Population Pharmacokinetic Modeling of Lucitanib in Patients with Advanced Cancer.

Background: Lucitanib is an oral, potent, selective inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1‒3, fibroblast growth factor receptors 1‒3, and platelet-derived growth factor receptors alpha/beta.

Objective: We aimed to develop a population pharmacokinetics (PopPK) model for lucitanib in patients with advanced cancers.

Methods: PopPK analyses were based on intensive and sparse oral pharmacokinetic data from 5 phase 1/2 clinical studies of lucitanib in a total of 403 patients with advanced cancers.

Maintenance treatment with rucaparib for recurrent ovarian carcinoma in ARIEL3, a randomized phase 3 trial: The effects of best response to last platinum-based regimen and disease at baseline on efficacy and safety.

Background: The efficacy and safety of rucaparib maintenance treatment in ARIEL3 were evaluated in subgroups based on best response to most recent platinum-based chemotherapy and baseline disease.

Methods: Patients were randomized 2:1 to receive either oral rucaparib at a dosage of 600 mg twice daily or placebo. Investigator-assessed PFS was assessed in prespecified, nested cohorts: BRCA-mutated, homologous recombination deficient (HRD; BRCA mutated or wild-type BRCA/high loss of heterozygosity), and the intent-to-treat (ITT) population.

The effect of age on efficacy, safety and patient-centered outcomes with rucaparib: A post hoc exploratory analysis of ARIEL3, a phase 3, randomized, maintenance study in patients with recurrent ovarian carcinoma.

Background: In the phase 3 trial ARIEL3, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib provided clinical benefit versus placebo for patients with recurrent, platinum-sensitive ovarian cancer. Here, we evaluate the impact of age on the clinical utility of rucaparib in ARIEL3.

Methods: Patients with platinum-sensitive, recurrent ovarian carcinoma with ≥2 prior platinum-based chemotherapies who responded to their last platinum-based therapy were enrolled in ARIEL3 and randomized 2:1 to rucaparib 600 mg twice daily or placebo.

Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial.

Background: In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival versus placebo. Here, we report prespecified, investigator-assessed, exploratory post-progression endpoints and updated safety data.

Methods: In this ongoing (enrolment complete) randomised, placebo-controlled, phase 3 trial, patients aged 18 years or older who had platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least two previous platinum-based chemotherapy regimens and responded to their last platinum-based regimen were randomly assigned (2:1) to oral rucaparib (600 mg twice daily) or placebo in 28-day cycles using a computer-generated sequence (block size of six with stratification based on homologous recombination repair gene mutation status, progression-free interval following penultimate platinum-based regimen, and best response to most recent platinum-based regimen).

Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, -mutated, high-grade ovarian cancer, and an update on safety.

Objective: To report results from an integrated efficacy and safety analysis supporting the European Commission's approval of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy treatment for relapsed, platinum-sensitive, -mutated ovarian cancer.

Methods: Efficacy was analyzed in platinum-sensitive patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who had high-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer and a deleterious or mutation and received two or more prior chemotherapies (including two or more platinum-based therapies). The primary end point was investigator-assessed, confirmed objective response rate (visit cut-off: April 10, 2017).

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.

Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries.

Curriculum inventory: Modeling, sharing and comparing medical education programs.

Abstract descriptions of how curricula are structured and run. The American National Standards Institute (ANSI) MedBiquitous Curriculum Inventory Standard provides a technical syntax through which a wide range of different curricula can be expressed and subsequently compared and analyzed. This standard has the potential to shift curriculum mapping and reporting from a somewhat disjointed and institution-specific undertaking to something that is shared among multiple medical schools and across whole medical education systems.

Developing the role of big data and analytics in health professional education.

As we capture more and more data about learners, their learning, and the organization of their learning, our ability to identify emerging patterns and to extract meaning grows exponentially. The insights gained from the analyses of these large amounts of data are only helpful to the extent that they can be the basis for positive action such as knowledge discovery, improved capacity for prediction, and anomaly detection. Big Data involves the aggregation and melding of large and heterogeneous datasets while education analytics involves looking for patterns in educational practice or performance in single or aggregate datasets.

Toward a common taxonomy of competency domains for the health professions and competencies for physicians.

Although health professions worldwide are shifting to competency-based education, no common taxonomy for domains of competence and specific competencies currently exists. In this article, the authors describe their work to (1) identify domains of competence that could accommodate any health care profession and (2) extract a common set of competencies for physicians from existing health professions' competency frameworks that would be robust enough to provide a single, relevant infrastructure for curricular resources in the Association of American Medical Colleges' (AAMC's) MedEdPORTAL and Curriculum Inventory and Reports (CIR) sites. The authors used the Accreditation Council for Graduate Medical Education (ACGME)/American Board of Medical Specialties six domains of competence and 36 competencies delineated by the ACGME as their foundational reference list.

Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice.

Lysosomal acid lipase (LAL) is an essential enzyme that hydrolyzes triglycerides (TGs) and cholesteryl esters (CEs) in lysosomes. Genetic LAL mutations lead to Wolman disease (WD) and cholesteryl ester storage disease (CESD). An LAL-null (lal(-/-)) mouse model resembles human WD/CESD with storage of CEs and TGs in multiple organs.

Shared governance: making the transition in practice and perception.

The shared governance literature contains numerous examples of how to design and implement nursing shared governance models. However, there is a major gap between design/implementation and a change in culture. A change in nursing culture will support viability of this governance model.

Protection of rabbits against cutaneous papillomavirus infection using recombinant tobacco mosaic virus containing L2 capsid epitopes.

Cottontail rabbit papillomavirus (CRPV) and rabbit oral papillomavirus (ROPV) represent distantly related, cutaneous and mucosal tissue tropic papillomaviruses respectively that can infect the same host. These two viruses were used to test the effectiveness of an L2 peptide-based vaccine (aa 94-122) that was delivered on the surface of recombinant tobacco mosaic virus (rTMV) particles. Groups of NZW rabbits received combinations of CRPVL2, ROPVL2 and CRPV+ROPVL2 rTMV vaccines, and were then challenged with infectious CRPV and ROPV.

Implementing an online curriculum management database in a problem-based learning curriculum.

Managing a medical school curriculum is a difficult challenge. The body of knowledge is large, diverse, and changing. Continuous oversight is required to ensure the proper balance of learning opportunities, to eliminate redundancies, and to fill in gaps.

Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group.

Purpose: Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study.

Patients And Methods: Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy.

Individualized human scFv vaccines produced in plants: humoral anti-idiotype responses in vaccinated mice confirm relevance to the tumor Ig.

We have developed a method for rapidly producing in plants the idiotype regions of the tumor-specific Ig as single-chain Fv (scFv) proteins for use in the treatment of non-Hodgkin's lymphoma. Variable region gene sequences were generated from either a tumor hybridoma or human tumor biopsy cells, and idiotype domains were joined by a novel linker and cloned into a modified tobacco mosaic virus (TMV) vector designed to secrete the scFv protein in infected Nicotiana benthamiana plants. Thirty-eight out of 44 human scFv proteins showed Coomassie visible material in crude secretory (interstitial fluid, IF) extracts, 21 of those between 100 and 800 microg/ml.

CurrMIT: a tool for managing medical school curricula.

The AAMC Curriculum Management & Information Tool (CurrMIT) is a relational database containing curriculum information from medical schools throughout the United States and Canada. CurrMIT can be used to document details of instruction, such as outcome objectives, resources, content, educational methods, assessment methods, and educational sites, which are being employed in curricula. CurrMIT contains basic information about nearly all required courses and clerkships being offered in the United States and Canada.

Phase I and pharmacologic study of liposomal lurtotecan, NX 211: urinary excretion predicts hematologic toxicity.

Purpose: To determine the maximum-tolerated and recommended dose, toxicity profile, and pharmacokinetics of the liposomal topoisomerase I inhibitor lurtotecan (NX 211) administered as a 30-minute intravenous infusion once every 3 weeks in cancer patients.

Patients And Methods: NX 211 was administered by peripheral infusion. Dose escalation decisions were based on all toxicities during the first cycle as well as pharmacokinetic parameters.