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Biomedical subjects

A N Barkun

Publications and source records attributed to A N Barkun.

At least 19 recordsLinked to original sources
PubMed2006

Hospitalization for gastrointestinal bleeding associated with non-steroidal anti-inflammatory drugs among elderly patients using low-dose aspirin: a retrospective cohort study.

OBJECTIVES: Many elderly patients are prescribed both low-dose aspirin (ASA), for cardiovascular protection and non-steroidal anti-inflammatory drugs (NSAIDs) for pain control. Compared with non-selective NSAIDs (NS-NSAIDs), celecoxib has a superior gastrointestinal (GI) safety profile in general. It is unclear, however, whether this fact holds good among patients taking ASA. We compared GI hospitalization rates among elderly patients taking celecoxib, NS-NSAIDs, celecoxib and ASA or NS-NSAIDs and ASA. METHODS: This was a retrospective cohort study using Quebec government databases. All patients 65 yrs of age or older who filled a prescription for celecoxib or an NS-NSAID between April 1999 and December 2002 were included. Cox regression models were used to compare the GI hospitalization rates between the four exposure categories adjusting for potential confounders. RESULTS: A total of 332 491 patients were included. Among 1 522 307 celecoxib prescriptions, 430 214 were filled by patients concurrently receiving ASA (celecoxib and ASA); 195 369 of 863 646 NS-NSAID prescriptions were filled by patients receiving ASA (NS-NSAID and ASA). Celecoxib without ASA was less likely than NS-NSAID without ASA to be associated with GI hospitalization [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.33-0.50]; celecoxib and ASA was also less likely to be associated with GI hospitalization than NS-NSAID and ASA (HR 0.62, 95% CI 0.48-0.80); GI hospitalization rates were similar for celecoxib and ASA and NS-NSAID without ASA (HR 1.01, 95% CI 0.81-1.25). CONCLUSION: Among elderly patients receiving cardiovascular protection with ASA and pain control with anti-inflammatory drugs, celecoxib may be safer with regards to GI toxicity than NS-NSAIDs.

Aged↗
PubMed2006

The prevalence of Barrett's oesophagus in a cohort of 1040 Canadian primary care patients with uninvestigated dyspepsia undergoing prompt endoscopy.

BACKGROUND: The prevalence of Barrett's oesophagus in patients undergoing gastroscopy may be influenced by possible referral bias. AIM: To present the prevalence of Barrett's oesophagus from the the Canadian Adult Dyspepsia Empirical Therapy Prompt Endoscopy study and to explore potential risk factors for its presence. METHODS: Patients had not been on treatment for dyspepsia for 2-4 weeks prior to endoscopy, which was performed within 10 working days of presentation. RESULTS: Barrett's oesophagus was endoscopically suspected in 53 of 1040 cases (5%) and histologically confirmed by the presence of intestinal metaplasia in 25 (2.4%). The prevalence of biopsy-proven Barrett's oesophagus was 4% in patients with dominant reflux-like symptoms. Sixty-four percent with confirmed Barrett's oesophagus had dominant reflux-like symptoms compared with 37% without Barrett's oesophagus. Barrett's oesophagus was more common in patients >50 years of age; 68% of cases were males. The mean duration of symptoms was 10 years, yet 16% had symptoms of <1-year duration. Endoscopic reflux oesophagitis was present in 68% of confirmed Barrett's oesophagus patients. CONCLUSIONS: Barrett's oesophagus is confirmed on biopsy in about half of endoscopically suspected Barrett's oesophagus patients. Barrett's oesophagus is more common in males, in those with dominant reflux-like symptoms, and in patients with a longer symptom history.

Aged↗
PubMed2006

Validation of a 7-point Global Overall Symptom scale to measure the severity of dyspepsia symptoms in clinical trials.

BACKGROUND: Currently there is no consensus on the optimal method to measure the severity of dyspepsia symptoms in clinical trials. AIM: To validate the 7-point Global Overall Symptom scale. METHODS: The Global Overall Symptom scale uses a 7-point Likert scale ranging from 1 = no problem to 7 = a very severe problem. Validation was performed in two randomized-controlled trials (n = 1121 and 512). Construct validity: Global Overall Symptom was compared with the Quality of Life in Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and 10 specific symptoms using Spearman correlation coefficients. Test-retest reliability: The Intraclass Correlation Coefficient was calculated for patients with stable dyspepsia defined by no change in Overall Treatment Effect score over two visits. Responsiveness: effect size and standardized response mean were also calculated. RESULTS: Construct validity: Change in Global Overall Symptom score correlated significantly with Quality of Life for Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and specific symptoms (all P < 0.0002). Reliability: The Intraclass Correlation Coefficient was 0.62 (n = 205) and 0.42 (n = 270). Responsiveness: There was a positive correlation between change in Global Overall Symptom and change in symptom severity. The effect size and standardized response mean were 1.1 and 2.1, respectively. CONCLUSION: The Global Overall Symptom scale is a simple, valid outcome measure for dyspepsia treatment trials.

Adolescent↗
PubMed2006

Validation of a symptom diary for patients with gastro-oesophageal reflux disease.

BACKGROUND: Symptom diaries are potentially attractive but, because of concerns about patient compliance, they have had limited use in clinical trials. We assessed the validity and responsiveness of a symptom diary for patients with gastro-oesophageal reflux disease. METHODS: We included 215 patients with gastro-oesophageal reflux disease after starting treatment for 4 weeks with 40 mg esomeprazole once daily. Patients recorded whether they experienced night-time heartburn (yes/no), the severity of daytime heartburn on a scale from 1 (no heartburn) to 4 (severe heartburn) and their antacid use. Patients also completed a number of disease-specific and preference-based Health-related Quality of Life questionnaires at baseline and follow-up. RESULTS: Consistent with a priori predictions, daytime heartburn showed moderate to strong correlations with the Quality of Life in Reflux and Dyspepsia questionnaire (0.36-0.67) and four scales of symptom severity (0.36-0.70) for baseline, follow-up and change scores, but low correlations with the Standard Gamble. Responsiveness of the daytime heartburn item was excellent with a mean change from baseline to follow-up of -1.3 (95% CI -1.4 to -1.1) and a standardized response mean of 1.33 while responsiveness of the daily antacid use item was moderate (mean change scores -1.8 tablets taken, 95% CI -2.3 to -1.3 and standardized response mean of 0.64). CONCLUSIONS: The excellent psychometric properties of this simple gastro-oesophageal reflux disease diary make it an attractive measure for future trials.

Antacids↗
PubMed2006

Review article: acid-related disease--what are the unmet clinical needs?

Proton pump inhibitors have dramatically improved the management options available for patients with acid-related disorders. In patients with gastro-oesophageal reflux disease, currently available proton pump inhibitors provide an excellent outcome for the majority; however, they do not provide optimal pH control in many. Proton pump inhibitors co-therapy reduces, but does not eliminate, the risk of gastrointestinal ulcers and complications in patients taking non-steroidal anti-inflammatory drugs, while in patients with upper gastrointestinal bleeding, it may be difficult to reach and maintain the current therapeutic target of intragastric pH of 6-7. This article reviews the effectiveness of current antisecretory therapy in these three acid-related diseases and areas of unmet clinical need. The potential role of a proton pump inhibitor with an extended duration of action and enhanced acid control from a single daily dose, particularly improved control at night, is discussed. Finally, therapy that could be administered without regard to time of day and/or food intake would offer dosing flexibility and thus have a positive effect on patients' compliance.

Antacids↗
PubMed2005

Heartburn-dominant, uninvestigated dyspepsia: a comparison of 'PPI-start' and 'H2-RA-start' management strategies in primary care--the CADET-HR Study.

BACKGROUND: There are few data on empiric, stepped therapy for heartburn relief or subsequent relapse in primary care. AIMS: To compare heartburn relief produced by a proton pump inhibitor-start or an H(2)-receptor antagonist-start with step-up therapy, as needed, followed by a treatment-free period to assess relapse. METHODS: Heartburn-dominant uninvestigated dyspepsia patients from 46 primary care centres were randomized to one of two active treatment strategies: omeprazole 20 mg daily (proton pump inhibitor-start) or ranitidine 150 mg bid (H2-receptor antagonist-start) for the first 4-8 weeks, stepping up to omeprazole 40 or 20 mg daily, respectively, for 4-8 weeks for persistent symptoms. Daily diaries documented heartburn relief (score < or = 3/7 on < or = of 7 prior days) and relapse (score > or = 4 on > or = 2 of 7 prior days). RESULTS: For 'proton pump inhibitor-start' (n = 196) vs. 'H2-receptor antagonist-start' (n = 194), respectively, heartburn relief occurred in 55.1% vs. 27.3% (P < 0.001) at 4 weeks and in 88.3% vs. 87.1% at 16 weeks. After therapy, 308 patients were heartburn-free (159 vs. 149); median times to relapse were 8 vs. 9 days and cumulative relapse rates were 78.6% vs. 75.8%, respectively. CONCLUSIONS: An empiric 'proton pump inhibitor-start' strategy relieves heartburn more effectively than an 'H2-receptor antagonist-start' strategy up to 12 weeks but has no effect on subsequent relapse, which is rapid in most patients.

Adolescent↗
PubMed2005

Meta-analysis: proton-pump inhibition in high-risk patients with acute peptic ulcer bleeding.

BACKGROUND: Recent data suggest that profound acid suppression may improve outcomes of patients in peptic ulcer bleeding. AIM: To better characterize the role of different pharmacological therapies in this population. METHODS: MEDLINE was used to identify randomized trials (01/1990-04/2003) that assessed the efficacy of pharmacological treatments for patients with bleeding peptic ulcers exhibiting high-risk stigmata (Forrest Ia-IIb). Three groups of treatment were assessed: proton-pump inhibitors given as high-dose bolus followed by intravenous constant infusion (40-80 mg and at least 6 mg/h), high-dose oral proton-pump inhibitors (at least twice the standard dosage), non-high-dose proton-pump inhibitors (other proton-pump inhibitors dosing schedules). Mixed-effect models were used to determine rate differences between treatment and control groups. RESULTS: Eighteen studies (1855 patients) were included. High-dose intravenous proton-pump inhibitors significantly reduced rebleeding (-14.6%), surgery (-5.4%) and mortality (-2.7%) compared with placebo, and rebleeding (-20.6%) compared with H(2)RA. Compared with placebo, high-dose oral proton-pump inhibitors significantly reduced only rebleeding (-11.8%), while non-high-dose proton-pump inhibitor treatment significantly improved all three outcomes. CONCLUSIONS: High-dose intravenous proton-pump inhibitor significantly decreases ulcer rebleeding, surgery and mortality. Early data on high-dose oral proton-pump inhibitor suggest improved rebleeding. The non-high-dose proton-pump inhibitor regimens, including a broad range of dosing, also improved outcomes, suggesting that doses inferior to those in the high-dose intravenous proton-pump inhibitor may be effective.

Administration, Oral↗
PubMed2004

Do physicians correctly assess patient symptom severity in gastro-oesophageal reflux disease?

BACKGROUND: The accuracy of physicians' assessment of the severity of gastro-oesophageal reflux disease is unclear. AIM: To correlate physician and patient assessment of gastro-oesophageal reflux disease severity and its response to treatment. METHODS: Adult uninvestigated gastro-oesophageal reflux disease patients (n = 217) completed symptom and health-related quality of life questionnaires at baseline and after treatment with esomeprazole 40 mg p.o. daily. Pearson coefficients quantified correlations between physician assessments and patient responses. RESULTS: At baseline, the strongest correlations were heartburn severity (0.31), overall symptom severity (0.44) and a domain of the quality of life in reflux and dyspepsia questionnaire (0.31) (P < 0.001). Correlations of change with treatment were greater than baseline correlations: heartburn (0.39), overall symptoms (0.50) and global rate of change -- stomach problems (0.72, all P < 0.001). The mean difference between the physicians' assessment of change and the patients' global rating of change was 0.20 (95% confidence intervals: 0.10-0.29) with physicians overestimating benefit. CONCLUSIONS: Correlations were often significant, although weak to moderate and better with symptom severity than with health-related quality of life instruments as well as with change after therapy than at baseline. Increasing attention to health-related quality of life may help physicians better understand patients' experience. In clinical trials, treatment success should be assessed by the patient as well as the physician.

Adolescent↗
PubMed2004

There is no difference in the disease severity of gastro-oesophageal reflux disease between patients infected and not infected with Helicobacter pylori.

BACKGROUND: The role of Helicobacter pylori in gastro-oesophageal reflux disease (GERD) is controversial. AIM: To compare the severity of GERD in infected vs. non-infected patients, as part of an ongoing randomized controlled trial that examines the impact of H. pylori eradication on GERD-related outcomes. METHODS: Consecutive GERD patients underwent urea breath testing and completed validated GERD symptom severity, and quality of life questionnaires as well as, 24-h pH-metry. These parameters, as well as demographics and endoscopic findings were assessed in double-blinded fashion and compared between H. pylori-infected and non-infected subjects. RESULTS: Helicobacter pylori-infected GERD patients (n=50) were significantly older and less educated than non-infected patients (n=51). They also used proton pump inhibitors less often but had no difference in symptoms (as measured with both the Spechler's Activity Index and the Gastrointestinal Symptom Rating Scale), quality of life, endoscopic findings or 24-h pH-metry findings. CONCLUSION: This prospective, double-blind study demonstrates, using excellent GERD quantifying measures including validated symptom severity scores, endoscopy, and 24-h pH-metry, that there exist no clinically significant differences in clinical or laboratory-related GERD manifestations between H. pylori-infected and non-infected GERD patients.

Adolescent↗
PubMed2004

The cost-effectiveness of high-dose oral proton pump inhibition after endoscopy in the acute treatment of peptic ulcer bleeding.

BACKGROUND: Recent data suggest a role for high-dose oral proton pump inhibition in ulcer bleeding. AIM: To compare the cost-effectiveness of oral high-dose proton pump inhibition to both high-dose intravenous proton pump inhibition and placebo administration. METHODS: The model adopted a 30-day time horizon, and focused on patients with ulcer haemorrhage initially treated endoscopically for high-risk stigmata. Re-bleeding rates were set a priori based on non-head-to-head data from the literature, and charges and lengths of stay from a national American database. Sensitivity analyses were carried across a broad range of clinically relevant assumptions. RESULTS: Re-bleeding rates for patients receiving intravenous, oral, or placebo therapies were 5.9%, 11.8%, and 27%, respectively. The mean lengths of stay and costs for admitted patients with and without re-bleeding were 4.7 and 3 days; $11,802, and $7993, respectively. High-dose intravenous proton pump inhibition was more effective and less costly (dominant) than high-dose oral proton pump inhibition with incremental savings of $136.40 per patient treated. The oral high-dose strategy in turn dominated placebo administration. Results remained robust according to one- and two-way sensitivity analyses. CONCLUSION: In patients undergoing endoscopic haemostasis, subsequent high-dose intravenous proton pump inhibition is more cost-effective than high-dose oral proton pump inhibition, which in turn dominates placebo. The results from this exploratory-type cost analysis require confirmation by head-to-head prospective trials performed in Western populations.

Cost-Benefit Analysis↗
PubMed2004

High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis.

BACKGROUND: The efficacy of high-dose intravenous proton pump inhibition has recently been shown, yet its cost-effectiveness remains poorly studied. AIM: To assess the cost-effectiveness of this approach separately for American and Canadian health care settings. METHODS: A validated decision model included patients with bleeding ulcers after successful endoscopic haemostasis. Probabilities were determined from the literature, and charges and lengths of stay from national databases. A third-party payer perspective was adopted over a 30-day time horizon. RESULTS: Re-bleeding rates were 5.9% for patients who received high-dose intravenous proton pump inhibition and 22.9% for those who did not. Hospitalization costs for patients with and without re-bleeding were 11,802 US dollars and 7993 US dollars, and 5220 Canadian dollars and 2696 Canadian dollars, respectively. High-dose intravenous proton pump inhibition was more effective and less costly than the alternative of not administering it. The cost-effectiveness ratios for high-dose and no high-dose intravenous proton pump inhibition were 9112 US dollars and 11,819 US dollars (3293 dollars and 4284 dollars for the Canadian case), respectively. Sensitivity and threshold analyses showed that the results were robust across a wide range of clinically relevant assumptions. CONCLUSION: In the USA and Canada, administering high-dose intravenous proton pump inhibition for 3 days is both more effective and less costly than not doing so for patients with bleeding ulcers after successful endoscopic haemostasis.

Anti-Ulcer Agents↗
PubMed2004

The Quebec Association of Gastroenterology position paper on colorectal cancer screening - 2003.

Colorectal cancer is a leading cause of death and the third most common cancer in Canada. Evidence suggests that screening can reduce mortality rates and the cost effectiveness of a program compares favourably with initiatives for breast and cervical cancer. The objectives of the Association des gastro-entérologues du Québec Task Force were to determine the need for a policy on screening for colorectal cancer in Quebec, to evaluate the testing methods available and to propose one or more of these alternatives as part of a formal screening program, if indicated. Fecal occult blood testing (FOBT), endoscopy (including sigmoidoscopy and colonoscopy), barium enema and virtual colonoscopy were considered. Although most clinical efficacy data are available for FOBT and sigmoidoscopy, there are limitations to programs based on these strategies. FOBT has a high false positive rate and a low detection yield, and even a combination of these strategies will miss 24% of cancers. Colonoscopy is the best strategy to both detect and remove polyps and to diagnose colorectal cancer, with double contrast barium enema also being a sensitive detection method. The Task Force recommended the establishment, in Quebec, of a screening program with five- to 10-yearly double contrast barium enema or 10-yearly colonoscopy for individuals aged 50 years or older at low risk. The program should include outcome monitoring, public and professional education to increase awareness and promote compliance, and central coordination with other provincial programs. The program should be evaluated; specific billing codes for screening for colorectal cancer would help facilitate this. Formal feasibility, effectiveness and cost-effectiveness studies in Quebec are now warranted.

Barium Sulfate↗
PubMed2003

The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia: the Canadian Adult Dyspepsia Empiric Treatment - Prompt Endoscopy (CADET-PE) study.

BACKGROUND: Uninvestigated dyspepsia is common in family practice. The prevalence of clinically significant upper gastrointestinal findings (CSFs) in adult uninvestigated dyspepsia patients, and their predictability based on history, is unknown. METHODS: Prompt endoscopy was performed within 10 days of referral, in 1040 adult patients presenting with uninvestigated dyspepsia at 49 Canadian family practitioner centres. Subsequent management strategies during a 6-month follow-up period were determined by the individual family practitioners. RESULTS: CSFs were identified in 58% (603/1040) of patients. Erosive oesophagitis was most common (43%; N = 451); peptic ulcer was uncommon (5.3%; N = 55). Alarm symptoms were uncommon (2.8%; N = 29). Most patients had at least three dyspepsia symptoms, more than 80% had at least six, and approximately half had eight or more. Based on the dominant symptom, 463 (45%) patients had ulcer-like, 393 (38%) had reflux-like and 184 (18%) had dysmotility-like dyspepsia. The patients' dominant symptom was not predictive of endoscopic findings. Oesophagitis was more common in those with dominant reflux-like symptoms and was the most common finding in all subgroups. The prevalence of gastroduodenal findings was similar in all symptom subgroups. Helicobacter pylori (H. pylori) infection (30%; 301/1013) was associated with gastroduodenal findings. CONCLUSIONS: Dyspepsia subclassifications, based on dominant symptom, are of limited value in predicting the presence and nature of CSFs. Oesophagitis was by far the most common diagnosis (43% of patients). CSFs were common in uninvestigated dyspepsia patients and their nature suggests patients could be initially treated effectively, without endoscopy, using empirical acid suppressive therapy.

Adolescent↗
PubMed2003

Helicobacter DNA in bile: correlation with hepato-biliary diseases.

BACKGROUND: Helicobacter has been identified in isolated cases of hepato-biliary diseases, but its role in the pathogenesis of these conditions remains unclear. AIM: To determine whether Helicobacter could be detected in bile obtained at endoscopic retrograde cholangiopancreatography, and to evaluate the prevalence of this infection in patients with hepato-biliary diseases. METHODS: Bile was collected from 125 patients with various hepato-biliary diseases undergoing endoscopic retrograde cholangiopancreatography. Among them, 75 were diagnosed with biliary stones, 15 with pancreatico-biliary malignancies and four with primary sclerosing cholangitis. The detection of Helicobacter in DNA extracted from these bile samples was performed using Helicobacter genus-specific primers (capable of detecting 100-1000 organisms/mL). RESULTS: Helicobacter was detected in all positive controls. Only three samples had polymerase chain reaction inhibitors. All remaining bile samples (122 patients with hepato-biliary diseases) were negative for Helicobacter DNA. CONCLUSIONS: Helicobacter can be detected in bile samples using polymerase chain reaction. This infection, however, was not present in any of our patients diagnosed with gallstones or hepato-biliary malignancies, raising doubt as to the possible association between Helicobacter and these entities. Given the low sample size of patients with primary sclerosing cholangitis, more studies are required to determine whether an association exists with this condition.

Adolescent↗
PubMed2003

The role of intravenous proton pump inhibitors in the modern management of nonvariceal upper gastrointestinal bleeding.

Upper gastrointestinal (GI) bleeding is a common cause of hospitalization and despite effective endoscopic treatments, it is responsible for a significant societal burden due to the associated morbidity, mortality and financial implications. As it has long been hypothesized that acid suppression may help to improve outcomes of patients with gastroduodenal ulcer bleeding, acid-suppressing agents such as histamine-2 receptor antagonists (H(2)RAs) and intravenous (i.v.) proton pump inhibitors (PPIs) have been the subject of study. However, results for H(2)RAs show little if any improvement in outcomes, which may be explained by their insufficient acid suppression and the existence of rapid drug tolerance. The advent of i.v. proton pump inhibition has made possible a more profound and sustained, predictable acid suppression without the development of tolerance to the drug. Recently published studies on the use of i.v. PPIs in over 1,500 patients have shown that they have an excellent safety profile. Cost-effectiveness decision models have also suggested, in a preliminary fashion, their cost- effectiveness for use following endoscopic hemostasis in patients with bleeding ulcers. The Canadian Registry of Patients with Upper Gastrointestinal Bleeding Undergoing Endoscopy (RUGBE) recorded information on patient characteristics, diagnosis and treatment from 1999-2002 and preliminary data indicate protective effects of endoscopic treatment and PPI use in specific patient subgroups. Randomized trials and meta-analyses have shown that acute high-dose i.v. PPI administration leads to improvements in patients undergoing endoscopic hemostasis for bleeding gastroduodenal ulcers and who also show high risk for rebleeding. However, the optimum dose, timing of administration and subgroups of patients who will benefit most from such treatment need to be further characterized.

Anti-Ulcer Agents↗