Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis

Rheumatoid arthritis is a chronic autoimmune disease that often leads to functional disability and reduced quality of life. The pathogenesis of synovial inflammation that is associated with this disease is thought to result from T-cell activation. To become fully activated, T cells require an antigen-specific signal through the T-cell receptor and a second signal through a costimulatory receptor. Abatacept is the first drug in a new class of disease-modifying antirheumatic drugs (DMARDs) known as selective costimulation modulators. Costimulation modulators block the second signal and decrease T-cell activation. Abatacept has been approved by the United States Food and Drug Administration for reducing signs and symptoms, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adults with moderate-to-severe active rheumatoid arthritis who have had an inadequate response to at least one other DMARD, such as methotrexate or tumor necrosis factor (TNF)-alpha inhibitors. Randomized controlled trials have shown that abatacept improves both clinical outcomes and health-related quality of life in patients who have had an inadequate response to other DMARDs. Abatacept has been shown to be well tolerated. In clinical trials, however, abatacept treatment was associated with a higher rate of infections compared with placebo. This finding was compounded when abatacept was used with TNF-alpha inhibitors; thus, this combination should be avoided. Abatacept appears to be a useful treatment option for patients with rheumatoid arthritis who have previously failed other DMARDs. However, additional clinical trials evaluating its long-term effect on patient safety and disease outcomes are needed.     

The evolving story of medical emergency teams in quality improvement

Adverse events affect approximately 3% to 12% of hospitalized patients. At least a third, but as many as half, of such events are considered preventable. Detection of these events requires investments of time and money. A report in a recent issue of Critical Care used the medical emergency team activation as a trigger to perform a prospective standardized evaluation of charts. The authors observed that roughly one fourth of calls were related to a preventable adverse event, which is comparable to the previous literature. However, while previous studies relied on retrospective chart reviews, this study introduced the novel element of real-time characterization of events by the team at the moment of consultation. This methodology captures important opportunities for improvements in local care at a rate far higher than routine incident-reporting systems, but without requiring substantial investments of additional resources. Academic centers are increasingly recognizing engagement in quality improvement as a distinct career pathway. Involving such physicians in medical emergency teams will likely facilitate the dual roles of these as a clinical outreach arm of the intensive care unit and in identifying problems in care and leading to strategies to reduce them.     

Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis

PURPOSE: Clinical trials evaluating acetylcysteine for the prevention of contrast-related nephropathy have reported mixed results. Although previous meta-analyses have concluded that acetylcysteine is beneficial, the recent availability of additional trials calls for reassessment of current evidence. METHODS: We performed a computerized search to identify relevant published and unpublished randomized clinical trials that evaluated acetylcysteine for the prevention of contrast-related nephropathy. Abstracted data from each trial included assessments of clinical outcomes, trial quality, and additional characteristics. The primary outcome of interest was the incidence of nephropathy after contrast administration. Data were combined using random-effects models with the performance of standard tests to assess for heterogeneity and publication bias. Subgroup analyses were also performed. RESULTS: Twenty trials involving 2195 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-related nephropathy was 0.73 (95% confidence interval: 0.52 to 1.0; P = 0.08), a nonsignificant trend towards benefit in patients treated with acetylcysteine. This effect varied, however, across the 20 trials (test of heterogeneity, P = 0.04). Although higher-quality trials demonstrated a stronger benefit for acetylcysteine in general, few reported important elements of study design, such as concealment of allocation, placebo-controls, or double-blinding. Heterogeneity was unexplained by subgroup analyses. CONCLUSION: Acetylcysteine may reduce the incidence of contrast-related nephropathy, but this finding is reported inconsistently across currently available trials. High-quality, large clinical trials are needed before acetylcysteine use in this indication can be recommended universally.