Search PubMed⌕ Search

Biomedical subjects

James D Douketis

Publications and source records attributed to James D Douketis.

At least 19 recordsLinked to original sources
PubMed2006

DHCR7 mutation carrier rates and prevalence of the RSH/Smith-Lemli-Opitz syndrome: where are the patients?

RSH/Smith-Lemli-Opitz (SLOS) is an inborn error of metabolism with protean manifestations. Its exact incidence and prevalence are not known; however, the carrier rate for the most frequently occurring mutation, the null mutation IVS8-1G > C, is approximately 1 in 100 for the Caucasian population in North America (1%) and possibly as high as 1 in 50 to 1 in 30 in Central European populations (2-3.3%). Based on the allele frequencies and the proportion of this mutation observed in various patient populations, the expected incidence of RSH/SLOS in those populations was calculated and reported to be between 1 in 1,590 and 1 in 17,000. However, around the world the observed prevalence and incidence are much lower than those calculated from the individual mutation carrier rates observed in any given population. The discrepancy between the expected incidence and prevalence can be explained only in part by the neonatal and infancy deaths of the most severely affected children with RSH/SLOS and the under ascertainment of mild and atypical cases at the mild end of the spectrum. RSH/SLOS may be responsible for a high number of miscarriages. Recent observations estimate the prevalence of SLOS at 16 weeks of gestation as similar to that observed at birth (approximately 1 in 60,000) suggesting that either reduced fertility of carrier couples or losses of affected embryos or fetuses in the first trimester play a significant role in reducing the second trimester prevalence of RSH/SLOS. It is possible that the estimates of carrier rates based on population screening for the most commonly occurring mutations may not reflect the true carrier rates in the population. In order to reconcile the above-mentioned paradoxes, we propose a model based on a higher than observed carrier frequency of the most common mutation and on very high fetal loss of homozygotes for that mutation.

Canada↗
PubMed2006

Does celecoxib potentiate the anticoagulant effect of warfarin? A randomized, double-blind, controlled trial.

BACKGROUND: The management of patients who are receiving warfarin therapy and have musculoskeletal problems that require treatment with a nonsteroidal antiinflammatory drug (NSAID) is problematic because NSAID use may increase the risk for bleeding. Cyclooxygenase-2 selective NSAIDs such as celecoxib may be less likely to promote gastrointestinal bleeding; however, there are concerns that they could potentiate the anticoagulation effect of warfarin. OBJECTIVE: To determine whether celecoxib potentiates the anticoagulant effect of warfarin, as measured by the international normalized ratio (INR). METHODS: We performed a randomized, controlled, crossover trial to assess the effect on INR of celecoxib versus codeine (control treatment) in 15 patients who were receiving warfarin therapy and required analgesic treatment for osteoarthritis. During Phase 1 of the study, patients were randomly allocated to receive celecoxib 200 mg/day or codeine phosphate 7-15 mg 3-4 times daily for 5 weeks. During Phase 2 of the study, patients stopped the first study medication and started the other study medication; there was no drug-free interval between phases. Weekly INR testing was performed during the 10 week study period. Adopting the intent-to-treat principle, we used generalized estimating equations to analyze the data. RESULTS: There was no significant difference in the mean INR values during each 5 week treatment period when patients received either celecoxib or codeine. There was, therefore, insufficient evidence to reject the hypothesis that these 2 treatments had an equal effect on the INR (mean difference [95% CI] 0.10 [-0.04 to 0.24]; p = 0.16) based on mean imputation. This finding was confirmed after we repeated the analysis with multiple imputations (mean difference [95% CI] 0.093 [-0.16 to 0.35]; p = 0.47). CONCLUSIONS: Our results suggest that treatment with celecoxib does not potentiate the INR when taken with warfarin. Larger randomized trials are warranted to address the effects of coadministered warfarin and celecoxib on clinical outcomes.

Aged↗
PubMed2006

Comparison of bleeding in patients with nonvalvular atrial fibrillation treated with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time course and sites of bleeding, and risk factors for bleeding.

BACKGROUND: Ximelagatran is a novel direct thrombin inhibitor that can be administered as a fixed oral dose, without the need for anticoagulant monitoring. METHODS: We undertook a pooled analysis of 7329 patients with nonvalvular atrial fibrillation from the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target international normalized ratio, 2.0-3.0). We determined annual risk of bleeding (any, major), case-fatality rate, time course and anatomic sites of major bleeding, and risk factors for major bleeding with ximelagatran and warfarin treatment. RESULTS: Annual incidence of any bleeding was 31.75% with ximelagatran and 38.82% with warfarin (relative risk reduction, 18.2%; 95% confidence interval [CI], 13.0-23.1; P<.001). Annual incidence of major bleeding was 2.01% with ximelagatran and 2.68% with warfarin (relative risk reduction, 25.1%; 95% CI, 3.2-42.1; P = .03). Case-fatality rate of bleeding was comparable in ximelagatran- and warfarin-treated patients (8.16% vs 8.09%; P = .98). Cumulative incidence of major bleeding was higher with warfarin than ximelagatran after 24 months of treatment (4.7% vs 3.7%; P = .04). Anatomic sites of bleeding were comparable with both treatments. Risk factors for bleeding with ximelagatran were as follows (hazard ratios and 95% CIs in parentheses): diabetes mellitus (1.81; 1.19-2.77; P = .006), previous stroke or transient ischemic attack (1.78; 1.16-2.73; P = .008), age 75 years or greater (1.70; 1.33-2.18; P<.001), and aspirin use (1.68; 1.08-2.59; P = .02). Risk factors for bleeding in warfarin-treated patients were previous liver disease (4.88; 1.55-15.39; P = .007); aspirin use (2.41; 1.69-3.43; P<.001); and age 75 years or greater (1.26; 1.03-1.52; P = .02). CONCLUSIONS: Treatment with ximelagatran, 36 mg twice daily, is associated with a lower risk of bleeding than warfarin in patients with nonvalvular atrial fibrillation. Aspirin use and increasing age were associated with an increased risk of bleeding in ximelagatran- and warfarin-treated patients.

Adolescent↗
PubMed2006

The management of patients who require temporary reversal of vitamin K antagonists for surgery: a practical guide for clinicians.

The management of patients who require temporary interruption of vitamin K antagonists is a common clinical problem, affecting an estimated 400 000 patients per year in Europe and North America. Managing such patients is challenging because of the lack of randomized trials assessing different perioperative anticoagulation management strategies and inconsistent recommendations from consensus groups. Recent non-randomized trials have helped to estimate the risks for arterial thromboembolism and bleeding with bridging anticoagulation involving low-molecular-weight heparin. The objectives of this review are to describe bridging anticoagulation and how it may be used with a short-acting heparin, such as unfractionated heparin or low-molecular-weight heparin, to discuss preoperative patient management, focusing on risk stratification for thromboembolic events and interruption of vitamin K antagonist therapy, and to discuss postoperative patient management, focusing on surgery-related bleeding risk and the resumption of bridging anticoagulation and vitamin K antagonist therapy.

Anticoagulants↗
PubMed2005

Are brand-name and generic warfarin interchangeable? A survey of Ontario patients and physicians.

BACKGROUND: The issue of therapeutic equivalence has been a source of controversy in Canada since the approval of generic warfarin products in 2000. OBJECTIVES: We surveyed Ontario patients and physicians on perceptions of generic warfarin and brand substitution. METHODS: Self-administered questionnaires employed 7.0-point Likert scales of agreement. Patient participants were drawn from a thromboembolism clinic in Hamilton, Ontario. Physician participants were from a random sample of 375 Ontario family physicians, internists, cardiologists and hematologists. RESULTS: Eighty-one patients responded: 52% female, mean age 63.4 years and 63% brand-name warfarin users. Overall, 33% of respondents agreed or strongly agreed that they would feel comfortable taking generic warfarin. However, seventeen percent agreed or strongly agreed that generic warfarin was neither as safe nor as effective as brand-name warfarin, with this view more common amongst patients taking brand-name than those taking generic warfarin. One hundred and ten (29.3%) physicians returned the survey--29% females, mean age 45.3 years, 22% family physicians. Forty-four percent agreed or strongly agreed that they would rather prescribe brand-name than generic warfarin for patients starting warfarin therapy, while 40.7% agreed or strongly agreed that they would not feel comfortable switching from brand-name to generic warfarin. However, only 19.4% of physicians who had switched patients from brand-name to generic warfarin actually reported difficulties in managing the switch. CONCLUSION: While most patients and physicians appear to have accepted the principle of therapeutic equivalence of generic and brand-name warfarin, a sizable minority has concerns that could influence prescribing and compliance.

Anticoagulants↗
PubMed2005

Low-molecular-weight heparins for the treatment of acute coronary syndrome and venous thromboembolism in patients with chronic renal insufficiency.

The clinical management of patients with renal insufficiency who develop an acute coronary syndrome or venous thromboembolism is a common clinical scenario that is problematic because of the lack of well-designed randomized trials assessing management strategies in such patients. Impaired renal function is common in patients who develop thromboembolic disorders, particularly in elderly patients in whom renal insufficiency is under-recognized. Low-molecular-weight heparins (LMWHs), which are the most widely used anticoagulant for the treatment of patients with an acute coronary syndrome or venous thromboembolism, are eliminated primarily by the kidney and, therefore, pose treatment challenges in patients with impaired renal function. However, there is emerging evidence regarding the use of LMWHs in patients with impaired renal function suggesting that some preparations may be safe in such patients. The objective of this review is to discuss the clinical management of patients with renal insufficiency who develop an acute coronary syndrome or venous thromboembolism, and to explore similarities and differences of LMWHs when used in this clinical setting.

Acute Disease↗
PubMed2005

Are brand-name and generic warfarin interchangeable? Multiple n-of-1 randomized, crossover trials.

BACKGROUND: Warfarin is a commonly used anticoagulant in North America. Several generic formulations have been approved, raising concern over the safety and efficacy of these products compared with brand-name Coumadin. OBJECTIVE: To ensure that generic warfarin products can be safely interchanged with Coumadin. METHODS: Multiple n-of-1 randomized, double-blind, crossover trials switched outpatients (N = 7) between a generic warfarin formulation (Apo-warfarin) and Coumadin over 30 weeks. Study patients took each drug for five 3-week periods, with international normalized ratio (INR) measurements taken twice per period. Inter- and intrapatient differences between generic warfarin and Coumadin were compared, and overall study patient results were compared with those of a Coumadin control group. RESULTS: There were no differences between warfarin products in terms of mean INR results or number of dosage adjustments required. There also was no difference in INR variation based on warfarin formulation (p > 0.69), nor was a patient and warfarin interaction found (p > 0.81). The INR results were not influenced by whether patients were maintained on Coumadin only (control group) or interchanged between Coumadin and generic warfarin (p = 0.98). CONCLUSIONS: It appears that patients can safely and effectively switch between generic warfarin and Coumadin.

Aged↗
PubMed2005

Systematic overview of warfarin and its drug and food interactions.

BACKGROUND: Warfarin is a highly efficacious oral anticoagulant, but its use is limited by a well-founded fear of bleeding. Drug and food interactions are frequently cited as causes of adverse events with warfarin. We provide an updated systematic overview of the quality, clinical effect, and importance of these reported interactions. DATA SOURCES: MEDLINE, TOXLINE, IPA, and EMBASE databases from October 1993 to March 2004. Database searches combined the keyword warfarin with drug interactions, herbal medicines, Chinese herbal drugs, and food-drug interactions. STUDY SELECTION: Eligible articles contained original reports of warfarin drug or food interactions in human subjects. Non-English articles were included if sufficient information could be abstracted. DATA EXTRACTION: Reports were rated independently by 2 investigators for interaction direction, clinical severity, and quality of evidence. Quality of evidence was based on previously validated causation criteria and study design. DATA SYNTHESIS: Of 642 citations retrieved, 181 eligible articles contained original reports on 120 drugs or foods. Inter-rater agreement was excellent, with weighted kappa values of 0.84 to 1.00. Of all reports, 72% described a potentiation of warfarin's effect and 84% were of poor quality, 86% of which were single case reports. The 31 incidents of clinically significant bleeding were all single case reports. Newly reported interactions included celecoxib, rofecoxib, and herbal substances, such as green tea and danshen. CONCLUSIONS: The number of drugs reported to interact with warfarin continues to expand. While most reports are of poor quality and present potentially misleading conclusions, the consistency of reports of interactions with azole antibiotics, macrolides, quinolones, nonsteroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, selective serotonin reuptake inhibitors, omeprazole, lipid-lowering agents, amiodarone, and fluorouracil, suggests that coadministration with warfarin should be avoided or closely monitored. More systematic study of warfarin drug interactions in patients is urgently needed.

Anticoagulants↗
PubMed2005

Influence of warfarin on symptoms of fatigue: findings of a randomized trial.

BACKGROUND: Some patients develop fatigue while taking warfarin, but causality is uncertain. OBJECTIVE: To assess whether warfarin use is associated with fatigue. METHODS: This investigation was a substudy of a randomized double-blind trial in 13 outpatient thromboembolism clinics. Subjects who had received one month of open-label warfarin therapy for venous thromboembolism due to a transient risk factor were randomly assigned to receive warfarin or placebo for 2 months and followed for another 9 months after stopping the study drug. Fatigue was measured using a Likert scale, and change of fatigue was measured by the patient's global rating. RESULTS: In 87 subjects, the overall ratings of fatigue were 0.1 unit lower (95% CI 0.6 units lower to 0.4 units higher) while taking warfarin. Global rating for change in fatigue intensity showed no increase of fatigue with warfarin use. CONCLUSIONS: The short-term use of warfarin was not associated with symptoms of fatigue.

Analysis of Variance↗
PubMed2005

Management of hypertension in overweight and obese patients: a practical guide for clinicians.

The association between obesity and cardiovascular disease is well established, and up to 60% of overweight or obese patients have hypertension. Dietary interventions associated with modest weight loss are effective in controlling blood pressure and in reducing use of antihypertensive drug therapy in overweight and obese patients. However, long-term maintenance of weight loss is achieved only in a small proportion of patients. Orlistat and sibutramine may help to achieve and maintain weight loss but may not be sufficient to control blood pressure in overweight and obese hypertensive patients. Consequently, antihypertensive drug therapy is often necessary in addition to weight loss interventions. Few studies have investigated different antihypertensive drugs, specifically in overweight and obese patients with hypertension. Based on studies involving obese and nonobese patients, first-line treatment options include a diuretic alone or an angiotensin-converting enzyme (ACE) inhibitor alone. If monotherapy is inadequate for blood pressure control, combination therapy with diuretic and ACE inhibitor and/or combining either of these drugs with a calcium channel blocker are reasonable treatment options. Additional studies to further clarify the management of these patients are warranted.

Anti-Obesity Agents↗
PubMed2005

Anticoagulant prophylaxis in special populations with an indwelling epidural catheter or renal insufficiency.

The prevention of deep venous thrombosis in postoperative patients who have an indwelling epidural catheter and patients with impaired renal function is a frequently encountered and challenging clinical management problem. Such patients make up a considerable proportion of patients in a medical-surgical intensive care unit. The management of such patients is problematic because low-molecular-weight heparins, the anticoagulant of choice as thromboprophylaxis for many clinical indications, are generally avoided in such patients. This review focuses on anticoagulant prophylaxis in such patients, including reasonable approaches for using low-molecular-weight heparins as thromboprophylaxis.

Analgesia, Epidural↗
PubMed2005

Obesity and cardiovascular disease: pathogenic mechanisms and potential benefits of weight reduction.

The prevalence of obesity in industrialized countries has reached epidemic proportions, with about one in three people being obese and another one in three people being overweight and at risk of developing obesity. In recent years, obesity has gained the traditional tetrad of cardiovascular risk factors of smoking: hypertension, dyslipidemia, and dysglycemia. Attention has also focused on the importance of abdominal (or central) obesity as a determinant of cardiovascular risk, independent of the body mass index. In addition to effects on coronary artery disease, obesity has an effect on cardiovascular disease, including stroke, ventricular function, peripheral arterial disease, and venous thromboembolism. The objectives of this review are to summarize the effects of obesity on cardiovascular disease, and the possible mechanisms for these associations, and to investigate the effects of weight-loss interventions on the burden of cardiovascular disease. Large ongoing clinical outcome trials, such as the SOS study, the Look-AHEAD trial, or the SCOUT study, should provide important information on the effects of surgical and nonsurgical obesity treatment on cardiovascular morbidity and mortality.

Adult↗
PubMed2005

Bridging anticoagulation with low-molecular-weight heparin after interruption of warfarin therapy is associated with a residual anticoagulant effect prior to surgery.

Bridging anticoagulation with low-molecular-weight heparin (LMWH) is common in patients who require temporary interruption of warfarin before surgery or a procedure, but whether such patients have a residual anticoagulant effect just before a procedure is not known. Consecutive patients who received bridging anticoagulation with LMWH had anti-Xa levels measured just before a procedure. The proportion of patients with a residual anticoagulant effect, defined as an anti-Xa level > or = 0.10 IU/ml, was determined. Multivariable regression analysis identified predictors of a residual anticoagulant effect, expressed as an odds ratio (OR) and corresponding 95% confidence interval (CI). A pre-procedure residual anticoagulant effect was detected in 12 of 73 (16%) patients overall, in 11 of 37 (30%) patients who received therapeutic-dose LMWH, and in 1 of 36 patients (3%) who received low-dose LMWH. Receiving therapeutic-dose LMWH (OR = 118.8; 95% CI: 5.8, 999.9), and increasing age (OR = 4.0; 95% CI: 1.3, 12.5) were predictors of a residual pre-procedure anticoagulant effect. In patients who require bridging anticoagulation with LMWH, a residual anticoagulant effect from LMWH is detected in 1 of 6 patients, and receiving therapeutic-dose LMWH is the strongest predictor of such an effect.

Age Factors↗
PubMed2005

Oral vitamin K produces a normal INR within 24 hours of its administration in most patients discontinuing warfarin.

A randomized, blinded study in 30 patients was undertaken. This study found that low dose oral vitamin K was more effective than placebo when used to correct the INR in patients who are discontinuing warfarin. Larger studies will be required to determine if the use of oral vitamin K, for example in patients who are temporarily discontinuing warfarin to undergo interventional procedures, is safe and effective.

Administration, Oral↗