bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does a GLP-1 receptor agonist change glucose tolerance in patients treated with antipsychotic medications? Design of a randomised, double-blinded, placebo-controlled clinical trial
Authors: Larsen Julie Rask , Vedtofte Louise , Holst Jens Juul , Oturai Peter , Kjær Andreas , Corell Christoph U , Vilsbøll Tina , Fink-Jensen Anders 
Published: March 2014

BackgroundMetabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among patients with antipsychotic treatment. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances. Additionally, patients with schizophrenia-spectrum disorders not infrequently consume alcohol. Glucagon-like peptide-1 (GLP-1) has shown to improve glycaemic control and reduce alcohol intake among patients with type 2 diabetes.ObjectivesTo investigate whether the beneficial effects of GLP-1 analogues on glycaemic control and alcohol intake, in patients with type 2 diabetes, can be extended to a population of pre-diabetic psychiatric patients receiving antipsychotic treatment.Methods and analysisTrial design, intervention and participants:The study is a 16-week, double-blinded, randomised, parallel-group, placebo-controlled clinical trial, designed to evaluate the effects of the GLP-1 analogue liraglutide on glycaemic control and alcohol intake compared to placebo in patients who are prediabetic, overweight (body mass index ≥27 kg/m2), diagnosed with a schizophrenia-spectrum disorder and on stable treatment with either clozapine or olanzapine.Outcomes: The primary endpointis the change in glucose tolerance from baseline (measured by area under the curve for the plasma glucose excursion following a 4 h 75 g oral glucose tolerance test) to follow-up at week 16.The secondary endpointsinclude changes of dysglycaemia, body weight, waist circumference, blood pressure, secretion of incretin hormones, insulin sensitivity and β cell function, dual-energy X-ray absorption scan (body composition), lipid profile, liver function and measures of quality of life, daily functioning, severity of the psychiatric disease and alcohol consumption from baseline to follow-up at week 16.Status:Currently recruiting patients.Ethics and disseminationEthical approval has been obtained. Before screening, all patients will be provided oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations.Trial registration numberClinicalTrials.gov:NCT01845259, EudraCT: 2013-000121-31.
Is adequate pain relief and time to analgesia associated with emergency department length of stay? A retrospective study
Authors: Sokoloff Catalina , Daoust Raoul , Paquet Jean , Chauny Jean-Marc 
Published: March 2014

ObjectivesEvaluate the association of adequate analgesia and time to analgesia with emergency department (ED) length of stay (LOS).Setting and DesignPost hoc analysis of real-time archived data.ParticipantsWe included all consecutive ED patients ≥18 years with pain intensity >6 (verbal numerical scale from 0 to 10), assigned to an ED bed, and whose pain was re-evaluated less than 1 h after receiving analgesic treatment.Outcome measuresThe main outcome was ED-LOS in patients who had adequate pain relief (AR=↓50% pain intensity) compared with those who did not have such relief (NR).ResultsA total of 2033 patients (mean age 49.5 years; 51% men) met our inclusion criteria; 58.3% were discharged, and 41.7% were admitted. Among patients discharged or admitted, there was no significant difference in ED-LOS between those with AR (median (25th–75th centile): 9.6 h (6.3–14.8) and 18.2 h (11.6–25.7), respectively) and NR (median (25th–75th centile): 9.6 h (6.6–16.0) and 17.4 h (11.3–26.5), respectively). After controlling for confounding factors, rapid time to analgesia (not AR) was associated with shorter ED-LOS of discharged and admitted patients (p<0.001 and <0.05, respectively). When adjusting for confounding variables, ED-LOS is shortened by 2 h (95% CI 1.1 to 2.8) when delay to receive analgesic is <90 min compared with >90 min for discharged and by 2.3 h (95% CI 0.17 to 4.4) for admitted patients.ConclusionsIn our study, AR was not linked with short ED-LOS. However, rapid administration of analgesia was associated with short ED-LOS.
The Champions League - Improving the quality of in-patient antibiotic prescription in Trauma and Orthopaedics
Authors: Evans Jonathan , Saxby Clair , Armstrong Alexander 
Published: March 2014

AbstractA Trust level audit demonstrated that the trauma and orthopaedic department did not reach its own standards in adhering to Trust antibiotic prescribing guidelines. Junior doctors are the main prescribers of antibiotics during inpatient stays. Local policy states that for all inpatients on antibiotics, the start date, duration, and indication for antibiotics must be documented on the drug card.Each patient drug card was reviewed by the department pharmacist and it was recorded whether the documentation was in line with Trust policy. A monthly league table, coined 'The Champions League', was created. It was published monthly and displayed in the doctors' office and other clinical areas to highlight which doctors had or had not adhered to the prescribing guidelines.In August 2012 the monthly audit for the trauma and orthopaedic department included 74 patients. The total number of antibiotic courses prescribed was 28; of these courses only 15 (53.5%) had an indication documented and 15 (53.5%) had a review/stop date documented.In December 2012, after two published league tables, 61 patients were reviewed. A total of 19 antibiotic courses were prescribed; 18 (94.7%) had the indication documented and 16 (84.2%) had the review/stop date documented.The standards of prescribing improved within the department and good prescribing practice became ingrained into each doctor's practice. The league table proved to be a novel tool that helped to raise the profile of antibiotic prescribing and change doctor prescribing habits. It created a competitive spirit within the department which improved morale. Doctors responded positively to feedback if they were not achieving the desirable standards, and enjoyed the challenge of improving the standard of prescribing.
Classifying emergency 30-day readmissions in England using routine hospital data 2004–2010: what is the scope for reduction?
Authors: Blunt Ian , Bardsley Martin , Grove Amy , Clarke Aileen 
Published: March 2014

BackgroundMany health systems across the globe have introduced arrangements to deny payment for patients readmitted to hospital as an emergency. The purpose of this study was to develop an exploratory categorisation based on likely causes of readmission, and then to assess the prevalence of these different types.MethodsRetrospective analysis of 82 million routinely collected National Health Service hospital records in England (2004–2010) was undertaken using anonymised linkage of records at person-level. Numbers of 30-day readmissions were calculated. Exploratory categorisation of readmissions was applied using simple rules relating to International Classification of Diseases (ICD) diagnostic codes for both admission and readmission.ResultsThere were 5 804 472 emergency 30-day readmissions over a 6-year period, equivalent to 7.0% of hospital discharges. Readmissions were grouped into hierarchically exclusive categories: potentially preventable readmission (1 739 519 (30.0% of readmissions)); anticipated but unpredictable readmission (patients with chronic disease or likely to need long-term care; 1 141 987 (19.7%)); preference-related readmission (53 718 (0.9%)); artefact of data collection (16 062 (0.3%)); readmission as a result of accident, coincidence or related to a different body system (1 101 818 (19.0%)); broadly related readmission (readmission related to the same body system (1 751 368 (30.2%)).ConclusionsIn this exploratory categorisation, a large minority of emergency readmissions (eg, those that are potentially preventable or due to data artefacts) fell into groups potentially amenable to immediate reduction. For other categories, a hospital's ability to reduce emergency readmission is less clear. Reduction strategies and payment incentives must be carefully tailored to achieve stated aims.
Endovascular treatment of unruptured wide-necked intracranial aneurysms: comparison of dual microcatheter technique and stent-assisted coil embolization
Authors: Starke Robert M , Durst Christopher R , Evans Avery , Ding Dale , Raper Daniel M S , Jensen Mary E , Crowley Richard W , Liu Kenneth C 
Published: March 2014

BackgroundEndovascular treatment of wide-necked aneurysms is challenging. Stent-assisted coiling (SAC) is associated with increased complications and requires dual antiplatelet therapy.ObjectiveTo compare treatment of unruptured, wide-necked aneurysms with a dual-microcatheter technique (DMT) versus SAC.MethodsBetween 2006 and 2011, 100 patients with unruptured wide-necked intracranial aneurysms were treated with DMT and 160 with SAC. Over time there was a significant decrease in the use of SAC and a corresponding increase in DMT. The investigators matched 60 patients treated with DMT blinded to outcome in a 1:2 fashion based on maximal aneurysm dome diameter with 120 patients treated with SAC. Outcomes were determined with conditional (matched) multivariate analysis.ResultsThere were no significant differences in patient or aneurysm characteristics between cohorts, including aneurysm diameter, neck width, or volume. Overall packing density and coil volume achieved was not significantly different between cohorts. There were higher rates of overall complications in those receiving SAC (19.2%) compared with DMT (5.0%; p=0.012), but no significant difference in major complications (8.3% vs 1.7%, respectively; p=0.103). At a mean follow-up of 27.0±18.9 months, rates of retreatment did not differ between DMT (15.1%) and SAC (17.7%). Delayed in-stent stenosis occurred in five patients and in-stent thrombosis in four patients treated with SAC. There was no difference in favorable functional outcome (modified Rankin score 0–2) between those treated with DMT (90.6%) compared with SAC (91.2%).ConclusionsDMT and SAC are effective endovascular approaches for unruptured, wide-necked aneurysms; however, DMT may result in less morbidity. Further long-term studies are necessary to determine the optimal indications for these treatment options.
A Surprising Cross-Species Conservation in the Genomic Landscape of Mouse and Human Oral Cancer Identifies a Transcriptional Signature Predicting Metastatic Disease
Authors: Onken Michael D. , Winkler Ashley E. , Kanchi Krishna-Latha , Chalivendra Varun , Law Jonathan H. , Rickert Charles G. , Kallogjeri Dorina , Judd Nancy P. , Dunn Gavin P. , Piccirillo Jay F. , Lewis James S. , Mardis Elaine R. , Uppaluri Ravindra 
Published: March 2014

Abstract
Purpose: Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance.
Experimental Design: Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes, and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature, and we assessed its representation in four independent human datasets comprising 324 patients using weighted voting and gene set enrichment analysis. Kaplan–Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A quantitative real-time PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy.
Results: NGS revealed conservation of human driver pathway mutations in mouse OSCC, including in Trp53, mitogen-activated protein kinase, phosphoinositide 3-kinase, NOTCH, JAK/STAT, and Fat1-4. Moreover, comparative analysis between The Cancer Genome Atlas and mouse samples defined AKAP9, MED12L, and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in four independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified patients with OSCC with a 93.5% accuracy.
Conclusions: These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. Clin Cancer Res; 20(11); 2873–84. ©2014 AACR.
Targeting Inhibitors of the Tumor Suppressor PP2A for the Treatment of Pancreatic Cancer
Authors: Farrell Amy S. , Allen-Petersen Brittany , Daniel Colin J. , Wang Xiaoyan , Wang Zhiping , Rodriguez Sarah , Impey Soren , Oddo Jessica , Vitek Michael P. , Lopez Charles , Christensen Dale J. , Sheppard Brett , Sears Rosalie C. 
Published: March 2014

Abstract
Pancreatic cancer is a deadly disease that is usually diagnosed in the advanced stages when few effective therapies are available. Given the aggressive clinical course of this disease and lack of good treatment options, the development of new therapeutic agents for the treatment of pancreatic cancer is of the upmost importance. Several pathways that have shown to contribute to pancreatic cancer progression are negatively regulated by the tumor suppressor protein phosphatase 2A (PP2A). Here, the endogenous inhibitors of PP2A, SET (also known as I2PP2A) and cancerous inhibitor of PP2A (CIP2A), were shown to be overexpressed in human pancreatic cancer, contributing to decreased PP2A activity and overexpression and stabilization of the oncoprotein c-Myc, a key PP2A target. Knockdown of SET or CIP2A increases PP2A activity, increases c-Myc degradation, and decreases the tumorigenic potential of pancreatic cancer cell lines both in vitro and in vivo. Moreover, treatment with a novel SET inhibitor, OP449, pharmacologically recapitulates the phenotypes and significantly reduces proliferation and tumorigenic potential of several pancreatic cancer cell lines, with an accompanying attenuation of cell growth and survival signaling. Furthermore, primary cells from patients with pancreatic cancer were sensitive to OP449 treatment, indicating that PP2A-regulated pathways are highly relevant to this deadly disease.
Implications: The PP2A inhibitors SET and CIP2A are overexpressed in human pancreatic cancer and are important for pancreatic cancer cell growth and transformation; thus, antagonizing SET and/or CIP2A may be an innovative approach for the treatment of human pancreatic cancer. Mol Cancer Res; 12(6); 924–39. ©2014 AACR.
Determination of the Longest Intrapatient Left Ventricular Electrical Delay May Predict Acute Hemodynamic Improvement in Patients After Cardiac Resynchronization Therapy
Authors: Zanon Francesco , Baracca Enrico , Pastore Gianni , Fraccaro Chiara , Roncon Loris , Aggio Silvio , Noventa Franco , Mazza Alberto , Prinzen Frits 
Published: March 2014

Background—
One of the reasons for patient nonresponse to cardiac resynchronization therapy is a suboptimal left ventricular (LV) pacing site. LV electric delay (Q-LV interval) has been indicated as a prognostic parameter of cardiac resynchronization therapy response. This study evaluates the LV delay for the optimization of the LV pacing site.

Methods and Results—

Thirty-two consecutive patients (23 men; mean age, 71±11 years; LV ejection fraction, 30±6%; 18 with ischemic cardiomyopathy; QRS, 181±25 ms; all mean±SD) underwent cardiac resynchronization therapy device implantation. All available tributary veins of the coronary sinus were tested, and the Q-LV interval was measured at each pacing site. The hemodynamic effects of pacing at different sites were evaluated by invasive measurement of LV d
P
/d
t
max
at baseline and during pacing. Overall, 2.9±0.8 different veins and 6.4±2.3 pacing sites were tested. In 31 of 32 (96.8%) patients, the highest LV d
P
/d
t
max
coincided with the maximum Q-LV interval. Q-LV interval correlated with the increase in LV d
P
/d
t
max
in all patients at each site (AR1 ρ=0.98;
P
<0.001). A Q-LV value >95 ms corresponded to a >10% in LV d
P
/d
t
max
. An inverse correlation between paced QRS duration and improvement in LV d
P
/d
t
max
was seen in 24 patients (75%).

Conclusions—

Pacing the LV at the latest activated site is highly predictive of the maximum increase in contractility, expressed as LV d
P
/d
t
max
. A positive correlation between Q-LV interval and hemodynamic improvement was found in all patients at every pacing site, a value of 95 ms corresponding to an increase in LV d
P
/d
t
max
of ≥10%.
Effects of Extracranial–Intracranial Bypass for Patients With Hemorrhagic Moyamoya Disease
Authors: Miyamoto Susumu , Yoshimoto Takashi , Hashimoto Nobuo , Okada Yasushi , Tsuji Ichiro , Tominaga Teiji , Nakagawara Jyoji , Takahashi Jun C. , Yamada Keisuke , Tomata Yasutake , Fukui Tsuguya , Fukuuchi Yasuo , Ohmoto Takashi , Kuwabara Yasuo , Nagata Izumi , Ono Junichi , Machida Toshio , Sakakibara Ryuji , Yamane Kanji , Okita Shinji , Iwama Toru , Kaku Yasuhiko , Saito Nobuhito , Fukuyama Hidenao , Houkin Kiyohiro , Kuroda Satoshi , Yabe Ichiro , Moriwaka Fumio , Ogawa Akira , Ogasawara Kuniaki , Yoshida Kenji , Fujii Kiyotaka , Yamada Masaru , Sato Kimitoshi , Akutsu Tsugio , Yamagata Sen , Takeuchi Shigekazu , Hayashi Kentaro , Horie Nobutaka , Yamada Kazuo , Osato Toshiaki , Watanabe Toshiichi , Honjo Kaori , Sako Kazuya , Nakase Hiroyuki , Kawaguchi Shoichiro , Nisimura Fumihiko , Yamao Junichi , Naritomi Hiroaki , Inoue Tooru , Abe Hiroshi , Suzuki Akifumi , Ishikawa Tatsuya , Akiyama Yoshinori , Suenaga Toshihiko , Fujimura Miki , Nagahiro Shinji , Uno Masaaki , Nishi Kyoko , Satomi Junichiro , Okada Yoshikazu , Kawashima Akiji , Yamaguchi Kohji , Tsutsumi Yukiko 
Published: March 2014

Background and Purpose—
About one half of those who develop adult-onset moyamoya disease experience intracranial hemorrhage. Despite the extremely high frequency of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not been established. The purpose of this study is to determine whether extracranial–intracranial bypass can reduce incidence of rebleeding and improve patient prognosis.

Methods—
This study was a multicentered, prospective, randomized, controlled trial conducted by 22 institutes in Japan. Adult patients with moyamoya disease who had experienced intracranial hemorrhage within the preceding year were given either conservative care or bilateral extracranial–intracranial direct bypass and were observed for 5 years. Primary and secondary end points were defined as all adverse events and rebleeding attacks, respectively.

Results—

Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events causing significant morbidity were observed in 6 patients in the surgical group (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan–Meier survival analysis revealed significant differences between the 2 groups (3.2%/y versus 8.2%/y;
P
=0.048). The hazard ratio of the surgical group calculated by Cox regression analysis was 0.391 (95% confidence interval, 0.148–1.029). Rebleeding attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the nonsurgical group (31.6%), significantly different in the Kaplan–Meier survival analysis (2.7%/y versus 7.6%/y;
P
=0.042). The hazard ratio of the surgical group was 0.355 (95% confidence interval, 0.125–1.009).

Conclusions—
Although statistically marginal, Kaplan–Meier analysis revealed the significant difference between surgical and nonsurgical group, suggesting the preventive effect of direct bypass against rebleeding.

Clinical Trial Registration—

URL:
http://www.umin.ac.jp/ctr/index.htm
. Unique identifier: C000000166.
Neurophysiological Signals of Ignoring and Attending Are Separable and Related to Performance during Sustained Intersensory Attention
Authors: Lenartowicz Agatha , Simpson Gregory V. , Haber Catherine M. , Cohen Mark S. 
Published: March 2014

Abstract
The ability to attend to an input selectively while ignoring distracting sensations is thought to depend on the coordination of two processes: enhancement of target signals and attenuation of distractor signals. This implies that attending and ignoring may be dissociable neural processes and that they make separable contributions to behavioral outcomes of attention. In this study, we tested these hypotheses in the context of sustained attention by measuring neurophysiological responses to attended and ignored stimuli in a noncued, continuous, audiovisual selective attention task. We compared these against responses during a passive control to quantify effects of attending and ignoring separately. In both sensory modalities, responses to ignored stimuli were attenuated relative to a passive control, whereas responses to attended stimuli were enhanced. The scalp topographies and brain activations of these modulatory effects were consistent with the sensory regions that process each modality. They also included parietal and prefrontal activations that suggest these effects arise from interactions between top–down and sensory cortices. Most importantly, we found that both attending and ignoring processes contributed to task accuracy and that these effects were not correlated—suggesting unique neural trajectories. This conclusion was supported by the novel observation that attending and ignoring differed in timing and in active cortical regions. The data provide direct evidence for the separable contributions of attending and ignoring to behavioral outcomes of attention control during sustained intersensory attention.
ERPs Recorded during Early Second Language Exposure Predict Syntactic Learning
Authors: Batterink Laura , Neville Helen J. 
Published: March 2014

Abstract
Millions of adults worldwide are faced with the task of learning a second language (L2). Understanding the neural mechanisms that support this learning process is an important area of scientific inquiry. However, most previous studies on the neural mechanisms underlying L2 acquisition have focused on characterizing the results of learning, relying upon end-state outcome measures in which learning is assessed after it has occurred, rather than on the learning process itself. In this study, we adopted a novel and more direct approach to investigate neural mechanisms engaged during L2 learning, in which we recorded ERPs from beginning adult learners as they were exposed to an unfamiliar L2 for the first time. Learners' proficiency in the L2 was then assessed behaviorally using a grammaticality judgment task, and ERP data acquired during initial L2 exposure were sorted as a function of performance on this task. High-proficiency learners showed a larger N100 effect to open-class content words compared with closed-class function words, whereas low-proficiency learners did not show a significant N100 difference between open- and closed-class words. In contrast, amplitude of the N400 word category effect correlated with learners' L2 comprehension, rather than predicting syntactic learning. Taken together, these results indicate that learners who spontaneously direct greater attention to open- rather than closed-class words when processing L2 input show better syntactic learning, suggesting a link between selective attention to open-class content words and acquisition of basic morphosyntactic rules. These findings highlight the importance of selective attention mechanisms for L2 acquisition.