Incidence of gastroduodenal ulcers associated with valdecoxib compared with that of ibuprofen and diclofenac in patients with osteoarthritis.

OBJECTIVE: To determine whether valdecoxib, at chronic arthritis doses, has the characteristics of a cyclo-oxygenase 2 (COX-2) specific inhibitor, as measured by a reduced incidence of upper-gastrointestinal ulceration compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: This double-blind, multicentre, placebo-controlled, parallel-group study compared the incidence of gastroduodenal ulcers associated with valdecoxib 10 mg daily (q.d.) and 20 mg q.d. with that of ibuprofen 800 mg three times daily (t.i.d.) or diclofenac 75 mg twice daily (b.i.d.) when administered over a 12-week period. The incidence of gastroduodenal ulcers was assessed by upper-gastrointestinal endoscopy, performed at baseline and again at the end of week 12 (or at early study termination). Efficacy assessments were performed at baseline and at weeks 2, 6 and 12 using Patient's and Physician's Global Assessments of Arthritis. RESULTS: A total of 1052 osteoarthritis patients were enrolled into the trial. The incidence of gastroduodenal ulcers over 12 weeks was 5% in patients receiving valdecoxib 10 mg q.d., 4% in patients receiving valdecoxib 20 mg q.d., 7% in patients receiving placebo, 16% in patients receiving ibuprofen 800 mg t.i.d. (P <0.05 v. placebo), and 17% in patients receiving diclofenac 75 mg b.i.d. (P <0.05 v. placebo). The incidence of gastroduodenal ulcers at week 12 seen in the ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. groups was significantly higher than that in the valdecoxib 10 mg q.d. and valdecoxib 20 mg q.d. groups (P <0.05). The incidence rates of gastroduodenal ulcers were not significantly different between the valdecoxib treatment groups or between valdecoxib- and placebo-treated patients. Efficacy responses to valdecoxib 10 mg and 20 mg q.d. were significantly greater than placebo and comparable with both ibuprofen 800 mg t.i.d. and diclofenac 75 mg b.i.d. CONCLUSIONS: The results of the study demonstrate that valdecoxib has an upper-gastrointestinal safety profile typical of a COX-2 specific inhibitor. Overall, the data indicate that administration of valdecoxib offers similar efficacy for the treatment of osteoarthritis but improved upper-gastrointestinal safety compared with the conventional NSAIDs, ibuprofen and diclofenac, based on the significantly lower incidence of gastroduodenal ulcers detected by endoscopy.

Randomized placebo-controlled trial comparing efficacy and safety of valdecoxib with naproxen in patients with osteoarthritis.

OBJECTIVE: We compared the efficacy and upper gastrointestinal safety of the cyclooxygenase-2-specific inhibitor valdecoxib with naproxen and placebo in treating moderate to severe osteoarthritis of the knee. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and upper gastrointestinal tract safety of valdecoxib at dosages of 5, 10, and 20 mg once daily with placebo and naproxen at the dosage of 500 mg twice daily. POPULATION: We included patients who had been diagnosed with moderate to severe osteoarthritis of the knee according to the modified criteria of the American College of Rheumatology. OUTCOMES MEASURED: The Patient's and Physician's Global Assessment of Arthritis (PaGAA, PhGAA), Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), and Western Ontario and McMaster's Universities (WOMAC) Osteoarthritis indices were assessed at baseline and at weeks 2, 6, and 12. Upper gastrointestinal ulceration was assessed by pre- and posttreatment endoscopies. RESULTS: Valdecoxib 10 and 20 mg once daily (but not 5 mg once daily) demonstrated similar efficacy to naproxen at 500 mg twice daily, and all 3 dosages were superior to placebo for the PaGAA, PhGAA, PAAP-VAS, and WOMAC Osteoarthritis indices at most assessments throughout the 12-week study (P <.05). The incidence of endoscopically proven ulcers was significantly higher in the naproxen group than in the 5- and 10-mg valdecoxib groups, but not in the 20-mg valdecoxib group. All 3 valdecoxib doses were comparable to placebo in ulcer incidence. CONCLUSIONS: Valdecoxib (10 and 20 mg once daily) is significantly superior to placebo and as effective as naproxen (500 mg twice daily) in improving moderate to severe osteoarthritis of the knee. Upper gastrointestinal tract safety of valdecoxib (5 and 10 mg) was comparable to that of placebo and significantly better than that of naproxen.

Antimicrobial acrylic materials with in situ generated silver nanoparticles.

UNLABELLED: Polymethyl methacrylate (PMMA) is widely used to treat traumatic head injuries (cranioplasty) and orthopedic injuries (bone cement), but there is a problem with implant-centered infections. With organisms such as Acinetobacter baumannii and methicillin-resistant staphylococcus aureus developing resistance to antibiotics, there is a need for novel antimicrobial delivery mechanisms without risk of developing resistant organisms. OBJECTIVES: To develop a novel antimicrobial implant material by generating silver nanoparticles (AgNP) in situ in PMMA. RESULTS: All PMMA samples with AgNP's (AgNP-PMMA) released Ag(+) ions in vitro for over 28 days. In vitro antimicrobial assays revealed that these samples (even samples with the slowest release rate) inhibited 99.9% of bacteria against four different strains of bacteria. Long-term antimicrobial assay showed a continued antibacterial effect past 28 days. Some AgNP-loaded PMMA groups had comparable Durometer-D hardness (a measure of degree of cure) and modulus to control PMMA, but all experimental groups had slightly lower ultimate transverse strengths. CONCLUSIONS: AgNP-PMMA demonstrated a tremendously broad-spectrum and long-intermediate-term antimicrobial effect with comparable mechanical properties to control PMMA. Current efforts are focused on further improving mechanical properties by reducing AgNP loading and assessing fatigue properties.

Efficacy and safety of the COX-2 specific inhibitor valdecoxib in the management of osteoarthritis of the hip: a randomized, double-blind, placebo-controlled comparison with naproxen.

OBJECTIVE: Non-steroidal antiinflammatory agents are commonly used to treat pain and inflammation associated with osteoarthritis (OA), but have poor gastrointestinal (GI) tolerability. This study compared the efficacy of the COX-2 specific inhibitor valdecoxib with naproxen and placebo, in treating symptomatic OA of the hip. DESIGN: This multicenter, randomized, double-blind 12-week study compared the efficacy and tolerability of single daily doses of valdecoxib 5 mg and 10 mg with placebo or naproxen 500 mg BID. Efficacy was assessed by Patient's and Physician's Global Assessment of Arthritis, and the WOMAC (Western Ontario and McMasters) OA Individual and Composite Indices. The incidence of adverse events was monitored throughout the study. RESULTS: Valdecoxib was clinically and statistically superior to placebo for Patient's and Physician's Global Assessment of Arthritis and for all WOMAC OA Indices over the 12 week study period (P

American pain society pain questionnaire and other pain measures in the assessment of osteoarthritis pain: a pooled analysis of three celecoxib pivotal studies.

The aim of this study was to evaluate the utility of the American Pain Society (APS) questionnaire in the assessment of osteoarthritis (OA) pain and to determine the onset of action of celecoxib in the treatment of acute flare pain in patients with OA of the knee or hip. Pooled data from three pivotal, randomized, double-blind, placebo-controlled, 12-week trials of patients with OA who exhibited a flare of disease activity after withdrawal of nonsteroidal anti-inflammatory drug or analgesic therapy were evaluated. Patients completed the APS Pain Measure Questionnaire, which evaluates pain intensity and quality of life, at baseline and daily for the first 7 days of therapy. In addition, patients underwent a range of standard OA assessments to evaluate the analgesic efficacy of celecoxib up to 12 weeks. Three thousand two hundred fifty-eight patients were enrolled in the three studies, of whom 2041 completed the APS questionnaire (1010 received celecoxib, 513 received naproxen, and 518 received placebo). Within the first 24 hours, celecoxib at a dose of 200 or 400 mg/d significantly reduced the amount of acute pain experienced compared with placebo for four of the five measures, and statistical significance for the remaining parameter, "pain in the last 24 hours," was achieved on day 2. Celecoxib at a dose of 200 to 400 mg/d provided similar efficacy to naproxen at a dose of 1000 mg/d. The pain relief observed with celecoxib was maintained for the APS evaluation period. Long-term efficacy assessments showed the efficacy of 200 mg/d of celecoxib to be continuous and maintained for at least the 12 weeks of the study and that it was equivalent to 400 mg/d of celecoxib and 1000 mg/d of naproxen. This study demonstrates that the APS questionnaire is a useful measure of pain and therapeutic response in OA. Celecoxib furthermore seems to be an effective acute and chronic analgesic in OA.