Is endovascular treatment alone as effective and safe as that with preceding intravenous thrombolysis for acute ischemic stroke? A meta-analysis of randomized controlled trials.

INTRODUCTION: This meta-analysis aimed to evaluate the safety and efficacy of direct endovascular therapy (EVT) and bridging therapy (EVT with preceding intravenous thrombolysis i.e. IVT), in acute anterior circulation, large vessel occlusion stroke. EVIDENCE ACQUISITION: Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Cochrane CENTRAL, SCOPUS and ClinicalTrials.gov. Outcomes of interest were measured by the modified Rankin Scale (mRS), and included: no disability (mRS0), no significant disability despite some symptoms (mRS1), slight disability (mRS2), moderate disability (mRS3), moderately severe disability (mRS4), severe disability (mRS5), mortality (mRS6). Additionally, we inspected patients having excellent outcome, functional independence outcome, and poor outcome, along with successful reperfusion and intracranial hemorrhage. We calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI). EVIDENCE SYNTHESIS: A total of seven RCTs involving 2,392 patients were finally included. The chances of achieving successful reperfusion were significantly more with IVT+EVT as compared to EVT alone (RR: 0.97; 95% CI: 0.94, 1.00; P=0.03) (I2=0%). There was no significant difference in the number of patients having outcomes ranging from mRS0 to mRS6, excellent outcome, functional independence, poor outcome or incidence of intracranial hemorrhage, who underwent either EVT alone or IVT+EVT. CONCLUSIONS: Additional trials are needed to determine if the absence of significant differences is due to insufficient sample size or if the combination therapy is truly not beneficial.

Simultaneous analysis of antiretroviral drugs abacavir and tenofovir in human hair by liquid chromatography-tandem mass spectrometry.

A sensitive and reproducible method has been developed and validated for the simultaneous quantification of the key antiretroviral drugs abacavir and tenofovir in hair using LC-MS/MS. The method was validated according to the US Food and Drug Administration (FDA) guidelines for the parameters: specificity, stability, limits of detection (LOD), limits of quantification (LOQ), linearity, accuracy, precision and recovery. Hair samples (50mg) were decontaminated and subjected to methanolic extraction, where 1 ml methanol was added along with the internal standard abacavir-d4 at a final concentration of 0.15 ng/mg hair. After 16 h, the drugs were recovered by liquid-liquid extraction using ammonium acetate buffer and a mixture of methyl tert-butyl ether:ethyl acetate (1:1). The samples were reconstituted with 200 µl acetonitrile:water (1:1) prior to injection for LC-MS/MS. The LOD and LOQ values were 0.06 and 0.12 ng/mg (drug/hair) for both drugs. Calibration curves were linear in the concentration range of 0.12-4.0 ng/mg of drug/hair with regression coefficient (r(2)) value of 0.999 for both drugs. The data for accuracy, precision and recovery were within the FDA limits. The concentrations of the drugs in the hair samples ranged from 0.12 ng/mg to 4.48 ng/mg and 0.32 ng/mg to 1.67 ng/mg for tenofovir and abacavir, respectively. This is the first full report of a method for the simultaneous determination of these two key antiretroviral drugs in hair. The newly developed method is useful for future routine analysis of tenofovir and abacavir in human hair and could be used in therapeutic drug monitoring and adherence to medicines studies, which would be helpful in decision making regarding treatment change in combination anti-retroviral therapies.

Quantitative analysis of mephedrone using liquid chromatography tandem mass spectroscopy: application to human hair.

Recent abuse of designer drugs such as mephedrone has presented a requirement for sensitive, reliable and reproducible methods for the detection of these controlled drugs in different matrices. This study focuses on a fully developed validated method for the quantitative analysis of mephedrone and its two metabolites 4-methylephedrine and 4-methylnorephedrine in human hair. The calibration curve was found to be linear in the range 5-100 pg/mg for mephedrone and 10-150 pg/mg for 4-methylephedrine and 4-methylnorephedrine. The method was successfully validated for the intraday precision, interday precision, limit of detection, accuracy and extraction recovery. Five out of 154 hair samples were confirmed to be positive for mephedrone. Due to the structural similarities to other methcathinones and amphetamines, one can propose the metabolism for mephedrone based on a similar pathway that has been previously used for these psychoactive drugs. The outlined method can be valuable for the future detection of mephedrone and its two metabolites in hair.