bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective cohort study to assess the association between treatment with tocilizumab and mortality among mechanically ventilated patients with COVID-19
Authors: Skarbinski Jacek , Liu Liyan , Hong Vennis , Amsden Laura B , Fireman Bruce H , Yau Vincent M , Incerti Devin , Qian Lei , Fischer Heidi , Ackerson Bradley K , Shaw Sally F , Tartof Sara Y 
Published: October 2022

ObjectivesAssess the association between tocilizumab administration and clinical outcomes among mechanically ventilated patients with COVID-19 pneumonia.DesignRetrospective cohort study.SettingLarge integrated health system with 9 million members in California, USA.Participants4185 Kaiser Permanente members hospitalised with COVID-19 pneumonia requiring invasive mechanical ventilation (IMV).InterventionsReceipt of tocilizumab within 10 days of initiation of IMV.Outcome measuresUsing a retrospective cohort of consecutive patients hospitalised with COVID-19 pneumonia who required IMV in a large integrated health system in California, USA, we assessed the association between tocilizumab administration and 28-day mortality, time to extubation from IMV and time to hospital discharge.ResultsAmong 4185 patients, 184 received tocilizumab and 4001 patients did not receive tocilizumab within 10 days of initiation of IMV. After inverse probability weighting, baseline characteristics were well balanced between groups. Patients treated with tocilizumab had a similar risk of death in the 28 days after intubation compared with patients not treated with tocilizumab (adjusted HR (aHR), 1.21, 95% CI 0.98 to 1.50), but did have a significantly longer time-to-extubation (aHR 0.71; 95% CI 0.57 to 0.88) and time-to-hospital-discharge (aHR 0.66; 95% CI 0.50 to 0.88). However, patients treated with tocilizumab ≤2 days after initiation of IMV had a similar risk of mortality (aHR 1.47; 95% CI 0.96 to 2.26), but significantly shorter time-to-extubation (aHR 0.37; 95% CI 0.23 to 0.58) and time-to-hospital-discharge (aHR 0.31; 95% CI CI 0.17 to 0.56) compared with patients treated with tocilizumab 3–10 days after initiation of IMV.ConclusionsAmong mechanically ventilated patients with COVID-19, the risk of death in the 28-day follow-up period was similar, but time-to-extubation and time-to-hospital-discharge were longer in patients who received tocilizumab within 10 days of initiation of IMV compared with patients who did not receive tocilizumab.
Phase III, randomised, double-blind, placebo-controlled, multicentre trial to evaluate the efficacy and safety of rhGAD65 to preserve endogenous beta cell function in adolescents and adults with recently diagnosed type 1 diabetes, carrying the genetic HLA DR3-DQ2 haplotype: the DIAGNODE-3 study protocol
Authors: Ludvigsson Johnny , Eriksson Linnea , Nowak Christoph , Teixeira Pedro F , Widman Martina , Lindqvist Anton , Casas Rosaura , Lind Marcus , Hannelius Ulf 
Published: October 2022

IntroductionType 1 diabetes (T1D) is an autoimmune disease leading to the destruction of the insulin-producing beta cells resulting in insulin deficiency and hyperglycaemic. Today, no approved therapy exists to halt this detrimental immunologic process. In a recent phase 2b study, intralymphatic administration of recombinant human glutamic acid decarboxylase 65 kDa (rhGAD65) adsorbed to Alhydrogel adjuvant to individuals recently diagnosed with T1D and carrying the HLA DR3-DQ2 haplotype showed promising results in preserving endogenous insulin secretion, confirming the results of a large meta-analysis of three randomised placebo-controlled trials of subcutaneous rhGAD65. The aim of the current precision medicine phase 3 study is to determine whether intralymphatic administration of rhGAD65 preserves insulin secretion and improves glycaemic control in presumed responder individuals with recently diagnosed T1D carrying HLA DR3-DQ2.Methods and analysisIndividuals ≥12 and <29 years recently diagnosed with T1D (<6 months) will be screened for the HLA DR3-DQ2 haplotype, endogenous insulin production estimated by fasting C-peptide and presence of GAD65 antibodies. 330 patients are planned to be randomised to 3 monthly intralymphatic injections of rhGAD65 or placebo (both accompanied by oral vitamin D supplementation), followed by 22 months of follow-up. The study is powered to detect a treatment effect in the two coprimary endpoints; change from baseline in AUC(0-120min)C-peptide levels during a mixed meal tolerance test, and change from baseline in glycaemic control estimated by haemoglobin A1c at 24 months. Secondary endpoints include effects on glucose patterns collected by masked continuous glucose monitoring, proportion of patients in partial remission and number of episodes of severe hypoglycaemia and/or diabetic ketoacidosis.Ethics and disseminationThe trial is approved by Ethics Committees in Poland (124/2021), the Netherlands (R21.089), Sweden (2021-05063), Czech Republic (EK-1144/21), Germany (2021361) and Spain (21/2021). Results will be published in international peer-reviewed scientific journals and presented at national and international conferences.Trial registration numberEudraCT identifier: 2021-002731-32, NCT identifier:NCT05018585.
Built Environments And Child Health in WalEs and AuStralia (BEACHES): a study protocol
Authors: Pedrick-Case Rebecca , Bailey Rowena , Beck Ben , Beesley Bridget , Boruff Bryan , Brophy Sinead , Cross Donna , Dhamrait Gursimran , Duncan John , Gething Peter , Johnson Rhodri D , Lyons Ronan A , Mizen Amy , Murray Kevin , Pouliou Theodora , Rafferty James , Robinson Trina , Rosenberg Michael , Schipperijn Jasper , Thompson Daniel A , Trost Stewart G , Watkins Alan , Stratton Gareth , Fry Richard , Christian Hayley , Griffiths Lucy J 
Published: October 2022

IntroductionChildhood obesity and physical inactivity are two of the most significant modifiable risk factors for the prevention of non-communicable diseases (NCDs). Yet, a third of children in Wales and Australia are overweight or obese, and only 20% of UK and Australian children are sufficiently active. The purpose of the Built Environments And Child Health in WalEs and AuStralia (BEACHES) study is to identify and understand how complex and interacting factors in the built environment influence modifiable risk factors for NCDs across childhood.Methods and analysisThis is an observational study using data from five established cohorts from Wales and Australia: (1) Wales Electronic Cohort for Children; (2) Millennium Cohort Study; (3) PLAY Spaces and Environments for Children’s Physical Activity study; (4) The ORIGINS Project; and (5) Growing Up in Australia: the Longitudinal Study of Australian Children. The study will incorporate a comprehensive suite of longitudinal quantitative data (surveys, anthropometry, accelerometry, and Geographic Information Systems data) to understand how the built environment influences children’s modifiable risk factors for NCDs (body mass index, physical activity, sedentary behaviour and diet).Ethics and disseminationThis study has received the following approvals: University of Western Australia Human Research Ethics Committee (2020/ET000353), Ramsay Human Research Ethics Committee (under review) and Swansea University Information Governance Review Panel (Project ID: 1001). Findings will be reported to the following: (1) funding bodies, research institutes and hospitals supporting the BEACHES project; (2) parents and children; (3) school management teams; (4) existing and new industry partner networks; (5) federal, state and local governments to inform policy; as well as (6) presented at local, national and international conferences; and (7) disseminated by peer-reviewed publications.
Influence of social networks in healthcare on preparation for selection procedures of health professions education: a Dutch interview study
Authors: Mulder Lianne , Wouters Anouk , Fikrat-Wevers Suzanne , Koster Andries S , Ravesloot Jan Hindrik , Croiset Gerda , Kusurkar Rashmi A 
Published: October 2022

ObjectivesHealth professions education (HPE) students are often not representative of the populations they will serve. The underrepresentation of non-traditional students is problematic because diversity is essential for promoting excellence in health education and care. This study aimed to understand the perceptions of traditional and non-traditional students regarding facilitators and barriers in preparing for HPE selection procedures, and to determine the role of social networks in their decision-making and preparations to apply.MethodsA qualitative study was conducted with 26 Dutch youth who were interested in university-level HPE programmes. Semistructured interviews and sociograms were analysed using thematic analysis, adopting a constructivist approach.ResultsTwenty-six high school students participated, with traditional and non-traditional backgrounds, with and without social networks in healthcare and higher education. Two themes were constructed. First, four high-impact facilitators helped to overcome barriers to apply and in preparation for selection: access to a social network connection working or studying in healthcare, to correct information, to healthcare experience and to a social network connection in higher education. Lack of information was the main barrier while access to social network connections in healthcare was the main facilitator to overcome this barrier. However, this access was unevenly distributed. Second, access alone is not enough: the need for agency to make use of available facilitators is also essential.ConclusionsThe themes are discussed using intersectionality. Traditional students with access to facilitators develop their self-efficacy and agency within social structures that privilege them, whereas non-traditional students must develop those skills without such structures. Our findings provide recommendations for the ways in which universities can remove barriers that cause unequal opportunities to prepare for the selection of HPE programmes. Along with equitable admissions, these recommendations can help to achieve a more representative student population and subsequently a better quality of health education and care.
Canadian infants presenting with Brief Resolved Unexplained Events (BRUEs) and validation of clinical prediction rules for risk stratification: a protocol for a multicentre, retrospective cohort study
Authors: Nama Nassr , Hosseini Parnian , Lee Zerlyn , Picco Kara , Bone Jeffrey N , Foulds Jessica L , Gagnon Josée Anne , Sehgal Anupam , Quet Julie , Drouin Olivier , Luu Thuy Mai , Vomiero Gemma , Kanani Ronik , Holland Joanna , Goldman Ran D , Kang Kristopher T , Mahant Sanjay , Jin Falla , Tieder Joel S , Gill Peter J 
Published: October 2022

IntroductionBrief Resolved Unexplained Events (BRUEs) are a common presentation among infants. While most of these events are benign and self-limited, guidelines published by the American Academy of Pediatrics inaccurately identify many patients as higher-risk of a serious underlying aetiology (positive predictive value 5%). Recently, new clinical prediction rules have been derived to more accurately stratify patients. This data were however geographically limited to the USA, with no large studies to date assessing the BRUE population in a different healthcare setting. The study’s aim is to describe the clinical management and outcomes of infants presenting to Canadian hospitals with BRUEs and to externally validate the BRUE clinical prediction rules in identified cases.Methods and analysisThis is a multicentre retrospective study, conducted within the Canadian Paediatric Inpatient Research Network (PIRN). Infants (<1 year) presenting with a BRUE at one of 11 Canadian paediatric centres between 1 January 2017 and 31 December 2021 will be included. Eligible patients will be identified using diagnostic codes.The primary outcome will be the presence of a serious underlying illness. Secondary outcomes will include BRUE recurrence and length of hospital stay. We will describe the rates of hospital admissions and whether hospitalisation was associated with an earlier diagnosis or treatment. Variation across Canadian hospitals will be assessed using intraclass correlation coefficient. To validate the newly developed clinical prediction rule, measures of goodness of fit will be evaluated. For this validation, a sample size of 1182 is required to provide a power of 80% to detect patients with a serious underlying illness with a significance level of 5%.Ethics and disseminationEthics approval has been granted by the UBC Children’s and Women’s Research Board (H21-02357). The results of this study will be disseminated as peer-reviewed manuscripts and presentations at national and international conferences.
Autologous cultured adipose derived mesenchymal stem cells combined with hyaluronic acid hydrogel in the treatment of discogenic low back pain: a study protocol for a phase II randomised controlled trial
Authors: Zhang Jing , Sun Tianze , Zhang Wentao , Yang Ming , Li Zhonghai 
Published: October 2022

IntroductionDiscogenic low back pain (DLBP) is a common disease, and its occurrence is closely related to intervertebral disc (IVD) degeneration. At present, none of the traditional treatment methods can repair the degenerated IVD. The emergence of stem cell therapy makes it possible to repair and regenerate IVD tissue, among which adipose derived mesenchymal stem cells (ADMSCs) transplantation therapy has become a hot spot of current research. Therefore, this trial aimed to investigate the safety and efficacy of using autologous cultured ADMSCs combined with hyaluronic acid (HA) hydrogel in the treatment of DLBP.Methods and analysisThis study is a randomised, dose-escalation, placebo-controlled, double-blind, single-centre, phase II clinical trial to evaluate the efficacy and safety of autologous cultured ADMSCs combined with HA hydrogel in the treatment of patients with DLBP. The 100 eligible patients will be randomly divided into three experimental groups with different doses and one placebo control group in a ratio of 1:1:1:1. All patients will undergo liposuction to obtain ADMSCs, followed by autologous cultured ADMSC mixtures or placebo transplantation after 3 weeks. The patients will be followed up to 24 months after the transplant. The primary end point of this trial is the Visual Analogue Scale. Secondary end points include the Oswestry Disability Index, Japanese Orthopaedic Association Scores, the Mos 36-item short form, the Modic classification, Pfirrmann grade, height and segment range of motion of the IVD, vital signs (temperature, pulse, respiration, blood pressure), blood routine, liver and kidney function, immunological examination, urinalysis and treatment emergent adverse events.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University and registered in the Chinese Clinical Trial Registry. Dissemination of the results will be presented at a conference and in peer-reviewed publications.Trial registration numberChiCTR2200058291.
Minimally invasivE versus open total GAstrectomy (MEGA): study protocol for a multicentre randomised controlled trial (DRKS00025765)
Authors: Nickel Felix , Studier-Fischer Alexander , Hausmann David , Klotz Rosa , Vogel-Adigozalov Sophia Lara , Tenckhoff Solveig , Klose Christina , Feisst Manuel , Zimmermann Samuel , Babic Benjamin , Berlt Felix , Bruns Christiane , Gockel Ines , Graf Sandra , Grimminger Peter , Gutschow Christian A , Hoeppner Jens , Ludwig Kaja , Mirow Lutz , Mönig Stefan , Reim Daniel , Seyfried Florian , Stange Daniel , Billeter Adrian , Nienhüser Henrik , Probst Pascal , Schmidt Thomas , Müller-Stich Beat Peter 
Published: October 2022

IntroductionThe only curative treatment for most gastric cancer is radical gastrectomy with D2 lymphadenectomy (LAD). Minimally invasive total gastrectomy (MIG) aims to reduce postoperative morbidity, but its use has not yet been widely established in Western countries. Minimally invasivE versus open total GAstrectomy is the first Western multicentre randomised controlled trial (RCT) to compare postoperative morbidity following MIG vs open total gastrectomy (OG).Methods and analysisThis superiority multicentre RCT compares MIG (intervention) to OG (control) for oncological total gastrectomy with D2 or D2+LAD. Recruitment is expected to last for 2 years. Inclusion criteria comprise age between 18 and 84 years and planned total gastrectomy after initial diagnosis of gastric carcinoma. Exclusion criteria include Eastern Co-operative Oncology Group (ECOG) performance status >2, tumours requiring extended gastrectomy or less than total gastrectomy, previous abdominal surgery or extensive adhesions seriously complicating MIG, other active oncological disease, advanced stages (T4 or M1), emergency setting and pregnancy.The sample size was calculated at 80 participants per group. The primary endpoint is 30-day postoperative morbidity as measured by the Comprehensive Complications Index. Secondary endpoints include postoperative morbidity and mortality, adherence to a fast-track protocol and patient-reported quality of life (QoL) scores (QoR-15, EUROQOL EuroQol-5 Dimensions-5 Levels (EQ-5D), EORTC QLQ-C30, EORTC QLQ-STO22, activities of daily living and Body Image Scale). Oncological endpoints include rate of R0 resection, lymph node yield, disease-free survival and overall survival at 60-month follow-up.Ethics and disseminationEthical approval has been received by the independent Ethics Committee of the Medical Faculty, University of Heidelberg (S-816/2021) and will be received from each responsible ethics committee for each individual participating centre prior to recruitment. Results will be published open access.Trial registration numberDRKS00025765.
Novel drug-repository contact lens for prolonging the antimicrobial-cornea interaction for bacterial keratitis treatment: randomised controlled trial results
Authors: Daniel Raj Ponniah Lional Raj , Ranilakshmi Velupillai , Anandan Heber , Caroline Jeyakumar , Arulanandham Antonysamy 
Published: October 2022

Background/AimsMicrobial keratitis can cause unilateral blindness, but the drug delivery treatment options are poor. Therefore, this study evaluated the efficacy of a novel therapeutic drug-depository contact lens (DDCL) for bacterial keratitis (BK) treatment. The lens was designed to increase the corneal lesion-antimicrobial drug interaction time.MethodsPatients with BK were randomised (1:1) into two groups: topical antimicrobial treatment only (group 1) and DDCL plus antimicrobial treatment (group 2). Both groups received 0.5% moxifloxacin. We evaluated BK recovery, anterior chamber (AC) reactions, corneal haze and pain (on a 10-point scale) 12 hours and 1, 3, 5 and 14 days after treatment.ResultsThe baseline corneal-infiltration (ie, BK severity) values were comparable for groups 1 (18 cases) and 2 (17 cases) (p=0.92). After 12 hours, the scores improved in both groups and continued to improve throughout the follow-up period; the improvements were more pronounced in group 2 than in group 1 (all p<0.05). Complete recovery occurred on days 14 and 5 in groups 1 and 2, respectively. Furthermore, the AC reaction resolved by day 3 in group 2. The baseline pain scores were also comparable between groups 1 and 2 (p=0.52) and decreased throughout the follow-up period (all p<0.05); the decrease was more pronounced in group 2.ConclusionsNovel DDCLs augment the drug-lesion interaction time by prolonging corneal antimicrobial availability, which hastens corneal healing in BK. Thus, a DDCL may decrease the antibiotic regimen and improve patient tolerance, eliminating the necessity for a loading dose.Trial registration numberCTRI/2020/08/027088.
Sociodemographic and psychological characteristics influencing patients’ willingness to participate in clinical trials
Authors: Gouveia Rita , Cruz Vitor Tedim , Almeida Luís 
Published: October 2022

Background/AimsClinical trials are fundamental for the development of new medicines and patient participation is based on free consent. Our study sought to identify psychological characteristics that may influence patient willingness to participate in a clinical trial.MethodsA total of 100 participants were invited to participate with 80% positive response rate. The psychological characteristics of each patient were evaluated using the following validated psychometric scales: Self-Efficacy Scale, Curiosity, Exploration Inventory-Trait, Social Support Satisfaction, State-Trait Anxiety Inventory and Social Avoidance and Distress, and Fear of Negative Evaluation.ResultsPatients who agreed to participate in the clinical trial were significantly younger than those who refused (p=0.028). There were no differences in sex, lifestyle, employment status, monthly income or education. After adjusting for age and sex, patients who agreed to participate scored significantly higher in the following: self-efficacy total score (p<0.001), effectiveness in adversity (p<0.001), social effectiveness (p<0.001) and initiation and persistence (p<0.001); social support total score (p<0.001), family satisfaction (p=0.015), friendship satisfaction (p<0.001), social activities satisfaction (p=0.002) and intimacy (p<0.001); total curiosity score (p<0.001), absorption (p<0.001) and exploration (p<0.001). Compared with patients who agreed to participate, those who refused scored significantly higher for both state (p<0.001) and trait anxiety (p<0.001), fear of negative evaluation (p<0.001) and social avoidance and distress (p<0.001).ConclusionsPatients who were willing to participate in clinical trials exhibited different psychological characteristics to patients who refused. Specifically, they were more curious and self-efficacious, less anxious and reported a higher level of social support than patients who declined to participate. Identifying characteristics that condition the individual’s decision to participate in a clinical trial has important implications for the development of patient-focused communication strategies and improved recruitment approaches.