Biomedical subjects

H Quan

Publications and source records attributed to H Quan.

At least 37 records · Page 2Linked to original sources

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↗

PubMed2000

Prognostic significance of diabetes as a predictor of survival after cardiac catheterization. APPROACH Investigators. Alberta Provincial Program for Outcome Assessment in Coronary Heart Disease.

PURPOSE: Diabetes is a recognized risk factor for the development of cardiac disease, but its importance as a prognostic factor among patients with known cardiovascular disease is less clear. We evaluated survival in patients with and without diabetes who underwent cardiac catheterization for presumed coronary artery disease. SUBJECTS AND METHODS: We analyzed data from a prospective cohort study that captures detailed clinical information and longitudinal outcomes for all patients who undergo cardiac catheterization in Alberta, Canada. We studied 11,468 patients, 1959 (17%) of whom had diabetes. Logistic regression was used to model predictors of 1-year mortality, and proportional hazards analysis was used to model predictors of survival up to 3 years after cardiac catheterization. RESULTS: One-year mortality was 7.6% for patients with diabetes versus 4.1% for those without diabetes (odds ratio = 1.9, 95% confidence interval [CI]: 1.6 to 2.3). After adjusting for other characteristics of the patients, including comorbid conditions, previous cardiac history, coronary anatomy, and renal function, the odds ratio for 1-year mortality was 1.1 (95% CI: 0.8 to 1.3). Similarly, the adjusted hazard ratio for longer term mortality was 1. 2 (95% CI: 1.0 to 1.4, mean follow-up of 702 days). CONCLUSIONS: These results suggest that there is little or no independent association between diabetes and mortality for up to 3 years after cardiac catheterization. Estimates of short- to intermediate-term prognosis for diabetic patients with coronary artery disease should be based on the presence of other prognostic factors associated with diabetes.

Aged↗

PubMed2000

Successful teaching in evidence-based medicine.

OBJECTIVES: Several published articles have described the importance of exposing medical trainees to the 'new paradigm' of evidence-based medicine (EBM). Recognizing this, we sought to develop and objectively evaluate a mini-course in EBM for third-year medical students. DESIGN: We developed a mini-course consisting of four sessions in which students learn to derive sequentially focused questions, search MEDLINE, review articles critically and apply information from the literature to specific clinical questions. To evaluate the teaching intervention, we performed a controlled educational study. Students at the intervention site (n=34) attended the EBM mini-course, while students at the control site (n=26) received more 'traditional' didactic teaching on various clinical topics. Intervention and control students were surveyed immediately before and after the mini-course to assess changes in reading and literature searching skills, as well as a tendency to use the literature to answer clinical questions. SETTING: Boston University School of Medicine. SUBJECTS: Third-year medical students. RESULTS: The intervention was associated with significant changes in students' self-assessed skills and attitudes. MEDLINE and critical appraisal skills increased significantly in the intervention group relative to the control group (significance of between group differences: P=0.002 for MEDLINE and P=0.0002 for critical appraisal), as did students' tendency to use MEDLINE and original research articles to solve clinical problems (significance of between group differences: P=0.002 and P=0.0008, respectively). CONCLUSIONS: We conclude that this brief teaching intervention in EBM has had a positive impact on student skills and attitudes at our medical school. We believe that the key elements of this intervention are (1) active student involvement, (2), clinical relevance of exercises and (3) integrated teaching targeting each of the component skills of EBM.

Education, Medical, Undergraduate↗

PubMed2000

A Canadian comparison of data sources for coronary artery bypass surgery outcome "report cards".

BACKGROUND: Prior comparisons of administrative versus clinical data for creating coronary artery bypass graft (CABG) surgery outcome "report cards" are all from the United States and yield inconsistent conclusions regarding the validity of administrative data report cards. In this study, we compared 2 CABG surgery outcome report cards for Ontario, Canada: one derived from clinical data from the Cardiac Care Network of Ontario and one derived from administrative data from the Canadian Institute for Health Information. METHODS: Data from 4 fiscal years, 1992-93 through 1995-96, were used. The Canadian Institute for Health Information report card was derived from administrative data only. The Cardiac Care Network report card drew on prospectively collected clinical information that included variables such as left ventricular ejection fraction but also required linkages to the Canadian Institute for Health Information data for ascertainment of selected comorbidities and in-hospital mortality rates. Logistic regression models were used to calculate risk-adjusted death rates for each of the 9 hospitals performing CABG surgery in Ontario. RESULTS: The risk-adjusted death rates were quite similar between data sources for 7 of the 9 hospitals. For 2 hospitals, rather large absolute differences in adjusted death rates of 0.58% and 0.64% were seen between report cards. There was a strong correlation between data sources for risk-adjusted hospital death rates (intraclass correlation coefficient = 0.927, P <.001) and for rankings of adjusted hospital death rates (Spearman correlation coefficient = 0.828, P =.02). CONCLUSION: These results from Ontario, Canada, reveal general similarities between administrative and clinical data report cards for CABG surgery. However, clinical data are likely needed if individual hospitals are to be publicly scrutinized in outcome report cards.

Adult↗

PubMed2000

The impact of a regional palliative care program on the cost of palliative care delivery.

In July 1995 the Edmonton Regional Palliative Care Program (ERPCP) was established in the City of Edmonton to increase the access of patients with terminal cancer to palliative care services, decrease the number of cancer deaths in acute-care facilities, and increase the participation of family physicians in the care of terminally ill patients. The objective of this retrospective study was to determine the cost of implementation of the ERPCP and savings in acute-care facility costs after its implementation. We did this by comparing the cost of care for patients during 1992-93 (prior to the ERPCP) and 1996-97 (with the ERPCP). The main outcome measures were the cost of care and the total hospital stay in days for all patients during their last acute-care hospital admission. The increased funding for the ERPCP was offset by a significant decrease in the overall cost of palliative care in the acute-care facilities. There was a substantial decrease in the palliative care costs in acute facilities from 11,963,846 dollars in 1992/93 to 3,449,055 dollars in 1996/97. This can be explained by the significant decrease in the number of palliative care patient days in acute-care facilities from 22,608 during 1992/93 to 6085 during 1996/97. Physician billings were slightly higher for 1996 as compared to 1992. In 1992, 90% (195,117/427,780) of the billings were made by the specialists (internists, surgeons, and other specialists), while in 1996/97 67% (359,869/537,342) of the payments were made to primary care practitioners (p < 0.0001). Overall, there were estimated saving of 1,650,689 dollars for palliative care costs in 1996/97 as compared to 1992/93. Our results suggest that the establishment of an integrated palliative care program reduced the cost of care. Prospective cost measurement studies are required.

Journal Article↗

PubMed2000

An endoscopic comparison of the effects of alendronate and risedronate on upper gastrointestinal mucosae.

OBJECTIVES: The nitrogen-containing bisphosphonates alendronate and risedronate have been reported to have upper gastrointestinal (GI) safety and tolerability profiles comparable to those of placebo. Nevertheless, both agents have demonstrated similar potential for irritation of gastric mucosa at high doses in preclinical studies. The present study compared the potential for alendronate and risedronate to produce endoscopic upper GI mucosal irritation using the highest approved dosage regimens for the two agents. METHODS: This was a multicenter, randomized, parallel-group, double-blind, placebo-controlled trial in which a total of 235 patients (men or postmenopausal women, aged 45-80 yr) with normal upper GI endoscopy at baseline received 28-day treatments with the following: alendronate 40 mg/day (N = 90), risedronate 30 mg/day (N = 89), placebo (N = 36), or placebo with aspirin 650 mg q.i.d. for the last 7 days (N = 20). Endoscopy was repeated on day 29 using standardized scoring scales. RESULTS: After 28 days of treatment, the alendronate and risedronate groups had comparable mean gastric and duodenal erosion scores that were significantly lower than those of the aspirin group. Esophageal scores were comparable in all groups. Gastric ulcers and/or large numbers of gastric erosions occurred in approximately 3% of alendronate and risedronate patients versus 60% with aspirin. Both bisphosphonates were clinically well tolerated. CONCLUSIONS: The potential for gastroduodenal irritation is similar for alendronate and risedronate and is markedly less than for aspirin. The findings of this study, together with the large placebo-controlled clinical trial experience with both agents and extensive epidemiological data for alendronate, suggest that the risk for clinically important gastric irritation with these bisphosphonates is very low, even at the highest available doses.

Aged↗

PubMed2000

COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: a double blind crossover study comparing rofecoxib with placebo and indomethacin.

BACKGROUND: Acute and chronic use of non-steroidal anti-inflammatory drugs can increase intestinal permeability. Rofecoxib, which selectively inhibits cyclooxygenase 2 (COX-2), is a novel anti-inflammatory drug with the potential to produce minimal gastrointestinal toxic effects while retaining clinical efficacy. AIMS: To assess the potential for rofecoxib to affect the intestine adversely, in comparison with placebo and indomethacin. SUBJECTS: Thirty nine healthy subjects (aged 24-30 years). METHOD: We performed a four period crossover trial to assess intestinal permeability before and after seven days of treatment. Permeability was measured by the urinary ratio of chromium-51 labelled ethylene diamine tetraacetate ((51)CrEDTA)/L-rhamnose (five hour collection). RESULTS: Indomethacin 50 mg three times daily produced greater increases in intestinal permeability compared with placebo or rofecoxib (25 or 50 mg) (p< or = 0.001); rofecoxib was not significantly different from placebo. Mean day 7 to baseline ratios (95% confidence intervals) for (51)CrEDTA/L-rhamnose were 0.97 (0.82, 1.16), 0.80 (0.68, 0.95), 0.98 (0.82, 1.17), and 1.53 (1.27, 1.85) for placebo, rofecoxib 25 mg, rofecoxib 50 mg, and indomethacin groups, respectively. Rofecoxib was generally well tolerated. CONCLUSION: In this study, treatment for one week with indomethacin 50 mg three times daily significantly increased intestinal permeability compared with placebo, while treatment with rofecoxib 25 mg or 50 mg daily did not. The absence of a significant effect of rofecoxib on intestinal permeability at doses at least twice those recommended to treat osteoarthritis was consistent with other studies that have demonstrated little or no injury to the gastrointestinal mucosa associated with rofecoxib therapy.

Adolescent↗

PubMed2000

Physicians' recommendations for patients who undergo noncardiac surgery.

OBJECTIVE: To investigate how consulting physicians attempt to modify perioperative cardiac risk for patients who undergo noncardiac surgery by comparing the preoperative cardiac recommendations of consulting physicians in 2 university centres. DESIGN: Retrospective cross-sectional analysis. SETTING: Five hospitals affiliated with 2 Canadian universities. PATIENTS: Three hundred and eight preoperative consultations were evaluated in 297 patients who were 40 years of age or older and scheduled for noncardiac surgery. OUTCOME MEASURES: Cardiac drug recommendations at the preoperative consultation [corrected]; overall recommendations and practice variation between the 2 centres. RESULTS: The greatest changes in drug management suggested by consultants were the initiation of nitrates in 13% of the patients and a decrease in acetylsalicylic acid administration from 27% to 17%. Centre A physicians recommended adding an angiotensin-converting enzyme inhibitor 11% of the time, whereas centre B physicians recommended such an inhibitor in only 1% of the patients (p = 0.001). In patients taking acetylsalicylic acid at the preoperative consultation, Centres A and B physicians recommended withholding the drug 47% and 22% of the time, respectively (p = 0.03). These differences persisted between the 2 centres after controlling for physician estimates of risk. CONCLUSIONS: Consultants frequently recommended perioperative changes in the use of cardiac medications, and there were differences in practice patterns between the 2 centres. These differences may be affecting patient outcomes and highlight the need for randomized clinical trials to determine the impact of perioperative drug administration on bleeding, myocardial infarction and death.

Adrenergic beta-Antagonists↗

PubMed2000

Frequency of symptom distress and poor prognostic indicators in palliative cancer patients admitted to a tertiary palliative care unit, hospices, and acute care hospitals.

The Edmonton Regional Palliative Care Program was established to increase access to palliative care for terminal cancer patients in the region. Inpatient care is delivered, in decreasing order to distress, at the tertiary palliative care unit, by consult teams in acute care facilities, and in hospices. We reviewed the admission data for all patients discharged from the program between November 1, 1997, and October 31, 1998, in order to determine if demographical and clinical variables suggested appropriate use of the three levels of care. Patients admitted to the tertiary palliative care unit were significantly younger than those admitted to acute care of hospices (61 years versus 68 years and 71 years respectively, p < 0.0001), had a higher frequency of positive screening for alcoholism in the CAGE questionnaire (27% versus 16% and 14% respectively, p < 0.0001), and a higher frequency of poor prognostic pain syndromes as compared to acute care admissions (87% versus 65%, p < 0.0001). Overall, frequency of symptoms and severe symptoms was significantly higher in patients admitted to the palliative care unit than those admitted to the other two settings. Our results suggest that patients with demographic and clinical indications of higher distress are more frequently admitted to the tertiary palliative care unit. The clinical tools are useful predictors of utilization that can be used for monitoring health care delivery.

Aged↗

PubMed1999

Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs.

CONTEXT: Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxic effects, such as upper GI tract perforations, symptomatic gastroduodenal ulcers, and upper GI tract bleeding (PUBs), are thought to be attributable to cyclooxygenase 1 (COX-1) inhibition. Rofecoxib specifically inhibits COX-2 and has demonstrated a low potential for causing upper GI injury. OBJECTIVE: To compare the incidence of PUBs in patients with osteoarthritis treated with rofecoxib vs NSAIDs. DESIGN: Prespecified analysis of all 8 double-blind, randomized phase 2b/3 rofecoxib osteoarthritis trials conducted from December 1996 through March 1998, including one 6-week dose-ranging study, two 6-week efficacy studies vs ibuprofen and placebo, two 1-year efficacy studies vs diclofenac, two 6-month endoscopy studies vs ibuprofen and placebo, and one 6-week efficacy study vs nabumetone and placebo. SETTING: Multinational sites. Participants Osteoarthritis patients (N = 5435; mean age, 63 years [range, 38-94 years]; 72.9% women). INTERVENTIONS: Rofecoxib, 12.5, 25, or 50 mg/d (n = 1209, 1603, and 545, respectively, combined) vs ibuprofen, 800 mg 3 times per day (n = 847), diclofenac, 50 mg 3 times per day (n = 590); or nabumetone, 1500 mg/d (n = 127) (combined). MAIN OUTCOME MEASURE: Cumulative incidence of PUBs for rofecoxib vs NSAIDs, based on survival analysis of time to first PUB diagnosis, using PUBs that met pre-specified criteria judged by a blinded, external adjudication committee. RESULTS: The incidence of PUBs over 12 months was significantly lower with rofecoxib vs NSAIDs (12-month cumulative incidence, 1.3% vs 1.8%; P = .046; rate per 100 patient-years, 1.33 vs 2.60; relative risk, 0.51; 95% confidence interval, 0.26-1.00). The cumulative incidence of dyspeptic GI adverse experiences was also lower with rofecoxib vs NSAIDS over 6 months (23.5% vs 25.5%; P = .02), after which the incidence rates converged. CONCLUSION: In a combined analysis of 8 trials of patients with osteoarthritis, treatment with rofecoxib was associated with a significantly lower incidence of PUBs than treatment with NSAIDs.

Adult↗

PubMed1999

CABG in Canada.

Explore the source record for details and available documents.

Canada↗

PubMed1999

Planning and analysis of repeated measures at key time-points in clinical trials sponsored by pharmaceutical companies.

In this paper we explore the possible reasons why medical papers reporting clinical trials sponsored by the pharmaceutical industry often analyse repeated measures data at certain key time-points instead of employing sophisticated models of repeated measures proposed by many statisticians. A survey indicated that the priority reason in the industry for having repeated measures in clinical trials is to monitor the trial and to utilize the early results for strategic decision making. We discuss what the common statistical methods do and do not offer for analysis of repeated measures in such clinical trials. We advocate the need to improve the understanding of the medical interest in conducting longitudinal trials in the industry, and to plan and analyse the repeated measures accordingly. We address the medical interest by formulating the problem and give illustrative examples for both phases II and III trials.

Alendronate↗

PubMed1999

Missed opportunities for prevention in general internal medicine.

BACKGROUND: According to the Canadian Society of Internal Medicine, the Canadian general internist is in the ideal position to promote patient health through disease prevention. To explore the general internist's contribution to disease prevention, the authors quantified the extent to which opportunities for prevention were addressed by the general internal medicine (GIM) service in an acute care teaching hospital in Calgary. METHODS: The authors interviewed 100 adult patients before discharge from the hospital's GIM service between May 14, 1997, and Dec. 2, 1997. The number of potential opportunities for preventive intervention were identified for each patient from 10 possible interventions recommended by the Canadian Task Force on the Periodic Health Examination (now the Canadian Task Force on Preventive Health Care): breast cancer screening, Papanicolaou smear for cervical cancer, counselling on menopausal hormone replacement therapy, digital rectal examination for prostate cancer, smoking cessation counselling, cholesterol measurement, therapy or monitoring for hypertension, influenza vaccination, pneumococcal vaccination and colorectal cancer screening. The authors determined which interventions the patient had undergone before the current admission to hospital and, using patient recall and postdischarge medical chart review, which opportunities for intervention were addressed by the GIM service during the current admission. An opportunity for preventive intervention was considered as addressed by the GIM service if it was performed during the current admission or if the general internist informed the patient or the patient's family physician of the need for such intervention in the near future. RESULTS: Among the 10 preventive interventions considered, a mean of 3.8 potential opportunities for prevention were identified for each patient. Of these, 46.5% had been addressed before the current admission, and 8.7% were addressed by the GIM service during the admission. Therefore, at the time of discharge, a mean of 55.2% of opportunities had been addressed. Among the opportunities not previously addressed, the GIM service most frequently addressed digital rectal examination for prostate cancer and cholesterol measurement. INTERPRETATION: General internists are discharging patients without sufficiently addressing opportunities for disease prevention. Preventive care protocols may be needed to limit the frequency of missed opportunities for prevention in patients admitted to tertiary care GIM services.

Acute Disease↗

PubMed1999

Physician estimates of perioperative cardiac risk in patients undergoing noncardiac surgery.

BACKGROUND: We know little about how physicians assess perioperative cardiac risk in patients undergoing noncardiac surgery. OBJECTIVES: To evaluate preoperative medical consultations and determine the extent to which consultants used validated cardiac risk indices and specialized noninvasive cardiac tests, and to assess agreement between physician ratings of cardiac risk (low, moderate, or high) and risk estimates derived using validated cardiac risk indices or, in the case of vascular surgery, a risk index. METHODS: This observational study was conducted at 5 Canadian teaching hospitals affiliated with 2 universities. We retrospectively evaluated 308 preoperative consultations performed in 297 patients and examined the frequency with which consultants recorded the use of validated cardiac risk indices. We used K statistics to quantify the extent to which physician ratings of cardiac risk agreed with risk estimates derived using validated cardiac risk indices. RESULTS: Physicians recorded use of a risk index in 31% of the consultations, but the index used was almost always the suboptimal classification of the American Society of Anesthesiologists. The agreement between physician estimates of cardiac risk and the validated cardiac risk indices was only fair, with a weighted K of 0.38 (95% confidence interval, 0.28-0.49). Overestimation and underestimation of cardiac risk occurred in 16% and 13% of the consultations, respectively. Consultants did not order dipyridamole thallium imaging or dobutamine stress echocardiography for any moderate-risk patients undergoing vascular surgery. CONCLUSIONS: Physicians underuse validated cardiac risk indices, and the agreement between the cardiac risk estimates and risk as determined by validated cardiac indices is suboptimal. Physicians are also underusing dipyridamole thallium imaging and dobutamine stress echocardiography for moderate-risk patients undergoing vascular surgery.

Alberta↗

PubMed1999

A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group.

BACKGROUND & AIMS: Prostaglandin production in the normal gastrointestinal tract, believed to be critical for mucosal integrity, is mediated by cyclooxygenase (COX)-1, whereas prostaglandin production at inflammatory sites seems to occur via induction of COX-2. We hypothesized that COX-2-specific inhibition with rofecoxib (25 mg once daily) in the treatment of patients with osteoarthritis would cause fewer gastroduodenal ulcers than an equally effective dose of ibuprofen (800 mg 3 times a day), a nonspecific COX inhibitor. METHODS: A total of 742 osteoarthritis patients without ulcers on baseline endoscopy were randomly assigned to receive rofecoxib (25 or 50 mg once daily), ibuprofen (800 mg 3 times daily), or placebo. Endoscopy was repeated at 6, 12, and 24 weeks. At 16 weeks, by study design, 95% of the placebo group and 5% of the other groups were discontinued. RESULTS: The cumulative incidence of gastroduodenal ulcers >/=3 mm with rofecoxib (25 or 50 mg once daily) was significantly (P < 0.001) lower than with ibuprofen and was statistically equivalent to placebo at week 12 (placebo, 9.9%; 25 mg rofecoxib, 4.1%; 50 mg rofecoxib, 7.3%; and ibuprofen, 27.7%). At 24 weeks, ulcer rates were 25 mg rofecoxib, 9. 6%; 50 mg rofecoxib, 14.7%; and ibuprofen, 45.8% (P < 0.001, ibuprofen vs. 25 and 50 mg rofecoxib). CONCLUSIONS: Rofecoxib, at doses 2-4 times the dose demonstrated to relieve symptoms of osteoarthritis, caused significantly less gastroduodenal ulceration than ibuprofen, with ulcer rates comparable to placebo.

Aged↗

PubMed1999

Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen.

BACKGROUND: Compared with currently available NSAIDs (which inhibit COX-1 and COX-2 isoforms of cyclooxygenase), MK-0966 (a specific COX-2 inhibitor) is expected to cause less gastrointestinal toxicity. AIM: To compare the effect on the upper gastrointestinal mucosae of a high dose of MK-0966 with that of conventional doses of ibuprofen and aspirin. METHODS: Healthy subjects (n = 170; age range 18-54 years) with endoscopically normal gastric and duodenal mucosa were randomized to either MK-0966 250 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7-day, double-blind, parallel-group study. The mucosae were evaluated by endoscopy using a predefined scale; scores could range from 0 to 4. The primary end-point was the percentage of subjects who developed a mucosal score >/= 2 (i.e. the development of one or more erosions). To evaluate COX-1 activity, serum thromboxane B2 levels were determined in a subset of the population. RESULTS: The percentage of subjects who developed a mucosal score >/= 2 in the MK-0966 group (12%) was significantly lower (P < 0.001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was similar to that in the placebo group (8%). Only ibuprofen and aspirin significantly (P < 0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated. CONCLUSIONS: In this acute short-term endoscopic study, MK-0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the signs and symptoms of osteoarthritis) produced significantly less gastrointestinal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q.d.s. and was comparable to placebo in this regard.

Adolescent↗

PubMed1999

Adjusted regression trend test for a multicenter clinical trial.

Studies using a series of increasing doses of a compound, including a zero dose control, are often conducted to study the effect of the compound on the response of interest. For a one-way design, Tukey et al. (1985, Biometrics 41, 295-301) suggested assessing trend by examining the slopes of regression lines under arithmetic, ordinal, and arithmetic-logarithmic dose scalings. They reported the smallest p-value for the three significance tests on the three slopes for safety assessments. Capizzi et al. (1992, Biometrical Journal 34, 275-289) suggested an adjusted trend test, which adjusts the p-value using a trivariate t-distribution, the joint distribution of the three slope estimators. In this paper, we propose an adjusted regression trend test suitable for two-way designs, particularly for multicenter clinical trials. In a step-down fashion, the proposed trend test can be applied to a multicenter clinical trial to compare each dose with the control. This sequential procedure is a closed testing procedure for a trend alternative. Therefore, it adjusts p-values and maintains experimentwise error rate. Simulation results show that the step-down trend test is overall more powerful than a step-down least significant difference test.

Aged↗

PubMed1999

Pharmacokinetics of intravenous alendronate.

Alendronate is a potent bisphosphonate that has been studied for the treatment of osteoporosis and Paget's disease of the bone. To examine the pharmacokinetics of this drug, several groups of postmenopausal women were dosed intravenously in several studies. Twelve patients with metastatic bone disease were administered an intravenous dose of 10 mg of 14C-labeled alendronate (approximately 26 muCi), and plasma, feces, and urine samples were collected for 72 hours. Radioactivity was excreted almost exclusively in urine, and all of it was accounted for by alendronate. Overall recovery accounted for 47% of dose, with the remainder presumed to be retained in bone. Metabolism of alendronate was not observed. Renal clearance of alendronate was 71 mL/min. An additional 10 subjects were given repeated i.v. administrations of alendronate to demonstrate that previous exposure does not alter the pharmacokinetic behavior of the drug. Examination of the findings from these and other studies in which alendronate was administered intravenously revealed that disposition of single doses is linear in the range of 0.125 to 10 mg. With the possible exception of a somewhat greater skeletal retention of a systemically administered dose, the pharmacokinetics of i.v. alendronate were found to be similar to those of other bisphosphonates.

Adult↗