Πέμπτη, 1 Φεβρουαρίου 2018

Eosinophil Counts in the Small Intestine and Colon of Children Without Apparent Gastrointestinal Disease-a Meta-analysis

ABSTRACTObjectives:The aim of the current study was to review the available data regarding eosinophil density in healthy tissue specimen originating from lower gastrointestinal segments to support suggested diagnostic cut-offs widely used in clinical practice.Methods:A systematic search was performed in three different databases. Calculations were made with Comprehensive MetaAnalysis software using random effects model. Cell number measurements were pooled using the random effects model and displayed on forest plots. Summary point estimations, 95% Confidence Intervals (CIs), and 95% Prediction Intervals (PIs) were calculated.Results:The cumulative mean cell numbers were 8.26 (95% CI: 3.49, 13.03) with PI of 0–25.32 for the duodenum, 11.51 (95% CI: 7.21, 15.82) with PI of 0–60.59 for the terminal ileum, and 11.10/HPF (95% CI: 9.11, 13.09) with PI of 0.96–21.23 in the large intestine and the rectum (HPF area = 0.2 mm2). Previous studies included control patients with irritable bowel syndrome (IBS) and functional GI disorders. As mucosal eosinophils have a role in their pathomechanism, those patients should have been excluded. A critical point of interpreting reported data is that HPF is relative to the technical parameters of the microscopes, therefore it is important to report findings in cell/mm2.Conclusions:The present meta-analysis does not support the higher (>20) or lower (20) or lower (

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NMDA-receptor Antagonism in Pediatric Pancreatitis: Use of Ketamine and Methadone in a Teenager With Refractory Pain

No abstract available

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Practice Differences in the Diagnosis and Management of Eosinophilic Esophagitis among Adult and Pediatric Gastroenterologists in Israel

ABSTRACTObjectives:Eosinophilic esophagitis (EoE) guidelines call for similar practices in adults and children with EoE. We compared the diagnostic and management practices of gastroenterologists treating adult and pediatric patients suspected of having, or diagnosed with, EoE.Methods:A 19 question multiple choice questionnaire was given to gastroenterologists treating either adults or children. Questions explored four areas of interest: Physician demographics, diagnosis and tissue sampling practices, management, and the need for societal publications on EoE.Results:Completed questionnaires were returned by 85/180 adult and 30/40 pediatric gastroenterologists. Compared to pediatric gastroenterologists, adult gastroenterologists took esophageal biopsies significantly less frequently in the following scenarios: endoscopy without esophageal symptoms or macroscopic endoscopic findings (10% vs. 57%; p 

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Should Giant Cell Hepatitis With Autoimmune Hemolytic Anemia Be Considered a Pediatric Autoimmune Liver Disease?

No abstract available

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Should Giant Cell Hepatitis With Autoimmune Hemolythic Anemia Be Considered A Pediatric Autoimmune Liver Disease?

No abstract available

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Survey on the Adherence to the 2009 NASPGHAN-ESPGHAN Gastroesophageal Reflux Guidelines by Brazilian Paediatricians

ABSTRACTObjective:To evaluate the management of gastroesophageal reflux in children among Brazilian pediatricians and adherence to the 2009 North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), and European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Guideline in Brazil.Methods:An observational cross-sectional study was conducted, applying a standard questionnaire with 12 questions about gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD) management in infants, children, and adolescents to the pediatricians during the 37th Brazilian Pediatrics Congress in October, 2015. Adherence to the 2009 NASPGHAN-ESPGHAN Guideline was verified through analyses of interviewees' answers. Pediatricians' demographic and professional characteristics were screened.Results:390 Brazilian pediatricians answered the questionnaire. None showed complete adherence to Guideline recommendations. GERD diagnosis by history alone was reported by 67%, irrespective of the child's age. The mean score for diagnostic adherence to the guidelines was 0.94 ± 0.86 (range 0–4). Working in public health services (p = 0.026) was the only variable retained as a significant predictor of poor adherence for GER/GERD diagnosis after multivariate logistic regression analysis. No significant statistical differences were found between Brazilian regions on total score (p = 0.774). Proton pump inhibitors (PPIs) were prescribed by 28.4% of the pediatricians independent of child's age, and 59% use PPI to treat babies with unexplained crying and/or distressed behavior.Conclusions:2009 NASPGHAN-ESPGHAN Guideline recommendations had poor adherence by Brazilian pediatricians. Studies evaluating the reasons for the poor adherence to NASPGHAN/ESPGHAN guidelines are urgently needed. Objective: To evaluate the management of gastroesophageal reflux in children among Brazilian pediatricians and adherence to the 2009 North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), and European Society of Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Guideline in Brazil. Methods: An observational cross-sectional study was conducted, applying a standard questionnaire with 12 questions about gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD) management in infants, children, and adolescents to the pediatricians during the 37th Brazilian Pediatrics Congress in October, 2015. Adherence to the 2009 NASPGHAN-ESPGHAN Guideline was verified through analyses of interviewees' answers. Pediatricians' demographic and professional characteristics were screened. Results: 390 Brazilian pediatricians answered the questionnaire. None showed complete adherence to Guideline recommendations. GERD diagnosis by history alone was reported by 67%, irrespective of the child's age. The mean score for diagnostic adherence to the guidelines was 0.94 ± 0.86 (range 0–4). Working in public health services (p = 0.026) was the only variable retained as a significant predictor of poor adherence for GER/GERD diagnosis after multivariate logistic regression analysis. No significant statistical differences were found between Brazilian regions on total score (p = 0.774). Proton pump inhibitors (PPIs) were prescribed by 28.4% of the pediatricians independent of child's age, and 59% use PPI to treat babies with unexplained crying and/or distressed behavior. Conclusions: 2009 NASPGHAN-ESPGHAN Guideline recommendations had poor adherence by Brazilian pediatricians. Studies evaluating the reasons for the poor adherence to NASPGHAN/ESPGHAN guidelines are urgently needed. Address correspondence and reprint requests to Sarah Cristina Fontes Vieira, Rua Claudio Batista, SN, Bairro Cidade Nova, ZIP code 49060-108, Aracaju-SE, Brazil (E-mail: sarahcfv@yahoo.com.br). Received 20 May, 2017 Accepted 22 December, 2017 Conflicts of interest and source of funding: None to declare. Institution: Federal University of Sergipe, Aracaju-Sergipe, Brazil. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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CHILD syndrome: A modified pathogenesis-targeted therapeutic approach

Congenital Hemidysplasia with Ichthyosiform nevus and Limb Defects (CHILD syndrome) is a rare X-linked dominant genodermatosis caused by mutations in the NAD(P) dependent steroid dehydrogenase-like protein gene. Its defect leads to accumulation of toxic metabolic intermediates upstream from the pathway block and to the deficiency of bulk cholesterol, probably leading to altered keratinocyte membrane function, resulting in the phenotype seen in CHILD syndrome. Symptomatic treatment using emollients and retinoids to reduce scaling has long been used until recently, whereby new therapeutic means based on the pathogenesis-targeted therapy have been developed. We subsequently chose to use the same pathogenesis-based therapy using a 2% cholesterol and 2% lovastatin cream with or without glycolic acid in two of our patients. Improvement in CHILD skin lesions was seen as early as 4 weeks after initiation. The addition of glycolic acid helped improve the penetrance of the cholesterol and lovastatin cream into the thick waxy scales. Our study confirms the efficacy of the pathogenesis-targeted therapy and introduces the possibility of modifying its formula by adding glycolic acid in order to improve the treatment.



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Umbilical cannulation optimizes circuit flows in premature lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND)

Abstract

EXTEND (EXTra-uterine Environment for Neonatal Development) is a novel system that promotes physiologic development by maintaining the premature lamb in a sterile fluid environment and providing gas exchange via a pumpless arteriovenous oxygenator circuit. During the development of EXTEND, different cannulation strategies evolved with the aim to improve circuit flow. This study examines how different cannulation strategies affect EXTEND circuit hemodynamics in extreme premature lambs. 17 premature lambs were cannulated at gestational ages 105–117 days (term 145–150 days) and supported on EXTEND for up to 4 weeks. Experimental groups were distinguished by cannulation strategy: carotid artery outflow and jugular vein inflow (CA/JV, n = 4); carotid artery outflow and umbilical vein inflow (CA/UV, n = 5); double umbilical artery outflow and umbilical vein inflow (UA/UV, n = 8). Circuit flows and pressures were measured continuously. As we transitioned from CA/JV to CA/UV to UA/UV cannulation, mean duration of circuit run and weight-adjusted circuit flows increased (P < 0.001) and frequency of flow interruptions declined (P < 0.05). Umbilical vessels generally accommodated larger-bore cannulas, and cannula caliber was directly correlated with circuit pressures and indirectly correlated with flow:pressure ratio (a measure of post-membrane resistance). We conclude that UA/UV cannulation in fetal lambs on EXTEND optimizes circuit flow dynamics and flow stability, and supports circuit flows that closely approximate normal placental flow.

This article is protected by copyright. All rights reserved



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Development of a 99mTc-Labeled CXCR4 Antagonist Derivative as a New Tumor Radiotracer

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Craniosynostosis as a clinical and diagnostic problem: molecular pathology and genetic counseling

Abstract

Craniosynostosis (occurrence: 1/2500 live births) is a result of premature fusion of cranial sutures, leading to alterations of the pattern of cranial growth, resulting in abnormal shape of the head and dysmorphic facial features. In approximately 85% of cases, the disease is isolated and nonsyndromic and mainly involves only one suture. Syndromic craniosynostoses such as Crouzon, Apert, Pfeiffer, Muenke, and Saethre–Chotzen syndromes not only affect multiple sutures, but are also associated with the presence of additional clinical symptoms, including hand and feet malformations, skeletal and cardiac defects, developmental delay, and others. The etiology of craniosynostoses may involve genetic (also somatic mosaicism and regulatory mutations) and epigenetic factors, as well as environmental factors. According to the published data, chromosomal aberrations, mostly submicroscopic ones, account for about 6.7–40% of cases of syndromic craniosynostoses presenting with premature fusion of metopic or sagittal sutures. The best characterized is the deletion or translocation of the 7p21 region containing the TWIST1 gene. The deletions of 9p22 or 11q23-qter (Jacobsen syndrome) are both associated with trigonocephaly. The genes related to the pathogenesis of the craniosynostoses itself are those encoding transcription factors, e.g., TWIST1, MSX2, EN1, and ZIC1, and proteins involved in osteogenic proliferation, differentiation, and homeostasis, such as FGFR1, FGFR2, RUNX2, POR, and many others. In this review, we present the clinical and molecular features of selected craniosynostosis syndromes, genotype–phenotype correlation, family genetic counseling, and propose the most appropriate diagnostic algorithm.



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Large inter-rater variability on EEG-reactivity is improved by a novel quantitative method

EEG-reactivity (EEG-R) has been defined as a change in EEG activity to stimulation (Hirsch et al., 2013). The most well-known type of EEG-R is the blocking of alpha activity to eye opening, which is most often present in healthy subjects. EEG-R is regarded as an important prognostic marker in comatose patients. In several studies, EEG-R predicts the comatose patient's awakening and recovery. This has been shown in patients with cardiac arrest (Wennervirta et al., 2009; Crepeau et al., 2013; Sandroni et al., 2013), after severe brain injury (Logi et al., 2011) and in ICU patients who are comatose due to anoxia, trauma, metabolic or infectious diseases (Young et al., 1999).

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Emergency medicine is about collaboration, not monopolisation

No abstract available

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Reply to: professionalisation rather than monopolisation is the future of emergency medicine in Europe

No abstract available

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History of anaesthesia: Nurse anaesthesia practice in the G7 countries (Canada, France, Germany, Italy, Japan, the United Kingdom and the United States of America)

imageMany factors determine whether nurses, physicians or both administer anaesthesia in any country. We examined the status of nurse-administered anaesthesia in the Group of Seven (G7) countries (Canada, France, Germany, Italy, Japan, the United Kingdom and the United States of America) and explored how historical factors, mixing global and local contexts (such as professional relations, medical and nursing education, social status of nurses, demographics and World Wars in the 20th century), help explain observed differences. Nearly equal numbers of physicians and nurses are currently engaged in the delivery of anaesthesia care in the United States but, remarkably, although the introduction or re-introduction of nurse anaesthesia in the 20th century was attempted in all the other G7 countries (except Japan), it has been successful only in France because of the cooperation with the United States during World War II.

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Reply to: emergency medicine is about collaboration, not monopolisation

No abstract available

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Does the β-receptor antagonist esmolol have analgesic effects?: A randomised placebo-controlled cross-over study on healthy volunteers undergoing the cold pressor test

imageBACKGROUND Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se. OBJECTIVES The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo. DESIGN Randomised, placebo-controlled cross-over study. SETTING Postoperative recovery area, Örebro University Hospital. Study period, November 2013 to February 2014. PARTICIPANTS Fourteen healthy volunteers. Exclusion criteria included ongoing medication, pregnancy and breastfeeding and participation in other medical trials. INTERVENTIONS At separate study sessions, participants received interventions: esmolol (0.7 mg kg−1 bolus over 1 min followed by infusion at 10 μg kg−1 min−1); 0.9% normal saline bolus then remifentanil infusion at 0.2 μg kg−1 min−1 and 0.9% normal saline bolus and infusion according to a random sequence. All infusions were administered over 30 min. MAIN OUTCOME MEASURES Perceived maximum pain intensity score, pain tolerance and haemodynamic changes during CPT, and occurrence of side-effects to interventions compared to placebo, respectively. RESULTS Esmolol did not reduce perceived pain intensity or pain tolerance during the CPT. The NRS-max score was similar for esmolol, 8.5 (±1.4) and placebo, 8.4 (±1.3). The mean difference was 0.1 [95% confidence interval (−1.2 to 1.4)], P value equal to 0.83. Remifentanil significantly reduced NRS-max scores, 5.4 (±2.1) compared to placebo, [mean difference −3.1 (95% confidence interval (−4.4 to −1.8)), P 

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Anaesthesiology and ethics: Can the anaesthesiologist ameliorate simply and rapidly the assessment of decision-making capacity in the elderly?

imageNo abstract available

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Standardised noxious stimulation-guided individual adjustment of remifentanil target-controlled infusion to prevent haemodynamic responses to laryngoscopy and surgical incision: A randomised controlled trial

imageBACKGROUND The surgical plethysmographic index (SPI) is one of the available indexes of the nociception–antinociception (NAN) balance. Individually adjusting the NAN balance to prevent somatic responses to noxious stimulation remains a challenge. OBJECTIVES To assess whether guiding remifentanil administration according to the SPI response to a calibrated noxious stimulus (NANCAL) can blunt the haemodynamic response to tracheal intubation and surgical incision. DESIGN Randomised multicentre study. SETTING Two Belgian university hospitals from January 2014 to April 2015. PATIENTS After ethic review board approval and informed consent, 48 American Society of Anesthesiologists I or II adult patients scheduled for surgery under general anaesthesia were enrolled. INTERVENTIONS Patients were randomly assigned to a SPI group, where remifentanil effect-site concentration was adjusted according to NANCAL, or a control group, where it was fixed at 4 ng ml−1. Propofol concentration was always adjusted to maintain the bispectral index close to 40. NANCAL consisted of a 100 Hz, 60 mA electrical tetanic stimulation during 30 s at the wrist before tracheal intubation and before surgical incision. MAIN OUTCOME MEASURES The primary endpoint was the efficacy of the NANCAL-guided remifentanil administration to prevent the haemodynamic response to tracheal intubation and surgical incision. The secondary aim was to compare the ability of SPI, analgesia nociception index, pupil diameter and mean arterial pressure response to NANCAL to predict the haemodynamic response to tracheal intubation and surgical incision. RESULTS Our SPI response to NANCAL-based correcting scheme for remifentanil administration was not superior to a fixed remifentanil concentration at blunting the haemodynamic response to tracheal intubation or surgical incision. Among all tested NAN balance indices, only mean arterial pressure had significant predictive ability with regard to the haemodynamic response to surgical incision. CONCLUSION Further research is needed to define the best NANCAL stimulus and the best remifentanil correcting scheme to help individualised tailoring of antinociception for each specific subpopulation of surgical patients. TRIAL REGISTRATION Clinicaltrials.gov NCT: 02884310; http://ift.tt/2B2PCiQ.

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Reply to: who takes the lead in critical illness?

No abstract available

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Neostigmine-based reversal of intermediate acting neuromuscular blocking agents to prevent postoperative residual paralysis: A systematic review

imageBACKGROUND Neostigmine is widely used to antagonise residual paralysis. Over the last decades, the benchmark of acceptable neuromuscular recovery has increased progressively to a train-of-four (TOF) ratio of at least 0.9. Raising this benchmark may impact on the efficacy of neostigmine. OBJECTIVE(S) The systematic review evaluates the efficacy of neostigmine to antagonise neuromuscular block to attain a TOF ratio of at least 0.9. DESIGN We performed a systematic search of the literature from January 1992 to December 2015. DATA SOURCES OR SETTING PubMed, EMBASE and the Cochrane Controlled Clinical Trials database were searched for randomised controlled human studies. Search was performed without language restrictions, using the following free text terms: 'neostigmine', 'sugammadex', 'edrophonium' or 'pyridostigmine' AND 'neuromuscular block', 'reversal' or 'reverse'. ELIGIBILITY CRITERIA Studies were accepted for inclusion if they used quantitative neuromuscular monitoring and neostigmine as the reversal agent. Selected trials were checked by two of the authors for data integrity. Trials relevant for inclusion had to report the number of patients included, the type of anaesthetic maintenance, the type of neuromuscular blocking agent used, the reversal agent and dose used, the depth of neuromuscular block when neostigmine was administered and the reversal time (time from injection of neostigmine until a TOF ratio ≥0.9 was attained). RESULTS 19 trials were eligible for quantitative analysis. In patients with deep residual block [T1 (first twitch height) 25% of baseline), or that a recovery time longer than 15 min be accepted.

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Reply to: collaboration in emergency medical care in Europe the ten principles of CRitical Emergency Medicine (CREM)

No abstract available

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Effects of magnesium chloride on rocuronium-induced neuromuscular blockade and sugammadex reversal in an isolated rat phrenic nerve–hemidiaphragm preparation: An in-vitro study

imageBACKGROUND Magnesium potentiates the effects of nondepolarising muscle relaxants. However, few studies have used magnesium chloride (MgCl2). Sugammadex reverses neuromuscular block by steroidal nondepolarising muscle relaxants. OBJECTIVES To assess the effects of MgCl2 on rocuronium-induced neuromuscular blockade and its reversal by sugammadex. DESIGN In-vitro experimental study. SETTING Animal laboratory, Asan Medical Center, Seoul, South Korea, from 20 March 2016 to 3 April 2016. ANIMALS Forty male Sprague Dawley rats. INTERVENTION Left phrenic nerve–hemidiaphragms from 40 Sprague Dawley rats were allocated randomly to four groups (1, 2, 3 and 4 mmol l-1 MgCl2 group, n = 10 each). Rocuronium was administered cumulatively until the first twitch of train-of-four (TOF) disappeared completely. Then, equimolar sugammadex was administered. MAIN OUTCOME MEASURES The effective concentration (EC) of rocuronium was obtained in each group. After administering sugammadex, recovery of the first twitch height and the TOF ratio were measured for 30 min. RESULTS EC50, EC90 and EC95 significantly decreased as the concentration of MgCl2 increased (all P ≤ 0.001), except the comparison between the 3 and 4 mmol l–1 MgCl2 groups. After administration of sugammadex, the maximal TOF ratio (%) was lower in the 4 mmol l-1 MgCl2 group than the 1 mmol l–1 MgCl2 group [median 91.7 interquartile range (83.4 to 95.8) vs. 98.3 interquartile range (92.2 to 103.4), P = 0.049]. The mean time (s) from sugammadex injection to achieving maximal first twitch was significantly prolonged in the 4 mmol l–1 MgCl2 group vs. the 1 mmol l–1 MgCl2 and 2 mmol l–1 MgCl2 groups [1483.9 (± 237.0) vs. 1039.0 (± 351.8) and 926.0 (± 278.1), P = 0.022 and 0.002, respectively]. CONCLUSION Increases in MgCl2 concentration reduce the ECs of rocuronium. In addition, administering sugammadex equimolar to the administered rocuronium shows limited efficacy as MgCl2 concentration is increased. TRIAL REGISTRATION The in-vitro study was not registered in a database.

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Effects of propofol on wound closure and barrier function of cultured endothelial cells: An in vitro experimental study

imageBACKGROUND Propofol is widely used in routine clinical practice for the induction and maintenance of anaesthesia. Although propofol is regarded as a well tolerated anaesthetic, its effect on intact or damaged endothelial cells has not yet been elucidated. OBJECTIVE The aim of this study was to investigate the effects of different concentrations of propofol on cell damage, metabolic activity, barrier function and wound healing capacity of human endothelial cells. DESIGN An in vitro investigation. SETTING Research Laboratory of the Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Kiel, Germany. MATERIALS In vitro cultures of primary human umbilical vein endothelial cells (HUVECs). INTERVENTIONS Intact HUVEC or wounded HUVEC monolayers were incubated with or without different concentrations of propofol (10, 30 and 100 μmol l-1). MAIN OUTCOME MEASURES Cell damage, metabolic activity, monolayer permeability, wound healing capacity, protein phosphorylation. RESULTS Propofol did not alter the morphology, induce cell damage or influence metabolic activity of intact HUVEC cells. Permeability of a HUVEC monolayer was increased by propofol 100 μmol l-1 (P 

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Who takes the lead in critically ill patients?

No abstract available

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Evaluation of recombinant factor VIIa, tranexamic acid and desmopressin to reduce prasugrel-related bleeding: A randomised, placebo-controlled study in a rabbit model

imageBACKGROUND Prasugrel is a thienopyridine that inhibits platelet aggregation more rapidly and effectively than clopidogrel, with an increased bleeding risk. OBJECTIVE The current study aimed to evaluate the efficacy of three nonspecific haemostatic drugs – recombinant activated factor VII (rFVIIa), tranexamic acid and desmopressin (DDAVP) – to limit blood loss after administration of prasugrel in a rabbit model of bleeding while also evaluating any prothrombotic effects. DESIGN Randomised, placebo-controlled study. SETTING Faculty of Medicine, University of Geneva, Switzerland, in 2013. ANIMALS Anaesthetised and artificially ventilated rabbits (n=56). INTERVENTIONS Animals were randomly allocated to one of five groups: control (placebo–placebo), prasugrel–placebo, rFVIIa (prasugrel–rFVIIa 150 μg kg−1), tranexamic acid (prasugrel–tranexamic acid 20 mg kg−1) or DDAVP (prasugrel–DDAVP 1 μg kg−1). Two hours after an oral prasugrel loading dose (4 mg kg−1), a stenosis and an injury were inflicted on the carotid artery to induce cyclic flow reductions (CFRs) due to thrombosis. Haemostatic drugs were administered during the ensuing observation period. MAIN OUTCOME MEASURES Standardised hepatosplenic sections were performed to evaluate the primary endpoint of blood loss, monitored for 15 min. Ear-immersion bleeding time and incidence of CFRs were secondary endpoints. RESULTS Prasugrel decreased ADP-induced platelet aggregation (light transmission method) from 66 ± 4% (mean ± SD) to 41 ± 7% (P 

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Professionalisation rather than monopolisation is the future of emergency medicine in Europe

No abstract available

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Impact of pectoral nerve block on postoperative pain and quality of recovery in patients undergoing breast cancer surgery: A randomised controlled trial

imageBACKGROUND In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery. The effect of PECS block on quality of recovery (QoR) after breast cancer surgery has not been evaluated. OBJECTIVES To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery. DESIGN Randomised controlled study. SETTING A tertiary hospital. PATIENTS Sixty women undergoing breast cancer surgery between April 2014 and February 2015. INTERVENTIONS The patients were randomised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a saline mock block (control group). The patients answered a 40-item QoR questionnaire (QoR-40) before and 1 day after breast cancer surgery. MAIN OUTCOME MEASURES Numeric Rating Scale score for postoperative pain, requirement for intra-operative propofol and remifentanil, and QoR-40 score on postoperative day 1. RESULTS PECS block combined with propofol–remifentanil anaesthesia significantly improved the median [interquartile range] pain score at 6 h postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P = 0.018]. PECS block also reduced propofol mean (± SD) estimated target blood concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group 2.65 (± 0.52) vs. Control group 3.08 (± 0.41) μg ml−1; P 

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Collaboration in emergency medical care in Europe: the patient is the winner

No abstract available

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Ultrasound with neurostimulation compared with ultrasound guidance alone for lumbar plexus block: A randomised single blinded equivalence trial

imageBACKGROUND Ultrasound-guided lumbar plexus blocks usually require confirmatory neurostimulation. A simpler alternative is to inject local anaesthetic inside the posteromedial quadrant of the psoas muscle under ultrasound guidance. OBJECTIVE We hypothesised that both techniques would result in similar total anaesthesia time, defined as the sum of performance and onset time. DESIGN A randomised, observer-blinded, equivalence trial. SETTING Ramathibodi Hospital and Maharaj Nakorn Chiang Mai Hospital (Thailand) from 12 May 2016 to 10 January 2017. PATIENTS A total of 110 patients undergoing total hip or knee arthroplasty, who required lumbar plexus block for postoperative analgesia. INTERVENTION In the combined ultrasonography-neurostimulation group, quadriceps-evoked motor response was sought at a current between 0.2 and 0.8 mA prior to local anaesthetic injection (30 ml of lidocaine 1% and levobupivacaine 0.25% with epinephrine 5 μg ml−1 and 5 mg of dexamethasone). In the ultrasound guidance alone group, local anaesthetic was simply injected inside the posteromedial quadrant of the psoas muscle. MAIN OUTCOMES MEASURES We measured the total anaesthesia time, the success rate (at 30 min), the number of needle passes, block-related pain, cumulative opioid consumption (at 24 h) and adverse events (vascular puncture, paraesthesia, local anaesthetic spread to the epidural space). The equivalence margin was 7.4 min. RESULTS Compared with ultrasound guidance alone, combined ultrasonography-neurostimulation resulted in decreased mean (±SD) total anaesthesia time [15.3 (±6.5) vs. 20.1 (±9.0) min; mean difference, −4.8; 95% confidence interval, −8.1 to −1.9; P = 0.005] and mean (±SD) onset time [10.2 (±5.6) vs. 15.5 (±9.0) min; P = 0.004). No inter-group differences were observed in terms of success rate, performance time, number of needle passes, block-related pain, opioid consumption or adverse events. CONCLUSION Although the ultrasonography-neurostimulation technique results in a shorter total anaesthesia time compared with ultrasound guidance alone, this difference falls within our accepted equivalence margin (±7.4 min). TRIAL REGISTRATION www.clinicaltrials in the (Study ID: TCTR20160427003).

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Ultrasound in Anesthesia, Critical Care, and Pain Management

No abstract available

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The Drosophila histone methyltransferase NSD is positively regulated by the DRE/DREF system

Abstract

The Drosophila nuclear receptor-binding SET domain protein (NSD) gene encodes the Drosophila ortholog of mammalian NSD family members that are important in many aspects of development and disease in humans. In this study, we observed that overexpression of Drosophila NSD in imaginal discs induces organ atrophy. Thus, to gain an understanding of the transcriptional regulation of the gene, we analyzed the NSD promoter region. First, we identified the presence of three putative DNA replication-related element (DRE) sequences in its promoter region, where DRE-binding factor (DREF) could bind for transcriptional activation. In the experiments with the fly GAL4-UAS system, we demonstrated that overexpressed DREF increased the endogenous NSD transcription. To confirm the role of DREF as a transcriptional activator on the NSD expression, we generated a series of luciferase reporter gene constructs containing deleted portions of the 5′-flanking regions as well as point mutations in the putative DRE sites. When transiently transfected into S2 cells, the deletion construct containing no DRE sites showed dramatic decrease in the NSD promoter activity, but only two sites near the transcriptional start site were important. Furthermore, we verified the direct interaction of DREF with the two positively cis-acting sequences on the NSD promoter by chromatin immunoprecipitation assay. Taken together, these results demonstrated that NSD is one of the downstream targets of the DRE/DREF pathway that is associated with various cellular processes in Drosophila, indicating that our findings may contribute to the understanding of molecular mechanisms in complex disorders associated with NSD family members in humans.



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Responsiveness of the Traumatic Brain Injury – Quality of Life (TBI-QOL) Measurement System

Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Julia M.P. Poritz, Mark Sherer, Pamela A. Kisala, David Tulsky, Luis Leon-Novelo, Esther Ngan
ObjectiveTo assess the responsiveness of the Traumatic Brain Injury – Quality of Life (TBI-QOL) measurement system.DesignParticipants completed the 20 TBI-QOL item banks and the Participation Assessment with Recombined Tools – Objective (PART-O) Productivity Subscale at baseline and 6-month follow-up assessments. Participants were categorized into three groups (increased productivity, unchanged productivity, and decreased productivity) based on PART-O Productivity scores. Paired sample t-tests were used to compare TBI-QOL scores at baseline and 6 months, and standardized response means and Cohen's d were computed to estimate effect sizes.Setting3 TBI Model Systems rehabilitation centers in the U.S.Participants201 community-dwelling adults with traumatic brain injury (TBI)InterventionsNot applicable.Main Outcome Measures20 TBI-QOL item banks.ResultsAs expected, given that there was no intervention, group mean TBI-QOL subdomain scores for the entire sample showed no change or small improvement over the 6-month study period. At the follow-up assessment, 72 participants reported increased productivity, 71 reported decreased productivity, and 58 reported the same level of productivity as they had 6 months prior. When compared with participants who reported unchanged or decreased productivity, participants who reported increased productivity on the PART-O had clinically meaningful (d ≥ 0.30) improvements on seven TBI-QOL measures. The largest improvement was in Independence (mean change, 7.06; d = .84), with differences also observed in the Mobility, Positive Affect and Well-Being, Resilience, Grief/Loss, Ability to Participate, and Satisfaction with Participation subdomains.ConclusionsThe 20 TBI-QOL item banks demonstrate responsiveness to change and measurement stability in a community-dwelling sample. Researchers may use the TBI-QOL to detect changes in HRQOL following a clinical intervention and clinicians may use it in their daily practices to monitor patient recovery.



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Predictors for employment status in people with multiple sclerosis: a 10-year longitudinal observational study

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Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Mia Forslin, Katharina Fink, Ulf Hammar, Lena von Koch, Sverker Johansson
ObjectiveTo identify predictors for employment status after 10 years in a cohort of people with multiple sclerosis (MS), with the aim to increase knowledge concerning factors present at an early stage important for working life and work-life balance.DesignA 10-year longitudinal observational cohort study.SettingPeople with a definite MS diagnosis, who at inclusion were outpatients at an MS Centre at a university hospital in Stockholm, Sweden.ParticipantsA consecutive sample of 154 people with MS of working age were included at baseline of which a total of 116 people participated in the 10-year follow-up – 27 people declined participation and 11 were deceased.MethodsBaseline data on personal factors and functioning were used as independent variables. Employment status 10 years after baseline, categorized as full-time work, part-time work and no work, was used as the dependent variable. A generalized ordinal logistic regression was used to analyse the predictive value of the independent variables.InterventionsNot applicable.Main outcome measureEmployment status.ResultsPredictors for full- or part-time work after 10 years were young age (p=0.002), low perceived physical impact of MS (p=0.02), fatigue (p=0.03), full-time work (p=0.001) and high frequency of social/lifestyle activities (p=0.001) at baseline. Low perceived physical impact of MS (p=0.02) at baseline also predicted full-time work after 10 years.ConclusionsThis study underlines the complexity of working life for people with MS, and indicates that it may be valuable to give more attention to the balance between working and private life, both in clinical practice and future research, in order to achieve a sustainable working life over time.



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The effect of whole body vibration on sagittal plane running mechanics in individuals with anterior cruciate ligament reconstruction: a randomized crossover trial

Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Derek N. Pamukoff, Melissa M. Montgomery, Kevin Choe, Tyler J. Moffit, Michael N. Vakula
ObjectiveTo examine the effect of whole body vibration (WBV) on running biomechanics in individuals with anterior cruciate ligament reconstruction (ACLR).DesignSingle-blind randomized crossover trial.SettingResearch laboratory.Participants20 individuals with unilateral ACLR (age=22.3 (3.3) years; mass=71.8 (15.3) kg; time since ACLR=44.9 (22.8) months; 15 females, 10 patellar tendon autograft, 7 hamstrings autograft, 3 allograft; International Knee Documentation Committee Score=83.5 (9.3)).Main Outcome MeasureParticipants performed isometric squats while being exposed to WBV or no vibration (control). WBV and control conditions were delivered in a randomized order during separate visits separated by 1-week washout periods. Running biomechanics of the injured and uninjured limbs were evaluated prior to and immediately following each intervention. Dependent variables included peak vertical ground reaction force (GRF) and loading rate (LR), peak knee flexion angle and external moment, and knee flexion excursion during the stance phase of running.ResultsThere was an increase in knee flexion excursion (+4.1°, 95% CI: 0.65, 7.5°), and a trend towards a reduction in instantaneous LR following WBV in the injured limb (-4.03 BW•sec-1, 95%CI: -0.38, -7.69). No effect was observed on peak GRF, peak knee flexion angle, or peak external knee flexion moment, and no effect was observed in the uninjured limb.ConclusionOur findings indicate that a single session of WBV acutely increases knee flexion excursion. WBV could be useful to improve running characteristics in individuals with knee pathology.



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Investigating the variability in mild traumatic brain injury definitions: a prospective cohort study

Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Louise M. Crowe, Stephen Hearps, Vicki Anderson, Meredith Borland, Natalie Phillips, Amit Kochar, Sarah Dalton, John A. Cheek, Yuri Gilhotra, Jeremy Furyk, Jocelyn Neutze, Mark D. Lyttle, Silvia Bressan, Susan Donath, Charlotte Molesworth, Ed Oakley, Stuart R. Dalziel, Franz E. Babl
ObjectiveTo prospectively compare the proportion of traumatic brain injuries (TBIs) that would be classified as 'mild' using different published definitions by applying published definitions of mild TBI to a large prospectively collected dataset and to examine the variability in the proportions included by various definitions. High rates of mild TBI in children makes it a major public health issue, however, there is a wide variation in how mild TBI is defined in literature and guidelines.DesignProspective observational study.SettingTen hospital emergency departments in the 'PREDICT' network based in Australia and New Zealand.ParticipantsThe sample included 11,907 children aged 3-16 years. The mean age was 8.2 years (SD = 3.9 years), 3,868 (32.5%) were female, and 7,374 (61.9%) of TBI were due to a fall. Median Glasgow Coma Score was 15.Main outcome measureWe applied 17 different definitions of mild TBI, identified through a published systematic review, to children aged 3-16 years. Adjustments and clarifications were made to some definitions. The number and percentage identified for each definition is presented.ResultsAdjustments had to be made to the 17 definitions to apply to the dataset: none in 7, minor to substantial in 10. The percentage classified as mild TBI across definitions varied from 7.1% (n = 841) to 98.7% (n = 11,756) and varied by age group.ConclusionsWhen applying the 17 definitions of mild TBI to a large prospective multicenter dataset of TBI there was wide variability in the number of cases classified. Clinicians and researchers need to be aware of this variability when examining literature concerning children with mild TBI.



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The effectiveness of botulinum toxin A for persistent upper limb pain after breast cancer treatment: a double-blinded randomized controlled trial

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Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): An De Groef, Nele Devoogdt, Marijke Van Kampen, Ines Nevelsteen, Ann Smeets, Patrick Neven, Inge Geraerts, Lore Dams, Elien Van der Gucht, Philippe Debeer
ObjectiveTo investigate the effect of a single Botulinum Toxin A infiltration in the pectoralis major muscle in addition to a standard physical therapy program for treatment of persistent upper limb pain in breast cancer survivors.DesignDouble-blinded (patient and assessor) randomized controlled trialSettingUniversity Hospital Leuven, BelgiumParticipantsFifty breast cancer patients with pain.InterventionThe intervention group received a single Botulinum Toxin A (BTX-A) infiltration. The control group received a placebo (saline) infiltration. Within one week after the infiltration, all patients attended an individual physical therapy program (12 sessions) during the first 3 months and a home exercise program up to 6 months after infiltration.Main outcome MeasuresThe primary outcome was change in pain intensity at the upper limb (Visual Analogue Scale (VAS) (0-100)) after 3 months. Secondary outcomes were prevalence rate of pain, pressure hypersensitivity, pain quality, shoulder function and quality of life. Measures were taken before the intervention and at 1, 3 and 6 months follow-up.ResultsNo significant difference in change in pain intensity after 3 months was found (mean difference in change of 3/100; 95% CI -13 to 19). From baseline up to 6 months, a significantly different change in upper limb pain intensity was found between groups in favor of the intervention group (mean difference in change of 16/100; 95% CI 1 to 31).ConclusionA single Botulinum Toxin A infiltration in combination with an individual physical therapy program has been found to significantly decrease pain intensity at the upper limb in breast cancer survivors up to 6 months. However, the effect size was not clinically relevant and no other beneficial effects were found.



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Hospital Readmissions among Total Hip Replacement Patients in 2009 and 2014

Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Michael P. Cary, Victoria Goode, Nancy Crego, Deirdre Thornlow, Cathleen Colón-Emeric, Helen M. Hoenig, Kayla Baba, Scarlet Fellingham, Elizabeth I. Merwin
ObjectiveTo document changes in 30-day hospital readmission rates and causes for returning to the hospital for care among THR patients in US hospitals in 2009 and 2014.DesignCross-sectional, retrospective descriptive. We used data from the Nationwide Readmissions Database (NRD) which is drawn from the Healthcare Cost and Utilization Project (HCUP) net – sponsored by the Agency for Healthcare Research and Quality (AHRQ).SettingThe AHRQ database, known as NRD, is based on a 20% sample of all hospital discharges in the nation.ParticipantsTHR patients (identified as ICD-9-CM procedure code 81.51) in 2009 (N=31,232) and (N = 32,863) in 2014.InterventionsNot applicable.Main outcome measure30-day hospital readmission.ResultsCompared to 2009, overall rates of 30-day readmissions after THR decreased by 1.3% in 2014. The decrease in readmission rates varied by groups with lesser improvements seen among THR patients who were younger, with private insurance, residing in lower-income and rural communities. Device complications were the leading cause for readmission among THR patients, increasing from 19.8% in 2009 to 23.9% in 2014.



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Importance of complete phenotyping in prenatal whole exome sequencing

Abstract

Whole exome sequencing (WES) is an emerging technique in prenatal diagnosis. In this retrospective study, we examined diagnostic utility and limitations of WES in prenatal cases with structural birth defects. DNA from 20 trios (fetal and parental), with normal karyotype and microarray findings, underwent WES and variant interpretation at a reference laboratory. The WES results were later re-evaluated in our academic center utilizing prenatal and postnatal phenotyping. Initial analysis using only prenatal ultrasound findings revealed no pathogenic or likely pathogenic variants in 20 pregnancies with structural birth defects. Re-analysis of WES variants and combination of prenatal and postnatal phenotyping yielded pathogenic variants in at least 20% of cases including PORCN gene in a fetus with split-hand/foot malformation, as well as variants of uncertain significance in NEB and NOTCH1 in fetuses with postnatal muscle weakness and Adams–Oliver syndrome, respectively. Furthermore, Sanger sequencing in a patient with holoprosencephaly, elucidated by postnatal MRI, revealed a pathogenic 47-base pairs deletion in ZIC2 which was missed by prenatal WES. This study suggests that incomplete prenatal phenotyping and lack of prenatal ultrasound-genotype databases are the limiting factors for current interpretation of WES data in prenatal diagnosis. Development of prenatal phenotype–genotype databases would significantly help WES interpretation in this setting. Patients who underwent prenatal clinical WES may benefit from the re-analysis based on detailed postnatal findings.



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Microsatellite DNA analysis reveals lower than expected genetic diversity in the threatened leopard cat ( Prionailurus bengalensis ) in South Korea

Abstract

To optimize conservation efforts, it is necessary to determine the risk of extinction by collecting reliable population information for a given species. We developed eight novel, polymorphic microsatellite markers and used these markers in conjunction with twelve existing markers to measure genetic diversity of South Korean populations of leopard cat (Prionailurus bengalensis), a species for which population size and habitat area data are unknown in the country, to assess its conservation status. The average number of alleles and the observed heterozygosity of the species were 3.8 and 0.41, respectively, and microsatellite diversity was lower than the average genetic diversity of 57 populations of 12 other felid species, and lower than that of other mammal populations occurring in South Korea, including the raccoon dog (Nyctereutes procyonoides), water deer (Hydropotes inermis), and endangered long-tailed goral (Naemorhedus caudatus). Furthermore, analysis of genetic structure in the national leopard cat population showed no clear genetic differentiation, suggesting that it is not necessary to divide the South Korean leopard cat population into multiple management units for the purposes of conservation. These results indicate that the genetic diversity of the leopard cat in South Korea is unexpectedly low, and that the risk of local extinction is, as a result, substantial. Thus, it is necessary to begin appropriate conservation efforts at a national level to conserve the leopard cat population in South Korea.



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The complete chloroplast genome of the green algae Hariotina reticulata (Scenedesmaceae, Sphaeropleales, Chlorophyta)

Abstract

In this study, the chloroplast genome of Hariotina reticulata was fully sequenced and compared to other Sphaeropleales chloroplast genomes. It is 210,757 bp larger than most Sphaeropleales cpDNAs. It presents a traditional chloroplast structure, and contains 103 genes, including 68 protein-coding genes, six rRNA genes and 29 tRNA genes. The coding region constitutes of 43% of the whole cpDNA. Eighteen introns are found in 11 genes and six introns are unique for Hariotina. 11 open reading frames are identified among these introns. The synteny between Hariotina and Acutodesmus cpDNAs is in general identical, while within Sphaeropleales order, high variability in cpDNA architecture is indicated by general high DCJ distances. Ankyra judayi exhibits the greatest dissimilarity in gene synteny to the others and share some unique gene clusters with Treubaria triappendiculata. The phylogenomic analyses show that A. judayi is clustered with Treubariaceae species and sister to Chlorophyceae incertae sedis and other Sphaeropleales species. The monophyly of Sphaeropleales is rejected.



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Dimensionality and R4P: A Health Equity Framework for Research Planning and Evaluation in African American Populations

Abstract

Introduction Existing health disparities frameworks do not adequately incorporate unique interacting contributing factors leading to health inequities among African Americans, resulting in public health stakeholders' inability to translate these frameworks into practice. Methods We developed dimensionality and R4P to integrate multiple theoretical perspectives into a framework of action to eliminate health inequities experienced by African Americans. Results The dimensional framework incorporates Critical Race Theory and intersectionality, and includes dimensions of time—past, present and future. Dimensionality captures the complex linear and non-linear array of influences that cause health inequities, but these pathways do not lend themselves to approaches to developing empirically derived programs, policies and interventions to promote health equity. R4P provides a framework for addressing the scope of actions needed. The five components of R4P are (1) Remove, (2) Repair, (3) Remediate, (4) Restructure and (5) Provide. Conclusion R4P is designed to translate complex causality into a public health equity planning, assessment, evaluation and research tool.



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Patients' perceived needs of healthcare providers for low back pain management: a systematic scoping review

Optimal management of low back pain (LBP) involves patients' active participation in care, facilitated by positive interactions with their healthcare provider(s) (HCP). An understanding of patients' perceived needs regarding their HCP is, therefore, necessary to achieve such outcomes. Therefore, the aim is to review the existing literature regarding patients' perceived needs of HCP managing LBP.

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Expanding the clinical and genetic spectra of NKX6-2-related disorder

ABSTRACT

Hypomyelinating leukodystrophies (HLDs) affect the white matter of the central nervous system, and manifest as neurological disorders. They are genetically heterogeneous. Very recently, biallelic variants in NKX6-2 have been suggested to cause a novel form of autosomal recessive HLD. Using whole exome or whole genome sequencing, we identified the previously reported c.196delC and c.487C>G variants in NKX6-2 in three and two unrelated index cases, respectively; the novel c.608G>A variant was identified in a sixth patient. All variants were homozygous in affected family members only. Our patients share a primary diagnosis of psychomotor delay, and show spastic quadriparesis, nystagmus and hypotonia. Seizures and dysmorphic features (observed in two families each) represent an addition to the phenotype, while developmental regression (observed in three families) appears to be a notable and previously underestimated clinical feature. Our findings extend the clinical and mutational spectra associated with this novel form of HLD. Comparative analysis of our 10 patients and the 15 reported previously did, however, not reveal clear evidence for a genotype-phenotype correlation.

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A Narrative Review of Cardiovascular Abnormalities After Spontaneous Intracerebral Hemorrhage

Background: The recommended cardiac workup of patients with spontaneous intracerebral hemorrhage (ICH) includes an electrocardiogram (ECG) and cardiac troponin. However, abnormalities in other cardiovascular domains may occur. We reviewed the literature to examine the spectrum of observed cardiovascular abnormalities in patients with ICH. Methods: A narrative review of cardiovascular abnormalities in ECG, cardiac biomarkers, echocardiogram, and hemodynamic domains was conducted on patients with ICH. Results: We searched PubMed for articles using MeSH Terms "heart," "cardiac," hypertension," "hypotension," "blood pressure," "electro," "echocardio," "troponin," "beta natriuretic peptide," "adverse events," "arrhythmi," "donor," "ICH," "intracerebral hemorrhage." Using Covidence software, 670 articles were screened for title and abstracts, 482 articles for full-text review, and 310 extracted. A total of 161 articles met inclusion and exclusion criteria, and, included in the manuscript. Cardiovascular abnormalities reported after ICH include electrocardiographic abnormalities (56% to 81%) in form of prolonged QT interval (19% to 67%), and ST-T changes (19% to 41%), elevation in cardiac troponin (>0.04 ng/mL), and beta-natriuretic peptide (BNP) (>156.6 pg/mL, up to 78%), echocardiographic abnormalities in form of regional wall motion abnormalities (14%) and reduced ejection fraction. Location and volume of ICH affect the prevalence of cardiovascular abnormalities. Prolonged QT interval, elevated troponin-I, and BNP associated with increased in-hospital mortality after ICH. Blood pressure control after ICH aims to preserve cerebral perfusion pressure and maintain systolic blood pressure between 140 and 179 mm Hg, and avoid intensive blood pressure reduction (110 to 140 mm Hg). The recipients of ICH donor hearts especially those with reduced ejection fraction experience increased early mortality and graft rejection. Conclusions: Various cardiovascular abnormalities are common after spontaneous ICH. The workup of patients with spontaneous ICH should involve 12-lead ECG, cardiac troponin-I, as well as BNP, and echocardiogram to evaluate for heart failure. Blood pressure control with preservation of cerebral perfusion pressure is a cornerstone of hemodynamic management after ICH. The perioperative implications of hemodynamic perturbations after ICH warrant urgent further examination. A.L. has received research support from Edge Therapeutics for NEWTON-2 study, Aqueduct Critical Care for the ASSESSED clinical trial, and from NIH/NINDS for the ATACH-II clinical trial, none of which are relevant to this study. The remaining authors have no funding or conflicts of interest to disclose. Address correspondence to: Abhijit Lele, MBBS, MD, MS, Department of Anesthesiology, Harborview Medical Center, University of Washington, 325, 9th Avenue, P.O. Box 356540, Seattle, WA 98104 (e-mail: abhijit2@uw.edu). Received October 17, 2017 Accepted December 31, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: First descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes

The earliest examples of neurofibromatosis (in this case type 1, NF1) can be traced in the Ebers Papyrus (Ancient Egypt, 1.500 B.C.), in a Hellenistic statuette (Smyrna, 323 B.C.), in the coinage of the Parthians kings (247 B.C.) and in some 13th century monks' drawings. These earlier examples are somewhat less well defined as compared to the most recent better defined reports credited as having NF1 including an Inca child mummy (1480—1650 AD), Ulisse Aldrovandi's homuncio ("Monstrorum Historia", 1592 A.D.) with mosaic NF1 or the illustrations seen in the 18th century "Buffon's Histoire Naturelle" and "Cruveilhier's Anatomie Pathologique du Corps Human". The first English language report on NF1 was made by Akenside in 1768 and the first systematic review by Robert William Smith in 1849, while Virchow's pupil, Friedrich Daniel von Recklinghausen, in 1882, was the first to understand the origin of skin tumors and to name them neurofibromas. The touching story of Joseph C. Merrick (the "Elephant man," (who had Proteus syndrome and not NF1), in 1884, played an important role in the later misconception of NF1, as did the novel by Vicotr Hugo on the hunchback Quasimodo. The studies by van der Hoeve (1921), Yakovlev and Guthrie (1931), and Van Bogaert (1935), categorized "von Recklinghausen's" neurofibromatosis among the phakomatoses and the neurocutaneous syndromes. The first known mention of an acoustic neuroma (at autopsy) is attributed to Eduard Sandifort (1777 AD) while John H. Wishart made the earliest autoptic description of neurofibromatosis type 2 (NF2), in 1822, in a 21-year-old man with bilateral acoustic neuromas, who manifested signs since his infancy (Wishart subtype NF2). Smith likely described the first case of schwannomatosis in 1849. Older, Virchow, von Recklinghausen, and Verocay first classified "neuromas" and Masson and Penfield first used the word "schwannoma" taking it from Theodore Schwann's works. In 1903 Henneberg and Koch described NF2 in detail. Young, Eldridge, and Gardner, in the late '70, established NF2 as a distinct familial entity (Gardner subtype NF2). Schwannomatosis, the late entry of the different forms of neurofibromatosis, was credited in the middle '90.



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Incidence, puberty, and fertility in 45,X/47,XXX mosaicism: Report of a patient and a literature review



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Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant

Mitochondrial NAD kinase deficiency (NADK2D, OMIM #615787) is a rare autosomal recessive disorder of NADPH biosynthesis that can cause hyperlysinemia and dienoyl-CoA reductase deficiency (DECRD, OMIM #616034). NADK2 deficiency has been reported in only three unrelated patients. Two had severe, unremitting disease; one died at 4 months and the other at 5 years of age. The third was a 10 year old female with CNS anomalies, ataxia, and incoordination. In two cases mutations in NADK2 have been demonstrated. Here, we report the fourth known case, a 15 year old female with normal intelligence and a mild clinical and biochemical phenotype presumably without DECRD. Her clinical symptoms, which are now stable, became evident at the age of 9 with the onset of decreased visual acuity, bilateral optic atrophy, nystagmus, episodic lower extremity weakness, peripheral neuropathy, and gait abnormalities. Plasma amino acid levels were within normal limits except for mean lysine and proline levels that were 3.7 and 2.5 times the upper limits of normal. Whole exome sequencing (WES) revealed homozygosity for a g.36241900 A>G p. Met1Val start loss mutation in the primary NADK2 transcript (NM_001085411.1) encoding the 442 amino acid isoform. This presumed hypomorphic mutation has not been previously reported and is absent from the v1000GP, EVS, and ExAC databases. Our patient's normal intelligence and stable disease expands the clinical heterogeneity and the prognosis associated with NADK2 deficiency. Our findings also clarify the mechanism underlying NADK2 deficiency and suggest that this disease should be ruled out in cases of hyperlysinemia, especially those with visual loss, and neurological phenotypes.



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Identifying the role of group III/IV muscle afferents in the carotid baroreflex control of mean arterial pressure and heart rate during exercise

Abstract

This study sought to comprehensively investigate the role of metabolically and mechanically sensitive group III/IV muscle afferents in carotid baroreflex responsiveness and resetting during both electrically-evoked (EVO, no central command) and voluntary (VOL, requiring central command) isometric single-leg knee-extension (15% of MVC) exercise. Participants (n = 8) were studied under control conditions (CTRL) and following lumbar intrathecal fentanyl injection (FENT) to inhibit μ-opioid receptor-sensitive lower limb muscle afferents. Spontaneous carotid baroreflex control of mean arterial pressure (MAP) and heart rate (HR) were assessed following rapid 5-s pulses of neck pressure (NP, +40 mmHg) or suction (NS, −60 mmHg). Resting MAP (87 ± 10 mmHg) and HR (70 ± 8 bpm) were similar between CTRL and FENT conditions (P>0.4). In terms of spontaneous carotid baroreflex responsiveness, FENT did not alter the change in MAP or HR responses to NP (+13 ± 5 mmHg, P = 0.85; +9 ± 3 bpm; P = 0.99) or NS (−13 ± 5 mmHg, P = 0.99; −24 ± 11 bpm; P = 0.49) at rest or during either exercise paradigm, which were of a remarkably similar magnitude to rest. In contrast, FENT administration reduced the exercise-induced resetting of the operating point for MAP and HR during both EVO (116 ± 10 mmHg to 100 ± 15 mmHg and 93 ± 14 bpm to 82 ± 10 bpm) and VOL (107 ± 13 mmHg to 100 ± 17 mmHg and 89 ± 10 bpm to 72 ± 10 bpm) exercise bouts. Together, these findings document that group III/IV muscle afferent feedback is critical for the resetting of the carotid baroreflex MAP and HR operating points, independent of exercise-induced changes in central command, but not for spontaneous carotid baroreflex responsiveness.

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Spread of Quadratus Lumborum Block to the Paravertebral Space Via Intramuscular Injection: A Volunteer Study

Background and Objectives Several types of quadratus lumborum block (QLB) are used for postoperative analgesia and are believed to be effective against both somatic and visceral pain via a local anesthetic (LA) effect in the paravertebral space (PVS). However, it remains unclear whether all QLB techniques result in LA spread into the PVS. We hypothesized that LA administered via intramuscular QLB would spread into the paravertebral space and investigated the spread and sensory block area of LA in intramuscular QLB. Methods This volunteer study included 5 healthy men and 1 woman, with no previous medical history. Intramuscular QLB and lateral transversus abdominis plane block were performed under real-time ultrasound guidance for comparison of sensory deprivation range. Two days later, the same procedure was performed on the contralateral side of the body. The spread of LA via intramuscular QLB spread to the PVS was assessed 1 hour after the first injections using magnetic resonance imaging. Sensory perception was also evaluated by the pinprick test at 90 minutes after injection. Results In total, we performed 11 intramuscular QLBs and 11 lateral transversus abdominis plane blocks. Magnetic resonance imaging showed that LA did not spread into the PVS after ultrasound-guided intramuscular QLB. The analgesic area corresponded to the side of the body that was ipsilateral to the block. Conclusions Ultrasound-guided intramuscular QLBs are not clinically useful for procedures requiring LA spread into the PVS but do result in an ipsilateral analgesic effect in healthy volunteers. Clinical Trial Registration This study was registered at University Hospital Medical Information Network Clinical Trials Registry, UMIN 000019149. Accepted for publication October 4, 2017. Address correspondence to: Takahiro Tamura, MD, PhD, Department of Anesthesiology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-Ku, Nagoya 466-8550, Japan (e-mail: takahiro@med.nagoya-u.ac.jp). Nagoya University Graduate School of Medicine and Japanese Red Cross Nagoya Daiichi Hospital funded this study by providing funding to the Department of Anesthesiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. This work was presented in part at the American Society of Anesthesiologists' Anesthesiology 2016 meeting; Chicago, IL; October 22 to 26, 2016. The authors declare no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Trauma and transfusion in the geriatric patient

Purpose of review The percentage of people over the age of 65 is growing rapidly and anesthesiologists must develop a medical understanding that is comprehensive to meet the unique medical needs of this population. The changing physiology of an elderly population makes them extremely vulnerable to trauma and the administration of blood products. Although most of these cases involve orthopedic attention, it is not less dangerous as a blunt trauma case. Recent findings This article addresses some of the main concerns for the anesthesiologists of providing a hemostatic resuscitation in the geriatric population. Should blood that is new lead to better outcomes than blood that was collected more than 14 days from the injury? What role does patient frailty have in trauma and transfusion outcomes? Is the massive transfusion protocol safe for the geriatric population? As this subset of the population grows, the number of patients on anticoagulation therapy will grow. Knowledge of the bone marrow plays an important role in geriatric trauma. How does head trauma in the elderly differ from the younger patient? Summary The information in this article is by no means comprehensive. Nongeriatric trauma protocols are far from being validated. Applying these protocols to the geriatric protocols must be investigated in terms of safety and benefits. Correspondence to Corey Scott Scher, Clinical Professor of Anesthesiology, New York University School of Medicine, Bellevue Hospital, 560 First Ave, New York City, NY 10016, USA. Tel: +1 646 753 2791; fax: +1 212 787 2721; e-mail: coreyscher@gmail.com;Corey.Scher@nyumc.org Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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For beginners in anaesthesia, self-training with an audiovisual checklist improves safety during anaesthesia induction: A prospective, randomised, controlled two-centre study

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BACKGROUND Beginners in residency programmes in anaesthesia are challenged because working environment is complex, and they cannot rely on experience to meet challenges. During this early stage, residents need rules and structures to guide their actions and ensure patient safety. OBJECTIVE We investigated whether self-training with an electronic audiovisual checklist app on a mobile phone would produce a long-term improvement in the safety-relevant actions during induction of general anaesthesia. DESIGN, SETTING AND PARTICIPANTS During the first month of their anaesthesia residency, we randomised 26 residents to the intervention and control groups. The study was performed between August 2013 and December 2014 in two university hospitals in Germany. INTERVENTION In addition to normal training, the residents of the intervention group trained themselves on well tolerated induction using the electronic checklist for at least 60 consecutive general anaesthesia inductions. MAIN OUTCOME MEASURES After an initial learning phase, all residents were observed during one induction of general anaesthesia. The primary outcome was the number of safety items completed during this anaesthesia induction. Secondary outcomes were similar observations 4 and 8 weeks later. RESULTS Immediately, and 4 weeks after the first learning phase, residents in the intervention group completed a significantly greater number of safety checks than residents in the control group 2.8 [95% confidence interval (CI) 0.4 to 5.1, P = 0.021, Cohen's d = 0.47] and 3.7 (95% CI 1.3 to 6.1, P = 0.003, Cohen's d = 0.61), respectively. The difference between the groups had disappeared by 8 weeks: mean difference in the number of safety checks at 8 weeks was 0.4, 95% CI −2.0 to 2.8, P = 0.736, Cohen's d = 0.07). CONCLUSION The use of an audiovisual self-training checklists improves safety-relevant behaviour in the early stages of a residency training programme in anaesthesia. Correspondence to Dr Stefanie Beck, Department of Anaesthesiology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany E-mail: st.beck@uke.de © 2018 European Society of Anaesthesiology

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