A walking model to assess the onset of analgesia in osteoarthritis knee pain.

OBJECTIVE: To assess a walking model utilizing a set of standardized treadmill walks to measure acute analgesic response in osteoarthritis (OA) of the knee. DESIGN: Randomized, double-blind, placebo-controlled, multiple dose, three-period crossover study. Patients > or =45 years of age (N=22) with symptomatic knee OA were randomized to naproxen 500 mg bid, tramadol/acetaminophen 37.5 mg/325 mg in forced titration, or placebo in each of three periods. Patients performed multiple 20-minute treadmill walks on Day 1 and Day 3 at a consistent self-selected pace predetermined at screening. Pain intensity (PI) during the walks was assessed on an 11-point numerical rating scale at 0, 3, 6, 9, 12, 15, 18, and 20 min. The primary endpoint was the time-weighted average (TWA) change from baseline PI on Day 3 for the two self-paced walks for the active treatments vs placebo. Time to moderate pain (TTMP) was a key secondary endpoint. RESULTS: Compared with placebo, the TWA change from baseline PI on Day 3 was significantly better with tramadol/acetaminophen (P=0.043) but not with naproxen (P=0.089). TWA change from baseline on Day 1 was also significantly better with both tramadol/acetaminophen (P=0.001) and naproxen (P=0.048) compared with placebo. TTMP was significantly better for tramadol/acetaminophen and naproxen than placebo (P<0.001 to P=0.015) for walks on Day 1 after a single dose and on Day 3. CONCLUSIONS: This novel OA pain model was able to discriminate both tramadol/acetaminophen and naproxen from placebo after single and multiple doses. ClinicalTrials.gov identifier: NCT00772967.

Responder analysis and correlation of outcome measures: pooled results from two identical studies comparing etoricoxib, celecoxib, and placebo in osteoarthritis.

OBJECTIVES: To determine the proportion of responders in two identical osteoarthritis (OA) trials using Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria and to assess the comparability and correlation of individual component measurements. METHODS: Data were pooled from two identical 26-week, double-blind, randomized, parallel, multicenter trials comparing once daily etoricoxib 30 mg (N=475), celecoxib 200 mg (N=488), and placebo (N=244) in patients with OA of the knee or hip. OMERACT-OARSI criteria were (1) improvement in pain or physical function > or =50% and an absolute change > or =20 mm on a 100-mm visual analog scale (VAS); or (2) improvement of > or =20% and with an absolute change > or =10 mm in at least two of the following three categories: pain, physical function, and patient's global assessment. Correlations were assessed between endpoints measured as time-weighted average change from baseline over 12 weeks using Pearson's correlation coefficient (r). RESULTS: There were significantly greater proportions of responders in the etoricoxib (66.2%) and celecoxib (63.5%) groups compared with the placebo group (43.0%; P<0.001). There was no difference between the two active treatment groups. There was high correlation between pain and physical function (r=0.903), pain and global assessment (r=0.778), and physical function and global assessment (r=0.820). There was high sensitivity (75-87%) and specificity (80-96%) for changes in individual component measurements to predict OMERACT-OARSI responders. CONCLUSIONS: Significantly more patients receiving etoricoxib or celecoxib than placebo were OMERACT-OARSI responders. The high correlation between individual scales composing this composite response measurement suggests some redundancies between individual components, particularly between pain and physical function.

Efficacy and safety of etoricoxib 30 mg and celecoxib 200 mg in the treatment of osteoarthritis in two identically designed, randomized, placebo-controlled, non-inferiority studies.

OBJECTIVE: To compare the efficacy of etoricoxib 30 mg with the generally maximum recommended dose of celecoxib, 200 mg, in the treatment of osteoarthritis (OA) in two identically designed studies. METHODS: Two multi-centre, 26-week, double-blind, placebo-controlled, non-inferiority studies were conducted, enrolling patients who were prior non-steroidal anti-inflammatory drug (NSAID) or acetaminophen users. There were 599 patients in study 1 and 608 patients in study 2 randomized 4:4:1:1 to etoricoxib 30 mg qd, celecoxib 200 mg qd or one of two placebo groups for 12 weeks. After 12 weeks, placebo patients were evenly distributed to etoricoxib or celecoxib based on their initial enrollment randomization schedule. The primary hypothesis was that etoricoxib 30 mg would be at least as effective as celecoxib 200 mg for the time-weighted average change from baseline over 12 weeks for Western Ontario and McMaster (WOMAC) Pain Subscale, WOMAC Physical Function Subscale and Patient Global Assessment of Disease Status. Active treatments were also assessed over the full 26 weeks. Adverse experiences were collected for safety assessment. RESULTS: In both studies, etoricoxib was non-inferior to celecoxib for all three efficacy outcomes over 12 and 26 weeks; both were superior to placebo (P < 0.001) for all three outcomes in each study over 12 weeks. The safety and tolerability of etoricoxib 30 mg qd and celecoxib 200 mg qd were similar over 12 and 26 weeks. CONCLUSIONS: Etoricoxib 30 mg qd was at least as effective as celecoxib 200 mg qd and had similar safety in the treatment of knee and hip OA; both were superior to placebo. ClinicalTrials.gov Identifiers: NCT00092768; NCT00092791.

Informed consent for emergency contraception: variability in hospital care of rape victims.

There is growing concern that rape victims are not provided with emergency contraceptives in many hospital emergency rooms, particularly in Catholic hospitals. In a small pilot study, we examined policies and practices relating to providing information, prescriptions, and pregnancy prophylaxis in emergency rooms. We held structured telephone interviews with emergency department personnel in 58 large urban hospitals, including 28 Catholic hospitals, from across the United States. Our results showed that some Catholic hospitals have policies that prohibit the discussion of emergency contraceptives with rape victims, and in some of these hospitals, a victim would learn about the treatment only by asking. Such policies and practices are contrary to Catholic teaching. More seriously, they undermine a victim's right to information about her treatment options and jeopardize physicians' fiduciary responsibility to act in their patients' best interests. We suggest that institutions must reevaluate their restrictive policies. If they fail to do so, we believe that state legislation requiring hospitals to meet the standard of care for treatment of rape victims is appropriate.

MRI in patients with intraspinal bullets.

The purpose of this study was to determine whether neurologic sequelae occur in patients with intraspinal bullets or bullet fragments who undergo magnetic resonance imaging (MRI). Nineteen patients with bullets or bullet fragments adjacent to the cord or nerve roots underwent clinical MRI studies at 1.5 T. Sequences included conventional spin echo, fast spin echo, gradient-recalled echo, and inversion recovery. Patients were queried during scanning for symptoms of discomfort, pain, or change in neurologic status. Detailed neurologic examinations were performed prior to MRI (baseline), post MRI, and at the patients' discharge. Sixteen patients were completely paralyzed (ASIA-A), and three were not paralyzed. The length of time from injury was 2-24 months. No patients experienced pain or discomfort during the procedure. No change in neurologic status occurred. Follow-up radiographic studies showed no bullet movement following the scanning. We conclude that in patients with complete spinal cord injury, MRI in patients with intraspinal bullets may be performed.