Time trends and predictors of laboratory-confirmed recurrent and severe Clostridioides difficile infections in Manitoba: a population-based study.

BACKGROUND: Many previous studies of Clostridioides difficile infection (CDI) epidemiology have used hospital discharge data codes, which can have limited accuracy. We used a data set of laboratory-confirmed cases of CDI in the province of Manitoba, Canada, to describe the epidemiology of CDI over a decade. METHODS: We conducted a population-based historical cohort study using Manitoba Health's population-wide laboratory-based CDI data set linked to administrative health databases. All individuals living in Manitoba and experiencing a CDI episode between 2005 and 2015 were included (n = 8471) and followed up from CDI diagnosis. We assessed time trends of CDI, incidence and predictors of recurrence and severe outcomes, and health care encounters after CDI diagnosis. CDI episodes were stratified by community versus hospital site of acquiring CDI. RESULTS: Between 2005 and 2009, overall CDI diagnoses decreased by an average of 12.6% per year (95% confidence interval [CI] -4.4 to -20.0), with no statistically significant change from 2010 to 2015. In stratified analysis, incident and recurrent CDI had a similar decrease in the initial study time period and then stabilized. The proportion of community-associated CDI cases increased by an average of 4.8% per year (95% CI 2.8 to 6.8) during the study period. CDI acquired in a health care facility had a higher recurrence rate and more severe outcomes. Recurrence of CDI increased the likelihood of admission to hospital. INTERPRETATION: Between 2005 and 2015, the rates of overall laboratory-confirmed CDI, incident CDI, recurrent CDI and severe outcomes following CDI initially decreased before stabilizing, and an increasing proportion of CDI cases were community-associated. There is an increasing need to test for CDI among outpatients with diarrhea and to increase efforts to prevent recurrent CDI.

Geographical Variation and Factors Associated With Inflammatory Bowel Disease in a Central Canadian Province.

BACKGROUND: We investigated temporal trends, geographical variation, and geographical risk factors for incidence of inflammatory bowel disease (IBD). METHODS: We used the University of Manitoba IBD Epidemiology Database to identify incident IBD cases diagnosed between 1990 and 2012, which were then geocoded to 296 small geographic areas (SGAs). Sociodemographic characteristics of the SGAs (proportions of immigrants, visible minorities, Indigenous people, and average household income) were obtained from the 2006 Canadian Census. The geographical variation of IBD incidence was modeled using a Bayesian spatial Poisson model. Time trends of IBD incidence were plotted using Joinpoint regression. RESULTS: The incidence of IBD decreased over the study years from 23.6 (per 100,000 population) in 1990 to 16.3 (per 100,000 population) in 2012. For both Crohn's disease (CD) and ulcerative colitis (UC), the highest incidence was in Winnipeg and the southern and central regions of Manitoba, whereas most of northern Manitoba had lower incidence. There was no effect of sociodemographic characteristics of SGAs, other than the proportion of Indigenous people, which was associated with lower IBD incidence. CONCLUSIONS: Although the incidence of IBD in Manitoba is decreasing over time, we have identified geographic areas with persistently higher IBD incidence that warrant further study for etiologic clues.

Direct cost of health care for individuals with community associated Clostridium difficile infections: A population-based cohort study.

BACKGROUND: Even though the incidence of community-acquired Clostridium difficile infection (CDI) is reported to be increasing, few studies have reported on the healthcare costs of community-acquired CDI. We estimated cost of care for individuals with community-associated CDI and compared with that for matched controls without CDI in the time period of six months before to one year after CDI. METHODS: All individuals in the province of Manitoba, diagnosed with CDI between July 2005 and March 2015 were matched up to 4 individuals without CDI. Health care utilization and direct costs resulting from hospitalizations, physician reimbursement claims and prescriptions were determined from the population based provincial databases. Quantile regressions were performed to determine predictors of cost of individuals with community associated CDI. RESULTS: Of all CDIs, 30-40% in each period of the study had community-associated CDI; of which 12% were recurrent CDIs. The incremental median and 90th percentile cost of care for individuals with community-associated CDI was $800 and $16,000 respectively in the six months after CDI diagnosis. After adjustment for age, co-morbidities, sex, socioeconomic status and magnitude of health care utilization prior to CDI, the median incremental cost for recurrent CDI was $1,812 and that for a subsequent episode of CDI was $3,139 compared to those with a single community-associated CDI episode. The median cost for a prescription of Vancomycin was $316 (IQR 209-489). CONCLUSIONS: Health care costs of an episode of community-associated CDI have been much more than the cost of antibiotic treatment. Our study provides population-based data for formal cost effectiveness analysis for use of newer treatments for community-associated CDI.

Trends and Predictors of Clostridium difficile Infection among Children: A Canadian Population-Based Study.

OBJECTIVE: To assess time trends in Clostridium difficile infection (CDI) rates, and predictors of CDIs, including recurrent CDIs, in children. STUDY DESIGN: Data were extracted from Manitoba Health Provider Claims, and other population registry datasets from 2005 to 2015. CDI was identified from the Manitoba Health Public Health Branch Epidemiology and Surveillance population-based laboratory-confirmed CDI dataset. Children aged 2-17 years with CDI were matched by age, sex, area of residence, and duration of residence in Manitoba with children without CDI. The rates and time trends of CDIs using previously recommended definitions were determined. Predictors of CDI subtypes were determined using multivariable logistic regression models. Cox regression analysis was used to assess for the potential predictors of recurrent CDI. RESULTS: Children with and without CDI were followed for 828 and 2753 persons-years, respectively. The overall CDI rate during the study period was 7.8 per 100 000 person-years. There was no significant change in CDI rates over the observation period. Comorbid conditions, more prevalent among children with CDI than matched controls, included Hirschsprung disease (P < .001) and inflammatory bowel disease (P < .0001). Recurrent CDIs (>2 occurrences) were responsible for 10% of CDI episodes (range, 2-6 infections). Predictors of recurrence included malignancy (hazard ratio, 3.0, 95% CI, 1.1-8.8), diabetes (hazard ratio, 4.8; 95% CI, 1.1-21.4), and neurodegenerative diseases (hazard ratio, 8.4; 95% CI, 1.9-37.5). CONCLUSIONS: The incidence of CDI is stable among children in Manitoba. Children with Hirschsprung disease and inflammatory bowel disease are more susceptible to CDI, and those with malignancy, diabetes. and neurodegenerative disorders are more likely to develop recurrent CDI.

Higher Incidence of Clostridium difficile Infection Among Individuals With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Studies of Clostridium difficile infections (CDIs) among individuals with inflammatory bowel disease (IBD) have used data from single centers or CDI administrative data codes of limited diagnostic accuracy. We determined the incidence, risk factors, and outcomes after CDI in a population-based cohort of patients with IBD and laboratory confirmation diagnoses of CDI. METHODS: We searched the University of Manitoba IBD Epidemiology Database and Manitoba Health CDI databases to identify individuals with CDI, with or without IBD, from July 1, 2005 through March 31, 2014. Time trends of incidence were assessed using joinpoint regression. Multivariable Cox regression analyses were performed to assess differences in CDI incidence rates and mortality after CDI between individuals with and without IBD. Conditional logistic regression was performed to determine predictors of CDI among individuals with IBD. RESULTS: Individuals with IBD had a 4.8-fold increase in risk of CDI than individuals without IBD; we found no difference between individuals with ulcerative colitis vs Crohn's disease. There was no increase in CDI incidence over the study time period in either group. Among individuals with IBD, exposure to corticosteroids, infliximab or adalimumab, metronidazole, hospitalizations, higher ambulatory care visits, shorter duration of IBD, and higher comorbidities were associated with an increased risk of CDI. Although CDI increased mortality among individuals with and without IBD, there was lower mortality after CDI among individuals with IBD than without IBD (hazard ratio, 0.65; 95% confidence interval, 0.44-0.96). CONCLUSIONS: CDI incidence is no longer increasing among individuals with IBD. We identified unique risk factors for CDI in patients with IBD. CDI is associated with a greater increase in mortality among individuals without IBD than with IBD.

Comparison of the population excess fraction of Chlamydia trachomatis infection on pelvic inflammatory disease at 12-months in the presence and absence of chlamydia testing and treatment: Systematic review and retrospective cohort analysis.

BACKGROUND: The impact of Chlamydia trachomatis (chlamydia) control on the incidence of pelvic inflammatory disease (PID) is theoretically limited by the proportion of PID caused by chlamydia. We estimate the population excess fraction (PEF) of treated chlamydia infection on PID at 12-months in settings with widespread chlamydia control (testing and treatment) and compare this to the estimated PEF of untreated chlamydia. METHODS: We used two large retrospective population-based cohorts of women of reproductive age from settings with widespread chlamydia control to calculate the PEF of treated chlamydia on PID at 12-months. We undertook a systematic review to identify further studies that reported the risk of PID in women who were tested for chlamydia (infected and uninfected). We used the same method to calculate the PEF in eligible studies then compared all estimates of PEF. RESULTS: The systematic review identified a single study, a randomised controlled trial of chlamydia screening (POPI-RCT). In the presence of testing and treatment <10% of PID at 12-months was attributable to treated (baseline) chlamydia infections (Manitoba: 8.86%(95%CI 7.15-10.75); Denmark: 3.84%(3.26-4.45); screened-arm POPI-RCT: 0.99%(0.00-29.06)). In the absence of active chlamydia treatment 26.44%(11.57-46.32) of PID at 12-months was attributable to untreated (baseline) chlamydia infections (deferred-arm POPI-RCT). The PEFs suggest that eradicating baseline chlamydia infections could prevent 484 cases of PID at 12-months per 100,000 women in the untreated setting and 13-184 cases of PID per 100,000 tested women in the presence of testing and treatment. CONCLUSION: Testing and treating chlamydia reduced the PEF of chlamydia on PID by 65% compared to the untreated setting. But in the presence of testing and treatment over 90% of PID could not be attributed to a baseline chlamydia infection. More information is needed about the aetiology of PID to develop effective strategies for improving the reproductive health of women.

Hospital discharge abstracts have limited accuracy in identifying occurrence of Clostridium difficile infections among hospitalized individuals with inflammatory bowel disease: A population-based study.

BACKGROUND: Hospital discharge databases are used to study the epidemiology of Clostridium difficile infections (CDI) among hospitalized patients with inflammatory bowel disease (IBD). CDI in IBD is increasingly important and accurately estimating its occurrence is critical in understanding its comorbidity. There are limited data on the reliability of the International Classification of Diseases 10th revision (ICD-10) (now widely used in North America) CDI code in determining occurrence of CDI among hospitalized patients. We compared the performance of ICD-10 CDI coding to laboratory confirmed CDI diagnoses. METHODS: The University of Manitoba IBD Epidemiology Database was used to identify individuals with and without IBD discharged with CDI diagnoses between 07/01/2005 and 3/31/2014. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ICD-10 CDI code was compared to laboratory CDI diagnoses recorded in a province wide CDI dataset. Multivariable logistic regression models were performed to test the predictors of diagnostic inaccuracy of ICD-10 CDI code. RESULTS: There were 273 episodes of laboratory confirmed CDI (hospitalized and non-hospitalized) among 7396 individuals with IBD and 536 among 66,297 matched controls. The sensitivity, specificity, PPV and NPV of ICD-10 CDI code in discharge abstracts was 72.8%, 99.6%, 64.1% and 99.7% among those with IBD and 70.8%, 99.9%, 79.0% and 99.9% among those without IBD. Predictors of diagnostic inaccuracy included IBD, older age, increased co-morbidity and earlier years of hospitalization. CONCLUSIONS: Identification of CDI using ICD-10 CDI code in hospital discharge abstracts may not identify up to 30% of CDI cases, with worse performance among those with IBD.

Nutrient and Food Group Intakes of Manitoba Children and Youth: A Population-Based Analysis by Pulse and Soy Consumption Status.

Poor eating habits among children are associated with negative health outcomes. The objective of this study was to use pulse/soy consumption as an indicator to evaluate the eating profile of young Manitobans. Data from the Canadian Community Health Survey Cycle 2.2 were used for analysis and restricted to Manitoba residents aged 2 to 18 years (n = 1840). Consumers were identified as individuals who reported eating at least 1 pulse/soy product during their recall. On any given day, 8.2% of Manitobans reported consumption of pulses/soy. Intakes of fibre, protein, magnesium, and zinc were higher in consumers only when expressed relative to total caloric intake. Consumers also reported increased intakes of meat and alternatives. Total intakes of vitamin D, fibre, and fruit and vegetable consumption were low among all groups. Sodium intakes in both groups were high when compared with levels recommended by health professionals. These results indicate that there are many dietary issues affecting Manitoba children, suggesting the need for more research targeting dietary habits of children and youth, the quality of the food supply, and effective strategies in nutrition education.

Chronic lung disease and multiple sclerosis: Incidence, prevalence, and temporal trends.

OBJECTIVES: We aimed to estimate the incidence and prevalence of chronic lung disease (CLD), including asthma and chronic obstructive pulmonary disease, in the MS population versus a matched cohort from the general population. METHODS: We used population-based administrative data from four Canadian provinces to identify 44,452 persons with MS and 220,849 age-, sex- and geographically-matched controls aged 20 years and older. We employed a validated case definition to estimate the incidence and prevalence of CLD over the period 1995-2005, and used Poisson regression to assess temporal trends. RESULTS: In 2005, the crude incidence of CLD per 100,000 persons was 806 (95%CI: 701-911) in the MS population, and 757 in the matched population (95%CI: 712-803). In 2005, the crude prevalence of CLD was 13.5% (95%CI: 13.1-14.0%) in the MS population, and 12.4% (95%CI: 12.3-12.6%) in the matched population. Among persons aged 20-44 years, the average annual incidence of CLD was higher in the MS population than in the matched population (RR 1.15; 95%CI: 1.02-1.30), but did not differ between populations for those aged ≥45 years. The incidence of CLD was stable, but the prevalence of CLD increased 60% over the study period. CONCLUSION: CLD is relatively common in the MS population. The incidence of CLD has been stable over time, but the prevalence of CLD has increased. Among persons aged 20-44 years, CLD is more common in the MS population than in a matched population. Given the prevalence of CLD in the MS population, further attention to the effects of CLD on outcomes in MS and approaches to mitigating those effects are warranted.

Examining the effects of comorbidities on disease-modifying therapy use in multiple sclerosis.

OBJECTIVE: Comorbidities are common in multiple sclerosis (MS) and adversely affect health outcomes. However, the effect of comorbidity on treatment decisions in MS remains unknown. We aimed to examine the effects of comorbidity on initiation of injectable disease-modifying therapies (DMTs) and on the choice of the initial DMT in MS. METHODS: We conducted a retrospective observational analysis using population-based health administrative and linked clinical databases in 3 Canadian provinces. MS cases were defined as any individual with ≥3 diagnostic codes for MS. Cohort entry (index date) was the first recorded demyelinating disease-related claim. The outcomes included choice of initial first-line DMTs and time to initiating a DMT. Logistic and Cox regression models were used to examine the association between comorbidity status and study outcomes, adjusting for sex, age, year of index date, and socioeconomic status. Meta-analysis was used to estimate overall effects across the 3 provinces. RESULTS: We identified 10,698 persons with incident MS, half of whom had ≥1 comorbidities. As the total number of comorbidities increased, the likelihood of initiating a DMT decreased. Comorbid anxiety and ischemic heart disease were associated with reduced initiation of a DMT. However, patients with depression were 13% more likely to initiate a DMT compared to those without depression at the index date (adjusted hazard ratio 1.13; 95% confidence interval 1.00-1.27). CONCLUSIONS: Comorbidities are associated with treatment decisions regarding DMTs in MS. A better understanding of the effects of comorbidity on effectiveness and safety of DMTs is needed.

High incidence and increasing prevalence of multiple sclerosis in British Columbia, Canada: findings from over two decades (1991-2010).

Province-wide population-based administrative health data from British Columbia (BC), Canada (population: approximately 4.5 million) were used to estimate the incidence and prevalence of multiple sclerosis (MS) and examine potential trends over time. All BC residents meeting validated health administrative case definitions for MS were identified using hospital, physician, death, and health registration files. Estimates of annual prevalence (1991-2008), and incidence (1996-2008; allowing a 5-year disease-free run-in period) were age and sex standardized to the 2001 Canadian population. Changes over time in incidence, prevalence and sex ratios were examined using Poisson and log-binomial regression. The incidence rate was stable [average: 7.8/100,000 (95 % CI 7.6, 8.1)], while the female: male ratio decreased (p = 0.045) but remained at or above 2 for all years (average 2.8:1). From 1991-2008, MS prevalence increased by 4.7 % on average per year (p < 0.001) from 78.8/100,000 (95 % CI 75.7, 82.0) to 179.9/100,000 (95 % CI 176.0, 183.8), the sex prevalence ratio increased from 2.27 to 2.78 (p < 0.001) and the peak prevalence age range increased from 45-49 to 55-59 years. MS incidence and prevalence in BC are among the highest in the world. Neither the incidence nor the incidence sex ratio increased over time. However, the prevalence and prevalence sex ratio increased significantly during the 18-year period, which may be explained by the increased peak prevalence age of MS, longer survival with MS and the greater life expectancy of women compared to men.

Heterogeneity in risk of pelvic inflammatory diseases after chlamydia infection: a population-based study in Manitoba, Canada.

BACKGROUND: The association between chlamydia infection and pelvic inflammatory disease (PID) is a key parameter for models evaluating the impact of chlamydia control programs. We quantified this association using a retrospective population-based cohort. METHODS: We used administrative health data sets to construct a retrospective population-based cohort of women and girls aged 12-24 years who were resident in Manitoba, Canada, between 1992 and 1996. We performed survival analysis on a subcohort of individuals who were tested for chlamydia to estimate the risk of PID diagnosed in a primary care, outpatient, or inpatient setting after ≥ 1 positive chlamydia test. RESULTS: A total of 73 883 individuals contributed 625 621 person years of follow-up. Those with a diagnosis of chlamydia had an increased risk of PID over their reproductive lifetime compared with those who tested negative (adjusted hazard ratio [AHR], 1.55; 95% confidence interval [CI], 1.43-1.70). This risk increased with each subsequent infection: the AHR was 1.17 for first reinfection (95% CI, 1.06-1.30) and 1.35 for the second (95% CI, 1.04-1.75). The increased risk of PID from reinfection was highest in younger individuals (AHR, 4.55 (95% CI, 3.59-5.78) in individuals aged 12-15 years at the time of their second reinfection, compared with individuals older than 30 years). CONCLUSIONS: There is heterogeneity in the risk of PID after a chlamydia infection. Describing the progression to PID in mathematical models as an average rate may be an oversimplification; more accurate estimates of the cost-effectiveness of screening may be obtained by using an individual-based measure of risk. Health inequalities may be reduced by targeting health promotion interventions at sexually active girls younger than 16 years and those with a history of chlamydia.

Trends in utilization of diagnostic and therapeutic ERCP and cholecystectomy over the past 25 years: a population-based study.

BACKGROUND: Comprehensive, population-based data on ERCP use over the last 30 years in North America are lacking. OBJECTIVE: To establish crude and age-adjusted population-based rates of ERCP, evaluate for changing indications for ERCP, and evaluate for interactions between cholecystectomy technique and ERCP use from 1984 to 2009. DESIGN: Retrospective, comprehensive, population-based study. SETTING: All inpatient and outpatient ERCPs and cholecystectomies in Manitoba, Canada from 1984 to 2009. PATIENTS: All residents of Manitoba, Canada with a history of ERCP and/or cholecystectomy. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Yearly crude and age-adjusted rates of ERCP (diagnostic and therapeutic) and cholecystectomy (open, laparoscopic, and with open bile duct exploration), and patient and/or procedure demographics. RESULTS: The rate of ERCP/10,000 people increased from 7.70 (1984) to 13.86/10,000 (2009) (P = .001). Diagnostic ERCP declined from 7.28/10,000 (1984) to 1.11/10,000 (2009), and therapeutic ERCP increased from 0.42/10,000 (1984) to 12.75/10,000 (2009) (P < .001). ERCPs were more common in women (62%) and in older populations (60-79 years, >80 years), with rates of therapeutic ERCP reaching 62.58/10,000 in the elderly. The primary indication for ERCP has changed over time, with biliary indications increasing from 50.3% to 67.3% and pancreatic indications decreasing from 18.3% to 8.1% (P < .05). The rate of therapeutic ERCP increased during the transition from open to laparoscopic cholecystectomy (1991-1994), whereas open bile duct exploration (OBDE) decreased from 2.0 to 0.18/10,000 (P < .001). LIMITATIONS: Retrospective analysis, administrative data. CONCLUSION: ERCP use increased steadily from 1984 to 2009, and changed from a diagnostic modality to a therapeutic one. Changes in cholecystectomy technique may have influenced therapeutic ERCP use and likewise, the availability of therapeutic ERCP has decreased the need for OBDE.

Model for equitable care and outcomes for remote full care hemodialysis units.

BACKGROUND AND OBJECTIVES: Remotely located patients not living close to a nephrologist present major challenges for providing care. Various models of remotely delivered care have been developed, with a gap in knowledge regarding the outcomes of these heterogeneous models. This report describes a satellite care model for remote full-care hemodialysis units managed homogenously in the province of Manitoba, Canada, without onsite nephrologists. Survival in remotely located full-care units is compared with a large, urban full-care center with onsite nephrologists. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from a Canadian provincial dialysis registry were extracted on 2663 patients between 1990 and 2005. All-cause mortality after initiation of chronic hemodialysis was assessed with Cox proportional hazards regression. Both short-term (1 year) and long-term (2 to 5 years) survival were analyzed. RESULTS: Survival for patients receiving remotely delivered care was shown to be better than for those receiving care in the urban care center with this particular Canadian model of care. Furthermore, there was no difference when assessing short- and long-term survival. This was independent of distance from the urban center. CONCLUSIONS: Chronic hemodialysis patients receiving remotely delivered care in a specialized facility attain comparable, if not better survival outcomes than their urban counterparts with direct onsite nephrology care. This model can potentially be adapted to other underserviced areas, including increasingly larger urban centers.