bluuebunny/crossref_metadata_2025_split huggingface dataset:
Realist evaluation of the implementation and impact of the NHS carbon reduction strategy in the UK
Authors: Husain Syed Aleem , Sidhu Manbinder 
Published: September 2021

ObjectivesTo evaluate the extent to which organisational factors facilitate or inhibit the implementation of the National Health Service (NHS) carbon reduction strategy within acute hospital settings.SettingA single acute NHS Trust with four satellite sites which serve more than 2 million patients annually in Central England.ParticipantsInterviews with a purposive sample of 10 stakeholders, including those who conceptualised the intervention and those who were responsible for its implementation.InterventionThe NHS is a major carbon emitter and therefore developed the ‘NHS carbon reduction strategy (NHSCRS)’ in 2009. NHS organisations are contractually obliged to develop a local carbon reduction strategy known as a Sustainable Development Management Plan (SDMP) which details carbon reduction measures (CRM), as described in the NHSCRS. However, the organisational context within which the SDMP is implemented is likely to determine the extent of its success. We undertook an adapted realist evaluation cycle to develop refined initial programme theories. Documents were analysed using thematic content analysis. Interview data were analysed using thematic analysis.ResultsCRM were most likely to be implemented if the Trust Board were sufficiently pressured by staff and reputational fears, and the potential impacts of CRM were perceived to align with wider organisational aims. Differences in implementation of CRM across hospital sites were related to logistical factors, accessibility to regional partners and contractual relationships. There were expected carbon, energy and long-term financial savings, with variability in the effectiveness of some CRM post implementation.ConclusionsOrganisational factors, particularly Board leadership and internal implementation pathways, have a significant bearing on whether CRM are implemented or not. However, greater national support and guidance is needed for NHS organisations to effectively reduce their carbon emissions. Further cycles of this evaluation are necessary in multiple case study sites to illuminate the path to a net-zero NHS carbon footprint by 2045.
Left atrial pressure overload and prognosis in elderly patients with heart failure and preserved ejection fraction: a prospective multicenter observational study
Authors: Hoshida Shiro , Tachibana Koichi , Shinoda Yukinori , Minamisaka Tomoko , Yamada Takahisa , Higuchi Yoshiharu , Nakagawa Yusuke , Abe Haruhiko , Fuji Hisakazu , Yasumura Yoshio , Hikoso Shungo , Nakatani Daisaku , Sakata Yasushi 
Published: September 2021

ObjectivesThe severity of diastolic dysfunction is assessed using a combination of several indices of left atrial (LA) volume overload and LA pressure overload. We aimed to clarify which overload is more associated with the prognosis in patients with heart failure and preserved ejection fraction (HFpEF).SettingA prospective, multicenter observational registry of collaborating hospitals in Osaka, Japan.ParticipantsWe enrolled hospitalised patients with HFpEF showing sinus rhythm (men, 79; women, 113). Blood tests and transthoracic echocardiography were performed before discharge. The ratio of diastolic elastance (Ed) to arterial elastance (Ea) was used as a relative index of LA pressure overload.Primary outcome measuresAll-cause mortality and admission for heart failure were evaluated at >1 year after discharge.ResultsIn the multivariable Cox regression analysis, Ed/Ea, but not LA volume index, was significantly associated with all-cause mortality or admission for heart failure (HR 2.034, 95% CI 1.059 to 3.907, p=0.032), independent of age, sex, and the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level. In patients with a higher NT-proBNP level, the effect of higher Ed/Ea on prognosis was prominent (p=0.015).ConclusionsEd/Ea, an index of LA pressure overload, was significantly associated with the prognosis in elderly patients with HFpEF showing sinus rhythm.Trial registration numberUMIN000021831.
Parental and healthcare professional concern in the diagnosis of paediatric sepsis: a protocol for a prospective multicentre observational study
Authors: Sever Zoe , Schlapbach Luregn J , Jessup Melanie , George Shane , Harley Amanda 
Published: September 2021

IntroductionPaediatric sepsis is a major contributor to morbidity and mortality worldwide. Assessing concern from parents and healthcare professionals to determine disease severity in a child evaluated for sepsis remains a field requiring further investigation. This study aims to determine the diagnostic accuracy of parental and healthcare professional concern in the diagnosis of children evaluated for sepsis.Methods and analysisThis prospective multicentre observational study will be conducted over a 24-month period in the paediatric emergency department (ED) at two tertiary Australian hospitals. A cross-sectional survey design will be used to assess the level of concern in parents, nurses and doctors for children presenting to ED and undergoing assessment for sepsis. The primary outcome is a diagnosis of sepsis, defined as suspected infection plus organ dysfunction at time of survey completion. Secondary outcomes include suspected or proven infection and development of organ dysfunction, defined as a Paediatric Sequential Organ Failure Assessment Score >0, within 48 hours of presentation, paediatric intensive care unit admission, confirmed or probable bacterial infection independent of organ dysfunction, and hospital length of stay.Ethics and disseminationEthics approval was obtained from Children’s Health Queensland’s Human Research Ethics Committee (HREC/17/QRCH/85). Findings will be shared with relevant stakeholders and disseminated via conferences and peer-reviewed journalsTrial registration numberWHO Universal Trial Number, U1111-1256-4537; ANZCTR number, ACTRN1262000134092.
Deep brain stimulation for locomotion in incomplete human spinal cord injury (DBS-SCI): protocol of a prospective one-armed multi-centre study
Authors: Stieglitz Lennart H , Hofer Anna-Sophie , Bolliger Marc , Oertel Markus F , Filli Linard , Willi Romina , Cathomen Adrian , Meyer Christian , Schubert Martin , Hubli Michèle , Kessler Thomas M , Baumann Christian R , Imbach Lukas , Krüsi Iris , Prusse Andrea , Schwab Martin E , Regli Luca , Curt Armin 
Published: September 2021

IntroductionSpinal cord injury (SCI) is a devastating condition with immediate impact on the individual’s health and quality of life. Major functional recovery reaches a plateau 3–4 months after injury despite intensive rehabilitative training. To enhance training efficacy and improve long-term outcomes, the combination of rehabilitation with electrical modulation of the spinal cord and brain has recently aroused scientific interest with encouraging results. The mesencephalic locomotor region (MLR), an evolutionarily conserved brainstem locomotor command and control centre, is considered a promising target for deep brain stimulation (DBS) in patients with SCI. Experiments showed that MLR-DBS can induce locomotion in rats with spinal white matter destructions of >85%.Methods and analysisIn this prospective one-armed multi-centre study, we investigate the safety, feasibility, and therapeutic efficacy of MLR-DBS to enable and enhance locomotor training in severely affected, subchronic and chronic American Spinal Injury Association Impairment Scale C patients in order to improve functional recovery. Patients undergo an intensive training programme with MLR-DBS while being regularly followed up until 6 months post-implantation. The acquired data of each timepoint are compared with baseline while the primary endpoint is performance in the 6-minute walking test. The clinical trial protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials checklist.Ethics and disseminationThis first in-man study investigates the therapeutic potential of MLR-DBS in SCI patients. One patient has already been implanted with electrodes and underwent MLR stimulation during locomotion. Based on the preliminary results which promise safety and feasibility, recruitment of further patients is currently ongoing. Ethical approval has been obtained from the Ethical Committee of the Canton of Zurich (case number BASEC 2016-01104) and Swissmedic (10000316). Results will be published in peer-reviewed journals and presented at conferences.Trial registration numberNCT03053791.
Improved diagnostics of infectious diseases in emergency departments: a protocol of a multifaceted multicentre diagnostic study
Authors: Skjøt-Arkil Helene , Heltborg Anne , Lorentzen Morten Hjarnø , Cartuliares Mariana Bichuette , Hertz Mathias Amdi , Graumann Ole , Rosenvinge Flemming S , Petersen Eva Rabing Brix , Østergaard Claus , Laursen Christian B , Skovsted Thor Aage , Posth Stefan , Chen Ming , Mogensen Christian Backer 
Published: September 2021

BackgroundThe major obstacle in prescribing an appropriate and targeted antibiotic treatment is insufficient knowledge concerning whether the patient has a bacterial infection, where the focus of infection is and which bacteria are the agents of the infection. A prerequisite for the appropriate use of antibiotics is timely access to accurate diagnostics such as point-of-care (POC) testing.The study aims to evaluate diagnostic tools and working methods that support a prompt and accurate diagnosis of hospitalised patients suspected of an acute infection. We will focus on the most common acute infections: community-acquired pneumonia (CAP) and acute pyelonephritis (APN). The objectives are to investigate (1) patient characteristics and treatment trajectory of the different acute infections, (2) diagnostic and prognostic accuracy of infection markers, (3) diagnostic accuracy of POC urine flow cytometry on diagnosing and excluding bacteriuria, (4) how effective the addition of POC analysis of sputum to the diagnostic set-up for CAP is on antibiotic prescriptions, (5) diagnostic accuracy of POC ultrasound and ultralow dose (ULD) computerized tomography (CT) on diagnosing CAP, (6) diagnostic accuracy of specialist ultrasound on diagnosing APN, (7) diagnostic accuracy of POC ultrasound in diagnosing hydronephrosis in patients suspected of APN.Methods and analysisIt is a multifaceted multicentre diagnostic study, including 1000 adults admitted with suspicion of an acute infection. Participants will, within the first 24 hours of admission, undergo additional diagnostic tests including infection markers, POC urine flow cytometry, POC analysis of sputum, POC and specialist ultrasound, and ULDCT. The primary reference standard is an assigned diagnosis determined by a panel of experts.Ethics, dissemination and registrationApproved by Regional Committees on Health Research Ethics for Southern Denmark, Danish Data Protection Agency and clinicaltrials.gov. Results will be presented in peer-reviewed journals, and positive, negative and inconclusive results will be published.Trial registration numbersNCT04661085, NCT04681963, NCT04667195, NCT04652167, NCT04686318, NCT04686292, NCT04651712, NCT04645030, NCT04651244.
Economic evaluations of scaling up strategies of evidence-based health interventions: a systematic review protocol
Authors: Brundisini Francesca , Zomahoun Hervé Tchala Vignon , Légaré France , Rhéault Nathalie , Bernard-Uwizeye Claude , Massougbodji José , Gogovor Amédé , Tchoubi Sébastien , Assan Odilon , Laberge Maude 
Published: September 2021

IntroductionScaling science aims to help roll out evidence-based research results on a wide scale to benefit more individuals. Yet, little is known on how to evaluate economic aspects of scaling up strategies of evidence-based health interventions.Methods and analysisUsing the Joanna Briggs Institute guidance on systematic reviews, we will conduct a systematic review of characteristics and methods applied in economic evaluations in scaling up strategies. To be eligible for inclusion, studies must include a scaling up strategy of an evidence-based health intervention delivered and received by any individual or organisation in any country and setting. They must report costs and cost-effectiveness outcomes. We will consider full or partial economic evaluations, modelling and methodological studies. We searched peer-reviewed publications in Medline, Web of Science, Embase, Cochrane Library Database, PEDE, EconLIT, INHATA from their inception onwards. We will search grey literature from international organisations, bilateral agencies, non-governmental organisations, consultancy firms websites and region-specific databases. Two independent reviewers will screen the records against the eligibility criteria and extract data using a pretested extraction form. We will extract data on study characteristics, scaling up strategies, economic evaluation methods and their components. We will appraise the methodological quality of included studies using the BMJ Checklist. We will narratively summarise the studies’ descriptive characteristics, methodological strengths/weaknesses and the main drivers of cost-effectiveness outcomes. This study will help identify what are the trade-offs of scaling up evidence-based interventions to allocate resources efficiently.Ethics and disseminationNo ethics approval is required as no primary data will be collected. The results will be published in a peer-reviewed, international journal and presented at national and international conferences.
Vitamin D supplementation and energy and metabolic homoeostasis in obese and overweight subjects: a protocol for a systematic review
Authors: He Yu , Yang Xiao , Li Min , Zhang Anren , Sun Nianyi 
Published: September 2021

IntroductionObesity and vitamin D deficiency are major public health problems. According to the pathophysiological mechanism of obesity as well as the bidirectional relationship between obesity and vitamin D metabolism and storage, vitamin D supplementation in obese and overweight subjects could have beneficial effects on the energy and metabolic homoeostasis. This review will assess the efficacy of vitamin D supplementation on the energy and metabolic homoeostasis in overweight and obese subjects.Methods and analysisIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols, we retrieved the relevant literature from the following electronic bibliographic databases: MEDLINE/PubMed, EMBASE and the Cochrane Central Register of Controlled Trials, from inception to June 2021. A manual search of the reference lists of all the relevant research articles will be performed to identify additional studies. We will include randomised controlled trials (RCTs) published in English that examine the effects of vitamin D supplementation on energy and metabolic homoeostasis in overweight and obese subjects. RCTs with multiple vitamin D groups will also be included. Two reviewers will independently complete the article selection, data extraction and rating. The bias tool from the Cochrane Handbook for Systematic Reviews of Interventions was used to assess the methodological quality of the included studies. A narrative or quantitative synthesis will be performed based on the available data. The planned start and end dates for the study were 1 February 2021 and 1 March 2022.Ethics and disseminationEthical approval will not be required for this review. The results of this review will be disseminated in a peer-reviewed journal.PROSPERO registration numberCRD42021228981.
Novel web application for self-assessment of distance visual acuity to support remote consultation: a real-world validation study in children
Authors: Allen Louise , Thirunavukarasu Arun James , Podgorski Simon , Mullinger Deborah 
Published: September 2021

ObjectiveThe difficulty in accurately assessing distance visual acuity (VA) at home limits the usefulness of remote consultation in ophthalmology. A novel web application, DigiVis, enables automated VA self-assessment using standard digital devices. This study aims to compare its accuracy and reliability in children with clinical assessment by a healthcare professional.Methods and AnalysisChildren aged 4–10 years were recruited from a paediatric ophthalmology service. Those with VA worse than +0.8 logMAR (Logarithm of the Minimum Angle of Resolution) or with cognitive impairment were excluded. Bland-Altman statistics were used to analyse both the accuracy and repeatability of VA self-testing. User feedback was collected by questionnaire.ResultsThe left eyes of 89 children (median 7 years) were tested. VA self-testing showed a mean bias of 0.023 logMAR, with a limit of agreement (LOA) of ±0.195 logMAR and an intraclass correlation coefficient (ICC) of 0.816. A second test was possible in 80 (90%) children. Test–retest comparison showed a mean bias of 0.010, with an LOA of ±0.179 logMAR, an ICC of 0.815 and a repeatability coefficient of 0.012. 96% of children rated the test as good or excellent, as did 99% of their parents.ConclusionDigital self-testing gave comparable distance VA assessments with clinical testing in children and was well accepted. Since DigiVis self-testing can be performed under direct supervision using medical video consultation software, it may be a useful tool to enable a proportion of paediatric eye clinic attendances to be moved online, reducing time off school and releasing face-to-face clinical capacity for those who need it.
Cancer-related fatigue—pharmacological interventions: systematic review and network meta-analysis
Authors: Chow Ronald , Bruera Eduardo , Sanatani Michael , Chiu Leonard , Prsic Elizabeth , Boldt Gabriel , Lock Michael 
Published: September 2021

IntroductionCancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed.MethodsMedline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model.ResultsThis review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil.ConclusionParoxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.
CD8+ TILs in NSCLC differentiate into TEMRA via a bifurcated trajectory: deciphering immunogenicity of tumor antigens
Authors: Lee Sung-Woo , Choi He Yun , Lee Gil-Woo , Kim Therasa , Cho Hyun-Ju , Oh In-Jae , Song Sang Yun , Yang Deok Hwan , Cho Jae-Ho 
Published: September 2021

BackgroundCD8+ tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA re-expressing CD8+ T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood.MethodsWe analyzed primary tumors and peripheral blood samples from 26 patients with non-small cell lung cancer and analyzed their phenotypes and functional characteristics using flow cytometry, RNA-sequencing, and bioinformatics.ResultsWe found that tumor-infiltrating Temra (tilTemra) cells largely differ from peripheral blood Temra (pTemra), with distinct transcriptomes and functional properties. Notably, although majority of the pTemra was CD27−CD28− double-negative (DN), a large fraction of tilTemra population was CD27+CD28+ double-positive (DP), a characteristic of early-stage, less differentiated effector cells. Trajectory analysis revealed that CD8+ TILs undergo a divergent sequence of events for differentiation into either DP or DN tilTemra. Such a differentiation toward DP tilTemra relied on persistent expression of CD27 and CD28 and was associated with weak T cell receptor engagement. Thus, a higher proportion of DP Temra was correlated with lower immunogenicity of tumor antigens and consequently lower accumulation of CD8+ TILs.ConclusionsThese data suggest a complex interplay between CD8+ T cells and tumors and define DP Temra as a unique subset of tumor-specific CD8+ TILs that are produced in patients with relatively low immunogenic cancer types, predicting immunogenicity of tumor antigens and CD8+ TIL counts, a reliable biomarker for successful cancer immunotherapy.
Organisational values of National Health Service trusts in England: semantic analysis and relation to performance indicators
Authors: Waheed Amina , Presswood Edward , Scott Gregory 
Published: September 2021

BackgroundOrganisational values are widely assumed to have positive effects on performance and staff. National Health Service (NHS) trusts in England have accordingly chosen their own organisational values. However, there has been no survey of the values adopted, and there is little evidence that the choice of values per se has consequences for outcomes. We comprehensively described trusts’ organisational values, using natural language processing to identify common themes. We tested whether the choice of themes was associated with outcomes for patients and staff.MethodsWe collected data on trusts’ values (from their websites), performance (Summary Hospital-level Mortality Indicator (SHMI) statistics, Care Quality Commission (CQC) ratings), sickness absence rates (SAR) and staff opinions (NHS Staff Survey responses). We first characterised values based on lexical properties then progressed to semantic analysis, using Google’s Universal Sentence Encoder, to transform values to high-dimensional embeddings, and k-means clustering of embeddings to semantically cluster values into 12 common themes. We tested for associations between trusts’ use of these themes and outcomes.ResultsOrganisational values were obtained for 221 of 228 NHS trusts, with 985 values in total (480 unique). Semantic clustering identified themes including ‘care’, ‘value respect’and ‘togetherness’. There was no significant association between themes and SHMI or CQC ratings. However, themes predicted trusts’ SAR (p=0.001, R2=0.159), with use of ‘care’,‘value respect’, ‘aspirational’and ‘people’all significant predictors ofincreasedsickness absence; themes also predicted staff opinions on ‘Equality, diversity and inclusion’(p=0.011, R2=0.116), but with ‘supportive’and ‘openness’predicting morenegativeresponses.ConclusionA trust’s adoption of individualised organisational values does not seem to make a positive difference to its patients or staff. These findings should give NHS managers pause for thought, challenging them to reconsider their reliance on value-defining initiatives, and to seek evidence that a focus on values has measurable benefits on outcomes.