bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid hormone receptor function in maturing ovine cardiomyocytes
Authors: Chattergoon Natasha N. , Louey Samantha , Scanlan Thomas , Lindgren Isa , Giraud George D. , Thornburg Kent L. 
Published: February 2019

Key points
Plasma thyroid hormone (tri‐iodo‐l‐thyronine; T3) concentrations rise near the end of gestation and is known to inhibit proliferation and stimulate maturation of cardiomyocytes before birth.
Thyroid hormone receptors are required for the action of thyroid hormone in fetal cardiomyocytes. Loss of thyroid hormone receptor (TR)α1 abolishes T3 signalling via extracellular signal‐related kinase and Akt in fetal cardiomyocytes.
The expression of TRα1 and TRβ1 in ovine fetal myocardium increases with age, although TRα1 levels always remain higher than those of TRβ1.
Near term fetal cardiac myocytes are more sensitive than younger myocytes to thyroid receptor blockade by antagonist, NH3, and to the effects of TRα1/α2 short interfering RNA.
Although T3 is known to abrogate ovine cardiomyocyte proliferation stimulated by insulin‐like growth factor 1, this effect is mediated via the genomic action of thyroid hormone receptors, with little evidence for non‐genomic mechanisms.
AbstractWe have previously shown that the late‐term rise in tri‐iodo‐l‐thyronine (T3) in fetal sheep leads to the inhibition of proliferation and promotion of maturation in cardiomyocytes. The present study was designed to determine whether these T3‐induced changes are mediated via thyroid hormone receptors (TRs) or by non‐genomic mechanisms. Fetal cardiomyocytes were isolated from 102 ± 3 and 135 ± 1 days of gestational age (dGA) sheep (n = 7 per age; term ∼145 dGA). Cells were treated with T3 (1.5 nm), insulin‐like growth factor (IGF)‐1 (1 μg mL–1) or a combination in the presence of TR antagonist NH3 (100 nm) or following short interfering RNA (siRNA) knockdown of TRα1/α2. Proliferation was quantified by 5‐bromo‐2′‐deoxyuridine (BrdU) uptake (10 μm). Western blots measured protein levels of extracellular signal‐related kinase (ERK), Akt, TRα1/β1 and p21. Age specific levels of TRα1/β1 were measured in normal hearts from fetuses [95 dGA (n = 8), 135 dGA (n = 7)], neonates (n = 8) and adult ewes (n = 7). TRα1 protein levels were consistently >50% more than TRβ1 at each gestational age (P < 0.05). T3 reduced IGF‐1 stimulated proliferation by ∼50% in 100 dGA and by ∼75% in 135 dGA cardiomyocytes (P < 0.05). NH3 blocked the T3 + IGF‐1 reduction of BrdU uptake without altering the phosphorylation of ERK or Akt at both ages. NH3 did not suppress T3‐induced p21 expression in 100 dGA cardiomyocytes in 135 dGA cardiomyocytes, NH3 alone reduced BrdU uptake (−28%, P < 0.05), as well as T3‐induced p21 (−75%, P < 0.05). In both ages, siRNA knockdown of TRα1/α2 blocked the T3 + IGF‐1 reduction of BrdU uptake and dramatically reduced ERK and Akt signalling in 135 dGA cardiomyocytes. In conclusion, TRs are required for normal proliferation and T3 signalling in fetal ovine cardiomyocytes, with the sensitivity to TR blockade being age‐dependent.
Moderately severe and severe acute pancreatitis : a systematic review of the outcomes in the USA and European Union-5
Authors: Sarri Grammati , Guo Yelan , Iheanacho Ike , Puelles Jorge 
Published: February 2019

Background and objectivesThe global incidence of hospitalisation due to acute pancreatitis (AP) has been rising in the recent decades. In the USA alone, there was a 13.2% increase between 2009 and 2012 compared with 2002–2005. There remains a lack of approved treatments to prevent disease progression, leaving many liable to developing complications that include multisystem organ failure (OF) and death. This therapeutic deficit raises questions about the scale of the current burden of illness (BOI) associated with severe forms of AP. The aim of the systematic literature review (SLR) was to assess clinical, humanistic, and economic outcomes associated with moderately severe AP (MSAP) and severe AP (SAP) in the USA and the European Union-5 (EU-5).MethodsSystematic searches were conducted in MEDLINE and Embase to identify studies published in English (between 2007 and 2017) that reported on the BOI of MSAP and/or SAP. Manual searches of ‘grey’ literature sources were also conducted.ResultsThe SLR identified 19 studies which indicated that 15%–20% of patients with AP progress to more severe forms of the disease, up to 10.5% of those with SAP require surgery for complications, and up to 40% die during hospitalisation. By contrast, there appears to be a lack of data on the extent to which SAP affects patients’ quality of life.ConclusionThe available evidence clearly demonstrates that the current management for MSAP and SAP in the USA and EU-5 does not adequately meet patients’ needs. Early identification and intervention for AP is crucial, given the evidence of high rates of morbidity and an associated economic burden that is considerable. Since many patients with the condition present to hospitals at a point when multisystem OF or death is highly likely, there is a particularly urgent need for effective treatment options to prevent disease progression.
Can differences in length of stay between Dutch university hospitals and other hospitals be explained by patient characteristics? A cross-sectional study
Authors: Ghielen Janine , Cihangir Sezgin , Hekkert Karin , Borghans Ine , Kool Rudolf Bertijn 
Published: February 2019

ObjectivesThe indicator unexpectedly long length of stay (UL-LOS) is used to gain insight into quality and safety of care in hospitals. The calculation of UL-LOS takes patients’ age, main diagnosis and main procedure into account. University hospitals have relatively more patients with a UL-LOS than other hospitals. Our main research question is whether the high number of patients with a UL-LOS in university hospitals is caused by differences in additional patient characteristics between university hospitals and other hospitals.DesignWe performed a cross-sectional study and used administrative data from 1 510 627 clinical admissions in 87 Dutch hospitals. Patients who died in hospital, stayed in hospital for 100 days or longer or whose country of residence was not the Netherlands were excluded from the UL-LOS indicator. We identified which patient groups were treated only in university hospitals or only in other hospitals and which were treated in both hospital types. For these last patient groups, we added supplementary patient characteristics to the current model to determine the effect on the UL-LOS model.ResultsPatient groups treated in both hospital types differed in terms of detailed primary diagnosis, socioeconomic status, source of admission, type of admission and amount of Charlson comorbidities. Nevertheless, when adding these characteristics to the current model, university hospitals still have a significantly higher mean UL-LOS score compared with other hospitals (p<0.001).ConclusionsThe difference in UL-LOS scores between both hospital types remains after adding patient characteristics in which both hospital types differ. We conclude that the high UL-LOS scores in university hospitals are not caused by the investigated additional patient characteristics that differ between university and other hospitals. Patients might stay relatively longer in university hospitals due to differences in work processes because of their education and research tasks or financing differences of both hospital types.
Cohort profile: the Danish Future Occupation of Children and Adolescents cohort (the FOCA cohort): education, work-life, health and living conditions in a life-course perspective
Authors: Lindholdt Louise , Lund Thomas , Andersen Johan Hviid , Hansen Claus D , Labriola Merete 
Published: February 2019

PurposeThe Future Occupation of Children and Adolescents cohort (the FOCA cohort) is a large population-based cohort study that was established as a resource for research in order to study adolescence factors and future educational and vocational trajectories in a life-course perspective. The cohort covers a broad array of themes within public health, including diseases and health behaviours. Through linkage to register data on the participants’ parents, the cohort allows investigation of parental effects over time on adolescents’ behaviours and interactions across generations.ParticipantsThe FOCA cohort consists of 13 100 adolescents attending ninth grade in Denmark during the first quarter of 2017, independent of school type.Findings to dateIncluded were 6685 girls (51.03%) and 6415 boys (48.97%) with an average age of 15.85 years, representing 650 schools (37.23%), covering all options in the Danish school system and widely distributed across the country. The use of the personal identification number allowed for a merge of parents to all adolescents in the cohort, resulting in the identification of 25 911 registered parents. Register data on parents’ socio-economic position and labour market history showed representativeness among the adolescents’ socio-economic background compared with the general population in Denmark.Future plansThe adolescents will be followed by ongoing linkage to administrative registers. Future studies will focus on factors affecting future health, education, work and well-being in a life-course perspective and for specific research projects, it will be possible to apply for permission to link data to further ongoing national registers covering all participants.
Industrially producedtransfat in popular foods in 15 countries of the former Soviet Union from 2015 to 2016: a market basket investigation
Authors: Stender Steen 
Published: February 2019

ObjectiveTo minimise the intake of industrially producedtransfat (I-TF) and decrease the risk of coronary heart disease, several countries have implemented a legislative restriction on I-TF in foods. The objective of this study was to investigate the presence of I-TF in biscuits/cakes/wafers in 15 countries of the former Soviet Union that all have a high coronary mortality rate compared with countries in Western Europe.MethodsThree large supermarkets in 15 capitals were visited in 2015 or 2016. Prepackaged biscuits/cakes/wafers were bought if the list of ingredients disclosed that the product contained more than 15 g of fat per 100 g of product and if partially hydrogenated fat or a similar term, including margarine, refined fat or confectionery fat, were mentioned. Samples of the foods were subsequently analysed for total fat and TF.ResultsSome 994 products contained more than 2% total fat as I-TF (illegal in Denmark). In Armenia, 91 different products had a mean value (SD) of 21 (11)% fat as I-TF. In Estonia, there were eight products with 14 (10)% fat as I-TF. The other 13 countries had values between those of Armenia and Estonia. In several countries, a major portion of the products was imported from Russia and Ukraine. The mean shelf life (SD) of 673 packages was 218 (75) days. The % TF in the fat of the products produced in Russia and in Ukraine in relation to the date of production both declined by approximately 10% points during the 2-year collection period.ConclusionsThe findings suggest that I-TF is used in popular foods in all 15 countries of the former Soviet Union. Therefore, these findings indicate a possible way for some reduction of the high coronary mortality rate in these countries.
Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial
Authors: Thomas Martin Geoffrey , Bayliss Carrie , Bond Simon , Dowling Francis , Galea James , Jairath Vipul , Lamb Christopher , Probert Christopher , Timperley-Preece Elizabeth , Watson Alastair , Whitehead Lynne , Williams John G , Parkes Miles , Kaser Arthur , Raine Tim 
Published: February 2019

IntroductionAcute severe ulcerative colitis (ASUC) is a severe manifestation of ulcerative colitis (UC) that warrants hospitalisation. Despite significant advances in therapeutic options for UC and in the medical management of steroid-refractory ASUC, the initial treatment paradigm has not changed since 1955 and is based on the use of intravenous corticosteroids. This treatment is successful in approximately 50% of patients but failure of this and subsequent medical therapy still occurs, with colectomy rates of up to 40% reported. TheInterleukin 1 (IL-1) blockade inAcuteSevere Colitis (IASO) trial aims to investigate whether antagonism of IL-1 signalling using anakinra in addition to intravenous corticosteroid treatment can improve outcomes in patients with ASUC.Methods and analysisIASO is a phase II, multicentre, two-arm (parallel group), randomised (1:1), placebo-controlled, double-blinded trial of short-duration anakinra in ASUC. Its primary outcome will be the incidence of medical (eg, infliximab/ciclosporin) or surgical rescue therapy (colectomy) within 10 days following the commencement of intravenous corticosteroid therapy. Secondary outcomes will include disease activity, time to clinical response, time to rescue therapy, colectomy incidence by day 98 post intravenous corticosteroids and safety. The trial aims to recruit 214 patients across 20 sites in the UK.Ethics and disseminationThe trial has received approval from the Cambridge Central Research Ethics Committee (Ref: 17/EE/0347), the Health Research Authority (Ref: 201505) and Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. We plan to present trial findings at scientific conferences and publish in high-impact peer-reviewed journals.Trial registration numberISRCTN43717130; EudraCT 2017-001389-10.
Frailty in the context of rehabilitation interventions for adults: protocol for a scoping review
Authors: Kokorelias Kristina M , Munce Sarah , McGilton Kathy S , Cronin Shawna M , Wang Chen D , Eftekhar Parvin , Cheng Darren K , Vellani Shirin , Jaglal Susan , Salbach Nancy M , Kontos Pia , Colella Tracey J F , Grigorovich Alisa , Cameron Jill I 
Published: February 2019

IntroductionAlthough a growing number of frail adults can benefit from rehabilitation services, few are included in rehabilitation services, and reasons for their exclusion are not well understood. To inform research directions in rehabilitation for all adults (aged 18 years and older), we will conduct a scoping review to describe (1) the characteristics of frail adult individuals included in rehabilitation interventions (eg, age range, inclusion and exclusion criteria that are applied), (2) the type of rehabilitation interventions that are used for individuals who are considered frail and (3) the commonly reported outcome measures used for these rehabilitation interventions.MethodsThis scoping review will be guided by Arksey and O’Malley’s methodological framework. Ageline, Cochrane CINAHL, Embase, MEDLINE, Pubmed, OTSeeker, PeDRO, PsycINFO and Scopus databases will be systematically searched for articles relevant to rehabilitation interventions and health services. To be eligible for inclusion, studies must report on the outcomes from an intervention that involves all individuals (aged 18 and older) who are considered frail. Only English-language, peer-reviewed publications between 1990 and 2018 will be included. A two-step screening process will consist of (1) a title and abstract review and (2) full-text review. In both levels of screening, a minimum of two investigators will independently screen the title and abstract of all retrieved citations for inclusion against a set of minimum inclusion criteria.AnalysisResults will be presented as a narrative synthesis to facilitate the integration of diverse evidence.Ethics and disseminationThis study does not require ethics approval. By examining the current state of rehabilitation interventions for frail adults, this scoping review can offer insight into rehabilitation needs and models of care. It can also guide future rehabilitation research for frail adults. We will share our results with frail adults during a consultation meeting and publish a manuscript in a peer-reviewed rehabilitation journal.
Comparison of the EQ-5D 3L and the SF-6D (SF-36) contemporaneous utility scores in patients with chronic kidney disease in Sri Lanka: a cross-sectional survey
Authors: Kularatna Sanjeewa , Senanayake Sameera , Gunawardena Nalika , Graves Nicholas 
Published: February 2019

ObjectivesThe aim of this study was to compare utility weights of EuroQoL-five-dimension-3 levels (EQ-5D-3L) and Short-Form six-dimension (SF-6D) in a representative cohort of patients with chronic kidney disease (CKD). A cost–utility analysis (CUA) is designed to report the change to costs required to achieve an estimated change to quality-adjusted life years (QALYs). The quality component of a QALY is measured by utility. Utility represents the preference of general population for a given health state. Classification systems of the multi-attribute utility instruments (MAUIs) are used to define these health states. Utility weights developed from different classification systems can vary and may affect the conclusions from CUAs.DesignA community-based cross-sectional study.SettingAnuradhapura, a rural district in Sri Lanka.ParticipantsA representative sample of 1096 patients with CKD, selected using the population-based CKD register, completed the EQ-5D-3L and SF-36. SF-6D was constructed from the SF-36 according to the published algorithm. The study assessed discrimination, correlation and differences across the two instruments.ResultsStudy participants were predominantly male (62.6%). Mean EQ-5D-3L utility score was 0.540 (SD 0.35) compared with 0.534 (SD 0.09) for the SF-6D (p=0.588). The correlation (r) between the scores was 0.40 (p<0.001). Utility scores were significantly different in both males and females between the two tools, but there was no difference in age and educational categories. Both MAUI scores were significantly lower (p<0.001) among those who were in more advanced stages of the disease and the corresponding utility scores of the two instruments in different CKD stages were also significantly different (p<0.05). The largest effect size was seen among the patients on dialysis.ConclusionsThe correlation between the scores was moderate. SF-6D had the lowest floor and ceiling effect and was better at detecting different stages of the disease. Thus, based on the evidence presented in this study, SF-6D appears to be more appropriate to be used among patients with CKD.
Systematic review of clinical outcome reporting in randomised controlled trials of burn care
Authors: Young Amber E , Davies Anna , Bland Sophie , Brookes Sara , Blazeby Jane M 
Published: February 2019

IntroductionSystematic reviews collate trial data to provide evidence to support clinical decision-making. For effective synthesis, there must be consistency in outcome reporting. There is no agreed set of outcomes for reporting the effect of burn care interventions. Issues with outcome reporting have been identified, although not systematically investigated. This study gathers empirical evidence on any variation in outcome reporting and assesses the need for a core outcome set for burn care research.MethodsElectronic searches of four search engines were undertaken from January 2012 to December 2016 for randomised controlled trials (RCTs), using medical subject headings and free text terms including ‘burn’, ‘scald’ ‘thermal injury’ and ‘RCT’. Two authors independently screened papers, extracted outcomes verbatim and recorded the timing of outcome measurement. Duplicate outcomes (exact wording ± different spelling), similar outcomes (albumin in blood, serum albumin) and identical outcomes measured at different times were removed. Variation in outcome reporting was determined by assessing the number of unique outcomes reported across all included trials. Outcomes were classified into domains. Bias was reduced using five researchers and a patient working independently and together.Results147 trials were included, of which 127 (86.4%) were RCTs, 13 (8.8%) pilot studies and 7 (4.8%) RCT protocols. 1494 verbatim clinical outcomes were reported; 955 were unique. 76.8% of outcomes were measured within 6 months of injury. Commonly reported outcomes were defined differently. Numbers of unique outcomes per trial varied from one to 37 (median 9; IQR 5,13). No single outcome was reported across all studies demonstrating inconsistency of reporting. Outcomes were classified into 54 domains. Numbers of outcomes per domain ranged from 1 to 166 (median 11; IQR 3,24).ConclusionsThis review has demonstrated heterogeneity in outcome reporting in burn care research which will hinder amalgamation of study data. We recommend the development of a Core Outcome Set.PROSPERO registration numberCRD42017060908.
Defining compassion in the digital health age: protocol for a scoping review
Authors: Wiljer David , Charow Rebecca , Costin Helen , Sequeira Lydia , Anderson Melanie , Strudwick Gillian , Tripp Tim , Crawford Allison 
Published: February 2019

IntroductionThe notion of compassion and compassionate care is playing an increasingly important role in health professional education and in the delivery of high-quality healthcare. Digital contexts, however, are not considered in the conceptualisation of compassionate care, nor is there guidance on how compassionate care is to be exercised while using digital health technologies. The widespread diffusion of digital health technologies provides new contexts for compassionate care, with both opportunities for new forms and instantiations of compassion as well as new challenges. How compassion is both understood and enacted within this evolving, digital realm has not been synthesised.Methods and analysisThis scoping review protocol follows Arksey and O’Malley’s methodology to examine dimensions of compassionate professional practice when digital technologies are integrated into clinical care. Relevant peer-reviewed literature will be identified using a search strategy developed by medical librarians, which applies to six databases of medical, computer and information systems disciplines. Eligibility of articles will be determined using the two-stage screening process consisting of (1) title and abstract scan, and (2) full-text review. Screening, abstracting and charting will be conducted by two independent reviewers, with a third reviewer available for resolution when consensus is not achieved. In order to look at the range of current research in this area, extracted data will be thematically analysed and validated by content experts. Descriptive statistics will be calculated where necessary.Ethics and disseminationResearch ethics approval and consent to participate is not required for this scoping review. The results of the review will inform resource development and strategy for Associated Medical Services (AMS) Healthcare, a Canadian charitable organisation at the forefront of advancing research and leadership development in health and humanities, as part of the AMS Phoenix Project: A Call to Caring, particularly for digital professionalism frameworks so that they are inclusive of a compassion competency.