Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.

Objectives: To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.

Methods: In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12.

Development of Therapeutic Proteins for a New Subcutaneous Route of Administration After the Establishment of Intravenous Dosages: A Systematic Review.

Therapeutic proteins may first be developed as intravenous (i.v.) therapies with new subcutaneous (s.

Altered Plasma Fatty Acid Abundance Is Associated with Cachexia in Treatment-Naïve Pancreatic Cancer.

Cachexia occurs in up to 80% of pancreatic ductal adenocarcinoma (PDAC) patients and is characterized by unintentional weight loss and tissue wasting. To understand the metabolic changes that occur in PDAC-associated cachexia, we compared the abundance of plasma fatty acids (FAs), measured by gas chromatography, of subjects with treatment-naïve metastatic PDAC with or without cachexia, defined as a loss of > 2% weight and evidence of sarcopenia (n = 43). The abundance of saturated, monounsaturated, and polyunsaturated FAs was not different between subjects with cachexia and those without.

Population Pharmacokinetic Analysis from First-in-Human Data for HDAC Inhibitor, REC-2282 (AR-42), in Patients with Solid Tumors and Hematologic Malignancies: A Case Study for Evaluating Flat vs. Body Size Normalized Dosing.

Background And Objectives: REC-2282 is a novel histone deacetylase inhibitor that has shown antitumor activity in in vitro and in vivo models of malignancy.  The aims of this study were to characterize the population pharmacokinetics of REC-2282 (AR-42) from the first-in-human (NCT01129193) and phase I acute myeloid leukemia trials (NCT01798901) and to evaluate potential sources of variability. Additionally, we sought to understand alternate body size descriptors as sources of inter-individual variability (IIV), which was significant for dose-normalized maximum observed concentration and area under the concentration-time curve (AUC).

Murine cancer cachexia models replicate elevated catabolic pembrolizumab clearance in humans.

Background: Monoclonal antibody (mAb) immune checkpoint inhibitor (ICI) therapies have dramatically impacted oncology this past decade. However, only about one-third of patients respond to treatment, and biomarkers to predict responders are lacking. Recent ICI clinical pharmacology data demonstrate high baseline drug clearance (CL) significantly associates with shorter overall survival, independent of ICI exposure, in patients receiving ICI mAb therapies.

Healthcare provider characteristics that influence the implementation of individual-level patient-centered outcome measure (PROM) and patient-reported experience measure (PREM) data across practice settings: a protocol for a mixed methods systematic review with a narrative synthesis.

Background: Substantial literature has highlighted the importance of patient-reported outcome and experience measures (PROMs and PREMs, respectively) to collect clinically relevant information to better understand and address what matters to patients. The purpose of this systematic review is to synthesize the evidence about how healthcare providers implement individual-level PROMs and PREMs data into daily practice.

Methods: This mixed methods systematic review protocol describes the design of our synthesis of the peer-reviewed research evidence (i.

Reconciling relationships with physical activity: a qualitative study of women's postnatal physical activity decision-making.

Background: Challenges with engaging in postnatal physical activity can negatively affect the health of women and their families. This study investigated women's physical activity decision-making processes and strategies to support their physical activity as part of a healthy postpartum transition.

Methods: Thirty healthy women with infants aged 2.

A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies.

Purpose: Given clinical activity of AR-42, an oral histone deacetylase inhibitor, in hematologic malignancies and preclinical activity in solid tumors, this phase 1 trial investigated the safety and tolerability of AR-42 in patients with advanced solid tumors, including neurofibromatosis type 2-associated meningiomas and schwannomas (NF2). The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Secondary objectives included determining pharmacokinetics and clinical activity.

Phase I study of AR-42 and decitabine in acute myeloid leukemia.

This phase I trial sought to determine a biologically safe and effective dose of AR-42, a novel histone deacetylase inhibitor, which would lead to a doubling of miR-29b prior to decitabine administration. Thirteen patients with previously untreated or relapsed/refractory AML were treated at 3 dose levels (DL): AR-42 20 mg qd on d1,3,5 in DL1, 40 mg qd on d1,3,5 in DL2 and 40 mg qd on d1,3,4,5 in DL3. Patients received decitabine 20 mg/m on d6-15 of each induction cycle and 20 mg/m on d6-10 of each maintenance cycle.

Overcoming resistance to anabolic SARM therapy in experimental cancer cachexia with an HDAC inhibitor.

No approved therapy exists for cancer-associated cachexia. The colon-26 mouse model of cancer cachexia mimics recent late-stage clinical failures of anabolic anti-cachexia therapy and was unresponsive to anabolic doses of diverse androgens, including the selective androgen receptor modulator (SARM) GTx-024. The histone deacetylase inhibitor (HDACi) AR-42 exhibited anti-cachectic activity in this model.

Collaborative peer review process as an informal interprofessional learning tool: Findings from an exploratory study.

Despite numerous studies on formal interprofessional education programes, less attention has been focused on informal interprofessional learning opportunities. To provide such an opportunity, a collaborative peer review process (CPRP) was created as part of a peer-reviewed journal. Replacing the traditional peer review process wherein two or more reviewers review the manuscript separately, the CPRP brings together students from different professions to collaboratively review a manuscript.

A comparison of actigraphy and sleep diaries for infants' sleep behavior.

Detecting the effectiveness of behavioral interventions to reduce infant night-waking requires valid sleep measures. Although viewed as an objective measure, actigraphy has overestimated night-waking. Sleep diaries are criticized for only documenting night-waking with infant crying.

Screening and identification of novel compounds with potential anti-proliferative effects on gallium-resistant lung cancer through an AXL kinase pathway.

The clinical application of gallium compounds as anticancer agents is hampered by development of resistance. As a potential strategy to overcome the limitation, eight series of compounds were identified through virtual screening of AXL kinase homology model. Anti-proliferative studies were carried using gallium-sensitive (S) and gallium-resistant (R) human lung adenocarcinoma (A549) cells.

Bioinformatics for precision medicine in oncology: principles and application to the SHIVA clinical trial.

Precision medicine (PM) requires the delivery of individually adapted medical care based on the genetic characteristics of each patient and his/her tumor. The last decade witnessed the development of high-throughput technologies such as microarrays and next-generation sequencing which paved the way to PM in the field of oncology. While the cost of these technologies decreases, we are facing an exponential increase in the amount of data produced.

Factors associated with differences in Canadian perinatal nurses' attitudes toward birth practices.

Objective: To test whether demographic characteristics predict registered nurses' attitudes toward birth practices.

Design: A secondary analysis of a cross-sectional survey, the National Maternity Care Attitudes Survey.

Setting: A national survey conducted with health care providers providing maternity care in Canada.

[Maternal body mass index and breast feeding].

Aim: The aim of this paper was to determine whether maternal BMI influences breast-feeding practice in quality and duration

Methods: A retrospective case-control study were included Fifty women with Body Max Index (BMI) ≥25 kg/m2 considered overweigh and obese and fifty controls with BMI<25 kg/m2 who delivered in our clinic between 2010 and 2011.

Results: The incidence of breast-feeding was significantly lower in overweight and obese women compared with normal weight. Breastfeeding length was negatively related to prepregnancy BMI but not to gestational weight gain, method of delivery or lactation integration.

Bone ultrasonometry measurements during pregnancy.

Purpose: During pregnancy we can have changes of the calcium metabolism that can determine a loss of bone mass. Some studies used single-photon absorptiometry (SPA) or dual-energy X-ray absorptiometry, but these exams are inadvisable in pregnancy for the teratogenic effects on the fetus. We used quantitative ultrasonometry (QUS).

Tumor genomic profiling and TP53 germline mutation analysis of first-degree relative familial gliomas.

About 5% of gliomas occur in a familial context, which suggests a genetic origin, but the predisposing molecular factors remain unknown in most cases. A series of nine familial gliomas were characterized with 1-megabase resolution BAC array-based comparative genomic hybridization (aCGH) together with germline sequence analysis of TP53. This series was compared with a literature series of familial gliomas and a personal series of sporadic gliomas, analyzed by chromosome CGH and aCGH, respectively.

ACTuDB, a new database for the integrated analysis of array-CGH and clinical data for tumors.

In recent years, an increasing number of projects have investigated tumor genome structure, using microarray-based techniques like array comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) arrays. The forthcoming studies have to integrate these former results and compare their findings to the existing sets of copy number data for validation. These sets also form the basis from which many comparative retrospective analyses can be carried out.

CAPweb: a bioinformatics CGH array Analysis Platform.

Assessing variations in DNA copy number is crucial for understanding constitutional or somatic diseases, particularly cancers. The recently developed array-CGH (comparative genomic hybridization) technology allows this to be investigated at the genomic level. We report the availability of a web tool for analysing array-CGH data.

VAMP: visualization and analysis of array-CGH, transcriptome and other molecular profiles.

Motivation: Microarray-based CGH (Comparative Genomic Hybridization), transcriptome arrays and other large-scale genomic technologies are now routinely used to generate a vast amount of genomic profiles. Exploratory analysis of this data is crucial in helping to understand the data and to help form biological hypotheses. This step requires visualization of the data in a meaningful way to visualize the results and to perform first level analyses.

Spatial normalization of array-CGH data.

Background: Array-based comparative genomic hybridization (array-CGH) is a recently developed technique for analyzing changes in DNA copy number. As in all microarray analyses, normalization is required to correct for experimental artifacts while preserving the true biological signal. We investigated various sources of systematic variation in array-CGH data and identified two distinct types of spatial effect of no biological relevance as the predominant experimental artifacts: continuous spatial gradients and local spatial bias.