Differential mortality and the excess burden of end-stage renal disease among First Nations people with diabetes mellitus: a competing-risks analysis.

BACKGROUND: Diabetes-related end-stage renal disease disproportionately affects indigenous peoples. We explored the role of differential mortality in this disparity. METHODS: In this retrospective cohort study, we examined the competing risks of end-stage renal disease and death without end-stage renal disease among Saskatchewan adults with diabetes mellitus, both First Nations and non-First Nations, from 1980 to 2005. Using administrative databases of the Saskatchewan Ministry of Health, we developed Fine and Gray subdistribution hazards models and cumulative incidence functions. RESULTS: Of the 90 429 incident cases of diabetes, 8254 (8.9%) occurred among First Nations adults and 82,175 (90.9%) among non-First Nations adults. Mean age at the time that diabetes was diagnosed was 47.2 and 61.6 years, respectively (p<0.001). After adjustment for sex and age at the time of diabetes diagnosis, the risk of end-stage renal disease was 2.66 times higher for First Nations than non-First Nations adults (95% confidence interval [CI] 2.24-3.16). Multivariable analysis with adjustment for sex showed a higher risk of death among First Nations adults, which declined with increasing age at the time of diabetes diagnosis. Cumulative incidence function curves stratified by age at the time of diabetes diagnosis showed greatest risk for end-stage renal disease among those with onset of diabetes at younger ages and greatest risk of death among those with onset of diabetes at older ages. INTERPRETATION: Because they are typically younger when diabetes is diagnosed, First Nations adults with this condition are more likely than their non-First Nations counterparts to survive long enough for end-stage renal disease to develop. Differential mortality contributes substantially to ethnicity-based disparities in diabetes-related end-stage renal disease and possibly to chronic diabetes complications. Understanding the mechanisms underlying these disparities is vital in developing more effective prevention and management initiatives.

Coding of heart failure diagnoses in Saskatchewan: a validation study of hospital discharge abstracts.

BACKGROUND: Validity of Heart Failure (HF) diagnoses from administrative records has not been extensively evaluated, especially with respect to small / unselected hospitals. OBJECTIVES: To determine the positive predictive value of a primary / most responsible diagnosis of HF among a general population of subjects discharged from Saskatchewan hospitals. METHODS: Using administrative health records from the Province of Saskatchewan, Canada, we identified subjects experiencing their first HF hospitalization between 1994 and 2003. From this cohort, we randomly selected 500 subjects for individual validation using Framingham and Carlson criteria. RESULTS: The 466 charts available for analysis, 74% (345/466) and 63.9% (298/466) of subjects met criteria for a clinical diagnosis of HF based on Framingham or Carlson criteria, respectively; 57.5% (268/466) met both criterion. Provincial hospitals (located in the largest urban centres) were associated with the highest proportion of confirmed HF diagnoses (87.8% by Framingham criteria) compared to progressively smaller hospitals (regional 77.9%; district 64.2%; and community 60.0%). Accuracy also differed when stratified by physician category. Cardiologists and internists were associated with the highest rates of confirmed diagnoses [(97.5% (39 / 40) and 85.0% (34 / 40)]) compared to general practitioners [(73.1% (95 / 130)]) and other physicians [(69.1% (177 / 256)]), by Framingham criteria. CONCLUSIONS: Hospital discharge abstracts indicating HF are frequently inaccurate. These findings have important implications for the epidemiologic study of HF as well as the clinical management of patients.

Epidemiology of diabetes mellitus among First Nations and non-First Nations adults.

BACKGROUND: First Nations people in Canada experience a disproportionate burden of type 2 diabetes mellitus. To increase our understanding of this evolving epidemic, we compared the epidemiology of diabetes between First Nations and non-First Nations adults in Saskatchewan from 1980 to 2005. METHODS: We used administrative databases to perform a population-based study of diabetes frequency, incidence and prevalence in adults by ethnic background, year, age and sex. RESULTS: We identified 8275 First Nations and 82,306 non-First Nations people with diabetes from 1980 to 2005. Overall, the incidence and prevalence of diabetes were more than 4 times higher among First Nations women than among non-First Nations women and more than 2.5 times higher among First Nations men than among non-First Nations men. The number of incident cases of diabetes was highest among First Nations people aged 40-49, while the number among non-First Nations people was greatest in those aged 70 or more years. The prevalence of diabetes increased over the study period from 9.5% to 20.3% among First Nations women and from 4.9% to 16.0% among First Nations men. Among non-First Nations people, the prevalence increased from 2.0% to 5.5% among women and from 2.0% to 6.2% among men. By 2005, almost 50% of First Nations women and more than 40% of First Nations men aged 60 or older had diabetes, compared with less than 25% of non-First Nations men and less than 20% of non-First Nations women aged 80 or older. INTERPRETATION: First Nations adults are experiencing a diabetes epidemic that disproportionately affects women during their reproductive years. This ethnicity-based pattern suggests diverse underlying mechanisms that may include differences in the diabetogenic impact of gestational diabetes.

Risk of upper gastrointestinal complications associated with cyclooxygenase-2 selective and nonselective nonsteroidal antiinflammatory drugs.

STUDY OBJECTIVE: To estimate the risk of upper gastrointestinal complications associated with use of cyclooxygenase-2 (COX-2) selective (celecoxib and rofecoxib) and individual nonselective nonsteroidal antiinflammatory drugs (NSAIDs) compared with nonuse of these drugs. DESIGN: Nested case-control study. DATA SOURCE: Administrative health care databases of Saskatchewan, Canada. PATIENTS: Among a population of men and women aged 20-89 years who were covered by public health insurance with prescription drug benefits between November 15, 1999, and December 31, 2001, 726 case patients with first hospitalization for upper gastrointestinal complications (with validation of cases through review of hospital medical records) were confirmed from 1,054,532 person-years of follow-up, and 20,002 control patients were randomly selected from all eligible controls, frequency matched to cases on their index date (+/- 3 mo). MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between upper gastrointestinal complications and use of NSAIDs. Current rofecoxib and naproxen users had the highest risk for upper gastrointestinal complications with adjusted ORs of 3.6 (95% CI 2.2-5.7) and 3.4 (95% CI 1.8-6.7), respectively. No association was found between the risk of upper gastrointestinal complications and use of celecoxib (OR 1.1, 95% CI 0.7-1.8) or the use of diclofenac plus misoprostol (OR 0.7, 95% CI 0.3-1.8). A dose-response relationship was observed for rofecoxib and naproxen with ORs for high dose of 5.2 (95% CI 2.5-10.6) and 5.1 (95% CI 2.1-12.3), respectively. Short-term users of celecoxib and naproxen had a higher risk than long-term users, whereas among users of rofecoxib the risk was higher among long-term than short-term users. CONCLUSION: These findings support the variability of individual NSAIDs in the elevated risk of upper gastrointestinal complications. Our results suggest that the risk for rofecoxib is similar to that for naproxen. Celecoxib users appear to have a similar risk for upper gastrointestinal complications as nonusers; however, the risk may be increased at the start of treatment with celecoxib.

The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada.

BACKGROUND: Meta-analyses of observational studies show variability in the risk of acute myocardial infarction (AMI) among non-steroidal anti-inflammatory drugs (NSAIDs), with an increase in risk for rofecoxib and diclofenac, and no increase in risk for celecoxib, naproxen, or ibuprofen. METHODS AND RESULTS: We identified a cohort of 364 658 individuals aged 40-84 years who were enrolled in Saskatchewan Health, Canada, from 15 November 1999 to 31 December 2001. A nested case-control analysis compared 3252 incident cases of hospitalized AMI and out-of-hospital CHD deaths with 20 002 controls randomly sampled from the cohort. The incidence of AMI/CHD was 5.1 per 1000 person-years (95%CI: 5.0-5.3). The adjusted ORs (95%CI) of AMI/CHD in current users of individual NSAIDs compared with non-use were: celecoxib (1.11; 0.84-1.47), rofecoxib (1.32; 0.91-1.91), diclofenac (1.02; 0.75-1.38), naproxen (1.57; 0.98-2.52), ibuprofen (1.59; 0.88-2.89), and indomethacin (1.34; 0.81-2.19). Long-term use of rofecoxib was compatible with an increased risk (OR = 1.46; 0.97-2.22) while estimates of other individual NSAIDs were close to unity. Overall NSAID use was associated with a 30% increased risk of nonfatal AMI but was absent for fatal AMI/CHD. CONCLUSIONS: This study showed a modest increased risk of AMI/CHD with various traditional NSAIDs and COX-2 inhibitors. Confidence intervals of estimated ORs included the null value for most comparisons. The study confirmed that the differentiation between traditional NSAIDs and COX-2 inhibitors is not a reliable tool for predicting cardiovascular risk associated with NSAIDs.

Positive predictive value of ICD-9 codes 410 and 411 in the identification of cases of acute coronary syndromes in the Saskatchewan Hospital automated database.

BACKGROUND: Case definitions are essential to epidemiological research. OBJECTIVES: To evaluate ICD-9 codes 410 and 411 to identify cases of acute coronary syndromes (ACS), and the clinical information availability in the administrative and hospital discharge records of Saskatchewan, Canada. METHODS: In the context of a safety cohort study, we identified hospitalisations with primary discharge codes 410 (2260) and 411 (799). We selected all records with code 411, and a random sample (200) with code 410. Based on information obtained by trained abstractors from hospital records, events were classified by two cardiologists as definite or possible according to adapted AHA/ESC criteria. The validity of 410 and 411 codes was assessed by calculating the positive predictive value (PPV). Completeness of the recorded information on risk factors and use of aspirin was explored. RESULTS: The PPVs of the codes 410 and 411 for ACS were 0.96 (95%CI: 0. 92-0.98) and 0.86 (95%CI: 0.83-0.88), respectively. The PPV of 410 for acute myocardial infarction (AMI) was 0.95 (95%CI: 0.91-0.98). The PPV of 411 was 0.73 (95%CI: 0.70-0.77) for primary unstable angina (UA) and 0.09 (95%CI: 0.07-0.11) for AMI. Hospital charts review revealed key information for clinical variables, smoking, obesity and use of aspirin at admission. CONCLUSIONS: ICD-9 410 code has high PPV for AMI cases, likewise 411 for UA cases. Case validation remains important in epidemiological studies with administrative health databases. Given the pathophysiology of ACS, both AMI and UA might be used as study end points. In addition to code 410, we recommend the use of 411 plus validation.

The safety of rosuvastatin in comparison with other statins in over 25,000 statin users in the Saskatchewan Health Databases.

PURPOSE: To compare mortality and the incidence of hospitalization for myopathy, rhabdomyolysis, acute renal failure and acute liver injury in patients receiving rosuvastatin and those taking other statins. METHODS: Patients prescribed a statin that they had not used before were selected from the Saskatchewan Health Databases (SHD) and followed up from 1 July 2003 until 31 March 2005. RESULTS: We studied 10,384 patients on rosuvastatin and 14,854 taking other statins. Two cases of myopathy were identified (one on rosuvastatin, one on another statin). The relative risk (RR) of myopathy in patients currently taking rosuvastatin compared with other statins was 1.31 (95% confidence interval [CI]: 0.13-13.41). Two cases of rhabdomyolysis were detected among current rosuvastatin users (incidence: 2.9 [95% CI: 0.8-10.7] per 10 000 person-years). No cases of acute liver injury occurred among rosuvastatin patients. Seventeen cases of acute renal failure were identified (five among rosuvastatin users, 12 taking other statins). The RR of acute renal failure in current rosuvastatin users compared with other statins was 0.49 (95% CI: 0.16-1.50). We identified 285 deaths during the study period (87 among rosuvastatin users, 198 taking other statins). The RR of death in current rosuvastatin users compared with other statins was 0.42 (95% CI: 0.32-0.57). CONCLUSIONS: We found no evidence that patients prescribed rosuvastatin were at greater risk of the study outcomes than patients prescribed other statins. There was no evidence of increased mortality among patients taking rosuvastatin, even after allowing for age, sex and prior statin use.

The relationship between diabetes and tuberculosis in Saskatchewan: comparison of registered Indians and other Saskatchewan people.

BACKGROUND: Saskatchewan Aboriginal people are experiencing epidemics of both type 2 diabetes (T2DM) and tuberculosis (TB). The purpose of this study was to determine if a relationship exists between diabetes and TB in Saskatchewan and to establish whether there is a difference in the degree of any association between Aboriginal and non-Aboriginal people. METHODS: Utilizing Saskatchewan Health databases, TB incidence (cases identified from 1986-2001) was compared between four subpopulations identified from 1991-1995: Registered Indians (RI) with and without diabetes, and other Saskatchewan people (OSKP) with and without diabetes. RESULTS: Diabetic women aged 20-59 years had higher average annual incidence rates of TB than non-diabetic women, but within-population rate ratios of TB in diabetic versus non-diabetic women were only significant in those aged 50-59 (2.7 [CI 1.28, 5.72] in RI and 3.9 [CI 1.58, 9.67] in OSKP). No other within-population diabetic subgroup had significantly higher rates of TB. The only male diabetic group that had a higher rate of TB were RI plus OSKP men aged 50-59 years. Overall, diabetes preceded TB in 87/111 individuals with both diseases (p < 0.0001). CONCLUSIONS: Our results suggest that T2DM is a predictor for TB in Saskatchewan women aged 20-59 but particularly in RI and OSKP women aged 50-59 years. This has implications for TB screening and prevention initiatives.

Chronic obstructive pulmonary disease severity and cardiovascular outcomes.

OBJECTIVE: To identify predictors of chronic obstructive pulmonary disease (COPD) severity and assess the relation between COPD severity and risk of cardiovascular outcomes. STUDY DESIGN AND SETTING: A cohort of patients with diagnosed and treated COPD was compiled from the Saskatchewan Health longitudinal databases. We used multivariate modeling to identify predictors of hospitalization for COPD as an indicator of COPD severity, and we used the model to characterize patients according to quintiles of COPD severity. These severity levels were used as independent variables in multivariate models of cardiovascular outcomes. RESULTS: Determinants of COPD severity included emphysema, recent nebulizer use, home oxygen services, corticosteroid use, frequent bronchodilator use, pneumonia and prior COPD exacerbation. The 20% of patients with the highest COPD severity were 1.27 (CI: 1.07-1.50) times more likely to have arrhythmia, 1.25 (CI: 1.07-1.46) times more likely to have ischemic heart disease, 1.38 (CI: 1.11-1.71) times more likely to have angina, 2.28 (CI: 1.95-2.66) times more likely to have congestive heart failure, and 1.63 (CI: 1.22-2.16) times more likely to die of cardiovascular causes than the least severe 20% of patients. CONCLUSIONS: Patients with more severe COPD, as defined by our model, had higher cardiovascular morbidity and mortality than patients with less severe COPD.

Use of antidepressants and risk of colorectal cancer: a nested case-control study.

BACKGROUND: Animal studies suggest that selective serotonin reuptake inhibitors (SSRI) retard the growth of colorectal tumours, whereas tricyclic antidepressants increase the risk of colorectal cancer. We aimed to assess whether SSRI use was associated with a decreased risk of colorectal cancer, and tricyclic-antidepressant use with an increased risk of colorectal cancer. METHODS: We did a population-based nested case-control study from Jan 1, 1981, to Dec 31, 2000, of people aged 5-85 years who were registered with Saskatchewan Health and eligible for prescription-drug benefit. Between Jan 1, 1981, and Dec 31, 2000, 6544 cases with colorectal cancer were identified from the Saskatchewan Cancer Agency registry and analysed for use of tricyclic antidepressants; between Jan 1, 1991, and Dec 31, 2000, 3367 cases with colorectal cancer were identified from the Saskatchewan Cancer Agency registry and analysed for SSRI use. For every case, four eligible controls matched for age, sex, and calendar time (ie, free of any cancer in calendar month of case diagnosis) were selected randomly by a statistician who used incidence density sampling. By use of conditional logistic regression, we assessed incidence-rate ratios of having colorectal cancer in association with use of antidepressants, analysing dose and time of use. FINDINGS: A decreased risk of colorectal cancer was associated with high (ie, >6.0x10(-6) mol per day) daily SSRI dose during 0-5 years before diagnosis (incidence-rate ratio 0.70 [95% CI 0.50-0.96], p for trend=0.0172), adjusted for age, sex, use of non-steroidal anti-inflammatory drugs in the same period, and SSRI use during 6-10 years before index date (ie, date of diagnosis for a case and the same date for matched controls). No consistent relation was recorded for risk of colorectal cancer and use of tricyclic antidepressants. INTERPRETATION: SSRI use might inhibit the growth of colorectal tumours through an antipromoter effect or direct cytotoxic effect. Further investigation is needed, with more complete assessment of confounders such as lifestyle factors (eg, diet), use of drugs, and comorbidity (eg, diabetes or inflammatory bowel disease) that might affect the occurrence of colorectal cancer.

Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients.

PURPOSE: To measure prevalence, incidence, and mortality of cardiovascular outcomes among persons with chronic obstructive pulmonary disease (COPD) and to assess the extent these outcomes differ from persons without COPD. METHODS: Retrospective cohort study in longitudinal health care databases maintained by the government of Saskatchewan, Canada. Subjects were persons age 40 years or older who were diagnosed with COPD during 1997-2000 and who received two or more prescriptions for bronchodilators within 6 months of diagnosis. Each subject was matched by age and sex to two controls without COPD or asthma. RESULTS: Of COPD patients (n = 11,493), 54% were male, and 74% were 65 years or older. Prevalence of all cardiovascular diseases was higher in the COPD group than in the comparison group. After adjusting for cardiovascular risk, odds ratios of prevalence were: arrhythmia 1.76 (confidence interval [CI]: 1.64-1.89), angina 1.61 (CI: 1.47-1.76), acute myocardial infarction 1.61 (CI: 1.43-1.81), congestive heart failure 3.84(CI: 3.56-4.14), stroke 1.11 (CI: 1.02-1.21), pulmonary embolism 5.46 (CI: 4.25-7.02). Risk of hospitalization due to each cardiovascular cause was elevated in the COPD group. The risk ratio for cardiovascular mortality was 2.07 (CI: 1.82-2.36) and all cause mortality was 2.82 (CI: 2.61-3.05). CONCLUSIONS: Persons with diagnosed and treated COPD are at increased risk for hospitalizations and deaths due to cardiovascular diseases.

Adherence to statins, beta-blockers and angiotensin-converting enzyme inhibitors following a first cardiovascular event: a retrospective cohort study.

BACKGROUND: Population studies of statin adherence are generally restricted to one to two years of follow-up and do not analyze adherence to other drugs. OBJECTIVES: To report long-term adherence rates for statins, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers in patients who recently experienced a first cardiovascular event. METHODS: Linked administrative databases in the province of Saskatchewan were used in this retrospective cohort study. Eligible patients received a new statin prescription within one year of their first cardiovascular event between 1994 and 2001. Adherence to statins, beta-blockers and ACE inhibitors was assessed from the first statin prescription to a subsequent cardiovascular event. RESULTS: Of 1221 eligible patients, the proportion of patients adherent to statin medications dropped to 60.3% at one year and 48.8% at five years. The decline in the proportion of adherent patients was most notable during the first two years (100% to 53.7%). Several factors were associated with statin adherence, including age (P = 0.012), number of physician service days (P = 0.037), chronic disease score (P = 0.032), beta-blocker adherence (P < 0.001) and ACE inhibitor adherence (P < 0.001). Adherence to beta-blockers and ACE inhibitors was very similar to adherence to statin medications at each year of follow-up. CONCLUSIONS: Patients who exhibit optimal adherence over one to two years after their initial cardiovascular event generally remain adherent over subsequent years. Also, adherence to beta-blockers and ACE inhibitors is significantly associated with statin adherence in a subset of patients; however, overall adherence to all three drugs was similarly poor.

An association of maternal age and birth weight with end-stage renal disease in Saskatchewan. Sub-analysis of registered Indians and those with diabetes.

AIMS: To determine links between birth related factors and end-stage renal disease (ESRD). METHODS: This 1:3 age, sex, and source population (registered Indians [SkRI] and other Saskatchewan people [OSkP]) matched case-control study, compared maternal age and parity, gestational age, low birth weight (LBW), and high birth weight (HBW), between subjects with and without ESRD. RESULTS: Of 1,162 subjects, 277 cases (48 SkRI and 229 OSkP) and 601 controls (112 SkRI and 489 OSkP) had birth weight information. A trend for increased LBW rates occurred among SkRI and OSkP cases compared to controls (10.4 vs. 5.3% and 6.6 vs. 4.3%), and was significant for OSkP female cases (OR 3.66; 95% confidence interval [CI] 1.05, 12.73). Higher HBW rates occurred in SkRI cases (14.6% compared to 11.6% controls; N/S), and 3/5 female SkRI diabetic ESRD (DESRD) cases were over 3,750 g compared to 1/14 controls (p < 0.05). Only maternal age >/=30 years was an independent predictor for ESRD, particularly for OSkP non-DESRD cases (OR 2.45; 95% CI 1.03, 5.8). Cases with older mothers had lower mean birth weights than controls (3,236 vs. 3,434 g; p = 0.005). CONCLUSIONS: Older maternal age may predispose offspring to ESRD through mechanisms that differ for DESRD versus non-DESRD, and that may relate to ethnicity.