Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2020
ReviewAnalgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action.
Acetaminophen is one of the most commonly used analgesic agents for treating acute and chronic pain. However, its metabolism is complex, and its analgesic mechanisms have not been completely understood. Previously, it was believed that acetaminophen induces analgesia by inhibiting cyclooxygenase enzymes; however, it has been considered recently that the main analgesic mechanism of acetaminophen is its metabolization to N-acylphenolamine (AM404), which then acts on the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid 1 receptors in the brain. ⋯ However, we also revealed that AM404 induces analgesia via TRPV1 receptors on the spinal dorsal horn in an inflammatory pain rat model, and these analgesic effects were stronger in the model than in naïve rats. The purpose of this review was to summarize the previous and new issues related to the analgesic mechanisms of acetaminophen. We believe that it will allow clinicians to consider new pain management techniques involving acetaminophen.
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Frontiers in pharmacology · Jan 2020
CFTR Modulator Therapy Enhances Peripheral Blood Monocyte Contributions to Immune Responses in People With Cystic Fibrosis.
CFTR modulators decrease some etiologies of CF airway inflammation; however, data indicate that non-resolving airway infection and inflammation persist in individuals with CF and chronic bacterial infections. Thus, identification of therapies that diminish airway inflammation without allowing unrestrained bacterial growth remains a critical research goal. Novel strategies for combatting deleterious airway inflammation in the CFTR modulator era require better understanding of cellular contributions to chronic CF airway disease, and how inflammatory cells change after initiation of CFTR modulator therapy. Peripheral blood monocytes, which traffic to the CF airway, can develop both pro-inflammatory and inflammation-resolving phenotypes, represent intriguing cellular targets for focused therapies. This therapeutic approach, however, requires a more detailed knowledge of CF monocyte cellular programming and phenotypes. ⋯ Our results demonstrate that ivacaftor causes acute changes in blood monocyte transcriptional profiles and plasma chemokines, and suggest that increased monocyte inflammatory signals and changes in myeloid cell trafficking may contribute to changes in airway inflammation in people taking CFTR modulators. To our knowledge, this is the first report investigating the transcriptomic response of circulating blood monocytes in CF subjects treated with a CFTR modulator.
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Frontiers in pharmacology · Jan 2020
ReviewEfficacy and Safety of CAR-Modified T Cell Therapy in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Prospective Clinical Trials.
Background: In recent years, chimeric antigen receptor-modified T (CAR-T) cell therapy for B-cell leukemia and lymphoma has shown high clinical efficacy. Similar CAR-T clinical trials have also been carried out in patients with refractory/relapsed multiple myeloma (RRMM). However, no systematic review has evaluated the efficacy and safety of CAR-T cell therapy in RRMM. ⋯ The most common grade ≥ 3 AEs were hematologic toxic effects. Conclusion: In heavily treated patients, CAR-T therapy associates with promising responses and tolerable AEs, as well as CRS in RRMM. However, additional information regarding the durability of CAR-T cell therapy, as well as further randomized controlled trials, is needed.
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Frontiers in pharmacology · Jan 2020
Efficacy and Safety of Corticosteroid Treatment in Patients With COVID-19: A Systematic Review and Meta-Analysis.
COVID-19 is a type of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that was identified in December 2019. Corticosteroid therapy was empirically used for clinical treatment in the early stage of the disease outbreak; however, data regarding its efficacy and safety are controversial. The aim of this study was to evaluate the efficacy and safety of corticosteroid therapy in patients with COVID-19. ⋯ The findings of our study indicate that corticosteroid therapy is not highly effective, but it appears to improve prognosis and promote clinical recovery in patients with severe COVID-19.
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Frontiers in pharmacology · Jan 2020
Funding and Service Organization to Achieve Universal Health Coverage for Medicines: An Economic Evaluation of the Best Investment and Service Organization for the Brazilian Scenario.
There are many health benefits since 31 years after the foundation of the National Health Service (NHS) in Brazil, especially the increase in life expectancy. However, family-income inequalities, insufficient funding, and suboptimal private sector-public sector collaboration are still areas for improvement. The efforts of Brazil to achieve universal health coverage (UHC) for medicines have resulted in increased public financing of medicines and their availability, reducing avoidable hospitalization and mortality. However, lack of access to medicines still remains. Due to historical reasons, pharmaceutical service organization in developing countries may have important differences from high-income countries. In some cases, developing countries finance and promote medicine access by using the public infrastructure of health care/medical units as dispensing sites and cover all costs of medicines dispensed. In contrast, many high-income countries use private community pharmacies and cover the costs of medicines dispensed plus a fee, which includes all logistic costs. In this study, we will undertake an economic evaluation to understand the funding needs of the Brazilian NHS to reduce inequalities in access to medicines through adopting a pharmaceutical service organization similar to that seen in many high-income countries with hiring/accrediting private pharmacies. ⋯ The results of the economic evaluation demonstrate potential savings for the NHS and society. Achieving UHC for medicines reduces household expenses with health costs, health litigation, outpatient care, hospitalization, and mortality. An optimal private sector-public sector collaboration model with private community pharmacy accreditation is economically dominant with a feasible medicine price negotiation. The results show the potential to improve access to medicines by 25% for all income classes. This is most beneficial to the poorest families, whose medicines account for 76% of their total health expenses, with potential savings of lives and public resources.