bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public knowledge and attitudes toward automated external defibrillators use among first aid eLearning course participants: a survey
Authors: Wang Yun-Ming , Lin Li-Ting , Jiang Jing-Hao , Jiang Yi , Jin Xiao-Qing 
Published: May 2022

Abstract
Objective
Survival from out-of-hospital cardiac arrest (OHCA) often depends on the effective and immediate use of automated external defibrillators (AEDs). Given that there have been few studies about AED use in China, the purpose of this study is to investigate the knowledge and attitudes regarding AED use among the Chinese public, then provide an effective suggestion for AED education strategies and legislation.

Method
The online survey was conducted among Chinese participants of the First Aid eLearning courses in June 2020.

Result
A total of 2565 (95.00%) surveys were completed, only 23.46% of respondents with non-medical related respondents reported having attended previous AED training courses. Regarding the basic knowledge of AEDs, few respondents (12.28%, n = 315) could answer all four questions correctly. 95.67% (n = 2454) were willing to learn AED use. Even if without the precondition of being skilled in AEDs, the female was more likely to rescue OHCA patients than the male (p = 0.003). Almost all respondents (96.65%) showed a strong willingness to rescue OHCA patients with training in using AEDs. The top four barriers to rescuing OHCA patients were lack of practical performing ability (60.47%), fear of hurting patients (59.30%), inadequate knowledge of resuscitation techniques (44.19%), and worry about taking legal responsibility (26.74%).

Conclusion
Our study reflects a deficiency of AED knowledge among the general public in China. However, positive attitudes towards rescuing OHCA patients and learning AED use were observed, which indicates that measures need to be taken to disseminate knowledge and use of AEDs.
Intravenous administration of a branched-chain amino-acid-free solution in children and adults with acute decompensation of maple syrup urine disease: a prospective multicentre observational study
Authors: Alili Jean-Meidi , Berleur Marie-Pierre , Husson Marie-Caroline , Mention Karine , Schiff Manuel , Arnoux Jean-Baptiste , Brassier Anaïs , Guemman Anne-Sophie , Grisel Coraline , Dubois Sandrine , Abi-Wardé Marie-Thérèse , Broissand Christine , Servais Aude , Dao Myriam , de Lonlay Pascale 
Published: May 2022

Abstract
Background
Patients with maple syrup urine disease (MSUD) experiencing metabolic decompensations have traditionally been treated with branched-chain amino acid (BCAA)-free mixture via oral or nasogastric administration routes. In some patients, enteral administration is not possible, either because the patient presents with vomiting, coma, or refuses nasogastric administration, thus intravenous (IV) BCAA-free solution is an appropriate intervention for these challenging cases.

Aims
This study aimed to evaluate the effectiveness and safety of managing metabolic decompensations by administering an IV BCAA-free solution.

Methods
This is an observational prospective study of data from MSUD patients hospitalised for decompensation episodes between 2010 and 2016 at 6 centres for rare metabolic diseases in France.

Results
A total of 24 patients (16 males; 8 females) experiencing 126 MSUD metabolic decompensation episodes (39 in children; 87 in adults) were admitted to hospital. At presentation, mean leucine plasma concentration was ≥ 381 µmol/L in 113/126 (89.7%) episodes. Children were treated with continuous IV BCAA-free solution at doses of 0.8 to 2.0 g/kg/day, for 4.8 days and adults for 3.8 days at doses of 0.5 to 2.6 g/kg/day. In the efficacy set of 102 analysable episodes leucine concentrations were normalised (to below 381 µmol/L) in 82% (n = 18/22) of episodes in children and in 84% (n = 67/80) of episodes in adults. Mean time to leucine normalisation was 3.0 days. This was significantly (p < 0.001) shorter than the algorithmically predicted time to leucine normalisation with traditional BCAA-free mixture. Duration of hospitalisation was significantly longer for children than for adults (7.1 days in children vs 5.2 days in adults, p = 0.012). No treatment-related adverse events were reported in any patients on IV BCAA-free solution.

Conclusion
The IV BCAA-free solution is safe and effective in normalising leucine concentrations during MSUD decompensation episodes in both children and adults, offering a practical treatment alternative for those patients who cannot receive BCAA-free mixture via oral or nasogastric routes.
Tissue engineering in age-related macular degeneration: a mini-review
Authors: Wu Andres , Lu Renhao , Lee Esak 
Published: May 2022

AbstractAge-related macular degeneration (AMD) is a progressive, degenerative disease of the macula, leading to severe visual loss in the elderly population. There are two types of AMD: non-exudative (‘dry’) AMD and exudative (‘wet’) AMD. Non-exudative AMD is characterized by drusen formation and macular atrophy, while the blood vessels are not leaky. Exudative AMD is a more advanced form of the disease, featured with abnormal blood vessel growth and vascular leakage. Even though anti-angiogenic therapies have been effective in treating wet AMD by normalizing blood vessels, there is no treatment available to prevent or treat dry AMD. Currently, the mechanisms of drusen formation and macular atrophy in the dry AMD are poorly understood, in part because the currently available in vivo models of AMD could not decouple and isolate the complex biological and biophysical factors in the macular region for a detailed mechanism study, including the complement system, angiogenesis factors, extracellular matrix, etc. In the present review article, we describe the biological background of AMD and the key cells and structures in AMD, including retinal epithelium, photoreceptor, Bruch’s membrane, and choriocapillaris. We also discuss pre-clinical animal models of AMD and in vivo tissue-engineered approaches, including cell suspension injection and organoid-derived cell sheet transplantation. We also discuss in vitro tissue-engineered models for AMD research. Specifically, we evaluate and compare currently available two- and three-dimensional AMD tissue-engineered models that mimic key anatomical players in AMD progression, including pathophysiological characteristics in Bruch’s membrane, photoreceptor, and choriocapillaris. Finally, we discuss the limitation of current AMD models and future directions.
Adolescent perspectives on participating in a feasibility trial investigating shoe inserts for patellofemoral pain
Authors: O'Sullivan Isobel C. , da Costa Nathalia Cordeiro , Franettovich Smith Melinda M. , Vicenzino Bill , Crossley Kay M. , Kamper Steven J. , van Middelkoop Marienke , Menz Hylton B. , Tucker Kylie , O'Leary Karina T. , Collins Natalie J. 
Published: May 2022

AbstractBackgroundPatellofemoral pain (PFP) affects one‐quarter of adolescents, yet there are few evidence‐informed recommendations to treat PFP in this population. HAPPi Kneecaps! is a randomised, controlled, participant‐ and assessor‐blind, parallel‐group feasibility trial of shoe inserts for adolescents with PFP. The aim of this qualitative study was to explore adolescents' perspectives of participating in HAPPi Kneecaps!.MethodsAll 36 adolescents with PFP from the HAPPi Kneecaps! study were invited to participate in semi‐structured interviews. We used a descriptive qualitative methodology underpinned by a relativist framework to investigate adolescents' perspectives on participating in the trial. Inductive thematic analysis was used to examine patterns regarding how each adolescent experienced the HAPPi Kneecaps! study within their social, cultural, and historical contexts.Results14 out of 36 HAPPi Kneecaps! participants provided consent and participated in interviews (12 females; mean [SD] age 14.9 [2.4] years). Overall, most adolescents responded positively when discussing their experience, such as improvements in their knee pain and satisfaction with how the study was run. Major themes that were generated from the analysis and feedback were: (1) shoe inserts require little effort to use; (2) perceptions of the program were generally positive; (3) participation in the trial could be made easier; (4) warm weather matters; and (5) life happens.ConclusionAdolescents with PFP who participated in the HAPPi Kneecaps! study found that shoe inserts were easy to wear. Most adolescents experienced an improvement in their symptoms and enhanced participation in sport and exercise. Adolescents with PFP prefer an option for warmer climates (e.g. flip flops or sandals), access to online logbooks, and clinicians who are easily accessible.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000957190. Date registered: 8/07/2019.
Trials using deferred consent in the emergency setting: a systematic review and narrative synthesis of stakeholders’ attitudes
Authors: Fitzpatrick Aran , Wood Fiona , Shepherd Victoria 
Published: May 2022

Abstract
Background
Patients with acute conditions often lack the capacity to provide informed consent, and narrow therapeutic windows mean there is no time to seek consent from surrogates prior to treatment being commenced. One method to enable the inclusion of this study population in emergency research is through recruitment without prior consent, often known as ‘deferred consent’. However, empirical studies have shown a large disparity in stakeholders’ opinions regarding this enrolment method. This systematic review aimed to understand different stakeholder groups’ attitudes to deferred consent, particularly in relation to the context in which deferred consent might occur.

Methods
Databases including MEDLINE, EMCare, PsychINFO, Scopus, and HMIC were searched from 1996 to January 2021. Eligible studies focussed on deferred consent processes for adults only, in the English language, and reported empirical primary research. Studies of all designs were included. Relevant data were extracted and thematically coded using a narrative approach to ‘tell a story’ of the findings.

Results
Twenty-seven studies were included in the narrative synthesis. The majority examined patient views (n = 19). Data from the members of the public (n = 5) and health care professionals (n =5) were also reported. Four overarching themes were identified: level of acceptability of deferred consent, research-related factors influencing acceptability, personal characteristics influencing views on deferred consent, and data use after refusal of consent or participant death.

Conclusions
This review indicates that the use of deferred consent would be most acceptable to stakeholders during low-risk emergency research with a narrow therapeutic window and where there is potential for patients to benefit from their inclusion. While the use of narrative synthesis allowed assessment of the included studies, heterogeneous outcome measures meant that variations in study results could not be reliably attributed to the different trial characteristics. Future research should aim to develop guidance for research ethics committees when reviewing trials using deferred consent in emergency research and investigate more fully the views of healthcare professionals which to date have been explored less than patients and members of the public.
Trial registration
PROSPERO CRD42020223623
Hope and meaning-making in phase 1 oncology trials: a systematic review and thematic synthesis of qualitative evidence on patient-participant experiences
Authors: Escritt Kate , Mann Mala , Nelson Annmarie , Harrop Emily 
Published: May 2022

Abstract
Background
Phase 1 drug trials are popular treatment options for patients with advanced disease, despite the greater levels of uncertainty associated with them. However, their meaning and consequences for patient-participants remains under-explored. This review synthesises the qualitative evidence of patients’ experiences of participating in phase 1 oncology trials, exploring their decisions to take part and the impacts of these trials on patient wellbeing.

Methods
A comprehensive literature search involving medical subject headings (MeSH) and keywords was undertaken in the following databases: MEDLINE, EMBASE, PsycINFO, Scopus, CINAHL, and Cochrane CENTRAL, with supplementary searches also conducted. Studies were independently screened for inclusion by two researchers. Included studies were critically appraised and data extracted using standardised forms. Qualitative results were analysed using thematic synthesis.

Results
Three main themes were identified across 13 studies: decision-making and joining the trial; experiences of taking part in the trial and hope and coping. Patients primarily joined trials hoping for therapeutic benefits, sentiments which prevailed and shaped their experiences across their trial journey. Rather than indicate therapeutic misconception based on poor understanding, patient perspectives more commonly pointed to differences between hope and expectation and cultural narratives of staying positive, trying everything and trusting in experts.

Conclusions
These findings challenge information-based models of consent, favouring coping frameworks which account for the role of hope and meaning-making during serious illness. Personalised consideration of existential and quality-of-life matters before and during trials is recommended, including palliative and supportive care alternatives to active treatment.

Review Registration
The review was registered with PROSPERO international prospective register of systematic reviews (CRD 42020163250).
Reduced anticoagulation targets in extracorporeal life support (RATE): study protocol for a randomized controlled trial
Authors: van Minnen Olivier , Oude Lansink-Hartgring Annemieke , van den Boogaard Bas , van den Brule Judith , Bulpa Pierre , Bunge Jeroen J. H. , Delnoij Thijs S. R. , Elzo Kraemer Carlos V. , Kuijpers Marijn , Lambermont Bernard , Maas Jacinta J. , de Metz Jesse , Michaux Isabelle , van de Pol Ineke , van de Poll Marcel , Raasveld S. Jorinde , Raes Matthias , dos Reis Miranda Dinis , Scholten Erik , Simonet Olivier , Taccone Fabio S. , Vallot Frederic , Vlaar Alexander P. J. , van den Bergh Walter M. 
Published: May 2022

Abstract
Background
Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT).
However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome.

Methods
We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2–2.5 times baseline aPTT, 1.5–2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months.

Discussion
We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO.

Trial registration
ClinicalTrials.gov NCT04536272. Registered on 2 September 2020. Netherlands Trial Register NL7969
Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial
Authors: Turner Nicholas A. , Zaharoff Smitha , King Heather , Evans Scott , Hamasaki Toshimitsu , Lodise Thomas , Ghazaryan Varduhi , Beresnev Tatiana , Riccobene Todd , Patel Rinal , Doernberg Sarah B. , Rappo Urania , Fowler Vance G. , Holland Thomas L. ,   on behalf of the Antibacterial Resistance Leadership Group (ARLG)
Published: May 2022

Abstract
Background
Staphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15–50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S. aureus bacteremia without the need for durable central venous access.

Methods
DOTS is a phase 2b, multicenter, randomized, assessor-blinded, superiority, active-controlled, parallel-group trial. The trial will enroll 200 adults diagnosed with complicated S. aureus bacteremia, including definite or possible right-sided infective endocarditis, who have been treated with effective antibiotic therapy for at least 72 h (maximum 10 days) and with subsequent clearance of bacteremia prior to randomization to study treatment. Subjects will be randomized 1:1 to complete their antibiotic treatment course with either two doses of dalbavancin on days 1 and 8, or with a total of 4–8 weeks of standard intravenous antibiotic therapy. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at day 70 for patients randomized to dalbavancin versus standard of care. Key secondary endpoints include quality of life outcomes and pharmacokinetic analyses of dalbavancin.

Discussion
The DOTS trial will establish whether dalbavancin is superior to standard parenteral antibiotic therapy for the completion of treatment of complicated S. aureus bacteremia.

Trial registration
US National Institutes of Health ClinicalTrials.govNCT04775953. Registered on 1 March 2021
Effectiveness of a clinical decision support system for hypertension management in primary care: study protocol for a pragmatic cluster-randomized controlled trial
Authors: Song Jiali , Wang Xiuling , Wang Bin , Gao Yan , Liu Jiamin , Zhang Haibo , Li Xi , Li Jing , Wang Ji-Guang , Cai Jun , Herrin Jeph , Armitage Jane , Krumholz Harlan M. , Zheng Xin ,   on behalf of the LIGHT Collaborative Group
Published: May 2022

Abstract
Background
Clinical decision support systems (CDSS) are low-cost, scalable tools with the potential to improve guideline-based antihypertensive treatment in primary care, but their effectiveness needs to be tested, especially in low- and middle-income countries such as China.

Methods
The Learning Implementation of Guideline-based decision support system for Hypertension Treatment (LIGHT) trial is a pragmatic, four-stage, cluster-randomized trial conducted in 94 primary care sites in China. For each city-based stage, sites are randomly assigned to either implementation of the CDSS for hypertension management (which guides doctors’ treatment recommendations based on measured blood pressure and patient characteristics), or usual care. Patients are enrolled during the first 3 months after site randomization and followed for 9 months. The primary outcome is the proportion of hypertension management visits at which guideline-based treatment is provided.
In a nested trial conducted within the CDSS, with the patient as the unit of randomization, the LIGHT-ACD trial, patients are randomized to receive different initial mono- or dual-antihypertensive therapy. The primary outcome of the LIGHT-ACD trial is the changes in blood pressure.

Discussion
The LIGHT trial will provide evidence on the effectiveness of a CDSS for improving guideline adherence for hypertension management in primary care in China. The nested trial, the LIGHT-ACD trial, will provide data on the effect of different initial antihypertensive regimens for blood pressure management in this setting.

Trial registration
ClinicalTrials.gov, identifier: LIGHT (NCT03636334) and LIGHT-ACD (NCT03587103). Registered on 3 July 2018.
Effectiveness of a health technician-delivered brief intervention for alcohol: a Bayesian reanalysis of a clinical trial
Authors: Barticevic Nicolas A. , Poblete Fernando , Bradshaw Laura , Bendtsen Marcus 
Published: May 2022

Abstract
Objective
To reanalyze a clinical trial on the effectiveness of a Brief Intervention (BI) delivered by non-professionals to reduce risky alcohol drinking. Our previous null-hypothesis test of the effects of the BI yielded a ‘non-significant’ p-value, yet remained uninformative. Here we use the Bayesian paradigm which allows for expressing the probability of different effect sizes to better inform public policy decisions.

Results
The posterior probability of the odds of risky drinking at follow-up favored a marked effect of the BI, with 96% of the probability mass being less than OR = 1, and 84% being less than OR = 0.8. Our findings show that there is a high probability that the BI delivered by health technicians lowered risky alcohol use. The posterior distributions of the BI’s effects are presented to help contextualize the evidence for policy making in Chile.
Folic acid intervention during pregnancy alters DNA methylation, affecting neural target genes through two distinct mechanisms
Authors: Ondičová Miroslava , Irwin Rachelle E. , Thursby Sara-Jayne , Hilman Luke , Caffrey Aoife , Cassidy Tony , McLaughlin Marian , Lees-Murdock Diane J. , Ward Mary , Murphy Michelle , Lamers Yvonne , Pentieva Kristina , McNulty Helene , Walsh Colum P. 
Published: May 2022

Abstract
Background
We previously showed that continued folic acid (FA) supplementation beyond the first trimester of pregnancy appears to have beneficial effects on neurocognitive performance in children followed for up to 11 years, but the biological mechanism for this effect has remained unclear. Using samples from our randomized controlled trial of folic acid supplementation in second and third trimester (FASSTT), where significant improvements in cognitive and psychosocial performance were demonstrated in children from mothers supplemented in pregnancy with 400 µg/day FA compared with placebo, we examined methylation patterns from cord blood (CB) using the EPIC array which covers approximately 850,000 cytosine–guanine (CG) sites across the genome. Genes showing significant differences were verified using pyrosequencing and mechanistic approaches used in vitro to determine effects on transcription.

Results
FA supplementation resulted in significant differences in methylation, particularly at brain-related genes. Further analysis showed these genes split into two groups. In one group, which included the CES1 gene, methylation changes at the promoters were important for regulating transcription. We also identified a second group which had a characteristic bimodal profile, with low promoter and high gene body (GB) methylation. In the latter, loss of methylation in the GB is linked to decreases in transcription: this group included the PRKAR1B/HEATR2 genes and the dopamine receptor regulator PDE4C. Overall, methylation in CB also showed good correlation with methylation profiles seen in a published data set of late gestation foetal brain samples.

Conclusion
We show here clear alterations in DNA methylation at specific classes of neurodevelopmental genes in the same cohort of children, born to FA-supplemented mothers, who previously showed improved cognitive and psychosocial performance. Our results show measurable differences at neural genes which are important for transcriptional regulation and add to the supporting evidence for continued FA supplementation throughout later gestation. This trial was registered on 15 May 2013 at www.isrctn.com as ISRCTN19917787.