Efficacy, safety and tolerability of GSK3858279, an anti-CCL17 monoclonal antibody and analgesic, in healthy volunteers and patients with knee osteoarthritis pain: a phase I, randomised, double-blind, placebo-controlled, proof-of-mechanism and proof-of-concept study.

Objectives: The objective of this study was to evaluate efficacy, safety and tolerability of the first-in-class, anti-CCL17 monoclonal antibody, GSK3858279, in treating knee osteoarthritis (OA) pain.

Methods: This was a phase I, randomised, placebo-controlled, two-part, proof-of-mechanism and proof-of-concept study. In part A, healthy participants were randomised 3:1 to receive GSK3858279 as either single intravenous (0.

Anticoagulation management: an interdisciplinary curriculum for family medicine residents.

Anticoagulants are high-risk medications with the potential to cause significant patient harm if inappropriately managed. Medical trainees and practicing physicians often report inadequate education and uncertainty in decision-making related to anticoagulation therapy. To address this gap, an interdisciplinary Anticoagulation Management Training Program was developed for family medicine residents at the Toronto Western Family Health Team.

JAK inhibitors disrupt T cell-induced proinflammatory macrophage activation.

Objectives: Macrophage subsets, activated by T cells, are increasingly recognised to play a central role in rheumatoid arthritis (RA) pathogenesis. Janus kinase (JAK) inhibitors have proven beneficial clinical effects in RA. In this study, we investigated the effect of JAK inhibitors on the generation of cytokine-activated T (Tck) cells and the production of cytokines and chemokines induced by Tck cell/macrophage interactions.

The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease.

To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs.

The impact of autoantibodies against citrullinated, carbamylated, and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis: an observational cohort study.

Background: A range of anti-modified protein antibodies (AMPAs) are associated with rheumatoid arthritis. We aimed to assess the relationship between AMPA profiles and radiographic progression in patients with new-onset rheumatoid arthritis.

Methods: In this cohort study, we obtained samples and data from the Scottish Early Rheumatoid Arthritis (SERA) inception cohort and biobank, which recruited patients with new-onset rheumatoid arthritis or undifferentiated arthritis who had at least one swollen joint from 20 hospitals across Scotland.

Chromopertubation of an Ectopic Pregnancy.

Background: An ectopic pregnancy is a nonviable pregnancy located outside of the endometrial cavity of the uterus, which can be managed medically or surgically.

Case: A 35-year-old woman with a prior ectopic pregnancy, who reported tubal surgery of unknown location and extent, presented with a recurrent ectopic pregnancy. Ultrasound imaging showed a complex cystic lesion adjacent to the ovary, moderate complex free fluid, and no intrauterine pregnancy.

Blood type and postpartum hemorrhage by mode of delivery: A retrospective cohort study.

Objective: To assess the relationship between postpartum hemorrhage and ABO blood type for vaginal delivery and cesarean delivery.

Study Design: This is a retrospective cohort study of data abstracted from the PeriBank database regarding demographics and delivery outcomes. All live singleton deliveries from January 2011 until March 2018 were included in this study.

Finite sample variance estimation for optimal dynamic treatment regimes of survival outcomes.

Deriving valid confidence intervals for complex estimators is a challenging task in practice. Estimators of dynamic weighted survival modeling (DWSurv), a method to estimate an optimal dynamic treatment regime of censored outcomes, are asymptotically normal and consistent for their target parameters when at least a subset of the nuisance models is correctly specified. However, their behavior in finite samples and the impact of model misspecification on inferences remain unclear.

Adaptive treatment strategies for chronic conditions: shared-parameter G-estimation with an application to rheumatoid arthritis.

Most estimation algorithms for adaptive treatment strategies assume that treatment rules at each decision point are independent from one another in the sense that they do not possess any common parameters. This is often unrealistic, as the same decisions may be made repeatedly over time. Sharing treatment-decision parameters across decision points offers several advantages, including estimation of fewer parameters and the clinical ease of a single, time-invariant decision to implement.

Utility and duration of leuprolide stimulation testing in children.

Objective Basal (unstimulated) LH levels and leuprolide stimulation tests are used to define pubertal status of children presenting with signs of early puberty. The primary aims of this study were to (i) confirm utility of detectable basal LH levels in precluding the need for leuprolide stimulation testing, and, (ii) determine whether duration of testing could be abbreviated from usual 3 h test without compromising sensitivity. Methods We reviewed morning basal and leuprolide-stimulated LH levels in 105 children, aged 1-9 years (mean 6.

Association of Immediate Postpartum Etonogestrel Implant Insertion and Venous Thromboembolism.

Objective: To estimate the rate of readmissions for postpartum venous thromboembolism (VTE) during the first 30 days postdelivery between women with and without the immediate postpartum insertion of the etonogestrel contraceptive implant.

Methods: The Nationwide Readmissions Database from 2016 was used to identify women with a singleton delivery, immediate postpartum insertion of the etonogestrel contraceptive implant, and readmission for VTE within 30 days of discharge. Those with a prior history of VTE or anticoagulant therapy were excluded.

Differential CpG DNA methylation in peripheral naïve CD4 T-cells in early rheumatoid arthritis patients.

Background: The genetic risk associated with rheumatoid arthritis (RA) includes genes regulating DNA methylation, one of the hallmarks of epigenetic re-programing, as well as many T-cell genes, with a strong MHC association, pointing to immunogenetic mechanisms as disease triggers leading to chronicity. The aim of our study was to explore DNA methylation in early, drug-naïve RA patients, towards a better understanding of early events in pathogenesis.

Result: Monocytes, naïve and memory CD4 T-cells were sorted from 6 healthy controls and 10 RA patients.

Minimally Invasive Surgery in Pregnancy.

If it is medically necessary to perform nonobstetrical abdominal surgery in pregnancy, a minimally invasive approach should be considered. The benefits of laparoscopy are well known and current studies promote the safety of laparoscopy in pregnancy, when certain guidelines are followed. This article will review the safety of surgery in pregnancy, maternal physiology, fetal considerations, maternal obesity, laparoscopic cerclage, large adnexal mass, and complications.

Quality Improvement Program Improves Time in Therapeutic Range for Hemodialysis Recipients Taking Warfarin.

Introduction: Studies have shown that achieving a time in therapeutic range (TTR) for warfarin of greater than 60% is associated with a lower risk of bleeding. However, many patients on hemodialysis (HD) do not achieve this target.

Methods: We audited TTR achievement at the in-center HD unit of our hospital in 2017 and found that only 40% of patients had achieved a TTR >60%.

Undernutrition and growth in the developing world.

Purpose Of Review: Despite targeted interventions, an estimated 150.8 million children under 5 years globally are still stunted, of which more than half live in Asia and more than one-third live in Africa. This review summarizes our current knowledge regarding how longitudinal bone growth is regulated by nutritional intake in the developing world.

A Call to Action to Address Gender Equity Within Our Specialty: Time's Up on Waiting for Change.

Although national attention has been focused on sexual harassment and gender inequity in the United States, leaders within the obstetrics and gynecology community have remained relatively silent. Sexual harassment and gender inequity remain pervasive in our specialty. This article serves as a call to action for leadership as well as physicians within obstetrics and gynecology to implement ethical and evidence-based approaches to reduce gender inequity and improve workplace culture within our specialty.

A Randomized Controlled Trial for Abdominal Binder Use after Laparoendoscopic Single-Site Surgery.

Study Objective: To compare postoperative pain in patients using an abdominal binder with a control group after laparoendoscopic single-site (LESS) surgery.

Design: A randomized controlled trial (Canadian Task Force classification level 1).

Setting: An academic gynecologic surgeon's practice.

Postoperative Pain After Single-Site Versus Multiport Hysterectomy.

Background And Objectives: With advances in laparoscopic surgery, the goal of surgeons and patients is to minimize pain to allow for faster recovery and return to normal daily activities. One of these advances is single-site surgery. In this study, we compared postoperative pain in laparoendoscopic single-site surgery (LESS) to that in traditional multiple-incision hysterectomy.

Bariatric surgery and associated adverse pregnancy outcomes among obese women.

Objective: To evaluate whether bariatric surgery is associated with intrauterine growth restriction (IUGR).

Methods: We performed a population-based retrospective cohort study to estimate the relationship between prior bariatric surgery and adverse pregnancy outcomes. The data were collected from the 2012 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS).

MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis.

Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis.

The pathogenesis of RA is a complex and ever-changing landscape but amid the chaos of the disease process we have found effective treatment regimes. However, our current therapeutics, although targeting various components of both the innate and adaptive immune response, do not result in disease remission. Protein kinase inhibitors are attractive targets due to their ability to influence downstream signalling and their oral bioavailability.

The liver X receptor pathway is highly upregulated in rheumatoid arthritis synovial macrophages and potentiates TLR-driven cytokine release.

Objectives: Macrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood.

Methods: We used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8).

PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis.

Objectives: Proteinase-activated receptor 2 (PAR(2)) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR(2) expression on rheumatoid arthritis (RA)-derived leucocyte subsets.

Methods: Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects.