Phytocannabinoids - An Overview of the Analytical Methodologies for Detection and Quantification of Therapeutically and Recreationally Relevant Cannabis Compounds.

The legalization of the cultivation of low Δ9-tetrahydrocannabinol (Δ9-THC) and high cannabidiol (CBD) Cannabis Sativa plants is gaining momentum around the world due to increasing demand for CBD-containing products. In many countries where CBD oils, extracts and CBD-infused foods and beverages are being sold in health shops and supermarkets, appropriate testing of these products is a legal requirement. Normally this involves determining the total Δ9-THC and CBD and their precursor tetrahydrocannabinolic acids (THCA) and cannabidiolic acid (CBDA). As our knowledge of the other relevant cannabinoids expands, it is likely so too will the demand for them as additives in many consumer products ensuring a necessity for quantification methods and protocols for their identification. This paper discusses therapeutically relevant cannabinoids found in Cannabis plant, the applicability and efficiency of existing extraction and analytical techniques as well as the legal requirements for these analyses.

Length of hospitalization and mortality for bleeding during treatment with warfarin, dabigatran, or rivaroxaban.

BACKGROUND: Different outcomes among patients hospitalized for bleeding after starting anticoagulation could influence choice of anticoagulant. We compared length of hospitalization, proportion of Intensive Care Unit (ICU) admissions, ICU length of stay, and 30- and 90-day mortality for adults with atrial fibrillation hospitalized for bleeding after starting warfarin, dabigatran, or rivaroxaban. METHODS: An US commercial database of 38 million members from 1 November 2010 to 31 March 2014 was used to examine adults with atrial fibrillation hospitalized for bleeding after starting warfarin (2,446), dabigatran (442), or rivaroxaban (256). Outcomes included difference in mean total length of hospitalization, proportion of ICU admissions, mean length of ICU stay, and all-cause 30- and 90-day mortality. RESULTS: Warfarin users were older and had more comorbidities. Multivariable regression modeling with propensity score weighting showed warfarin users were hospitalized 2.0 days longer (95% CI 1.8-2.3; p < 0.001) than dabigatran users and 2.6 days longer (95% CI 2.4-2.9; p < 0.001) than rivaroxaban users. Dabigatran users were hospitalized 0.6 days longer (95% CI 0.2-1.0; p = 0.001) than rivaroxaban users. There were no differences in the proportion of ICU admissions. Among ICU admissions, warfarin users stayed 3.0 days (95% CI 1.9-3.9; p < 0.001) longer than dabigatran users and 2.4 days longer (95% CI 0.9-3.7; p = 0.003) than rivaroxaban users. There was no difference in ICU stay between dabigatran and rivaroxaban users. There were no differences in 30- and 90-day all-cause mortality. CONCLUSIONS: Rivaroxaban and dabigatran were associated with shorter hospitalizations; however, there were no differences in 30- and 90-day mortality. These findings suggest bleeding associated with the newer agents is not more dangerous than bleeding associated with warfarin.

Major Bleeding Risk During Anticoagulation with Warfarin, Dabigatran, Apixaban, or Rivaroxaban in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The use of non-vitamin K oral anticoagulants (NOACs) has increased steadily following marketing approval; however, their relative safety in nonvalvular atrial fibrillation (NVAF) patients in real-world clinical practice remains unclear. OBJECTIVE: To compare the risk of major bleeding during anticoagulation therapy between warfarin and NOACs. METHODS: This retrospective cohort study analyzed administrative claims data on new NVAF users of warfarin, dabigatran, apixaban, or rivaroxaban in routine clinical care from November 2010 to February 2015 in a commercially insured population in the United States. The primary outcome was time to first major bleeding event requiring hospitalization. Patients were followed until discontinuation or switch of anticoagulants, health plan disenrollment, death, or end of study. All patient characteristics were balanced after propensity score inverse probability of treatment (IPT) weighting. Event rates by type of anticoagulant exposure were compared using IPT-weighted Cox proportional hazards models. RESULTS: The study cohort comprised 44,057 patients who used warfarin (n = 23,431), dabigatran (n = 8,539), apixaban (n = 3,689), and rivaroxaban (n = 8,398). Overall mean (SD) age was 70 (12) years, and 41% of the patients were women. A total of 2,337 major bleeding events occurred during 36,636.2 person-years of follow-up. The unadjusted rate of major bleeding with warfarin was 6.0 per 100 person-years versus 2.8 with dabigatran, 3.3 with apixban, and 5.0 with rivaroxaban. Relative to warfarin, major bleeding risk was lower with dabigatran (HR = 0.67, 95% CI = 0.60-0.76) and apixaban (HR = 0.52, 95% CI = 0.41-0.67). Compared with rivaroxaban, major bleeding risk was also lower with dabigatran (HR = 0.67, 95% CI = 0.58-0.78) and apixaban (HR = 0.52, 95% CI = 0.40-0.68). Major bleeding risk was similar for rivaroxaban and warfarin. Relative to apixaban, dabigatran was associated with a significantly higher risk of major gastrointestinal bleeding (HR = 1.43, 95% CI = 1.09-1.88). CONCLUSIONS: Study results were consistent with safety findings from pivotal clinical trials comparing NOACs with warfarin and added the perspective of a large real-world observational study that compared bleeding risks associated with NOACs during anticoagulation therapy. Apixaban and dabigatran were associated with lower major bleeding risk compared with warfarin or rivaroxaban; however, apixaban had a lower risk of major gastrointestinal bleeding than dabigatran. These findings can help inform the choice of an optimal agent, which must balance effectiveness and bleeding risk in complex patients. DISCLOSURES: This study was funded by Anthem. Adeboyeje, Sylwestrzak, and Barron are employees of HealthCore, a wholly owned and independently operated subsidiary of Anthem. White, Rosenberg, Abarca, and Crawford are employees of Anthem. Study concept and design were primarily contributed by Adeboyeje and Sylwestrzak, along with the other authors. Adeboyeje took the lead in data collection, along with Sylwestrzak and Barron. Data interpretation was performed primarily by Rosenberg, Crawford, and Redberg, with assistance from the other authors. The manuscript was written by all the authors and revised primarily by White, Abarca, and Redberg, along with the other authors.