Inflammatory Bowel Disease Clinical and Research Centre, University of Manitoba, Manitoba, Canada; Department of Community Health Sciences, University of Manitoba, Manitoba, Canada.
As for many complex diseases, the incidence of inflammatory bowel disease (IBD) is higher among individuals born during certain seasons. This difference could arise from seasonal variations in many factors, including exposure to sunlight, antibiotics, or infectious agents. We investigated the relationship between season of birth, early childhood exposure to antibiotics, and incidence of IBD.
We performed a nested case-control analysis using data from the University of Manitoba inflammatory bowel disease epidemiology database. We compared seasons of birth among 11,145 individuals with IBD (cases) and 108,633 controls using conditional logistic regression models. We collected data on use of antibiotics in the first year of life for cases and controls from the Manitoba Drug Program Information Network-a comprehensive database of all prescriptions given to residents of Manitoba since 1995.
Approximately 27.0% of cases were born from April through June, compared with 25.6% of controls (odds ratio, 1.07; 95% confidence interval, 1.02-1.12; P = .002). Comparisons made by sex (male vs female) and type of IBD (ulcerative colitis vs Crohn's disease) showed statistical significance only for men with Crohn's disease (odds ratio, 1.13; 95% confidence interval, 1.03-1.25; P = .009). At ages 6 months and older, cases and controls born from April through June received a significantly greater number of prescriptions for antibiotics than cases and controls born in other months.
Men with Crohn's disease are more likely to have been born in the months of April through June.
Comparing resource utilization and gastrointestinal outcomes in patients treated with either standard-dose or high-dose proton pump inhibitors: a matched cohort study.
The use of double-dose proton pump inhibitors (PPIs) for initial management of upper gastrointestinal (UGI) symptoms is common, though little evidence supports this practice. The aim of this study was to determine whether initial prescription of double-dose PPIs in outpatients with UGI complaints is superior to standard-dose PPIs prescription in reducing resource utilization. Patients in the Manitoba Health database prescribed double-dose PPIs were matched to individuals prescribed PPIs at standard doses. UGI-related inpatient and outpatient resource utilization and prescription drug usage were compared for both groups over the following year. Cases and controls had a similar duration of PPI use, and no difference in either UGI-related outpatient visits or UGI-related hospital admissions. Twelve-month UGI related costs were higher for double-dose PPI users. Initial therapy with double-dose PPIs does not reduce GI-related resource utilization. Prescription of double-dose PPIs as initial therapy for upper gastrointestinal symptoms should be discouraged.
The cost-effectiveness of colonic stenting as a bridge to curative surgery in patients with acute left-sided malignant colonic obstruction: a Canadian perspective.
Over the past several years, colonic stenting has been advocated as an alternative to the traditional surgical approach for relieving acute malignant left-sided colonic obstruction. The aim of the present study was to determine the most cost-effective strategy in a Canadian setting. patients and
A decision analytical model was developed to compare three competing strategies: CS - emergent colonic stenting followed by elective resective surgery and reanastomosis; RS - emergent resective surgery followed by creation of either a diverting colostomy or primary reanastomosis; and DC - emergent diverting colostomy followed by elective resective surgery and reanastomosis. The costs were estimated from the perspective of the Manitoba provincial health plan.
The use of CS resulted in fewer total operative procedures per patient (mean CS 1.03, RS 1.32, DC 1.9), lower mortality rate (CS 5%, RS 11%, DC 13%) and lower likelihood of requiring a permanent stoma (CS 7%, RS 14%, DC 14%). CS is slightly more expensive than DC, but less costly than RS (DC 11,851 dollars, CS 13,164 dollars, RS 13,820 dollars). The incremental cost-effectiveness ratio associated with the use of CS versus DC is 1,415 dollars to prevent a temporary stoma, 1,516 dollars to prevent an additional operation and 15,734 dollars to prevent an additional death.
Colonic stenting for patients with acute colonic obstruction secondary to a resectable colonic tumour is comparable in cost with surgical options, and reduces the likelihood of requiring both temporary and permanent stomas. Colonic stenting should be offered as the initial therapeutic modality for Canadian colorectal cancer patients presenting with acute obstruction as a bridge to definitive RS.
To review proper use of gastroprotective strategies in family medicine for patients requiring chronic nonsteroidal anti-inflammatory drug (NSAID) therapy.
Evidence of the efficacy and safety of strategies currently in use (prostaglandin analogues, cyclooxygenase-2 inhibitors, proton pump inhibitors) is derived from randomized controlled trials (level I evidence). The simultaneous use of multiple medications for very high-risk NSAID users is supported only by expert opinion (level III evidence).
Gastroprotective strategies should be reserved for NSAID users at substantially increased risk of gastrointestinal complications; low-risk patients can safely use NSAIDs alone. Cyclooxygenase-2 inhibitors, prostaglandin analogues, and proton pump inhibitors reduce the risk of NSAID-related gastointestinal complications by 40% to 90%. Cyclooxygenase-2 inhibitors should be avoided by patients who have or are at risk for cardiovascular disease.
Chronic NSAID use has been implicated in the development of severe and potentially life-threatening gastointestinal complications, though certain strategies are known to decrease the risk of these NSAID-related gastointestinal complications. Prescribing physicians must know which of their patients should be prescribed medications and which strategies are appropriate for particular patients.
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A high prevalence of osteoporosis has been reported among individuals with inflammatory bowel disease (IBD). We performed a population-based analysis to determine whether IBD is itself a risk factor for low bone mineral density (BMD) or whether low BMD results from other factors associated with IBD.
We identified 1230 subjects with IBD in the Manitoba BMD Database, which contains results of BMD tests performed on all Manitobans since 1997 (n = 45,714). BMD was assessed at the lumbar spine (mean value, L1-L4), hip (total), femoral neck, and trochanter. Multivariate linear and logistic regression analyses were performed to determine the independent effects of IBD, Crohn's disease (CD), or ulcerative colitis (UC) on T score and the presence of osteoporosis (a low T score was equal to or less than -2.5) at any site; we controlled for age, sex, body mass index, hormone replacement therapy, osteoprotective medications, and corticosteroid use. We also performed regression analysis within the IBD population to determine the effect of IBD-specific factors on T score and osteoporosis.
IBD was associated with a statistically significant but small effect on T score; IBD did not increase the risk for osteoporosis at any site measured. CD was associated with an increased risk of osteoporosis at the lumbar spine and trochanter, but UC was not associated with an increased risk of osteoporosis or low T score. No IBD-specific variables were associated with increased risk of osteoporosis or low T score.
IBD has a small effect on BMD; CD poses a greater risk than UC. The risk of osteoporosis in patients with IBD appears to be related to other known osteoporosis risk factors.
Acute nonvariceal upper gastrointestinal hemorrhage (UGIH) remains a common indication for hospital admission. Differences in the structure, process and outcomes of care in the management of acute nonvariceal UGIH between providers in Canada and the United States have not been previously characterized. The aim of the present study was to compare the structure, process and outcomes of care between a Canadian and an American tertiary care medical centre in the management of acute nonvariceal UGIH.
Data were collected from identified cases of acute non-variceal UGIH at the two medical centres over two years. Process measures analyzed included the level of care (intensive care unit [ICU] monitored bed versus unmonitored bed) and hospital length of stay (HLOS). Outcomes assessed included rebleeding, inhospital mortality and readmission and/or death within 30 days of admission.
One hundred seventy-five and 83 cases of acute non-variceal UGIH were identified at the American and Canadian centres, respectively. Cases at the American centre had a lower median HLOS, (2.6 versus 3.9 days, P
High-intensity proton pump inhibitor (PPI) use is often recommended by physicians, though there is little proven benefit over standard PPI dosing in many clinical situations. We therefore sought to calculate the prevalence and predictors of high-intensity PPI use.
We used a Canadian provincial administrative database to capture all PPI prescriptions between 1996 and 2004. A person was defined as a high-intensity user if he used PPIs at more than 1.5 times the standard PPI dose for greater than 45 of 90 days before the index date. The prevalence of high-intensity use was calculated at four index dates annually. Stepwise logistic regression was performed to determine clinical and demographic factors associated with high-intensity PPI use.
The prevalence of high-intensity PPI use increased from 9.7% in 1997 to 14.2% in 2004. Polypharmacy, concomitant use of antispasmodic/promotility agents, and recent endoscopy were most strongly predictive of high-intensity PPI use. Severity of gastroesophageal reflux disease (GERD) (as assessed by the number of GERD-related physician visits) was relatively weakly predictive of high-intensity PPI use.
High-intensity PPI use is becoming more prevalent over time, and its use is strongly associated with factors suggestive of a high degree of comorbidity and treatment failure. Further research into factors that drive high-intensity PPI prescription and use are required.
Recent studies have shown an association between proton-pump inhibitor use (PPI) and hip fracture. The mechanism by which PPI use promotes the development of hip fracture is uncharacterized. Therefore, we sought to determine whether PPI use is associated with osteoporosis or accelerated bone mineral density (BMD) loss.
We used the Manitoba Bone Mineral Density Database to determine the relationship between chronic PPI use and osteoporosis on an initial assessment of BMD and on BMD loss between successive assessments of BMD. In the cross-sectional study, cases with osteoporosis at the hip or lumbar vertebrae (T-score or =-1.0). In the longitudinal analysis, the change in BMD among PPI users and nonusers between successive BMD assessments was assessed. Conditional logistic regression and multivariate linear regression were used to obtain estimates of the association between PPI use and osteoporosis and of the annualized change in BMD associated with PPI use.
PPI use was not associated with having osteoporosis at either the hip (OR, 0.84; 95% CI, 0.55-1.34) or the lumbar spine (OR, 0.79; 95% CI, 0.59-1.06) for PPI use >1500 doses over the previous 5 years. In the longitudinal study no significant decrease was observed in BMD at either site attributable to PPI use.
PPI use does not appear to be associated with either the presence of osteoporosis or accelerated BMD loss. The association between PPI use and hip fracture is probably related to factors independent of osteoporosis.
The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos).
Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk.
We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years.
In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up.
PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.
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Comment In: Evid Based Med. 2013 Oct;18(5):192-323220469
There are numerous gastroprotective strategies recommended for reducing the risk of upper gastrointestinal (GI) complications in long-term users of nonsteroidal anti-inflammatory drugs (NSAIDs). The relative efficacy of the different strategies alone or in combination is uncertain.
We used the Manitoba Population Health Research Data Repository to perform a population-based matched case-control analysis. All NSAID users (nonselective and cyclooxygenase [COX]-2-specific) users admitted to the hospital with a primary diagnosis for an upper gastrointestinal complication were matched to NSAID-using controls in the community. We used conditional logistic regression analysis to determine the relative efficacy of different gastroprotective strategies (proton pump inhibitors [PPIs], COX-2 inhibitors, and low-dose/high-dose misoprostol) either alone or in combination and to adjust for multiple pertinent covariates.
A total of 1382 NSAID/COX-2 users with upper GI complications were matched to 33,957 age- and sex-matched controls. Cotherapy with PPIs or misoprostol or use of a COX-2 inhibitor all significantly reduced the risk of upper GI complications. COX-2 inhibitors were not statistically more likely to prevent upper GI complications than PPIs, although they were superior to low-dose misoprostol. The combination of COX-2 inhibitors with a PPI was associated with the greatest degree of upper GI complication risk reduction.
All of the commonly accepted gastroprotective strategies reduce the risk of upper GI complications in NSAID users, although the combination of COX-2 inhibitors with PPIs promotes the greatest risk reduction for NSAID-related upper GI complications. Celecoxib use specifically may be superior to the combination of nonselective NSAIDs with a PPI.
