Drug safety
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The rapid expansion of the Internet and computing power in recent years has opened up the possibility of using social media for pharmacovigilance. While this general concept has been proposed by many, central questions remain as to whether social media can provide earlier warnings for rare and serious events than traditional signal detection from spontaneous report data. ⋯ An efficient semi-automated approach to social media monitoring may provide earlier insights into certain adverse events. More work is needed to elaborate additional uses for social media data in pharmacovigilance and to determine how they can be applied by regulatory agencies.
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Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), and is being investigated for the treatment of psoriasis. Both conditions can present in women of child-bearing potential, but pregnancy was an exclusion and discontinuation criterion in tofacitinib randomized controlled trials (RCTs) because of the unknown effects of tofacitinib on mother and child. Tofacitinib is a small molecule that has the potential to cross the placenta. ⋯ The pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored.
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Numerous preclinical and clinical studies investigating the neurodevelopmental and neurocognitive effects of exposure to anesthesia and the combination of anesthesia and surgery have demonstrated histopathological and both temporary and long-term cognitive and behavioral effects at the extremes of the human age spectrum. Increasing coverage in the lay press for both our youngest and oldest patient populations has led to heightened concerns regarding the potential harmful side effects of almost all commonly used anesthetic drug regimens. ⋯ Given this information, no single anesthetic or group of anesthetics can be recommended over any other in terms of causing or preventing negative neurocognitive outcomes in either population. This review summarizes the growing body of preclinical and clinical literature dedicated to the detrimental effects of anesthesia on both the developing and the aging brain.
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Clinical pharmacology QT/QTc studies can be smaller if they more efficiently use the data generated. ⋯ The QT/RR hysteresis model with 95 % adaptation in 120 s is universally applicable to healthy subjects, providing small QTc variability. Supine positions do not generally stabilize heart rates in healthy subjects. Universally applicable QT/RR hysteresis correction allows clinical QT/QTc studies to include variable heart rate episodes in the time points.
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Combining a long-acting β2-agonist (LABA) with a long-acting anti-muscarinic agent (LAMA) provides synergistic benefit on airway smooth muscle relaxation, which may have major implications for the use of LABA/LAMA combinations in the treatment of chronic obstructive pulmonary disease (COPD). There are four different approved LAMA/LABA fixed-dose combinations (FDCs)-glycopyrronium/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, and aclidinium/formoterol-and another, glycopyrronium/formoterol, that is still under clinical development. Many pivotal trials have shown that all of these FDCs are more effective than monotherapies in inducing bronchodilation and do not amplify the possible adverse events (AEs) that are characteristic of LAMAs and LABAs when used as monotherapy. ⋯ Therefore, it is questionable whether such data can be extrapolated to a larger, 'real-life' population of patients with COPD, especially given that COPD patients with co-morbidities are often excluded from clinical trials, COPD is a major risk factor for most cardiovascular diseases, and both LAMAs and LABAs have a high potential to impact cardiac activities. All clinical trials have been conducted under widely varying conditions and, consequently, AE rates of a drug observed in a clinical trial cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Head-to-head studies comparing the different LAMA/LABA FDCs that will include the true patients that we meet in our everyday practice are absolutely essential if we wish to make a therapeutic choice that is not purely empirical.