The κ-opioid receptor (KOR), a member of the opioid receptor family, is widely expressed in the central nervous system and peripheral tissues. Substantial evidence has shown that activation of KOR by agonists and endogenous opioid peptides in vivo may produce a strong analgesic effect that is free from the abuse potential and the adverse side effects of µ-opioid receptor (MOR) agonists, such as morphine. In addition, activation of the KOR has also been shown to exert an inverse effect on morphine-induced adverse actions, such as tolerance, reward, and impairment of learning and memory. Therefore, the KOR has received much attention in the effort to develop alternative analgesics to MOR agonists and agents for the treatment of drug addiction. However, KOR agonists also produce several severe undesirable side effects such as dysphoria, water diuresis, salivation, emesis, and sedation in nonhuman primates, which may limit the clinical utility of KOR agonists for pain and drug abuse treatment. This article will review the role of KOR activation in mediating antinociception and addiction. The possible therapeutic application of κ-agonists in the treatment of pain and drug addiction is also discussed.
Objective:
The objectives were to investigate and compare the risks and incidences of venous thromboembolism (VTE) between the 2 groups of patients with coronavirus disease 2019 (COVID-19) pneumonia and community-acquired pneumonia (CAP).
Approach and Results:
Medical records of 616 pneumonia patients who were admitted to the Yichang Central People’s Hospital in Hubei, China, from January 1 to March 23, 2020, were retrospectively reviewed. The patients with COVID-19 pneumonia were treated in the dedicated COVID-19 units, and the patients with CAP were admitted to regular hospital campus. Risks of VTE were assessed using the Padua prediction score. All the patients received pharmaceutical or mechanical VTE prophylaxis. VTE was diagnosed using Duplex ultrasound or computed tomography pulmonary angiogram. Differences between COVID-19 and CAP groups were compared statistically. All statistical tests were 2 sided, and
P
<0.05 was considered as statistically significant. All data managements and analyses were performed by IBM SPSS, version 24, software (SPSS, Inc, Chicago, IL). Of the 616 patients, 256 had COVID-19 pneumonia and 360 patients had CAP. The overall rate of VTE was 2% in COVID-19 pneumonia group and 3.6% in CAP group, respectively (
P
=0.229). In these two groups, 15.6% of the COVID-19 pneumonia patients and 10% of the CAP patients were categorized as high risk for VTE (Padua score, >4), which were significantly different (
P
=0.036). In those high-risk patients, the incidence of VTE was 12.5% in COVID-19 pneumonia group and 16.7% in CAP group (
P
=0.606). Subgroup analysis of the critically ill patients showed that VTE rate was 6.7% in COVID-19 group versus 13% in CAP group (
P
=0.484). In-hospital mortality of COVID-19 and CAP was 6.3% and 3.9%, respectively (
P
=0.180).
Conclusions:
Our study suggested that COVID-19 pneumonia was associated with hypercoagulable state. However, the rate of VTE in COVID-19 pneumonia patients was not significantly higher than that in CAP patients.
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