Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages.

Macrophages are innate immune cells that are known for their extreme plasticity, enabling diverse phenotypes that lie on a continuum. In a simplified model, they switch between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes depending on surrounding microenvironmental cues, which have been implicated in disease outcomes. Although considerable research has been focused on macrophage response to biochemical cues and mechanical signals, there is a scarcity of knowledge surrounding their behavior in response to shear stress.

DONSON facilitates Cdc45 and GINS chromatin association and is essential for DNA replication initiation.

Faithful cell division is the basis for the propagation of life and DNA replication must be precisely regulated. DNA replication stress is a prominent endogenous source of genome instability that not only leads to ageing, but also neuropathology and cancer development in humans. Specifically, the issues of how vertebrate cells select and activate origins of replication are of importance as, for example, insufficient origin firing leads to genomic instability and mutations in replication initiation factors lead to the rare human disease Meier-Gorlin syndrome.

Let sleeping bats lie: Analyzing institutional adaptation to environmental regulatory change through Adaptive Management theory.

Employing a case of a state transportation agency, we examine how complex institutions which integrate outsourcing within a bureaucratic process adapt to environmental regulatory changes. In 2012, two endangered species of bats were located outside of their established ranges in northern Georgia. These discoveries required the Georgia Department of Transportation (GDOT) to comply with a new set of federal regulations relating to those species when developing its projects.

Variable impacts of different remission states on health-related quality of life in rheumatoid arthritis.

Objectives: Targeting remission in rheumatoid arthritis (RA) improves health-related quality of life (HRQoL) and disability. However, the impacts of different remission criteria and durations and their frequencies are uncertain. Our observational study assessed these factors.

Changing clinical patterns in rheumatoid arthritis management over two decades: sequential observational studies.

Background: Rheumatoid arthritis (RA) treatment paradigms have shifted over the last two decades. There has been increasing emphasis on combination disease modifying anti-rheumatic drug (DMARD) therapy, newer biologic therapies have become available and there is a greater focus on achieving remission. We have evaluated the impact of treatment changes on disease activity scores for 28 joints (DAS28) and disability measured by the health assessment questionnaire scores (HAQ).

Assessing the effectiveness of synthetic and biologic disease-modifying antirheumatic drugs in psoriatic arthritis - a systematic review.

Background: Psoriatic arthritis is an inflammatory arthritis the primary manifestations of which are locomotor and skin disease. Although a number of guidelines have been published citing strategies for reducing disease progression, the evidence base for disease-modifying agents is unclear. This forms the focus of this systematic review.

Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial.

Objective: To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs.

Design: Open label pragmatic randomised multicentre two arm non-inferiority trial over 12 months.

Setting: 24 rheumatology clinics in England.

Calprotectin as a biomarker for rheumatoid arthritis: a systematic review.

Objective: Calprotectin (myeloid-related protein 8/14), a heterodimeric complex of calcium-binding proteins, is expressed in granulocytes and monocytes. Calprotectin levels are high in synovial tissue, particularly in activated cells adjacent to the cartilage-pannus junction. This systematic review evaluates the use of calprotectin as an indicator of disease activity, therapeutic response, and prognosis in rheumatoid arthritis (RA).

Randomised controlled trial of tumour necrosis factor inhibitors against combination intensive therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews.

Background: Rheumatoid arthritis (RA) is initially treated with methotrexate and other disease-modifying antirheumatic drugs (DMARDs). Active RA patients who fail such treatments can receive tumour necrosis factor inhibitors (TNFis), which are effective but expensive.

Objective: We assessed whether or not combination DMARDs (cDMARDs) give equivalent clinical benefits at lower costs in RA patients eligible for TNFis.

The impact of rheumatoid arthritis on quality-of-life assessed using the SF-36: a systematic review and meta-analysis.

Objective: The assessment of health-related quality-of-life (HRQoL) in rheumatoid arthritis (RA) is becoming increasingly common in both research and clinical practice. One of the most widely used tools for measuring HRQoL is the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). We conducted a systematic review examining the impact of RA on HRQoL, measured through the SF-36.

Can we discontinue synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis?

Objectives: When rheumatoid arthritis (RA) patients have achieved sustained good clinical responses can their disease-modifying anti-rheumatic drugs (DMARDs) be reduced or discontinued? This review addresses this question by summarising the clinical evidence about DMARD withdrawal. It includes an assessment of predictive factors for sustained DMARD-free remissions.

Methods: We evaluated the evidence for discontinuing DMARDs in stable RA in both randomised controlled trials (RCTs) and observational studies.

A randomized placebo-controlled trial of methotrexate in psoriatic arthritis.

Objective: MTX is widely used to treat synovitis in PsA without supporting trial evidence. The aim of our study was to test the value of MTX in the first large randomized placebo-controlled trial (RCT) in PsA.

Methods: A 6-month double-blind RCT compared MTX (15 mg/week) with placebo in active PsA.

Current limitations in the management of cardiovascular risk in rheumatoid arthritis.

Objectives: Rheumatoid arthritis (RA) is associated with excess cardiovascular (CV) disease. Many studies have shown subclinical atherosclerosis in RA is associated with CV risk factors and inflammation. Their relationship with CV events has however received less attention.

Quality of life and the outcome of established rheumatoid arthritis.

Rheumatoid arthritis (RA) is a long-term condition causing joint pain and swelling and sometimes systemic involvement. The aims of treatment are, first, to reduce the impact the disease has on a patient and, second, to halt progression of disease. The advent of intensive therapy, including biologics, has led to a major improvement in outcome.

The impact of disease activity, pain, disability and treatments on fatigue in established rheumatoid arthritis.

We investigate a range of clinical factors and anti-rheumatic treatments, for their degree of association with rheumatoid arthritis (RA) fatigue in 557 patients. A range of clinical measures concerning disability, pain and disease activity together with drug history were recorded as part of routine clinical visits. Fatigue was measured using the Functional Assessment of Chronic Illness Therapy (FACIT-F) questionnaire.

Perceived barriers to integrated care in rheumatoid arthritis: views of recipients and providers of care in an inner-city setting.

Background: A number of recent reports published in the UK have put the quality of care of adults with Rheumatoid Arthritis (RA) centre stage. These documents set high standards for health care professionals and commissioning bodies that need to be implemented into routine clinical practice. We therefore have obtained the views of recipients and providers of care in inner city settings as to what they perceive are the barriers to providing integrated care.

Remission in early rheumatoid arthritis.

Objective: We systematically reviewed remission as an outcome measure in observational studies and randomized controlled trials (RCT) in early rheumatoid arthritis (RA). Our objectives were to identify its frequency using different criteria, to determine the influence of different treatment strategies on remission, and to review the effects of remission on radiological outcomes.

Methods: Pubmed, Medline and Embase were searched using the following terms: Early Rheumatoid Arthritis or Early RA combined with Remission, Treatment, anti-Tumor Necrosis Factor (TNF) or Disease-modifying Antirheumatic Drugs (DMARD).

Clinical effectiveness of biologics in clinical practice.

TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA), particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness of TNF inhibitors as initial treatment for active RA. New data from the National Data Bank for Rheumatic Diseases now question the current consensus in methotrexate failures.

Fibromyalgic rheumatoid arthritis and disease assessment.

Objective: We evaluated fibromyalgic RA to determine its clinical impact, identification using core clinical assessments and influence identifying active disease using disease activity scores (DAS-28).

Methods: We examined the impact and identification using core clinical assessments (tender minus swollen joint counts) of fibromyalgic RA (> or =11 tender points) in initial (105 patients) and replicate (100 patients) cohorts. Receiver operator characteristic (ROC) curves optimized the cut-off points using tender minus swollen joint counts; their validity was confirmed in a routine practice cohort (321 patients).

A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis.

Objective: We examined how combination DMARD therapies and TNF inhibitors therapies plus MTX (TNF/MTX) affect clinical and radiological outcomes compared with MTX monotherapy in early RA.

Methods: We systematically searched EMBASE, PubMed and Ovid Medline for randomized controlled trials (RCTs) of combination therapy in early RA. We evaluated ACR responses, withdrawals for inefficacy and toxicity, HAQ and radiographic progression.

Non-steroidal anti-inflammatory drugs and cardiac failure: meta-analyses of observational studies and randomised controlled trials.

Aims: To determine the risks of cardiac failure with non-steroidal anti-inflammatory drugs (NSAIDs) and the specific risks with Cox-2 specific NSAIDs (COXIBs).

Methods: We performed meta-analyses examining the risks of developing cardiac failure in observational studies and in randomised controlled trials (RCTs) involving patients with arthritis and non-rheumatic disorders. Electronic databases and published bibliographies were systematically searched (1997-2008).

Management of septic arthritis: a systematic review.

Objective: To evaluate the existing evidence on the diagnosis and management of septic arthritis in native joints.

Design: Systematic review.

Data Sources: Cochrane Library, Medline, Embase, National Electronic Library for Health, reference lists, national experts.