Frontiers in pharmacology
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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
Haplotypic and Genotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia.
Treatment-resistant schizophrenia (TRS) continues to be a challenge. It was related to different factors, including alterations in the activity of brain dopaminergic system, which could be influenced by the dopamine-degrading enzyme, catechol-O-methyltransferase (COMT). Variants of the COMT gene have been extensively studied as risk factors for schizophrenia; however, their association with TRS has been poorly investigated. ⋯ In women with TRS, the high activity G-G/G-G haplotype was rare, while carriers of other haplotypes were overrepresented (p = 0.009). Such associations of COMT rs4680 and rs4818 high-activity (G variants), as well as G-G/G-G haplotype, with the lower risk of TRS in females, but not in males, suggest significant, but sex-specific influence of COMT variants on the development of treatment-resistance in patients with schizophrenia. However, due to relatively low number of females, those findings require replication in a larger sample.
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Frontiers in pharmacology · Jan 2018
Pan-Canadian Pharmaceutical Alliance (pCPA): Timelines Analysis and Policy Implications.
This analysis follows our recent study showing that Canadian public reimbursement delays have lengthened from regulatory approval to listing decisions by public drug plans and delayed public access to innovative medicines, mainly due to processes following the Common Drug Review (CDR) and the pan-Canadian Oncology Drug Review (pCODR). Public drug plans participate in a pan-Canadian Pharmaceutical Alliance (pCPA) joint negotiation process before making decisions about whether or not to reimburse a product reviewed through CDR and pCODR. This research aims to report the findings from a comprehensive analysis of pCPA process times, times to reimbursement by public payers in Canada, and to explore the opportunities to reduce total delays in public reimbursement with a specific focus on the pCPA process. ⋯ Listing rates also appear to be declining for non-oncology products, although this trend is less conclusive for oncology products. Challenges need to be addressed to improve efficiency, transparency, and ultimately reduce pCPA timelines and total timelines to public reimbursement. Suggested ways to improve and streamline the listing process are: (1) transparent target timelines and associated performance incentives for the pCPA and public plan decisions, (2) parallel HTA-pCPA processes to enable pCPA negotiations to start part-way through the HTA review and allow pCPA negotiation information to be fed back into the HTA review, and (3) innovative agreements that consider patient input and earlier coverage with real-world evidence development.
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Frontiers in pharmacology · Jan 2018
In vitro and in vivo Pharmacological Activities of 14-O-Phenylpropyloxymorphone, a Potent Mixed Mu/Delta/Kappa-Opioid Receptor Agonist With Reduced Constipation in Mice.
Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs. Opioids are the mainstay for the treatment of moderate to severe pain. ⋯ POMO-induced antinociception is mediated through the activation of the mu-opioid receptor, and it does not involve delta- and kappa-opioid receptors. In the charcoal test, POMO produced fourfold less inhibition of the gastrointestinal transit than 14-OMO and morphine. In summary, POMO emerges as a new potent mixed mu/delta/kappa-opioid receptor agonist with reduced liability to cause constipation at antinociceptive doses.