Managing Opioid-Tolerant Patients in the Perioperative Surgical Home.

Management of acute postoperative pain is important to decrease perioperative morbidity and improve patient satisfaction. Opioids are associated with potential adverse events that may lead to significant risk. Uncontrolled pain is a risk factor in the transformation of acute pain to chronic pain. Balancing these issues can be especially challenging in opioid-tolerant patients undergoing surgery, for whom rapidly escalating opioid doses in an effort to control pain can be associated with increased complications. In the perioperative surgical home model, anesthesiologists are positioned to coordinate a comprehensive perioperative analgesic plan that begins with the preoperative assessment and continues through discharge

The Efficacy of Peripheral Opioid Antagonists in Opioid-Induced Constipation and Postoperative Ileus: A Systematic Review of the Literature.

Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective μ-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting μ-opioid receptor antagonists target the μ-opioid receptor without reversing analgesia. Three such agents are US Food and Drug Administration approved. We reviewed the literature for randomized controlled trials that studied the efficacy of alvimopan, methylnaltrexone, and naloxegol in treating either opioid-induced constipation or postoperative ileus. Peripherally acting μ-opioid receptor antagonists may be effective in treating both opioid-induced bowel dysfunction and postoperative ileus, but definitive conclusions are not possible because of study inconsistency and the relatively low quality of evidence. Comparisons of agents are difficult because of heterogeneous end points and no head-to-head studies

Circulating skeletal muscle related microRNAs profile in Piedmontese cattle during different age

Piedmontese cattle is known for double-muscle phenotype. MicroRNAs (miRNAs) play important role as regulators in skeletal muscle physiological processes, and we hypothesize that plasma miRNAs expression profiles could be affected by skeletal muscle growth status related to age. Plasma samples of cattle were collected during four different ages from first week of life until the time of commercial end of the fattening period before slaughter. Small-RNA sequencing data analysis revealed the presence of 40% of muscle-related miRNAs among the top 25 highly expressed miRNAs and, 19 miRNAs showed differential expression too. Using qRT-PCR, we validated in a larger bovine population, miRNAs involved in skeletal muscle physiology pathways. Comparing new-born with the other age groups, miR-10b, miR-126-5p, miR-143 and miR-146b were significantly up-regulated, whereas miR-21-5p, miR-221, miR-223 and miR-30b-5p were significantly down-regulated. High expression levels of miR-23a in all the groups were found. Myostatin, a negative regulator of skeletal muscle hypertrophy, was predicted as the target gene for miR-23a and miR-126-5p and we demonstrated their direct binding. Correlation analysis revealed association between miRNAs expression profiles and animals’ weights along the age. Circulating miRNAs could be promising for future studies on their biomarker potentialities to beef cattle selection

Circulating skeletal muscle related microRNAs profile in Piedmontese cattle during different age

Abstract Piedmontese cattle is known for double-muscle phenotype. MicroRNAs (miRNAs) play important role as regulators in skeletal muscle physiological processes, and we hypothesize that plasma miRNAs expression profiles could be affected by skeletal muscle growth status related to age. Plasma samples of cattle were collected during four different ages from first week of life until the time of commercial end of the fattening period before slaughter. Small-RNA sequencing data analysis revealed the presence of 40% of muscle-related miRNAs among the top 25 highly expressed miRNAs and, 19 miRNAs showed differential expression too. Using qRT-PCR, we validated in a larger bovine population, miRNAs involved in skeletal muscle physiology pathways. Comparing new-born with the other age groups, miR-10b, miR-126-5p, miR-143 and miR-146b were significantly up-regulated, whereas miR-21-5p, miR-221, miR-223 and miR-30b-5p were significantly down-regulated. High expression levels of miR-23a in all the groups were found. Myostatin, a negative regulator of skeletal muscle hypertrophy, was predicted as the target gene for miR-23a and miR-126-5p and we demonstrated their direct binding. Correlation analysis revealed association between miRNAs expression profiles and animals’ weights along the age. Circulating miRNAs could be promising for future studies on their biomarker potentialities to beef cattle selection

Solid CO_2 in low-mass young stellar objects: Comparison between Spitzer and laboratory spectra

Context. Solid interstellar CO_2 is an abundant component of ice dust mantles. Its ubiquity towards quiescent molecular clouds, as well as protostellar envelopes, has recently been confirmed by the IRS (InfraRed Spectrograph) aboard the Spitzer Space Telescope. Although it has been shown that CO_2 cannot be efficiently formed in the gas phase, the CO_2 surface formation pathway is still unclear. To date several CO_2 surface formation mechanisms induced by energetic (e.g., UV photolysis and cosmic ray irradiation) and non-energetic (e.g., cold atom addition) input have been proposed. Aims. Our aim is to investigate the contribution of cosmic ray irradiation to the formation of CO_2 in different regions of the interstellar medium (ISM). To achieve this goal we compared quantitatively laboratory data with the CO_2 bending mode band profile observed towards several young stellar objects (YSOs) and a field star by the Spitzer Space Telescope. Methods. All the experiments presented here were performed at the Laboratory for Experimental Astrophysics in Catania (Italy). The interstellar relevant samples were all irradiated with fast ions (30−200 keV) and subsequently annealed in a stainless steel high vacuum chamber (P < 10^(-7) mbar). Chemical and structural modifications of the ice samples were monitored by means of infrared spectroscopy. Laboratory spectra were then used to fit some thirty observational spectra. Results. A qualitative analysis shows that a good fit can be obtained with a minimum of two components. The choice of the laboratory components is based on the chemical-physical condition of each source. A quantitative analysis of the sources with known visual extinction (A_V) and methanol abundances highlights that the solid carbon dioxide can be efficiently and abundantly formed after ion irradiation of interstellar ices in all the selected YSOs in a time compatible with cloud lifetimes (3 × 10^7 years). Only in the case of field stars can the expected CO_2 column density formed upon energetic input not explain the observed abundances. This result, to be confirmed along the line of sight to different quiescent clouds, gives an indirect indication that CO_2 can also be formed in an early cloud stage through surface reactions induced by non-energetic mechanisms. In a later stage, when ices are exposed to higher UV and cosmic ray doses, the CO_2 total abundance is strongly affected by energetic formation mechanisms. Conclusions. Our results indicate that energetic processing of icy grain mantles significantly contribute to the formation of solid phase interstellar CO_2

Analysis of the Cooling Performance of a Cylindrical Hole Designed for the Suction Side of the LS89 Vane under Transitional Conditions

Thermal performance of film cooling in a transonic high-pressure vane is studied by means of two different turbulence modelling strategies: the γ-ReΘ transition model and the fully turbulent k-ω SST model. Selected test case is the LS89 vane, appropriately modified to include a cylindrical film cooling device. The MUR237 transonic configuration is selected as representative of highly loaded vanes without shocks, with transonic Mach number over the suction side. The specifically designed cooling system is based on the non-dimensional geometrical and operating conditions of the high-pressure transonic MT1 cooled vane. Transition model constants are initially tuned to match the available experimental data for the original (uncooled) configuration. Eventually, results obtained with both models are compared with each other for several jet conditions, showing non-negligible influence of turbulence modelling on flow distribution and mixing between coolant and main-flow

Cosmological inference including massive neutrinos from the matter power spectrum: biases induced by uncertainties in the covariance matrix

Data analysis from upcoming large galaxy redshift surveys, such as Euclid and DESI will significantly improve constraints on cosmological parameters. To optimally extract the information from these galaxy surveys, it is important to control with a high level of confidence the uncertainty and bias arising from the estimation of the covariance that affects the inference of cosmological parameters. In this work, we are addressing two different but closely related issues: (i) the sampling noise present in a covariance matrix estimated from a finite set of simulations and (ii) the impact on cosmological constraints of the non-Gaussian contribution to the covariance matrix of the power spectrum. We focus on the parameter estimation obtained from fitting the matter power spectrum in real space, using the DEMNUni N-body simulations. Regarding the first issue, we adopt two different approaches to reduce the sampling noise in the precision matrix that propagates in the parameter space: on the one hand using an alternative estimator of the covariance matrix based on a non-linear shrinkage, NERCOME; and on the other hand employing a method of fast generation of approximate mock catalogs, COVMOS. We find that NERCOME can significantly reduce the noise induced on the posterior distribution of parameters, but at the cost of a systematic overestimation of the error bars on the cosmological parameters. We show that using a COVMOS covariance matrix estimated from a large number of realisations (10~000) results in unbiased cosmological constraints. Regarding the second issue, we quantify the impact on cosmological constraints of the non-Gaussian part of the power spectrum covariance purely coming from non-linear clustering. We find that when this term is neglected, both the errors and central values of the estimated parameters are affected for a scale cut \kmax > 0.2\ \invMpc.Comment: 21 pages, 2 appendices, 20 figures. Submitted to A&

Anesthesia clinical workload estimated from electronic health record documentation vs billed relative value units

IMPORTANCE: Accurate measurements of clinical workload are needed to inform health care policy. Existing methods for measuring clinical workload rely on surveys or time-motion studies, which are labor-intensive to collect and subject to biases. OBJECTIVE: To compare anesthesia clinical workload estimated from electronic health record (EHR) audit log data vs billed relative value units. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of anesthetic encounters occurring between August 26, 2019, and February 9, 2020, used data from 8 academic hospitals, community hospitals, and surgical centers across Missouri and Illinois. Clinicians who provided anesthetic services for at least 1 surgical encounter were included. Data were analyzed from January 2022 to January 2023. EXPOSURE: Anesthetic encounters associated with a surgical procedure were included. Encounters associated with labor analgesia and endoscopy were excluded. MAIN OUTCOMES AND MEASURES: For each encounter, EHR-derived clinical workload was estimated as the sum of all EHR actions recorded in the audit log by anesthesia clinicians who provided care. Billing-derived clinical workload was measured as the total number of units billed for the encounter. A linear mixed-effects model was used to estimate the relative contribution of patient complexity (American Society of Anesthesiology [ASA] physical status modifier), procedure complexity (ASA base unit value for the procedure), and anesthetic duration (time units) to EHR-derived and billing-derived workload. The resulting β coefficients were interpreted as the expected effect of a 1-unit change in each independent variable on the standardized workload outcome. The analysis plan was developed after the data were obtained. RESULTS: A total of 405 clinicians who provided anesthesia for 31 688 encounters were included in the study. A total of 8 288 132 audit log actions corresponding to 39 131 hours of EHR use were used to measure EHR-derived workload. The contributions of patient complexity, procedural complexity, and anesthesia duration to EHR-derived workload differed significantly from their contributions to billing-derived workload. The contribution of patient complexity toward EHR-derived workload (β = 0.162; 95% CI, 0.153-0.171) was more than 50% greater than its contribution toward billing-derived workload (β = 0.106; 95% CI, 0.097-0.116; P \u3c .001). In contrast, the contribution of procedure complexity toward EHR-derived workload (β = 0.033; 95% CI, 0.031-0.035) was approximately one-third its contribution toward billing-derived workload (β = 0.106; 95% CI, 0.104-0.108; P \u3c .001). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of 8 hospitals, reimbursement for anesthesiology services overcompensated for procedural complexity and undercompensated for patient complexity. This method for measuring clinical workload could be used to improve reimbursement valuations for anesthesia and other specialties

Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain

The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients’ quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations