Youssef Toubouti - Academia.edu (original) (raw)

Papers by Youssef Toubouti

Research paper thumbnail of Coefficient of Friction of Human Corneal Tissue

Cornea, 2015

A novel property evaluation methodology was used to determine the elusive value for the human cor... more A novel property evaluation methodology was used to determine the elusive value for the human corneal coefficient of friction (CoF). Using a microtribometer on 28 fresh human donor corneas with intact epithelia, the CoF was determined in 4 test solutions (≥5 corneas/solution): tear-mimicking solution (TMS) in borate-buffered saline (TMS-PS), TMS in phosphate-buffered saline (TMS-PBS), TMS with HEPES-buffered saline (TMS-HEPES), and tear-like fluid in PBS (TLF-PBS). Mean (SD) CoF values ranged from 0.006 to 0.015 and were 0.013 (0.010) in TMS-PS, 0.006 (0.003) in TMS-PBS, 0.014 (0.005) in TMS-HEPES, and 0.015 (0.009) in TLF-PBS. Statistically significant differences were shown for TMS-PBS versus TLF (P = 0.0424) and TMS-PBS versus TMS-HEPES (P = 0.0179), but not for TMS-PBS versus TMS-PS (P = 0.2389). Successful measurement of the fresh human corneal tissue CoF was demonstrated, with values differing in the evaluated buffer solutions, within this limited sample size.

Research paper thumbnail of Are medications that affect platelet function associated with bleeding following therapeutic endoscopy? a case-control study

American Journal of Gastroenterology, 2003

Research paper thumbnail of The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): Endoscopic Hemostasis and Proton Pump Inhibition are Associated with Improved Outcomes in a Real-Life Setting

The American Journal of Gastroenterology, 2004

From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE)... more From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), we determined clinical outcomes and explored the roles of endoscopic and pharmacologic therapies in a contemporary real-life setting.

Research paper thumbnail of Therapy switching and associated costs in elderly patients receiving COX-2 selective inhibitors or non-selective non-steroidal anti-inflammatory drugs in Quebec, Canada

Rheumatology, 2006

Objectives. Lack of efficacy or tolerability of some non-steroidal anti-inflammatory drugs (NSAID... more Objectives. Lack of efficacy or tolerability of some non-steroidal anti-inflammatory drugs (NSAIDs) may lead to switching between non-selective NSAIDs (nsNSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs), potentially increasing treatment costs due to additional physician visits and wastage of medication. This study assessed drug switching and associated costs among elderly chronic NSAID users. Methods. Data for patients who filled their first prescription for a coxib or nsNSAID in 2001 were obtained from the Quebec Health Insurance Agency. Follow-up was terminated at the earliest of: 1 yr, the first day without NSAID exposure following the index filling date, or death. Patients could switch NSAIDs several times during follow-up. Person-days of exposure were categorized by the NSAID most recently dispensed: rofecoxib, celecoxib, Arthrotec Õ or non-Arthrotec (nA) nsNSAID. Cox regression models compared time to switch between groups, adjusting for patient baseline characteristics. Upon a switch, pills remaining from the previous prescription were considered wasted. The costs of wasted pills and switch-associated physician visits were estimated. Results. Throughout follow-up, patients filled 38 267 prescriptions for rofecoxib, 31 282 for celecoxib, 1108 for Arthrotec and 4388 for nA-nsNSAIDs. Adjusted hazard ratios (95% confidence interval) for switching versus nA-nsNSAIDs were: rofecoxib, 0.39 (0.35-0.44); celecoxib, 0.43 (0.38-0.48). Compared with nA-nsNSAID prescriptions, adjusted switching-related healthcare costs were 53 and 47% lower on average for rofecoxib and celecoxib prescriptions, respectively. These costs were 34% higher for Arthrotec prescriptions than for nA-nsNSAIDs. Conclusions. Compared with recipients of nsNSAIDs, coxib recipients were less likely to switch medications and had approximately half the adjusted costs for switching-related wasted resources per prescription.

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

Rheumatology, 2006

Objectives. Many elderly patients are prescribed both low-dose aspirin (ASA), for cardiovascular ... more 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.

Research paper thumbnail of Impact of Infliximab on Serum Leptin Levels in Patients with Crohn’s Disease

The Journal of Clinical Endocrinology & Metabolism, 2005

In mice, body weight is regulated by adipocyte-derived leptin. TNFalpha is a critical mediator of... more In mice, body weight is regulated by adipocyte-derived leptin. TNFalpha is a critical mediator of inflammation-induced cachexia in Crohn's disease (CD). The regulation of leptin by TNFalpha is poorly understood in CD. Pharmacological neutralization of TNFalpha with infliximab offers a unique opportunity to study TNFalpha-mediated regulation of leptin in CD patients. We prospectively followed up CD patients treated with infliximab (n = 20). Body composition was assessed before and after treatment at 1 and 4 wk. Serum leptin, IL-6, soluble TNF receptor type II, and soluble intercellular antiadhesion molecule-1 levels were measured as well as cholesterol levels and free urinary cortisol. Because methylprednisolone (MP) increases leptin production in vivo, CD patients treated with MP (n = 9) were studied separately as a positive control group. Infliximab induced clinical remission and a significant decrease in C-reactive protein (P < 0.01) and IL-6 (P < 0.05) levels in all CD patients and increased body weight (P = 0.013) at 4 wk. Leptinemia was significantly increased after infliximab administration at 1 wk (P = 0.014) and 4 wk (P < 0.001). This increase in serum leptin occurred early at 1 wk, when no significant weight and fat mass changes could be observed and was associated with the down-regulation of TNFalpha-regulated mediators, soluble TNF receptor type II (P = 0.015), and soluble intercellular antiadhesion molecule-1 (P = 0.007). Moreover, infliximab increased cholesterol levels at 1 wk (P = 0.001). Twenty-four-hour cortisol secretion was not altered by infliximab. Leptinemia increased at 1 wk after MP administration (P = 0.028). Infliximab increases leptinemia in CD. This study suggests that TNFalpha exerts major inhibitory actions on leptin production in CD patients.

Research paper thumbnail of Combination of Hemoclipping and Epinephrine Injection Decrease Re-Bleeding and Surgery in High-Risk Patients with Acute Peptic Ulcer Bleeding: A Meta-Analysis

Gastrointestinal Endoscopy, 2007

No abstract is available. To read the body of this article, please view the Full Text online. ...... more No abstract is available. To read the body of this article, please view the Full Text online. ... © 2007 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved. ... Visit SciVerse ScienceDirect to see if you have access via your institution.

Research paper thumbnail of Self-Expanding Metal Stents Confer a Survival Advantage in the Palliation of Distal Malignant Biliary Obstruction

Gastrointestinal Endoscopy, 2005

Background: Plastic and self-expanding metal stents are used to palliate malignant biliary obstru... more Background: Plastic and self-expanding metal stents are used to palliate malignant biliary obstruction, yet can be complicated by occlusion. A previous set of meta-analyses by our group showed that no plastic stent design is superior and that adjuvant therapy does not improve stent patency or prolong patient survival. Objectives: To determine the effect of metal stent technologies compared with plastic stent insertion on duration of stent patency and patient survival in malignant biliary obstruction. Methods: Relevant English RCTs (1980-2004 were assessed by 2 reviewers for methodological quality using a validity assessment score created for this analysis. Data were abstracted regarding patient characteristics of stent insertion (ERCP vs. percutaneous) for distal malignant biliary obstruction, excluding hepatic metastases. Only trials with sufficient statistical information were included. The main outcomes were median stent occlusion and median patient survival. The difference of log-transformed median stent patency or survival ratio of the treatment stent vs. control was calculated for each study. Data were pooled using a random effect model and then re-transformed to the original scale to provide pooled estimates and 95% CI. Sensitivity analysis was done. SAS software (v 8.2) was used for statistical analysis. Results: A meta-analysis of 3 trials with 184 patients treated with plastic vs. self-expanding metal stent insertion showed a significant benefit for metal stents in terms of median patency (ratio 0.3, 95% CI 0.131 to 0.599 p Z 0.001). A survival advantage was also noted that favored metal stents (0.69, p Z 0.03, 95% CI 0.486 to 0.968). Conclusions: The use of metal stents results in a prolonged median patency when compared with plastic, which confirms results of individual trials. The use of SEMS was shown in this meta-analysis to provide a survival advantage when compared to plastic stents-this has never been shown in individual trials, probably due to insufficient statistical power but bears significant clinical implications. Additional high quality clinical data are required to assess this important finding.

Research paper thumbnail of Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses

Gastrointestinal Endoscopy, 2009

Background and Objective: Optimal endoscopic hemostasis remains undetermined. This was a systemat... more Background and Objective: Optimal endoscopic hemostasis remains undetermined. This was a systematic review of contemporary methods of endoscopic hemostasis for patients with bleeding ulcers that exhibited high-risk stigmata.

Research paper thumbnail of Newer endoscopic therapies decrease both re-bleeding and mortality in high-risk patients with acute peptic ulcer bleeding: A series of meta-analyses

Gastroenterology, 2003

Folate is a B vitamin that inversely modulates colorectal carcinogenesis. Folate status is also a... more Folate is a B vitamin that inversely modulates colorectal carcinogenesis. Folate status is also an important determinant in chemotherapeutic response. Mediating the transfer of onecarbon moieties is the sole biochemical function known for folate, and in this role folate plays a critical role in DNA synthesis, repair and methylation This study determined the gene expression profiles induced by tolate deficiency in 2 human colon adenocarcinoma cell lines, HCT116 and Caco2. Cells were grown in either standard (2.3 ~tM Mate) or folate deficient (0 ~M) RPMI medium for 20 days. Folate-deficient HCTll6 and Caco2 cells showed sigmficantly reduced growth rates and had sigmficantly decreased (by 80-90%) intracellular folate concentrations compared with corresponding folate-sufficient ceils (P<O.001 ). The deoxyuridine suppression test confirmed functionally significant intracellular folate depletion in folate-deficlent cells (P<0.01). Total RNA from folate-deficient and sufficient ceils of each cell line was hybridized onto 2 commercially available human cancer pathway (a panel of key genes involved in 6 biological pathways frequently altered during transformation and tumongenesis) and apoptosis (a panel of key genes involved in apoptosis) cDNA arrays and differentially expressed genes were identified RT-PCR analysis was used to confirm the results of cDNA array. A total of 13 and 22 cancer pathway genes were differential expressed in folate-defictent HCT116 and Caco2 cells, respectively, compared with corresponding folate-sufficient cells; 4 genes were differentially expressed in both folatedeficient ceils Most notably affected changes were upregulated ATM and downregulated MDM2 in folate-deficient Caco2 cells, upregulated p21 in folate-deficient HCT 116 cells and upregulated b-catenin and VEGF in both folate-deficient ceils. A total of 5 and 12 apoptosis genes were difterentially expressed in folate-deficient HCT 116 and Caco2 cells, respectively, compared with corresponding folate-sufficient cells; 1 gene was differentially expressed in both fofate-deficient cells. Most significantly altered changes were downregulated MDM2 and BAX in folate-deficient Caco2 cells and upregulated B1RC3 in both folate-deficient HCT116 and Caco2 cells. These data suggest that folate deficiency affects the expression of key genes that are related to cell cycle control, DNA damage and repair, apoptosis, signal transduction and angiogenesis in colon cancer cells in a cell-specific manner.

Research paper thumbnail of High dose intravenous proton pump inhibition decrease both re-bleeding and mortality in high-risk patients with acute peptic ulcer bleeding: A series of meta-analyses

Gastroenterology, 2003

« PreviousNext »Gastroenterology Volume 124, Issue 4, Supplement 1 , Page A625, April 2003.High d... more « PreviousNext »Gastroenterology Volume 124, Issue 4, Supplement 1 , Page A625, April 2003.High dose intravenous proton pump inhibition decrease both re-bleeding and mortality inhigh-risk patients with acute peptic ulcer bleeding: A series of meta-analyses. ...

Research paper thumbnail of The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence

Gastroenterology, 2003

Colorectal cancer is one of the leading causes of cancer death. Most colorectal cancers are belie... more Colorectal cancer is one of the leading causes of cancer death. Most colorectal cancers are believed to develop from colorectal adenomas. We examined the effect of the selective cyclooxygenase-2 inhibitors rofecoxib and celecoxib, nonselective nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen on colorectal neoplasia (colorectal cancer, colorectal adenoma, or both). Methods: This was a nested case-control study, which used data from a government insurance database on patients 65 years and older who underwent a diagnostic test or procedure for colorectal neoplasia between January and June 2001. Logistic regression models were used to determine the effect of exposure to the drugs of interest for at least 3 months on the occurrence or recurrence of colorectal neoplasia. Results: The control group included 2568 patients found to be free of colorectal neoplasia; 730 patients were diagnosed with colorectal adenoma, and 179 were diagnosed with colorectal cancer. Patients more likely to have colorectal adenoma (odds ratio, 95% confidence interval) were those diagnosed with colorectal adenoma (4.12, 3.27-5.18) or colorectal cancer (3.74, 2.32-6.03) in the previous 1-3 years and those with hemorrhage of the rectum or unspecified anemia in the prior month (3.19, 2.46 -4.12). Exposures to rofecoxib (0.67, 0.46 -0.98) and nonselective nonsteroidal anti-inflammatory drugs (0.41, 0.21-0.83) reduced the risk of colorectal adenoma. Rofecoxib, celecoxib, and nonselective nonsteroidal anti-inflammatory drugs were all protective against both neoplasias (0.64, 0.45-0.91; 0.73, 0.54 -0.99; and 0.47, 0.26 -0.86, respectively). Conclusions: Rofecoxib, celecoxib, and nonselective nonsteroidal antiinflammatory drugs seem to protect against the development of colorectal neoplasia.

Research paper thumbnail of Retrospective analysis of utilization patterns and cost implications of coxibs among seniors in Quebec, Canada: What is the potential impact of the withdrawal of rofecoxib?

Arthritis & Rheumatism, 2006

Objective. In September 2004, the manufacturer of rofecoxib announced a voluntary worldwide withd... more Objective. In September 2004, the manufacturer of rofecoxib announced a voluntary worldwide withdrawal of the drug. The impact of this withdrawal on drug budgets is unclear. This study evaluated average daily doses and costs of rofecoxib and celecoxib and concomitant use of gastroprotective agents (GPAs) in elderly patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in Quebec, prior to the rofecoxib withdrawal. Methods. This retrospective cohort study used prescription drug and medical service data from the Quebec government health agency administrative database and included coxib users >66 years of age with OA or RA who filled >3 consecutive rofecoxib or celecoxib prescriptions in 2001-2002. Results were adjusted for gastrointestinal risk factors and other patient baseline characteristics. Results. Data were analyzed for 11,975 rofecoxib and 12,480 celecoxib users. Mean daily dosages were 20.7 mg for rofecoxib and 231.3 mg for celecoxib. Rofecoxib users consumed a mean ؎ SD of 0.95 ؎ 0.43 pills per day, and celecoxib users took 1.34 ؎ 0.65 pills per day. Mean ؎ SD unadjusted daily acquisition costs were 1.18؎1.18 ؎ 1.18؎0.53 (Canadian) for rofecoxib and 1.45؎1.45 ؎ 1.45؎0.74 for celecoxib. After adjusting for patient baseline characteristics, the mean daily acquisition cost for rofecoxib was $0.25 lower than for celecoxib. Rofecoxib users were less likely than celecoxib users to fill a GPA coprescription (odds ratio 0.88; 95% confidence interval 0.81, 0.95). Subgroup analyses yielded comparable results.

Research paper thumbnail of Meta-analysis: proton-pump inhibition in high-risk patients with acute peptic ulcer bleeding

Alimentary Pharmacology and Therapeutics, 2005

Background: Recent data suggest that profound acid suppression may improve outcomes of patients i... more 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.

Research paper thumbnail of The safety of endoscopic sphincterotomy in patients receiving antiplatelet agents - a case-control study

Alimentary Pharmacology & Therapeutics, 2006

To determine whether antiplatelet agents are associated with endoscopic sphincterotomy-related ha... more To determine whether antiplatelet agents are associated with endoscopic sphincterotomy-related haemorrhage as few well-controlled data exist on this controversial issue.

Research paper thumbnail of Impact of a general practitioner educational intervention on osteoarthritis treatment in an elderly population

The American Journal of Medicine, 2005

We examined whether a continuing medical education intervention increased general practitioners&a... more We examined whether a continuing medical education intervention increased general practitioners&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; ability to select the proper pharmacological treatment for patients with osteoarthritis. Eight towns in Quebec, Canada were randomly allocated to one of four intervention options, workshop and decision tree, workshop, decision tree, or no intervention. All general practitioners practicing in each town were eligible to participate. We evaluated all dispensed prescriptions for either a cyclooxygenase (COX)-2 inhibitor, nonselective nonsteroidal anti-inflammatory drug or acetaminophen written by eligible general practitioners between May 2000 and June 2001 to elderly patients suffering from osteoarthritis. We used a multi-level Bayesian hierarchical model to assess the impact of the interventions on prescription adequacy. We analyzed 5318 dispensed prescriptions written by 249 general practitioners in the five-month preintervention period and 4610 dispensed prescriptions written by the same physicians in the five-month postintervention period. A score of zero or one was given to every prescription, with one indicating prescription adequacy according to guidelines provided during the interventions. Bayesian hierarchical models showed some improvement in scores in the post- versus preintervention periods in all four groups. The probability of an improvement in the towns allocated the workshop and decision tree over the control was 94%, compared with 74% in the workshop group and 55% in the decision tree group. An interactive approach offered by peers and complemented by easy to use guidelines may enhance the general practitioner&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s ability to manage osteoarthritis patients.

Research paper thumbnail of Coefficient of Friction of Human Corneal Tissue

Cornea, 2015

A novel property evaluation methodology was used to determine the elusive value for the human cor... more A novel property evaluation methodology was used to determine the elusive value for the human corneal coefficient of friction (CoF). Using a microtribometer on 28 fresh human donor corneas with intact epithelia, the CoF was determined in 4 test solutions (≥5 corneas/solution): tear-mimicking solution (TMS) in borate-buffered saline (TMS-PS), TMS in phosphate-buffered saline (TMS-PBS), TMS with HEPES-buffered saline (TMS-HEPES), and tear-like fluid in PBS (TLF-PBS). Mean (SD) CoF values ranged from 0.006 to 0.015 and were 0.013 (0.010) in TMS-PS, 0.006 (0.003) in TMS-PBS, 0.014 (0.005) in TMS-HEPES, and 0.015 (0.009) in TLF-PBS. Statistically significant differences were shown for TMS-PBS versus TLF (P = 0.0424) and TMS-PBS versus TMS-HEPES (P = 0.0179), but not for TMS-PBS versus TMS-PS (P = 0.2389). Successful measurement of the fresh human corneal tissue CoF was demonstrated, with values differing in the evaluated buffer solutions, within this limited sample size.

Research paper thumbnail of Are medications that affect platelet function associated with bleeding following therapeutic endoscopy? a case-control study

American Journal of Gastroenterology, 2003

Research paper thumbnail of The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): Endoscopic Hemostasis and Proton Pump Inhibition are Associated with Improved Outcomes in a Real-Life Setting

The American Journal of Gastroenterology, 2004

From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE)... more From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), we determined clinical outcomes and explored the roles of endoscopic and pharmacologic therapies in a contemporary real-life setting.

Research paper thumbnail of Therapy switching and associated costs in elderly patients receiving COX-2 selective inhibitors or non-selective non-steroidal anti-inflammatory drugs in Quebec, Canada

Rheumatology, 2006

Objectives. Lack of efficacy or tolerability of some non-steroidal anti-inflammatory drugs (NSAID... more Objectives. Lack of efficacy or tolerability of some non-steroidal anti-inflammatory drugs (NSAIDs) may lead to switching between non-selective NSAIDs (nsNSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs), potentially increasing treatment costs due to additional physician visits and wastage of medication. This study assessed drug switching and associated costs among elderly chronic NSAID users. Methods. Data for patients who filled their first prescription for a coxib or nsNSAID in 2001 were obtained from the Quebec Health Insurance Agency. Follow-up was terminated at the earliest of: 1 yr, the first day without NSAID exposure following the index filling date, or death. Patients could switch NSAIDs several times during follow-up. Person-days of exposure were categorized by the NSAID most recently dispensed: rofecoxib, celecoxib, Arthrotec Õ or non-Arthrotec (nA) nsNSAID. Cox regression models compared time to switch between groups, adjusting for patient baseline characteristics. Upon a switch, pills remaining from the previous prescription were considered wasted. The costs of wasted pills and switch-associated physician visits were estimated. Results. Throughout follow-up, patients filled 38 267 prescriptions for rofecoxib, 31 282 for celecoxib, 1108 for Arthrotec and 4388 for nA-nsNSAIDs. Adjusted hazard ratios (95% confidence interval) for switching versus nA-nsNSAIDs were: rofecoxib, 0.39 (0.35-0.44); celecoxib, 0.43 (0.38-0.48). Compared with nA-nsNSAID prescriptions, adjusted switching-related healthcare costs were 53 and 47% lower on average for rofecoxib and celecoxib prescriptions, respectively. These costs were 34% higher for Arthrotec prescriptions than for nA-nsNSAIDs. Conclusions. Compared with recipients of nsNSAIDs, coxib recipients were less likely to switch medications and had approximately half the adjusted costs for switching-related wasted resources per prescription.

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

Rheumatology, 2006

Objectives. Many elderly patients are prescribed both low-dose aspirin (ASA), for cardiovascular ... more 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.

Research paper thumbnail of Impact of Infliximab on Serum Leptin Levels in Patients with Crohn’s Disease

The Journal of Clinical Endocrinology & Metabolism, 2005

In mice, body weight is regulated by adipocyte-derived leptin. TNFalpha is a critical mediator of... more In mice, body weight is regulated by adipocyte-derived leptin. TNFalpha is a critical mediator of inflammation-induced cachexia in Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (CD). The regulation of leptin by TNFalpha is poorly understood in CD. Pharmacological neutralization of TNFalpha with infliximab offers a unique opportunity to study TNFalpha-mediated regulation of leptin in CD patients. We prospectively followed up CD patients treated with infliximab (n = 20). Body composition was assessed before and after treatment at 1 and 4 wk. Serum leptin, IL-6, soluble TNF receptor type II, and soluble intercellular antiadhesion molecule-1 levels were measured as well as cholesterol levels and free urinary cortisol. Because methylprednisolone (MP) increases leptin production in vivo, CD patients treated with MP (n = 9) were studied separately as a positive control group. Infliximab induced clinical remission and a significant decrease in C-reactive protein (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and IL-6 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) levels in all CD patients and increased body weight (P = 0.013) at 4 wk. Leptinemia was significantly increased after infliximab administration at 1 wk (P = 0.014) and 4 wk (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). This increase in serum leptin occurred early at 1 wk, when no significant weight and fat mass changes could be observed and was associated with the down-regulation of TNFalpha-regulated mediators, soluble TNF receptor type II (P = 0.015), and soluble intercellular antiadhesion molecule-1 (P = 0.007). Moreover, infliximab increased cholesterol levels at 1 wk (P = 0.001). Twenty-four-hour cortisol secretion was not altered by infliximab. Leptinemia increased at 1 wk after MP administration (P = 0.028). Infliximab increases leptinemia in CD. This study suggests that TNFalpha exerts major inhibitory actions on leptin production in CD patients.

Research paper thumbnail of Combination of Hemoclipping and Epinephrine Injection Decrease Re-Bleeding and Surgery in High-Risk Patients with Acute Peptic Ulcer Bleeding: A Meta-Analysis

Gastrointestinal Endoscopy, 2007

No abstract is available. To read the body of this article, please view the Full Text online. ...... more No abstract is available. To read the body of this article, please view the Full Text online. ... © 2007 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved. ... Visit SciVerse ScienceDirect to see if you have access via your institution.

Research paper thumbnail of Self-Expanding Metal Stents Confer a Survival Advantage in the Palliation of Distal Malignant Biliary Obstruction

Gastrointestinal Endoscopy, 2005

Background: Plastic and self-expanding metal stents are used to palliate malignant biliary obstru... more Background: Plastic and self-expanding metal stents are used to palliate malignant biliary obstruction, yet can be complicated by occlusion. A previous set of meta-analyses by our group showed that no plastic stent design is superior and that adjuvant therapy does not improve stent patency or prolong patient survival. Objectives: To determine the effect of metal stent technologies compared with plastic stent insertion on duration of stent patency and patient survival in malignant biliary obstruction. Methods: Relevant English RCTs (1980-2004 were assessed by 2 reviewers for methodological quality using a validity assessment score created for this analysis. Data were abstracted regarding patient characteristics of stent insertion (ERCP vs. percutaneous) for distal malignant biliary obstruction, excluding hepatic metastases. Only trials with sufficient statistical information were included. The main outcomes were median stent occlusion and median patient survival. The difference of log-transformed median stent patency or survival ratio of the treatment stent vs. control was calculated for each study. Data were pooled using a random effect model and then re-transformed to the original scale to provide pooled estimates and 95% CI. Sensitivity analysis was done. SAS software (v 8.2) was used for statistical analysis. Results: A meta-analysis of 3 trials with 184 patients treated with plastic vs. self-expanding metal stent insertion showed a significant benefit for metal stents in terms of median patency (ratio 0.3, 95% CI 0.131 to 0.599 p Z 0.001). A survival advantage was also noted that favored metal stents (0.69, p Z 0.03, 95% CI 0.486 to 0.968). Conclusions: The use of metal stents results in a prolonged median patency when compared with plastic, which confirms results of individual trials. The use of SEMS was shown in this meta-analysis to provide a survival advantage when compared to plastic stents-this has never been shown in individual trials, probably due to insufficient statistical power but bears significant clinical implications. Additional high quality clinical data are required to assess this important finding.

Research paper thumbnail of Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses

Gastrointestinal Endoscopy, 2009

Background and Objective: Optimal endoscopic hemostasis remains undetermined. This was a systemat... more Background and Objective: Optimal endoscopic hemostasis remains undetermined. This was a systematic review of contemporary methods of endoscopic hemostasis for patients with bleeding ulcers that exhibited high-risk stigmata.

Research paper thumbnail of Newer endoscopic therapies decrease both re-bleeding and mortality in high-risk patients with acute peptic ulcer bleeding: A series of meta-analyses

Gastroenterology, 2003

Folate is a B vitamin that inversely modulates colorectal carcinogenesis. Folate status is also a... more Folate is a B vitamin that inversely modulates colorectal carcinogenesis. Folate status is also an important determinant in chemotherapeutic response. Mediating the transfer of onecarbon moieties is the sole biochemical function known for folate, and in this role folate plays a critical role in DNA synthesis, repair and methylation This study determined the gene expression profiles induced by tolate deficiency in 2 human colon adenocarcinoma cell lines, HCT116 and Caco2. Cells were grown in either standard (2.3 ~tM Mate) or folate deficient (0 ~M) RPMI medium for 20 days. Folate-deficient HCTll6 and Caco2 cells showed sigmficantly reduced growth rates and had sigmficantly decreased (by 80-90%) intracellular folate concentrations compared with corresponding folate-sufficient ceils (P<O.001 ). The deoxyuridine suppression test confirmed functionally significant intracellular folate depletion in folate-deficlent cells (P<0.01). Total RNA from folate-deficient and sufficient ceils of each cell line was hybridized onto 2 commercially available human cancer pathway (a panel of key genes involved in 6 biological pathways frequently altered during transformation and tumongenesis) and apoptosis (a panel of key genes involved in apoptosis) cDNA arrays and differentially expressed genes were identified RT-PCR analysis was used to confirm the results of cDNA array. A total of 13 and 22 cancer pathway genes were differential expressed in folate-defictent HCT116 and Caco2 cells, respectively, compared with corresponding folate-sufficient cells; 4 genes were differentially expressed in both folatedeficient ceils Most notably affected changes were upregulated ATM and downregulated MDM2 in folate-deficient Caco2 cells, upregulated p21 in folate-deficient HCT 116 cells and upregulated b-catenin and VEGF in both folate-deficient ceils. A total of 5 and 12 apoptosis genes were difterentially expressed in folate-deficient HCT 116 and Caco2 cells, respectively, compared with corresponding folate-sufficient cells; 1 gene was differentially expressed in both fofate-deficient cells. Most significantly altered changes were downregulated MDM2 and BAX in folate-deficient Caco2 cells and upregulated B1RC3 in both folate-deficient HCT116 and Caco2 cells. These data suggest that folate deficiency affects the expression of key genes that are related to cell cycle control, DNA damage and repair, apoptosis, signal transduction and angiogenesis in colon cancer cells in a cell-specific manner.

Research paper thumbnail of High dose intravenous proton pump inhibition decrease both re-bleeding and mortality in high-risk patients with acute peptic ulcer bleeding: A series of meta-analyses

Gastroenterology, 2003

« PreviousNext »Gastroenterology Volume 124, Issue 4, Supplement 1 , Page A625, April 2003.High d... more « PreviousNext »Gastroenterology Volume 124, Issue 4, Supplement 1 , Page A625, April 2003.High dose intravenous proton pump inhibition decrease both re-bleeding and mortality inhigh-risk patients with acute peptic ulcer bleeding: A series of meta-analyses. ...

Research paper thumbnail of The cyclooxygenase-2-selective inhibitors rofecoxib and celecoxib prevent colorectal neoplasia occurrence and recurrence

Gastroenterology, 2003

Colorectal cancer is one of the leading causes of cancer death. Most colorectal cancers are belie... more Colorectal cancer is one of the leading causes of cancer death. Most colorectal cancers are believed to develop from colorectal adenomas. We examined the effect of the selective cyclooxygenase-2 inhibitors rofecoxib and celecoxib, nonselective nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen on colorectal neoplasia (colorectal cancer, colorectal adenoma, or both). Methods: This was a nested case-control study, which used data from a government insurance database on patients 65 years and older who underwent a diagnostic test or procedure for colorectal neoplasia between January and June 2001. Logistic regression models were used to determine the effect of exposure to the drugs of interest for at least 3 months on the occurrence or recurrence of colorectal neoplasia. Results: The control group included 2568 patients found to be free of colorectal neoplasia; 730 patients were diagnosed with colorectal adenoma, and 179 were diagnosed with colorectal cancer. Patients more likely to have colorectal adenoma (odds ratio, 95% confidence interval) were those diagnosed with colorectal adenoma (4.12, 3.27-5.18) or colorectal cancer (3.74, 2.32-6.03) in the previous 1-3 years and those with hemorrhage of the rectum or unspecified anemia in the prior month (3.19, 2.46 -4.12). Exposures to rofecoxib (0.67, 0.46 -0.98) and nonselective nonsteroidal anti-inflammatory drugs (0.41, 0.21-0.83) reduced the risk of colorectal adenoma. Rofecoxib, celecoxib, and nonselective nonsteroidal anti-inflammatory drugs were all protective against both neoplasias (0.64, 0.45-0.91; 0.73, 0.54 -0.99; and 0.47, 0.26 -0.86, respectively). Conclusions: Rofecoxib, celecoxib, and nonselective nonsteroidal antiinflammatory drugs seem to protect against the development of colorectal neoplasia.

Research paper thumbnail of Retrospective analysis of utilization patterns and cost implications of coxibs among seniors in Quebec, Canada: What is the potential impact of the withdrawal of rofecoxib?

Arthritis & Rheumatism, 2006

Objective. In September 2004, the manufacturer of rofecoxib announced a voluntary worldwide withd... more Objective. In September 2004, the manufacturer of rofecoxib announced a voluntary worldwide withdrawal of the drug. The impact of this withdrawal on drug budgets is unclear. This study evaluated average daily doses and costs of rofecoxib and celecoxib and concomitant use of gastroprotective agents (GPAs) in elderly patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in Quebec, prior to the rofecoxib withdrawal. Methods. This retrospective cohort study used prescription drug and medical service data from the Quebec government health agency administrative database and included coxib users >66 years of age with OA or RA who filled >3 consecutive rofecoxib or celecoxib prescriptions in 2001-2002. Results were adjusted for gastrointestinal risk factors and other patient baseline characteristics. Results. Data were analyzed for 11,975 rofecoxib and 12,480 celecoxib users. Mean daily dosages were 20.7 mg for rofecoxib and 231.3 mg for celecoxib. Rofecoxib users consumed a mean ؎ SD of 0.95 ؎ 0.43 pills per day, and celecoxib users took 1.34 ؎ 0.65 pills per day. Mean ؎ SD unadjusted daily acquisition costs were 1.18؎1.18 ؎ 1.18؎0.53 (Canadian) for rofecoxib and 1.45؎1.45 ؎ 1.45؎0.74 for celecoxib. After adjusting for patient baseline characteristics, the mean daily acquisition cost for rofecoxib was $0.25 lower than for celecoxib. Rofecoxib users were less likely than celecoxib users to fill a GPA coprescription (odds ratio 0.88; 95% confidence interval 0.81, 0.95). Subgroup analyses yielded comparable results.

Research paper thumbnail of Meta-analysis: proton-pump inhibition in high-risk patients with acute peptic ulcer bleeding

Alimentary Pharmacology and Therapeutics, 2005

Background: Recent data suggest that profound acid suppression may improve outcomes of patients i... more 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.

Research paper thumbnail of The safety of endoscopic sphincterotomy in patients receiving antiplatelet agents - a case-control study

Alimentary Pharmacology & Therapeutics, 2006

To determine whether antiplatelet agents are associated with endoscopic sphincterotomy-related ha... more To determine whether antiplatelet agents are associated with endoscopic sphincterotomy-related haemorrhage as few well-controlled data exist on this controversial issue.

Research paper thumbnail of Impact of a general practitioner educational intervention on osteoarthritis treatment in an elderly population

The American Journal of Medicine, 2005

We examined whether a continuing medical education intervention increased general practitioners&a... more We examined whether a continuing medical education intervention increased general practitioners&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; ability to select the proper pharmacological treatment for patients with osteoarthritis. Eight towns in Quebec, Canada were randomly allocated to one of four intervention options, workshop and decision tree, workshop, decision tree, or no intervention. All general practitioners practicing in each town were eligible to participate. We evaluated all dispensed prescriptions for either a cyclooxygenase (COX)-2 inhibitor, nonselective nonsteroidal anti-inflammatory drug or acetaminophen written by eligible general practitioners between May 2000 and June 2001 to elderly patients suffering from osteoarthritis. We used a multi-level Bayesian hierarchical model to assess the impact of the interventions on prescription adequacy. We analyzed 5318 dispensed prescriptions written by 249 general practitioners in the five-month preintervention period and 4610 dispensed prescriptions written by the same physicians in the five-month postintervention period. A score of zero or one was given to every prescription, with one indicating prescription adequacy according to guidelines provided during the interventions. Bayesian hierarchical models showed some improvement in scores in the post- versus preintervention periods in all four groups. The probability of an improvement in the towns allocated the workshop and decision tree over the control was 94%, compared with 74% in the workshop group and 55% in the decision tree group. An interactive approach offered by peers and complemented by easy to use guidelines may enhance the general practitioner&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s ability to manage osteoarthritis patients.