bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delivering clinical trials at home: protocol, design and implementation of a direct-to-family paediatric lupus trial
Authors: Randell Rachel L , Singler Lindsay , Cunningham Anthony , Schanberg Laura E , Cohen-Wolkowiez Michael , Hornik Christoph P , Balevic Stephen J 
Published: May 2021

IntroductionDirect-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.MethodsSeveral design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and disseminationDirect-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration numberClinicalTrials.gov Registry (NCT04358302).
Yachts and marinas as hotspots of coastal risk
Authors: Lazarus Eli D. , Ziros Leonidas A. 
Published: May 2021

Abstract
Despite being exceptional concentrations of valuable economic assets, yachts and marinas are typically overlooked in the geography of coastal risk. Focusing on the Mediterranean, which hosts the majority of the world’s yacht activity, we examine three decades of yacht insurance claims in the context of natural hazards and marina development. We find indications that yachts and marinas manifest the same generic relationships between exposure, hazard, and vulnerability observed in terrestrial coastal-risk systems. Given the fundamental importance of yachts and marinas to nautical tourism and strategies for “Blue Economy” growth, particularly in Europe, the role of yachts and marinas in the dynamics of coastal risk must be better understood—but any such insight will first require standardised, comprehensive datasets of yacht movements and marina infrastructure.
Effects of Vitamin D Supplementation on Cardiovascular and Glycemic Biomarkers
Authors: Miao Jennifer , Bachmann Katherine N. , Huang Shi , Su Yan Ru , Dusek Jeffery , Newton‐Cheh Christopher , Arora Pankaj , Wang Thomas J. 
Published: May 2021

Background
Experimental and observational studies have suggested a link between vitamin D and cardiovascular and metabolic disease, but this has not been confirmed in randomized controlled trials. We sought to determine whether vitamin D supplementation reduces biomarkers of insulin resistance, inflammation, neurohormonal activation, and lipids.

Methods and Results

This was a prespecified, secondary analysis of the DAYLIGHT (Vitamin D Therapy in Individuals at High Risk of Hypertension) randomized controlled trial. We measured circulating homeostatic model assessment of insulin resistance, hs‐CRP (high‐sensitivity C‐reactive protein), N‐terminal pro‐B‐type natriuretic peptide, renin, aldosterone, and lipids at baseline and at 6 months in 289 individuals with low vitamin D status (25‐hydroxyvitamin‐D [25‐OH‐D] ≤25 ng/mL) receiving low‐dose (400 IU/d) versus high‐dose (4000 IU/d) vitamin D3 for 6 months. A meta‐analysis of randomized controlled trials reporting biomarker changes after vitamin D supplementation was then performed. Levels of 25‐OH‐D increased in the high‐dose relative to the low‐dose vitamin D group (+15.5 versus +4.6 ng/mL,
P
<0.001). Changes in biomarkers of glycemia, inflammation, and neurohormonal activation did not differ by dose. Lipids did not differ between groups, other than triglycerides, which increased in the high‐dose compared with the low‐dose group (+11.3 versus −6.2 mg/dL,
P
<0.001). The meta‐analysis showed potential modest decreases in homeostatic model assessment of insulin resistance and hs‐CRP, but no changes in low‐density lipoprotein, after vitamin D supplementation compared with control groups.

Conclusions
In the DAYLIGHT randomized controlled trial, high‐dose vitamin D supplementation did not improve biomarkers of glycemia, inflammation, neurohormonal activation, or lipids.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01240512.
SETBP1 overexpression acts in the place of class-defining mutations to drive FLT3-ITD–mutant AML
Authors: Pacharne Suruchi , Dovey Oliver M. , Cooper Jonathan L. , Gu Muxin , Friedrich Mathias J. , Rajan Sandeep S. , Barenboim Maxim , Collord Grace , Vijayabaskar M. S. , Ponstingl Hannes , De Braekeleer Etienne , Bautista Ruben , Mazan Milena , Rad Roland , Tzelepis Konstantinos , Wright Penny , Gozdecka Malgorzata , Vassiliou George S. 
Published: May 2021

Abstract
Advances in cancer genomics have revealed genomic classes of acute myeloid leukemia (AML) characterized by class-defining mutations, such as chimeric fusion genes or in genes such as NPM1, MLL, and CEBPA. These class-defining mutations frequently synergize with internal tandem duplications in FLT3 (FLT3-ITDs) to drive leukemogenesis. However, ∼20% of FLT3-ITD–positive AMLs bare no class-defining mutations, and mechanisms of leukemic transformation in these cases are unknown. To identify pathways that drive FLT3-ITD mutant AML in the absence of class-defining mutations, we performed an insertional mutagenesis (IM) screening in Flt3-ITD mice, using Sleeping Beauty transposons. All mice developed acute leukemia (predominantly AML) after a median of 73 days. Analysis of transposon insertions in 38 samples from Flt3-ITD/IM leukemic mice identified recurrent integrations at 22 loci, including Setbp1 (20/38), Ets1 (11/38), Ash1l (8/38), Notch1 (8/38), Erg (7/38), and Runx1 (5/38). Insertions at Setbp1 led exclusively to AML and activated a transcriptional program similar, but not identical, to those of NPM1-mutant and MLL-rearranged AMLs. Guide RNA targeting of Setbp1 was highly detrimental to Flt3ITD/+/Setbp1IM+, but not to Flt3ITD/+/Npm1cA/+, AMLs. Also, analysis of RNA-sequencing data from hundreds of human AMLs revealed that SETBP1 expression is significantly higher in FLT3-ITD AMLs lacking class-defining mutations. These findings propose that SETBP1 overexpression collaborates with FLT3-ITD to drive a subtype of human AML. To identify genetic vulnerabilities of these AMLs, we performed genome-wide CRISPR-Cas9 screening in Flt3ITD/+/Setbp1IM+ AMLs and identified potential therapeutic targets, including Kdm1a, Brd3, Ezh2, and Hmgcr. Our study gives new insights into epigenetic pathways that can drive AMLs lacking class-defining mutations and proposes therapeutic approaches against such cases.
Mapping the (mis)match of university degrees in the graduate labor market
Authors: Salas-Velasco Manuel 
Published: May 2021

AbstractThis paper contributes to the scarce literature on the topic of horizontal education-job mismatch in the labor market for graduates of universities. Field-of-study mismatch or horizontal mismatch occurs when university graduates, trained in a particular field, work in another field at their formal qualification level. The data used in the analysis come from the first nationally representative survey of labor insertion of recent university graduates in Spain. By estimating a multinomial logistic regression, we are able to identify the match status 4 years after graduation based on self-assessments. We find a higher likelihood of horizontal mismatch among graduates of Chemistry, Mathematics, Physics, Pharmacy, and Languages and Literature. Only graduates in Medicine increase the probability of being adequately matched in their jobs. It may be hypothesized that horizontal mismatch is more likely among those graduates in degree fields that provide more general skills and less likely among those from degree fields providing more occupation-specific skills. Other degrees such as Business Studies, and Management and Economics Studies increase the probability of being vertically mismatched (over-educated). Vertical mismatch preserves at least some of the specific human capital gained through formal educational qualifications. However, some workers with degrees in Labor Relations and Social Work are in non-graduate positions and study areas unrelated to their studies. The paper also shows that graduates in the fields of health sciences and engineering/architecture increase the probability of achieving an education-job match after external job mobility.
Improving the precision of depression diagnosis in general practice: a cluster-randomized trial
Authors: Brinck-Claussen Ursula Ødum , Curth Nadja Kehler , Christensen Kaj Sparle , Davidsen Annette Sofie , Mikkelsen John Hagel , Lau Marianne Engelbrecht , Lundsteen Merete , Csillag Claudio , Hjorthøj Carsten , Nordentoft Merete , Eplov Lene Falgaard 
Published: May 2021

Abstract
Background
Methods to enhance the accuracy of the depression diagnosis continues to be of relevance to clinicians. The primary aim of this study was to compare the diagnostic precision of two different diagnostic strategies using the Mini International Neuropsychiatric Interview (MINI) as a reference standard. A secondary aim was to evaluate accordance between depression severity found via MINI and mean Major Depression Inventory (MDI) sum-scores presented at referral.

Methods
This study was a two-armed, cluster-randomized superiority trial embedded in the Collabri trials investigating collaborative care in Danish general practices. GPs performing case-finding were instructed always to use MDI when suspecting depression. GPs performing usual clinical assessment were instructed to detect depression as they would normally do. According to guidelines, GPs would use MDI if they had a clinical suspicion, and patients responded positively to two or three core symptoms of depression. We compared the positive predictive value (PPV) in the two groups.

Results
Fifty-one GP clusters were randomized. In total, 244 participants were recruited in the case-finding group from a total of 19 GP clusters, and 256 participants were recruited in the usual clinical assessment group from a total of 19 GP clusters. The PPV of the GP diagnosis, when based on case-finding, was 0.83 (95% CI 0.78–0.88) and 0.93 (95% CI 0.89–0.96) when based on usual clinical assessment. The mean MDI sum-scores for each depression severity group indicated higher scores than suggested cut-offs.

Conclusions
In this trial, systematic use of MDI on clinical suspicion of depression did not improve the diagnostic precision compared with the usual clinical assessment of depression.

Trial registration
The trial was retrospectively registered on 07/02/2016 at ClinicalTrials.gov. No. NCT02678845.
The role of endoscopy and findings in COVID-19 patients, an early North American Cohort
Authors:   North American Alliance for the Study of Digestive Manifestations of Covid-19, Kuftinec Gabriela , Elmunzer B. Joseph , Amin Sunil 
Published: May 2021

Abstract
Background and aims
Gastrointestinal manifestations in patients with COVID-19 are common but the role of endoscopy in this patient population remains unclear. We investigated the need for endoscopic procedures, their findings, and impact on patient care in a systematic and geographically diverse sample of patients hospitalized with COVID-19.

Methods
As part of the North American Alliance for the Study of Digestive Manifestations of COVID-19, we identified consecutive patients hospitalized with COVID-19 at 36 medical centers in the USA and Canada. We performed a secondary analysis of patients who underwent endoscopy, collecting information on endoscopic indications, findings, interventions, staffing, procedure location, anesthesia utilization, and adverse events.

Results
Data were collected on 1992 patients; 24 (1.2%) underwent 27 endoscopic procedures (18 upper endoscopies, 7 colonoscopies, 2 endoscopic retrograde cholangiopancreatographies). The most common indications were: gastrointestinal bleeding (13) and enteral access (6). The most common findings were erosive or inflammatory changes. Ten patients underwent an endoscopic intervention for hemostatic therapy (2), enteral access (6), or biliary obstruction (2). Half of cases employed anesthesiology support; no sedation-related adverse events were reported. One-third of cases were performed in the intensive care setting and one quarter in the endoscopy unit.

Conclusions
In this large, systematic, geographically diverse cohort of patients hospitalized with COVID-19 in North America, very few patients underwent endoscopy despite a high prevalence of gastrointestinal manifestations. Almost all endoscopic findings and interventions were thought related to critical illness rather than direct viral injury. This systematic assessment of endoscopic necessity and outcomes may help guide resource allocation in the event of ongoing and future surges.
Self-management interventions for adolescents living with HIV: a systematic review
Authors: Crowley Talitha , Rohwer Anke 
Published: May 2021

Abstract
Background
Self-management interventions aim to enable people living with chronic conditions to increase control over their condition in order to achieve optimal health and may be pertinent for young people with chronic illnesses such as HIV. Our aim was to evaluate the effectiveness of self-management interventions for improving health-related outcomes of adolescents living with HIV (ALHIV) and identify the components that are most effective, particularly in low-resource settings with a high HIV burden.

Methods
We considered randomised controlled trials (RCTs), cluster RCTs, non-randomised controlled trials (non-RCTs) and controlled before-after (CBA) studies. We did a comprehensive search up to 1 August 2019. Two authors independently screened titles, abstracts and full texts, extracted data and assessed the risk of bias. We synthesised results in a meta-analysis where studies were sufficiently homogenous. In case of substantial heterogeneity, we synthesised results narratively. We assessed the certainty of evidence using GRADE and presented our findings as summaries in tabulated form.

Results
We included 14 studies, comprising 12 RCTs and two non-RCTs. Most studies were conducted in the United States, one in Thailand and four in Africa. Interventions were diverse, addressing a variety of self-management domains and including a combination of individual, group, face-to-face, cell phone or information communication technology mediated approaches. Delivery agents varied from trained counsellors to healthcare workers and peers. Self-management interventions compared to usual care for ALHIV made little to no difference to most health-related outcomes, but the evidence is very uncertain. Self-management interventions may increase adherence and decrease HIV viral load, but the evidence is very uncertain. We could not identify any particular components of interventions that were more effective for improving certain outcomes.

Conclusion
Existing evidence on the effectiveness of self-management interventions for improving health-related outcomes of ALHIV is very uncertain. Self-management interventions for ALHIV should take into account the individual, social and health system contexts. Intervention components need to be aligned to the desired outcomes.

Systematic review registration
PROSPERO CRD42019126313.
Impact of high dose of baricitinib in severe COVID-19 pneumonia: a prospective cohort study in Bangladesh
Authors: Hasan Md. Jahidul , Rabbani Raihan , Anam Ahmad Mursel , Huq Shihan Mahmud Redwanul , Polash Mohammad Mufizul Islam , Nessa Shahzadi Sayeeda Tun , Bachar Sitesh C. 
Published: May 2021

AbstractPurposeHyperinflammation in severe COVID-19 infection increases the risk of respiratory failure and one of the cogent reasons of mortality associated with COVID-19. Baricitinib, a janus kinases inhibitor, can potentially suppress inflammatory cascades in severe COVID-19 pneumonia.MethodsThe objective of this study was to compare the clinical outcomes of high dose of baricitinib with its usual dose in patients with severe COVID-19 pneumonia. This prospective cohort study was conducted on 238 adult patients with severe COVID-19 pneumonia. Eight milligram and 4 mg of baricitinib was given orally to 122 patients in the high dose (HD) group and 116 patients the usual dose (UD) group, respectively daily for 14 days, and clinical outcomes were compared among the groups.ResultsBlood oxygen saturation level was stabilized (≥94% on room air) earlier in the HD group compared to the UD group [5 (IQR: 4–5)/8 (IQR: 6–9),P < 0.05]. Patients in the HD group required intensive care unit (ICU) and intubation supports more in the UD group than that in patients of the HD group [17.2%/9%,P < 0.05; 11.2%/4.1%,P > 0.05;N = 116/122, respectively]. The 30-day mortality and 60-day rehospitalization rate were higher in the UD group than the HD group [6%/3.3%,P < 0.01; 11.9%/7.6%,P > 0.05;N = 116/122, respectively].ConclusionThe daily high dose of baricitinib in severe COVID-19 results in early stabilization of the respiratory functions, declined requirements of critical care supports, reduced rehospitalization with mortality rate compared to its daily usual dose.
Prevalence of cystic echinococcosis in slaughtered livestock in Iran: a systematic review and meta-analysis
Authors: Vaisi-Raygani Aliakbar , Mohammadi Masoud , Jalali Rostam , Salari Nader , Hosseinian-Far Melika 
Published: May 2021

Abstract
Background
Hydatidosis is a zoonotic disease and has a great general and economic health importance in both developed and developing countries. Therefore, this systematic and meta-analytic study was conducted to determine the prevalence of cystic echinococcosis in slaughtered livestock in Iran.

Methods
The present study was conducted as a systematic review and meta-analysis. The SID & Magiran, MEDLINE (PubMed), ScienceDirect, Scopus, and Google Scholar databases were searched with a view to selecting relevant research works. As a result, 31 articles published from April 1970 to April 2020 were selected. The heterogeneity of the studies was assessed using the I2 index. Data analysis was conducted within the Comprehensive Meta-Analysis software (CMA) v.3.0 (Biostat, Englewood, NJ, USA) and Arc map (ArcGIS 10.3) software.

Results
The heterogeneity of the studies was evaluated using the I2 test which value was 99% showing a high heterogeneity in the studies. The results of publication bias in studies were evaluated by the Egger test, which were not statistically significant (P = 0.144). The overall prevalence of cystic echinococcosis in slaughtered livestock in Iran is 13.9% (95%CI: 10.7–17.7%). The results of the meta-regression analysis indicate the increasing trend of the hydatid cyst prevalence with the increase of sample size and publication year (P < 0.05).

Conclusion
According to the results of this study and the relatively high prevalence of cystic echinococcosis in slaughtered livestock in Iran, health policy makers should make effective decisions in this regard, and implement careful inspections and interventions by experts and health authorities.
Phase 3 multicenter randomized trial of PSMA PET/CT prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: study protocol
Authors: Calais Jeremie , Zhu Shaojun , Hirmas Nader , Eiber Matthias , Hadaschik Boris , Stuschke Martin , Herrmann Ken , Czernin Johannes , Kishan Amar U. , Nickols Nicholas G. , Elashoff David , Fendler Wolfgang P. 
Published: May 2021

Abstract
Background
Definitive radiation therapy (dRT) is an effective initial treatment of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). PSMA PET/CT is superior to standard of care imaging (CT, MRI, bone scan) for detecting regional and distant metastatic PCa. PSMA PET/CT thus has the potential to guide patient selection and the planning for dRT and improve patient outcomes.

Methods
This is a multicenter randomized phase 3 trial (NCT04457245). We will randomize 312 patients to proceed with standard dRT (control Arm, n = 150), or undergo a PSMA PET/CT scan at the study site (both 18F-DCFPyL and 68Ga-PSMA-11 can be used) prior to dRT planning (intervention arm, n = 162). dRT will be performed at the treating radiation oncologist facility. In the control arm, dRT will be performed as routinely planned. In the intervention arm, the treating radiation oncologist can incorporate PSMA PET/CT findings into the RT planning. Androgen deprivation therapy (ADT) is administered per discretion of the treating radiation oncologist and may be modified as a result of the PSMA PET/CT results. We assume that approximately 8% of subjects randomized to the PSMA PET arm will be found to have M1 disease and thus will be more appropriate candidates for long-term systemic or multimodal therapy, rather than curative intent dRT. PET M1 patients will thus not be included in the primary endpoint analysis. The primary endpoint is the success rate of patients with unfavorable IR and HR PCa after standard dRT versus PSMA PET-based dRT. Secondary Endpoints (whole cohort) include progression free survival (PFS), metastasis-free survival after initiation of RT, overall survival (OS), % of change in initial treatment intent and Safety.

Discussion
This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa who receive dRT. In this trial the incorporation of PSMA PET/CT may improve the success rate of curative intent radiotherapy in two ways: to optimize patient selection as a biomarker and to personalizes the radiotherapy plan.

Clinical trial registration
UCLA

IND#147591

○ Submission: 02.27.2020

○ Safe-to-proceed letter issued by FDA: 04.01.2020

UCLA IRB #20–000378

ClinicalTrials.gov Identifier NCT04457245. Date of Registry: 07.07.2020.

Essen

EudraCT 2020–003526-23