Elham Rahme

Congenital Heart Disease in the General Population Changing Prevalence and Age Distribution

Background— Empirical data on the changing epidemiology of congenital heart disease (CHD) are scant. We determined the prevalence, age distribution, and proportion of adults and children with severe and other forms of CHD in the general population from 1985 to 2000. Methods and Results— Where healthcare access is universal, we used administrative databases that systematically recorded all diagnoses and claims. Diagnostic codes conformed to the International Classification of Disease, ninth revision. Severe CHD was defined as tetralogy of Fallot, truncus arteriosus, transposition complexes, endocardial cushion defects, and univentricular heart. Prevalence of severe and other CHD lesions was determined in l985, 1990, 1995, and 2000 using population numbers in Quebec. Children were subjects <18 years of age. The prevalence was 4.09 per 1000 adults in the year 2000 for all CHD and 0.38 per 1000 (9%) for those with severe lesions. Female subjects accounted for 57% of the adult CHD population. The median age of all patients with severe CHD was 11 years (interquartile range, 4 to 22 years) in 1985 and 17 years (interquartile range, 10 to 28 years) in 2000 (P<0.0001). The prevalence of severe CHD increased from 1985 to 2000, but the increase in adults was significantly higher than that observed in children. In the year 2000, 49% of those alive with severe CHD were adults. Conclusions— The prevalence in adults and median age of patients with severe CHD increased in the general population from 1985 to 2000. In 2000, there were nearly equal numbers of adults and children with severe CHD.

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

OBJECTIVES: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.METHODS:Analysis of randomly selected patients endoscoped for nonvariceal upper gastrointestinal bleeding at 18 community and tertiary care institutions between 1999 and 2002. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression models identified predictors of outcomes.RESULTS:One thousand eight-hundred and sixty-nine patients were included (66 ± 17 yr, 38% female, 2.5 ± 1.6 comorbid conditions, hemoglobin, 96 ± 27 g/L, 54% received a mean of 2.9 ± 1.7 units of blood). Endoscopy was performed within 24 h in 76%, with ulcers (55%) most commonly noted. High-risk endoscopic stigmata and endoscopic therapy were reported in 37%. Rebleeding, surgery, and mortality rates were 14.1%, 6.5%, and 5.4%, respectively. Decreased rebleeding was significantly and independently associated with PPI use (85% of patients, mean daily dose 56 ± 53 mg) in all patients regardless of endoscopic stigmata, (odds ratio (OR):0.53, 95% confidence interval, 95% CI:0.37–0.77) and endoscopic hemostasis in patients with high-risk stigmata (OR:0.39, 95% CI:0.25–0.61). PPI use (OR:0.18, 95% CI:0.04–0.80) and endoscopic therapy (OR:0.31, 95% CI:0.11–0.91) were also each independently associated with decreased mortality in patients with high-risk stigmata.CONCLUSIONS:These results appear to confirm the protective role of endoscopic therapy in patients with high-risk stigmata, and suggest that acute use of PPIs may be associated with a reduction of rebleeding in all patients, and lower mortality in patients with high-risk stigmata. Independent prospective validation of these observational findings is now required.

Magnetic Resonance Cholangiopancreatography: A Meta-Analysis of Test Performance in Suspected Biliary Disease

Context Noninvasive imaging of the biliary tree with magnetic resonance cholangiopancreatography (MRCP) may detect certain abnormalities better than others. Contribution This meta-analysis summarized 67 studies that compared MRCP with other gold standard tests for diagnosing biliary obstruction (for example, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and intraoperative or intravenous cholangiography). Magnetic resonance cholangiopancreatography compared well with most other tests, but it seemed slightly less sensitive for diagnosing stones (92%) and for differentiating benign from malignant obstruction (85%) than it was for identifying the presence (99%) and level (96%) of biliary obstruction. Cautions Study quality varied, and some sensitivity estimates had wide confidence intervals. The Editors Biliary diseases and conditions associated with biliary obstruction are a major cause of morbidity and mortality in North America. The accurate diagnosis of the presence and cause of biliary obstruction is key to the cost-effective work-up of patients with suspected biliary disease. Since its introduction in 1968, endoscopic retrograde cholangiopancreatography (ERCP) has become the gold standard in this setting. However, 1.3% to 9% of patients undergoing ERCP will have clinically significant pancreatitis, and 0.2% to 0.5% of patients will die of procedural complications (1-5). In a larger series, diagnostic ERCP was associated with a mortality rate of 0.2% and a moderate to severe pancreatitis rate of 0.7% (1). In 1992, the development of magnetic resonance cholangiopancreatography (MRCP), which used heavy T2-weighting and rapid image acquisition (thus avoiding breathing artifact), allowed the accurate noninvasive imaging of the biliary and pancreatic trees. The weighting involved in selected MRCP sequences is unique because it allows relatively stagnant fluids, such as bile and pancreatic juice, to have a high-signal intensity. Without use of a contrast agent, these fluids appear bright compared with the dark, low-signal intensity of adjacent solid hepatic and pancreatic tissue and fast-flowing fluids (such as circulating blood). Concurrently performed enhanced T1-weighted magnetic resonance imaging (MRI) of the liver and pancreatic parenchyma can complement MRCP by adding important staging information when a malignant disorder is suspected. Although MRCP offered the potential of avoiding ERCP and its attendant risks, evidence for this is lacking because some patients undergoing MRCP will also require ERCP for invasive diagnostic tests (for example, bile sampling or cytologic testing) or for therapy (sphincterotomy, stone removal, or stenting) (6). The possible morbid implication of false-positive and false-negative results also needs to be considered. The identification of clinical scenarios for which MRCP may have limitations is therefore important for the development of adapted clinical guidelines and work-up algorithms in this area. Over the past decade, a plethora of reports have dealt with the accuracy of MRCP in biliary imaging. Most have shown excellent performance in comparison to ERCP or composite gold standards that have included computed tomography (CT), percutaneous transhepatic cholangiography, intraoperative cholangiography, intravenous cholangiography, endoscopic ultrasonography, and surgery, with or without subsequent clinical follow-up (772). However, individually, the studies are too small to allow precise comment on the performance of MRCP in selected diagnostic subgroups, such as patients with suspected stone disease or biliary cancer. In addition, because of variation in study quality, patient samples, MRI technology, and gold standards used, simple pooling of performance characteristics would be inappropriate and potentially misleading. Therefore, we undertook a meta-analysis to better characterize MRCP performance, stratified by clinically important diagnostic scenarios. Methods Search Strategy We searched MEDLINE (from January 1987 to March 2003) and bibliographies using magnetic resonance imaging and biliary tract diseases as Medical Subject Headings terms. The search was a priori restricted to English- and French-language articles. Because of the nature of the articles and subject matter of interest, we believed that MEDLINE would contain all relevant articles and that the use of other databases would be unlikely to reveal additional published studies. We manually screened and assessed abstracts to identify comparative studies with a single or composite gold standard. Most abstracts described articles that were reviews, comparisons of MRI techniques, or case series without comparison with any gold standard (Figure 1). Figure 1. Flowchart of study and abstract exclusions. Inclusion Criteria We included the following types of articles: 1) comparative studies with a defined single or composite gold standard and 2) articles that contained sufficient detail to reconstruct 2 2 tables expressing MRCP results by disease status. Acceptable gold standards included ERCP, intraoperative cholangiography, percutaneous transhepatic cholangiography, intravenous cholangiography, endoscopic ultrasonography, and surgical exploration. We also allowed composite gold standards, including CT and clinical follow-up until clinical and biological abnormalities had resolved or until a diagnosis had been made. If the study type was unclear from the abstract or if no abstract was available but the title suggested a comparative study, the full manuscript was manually reviewed. For bibliographic screening, we also examined relevant reviews. Two international experts were also contacted in an attempt to identify any additional relevant unpublished reports; however, no such reports were found. Exclusion Criteria We excluded case series of patients with a particular diagnosis who were undergoing MRCP and studies in which only patients with positive results on MRCP had other imaging techniques or ERCP to confirm the diagnosis. If a comparative study preselected only patients with a positive test result by using a gold standard to see how MRCP could visualize the abnormalities, we judged the study to be inadequate (even if a group of healthy control persons had been added for comparison). In addition to an artificially set prevalence of disease in such studies and somewhat artificial corresponding predictive values, hand selection of clearly positive and clearly healthy cases may lead to bias. This spectrum bias can occur when a diagnostic test seems to have better performance because more easily diagnosed extremes have been chosen (73, 74). If more than 1 study was included from the same author, we carefully assessed the absence of overlap by using the recruitment periods noted in the manuscript or by contacting the author if the report did not provide these data. Quality Assessment Two authors independently assessed the quality of acceptable manuscripts, and a third author independently settled discrepancies. Studies were graded by using 4 criteria for quality, defined a priori, as described by Irwig and colleagues [75, 76]: 1) blinding, 2) consecutive recruitment of patients, 3) single [versus composite] gold standards, and 4) the nonselective use of the gold standard (that is, the gold standard was performed in all patients). The latter criterion was used to avoid verification bias, which occurs when only abnormal results on the index test lead to the performance of the gold standard to verify the diagnosis (77, 78). To compare the result of MRCP versus that of the gold standard, we then reconstructed 2 2 tables from each study to determine the presence, level, and cause of biliary obstruction, as well as to distinguish benign from malignant obstruction and to detect common bile duct stones. In a particular study, if 22 tables could be reconstructed for more than 1 radiologist, we used the overall results reported in this study, as determined by consensus or a third-party arbitrator, depending on the protocol of the study. Data Stratification and Definition of Imaging End Points We extracted data from the studies and categorized the imaging end points into 4 groupings to diagnose 1) the presence of obstruction; 2) the level of obstruction (here, a diseased patient in terms of the 2 2 table was considered to have hilar or intrahepatic disease, except for the study by Zidi and colleagues [35], which exclusively studied hilar tumors and considered intrahepatic extension to be diseased]; and the presence of either 3) biliary lithiasis or 4) malignancy. Only studies that had more than 5 patients with common bile duct stones were considered in the stone detection subcategory. Potential Confounders We considered 4 other variables, apart from study quality, to be of potential importance for explaining heterogeneity and interstudy variability: 1) imaging end point of the study [presence of obstruction, level of obstruction, presence of common bile duct stones, or presence of malignancy]; 2) clinical context [suspicion of stone, suspicion of malignancy, suspicion of either stone or malignancy, or suspicion of a wide variety of pancreaticobiliary diseases]; 3) MRCP technology era [dichotomized at December 1996, 5 years after its introduction in 1991]; 4) frequency of direct visualization (79-81) of the common bile duct by a conventional gold standard [dichotomized at greater or less than 90% of patients having had ERCP, intraoperative cholangiography, or percutaneous transhepatic cholangiography]; and 4) prevalence of disease. For the MRCP technology era variable, we divided patients into the post-1996 category if most patients seemed to have been recruited after 1 January 1997. Meta-Analytic Statistical Methods and Modeling We assessed the sensitivity and specificity of MRCP by noting the number of true-positive, false-positive, true-negative, and false-negative results. The overall observed sensit

Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis

Background— Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. Methods and Results— We conducted a population-based retrospective cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from 1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin users according to the first prescription filled for warfarin within 30 days after AF hospital discharge. We determined the association between warfarin use and the risk for stroke and bleeding in dialysis and nondialysis patients. The cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among dialysis patients, warfarin users had more congestive heart failure and diabetes mellitus, but fewer prior bleeding events in comparison with the no-warfarin users. Among dialysis patients, warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95% confidence interval, 0.78–1.67) but was associated with a 44% higher risk for bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13–1.85) after adjusting for potential confounders. Propensity score–adjusted analyses yielded similar results. Conclusions— Our results suggest that warfarin use is not beneficial in reducing stroke risk, but it is associated with a higher bleeding risk in patients with AF undergoing dialysis.

Sex Differences in Stroke Risk Among Older Patients With Recently Diagnosed Atrial Fibrillation

CONTEXT Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some studies suggest that undertreatment with warfarin may be a cause. OBJECTIVE To compare utilization patterns of warfarin and the risk of subsequent stroke between older men and women with AF at the population level. DESIGN, SETTING, AND PATIENTS Population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007, using administrative data with linkage between hospital discharge, physicians, and prescription drug claims databases. MAIN OUTCOME MEASURES Risk of stroke. RESULTS The cohort comprised 39,398 men (47.2%) and 44,115 women (52.8%). At admission, women were older and had a higher CHADS(2) (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001). At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin prescription. In adjusted analysis, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001). Adherence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person-years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid conditions, individual components of the CHADS(2) score, and warfarin treatment. CONCLUSION Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use.

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

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. SETTING Randomized trials that evaluated injection, thermocoagulation, clips, or combinations of these were evaluated from MEDLINE, EMBASE, and CENTRAL (1990-2006). PATIENTS A total of 4261 patients were evaluated. OUTCOMES Outcomes were rebleeding (primary), surgery, and mortality (secondary). Summary statistics were determined; publication bias and heterogeneity were sought by using funnel plots or by subgroup analyses and meta-regression. RESULTS Forty-one trials assessed 4261 patients. All endoscopic therapies decreased rebleeding versus pharmacotherapy alone, including sole intravenous (IV) proton pump inhibition (PPI) (OR 0.56 [95% CI, 0.34-0.92]); only one trial assessed high-dose IV PPI. Injection alone was inferior compared with other methods, except for thermal hemostasis (OR 1.02 [95% CI, 0.74-1.40]), with a strong trend of increased rebleeding if 1 injectate is used rather than 2 (OR 1.40 [95% CI, 0.95-2.05]). Injection followed by thermal therapy did not decrease rebleeding compared with clips (OR 0.82 [95% CI, 0.28-2.38]) or thermal therapy alone (OR 0.79 [95% CI, 0.24-2.62]). Subgroup analysis, however, suggested that injection followed by thermal therapy was superior to thermal therapy alone. Clips were superior to thermal therapy (OR 0.24 [95% CI, 0.06-0.95]) but, when followed by injection, were not superior to clips alone (OR 1.30 [95% CI, 0.36-4.76]). Surgery or mortality was not altered in most comparisons. CONCLUSIONS All endoscopic treatments are superior to pharmacotherapy alone; only 1 study assessed high-dose IV PPI. Optimal endoscopic therapies include thermal therapy or clips, either alone or in combination with other methods. Additional data are needed that compare injection followed by thermal therapy to clips alone or clips combined with another method.

Osteoporosis among patients with type 1 and type 2 diabetes.

Both diabetes and fractures are prevalent in adults. The relationship between diabetes and osteoporosis is complex and, although it has been investigated extensively, the subject remains controversial. While low bone mineral density (BMD) is consistently observed in type 1 diabetes, the relationship is less clear in type 2 diabetes, with some studies reporting modestly increased or unchanged BMD. Both type 1 and type 2 diabetes have been associated with a higher risk of fractures. Despite discrepancies between BMD and fracture rates, clinical trials uniformly support the fact that new bone formation and bone microarchitecture and, thus, bone quality, are altered in both types of diabetes. Although a causal association between diabetes and osteoporosis cannot be established on the basis of existing data, it is possible to conclude from many studies and from a better understanding of the physiopathology of diabetes that it can increase the risk of fractures through skeletal (decreased BMD and bone quality) and extraskeletal (increased risk of falls) factors. Even though osteoporosis screening or prophylactic treatment in all patients with type 1 and type 2 diabetes is not being recommended at present, such patient populations should be given general guidelines regarding calcium and vitamin D intakes, exercise and the avoidance of potential risk factors for osteoporosis. The extent of diagnostic and therapeutic interventions should be based on the individuals risk profile for fractures.

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.

Hospitalizations for upper and lower GI events associated with traditional NSAIDs and acetaminophen among the elderly in Quebec, Canada.

BACKGROUND:The risk of upper/lower gastrointestinal (GI) adverse events associated with the concomitant use of traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) with acetaminophen has not been assessed. Among users of these drugs, the concomitant use of proton pump inhibitors (PPIs) with tNSAIDs may reduce the risk of upper GI adverse events, but its effect on lower GI events is not clear.OBJECTIVE:To compare the rates of GI hospitalization (ulceration, perforation, or bleeding in the upper or lower GI tract) among elderly patients taking tNSAIDs or the combination of a tNSAID and acetaminophen with and without a PPI versus those taking acetaminophen alone.METHODS:We conducted a population-based retrospective cohort study using data obtained from the government of Quebec health insurance agency databases and the hospital discharge summary database. Patients of 65 yr of age or older who filled a prescription for acetaminophen or a tNSAID between January 1998 and December 2004 were entered in the cohort at the date of the first filled prescription from either of these medications (index date). Follow-up ended at the first date of a GI hospitalization, death, or the end of the study period.RESULTS:The cohort included 644,183 elderly patients. These patients received 1,778,541 prescriptions for tNSAIDs (315,222, 17.7% with a PPI), 158,711 for the combination of a tNSAID and acetaminophen (40,797, 25.7% with a PPI), 1,597,725 for acetaminophen (>3 g/day) (504,939, 31.6% with a PPI), and 3,641,140 for acetaminophen (≤3 g/day) (1,031,939, 28.3% with a PPI). Using Cox regression models that adjusted for time-dependent variables (aspirin, anticoagulants, and clopidogrel) and other fixed patient baseline characteristics, we found similar risks of GI hospitalizations among time periods when patients were exposed to either a tNSAID with a PPI, acetaminophen (>3 g/day) with a PPI, or acetaminophen (≤3 g/day) with a PPI. The risk of GI hospitalization among users of PPIs during exposure to the combination of acetaminophen with a tNSAID was twice as high as that of the reference category, acetaminophen (≤3 g/day) without a PPI (hazard ratio [HR] 2.15, 95% confidence interval [CI] [1.35–3.40]). Among nonusers of PPIs, the risk of GI hospitalization was 1.20 (1.03–1.40) during exposure to acetaminophen (>3 g/day), 1.63 (1.44–1.85) during exposure to tNSAIDs, and 2.55 (1.98–3.28) during exposure to the combination of a tNSAID and acetaminophen compared with the reference category.CONCLUSION:Among elderly patients requiring analgesic/anti-inflammatory treatment, use of the combination of a tNSAID and acetaminophen may increase the risk of GI bleeding compared with either agent alone.

Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases

Objective To evaluate the incremental increase in new onset diabetes from higher potency statins compared with lower potency statins when used for secondary prevention. Design Eight population based cohort studies and a meta-analysis. Setting Six Canadian provinces and two international databases from the UK and US. Participants 136 966 patients aged ≥40 years newly treated with statins between 1 January 1997 and 31 March 2011. Methods Within each cohort of patients newly prescribed a statin after hospitalisation for a major cardiovascular event or procedure, we performed as-treated, nested case-control analyses to compare diabetes incidence in users of higher potency statins with incidence in users of lower potency statins. Rate ratios of new diabetes events were estimated using conditional logistic regression on different lengths of exposure to higher potency versus lower potency statins; adjustment for confounding was achieved using high dimensional propensity scores. Meta-analytic methods were used to estimate overall effects across sites. Main outcome measures Hospitalisation for new onset diabetes, or a prescription for insulin or an oral antidiabetic drug. Results In the first two years of regular statin use, we observed a significant increase in the risk of new onset diabetes with higher potency statins compared with lower potency agents (rate ratio 1.15, 95% confidence interval 1.05 to 1.26). The risk increase seemed to be highest in the first four months of use (rate ratio 1.26, 1.07 to 1.47). Conclusions Higher potency statin use is associated with a moderate increase in the risk of new onset diabetes compared with lower potency statins in patients treated for secondary prevention of cardiovascular disease. Clinicians should consider this risk when prescribing higher potency statins in secondary prevention patients.