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H Quan

Publications and source records attributed to H Quan.

At least 19 recordsLinked to original sources
PubMed2003

Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib.

BACKGROUND: Cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs are intended to preserve cyclo-oxygenase-1-mediated gastroprotection and platelet function, whilst inhibiting cyclo-oxygenase-2-mediated inflammation. AIM: To assess the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib vs. non-selective non-steroidal anti-inflammatory drugs. METHODS: Two randomized, double-blind, placebo- and active-controlled studies were performed: (i) daily faecal red blood cell loss was measured in 62 subjects receiving etoricoxib (120 mg once daily), ibuprofen (800 mg t.d.s.) or placebo for 28 days; (ii) the incidence of endoscopically detectable gastric/duodenal ulcers was determined in 742 osteoarthritis or rheumatoid arthritis patients receiving etoricoxib (120 mg once daily), naproxen (500 mg b.d.) or placebo over 12 weeks. RESULTS: In the first study, the between-treatment ratio of faecal blood loss for etoricoxib vs. placebo (1.06) was not significantly different from unity; however, the ratios for ibuprofen vs. placebo (3.26) and etoricoxib (3.08) were significantly greater than unity (P < 0.001). In the second study, the incidence of ulcers of > or = 3 mm with naproxen (25.3%) was significantly higher than that with etoricoxib (7.4%) or placebo (1.4%; P < 0.001); the results were similar for ulcers of > or = 5 mm. CONCLUSIONS: The reduced toxicity of etoricoxib (less faecal blood loss and fewer endoscopically detectable lesions) suggests that use of this drug will may be associated with a reduced incidence of gastrointestinal perforations, ulcers and bleeds.

Adolescent↗
PubMed2003

Incidence of gastroduodenal ulcers in patients with rheumatoid arthritis after 12 weeks of rofecoxib, naproxen, or placebo: a multicentre, randomised, double blind study.

BACKGROUND: Previous studies in patients with osteoarthritis have suggested that the selective cyclooxygenase (COX)-2 inhibitor rofecoxib results in less gastrointestinal damage than non-selective non-steroidal antiinflammatory drugs (NSAIDs). This study compared the incidence of endoscopically detected gastroduodenal ulcers in rheumatoid arthritis patients treated with rofecoxib or a non-selective NSAID. METHODS: In this multicentre, randomised, double blind, 12 week study, patients with rheumatoid arthritis were allocated to rofecoxib 50 mg once daily (n=219), naproxen 500 mg twice daily (n=220), or placebo (n=221). Endoscopy was performed at baseline and at six and 12 weeks. Lifetable analysis and log rank tests were used to analyse the incidence of gastroduodenal ulcers > or =3 mm. Gastric or duodenal ulcers > or =5 mm and erosions were also evaluated as secondary end points. Tolerability was assessed by adverse events. RESULTS: The cumulative incidence of ulcers > or =3 mm at 12 weeks was significantly higher in patients on naproxen (25.5%) than in patients receiving rofecoxib (6.8%; difference 18.7% (95% confidence interval (CI) 11.7%, 25.7%); p<0.001) or placebo (2.9%; difference 22.6% (95% CI 16.1%, 29.1%); p<0.001). The difference between rofecoxib (6.8%) and placebo (2.9%) did not reach statistical significance (p=0.066). Results were similar for ulcers > or =5 mm and for mean changes from baseline in the number of gastroduodenal erosions. The overall incidence of clinical adverse events was similar among treatment groups (61% of patients on placebo, 62% in patients on rofecoxib, and 66% in patients on naproxen). CONCLUSIONS: Rofecoxib 50 mg daily (twice the dose recommended for this patient population) resulted in a lower incidence of endoscopically detected gastroduodenal ulcers and erosions than treatment with naproxen 500 mg twice daily.

Adult↗
PubMed2001

Use of chelation therapy after coronary angiography.

PURPOSE: Among patients who had undergone coronary angiography, we sought to determine the proportion of chelation therapy users, their sociodemographic and clinical characteristics, and the association of chelation therapy with subsequent revascularization. METHODS: We studied all patients who underwent coronary angiography in the province of Alberta, Canada, during 1995 and 1996. The cohort was followed for up to 6 years to determine subsequent revascularization status. Use of chelation therapy was determined by a mailed survey 1 year after angiography. RESULTS: Among the 5854 patients who responded to the mail survey (70% response rate), 210 (3.6%) reported current use of chelation therapy and 252 (4.3%) reported past use. Current use of chelation therapy was associated with extensive coronary artery disease (adjusted odds ratio [OR] = 3.3; 95% confidence interval [CI]: 1.9 to 5.7 for 3-vessel disease; and OR = 2.7; 95% CI: 1.2 to 6.0 for left main disease, as compared with those with normal anatomy) and the absence of diabetes (OR = 0.6; 95% CI: 0.4 to 0.9). Current users were less likely to have undergone percutaneous transluminal coronary angioplasty (OR = 0.7; 95% CI: 0.5 to 0.9) and coronary artery bypass graft (CABG) surgery (OR = 0.3; 95% CI: 0.2 to 0.5) in the first year after angiography, but were as likely as nonusers of chelation therapy to have undergone CABG surgery in the subsequent 3- to 5-year period (adjusted hazard ratio [HR] = 1.1; 95% CI: 0.7 to 1.9). Past use of chelation therapy was associated with a history of CABG surgery before coronary angiography (OR = 1.6; 95% CI: 1.1 to 2.3) and extensive coronary artery disease. Past users were also more likely to have undergone CABG surgery in the follow-up period (HR = 1.7; 95% CI: 1.1 to 2.6). CONCLUSIONS: About 8% of patients who underwent cardiac catheterization for coronary artery disease were using or had previously tried chelation therapy. Users may have foregone revascularization in favor of this less invasive yet unproven treatment, with some users subsequently undergoing conventional treatment after chelation. Alternatively, some patients may have turned to chelation as a "last resort" after having been judged unsuitable for revascularization.

Aged↗
PubMed2001

Assessment of equivalence on multiple endpoints.

Some clinical trials aim to demonstrate therapeutic equivalence on multiple primary endpoints. For example, therapeutic equivalence studies of agents for the treatment of osteoarthritis use several primary endpoints including investigator's global assessment of disease activity, patient's global assessment of response to therapy, and pain. In this paper, thoughts on simultaneous equivalence assessment on three endpoints are presented. As pointed out by Berger and Hsu (1996), the conventional intersection-union test can be conservative. Simulation and computation are conducted to provide an insight on the conservativeness. We also provide a method to lower the confidence level and at the same time maintain the type I error when endpoints have normal distributions and are independent. If, in a particular analysis, the goal is to demonstrate equivalence on as many endpoints as possible, a step-up procedure can be used for selecting those endpoints for which equivalence may be demonstrated. This step-up procedure at the same time controls experimentwise error rate. The techniques are illustrated by a data example.

Biometry↗
PubMed2001

Comparison of 2 methods for calculating adjusted survival curves from proportional hazards models.

CONTEXT: Adjusted survival curves are often presented in medical research articles. The most commonly used method for calculating such curves is the mean of covariates method, in which average values of covariates are entered into a proportional hazards regression equation. Use of this method is widespread despite published concerns regarding the validity of resulting curves. OBJECTIVE: To compare the mean of covariates method to the less widely used corrected group prognosis method in an analysis evaluating survival in patients with and without diabetes. In the latter method, a survival curve is calculated for each level of covariates, after which an average survival curve is calculated as a weighted average of the survival curves for each level of covariates. DESIGN, SETTING, AND PATIENTS: Analysis of cohort study data from 11 468 Alberta residents undergoing cardiac catheterization between January 1, 1995, and December 31, 1996. MAIN OUTCOME MEASURES: Crude and risk-adjusted survival for up to 3 years after cardiac catheterization in patients with vs without diabetes, analyzed by the mean of covariates method vs the corrected group prognosis method. RESULTS: According to the mean of covariates method, adjusted survival at 1044 days was 94.1% and 94.9% for patients with and without diabetes, respectively, with misleading adjusted survival curves that fell above the unadjusted curves. With the corrected group prognosis method, the corresponding survival values were 91.3% and 92.4%, with curves that fell more appropriately between the unadjusted curves. CONCLUSIONS: Misleading adjusted survival curves resulted from using the mean of covariates method of analysis for our data. We recommend using the corrected group prognosis method for calculating risk-adjusted curves.

Aged↗
PubMed2001

Reviewing the reviewers: the quality of reporting in three secondary journals.

BACKGROUND: Secondary journals such as ACP Journal Club (ACP), Journal Watch (JW) and Internal Medicine Alert (IMA) have enormous potential to help clinicians remain up to date with medical knowledge. However, for clinicians to evaluate the validity and applicability of new findings, they need information on the study design, methodology and results. METHODS: Beginning with the first issue in March 1997, we selected 50 consecutive summaries of studies addressing therapy or prevention and internal medicine content from each of the ACP, JW and IMA. We evaluated the summaries for completeness of reporting key aspects of study design, methodology and results. RESULTS: All of the summaries in ACP reported study design, as compared with 72% of the summaries in JW and IMA (p < 0.001). In summaries of randomized controlled trials the 3 secondary journals were similar in reporting concealment of patient allocation (none reported this), blinding status of participants (ACP 62%, JW 70% and IMA 70% [p = 0.7]), blinding status of health care providers (ACP 12%, JW 4% and IMA 4% [p = 0.4]) and blinding status of judicial assessors of outcomes (ACP 4%, JW 4% and IMA 0% [p = 0.4]). ACP was the only one to report whether investigators conducted an intention-to-treat analysis (in 38% of summaries [p < 0.001]), and it was more likely than the other 2 journals to report the precision of the treatment effect (as a p value or 95% confidence interval) (ACP 100%, JW 0% and IMA 55% [p < 0.001]). INTERPRETATION: Although ACP provided more information on study design, methodology and results, all 3 secondary journals often omitted important information. More complete reporting is necessary for secondary journals to fulfill their potential to help clinicians evaluate the medical literature.

Chi-Square Distribution↗
PubMed2001

A case study of hospital closure and centralization of coronary revascularization procedures.

BACKGROUND: Despite nation-wide efforts to reduce health care costs through hospital closures and centralization of services, little is known about the impact of such actions. We conducted this study to determine the effect of a hospital closure in Calgary and the resultant centralization of coronary revascularization procedures from 2 facilities to a single location. METHODS: Administrative data were used to identify patients who underwent coronary artery bypass grafting (CABG), including those who had combined CABG and valve procedures, and patients who underwent percutaneous transluminal angioplasty (PTCA) in the Calgary Regional Health Authority from July 1994 to March 1998. This period represents the 21 months preceding and the 24 months following the March 1996 hospital closure. Measures, including mean number of discharges, length of hospital stay, burden of comorbidity and in-hospital death rates, were compared before and after the hospital closure for CABG and PTCA patients. Multivariate analyses were used to derive risk-adjustment models to control for sociodemographic variables and comorbidity. RESULTS: The number of patients undergoing CABG was higher in the year following than in the year preceding the hospital closure (51.6 per 100,000 before v. 67.3 per 100,000 after the closure); the same was true for the number of patients undergoing PTCA (129.8 v. 143.6 per 100,000). The burden of comorbidity was significantly higher after than before the closure, both for CABG patients (comorbidity index 1.3 before v. 1.5 after closure, p < 0.001) and for PTCA patients (comorbidity index 1.0 before v. 1.1 after, p = 0.04). After adjustment for comorbidity, the mean length of hospital stay was significantly lower after than before the closure for CABG patients (by 1.3 days) and for PTCA patients (by 1.0 days). The adjusted rates of death were slightly lower after than before the closure in the CABG group. The adjusted rates of death or CABG in the PTCA group did not differ significantly between the 2 periods. INTERPRETATION: Hospital closure and the centralization of coronary revascularization procedures in Calgary was associated with increased population rates of procedures being performed, on sicker patients, with shorter hospital stays, and, for CABG patients, a trend toward more favourable short-term outcomes. Our findings indicate that controversial changes to the structure of the health care system can occur without loss of efficiency and reduction in quality of care.

Aged↗
PubMed2001

Physician interpretations and textbook definitions of blinding terminology in randomized controlled trials.

CONTEXT: When clinicians assess the validity of randomized controlled trials (RCTs), they commonly evaluate the blinding status of individuals in the RCT. The terminology authors often use to convey blinding status (single, double, and triple blinding) may be open to various interpretations. OBJECTIVE: To determine physician interpretations and textbook definitions of RCT blinding terms. DESIGN AND SETTING: Observational study undertaken at 3 Canadian university tertiary care centers between February and May 1999. PARTICIPANTS: Ninety-one internal medicine physicians who responded to a survey. MAIN OUTCOME MEASURES: Respondents identified which of the following groups they thought were blinded in single-, double-, and triple-blinded RCTs: participants, health care providers, data collectors, judicial assessors of outcomes, data analysts, and personnel who write the article. Definitions from 25 systematically identified textbooks published since 1990 providing definitions for single, double, or triple blinding. RESULTS: Physician respondents identified 10, 17, and 15 unique interpretations of single, double, and triple blinding, respectively, and textbooks provided 5, 9, and 7 different definitions of each. The frequencies of the most common physician interpretation and textbook definition were 75% (95% confidence interval [CI], 65%-83%) and 74% (95% CI, 52%-90%) for single blinding, 38% (95% CI, 28%-49%) and 43% (95% CI, 24%-63%) for double blinding, and 18% (95% CI, 10%-28%) and 14% (95% CI, 0%-58%) for triple blinding, respectively. CONCLUSIONS: Our study suggests that both physicians and textbooks vary greatly in their interpretations and definitions of single, double, and triple blinding. Explicit statements about the blinding status of specific groups involved in RCTs should replace the current ambiguous terminology.

Double-Blind Method↗
PubMed2001

Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1.

PDZ domain-containing proteins play an important role in the targeting and localization of synaptic membrane proteins. Here, we report an interaction between the PDZ domain-containing protein PICK1 and monoamine neurotransmitter transporters in vitro and in vivo. In dopaminergic neurons, PICK1 colocalizes with the dopamine transporter (DAT) and forms a stable protein complex. Coexpression of PICK1 with DAT in mammalian cells and neurons in culture results in colocalization of the two proteins in a cluster pattern and an enhancement of DAT uptake activity through an increase in the number of plasma membrane DAT. Deletion of the PDZ binding site at the carboxyl terminus of DAT abolishes its association with PICK1 and impairs the localization of the transporter in neurons. These findings indicate a role for PDZ-mediated protein interactions in the localization, expression, and function of monoamine transporters.

Animals↗
PubMed2001

Risk adjustment using administrative data: impact of a diagnosis-type indicator.

OBJECTIVES: To determine the frequency with which commonly coded clinical variables are complications, as opposed to baseline comorbidities, and to compare the results of 2 risk-adjusted outcome analyses for coronary artery bypass graft surgery for which we either (a) ignored, or (b) used the available "diagnosis-type indicator." DESIGN: Analysis of existing administrative data. SETTING: Twenty-three Canadian hospitals. PATIENTS: A total of 50,357 coronary artery bypass graft surgery cases. MEASUREMENTS AND MAIN RESULTS: Among 21 clinical variables whose definitions involve the diagnosis-type indicator, 14 were predominantly (> or =97%) baseline risk factors when present. Seven variables were often complication diagnoses: renal disease (when present, 13% coded as complications), recent myocardial infarction (15%), peptic ulcer disease (15%), congestive heart failure (17%), cerebrovascular disease (26%), hemiplegia (34%), and severe liver disease (35%). The results of risk adjustment analyses predicting in-hospital mortality differed when the diagnosis-type indicator was either used or ignored, and as a result, adjusted hospital mortality rates and rankings changed, often dramatically, with rankings increasing for 10 hospitals, decreasing for 9 hospitals, and remaining the same for only 4 hospitals. CONCLUSIONS: The results of analyses performed using the diagnosis-type indicator in Canadian administrative data differ considerably from analyses that ignore the indicator. The widespread introduction of such an indicator should be considered in other countries, because risk-adjustment analyses performed without a diagnosis-type indicator may yield misleading results.

Canada↗
PubMed2001

Poor long-term survival after coronary angiography in patients with renal insufficiency.

Cardiovascular disease is common among dialysis patients, but much less is known regarding non-dialysis-dependent renal insufficiency (NDDRI) and its association with cardiac disease. We undertook a study to assess the impact of renal insufficiency on survival post-coronary angiography by comparing three groups of patients: dialysis-dependent patients, patients with NDDRI (creatinine > 2.3 mg/dL), and a reference group with creatinine levels less than 2.3 mg/dL and not on dialysis therapy. We used a prospective cohort that consisted of all patients undergoing coronary angiography in Alberta, Canada, from January 1, 1995, to December 31, 1997. Of the 16,989 patients, 196 patients (1.2%) were on dialysis therapy, 262 patients (1.5%) had NDDRI, and 16,531 patients (97.3%) formed the reference group. Mortality rates 1 year after angiography were 30.2% for patients with NDDRI, 15.8% for dialysis patients, and 4.1% for the reference group. Compared with the reference group, crude 4-year survival was significantly worse for dialysis patients and those with NDDRI, with hazard ratios of 4.05 (95% confidence interval, 3.02 to 5.42) and 7.32 (95% confidence interval, 5.97 to 8.97), respectively. Even after adjusting for clinical risk factors, survival remained worse for dialysis patients and those with NDDRI, with hazard ratios of 2.59 (95% confidence interval, 1.92 to 3.49) and 2.51 (95% confidence interval, 2.02 to 3.12), respectively. We conclude that renal insufficiency, both dialysis dependent and non-dialysis dependent, is an independent risk factor for increased mortality and poor long-term survival among patients undergoing coronary angiography.

Aged↗
PubMed2001

Geographic variation in the rate of carotid endarterectomy in Canada.

UNLABELLED: Background and Purpose-- Carotid endarterectomy (CEA) is an important method of stroke prevention, but its usage in Canada is not well known. The indications for CEA have been well informed by the recent clinical trials, but the impact of this information on the rate and regional variation in the rate of CEA is unknown. This study sought to determine the rate and the regional variation in the rate of CEA in Canada, its provinces, and census divisions for 1994-1997. METHODS: Discharge data from all hospitals in Canada except Quebec were obtained from the Canadian Institute for Health Information for 1994-1997 and were searched for CEA by residential site. Rates and variations in rates were calculated. RESULTS: The national age- and sex-adjusted rate per 100 000 people of CEA for those aged >/=40 years rose from 31.7 in 1994 to 40.5 in 1997. Provincial rates in 1997 varied from a low of 25.7 in Saskatchewan to high of 82.8 in Prince Edward Island. The census division rates varied even more, from a low of 0 in several divisions to a high of 179. CONCLUSIONS: The recent slight increase in CEA rates may reflect the release of new efficacy results for CEA, especially for asymptomatic carotid stenosis, but the rates are still far below US levels. The marked regional variation in rates may reflect differing views on the appropriateness of indications such as asymptomatic carotid stenosis for CEA and the inconsistency of published clinical practice guidelines.

Adult↗
PubMed2001

Palliative care on the net: an online survey of health care professionals.

A survey was conducted to explore Internet use by palliative care health professionals (HCP). The survey was placed on the World Wide Web with an underlying database, and palliative care HCP were invited to participate via a palliative-care-related website, listserv, and newsletter. A total of 417 evaluable responses were received over a four-month period. Of these, 36% indicated they were from physicians and 30% from nurses, a third of respondents were practicing palliative care full time. Although 63% of respondents were from North America, regions from all over the world were represented. Eighty-eight percent of respondents were searching the Internet for clinical information, 80% were using email, 69% were accessing online medical journals, and 59% were subscribers to a palliative-care-related listserv or newsgroup. This survey illustrates the global outreach of the Internet and draws attention to the growing interest in the use of the Internet for education, research, and clinical use. Further development of online resources should address the needs of users. Evaluation of these resources is called for.

Adult↗
PubMed2000

Gastrointestinal tolerability of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in osteoarthritis.

BACKGROUND: Most nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective cyclooxygenase (COX-1 and COX-2) inhibitors and are associated with a variety of upper gastrointestinal (GI) tract symptoms. The roles of COX-1 and COX-2 in the pathogenesis of these symptoms are unclear. To test whether COX-2 inhibition with rofecoxib would have greater GI tolerability than nonselective COX-1 and COX-2 inhibition, we compared the incidences of (1) treatment discontinuations for GI adverse events (AEs) and (2) prespecified dyspeptic-type GI AEs among patients with osteoarthritis treated with rofecoxib vs NSAIDs. METHODS: A prespecified, combined analysis of investigator-reported GI AEs in all 8 double-blind, randomized, phase 2b/3 osteoarthritis trials of rofecoxib was conducted. Patients included men and women with osteoarthritis (N = 5435); there was no upper age limit for entry. Treatments tested included rofecoxib, 12.5, 25, or 50 mg (combined), vs ibuprofen, diclofenac, or nabumetone (combined). Primary outcomes were the time (by survival analysis) to (1) treatment discontinuation due to GI AEs and (2) first reported dyspeptic-type GI AE. Between-treatment comparisons were made by log-rank test. RESULTS: The number of treatment discontinuations caused by GI AEs during 12 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (8.2 vs 12.0 per 100 patient-years; relative risk, 0.70; 95% confidence interval, 0.52-0.94). The incidence of prespecified dyspeptic-type GI AEs during the first 6 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (69.3 vs 85.2 per 100 patient-years; relative risk, 0.85; 95% confidence interval, 0.74-0.97). However, the difference between treatments in dyspeptic-type GI AEs was attenuated after 6 months. CONCLUSION: Rofecoxib was associated with a lower incidence of treatment discontinuations due to GI AEs over 12 months and a lower incidence of dyspeptic-type GI AEs over 6 months than treatment with nonselective COX inhibitors, or NSAIDs. Arch Intern Med. 2000;160:2998-3003

Abdominal Pain↗
PubMed2000

A randomized trial measuring fecal blood loss after treatment with rofecoxib, ibuprofen, or placebo in healthy subjects.

PURPOSE: Gastrointestinal microbleeding, as assessed by the measurement of (51)chromium-labeled red blood cells, is a marker of the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs. This study tested the hypotheses that cyclooxygenase-2 specific inhibition with rofecoxib would cause less fecal blood loss than a therapeutic dose of ibuprofen and would be equivalent to placebo. SUBJECTS AND METHODS: In this randomized, double-blind group study, gastrointestinal blood loss was assessed by measurement of fecal (51)chromium radioactivity during a 1-week placebo baseline period and during 4 weeks of treatment with rofecoxib (25 mg or 50 mg once daily), ibuprofen (800 mg three times daily), or placebo in 67 healthy subjects. Gastrointestinal blood loss during treatment weeks 2 to 4 (versus the baseline period) was expressed as the geometric mean ratio of fecal radioactivity in weeks 2 to 4 compared with baseline. RESULTS: Ibuprofen caused significantly (P <0.001) greater gastrointestinal blood loss (geometric mean ratio of 5.2, 95% confidence interval [CI]: 4.2 to 6.3) than the 25-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.1), the 50-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.0), or placebo (2.1, 95% CI: 1.8 to 2.5). In contrast, gastrointestinal blood loss with both doses of rofecoxib were equivalent to placebo by a predetermined clinical similarity bound. CONCLUSIONS: In healthy subjects, treatment with rofecoxib, at 2 to 4 times the doses that are currently recommended for the treatment of patients with osteoarthritis, produced significantly less fecal blood loss than a therapeutic dose of ibuprofen and was equivalent to placebo.

Adult↗
PubMed2000

Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial.

BACKGROUND: Most nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 (COX-1), whose inhibition is associated with gastrointestinal ulceration, and COX-2, whose inhibition is associated with therapeutic benefits. Although agents that do not produce COX-1 activity may have fewer adverse effects, targeted disruption of the COX-2 allele in mice has resulted in severe renal problems, suggesting that COX-2 inhibition may also produce adverse effects. OBJECTIVE: To determine the effect of rofecoxib, a member of the coxib class of drugs and a specific inhibitor of the COX-2 enzyme, on renal function in elderly patients. DESIGN: A randomized, three-period, single-dose crossover study and a randomized, parallel-group, multiple-dose study. SETTING: Clinical research units. PATIENTS: 75 patients 60 to 80 years of age. INTERVENTION: In the first study, single doses of rofecoxib, 250 mg (about 5-fold to 20-fold the recommended dose); indomethacin, 75 mg; and placebo were administered to 15 patients. In the second study, multiple doses of rofecoxib, 12.5 or 25 mg/d; indomethacin, 50 mg three times daily; or placebo were administered to 60 patients. Patients in both studies received a low-sodium diet MEASUREMENTS: Glomerular filtration rate, creatinine clearance, and urinary and serum sodium and potassium values. RESULTS: Compared with placebo, single doses of rofecoxib and indomethacin decreased the glomerular filtration rate by 0.23 m/s (P < 0.001) and 0.18 mL/s (P = 0.003), respectively. In contrast, respective decreases of 0.14, 0.13, and 0.10 mL/s were observed after multiple doses of rofecoxib, 12.5 mg/d (P = 0.019); rofecoxib, 25 mg (P = 0.029), and indomethacin (P = 0.086) were administered. Changes in creatinine clearance and serum and urinary sodium and potassium were less pronounced. CONCLUSIONS: The effects of COX-2 inhibition on renal function are similar to those observed with nonselective NSAIDs. Thus, COX-2 seems to play an important role in human renal function.

Aged↗
PubMed2000

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.

Cyclooxygenase Inhibitors↗