Anesthesia and analgesia
-
Anesthesia and analgesia · Mar 2018
Truncated μ-Opioid Receptors With 6 Transmembrane Domains Are Essential for Opioid Analgesia.
Most clinical opioids act through μ-opioid receptors. They effectively relieve pain but are limited by side effects, such as constipation, respiratory depression, dependence, and addiction. Many efforts have been made toward developing potent analgesics that lack side effects. Three-iodobenzoyl-6β-naltrexamide (IBNtxA) is a novel class of opioid active against thermal, inflammatory, and neuropathic pain, without respiratory depression, physical dependence, and reward behavior. The μ-opioid receptor (OPRM1) gene undergoes extensive alternative precursor messenger ribonucleic acid splicing, generating multiple splice variants that are conserved from rodents to humans. One type of variant is the exon 11 (E11)-associated truncated variant containing 6 transmembrane domains (6TM variant). There are 5 6TM variants in the mouse OPRM1 gene, including mMOR-1G, mMOR-1M, mMOR-1N, mMOR-1K, and mMOR-1L. Gene-targeting mouse models selectively removing 6TM variants in E11 knockout (KO) mice eliminated IBNtxA analgesia without affecting morphine analgesia. Conversely, morphine analgesia is lost in an exon 1 (E1) KO mouse that lacks all 7 transmembrane (7TM) variants but retains 6TM variant expression, while IBNtxA analgesia remains intact. Elimination of both E1 and E11 in an E1/E11 double KO mice abolishes both morphine and IBNtxA analgesia. Reconstituting expression of the 6TM variant mMOR-1G in E1/E11 KO mice through lentiviral expression rescued IBNtxA but not morphine analgesia. The aim of this study was to investigate the effect of lentiviral expression of the other 6TM variants in E1/E11 KO mice on IBNtxA analgesia. ⋯ Our study demonstrated the pharmacological relevance of mouse 6TM variants in IBNtxA analgesia and established that a common functional core of the receptors corresponding to the transmembrane domains encoded by exons 2 and 3 is sufficient for activity. Thus, 6TM variants offer potential therapeutic targets for a distinct class of analgesics that are effective against broad-spectrum pain models without many side effects associated with traditional opioids.
-
Anesthesia and analgesia · Mar 2018
Reductions in Average Lengths of Stays for Surgical Procedures Between the 2008 and 2014 United States National Inpatient Samples Were Not Associated With Greater Incidences of Use of Postacute Care Facilities.
Diagnosis-related group (DRG) based reimbursement creates incentives for reduction in hospital length of stay (LOS). Such reductions might be accomplished by lesser incidences of discharges to home. However, we previously reported that, while controlling for DRG, each 1-day decrease in hospital median LOS was associated with lesser odds of transfer to a postacute care facility (P = .0008). The result, though, was limited to elective admissions, 15 common surgical DRGs, and the 2013 US National Readmission Database. ⋯ In the United States, reductions in hospital LOS, averaged over many surgical procedures, are not accomplished through a greater incidence of use of postacute care.
-
Anesthesia and analgesia · Mar 2018
Chinese Anesthesiologists Have High Burnout and Low Job Satisfaction: A Cross-Sectional Survey.
The Chinese health care system must meet the needs of 19% of the world's population. Despite recent economic growth, health care resources are unevenly distributed. This creates the potential for job stress and burnout. We therefore conducted a survey among anesthesiologists in the Beijing-Tianjin-Hebei region focusing on job satisfaction and burnout to determine the incidence and associated factors. ⋯ The anesthesiologists in the Beijing-Tianjin-Hebei region of China expressed a below-average level of job satisfaction, and suffered a significant degree of burnout. Improvement in job satisfaction and burnout might create a positive work climate that could benefit both the quality of patient care and the profession of anesthesiology in China.
-
Anesthesia and analgesia · Mar 2018
A Retrospective Analysis of Clinical Research Misconduct Using FDA-Issued Warning Letters and Clinical Investigator Inspection List From 2010 to 2014.
The US Food and Drug Administration (FDA) conducts inspections of clinical investigation sites as a component of clinical trial regulation. The FDA describes the results of these inspections in the Clinical Investigator Inspection List (CLIIL). More serious violations are followed up in FDA warning letters issued to investigators. The primary objective of the current study is to qualitatively and quantitatively describe the CLIIL data and contents of FDA-issued warning letters from 2010 to 2014. ⋯ The overall decrease in violations is encouraging. But, the high proportion of violations related to failure to follow the investigational plan is concerning as the complexity of trials increases. We conclude that more detailed information is necessary to accurately evaluate these violations. The current study provides a model for creating more granular data of violations to better inform clinical investigators and improve clinical trials.