Bleeding and thrombosis outcomes in hospitalised COVID-19 patients on low-molecular-weight heparin and antiplatelet therapy

Background. An increased incidence of thromboembolic events in hospitalised COVID­19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis.Objectives. To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID­19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH.Methods. We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID­19 wave, in 808 hospitalised patients with confirmed COVID­19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant.Results. Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7).Conclusion. The bleeding risk in COVID­19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID­19.

An overview of analgesics: NSAIDs, paracetamol, and topical analgesics

Pain is a complex and unique experience. It encompasses several pathways, involving nociceptive signal generation (transduction) and propagation (transmission), as well as perception and modulation of the nociceptive stimuli. Nonsteroidal anti-inflammatory drugs (NSAIDs) primarily exert their analgesic effects through inhibition of cyclooxygenase (COX) enzymes, thereby attenuating prostaglandin synthesis. The COX-2 selective NSAIDs (coxibs) and aspirin have also been shown to reduce colorectal cancers,presumably by prostaglandin-inhibition mechanisms. Paracetamol appears to have both peripheral and central effects. The postulated mechanism for its peripheral effects is indirect COX inhibition, while the central effects are thought to be mediated by modulation of descending pain inhibition pathways. Topical analgesics are available in various formulations. The topical NSAIDs have the same mechanism of action as the systemic formulations, but with less systemic absorption and effects. The local anaesthetics provide a dense sensory block via inhibition of nerve impulse transmission, and are available in percutaneous and transdermal preparations. Capsicum is effective forneuropathic pain, and acts by stimulating and then desensitising peripheral sensory nerves

An overview of analgesics - anticonvulsants, antidepressants, and other medications (Part 3)

Pain is classified by various descriptions. Chronic pain has been described as being neuropathic (due to nervous system lesions), nociceptive (due to tissue damage), or mixed (a combination of neuropathic and nociceptive). The addition of the term nociplastic pain is used to describe patients who experience chronic pain without tissue damage or nervous system lesions. Chronic pain is often difficult to manage, particularly neuropathic pain. Evidence-based pharmacological treatment options include anticonvulsants and antidepressants. The choice of medication will depend on various factors, including patient profile, type of pain, and associated conditions. Medications with the best evidence of efficacy for first-line use in neuropathic pain are the gabapentinoids, carbamazepine, the tricyclic antidepressants, and the serotonin-noradrenaline reuptake inhibitors duloxetine and venlafaxine. The cannabinoids and ketamine are being actively investigated for use in chronic pain. Currently the cannabinoids'potential benefit is outweighed by the adverse effects, and recommendations for the use of ketamine is limited by its parenteral route of administration and low evidence of efficacy in chronic pain

An overview of analgesics: opioids, tramadol, and tapentadol (Part 2)

Pain can be caused by several mechanisms, and the development of chronic pain (also known as pain chronification) is a complex and often unpredictable process. Opioids, tramadol, and tapentadol provide pharmacological solutions to chronic pain of cancer or non-cancer origins, particularly if central sensitization is present. It may also be indicated for short-term use in acute pain.Despite large studies and meta-analyses of opioids for a variety of pain conditions, the evidence for its clinical effectiveness is still unclear. This is, however, mostly due to significant heterogeneity and bias between studies assessed. The dual analgesic mechanisms of tramadol and tapentadol appear to be effective options for pain relief, with an overall lower incidence of opioidrelated adverse effects. Tapentadol has an analgesic effect comparable to the strong opioids,which appearto be mediated by itsgreater mu opioid receptor activity and more selective noradrenaline reuptake inhibition. Tramadol produces less analgesia than tapentadol, but it is also associated with reduced opioid-related adverse effects and dependence. The opioids and tramadol may be significantly affected by polymorphisms of CYP2D6, while this effect is lessened with tapentadol

The Role of Educational Strategies to Reverse the Inverse Performance Spiral in Academically Isolated Rural Hospitals

The importance of continuous professional development for health care workers is widely acknowledged; but the identification of optimal implementation strategies remains a challenge; particularly in academically isolated rural areas. We report the results of a qualitative study that evaluated the effect of an educational intervention aimed at rural doctors in the Western Cape Province; South Africa. We also present a conceptual framework for developing best practice educational strategies to reverse the inverse performance spiral in academically isolated rural hospitals. Doctors felt that participation in relevant learning activities improved their competence; increased the levels of job satisfaction they experienced; increased their willingness to stay in a rural environment; and impacted positively on the quality of services provided. However; the success of educational strategies is heavily dependant on the local environment (context); as well as the practical applicability and clinical relevance of the activities (process). Successful educational strategies may help to reverse the inverse performance spiral previously described in academically isolated rural hospitals; however; this requires effective local leadership that creates a positive learning environment and supports clinically relevant learning activities. The study findings also indicate the need for health care providers and institutions of higher education to join forces to improve the quality of rural health care