bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of adults with sepsis in the prehospital environment: a systematic review
Authors: Smyth Michael A , Brace-McDonnell Samantha J , Perkins Gavin D 
Published: August 2016

ObjectiveEarly identification of sepsis could enable prompt delivery of key interventions such as fluid resuscitation and antibiotic administration which, in turn, may lead to improved patient outcomes. Limited data indicate that recognition of sepsis by paramedics is often poor. We systematically reviewed the literature on prehospital sepsis screening tools to determine whether they improved sepsis recognition.DesignSystematic review. The electronic databases MEDLINE, EMBASE, CINAHL, the Cochrane Library and PubMed were systematically searched up to June 2015. In addition, subject experts were contacted.SettingPrehospital/emergency medical services (EMS).Study selectionAll studies addressing identification of sepsis (including severe sepsis and septic shock) among adult patients managed by EMS.Outcome measuresRecognition of sepsis by EMS clinicians.ResultsOwing to considerable variation in the methodological approach adopted and outcome measures reported, a narrative approach to data synthesis was adopted. Three studies addressed development of prehospital sepsis screening tools. Six studies addressed paramedic diagnosis of sepsis with or without use of a prehospital sepsis screening tool.ConclusionsRecognition of sepsis by ambulance clinicians is poor. The use of screening tools, based on the Surviving Sepsis Campaign diagnostic criteria, improves prehospital sepsis recognition. Screening tools derived from EMS data have been developed, but they have not yet been validated in clinical practice. There is a need to undertake validation studies to determine whether prehospital sepsis screening tools confer any clinical benefit.
Combined cognitive–behavioural and mindfulness programme for people living with dystonia: a proof-of-concept study
Authors: Sandhu H , Bernstein C J , Davies G , Tang N K Y , Belhag M , Tingle A , Field M , Foss J , Lindahl A , Underwood M , Ellard D R 
Published: August 2016

ObjectivesTo design and test the delivery of an intervention targeting the non-motor symptoms of dystonia and pilot key health and well-being questionnaires in this population.DesignA proof-of-concept study to test the delivery, acceptability, relevance, structure and content for a 3-day group residential programme for the management of dystonia.SettingParticipants were recruited from a single botulinum toxin clinic. The intervention was delivered in the community.Participants14 participants consented to take part (2 withdrew prior to the starting of intervention). The average age was 60 years (range 44–77), 8 of whom were female. After drop-out, 9 participants completed the 3-day programme.InterventionA 3-day group residential programme.Primary and secondary outcome measuresProcess evaluation and interviews were carried out before and after the intervention to explore participant's views and expectations, as well as experiences of the intervention. Select questionnaires were completed at baseline, 1-month and 3-month follow-up.ResultsAlthough participants were not sure what to expect from the programme, they found it informative and for many this together with being in a group with other people with dystonia legitimised their condition. Mindfulness was accepted and adopted as a coping strategy. This was reflected in the 1-month follow-up.ConclusionsWe successfully delivered a 3-day residential programme to help those living with dystonia manage their condition. Further improvements are suggested. The quantitative outcome measures were acceptable to this group of patients with dystonia.
Comparing the accuracy of quantitative versus qualitative analyses of interim PET to prognosticate Hodgkin lymphoma: a systematic review protocol of diagnostic test accuracy
Authors: Procházka Vít , Klugar Miloslav , Bachanova Veronika , Klugarová Jitka , Tučková Dagmar , Papajík Tomáš 
Published: August 2016

IntroductionHodgkin lymphoma is an effectively treated malignancy, yet 20% of patients relapse or are refractory to front-line treatments with potentially fatal outcomes. Early detection of poor treatment responders is crucial for appropriate application of tailored treatment strategies. Tumour metabolic imaging of Hodgkin lymphoma using visual (qualitative) 18-fluorodeoxyglucose positron emission tomography (FDG-PET) is a gold standard for staging and final outcome assessment, but results gathered during the interim period are less accurate. Analysis of continuous metabolic–morphological data (quantitative) FDG-PET may enhance the robustness of interim disease monitoring, and help to improve treatment decision-making processes. The objective of this review is to compare diagnostic test accuracy of quantitative versus qualitative interim FDG-PET in the prognostication of patients with Hodgkin lymphoma.MethodsThe literature on this topic will be reviewed in a 3-step strategy that follows methods described by the Joanna Briggs Institute (JBI). First, MEDLINE and EMBASE databases will be searched. Second, listed databases for published literature (MEDLINE, Tripdatabase, Pedro, EMBASE, the Cochrane Central Register of Controlled Trials and WoS) and unpublished literature (Open Grey, Current Controlled Trials, MedNar, ClinicalTrials.gov, Cos Conference Papers Index and International Clinical Trials Registry Platform of the WHO) will be queried. Third, 2 independent reviewers will analyse titles, abstracts and full texts, and perform hand search of relevant studies, and then perform critical appraisal and data extraction from selected studies using the DATARI tool (JBI). If possible, a statistical meta-analysis will be performed on pooled sensitivity and specificity data gathered from the selected studies. Statistical heterogeneity will be assessed. Funnel plots, Begg's rank correlations and Egger's regression tests will be used to detect and/or correct publication bias.Ethics and disseminationThe results will be disseminated by publishing in a peer-reviewed journal. Ethical assessment will not be needed; only existing sources of literature will be searched.Trial registration numberCRD42016027953.
Understanding and reducing the prescription of hypnotics and sedatives at the interface of hospital care and general practice: a protocol for a mixed-methods study
Authors: Heinemann Stephanie , Weiß Vivien , Straube Kati , Nau Roland , Grimmsmann Thomas , Himmel Wolfgang , Hummers-Pradier Eva 
Published: August 2016

IntroductionHypnotics and sedatives, especially benzodiazepines and Z-drugs, are frequently prescribed for longer periods than recommended—in spite of potential risks for patients. Any intervention to improve this situation has to take into account the interplay between different actors, interests and needs. The ultimate goal of this study is to develop—together with the professionals involved—ideas for reducing the use of hypnotics and sedatives and then to implement and evaluate adequate interventions in the hospital and at the primary and secondary care interface.Methods and analysisThe study will take place in a regional hospital in northern Germany and in some general practices in this region. We will collect data from doctors, nurses, patients and a major social health insurer to define the problem from multiple perspectives. These data will be explored and discussed with relevant stakeholders to develop interventions. The interventions will be implemented and, in a final step, evaluated. Both quantitative and qualitative data, including surveys, interviews, chart reviews and secondary analysis of social health insurance data, will be collected to obtain a full understanding of the frequency and the reasons for using hypnotics and sedatives.Ethics and disseminationApproval has been granted from the ethics review committee of the University Medical Center Göttingen, Germany. Results will be disseminated to researchers, clinicians and policy makers in peer-reviewed journal articles and conference publications. One or more dissemination events will be held locally during continuous professional development events for local professionals, including (but not confined to) the study participants.
Study on the development of an infectious disease-specific health literacy scale in the Chinese population
Authors: Tian Xiangyang , Di Zeqing , Cheng Yulan , Ren Xuefeng , Chai Yan , Ding Fan , Chen Jibin , Southerland Jodi L , Cui Zengwei , Hu Xiuqiong , Xu Jingdong , Xu Shuiyang , Qian Guohong , Wang Liang 
Published: August 2016

ObjectivesTo develop a scale to assess infectious disease-specific health literacy (IDSHL) in China and test its initial psychometric properties.MethodsItem pooling, reduction and assessment of psychometric properties were conducted. The scale was divided into 2 subscales; subscale 1 assessed an individual's skills to prevent/treat infectious diseases and subscale 2 assessed cognitive ability. In 2014, 9000 people aged 15–69 years were randomly sampled from 3 provinces and asked to complete the IDSHL questionnaire. Cronbach's α was calculated to assess reliability. Exploratory factor analysis, t-test, correlations, receiver operating characteristic (ROC) curve and logistic regression were used to examine validity.ResultsEach of the 22 items in subscale 1 had a content validity index >0.8. In total, 8858 people completed the scale. The principal components factor analysis suggested a 5-factor solution. All factor loadings were >0.40 (p<0.05). The IDSHL score was 22.07±7.91 (mean±SD; total score=38.62). Significant differences were observed across age (r=−0.276), sex (males: 21.65±8.03; females: 22.47±7.78), education (14.16±8.19 to 26.55±6.26), 2-week morbidity (present: 20.62±8.17, absent: 22.35±7.83; p<0.001) and health literacy of the highest and lowest 27% score groups (all p<0.05). The ROC curve indicated that 76.2% of respondents were adequate in IDSHL. Binary logistic regression analysis revealed 12 predictors of IDSHL adequacy (p<0.05). Among the 22 remaining items, Corrected Item-Total Correlation ranged from 0.316 to 0.504 and Cronbach's α values ranged from 0.754 to 0.810 if the items were deleted. The overall α value was 0.839 and the difficulty coefficient ranged from 1.19 to 4.08. For subscale 2, there were statistically significant differences between the mean scores of those with a correct/incorrect answer (all p<0.001).ConclusionsThe newly developed 28-item scale provides an efficient, psychometrically sound and user-friendly measure of IDSHL in the Chinese population.
Effect of warning symbols in combination with education on the frequency of erroneously crushing medication in nursing homes: an uncontrolled before and after study
Authors: van Welie Steven , Wijma Linda , Beerden Tim , van Doormaal Jasperien , Taxis Katja 
Published: August 2016

ObjectivesResidents of nursing homes often have difficulty swallowing (dysphagia), which complicates the administration of solid oral dosage formulations. Erroneously crushing medication is common, but few interventions have been tested to improve medication safety. Therefore, we evaluated the effect of warning symbols in combination with education on the frequency of erroneously crushing medication in nursing homes.SettingThis was a prospective uncontrolled intervention study with a preintervention and postintervention measurement. The study was conducted on 18 wards (total of 200 beds) in 3 nursing homes in the North of the Netherlands.ParticipantsWe observed 36 nurses/nursing assistants (92% female; 92% nursing assistants) administering medication to 197 patients (62.9% female; mean age 81.6).InterventionThe intervention consisted of a set of warning symbols printed on each patient's unit dose packaging indicating whether or not a medication could be crushed as well as education of ward staff (lectures, newsletter and poster).Primary outcome measureThe relative risk (RR) of a crushing error occurring in the postintervention period compared to the preintervention period. A crushing error was defined as the crushing of a medication considered unsuitable to be crushed based on standard reference sources. Data were collected using direct (disguised) observation of nurses during drug administration.ResultsThe crushing error rate decreased from 3.1% (21 wrongly crushed medicines out of 681 administrations) to 0.5% (3/636), RR=0.15 (95% CI 0.05 to 0.51). Likewise, there was a significant reduction using data from patients with swallowing difficulties only, 87.5% (21 errors/24 medications) to 30.0% (3/10) (RR 0.34, 95% CI 0.13 to 0.89). Medications which were erroneously crushed included enteric-coated formulations (eg, omeprazole), medication with regulated release systems (eg, Persantin; dipyridamol) and toxic substances (eg, finasteride).ConclusionsWarning symbols combined with education reduced erroneous crushing of medication, a well-known and common problem in nursing homes.
DNA hypermethylation analysis in sputum of asymptomatic subjects at risk for lung cancer participating in the NELSON trial: argument for maximum screening interval of 2 years
Authors: Hubers A Jasmijn , Heideman Daniëlle A M , Duin Sylvia , Witte Birgit I , de Koning Harry J , Groen Harry J M , Prinsen Clemens F M , Bolijn Anne S , Wouters Mandy , van der Meer Susanne E , Steenbergen Renske D M , Snijders Peter J F , Uyterlinde Anne , Berkhof Hans , Smit Egbert F , Thunnissen Erik 
Published: August 2016

AimsLung cancer is the major contributor to cancer mortality due to metastasised disease at time of presentation. The current study investigated DNA hypermethylation of biomarkersRASSF1A,APC, cytoglobin,3OST2, FAM19A4, PHACTR3andPRDM14in sputum of asymptomatic high-risk individuals from the NELSON lung cancer low-dose spiral CT screening trial to detect lung cancer at preclinical stage.MethodsSubjects were selected with (i) lung cancer in follow-up (cases; n=65), (ii) minor cytological aberrations (controls; n=120) and (iii) a random selection of subjects without cytological aberrations (controls; n=99). Median follow-up time for controls was 80 months. Cut-off values were based on high specificity to assess diagnostic value of the biomarkers.ResultsRASSF1Amay denote presence of invasive cancer because of its high specificity (93% (95% CI 89% to 96%); sensitivity 17% (95% CI 4% to 31%), with best performance in a screening interval of 2 years. The panel ofRASSF1A, 3OST2andPRDM14detected 28% (95% CI 11% to 44%) of lung cancer cases within 2 years, with specificity of 90% (95% CI 86% to 94%). Sputum cytology did not detect any lung cancers.ConclusionsIn a lung cancer screening setting with maximum screening interval of 2 years, DNA hypermethylation analysis in sputum may play a role in the detection of preclinical disease, but complementary diagnostic markers are needed to improve sensitivity.
Acute leukaemia and myelodysplastic syndromes with chromosomal rearrangement involving 11q23 locus, but notMLLgene
Authors: Zuo Wenli , Wang Sa A , DiNardo Courtney , Yabe Mariko , Li Shaoying , Medeiros L Jeffrey , Tang Guilin 
Published: August 2016

AimsChromosome 11q23 translocations, resulting inMLL (KMT2A) rearrangement, have been well characterised in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). However, little is known of haematopoietic neoplasms associated with 11q23 translocation but withoutMLLrearrangement (11q23+/MLL−). The aim of this study is to characterise such cases with 11q23+/MLL−.Methods and resultsWe retrospectively searched our database for cases with haematopoietic malignancies with 11q23+/MLL−. We identified nine patients, two with AML, two with B-lymphoblastic leukaemia (B-ALL); two with T-lymphoblastic leukaemia (T-ALL), two with myelodysplastic syndrome (MDS) and one with chronic myelomonocytic leukaemia (CMML). The translocations included t(X;11)(p11.2;q23), t(2;11)(p21;q23), t(6;11)(q27;q23), t(8;9;11)(q13;q13;q23), t(11;11)(p15;q23), t(11;14)(q23;q24) and t(11;15)(q23;q14). Five of six patients with acute leukaemia had received chemotherapy and detection of 11q23 translocation occurred at time of disease relapse. Both patients with MDS and the patient with CMML had 11q23 translocation detected at time of initial diagnosis, all three patients progressed to AML after >1 year on hypomethylating agent therapy. All patients received risk-adapted therapies, including stem cell transplant in five patients. At the last follow-up, eight patients died with a median overall survival of 14 months.Conclusions11q23+/MLL− occurs rarely, involving different partner chromosomes and showing clinical and pathological features and disease subtypes different from those cases withMLLrearrangement. 11q23+/MLL− appears to be associated with clonal evolution/disease progression in acute leukaemia, a high risk for AML progression in MDS/CMML and a high incidence of disease relapse.
Developments in the practice of physician-assisted dying: perceptions of physicians who had experience with complex cases
Authors: Snijdewind Marianne C , van Tol Donald G , Onwuteaka-Philipsen Bregje D , Willems Dick L 
Published: August 2016

BackgroundSince the enactment of the euthanasia law in the Netherlands, there has been a lively public debate on assisted dying that may influence the way patients talk about euthanasia and physician-assisted suicide (EAS) with their physicians and the way physicians experience the practice of EAS.AimTo show what developments physicians see in practice and how they perceive the influence of the public debate on the practice of EAS.MethodsWe conducted a secondary analysis of in-depth interviews with 28 Dutch physicians who had experience with a complex case of EAS. Respondents were recruited both by the network of physicians working for SCEN (Support and Consultation for Euthanasia in the Netherlands) as well as via a national questionnaire, wherein participating physicians could indicate their willingness to be interviewed.ResultsThree themes came up in analysing the interviews. First, the interviewed physicians experienced a change in what (family of) patients would expect from them: from a role as an involved caregiver to being the mere performer of EAS. Second, interviewees said that requests for EAS based on non-medical reasons came up more frequently and wondered if EAS was the right solution for these requests. Last, respondents had the impression that the standards of EAS are shifting and that the boundaries of the EAS regulation were stretched.ConclusionsThe perceived developments could make physicians less willing to consider a request for EAS. Our results also raise questions about the role of physicians and of EAS in society.
Simulation of High-Resolution Precipitable Water Data by a Stochastic Model with a Random Trigger
Authors: Leung Kimberly , Velado Max , Subramanian Aneesh , Zhang Guang J. , Somerville Richard C. J. , Shen Samuel S. P. 
Published: August 2016

We use a stochastic differential equation (SDE) model with a random precipitation trigger for mass balance to simulate the 20 s temporal resolution column precipitable water vapor (PWV) data during the tropical warm pool international cloud experiment (TWP-ICE) period of January 20 to February 15, 2006 at Darwin, Australia. The trigger is determined by an exponential cumulative distribution function, the time step size in the SDE simulation, and a random precipitation indicator uniformly distributed over [0, 1]. Compared with the observed data, the simulations have similar means, extremes, skewness, kurtosis, and overall shapes of probability distribution, and are temporally well synchronized for increasing and decreasing, but have about 20% lower standard deviation. Based on a 1000-day run, the correlations between the model data and the observations in TWP-ICE period were computed in a moving time window of 25 days and show quasi-periodic variations between (−0.675, 0.697). This shows that the results are robust for the stochastic model simulation of the observed PWV data, whose fractal dimension is 1.9, while the dimension of the simulated data is also about 1.9. This agreement and numerous sensitivity experiments form a test on the feasibility of using an SDE model to simulate precipitation processes in more complex climate models.
Accumulation of MDSC and Th17 Cells in Patients with Metastatic Colorectal Cancer Predicts the Efficacy of a FOLFOX–Bevacizumab Drug Treatment Regimen
Authors: Limagne Emeric , Euvrard Romain , Thibaudin Marion , Rébé Cédric , Derangère Valentin , Chevriaux Angélique , Boidot Romain , Végran Frédérique , Bonnefoy Nathalie , Vincent Julie , Bengrine-Lefevre Leila , Ladoire Sylvain , Delmas Dominique , Apetoh Lionel , Ghiringhelli François 
Published: August 2016

Abstract
Host immunity controls the development of colorectal cancer, and chemotherapy used to treat colorectal cancer is likely to recruit the host immune system at some level. Athough preclinical studies have argued that colorectal cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin, exert such effects, their combination as employed in the oncology clinic has not been evaluated. Here, we report the results of prospective immunomonitoring of 25 metastatic colorectal cancer (mCRC) patients treated with a first-line combination regimen of 5-FU, oxaliplatin, and bevacizumab (FOLFOX–bevacizumab), as compared with 20 healthy volunteers. Before this therapy was initiated, T regulatory cells (Treg), Th17, and granulocytic myeloid-derived suppressor cells (gMDSC) were increased significantly in mCRC, but only a high level of gMDSC was associated with a poor prognosis. Chemotherapy modulated the Treg/Th17 balance by decreasing Treg and increasing Th17 cell frequency by 15 days after the start of treatment. Increased Th17 frequency was associated with a poor prognosis. FOLFOX–bevacizumab treatment elicited a decrease in gMDSC in 15 of 25 patients and was associated with a better survival outcome. Notably, the gMDSCs that expressed high levels of PD-L1, CD39, and CD73 exerted a robust immunosuppressive activity, relative to other myeloid cells present in blood, which could be reversed by blocking the CD39/CD73 and PD-1/PD-L1 axes. Our work underscores the critical prognostic impact of early modifications in Th17 and gMDSC frequency in mCRC. Furthermore, it provides a clinical rationale to combine FOLFOX–bevacizumab chemotherapy with inhibitors of ATP ectonucleotidases and/or anti-PD-1/PD-L1 antibodies to more effectively treat this disease. Cancer Res; 76(18); 5241–52. ©2016 AACR.
Cancer-Associated Fibroblasts in Pancreatic Cancer Are Reprogrammed by Tumor-Induced Alterations in Genomic DNA Methylation
Authors: Xiao Qian , Zhou Donger , Rucki Agnieszka A. , Williams Jamila , Zhou Jiaojiao , Mo Guanglan , Murphy Adrian , Fujiwara Kenji , Kleponis Jennifer , Salman Bulent , Wolfgang Christopher L. , Anders Robert A. , Zheng Shu , Jaffee Elizabeth M. , Zheng Lei 
Published: August 2016

Abstract
Stromal fibrosis is a prominent histologic characteristic of pancreatic ductal adenocarcinoma (PDAC), but how stromal fibroblasts are regulated in the tumor microenvironment (TME) to support tumor growth is largely unknown. Here we show that PDAC cells can induce DNA methylation in cancer-associated fibroblasts (CAF). Upon direct contact with PDAC cells, DNA methylation of SOCS1 and other genes is induced in mesenchymal stem cells or in CAF that lack SOCS1 methylation at baseline. Silencing or decitabine treatment to block the DNA methylation enzyme DNMT1 inhibited methylation of SOCS1. In contrast, SOCS1 gene methylation and downregulation in CAF activated STAT3 and induced insulin-like growth factor-1 expression to support PDAC cell growth. Moreover, CAF facilitated methylation-dependent growth of PDAC tumor xenografts in mice. The ability of patient-derived CAF with SOCS1 methylation to promote PDAC growth was more robust than CAF without SOCS1 methylation. Overall, our results reveal how PDAC cells can reprogram CAF to modify tumor–stromal interactions in the TME, which promote malignant growth and progression. Cancer Res; 76(18); 5395–404. ©2016 AACR.