Therapeutic Drug Monitoring in Patients with Systemic Lupus Erythematosus: Utility and Gaps.

Despite advances in the treatment of patients with systemic lupus erythematous (SLE), outcomes have remained suboptimal. Persistent disease activity, patient comorbidities and drug toxicities contribute to the accrual of progressive irreversible damage and high rates of morbidity and mortality. Currently, similar drug doses and regimens are promulgated in the treatment guidelines for all SLE patients, despite the vast differences in patient and environmental factors that affect the drugs' metabolism and blood concentrations. This causes a disconnect between drug dosing and drug blood concentrations, which can then result in unpredictability in drug toxicities and therapeutic effects. In this review, we discuss commonly used oral immunosuppressive medications in SLE, their pharmacogenomics, and factors affecting their metabolism and blood concentrations. Further, we highlight the role of therapeutic drug monitoring in SLE, which is the first accessible step to individualising therapy.

Changes of Drug Pharmacokinetics in Patients with Short Bowel Syndrome: A Systematic Review.

BACKGROUND AND OBJECTIVES: Short bowel syndrome is a clinical condition defined by malabsorption of nutrients and micronutrients, most commonly following extensive intestinal resection. Due to a loss of absorptive surfaces, the absorption of orally administered drugs is also often affected. The purpose of this study was to systematically review the published literature and examine the effects of short bowel syndrome on drug pharmacokinetics and clinical outcomes. METHODS: Studies were identified through searches of databases MEDLINE, EMBASE, Web of Science, and SCOPUS, in addition to hand searches of studies' reference lists. Two reviewers independently assessed studies for inclusion, yielding 50 studies involving 37 different drugs in patients with short bowel syndrome. RESULTS: Evidence of decreased drug absorption was observed in 29 out of 37 drugs, 6 of which lost therapeutic effect, and 14 of which continued to demonstrate clinical benefit through drug monitoring. CONCLUSIONS: The influence of short bowel syndrome on drug absorption appears to be drug-specific and dependent on the location and extent of resection. The presence of a colon in continuity may also influence drug bioavailability as it can contribute significantly to the absorption of drugs (e.g., metoprolol); likewise, drugs that have a wide absorption window or are known to be absorbed in the colon are least likely to be malabsorbed. Individualized dosing may be necessary to achieve therapeutic efficacy, and therapeutic drug monitoring, where available, should be considered in short bowel syndrome patients, especially for drugs with narrow therapeutic indices.

Neurologic and cognitive outcomes associated with the clinical use of xenon: a systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: Xenon has been shown to have positive neurologic effects in various pre-clinical models. This study systematically reviewed the randomized-controlled trials (RCTs) investigating neurologic and cognitive outcomes associated with the clinical use of xenon. METHODS: We searched PubMed, CENTRAL, EMBASE, CINAHL, elibrary.ru (for Russian studies), Google Scholar (for Russian studies), and Wanfang (for Chinese studies) for appropriate RCTs comparing neurologic or cognitive outcomes after clinical use of xenon with control treatment or with other anesthetic agents. RESULTS: Seventeen RCTs met the inclusion criteria. Two studies investigated the effects of xenon plus therapeutic hypothermia to treat neonatal asphyxia or out-of-hospital cardiac arrest. Compared with therapeutic hypothermia alone, xenon and therapeutic hypothermia reduced cerebral white matter abnormalities after cardiac arrest but had no effect on neurocognitive outcome and mortality. Xenon had no added value when used to treat neonatal asphyxia. Thirteen RCTs compared neurocognitive effects of xenon with other anesthetic agents in surgical patients. While xenon may be associated with improved short-term (< three hours) cognitive outcome, no medium-term (six hours to three months) advantage was observed, and longer-term data are lacking. No differences in biochemical (S-100ß, neuron-specific enolase) and neuropsychologic (attentional performance) outcomes were found with xenon compared with other anesthetic drugs. Finally, two studies suggest that brief, intermittent administration of sub-anesthetic doses of xenon to patients during the acute phase of substance withdrawal may improve neurocognitive outcomes. CONCLUSIONS: Despite promising pre-clinical results, the evidence for positive clinical neurologic and cognitive outcomes associated with xenon administration is modest. Nevertheless, there is some evidence to suggest that xenon may be associated with better neurologic outcomes compared with the standard of care therapy in certain specific clinical situations. More clinical trials are needed to determine any potential benefit linked to xenon administration.

Xenon Anesthesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Xenon anesthesia has been studied for decades. However, no meta-analysis of randomized controlled trials (RCTs) on xenon anesthesia has been conducted. The aim of this study was to systematically review all available evidence from RCTs comparing xenon and other inhaled and IV anesthetics on anesthetic outcomes. Our meta-analysis attempted to quantify the effects of xenon anesthesia on clinical outcomes in relation to other anesthetics. METHODS: We found 43 RCTs from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL (until January 2015). A total of 31 studies comparing xenon (841 patients) with other inhaled agents (836 patients) and 12 studies comparing xenon (373 patients) with propofol (360 patients) were found. We evaluated clinical outcomes, such as intraoperative hemodynamics, emergence, and postoperative nausea and vomiting (PONV). RESULTS: Patients undergoing xenon anesthesia had a lower heart rate and higher mean arterial pressure (MAP) intraoperatively than those receiving volatile anesthesia (mean difference = -6 min⁻¹ [99% confidence interval {99% CI} -10.0 to -2.3]; mean difference = 9 mm Hg [99% CI 3.1-14.4]) and propofol anesthesia (mean difference = -10 min⁻¹ [99% CI -12.4 to -6.6]; mean difference = 7 mm Hg [99% CI 0.85-13.2]). Compared with baseline, intraoperative MAP remained relatively stable (change < 5.5%, 99% CI within ±20% of the baseline) under xenon anesthesia, but MAP decreased by ≥15% under volatile (mean difference = -17 mm Hg [99% CI -29.5 to - 4.9], percentage change = -17.5%) and propofol (mean difference = -14 mm Hg [99% CI -26.1 to -2.5], percentage change = -15.0%) anesthesia. Patients had faster emergence from xenon than from volatile anesthesia: eyes opening (versus all volatile agents: mean 4 vs 7 minutes, percentage change = -49.8% [99% CI -55.1% to -44.0%]), tracheal extubation (versus all volatile agents: mean 4 vs 8 minutes percentage change = -44.6% [99% CI -57.3% to -28.1%]), orientation (versus sevoflurane: mean 5 vs 10 minutes, percentage change = -45.1% [99% CI -58.5% to -28.1%]), countdown (versus sevoflurane: mean 6 vs 10 minutes, percentage change = -41.7% [99% CI -50.3% to -31.6%]; versus isoflurane: mean 6 vs 14 minutes, percentage change = -57.7% [99% CI -65.7% to -48.3%]), and reaction on demand (versus sevoflurane: mean 4 vs 8 minutes, percentage change = -53.2% [99% CI -65.7% to -35.6%]). However, xenon anesthesia increased the risks of PONV (incidence 34.4% vs 19.9%; risk ratio = 1.72 [99% CI 1.10-2.69], risk difference = 0.19 [99% CI 0.04-0.33]). CONCLUSIONS: Xenon anesthesia provides relatively more stable intraoperative blood pressure, lower heart rate, and faster emergence from anesthesia than volatile and propofol anesthesia. However, xenon is associated with a higher incidence of PONV.