bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of a randomised controlled trial of the effects of empagliflozin on myocardial perfusion, function and metabolism in type 2 diabetes patients at high cardiovascular risk (the SIMPLE trial)
Authors: Jürgens Mikkel , Schou Morten , Hasbak Philip , Kjær Andreas , Wolsk Emil , Zerahn Bo , Wiberg Mikkel , Brandt Niels Høgh , Gæde Peter Haulund , Rossing Peter , Faber Jens , Inzucchi Silvio , Gustafsson Finn , Kistorp Caroline Michaela 
Published: April 2023

IntroductionA diagnosis of type 2 diabetes (T2D) more than doubles the risk of cardiovascular disease (CVD), with heart failure (HF) being one of the most common complications with a severe prognosis. The landmark Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Paitients (EMPA-REG OUTCOME) study demonstrated that treatment with the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin rapidly and significantly reduces CVD mortality and admission rates for HF. However, the mechanisms behind this reduction in clinical events are unknown.This study was designed to investigate the effects of the SGLT-2 inhibitor empagliflozin on myocardial perfusion and function in patients with T2D and high CVD risk.Methods and analysisIn this investigator-initiated, randomised, double-blind controlled clinical trial, 92 patients with T2D and established CVD or high CVD risk will be randomised to treatment with empagliflozin 25 mg or a matching placebo for 13 weeks. The primary outcome measure is change in myocardial flow reserve measured quantitatively by Rubidium-82 position emission tomography. In a substudy, invasive haemodynamics at rest and during exercise will be measured at baseline and following the intervention, using right heart catheterisation.Ethics and disseminationThe study protocol (v7, 02/08/2018) has been approved by the Ethics Committee of the Capital Region, Danish Data Protection Board and the Danish Medicines Agency, and it will be monitored according to the Good Clinical Practice regulations from the International Conference on Harmonization. The results be submitted to international peer-reviewed journals and be presented at conferences. The data will be made available to the public via EudraCT andwww.clinicaltrials.gov.Trial registration numberNCT03151343.
Efficacy and safety of modified-release paracetamol for acute and chronic pain: a systematic review protocol
Authors: Margan Koletic Zeljana , Dosenovic Svjetlana , Puljak Livia 
Published: April 2023

IntroductionParacetamol (acetaminophen) is widely used for management of mild-to-moderate pain and reduction of fever. It is available as immediate release (IR) and modified-release (MR) formulation. In 2017, European Medicines Agency recommended a suspension of marketing of MR paracetamol in the European Union. Benefit-risk balance of these products has been assessed as negative as data showed that existing procedures for overdose management may not be efficient. Since MR paracetamol is still available in other countries (Australia and USA) and there is no available systematic review (SR) of efficacy and safety of MR paracetamol in the literature, we have decided to perform one to evaluate available data from randomised clinical trials (RCTs).Methods and analysisUsing predefined search criteria, we will search EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform to identify RCTs evaluating efficacy and safety of MR paracetamol alone in any dose or duration for any pain. Participants are defined as adults and adolescents (over 12 years). Primary efficacy outcomes will be pain intensity, pain relief and sleep. Primary safety outcomes will be the number of patients experiencing any (serious) adverse event, the number of patients withdrawn due to adverse events and the number of patients with gastrointestinal and hepatic adverse events. Data analysis will be subdivided based on different clinical syndromes. Meta-analysis will be conducted if possible. Cochrane risk of bias (RoB) tool with seven dimensions will be used to assess RoB of individual studies.Ethics and disseminationThis SR will include only data collected from trial reports; therefore, an ethical approval will not be sought. We will publish the protocol and our findings in peer-reviewed journals.PROSPERO registration numberNCT42018115769.
Rehabilitation of cognitive deficits poststroke: protocol for a systematic review and meta-analysis of randomised controlled trials of non-pharmacological interventions
Authors: O Donoghue Mairead , Boland Pauline , Galvin Rose , Coote Susan , Hayes Sara 
Published: April 2023

IntroductionStroke is among the leading causes of death and disability worldwide. Poststroke cognitive impairment is a common sequela of stroke. The burden of cognitive impairment poststroke has significant impacts on the individual poststroke, their family and wider society. Despite the prevalence and associated burden of poststroke cognitive impairment, the optimal approach to rehabilitate cognitive deficits poststroke has yet to be established. A range of conservative interventions for cognitive impairment poststroke exist including self-efficacy training, physical activity interventions, neuropsychological interventions, electronic interventions, music therapy and occupational therapies. This systematic review aims to explore the totality of evidence with regard to non-pharmacological rehabilitation interventions wherein the primary or secondary aim is to improve cognitive function in individuals poststroke.Methods and analysisA systematic review of randomised controlled trials which investigate the effectiveness of interventions wherein the primary or secondary aim is to improve cognitive function in individuals poststroke will be conducted (August 2019). The following electronic databases will be searched: PubMed, Embase, CINAHL, CENTRAL and PsycInfo. Reference lists of all identified studies will be reviewed to identify additional studies for inclusion. Titles and abstracts will be screened independently by two review authors for inclusion and exclusion. Any disagreement regarding inclusion will be resolved by discussion or by referral to a third assessor if necessary. Methodological quality will be assessed using the Cochrane Risk of Bias Tool for Randomised Controlled Trials. Meta-analyses will be performed if studies are sufficiently homogeneous. The review will be reported in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Ethics and disseminationAs this systematic review will collect secondary data only, ethical approval is not required. Findings will be disseminated through presentations and peer-reviewed journals.Trial registration numberNCT42019125289.
Hybrid cardiac rehabilitation trial (HYCARET): protocol of a randomised, multicentre, non-inferiority trial in South America
Authors: Serón Pamela , Oliveros Maria J , Marzuca-Nassr Gabriel N , Lanas Fernando , Morales Gladys , Román Claudia , Muñoz Sergio R , Saavedra Nicolás , Grace Sherry L 
Published: April 2023

IntroductionCardiac rehabilitation (CR) programmes are well established, and their effectiveness and cost-effectiveness are proven. In spite of this, CR remains underused, especially in lower-resource settings such as Latin America. There is an urgent need to create more accessible CR delivery models to reach all patients in need. This trial aims to evaluate if the prevention of recurrent cardiovascular events is not inferior in a hybrid CR programme compared with a standard programme.Method and analysisA non-inferiority, pragmatic, multicentre, parallel (1:1), prospective, randomised and open with blinded endpoint assessment clinical trial will be conducted. 308 patients with coronary artery disease will be recruited consecutively. Participants will be randomised to hybrid or standard rehabilitation programme. The hybrid CR programme includes 10 supervised exercise sessions and individualised lifestyle counselling by a physiotherapist, with a transition after 4–6 weeks to unsupervised delivery via text messages and phone calls. The standard CR consists of 18–22 supervised exercise sessions, as well as group education sessions about lifestyle. Intervention in both groups is between 8 and 12 weeks. The primary outcome is a composite of cardiovascular mortality and hospitalisations due to cardiovascular causes. Secondary outcomes are health-related quality of life, exercise capacity, muscle strength, heart-healthy behaviour, return-to-work, cardiovascular risk factor, adherence, and exercise-related adverse events. The outcomes will be measured at the end of intervention, at 6 months and at 12 months follow-up from recruitment. The primary outcome will be tracked through the end of the trial. Per-protocol and intention-to-treat analysis will be undertaken.Cox regression model will be used to compare primary outcome among study groups.Ethics and disseminationEthics committees at the sponsor institution and each centre where participants will be recruited approved the study protocol and the Informed Consent. Research findings will be published in peer-reviewed journals; additionally, results will be disseminated among region stakeholders.Trial registration numberNCT03881150.Date and version01 October 2019.
ALADDIN study: does assisted hatching of vitrified/warmed blastocysts improve live birth rate? Protocol for a multicentric randomised controlled trial
Authors: Alteri Alessandra , Guarneri Cristina , Corti Laura , Restelli Liliana , Reschini Marco , Giardina Paolo , Papaleo Enrico , Somigliana Edgardo , Viganò Paola , Paffoni Alessio 
Published: April 2023

IntroductionRecent data suggest a higher clinical pregnancy rate performing assisted hatching (AH) on previously cryopreserved embryos but fail to demonstrate significant effects on live birth rate. However, current evidence is based on studies with a small sample size and may hide a type II error. Moreover, poor attention has been given to the specific effect of AH on frozen/thawed blastocysts. To shed light on this topic, we developed the present protocol for a randomised trial to investigate the benefits of the laser-mediated partial removal of the zona pellucida in vitrified/warmed blastocysts.Methods and analysisThe pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN) study is a multicentric prospective comparative study with a parallel randomised controlled design aiming to investigate whether AH performed on warmed blastocysts before embryo transfer can improve live birth rate. Women allocated to the control group will undergo embryo transfer of blastocysts not previously subjected to AH. Two infertility units will be involved in the study. Enrolment of patients will last 18 months with quarterly monitoring and the entire study is foreseen to be closed in 36 months. Secondary outcomes include: proportion of transferred blastocysts/thawed blastocyst, morphological features of blastocysts before embryo transfer, implantation, biochemical pregnancy, clinical pregnancy (ultrasound visible gestational sac), miscarriage, multiple pregnancy, preterm birth (<37 weeks of gestation), obstetrical and neonatal complications and congenital anomaly rates.Ethics and disseminationThis protocol received a favourable ethical opinion from the Ethical Committee of IRCCS San Raffaele Scientific Institute and the Ethical Committee Area 2 Milan. Each participant will provide written consent to participate and remain encoded during the study. The trial results will be published in peer-reviewed journals and presented at conferences.Trial registration numberNCT03623659.
Protocol for a pilot randomised controlled trial evaluating feasibility and acceptability of cognitive remediation group therapy compared with mutual aid group therapy for people ageing with HIV-associated neurocognitive disorder (HAND) in Toronto, Canada
Authors: Eaton Andrew David , Walmsley Sharon L , Craig Shelley L , Rourke Sean B , Sota Teresa , McCullagh John W , Fallon Barbara A 
Published: April 2023

IntroductionHIV-associated neurocognitive disorder (HAND) may affect 30%–50% of people ageing with HIV. HAND may increase stress and anxiety, and impede coping. Psychosocial group therapy may ameliorate HAND’s symptoms, yet the ideal intervention is unclear. This protocol outlines a pilot randomised controlled trial (RCT)—designed using community-based participatory research—to pilot cognitive remediation group therapy (CRGT) against an active comparator.Methods and analysisThis is a pilot, parallel design, two-arm RCT that will recruit participants diagnosed with the mild neurocognitive disorder form of HAND from a neurobehavioural research unit at a tertiary care hospital in Toronto, Canada. Eligibility criteria include age ≥40 years, known HIV status for 5+ years, English fluency, able to consent and able to attend 8 weeks of group therapy. Eligible participants will be randomised to one of two treatment arms, each consisting of eight-session group interventions delivered once weekly at 3 hours per session. Arm 1 (novel) is CRGT, combining mindfulness-based stress reduction with brain training activities. Arm 2 (active control) is mutual aid group therapy. The primary outcomes are feasibility, measured by proportions of recruitment and completion, and acceptability, determined by a satisfaction questionnaire. The secondary outcome is intervention fidelity, where content analysis will be used to assess facilitator session reports. A between-group analysis will be conducted on exploratory outcomes of stress, anxiety, coping and use of intervention activities that will be collected at three time points.Ethics and disseminationEthical approval was obtained from the Research Ethics Boards of St. Michael’s Hospital and the University of Toronto. Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. This study could provide insight into design (eg, recruitment, measures) and intervention considerations (eg, structure, content) for a larger trial to lessen the burden of cognitive decline among people ageing with HIV.Trial registration numberNCT03483740
Rationale and design of the Lowlands Saves Lives trial: a randomised trial to compare CPR quality and long-term attitude towards CPR performance between face-to-face and virtual reality training with the Lifesaver VR app
Authors: Nas Joris , Thannhauser Jos , Vart Priya , van Geuns Robert-Jan , van Royen Niels , Bonnes Judith L , Brouwer Marc A 
Published: April 2023

IntroductionLayperson cardiopulmonary resuscitation (CPR) is a key aspect in the chain of survival after cardiac arrest. New, low-cost, easily accessible training methods such as virtual reality (VR) training with a smartphone application may reach broader populations, but data on CPR performance are scarce.Methods and analysisThe Lowlands Saves Lives trial is a prospective randomised open-blinded end-point evaluation study, comparing two 20 min CPR training protocols: standardised, certified instructor-led face-to-face training complying with current education guidelines (using Laerdal Little Anne manikins), and VR training, using the UK Resuscitation Council endorsed Lifesaver VR app. In the latter, chest compressions are practiced on a pillow.During VR training, participants learn to resuscitate by completing a filmed CPR scenario while wearing VR goggles and headphones. Eligible for inclusion are adult attendees of Lowlands Science, a specific section of the 3-day Lowlands music festival (50 000 attendees), dedicated exclusively to science. Following the training, all participants will perform a CPR test on a Laerdal Resusci Anne QCPR manikin. Primary outcome measures are depth and rate of chest compressions, measured using CPR manikins. The key secondary outcome is overall CPR performance, with real-time examination (blinded for study group) of all items of a European Resuscitation Council endorsed checklist, and evaluation of a sample of videotaped CPR tests by a blinded event committee.Given the unique setting of a festival, the primary additional analysis will address the impact of alcohol levels on CPR quality parameters and overall performance. Follow-up questionnaires will evaluate the attitude towards performing CPR. This unique study may provide important insights into innovative CPR training methods, factors that impact CPR performance and the impact on long-term attitude towards resuscitation.Ethics and disseminationThis study received approval from the research ethics committee of the Radboudumc. All participants will provide written informed consent. The results of this study will be published in peer-reviewed journals and presented at (inter)national conferences.Trial registration numberClinicalTrials.gov registry (NCT04013633).
One-to-one befriending for people with intellectual disability and symptoms of depression: protocol for a pilot randomised controlled trial
Authors: Ali Afia , Mckenzie Emma , Hassiotis Angela , Priebe Stefan , Lloyd-Evans Brynmor , Omar Rumana , Jones Rebecca , Panca Monica , Fernandez Vincent , Finning Sally , Moore Shirley , O'Connor Danielle , Roe Christine , King Michael 
Published: April 2023

IntroductionPeople with intellectual disability (ID) are more likely to experience loneliness and have smaller social networks, which increases vulnerability to depression. Befriending may reduce depressive symptoms in other populations, but randomised controlled trials (RCTs) have not been carried out in this population. This pilot study aims to assess the acceptability and feasibility of carrying out a full RCT of one-to-one befriending by volunteers for people with ID, compared with an active control group.Methods and analysisThe trial aims to recruit 40 participants with ID. Participants in the intervention arm will receive weekly visits from a volunteer over 6 months. Community befriending schemes will recruit, train, supervise volunteers and match them to individuals with ID. Both groups will receive a booklet about local activities and have access to usual care. Health and social outcomes will be measured at the end of the intervention and 6 months’ follow-up. The following outcomes will be assessed: (1) recruitment and retention of individuals with ID and volunteers in the trial, (2) adverse events related to the intervention, (3) the acceptability of the intervention, (4) whether the intervention is delivered as intended, (5) changes in health and social outcomes and (6) the feasibility of carrying out a cost-effectiveness analysis in a full trial. Qualitative data from participants, volunteers, staff and carers will identify barriers and facilitators of a future full trial.Ethics and disseminationThe study has been approved by the London City and East Research Ethics Committee (reference 18/LO/2188). The findings will be presented at conferences and published in a peer-reviewed journal and in the National Institute of Health Research journals library. A public engagement seminar will be held at the end of the study aimed at key stakeholders.Trial registration numberNCT63779614.
REFRESH protocol: a non-inferiority randomised clinical trial comparing internet and teleconference to in-person ‘Managing Fatigue’ interventions on the impact of fatigue among persons with multiple sclerosis
Authors: Plow Matthew , Packer Tanya , Mathiowetz Virgil G. , Preissner Kathy , Ghahari Setareh , Sattar Abdus , Bethoux Francois , Finlayson Marcia 
Published: April 2023

IntroductionMultiple sclerosis (MS) is an immune-mediated disease of the central nervous system. It is considered a major cause of non‐traumatic disability in young adults. One of the most common and disabling symptoms of MS is fatigue. MS fatigue can impact all aspects of quality of life, including physical, mental and social function. Fortunately, fatigue self-management interventions, such as ‘Managing Fatigue: A 6 week energy conservation course’, can decrease the impact of fatigue and improve health-related quality of life. The purpose of this study is to compare three modes of delivering theManaging Fatigueintervention—two remote delivery formats (teleconference and internet) and one in-person format—on perceptions of fatigue and its impact on physical, mental and social function.Methods and analysisA non-inferiority randomised clinical trial is being conducted to compare the three delivery formats (1:1:1 allocation ratio) among 582 participants with MS living in the Midwestern and Northeastern United States. The hypothesis is that teleconference and internet versions of the intervention are non-inferior to the traditional mode of clinical service delivery (ie, one to one, in person) in terms of the primary outcome of self-reported fatigue impact (ie, Fatigue Impact Scale) and the secondary outcome of health-related quality of life (ie, Multiple Sclerosis Impact Scale). Outcomes are being measured at baseline, 2 months, 3 months and 6 months. The primary analysis tool will be linear mixed effects model. The prespecified inferiority margin for the primary outcome is 10 points. We will also examine whether baseline characteristics (eg, sociodemographic) moderate outcomes of theManaging Fatigueintervention and whether changes in self-efficacy and fatigue self-management behaviours mediate changes in outcomes.Ethics and disseminationThe protocol is approved centrally by the institutional review board at Case Western Reserve University. Eligible participants give consent before being enrolled and randomised into the study. The study results will be disseminated through relevant advocacy organisations, newsletters to participants, publication in peer-reviewed journals and presentations at scientific conferences.Trial registration numberNCT03550170.
Attitudes of at-risk older adults about prevention of cardiovascular disease and dementia using eHealth: a qualitative study in a European context
Authors: Akenine Ulrika , Barbera Mariagnese , Beishuizen Cathrien RL , Fallah Pour Mandana , Guillemont Juliette , Rosenberg Anna , Coley Nicola , Mangialasche Francesca , Salo Lotta , Savy Stephanie , Pols A Jeannette , Andrieu Sandrine , Richard Edo , Soininen Hilkka , Moll van Charante Eric , Kivipelto Miia 
Published: April 2023

ObjectivesPrevention of cardiovascular disease (CVD) and dementia is a key health priority among older adults. Understanding individuals’ attitudes to, the prevention of these conditions, particularly when delivered through novel eHealth tools, could help in designing effective prevention programmes. The aim of the study was to explore the attitudes of older adults at increased risk of CVD and dementia regarding engagement in eHealth self-management prevention programmes, and to describe the facilitators and barriers.DesignA qualitative research approach was used. Data were collected through eight focus groups in Finland, France and the Netherlands. Data were analysed following the principles of grounded theory.Setting and participantsForty-four community-dwellers aged 65+ at risk of CVD were recruited from a previous trial cohort in Finland, and through general practices in France and the Netherlands.ResultsThe study identified three categories: access to reliable information, trust in the healthcare providers and burden and stigma of dementia. A core category was also identified: the interactive process of the three categories influencing engagement in self-management prevention programme. The categories were interconnected through an interactive process and influenced by the local healthcare culture and context which shaped them differently, becoming either facilitators or barriers to engage in eHealth self-management prevention programmes.ConclusionsThe study emphasises the importance of considering the interactions between the identified categories in this study, grounded in the local healthcare culture and context in further developments of eHealth self-management interventions that aim to prevent CVD and dementia.Trial registration numberNCT48151589