Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group.

OBJECTIVE: This randomized, double-blind study tested the hypothesis that rofecoxib, a drug that specifically inhibits cyclooxygenase 2, would cause fewer gastroduodenal ulcers than ibuprofen (in a multicenter trial), and its side effects would be equivalent to those of placebo (in a prespecified analysis combining the results with another trial of identical design). METHODS: Seven hundred seventy-five patients with osteoarthritis were randomized to receive rofecoxib at a dosage of 25 mg or 50 mg once daily, ibuprofen 800 mg 3 times daily, or placebo. Gastroduodenal ulceration was assessed by endoscopy at 6, 12, and (for active treatment) 24 weeks. The primary and secondary end points were the incidence of gastroduodenal ulcers at 12 and 24 weeks, respectively. RESULTS: Ulcers were significantly less common (P < 0.001) following treatment with rofecoxib (25 mg or 50 mg) than with ibuprofen after 12 weeks (5.3% and 8.8% versus 29.2%, respectively) or 24 weeks (9.9% and 12.4% versus 46.8%, respectively). In the combined analysis, the 12-week ulcer incidence with 25 mg rofecoxib (4.7%) and with placebo (7.3%) satisfied prespecified criteria for equivalence. CONCLUSION: At 2-4 times the therapeutically effective dose, rofecoxib caused fewer endoscopically detected ulcers than did ibuprofen. Rofecoxib at a dose of 25 mg (the highest dose recommended for osteoarthritis) satisfied prespecified criteria for equivalence to placebo.

Effect of multiple doses of montelukast, a CysLT1 receptor antagonist, on digoxin pharmacokinetics in healthy volunteers.

The effect of multiple oral doses of montelukast, a cysLT1 receptor antagonist, on the pharmacokinetics of oral digoxin was studied in healthy male volunteers in a randomized double-blind two-period crossover study. Subjects received 10 mg of montelukast or placebo daily for 11 days. On day 7, they received a single 0.5 mg oral dose of digoxin elixir. The pharmacokinetic parameters of digoxin (AUC0-->24' AUC0-->infinity' Cmax' tmax' t1/2) and cumulative urinary excretion over 120 hours were not affected by the multiple doses of montelukast. The 90% confidence interval for each of these parameters fell within prespecified clinically acceptable bounds. Side effects were mild and transient. This suggests that concurrent administration of montelukast and digoxin was well tolerated. Concurrent treatment with montelukast has no effect on the pharmacokinetics of digoxin.

Testing for treatment effect in the presence of regression toward the mean.

We are often faced with the statistical problem of evaluating the effect of a treatment in the extreme of a population. This requires taking measurements on truncated random variables and, hence, it becomes necessary to take proper account of the effect of regression toward the mean. The usual statistical procedures are inappropriate for testing treatment effect in the presence of regression toward the mean. Likelihood ratio and score tests based on truncated distributions should provide valid statistical inferences in these situations. We conducted simulation studies to investigate the properties of these methods and found that the likelihood ratio test performs well even when the sample size is moderate, whereas the score test does not seem to control the nominal significance level. We compared the likelihood ratio test to a regression-based t-test, assuming the mean of the baseline distribution to be known, and found the likelihood ratio test more powerful. In the case where the baseline mean is unknown, we also investigated Wald's test and compared it with the likelihood ratio test and score test with respect to validity and power using simulation. Wald's test and the score test do not control the nominal significance level unless the sample size is extremely large. Overall, the likelihood ratio test has the best performance among all the methods studied. The proposed likelihood ratio test is illustrated using an example of a cholesterol study.

Delayed hypersensitivity skin tests and subsequent renal transplant outcome.

BACKGROUND: Some studies in the literature have supported, while others have denied, the relationship between results of delayed hypersensitivity skin tests (DHST), renal allograft and patient survival rates. Several factors contribute to the unreliability of these studies. For example, most of these studies were performed in the precyclosporine era, furthermore, other variables which influence renal allografts and patient survival rates were not controlled in those studies. OBJECTIVE: The purpose of this study was to investigate the relationship between results of DHST performed in the pretransplant period with the subsequent renal transplant outcome in the cyclosporine era. METHODS: The study included 103 first cadaveric renal transplant recipients. DHST were performed during pretransplant evaluation by intradermal injections of a battery of recall antigens. Based on skin-test results, the patients were assigned to two groups--those with a positive skin test (STP+) and those with a negative (anergic) skin test. These two groups were compared with each other regarding allograft survival, patient survival, and other variables known to influence survival rates. RESULTS: The mean age, sex and racial distribution, degree of HLA matches between recipients and donors, number of acute rejection episodes, and number of patients with acute tubular necrosis were similar between the two groups. Renal allograft survival rates in the anergic group at 6 months, 1 year, 2 years, and 3 years were 97%, 90%, 84%, and 57%, respectively. The survival rate for renal allografts in the STP+ group for the same time points was 90%, 86%, 80%, and 72%, respectively. Patient survival rates for the anergic group at 6 months, 1 year, 2 years, and 3 years were 95%, 94%, 89%, and 85%, respectively, while those for the STP+ group were 98%, 98%, 98%, and 97% respectively. Differences between the STP+ and anergic groups, with regard to patient and allograft survival rates, were not significant. CONCLUSION: We conclude that DHST is not helpful in predicting outcome of patient or renal allograft survival rates over a 3-year time period.

Padded vs unpadded spine board for cervical spine immobilization.

OBJECTIVES: To determine whether padding the long spine board improves patient comfort, affects cervical spine (c-spine) immobilization, or increases sacral transcutaneous O2 tension. METHODS: A prospective randomized, controlled crossover study of healthy volunteers was conducted over a two-week period. Participants included 30 volunteers with no previous history of c-spine injury or disease. The subjects were randomized to either padded or unpadded long spine board immobilization with serial measurements of discomfort (using a visual analog scale) and transcutaneous tissue O2 tension obtained at zero and 30 minutes. Measurements of ability to flex, extend, rotate, and laterally bend the c-spine were made using a goniometer. The subjects then returned a minimum of three days later to complete the opposite half of the study (padded vs unpadded boards). RESULTS: Subject discomfort was significantly reduced in the padded group compared with the unpadded group (p = 0.024). There was no significant difference in flexion (p = 0.410), extension (p = 0.231), rotation (p = 0.891), or lateral bending (p = 0.230) for the two groups. There was no significant difference in the actual drop in sacral transcutaneous O2 tension from time zero to 30 minutes for the padded and the unpadded groups (mean drop = 14.8% +/- 17.5% vs 12.2% +/- 16.8%, respectively; p = 0.906). CONCLUSION: Adding closed-cell foam padding to a long spine board significantly improves comfort without compromising c-spine immobilization. Sacral tissue oxygenation does not appear affected by such padding for healthy volunteers.

Fitting growth curve models to longitudinal data with missing observations.

We discuss the analysis of growth curve data with missing or incomplete information. The approach is to fit subject-specific models and then to carry out an analysis in terms of the estimated parameters. This achieves reduction of data and eliminates the need for special considerations for subjects with missing data. Although there is no perfect substitute for complete data, our approach provides a way to handle missing data using a straightforward application of well-known statistical methodology.

Traumatic heart disease.

Five cases of traumatic heart disease (THD) who sustained blunt chest injury in road accidents are reported. In addition to fracture of the ribs (observed in all the cases), there was fracture of the sternum and rupture of the liver and spleen in one case each. Two patients had flail chest. One presented with recurrent ventricular tachycardia lasting for 72 hours followed by changes suggestive of subendocardial infarction. The second case also had changes like subendocardial infarction and it was preceded by junctional tachycardia with aberrant conduction during the first 48 hours. Ventricular premature beats (VPB) were the only abnormality noted in one case and the remaining two had ST-T wave changes suggestive of inferolateral ischaemia without any arrhythmias. The patient with VPB developed pericardial rub without effusion. There was one death and postmortem revealed ruptured liver and spleen in addition to laceration of the right ventricle and haemopericardium. The electrocardiographic changes persisted for two to eight weeks. All four cases were symptom-free at 12 weeks and treadmill exercise test done after 12 to 18 weeks was normal.

Clinical significance of heat labile Regan isoenzyme variant in Hodgkin's disease.

The activity of a heat labile variant of Regan type alkaline phosphatase (HLRI) was studied in the serum of 38 histologically proved patients with Hodgkin's disease. The activity was also studied in 40 normal healthy adults matched for age and sex as control. HLRI was significantly elevated in patients with Hodgkin's disease in comparison with normal controls (1.12 +/- 0.12 units/ml vs 0.09 +/- 0.01 units/ml; P less than 0.001). The mean values of the isoenzyme tended to increase progressively with increasing stages of disease, reflecting a significant linear trend (P less than 0.001). The serial measurement of this variant may serve as a useful parameter in assessing disease activity and response to chemotherapy.