British journal of clinical pharmacology
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Br J Clin Pharmacol · Aug 2021
Tapentadol and oxycodone reduce cingulate glutamate in healthy volunteers.
Tapentadol and oxycodone are commonly used analgesics. Preclinical studies have shown that oxycodone modulates brain metabolites related to opioid pathways, whereas tapentadol also affects noradrenergic activity. However, knowledge about the function of the medications in the human brain is limited. ⋯ Magnetic resonance spectroscopy was obtained in 21 healthy subjects from the anterior cingulate cortex, prefrontal cortex, and insula at baseline and after 14 days of treatment with either 50 mg tapentadol, 10 mg oxycodone (equipotent dose, both extended release) or placebo twice daily in a randomized double-blind cross-over study. Compared to baseline, decreased glutamate/creatine levels were identified in anterior cingulate cortex after tapentadol (1.26 ± 0.14 vs. 1.35 ± 0.18, P = .04) and oxycodone (1.26 ± 0.10 vs. 1.35 ± 0.12, P = .05) treatments, both with 7% reduction. This indicates that both analgesics modulate the glutamatergic system at the supraspinal level in humans.
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Br J Clin Pharmacol · Jun 2021
Review Meta AnalysisComparison of infection risks and clinical outcomes in patients with and without SARS-CoV-2 lung infection under renin-angiotensin-aldosterone system blockade: Systematic review and meta-analysis.
Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2. Animal studies suggest that renin-angiotensin-aldosterone system (RAAS) blockers might increase the expression of ACE2 and potentially increase the risk of SARS-CoV-2 infection. ⋯ ACEIs reduce the risk of getting infected with the SARS-CoV-2 virus. Blocking the RAAS may decrease all-cause mortality in COVID-19 patients. ACEIs also reduce the risk of non-COVID pneumonia. All-cause mortality due to non-COVID pneumonia is reduced by ACEI and potentially by ARBs.
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Br J Clin Pharmacol · Apr 2021
ReviewEfficacy and safety outcomes of proposed randomized controlled trials investigating hydroxychloroquine and chloroquine during the early stages of the COVID-19 pandemic.
To assess whether randomized clinical trials (RCTs) proposed to evaluate the treatment of patients with COVID-19 with hydroxychloroquine (HQ) or chloroquine early in the pandemic included plans to measure outcomes that would translate into meaningful efficacy/effectiveness and safety outcomes. ⋯ The RCTs investigating HQ or chloroquine during the early stages of the COVID-19 pandemic included heterogeneous and insufficient approaches to measure efficacy/effectiveness and safety relevant to patients and clinical practice. These findings provide insights to inform clinical and regulatory decisions that can be drawn about the efficacy/effectiveness and safety of these agents in patients with COVID-19. Trialists need to adapt quickly to the research progress on COVID-19, ensuring that core outcome measures are assessed in ongoing RCTs.
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Br J Clin Pharmacol · Jul 2021
ReviewSubgroup analysis in haematologic malignancies phase III clinical trials: A systematic review.
To assess the appropriateness of the use and interpretation of subgroup analysis in haematology randomized clinical trials (RCTs). ⋯ The subgroup claims reported in haematology RCTs lack credibility, even when the claims are strong. Information about subgroup difference should be interpreted cautiously.