bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of point-of-care C reactive protein in ambulatory care: a systematic review and meta-analysis
Authors: Verbakel Jan Y , Lee Joseph J , Goyder Clare , Tan Pui San , Ananthakumar Thanusha , Turner Philip J , Hayward Gail , Van den Bruel Ann 
Published: February 2019

ObjectiveThe aim of this review was to collate all available evidence on the impact of point-of-care C reactive protein (CRP) testing on patient-relevant outcomes in children and adults in ambulatory care.DesignThis was a systematic review to identify controlled studies assessing the impact of point-of-care CRP in patients presenting to ambulatory care services. Ovid Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, DARE, Science Citation Index were searched from inception to March 2017.Eligibility criteria for selecting studiesControlled studies assessing the impact of point-of-care CRP in patients presenting to ambulatory care services, measuring a change in clinical care, including but not limited to antibiotic prescribing rate, reconsultation, clinical recovery, patient satisfaction, referral and additional tests. No language restrictions were applied.Data extractionData were extracted on setting, date of study, a description of the intervention and control group, patient characteristics and results. Methodological quality of selected studies and assessment of potential bias was assessed independently by two authors using the Cochrane Risk of Bias tool.Results11 randomised controlled trials and 8 non-randomised controlled studies met the inclusion criteria, reporting on 16 064 patients. All included studies had a high risk of performance and selection bias. Compared with usual care, point-of-care CRP reduces immediate antibiotic prescribing (pooled risk ratio 0.81; 95% CI 0.71 to 0.92), however, at considerable heterogeneity (I2=72%). This effect increased when guidance on antibiotic prescribing relative to the CRP level was provided (risk ratios of 0.68; 95% CI 0.63 to 0.74 in adults and 0.56; 95% CI 0.33 to 0.95 in children). We found no significant effect of point-of-care CRP testing on patient satisfaction, clinical recovery, reconsultation, further testing and hospital admission.ConclusionsPerforming a point-of-care CRP test in ambulatory care accompanied by clinical guidance on interpretation reduces the immediate antibiotic prescribing in both adults and children. As yet, available evidence does not suggest an effect on other patient outcomes or healthcare processes.PROSPERO registration numberCRD42016035426; Results.
Systematic scoping review protocol for clinical prediction rules (CPRs) in the management of patients with spinal cord injuries
Authors: Boggenpoel Blake , Madasa Vuyolwethu , Jeftha Tarryn , Joseph Conran 
Published: February 2019

IntroductionThe upsurge in the use of clinical prediction models in general medical practice is a result of evidence-based practice. However, the total number of clinical prediction rules (CPRs) currently being used or undergoing impact analysis in the management of patients who have sustained spinal cord injuries (SCIs) is unknown. This scoping review protocol will describe the current CPRs being used and highlight their possible strengths and weaknesses in SCI management.Methods and analysisArksey and O’Malley’s scoping review framework will be used. The following databases will be searched to identify relevant literature relating to the use of CPRs in the management of patients who have sustained an SCI: PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), ScienceDirect, EBSCOhost, Medline, OvidMedline and Google Scholar. Grey literature as well as reference lists of included studies will be searched. All studies relating to the use of CPRs in the management of patients with SCIs will be included. Literature searches and data extraction will be performed independently by two groups of reviewers.Ethics and disseminationEthical clearance is not required for this scoping review study since only secondary data sources will be used. The findings of this review will be disseminated by means of peer-reviewed publication and conference proceedings. The final paper will be submitted for publication. Results of this review will also be presented at relevant conferences and disseminated to important stakeholders such as practicing physicians within specialised spinal care facilities within South Africa.
Online tool for monitoring adverse events in patients with cancer during treatment (eRAPID): field testing in a clinical setting
Authors: Warrington Lorraine , Absolom Kate , Holch Patricia , Gibson Andrea , Clayton Beverly , Velikova Galina 
Published: February 2019

ObjectivesElectronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is an online system developed to support patient care during cancer treatment by improving the detection and management of treatment-related symptoms. Patients can complete symptom reports from home and receive severity-based self-management advice, including notifications to contact the hospital for severe symptoms. Patient data are available in electronic records for staff to review. Prior to the commencement of a randomised controlled trial (RCT), field testing of the intervention was undertaken to troubleshoot practical issues with intervention integration in clinical practice.DesignObservational clinical field testing.SettingMedical oncology breast service in a UK cancer centre.Participants12 patients receiving chemotherapy for early breast cancer and 10 health professionals (oncologists and specialist nurses).InterventionPatients were asked to use the eRAPID intervention and complete weekly online symptom reports during four cycles of chemotherapy. Clinical staff were invited to access and use patient data in clinical assessments.AnalysisDescriptive data on the frequency of online symptom report completion and severe symptom notifications were collated. Verbal and written feedback was collected from patients and staff and semistructured interviews were conducted to explore patient experiences. Interviews were transcribed and analysed thematically.ResultsThe testing ran from January 2014 to March 2014. Feedback from patients and staff was largely positive. Patients described eRAPID as ‘reassuring’ and ‘comforting’ and valued the tailored management advice. Several changes were made to refine eRAPID. In particular, improvement of the clinical notification, patient reminder systems and changes to patient and staff training.ConclusionsThe field testing generated valuable results used to guide refinement of eRAPID prior to formal intervention evaluation. Feedback indicated that eRAPID has the potential to improve patients’ self-efficacy, knowledge and confidence with managing symptoms during treatment. A large-scale RCT is underway with data collection due to finish in October 2018.
Assisted ventilation in motor neurone disease during inpatient palliative care: barriers and utilisation
Authors: Gleeson Aoife , Johnson Faye 
Published: February 2019

ObjectivesAn increasing number of patients with motor neuron disease (MND) in the UK and Ireland use assisted ventilation, and a small proportion of these use long-term tracheostomy ventilation (TV).1 2 NICE guidelines recommend that patients with MND should routinely receive specialist palliative care input.3 The aim was to establish the extent to which hospices and specialist palliative care units (SPCUs) in the UK and Ireland currently manage patients with MND using assisted ventilation especially TV and to identify any associated barriers.MethodsA 25-item questionnaire was developed in Survey Monkey. A link to the questionnaire was emailed to every medical director (n=185) of inpatient hospices/SPCUs in the UK and Ireland.ResultsThe response rate was 42.4% (n=78). 97.4% of units admit patients with MND on non-invasive ventilation (NIV), but only 28.2% admit those using TV. 80.8% of units have adequate expertise in the management of NIV, compared with 7.7% for managing TV. 35.9% and 2.6% of units have a policy for managing patients using NIV and TV, respectively. 14.1% respondents had been involved in the care of patients with MND using TV, in the specialist palliative care setting in the last 5 years.ConclusionsA minority of UK and Irish hospices/SPUs provide support to TV MND patients and few units currently have management or admission policies for this cohort of patients. Respondents indicated a lack of appropriate expertise and experience. Further exploration of these barriers is required to establish how to optimise care for TV MND patients in this setting.
Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohn’s disease: the LIR!C Trial
Authors: de Groof E Joline , Stevens Toer W , Eshuis Emma J , Gardenbroek Tjibbe J , Bosmans Judith E , van Dongen JM , Mol Bregje , Buskens Christianne J , Stokkers Pieter C F , Hart Ailsa , D’Haens Geert R , Bemelman Willem A , Ponsioen Cyriel Y 
Published: February 2019

ObjectiveEvaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn’s disease failing conventional therapy.DesignA multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn’s disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty.ResultsIn total, 143 patients were randomised. Mean Crohn’s disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference €−8931; 95% CI €−12 087 to €−5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference €−5729, 95% CI €−10 606 to €172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of €20 000/QALY gained and 0.99 at a WTP of €500/point of improvement in IBDQ Score.ConclusionLaparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab.Clinical trial registration numberDutch Trial Registry NTR1150; EudraCT number 2007-005042-20 (closed on 14 October 2015).
RSPO2 gene rearrangement: a powerful driver of β-catenin activation in liver tumours
Authors: Longerich Thomas , Endris Volker , Neumann Olaf , Rempel Eugen , Kirchner Martina , Abadi Zahra , Uhrig Sebastian , Kriegsmann Mark , Weiss Karl Heinz , Breuhahn Kai , Mehrabi Arianeb , Weber Tim Frederik , Wilkens Ludwig , Straub Beate K , Rosenwald Andreas , Schulze Falko , Brors Benedikt , Froehling Stefan , Pellegrino Rossella , Budczies Jan , Schirmacher Peter , Stenzinger Albrecht 
Published: February 2019

ObjectiveWe aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC).DesignLarge cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational status of the CTNNB1 gene was determined in ß-catenin-activated HCA (b-HCA) and HCC with at least moderate nuclear CTNNB1 accumulation. Ultra-deep sequencing was used to characterise CTNNB1wild-type and ß-catenin-activated HCA and HCC. Expression profiling of HCA subtypes was performed.ResultsA roof plate-specific spondin 2 (RSPO2) gene rearrangement resulting from a 46.4 kb microdeletion on chromosome 8q23.1 was detected as a new morphomolecular driver of β-catenin-activated HCA. RSPO2 fusion positive HCA displayed upregulation of RSPO2 protein, nuclear accumulation of β-catenin and transcriptional activation of β-catenin-target genes indicating activation of Wingless-Type MMTV Integration Site Family (WNT) signalling. Architectural and cytological atypia as well as interstitial invasion indicated malignant transformation in one of the RSPO2 rearranged b-HCAs. The RSPO2 gene rearrangement was also observed in three β-catenin-activated HCCs developing in context of chronic liver disease. Mutations of the human telomerase reverse transcriptase promoter—known to drive malignant transformation of CTNNB1-mutated HCA—seem to be dispensable for RSPO2 rearranged HCA and HCC.ConclusionThe RSPO2 gene rearrangement leads to oncogenic activation of the WNT signalling pathway in HCA and HCC, represents an alternative mechanism for the development of b-HCA and may drive malignant transformation without additional TERT promoter mutation.
Socioeconomic inequality in drug reimbursement during end-of-life care: a nationwide study
Authors: Daugaard Cecilie , Neergaard Mette Asbjoern , Vestergaard Anne Høy Seeman , Nielsen Mette Kjærgaard , Johnsen Søren Paaske 
Published: February 2019

BackgroundIn Denmark, patients who are terminally ill have the right to drug reimbursement due to terminal illness (DRTI). DRTI, a proxy marker of planned end-of-life care, is intended to be equally accessible regardless of socioeconomic position. This study examined social and socioeconomic differences in DRTI among Danish patients who are terminally ill.MethodsThis cross-sectional study based on individual-level nationwide data included all patients dying from cancer, dementia, ischaemic heart disease, chronic obstructive pulmonary disease, chronic liver disease, congestive heart failure, diabetes or stroke in 2006–2015 (n=307 188). We analysed associations between social and socioeconomic position (education, income, cohabiting status, migrant status and employment) and DRTI. Prevalence ratios (PR) and 95% CIs were estimated using log-linear models adjusted for age, gender, comorbidity, cause of death and residence.ResultsOverall, 27.9% of patients received DRTI (n=85 616). A substantial difference in likelihood of receiving DRTI was observed among patients with a social and socioeconomic profile associated with the highest versus lowest probability of DRTI (adjusted PR 1.44, 95% CI 1.18 to 1.75). The probability of DRTI was higher among patients with high income compared with low income (adjusted PR 1.22, 95% CI 1.17 to 1.26). Also, living with a partner and being immigrant or descendant of such were associated with higher probability of DRTI compared with living alone and of Danish origin, whereas employment was associated with lower probability of DRTI compared with retirement.ConclusionSocial and socioeconomic position was associated with the likelihood of receiving DRTI, which indicates that planned end-of-life care is not equally accessible in Denmark.
H2AFY promoter deletion causes PITX1 endoactivation and Liebenberg syndrome
Authors: Kragesteen Bjørt K , Brancati Francesco , Digilio Maria Cristina , Mundlos Stefan , Spielmann Malte 
Published: February 2019

BackgroundStructural variants (SVs) affecting non-coding cis-regulatory elements are a common cause of congenital limb malformation. Yet, the functional interpretation of these non-coding variants remains challenging. The human Liebenberg syndrome is characterised by a partial transformation of the arms into legs and has been shown to be caused by SVs at the PITX1 locus leading to its misregulation in the forelimb by its native enhancer element Pen. This study aims to elucidate the genetic cause of an unsolved family with a mild form of Liebenberg syndrome and investigate the role of promoters in long-range gene regulation.MethodsHere, we identify SVs by whole genome sequencing (WGS) and use CRISPR-Cas9 genome editing in transgenic mice to assign pathogenicity to the SVs.ResultsIn this study, we used WGS in a family with three mildly affected individuals with Liebenberg syndrome and identified the smallest deletion described so far including the first non-coding exon of H2AFY. To functionally characterise the variant, we re-engineered the 8.5 kb deletion using CRISPR-Cas9 technology in the mouse and showed that the promoter of the housekeeping gene H2afy insulates the Pen enhancer from Pitx1 in forelimbs; its loss leads to misexpression of Pitx1 by the pan-limb activity of the Pen enhancer causing Liebenberg syndrome.ConclusionOur data indicate that housekeeping promoters may titrate promiscuous enhancer activity to ensure normal morphogenesis. The deletion of the H2AFY promoter as a cause of Liebenberg syndrome highlights this new mutational mechanism and its role in congenital disease.
Systematic review of prehospital haemostatic dressings
Authors: Welch Matthew , Barratt J , Peters A , Wright C 
Published: February 2019

IntroductionHaemorrhage is one of the leading causes of battlefield and prehospital death. Haemostatic dressings are an effective method of limiting the extent of bleeding and are used by military forces extensively. A systematic review was conducted with the aim of collating the evidence on current haemostatic products and to assess whether one product was more effective than others.MethodsA systematic search and assessment of the literature was conducted using 13 health research databases including MEDLINE and CINAHL, and a grey literature search. Two assessors independently screened the studies for eligibility and quality. English language studies using current-generation haemostatic dressings were included. Surgical studies, studies that did not include survival, initial haemostasis or rebleeding and those investigating products without prehospital potential were excluded.Results232 studies were initially found and, after applying exclusion criteria, 42 were included in the review. These studies included 31 animal studies and 11 clinical studies. The outcomes assessed were subject survival, initial haemostasis and rebleeding. A number of products were shown to be effective in stopping haemorrhage, with Celox, QuikClot Combat Gauze and HemCon being the most commonly used, and with no demonstrable difference in effectiveness.ConclusionsThere was a lack of high-quality clinical evidence with the majority of studies being conducted using a swine haemorrhage model. Iterations of three haemostatic dressings, Celox, HemCon and QuikClot, dominated the studies, probably because of their use by international military forces and all were shown to be effective in the arrest of haemorrhage.
20 Armoured Infantry Brigade downgrade study: epidemiology of principal conditions and plugging leaks in the rehabilitation pipeline
Authors: Papworth James , Osborne L , Shimmings M A , Roberts C C S 
Published: February 2019

IntroductionIn April 2017, 22% of Army Full-time Trade Trained Strength was downgraded, reducing fully deployable strength to 60 546, against a target of 82 000. In June 2017, Commander 20 Armoured Infantry Brigade (20 AI Bde) initiated a study to look at the principal conditions causing medical downgrading, as a stepping stone to finding ways of reducing injury, enhancing rehabilitation and improving deployability.MethodThe Defence Medical Information Capability Programme medical records for every downgraded soldier in 20 AI Bde and supporting units were scrutinised to identify their Medical Deployment Standard and the primary condition causing downgrading.ResultsA total of 842 downgraded soldiers were identified from a held strength of 3827 personnel. Sixty-five per cent of these downgrades were due to musculoskeletal injury (MSKI). Of this 65%, the majority were due to knee (31%), spine (28%) and foot/ankle (23%). Of the remaining 35%, the majority were due to noise-induced hearing loss (NIHL) (22%), adjustment disorders (19%) and non-freezing cold injury (NFCI) (13%).Several factors that slowed an individual’s recovery pathway were identified. They mainly relate to soldiers being lost to follow-up through lack of active case management.ConclusionsMSKI is responsible for most downgraded personnel at Brigade level. The distribution of principal conditions is similar to previous studies looking at recruits and individual units.The creation of a rehabilitation troop, delivering active case management, can reduce the number of soldiers leaking out of the rehabilitation pipeline.
Using machine learning to optimize selection of elderly patients for endovascular thrombectomy
Authors: Alawieh Ali , Zaraket Fadi , Alawieh Mohamed Baker , Chatterjee Arindam Rano , Spiotta Alejandro 
Published: February 2019

BackgroundEndovascular thrombectomy (ET) is the standard of care for treatment of acute ischemic stroke (AIS) secondary to large vessel occlusion. The elderly population has been under-represented in clinical trials on ET, and recent studies have reported higher morbidity and mortality in elderly patients than in their younger counterparts.ObjectiveTo use machine learning algorithms to develop a clinical decision support tool that can be used to select elderly patients for ET.MethodsWe used a retrospectively identified cohort of 110 patients undergoing ET for AIS at our institution to train a regression tree model that can predict 90-day modified Rankin Scale (mRS) scores. The identified algorithm, termed SPOT, was compared with other decision trees and regression models, and then validated using a prospective cohort of 36 patients.ResultsWhen predicting rates of functional independence at 90 days, SPOT showed a sensitivity of 89.36% and a specificity of 89.66% with an area under the receiver operating characteristic curve of 0.952. Performance of SPOT was significantly better than results obtained using National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT score, or patients’ baseline deficits. The negative predictive value for SPOT was >95%, and in patients who were SPOT-negative, we observed higher rates of symptomatic intracerebral hemorrhage after thrombectomy. With mRS scores prediction, the mean absolute error for SPOT was 0.82.ConclusionsSPOT is designed to aid clinical decision of whether to undergo ET in elderly patients. Our data show that SPOT is a useful tool to determine which patients to exclude from ET, and has been implemented in an online calculator for public use.