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OBJECTIVE: To examine trends in the treatment of diabetes using the biannual interviews of the longitudinal National Population Health Survey (NPHS), 1994-2004 as they relate to changes in Clinical Practice Guidelines (CPGs). METHODS: A sample of 17 276 Canadians 18 years and older was selected for repeated interviews at two-year intervals from 1994 to 2004 for the NPHS. The population used for this study includes all respondents aged 40 to 79 for any of the cycles. RESULTS: CPGs issued by the Canadian Diabetes Association in 1998 and 2004 recommend a stepwise introduction of lifestyle changes, to be followed by single then multiple oral antidiabetic agents (OA), and finally insulin until adequate control is achieved. While the use of OA increased, only a small proportion indicated diet or physical exercise as part of their treatment; those with no drug treatment reported less diet modification and physical exercise. Antihypertensives and statin use in Canadians with diabetes increased to double that of Canadians overall, but remained underutilized. CONCLUSION: This study provides an update on the treatment of diabetes in Canada between 1994 and 2004. While some changes in diabetes treatment were compatible with CPGs, there is room for improvement, especially in lifestyle modifications.

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The aim of this study was to evaluate the treatment patterns of adolescents with cancer in Canada to ensure this population is receiving the most appropriate care. The Treatment and Outcome Surveillance (TOS) system was compared with the Canadian Cancer Registry (CCR) to estimate the proportion of adolescents (15-19 years) treated in Canadian paediatric oncology centres from 1995 to 2000 inclusive. Using TOS, the demographic, disease, and clinical characteristics of adolescents treated in paediatric versus adult centres in the Prairies were compared and differences were tested statistically. Approximately 30% of Canadian adolescents with cancer were treated in a paediatric centre. Adolescents treated in an adult centre were older at diagnosis and more likely to have carcinoma or germ cell tumours. The time between symptom onset and first treatment was longer for these adolescents, primarily due to the time between first health-care contact and assessment by a treating oncologist or surgeon. They were less likely to be enrolled in a clinical trial. These results suggest that care for adolescents with cancer in Canada is less satisfactory than for younger children, and can be improved.

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Recent reports have suggested a link between low serum total cholesterol and risk of death from suicide. We examined this association using participants in the 1970-1972 Nutrition Canada Survey. We determined the mortality experience of Nutrition Canada Survey participants older than 11 years of age at baseline through 1993 by way of record linkage to the Canadian National Mortality Database. The relation between low serum total cholesterol and mortality from suicide was assessed using a stratified analysis (N = 11,554). There were 27 deaths due to suicide. Adjusting for age and sex, we found that those in the lowest quartile of serum total cholesterol concentration (<4.27 mmol/liter) had more than six times the risk of committing suicide (rate ratio = 6.39; 95% confidence interval = 1.27-32.1) as did subjects in the highest quartile (>5.77 mmol/liter). Increased rate ratios of 2.95 and 1.94 were observed for the second and third quartiles, respectively. The effect persisted after the exclusion from the analysis of the first 5 years of follow-up and after the removal of those who were unemployed or who had been treated for depression. These data indicate that low serum total cholesterol level is associated with an increased risk of suicide.

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BACKGROUND: Men in the United States undergoing renal replacement therapy are more likely than women to receive a kidney transplant. However, the ability to pay may, in part, be responsible for this finding. OBJECTIVE: To compare adult male and female transplantation rates in a setting in which equal access to medical treatment is assumed. METHODS: Using data from the Canadian Organ Replacement Register, the rate of first transplantations was computed for the 20, 131 men and the 13,458 women aged 20 years or older who initiated renal replacement therapy between January 1, 1981, and December 31, 1996. Poisson regression analysis was used to estimate the male-female transplantation rate ratio, adjusting for age, race, province, calendar period, underlying disease leading to renal failure, and dialytic modality. Actuarial survival methods were used to compare transplantation probability for covariable-matched cohorts of men and women. RESULTS: Men experienced 20% greater covariable-adjusted kidney transplantation rates relative to women (rate ratio, 1.20; 95% confidence interval, 1.13-1.27). The sex disparity was stronger for cadaveric transplants (rate ratio, 1.23) compared with those from living donors (rate ratio, 1.10). The 5-year probability of receiving a transplant was 47% for men and 39% for women within covariable-matched cohorts (P<.001). The sex disparity in transplantation rates increased with increasing age. The sex effect was weaker among whites and Oriental persons (Chinese, Japanese, Vietnamese, Cambodian, Laotian, Filipino, Malaysian, Indonesian, and Korean) and stronger among blacks, Asian Indians (Indian, Pakistani, and Sri Lankan), and North American Indians (aboriginal). CONCLUSION: Since survival probability and quality of life are superior for patients who undergo transplantation relative to those who undergo dialysis, an increased effort should be made to distribute kidneys available for transplantation more equitably by sex among patients undergoing renal replacement therapy.

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BACKGROUND: The incidence and prevalence of end-stage renal disease (ESRD) have increased greatly in Canada over the last 2 decades. Because of the high cost of therapy, predicting numbers of patients who will require dialysis and transplantation is necessary for nephrologists and health care planners. METHODS: The authors projected ESRD incidence rates and therapy-specific prevalence by province to the year 2005 using 1981-1996 data obtained from the Canadian Organ Replacement Register. The model incorporated Poisson regression to project incidence rates, and a Markov model for patient follow-up. RESULTS: Continued large increases in ESRD incidence and prevalence were projected, particularly among people with diabetes mellitus. As of Dec. 31, 1996, there were 17,807 patients receiving renal replacement therapy in Canada. This number was projected to climb to 32,952 by the end of 2005, for a relative increase of 85% and a mean annual increase of 5.8%. The increased prevalence was projected to be greatest for peritoneal dialysis (6.0% annually), followed by hemodialysis (5.9%) and functioning kidney transplant (5.7%). The projected annual increases in prevalence by province ranged from 4.4%, in Saskatchewan, to 7.5%, in Alberta. INTERPRETATION: The projected increases are plausible when one considers that the incidence of ESRD per million population in the United States and other countries far exceeds that in Canada. The authors predict a continued and increasing short-fall in resources to accommodate the expected increased in ESRD prevalence.

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The expected number of deaths in four hypothetical Canadian cohorts (male current smokers, male never-smokers, female current smokers and female never-smokers) was examined by constructing abridged life tables. The expected number of premature deaths (before age 70) among lifelong smokers was found to be about twice that expected among lifelong never-smokers for both males (2.3) and females (1.9). The higher number of premature deaths in the smoking cohorts resulted mainly from cancer and coronary heart disease. The results of this paper highlight the dramatic impact that smoking has on premature mortality.

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BACKGROUND: Recent reports have implicated periodontal disease as a risk factor for coronary heart disease (CHD). METHODS: A retrospective cohort study was conducted using participants in the 1970-1972 Nutrition Canada Survey (NCS). The mortality experience of male and female NCS participants aged 35-84 years without self-reported CHD (n = 10,368) or cerebrovascular disease (CVD) (n = 11,251) was determined through 1993. The relation between dental health and the risk of fatal CHD and CVD was assessed using Poisson regression modeling. RESULTS: In total, 466 CHD and 210 CVD deaths were observed; missing confounder data reduced these numbers to 416 CHD and 182 CVD deaths. Adjusted for age, sex, diabetes status, serum total cholesterol, smoking, hypertensive status, and province, we found a statistically significant association between periodontal disease and risk of fatal CHD. Rate ratios (RR) of 2.15 [95% confidence interval (CI) 1.25-3.72) and 1.90 (95% CI 1.17-3.10) were observed for severe gingivitis and edentulous status, respectively. Non-statistically significantly increased RRs of 1.81 and 1.63 were observed for severe gingivitis and edentulous status for CVD. CONCLUSIONS: These data indicate that poor dental health is associated with an increased risk of fatal CHD.

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OBJECTIVE: To compare mortality rates on hemodialysis (HD) to rates on continuous ambulatory/cyclic peritoneal dialysis (CAPD/CCPD), to contrast our results with those of other recent investigations, and to discuss reasons for discrepancies. DATA SOURCES: Patient-specific data obtained from the Canadian Organ Replacement Register on patients initiating renal replacement therapy (RRT) between 1 January 1990 and 31 December 1995 (n = 14 483). Recent mortality comparisons of CAPD and HD. MAIN OUTCOME MEASURES: Mortality rate ratio (RR) based on "as-treated" (AT) analysis incorporating treatment modality switches and adjusting for age, primary renal diagnosis, and comorbid conditions using Poisson regression. Hazard ratios (HR) were estimated using Cox regression and based on an "intent-to-treat" (ITT) analysis wherein patients were classified based on dialytic modality received on follow-up day 90. RESULTS: Adjusted mortality rates were significantly decreased on CAPD/CCPD relative to HD [RR = 0.73, 95% confidence interval (CI) = (0.69, 0.77)] based on the AT analysis. Most of the protective effect of CAPD/CCPD was concentrated in the first 2 years of follow-up post-RRT initiation. Based on the ITT analysis, the estimated CAPD/ CCPD effect was greatly reduced, with HR = 0.93 (0.87, 0.99). CONCLUSIONS: We provide further evidence that CAPD/CCPD is not an inferior dialytic modality to HD, particularly in the short term. Comparing mortality rates on CAPD/CCPD and HD is inherently difficult due to the potential for bias. Discrepancies between our results and those of previous investigations, and variability in findings among previous studies, relate to differences in clinical and demographic setting, patient populations, study design, statistical methods, and interaction between the dialytic modality effect and various other covariables.

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This study assessed the survival of a nationally representative sample of older Canadian men, taking into account common comorbid conditions. Mortality follow-up between 1978 and 1989 was conducted for male participants of the Canada Health Survey who were at least 60 years of age at baseline. The proportional hazards model and life table methods were used to examine survival by comorbidity status. Comorbid conditions examined included history of stroke and/or heart disease, high blood pressure, chronic bronchitis or emphysema, diabetes and smoking status, but excluded cancer because of small numbers. For those subjects aged 80 and older, comorbidity was not a significant predictor of survival. A large portion of men between the ages of 60 and 79, even those with pre-existing comorbid conditions, survived at least 10 years after interview. In a clinical setting, more detailed information on comorbid conditions can be obtained to better estimate long-term survival. Notwithstanding, our findings may have implications for the administration of population-based health interventions (e.g. the use of prostate-specific antigen [PSA] blood tests for the early detection of prostate cancer). In particular, our results suggest that there may be little benefit in restricting access to PSA screening based on survival probability in men under age 80.

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We examined the relation between physical activity, physical fitness, and all-cause mortality in a national population-based study of Canadians. We followed men and women ages 20-69 years who had participated in the Canada Fitness Survey between 1981 and 1988. We assessed risk factors for 6,246 men and 8,196 women using multivariate Poisson regression analysis. At baseline, all subjects were asymptomatic according to self-reported screening questions for cardiovascular disease. Men who expended > or =0.5 kilocalories per kilogram of body weight per day (KKD) experienced a 20% decline in risk of mortality [rate ratio (RR) = 0.82; 95% confidence interval (CI) = 0.65-1.04] when compared with subjects expending <0.5 KKD. We observed a 30% decline in risk of mortality among women expending > or =3.0 KKD relative to those expending <0.5 KKD (RR = 0.71; 95% CI = 0.45-1.11). Similar patterns of risk were evident for both men and women when analyses were restricted to participation in nonvigorous activities. Those who perceived themselves to be of less than average fitness were at increased risk of mortality (male RR = 1.64, 95% CI = 1.21-2.22; female RR = 1.66, 95% CI = 1.21-2.26). Subjects with undesirable cardiorespiratory fitness levels were more likely to die, compared with those having recommended fitness levels (RR = 1.52; 95% CI = 0.72-3.18). Fifty-three per cent of men and 35% of women reported participating in a vigorous activity. The relation between daily energy expenditure and risk of mortality in these subjects could not be evaluated, as there were few deaths. Nonetheless, our results among participants reporting no vigorous activities support the hypothesis that there is a reduction in mortality risk associated with even modest participation in activities of low intensity.

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BACKGROUND: An exploratory, case-control study was used to investigate a new hypothesis about suicide among farm operators. This hypothesis suggested a biologically plausible link between exposures to certain pesticides and the occurrence of suicide among farm operators. These analyses were based on data from the Canadian Farm Operator Cohort. METHODS: Canadian male farm operators who committed suicide between 1971-1987 (n = 1,457) were compared with a frequency matched (by age and province) sample of control farm operators (n = 11,656) who were alive at the time of death of individual cases. Comparisons focused on past exposures to pesticides reported to the 1971 Canada Census of Agriculture. RESULTS: Multivariate logistic regression analyses indicated no associations between suicide and (1) acres sprayed with herbicides, (2) acres sprayed with insecticides, and (3) the costs of agricultural chemicals purchased; after controlling for important covariates. There was, however, a suggestive increase in risk for suicide associated with herbicide and insecticide spraying among a subgroup of farm operators who were most likely to be directly exposed to pesticides: OR = 1.71 (95% CI = 1.08-2.71) for 1-48 vs. 0 acres sprayed. Additional risk factors that were identified included seasonal vs. year-round farm work (OR = 1.68; 95% CI = 1.15-2.46); and high levels of paid labor on the farm (e.g., OR = 1.61; 95% CI = 1.24-2.10, for > 13 vs. 0 weeks per year). Factors that were protective included marriage (odds ratio (OR) = 0.69; 95% confidence interval (CI) = 0.58-0.81), having more than one person resident in the farm house (e.g., two vs. one person; OR = 0.62; 95% CI = 0.42-0.92); and higher levels of education (e.g., postsecondary vs. primary; OR = 0.40; 95% CI = 0.17-0.96). CONCLUSIONS: This study does not provide strong support for the main hypothesis under study, that exposure to pesticides is an important risk factor for suicide among farmers. Although secondary to the main hypothesis, a number of other risk factors for suicide were suggested. These have implications for the future study and targeting of suicide prevention programs in rural Canada.

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Although radon is a well-established lung carcinogen, there are uncertainties concerning the exposure-response relationship, whether exposures in early life are particularly hazardous, and how smoking affects the risks associated with radon exposure. A cohort study of the mortality experience of 1,743 underground fluorspar miners and 321 surface workers from 1950 to 1984 reported previously has been extended to include 6 additional years of follow-up (1985-1990). A statistically significant relationship was noted between radon-progeny exposure and risk of lung cancer mortality. Our analysis found no effect for age at first exposure. Attained age was strongly predictive of excess relative risk (ERR) per working level month (WLM) of radon exposure, falling from 0.025 for those aged less than 50 years to 0.002 for those 70 years or older. An inverse exposure-rate effect was also observed, wherein for equal total exposure, a high exposure rate (and short duration) is less harmful than a low exposure rate (and long duration). The ERR/WLM increased from 0.0019 for exposures of less than 10 years to 0.0076 for exposures of 20 or more years. The analysis of time-since-exposure windows revealed a greater ERR/WLM for exposures received in more recent periods, similar to the result for time since last exposure. Excess relative risks per WLM were higher for current smokers than for nonsmokers (never and former smokers). Analyses were consistent with a multiplicative relationship between radon-progeny exposure and current smoking and the risk of lung cancer. The assessment of radon exposure and lung cancer risk should incorporate the effects of exposure rate, time since exposure, smoking status and attained age.

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BACKGROUND: End-stage renal disease (ESRD) incidence and prevalence are increasing in many countries worldwide. Due to the high cost of therapy, predicting future numbers of patients requiring dialysis and transplantation is necessary for health care planners. Projecting therapy-specific chronic disease prevalence is inherently problematic, and examples of suitable models and their application are sparse. When applied, rarely was the adequacy of such models evaluated. METHODS: We describe and illustrate a method for projecting therapy-specific ESRD prevalence in Canada for 1995-2005 using data obtained from the Canadian Organ Replacement Register. The projections combine the Poisson model for incidence rates and a Markov model for patient follow-up. Model adequacy is empirically validated by data-splitting. RESULTS: Large increases in ESRD prevalence are expected in Canada, with an average annual increase of 6.9% projected for 1995-2005. Upon validation, the projection model based on 1981-1987 data was able to predict 1994 prevalence within 1%, while projected therapy-specific prevalences closely approximated those observed. CONCLUSIONS: Therapy-specific ESRD prevalence was successfully projected using Poisson and Markov models. Where multistate prevalence forecasts are required, the method could be augmented for application to various other chronic diseases.

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Preexisting computerized databases are potentially valuable sources of epidemiologic data. Since such databases are infrequently created specifically for etiologic research, data may be available for the exposure of interest and, through record linkage, for the endpoint of interest, but lacking for potential confounders. Because of the size of these databases, two-stage sampling is an efficient alternative to surveying the entire study population for confounder data. At stage 1, information on exposure and disease status is obtained for the entire study population. Confounder data are collected for probability-selected subsamples at stage 2. Logistic regression is performed on the stage 2 samples, with the parameter estimates and variances appropriately corrected to account for the stage 1 data. In this paper, the authors present methods for determining the required stage 2 sample size in the case of categorical exposure and confounding variables. Sample size tables, power curves, and a computer program have been produced to accommodate a binary exposure and a single binary confounder. With the increasing availability of preexisting yet incomplete databases, the potential for use of two-stage sampling will greatly increase in the future. This investigation provides a basis for estimating the number of participants to sample for the collection of confounder data at the second stage.

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Although kidney transplantation is the preferred treatment method for patients with ESRD, most patients are placed on dialysis either while awaiting transplantation or as their only therapy. The question of which dialytic method provides the best patient survival remains unresolved. Survival analyses comparing hemodialysis and continuous ambulatory peritoneal dialysis/continuous cyclic peritoneal dialysis (CAPD/CCPD), a newer and less costly dialytic modality, have yielded conflicting results. Using data obtained from the Canadian Organ Replacement Register, we compared mortality rates between hemodialysis and CAPD/CCPD among 11,970 ESRD patients who initiated treatment between 1990 and 1994 and were followed-up for a maximum of 5 years. Factors controlled for include age, primary renal diagnosis, center size, and predialysis comorbid conditions. The mortality rate ratio (RR) for CAPD/CCPD relative to hemodialysis, as estimated by Poisson regression, was 0.73 (95% confidence interval: 0.68 to 0.78). No such relationship was found when an intent-to-treat Cox regression model was fit. Decreased covariable-adjusted mortality for CAPD/CCPD held within all subgroups defined by age and diabetes status, although the RRs increased with age and diabetes prevalence. The increased mortality on hemodialysis compared with CAPD/CCPD was concentrated in the first 2 years of follow-up. Although continuous peritoneal dialysis was associated with significantly lower mortality rates relative to hemodialysis after adjusting for known prognostic factors, the potential impact of unmeasured patient characteristics must be considered. Notwithstanding, we present evidence that CAPD/CCPD, a newer and less costly method of renal replacement therapy, is not associated with increased mortality rates relative to hemodialysis.

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OBJECTIVES: The association between cumulative radon exposure and coronary heart disease mortality was studied in a retrospective cohort investigation of Newfoundland fluorspar miners. METHODS: Multivariate Poisson regression techniques were used to estimate relative risks of coronary heart disease mortality by level of radon exposure. Relative risks (RR) were adjusted by attained age, calendar period, duration of exposure, and smoking status. Death from coronary heart disease was the outcome measure of interest and was identified by record linkage to the Canadian Mortality Database. RESULTS: An elevated risk of mortality from coronary heart disease was observed among miners with a cumulative radon exposure exceeding 1000 working-level months [RR 1.5, 95% confidence interval (95% CI) 0.77-2.75]. The association between radon exposure and coronary heart disease was not statistically significant according to a test for trend across exposure categories (P = 0.09). The smokers were 1.8 times more likely than the nonsmokers to die from coronary heart disease (95% CI 1.1-2.8). CONCLUSIONS: These results suggest a positive association between coronary heart disease and radon exposure. However, these findings should be interpreted cautiously due to the inability to control for the confounding influence of other known risk factors of coronary heart disease.

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Some recent estimates of lung cancer risk from exposure to radon progeny in homes have been based on models developed from a pooled analysis of 11 cohorts of underground miners exposed to radon. While some miners were exposed to over 10,000 working level months (WLM), mean exposure among exposed miners was 162 WLM, about 10 times the exposure from lifetime residence in an average house and about three times the exposure from lifetime residence at the "action level" suggested by the U.S. Environmental Protection Agency. The extrapolation of lung cancer risk from the higher exposures in the miners to the generally lower exposures in the home is a substantial source of uncertainty in the assessment of the risk of indoor radon. Using the pooled data for the miners, analyses of lung cancer risk were carried out on data restricted to lower exposures, either <50 WLM or <100 WLM. In the pooled data, there were 115 lung cancer cases among workers with no occupational WLM exposure and 2,674 among exposed miners, with 353 and 562 lung cancer cases in miners with <50 WLM and <100 WLM, respectively. Relative risks (RRs) for categories of WLM based on deciles exhibited a statistically significant increasing trend with exposure in each of the restricted data sets. In the restricted data, there was little evidence of departures from a linear excess relative risk model in cumulative exposure, although power to assess alternative exposure-response trends was limited. The general patterns of declining excess RR per WLM with attained age, time since exposure and exposure rate seen in the unrestricted data were similar to the patterns found in the restricted data. Risk models based on the unrestricted data for miners provided an excellent fit to the restricted data, suggesting substantial internal validity in the projection of risk from miners with high exposures to those with low exposures. Estimates of attributable risk for lung cancer (10-14%) in the U.S. from residential radon based on models from the unrestricted data were similar to estimates based on the data for miners receiving low exposures.

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OBJECTIVE: To assess the relationship between serum folate level and the risk of fatal coronary heart disease (CHD) among men and women. DESIGN: Retrospective cohort study with serum folate levels measured from September 1970 to December 1972, with follow-up through 1985. SETTING: Participants in the Nutrition Canada Survey. PARTICIPANTS: A total of 5056 Canadian men and women aged 35 to 79 years with no history of self-reported CHD. MAIN OUTCOME MEASURE: Fifteen-year CHD mortality. RESULTS: A total of 165 CHD deaths were observed. We found a statistically significant association between serum folate level and risk of fatal CHD, with rate ratios for individuals in the lowest serum folate level category (<6.8 nmol/L [3 ng/mL]) compared with the highest category (>13.6 nmol/L [6 ng/mL]) of 1.69 (95% confidence interval, 1.10-2.61). CONCLUSIONS: These data indicate that low serum folate levels are associated with an increased risk of fatal CHD.

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Recent models for radon-induced lung cancer assume that at high levels of cumulative exposure, as experienced historically by many underground miners of uranium and other ores, the risk of lung cancer follows an inverse dose-rate (protraction enhancement) pattern. That is, for equal total dose, a greater risk is incurred by those whose total dose is accumulated at a lower rate over a longer duration than at a higher rate over a shorter duration. This inverse dose-rate effect is hypothesized to be the consequence of multiple traversals of the nucleus of a target cell by alpha particles. It has recently been concluded, however, that for low total doses, as in most residential settings, the inverse dose-rate effect should diminish and perhaps even disappear, since at very low doses the probability that more than one alpha particle would traverse a cell is small and there would be no possibility for interactions from multiple hits. Pooling original data from 11 cohort studies of underground miners, including nearly 1.2 million person-y of observation and 2,701 lung cancer deaths, we evaluate the presence of an inverse dose-rate effect and its modification by total dose. An inverse dose-rate effect was confirmed in each cohort, except one, and overall in the pooled data. There also appears to be a diminution of the inverse dose-rate effect below 50 Working Level Months (WLM), although analyses were necessarily hampered by a limited range of exposure rates at low total WLM. These data support both the presence of an inverse dose-rate effect, as well as its diminution at low total dose. As a consequence, assessment of risks of radon progeny exposure in homes (on average 15-20 WLM for a lifetime) using miner-based models should not assume an ever-increasing risk per unit dose. Rather, it is more appropriate to apply risk models that take into account protraction enhancement and its diminution.

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