Patient and health professional views on risk-stratified monitoring of immune-suppressing treatment in adults with inflammatory diseases.

Objective: To explore the acceptability of an individualised risk-stratified approach to monitoring for target-organ toxicity in adult patients with immune-mediated inflammatory diseases established on immune-suppressing treatment(s).

Methods: Adults (≥18 years) taking immune-suppressing treatment(s) for at-least six months, and healthcare professionals (HCPs) with experience of either prescribing and/or monitoring immune-suppressing drugs were invited to participate in a single, remote, one-to-one, semi-structured interview. Interviews were conducted by a trained qualitative researcher and explored their views and experiences of current monitoring and acceptability of a proposed risk-stratified monitoring plan.

Design and synthesis of endocannabinoid enzyme inhibitors for ocular indications.

A small library of FAAH and dual FAAH/MAGL inhibitors designed for peripheral selectivity were targeted. Of these compounds, three were identified to have desirable FAAH inhibition and reduced permeability in a PAMPA assay. Those three compounds were advanced into a MAGL inhibitor assay and one was found to be a relative selective FAAH inhibitor, FAAH to MAGL IC ratio of 1:27, and one was found to be more characteristic of a true dual enzyme inhibitor, FAAH to MAGL IC ratio of 1:4.

A Framework for Pediatric Intensivists Providing Compassionate Extubation at Home.

For families facing end-of-life decisions for their critically ill children, compassionate extubation at home is a valuable service that pediatric intensivists can provide. Compassionate extubation at home is resource intensive and can be logistically challenging. Discouragingly, guidance on compassionate extubation at home in the literature is limited.

Incorporating a Trauma-Informed Care Protocol Into Pediatric Trauma Evaluation: The Pediatric PAUSE Does Not Delay Imaging or Disposition.

Objectives: Trauma evaluation in the emergency department (ED) can be a stressful event for children. With the goal of minimizing pain, anxiety, and unneeded interventions in stable patients, we implemented the Pediatric PAUSE at our level 1 adult/level 2 pediatric trauma center. The Pediatric PAUSE is a brief protocol performed after the primary survey, which addresses Pain/Privacy, Anxiety/IV Access, Urinary Catheter/Rectal exam/Genital exam, Support from family or staff, and Explain to patient/Engage with PICU team.

Discrepancies in categorizing rheumatoid arthritis patients by DAS-28(ESR) and DAS-28(CRP): can they be reduced?

Objectives: The 28-joint disease activity score (DAS-28) guides the use of biologics in RA. The aims of this study were to investigate agreement between the ESR- and CRP-based DAS-28 definitions, and to examine how this agreement may be improved.

Methods: Data were obtained from registers of early (n = 520) and established RA (n = 364) patients.

Therapy of patients with rheumatoid arthritis: outcome of infliximab failures switched to etanercept.

Objective: The role of alternative tumor necrosis factor (TNF) antagonist therapies in the context of failure of initial TNF antagonist therapy in patients with rheumatoid arthritis (RA) has yet to be clearly defined. The goal of this study was to determine the efficacy of etanercept in patients who failed to respond to infliximab.

Methods: Ninety-five patients with RA who failed to respond to infliximab and methotrexate were treated with etanercept (with continuation of concomitant methotrexate).

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia.

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis.

C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis: defining subtypes of nonresponse and subsequent response to etanercept.

Objective: Nonresponse to anti-tumor necrosis factor alpha in patients with rheumatoid arthritis (RA) is poorly understood. The aims of this study were to define nonresponse patterns using infliximab and C-reactive protein (CRP) profiles, to assess the predictive power of a CRP response for outcome, and to correlate these findings with subsequent response to etanercept.

Methods: We studied 207 patients with resistant RA who were started on treatment with infliximab.

Autologous stem cell transplantation for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is responsive to treatment with immunosuppressives and steroids, but often pursues a relapsing or refractory course resulting in increasing incapacity and reduced survival. Autologous stem cell transplantation (ASCT) following immunoablative chemotherapy is a newer therapy for autoimmune disease of potential use in severe SLE. A retrospective registry survey was carried out by the European Blood and Marrow Transplant and European League Against Rheumatism (EBMT/EULAR) registry.

Lack of response to anakinra in rheumatoid arthritis following failure of tumor necrosis factor alpha blockade.

Objective: In patients with rheumatoid arthritis (RA) treated with tumor necrosis factor alpha (TNF alpha)- blocking therapy, there is heterogeneity of response. This raises the possibility that in certain circumstances, cytokines such as interleukin-1 (IL-1) may dominate the drive toward joint inflammation. This study was undertaken to investigate whether blocking the action of IL-1 with an IL-1 receptor antagonist (IL-1Ra) is efficacious in patients with disease that did not respond to TNF alpha blockade.

Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR.

Objective: Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis.

Anti-tumor necrosis factor-alpha therapy-induced vasculitis: case series.

As experience with anti-tumor necrosis factor (TNF-alpha) therapy increases, there has been the expected emergence of reports on uncommon side effects. Large clinical trials identified the development of autoantibodies and postmarketing surveillance has identified problems including tuberculosis. There have been several case reports of drug-induced systemic lupus erythematosus.

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4(+) T cells than healthy controls.