Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2018
South-West of England's Experience of the Safety and Tolerability Pirfenidone and Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis (IPF).
Purpose: Pirfenidone and nintedanib are two novel antifibrotic agents licensed for the treatment IPF. Prior to being approved for use in England for patients with FVC >50% and <80%, these were made available for all IPF patients under the Mild Patient Program (MPP) and Patient In Need Scheme (PIN). Prescribing of these medications is restricted to specialist centers. ⋯ The TEAE profile of pirfenidone was higher than clinical trial data would suggest, although comparable to real-world datasets. Further work is required to explore the possible reasons underpinning this finding, including whether this is related to population co-morbidities or center threshold. No new safety concerns were identified.
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Frontiers in pharmacology · Jan 2018
Mu-Opioid Receptor Agonist Induces Kir3 Currents in Mouse Peripheral Sensory Neurons - Effects of Nerve Injury.
Neuropathic pain often arises from damage to peripheral nerves and is difficult to treat. Activation of opioid receptors in peripheral sensory neurons is devoid of respiratory depression, sedation, nausea, and addiction mediated in the brain, and ameliorates neuropathic pain in animal models. Mechanisms of peripheral opioid analgesia have therefore gained interest, but the role of G protein-coupled inwardly rectifying potassium (Kir3) channels, important regulators of neuronal excitability, remains unclear. ⋯ DAMGO-induced currents in naïve and CCI groups were reversed by barium and a more selective Kir3 channel blocker tertiapin-Q. These data indicate the coupling of Kir3 channels with MOR in mouse peripheral sensory neuron cell bodies, which was unchanged after CCI. A comparative analysis of opioid-induced potassium conductance at the axonal injury site and peripheral terminals of DRG neurons could clarify the role of Kir3 channel-MOR interactions in peripheral nerve injury and opioid analgesia.
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Frontiers in pharmacology · Jan 2018
Multiple Sessions of Transcranial Direct Current Stimulation (tDCS) Reduced Craving and Relapses for Alcohol Use: A Randomized Placebo-Controlled Trial in Alcohol Use Disorder.
Background: Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, has been studied as an adjunctive therapeutic agent for alcohol dependence. In a previous study, we showed that five consecutive sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced relapse to the use of alcohol in alcohol use disorder (AUD) outpatients. However, no changes on craving scores were observed. ⋯ Furthermore, in a 3-months follow-up after intervention, 72.2% of sham-tDCS group relapsed to the alcohol use whereas 72.7% of tDCS group were abstinent. Conclusions: Multiple sessions of bilateral prefrontal tDCS were well tolerated with no significant adverse events. Thus, extended repetitive bilateral tDCS over the dlPFC is a promising adjunctive clinical tool that could be used to reduce alcohol craving and relapses and facilitate alcoholism cessation.
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Frontiers in pharmacology · Jan 2018
Efficacy and Safety of Xuebijing Injection Combined With Ulinastatin as Adjunctive Therapy on Sepsis: A Systematic Review and Meta-Analysis.
Background: Xuebijing injection (XBJ), transforming from Xuefuzhuyu decoction, is the only Chinese medicine injection approved for sepsis. XBJ and ulinastatin (UTI) combination therapy is supposed to be beneficial for sepsis patients. To fill the gap between the lack of evidence for the efficacy of combination therapy and its increasing application among patients, an extensive meta-analysis was performed. ⋯ Three studies involving 14 patients reported the occurrences of adverse events. Conclusions: Comparing with UTI alone, XBJ and UTI combination therapy appeared to be more effective for sepsis. However, owing to the limitations of this meta-analysis, additional RCTs with higher-quality and more rigorous design are needed to confirm our findings.
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Frontiers in pharmacology · Jan 2018
Managed Entry Agreements for Pharmaceuticals in the Context of Adaptive Pathways in Europe.
As per the EMA definition, adaptive pathways is a scientific concept for the development of medicines which seeks to facilitate patient access to promising medicines addressing high unmet need through a prospectively planned approach in a sustainable way. This review reports the findings of activities undertaken by the ADAPT-SMART consortium to identify enablers and explore the suitability of managed entry agreements for adaptive pathways products in Europe. We found that during 2006-2016 outcomes-based managed entry agreements were not commonly used for products with a conditional marketing authorization or authorized under exceptional circumstances. The barriers and enablers to develop workable managed entry agreements models for adaptive pathways products were discussed through interviews and a multi-stakeholder workshop with a number of recommendations made in this paper.