Obesity Alters Endoxifen Plasma Levels in Young Breast Cancer Patients: A Pharmacometric Simulation Approach

Endoxifen is the most important metabolite of the prodrug tamoxifen. High interindividual variability in endoxifen steady-state concentrations (CSS,min ENDX) is observed under tamoxifen standard dosing breast cancer patients that do not reach endoxifen concentrations above a proposed therapeutic threshold of 5.97 ng/mL may be at higher recurrence risk. In this investigation, 10 clinical tamoxifen studies were pooled (nPatients=1388) to investigate influential factors on CSS,min ENDX using nonlinear mixed-effects modelling. Age and body weight were found to significantly impact CSS,min ENDX in addition to CYP2D6 phenotype. Compared to post-menopausal patients, pre-menopausal patients had a 30% higher risk for subtarget CSS,min ENDX at tamoxifen 20 mg per day. In treatment simulations for distinct patient subpopulations, young overweight patients had a 3.1-13.8-fold higher risk for subtarget CSS,min ENDX compared to elderly low-weight patients. Considering ever-rising obesity rates and the clinical importance of tamoxifen for pre-menopausal patients, this subpopulation may benefit most from individualised tamoxifen dosing

Supplementary Material for: Precision Genetic and Genomic Medicine in the Middle East and North Africa Region: Are We There Yet?

<p><b><i>Purpose:</i></b> As precision medicine continues its expansion into clinical practice and research settings, it is time to investigate genetic and genomic research in the Middle East and North Africa (MENA) region to identify the strengths and deficits and to provide suggestions for future development. <b><i>Methods:</i></b> We performed a literature review of any genetic or genomic publications on breast cancer and type 2 diabetes for the years 2000-2015 and evaluated the translational value of the research using multiple evaluation metrics, including the “continuum of translation” and the Health Impact Pyramid. <b><i>Results:</i></b> A total of 138 type 2 diabetes and 231 breast cancer publications were included. There were few cohort studies or randomized controlled trials, and there was a distinct lack of pharmacogenetic or pharmacogenomic papers. Most studies were not interventional but instead evaluated susceptibility, and when placed on the continuum of translation, more than 90% of the studies were T1. <b><i>Conclusion:</i></b> This study suggests that the translational value of genetic and genomic research in the MENA region is currently suboptimal. Moving forward requires international cooperation and a collaborative cohort program in order to implement precision medicine in this area of the world.</p

Clinical outcomes of intravenous immune globulin in severe clostridium difficile-associated diarrhea

Objectives: Our objective was to determine if use of intravenous immune globulin (IVIG) decreases the incidence of mortality, colectomies, and length of stay in the hospital in patients presenting with severe Clostridium dfficile-associated diarrhea (CDAD)