bluuebunny/crossref_metadata_2025_split huggingface dataset:
Penicillin allergy status and its effect on antibiotic prescribing, patient outcomes and antimicrobial resistance (ALABAMA): protocol for a multicentre, parallel-arm, open-label, randomised pragmatic trial
Authors: Armitage Kelsey Fiona , Porter Catherine E , Ahmed Shadia , Cook Johanna , Boards Jenny , Bongard Emily , Butler Christopher C , Corfield Kate , Davoudianfar Mina , Galal Ushma , Howard Philip , Mujica-Mota Ruben , Saman Razan , Santillo Marta , Savic Sinisa , Shinkins Bethany , Tonkin-Crine Sarah , Wanat Marta , West Robert M , Yu Ly-Mee , Pavitt Sue , Sandoe Jonathan A T 
Published: February 2024

IntroductionIncorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England. Penicillin allergy records are associated with worse health outcome and antimicrobial resistance. The ALlergy AntiBiotics And Microbial resistAnce (ALABAMA) trial aims to determine if an intervention package, centred around a penicillin allergy assessment pathway (PAAP) initiated in primary care, is safe and effective in improving patient health outcomes and antibiotic prescribing.Methods and analysisThe ALABAMA trial is a multicentre, parallel-arm, open-label, randomised pragmatic trial with a nested pilot study. Adults (≥18 years) with a penicillin allergy record and who have received antibiotics in the previous 24 months will be eligible for participation. Between 1592 and 2090 participants will be recruited from participating National Health Service general practices in England. Participants will be randomised to either usual care or intervention to undergo a pre-emptive PAAP using a 1:1 allocation ratio. The primary outcome measure is the percentage of treatment response failures within 28 days of an index prescription. 2090 and 1592 participants are estimated to provide 90% and 80% power, respectively, to detect a clinically important absolute difference of 7.9% in primary outcome at 1 year between groups. The trial includes a mixed-methods process evaluation and cost-effectiveness evaluation.Ethics and disseminationThis trial has been approved by London Bridge Research Ethics Committee (ref: 19/LO/0176). It will be conducted in compliance with Good Clinical Practice guidelines according to the Declaration of Helsinki. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to an international, peer-reviewed journal.Trial registrationISRCTN20579216.
Evaluation of an integrated care pathway for out-of-hospital treatment of older adults with an acute moderate-to-severe lower respiratory tract infection or pneumonia: protocol of a mixed methods study
Authors: Roos Rick , Pepping Rianne M C , van Aken Maarten O , Labots Geert , Lahdidioui Ali , van den Berg Johanna M W , Kolfschoten Nikki E , Pasha Sharif M , ten Holder Joris T , Mollink Susan M , van den Bos Frederiek , Kant Jojanneke , Kroon Ingrid , Vos Rimke C , Numans Mattijs E , van Nieuwkoop Cees 
Published: February 2024

IntroductionOlder adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagnostic and treatment possibilities in primary care, and the presence of financial barriers. We will evaluate the implementation of an integrated regional care pathway (‘The Hague RTI Care Bridge’) developed with the aim to treat and coordinate care for these patients outside the hospital.Methods and analysisThis is a prospective mixed methods study. Participants will be older adults (age≥65 years) with an acute moderate-to-severe LRTI or pneumonia treated outside the hospital (care pathway group) versus those treated in the hospital (control group). In addition, patients, their informal caregivers and treating physicians will be asked about their experiences with the care pathway. The primary outcome of this study will be the feasibility of the care pathway, which is defined as the percentage of patients treated outside the hospital, according to the care pathway, whom fully complete their treatment without the need for hospitalisation within 30 days of follow-up. Secondary outcomes include the safety of the care pathway (30-day mortality and occurrence of complications (readmissions, delirium, falls) within 30 days); the satisfaction, usability and acceptance of the care pathway; the total number of days of bedridden status or hospitalisation; sleep quantity and quality; functional outcomes and quality of life.Ethics and disseminationThe Medical Research Ethics Committee Leiden The Hague Delft (reference number N22.078) has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. The results will be published in international peer-reviewed journals.Trial registration numberISRCTN68786381.
Integrating 4 methods to evaluate physical function in patients with cancer (In4M): protocol for a prospective cohort study
Authors: Thanarajasingam Gita , Kluetz Paul , Bhatnagar Vishal , Brown Abbie , Cathcart-Rake Elizabeth , Diamond Matthew , Faust Louis , Fiero Mallorie H , Huntington Scott , Jeffery Molly Moore , Jones Lee , Noble Brie , Paludo Jonas , Powers Brad , Ross Joseph S , Ritchie Jessica D , Ruddy Kathryn , Schellhorn Sarah , Tarver Michelle , Dueck Amylou C , Gross Cary 
Published: February 2024

IntroductionAccurate, patient-centred evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterise the longitudinal measurement characteristics of physical function assessments, including clinician-reported outcome, patient-reported ported outcome (PRO), performance outcome tests and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice.Methods and analysisIn this prospective study, we are enrolling 200 English-speaking and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centred health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multimodal physical function data collection in real-world patients with breast cancer or lymphoma will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform and PROs.Ethics and disseminationThis study has received approval from IRBs at Mayo Clinic, Yale University and the US Food and Drug Administration. Results will be made available to participants, funders, the research community and the public.Trial registration numberNCT05214144; Pre-results.
Assessment of oxygen extraction rate changes following red blood cell transfusion in the intensive care unit: a protocol for a prospective observational non-interventional study
Authors: Tüzen Ahmet Salih , Aksun Murat , Sencan Atilla , Girgin Senem , Gölboyu Birzat Emre , Kırbaş Gizem , Şanlı Ozan 
Published: February 2024

IntroductionHaemoglobin transfusion thresholds have been used in the intensive care unit (ICU) to guide red blood cell transfusion (RBCT) decisions. Recent research has also focused on physiological indicators of tissue oxygenation as trigger points for blood transfusion. This study aims to assess the oxygen extraction rate (O2ER) as a critical indicator of the oxygen delivery–consumption balance in tissues and investigate its potential as a reliable trigger for blood transfusion in ICU patients by analysing clinical outcomes. The utilisation of physiological indicators may expedite the decision-making process for RBCT in patients requiring immediate intervention, while simultaneously minimising the risks associated with unnecessary transfusions.Methods and analysisThis prospective, single-centre, observational cohort study will include 65 ICU patients undergoing RBCT. We will evaluate essential markers such as arterial oxygen content, central venous oxygen content, arteriovenous oxygen difference, O2ER and near-infrared spectroscopy before and 15 min after transfusion. The primary outcome is the percentage increase in O2ER between the two groups relative to the initial O2ER level. Secondary outcomes will assess complications and patient outcomes in relation to baseline O2ER. A 90-day comprehensive follow-up period will be implemented for all enrolled patients.Ethics and disseminationThis study has obtained ethics committee approval from the Izmir Katip Celebi University Non-Interventional Clinical Studies Institutional Review Board. Written informed consent will be obtained from all patients before their enrolment in the study. The findings will be disseminated through publication in peer-reviewed journals and presentation at national or international conferences.Trial registration numberNCT05798130
Impact of a deprescribing tool on the use of sedative hypnotics among older patients: study protocol for a cluster randomised controlled trial in Swiss primary care (the HYPE trial)
Authors: Weiss Katja , Pichierri Giuseppe , Grischott Thomas , Groth Susan , Neuner-Jehle Stefan 
Published: February 2024

IntroductionBenzodiazepines and other sedative hypnotics (BSH) are potentially inappropriate and harmful medications in older people due to their higher susceptibility for adverse drug events. BSH prescription rates are constantly high among elderly patients and even increase with higher age and comorbidity. Deprescribing BSH can be challenging both for healthcare providers and for patients for various reasons. Thus, physicians and patients may benefit from a supportive tool to facilitate BSH deprescribing in primary care consultations. This study intends to explore effectiveness, safety, acceptance and feasibility of such a tool.Methods and analysisIn this prospective, cluster randomised, controlled, two-arm, double-blinded trial in the ambulatory primary care setting, we will include general practitioners (GPs) from German-speaking Switzerland and their BSH consuming patients aged 65 years or older, living at home or in nursing homes. GPs will be randomly assigned to either intervention or control group. In the intervention group, GPs will participate in a 1-hour online training on how to use a patient support tool (decision-making guidance plus tapering schedule and non-pharmaceutical alternative treatment suggestions for insomnia). The control group GPs will participate in a 1-hour online instruction about BSH epidemiology and sleep hygiene counselling. This minimal intervention aims to prevent unblinding of control group GPs without jeopardising their ‘usual care’.The primary outcome will be the percentage of patients who change their BSH use (ie, stop, reduce or switch to a non-BSH insomnia treatment) within 6 months from the initial consultation.Expected benefitBased on the results of the study, we will learn how GPs and their patients benefit from a supportive tool that facilitates BSH deprescribing in primary care consultations. The study will emphasise on exploring barriers and facilitators to BSH deprescribing among patients and providers. Positive results given, the study will improve medication safety and the quality of care for patients with sleeping disorders.Ethics and disseminationThe study has been approved by the Ethics Committee of the Canton of Zurich (KEK-ZH Ref no. 2023-00054, 4 April 2023). Informed consent will be sought from all participating GPs and patients. The results of the study will be publicly disseminated.Trial registration numberISRCTN34363838
Rationale and protocol of the LAQUA-HF trial: a factorial randomised controlled trial evaluating the effects of neurohormonal and diuretic agents on health-status reported outcomes in heart failure patients
Authors: Shiraishi Yasuyuki , Ikemura Nobuhiro , Urashima Mitsuyoshi , Kohno Takashi , Nakano Shintaro , Tanaka Toshikazu , Nagatomo Yuji , Ikoma Takenori , Ono Tomohiko , Numasawa Yohei , Sakamoto Munehisa , Nishikawa Kei , Takei Makoto , Hakuno Daihiko , Nakamaru Ryo , Ueda Ikuko , Kohsaka Shun 
Published: February 2024

IntroductionThe current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects.Methods and analysisIn a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients’ QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients’ health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint.Ethics and disseminationThe medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses.Trial registration numberUMIN000045229
Remote ischaemic conditioning combined with bimanual task training to enhance bimanual skill learning and corticospinal excitability in children with unilateral cerebral palsy: a study protocol of a single centre, phase II randomised controlled trial
Authors: Surkar Swati M , Willson John D , Cassidy Jessica M , Kantak Shailesh , Patterson Charity G 
Published: February 2024

IntroductionChildren with unilateral cerebral palsy (UCP) have difficulty in bimanual coordination that restricts the child’s independence in daily activities. Although several efficacious interventions to improve bimanual coordination exist, these interventions often require higher training doses and have modest effect sizes. Thus, there is a critical need to find an effective priming agent that, when paired with task-specific training, will facilitate neurobiological processes to enhance the magnitude of training effects and subsequently improve functional capabilities of children with UCP. The aim of this study is to determine the effects of a novel priming agent, remote ischaemic conditioning (RIC), combined with bimanual training on bimanual skill learning and corticospinal excitability in children with UCP.Methods and analyses46 children, aged 8–16 years, will be randomly assigned to receive RIC or sham conditioning combined with 5 days of bimanual skill (cup stacking) training (15 trials per session). RIC or sham conditioning will be performed with a standard conditioning protocol of five cycles of alternative inflation and deflation of a pressure cuff on the affected arm with the pressure of at least 20 mm Hg above systolic blood pressure for RIC and 25 mm Hg for sham conditioning. Primary outcomes will be movement time and corticospinal excitability measures determined with a single-pulse transcranial magnetic stimulation (TMS). Secondary outcomes include Assisting Hand Assessment, spatio-temporal kinematic variables and paired pulse TMS measures. All measures will be conducted before and immediately after the intervention. A mixed model analysis of variance will test the group×time interaction for all outcomes with group (RIC and sham) as between-subject and time (preintervention, postintervention) as within-subject factors.Ethics and disseminationThe study has been approved by the University Medical Centre Institutional Review Board (UMCIRB #21-001913). We will disseminate the study findings via peer-reviewed publications and presentations at professional conferences.Trial registration numberNCT05777070
Personalised human albumin in patients with cirrhosis and ascites: design and rationale for the ALB-TRIAL - a randomised clinical biomarker validation trial
Authors: Torp Nikolaj , Israelsen Mads , Coenraad Minneke , Papp Maria , Shawcross Debbie , Korenjak Marko , Angeli Paolo , Laleman Wim , Juanola Adria , Gines Pere , Trebicka Jonel , Krag Aleksander 
Published: February 2024

IntroductionHuman albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites.Methods and analysisALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis.Ethics and disseminationThe trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion.Trial registration numberNCT05056220EU CT: 2022-501006-34-01
Quantifying non-adherence to anti-tuberculosis treatment due to early discontinuation: a systematic literature review of timings to loss to follow-up
Authors: Walker Elizabeth F , Flook Mary , Rodger Alison J , Fielding Katherine L , Stagg Helen R 
Published: February 2024

BackgroundThe burden of non-adherence to anti-tuberculosis (TB) treatment is poorly understood. One type is early discontinuation, that is, stopping treatment early. Given the implications of early discontinuation for treatment outcomes, we undertook a systematic review to estimate its burden, using the timing of loss to follow-up (LFU) as a proxy measure.MethodsWeb of Science, Embase and Medline were searched up to 14 January 2021 using terms covering LFU, TB and treatment. Studies of adults (≥ 18 years) on the standard regimen for drug-sensitive TB reporting the timing of LFU (WHO definition) were included. A narrative synthesis was conducted and quality assessment undertaken using an adapted version of Downs and Black. Papers were grouped by the percentage of those who were ultimately LFU who were LFU by 2 months. Three groups were created: <28.3% LFU by 2 months, ≥28.3–<38.3%, ≥38.3%). The percentage of dose-months missed due to early discontinuation among (1) those LFU, and (2) all patients was calculated.ResultsWe found 40 relevant studies from 21 countries. The timing of LFU was variable within and between countries. 36/40 papers (90.0%) reported the percentage of patients LFU by the end of 2 months. 31/36 studies (86.1%) reported a higher than or as expected percentage of patients becoming LFU by 2 months. The percentage of dose-months missed by patients who became LFU ranged between 37% and 77% (equivalent to 2.2–4.6 months). Among all patients, the percentage of dose-months missed ranged between 1% and 22% (equivalent to 0.1–1.3 months).ConclusionsA larger than expected percentage of patients became LFU within the first 2 months of treatment. These patients missed high percentages of dose months of treatment due to early discontinuation. Interventions to promote adherence and retain patients in care must not neglect the early months of treatment.PROSPERO registration numberCRD42021218636.
Inversion points of the accretion flows onto super-spinning Kerr attractors
Authors: Pugliese D. , Stuchlík Z. 
Published: February 2024

AbstractWe study the accretion flows towards a central Kerr super-spinning attractor, discussing the formation of the flow inversion points, defined by condition $$u^{\phi }=0$$

u
ϕ

=
0

on the particles flow axial velocity. We locate two closed surfaces, defining inversion coronas (spherical shells), surrounding the central attractor. The coronas analysis highlights observational aspects distinguishing the central attractors and providing indications on their spin and the orbiting fluids. The inversion corona is a closed region, generally of small extension and thickness, which is for the counter-rotating flows of the order of $$\lesssim 1.4 M$$

≲
1.4
M

(central attractor mass) on the vertical rotational axis. There are no co-rotating inversion points (from co-rotating flows). The results point to strong signatures of the Kerr super-spinars, provided in both accretion and jet flows. With very narrow thickness, and varying little with the fluid initial conditions and the emission process details, inversion coronas can have remarkable observational significance for primordial Kerr super-spinars predicted by string theory. The corona region closest to the central attractor is the most observably recognizable and active part, distinguishing black holes solutions from super-spinars. Our analysis expounds the Lense–Thirring effects and repulsive gravity effects in the super-spinning ergoregions.