bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of carbon dioxide control during pressure controlled versus pressure-regulated volume controlled ventilation in children (CoCO2): protocol for a pilot digital randomised controlled trial in a quaternary paediatric intensive care unit
Authors: Mozun Rebeca , Chopard Daphné , Zapf Florian , Baumann Philipp , Brotschi Barbara , Adam Anika , Jaeggi Vera , Bangerter Beat , Gibbons Kristen S , Burren Juerg , Schlapbach Luregn J 
Published: January 2025

IntroductionDigital trials are a promising strategy to increase the evidence base for common interventions and may convey considerable efficiency benefits in trial conduct. Although paediatric intensive care units (PICUs) are rich in routine electronic data, highly pragmatic digital trials in this field remain scarce. There are unmet evidence needs for optimal mechanical ventilation modes in paediatric intensive care. We aim to test the feasibility of a digital PICU trial comparing two modes of invasive mechanical ventilation using carbon dioxide (CO2) control as the outcome measure.Methods and analysisSingle-centre, open-labelled, randomised controlled pilot trial with two parallel treatment arms comparing pressure control versus pressure-regulated volume control. Patients are eligible if aged <18 years, weighing >2 kg, have an arterial line and require >60 min of mechanical ventilation during PICU hospitalisation at the University Children’s Hospital Zurich. Exclusion criteria include cardiac shunt lesions, pulmonary hypertension under treatment and intracranial hypertension. CO2is measured using three methods: end-tidal (continuous), transcutaneous (continuous) and blood gas analyses (intermittent). Baseline, intervention and outcome data are collected electronically from the patients’ routine electronic health records. The primary feasibility outcome is adherence to the assigned ventilation mode, while the primary physiological outcome is the proportion of time spent within the target range of CO2(end-tidal, normocarbia defined as CO2≥ 4.5 and ≤ 6 kPa). Both primary outcomes are captured digitally every minute from randomisation until censoring (at 48 hours after randomisation, extubation, discharge or death, whichever comes first). Analysis will occur on an intention-to-treat basis. We aim to enrol 60 patients in total. Recruitment started in January 2024 and continued for 9 months.Ethics and disseminationThis study received ethical approval from the Cantonal Ethics Commission of Zurich (identification number: 2022–00829). Study results will be disseminated through publication in a peer-reviewed journal and other media like podcasts.Trial registration numberNCT05843123.
Digital screening tool for the assessment of cognitive impairment in unsupervised setting—digiDEM-SCREEN: study protocol for a validation study
Authors: Zeiler Michael , Dietzel Nikolas , Kammerer Klaus , Frick Ulrich , Pryss Rüdiger , Heuschmann Peter , Prokosch Hans-Ulrich , Graessel Elmar , Kolominsky-Rabas Peter L 
Published: January 2025

IntroductionDementia is one of the most relevant widespread diseases, with a prevalence of currently 55 million people with dementia worldwide. However, about 60–75% of people with dementia have not yet received a formal diagnosis. Asymptomatic screening of cognitive impairments using neuropsychiatric tests has been proven to efficiently enhance diagnosis rates. Digital screening tools, in particular, provide the advantage of being accessible without spatial or time restrictions. The study aims to validate a digital cognitive screening test (digiDEM-SCREEN) as an app in the German language.Methods and analysisThis is a multicentre study in Bavaria. Participants are people with mild cognitive impairment, people with dementia in an early stage and cognitively healthy people. Recruitment will take place in specialised diagnostic facilities (memory outpatient clinics). 135 participants are aimed based on a power analysis. Sociodemographic data, diagnosis and results of neuropsychiatric tests (Consortium to Establish a Registry for Alzheimer’s Disease, Montreal Cognitive Assessment, digiDEM-SCREEN) will be collected at one point per person via electronic data capturing. The sensitivity, specificity and corresponding cut-off values will be determined based on receiver-operating-characteristic curves. The correlation of the digiDEM-SCREEN test with existing cognitive screening/testing procedures will be analysed.Ethics and disseminationThe study obtained ethical approval from the Ethics Committee of the Julius-Maximilians-Universität of Würzburg (JMU) (application number: 177/23-sc). The test will give feedback about the current cognitive status and possible cognitive impairments that should lead to the users seeking further diagnostic measures by medical professionals. It will be accessible free of charge in established app stores. The results of the validation study will be published in peer-reviewed journals.
Neoadjuvant adebrelimab combined with chemotherapy (cisplatin/carboplatin and etoposide) for limited-stage small-cell lung cancer: a study protocol of phase 2 trial (NIUS)
Authors: Liu Yanyang , Huang Qian , Tian Long , Zheng Xi , Chen Guizhi , Xu Hongyu , Li Mengxia , Zhu Daxing , Zhang Yan 
Published: January 2025

IntroductionSmall-cell lung cancer (SCLC) is a highly malignant neuroendocrine tumour, and concurrent chemoradiotherapy is the current recommended treatment for limited-stage SCLC. However, the overall survival (OS) of patients with SCLC remains poor. Therefore, improving the survival of patients with SCLC and benefitting more patients are urgent clinical requirements. Immunotherapy has achieved good efficacy in extensive-stage SCLC and non-SCLC. However, the use of neoadjuvant immunotherapy in limited-stage SCLC is unknown but promising. To this end, we plan to conduct a study on adebrelimab in combination with chemotherapy for the neoadjuvant treatment of limited-stage SCLC.Methods and analysisThis will be a single-arm, prospective study. The primary endpoint of this study will be a pathological complete remission rate. The secondary endpoints will be a major pathological response, objective response rate, event-free survival, OS, R0 resection rate, safety and potential predictive biomarker parameters related to efficacy in peripheral blood samples, including minimal residual disease, circulating tumour cells and cluster of differentiation (CD) 4/CD8. This study will enrol 28 patients.Ethics and disseminationThis study was approved by the Biomedical Ethics Review Committee of West China Hospital, Sichuan University, on 1 August 2023 (grant number 2023[987]). The version of this study protocol is V7.0. The patients have been enrolled since September 2023. This study will conclude in January 2026, and the results will be presented to peer-reviewed medical journals and international scientific conferences in 2027. This study will provide important data on whether neoadjuvant treatment with adebrelimab combined with chemotherapy is clinically beneficial in patients with limited-stage SCLC.(Prospective study of neoadjuvant adebrelimab combined with chemotherapy in limited-stage SCLC; Chinese Clinical Trial Registry (ChiCTR),www.chictr.org.cn/; Number, ChiCTR2300074591.)Trial registration numberChiCTR2300074591
Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke
Authors: Matusevicius Marius , Paiva Nunes Ana , Krishnan Manju , Egido Jose , Concari Letizia , Dixit Anand , Reggiani Monica , Pagès Alain , Danays Thierry , Toni Danilo , Ahmed Niaz 
Published: January 2025

ObjectivesTo investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in several European and non-European countries during 2018–2019.DesignThis is an observational registry study using prospectively collected data from the Safe Implementation of Treatment in Stroke (SITS) registry. Comparisons will be performed between patients treated post-approval (July 2018 to December 2021) period with those treated pre-approval (June 2015 to June 2018) period using propensity score matching (PSM).SettingThis is a multicentre international study in hospitals treating AIS with IVT.ParticipantsPatients aged >80 years who otherwise followed the IVT Summary of Product Characteristics of European countries as part of the mutual recognition procedure.Primary and secondary outcomesThe main outcomes were symptomatic intracerebral haemorrhage per SITS monitoring study definition, death and functional independency as defined by a modified Rankin Scale score of 0–2 at 90 days.ResultsAfter PSM, 614 patients remained in each group (mean age 87 years, 39% males). All baseline data were well balanced after PSM. There were no statistically significant differences in outcomes between pre- and post-approval patients for SICH (2.5% vs 2.3%, risk ratio (RR) 1.064, 95% CI 0.345–1.784), death (25.3% vs 28.4%, RR 0.889, 0.699–1.08) and functional independency at 90 days (40.3% vs 37%, RR 1.089, 0.942–1.237).ConclusionsIn this observational study of IVT treatment in patients >80 years of age with AIS before and after formal approval for this treatment, we did not find any difference in outcomes between the pre- and post-approval periods.
Cost–utility analysis of MR imaging-guided transurethral ultrasound ablation for the treatment of low- to intermediate-risk localised prostate cancer
Authors: Muhler Paul , Akuamoa-Boateng Dennis , Rosenbrock Johannes , Stock Stephanie , Müller Dirk , Heidenreich Axel , Simões Corrêa Galendi Julia 
Published: January 2025

BackgroundMagnetic resonance-guided transurethral ultrasound ablation (MR-TULSA) is a new focal therapy for treating localised prostate cancer that is associated with fewer adverse effects (AEs) compared with established treatments. To support large-scale clinical implementation, information about cost-effectiveness is required.ObjectiveTo evaluate the cost–utility of MR-TULSA compared with robot-assisted radical prostatectomy (RARP), external beam radiation therapy (EBRT) and active surveillance (AS) for patients with low- to favourable intermediate-risk localised prostate cancer.Design, setting and participantsA Markov model was developed targeting 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer over a time horizon of 40 years from the German Statutory Health Insurance (SHI) perspective. To assess the robustness of the results, deterministic and probabilistic sensitivity analyses were performed.InterventionFour different treatment strategies were compared: minimally invasive MR-TULSA, two definitive approaches (RARP and EBRT) and one observational strategy (AS).Outcome measurements and statistical analysisOutcomes were measured in overall costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER).ResultsAS generated the highest number of QALYs (12.67), followed by MR-TULSA (12.35), EBRT (12.35) and RARP (12.20). RARP generated the lowest costs (€ 46 997) over one patient’s lifetime, while MR-TULSA was a slightly more expensive alternative (€48 826). The incremental cost-effectiveness ratio (ICER) of AS compared with RARP was €11 600 per QALY and of MR-TULSA compared with RARP was €12 193 per QALY, while EBRT was dominated. At a willingness-to-pay of €20 000 per QALY, the probability of being cost-effective is 44% for AS, 25% for RARP, 25% for MR-TULSA and 6% for EBRT.ConclusionsAll treatment options for 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer are affected by considerable uncertainty. Accepting high follow-up costs by applying a higher willingness-to-pay, AS is the most favourable treatment option.
Understanding the work-related challenges of organ and tissue donation coordinators during the COVID-19 pandemic: a mixed-method study
Authors: Silva e Silva Vanessa , Minervini Alessandra , Dupuis Kendra-Lee , Lotherington Ken , Dhanani Sonny , Silva Amina 
Published: January 2025

ObjectivesThis study aimed to explore the perceptions of donation coordinators in Canada and understand how the COVID-19 pandemic impacted their work activities.DesignA sequential mixed-method design incorporating a cross-sectional survey investigating demographic data, substance use and abuse and perceived stress related to the pandemic and semistructured qualitative interviews to further investigate those.SettingOrgan donation organisations across Canada.ParticipantsCanadian organ and tissue donation coordinators working within deceased donation programmes. Participants were recruited using a purposive sampling technique for the survey and qualitative interviews. Recruitment and data collection took place between January 2022 and March 2023.AnalysisThe data were analysed using descriptive statistics for the quantitative findings and content analysis for the qualitative data.ResultsOf the 175 available coordinators, 120 participated in the survey, and 39 participated in the qualitative interviews. The great majority were female (n=98; 81.7%), registered nurses (n=117; 97.5%) and on average 42 years old (SD=9.64). The survey result for perceived stress showed that, on average, coordinators did not experience high stress levels during the pandemic. We also identified an increase in the consumption of substances to manage workplace stress near the pandemic’s beginning. The qualitative interviews yielded two main themes (Personal Life Changes and Workplace Adjustments) in which coordinators reported their views on challenges with uncertainties, effects on their personal lives, redeployment, stressors and among others.ConclusionOur study’s results provide a comprehensive understanding of the perceptions and experiences of coordinators in Canada during the COVID-19 pandemic. Using a combination of methods, we identified various ways coordinators were affected by the pandemic in their personal and professional lives. These findings highlight the need to support the development of adaptive strategies and promote resilience during crises.
Experiences of Māori and Pacific women recruited into a pregnancy clinical trial in Aotearoa, New Zealand: a Kaupapa Māori qualitative study
Authors: Enright Richard , Roskvist Rachel , Rahiri Jamie-Lee , Mullane Tania , Albert Benjamin B , Satokar Vidit Vinod , Harwood Matire 
Published: January 2025

ObjectivesTo explore the perspectives of Māori and Pacific women who participated in the Fish Oil study to ascertain what barriers and facilitators may exist for successfully recruiting Māori and Pacific women into clinical trials.DesignA Kaupapa Māori qualitative study.SettingAuckland, New Zealand.Participants16 Māori and Pacific women who participated in the fish oil supplementation during pregnancy study (ACTRN12617001078347p) between 1 January 2017 and 31 December 2020.Main outcome measuresSemistructured in-depth interviews were conducted, recorded and transcribed and then subjected to inductive thematic analysis to identify key themes related to barriers and facilitators of successful Māori and Pacific women recruitment into a clinical trial.ResultsOf 37 eligible Māori and Pacific women who participated in the original Fish Oil study, 16 women consented to participate in this study. Three key themes were identified: (1) relationships matter, (2) privileges and barriers and (3) the study experience. Key facilitators for recruitment included having solid relationships with research team members, practising exemplary professionalism, having clear communication and having the ability to establish rapport and research team flexibility. The desire to create a better future for participants’ babies and to give back to Māori and Pacific communities through participating in a clinical trial were also key drivers of successful recruitment. In contrast, the major barriers described were time pressures and the distance to the research facility.ConclusionsSixteen Māori and Pacific women who participated in a double-blinded randomised controlled trial shared that successful recruitment of Māori and Pacific women into clinical trials can be promoted by research flexibility participants’ whānau/family responsibilities, effective and culturally safe communication, and research teams striving to build and maintain relationships with participants throughout the trial.Trial registeration numberAustralian New Zealand Clinical Trials Registry, ACTRN12617001078347p. Universal Trial Number (U1111-1199-5860).
Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial
Authors: Gaston David C , Humphries Romney M , Lewis Ariel A , Gatto Cheryl L , Wang Li , Nelson George E , Stollings Joanna L , Ereshefsky Benjamin J , Christensen Matthew A , Dear Mary Lynn , Banerjee Ritu , Miller Karen F , Self Wesley H , Semler Matthew W , Qian Edward T 
Published: January 2025

IntroductionPatients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance genes from whole blood samples within hours of collection could enable earlier antibiotic optimisation for patients suspected to have bacterial infections. However, few randomised trials have evaluated the effect of using direct-from-blood bacterial testing on antibiotic administration and clinical outcomes. This manuscript describes the protocol and statistical analysis plan for a randomised trial designed to evaluate the effect of blood cultures plus direct-from-blood bacterial testing results compared with blood culture results alone on antibiotic administration and clinical outcomes.Methods and analysisWe are conducting a prospective, single-centre, parallel-group, non-blinded, pragmatic, randomised trial. The trial will enrol 500 adult patients presenting to the emergency department at Vanderbilt University Medical Center with suspected bacterial infection who have been initiated on empiric intravenous vancomycin. Eligible patients are randomised 1:1 to receive Food and Drug Administration-approved direct-from-blood bacterial testing in addition to blood cultures or blood cultures alone. The primary outcome is the time to the last dose of intravenous vancomycin within 14 days of randomisation. The secondary outcome is the time to the last dose of systemic antipseudomonal beta-lactam antibiotics within 14 days of randomisation. Additional outcomes include highest stage of acute kidney injury, lowest platelet count and receipt of kidney replacement therapy within 14 days of randomisation, as well as hospital-free days, intensive care unit-free-days and all-cause, in-hospital mortality within 28 days of randomisation. Enrolment began on 13 December 2023.Ethics and disseminationThe trial involves human participants and was approved by the Vanderbilt University Medical Center institutional review board with a waiver of informed consent (IRB#231229). Results will be submitted in a peer-reviewed journal and presented at scientific conferences.Trial registration numberNCT06069206.
Brain health in Norwegian female former top-level football players: a protocol for a longitudinal cohort study
Authors: Dahlén Sara Christina , Bjørneboe John , Sandmo Stian Kirkerud , Bache-Mathisen Lena , Filipcik Peter , Howe Emilie Isager , Høgestøl Einar August , Selbæk Geir , Straume-Næsheim Truls , Westlye Lars T , Bahr Roald , Andersen Thor Einar 
Published: January 2025

IntroductionRepetitive head impacts (RHI) in sports may represent a risk factor for long-term cognitive and neurological sequelae. Recent studies have identified an association between playing football at the top level and an elevated risk of cognitive impairment and neurodegenerative disease. However, these were conducted on men, and there is a knowledge gap regarding these risks in female athletes. This study aims to investigate the effect of head impacts on brain health in female former top-level football players.Methods and analysisThis is a prospective cohort study, enroling female former football players and top-level athletes from sports without an inherent risk of RHI. All participants are born in 1980 or earlier. We plan to perform follow-up assessments at least three times over 20 years.The protocol includes neurocognitive assessments, self-reported neurocognitive outcomes, neurological examination, advanced brain MRI, and fluid biomarkers.Ethics and disseminationThe study has been approved by the South-East Regional Ethics Committee for Medical Research in Norway (2023/178330) and the Norwegian Agency for Shared Services in Education and Research (SIKT). A Data Protection Impact Assessment was developed by the research group and approved by SIKT and the Norwegian School of Sport Sciences. We will disseminate the results through peer-reviewed publications, academic conference presentations and webinars. We will communicate with the public and key stakeholders in football worldwide to inform and promote the development and implementation of potential preventive measures based on our study findings.
Cataract surgery has minimal effect on corneal shape
Authors: Alfaqawi Fadi , Pagano Luca , Arbabi Esmaeil M , Romano Vito , Al-Maskari Ahmed , McLean Keri , Czanner Gabriella , Kaye Stephen B 
Published: January 2025

PurposeTo quantify the effect of cataract surgery on cornea shape.MethodsPatients undergoing cataract surgery with standardised 2.75 mm surgical incisions at 110 degrees with a side port at 50 degrees were included. Repeat biometric measurements were taken before surgery and at 6 weeks on both operated and unoperated fellow eyes. Data were transformed into Long’s formalism for analysis. Device-specific measurement error was determined. The main outcome measure was the change in keratometry taking into account the change in keratometry of the unoperated fellow eye. Secondary outcome measures included the variability introduced due to location of the incision.Results132 patients were included. The mean change in keratometry of the operated eye was −0.23@111/+0.21@21 (95% CI −1.43@122/+0.04@32 to +1.04@135/+0.30@45). The flattening effect of the surgical incision was greater and more variable than the steepening effect (p<0.01), particularly if the incision was in the flat meridian. Coupling, defined as ratio of the keratometric change in the preoperative meridians of K2 and K1, varied from 0.91 (SD 2.31) for eyes with an incision in the steep meridian, 0.75 (SD 1.81) for an incision in the flat meridian to 0.28 (SD 2.06) when the incision was made in a neutral meridian.ConclusionCataract surgery has a slightly greater flattening than steepening effect on corneal shape. Although the effects are very small and variable with incomplete coupling, it is preferable to place the incision in the steep meridian. Greater emphasis, however, should be placed on eye-specific factors, such as biometry, or patient-related factors to optimise refractive outcomes.