bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of nocturnal cough in asthma and its potential as a marker for asthma control (MAC) in combination with sleep quality: protocol of a smartphone-based, multicentre, longitudinal observational study with two stages
Authors: Tinschert Peter , Rassouli Frank , Barata Filipe , Steurer-Stey Claudia , Fleisch Elgar , Puhan Milo Alan , Brutsche Martin , Kowatsch Tobias 
Published: May 2020

IntroductionNocturnal cough is a burdensome asthma symptom. However, knowledge about the prevalence of nocturnal cough in asthma is limited. Furthermore, prior research has shown that nocturnal cough and impaired sleep quality are associated with asthma control, but the association between these two symptoms remains unclear. This study further investigates the potential of these symptoms as markers for asthma control and the accuracy of automated, smartphone-based passive monitoring for nocturnal cough detection and sleep quality assessment.Methods and analysisThe study is a multicentre, longitudinal observational study with two stages. Sensor and questionnaire data of 94 individuals with asthma will be recorded for 28 nights by means of a smartphone. On the first and the last study day, a participant’s asthma will be clinically assessed, including spirometry and fractionated exhaled nitric oxide levels. Asthma control will be assessed by the Asthma Control Test and sleep quality by means of the Pittsburgh Sleep Quality Index. In addition, nocturnal coughs from smartphone microphone recordings will be labelled and counted by human annotators. Relatively unrestrictive eligibility criteria for study participation are set to support external validity of study results. Analysis of the first stage is concerned with the prevalence and trends of nocturnal cough and the accuracies of smartphone-based automated detection of nocturnal cough and sleep quality. In the second stage, patient-reported asthma control will be predicted in a mixed effects regression model with nocturnal cough frequencies and sleep quality of past nights as the main predictors.Ethics and disseminationThe study was reviewed and approved by the ethics commission responsible for research involving humans in eastern Switzerland (BASEC ID: 2017–01872). All study data will be anonymised on study termination. Results will be published in medical and technical peer-reviewed journals.Trial registration numberNCT03635710; Pre-results.
Protocol for a mixed-methods exploratory investigation of care following intensive care discharge: the REFLECT study
Authors: Vollam Sarah , Gustafson Owen , Hinton Lisa , Morgan Lauren , Pattison Natalie , Thomas Hilary , Young J Duncan , Watkinson Peter 
Published: May 2020

IntroductionA substantial number of patients discharged from intensive care units (ICUs) subsequently die without leaving hospital. It is unclear how many of these deaths are preventable. Ward-based management following discharge from ICU is an area that patients and healthcare staff are concerned about. The primary aim of REFLECT (Recovery Following Intensive Care Treatment) is to develop an intervention plan to reduce in-hospital mortality rates in patients who have been discharged from ICU.Methods and analysisREFLECT is a multicentre mixed-methods exploratory study examining ward care delivery to adult patients discharged from ICU. The study will be made up of four substudies. Medical notes of patients who were discharged from ICU and subsequently died will be examined using a retrospective case records review (RCRR) technique. Patients and their relatives will be interviewed about their post-ICU care, including relatives of patients who died in hospital following ICU discharge. Staff involved in the care of patients post-ICU discharge will be interviewed about the care of this patient group. The medical records of patients who survived their post-ICU stay will also be reviewed using the RCRR technique. The analyses of the substudies will be both descriptive and use a modified grounded theory approach to identify emerging themes. The evidence generated in these four substudies will form the basis of the intervention development, which will take place through stakeholder and clinical expert meetings.Ethics and disseminationEthical approval has been obtained through the Wales Research and Ethics Committee 4 (17/WA/0107). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media.Trial registration numberISRCTN14658054.
Incidentally diagnosed cancer and commonly preceding clinical scenarios: a cross-sectional descriptive analysis of English audit data
Authors: Koo Minjoung Monica , Rubin Greg , McPhail Sean , Lyratzopoulos Georgios 
Published: May 2020

ObjectivesCancer can be diagnosed in the absence of tumour-related symptoms, but little is known about the frequency and circumstances preceding such diagnoses which occur outside participation in screening programmes. We aimed to examine incidentally diagnosed cancer among a cohort of cancer patients diagnosed in England.DesignCross-sectional study of national primary care audit data on an incident cancer patient population.SettingWe analysed free-text information on the presenting features of cancer patients aged 15 or older included in the English National Audit of Cancer Diagnosis in Primary Care (2009–2010). Patients with screen-detected cancers or prostate cancer were excluded. We examined the odds of incidental cancer diagnosis by patient characteristics and cancer site using logistic regression, and described clinical scenarios leading to incidental diagnosis.ResultsAmong the studied cancer patient population (n=13 810), 520 (4%) patients were diagnosed incidentally. The odds of incidental cancer diagnosis increased with age (p<0.001), with no difference between men and women after adjustment. Incidental diagnosis was most common among patients with leukaemia (23%), renal (13%) and thyroid cancer (12%), and least common among patients with brain (0.9%), oesophageal (0.5%) and cervical cancer (no cases diagnosed incidentally). Variation in odds of incidental diagnosis by cancer site remained after adjusting for age group and sex.There was a range of clinical scenarios preceding incidental diagnoses in primary or secondary care. These included the monitoring or management of pre-existing conditions, routine testing before or after elective surgery, and the investigation of unrelated acute or new conditions.ConclusionsOne in 25 patients with cancer in our population-based cohort were diagnosed incidentally, through different mechanisms across primary and secondary care settings. The epidemiological, clinical, psychological and economic implications of this phenomenon merit further investigation.
Management of hyperglycaemia in persons with non-insulin-dependent type 2 diabetes mellitus who are started on systemic glucocorticoid therapy: a systematic review
Authors: Tatalovic Milos , Lehmann Roger , Cheetham Marcus , Nowak Albina , Battegay Edouard , Rampini Silvana K 
Published: May 2020

ObjectivesWhat is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on systemic glucocorticoid therapy?DesignWe conducted a systematic literature review.Data sourcesWe searched MEDLINE, Embase and Cochrane Library databases and Google for articles from 2002 to July 2018.Eligibility criteriaWe combined search terms relating to DM (patients, >16 years of age), systemic glucocorticoids, glycaemic control, randomised controlled trials (RCTs) and observational studies.Data extraction and synthesisWe screened and evaluated articles, extracted data and assessed risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development and Evaluation guidelines.ResultsEight of 2365 articles met full eligibility criteria. Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective but provided insufficient glucose control, depending on time of day. BBI strategy with long-acting insulin and neutral protamin Hagedorn as basal insulin provided similar overall glycaemic control. Addition of various insulin strategies to standard BBI delivered mixed results. Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits, and glycaemic control with sliding scale insulin was inferior to BBI or IMI. No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control.ConclusionThe lack of suitably designed RCTs and observational studies, heterogeneity of interventions, target glucose levels and glucose monitoring, poor control of DM subgroups and low to moderate quality of evidence render identification of optimal pharmacological interventions for glycaemic control and insulin management difficult. Even findings on the widely recommended BBI regimen as intensive insulin therapy for patients with DM on glucocorticoids are inconclusive. High-quality evidence from studies with well-defined DM phenotypes, settings and treatment approaches is needed to determine optimal pharmacological intervention for glycaemic control.PROSPERO registration numberCRD42015024739.
General practitioners’ predictions of their own patients’ health literacy: a cross-sectional study in Belgium
Authors: Storms Hannelore , Aertgeerts Bert , Vandenabeele Frank , Claes Neree 
Published: May 2020

ObjectivesTo support patients in their disease management, providing information that is adjusted to patients’ knowledge and ability to process health information (ie, health literacy) is crucial. To ensure effective health communication, general practitioners (GPs) should be able to identify people with limited health literacy. To this end, (dis)agreement between patients’ health literacy and GPs’ estimations thereof was examined. Also, characteristics impacting health literacy (dis)agreement were studied.DesignCross-sectional survey of general practice patients and GPs undertaken in 2016–17.SettingForty-one general practices in two Dutch-speaking provinces in Belgium.ParticipantsPatients (18 years of age and older) visiting general practices. Patients were excluded when having severe impairments (physical, mental, sensory).Main outcome measuresPatients’ health literacy was assessed with 16-item European Health Literacy Survey Questionnaire. GPs indicated estimations on patients’ health literacy using a simple scale (inadequate; problematic; adequate). (Dis)agreement between patients’ health literacy and GPs’ estimations thereof (GPs’ estimations being equal to/higher/lower than patients’ health literacy) was measured using Kappa statistics. The impact of patient and GP characteristics, including duration of GP–patient relationships, on this (dis)agreement was examined using generalised linear logit model.ResultsHealth literacy of patients (n=1375) was inadequate (n=201; 14.6%), problematic (n=299; 21.7%), adequate (n=875; 63.6%). GPs overestimated the proportion patients with adequate health literacy: adequate (n=1241; 90.3%), problematic (n=130; 9.5%) and inadequate (n=4; 0.3%). Overall, GPs’ correct; over-/underestimations of health literacy occurred for, respectively, 60.9%; 34.2%; 4.9% patients, resulting in a slight agreement (κ=0.033). The likelihood for GPs to over-/underestimate patients’ health literacy increases with decreasing educational level of patients; and decreasing number of years patients have been consulting with their GP.ConclusionsIntuitively assessing health literacy is difficult. Patients’ education, the duration of GP–patient relationships and GPs’ gender impact GPs’ perceptions of patients’ health literacy.
Investigating SOcial Competence and Isolation in children with Autism taking part in LEGO-based therapy clubs In School Environments (I-SOCIALISE): study protocol
Authors: Varley Danielle , Wright Barry , Cooper Cindy , Marshall David , Biggs Katie , Ali Shehzad , Chater Tim , Coates Elizabeth , Gilbody Simon , Gomez de la Cuesta Gina , Kingsley Ellen , Le Couteur Ann , McKelvey Anne , Shephard Neil , Teare Dawn 
Published: May 2020

IntroductionSocial skills training interventions for children with autism spectrum disorder (ASD) typically focus on a skills deficit model rather than building on existing skills or encouraging the child to seek their own solutions. LEGO-based therapy is a child-oriented intervention to help improve social interactional skills and reduce isolation. The therapy is designed for school-age children with ASD and uses group-based play in a school setting to encourage peer relationships and social learning. Despite the reported potential benefits of LEGO-based therapy in a prior randomised controlled trial (RCT) and its adoption by many schools, the evidence to support its effectiveness on the social and emotional well-being of children with ASD is limited and includes no assessment of cost-effectiveness.Methods and analysisThis multicentre, pragmatic, cluster RCT will randomise 240 participants (aged 7–15 years) with a clinical diagnosis of ASD to receive usual care or LEGO-based therapy with usual care. Cluster randomisation will be conducted on a school level, randomising each school as opposed to each individual child within a school. All prospective participants will be screened for eligibility before assenting to the study (with parents giving informed consent on behalf of their child). All participants will be followed up at 20 and 52 weeks after randomisation to assess for social, emotional and behavioural changes. The primary outcome measure is the social skills subscale of the Social Skills Improvement System completed by a teacher or teaching assistant associated with participating children at the 20-week follow-up time point.Ethics and disseminationEthics approval has been obtained via the University of York Research Ethics Committee. The results of the trial will be submitted for publication in a peer-reviewed journal and will be disseminated to participating families, education practitioners and the third sector including voluntary and community organisations.Trial registration numberISRCTN64852382; Pre-results.
Effectiveness and safety of acupuncture and moxibustion for defecation dysfunction after sphincter-preserving surgery for rectal cancer: protocol for systematic review and meta-analysis
Authors: Xu Guixing , Xiao Qiwei , Lei Hanzhou , Fu Yanan , Kong Jing , Zheng Qianhua , Zhao Ling , Liang Fanrong 
Published: May 2020

IntroductionDefecation dysfunction (DD) is one of the most common complications following sphincter-preserving surgery for rectal cancer. And there is no effective treatment of DD after sphincter-preserving surgery for rectal cancer. Although some studies suggested that acupuncture and moxibustion (AM) is effective and safe for DD after sphincter-preserving surgery for rectal cancer, lacking strong evidence, for instance, the relevant systematic review, meta-analysis and randomised controlled trial (RCT) of a large, multicentre sample, makes the effects and safety remain uncertain. The present protocol is described for a systematic review and meta-analysis to investigate the effectiveness and safety of AM for DD after sphincter-preserving surgery for rectal cancer.Methods and analysisWe will search nine online databases from inception to 1 October 2019; the language of included trials will not be restricted. This study will include RCTs that performed AM as the main method of the experimental group for patients with DD after sphincter-preserving surgery for rectal cancer. Two of the researchers will independently select the studies, conduct risk of bias assessment and extract the data. We will use the fixed-effects model or random-effects model of RevMan V.5.2 software to analyse data synthesis. The risk ratios with 95% CIs and weighted mean differences or standardised mean differences with 95% CIs will be used to present the data synthesis outcome of dichotomous data respectively and the continuous data. Evidence quality of outcome will be assessed by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.Ethics and disseminationEthical approval is not required in this secondary research evidence, and we will publish the results of this study in a journal or concerned conferences.Trial registration numberCRD42019140097.
Tranexamic acid administration during total joint arthroplasty surgery is not associated with an increased risk of perioperative seizures: a national database analysis
Authors: Kirksey Meghan A , Wilson Lauren A , Fiasconaro Megan , Poeran Jashvant , Liu Jiabin , Memtsoudis Stavros G 
Published: May 2020

BackgroundTranexamic acid (TXA) has been used extensively to minimize blood loss in cardiac surgery and more recently in orthopedic surgery. Despite a generally good safety profile, an increased risk of seizures has been observed in patients with cardiac disease. However, this issue has not been adequately addressed in the orthopedic literature.MethodsAfter institutional review board approval, we queried a large national database to identify patients who had undergone total hip and total knee arthroplasties (2012–2016). Patients were divided based on their exposure to TXA and history of seizures. The main outcome of interest was a perioperative seizure. We conducted univariable comparisons and a multivariable regression analysis to elucidate a potential independent association between TXA administration and seizures in the perioperative period (with or without a history of seizures).ResultsTXA was used overall in 45.9% (n=4 21 890) of joint arthroplasty recipients (n=9 18 918), with more frequent use over time. Utilization rates did not differ between those with and without a history of seizures; 42.2% (3487/8252) of patients with a seizure history received TXA. Rates of perioperative seizure were low and did not differ between those who did and did not receive TXA (0.01% vs 0.02%, p=0.11); when subgrouping patients by history of seizures, we found no difference in incidence of perioperative seizures between groups (0.06% vs 0.02%, p=0.39). Our adjusted analysis further confirmed these results.ConclusionDespite increasing TXA utilization in total joint arthroplasty, we found an overall low seizure incidence. TXA use was not associated with elevated odds of perioperative seizure, even in patients with history of seizure.
Effects of nonlinearity of f(R) gravity and perfect fluid in Kaluza–Klein models with spherical compactification
Authors: Canay Ezgi , Eingorn Maxim , Zhuk Alexander 
Published: May 2020

AbstractWe study the effects associated with nonlinearity of f(R) gravity and of the background perfect fluid manifested in the Kaluza–Klein model with spherical compactification. The background space-time is perturbed by a massive gravitating source which is pressureless in the external space but has an arbitrary equation of state (EoS) parameter in the internal space. As characteristics of a nonlinear perfect fluid, the squared speeds of sound are not equal to the background EoS parameters in the external and internal spaces. In this setting, we find exact solutions to the linearized Einstein equations for the perturbed metric coefficients. For nonlinear models with $$f^{\prime \prime }(R_0)\ne 0$$f″(R0)≠0, we show that these coefficients acquire correction terms in the form of two summed Yukawa potentials and that in the degenerated case, the solutions are reduced to a single Yukawa potential with some “corrupted” prefactor (in front of the exponential function), which, in addition to the standard 1/r term, contains a contribution independent of the three-dimensional distance r. In the linear $$f''(R)=0$$f′′(R)=0 model, we generalize the previous studies to the case of an arbitrary nonlinear perfect fluid. We also investigate the particular case of the nonlinear background perfect fluid with zero speed of sound in the external space and demonstrate that a non-trivial solution exists only in the case of $$f''(R_0)=0$$f′′(R0)=0.
Comparative analysis of layered structures in empirical investor networks and cellphone communication networks
Authors: Wang Peng , Ma Jun-Chao , Jiang Zhi-Qiang , Zhou Wei-Xing , Sornette Didier 
Published: May 2020

AbstractEmpirical investor networks (EIN) proposed by Ozsoylev et al. are assumed to capture the information spreading path among investors. Here, we perform a comparative analysis between the EIN and the cellphone communication networks (CN) to test whether EIN is an information exchanging network from the perspective of the layer structures of ego networks. We employ two clustering algorithms (k-means algorithm and $H/T$H/T break algorithm) to detect the layer structures for each node in both networks. We find that the nodes in both networks can be clustered into two groups, that one has a layer structure similar to the theoretical Dunbar Circle that alters in ego networks exhibit a four-layer hierarchical structure with the cumulative number of 5, 15, 50 and 150 from the inner layer to the outer layer, and the other one has an additional inner layer with about 2 alters compared with the Dunbar Circle. We also find that the scale ratios, which are estimated based on the unique parameters in the theoretical model of layer structures, conform to a log-normal distribution for both networks. Our results not only deepen our understanding on the topological structures of EIN, but also provide empirical evidence of the channels of information diffusion among investors.
The Dysregulated Pharmacology of Clinically Relevant ESR1 Mutants is Normalized by Ligand-activated WT Receptor
Authors: Andreano Kaitlyn J. , Baker Jennifer G. , Park Sunghee , Safi Rachid , Artham Sandeep , Oesterreich Steffi , Jeselsohn Rinath , Brown Myles , Sammons Sarah , Wardell Suzanne E. , Chang Ching-yi , Norris John D. , McDonnell Donald P. 
Published: May 2020

Abstract
The estrogen receptor (ER/ESR1) is expressed in a majority of breast cancers and drugs that inhibit ER signaling are the cornerstone of breast cancer pharmacotherapy. Currently, aromatase inhibitors are the frontline endocrine interventions of choice although their durability in metastatic disease is limited by activating point mutations within the ligand-binding domain of ESR1 that permit ligand-independent activation of the receptor. It has been suggested that the most commonly occurring ESR1 mutations would likely compromise the clinical activity of selective estrogen receptor downregulators and selective estrogen receptor modulators (SERMs) when used as second-line therapies. It was unclear, however, how these mutations, which are likely coexpressed in cells with ERWT, may impact response to ER ligands in a clinically meaningful manner. To address this issue, we dissected the molecular mechanism(s) underlying ESR1-mutant pharmacology in models relevant to metastatic disease. These studies revealed that the response of ESR1 mutations to ligands was dictated primarily by the relative coexpression of ERWT in cells. Specifically, dysregulated pharmacology was only evident in cells in which the mutants were overexpressed relative to ligand-activated ERWT; a finding that highlights the role of allelism in determining ER-mutant pharmacology. Importantly, we demonstrated that the antagonist activity of the SERM, lasofoxifene, was not impacted by mutant status; a finding that has led to its clinical evaluation as a treatment for patients with advanced ER-positive breast cancer whose tumors harbor ESR1 mutations.