Σάββατο, 19 Μαΐου 2018

Comprehensive Statistical Analysis of the Gait Parameters in Neurodegenerative Diseases

Neurodegenerative diseases significantly alter the gait dynamics and, hence, various gait parameters. In this paper, we present results of a comprehensive statistical analysis of the gait time parameters, namely swing interval, stance interval, stride interval, and double support interval, in healthy individuals and patients suffering from neurodegenerative diseases (Huntington's, HD, Parkinson's, PD, and amyotrophic lateral sclerosis, ALS). Multivariate analysis of variance (MANOVA) along with other tests, including univariate tests, post-hoc tests, and discriminant analysis, were employed in this study. Results of discriminant analysis demonstrated that the groups differed significantly from each other with respect to the dependent variables (P < 0.05). All the variables had a strong positive relationship with the first variate or factor, and the left swing, right swing, right stride, and left stride had a positive relationship with the second variate; the double support had a negative relationship. Results of our analyses provide a direction for the selection of certain gait parameters for automatic classification of neurodegenerative diseases based on these parameters.



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Anticipatory Inhibition of EMG Activity of the Human M. Soleus at Voluntary Contraction of Its Antagonists

Quantitative changes in background tonic EMG activity of m. soleus within a premotor period of voluntary contraction of its antagonists were examined in healthy humans. The above activity was recorded in the lying position at voluntary moderate tonic tension of this muscle and in the upright position, where the body was supported by both legs. The effect of voluntary flexion of the ipsilateral ankle joint (a simple motor reaction to a light signal) was examined. It was found that the intensity of soleus EMG in both tested positions, began to decrease 30–60 msec before the appearance of EMG activity recorded from the ankle flexor m. tibialis anterior, and such inhibition reached the maximum at the end of the premotor period. The observed dynamics of tonic EMG in the m. soleus show that an anticipatory drop in the activity of soleus motoneurons develops before the beginning of voluntary movements. Possible physiological mechanisms underlying this phenomenon are discussed. We believe that, within the premotor period, impulsation coming via mostly the corticospinal tract to soleus motoneurons decreases due to the action of central motor commands, and this leads to lowering of tonic tension of this muscle.



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Effects of Intrahippocampal Injections of Melipramin on EEG, Brain Self-Stimulation, and Behavioral Indices of Rats under Conditions of Neurogenic Stress

In young (3-month-old) male Wistar rats, we studied the effects of intrahippocampal microinjections of melipramin under conditions of emotional stress induced by sessions of electrical nociceptive stimulation of the limbs. In most cases, seven-day-long stressing resulted in suppression of electrical activity of the hippocampus, exerted ambivalent effects on the frequency of brain self-stimulation (BSS) events, decreased the communicability of animals in the two-chamber test, and increased the latencies of going of the animal from the arena center and grooming episodes in the open field test. Injections of melipramin interfered with the development of stress-induced disorders in the hippocampus, decreased the normalized content of beta oscillations in the neocortex and the theta-index in the hypothalamus, increased the BSS frequency, and decreased the level of negativation of the behavioral manifestations of this phenomenon. The duration of stay of a rat near the partition in the two-chamber test increased, the mobility and number of grooming episodes in the open field enhanced, but the latency of leaving the arena center also increased (similarly to what was observed in the control). On the 8th–9th day of the poststress period, behavioral disorders of rats of the control group in the two-chamber test were smoothed to a significant extent. The stability of the examined indices or the reverse development of stress-induced disorders within the above period in animals injected with melipramin were indicative of a significant role of the hippocampus in the formation of central effects of this antidepressant and also of adaptogenic and stress-protective properties of this drug.



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Pharmacodynamics of Interaction between Propoxazepam and a GABA-Benzodiazepine Receptor-Ionofor Complex

Effects of a propyloxy derivative of 1.4-benzodiazepine, propoxazepam, on GABA-benzodiazepine receptor complexes (GABA RCs) were examined in vitro and in vivo. The parameters of propoxazepam binding to synaptosomes from the rat brain were estimated in vitro. The Ki constant for inhibition of [3H] flumazenil binding by this agent was 3.5 ± 0.3 nM, on average. Considering the value of the GABA shift (1.9), propoxazepam can be considered as GABA-RC full agonist. On the model of picrotoxin-induced seizures in vivo, the propoxazepam average effective dose was estimated as 4.1 ± ± 0.21 mmol/kg. It was found that the parameters of myoclonic components (latent period of the onset of myoclonic seizures and their number), as well as death time of the tested animals, characterize adequately an anticonvulsant action of propoxazepam of picrotoxin-induced seizures in mice. Competitive interaction with picrotoxin is the possible mechanism of these effects at the level of GABAARCs. Significant deviations from a competitive model of monomolecular and cooperative binding of the agent at the receptor level have been found.



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Effects of Vitamin/Sorbent Complexes on Behavioral Activity of Gamma-Irradiated Rats in the Open Field

The dynamics of behavioral indices of male albino rats were examined in the open field test. Total gamma irradiation (absorbed dose 5 Gy) resulted in decreases in the indices of all types of motor and orientational/research activity and increased emotional tension. The treatment of animals with the chitin/protein and carotene-tocopherol complexes (0.35 and .6.67 g/kg, respectively) before and after irradiation, due to the antioxidant and enterosorbent properties of these complexes, significantly moderated the negative effects of irradiation and provided a clear trend toward normalization of the measured behavioral indices (period of observation 30 days).



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Effects of Melatonin on the Behavioral Indices and Structural Characteristics of Cerebral and Spinal Neurons of Rats with Experimental Hemiparkinsonism

In adult Wistar rats, a model of experimental hemiparkinsonism (EHP) was induced by stereotaxic microinjection of 8.0 μg 6-hydroxydopamine (6-HODA) into the left forebrain lateral ascending bundle. In such animals, we studied behavioral indices in the open field and elevated plus maze tests and also structural changes in the cerebral substantia nigra and spinal L5 ventral horn neurons. Six groups of animals were formed (in each group, n = 8): intact rats (I), animals that obtained microinjections of saline into the above lateral bundle (sham-injected, ShI), two groups with weak and intense motor EHP manifestations (frequency of circulatory movements in the apomorphine test less than one and six and more per 1 min, groups HP<1 and HP≥6, respectively), and two groups of rats with weak and intense EHP manifestations, which obtained daily i.p. injections of 10 mg/kg melatonin during 18 days (groups HP<1+M and HP≥6+M). In the open-field test, we observed in groups HP<1 and HP≥6 significant suppression of horizontal motor activity (very intense in the latter of the above-mentioned groups) and also significant weakening of vertical activity (number of rearings). Changes in the number of defecation acts were less expressed. In the elevated plus maze, manifestations of a significantly increased anxiety level were observed in rats of the above two groups. In the substantia nigra of animals with EHP, a considerable part of the neurons demonstrated clear signs of negative structural modifications; the number of neurons with the normal structure was considerably smaller than in the control. Analogous negative morphological changes were found in the lumbar segment of the spinal cord. Course injections of melatonin into rats with EHP noticeable weakened negative shifts in both open-field behavioral indices and level of anxiety (according to estimates in the elevated plus maze). Under the action of melatonin, morphological characteristics of neurons and gliocytes in the substantia nigra and spinal cord of rats with EHP demonstrated appreciable normalization. The mechanisms underlying functionaland structural disorders in the CNS of animals after central microinjections of the 6-HODA neurotoxin and also neuroprotective effects of melatonin, which provide weakening of such disorders, are discussed.



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Extraction of Parkinson’s Disease-Related Features from Local Field Potentials for Adaptive Deep Brain Stimulation

Despite the efficiency of deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD), the respective systems need to be further optimized. The lack of accurate PD-related quantitative biomarkers limits the improvement of adaptive DBS (aDBS) systems. Now, most DBS devices are open-loop sets with fixed stimulation parameters, which prevents them from coping with movement fluctuations and rapid changes of the symptoms. At the same time, ample evidence has shown that abnormal oscillations in the composition of local field potential (LFP) signals recorded in PD patients can reflect, to a certain extent, the crucial symptoms of the desease. Therefore, acquisition of LFP signals, extraction of abnormal oscillations, and acquisition of indicative biomarkers is the core technical issue with respective to the aDBS systems. Here, we review the current feature extraction methods in PD, summarize results of the latest research, analyze the difficulties of extracting the quantitative biomarkers, and discuss the developmental trend of feature extraction for aDBS.



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Ethical Responsibilities of the Authors



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Heart rate variability response to affective pictures processed in and outside of conscious awareness: Three consecutive studies on emotional regulation

Publication date: Available online 19 May 2018
Source:International Journal of Psychophysiology
Author(s): Necati Serkut Bulut, Axel Würz, Neşe Yorguner Küpeli, Gresa Çarkaxhıu Bulut, Mehmet Zihni Sungur
Previous research has increased understanding of the neurobiological basis of emotional regulation. However, less is known concerning the unconscious processing of affective information. Three experiments were performed to investigate the extent to which complex affective stimuli can be processed outside of consciousness and demonstrate possible mechanisms for regulation of resulting emotional responses. In Experiment 1, participants were either instructed to passively observe blocked-picture cues (neutral and negative) or to downregulate their emotions by distancing. Resulting emotional regulation activity was assessed with 0.1-Hz heart rate variability (HRV) indices. In Experiment 2, participants were presented with affective pictures that were rendered consciously invisible by means of continuous flash suppression (CFS). In Experiment 3, two equivalent sets of negative affective pictures were covertly presented and the effect of a cognitive task on emotional regulation was evaluated. Our findings revealed that 0.1-Hz HRV indices exhibited greater change over baseline in response to negative compared to neutral stimuli for both presentation conditions (consciously perceived or not). The implementation of distancing and the cognitive task were both associated with higher 0.1-Hz HRV change scores. These results indicate that even complex affective stimuli can be processed without awareness, resulting in a congruent emotional response that is physiologically detectable. Cognitive strategies can help more effectively regulate this response, implying that conscious perception of a triggering stimulus may not be essential for cognitive regulation.



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Response to “The combination therapy with cytapheresis plus vedolizumab in a corticosteroid-dependent patient with ulcerative colitis and previous Anti-TNF alfa failure” by Sáez-González and coworkers MariamAguas, José M.Huguet, PilarNos, Belén Beltrán



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Response to “The combination therapy with cytapheresis plus vedolizumab in a corticosteroid-dependent patient with ulcerative colitis and previous Anti-TNF alfa failure” by Sáez-González and coworkers MariamAguas, José M.Huguet, PilarNos, Belén Beltrán



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Development of a Novel Self-administered Cognitive Assessment Tool and Normative Data for Older Adults

Background: Preexisting cognitive impairment in surgical patients is one of the leading risk factors for adverse cognitive outcomes such as postoperative delirium and postoperative cognitive dysfunction. We developed a self-administered tablet computer application intended to assess the individual risk for adverse postoperative cognitive outcomes. This cross-sectional study aimed to establish normative data for the tool. Materials and Methods: Healthy volunteers aged 65 years and above were administered the Mini-Mental State Examination, Geriatric Depression Scale, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery to assess cognitive health. All subjects completed the tablet computer application without assistance. Primary outcome measure was the test performance. Regression models were built for each cognitive domain score with the covariates age, sex, and education in cognitively healthy subjects. Demographically adjusted standard scores (z-scores) were computed for each subtest. Results: A total of 283 participants (155 women, 128 men) were included in the final analysis. Participants' age was 73.8±5.2 years (mean±SD) and their level of education was 13.6±2.9 years. Mini-Mental State Examination score was 29.2±0.9 points, Geriatric Depression Scale score was 0.4±0.7 points, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery total score was 98.7±5.7 points. Older age was associated with poorer performance in the visual recognition task and in Trail Making Test B (P

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Glasgow Coma Scale Score Fluctuations are Inversely Associated With a NIRS-based Index of Cerebral Autoregulation in Acutely Comatose Patients

Background: The Glasgow Coma Scale (GCS) is an essential coma scale in critical care for determining the neurological status of patients and for estimating their long-term prognosis. Similarly, cerebral autoregulation (CA) monitoring has shown to be an accurate technique for predicting clinical outcomes. However, little is known about the relationship between CA measurements and GCS scores among neurological critically ill patients. This study aimed to explore the association between noninvasive CA multimodal monitoring measurements and GCS scores. Methods: Acutely comatose patients with a variety of neurological injuries admitted to a neurocritical care unit were monitored using near-infrared spectroscopy–based multimodal monitoring for up to 72 hours. Regional cerebral oxygen saturation (rScO2), cerebral oximetry index (COx), GCS, and GCS motor data were measured hourly. COx was calculated as a Pearson correlation coefficient between low-frequency changes in rScO2 and mean arterial pressure. Mixed random effects models with random intercept was used to determine the relationship between hourly near-infrared spectroscopy–based measurements and GCS or GCS motor scores. Results: A total of 871 observations (h) were analyzed from 57 patients with a variety of neurological conditions. Mean age was 58.7±14.2 years and the male to female ratio was 1:1.3. After adjusting for hemoglobin and partial pressure of carbon dioxide in arterial blood, COx was inversely associated with GCS (β=−1.12, 95% confidence interval [CI], −1.94 to −0.31, P=0.007) and GCS motor score (β=−1.06, 95% CI, −2.10 to −0.04, P=0.04). In contrast rScO2 was not associated with GCS (β=−0.002, 95% CI, −0.01 to 0.01, P=0.76) or GCS motor score (β=−0.001, 95% CI, −0.01 to 0.01, P=0.84). Conclusions: This study showed that fluctuations in GCS scores are inversely associated with fluctuations in COx; as COx increases (impaired autoregulation), more severe neurological impairment is observed. However, the difference in COx between high and low GCS is small and warrants further studies investigating this association. CA multimodal monitoring with COx may have the potential to be used as a surrogate of neurological status when the neurological examination is not reliable (ie, sedation and paralytic drug administration). C.W.H. receives research funding from Medtronic/Covidien, Dublin, IR. C.W.H. is the PI on an NIH-sponsored clinical study (R01 HL 92259) and he serves as a consultant to Medtronic/Covidien and Ornim Medical Inc., Foxborough, MA. L.R.-L. is the PI on an American Academy of Neurology/American Brain Foundation, Covidien/Metronic, and Ornim grant. The remaining authors have no conflicts of interest to disclose. Address correspondence to: Ryan J. Healy, BSc, Departments of Neurology, Anesthesiology and Critical Care Medicine, The Johns Hopkins School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD 21287 (e-mail: ryanhealy@comcast.net). Received November 21, 2017 Accepted April 19, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Effects of gait training with auditory feedback on walking and balancing ability in adults after hemiplegic stroke: a preliminary, randomized, controlled study

The aim of this study was to identify a gait training type that better improves the walking and balancing abilities of adult patients with chronic hemiplegic stroke. Single-blinded, randomized, controlled, comparative preliminary study was carried out. Patients were recruited from the inpatient unit of a Rehabilitation Hospital. Thirty-one patients who had experienced hemiplegic stroke were randomly assigned to three groups: the heel group (gait training by active weight bearing on the paretic heel with auditory feedback), the forefoot group (gait training with auditory feedback from paretic metatarsals), and the control group (general gait intervention). All patients performed 30 min of comprehensive rehabilitation therapy followed by an additional 20 min of gait intervention with or without auditory feedback three times a week for 6 weeks. Significant improvements in walking and balancing variables were observed after gait training in all three groups (P

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Frozen in Time: A History of the Synthesis of Nitrous Oxide and How the Process Remained Unchanged for Over 2 Centuries

Three major factors have contributed to the unrivaled popularity of nitrous oxide (N2O) among anesthetists in the 20th century and beyond: its impressive safety profile, its affordability, and its rapid induction and emergence times. These 3 characteristics of N2O have been discussed and written about extensively throughout the medical literature. Nonetheless, the characteristic that contributed most to N2O's initial discovery—the elegance and simplicity of its synthesis—has received substantially less attention. Although N2O was first used as an anesthetic in Hartford, CT, in 1844, it had been identified and synthesized as a distinct gas in the late 18th century. In this article, we track the developments in the recognition and early synthesis of N2O, highlight the major players credited with its discovery, and examine its evolution from the late 1700s to today. The discovery and assimilation of N2O into common medical practice, alongside ether and chloroform, heralded a new paradigm in surgical medicine—one that no longer viewed pain as a fundamental component of surgical medicine. Its continued usage in modern medicine speaks to the brilliance and skill of the chemists and scientists involved in its initial discovery. Accepted for publication March 30, 2018. Funding: Intramural. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Manisha S. Desai, MD, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655. Address e-mail to manisha.desai@umassmemorial.org. © 2018 International Anesthesia Research Society

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In Response

No abstract available

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Is Neuraxial Anesthesia Appropriate for Cesarean Delivery in All Cases of Morbidly Adherent Placenta?

No abstract available

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Understanding Conflict Management Styles in Anesthesiology Residents

BACKGROUND: Successful conflict resolution is vital for effective teamwork and is critical for safe patient care in the operating room. Being able to appreciate the differences in training backgrounds, individual knowledge and opinions, and task interdependency necessitates skilled conflict management styles when addressing various clinical and professional scenarios. The goal of this study was to assess conflict styles in anesthesiology residents via self- and counterpart assessment during participation in simulated conflict scenarios. METHODS: Twenty-two first-year anesthesiology residents (first postgraduate year) participated in this study, which aimed to assess and summarize conflict management styles by 3 separate metrics. One metric was self-assessment with the Thomas-Kilmann Conflict Mode Instrument (TKI), summarized as percentile scores (0%–99%) for 5 conflict styles: collaborating, competing, accommodating, avoiding, and compromising. Participants also completed self- and counterpart ratings after interactions in a simulated conflict scenario using the Dutch Test for Conflict Handling (DUTCH), with scores ranging from 5 to 25 points for each of 5 conflict styles: yielding, compromising, forcing, problem solving, and avoiding. Higher TKI and DUTCH scores would indicate a higher preference for a given conflict style. Sign tests were used to compare self- and counterpart ratings on the DUTCH scores, and Spearman correlations were used to assess associations between TKI and DUTCH scores. RESULTS: On the TKI, the anesthesiology residents had the highest median percentile scores (with first quartile [Q1] and third quartile [Q3]) in compromising (67th, Q1–Q3 = 27–87) and accommodating (69th, Q1–Q3 = 30–94) styles, and the lowest scores for competing (32nd, Q1–Q3 = 10–57). After each conflict scenario, residents and their counterparts on the DUTCH reported higher median scores for compromising (self: 16, Q1–Q3 = 14–16; counterpart: 16, Q1–Q3 = 15–16) and problem solving (self: 17, Q1–Q3 = 16–18; counterpart: 16, Q1–Q3 = 16–17), and lower scores for forcing (self: 13, Q1–Q3 = 10–15; counterpart: 13, Q1–Q3 = 13–15) and avoiding (self: 14, Q1–Q3 = 10–16; counterpart: 14.5, Q1–Q3 = 11–16). There were no significant differences (P > .05) between self- and counterpart ratings on the DUTCH. Overall, the correlations between TKI and DUTCH scores were not statistically significant (P > .05). CONCLUSIONS: Findings from our study demonstrate that our cohort of first postgraduate year anesthesiology residents predominantly take a more cooperative and problem-solving approach to handling conflict. By understanding one's dominant conflict management style through this type of analysis and appreciating the value of other styles, one may become better equipped to manage different conflicts as needed depending on the situations. Accepted for publication April 4, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Brenda G. Fahy, MD, MCCM, Department of Anesthesiology, University of Florida College of Medicine, 1600 SW Archer Rd, PO Box 100254, Gainesville, FL 32610. Address e-mail to bfahy@anest.ufl.edu. © 2018 International Anesthesia Research Society

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Hagberg and Benumof’s Airway Management, 4th ed

No abstract available

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Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

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Perioperative Management in Robotic Surgery, 1st ed

No abstract available

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Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 2 Safety: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, a public–private partnership with the US Food and Drug Administration, convened a second meeting of sedation experts from a variety of clinical specialties and research backgrounds to develop recommendations for procedural sedation research. The previous meeting addressed efficacy and patient- and/or family-centered outcomes. This meeting addressed issues of safety, which was defined as "the avoidance of physical or psychological harm." A literature review identified 133 articles addressing safety measures in procedural sedation clinical trials. After basic reporting of vital signs, the most commonly measured safety parameter was oxygen saturation. Adverse events were inconsistently defined throughout the studies. Only 6 of the 133 studies used a previously validated measure of safety. The meeting identified methodological problems associated with measuring infrequent adverse events. With a consensus discussion, a set of core and supplemental measures were recommended to code for safety in future procedural clinical trials. When adopted, these measures should improve the integration of safety data across studies and facilitate comparisons in systematic reviews and meta-analyses. Accepted for publication March 5, 2018. Funding: None. The authors declare no conflicts 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 website (https://ift.tt/KegmMq). The views expressed in this article are those of the authors, none of whom has financial conflicts of interest specifically related to the issues discussed. At the time of the meeting (November 17–19, 2016) on which this article is based, several authors were employed by a pharmaceutical company or had received consulting fees or honoraria from 1 or more pharmaceutical or device companies. The authors of this article who were not employed by industry at the time of the meeting received (or their universities received) travel stipends, hotel accommodations, and meals during the meeting from the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership. No official endorsement by the US Food and Drug Administration or the pharmaceutical and device companies that have provided unrestricted grants to support the activities of ACTTION should be inferred. Financial support for this project was provided by ACTTION, which has received research contracts, grants, or other revenue from the US Food and Drug Administration, multiple pharmaceutical and device companies, philanthropy, and other sources. Reprints will not be available from the authors. Address correspondence to Denham S. Ward, MD, PhD, Department of Anesthesiology and Perioperative Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 604, Rochester, NY 14642. Address e-mail to Denham_Ward@URMC.Rochester.edu. © 2018 International Anesthesia Research Society

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The Impact of Anesthesia-Influenced Process Measure Compliance on Length of Stay: Results From an Enhanced Recovery After Surgery for Colorectal Surgery Cohort

BACKGROUND: Process measure compliance has been associated with improved outcomes in enhanced recovery after surgery (ERAS) programs. Herein, we sought to assess the impact of compliance with measures directly influenced by anesthesiology in an ERAS for colorectal surgery cohort. METHODS: From January 2013 to April 2015, data from 1140 consecutive patients were collected for all patients before (pre-ERAS) and after (ERAS) implementation of an ERAS program. Compliance with 9 specific process measures directly influenced by the anesthesiologist or acute pain service was analyzed to determine the impact on hospital length of stay (LOS). RESULTS: Process measure compliance was associated with a stepwise reduction in LOS. Patients who received >4 process measures (high compliance) had a significantly shorter LOS (incident rate ratio [IRR], 0.77; 95% CI, 0.70–0.85); P

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Population Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Children Undergoing Ambulatory Surgery

BACKGROUND: Dexmedetomidine (DEX) is an α-2 adrenergic agonist with sedative and analgesic properties. Although not approved for pediatric use by the Food and Drug Administration, DEX is increasingly used in pediatric anesthesia and critical care. However, very limited information is available regarding the pharmacokinetics of DEX in children. The aim of this study was to investigate DEX pharmacokinetics and pharmacodynamics (PK–PD) in Mexican children 2–18 years of age who were undergoing outpatient surgical procedures. METHODS: Thirty children 2–18 years of age with American Society of Anesthesiologists physical status score of I/II were enrolled in this study. DEX (0.7 µg/kg) was administered as a single-dose intravenous infusion. Venous blood samples were collected, and plasma DEX concentrations were analyzed with a combination of high-performance liquid chromatography and electrospray ionization-tandem mass spectrometry. Population PK–PD models were constructed using the Monolix program. RESULTS: A 2-compartment model adequately described the concentration–time relationship. The parameters were standardized for a body weight of 70 kg by using an allometric model. Population parameters estimates were as follows: mean (between-subject variability): clearance (Cl) (L/h × 70 kg) = 20.8 (27%); central volume of distribution (V1) (L × 70 kg) = 21.9 (20%); peripheral volume of distribution (V2) (L × 70 kg) = 81.2 (21%); and intercompartmental clearance (Q) (L/h × 70 kg) = 75.8 (25%). The PK–PD model predicted a maximum mean arterial blood pressure reduction of 45% with an IC50 of 0.501 ng/ml, and a maximum heart rate reduction of 28.9% with an IC50 of 0.552 ng/ml. CONCLUSIONS: Our results suggest that in Mexican children 2–18 years of age with American Society of Anesthesiologists score of I/II, the DEX dose should be adjusted in accordance with lower DEX clearance. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication March 27, 2018. Funding: None. The authors declare no conflicts 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 website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Gustavo Lugo-Goytia, PhD, Departamento de Anestesiología y Medicina Crítica, Instituto Nacional de Ciencias Médicas y Nutrición, México; and Respiratory Intensive Care Unit, Instituto Nacional de Enfermedades Respiratorias, México. Address e-mail to lugogoy@yahoo.com.mx. © 2018 International Anesthesia Research Society

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Benefit and Harm of Adding Epinephrine to a Local Anesthetic for Neuraxial and Locoregional Anesthesia: A Meta-analysis of Randomized Controlled Trials With Trial Sequential Analyses

BACKGROUND: This systematic review examines the benefit and harm of adding epinephrine to local anesthetics for epidural, intrathecal, or locoregional anesthesia. METHODS: We searched electronic databases to October 2017 for randomized trials comparing any local anesthetic regimen combined with epinephrine, with the same local anesthetic regimen without epinephrine, reporting on duration of analgesia, time to 2 segments regression, or any adverse effects. Trial quality was assessed using the Cochrane risk of bias tool and a random-effects model was used. Trial sequential analyses (TSA) were applied to identify the information size (IS; number of patients needed to reach a definite conclusion) and were set to detect an increase or decrease of effect of 30%–50%, depending on the end point considered. Alpha levels were adjusted (1%) for multiple outcome testing. RESULTS: We identified 70 trials (3644 patients, 17 countries, from 1970 to 2017). Median number of patients per trial was 44 (range, 9–174). Thirty-seven trials (1781 patients) tested epinephrine for epidural, 27 (1660) for intrathecal, and 6 (203) for locoregional anesthesia (sciatic, femoral, popliteal, axillary blocks). TSA enabled us to conclude that adding epinephrine to epidural local anesthetics could not decrease postoperative pain intensity by 30%, and did not impact the risk of intraoperative arterial hypotension. IS was insufficient to conclude on the impact of epinephrine on the risk of motor block (IS, 4%), arterial hypotension (20%), urinary retention (23%), or pain intensity at rest (27%) during labor. TSA confirmed that adding epinephrine to intrathecal local anesthetics increased the duration of motor block (weighted mean difference [WMD] 64 minutes; 99% CI, 37–91), analgesia (WMD 34 minutes; 99% CI, 6–62), and the time to 2 segments regression (WMD 20 minutes; 99% CI, 11–28). IS was insufficient to conclude on its impact on arterial hypotension (IS, 15%), or when administrated in a combined spinal-epidural, on motor block (IS, 11%) or arterial hypotension (IS, 11%). Adding epinephrine to local anesthetics for a locoregional block increased the duration of analgesia (WMD 66 minutes; 98% CI, 32–100]). CONCLUSIONS: Adding epinephrine to intrathecal or locoregional local anesthetics prolongs analgesia and motor block by no more than 60 minutes. The impact of adding epinephrine to epidural local anesthetics or to a combined spinal-epidural remains uncertain. Accepted for publication March 27, 2018. Funding: None. The authors declare no conflicts 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 website (https://ift.tt/KegmMq). Protocol registration: International prospective register of systematic reviews (PROSPERO) (CRD: 42015026148). Reprints will not be available from the authors. Address correspondence to Clément Tschopp, MD, MSc, Division of Anesthesiology, University Hospital of Zürich, Rämistrasse 100, Zürich CH-8091, Switzerland. Address e-mail to clement.tschopp@usz.ch. © 2018 International Anesthesia Research Society

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Can Pallars i Llobateres: A new hominoid-bearing locality from the late Miocene of the Vallès-Penedès Basin (NE Iberian Peninsula)

Publication date: Available online 18 May 2018
Source:Journal of Human Evolution
Author(s): David M. Alba, Isaac Casanovas-Vilar, Marc Furió, Israel García-Paredes, Chiara Angelone, Sílvia Jovells-Vaqué, Àngel H. Luján, Sergio Almécija, Salvador Moyà-Solà
In the Iberian Peninsula, Miocene apes (Hominoidea) are generally rare and mostly restricted to the Vallès-Penedès Basin. Here we report a new hominoid maxillary fragment with M2 from this basin. It was surface-collected in March 2017 from the site of Can Pallars i Llobateres (CPL, Sant Quirze del Vallès), where fossil apes had not been previously recorded. The locality of provenance (CPL-M), which has delivered no further fossil remains, is located very close (ca. 50 m) to previously known CPL outcrops, and not very far (ca. 500 m in NW direction) from the classical hominoid-bearing locality of Can Poncic 1. Here we describe the new fossil and, based on the size and proportions of the M2, justify its taxonomic attribution to Hispanopithecus cf. laietanus, a species previously recorded from several Vallesian sites of the Vallès-Penedès Basin. Based on the associated mammalian fauna from CPL, we also provide a biochronological dating and a paleoenvironmental reconstruction for the site. The associated fauna enables an unambiguous correlation to the Cricetulodon hartenbergeri – Progonomys hispanicus interval local subzone, with an estimated age of 9.98–9.73 Ma (late Vallesian, MN10). Therefore, CPL-M is roughly coeval with the Hispanopithecus laietanus-bearing localities of Can Llobateres 1 and Can Feu 1, and minimally older than those of La Tarumba 1 and Can Llobateres 2. In contrast, CPL-M is younger than the early Vallesian (MN9) localities of Can Poncic 1 (the type locality of Hispanopithecus crusafonti) as well as Polinyà 2 (Gabarró) and Estació Depuradora d'Aigües Residuals–Riu Ripoll 13, where Hispanopithecus sp. is recorded. The associated fauna from CPL indicates a densely forested and humid paleoenvironment with nearby freshwater. This supports the view that Hispanopithecus might have been restricted to dense wetland forests soon before its extinction during the late Vallesian, due to progressive climatic deterioration. Coupled with the existence of other fossiliferous outcrops in the area, this find is most promising for the prospect of discovering additional fossil hominoid remains in the future.



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Neuropsychiatric expression and catatonia in 22q11.2 deletion syndrome: An overview and case series

American Journal of Medical Genetics Part A, EarlyView.


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Current clinical evidence does not support a link between TBL1XR1 and Rett syndrome: Description of one patient with Rett features and a novel mutation in TBL1XR1, and a review of TBL1XR1 phenotypes

American Journal of Medical Genetics Part A, EarlyView.


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Correction to: Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study

The co-author name Immaculata DeVivo was incorrectly published. The correct name is given below:



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The Impact of an Adolescent Depressive Disorders Clinical Pathway on Healthcare Utilization

Abstract

Clinical pathways are known to improve the value of health care in medical and surgical settings but have been rarely studied in the psychiatric setting. This study examined the association between level of adherence to an adolescent depressive disorders inpatient clinical pathway and length of stay (LOS), cost, and readmissions. Patients in the high adherence category had significantly longer LOS and higher costs compared to the low adherence category. There was no difference in the odds of 30-day emergency department return visits or readmissions. Understanding which care processes within the pathway are most cost-effective for improving patient-centered outcomes requires further investigation.



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Unanticipated hospital admission in pediatric patients with congenital heart disease undergoing ambulatory noncardiac surgical procedures

Pediatric Anesthesia, EarlyView.


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