bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk-adjusted survival for adults following in-hospital cardiac arrest by day of week and time of day: observational cohort study
Authors: Robinson Emily J , Smith Gary B , Power Geraldine S , Harrison David A , Nolan Jerry , Soar Jasmeet , Spearpoint Ken , Gwinnutt Carl , Rowan Kathryn M 
Published: January 2016

BackgroundInternationally, hospital survival is lower for patients admitted at weekends and at night. Data from the UK National Cardiac Arrest Audit (NCAA) indicate that crude hospital survival was worse after in-hospital cardiac arrest (IHCA) at night versus day, and at weekends versus weekdays, despite similar frequency of events.ObjectiveTo describe IHCA demographics during three day/time periods—weekday daytime (Monday to Friday, 08:00 to 19:59), weekend daytime (Saturday and Sunday, 08:00 to 19:59) and night-time (Monday to Sunday, 20:00 to 07:59)—and to compare the associated rates of return of spontaneous circulation (ROSC) for >20 min (ROSC>20 min) and survival to hospital discharge, adjusted for risk using previously developed NCAA risk models. To consider whether any observed difference could be attributed to differences in the case mix of patients resident in hospital and/or the administered care.MethodsWe performed a prospectively defined analysis of NCAA data from 27 700 patients aged ≥16 years receiving chest compressions and/or defibrillation and attended by a hospital-based resuscitation team in response to a resuscitation (2222) call in 146 UK acute hospitals.ResultsRisk-adjusted outcomes (OR (95% CI)) were worse (p<0.001) for both weekend daytime (ROSC>20 min 0.88 (0.81 to 0.95); hospital survival 0.72 (0.64 to 0.80)), and night-time (ROSC>20 min 0.72 (0.68 to 0.76); hospital survival 0.58 (0.54 to 0.63)) compared with weekday daytime. The effects were stronger for non-shockable than shockable rhythms, but there was no significant interaction between day/time of arrest and age, or day/time of arrest and arrest location. While many daytime IHCAs involved procedures, restricting the analyses to IHCAs in medical admissions with an arrest location of ward produced results that are broadly in line with the primary analyses.ConclusionsIHCAs attended by the hospital-based resuscitation team during nights and weekends have substantially worse outcomes than during weekday daytimes. Organisational or care differences at night and weekends, rather than patient case mix, appear to be responsible.
From the closest observers of patient care: a thematic analysis of online narrative reviews of hospitals
Authors: Bardach Naomi S , Lyndon Audrey , Asteria-Peñaloza Renée , Goldman L Elizabeth , Lin Grace A , Dudley R Adams 
Published: January 2016

ObjectivePatient-centred care has become a priority in many countries. It is unknown whether current tools capture aspects of care patients and their surrogates consider important. We investigated whether online narrative reviews from patients and surrogates reflect domains in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) and we described additional potential domains.DesignWe used thematic analysis to assess online narrative reviews for reference to HCAHPS domains and salient non-HCAHPS domains and compared results by reviewer type (patient vs surrogate).SettingWe identified hospitals for review from the American Hospital Association database using a stratified random sampling approach. This approach ensured inclusion of reviews of a diverse set of hospitals. We searched online in February 2013 for narrative reviews from any source for each hospital.ParticipantsWe included up to two narrative reviews for each hospital. Exclusions: Outpatient or emergency department reviews, reviews from self-identified hospital employees, or reviews of <10 words.Results50.0% (n=122) of reviews (N=244) were from patients and 38.1% (n=93) from friends or family members. Only 57.0% (n=139) of reviews mentioned any HCAHPS domain. Additional salient domains were: Financing, including unexpected out-of-pocket costs and difficult interactions with billing departments; system-centred care; and perceptions of safety. These domains were mentioned in 51.2% (n=125) of reviews. Friends and family members commented on perceptions of safety more frequently than patients.ConclusionsA substantial proportion of consumer reviews do not mention HCAHPS domains. Surrogates appear to observe care differently than patients, particularly around safety.
A ‘paperless’ wall-mounted surgical safety checklist with migrated leadership can improve compliance and team engagement
Authors: Ong Aaron Pin Chien , Devcich Daniel A , Hannam Jacqueline , Lee Tracey , Merry Alan F , Mitchell Simon J 
Published: January 2016

BackgroundOutcome benefits of using the WHO Surgical Safety Checklist rely on compliance with checklist administration.ObjectiveTo evaluate engagement of operating room (OR) subteams (anaesthesia, surgery and nursing), and compliance with administering checklist domains (Sign In, Time Out and Sign Out) and checklist items, after introducing a wall-mounted paperless checklist with migration of process leadership (Sign In, Time Out and Sign Out led by anaesthesia, surgery and nursing, respectively).MethodsThis was a pre-post observational study in which 261 checklist domains in 111 operations were observed 2 months after changing the checklist administration paradigm. Compliance with administration of the checklist domains and individual checklist items was recorded, as was the number of OR subteams engaged. Comparison was made with 2013 data from the same OR suite prior to the paradigm change.ResultsData are presented as 2013 versus the present study. The Sign In, Time Out and Sign Out domains were administered in 96% vs 98% (p=0.69), 99% vs 99% (p=1.00) and 22% vs 84% (p<0.001) of cases, respectively. The percentage of relevant checklist items administered in each domain was 60% vs 92%, 84 vs 93% and 80% vs 99%, respectively (p<0.001 for all comparisons). Two-subteam (or better) engagement at Sign In (surgeons usually absent) was 40% vs 94% of cases. Three-subteam (or all staff present) engagement at Time Out and Sign Out was 15% vs 92% and 9% vs 25% of cases, respectively (p<0.001 for all comparisons).ConclusionsImprovements in team engagement and compliance with administering checklist items followed introduction of migrated leadership of checklist administration and a wall-mounted checklist. This paradigm change was relatively simple and inexpensive.
The ‘pit-crew’ model for improving door-to-needle times in endovascular stroke therapy: a Six-Sigma project
Authors: Rai Ansaar T , Smith Matthew S , Boo SoHyun , Tarabishy Abdul R , Hobbs Gerald R , Carpenter Jeffrey S 
Published: January 2016

BackgroundDelays in delivering endovascular stroke therapy adversely affect outcomes. Time-sensitive treatments such as stroke interventions benefit from methodically developed protocols. Clearly defined roles in these protocols allow for parallel processing of tasks, resulting in consistent delivery of care.ObjectiveTo present the outcomes of a quality-improvement (QI) process directed at reducing stroke treatment times in a tertiary level academic medical center.MethodsA Six-Sigma-based QI process was developed over a 3-month period. After an initial analysis, procedures were implemented and fine-tuned to identify and address rate-limiting steps in the endovascular care pathway. Prospectively recorded treatment times were then compared in two groups of patients who were treated ‘before’ (n=64) or ‘after’ (n=30) the QI process. Three time intervals were measured: emergency room (ER) to arrival for CT scan (ER–CT), CT scan to interventional laboratory arrival (CT–Lab), and interventional laboratory arrival to groin puncture (Lab–puncture).ResultsThe ER–CT time was 40 (±29) min in the ‘before’ and 26 (±15) min in the ‘after’ group (p=0.008). The CT–Lab time was 87 (±47) min in the ‘before’ and 51 (±33) min in the ‘after’ group (p=0.0002). The Lab–puncture time was 24 (±11) min in the ‘before’ and 15 (±4) min in the ‘after’ group (p<0.0001). The overall ER–arrival to groin-puncture time was reduced from 2 h, 31 min (±51) min in the ‘before’ to 1 h, 33 min (±37) min in the ‘after’ group, (p<0.0001). The improved times were seen for both working hours and off-hours interventions.ConclusionsA protocol-driven process can significantly improve efficiency of care in time-sensitive stroke interventions.
IL6 Trans-signaling Promotes KRAS-Driven Lung Carcinogenesis
Authors: Brooks Gavin D. , McLeod Louise , Alhayyani Sultan , Miller Alistair , Russell Prudence A. , Ferlin Walter , Rose-John Stefan , Ruwanpura Saleela , Jenkins Brendan J. 
Published: January 2016

Abstract
Oncogenic KRAS mutations occur frequently in lung adenocarcinoma. The signaling pathways activated by IL6 promote Kras-driven lung tumorigenesis, but the basis for this cooperation is uncertain. In this study, we used the gp130F/F (Il6st) knock-in mouse model to examine the pathogenic contribution of hyperactivation of the STAT3 arm of IL6 signaling on KRAS-driven lung tumorigenesis. Malignant growths in the gp130F/F:KrasG12D model displayed features of atypical adenomatous hyperplasia, adenocarcinoma in situ, and invasive adenocarcinoma throughout the lung, as compared with parental KrasG12D mice, where STAT3 was not hyperactivated. Among IL6 family cytokines, only IL6 was upregulated in the lung. Accordingly, normalization of pulmonary STAT3 activity, by genetic ablation of either Il6 or Stat3, suppressed the extent of lung cancer in the model. Mechanistic investigations revealed elevation in the lung of soluble IL6 receptor (sIL6R), the key driver of IL6 trans-signaling, and blocking this mechanism via interventions with an anti-IL6R antibody or the inhibitor sgp130Fc ameliorated lung cancer pathogenesis. Clinically, expression of IL6 and sIL6R was increased significantly in human specimens of lung adenocarcinoma or patient serum. Our results offer a preclinical rationale to clinically evaluate IL6 trans-signaling as a therapeutic target for the treatment of KRAS-driven lung adenocarcinoma. Cancer Res; 76(4); 866–76. ©2016 AACR.
Development of an enzyme-linked immunosorbent assay for thrombospondin-1 and comparison of human plasma and serum concentrations
Authors: Barclay Johanna L , Keshvari Sahar , Whitehead Jonathan P , Inder Warrick J 
Published: January 2016

Background Thrombospondin-1 (TSP-1) is a circulating matricellular glycoprotein produced from many cell types including platelets. Currently TSP-1 is measured in either plasma or serum, using expensive commercial assays. Aim To develop and validate a cost effective in-house immunoassay for human TSP-1 suitable for quantitating levels from both plasma and serum. Methods An in-house enzyme-linked immunosorbent assay (ELISA) was developed for the measurement of human TSP-1. Sixteen healthy volunteers (8 male and 8 female), mean age 29 years (range 21–49), body mass index (BMI) mean 23.3 kg/m2 (range 17.3–26.7) had non-fasted venous blood sampled at 0800 h and 1600 h for both plasma and serum TSP-1. Results The assay limit of quantitation was 7.8  μg/L, inter assay CV was 17–31%, intra assay CV was 3–4% for plasma and <9% for serum. Plasma TSP-1 ranged from 133 to 478  μg/L (mean concentration 290  μg/L) in normal volunteers. Serum TSP-1 was approximately 100-fold higher, ranging from 13,700 to 44,400  μg/L (mean concentration 257,00  μg/L). There was no correlation between plasma and serum TSP-1. Conclusions TSP-1 can be readily measured in human plasma using ELISA. Serum concentrations are 100-fold higher, reflecting documented TSP-1 release by platelets, and does not provide a meaningful measure of circulating concentrations.
1-Adamantylamine a simple urine marker for screening for third generation adamantyl-type synthetic cannabinoids by ultra-performance liquid chromatography tandem mass spectrometry
Authors: Ford Loretta T , Berg Jonathan D 
Published: January 2016

Background Synthetic cannabinoids (NOIDS) are novel psychotropic drugs (NPS) currently freely sold in the United Kingdom as ‘research chemicals’. Detection of NOIDS use is not available in current routine methods. Here we describe a marker which helps determine which patients have used these substances. Methods In a test case, ultra-performance liquid chromatography mass spectrometry (UPLC-Tof) was used to screen the legal high Herbal Haze II, the contents of hand-rolled cigarettes and five patient samples for NOIDS and their metabolites. Results Analysis of legal high Herbal Haze II and cigarettes identified the third generation adamantyl-type NOIDS N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), 5F-AKB-48 and N-adamantyl-1-fluoropentylindole-3-carboxamide (STS-135). Out of 18 potential metabolites, 1-adamantylamine (C10H17N) was detected in all five urine samples. This adamantyl-type NOID marker was incorporated into our routine LC-MS/MS urine screen. Out of 14,436 random urine samples screened over eight months, 296 (2.05%) tested positive for the adamantyl-type NOID marker. Conclusion We have discovered a urine marker for identifying patients smoking legal high products containing the third generation adamantyl-type NOIDS such as AKB-48 and its fluoropentyl analogue 5F-AKB-48, which are among the most popular NOIDS currently available in legal high products sold in UK. This marker can be incorporated into routine LC-MS/MS drug screening alongside classic drugs of abuse. Positive detection rates for this new legal high marker are greater than for established classic drugs that are routinely screened such as amphetamine. This work highlights the need for a flexible toxicology screening service capable of adapting to changes in drug use such as the growing popularity of legal highs/NPS.
Molecular testing for familial hypercholesterolaemia-associated mutations in a UK-based cohort: development of an NGS-based method and comparison with multiplex polymerase chain reaction and oligonucleotide arrays
Authors: Reiman Anne , Pandey Sarojini , Lloyd Kate L , Dyer Nigel , Khan Mike , Crockard Martin , Latten Mark J , Watson Tracey L , Cree Ian A , Grammatopoulos Dimitris K 
Published: January 2016

Background Detection of disease-associated mutations in patients with familial hypercholesterolaemia is crucial for early interventions to reduce risk of cardiovascular disease. Screening for these mutations represents a methodological challenge since more than 1200 different causal mutations in the low-density lipoprotein receptor has been identified. A number of methodological approaches have been developed for screening by clinical diagnostic laboratories. Methods Using primers targeting, the low-density lipoprotein receptor, apolipoprotein B, and proprotein convertase subtilisin/kexin type 9, we developed a novel Ion Torrent-based targeted re-sequencing method. We validated this in a West Midlands-UK small cohort of 58 patients screened in parallel with other mutation-targeting methods, such as multiplex polymerase chain reaction (Elucigene FH20), oligonucleotide arrays (Randox familial hypercholesterolaemia array) or the Illumina next-generation sequencing platform. Results In this small cohort, the next-generation sequencing method achieved excellent analytical performance characteristics and showed 100% and 89% concordance with the Randox array and the Elucigene FH20 assay. Investigation of the discrepant results identified two cases of mutation misclassification of the Elucigene FH20 multiplex polymerase chain reaction assay. A number of novel mutations not previously reported were also identified by the next-generation sequencing method. Conclusions Ion Torrent-based next-generation sequencing can deliver a suitable alternative for the molecular investigation of familial hypercholesterolaemia patients, especially when comprehensive mutation screening for rare or unknown mutations is required.
Becoming Brigadistas: Jewish Volunteers from Palestine in the Spanish Civil War
Authors: Rein Raanan , Ofer Inbal 
Published: January 2016

Nearly two hundred men and women left Mandatory Palestine between the years 1936–1938 in order to defend the Second Spanish Republic. Despite the expressions of solidarity with the Spanish Republic, most of the political parties in the Jewish Yishuv were against sending youth from Palestine to join the International Brigades. The goal of strengthening the Jewish presence in Palestine was given priority over and above international solidarity or the anti-Fascist struggle. Therefore, most of the volunteers were Jewish members of the Palestine Communist Party. This article relies on autobiographical writings, individual testimonies and personal correspondence, analysed here for the first time. It is here that the private voices of the Jewish men and women who left Palestine in order to fight against the nationalist rebellion in Spain ring more clearly. The paper examines the history of these Jewish volunteers, their motivations, and the process that they went through from the time they left Palestine until they became active members of the International Brigades. As Communists, most volunteers who left Palestine to fight in Spain tended to emphasize the international solidarity of the working class and similar universalistic motivations. The idea of affirming their Jewish identity was alien to them. Reading their letters and testimonies, however, it becomes clear that their ethnic identity as Jews was certainly a key factor in their decision to risk their lives in the Spanish fratricide.
The development of ethical guidelines for nurses’ collegiality using the Delphi method
Authors: Kangasniemi Mari , Arala Katariina , Becker Eve , Suutarla Anna , Haapa Toni , Korhonen Anne 
Published: January 2016

Background: Nurses’ collegiality is topical because patient care is complicated, requiring shared knowledge and working methods. Nurses’ collaboration has been supported by a number of different working models, but there has been less focus on ethics. Aim: This study aimed to develop nurses’ collegiality guidelines using the Delphi method. Method: Two online panels of Finnish experts, with 35 and 40 members, used the four-step Delphi method in December 2013 and January 2014. They reformulated the items of nurses’ collegiality identified by the literature and rated based on validity and importance. Content analysis and descriptive statistical methods were used to analyze the data, and the nurses’ collegiality guidelines were formulated. Ethical considerations: Organizational approval was received, and an informed consent was obtained from all participants. Information about the voluntary nature of participation was provided. Results: During the first Delphi panel round, a number of items were reformulated and added, resulting in 32 reformulated items. As a result of the second round, 8 of the 32 items scored an agreement rate of more than 75%, with the most rated item being collegiality means that professionals respect each other. The item with second highest rating was collegiality has a common objective: what is best for patients, followed by the third highest which was professional ethics is the basis of collegiality. Conclusion: Nurses’ collegiality and its content are well recognized in clinical practice but seldom studied. Collegiality can be supported by guidelines, and nurses working in clinical practice, together with teachers and managers, have shared responsibilities to support and develop it. More research in different nursing environments is needed to improve understanding of the content and practice of nursing collegiality.
White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis
Authors: Meijer Kim A , Muhlert Nils , Cercignani Mara , Sethi Varun , Ron Maria A , Thompson Alan J , Miller David H , Chard Declan , Geurts Jeroen JG , Ciccarelli Olga 
Published: January 2016

Background: While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. Objective: The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Methods: Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). Results: A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance ( R2 = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Conclusion: Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients.
MS arising during Tocilizumab therapy for rheumatoid arthritis
Authors: Beauchemin Philippe , Carruthers Robert 
Published: January 2016

Background: Interleukin-6 (IL6) blockage is a treatment strategy used in many inflammatory conditions. Trials in Neuromyelitis Optica Spectrum Disorder (NMOSD) are ongoing. Secondary auto-immunity affecting the central nervous system (CNS) is well described with some biologic agents, mainly tumor necrosis factor (TNF)-alpha inhibitors. These treatments can also aggravate patients with known multiple sclerosis (MS). Objectives: To describe a case of a patient who developed MS using another biologic, IL6 receptor antibody Tocilizumab. Results: A 48-year-old woman developed MS while on treatment with Tocilizumab for Rheumatoid Arthritis (RA). This is the first published report of this association. It has obvious implications for NMOSD patients receiving anti-IL6 therapy. Development of new white matter lesions suggestive of MS in a patient treated with anti-IL6 therapy might represent an important complication of therapy. Conclusion: This case illustrates that Tocilizumab might cause secondary auto-immunity in CNS. It is important to be aware of this potential complication as anti-IL6 therapy might become an option for the treatment NMOSD.