bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of pain management in reducing limb and spine radiography in stable traumatic patients admitted to the emergency department
Authors: Torabi Mehdi , Mehri Ali , Mirzaei Moghaddameh 
Published: February 2018

Introduction Musculoskeletal pain caused by trauma is one of the common complaints of patients referred to the emergency department. Due to the lack of a proper pain control protocol, doctors and nurses do not pay attention to pain, and physicians may tend to request too many radiographs, many of which will be unnecessary. We aimed to study the effect of pain management by fentanyl in reducing the number of radiographs, reducing hospital costs and increasing satisfaction in the patients on patients with isolated trauma in limbs and spine causing musculoskeletal pain. Patients and methods A cohort of patients who were referred to the fast-track emergency department with isolated trauma of the upper and lower limbs or spine and triage levels 3, 4 and 5, were visited twice by an emergency medicine resident – before and after application of a pain management protocol using intravenous fentanyl as the principle analgesic. The primary outcome measure was the reduction in the number of radiographs requested; secondary outcomes included alterations in pain levels and patient satisfaction. Results A total of 158 patients were included in the study. The median age was 27.5 years, three quarters were male and 20.88% had a positive history of opium addiction. The number and costs of diagnostic radiography significantly decreased after the administration of fentanyl (P < 0.0001), as did pain levels measured on visual analogue scale with a consequent increase in patient satisfaction. There were only six complications resulting from fentanyl administration which were mild and transient. Follow-up after 24–72 h, revealed no missed fractures. Conclusions The administration of fentanyl as a strong analgesic as part of an emergency department pain management protocol for trauma patients can be performed with limited minor complications; it can reduce the number of unnecessary X-rays performed, exposure to ionizing radiation and hospital costs as well as improving patient satisfaction without missing fractures.
Managing in-hospital quality improvement: An importance-performance analysis to set priorities for ST-elevation myocardial infarction care
Authors: Aeyels Daan , Seys Deborah , Sinnaeve Peter R , Claeys Marc J , Gevaert Sofie , Schoors Danny , Sermeus Walter , Panella Massimiliano , Bruyneel Luk , Vanhaecht Kris 
Published: February 2018

Background: A focus on specific priorities increases the success rate of quality improvement efforts for broad and complex-care processes. Importance-performance analysis presents a possible approach to set priorities around which to design and implement effective quality improvement initiatives. Persistent variation in hospital performance makes ST-elevation myocardial infarction care relevant to consider for importance-performance analysis. Aims: The purpose of this study was to identify quality improvement priorities in ST-elevation myocardial infarction care. Methods: Importance and performance levels of ST-elevation myocardial infarction key interventions were combined in an importance-performance analysis. Content validity indexes on 23 ST-elevation myocardial infarction key interventions of a multidisciplinary RAND Delphi Survey defined importance levels. Structured review of 300 patient records in 15 acute hospitals determined performance levels. The significance of between-hospital variation was determined by a Kruskal–Wallis test. A performance heat-map allowed for hospital-specific priority setting. Results: Seven key interventions were each rated as an overall improvement priority. Priority key interventions related to risk assessment, timely reperfusion by percutaneous coronary intervention and secondary prevention. Between-hospital performance varied significantly for the majority of key interventions. The type and number of priorities varied strongly across hospitals. Conclusions: Guideline adherence in ST-elevation myocardial infarction care is low and improvement priorities vary between hospitals. Importance-performance analysis helps clinicians and management in demarcation of the nature, number and order of improvement priorities. By offering a tailored improvement focus, this methodology makes improvement efforts more specific and achievable.
The Outcome of Anticoagulation on Endovenous Laser Therapy for Superficial Venous Incompetence
Authors: Vatish Jamie , Iqbal Nusrat , Rajalingam Viswa Retnasingam , Tiwari Alok 
Published: February 2018

Objectives: The purpose of this study was to evaluate whether anticoagulation (warfarin or direct oral inhibitors) affected the success of endovenous treatment. Methods: Patients taking anticoagulation (warfarin or direct oral inhibitors) undergoing endovenous treatment in the form of endovenous laser ablation (EVLA) were matched against controls for sex, age, leg, and vein. Data were collected prospectively between January 2012 and March 2017. The primary endpoint was failure of treatment at 6-week postoperative duplex scan. The rates of major bleeding, hematoma, endothermal heat-induced thrombosis, venous thromboembolism, or pulmonary embolism were also compared between groups. Results: Two hundred eighty-four limbs underwent EVLA during the study period. Of this, 23/284 (8.1%) procedures were done in patients on anticoagulation. 21/23 (91.3%) limbs had venous occlusion at follow-up compared with 23/23 (100%) of controls ( P = .49). The patient who failed treatment in the anticoagulation group had undergone small saphenous vein (SSV) ablation. There was no difference in the complication rates between groups. Discussion: This study demonstrates that anticoagulation does not affect success rates of EVLA though there was higher recanalization rate in patients undergoing SSV ablation. Anticoagulation can be continued safely in patients undergoing this procedure.
A randomized controlled trial comparing ketorolac and triamcinolone injections in adults with trigger digits
Authors: Leow Mabel Qi He , Hay Aik Siew Robyn , Ng Shu Li , Choudhury Muntasir Mannan , Li Huihua , McGrouther Duncan Angus , Tay Shian Chao 
Published: February 2018

We assessed the efficacy of ketorolac trometamol injections compared with triamcinolone acetonide injections in trigger digits. Patients with trigger digits were randomized to receive either ketorolac or triamcinolone. They were followed up at 3, 6, 12 and 24 weeks, and monitored for resolution of triggering, pain and total active motion. One hundred and twenty-one patients with single trigger digits were recruited (59 ketorolac, 62 triamcinolone). At 6 weeks, 54% of patients in the triamcinolone group had complete resolution of trigger, whereas no patients in the ketorolac group had resolution. At 12 weeks, 58% of patients in the triamcinolone group had complete resolution of trigger compared with 6.7% in the ketorolac group. At 24 weeks, both groups had comparable rates of resolution at 26% and 25%, respectively. Patients in the triamcinolone group had significantly better resolution of pain at 3, 6 and 12 weeks. But at 24 weeks, there was no significant difference in pain between both groups. Significantly less flexion deformity was reported at 3 weeks and 6 weeks in the triamcinolone group. In the short term, ketorolac was less effective in relieving symptoms of trigger digit than triamcinolone. Level of evidence: I
The UVA/Padova Type 1 Diabetes Simulator Goes From Single Meal to Single Day
Authors: Visentin Roberto , Campos-Náñez Enrique , Schiavon Michele , Lv Dayu , Vettoretti Martina , Breton Marc , Kovatchev Boris P. , Dalla Man Chiara , Cobelli Claudio 
Published: February 2018

Background: A new version of the UVA/Padova Type 1 Diabetes (T1D) Simulator is presented which provides a more realistic testing scenario. The upgrades to the previous simulator, which was accepted by the Food and Drug Administration in 2013, are described. Method: Intraday variability of insulin sensitivity (SI) has been modeled, based on clinical T1D data, accounting for both intra- and intersubject variability of daily SI. Thus, time-varying distributions of both subject’s basal insulin infusion and insulin-to-carbohydrate ratio were calculated and made available to the user. A model of “dawn” phenomenon based on clinical T1D data has been also included. Moreover, the model of subcutaneous insulin delivery has been updated with a recently developed model of commercially available fast-acting insulin analogs. Models of both intradermal and inhaled insulin pharmacokinetics have been included. Finally, new models of error affecting continuous glucose monitoring and self-monitoring of blood glucose devices have been added. Results: One hundred in silico adults, adolescent, and children have been generated according to the above modifications. The new simulator reproduces the intraday glucose variability observed in clinical data, also describing the nocturnal glucose increase, and the simulated insulin profiles reflect real life data. Conclusions: The new modifications introduced in the T1D simulator allow to extend its domain of validity from “single-meal” to “single-day” scenarios, thus enabling a more realistic framework for in silico testing of advanced diabetes technologies including glucose sensors, new insulin molecules and artificial pancreas.
Different Indexes of Glycemic Variability as Identifiers of Patients with Risk of Hypoglycemia in Type 2 Diabetes Mellitus
Authors: Gómez Ana M. , Muñoz Oscar M. , Marin Alejandro , Fonseca Maria Camila , Rondon Martin , Robledo Gómez María Alejandra , Sanko Andrei , Lujan Dilcia , García-Jaramillo Maira , León Vargas Fabian Mauricio 
Published: February 2018

Introduction: Recent publications frequently introduce new indexes to measure glycemic variability (GV), quality of glycemic control, or glycemic risk; however, there is a lack of evidence supporting the use of one particular parameter, especially in clinical practice. Methods: A cohort of type 2 diabetes mellitus (T2DM) patients in ambulatory care were followed using continuous glucose monitoring sensors (CGM). Mean glucose (MG), standard deviation, coefficient of variation (CV), interquartile range, CONGA1, 2, and 4, MAGE, M value, J index, high blood glucose index, and low blood glucose index (LBGI) were estimated. Hypoglycemia incidence (<54 mg/dl) was calculated. Area under the curve (AUC) was determined for different indexes as identifiers of patients with risk of hypoglycemia (IRH). Optimal cutoff thresholds were determined from analysis of the receiver operating characteristic curves. Results: CGM data for 657 days from 140 T2DM patients (4.69 average days per patient) were analyzed. Hypoglycemia was present in 50 patients with 144 hypoglycemic events in total (incidence rate of 0.22 events per patient/day). In the multivariate analysis, both CV (OR 1.20, 95% CI 1.12-1.28, P < .001) and LBGI (OR 4.83, 95% CI 2.41-9.71, P < .001) were shown to have a statistically significant association with hypoglycemia. The highest AUC were for CV (0.84; 95% CI 0.77-0.91) and LBGI (0.95; 95% CI 0.92-0.98). The optimal cutoff threshold for CV as IRH was 34%, and 3.4 for LBGI. Conclusion: This analysis shows that CV can be recommended as the preferred parameter of GV to be used in clinical practice for T2DM patients. LBGI is the preferred IRH between glycemic risk indexes.
An exhaled carbon monoxide self-monitoring device linked to social media to support smoking cessation: A proof of concept pilot study
Authors: Tan Ngiap Chuan , Mohd Mohtar Zulidiah bte , Koh Eileen Yi Ling , Sankari Usha , Tay David Hong Chuan , Yu Shaun , Tan William Boon Wee 
Published: February 2018

Background: A recent systematic review alludes to the effectiveness of social media in facilitating smoking cessation. However, most interventions center on mobile applications in engaging smokers. A novel portable exhaled-carbon-monoxide self-monitoring device, the Smoke-analyzer to Track and Expedite Actions and Decisions to Eliminate Smoking (STEADES) linked to a specially-designed mobile phone application has been developed, which relays exhaled carbon monoxide-related data from the smokers to their selected quit supporters via social media. Aim: The study aimed to determine the precision and feasibility of using the STEADES device among smokers in primary care. Method: This pilot study recruited 15 Asian adult smokers from a primary care polyclinic in Singapore. Their exhaled carbon monoxide measurements were measured serially using STEADES, compared to a commercial smokerlyzer as reference. The subjects could use the device to transmit their exhaled carbon monoxide measurements via mobile application and social media to their acquaintances in the next two weeks. Data on the subjects’ demographic and clinical characteristics, their views on STEADES (from a questionnaire), and its utility (from the application) were collated on enrolment and at the end of study. Results: Measurements using STEADES were significantly correlated with those from a commercial smokerlyzer (Pearson correlation=0.882, p<0.01). The majority of the subjects perceived that the exhaled carbon monoxide data would allow them to track progress of their quit attempts, perceived recipients of these data would support their smoking cessation (92.3%), and reported willingness to use it with improved accuracy. Conclusion: The STEADES prototype had shown feasibility in this proof of concept study. Most subjects were in favor of using it to support their smoking cessation but its accuracy required enhancement.
Intrauterine contraceptive device insertion simulation training in primary care
Authors: Ng Lai Peng , Koh Eileen Yi Ling 
Published: February 2018

Background and objectives: Insertion of a intrauterine contraceptive device (IUCD) is one of the services provided at our public primary care polyclinics. We evaluate the effectiveness of a simulation workshop using low-fidelity mannequins to train primary care doctors. Methods: Questionnaire feedback was collected before and after the workshop. Participants rated their confidence level in performing the insertion of IUCDs using a 10-point scale. Results: A total of 37 out of 44 (84%) participants completed the survey. The median score for confidence level in performing the procedure increased from 2 out of 10 (interquartile range (IQR) 1 to 5) before the workshop to 8 out of 10 (IQR 7 to 9) after the workshop ( p < 0.01). The increase in confidence level was most pronounced among the participants with no previous experience with the procedure and those who had inserted only one or two IUCDs before the workshop. Participants rated a median score of 9 out of 10 (IQR 8 to 10) in their interest level to perform the procedure after the workshop. The overall experience of the workshop recorded a median score of 5 out of 5 using a five-point Likert scale. Conclusions: Bedside procedural training has been challenging. The teaching of the procedure via a structured workshop format including a simulation of the procedure using a low-fidelity mannequin increases the confidence level of participants to perform the procedure. A similar format can be employed for training of other primary care procedural skills.
Chronicity of Anterior Cruciate Ligament Deficiency, Part 2: Radiographic Predictors of Early Graft Failure
Authors: Tanaka Yoshinari , Kita Keisuke , Takao Rikio , Amano Hiroshi , Uchida Ryohei , Shiozaki Yoshiki , Yonetani Yasukazu , Kinugasa Kazutaka , Mae Tatsuo , Horibe Shuji 
Published: February 2018

Background: Accumulating evidence suggests that long-term anterior cruciate ligament (ACL) deficiency can give rise to an abnormal tibiofemoral relationship and subsequent intra-articular lesions. However, the effects of chronic ACL deficiency (ACLD) on early graft failure after anatomic reconstruction remain unclear. Hypothesis: We hypothesized that patients with long-term ACLD lasting more than 5 years would have a greater rate of early graft failure due to insufficient intraoperative reduction of the tibia and that the preoperative and immediately postoperative abnormal tibiofemoral relationship in the sagittal plane, such as anterior tibial subluxation (ATS), would correlate with the graft status on postoperative magnetic resonance imaging (MRI). Study Design: Cohort study; Level of evidence, 3. Methods: A total of 358 patients who had undergone anatomic ACL reconstruction with hamstring grafts were divided into 5 groups based on chronicity of ACLD: (1) 0 to 6 months, (2) 6 months to 1 year, (3) 1 to 2 years, (4) 2 to 5 years, and (5) longer than 5 years. Preoperatively and immediately postoperatively, lateral radiographs in full extension were taken in all patients to evaluate the tibiofemoral relationship, specifically with regard to ATS, space for the ACL (sACL), and extension angle. All patients underwent MRI at 6 months to reveal graft status. Groups with a high rate of graft failure were further analyzed to compare demographic and radiographic factors between the intact and failure subgroups, followed by multivariate logistic regression analysis to identify predisposing factors. Results: Graft failure without trauma was observed in 4 (1.8%), 0 (0%), 1 (3.7%), 3 (9.7%), and 8 patients (17.7%) in groups 1, 2, 3, 4, and 5, respectively. Of the 76 patients in groups 4 and 5, significant differences were noted between the failure and intact subgroups in preoperative ATS (4.9 vs 2.4 mm, respectively; P < .01), side-to-side differences in sACL (sACL-SSD) (4.7 vs 1.9 mm, respectively; P < .01), extension deficit (4.4° vs 1.3°, respectively; P < .01), and chondral lesions ( P = .02), while postoperative ATS and sACL-SSD showed no differences. Multivariate logistic regression analysis revealed that of these factors, preoperative sACL-SSD could be a risk factor for early graft failure (odds ratio, 3.2; 95% CI, 1.37-7.46). Conclusion Early graft failure at 6 months increased in patients with ACLD longer than 2 years. In this population, preoperative sACL-SSD was the most significant risk factor for early graft failure on MRI. However, immediately postoperative radiographic measurements had no effect on graft failure rates.
Transcriptional regulation of ependymal cell maturation within the postnatal brain
Authors: Vidovic Diana , Davila Raul Ayala , Gronostajski Richard M. , Harvey Tracey J. , Piper Michael 
Published: February 2018

Abstract
Background
Radial glial stem cells within the developing nervous system generate a variety of post-mitotic cells, including neurons and glial cells, as well as the specialised multi-ciliated cells that line the walls of the ventricular system, the ependymal cells. Ependymal cells separate the brain parenchyma from the cerebrospinal fluid and mediate osmotic regulation, the flow of cerebrospinal fluid, and the subsequent dispersion of signalling molecules via the co-ordinated beating of their cilia. Deficits to ependymal cell development and function have been implicated in the formation of hydrocephalus, but the transcriptional mechanisms underpinning ependymal development remain poorly characterised.

Findings
Here, we demonstrate that the transcription factor nuclear factor IX (NFIX) plays a central role in the development of the ependymal cell layer of the lateral ventricles. Expression of ependymal cell-specific markers is delayed in the absence of Nfix. Moreover, Nfix-deficient mice exhibit aberrant ependymal cell morphology at postnatal day 15, culminating in abnormal thickening and intermittent loss of this cell layer. Finally, we reveal Foxj1, a key factor promoting ependymal cell maturation, as a target for NFIX-mediated transcriptional activation.

Conclusions
Collectively, our data indicate that ependymal cell development is reliant, at least in part, on NFIX expression, further implicating this transcription factor as a mediator of multiple aspects of radial glial biology during corticogenesis.
Correction to: Neisseria lactamica Y92–1009 complete genome sequence
Authors: Pandey Anish K. , Cleary David W. , Laver Jay R. , Maiden Martin C. J. , Didelot Xavier , Gorringe Andrew , Read Robert C. 
Published: February 2018

Correction
After publication of the original article [1] it was identified that an incorrect version of the manuscript has been published. This was caused by a technical error which led to a discrepancy between the editorially-accepted version of the manuscript, and the published version.
Large-Cell Neuroendocrine Carcinoma of the Lung: A Focused Analysis of
BRAF
Alterations and Case Report of a
BRAF
Non-V600–Mutated Tumor Responding to Targeted Therapy
Authors: Chae Young Kwang , Tamragouri Keerthi B. , Chung Jon , Lin Xiaoqi , Miller Vincent , Ali Siraj M. , Giles Francis J. 
Published: February 2018

Purpose

In advanced stages, large-cell neuroendocrine carcinoma of the lung (L-LCNEC) mimics small-cell lung cancer despite its traditional classification as a non–small-cell lung cancer. Here we present a focused analysis of
BRAF
mutations in this population.

Patients and Methods
Comprehensive genomic profiling of tumor tissues was performed from a cohort of 300 patients with biopsy-proven L-LCNEC. Specimens were either from a primary lung lesion or metastatic site.

Results

In 13 patients, 14 unique
BRAF
alterations (amplifications, mutations) were identified. The importance of biomarker-driven therapy is subsequently highlighted with our case of a 69-year-old man diagnosed with metastatic L-LCNEC who did not respond to cisplatin plus etoposide. A significant durable response was then demonstrated with therapy targeted toward a
BRAF
non-V600E activating mutation (G469R) associated with biomarker response identified through circulating cell-free tumor DNA analysis. A change in clonal allele frequency from nearly 40% to nondetectable was observed.

Conclusion
Although uncommon, L-LCNEC does seem to contain activating and therefore actionable alterations. We thus highlight the value of pursuing next-generation sequencing for patients with this disease.
SNAIL Mediates TGF-β1–Induced Downregulation of Pentraxin 3 Expression in Human Granulosa Cells
Authors: Li Hui , Chang Hsun-Ming , Shi Zhendan , Leung Peter C K 
Published: February 2018

AbstractTransforming growth factor-β (TGF-β) 1 plays a critical role in regulating follicular development, and its dysregulation has been shown to be involved in the pathogenesis of ovulation dysfunction. SNAIL is a well-known transcriptional repressor that mediates TGF-β1–induced cellular functions. Pentraxin 3 (PTX3) is a key enzyme for the assembly and stabilization of the cumulus oophorus extracellular matrix, which is essential for cumulus expansion during the periovulatory stage. The purpose of the present study was to investigate the roles of TGF-β1 and SNAIL in the regulation of PTX3 expression and to examine the underlying mechanism. An established immortalized human granulosa cell (GC) line (SVOG), a GC tumor cell line (KGN), and primary human granulosa-lutein cells were used as study models. We demonstrated that TGF-β1 treatment substantially decreased the messenger RNA and protein levels of PTX3. This suppressive effect was abolished by cotreatment with the soluble TGF-β type II receptor (TβRII) or the ALK4/5/7 inhibitor SB431542. Knockdown of ALK5, SMAD2/3, or SMAD4 reversed the effects of TGF-β1–induced SNAIL upregulation and PTX3 suppression. These results indicate that TGF-β1 upregulates SNAIL and downregulates PTX3 expression via a TβRII-ALK5–mediated SMAD-dependent signaling pathway in human GCs. Additionally, TGF-β1–induced PTX3 suppression was mediated by upregulation of the SNAIL transcription factor, as knockdown of SNAIL completely reversed the suppression of PTX3 in response to TGF-β1. These findings could inform the roles of TGF-β1 and SNAIL in the regulation of follicular function and might provide therapeutic targets for the treatment of ovulation dysfunction.