bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive care unit admission protocol controlled by intensivists can reduce transfer delays from the emergency department in critically ill patients
Authors: Kim Ji Eun , Lee Seul , Jeong Jinwoo , Lee Dong Hyun , Jeong Jin-Heon 
Published: July 2018

Background: Delayed transfer of patients from the emergency department to the intensive care unit is associated with adverse clinical outcomes. Critically ill patients with delayed admission to the intensive care unit had higher in-hospital mortality and increased hospital length of stay. Objectives: We investigated the effects of an intensive care unit admission protocol controlled by intensivists on the emergency department length of stay among critically ill patients. Methods: We designed the intensive care unit admission protocol to reduce the emergency department length of stay in critically ill patients. Full-time intensivists determined intensive care unit admission priorities based on the severity of illness. Data were gathered from patients who were admitted from the emergency department to the intensive care unit between 1 April 2016 and 30 November 2016. We retrospectively analyzed the clinical data and compared the emergency department length of stay between patients admitted from the emergency department to the intensive care unit before and after intervention. Results: We included 292 patients, 120 and 172 were admitted before and after application of the intensive care unit admission protocol, respectively. The demographic characteristics did not differ significantly between the groups. After intervention, the overall emergency department length of stay decreased significantly from 1045.5 (425.3–1665.3) min to 392.0 (279.3–686.8) min (p < 0.001). Intensive care unit length of stay also significantly decreased from 6.0 (4.0–11.8) days to 5.0 (3.0–10.0) days (p = 0.015). Conclusion: Our findings suggest that introduction of the intensive care unit admission protocol controlled by intensivists successfully decreased the emergency department length of stay and intensive care unit length of stay among critically ill patients at our institution.
Short 2-H in Situ Trauma Team Simulation Training Effectively Improves Non-Technical Skills of Hospital Trauma Teams
Authors: Rosqvist E. , Lauritsalo S. , Paloneva J. 
Published: July 2018

Background and Aims: As conducting the regular trauma team simulation training is expensive and time-consuming, its effects must be explored. The objective was to evaluate the efficacy of a structured 2-h in situ multiprofessional trauma team simulation training course on non-technical skills. Materials and Methods: This prospective study comprised 90 trauma teams with 430 participants. The structured, 2-h course consisted of an introductory lecture and two different simulations with debriefings. Data were collected using a pre–post self-assessment questionnaire. In addition, the expert raters used the T-NOTECHS scale. Results: The following non-technical skills improved significantly among both medical doctors and nurses: knowledge of the trauma resuscitation guidelines, problem identification, decision making, situation awareness/coping with stress, communication and interaction, time management, being under authority, and confidence in one’s role in a team. The teams improved significantly in leadership, cooperation and resource management, communication and interaction, assessment and decision making, and situation awareness/coping with stress. Conclusion: A short, structured 2-h in situ trauma team simulation training course is effective in improving non-technical skills.
KCNQ2/3/5 channels in dorsal root ganglion neurons can be therapeutic targets of neuropathic pain in diabetic rats
Authors: Yu Ting , Li Lei , Liu Huaxiang , Li Hao , Liu Zhen , Li Zhenzhong 
Published: July 2018

Background Diabetic neuropathic pain is poorly controlled by analgesics, and the precise molecular mechanisms underlying hyperalgesia remain unclear. The KCNQ2/3/5 channels expressed in dorsal root ganglion neurons are important in pain transmission. The expression and activity of KCNQ2/3/5 channels in dorsal root ganglion neurons in rats with diabetic neuropathic pain were investigated in this study. Methods The mRNA levels of KCNQ2/3/5 channels were analyzed by real-time polymerase chain reaction. The protein levels of KCNQ2/3/5 channels were evaluated by Western blot assay. KCNQ2/3/5 channel expression in situ in dorsal root ganglion neurons was detected by double fluorescent labeling technique. M current (IM) density and neuronal excitability were determined by whole-cell voltage and current clamp recordings. Mechanical allodynia and thermal hyperalgesia were assessed by von Frey filaments and plantar analgesia tester, respectively. Results The mRNA and protein levels of KCNQ2/3/5 channels significantly decreased, followed by the reduction of IM density and elevation of neuronal excitability of dorsal root ganglion neurons from diabetic rats. Activation of KCNQ channels with retigabine reduced the hyperexcitability and inhibition of KCNQ channels with XE991 enhanced the hyperexcitability. Administration of retigabine alleviated both mechanical allodynia and thermal hyperalgesia, while XE991 augmented both mechanical allodynia and thermal hyperalgesia in diabetic neuropathic pain in rats. Conclusion The findings elucidate the mechanisms by which downregulation of the expression and reduction of the activity of KCNQ2/3/5 channels in diabetic rat dorsal root ganglion neurons contribute to neuronal hyperexcitability, which results in hyperalgesia. These data provide intriguing evidence that activation of KCNQ2/3/5 channels might be the potential new targets for alleviating diabetic neuropathic pain symptoms.
The plasma Epstein–Barr virus DNA level guides precision treatment for nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: a large population-based cohort study from an endemic area
Authors: Liang Hu , Lv Xing , Wang Lin , Wu Yi-Shan , Sun Rui , Ye Yan-Fang , Ke Liang-Ru , Yang Qin , Yu Ya-Hui , Qiu Wen-Ze , Liu Guo-Ying , Huang Xin-Jun , Li Wang-Zhong , Lv Shu-Hui , Guo Xiang , Xiang Yan-Qun , Xia Wei-Xiong 
Published: July 2018

Background: In the intensity-modulated radiotherapy (IMRT) era, the survival benefit of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains undetermined. This study aimed to evaluate the benefits of IMRT with concurrent chemotherapy compared with IMRT alone for LA-NPC patients with different plasma Epstein–Barr virus (EBV) DNA levels. Methods: Patients were identified from a prospectively maintained database in an endemic area between November 2002 and December 2013. Cox proportional hazards models, propensity score matching, and inverse probability weighting models were established for survival analysis. Stratification analysis was performed based on interaction effects analysis. Finally, sensitivity analysis was performed considering unmeasured confounders. Results: A total of 1357 eligible patients were enrolled (median follow up 62.4 months; range 3.5–155.8 months). No significant survival differences were observed between groups in the entire cohort. Notably, a significant interaction effect was observed between treatment regimens and EBV DNA levels. In patients with high EBV DNA levels (>4000 copies/ml), all three models showed that IMRT with concurrent chemotherapy significantly improved overall survival [hazard ratio (HR) 2.521, 95% confidence interval (CI) 1.218–5.216], disease-free survival (HR 2.168, 95% CI 1.349–3.483), and distant metastasis-free survival (HR 2.331, 95% CI 1.194–4.551) compared with IMRT alone. No differences were found in patients with low EBV DNA levels. Sensitivity analysis confirmed the robustness of the results. Conclusion: In the IMRT era, concurrent chemotherapy treatment of LA-NPC patients with high EBV DNA levels is reasonable. However, the optimal regimen for LA-NPC patients with low EBV DNA levels needs further validation in randomized clinical trials.
Attentional, interpretation and memory biases for sensory-pain words in individuals with chronic headache
Authors: Schoth Daniel E , Beaney Rebecca , Broadbent Philippa , Zhang Jin , Liossi Christina 
Published: July 2018

Introduction: Cognitive biases in attention, interpretation and less consistently memory have been observed in individuals with chronic pain and play a critical role in the onset and maintenance of chronic pain. Despite operating in combination cognitive biases are typically explored in isolation. Aim: The primary aim of this study was to explore attentional, interpretation and memory biases and their interrelationship in individuals with chronic headache. Methods: Twenty-eight participants with chronic headache and 34 healthy controls completed paradigms assessing attentional, interpretation and memory biases with ambiguous sensory-pain and neutral words. Results: Individuals with chronic pain showed significantly greater pain-related attentional and interpretation biases relative to controls, with no differences in memory bias. No significant correlation was found between any of the three forms of cognitive bias assessed. Discussion and conclusion: The clinical implications of cognitive biases in individuals with chronic pain remain to be fully explored, although one avenue for future research would be specific investigation of the implications of biased interpretations considering the consistency of results found across the literature for this form of bias.
Short‐term histological evaluations after achieving a sustained virologic response to direct‐acting antiviral treatment for chronic hepatitis C
Authors: Enomoto Masaru , Ikura Yoshihiro , Tamori Akihiro , Kozuka Ritsuzo , Motoyama Hiroyuki , Kawamura Etsushi , Hagihara Atsushi , Fujii Hideki , Uchida-Kobayashi Sawako , Morikawa Hiroyasu , Murakami Yoshiki , Kawada Norifumi 
Published: July 2018

BackgroundInterferon‐free, direct‐acting antiviral treatments can result in a sustained virologic response in nearly 100% of patients with chronic hepatitis C virus infection.AimsThe purpose of this study was to evaluate histological improvement after achieving a sustained virologic response to direct‐acting antiviral treatments in patients with chronic hepatitis C.MethodsAmong 691 patients with chronic hepatitis C who achieved a sustained virologic response to direct‐acting antivirals, 51 underwent liver biopsy 41 ± 20 weeks after the end of treatment despite normal transaminase levels. In 20 patients, liver biopsy specimens obtained a median of 1.2 years before the start of treatment were available.ResultsAmong the 51 patients who underwent post‐sustained virologic response biopsies, the grade of inflammation was A0 in 18 patients, A1 in 24, A2 in eight, and A3 in one; the stage of fibrosis was F0 in three patients, F1 in 20, F2 in 15, F3 in nine, and F4 in four. Among the nine post‐sustained virologic response biopsy specimens with moderate‐to‐severe inflammation (≥A2), four showed S1‐to‐S3 steatosis (>5% of hepatocytes affected). In the 20 paired biopsy specimens, the inflammation grade significantly regressed (p = 0.0043), but the fibrosis stage did not (p = 0.45). Histological improvement, defined as a ≥ 2‐point decrease in the Knodell inflammatory score and no worsening of the fibrosis, was found in 11 (55%) patients. The iron accumulation had significantly regressed (p = 0.0093), but the steatosis had not (p = 0.10).ConclusionsEven if transaminases become normal after obtaining a sustained virologic response, significant histological inflammation of unknown cause was found in some patients. Additionally, improvement in liver fibrosis was not evident in the short term.
Extended-spectrum β-lactamase prevalence and virulence factor characterization of enterotoxigenic Escherichia coli responsible for acute diarrhea in Nepal from 2001 to 2016
Authors: Margulieux Katie R. , Srijan Apichai , Ruekit Sirigade , Nobthai Panida , Poramathikul Kamonporn , Pandey Prativa , Serichantalergs Oralak , Shrestha Sanjaya K. , Bodhidatta Ladaporn , Swierczewski Brett E. 
Published: July 2018

Abstract
Background
Multidrug-resistant (MDR) Gram-negative bacterial species are an increasingly dangerous public health threat, and are now endemic in many areas of South Asia. However, there are a lack of comprehensive data from many countries in this region determining historic and current MDR prevalence. Enterotoxigenic Escherichia coli (ETEC) is a leading cause of both acute infant diarrhea and traveler’s diarrhea in Nepal. The MDR prevalence and associated resistance mechanisms of ETEC isolates responsible for enteric infections in Nepal are largely unknown.

Methods
A total of 265 ETEC isolates were obtained from acute diarrheal samples (263/265) or patient control samples (2/265) at traveler’s clinics or regional hospitals in Nepal from 2001 to 2016. Isolates were screened for antibiotic resistance, to include extended spectrum beta-lactamase (ESBL) production, via the Microscan Automated Microbiology System. ETEC virulence factors, specifically enterotoxins and colonization factors (CFs), were detected using multiplex PCR, and prevalence in the total isolate population was compared to ESBL-positive isolates. ESBL-positive isolates were assessed using multiplex PCR for genetic markers potentially responsible for observed resistance.

Results
A total of 118/265 (44.5%) ETEC isolates demonstrated resistance to ≥2 antibiotics. ESBL-positive phenotypes were detected in 40/265 isolates, with isolates from 2008, 2013, 2014, and 2016 demonstrating ESBL prevalence rates of 1.5, 34.5, 31.2, and 35.0% respectively. No difference was observed in overall enterotoxin characterization between the total ETEC and ESBL-positive populations. The CFs CS2 (13.6%), CS3 (25.3%), CS6 (30.2%), and CS21 (62.6%) were the most prevalent in the total ETEC population. The ESBL-positive ETEC isolates exhibited a higher association trend with the CFs CS2 (37.5%), CS3 (35%), CS6 (42.5%), and CS21 (67.5%). The primary ESBL gene identified was blaCTX-M-15 (80%), followed by blaSHV-12 (20%) and blaCTX-M-14 (2.5%). The beta-lactamase genes blaTEM-1 (40%) and blaCMY-2 (2.5%) were also identified. It was determined that 42.5% of the ESBL-positive isolates carried multiple resistance genes.

Conclusion
Over 30% of ETEC isolates collected post-2013 and evaluated in this study demonstrated ESBL resistance. Persistent surveillance and characterization of enteric ETEC isolates are vital for tracking the community presence of MDR bacterial species in order to recommend effective treatment strategies and help mitigate the spread of resistant pathogens.
Sexual boundary violations: victims, perpetrators and risk reduction
Authors: Hook John , Devereux Dawn 
Published: July 2018

SUMMARYSexual boundary violations by healthcare professionals is a subject that has largely been ignored in the UK. There has been little research into the field. It is rarely taught on professional training courses and practitioners appear to know very little about it. The history of sexual boundary violations is littered with failures to notice, failures to report and inadequate justice for victims and perpetrators alike. Perpetrators are commonly assumed to be predators. Given the many widely reported recent events in our media of both predatory and other sexual offenders, we believe it is timely for all healthcare and other professions working with vulnerable people to take the problem seriously, to provide appropriate services for victims, evaluation and assessment of perpetrators, and sanctions that fit the crime in order to regain public trust.LEARNING OBJECTIVES•Develop greater understanding of the problem of sexual boundary violations by professionals•Be able to manage the care of a patient who has been the victim of a sexual boundary violation•Understand factors in professionals that may lead to a sexual boundary violationDECLARATION OF INTERESTNone.
Defining a mood stabiliser: novel framework for research and clinical practice
Authors: Malhi Gin S. , Porter Richard , Irwin Lauren , Hamilton Amber , Morris Grace , Bassett Darryl , Baune Bernhard T. , Boyce Philip , Hopwood Malcolm J. , Mulder Roger , Parker Gordon , Mannie Zola , Outhred Tim , Das Pritha , Singh Ajeet B. 
Published: July 2018

SummaryThe term ‘mood stabiliser’ is ill-defined and lacks clinical utility. We propose a framework to evaluate medications and effectively communicate their mood stabilising properties – their acute and prophylactic efficacy across the domains of mania and depression. The standardised framework provides a common definition to facilitate research and clinical practice.Declaration of interestThe Treatment Algorithm Group (TAG) was supported logistically by Servier who provided financial assistance with travel and accommodation for those TAG members travelling interstate or overseas to attend the meeting in Sydney (held on 18 November 2017). None of the committee were paid to participate in this project and Servier have not had any input into the content, format or outputs from this project.
The benefits of antidepressants: news or fake news?
Authors: Parker Gordon 
Published: July 2018

SummaryAlthough antidepressant drugs are commonly effective, several meta-analyses of antidepressant drug trials undertaken decades after their introduction suggested that they were effectively acting as placebos. A recent meta-analysis concluded that they were effective. Both conclusions have been widely taken up by the media. This paper seeks to explain the disconnect.Declaration of interestNone.
Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials
Authors: Gridelli Cesare , Morabito Alessandro , Cavanna Luigi , Luciani Andrea , Maione Paolo , Bonanno Laura , Filipazzi Virginio , Leo Silvana , Cinieri Saverio , Ciardiello Fortunato , Burgio Marco Angelo , Bilancia Domenico , Cortinovis Diego , Rosetti Francesco , Bianco Roberto , Gebbia Vittorio , Artioli Fabrizio , Bordonaro Roberto , Fregoni Vittorio , Mencoboni Manlio , Nelli Fabrizio , Riccardi Ferdinando , di Isernia Giuditta , Costanzo Raffaele , Rocco Gaetano , Daniele Gennaro , Signoriello Simona , Piccirillo Maria Carmela , Gallo Ciro , Perrone Francesco 
Published: July 2018

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.
Hyperosmolar Duodenal Saline Infusion Lowers Circulating Ghrelin and Stimulates Intestinal Hormone Release in Young Men
Authors: Veedfald Simon , Wu Tongzhi , Bound Michelle , Grivell Jacqueline , Hartmann Bolette , Rehfeld Jens F , Deacon Carolyn F , Horowitz Michael , Holst Jens J , Rayner Christopher K 
Published: July 2018

AbstractContextThe mechanisms regulating the postprandial suppression of ghrelin secretion remain unclear, but recent observations in rats indicate that an increase in duodenal osmolarity is associated with a reduction in ghrelin levels. Several hormones have been implicated in the regulation of ghrelin.ObjectiveWe hypothesized that intraduodenal infusion of a hyperosmolar solution would lower plasma ghrelin concentrations.Design, Setting, Participants, and InterventionsEighteen healthy young men were studied after an overnight fast on two occasions in a randomized double-blinded fashion. A nasoduodenal catheter was positioned and isoosmolar (300 mOsm/L) or hyperosmolar (1500 mOsm/L) saline was infused intraduodenally (4 mL/min, t = 0 to 45 minutes). Venous blood was sampled at t = −45, −30, −15, 0, 15, 30, 45, 60, 75, 90, 120, and 180 minutes.Main Outcome MeasuresPlasma concentrations of ghrelin, glucagonlike peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), glucagon, pancreatic polypeptide (PP), neurotensin (NT), peptide YY (PYY), motilin, and glucose.ResultsGhrelin concentrations were suppressed with hyperosmolar when compared with isoosmolar saline, and remained lower until t = 180 minutes. CCK, NT, GLP-1, PYY, and glucagon all increased during hyperosmolar, but not isoosmolar, saline infusion (P &lt; 0.01 for all), whereas GIP, PP, and motilin levels were not affected by either infusion.ConclusionsPlasma ghrelin concentrations are lowered, whereas CCK, GLP-1, PYY, NT, and glucagon concentrations are augmented, by hyperosmolar duodenal content in healthy individuals. These observations have implications for the evaluation of studies comparing the effects of different types and loads of nutrients and chemicals on gut hormone secretion.
Stress granule formation is induced by a threshold temperature rather than a temperature difference in Arabidopsis
Authors: Hamada Takahiro , Yako Mako , Minegishi Marina , Sato Mayuko , Kamei Yasuhiro , Yanagawa Yuki , Toyooka Kiminori , Watanabe Yuichiro , Hara-Nishimura Ikuko 
Published: July 2018

ABSTRACT
Stress granules, a type of cytoplasmic RNA granule in eukaryotic cells, are induced in response to various environmental stresses, including high temperature. However, how high temperatures induce the formation of these stress granules in plant cells is largely unknown. Here, we characterized the process of stress granule formation in Arabidopsis thaliana by combining live imaging and electron microscopy analysis. In seedlings grown at 22°C, stress granule formation was induced at temperatures above a critical threshold level of 34°C in the absence of transpiration. The threshold temperature was the same, regardless of whether the seedlings were grown at 22°C or 4°C. High-resolution live imaging microscopy revealed that stress granule formation is not correlated with the sizes of pre-existing RNA processing bodies (P-bodies) but that the two structures often associated rapidly. Immunoelectron microscopy revealed a previously unidentified characteristic of the fine structures of Arabidopsis stress granules and P-bodies: the lack of ribosomes and the presence of characteristic electron-dense globular and filamentous structures. These results provide new insights into the universal nature of stress granules in eukaryotic cells.