Faculty Bibliography

OBJECTIVE: To examine cyclooxygenase 2 inhibitor (coxib) utilization by rheumatologists for patients receiving nonsteroidal antiinflammatory drugs (NSAIDs) prior to the coxib market withdrawals. METHODS: A prospective study of patients with rheumatoid arthritis enrolled in the Consortium of Rheumatology Researchers of North America registry was performed. RESULTS: Of 1,833 patients receiving prescription NSAIDs, 1,380 (75.3%) received gastroprotection, defined as either coxib monotherapy and/or gastroprotective agent (GPA) cotherapy, and 1,207 (65.8%) received coxibs. The distribution of gastroprotective strategies included 860 (46.9%) patients who were prescribed coxib monotherapy, 347 (18.9%) prescribed dual coxib plus GPA cotherapy, 173 (9.4%) prescribed a nonselective NSAID (NS-NSAID) plus GPA cotherapy, and 453 (24.7%) prescribed an NS-NSAID without GPA cotherapy. For patients with 0, 1, and > or =2 identifiable gastrointestinal (GI) risk factors, coxib prescribing rates as a proportion of NSAID agents were 64.1%, 66.4%, and 68.6%, respectively; among dual aspirin/NSAID users, coxib prescribing rates were 66.2%, 78.3%, and 68.5% of NSAID prescriptions, respectively. CONCLUSION: The majority of NSAID users were prescribed a gastroprotective strategy, primarily attributable to coxib utilization. Coxib utilization rates were consistently high across all levels of GI risk, including patients without identifiable risk factors. These data indicate that rheumatologists broadly adopted the coxib class of NSAIDs in a nonselective manner with respect to underlying GI risk and concomitant aspirin use. As novel therapeutic classes are introduced, early evaluation of prescribing patterns using arthritis registries can determine the appropriateness of prescribing patterns and may improve patient outcomes

Osteoarthritis (OA) can be a progressive, disabling disease, leading to diminished quality of life, and, for over 500,000 individuals annually in the US, total joint replacement. The etiology of OA will vary among individuals, with potential roles for systemic factors (such as genetics and obesity) as well as for local biomechanical factors (such as muscle weakness, joint laxity and traumatic injury). Joint deterioration occurs over extended periods of time, and the diverse molecular mechanisms that mediate pathogenic events of early, mid and late disease are not yet fully understood. The success of biologic therapies in the treatment of rheumatoid arthritis has demonstrated that the blockade of a single dominant cytokine or regulatory molecule can prevent cartilage destruction in a complex disease, and has raised expectations that mechanism-based treatments could also be developed for patients with OA. In this review, we will address the biological mechanisms that mediate structural damage in OA and examine current targets that are candidates for disease modification. The challenges to drug development and the obstacles to disease modification strategies will also be addressed

The osteoarthritis disease process affects not only the cartilage but also the entire joint structure, including the synovium, bone and periarticular muscles. Characteristically, abnormal biomechanical forces result in an imbalance between chondrocyte anabolic and catabolic pathways, which ultimately leads to progressive joint destruction. Within cartilage and synovium, pro-inflammatory cytokines, particularly IL-1b and TNF-a, auto-catalytically stimulate their own production and induce chondrocytes to produce additional catabolic mediators, including proteases, chemokines, nitric oxide, and prostaglandins. The success of targeted biological therapy in rheumatoid arthritis has taught that the blockade of a single dominant cytokine can lead to remarkable clinical benefit, even in complex disease. The effectiveness of biologicals in inflammatory arthritides as disease modifying agents has increased the likelihood that similar strategies can be developed to target specific molecular mechanisms in osteoarthritis (OA). However, since the clinical development program for disease-modifying OA drugs (DMOADs) is complicated by the slow progression of disease in many patients, the introduction of DMOADs will be greatly enhanced by advances in imaging and biomarkers that serve as validated surrogate endpoints for meaningful clinical outcomes

Drug discovery and delivery to retard the degeneration of joint tissues are challenging. Current treatment is generally inadequate. This commentary places in perspective the inadequacy characteristic of existing therapeutics and the promising developments embodied in the newer therapeutics administered via the oral or intra-auricular routes

Percutaneous tracheostomy has become a common alternative to the classical open tracheostomy because of its convenience, cost effectiveness, and decreased complication rates. We retrospectively reviewed our intensive care practice using a guidewire dilatating forceps percutaneous tracheostomy technique with an endotracheal tube, as compared with the Classic Laryngeal Mask Airway (LMA) for these procedures. From 1998 to 2004, 274 patients underwent a tracheostomy procedure. Two-hundred-fifty-four (92.7%) of these patients underwent a guidewire dilatating forceps tracheostomy and 20 (7.3%) underwent a surgical tracheostomy. In the guidewire dilatating forceps group, 188 (74%) were performed by endoscopy via LMA-guided bronchoscopy, and 66 (26%) were performed through an endotracheal tube. Endoscopic views obtained via the LMA were subjectively better than those obtained with the endotracheal tube. Acute complications were significantly more frequent when using an endotracheal tube as compared with the LMA (6 of 66 versus 4 of 188; P = 0.022 Fisher's exact test, odds ratio = 4.6). There was a significant difference in terms of acute (10 of 254 versus 6 of 20; P < 0.001, odds ratio = 10.5) and chronic (0 of 254 versus 4 of 20; P < 0.001) complications between the 2 groups. There were no ventilatory complications or reports of gastric aspiration. The LMA provides a safe and effective alternative to an endotracheal tube for airway management during guidewire dilatating forceps tracheostomies in selected patients