bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role development, implementation and evaluation of nurse practitioners in a Belgian university hospital: a mixed methods study protocol
Authors: Dehennin Laurence , Kinnaer Lise-Marie , Vermassen Frank , Van Hecke Ann 
Published: May 2023

IntroductionDue to the increased prevalence of chronic conditions, multimorbidity and an increased complexity of care, the burden on healthcare teams is high resulting in unmet needs of patients and their family and a high workload on healthcare professionals. To respond to these challenges, care models integrating nurse practitioners were introduced. Despite the proven benefits, implementation in Belgium is at an early stage. The aim of this study is to develop, implement and evaluate nurse practitioner roles in a Belgian university hospital. Insights into development and implementation processes can inform healthcare managers and policymakers for future (nationwide) implementation.Methods and analysisFor the development, implementation and (process-)evaluation of nurse practitioner roles in three departments in a Belgian university hospital, a participatory action research approach involving interdisciplinary teams of healthcare professionals, healthcare managers and researchers will be used. To investigate the effectiveness at patient (eg, quality of care), healthcare providers (eg, team effectiveness) and organisational level (eg, utility) a longitudinal (matched controlled) pre–post mixed methods study will be set up. Quantitative data (surveys, data from electronic patient files, administrative files) will be analysed using SPSS V.28.0. Qualitative data will be collected throughout the whole process and will consist of the meetings, (focus group) interviews and field notes. All qualitative data will be analysed thematically both across-case and within-case. This study is designed and will be reported based on the Standard Protocol Items: Recommendations for Interventional Trials 2013 statement.Ethics and disseminationEthical approval for all parts of this study was obtained from the Ethics Committee of the participating university hospital (February–August 2021). All participants throughout the study parts will receive written and verbal information and will be asked written consent. All data will be stored on a secured server. Only the primary researchers will have access to the data set.Trial registration numberNCT05520203.
Protocol for a feasibility, acceptability and safety study of the PICO device (negative pressure wound therapy) in acute paediatric burns
Authors: Lumsden Emma Joan , Kimble Roy M , McMillan Catherine , Storey Kristen , Ware Robert S , Griffin Bronwyn 
Published: May 2023

IntroductionNegative pressure wound therapy (NPWT) in acute burn care may decrease the time to re-epithelialisation by more than 20%. Despite this, the perceived burden of use; including therapeutic, physical and financial, have limited the use of NPWT in acute burn care. This might be minimised by using the small, ultraportable, single-use NPWT device PICO as opposed to larger devices, which to date has never been studied in acute burn care. This research will; therefore, primarily assess the feasibility, acceptability and safety of PICO in paediatric burns. Secondary outcomes include time to re-epithelialisation, pain, itch, cost and scar formation.Methods and analysisThis protocol details a clinical trial methodology and is pre-results. This single site, prospective, pilot randomised controlled trial will be conducted in an Australian quaternary paediatric burns centre. Participants must be aged ≤16 years, otherwise well and managed within 24 hours of sustaining a burn that fits beneath a PICO dressing. Thirty participants will be randomised to one of three groups: group A: Mepitel and ACTICOAT, group B: Mepitel, ACTICOAT and PICO and group C: Mepitel, ACTICOAT Flex and PICO. Patient outcomes will be recorded at each dressing change to assess efficacy and safety outcomes until 3 months postburn wound re-epithelialisation. Surveys, randomisation and data storage will be undertaken via online platforms and physical data storage collated at the Centre for Children’s Health Research, Brisbane, Australia. Analysis will be done by using StataSE 17.0 statistical software.Ethics and disseminationEthics has been obtained from Queensland Health and Griffith Human Research Ethics committees including a site-specific approval. These data will be disseminated via clinical meetings, conference presentations and peer-reviewed journals.Trial registration numberACTRN12622000009718.
Efficacy and safety of ceftazidime–avibactam versus polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infection: a systematic review and meta-analysis
Authors: Yang Ping , Li Yinyan , Wang Xiaojuan , Chen Na , Lu Xiaoyang 
Published: May 2023

ObjectivesCarbapenem-resistant Enterobacteriaceae is increasingly recognised as a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) and polymyxins are considered as the last therapeutic options worldwide. This is the first meta-analysis of recently published data to compare the clinical efficacy and safety of CAZ-AVI with polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase and the Cochrane Library were systematically searched, for publications in any language, from database inception to February 2023.Eligibility criteria for selecting studiesStudies comparing the clinical efficacy and safety of CAZ-AVI with polymyxins were included. Mortality, clinical success, microbiological eradication and nephrotoxicity were assessed as the main outcomes.Data extraction and synthesisLiterature screening, data extraction and the quality evaluation of studies were conducted by two researchers independently, with disagreements resolved by another researcher. The Newcastle–Ottawa Scale was used to assess the bias risk for the included studies. Review Manager V.5.3 was employed for the meta-analysis.ResultsThe meta-analysis included seven retrospective and four prospective cohort studies with 1111 patients enrolled. The CAZ-AVI groups demonstrated a lower 30-day mortality (risk ratio (RR)=0.48, 95% CI of 0.37 to 0.63, I2=10%, p<0.0001) in nine studies with 766 patients; higher clinical success (RR=1.71, 95% CI 1.33 to 2.20, I2=35%, p<0.0001) in four studies with 463 patients; and lower nephrotoxicity in seven studies with 696 patients (RR=0.42, 95% CI 0.23 to 0.77, I2=35%, p<0.05). However, no significant difference in microbiological eradication rates was observed in 249 patients from two studies (RR=1.16, 95% CI 0.97 to 1.39, I2=0, p>0.05).ConclusionAvailable evidence suggested that CAZ-AVI treatment held a dominant position with respect to efficacy and safety compared with polymyxins in carbapenem-resistant Enterobacteriaceae infections. However, the analysis included only observational studies, and high-quality, large-scale, multicentre, double-blind randomised controlled trials are needed to confirm the advantage of CAZ-AVI.
OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction (OPTICORE): study protocol of a multicentre, retrospective cohort study
Authors: van de Meent Mette , Kleuskens Dianne G. , Ganzevoort Wessel , Gordijn Sanne J. , Kooi Elisabeth M. W. , Onland Wes , van Rijn Bas B. , Duvekot Johannes J. , Kornelisse René F. , Al-Nasiry Salwan , Jellema Reint K. , Knol H. Marieke , Manten Gwendolyn T. R. , Mulder-de Tollenaer Susanne M. , Derks Jan B. , Groenendaal Floris , Bekker Mireille N. , Schuit Ewoud , Lely A. Titia , Kooiman Judith 
Published: May 2023

IntroductionEarly-onset fetal growth restriction (FGR) requires timely, often preterm, delivery to prevent fetal hypoxia causing stillbirth or neurologic impairment. Antenatal corticosteroids (CCS) administration reduces neonatal morbidity and mortality following preterm birth, most effectively when administered within 1 week preceding delivery. Optimal timing of CCS administration is challenging in early-onset FGR, as the exact onset and course of fetal hypoxia are unpredictable. International guidelines do not provide a directive on this topic. In the Netherlands, two timing strategies are commonly practiced: administration of CCS when the umbilical artery shows (A) a pulsatility index above the 95thhcentile and (B) absent or reversed end-diastolic velocity (a more progressed disease state). This study aims to (1) use practice variation to compare CCS timing strategies in early-onset FGR on fetal and neonatal outcomes and (2) develop a dynamic tool to predict the time interval in days until delivery, as a novel timing strategy for antenatal CCS in early-onset FGR.Methods and analysisA multicentre, retrospective cohort study will be performed including pregnancies complicated by early-onset FGR in six tertiary hospitals in the Netherlands in the period between 2012 and 2021 (estimated sample size n=1800). Main exclusion criteria are multiple pregnancies and fetal congenital or genetic abnormalities. Routinely collected data will be extracted from medical charts. Primary outcome for the comparison of the two CCS timing strategies is a composite of perinatal, neonatal and in-hospital mortality. Secondary outcomes include the COSGROVE core outcome set for FGR. A multivariable, mixed-effects model will be used to compare timing strategies on study outcomes. Primary outcome for the dynamic prediction tool is ‘days until birth’.Ethics and disseminationThe need for ethical approval was waived by the Ethics Committee (University Medical Center Utrecht). Results will be published in open-access, peer-reviewed journals and disseminated by presentations at scientific conferences.Trial registration numberClinicalTrials.gov:NCT05606497
COllaborative Neonatal Network for the first European CPAM Trial (CONNECT): a study protocol for a randomised controlled trial
Authors: Kersten Casper M , Hermelijn Sergei M , Dossche Louis W J , Muthialu Nagarajan , Losty Paul D , Schurink Maarten , Rietman André B , Poley Marten J , van Rosmalen Joost , Zanen - van den Adel Tabitha P L , Ciet Pierluigi , von der Thüsen Jan , Brosens Erwin , Ijsselstijn Hanneke , Tiddens Harm A W M , Wijnen Rene M H , Schnater J Marco 
Published: May 2023

IntroductionConsensus is lacking on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM). For future studies, the CONNECT consortium (the COllaborative Neonatal Network for the first European CPAM Trial)—an international collaboration of specialised caregivers—has established consensus on a core outcome set of outcome parameters concerning respiratory insufficiency, surgical complications, mass effect and multifocal disease. These outcome parameters have been incorporated in the CONNECT trial, a randomised controlled trial which, in order to develop evidence-based practice, aims to compare conservative and surgical management of patients with an asymptomatic CPAM.Methods and analysisChildren are eligible for inclusion after the CPAM diagnosis has been confirmed on postnatal chest CT scan and they remain asymptomatic. On inclusion, children are randomised to receive either conservative or surgical management. Subsequently, children in both groups are enrolled into a standardised, 5-year follow-up programme with three visits, including a repeat chest CT scan at 2.5 years and a standardised exercise tolerance test at 5 years.The primary outcome is exercise tolerance at age 5 years, measured according to the Bruce treadmill protocol. Secondary outcome measures are molecular genetic diagnostics, validated questionnaires—on parental anxiety, quality of life and healthcare consumption—, repeated imaging and pulmonary morbidity during follow-up, as well as surgical complications and histopathology. This trial aims to end the continuous debate surrounding the optimal management of asymptomatic CPAM.Ethics and disseminationThis study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Centre Rotterdam, The Netherlands, has approved this protocol (MEC-2022–0441). Results will be disseminated through peer-reviewed scientific journals and conference presentations.Trial registration numberNCT05701514.
Extent of axial damage in psoriatic arthritis and spondyloarthritis: comparative data from the BEPAS and (Be-)GIANT multicentre cohorts
Authors: de Hooge Manouk , Ishchenko Alla , De Craemer Ann-Sophie , Steinfeld Serge , Nzeusseu Adrien , Elewaut Dirk , Lories Rik , de Vlam Kurt , Van den Bosch Filip 
Published: May 2023

BackgroundTo examine radiographic axial damage of the sacroiliac joints and spine in patients with psoriatic arthritis (PsA) and spondyloarthritis (SpA) in private and academic Belgian practices.MethodsPatients with PsA with clinical diagnosis of PsA and fulfilling the Classification Criteria for Psoriatic Arthritis from the prospective Belgian Epidemiological Psoriatic Arthritis Study and patients with SpA fulfilling the Assessment of SpondyloArthritis international Society classification criteria for SpA originate from the Ghent and BelGian Inflammatory Arthritis and spoNdylitis cohorTs were included in this study. Baseline pelvic and spinal radiographs were analysed by two calibrated readers. Blinded for the origin of the cohort or clinical data readers assessed the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and modified New York criteria on spinal and pelvic radiographs, respectively. Data were compared between both patient groups.ResultsOf the 525 patients included (312 PsA and 213 SpA), most patients showed normal spinal radiographs: 87.5% of the patients with PsA and 92.0% of the patients with SpA. Patients with SpA with spinal damage show higher mSASSS than the patients with PsA (p<0.05). In patients with PsA, cervical spine is more often affected; 24/33 patients (72.7%) compared with lumbar spine 11/33 (33.3%). While in patients with SpA, syndesmophyte location was more evenly distributed; cervical 9/14 (64.3%) and lumbar 10/14 (71.4%).ConclusionMinimal radiographic spinal damage was observed in Belgian patients with PsA or SpA. Patients with SpA tend to have higher mSASSS values and more syndesmophytes compared with PsA. Syndesmophytes were more often located in the cervical spine of patients with PsA, while the location was equally distributed in axSpA.
Medical cannabis is effective for cancer-related pain: Quebec Cannabis Registry results
Authors: Aprikian Saro , Kasvis Popi , Vigano MariaLuisa , Hachem Yasmina , Canac-Marquis Michelle , Vigano Antonio 
Published: May 2023

ObjectivesTo evaluate the safety and effectiveness of medical cannabis (MC) in reducing pain and concurrent medications in patients with cancer.MethodsThis study analysed data collected from patients with cancer who were part of the Quebec Cannabis Registry. Brief Pain Inventory (BPI), revised Edmonton Symptom Assessment System (ESAS-r) questionnaires, total medication burden (TMB) and morphine equivalent daily dose (MEDD) recorded at 3-month, 6-month, 9-month and 12-month follow-ups were compared with baseline values. Adverse events were also documented at each follow-up visit.ResultsThis study included 358 patients with cancer. Thirteen out of 15 adverse events reported in 11 patients were not serious; 2 serious events (pneumonia and cardiovascular event) were considered unlikely related to MC. Statistically significant decreases were observed at 3-month, 6-month and 9-month follow-up for BPI worst pain (5.5±0.7 baseline, 3.6±0.7, 3.6±0.7, 3.6±0.8; p<0.01), average pain (4.1±0.6 baseline, 2.4±0.6, 2.3±0.6, 2.7±0.7; p<0.01), overall pain severity (3.7±0.5 baseline, 2.3±0.6, 2.3±0.6, 2.4±0.6; p<0.01) and pain interference (4.3±0.6 baseline, 2.4±0.6, 2.2±0.6, 2.4±0.7, p<0.01). ESAS-r pain scores decreased significantly at 3-month, 6-month and 9-month follow-up (3.7±0.6 baseline, 2.5±0.6, 2.2±0.6, 2.0±0.7, p<0.01). THC:CBD balanced strains were associated with better pain relief as compared with THC-dominant and CBD-dominant strains. Decreases in TMB were observed at all follow-ups. Decreases in MEDD were observed at the first three follow-ups.ConclusionsReal-world data from this large, prospective, multicentre registry indicate that MC is a safe and effective complementary treatment for pain relief in patients with cancer. Our findings should be confirmed through randomised placebo-controlled trials.
Compost  and biosolids increase long-term soil organic carbon stocks
Authors: Badewa Emmanuel A. , Yeung Chun C. , Whalen Joann K. , Oelbermann Maren 
Published: May 2023

Biobased residues derived from organic urban waste materials can be processed to produce soil amendments that enhance soil fertility and carbon sequestration. However, the extent of carbon sequestration by biobased residues depends on the interaction between their physicochemical properties, climate, and agroecosystem management practices. Our objective was to predict how different biobased residues (compost, anaerobic digestate, or biosolids), compared to nitrogen fertilizer, affect soil organic carbon stocks under continuous cropping and crop rotation in Ontario, Canada, using the Century model. The Century model was calibrated and validated with data, from a three-year field study located in Elora, Ontario, Canada, that was used to predict long-term changes in soil organic carbon. Our results showed that after 150 years, soil amended with compost and biosolids increased soil organic carbon stocks significantly ( p < 0.05) compared to anaerobic digestate and nitrogen fertilizer. Soil organic carbon stocks were 1%–27% greater with crop rotation compared to continuous cropping. Model performance indicated a strong correlation between measured and simulated soil organic carbon stocks ( R2 = 0.26–0.82; RMSD = 432–727 g m−2). Our findings suggested that compost had the greatest soil carbon sequestration potential of the tested soil amendments, and this difference was due to the quantity and quality of carbon input.
Measurement of fast neutron background in the Gran Sasso underground laboratory using a geyser-concept bubble-chamber
Authors: Bertoni R. , Bruno G. , Burgio N. , Corcione M. , Cretara L. , Frullini M. , Fulgione W. , De Matteis M. , Quintino A. , Redaelli N. , Santagata A. , Vallicelli E. A. , Zanotti L. 
Published: May 2023

AbstractA measurement of the fast neutron background in the Gran Sasso underground laboratory has been performed by the MOSCAB thermodynamic bubble chamber, a neutron detector which identifies fast neutrons passing through the metastable fluid by scattering ions. The result of this measurement confirms the results previously obtained using detectors based on totally different techniques, thus corroborating the previous results in terms of both integral intensity and spectral characteristics, at least in the energy region where the current measurement technique is sensitive.
Intravenous N-Acetylcysteine to Prevent Cisplatin-Induced Hearing Loss in Children: A Nonrandomized Controlled Phase I Trial
Authors: Orgel Etan , Knight Kristin R. , Chi Yueh-Yun , Malvar Jemily , Rushing Teresa , Mena Victoria , Eisenberg Laurie S. , Rassekh Shahrad R. , Ross Colin J.D. , Scott Erika N. , Neely Michael , Neuwelt Edward A. , Muldoon Leslie L. , Freyer David R. 
Published: May 2023

Abstract

Purpose:
Cisplatin-induced hearing loss (CIHL) is common and permanent. As compared with earlier otoprotectants, we hypothesized N-acetylcysteine (NAC) offers potential for stronger otoprotection through stimulation of glutathione (GSH) production. This study tested the optimal dose, safety, and efficacy of NAC to prevent CIHL.

Patients and Methods:
In this nonrandomized, controlled phase Ia/Ib trial, children and adolescents newly diagnosed with nonmetastatic, cisplatin-treated tumors received NAC intravenously 4 hours post-cisplatin. The trial performed dose-escalation across three dose levels to establish a safe dose that exceeded the targeted peak serum NAC concentration of 1.5 mmol/L (as identified from preclinical models). Patients with metastatic disease or who were otherwise ineligible were enrolled in an observation-only/control arm. To evaluate efficacy, serial age-appropriate audiology assessments were performed. Integrated biology examined genes involved in GSH metabolism and post-NAC GSH concentrations.

Results:
Of 52 patients enrolled, 24 received NAC and 28 were in the control arm. The maximum tolerated dose was not reached; analysis of peak NAC concentration identified 450 mg/kg as the recommended phase II dose (RP2D). Infusion-related reactions were common. No severe adverse events occurred. Compared with the control arm, NAC decreased likelihood of CIHL at the end of cisplatin therapy [OR, 0.13; 95% confidence interval (CI), 0.021–0.847; P = 0.033] and recommendations for hearing intervention at end of study (OR, 0.082; 95% CI, 0.011–0.60; P = 0.014). NAC increased GSH; GSTP1 influenced risk for CIHL and NAC otoprotection.

Conclusions:
NAC was safe at the RP2D, with strong evidence for efficacy to prevent CIHL, warranting further development as a next-generation otoprotectant.
Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
Authors: Sah Vasu R. , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M. , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars 
Published: May 2023

Purpose:
Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.

Patients and Methods:
We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tumor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.

Results:
Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of responding patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling tertiary lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.

Conclusions:
This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.

Significance:
The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomarkers needing validation and become hypothesis generating for experimental research.