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rved.INTRODUCTION There is a large variation in cannabidiol (CBD) pharmacokinetics and little information on its bioavailability. This study aims to establish the CBD dose-exposure relationship and to evaluate the effects of dosage forms, food, and doses on CBD absorption. METHODS Single-dose (range 5-6000 mg) CBD plasma concentration-time profiles administered as oral solution (OS), oral capsule (OC), or oromucosal spray/drop (OM) from healthy volunteers were extracted from 15 published clinical studies. A dose-exposure proportionality assessment was performed, and a population-based meta-analysis of CBD pharmacokinetics and systemic bioavailability was conducted with a nonlinear mixed-effects modeling. A three-compartment model with a Weibull or zero-order absorption model was used to describe CBD disposition and absorption kinetics. Dosage form, food, and dose were assessed for covariation. RESULTS Oral solution CBD exposures increased less than proportionally with doses of 750 mg or greater, and bioavailability (6.5% at 3000 mg) decreased with increasing dose. The bioavailability of OC (5.6%) and fed-state OM (6.2%) were similar, whereas it was lower in fasted-state OM (0.9%). The Weibull absorption model best described OS, OC, and fed-state OM profiles. The slowest absorption rate was observed in OS, resulting in a time of maximum concentration of 4.75 hours, followed by fed-state OM (3.13 hrs) and OC (2.1 hrs). The absorption kinetics of fasted-state OM was best described by a zero-order absorption for the duration of 1.71 hours. CONCLUSION The effects of doses, dosage forms, and feeding status on CBD pharmacokinetics were quantified and should be taken into consideration for dose optimization. © 2020 Pharmacotherapy Publications, Inc.The demand for whiter teeth has been increasing, and home-based remedies are a popular way of whitening the teeth. These products may be prescribed by the dentist or purchased over the counter and comprise different modes to whiten the teeth and are administered in a range of ways by the person. This review found that the evidence was insufficient to draw reliable conclusions about the intervention, i.e., the use of these whitening products. The results indicated that people may experience side effects that irritate the mouth and gums. Therefore, nurses should direct people who are interested in teeth whitening to their dental professional for a discussion. © 2020 Wiley Periodicals, Inc.Polypharmacy is widespread and associated with medication-related harms, including adverse drug reactions, medication errors and poor treatment adherence. General practitioners and pharmacists cite limited time and training to perform effective medication reviews for patients with complex polypharmacy, yet no specialist referral mechanism exists. AIMS To develop a structured framework for specialist review of primary care patients with complex polypharmacy. METHODS We developed the Clinical Pharmacology Structured Review (CPSR) and Stopping By Indication Tool (SBIT). We tested these in an age-sex stratified sample of 100 people with polypharmacy aged 65-84 years from the Clinical Practice Research Datalink, an anonymised primary care database. Simulated medication reviews based on electronic records using the CPSR and SBIT were performed. We recommended medication changes or review to optimise treatment benefits, reduce risk of harm or reduce treatment burden. RESULTS Recommendations were made for all patients, for almost half (4.8±2.4) of existing medicines (9.8±3.1), most commonly stopping a drug (1.7±1.3/patient) or reviewing with patient (1.4±1.2/patient). At least one new medicine (0.7±0.9) was recommended for 51% patients. https://www.selleckchem.com/products/rbn-2397.html Recommendations predominantly aimed to reduce harm (44%). There was no relationship between number of recommendations made and time since last primary care medication review. We identified a core set of clinical information and investigations (polypharmacy workup) that could inform a standard screen prior to specialist review. CONCLUSIONS The CPSA, SBIT and polypharmacy workup could form the basis of a specialist review for patients with complex polypharmacy. Further research is needed to test this approach in patients in general practice. This article is protected by copyright. All rights reserved.OBJECTIVE Chronic lymphocytic leukemia (CLL) treatment has changed dramatically, and landscape of second hematologic malignancies (SHM) evolves in the new era of targeted therapy. No data were available about the real-world burden of SHM. METHODS All 2631 patients with CLL in the Cancer registry of Norway registered 2003-2012 were included. RESULTS After median follow-up of 6.6 years, 103 patients (4%) developed SHM. Diffuse large B-cell lymphoma (DLBCL) was most common (n = 65; 63%). Median survival was 9.3 years (95% CI; 8.9-9.8) in non-SHM patients and 1.7 years in DLBCL, 0.8 years in Hodgkin lymphoma (n = 12), and 2.8 years in myeloid neoplasia (n = 15; 95% CI 0.3-2.6, 0.6-2.9, and 0.4-5.3, respectively; P  less then  .001). Outcomes were poorest for SHM patients treated for CLL (HR 2.76, 95% CI 1.4-5.5, P = 0.003). A higher proportion of men and younger age were found in SHM patients (median age 66 vs 72 years in non-SHM; P  less then  .001; men 68% vs 57%, P = .03). Myeloid neoplasia was rare (incidence rate 1/1000 person-years; 95% CI 0.6-1.5) and tended to occur later than DLBCL in patients treated for CLL (median time from CLL to SHM 62 vs 45 months; P = .09). CONCLUSIONS SHM and especially myeloid malignancies were rare in chemoimmunotherapy era. © 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.We report a case of culture-negative aortic valve endocarditis secondary to Tropheryma whipplei infection. Our patient underwent aortic valve replacement after 4 weeks of antibiotic therapy with persistently negative blood culture results. Despite a technically uneventful operation, the patient showed continued sepsis and was unresponsive to a broad-spectrum of antibiotic therapy with subsequent multiorgan failure. He died on the 5th postoperative day, and diagnosis was established at postmortem examination. In this case report, we discuss the diagnosis and treatment of a rare type of endocarditis caused by T. whipplei. © 2020 Wiley Periodicals, Inc.