bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol for the SMART2D adaptive implementation trial: a cluster randomised trial comparing facility-only care with integrated facility and community care to improve type 2 diabetes outcomes in Uganda, South Africa and Sweden
Authors: Guwatudde David , Absetz Pilvikki , Delobelle Peter , Östenson Claes-Göran , Olmen Van Josefien , Alvesson Helle Molsted , Mayega Roy William , Ekirapa Kiracho Elizabeth , Kiguli Juliet , Sundberg Carl Johan , Sanders David , Tomson Göran , Puoane Thandi , Peterson Stefan , Daivadanam Meena 
Published: March 2018

IntroductionType 2 diabetes (T2D) is increasingly contributing to the global burden of disease. Health systems in most parts of the world are struggling to diagnose and manage T2D, especially in low-income and middle-income countries, and among disadvantaged populations in high-income countries. The aim of this study is to determine the added benefit of community interventions onto health facility interventions, towards glycaemic control among persons with diabetes, and towards reduction in plasma glucose among persons with prediabetes.Methods and analysisAn adaptive implementation cluster randomised trial is being implemented in two rural districts in Uganda with three clusters per study arm, in an urban township in South Africa with one cluster per study arm, and in socially disadvantaged suburbs in Stockholm, Sweden with one cluster per study arm. Clusters are communities within the catchment areas of participating primary healthcare facilities. There are two study arms comprising a facility plus community interventions arm and a facility-only interventions arm. Uganda has a third arm comprising usual care. Intervention strategies focus on organisation of care, linkage between health facility and the community, and strengthening patient role in self-management, community mobilisation and a supportive environment. Among T2D participants, the primary outcome is controlled plasma glucose; whereas among prediabetes participants the primary outcome is reduction in plasma glucose.Ethics and disseminationThe study has received approval in Uganda from the Higher Degrees, Research and Ethics Committee of Makerere University School of Public Health and from the Uganda National Council for Science and Technology; in South Africa from the Biomedical Science Research Ethics Committee of the University of the Western Cape; and in Sweden from the Regional Ethical Board in Stockholm. Findings will be disseminated through peer-reviewed publications and scientific meetings.Trial registration numberISRCTN11913581; Pre-results.
Development and validation of a casemix classification to predict costs of specialist palliative care provision across inpatient hospice, hospital and community settings in the UK: a study protocol
Authors: Guo Ping , Dzingina Mendwas , Firth Alice M , Davies Joanna M , Douiri Abdel , O’Brien Suzanne M , Pinto Cathryn , Pask Sophie , Higginson Irene J , Eagar Kathy , Murtagh Fliss E M 
Published: March 2018

IntroductionProvision of palliative care is inequitable with wide variations across conditions and settings in the UK. Lack of a standard way to classify by case complexity is one of the principle obstacles to addressing this. We aim to develop and validate a casemix classification to support the prediction of costs of specialist palliative care provision.Methods and analysisPhase I: A cohort study to determine the variables and potential classes to be included in a casemix classification. Data are collected from clinicians in palliative care services across inpatient hospice, hospital and community settings on: patient demographics, potential complexity/casemix criteria and patient-level resource use. Cost predictors are derived using multivariate regression and then incorporated into a classification using classification and regression trees. Internal validation will be conducted by bootstrapping to quantify any optimism in the predictive performance (calibration and discrimination) of the developed classification. Phase II: A mixed-methods cohort study across settings for external validation of the classification developed in phase I. Patient and family caregiver data will be collected longitudinally on demographics, potential complexity/casemix criteria and patient-level resource use. This will be triangulated with data collected from clinicians on potential complexity/casemix criteria and patient-level resource use, and with qualitative interviews with patients and caregivers about care provision across difference settings. The classification will be refined on the basis of its performance in the validation data set.Ethics and disseminationThe study has been approved by the National Health Service Health Research Authority Research Ethics Committee. The results are expected to be disseminated in 2018 through papers for publication in major palliative care journals; policy briefs for clinicians, commissioning leads and policy makers; and lay summaries for patients and public.Trial registration numberISRCTN90752212.
Dementia case-finding in hospitals: a qualitative study exploring the views of healthcare professionals in English primary care and secondary care
Authors: Burn Anne-Marie , Fleming Jane , Brayne Carol , Fox Chris , Bunn Frances 
Published: March 2018

ObjectivesIn 2012–2013, the English National Health Service mandated hospitals to conduct systematic case-finding of people with dementia among older people with unplanned admissions. The method was not defined. The aim of this study was to understand current approaches to dementia case-finding in acute hospitals in England and explore the views of healthcare professionals on perceived benefits and challenges.DesignQualitative study involving interviews, focus groups and thematic content analysis.SettingPrimary care and secondary care across six counties in the East of England.ParticipantsHospital staff involved in dementia case-finding and primary care staff in the catchment areas of those hospitals.ResultsWe recruited 23 hospital staff and 36 primary care staff, including 30 general practitioners (GPs). Analysis resulted in three themes: (1) lack of consistent approaches in case-finding processes, (2) barriers between primary care and secondary care which impact on case-finding outcomes and (3) perceptions of rationale, aims and impacts of case-finding. The study shows that there were variations in how well hospitals recorded and reported outcomes to GPs. Barriers between primary care and secondary care, including GPs’ lack of access to hospital investigations and lack of clarity about roles and responsibilities, impacted case-finding outcomes. Staff in secondary care were more positive about the initiative than primary care staff, and there were conflicting priorities for primary care and secondary care regarding case-finding.ConclusionsThe study suggests a more evidence-based approach was needed to justify approaches to dementia case-finding. Information communicated to primary care from hospitals needs to be comprehensive, appropriate and consistent before GPs can effectively plan further investigation, treatment or care. Follow-up in primary care further requires access to options for postdiagnostic support. There is a need to evaluate the outcomes for patients and the economic impact on health and care services across settings.
Anaesthesia workload measurement devices: qualitative systematic review
Authors: Almghairbi Dalal S , Marufu Takawira C , Moppett Iain K 
Published: March 2018

BackgroundManagement of mental workload is a key aspect of safety in anaesthesia but there is no gold-standard tool to assess mental workload, risking confusion in clinical and research use of such tools.ObjectiveThis review assessed currently used mental workload assessment tools.MethodsA systematic literature search was performed on the following electronic databases; Cochrane, EMBASE, MEDLINE, SCOPUS and Web of Science. Screening and data extraction were performed individually by two authors. We included primary published papers focusing on mental workload assessment tools in anaesthesia.ResultsA total of 2331 studies were screened by title, 32 by full text and 24 studies met the inclusion criteria. Six mental workload measurement tools were observed across included studies. Reliability for the Borg rating scales and Vibrotactile device was reported in two individual studies. The rest of the studies did not record reliability of the tool measurements used. Borg rating scales, NASA-TLX and task-oriented mental work load measurements are subjective, easily available, readily accessible and takes a few minutes to complete. However, the vibrotactile and eye-tracking methods are objective, require more technical involvement, considerable time for the investigator and moderately expensive, impacting their potential use.ConclusionWe found that the measurement of mental workload in anaesthesia is an emerging field supporting patient and anaesthetist safety. The self-reported measures have the best evidence base.
Phosphorylated Hsp27 is mutually exclusive with ATRX loss and the IDH1R132Hmutation and may predict better prognosis among glioblastomas without the IDH1 mutation and ATRX loss
Authors: Cai Hong-Qing , Wang Peng-Fei , Zhang Hai-Peng , Cheng Zhi-Jian , Li Shou-Wei , He Jie , Zhang Yu , Hao Jia-Jie , Wang Ming-Rong , Yan Chang-Xiang , Wan Jing-Hai 
Published: March 2018

AimTo identify biomarkers for accurate classification of glioma.Patients and methodsWe evaluated the heat shock protein 27 (Hsp27), phosphorylated Hsp27 (p-Hsp27), ATRX and IDH1R132Hproteins using immunohistochemistry in 421 glioma tissues. The χ2test was used to assess the relationship between molecular alterations and clinico-pathological parameters. Kaplan-Meier survival curves were constructed, and differences were detected by the log-rank test.ResultsWe found that Hsp27 and p-Hsp27 were mainly expressed in aggressive astrocytic gliomas. However, neither Hsp27 nor p-Hsp27 expression was related to survival time for any grade of glioma. Interestingly, p-Hsp27 was mutually exclusive with ATRX loss (ATRX−) and the IDH1R132Hmutation, except for one case of anaplastic astrocytoma. We classified glioblastomas (GBMs) into three subtypes: ATRX−/IDH1R132H, high p-Hsp27 expression (p-Hsp27+) and none of these three markers. ATRX-/IDH1R132Hshowed the longest median survival (19.6 months). The prognostic difference between p-Hsp27+and none of these three markers was significant (15.0 vs 13.1 months, P=0.045). Moreover, p-Hsp27+predicted better sensitivity for standard therapy among GBMs without the IDH1 mutation and ATRX loss (26.3 vs 15.5 months, P=0.008).Conclusionp-Hsp27 is a novel biomarker of glioma and might have important clinical value for further classification of patients with wild-type IDH1 and normal ATRX expression, for evaluating prognosis and for guidance for adjuvant therapy.
Clinical characteristics and patient-reported outcomes in patients with inadequately controlled rheumatoid arthritis despite ongoing treatment
Authors: Taylor Peter C , Alten Rieke , Gomez-Reino Juan J , Caporali Roberto , Bertin Philippe , Sullivan Emma , Wood Robert , Piercy James , Vasilescu Radu , Spurden Dean , Alvir Jose , Tarallo Miriam 
Published: March 2018

BackgroundDespite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA.MethodsData were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy ≥3 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 ≤3.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests.ResultsOf 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort.ConclusionRA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients.
Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons
Authors: Amarillo Yimy , Tissone Angela I. , Mato Germán , Nadal Marcela S. 
Published: March 2018

Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current IKir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of IKir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of IKir and hyperpolarization-activated cationic current Ih that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that IKir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with Ih and increases the robustness of low threshold-activated calcium current IT-mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current IKir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that IKir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current Ih; and increases the robustness of oscillations mediated by the low threshold-activated calcium current IT. Upregulation of IKir in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).
Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma
Authors: Dettling Steffen , Stamova Slava , Warta Rolf , Schnölzer Martina , Rapp Carmen , Rathinasamy Anchana , Reuss David , Pocha Kolja , Roesch Saskia , Jungk Christine , Warnken Uwe , Eckstein Volker , Grabe Niels , Schramm Christoph , Weigand Markus A. , von Deimling Andreas , Unterberg Andreas , Beckhove Philipp , Herold-Mende Christel 
Published: March 2018

Abstract
Purpose: Successful immunotherapies for IDHmut gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous T-cell responses using an unbiased proteomic approach.
Experimental Design: Protein fractionations of tissue lysates from IDHmut gliomas (n = 4) were performed. Fractions were tested by IFNγ ELISpot assay for recognition through patients' T cells. Proteins of immunogenic fractions were identified by mass spectrometry and validated by in silico-predicted synthetic long peptides in patients of origin, additional IDHmut glioma patients (n = 16), and healthy donors (n = 13). mRNA and protein expression of immunogenic antigens was analyzed in tumor tissues and IDHmut glioma stem-like cells (GSC). HLA-A*02–restricted T-cell epitopes were functionally determined by short peptides and numbers of antigen-specific T cells by HLA-peptide tetramer analysis.
Results: A total of 2,897 proteins were identified in immunogenic tumor fractions. Based on a thorough filter process, 79 proteins were selected as potential T-cell antigens. Twenty-six of these were recognized by the patients’ T cells, and five of them (CRKII, CFL1, CNTN1, NME2, and TKT) in up to 56% unrelated IDHmut glioma patients. Most immunogenic tumor-associated antigens (TAA) were expressed in IDHmut gliomas and GSCs, while being almost absent in normal brain tissues. Finally, we identified HLA-A*02–restricted epitopes for CRKII, NME2, and TKT that were recognized by up to 2.82% of antigen-specific peripheral cytotoxic T cells in IDHmut glioma patients.
Conclusions: By analyzing the repertoire of T-cell target antigens in IDHmut glioma patients, we identified five novel immunogenic TAAs and confirmed their expression on IDHmut tumors and GSCs. Clin Cancer Res; 24(12); 2951–62. ©2018 AACR.
Hypereosinophilic syndrome preceding a diagnosis of B-cell lymphoma
Authors: Samarghandi Arash , Ahuja Shradha , Jindal Vishal , Gupta Sorab , Fulger Ilmana 
Published: March 2018

Introduction: Hypereosinophilic syndrome (HES) is a rare condition characterized by eosinophilia and organ destruction secondary to eosinophilic infiltration. The coexistence of primary B-cell lymphoma and hypereosinophilic syndrome is extremely rare. We present a case of HES that preceded the diagnosis of diffuse large B-cell lymphoma. Case report: A 70-year-old man presented with a 3-month history of diarrhea and 30-pound weight loss. Complete blood count showed a white blood cell count of 7452/µL with eosinophils of 42% (absolute eosinophil count 3130). Colonoscopy showed eosinophilic infiltrate in the lamina propria and muscularis mucosa. Bone marrow biopsy showed elevated myeloid: erythroid ratio (6:1), increased mature and immature eosinophilic infiltration (10% of nucleated cells). Molecular studies were negative for Fip1-like1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) translocation and PDGFRB and FGFR mutations, indicating nonclonal eosinophilia. Treatment was initiated with prednisone (1 mg/kg) and hydroxyurea 500 mg twice daily. He responded with complete resolution of symptoms. Five months later, the patient presented with right lower quadrant pain. Abdominal/pelvis computed tomography (CT) showed bulky right inguinal lymphadenopathy and biopsy revealed CD10+ diffuse large B-cell lymphoma (DLBCL). Further staging workup showed the stage to be IIB. He received 6 cycles of chemotherapy and involved field radiation therapy. He achieved complete remission. Conclusion: Reviewing the literature indicates only one case of similar presentation with concomitant HES and DLBCL. Eosinophilia is routinely encountered in clinical practice and as such physicians must be aware of the rarer, more malevolent underlying associations of this condition so as to aid early diagnosis and prompt treatment.
Oral Health–Related Quality of Life of Children Born With Orofacial Clefts in Ethiopia and Their Parents
Authors: Abebe Mekonen Eshete , Deressa Wakgari , Oladugba Victoria , Owais Arwa , Hailu Taye , Abate Fikre , Hailu Abiye , Demissie Yohannes , Degu Shiferaw , Alemayehu Bezuwork , Gessesse Mulualem , Deribew Milliard , Gravem Paul Egl , Mossey Peter , Butali Azeez 
Published: March 2018

Objective: To assess the oral health–related quality of life (OH-RQoL) using a translated standardized measure in an understudied population of Ethiopian children born with orofacial clefts (OFCs) and their parents. Methods: Using a descriptive study design, we assessed the OH-RQoL of 41 patients with OFCs between the ages of 8 and 17 years and their parents. Participants received multidisciplinary cleft care from 2008 to 2016. They completed an Amharic translation of the Child Oral Health Impact Profile (COHIP). Results: There was strong internal reliability with the translated COHIP for parents and patients. Parents’ COHIP scores ranged from 67 to 186, and patients’ scores were 78 to 190. The mean for patients and parents was 155, indicating good OH-RQoL. Conclusion: The Amharic translation of the COHIP appears appropriate for use with families in Ethiopia. Both parents and patients reported OH-RQoL at similar levels as other international populations.
Elevated Body Mass Index Is Not a Risk Factor for Adverse Outcomes Following Ventricular Assist Device Implantation
Authors: Hullmann Jonathan E. , Mather Paul J. 
Published: March 2018

Background: Despite ventricular assist devices (VADs) becoming more common in heart failure (HF) treatment, it is still uncertain which patients are more prone to complications. One potential risk factor is increased body mass index (BMI), which is known to increase both all-cause mortality and mortality from ischemic heart disease; however, the role of the BMI in predicting morbidity and mortality following device implantation is unclear. Methods: The study population for this single-institution retrospective chart review consisted of 136 patients with HF, who underwent VAD implantation between 2004 and 2015. Patients were divided into 2 groups based on their BMI: a nonobese group (18.5 < BMI < 30.0; n = 82) or an obese group (BMI >30.0; n = 54). These groups were compared at baseline and after implantation for survival, hospital readmission, and adverse events. Results: No significant difference was found in initial hospital length of stay, number or length of readmissions, or readmission diagnosis. At 1 year, rates of ongoing device support, orthotopic heart transplant (OHT), and death were not significantly different between groups ( P = .89, P = .90, and P = .70, respectively). Multivariate analysis did not identify obesity as an independent predictor of mortality ( P = .90); only biventricular assist device implantation was associated with decreased survival (hazard ratio [HR] = 5.90, P = .002). Conclusion: Obesity in itself should not preclude the use of VAD support in patients with HF, as carefully selected obese patients were shown to have similar rates of hospital readmission, 1-year outcomes, and survival following device implantation compared to nonobese patients.