bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early medical therapy for acute laryngeal injury (ALgI) following endotracheal intubation: a protocol for a prospective single-centre randomised controlled trial
Authors: Lowery Anne S , Kimura Kyle , Shinn Justin , Shannon Chevis , Gelbard Alexander 
Published: July 2019

IntroductionRespiratory failure requiring endotracheal intubation accounts for a significant proportion of intensive care unit (ICU) admissions. Little attention has been paid to the laryngeal consequences of endotracheal intubation. Acute laryngeal injury (ALgI) after intubation occurs at the mucosal interface of the endotracheal tube and posterior larynx and although not immediately manifest at extubation, can progress to mature fibrosis, restricted glottic mobility and clinically significant ventilatory impairment. A recent prospective observational study has shown that >50% of patients intubated >24 hours in an ICU develop ALgI. Strikingly, patients with AlgI manifest significantly worse subjective breathing at 12 weeks. Current ALgI treatments are largely surgical yet offer a marginal improvement in symptoms.In this study, we will examine the ability of a postextubation medical regime (azithromycin and inhaled budesonide) to improve breathing 12 weeks after ALgI.Methods and analysisA prospective, single-centre, double-blinded, randomised, control trial will be conducted at Vanderbilt Medical Center. Participants will be recruited from adult patients in ICUs. Participants will undergo a bedside flexible nasolaryngoscopy for the identification of ALgI within 72 hours postextubation. In addition, participants will be asked to complete peak expiratory flow measurements immediately postintubation. Patients found to have ALgI will be randomised to the placebo control or medical therapy group (azithromycin 250 mg and budesonide 0.5 mg for 14 days). Repeat peak expiratory flow, examination of the larynx and patient-reported Clinical COPD (chronic obstructive pulmonary disease) Questionnaire, Voice Handicap Index and 12-Item Short Form Health Survey questionnaires will be conducted at 12 weeks postextubation. Consented patients will also have patient-specific, disease-specific and procedure-specific covariates abstracted from their medical record.Ethics and disseminationThe Institutional Review Board (IRB) Committee of the Vanderbilt University Medical Center has approved this protocol (IRB #171066). The findings of the trial will be disseminated through peer-reviewed journals, national and international conferences.Trial registration numberNCT03250975
Impact of general anaesthesia in overall and disease-free survival compared to other types of anaesthesia in patients undergoing surgery for cutaneous melanoma: a systematic review and meta-analysis protocol
Authors: Araujo Bruno Luís de Castro , de Oliveira Jadivan Leite , Corrêa Flavia de Miranda , Fontes Luis Eduardo Santos , de Melo Andreia Cristina , Thuler Luiz Claudio Santos 
Published: July 2019

IntroductionCutaneous melanoma is an aggressive type of skin cancer. Anaesthetic agents may have an impact on the immune response, postoperative neurohumoral response and tumour progression. This systematic review aims to evaluate the impact of general anaesthesia on overall and disease-free survival compared with other types anaesthesia in patients undergoing surgery for cutaneous melanoma.Methods and analysisThe review will analyse data from controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia compared with other types of anaesthesia. The primary outcomes are overall survival and disease-free survival. The secondary outcomes are health-related quality of life, time to tumour progression, distant disease-free survival, time to treatment failure, cancer-specific survival, biochemical recurrence, return of intended oncological therapy, days alive and out of the hospital at 90 days, cost analysis and adverse events. A comprehensive literature search will be performed using the MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, LILACS and IBECS databases. Grey literature will also be searched. Risk of methodological bias will be assessed using The Cochrane Collaboration’s revised tool for assessing risk of bias in randomised trials (RoB 2.0) and the Newcastle–Ottawa scale. Two reviewers will independently assess the eligibility of studies and risk of bias; a third author will solve discrepancies. One author will perform data extraction and the other will check the process and data. Qualitative analysis will be carried out using all included studies. A meta-analysis using a random-effects model for pooled risk estimates will be carried out for the two main outcomes and for selected secondary outcomes if they conform to previously stated criteria. The GRADE approach will be used to summarise the quality of evidence.Ethics and disseminationEthics approval is not required as we analyse data from previously reported studies.PROSPERO registration numberCRD42018114918.
Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer
Authors: Emaus Marleen J , Išgum Ivana , van Velzen Sanne G M , van den Bongard H J G Desirée , Gernaat Sofie A M , Lessmann Nikolas , Sattler Margriet G A , Teske Arco J , Penninkhof Joan , Meijer Hanneke , Pignol Jean-Philippe , Verkooijen Helena M 
Published: July 2019

IntroductionCardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECG-triggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called ‘cardiovascular calcifications’) measured automatically on planning CT scans of patients with breast cancer and CVD risk.Methods and analysisIn a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600).Ethics and disseminationThe Institutional Review Boards of the participating hospitals decided that the Medical Research Involving Human Subjects Act does not apply. Findings will be published in peer-reviewed journals and presented at conferences.Trial registration numberNCT03206333.
Novel ACT-based eHealth psychoeducational intervention for students with mental distress: a study protocol for a mixed-methodology pilot trial
Authors: Edwards Darren J , Rainey Elinor , Boukouvala Vasiliki , Wells Yasmin , Bennett Paul , Tree Jeremy , Kemp Andrew H 
Published: July 2019

IntroductionRecent studies have revealed a high prevalence of depression, anxiety and stress symptoms among university students, highlighting an urgent need for preventative measures at low cost to better support often overwhelmed support services.ObjectiveHere we propose a protocol for assessing the feasibility of a randomised controlled trial (RCT) for an online transdiagnostic psychoeducational intervention called ‘A Bite of ACT’ compared with a waitlist control.Methods and analysisThis is an RCT with crossover design involving baseline assessments and two follow-up periods. The primary outcome measure will be the Acceptance Checklist for Clinical Effectiveness Pilot Trials (ACCEPT) for measuring the feasibility of the trial design and methods. Secondary outcomes include measures of well-being, social connectedness, quality of life (EuroQol Five Dimensions), depression, anxiety and stress (Depression Anxiety Stress Scales-21), as well as the process measures: psychological flexibility (Acceptance and Action Questionnaire-Second Version and the Mindful Attention Awareness Scale) and heart rate variability. Analysis will involve calculating descriptive statistics, examining trial feasibility outcomes through ACCEPT, and determining effect size measures to determine the sample size needed in a future trial (if indicated). Qualitative interviews and preliminary health economics analysis will provide additional insights into the feasibility of the intervention and trial methods.Ethics and disseminationThis study has been approved by the Department of Psychology Research Ethics Committee in the College of Human and Health Sciences at Swansea University. Dissemination will involve publication in international peer-reviewed journals, presentation of findings at relevant local, national and international conferences, and promotion of study outcomes using social media and other channels for disseminating findings to the wider community.Trial registration numberNCT03810131; Pre-results.
Changes in the upper airway following induction of anaesthesia: a prospective observational study protocol to determine the use of ultrasound in the assessment of a difficult airway in China
Authors: Dong Fang , Wang Yong , Wang Xia , Zhao Huanyi , Ma Wuhua 
Published: July 2019

IntroductionDifficult airway management is closely related to the safety and quality of medical care. However, the low incidence of correct prediction of difficult airway in clinical screening tests presents physicians with a dilemma. Depressed airway neuromuscular tension during sleep and anaesthesia tends to cause collapse of fragile parts of the upper airway. Although previous studies have confirmed that anterior cervical tissue thickness is associated with difficult airways, there is no evidence to support a correlation between a difficult airway and specific patterns or findings of anaesthesia-induced airway collapse. Thus, this study aims to examine changes in airway dimensions before and after induction of general anaesthesia to explore whether it could provide useful information regarding the specific anatomic changes occurring which may cause difficult airways.Methods and analysisThis will be a single-centre prospective observational single-blinded study, conducted in a tertiary teaching hospital in Guangzhou, China. Subjects will be recruited from patients (aged 18–65 years) scheduled for elective surgery under general anaesthesia. Sonographic measurement will be performed to detect changes in the thickness of the anterior cervical soft tissue before and after anaesthetic induction. Based on the resulting data distribution, analyses will initially compare these changes using a paired t-test or the Wilcoxon signed-rank test. The correlation of sonographic changes and Cormack–Lehane grade will be evaluated by using receiver-operating characteristic curves to detect the sensitivity and specificity of a measurement for detecting difficulties. Linear stepwise regression analysis will be used to assess the correlation between airway changes and demographic variables as well as clinical tests.Ethics and disseminationEthical approval has been obtained from the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (ZYYECK (2018) 041). The results will be disseminated through conference presentations, professional journals and peer-reviewed publications.Trial registration numberChiCTR1900021123; Pre-results.
Primary Palliative Care for Emergency Medicine (PRIM-ER): Protocol for a Pragmatic, Cluster-Randomised, Stepped Wedge Design to Test the Effectiveness of Primary Palliative Care Education, Training and Technical Support for Emergency Medicine
Authors: Grudzen Corita R , Brody Abraham A , Chung Frank R , Cuthel Allison M , Mann Devin , McQuilkin Jordan A , Rubin Ada L , Swartz Jordan , Tan Audrey , Goldfeld Keith S 
Published: July 2019

IntroductionEmergency departments (ED) care for society’s most vulnerable older adults who present with exacerbations of chronic disease at the end of life, yet the clinical paradigm focuses on treatment of acute pathologies. Palliative care interventions in the ED capture high-risk patients at a time of crisis and can dramatically improve patient-centred outcomes. This study aims to implement and evaluate Primary Palliative Care for Emergency Medicine (PRIM-ER) on ED disposition, healthcare utilisation and survival in older adults with serious illness.Methods and analysisThis is the protocol for a pragmatic, cluster-randomised stepped wedge trial to test the effectiveness of PRIM-ER in 35 EDs across the USA. The intervention includes four core components: (1) evidence-based, multidisciplinary primary palliative care education; (2) simulation-based workshops; (3) clinical decision support; and (4) audit and feedback. The study is divided into two phases: a pilot phase, to ensure feasibility in two sites, and an implementation and evaluation phase, where we implement the intervention and test the effectiveness in 33 EDs over 2 years. Using Centers for Medicare and Medicaid Services (CMS) data, we will assess the primary outcomes in approximately 300 000 patients: ED disposition to an acute care setting, healthcare utilisation in the 6 months following the ED visit and survival following the index ED visit. Analysis will also determine the site, provider and patient-level characteristics that are associated with variation in impact of PRIM-ER.Ethics and disseminationInstitutional Review Board approval was obtained at New York University School of Medicine to evaluate the CMS data. Oversight will also be provided by the National Institutes of Health, an Independent Monitoring Committee and a Clinical Informatics Advisory Board. Trial results will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03424109; Pre-results
Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC)
Authors: Rovers Koen P , Lurvink Robin J , Wassenaar Emma CE , Kootstra Thomas JM , Scholten Harm J , Tajzai Rudaba , Deenen Maarten J , Nederend Joost , Lahaye Max J , Huysentruyt Clément JR , van ’t Erve Iris , Fijneman Remond JA , Constantinides Alexander , Kranenburg Onno , Los Maartje , Thijs Anna MJ , Creemers Geert-Jan M , Burger Jacobus WA , Wiezer Marinus J , Boerma Djamila , Nienhuijs Simon W , de Hingh Ignace HJT 
Published: July 2019

IntroductionRepetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics in this setting. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy.Methods and analysisThis multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2body surface area (BSA)) with intravenous leucovorin (20 mg/m2BSA) and bolus 5-fluorouracil (400 mg/m2BSA) every 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. The primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response.Ethics and disseminationThis study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders.Trial registration numberNCT03246321, Pre-results;ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.
Barriers and facilitators experienced by patients, carers and healthcare professionals when managing symptoms in infants, children and young people at end-of-life: a mixed methods systematic review protocol
Authors: Greenfield Katie , Holley Simone , Schoth Daniel Eric , Harrop Emily , Howard Richard , Bayliss Julie , Brook Lynda , Jassal Satbir , Johnson Margaret , Wong Ian , Liossi Christina 
Published: July 2019

IntroductionThis protocol describes the objective and methods of a systematic review of barriers and facilitators experienced by patients, carers and healthcare professionals when managing symptoms in infants, children and young people (ICYP) at end-of-life.Methods and analysisThe Cochrane Library, PROSPERO, CINAHL, MEDLINE, PsycINFO, Web of Science Core Collection, ProQuest Dissertations & Theses Database, Evidence Search and OpenGrey will be electronically searched. Reference screening of relevant articles and inquiries to researchers in the field will be undertaken. Studies will be selected if they apply qualitative, quantitative or mixed-methods designs to explore barriers and facilitators experienced by patients, carers and healthcare professionals when managing symptoms in ICYP at end-of-life.Articles will be screened by title and abstract by one reviewer with a second reviewer assessing 10% of the articles. Both reviewers will read and screen all remaining potentially relevant articles. For included articles, one reviewer will extract study characteristics and one will check this.Both reviewers will undertake independent quality assessments of included studies using established and appropriate checklists including The Critical Appraisal Skills Programme Qualitative Checklist; The evaluative criteria of credibility, transferability, dependability and confirmability; The Quality Assessment Tool for Quantitative Studies, and The Mixed Methods Appraisal Tool. Data synthesis methods will be decided after data extraction and assessment.Ethics and disseminationThis review will inform our understanding of symptom management in ICYP at end-of-life. The findings will be reported in a peer-reviewed journal and presented at conferences. The study raises no ethical issues.PROSPERO registration numberCRD42019124797
123 Gemcitabine-related radiation recall as a cause of focal myositis and muscle necrosis
Authors: Byrnes Sean 
Published: July 2019

IntroductionRadiation recall is a phenomenon in which chemotherapy triggers an inflammatory response in tissue previously subjected to radiation therapy. A wide variety of agents have been implicated. Cutaneous tissue is most frequently affected but other tissue can be involved; myositis has been associated with administration of gemcitabine in particular. Incidence has been estimated at less than 6% and the pathophysiology is not understood. We present a case report from Gosford Hospital, with the additional feature of positive SRP antibodies.CaseA 74 year old female presented with a one day history of left hip pain and inability to weight bear. She had been diagnosed with metastatic squamous cell carcinoma of the lung five months earlier and underwent palliative radiotherapy to a left acetabular metastasis. 12 days prior to presentation she completed her second cycle of chemotherapy with carboplatin and gemcitabine. Pre- and post-contrast CT and MRI demonstrated necrosis in left sartorius, with foci of myositis in other muscles of the thigh, and surrounding soft tissue oedema. Symptoms improved after chemotherapy was ceased. Myositis antibody studies subsequently revealed low level positive Ku and SRP antibodies.ConclusionRadiation recall should be considered in the differential diagnosis of myositis in oncology patients. The serum of our patient contained SRP antibodies, which are associated with immune mediated necrotising myopathy. A previous case study reported gemcitabine-induced radiation recall muscle necrosis associated with dermatomyositis. These findings hint that radiation recall myositis may occur in the setting of a predisposition to immune mediated myopathy.
002 Therapeutic lag in relapsing multiple sclerosis
Authors: Roos Izanne , Frascoli Federico , Lechner-Scott Jeannette , McCombe Pamela , Macdonell Richard , Butzkueven Helmut , Malpas Charles , Kalincik Tomas 
Published: July 2019

IntroductionIn multiple sclerosis (MS), treatment start or switch is prompted disease activity, often represented by relapses. Immunomodulatory therapies have potent effects on relapse rates but the time required to attain maximal effect is unclear. We aim to develop a method that allows identification of the time to full clinically manifest effect of treatment on relapses.MethodsData from MSBase, a multinational MS registry, were used. Inclusion criteria consisted of patients with remitting relapsing MS or clinically isolated syndrome (CIS), minimum 3-year pre-treatment follow up, 1-year treatment persistence, yearly review and availability of the minimum dataset. Stratified by therapy, density curves representing relapses occurrence were created. The first local minimum of the first derivative after treatment start was identified, representing stabilisation of treatment effect. Similar method was utilised to calculate the last pre-treatment point of stabilisation. Annualised relapse rates (ARR) were compared in the pre-treatment pre stabilisation and post-treatment post stabilisation periods.Results4979 eligible patients with 6218 treatment epochs were identified for analysis. Time, in years, to treatment effect was shortest for interferon beta-1a sc (0.22, 0.19–0.22), interferon beta-1b (0.24, 0.21–0.24) and fingolimod (0.26, 0.23–0.26) and longest for dimethyl fumarate (0.54, 0.51–0.54) and glatiramer acetate (0.62, 0.60–0.62). Significant differences in pre vs post treatment ARR were present for patients on natalizumab, fingolimod and dimethyl fumarate. A sequential analysis confirmed outcome stability after approximately 1000 recorded number of events.ConclusionsWe have developed a method to objectively quantify time from commencing therapy to its full effect. Time to full effect varies among therapies.