bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing hyperglycaemia post-kidney and liver transplant: a quality improvement initiative
Authors: Clemens Kristin K , Brahmania Mayur , Weernink Corrine , Lofty Khaled , Rjoob Hani , Berberich Amanda , Gob Alan 
Published: May 2022

BackgroundIn-hospital glycaemic management can reduce post-transplant morbidity, but is not always part of transplant care.ObjectiveWe aimed to reduce the mean number of postoperative days in hyperglycaemia (≥2 blood glucose >12 mmol/L in 24 hours) in kidney and liver transplant recipients by 30%. We also aimed to reduce the mean number of days between transplant admission to endocrine consult by 2.0 days.Design, setting, participantsWe conducted a quality improvement project in liver and kidney transplant recipients admitted to an academic transplant unit in Canada between 1 March 2019 and 1 May 2021.InterventionWe developed a bedside algorithm to monitor post-transplant capillary blood glucose; the algorithm also included thresholds for nursing-initiated inpatient endocrinology consultation.Main outcome and measuresWe examined outcome (postoperative days in hyperglycaemia, days to inpatient endocrine consultation), process (nursing documentation of postoperative blood sugars) and balancing measures (nursing workload, postoperative days in hypoglycaemia) following implementation of our algorithm. We used Plan-Do-See-Act cycles to study three iterations of our algorithm, and used box plots to present outcomes before and after algorithm implementation.ResultsIn the pre-intervention period, 21 transplant recipients spent a mean of 4.1 (SD 2.4) postoperative days in hyperglycaemia before endocrine consultation. The mean number of days between hospital admission to endocrine consult was 10.7 (SD 13.0) days.In the post-intervention period, we observed a 62% reduction in postoperative days in hyperglycaemia. The mean number of days between admission and endocrine consult was reduced by 6.3 days (59% reduction).ConclusionsImplementation of a simple, bedside algorithm for postoperative glucose monitoring and detection of hyperglycaemia in transplant patients, reduced the mean number of postoperative days in hyperglycaemia and time to inpatient endocrine consultation. Our algorithm continues to be used in our academic transplant unit.
Diagnosis and management of asthma in children
Authors: Martin Joanne , Townshend Jennifer , Brodlie Malcolm 
Published: May 2022

Asthma is the the most common chronic respiratory condition of childhood worldwide, with around 14% of children and young people affected. Despite the high prevalence, paediatric asthma outcomes are inadequate, and there are several avoidable deaths each year. Characteristic asthma features include wheeze, shortness of breath and cough, which are typically triggered by a number of possible stimuli. There are several diagnostic challenges, and as a result, both overdiagnosis and underdiagnosis of paediatric asthma remain problematic.Effective asthma management involves a holistic approach addressing both pharmacological and non-pharmacological management, as well as education and self-management aspects. Working in partnership with children and families is key in promoting good outcomes. Education on how to take treatment effectively, trigger avoidance, modifiable risk factors and actions to take during acute attacks via personalised asthma action plans is essential.This review aimed to provide an overview of good clinical practice in the diagnosis and management of paediatric asthma. We discuss the current diagnostic challenges and predictors of life-threatening attacks. Additionally, we outline the similarities and differences in global paediatric asthma guidelines and highlight potential future developments in care. It is hoped that this review will be useful for healthcare providers working in a range of child health settings.
Mortality before and after reconfiguration of the Danish hospital-based emergency healthcare system: a nationwide interrupted time series analysis
Authors: Flojstrup Marianne , Bogh Søren Bie Bie , Bech Mickael , Henriksen Daniel Pilsgaard , Johnsen Søren Paaske , Brabrand Mikkel 
Published: May 2022

ObjectivesThe study aimed to investigate how the ‘natural experiment’ of reconfiguring the emergency healthcare system in Denmark affected in-hospital and 30-day mortality on a national level. The reconfiguration included the centralisation of hospitals and the establishment of emergency departments with specialists present around the clock.DesignHospital-based cohort study.SettingAll public hospitals in Denmark.ParticipantsPatients with an unplanned contact from 1 January 2007 until 31 December 2016.InterventionsStepped-wedge reconfiguration of the Danish emergency healthcare system.Main outcome measuresWe determined the adjusted ORs for in-hospital mortality and HRs for 30-day mortality using logistic and Cox regression analysis adjusted for sex, age, Charlson Comorbidity Index, income, education, mandatory referral and the changes in the out of hours system in the Capital Region. The main outcomes were stratified by the time of arrival. We performed subgroup analyses on selected diagnoses: myocardial infarction, stroke, pneumonia, aortic aneurysm, bowel perforation, hip fracture and major trauma.ResultsWe included 11 367 655 unplanned hospital contacts. The adjusted OR for overall in-hospital mortality after reconfiguration of the emergency healthcare system was 0.998 (95% CI 0.968 to 1.010; p=0.285), and the adjusted OR for 30-day mortality was 1.004 (95% CI 1.000 to 1.008; p=0.045)). Subgroup analyses showed some possible benefits of the reconfiguration such as a reduction in-hospital and 30-day mortality for myocardial infarction, stroke, aortic aneurysm and major trauma.ConclusionsThe Danish emergency care reconfiguration programme was not associated with an improvement in overall in-hospital mortality trends and was associated with a slight slowing of prior improvements in 30-day mortality trends.
Frailty assessment for COVID-19 follow-up: a prospective cohort study
Authors: Müller Ilena , Mancinetti Marco , Renner Anja , Bridevaux Pierre-Olivier , Brutsche Martin H , Clarenbach Christian , Garzoni Christian , Lenoir Alexandra , Naccini Bruno , Ott Sebastian , Piquilloud Lise , Prella Maura , Que Yok-Ai , Soccal Paola Marina , von Garnier Christophe , Geiser Thomas K , Funke-Chambour Manuela , Guler Sabina 
Published: May 2022

BackgroundThe Clinical Frailty Scale (CFS) is increasingly used for clinical decision making in acute care but little is known about frailty after COVID-19.ObjectivesTo investigate frailty and the CFS for post-COVID-19 follow-up.MethodsThis prospective multicentre cohort study included COVID-19 survivors aged ≥50 years presenting for a follow-up visit ≥3 months after the acute illness. Nine centres retrospectively collected pre-COVID-19 CFS and prospectively CFS at follow-up. Three centres completed the Frailty Index (FI), the short physical performance battery (SPPB), 30 s sit-to-stand test and handgrip strength measurements. Mixed effect logistic regression models accounting for repeated measurements and potential confounders were used to investigate factors associated with post-COVID-19 CFS. Criterion and construct validity were determined by correlating the CFS to other concurrently assessed frailty measurements and measures of respiratory impairment, respectively.ResultsOf the 288 participants 65% were men, mean (SD) age was 65.1 (9) years. Median (IQR) CFS at follow-up was 3 (2–3), 21% were vulnerable or frail (CFS ≥4). The CFS was responsive to change, correlated with the FI (r=0.69, p<0.001), the SPPB score (r=−0.48, p<0.001) (criterion validity) and with the St George’s Respiratory Questionnaire score (r=0.59, p<0.001), forced vital capacity %-predicted (r=−0.25, p<0.001), 6 min walk distance (r=−0.39, p<0.001) and modified Medical Research Council (mMRC) (r=0.59, p<0.001). Dyspnoea was significantly associated with a higher odds for vulnerability/frailty (per one mMRC adjusted OR 2.01 (95% CI 1.13 to 3.58), p=0.02).ConclusionsThe CFS significantly increases with COVID-19, and dyspnoea is an important risk factor for post-COVID-19 frailty and should be addressed thoroughly.
Dyspnoea at the end of life: instrument development and validation-the CONFORTO Strategy
Authors: Teixeira Isadora Crosara Alves , Carvas Ana Maria Porto , Silva Ricardo Borges da , Borges Eliza , Corrêa-Faria Patrícia , Rabahi Marcelo Fouad 
Published: May 2022

ObjectiveTo describe the construction and validation of the algorithm forCriteria for inclusion;Objective of dyspnoea;Notification of patient/family/health professionals;Facial air flow;Oxygen;Relaxion and breathing;Treating causes of dyspnoea andOpioid (CONFORTO), an instrument to guide health professionals in managing dyspnoea in patients with an advance stage of the disease at the end-of-life.MethodsThe study was carried out in three stages: (1) literature review and construction of CONFORTO; (2) semantic validation; (3) application of the CONFORTO Strategy to health professionals as a test (before video lessons) and post-test (20 days after watching video lessons) methodology. The scores obtained in the pretest and post-test were compared using the Wilcoxon test.ResultsSeventy-four professionals from different internal medicine and intensive care units participated in the study. The CONFORTO Strategy involved eight acronym-forming items:Criteria for inclusion;Objective of dyspnoea;Notification of patient/family/health professionals;Facial air flow;Oxygen;Relaxion and breathing;Treating causes of dyspnoea andOpioid. The post-test indicated a significant increase in the score for the following items: facial air flow (p=0.016); oxygen (p=0.002); relaxation and breathing (p=0.002) and treating the causes of dyspnoea (p=0.011). The increase in score occurred after the training sessions with video lessons.ConclusionThe CONFORTO Strategy proved valid and reliable for managing dyspnoea in patients with an advanced stage of the disease at the end-of-life. Because the instrument is easy-to-use, it can be used by the entire health team at any assistance-providing location, and can, thus, contribute to improving dyspnoea management for these patients.
UK Palliative trainees Research Collaborative (UK-PRC): the first 5 years – 0–100 study sites
Authors: Wakefield Donna , Etkind Simon Noah , Bemand-Qureshi Lucy , Sutherland Anna , Koffman Jonathan , Dewhurst Felicity , Noble Simon , Chamberlain Charlotte 
Published: May 2022

ObjectivesPalliative care research suffers from underfunding and a workforce spread across multiple settings leading to a lack of large-scale studies. To facilitate multisite research and audit we set up the UK Palliative trainees Research Collaborative (UKPRC), the first national trainee-led audit and research collaborative in palliative care. Here, we critically review the progress and potential of the UKPRC since its inception in 2016, identifying key challenges and facilitators. Members of the UKPRC steering committee collaborated to write this reflection, reviewing existing evidence regarding trainee-led research collaboratives.FindingsThe UKPRC has representation from 16/19 UK training regions. Projects are run by a core team; local collaborators collect data at each site. The collaborative is supported by academic leads and newly qualified consultants to develop a culture of continuous improvement in practice. We have conducted four national projects to date, including an audit covering 119 sites. Facilitators for our work include a focus on inclusivity and national representation; support from recently qualified consultants to ensure continuity; and taking a pragmatic approach, focusing initially on straightforward projects to build momentum. Challenges include the step from national audit to multisite, patient-facing research and maintaining continuity in a membership with high turnover.ConclusionsThere is potential to change practice through large scale data collection via the trainee-led collaborative model. Collaboration is especially important in a small specialty with limited resources. The UKPRC has demonstrated ‘proof of concept’ and has the potential to support and sustain a culture where research can flourish within palliative care.
745 Thunderclap headache syndrome presenting to the emergency department: an international multicentre observational cohort study
Authors: Roberts Tom , Horner Daniel , Chu Kevin , Than Martin , Kelly Anne-Maree , Investigators HEADStudy 
Published: May 2022

BackgroundAcute headache is a common reason for presentation to emergency departments. Some have significant structural pathology requiring further intervention. Emergency clinicians often rely on presenting headache features (such as thunderclap onset) to guide the need for neuroimaging and further investigation. It is unclear whether these features discriminate accurately or how the investigations of patients presenting with thunderclap headache differs internationally.ObjectivesTo determine the proportion of patients presenting with thunderclap onset of headache from a general headache cohort and compare demographics, investigation strategy and final diagnosis, across an international sample of patients.MethodsAn international, multicentre, observational prospective cohort study. This planned sub-study focussed on patients presenting with thunderclap onset headache, with characteristics compared to the general headache cohort. The prospective observational design was chosen to capture real-world data on current international practice.ResultsThe study recruited 4536 patients across 67 hospitals and 10 countries during 2019. Of this, 644 patients presented with thunderclap headache onset (14.2%). Median age was 44. The majority of patients self-referred to hospital. CT brain imaging was performed in 62.7% cases and lumbar puncture in 10.6%, with wide international variation. New Zealand reported the highest rate of neuroimaging, 78.4% of patients presenting with thunderclap headache, compared to 25.0% in Romania. All cases of subarachnoid haemorrhage (SAH) were diagnosed on CT imaging results.When compared with the parent cohort of all headache patients presenting to the ED, those with thunderclap headache had a significantly higher rate of serious cranial pathology (13.7% vs 8.5%, p<0.001) and final diagnosis of SAH (3.6% vs 0.8% p<0.001).ConclusionsThunderclap headache presenting to the ED appears to correlate with a higher risk for serious intracranial pathology and/or SAH. Investigation strategies varied within this international cohort. Neuroimaging rates did not align with international guidelines, suggesting potential for further work on standardisation.
Faecal occult blood loss accurately predicts future detection of colorectal cancer. A prognostic model
Authors: Meester Reinier G S , van de Schootbrugge-Vandermeer Hilliene J , Breekveldt Emilie C H , de Jonge Lucie , Toes-Zoutendijk Esther , Kooyker Arthur , Nieboer Daan , Ramakers Christian R , Spaander Manon C W , van Vuuren Anneke J , Kuipers Ernst J , van Kemenade Folkert J , Nagtegaal Iris D , Dekker Evelien , van Leerdam Monique E , Lansdorp-Vogelaar Iris 
Published: May 2022

ObjectivesTo examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC).DesignPrognostic model.SettingDutch biennial FIT-based screening programme during 2014–2018.Participants265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 µg Hb/g faeces) in rounds 1 and 2.InterventionsColonoscopy follow-up in participants with a positive FIT (F-Hb ≥47 µg Hb/g faeces).Main outcomesWe evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5–1.0), the degree of risk stratification and C-statistics in external validation.ResultsAmong study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept −0.008 to −0.099; slope 0.982–0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91).ConclusionParticipants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information.
Development of a LAG-3 immunohistochemistry assay for melanoma
Authors: Johnson Lori , McCune Bryan , Locke Darren , Hedvat Cyrus , Wojcik John B , Schroyer Caitlin , Yan Jim , Johnson Krystal , Sanders-Cliette Angela , Samala Sujana , Dillon Lloye M , Anderson Steven , Shuster Jeffrey 
Published: May 2022

AimsA robust immunohistochemistry (IHC) assay was developed to detect lymphocyte-activation gene 3 (LAG-3) expression by immune cells (ICs) in tumour tissues. LAG-3 is an immuno-oncology target with demonstrable clinical benefit, and there is a need for a standardised, well-characterised assay to measure its expression. This study aims to describe LAG-3 scoring criteria and present the specificity, sensitivity, analytical precision and reproducibility of this assay.MethodsThe specificity of the assay was investigated by antigen competition and withLAG3knockout cell lines. A melanin pigment removal procedure was implemented to prevent melanin interference in IHC interpretation. Formalin-fixed paraffin-embedded (FFPE) human melanoma samples with a range of LAG-3 expression levels were used to assess the sensitivity and analytical precision of the assay with a ≥1% cut-off to determine LAG-3 positivity. Interobserver and intraobserver reproducibility were evaluated with 60 samples in intralaboratory studies and 70 samples in interlaboratory studies.ResultsThe LAG-3 IHC method demonstrated performance suitable for analysis of LAG-3 IC expression in clinical melanoma samples. The pretreatment step effectively removed melanin pigment that could interfere with interpretation. LAG-3 antigen competition and analysis ofLAG3knockout cell lines indicated that the 17B4 antibody clone binds specifically to LAG-3. The intrarun repeatability, interday, interinstrument, interoperator and inter-reagent lot reproducibility demonstrated a high scoring concordance (>95%). The interobserver and intraobserver reproducibility and overall interlaboratory and intralaboratory reproducibility also showed high scoring concordance (>90%).ConclusionsWe have demonstrated that the assay reliably assesses LAG-3 expression in FFPE human melanoma samples by IHC.
Soluble HLA peptidome of pleural effusions is a valuable source for tumor antigens
Authors: Khazan-Kost Sofia , Cafri Gal , Melamed Kadosh Dganit , Mooshayef Navit , Chatterji Sumit , Dominissini Dan , Manor Sigal , Zisser Bracha , Broday Limor , Talalai Efrosiniia , Shemer Anat , Zadok Oranit , Ofek Efrat , Onn Amir , Admon Arie , Peled Michael 
Published: May 2022

BackgroundSoluble human leucocyte antigen (sHLA) molecules, released into the plasma, carry their original peptide cargo and provide insight into the protein synthesis and degradation schemes of their source cells and tissues. Other body fluids, such as pleural effusions, may also contain sHLA-peptide complexes, and can potentially serve as a source of tumor antigens since these fluids are drained from the tumor microenvironment. We explored this possibility by developing a methodology for purifying and analyzing large pleural effusion sHLA class I peptidomes of patients with malignancies or benign diseases.MethodsCleared pleural fluids, cell pellets present in the pleural effusions, and the primary tumor cells cultured from cancer patients’ effusions, were used for immunoaffinity purification of the HLA molecules. The recovered HLA peptides were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and the resulting LC-MS/MS data were analyzed with the MaxQuant software tool. Selected tumor antigen peptides were tested for their immunogenicity potential with donor peripheral blood mononuclear cells (PBMCs) in an in vitro assay.ResultsMass spectrometry analysis of the pleural effusions revealed 39,669 peptides attributable to 11,305 source proteins. The majority of peptides identified from the pleural effusions were defined as HLA ligands that fit the patients’ HLA consensus sequence motifs. The membranal and soluble HLA peptidomes of each individual patient correlated to each other. Additionally, soluble HLA peptidomes from the same patient, obtained at different visits to the clinic, were highly similar. Compared with benign effusions, the soluble HLA peptidomes of malignant pleural effusions were larger and included HLA peptides derived from known tumor-associated antigens, including cancer/testis antigens, lung-related proteins, and vascular endothelial growth factor pathway proteins. Selected tumor-associated antigens that were identified by the immunopeptidomics were able to successfully prime CD8+ T cells.ConclusionsPleural effusions contain sHLA-peptide complexes, and the pleural effusion HLA peptidome of patients with malignant tumors can serve as a rich source of biomarkers for tumor diagnosis and potential candidates for personalized immunotherapy.