bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of contralaterally controlled functional electrical stimulation compared to cyclic neuromuscular electrical stimulation and task-oriented training for recovery of hand function after stroke: study protocol for a multi-site randomized controlled trial
Authors: Knutson Jayme S. , Friedl Amy S. , Hansen Kristine M. , Harley Mary Y. , Barrett A. M. , Raghavan Preeti , Plow Ela B. , Gunzler Douglas D. , Chae John 
Published: May 2022

AbstractBackgroundMulti-site studies in stroke rehabilitation are important for determining whether a technology and/or treatment can be successfully administered by sites other than the originating site and with similar positive outcomes. This study is the first multi-site clinical trial of a novel intervention for post-stroke upper limb rehabilitation called contralaterally controlled functional electrical stimulation (CCFES). Previous pilot and single-site studies showed positive effects of CCFES on upper limb impairment and hand dexterity in stroke survivors. The main purpose of this study is to confirm and demonstrate the efficacy of CCFES in a larger group of most likely responders across multiple clinical sites.MethodsUp to 129 stroke survivors with moderate to severe upper extremity hemiparesis at 4 clinical trial sites will be randomized to CCFES, cyclic neuromuscular electrical stimulation (cNMES), or task-oriented-training (TOT). Participants will receive 12 weeks of group-specific therapy. Blinded assessments of upper limb impairment and activity limitation, quality of life, and neurophysiology will be used to compare outcomes at baseline, after treatment, and up to 6 months post-treatment. The primary endpoint is change in dexterity from baseline to 6 months post-treatment.DiscussionLoss of hand function following stroke is a major rehabilitation problem affecting millions of people per year globally. More effective rehabilitation therapies are needed to restore hand function in these individuals. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or TOT, and will begin to elucidate the different mechanisms underlying each of the three treatments. This multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination.Trial registrationClinicalTrials.govNCT03574623. Registered prior to first enrollment; July 2, 2018.
How to embed qualitative research in trials: insights from the feasibility study of the SAFER trial programme
Authors: Powell Alison , Hoare Sarah , Modi Rakesh , Williams Kate , Dymond Andrew , Chapman Cheryl , Griffin Simon , Mant Jonathan , Burt Jenni 
Published: May 2022

AbstractQualitative research can enhance the design, conduct and interpretation of trials. Despite this, few trials incorporate qualitative methods, and those that do may not realise their full potential. In this commentary, we highlight how qualitative research can contribute to the design, conduct and day-to-day running of a trial, outlining the working arrangements and relationships that facilitate these contributions. In doing so, we draw on (i) existing frameworks on the role of qualitative research alongside trials and (ii) our experience of integrated qualitative research conducted as part of the feasibility study of the SAFER trial (Screening for Atrial Fibrillation with ECG to Reduce stroke), a cluster randomised controlled trial of screening people aged 70 and above for atrial fibrillation in primary care in England. The activities and presence of the qualitative team contributed to important changes in the design, conduct and day-to-day running of the SAFER feasibility study, and the subsequent main trial, informing diverse decisions concerning trial documentation, trial delivery, timing and content of measures and the information given to participating patients and practices. These included asking practices to give screening results to all participants and not just to ‘screen positive’ participants, and greater recognition of the contribution of practice reception staff to trial delivery. These changes were facilitated by a ‘one research team’ approach that underpinned all formal and informal working processes from the outset and maximised the value of both qualitative and trial coordination expertise. The challenging problems facing health services require a combination of research methods and data types. Our experience and the literature show that the benefits of embedding qualitative research in trials are more likely to be realised if attention is given to both structural factors and relationships from the outset. These include sustained and sufficient funding for qualitative research, embedding qualitative research fully within the trial programme, providing shared infrastructure and resources and committing to relationships based on mutual recognition of and respect for the value of different methods and perspectives. We outline key learning for the planning of future trials.Trial registration: Screening for atrial fibrillation with ECG to reduce stroke ISRCTN16939438 (feasibility study); Screening for atrial fibrillation with ECG to reduce stroke – a randomised controlled trial ISRCTN72104369.
Brief Educational Video plus Telecare to Enhance Recovery for Older Emergency Department Patients with Acute Musculoskeletal Pain: an update to the study protocol for a randomized controlled trial
Authors: Hurka-Richardson Karen , Platts-Mills Timothy F. , McLean Samuel A. , Weinberger Morris , Stearns Sally C. , Bush Montika , Quackenbush Eugenia , Chari Srihari , Aylward Aileen , Kroenke Kurt , Kerns Robert D. , Weaver Mark A. , Keefe Francis J. , Berkoff David , Meyer Michelle L. 
Published: May 2022

Abstract
Background
This update describes changes to the Brief Educational Tool to Enhance Recovery (BETTER) trial in response to the COVID-19 pandemic.

Methods/design
The original protocol was published in Trials. Due to the COVID-19 pandemic, the BETTER trial converted to remote recruitment in April 2020. All recruitment, consent, enrollment, and randomization now occur by phone within 24 h of the acute care visit. Other changes to the original protocol include an expansion of inclusion criteria and addition of new recruitment sites. To increase recruitment numbers, eligibility criteria were expanded to include individuals with chronic pain, non-daily opioid use within 2 weeks of enrollment, presenting musculoskeletal pain (MSP) symptoms for more than 1 week, hospitalization in past 30 days, and not the first time seeking medical treatment for presenting MSP pain. In addition, recruitment sites were expanded to other emergency departments and an orthopedic urgent care clinic.

Conclusions
Recruiting from an orthopedic urgent care clinic and transitioning to remote operations not only allowed for continued participant enrollment during the pandemic but also resulted in some favorable outcomes, including operational efficiencies, increased enrollment, and broader generalizability.

Trial registration
ClinicalTrials.gov NCT04118595. Registered on October 8, 2019.
Self-guided virtual reality therapy for social anxiety disorder: a study protocol for a randomized controlled trial
Authors: Hildebrand Anne Sophie , Roesmann Kati , Planert Jari , Machulska Alla , Otto Esra , Klucken Tim 
Published: May 2022

Abstract
Background
Social anxiety disorder (SAD) is a highly prevalent mental disorder associated with enormous stress and suffering. Cognitive behavior therapy (CBT) is the first-line treatment for SAD, yet its accessibility is often constrained with long waiting times. Digital therapeutic applications, including psychoeducation and self-guided behavioral experiments in virtual reality (VR), could facilitate access and reduce waiting times. The study aims to investigate if ultra-short-time therapy involving self-guided digital therapeutic applications with VR components can reduce the severity of SAD.

Methods
Forty SAD patients will participate in this randomized controlled trial. Half will get access to a self-guided, digital therapeutic application with exposure-based behavioral experiments in VR, while the other half will receive a control treatment. Both treatments include four therapeutic appointments. Changes in the severity of SAD will be measured after each appointment and on a 6-week follow-up assessment and will be compared between groups, with the change in SAD measured at baseline- and post-assessment as primary outcome.

Discussion
Self-guided digital therapeutic applications including ultra-short-time therapy combined with VR could help reduce the waiting time for patients and relieve the health system. The results of this study may inform psychotherapists regarding the potential of self-guided digital therapeutic applications including exposure-based behavioral experiments in VR for SAD and will provide important insight for future research on VR therapy.

Trial registration
Current Controlled Trials ISRCTN18013983. Registered on 1 February 2022.
Elucidating treatment targets and mediators within a confirmatory efficacy trial: study protocol for a randomized controlled trial of cognitive-behavioral therapy vs. light therapy for winter depression
Authors: Rohan Kelly J. , Franzen Peter L. , Roeckelin Kathryn A. , Siegle Greg J. , Kolko David J. , Postolache Teodor T. , Vacek Pamela M. 
Published: May 2022

Abstract
Background
This study is a confirmatory efficacy trial of two treatments for winter seasonal affective disorder (SAD): SAD-tailored group cognitive-behavioral therapy (CBT-SAD) and light therapy (LT). In our previous efficacy trial, post-treatment outcomes for CBT-SAD and LT were very similar, but CBT-SAD was associated with fewer depression recurrences two winters later than LT (27.3% in CBT-SAD vs. 45.6% in LT). CBT-SAD engaged and altered a specific mechanism of action, seasonal beliefs, which mediated CBT-SAD’s acute antidepressant effects and CBT-SAD’s enduring benefit over LT. Seasonal beliefs are theoretically distinct from LT’s assumed target and mechanism: correction of circadian phase. This study applies the experimental therapeutics approach to determine how each treatment works when it is effective and to identify the best candidates for each. Biomarkers of LT’s target and effect include circadian phase angle difference and the post-illumination pupil response. Biomarkers of CBT-SAD’s target and effect include decreased pupillary and sustained frontal gamma-band EEG responses to seasonal words, which are hypothesized as biomarkers of seasonal beliefs, reflecting less engagement with seasonal stimuli following CBT-SAD. In addition to determining change mechanisms, this study tests the efficacy of a “switch” decision rule upon recurrence to inform clinical decision-making in practice.

Methods
Adults with SAD (target N = 160) will be randomzied to 6-weeks of CBT-SAD or LT in winter 1; followed in winter 2; and, if a depression recurrence occurs, offered cross-over into the alternate treatment (i.e., switch from LT➔CBT-SAD or CBT-SAD➔LT). All subjects will be followed in winter 3. Biomarker assessments occur at pre-, mid-, and post-treatment in winter 1, at winter 2 follow-up (and again at mid-/post-treatment for those crossed-over), and at winter 3 follow-up. Primary efficacy analyses will test superiority of CBT-SAD over LT on depression recurrence status (the primary outcome). Mediation analyses will use parallel process latent growth curve modeling.

Discussion
Consistent with the National Institute of Mental Health’s priorities for demonstrating target engagement at the level of Research Domain Criteria-relevant biomarkers, this work aims to confirm the targets and mechanisms of LT and CBT-SAD to maximize the impact of future dissemination efforts.

Trial registration
ClinicalTrials.gov identifier: NCT03691792. Registered on October 2, 2018.
Comparison of BARD®LIFESTREAM™ covered balloon-expandable stent versus GORE® VIABAHN™ covered self-expandable stent in treatment of aortoiliac obstructive disease: study protocol for a prospective randomized controlled trial (NEONATAL trial)
Authors: Qi Yuhan , Wang Jiarong , Zhao Jichun , Huang Bing , Xiong Fei , Du Xiaojiong , Chen Xiyang , Guo Qiang , Wang Tiehao , Yuan Ding 
Published: May 2022

Abstract
Background
Covered stent has become one of the mainstream therapies for aortoiliac obstructive disease (AIOD), with a higher patency rate than bare metal stent. Covered balloon-expandable (CBE) stent can be placed more accurately with higher a radial support force, while covered self-expanding (CSE) stent has greater elasticity and higher trackability. However, there is no level I evidence regarding the comparison safety and efficacy between the CSE stent and CBE stent in AIOD to date. Therefore, this study aims to compare the efficacy and safety of CBE stent (BARD®LIFESTREAM™) and CSE stent (GORE® VIABAHN™) in AIOD.

Methods
This trial is a prospective, single-center, parallel, noninferiority, randomized controlled trial. A total of 106 patients will be enrolled and these patients will be randomized to either the CBE stent group or the CSE stent group. The primary end point of the study is the occurrence of target lesion revascularization (TLR) at 12 months after the intervention.

Discussion
To our knowledge, the ballooN sElf cOver steNt AorToiliAc occuLusive (NEONATAL) trial is the first RCT to compare CBE and CSE stent in AIOD patients. The main aim is to compare the TLR of the target lesion between CBE stent and CSE stent at 12 months post-procedure. The results of clinical trials may contribute to establishing a strategic guideline for choosing the optimal type of covered stent in the treatment of AIOD patients.

Trial registration
Chinese Clinical Trials Registry ChiCTR2100046734. Registered on 27 May 2021
E-Consent—a guide to maintain recruitment in clinical trials during the COVID-19 pandemic
Authors: Almeida-Magana Ricardo , Maroof Hanna , Grierson Jack , Clow Rosie , Dinneen Eoin , Al-Hammouri Tarek , Muirhead Nicola , Brew-Graves Chris , Kelly John , Shaw Greg 
Published: May 2022

Abstract
Background
The COVID-19 pandemic has posed daunting challenges when conducting clinical research. Adopting new technologies such as remote electronic consent (e-Consent) can help overcome them. However, guidelines for e-Consent implementation in ongoing clinical trials are currently lacking. The NeuroSAFE PROOF trial is a randomized clinical trial evaluating the role of frozen section analysis during RARP for prostate cancer. In response to the COVID-19 crisis, recruitment was halted, and a remote e-Consent solution was designed. The aim of this paper is to describe the process of implementation, impact on recruitment rate, and patients’ experience using e-Consent.

Methods
A substantial amendment of the protocol granted the creation of a remote e-Consent framework based on the REDCap environment, following the structure and content of the already approved paper consent form. Although e-Consent obviated the need for in-person meeting, there was nonetheless counselling sessions performed interactively online. This new pathway offered continuous support to patients through remote consultations. The whole process was judged to be compliant with regulatory requirements before implementation.

Results
Before the first recruitment suspension, NeuroSAFE PROOF was recruiting an average of 9 patients per month. After e-Consent implementation, 63 new patients (4/month) have been enrolled despite a second lockdown, none of whom would have been recruited using the old methods given restrictions on face-to-face consultations. Patients have given positive feedback on the use of the platform. Limited troubleshooting has been required after implementation.

Conclusion
Remote e-Consent-based recruitment was critical for the continuation of the NeuroSAFE PROOF trial during the COVID-19 pandemic. The described pathway complies with ethical and regulatory guidelines for informed consent, while minimizing face-to-face interactions that increase the risk of COVID-19 transmission. This guide will help researchers integrate e-Consent to ongoing or planned clinical trials while uncertainty about the course of the pandemic continues.

Trial registration
NeuroSAFE PROOF trial NCT03317990. Registered on 23 October 2017. Regional Ethics Committee reference 17/LO/1978.
Behavioural optimisation to address trial conduct challenges: case study in the UK-REBOA trial
Authors: Lawrie Louisa , Duncan Eilidh M. , Jansen Jan O. , Campbell Marion K. , Brunsdon Dan , Skea Zoë , Coffey Taylor , Cochran Claire , Gillies Katie 
Published: May 2022

Abstract
Background
Clinical trials comprise multiple processes at various stages of the trial lifecycle. These processes often involve complex behaviours such as recruiting vulnerable patient populations and clinicians having to deliver complex trial interventions successfully. Few studies have utilised a behavioural framework to assess challenges and develop strategies for effective trial recruitment and delivery of trial interventions. This study reports the application of an innovative methodological approach to understand core trial processes, namely recruitment and intervention delivery, using a behavioural science approach to develop strategies designed to mitigate trial process problems.

Methods
The UK-REBOA trial aims to evaluate the clinical and cost-effectiveness of resuscitative endovascular balloon occlusion of the aorta (a novel intervention) in injured patients with exsanguinating haemorrhage. A behavioural investigation (‘diagnosis’) was conducted using theory-informed (Theoretical Domains Framework, TDF) semi-structured interviews with site staff from the UK-REBOA trial to examine trial processes which could be improved in relation to trial recruitment and delivery of the intervention. Interviews were analysed using the TDF to identify influences on behaviour, which were then mapped to techniques for behaviour change and developed into potential solutions.

Results
The behavioural diagnosis of the challenges experienced during trial processes highlighted factors relevant to a range of TDF domains: Skills, Environmental context and resources, Beliefs about capabilities, Beliefs about consequences, Social influences, and Memory, attention, and decision-making processes. Within the solution development phase, we identified 24 suitable behaviour change techniques that were developed into proposed solutions to target reported process problems with the aim of changing behaviour to improve recruitment and/or intervention delivery. Proposed solutions included targeted changes to trial training content, suggestions to restructure the environment (e.g. reinforced the purpose of the trial with information about the social and environmental consequences) and other strategies to reduce barriers to recruitment and intervention delivery.

Conclusions
This study demonstrates the feasibility of applying a behavioural approach to investigate (‘diagnose’) behavioural trial process problems and subsequently develop and implement targeted solutions (‘treatment’) in an active trauma trial. Understanding the factors that affected behaviour, attitudes and beliefs in this trauma trial allowed us to implement theoretically informed, evidence-based solutions designed to enhance trial practices.

Trial registration
ISRCTN 16,184,981
The effect of delivery ball and warm shower on the childbirth experience of nulliparous women: a randomized controlled clinical trial
Authors: Sharifipour Parvaneh , Kheirkhah Masoomeh , Rajati Mojgan , Haghani Hamid 
Published: May 2022

AbstractIntroductionChildbirth is a unique experience that affects women’s life. Midwives can play an effective role in creating positive birth experiences for women using non-pharmacological and supportive methods. Accordingly, this study aims to determine the effect of delivery balls and warm showers on childbirth experiences of primiparous women.MethodsThis clinical trial was conducted on primiparous pregnant women who referred to the Motazedi Hospital in Kermanshah, Iran. Sampling was done from eligible individuals by a continuous method, and pregnant women were assigned to the three groups of delivery balls plus warm showers or A (n = 35), delivery balls or B (n = 35), and control or C (n = 35). The use of the ball at the dilation of 4 cm was similar in the two groups of A and B, but the first group used a warm shower at the dilatation of 7 cm as well. The control group also received routine delivery care. Besides, demographic information forms consisting of the pregnancy history and some information about the mother and her infant were completed. Additionally, childbirth experience questionnaires (CEQ) were completed by the women two hours after childbirth. The analysis of intervention effects was performed as per-protocol analysis.ResultsThere was a statistically significant difference in the mean score of the childbirth experience between the two groups of A and C (p = 0.001) after the intervention as well as between the groups of B and C (p = 0.001).ConclusionThe use of delivery balls and warm showers was effective in creating a positive childbirth experience. To create a positive childbirth experience in mothers, the use of both interventions (delivery balls and warm showers) is recommended.Trial registrationTCTR20200408002. Prospectively registered on March 21, 2020.
Recent large-scale philophthalmosis outbreak in Portugal: inefficacy of common antihelminthic agents
Authors: Heneberg Petr , Casero María 
Published: May 2022

AbstractBackgroundParasitic conjunctivitis caused byPhilophthalmusspp. is a common ophthalmic disease in birds, with localized outbreaks occurring worldwide. There is no consensus on treating this disease; mechanical removal is considered a standard recommendation, but is associated with disease relapses within days or weeks.MethodsFrom 2015 to 2020, we examined 4295Larus michahellisandLarus fuscusgulls in southern Portugal for the presence ofPhilophthalmusspp. Due to the need to treat dozens of infected gulls in the rescue station, we tested three treatment regimens aimed at targetingPhilophthalmus lucipetusin the infected gulls: (I) the ophthalmic application of levamisole; (II) the oral application of milbemycin in combination with praziquantel; and (III) the subcutaneous application of ivermectin.ResultsThe outbreak of philophthalmosis in gulls in southern Portugal has been ongoing since the first cases were reported in 2015–2016. The prevalence of philophthalmosis has fluctuated annually, peaking a maximum of 10.3% inL. fuscusin 2017 and at 2.1% inL. michahellisin 2016. The infection intensity peaked at a median of 11.5 eye-flukes per host bird inL. fuscusin 2016 and a median of six eye-flukes per host bird inL. michahellisin 2017. Nine gulls were infected with >50 eye-flukes. None of the treatment options were effective at treatingP. lucipetusinfections: the numbers of eye-flukes in the infected birds did not decrease, and the clinical signs of the disease did not change.ConclusionsAn outbreak of philophthalmosis in southern Portugal has massively affected two species of gulls in the region. Two previously suggested philophthalmosis treatments (ocular levamisole and praziquantel given orally), as well as a third mode of treatment with a previously failed compound (ivermectin administered subcutaneously) were used. However, the treatments did not affect the numbers ofP. lucipetusin the eyes of the treated gulls. Further research should address ophthalmic gel formulations or sub-conjunctival delivery mode for antihelminthic drugs that are effective againstPhilophthalmusspp. in vitro.Graphical abstract