bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant rituximab, a potential treatment for the young patient with Graves’ hyperthyroidism (RiGD): study protocol for a single-arm, single-stage, phase II trial
Authors: Cole Michael , Hynes Ann Marie , Howel Denise , Hall Lesley , Abinun Mario , Allahabadia Amit , Barrett Timothy , Boelaert Kristien , Drake Amanda J , Dimitri Paul , Kirk Jeremy , Zammitt Nicola , Pearce Simon , Cheetham Tim 
Published: January 2019

IntroductionGraves’ disease (Graves’ hyperthyroidism) is a challenging condition for the young person and their family. The excess thyroid hormone generated by autoimmune stimulation of the thyroid stimulating hormone receptor on the thyroid gland can have a profound impact on well-being. Managing the young person with Graves’ hyperthyroidism is more difficult than in older people because the side effects of conventional treatment are more significant in this age group and because the disease tends not to resolve spontaneously in the short to medium term. New immunomodulatory agents are available and the anti-B cell monoclonal antibody rituximab is of particular interest because it targets cells that manufacture the antibodies that stimulate the thyroid gland in Graves’.Methods and analysisThe trial aims to establish whether the combination of a single dose of rituximab (500 mg) and a 12-month course of antithyroid drug (usually carbimazole) can result in a meaningful increase in the proportion of patients in remission at 2 years, the primary endpoint. A single-stage, phase II A’Hern design is used. 27 patients aged 12–20 years with newly presenting Graves’ hyperthyroidism will be recruited. Markers of immune function, including lymphocyte numbers and antibody levels (total and specific), will be collected regularly throughout the trial.DiscussionThe trial will determine whether the immunomodulatory medication, rituximab, will facilitate remission above and beyond that observed with antithyroid drug alone. A meaningful increase in the expected proportion of young patients entering remission when managed according to the trial protocol will justify consideration of a phase III trial.Ethics and dissemination The trial has received a favourable ethical opinion (North East - Tyne and Wear South Research Ethics Committee, reference 16/NE/0253, EudraCT number 2016-000209-35). The results of this trial will be distributed at international endocrine meetings, in the peer-reviewed literature and via patient support groups.Trial registration numberISRCTN20381716.
Developing an intervention to increase REferral and uptake TO pulmonary REhabilitation in primary care in patients with chronic obstructive pulmonary disease (the REsTORE study): mixed methods study protocol
Authors: Early Frances , Wilson Patricia , Deaton Christi , Wellwood Ian , Dickerson Terry , Ward James , Jongepier Lianne , Barlow Ruth , Singh Sally J , Benson John , Brimicombe James , Kim Lois , Haque Hena , Fuld Jonathan 
Published: January 2019

IntroductionChronic obstructive pulmonary disease (COPD) is a progressive lung disease associated with breathlessness, inability to exercise, frequent infections, hospitalisation and reduced quality of life. Pulmonary rehabilitation (PR), providing supervised exercise and education, is an effective and cost-effective treatment for COPD but is significantly underused. Interventions to improve referral and uptake have been tested and some positive results reported. However, interventions are diverse and no clear recommendations for practice can be made. This study aims to understand the challenges to referral and uptake in primary care, where most referrals originate, and to develop a flexible toolkit of resources to support referral and uptake to PR in primary care in the UK.Methods and analysisThis is a mixed methods study informed by normalisation process theory and burden of treatment theory. In the first phase, general practitioners, practice nurses and PR providers will be invited to complete an online survey to inform a broad exploration of the topic areas. In phase 2 interviews and focus groups will be conducted with patients, healthcare professionals (HCP) in primary care, PR providers and commissioners to gain an in-depth understanding of the issues and needs. Toolkit development in phase 3 will draw together the learning from phases 1 and 2 and employ an iterative development process to build the toolkit jointly with patients and HCPs. It will be tested in primary care for usability and acceptability.Ethics and disseminationThe study has ethical and Health Research Authority approval (Research Ethics Committee reference number 17/EE/0136). It is registered with the International Standard Registered Clinical/Social Study Number (ISRCTN) registry (trial ID:ISRCTN20669629, assignment date 20 March 2018, trial start date 1 April 2016). Dissemination will be aimed at patients, carers/families, service providers, commissioners and national interest groups. Methods will include conferences, presentations, academic publications and plain English reports and will be supported by the British Lung Foundation.Trial registration numberISRCTN20669629; Pre-results.
Impact of palliative home care support on the quality and costs of care at the end of life: a population-level matched cohort study
Authors: Maetens Arno , Beernaert Kim , De Schreye Robrecht , Faes Kristof , Annemans Lieven , Pardon Koen , Deliens Luc , Cohen Joachim 
Published: January 2019

ObjectivesTo evaluate the impact of palliative home care support on the quality of care and costs in the last 14 days of life.DesignMatched cohort study using linked administrative databases.SettingAll people who died in Belgium in 2012 (n=107 847).Participants8837 people who received palliative home care support in the last 720 to 15 days of life matched 1:1 by propensity score to 8837 people who received usual care.InterventionReceiving the allowance for palliative home patients, multidisciplinary palliative home care team visit or palliative nurse or physiotherapist visit at home.Main outcome measuresHome death, number of family physician contacts, number of primary caregiver contacts, hospital death, hospital admission, intensive care unit (ICU) admission, emergency department (ED) admission, diagnostic testing, blood transfusion and surgery. Total inpatient and outpatient costs. All outcomes were measured in the last 14 days of life.ResultsIn the unmatched cohort, 11 149 (13.5%) people received palliative home care support in the last 720 to 15 days of life. After matching, those using palliative home care support had, compared with those who did not, more family physician contacts (mean 3.1 [SD=6.5] vs 0.8 [SD=1.2]), more chance of home death (56.2%vs13.8%; relative risk [RR]=4.08, 95% CI 3.86 to 4.31), lower risk of hospital admission (27.4%vs60.8%; RR=0.45, 95% CI 0.43 to 0.46), ICU admission (18.3%vs40.4%; RR=0.45, 95% CI 0.43 to 0.48) or ED admission (15.2%vs28.1%; RR=0.54, 95% CI 0.51 to 0.57). Mean total costs of care were lower for those using palliative home care support (€3081 [95% CI €3025 to €3136] vs €4698 [95% CI €4610 to €4787]; incremental cost: −€1617 [p<0.001]).ConclusionsPalliative home care support use positively impacts quality of care and reduces total costs of care at the end of life in Belgium. Policy makers and healthcare practitioners should increasingly focus on communicating the existing options for palliative home care support to patients and their caregivers.
Transgender persons’ HIV care (dis)engagement: a qualitative evidence synthesis protocol from an ecological systems theory perspective
Authors: Canoy Nico , Thapa Subash , Hannes Karin 
Published: January 2019

IntroductionThere seems to be little information on interactional patterns of enabling and constraining factors contributing to HIV care engagement across systems and across time. Understanding these patterns from a (micro–meso–macro–exo) systems perspective can provide rich insights on relevant social networks affecting transgender populations. In this review, we will synthesise the wealth of literature on transgender persons’ engagement in the HIV care continuum.Methods and analysisWe will perform a networked systems approach to qualitative evidence synthesis of relevant qualitative research data generated from primary qualitative, mixed-method and evaluation studies exploring HIV care engagement among diverse transgender populations. Studies not using qualitative methods and studies not published in English will be excluded from this review. Empirical studies will be identified via a search in major databases such as PubMed, Scopus, ERIC, Embase, Web of Science, Sociological Abstracts, PsychInfo and Social Services Abstract in January 2019. Two reviewers will independently screen the studies for inclusion, assess their quality and extract data. In case some of the system levels in the network are ill-covered by empirical studies, non-empirical studies will be considered for inclusion. The qualitative evidence synthesis includes a summary of descriptive data (first order), an exploration of relationships between system levels or their components (second order) and a structured summary of research evidence through narrative synthesis. The narrative synthesis will be extended with an overall social network analysis that visualises important nodes and links cutting across ecological systems.Ethics and disseminationEthical approval is not required to conduct this review. Review findings will be disseminated via peer-reviewed academic journals and a targeted information campaign towards organisations that work with our population of interest.PROSPERO registration numberCRD42018089956.
The effect of ketorolac on posterior thoracolumbar spinal fusions: a prospective double-blinded randomised placebo-controlled trial protocol
Authors: Claus Chad F , Lytle Evan , Tong Doris , Sigler Diana , Lago Dominick , Bahoura Matthew , Dosanjh Amarpal , Lawless Michael , Slavnic Dejan , Kelkar Prashant , Houseman Clifford , Bono Peter , Richards Boyd , Soo Teck M 
Published: January 2019

IntroductionKetorolac has been shown to provide quality postoperative pain control and decrease opioid requirement with minimal side effects following spinal surgery. However, the literature addressing its use in spinal fusions is highly variable in both its effectiveness and complications, such as pseudarthrosis. Recent literature postulates that ketorolac may not affect fusion rates and large randomised controlled trials are needed to demonstrate ketorolac as a safe and effective adjuvant treatment to opioids for postoperative pain control.Methods and analysisThis is a multihospital, prospective, double-blinded, randomised placebo-controlled trial. Data concerning fusion rates, postoperative opioid use, pain scores, length of stay will be recorded with the aim of demonstrating that the use of ketorolac does not decrease thoracolumbar spinal fusion rates while identifying possible adverse events related to short-term minimal effective dose compared with placebo. Additionally, this investigation aims to demonstrate a decrease in postoperative opioid use demonstrated by a decrease in morphine equivalence while showing equivalent postoperative pain control and decrease the average length of stay.Ethics and disseminationEthical approval was obtained at all participating hospitals by the institutional review board. The results of this study will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03278691.
Two-peaked increase of serum myosin heavy chain-α after triathlon suggests heart muscle cell death
Authors: Danielsson Tom , Schreyer Hendrik , Woksepp Hanna , Johansson Therese , Bergman Patrick , Månsson Alf , Carlsson Jörg 
Published: January 2019

ObjectiveIt has been suggested that the mechanism behind cardiac troponin elevation after strenuous exercise is passage through a cell membrane with changed permeability rather than myocardial cell death. We hypothesised that an increase of cardiac specific myosin heavy chain-alpha (MHC-α; 224 kDa compared with cardiac troponin T’s (cTnT) 37 kDa) could hardly be explained by passage through a cell membrane.MethodsBlood samples were collected from 56 athletes (15 female, age 42.5±9.7, range 24–70 years) before, directly after and on days 1–8 after an Ironman. Biomarkers (C reactive protein (CRP), cTnT, creatine kinase (CK), MHC-α, myoglobin (MG), creatinine (C) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were measured.ResultsThe course of MHC-α concentration (µg/L) was 1.33±0.53 (before), 2.57±0.78 (directly after), 1.51±0.53 (day 1), 2.74±0.55 (day 4) and 1.83±0.76 (day 6). Other biomarkers showed a one-peaked increase with maximal values either directly after the race or at day 1: cTnT 76 ± 80 ng/L (12–440; reference<15), NT-proBNP 776±684 ng/L (92–4700; ref.<300), CK 68±55 µkat/L (5–280; ref.<1.9), MG 2088±2350 µg/L (130–17 000; ref.<72) and creatinine 100±20 µmol/L (74–161; ref.<100), CRP 49±23 mg/L (15–119; ref.<5).ConclusionMHC-α exhibited a two-peaked increase which could represent a first release from the cytosolic pool and later from cell necrosis. This is the first investigation of MHC-α plasma concentration after exercise.
Simple and powerful: a consultant and governance-led bereavement service
Authors: Grimes Caris E , Stringer Belinda , Roberts-Jones Linda 
Published: January 2019

BackgroundFollowing bereavement, families can be left with unanswered questions or issues of concern. We piloted a bereavement service model which was consultant and governance-led with the aim to reduce complaints, reduce litigation, reduce coroners' inquests and support families.MethodsFollowing the death of a patient, the next of kin was sent an invitation. Those that responded were offered a 1-hour appointment with a consultant, senior sister and a member of the governance team. Notes were taken to track themes and feedback sheets were introduced to gauge the usefulness of the service to families.ResultsOf 121 invitations sent out, 18 families (14.8%) used the service. Two families had already sought legal advice. Neither acted further. 44% said they would have made a complaint if the service had not been available. 78% stated that they had obtained closure.ConclusionA bereavement service model which is consultant and governance led may reduce complaints and reduce litigation.
Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibres on intestinal inflammation
Authors: Singh Vishal , Yeoh Beng San , Walker Rachel E , Xiao Xia , Saha Piu , Golonka Rachel M , Cai Jingwei , Bretin Alexis Charles Andre , Cheng Xi , Liu Qing , Flythe Michael D , Chassaing Benoit , Shearer Gregory C , Patterson Andrew D , Gewirtz Andrew T , Vijay-Kumar Matam 
Published: January 2019

ObjectiveDiets rich in fermentable fibres provide an array of health benefits; however, many patients with IBD report poor tolerance to fermentable fibre-rich foods. Intervention studies with dietary fibres in murine models of colonic inflammation have yielded conflicting results on whether fibres ameliorate or exacerbate IBD. Herein, we examined how replacing the insoluble fibre, cellulose, with the fermentable fibres, inulin or pectin, impacted murine colitis resulting from immune dysregulation via inhibition of interleukin (IL)-10 signalling and/or innate immune deficiency (Tlr5KO).DesignMice were fed with diet containing either cellulose, inulin or pectin and subjected to weekly injections of an IL-10 receptor (αIL-10R) neutralising antibody. Colitis development was examined by serological, biochemical, histological and immunological parameters.ResultsInulin potentiated the severity of αIL10R-induced colitis, while pectin ameliorated the disease. Such exacerbation of colitis following inulin feeding was associated with enrichment of butyrate-producing bacteria and elevated levels of caecal butyrate. Blockade of butyrate production by either metronidazole or hops β-acids ameliorated colitis severity in inulin-fed mice, whereas augmenting caecal butyrate via tributyrin increased colitis severity in cellulose containing diet-fed mice. Elevated butyrate levels were associated with increased IL-1β activity, while inhibition of the NOD-like receptor protein 3 by genetic, pharmacologic or dietary means markedly reduced colitis.ConclusionThese results not only support the notion that fermentable fibres have the potential to ameliorate colitis but also caution that, in some contexts, prebiotic fibres can lead to gut dysbiosis and surfeit colonic butyrate that might exacerbate IBD.
Neuroform Atlas Stent System for the treatment of intracranial aneurysm: primary results of the Atlas Humanitarian Device Exemption cohort
Authors: Jankowitz Brian T , Hanel Ricardo , Jadhav Ashutosh P , Loy David N , Frei Donald , Siddiqui Adnan H , Puri Ajit S , Khaldi Ahmad , Turk Aquilla S , Malek Adel M , Sauvageau Eric , Hetts Steven W , Zaidat Osama O 
Published: January 2019

Background and objectiveStent-assisted coil embolization is a well-established treatment of intracranial wide-necked aneurysms. The Neuroform Atlas Stent System is a new generation microstent designed to enhance coil support, conformability, deliverability, and improve deployment accuracy. We present the 1-year efficacy and angiographic results of the Humanitarian Device Exemption (HDE) cohort from the Atlas Investigational Device Exemption (IDE) clinical trial.MethodThe Atlas IDE trial is a prospective, multicenter, single-arm, open-label study of unruptured wide-necked intracranial aneurysms treated with the Neuroform Atlas stent and approved coils. The primary efficacy endpoint was the rate of 12-month complete aneurysm angiographic occlusion (Raymond class I) without target aneurysm retreatment or significant parent artery stenosis (>50%) at the target location. The primary safety endpoint was the rate of major ipsilateral stroke or neurological death within 12 months. Imaging core laboratory and Clinical EventsCommittee adjudicated the primary endpoints.Results30 patients were enrolled at eight US centers, with 27 patients completing the 12-month angiographic follow-up. The mean age was 59.4±11.8 years and 24/30 patients (80%) were women. The mean aneurysm size was 5.3±1.7 mm and the dome:neck ratio was 1.1±0.2. Procedural technical success of Neuroform Atlas Stent deployment was 100%. 27 patients completed 12-month angiographic follow-up and 30 patients completed their 6-month follow-up. When applying the last observation carried forward method, the primary efficacy endpoint was observed in 26/30 patients (86.7%, 95% CI 69.3% to 96.2%) compared with 25/27 patients (92.6%, 95% CI 75.7% to 99.1%) who completed the 12-month angiographic follow-up. The primary safety endpoint of stroke occurred in one patient (3.3%), who made a complete clinical recovery at discharge. There were no neurological deaths.ConclusionThe Neuroform Atlas stent in conjunction with coils demonstrated a high rate of complete aneurysm occlusion at 12-month angiographic follow-up, with an improved safety profile in the HDE cohort.Clinical trial.gov registration numberNCT0234058;Results
Significance of simulated conventional images on dual energy CT after endovascular treatment for ischemic stroke
Authors: Ebashi Ryo , Ogata Atsushi , Nishihara Masashi , Inoue Kohei , Yoshioka Fumitaka , Takase Yukinori , Masuoka Jun , Yakushiji Yusuke , Irie Hiroyuki , Hara Hideo , Abe Tatsuya 
Published: January 2019

Background and purposeCT scans often reveal post-interventional cerebral hyperdensities (PCHDs) immediately after intra-arterial thrombectomy (IAT) for ischemic stroke. Dual energy CT (DE-CT) can indicate whether PCHDs are caused by hemorrhage or iodinated contrast. Hyperdense lesions, detected on DE-CT with the use of iodinated contrast, could be associated with delayed hemorrhagic transformation and poor outcome. However, the quantitative indicators in DE-CT for predicting delayed hemorrhagic transformation remain unclear. We assessed such indicators for predicting delayed hemorrhagic transformation.Material and methodsWe retrospectively analyzed 52 consecutive acute ischemic stroke patients who underwent IAT. Simulated conventional CT (sCCT) images were obtained immediately after a DE-CT scan. Virtual, unenhanced, non-contrast (VNC) imaging was performed after reconstruction. Hounsfield units (HU) of the infarct areas observed on the sCCT were measured. The association of HU on sCCT with hemorrhage on VNC and delayed parenchymal hemorrhage (PH) was evaluated.ResultsThe HU of sCCT with hemorrhage on VNC was significantly higher than without it (377.9±385 HU vs 83.5±37.9 HU; P<0.0001). The cut-off index was 80 HU, which displayed 100% sensitivity, 63.8% specificity, 22.3% positive predictive value, and 100% negative predictive value (P=0.0001, area under the curve (AUC)=0.89). The HU with delayed PH was substantially higher than without it (250.8±382.2 HU vs 93.7±64.8 HU; P=0.01). The cut-off index was 78 HU, which showed 100% sensitivity, 61% specificity, 25% positive predictive value, and 100% negative predictive value (P=0.049, AUC=0.76).ConclusionsCCT images on DE-CT are useful for excluding intracerebral hemorrhage and delayed PH.
Statistical ranking of electromechanical dyssynchrony parameters for CRT
Authors: Cazeau Serge , Toulemont Matthieu , Ritter Philippe , Reygner Julien 
Published: January 2019

ObjectiveMechanical evaluation of dyssynchrony by echocardiography has not replaced ECG in routine cardiac resynchronisation therapy (CRT) evaluation because of its complexity and lack of reproducibility. The objective of this study was to evaluate the potential correlations between electromechanical parameters (atrioventricular, interventricular and intraventricular from the dyssynchrony model presented in 2000), their ability to describe dyssynchrony and their potential use in resynchrony.Methods455 sets of the 18 parameters of the model obtained in 91 patients submitted to various pacing configurations were evaluated two by two using a Pearson correlation test and then by groups according to their ability to describe dyssynchrony, using the Column selection method of machine learning.ResultsThe best parameter is duration of septal contraction, which alone describes 25% of dyssynchrony. The best groups of 3, 4 and ≥8 variables describe 59%, 73% and almost 100% of dyssynchrony, respectively. Left pre-ejection interval is highly and significantly correlated to a maximum of other variables, and its decrease is associated with the favourable evolution of all other correlated parameters. Increase in filling duration and decrease in duration of septum to lateral wall contraction difference are not associated with the favourable evolution of other parameters.ConclusionsNo single electromechanical parameter alone can fully describe dyssynchrony. The 18-parameter model can be simplified, but still requires at least 4–8 parameters. Decrease in left pre-ejection interval favourably drives resynchrony in a maximum of other parameters. Increase in filling duration and decrease in septum–lateral wall difference do not appear to be good CRT targets.