05290025. Registered on 22 March 2022
Study protocol of a multiphase optimization strategy trial (MOST) for delivery of smoking cessation treatment in lung cancer screening settings
Authors: Ostroff Jamie S. , Shelley Donna R. , Chichester Lou-Anne , King Jennifer C. , Li Yuelin , Schofield Elizabeth , Ciupek Andrew , Criswell Angela , Acharya Rashmi , Banerjee Smita C. , Elkin Elena B. , Lynch Kathleen , Weiner Bryan J. , Orlow Irene , Martin Chloé M. , Chan Sharon V. , Frederico Victoria , Camille Phillip , Holland Susan , Kenney Jessica 
Published: August 2022

AbstractBackgroundThere is widespread agreement that the integration of cessation services in lung cancer screening (LCS) is essential for achieving the full benefits of LCS with low-dose computed tomography (LDCT). There is a formidable knowledge gap about how to best design feasible, effective, and scalable cessation services in LCS facilities. A collective of NCI-funded clinical trials addressing this gap is the Smoking Cessation at Lung Examination (SCALE) Collaboration.MethodsThe Cessation and Screening to Save Lives (CASTL) trial seeks to advance knowledge about the reach, effectiveness, and implementation of tobacco treatment in lung cancer screening. We describe the rationale, design, evaluation plan, and interventions tested in this multiphase optimization strategy trial (MOST). A total of 1152 screening-eligible current smokers are being recruited from 18 LCS sites (n= 64/site) in both academic and community settings across the USA. Participants receive enhanced standard care (cessation advice and referral to the national Quitline) and are randomized to receive additional tobacco treatment components (motivational counseling, nicotine replacement patches/lozenges, message framing). The primary outcome is biochemically validated, abstinence at 6 months follow-up. Secondary outcomes are self-reported smoking abstinence, quit attempts, and smoking reduction at 3 and 6 months. Guided by the Implementation Outcomes Framework (IOF), our evaluation includes measurement of implementation processes (reach, fidelity, acceptability, appropriateness, sustainability, and cost).ConclusionWe will identify effective treatment components for delivery by LCS sites. The findings will guide the assembly of an optimized smoking cessation package that achieves superior cessation outcomes. Future trials can examine the strategies for wider implementation of tobacco treatment in LDCT-LCS sites.Trial registrationClinicalTrials.govNCT03315910
The effect of continuing versus withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers on mortality and major adverse cardiovascular events in hypertensive patients undergoing elective non-cardiac surgery: study protocol for a multi-centric open-label randomised controlled trial
Authors: Misra Satyajeet , Parida Satyen , Sahajanandan Raj , Behera Bikram Kishore , Senthilnathan Muthapillai , Mariappan Ramamani , Chandy Tony Thomson ,   For the ACE investigators
Published: August 2022

Abstract
Background
Angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) are commonly prescribed to patients with hypertension. These drugs are cardioprotective in addition to their blood pressure-lowering effects. However, it is debatable whether hypertensive patients who present for non-cardiac surgery should continue or discontinue these drugs preoperatively. Continuing the drugs entails the risk of perioperative refractory hypotension and/or angioneurotic oedema, while discontinuing the drugs entails the risk of rebound hypertension and myocardial ischaemia. The aim of this study is to evaluate the effect of continuation vs withholding of ACEIs/ARBs on mortality and other major outcomes in hypertensive patients undergoing elective non-cardiac surgery.

Methods
The continuing vs withholding of ACEIs/ARBs in patients undergoing non-cardiac surgery is a prospective, multi-centric, open-label randomised controlled trial. Two thousand one hundred hypertensive patients receiving ACEIs/ARBs and planned for elective non-cardiac surgery will be enrolled. They will be randomised to either continue the ACEIs/ARBs including on the day of surgery (group A) or to withhold it 24–36 h before surgery (group B). The primary endpoint will be the difference in the composite outcome of all-cause in-hospital/30-day mortality and major adverse cardiovascular and non-cardiovascular events. Secondary endpoints will be to evaluate the differences in perioperative hypotension, angioneurotic oedema, myocardial injury, ICU and hospital stay. The impact of the continuation vs withholding of the ACEIs/ARBs on the incidence of case cancellation will also be studied.

Discussion
The results of this trial should provide sufficient evidence on whether to continue or withhold ACEIs/ARBs before major non-cardiac surgery.

Trial registration
Clinical Trials Registry of India CTRI/2021/01/030199. Registered on 4 January 2021
Timing of transcranial direct current stimulation (tDCS) combined with speech and language therapy (SLT) for aphasia: study protocol for a randomized controlled trial
Authors: Ashaie Sameer A. , Engel Samantha , Cherney Leora R. 
Published: August 2022

Abstract
Background
Studies suggest that language recovery in aphasia may be improved by pairing speech-language therapy with transcranial direct current stimulation. However, results from many studies have been inconclusive regarding the impact transcranial direct current stimulation may have on language recovery in individuals with aphasia. An important factor that may impact the efficacy of transcranial direct current stimulation is its timing relative to speech-language therapy. Namely, online transcranial direct current stimulation (paired with speech-language therapy) and offline transcranial direct current stimulation (prior to or following speech-language therapy) may have differential effects on language recovery in post-stroke aphasia. Transcranial direct current stimulation provided immediately before speech-language therapy may prime the language system whereas stimulation provided immediately after speech-language therapy may aid in memory consolidation. The main aim of this study is to investigate the differential effects of offline and online transcranial direct stimulation on language recovery (i.e., conversation) in post-stroke aphasia.

Methods/design
The study is a randomized, parallel-assignment, double-blind treatment study. Participants will be randomized to one of four treatment conditions and will participate in 15 treatment sessions. All groups receive speech-language therapy in the form of computer-based script practice. Three groups will receive transcranial direct current stimulation: prior to speech-language therapy, concurrent with speech-language therapy, or following speech-language therapy. One group will receive sham stimulation (speech-language therapy only). We aim to include 12 participants per group (48 total). We will use fMRI-guided neuronavigation to determine placement of transcranial direct stimulation electrodes on participants’ left angular gyrus. Participants will be assessed blindly at baseline, immediately post-treatment, and at 4 weeks and 8 weeks following treatment. The primary outcome measure is change in the rate and accuracy of the trained conversation script from baseline to post-treatment.

Discussion
Results from this study will aid in determining the optimum timing to combine transcranial direct current stimulation with speech-language therapy to facilitate better language outcomes for individuals with aphasia. In addition, effect sizes derived from this study may also inform larger clinical trials investigating the impact of transcranial direct current stimulation on functional communication in individuals with aphasia.

Trial registration
ClinicalTrials.gov NCT03773406. December 12, 2018.
The CORE-KDT study: a mixed methods protocol to establish core outcomes for refractory childhood epilepsy treated with ketogenic diet therapy
Authors: Carroll Jennifer H. , Cross J. Helen , Hickson Mary , Williams Emma , Aldridge Valerie , Collinson Avril 
Published: August 2022

Abstract
Background
A core outcome set defines the minimum outcomes that should be included in clinical trials, audit or practice. The aim being to increase the quality and relevance of research by ensuring consistency in the measurement and reporting of outcomes. Core outcome sets have been developed for a variety of disease states and treatments. However, there is no established set of core outcomes for refractory childhood epilepsy treated with ketogenic diet therapy. This should be developed using a patient-centred approach to ensure the outcomes measured are relevant to patients and clinical practice.

Methods
This is a mixed methods study of four phases to develop a core outcome set for refractory childhood epilepsy treated with ketogenic diet therapy. In phase 1, a systematic scoping review of the literature will establish which outcomes are measured in trials of refractory epilepsy treated with ketogenic diet therapy. In phase 2, qualitative interviews with parents and carers will aim to identify the outcomes of importance to these stakeholders. Phase 3 will see a comprehensive list of outcomes collated from the first two phases, grouped into domains according to an outcome taxonomy. Phase 4 will invite parents, health care professionals and researchers to participate in a two-round Delphi study to rate the importance of the presented outcomes. Following which, the core outcome set will be ratified at a face to face consensus meeting.

Discussion
This study will guide outcome measurement in future studies of childhood epilepsy treated with ketogenic diet therapy and clinical practice through audit and service evaluation.
Efficacy and safety of Dengyinnaotong Capsule in patients with Cognitive impairment caused by cerebral Small Vessel Disease: study protocol of a multicenter, randomized, open-label, controlled trial (De-CSVD trial)
Authors: Li Yan-Xia , Li Jin-Cun , Tian Min , Zheng Mao-Yong , Zhang Li-Ping , Zhang Jin-Lu , Yu Feng , Li Yi-Zhao , Zhang Qing-Hua 
Published: August 2022

Abstract
Background
Cerebral small vessel disease (CSVD) is a common syndrome in the older population, with a prevalence ranging from 5% in subjects aged 50 years to almost 100% in those aged 90 years and older. It is regarded to be a major cause of vascular cognitive impairment. Existing prevention and treatment approaches have not yet shown ideal clinical outcomes. Dengyinnaotong Capsule has shown great potential for improving cognitive function. This trial (De-CSVD trial) is designed to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive function in patients with CSVD .

Methods
This multicenter, randomized, open-label, controlled trial is planned to recruit at least 270 patients with mild cognitive impairment related to CSVD in 25 centers in China. Recruitment started on 10 May 2021 and is foreseen to end on 31 December 2022. The final follow-up of participants will be completed by the end of March 2023. Participants will be randomized in a ratio of 1:1 to the experimental group (routine basic treatment plus Dengyinnaotong Capsule) or the control group (routine basic treatment). The primary outcome is the change in the Montreal Cognitive Assessment score from baseline to week 12. Secondary outcomes are changes in Shape Trail Test, Activities of Daily Living, Geriatric Depression Scale, and Dizziness Handicap Inventory score from baseline to week 12, new vascular events, and the changes in serum level of homocysteine, high-sensitivity C-reactive protein, and D-dimer from baseline to week 4 and 12, respectively. The exploratory outcome is the changes in the Tinetti performance-oriented mobility assessment score from baseline to week 12. Safety assessment is performed by monitoring vital signs, general biochemical examinations, 12-lead electrocardiogram examinations, and incidence of cardiovascular and cerebrovascular ischemia or bleeding events. Visits will be performed at week 0 (baseline, pre-randomization), week 4, and week 12 in the treatment period (post-randomization).

Discussion
This trial is the first to investigate the efficacy and safety of Dengyinnaotong Capsule on cognitive impairment in patients with CSVD. The findings of this study might provide convincing evidence regarding the efficacy of Dengyinnaotong Capsule in patients with mild cognitive impairment related to CSVD.

Trial registration
Chinese Clinical Trial Registry ChiCTR2100045831. Registered on 25 April 2021.
Shoulder-specific rehabilitation combined with aerobic exercises versus solely shoulder-specific rehabilitation in patients with type 2 diabetes mellitus: study protocol for a randomized controlled superiority trial
Authors: Habechian Fernanda A. P. , Flores Quezada Mauricio E. , Cools Ann M. , Kjaer Birgitte Hougs , Cuevas Cid Rodrigo I. , Zanca Gisele G. 
Published: August 2022

Abstract
Background
Musculoskeletal disorders are very common in patients with diabetes mellitus (DM). The upper limb is one of the regions that is most frequently affected generally presenting limited joint mobility, pain, and a decreased muscle strength. Most clinical trials with a focus on shoulder musculoskeletal rehabilitation are carried out in patients who do not present DM. Thus, the purpose of the present study is to compare the effects of two distinct treatment protocols (conventional shoulder musculoskeletal rehabilitation combined with aerobic exercises versus solely conventional shoulder musculoskeletal rehabilitation) on shoulder pain, function, strength, kinematics, and supraspinatus tendon thickness in patients with type 2 DM after 12 weeks of intervention and a subsequent follow-up at week 20.

Methods
A randomized controlled superiority trial will be conducted. Participants with a clinical diagnosis of type 2 DM of both sexes, age between 40 and 70 years, presenting shoulder pain will be randomly assigned to one of the following groups: (1) conventional shoulder musculoskeletal rehabilitation combined with aerobic exercises; (2) solely conventional shoulder musculoskeletal rehabilitation. All individuals will be evaluated before starting the treatment protocol (baseline) and at the end of treatment (post 12 weeks) and as a follow-up at 20 weeks. The shoulder function assessed by the SPADI (Shoulder Pain and Disability Index) questionnaire will be considered as primary outcome; the secondary outcome will be shoulder pain, measured with NPRS scales. Other outcomes will include range of motion, measured using a digital inclinometer; isometric shoulder muscle strength, measured using a manual muscle dynamometer; shoulder kinematics, measured using three-dimensional inertial units measurement; supraspinatus tendon thickness, measured using an ultrasound; AGE accumulation, using a skin autofluorescence measurement; and HbA1c (hemoglobin a1c), fasting glucose and lipid profile measured by a simple blood test.

Discussion
DM is a highly prevalent disease and a public health problem worldwide, and the upper extremity musculoskeletal disorders in DM are barely recognized and largely underestimated. In this way, it would be interesting to analyze if the combination of aerobic exercises with conventional musculoskeletal rehabilitation protocols could generate better results in the functionality, pain, mobility and an improvement in the biochemical aspects related to the hyperglycemia of these patients compared to solely the conventional musculoskeletal rehabilitation.

Trial registration
ClinicalTrials.gov NCT04817514. Registered on March 26, 2021.
Post-operative rehabilitation using a digital healthcare system in patients who had undergone rotator cuff repair: protocol for a single-center randomized controlled trial
Authors: Chang Won Kee , Lee Jong In , Hwang Ji Hye , Lim Jae-Young 
Published: August 2022

Abstract
Background
Operative repair of a rotator cuff tear requires up to 12 weeks of post-operative (post-op) home-based rehabilitation. Maintaining patients’ compliance in the post-op rehabilitation program is a pivotal component for generating successful outcomes. By developing a post-op rehabilitation-oriented digital healthcare system and applying it in patients who had undergone rotator cuff repair, we aim to increase the efficacy of the rehabilitation program and raise patients’ compliance levels. Here, we present a protocol developed for comparing the efficacy of rehabilitation using a newly developed augmented reality (AR)-based digital healthcare system with that of conventional rehabilitation for post-op rehabilitation of rotator cuff repair.

Methods
This study will recruit a total of 115 patients who had undergone rotator cuff repair within 3 days after surgery. Patients will be randomly allocated to rehabilitation using an AR-based digital healthcare system (digital group) or conventional rehabilitation (conventional group). Patients in both groups will perform brochure-based exercises from the immediate post-op period to post-op 6 weeks. From post-op 6 weeks to 12 weeks, patients in the digital group will use the AR-based system for post-op exercises, whereas patients in the conventional group will continue brochure-based rehabilitation exercises. The primary outcome will be scores on the Simple Shoulder Test at post-op 12 weeks. Secondary outcomes include numeric rating scale scores for pain, measures of range of motion and muscle strength of the affected shoulder, grip strength of the affected arm, scores on the Disabilities of the Arm, Shoulder and Hand test, the Shoulder Pain and Disability Index, and the EuroQoL-5D-5L quality-of-life measure. Analyses will be conducted using an intention-to-treat approach.

Discussion
This study will examine the effectiveness of an AR-based digital healthcare system for post-op rehabilitation in the patients after rotator cuff repair. The study will add evidence for the application of digital healthcare systems in post-op rehabilitation.

Trial registration
ClinicalTrials.gov NCT04511377. Registered on 10 August 2020.