CNS drugs
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Benzodiazepine use is highly prevalent in elderly and late middle-aged populations and may be associated with an increased risk of dementia. Observational studies have suggested that benzodiazepine use may increase the risk of dementia, however there have been significant concerns regarding protopathic bias in these studies, precluding conclusive findings. ⋯ Our findings indicate that the association between benzodiazepine use and dementia incidence is not purely an artefact due to protopathic bias. Reduction of inappropriate benzodiazepine prescription is likely to attenuate dementia risk.
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Ketamine and its enantiomer S-ketamine (esketamine) are promising candidates to produce a rapid-onset antidepressant effect in treatment-resistant depression. Ketamine causes continued blockade of the glutamate N-methyl-D-aspartate (NMDA) receptor, though this might not primarily mediate the antidepressant effect. Alternative hypotheses include selectivity for the NMDA receptor subtype containing the NMDA receptor subunit 2B (NR2B), inhibition of the phosphorylation of the eukaryotic elongation factor 2 (eEF2) kinase, increased expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB), and activation of the mammalian target of rapamycin (mTOR) signaling pathway, alongside other independent actions attributed to the ketamine metabolism to R-hydroxynorketamine (R-HNK). ⋯ Intranasal esketamine has shown a comparable antidepressant effect, which has resulted in the US FDA granting the drug a "breakthrough therapy" designation, and theoretically it may offer an improved tolerability profile. However, major concerns remain regarding an effective protocol to maintain the clinical antidepressant effect of ketamine seen with acute administration and the safety of ketamine and esketamine in the long term, specifically related to potential neurocognitive and urologic toxicity, together with the potential induction of substance use disorders. Ketamine and esketamine are not currently approved treatments for depression, but the clinical use of ketamine is increasing in a variety of practice settings internationally.
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Meta Analysis
Prescribed Dose of Opioids and Overdose: A Systematic Review and Meta-Analysis of Unintentional Prescription Opioid Overdose.
The rate of an unintentional drug overdose involving prescription opioids continues to rise. An understanding of the threshold dose and dose(s) associated with unintentional prescription opioid overdose will help to mitigate this epidemic. ⋯ This protocol was registered with PROSPERO 2017: CRD42017058426.
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Glioblastoma is the most frequent malignant brain tumor and is characterized by poor prognosis, increased invasiveness, and high recurrence rates. Standard treatment for glioblastoma includes maximal safe surgical resection, radiation, and chemotherapy with temozolomide. Despite treatment advances, only 15-20% of glioblastoma patients survive to 5 years, and no therapies have demonstrated a durable survival benefit in recurrent disease. ⋯ In brain tumors, such as in other solid tumors, we have entered an era of immune-oncology. Immunotherapy seems to have an acceptable safety and tolerability profile in the recurrent setting and is under investigation in clinical trials in newly diagnosed glioblastoma patients. This review focuses on novel targeted therapies recently developed for the management of newly diagnosed and recurrent glioblastomas.
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Review Meta Analysis Comparative Study
Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis.
Lamotrigine is used in pregnancy to control epilepsy and mood disorders. The reproductive safety of this widely used drug remains undefined and may represent a significant public health concern. ⋯ No association was found between prenatal lamotrigine monotherapy and increased rates of birth defects and other explored variables related to adverse pregnancy outcomes.