Predictors of suicide at time of diagnosis in schizophrenia spectrum disorder: A 20-year total population study in Ontario, Canada.

BACKGROUND: Suicide is a major cause of mortality for individuals with schizophrenia spectrum disorders (SSD). Understanding the risk factors for suicide at time of diagnosis can aid clinicians in identifying people at risk. METHODS: Records from linked administrative health databases in Ontario, Canada were used to identify individuals aged 16 through 45 years who received a first lifetime diagnosis of SSD (schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified (NOS)) using a validated algorithm between 01/01/1993 and 12/31/2010. The main outcome was death by suicide following cohort entry until 12/31/2012. OUTCOMES: 75,989 individuals with a first SSD diagnosis (60.1% male, 39.9% female) were followed for an average of 9.56 years. During this period, 1.71% of the total sample (72.1% male, 27.9% female) died by suicide, after an average of 4.32 years. Predictors of suicide death included male sex (HR 2.00, 95% CI 1.76-2.27), age at diagnosis between 26 and 35 (HR 1.27, 95% CI 1.10-1.45) or 36-45 (HR 1.34, 95% CI 1.16-1.54), relative to 16-25, and suicide attempt (HR 2.23, 95% CI 1.86-2.66), drug use disorder (HR 1.21, 95% CI 1.04-1.41), mood disorder diagnosis (HR 1.32, 95% CI 1.17-1.50), or mental health hospitalization (HR 1.30 95% CI 1.13-1.49) in the 2 years prior to SSD diagnosis. INTERPRETATION: Death by suicide occurs in 1 out of every 58 individuals and occurred early following first diagnosis of SSD. Psychiatric hospitalizations, mood disorder diagnoses, suicide attempts prior to SSD diagnosis, as well as a later age at first diagnosis, are all predictors of suicide and should be integrated into clinical assessment of suicide risk in this population.

Methodological approaches to population based research of screening procedures in the presence of selection bias and exposure measurement error: colonoscopy and colorectal cancer outcomes in Ontario.

BACKGROUND: The study describes the methodological challenges encountered in an observational study estimating the effectiveness of colonoscopy in reducing colorectal cancer (CRC) incidence and mortality. METHODS: Using Ontario provincial administrative data, we conducted a population-based retrospective cohort study to assess CRC incidence and mortality in a group of average-risk subjects aged 50-74 years who underwent colonoscopy between 1996-2000. We created two study cohorts; unselected and restricted. The unselected cohort consists of subjects aged 50-74 years who were eligible for CRC screening and who had the same primary care physician (PCP) during the period 1996-2000 with at least two years of follow-up. PCPs are general practioners/family physicians who are the main source of health care for Ontarians. The restricted cohort was a nested sample of unselected cohort who were alive and free of CRC as on January 1, 2001 and whose PCPs had at least 10 screen-eligible patients with a colonoscopy referral rate of more than 3%. We compared the outcomes in the two study cohorts; unselected vs. restricted. We then estimated the absolute risk reduction associated with colonoscopy in preventing CRC incidence and mortality in the restricted cohort, using traditional regression analysis, propensity score analysis and instrumental variable analysis. RESULTS: The unselected cohort (N = 1,341,612) showed that colonoscopy was associated with an increase in CRC incidence (1.61% vs. 4.61%) and mortality (0.36% vs. 1.16%), whereas the restricted cohort (N = 1,089,998) showed that colonoscopy was associated with a reduction in CRC incidence (1.36% vs. 0.84%) and mortality (0.23% vs. 0.15%). For CRC incidence, the absolute risk reduction (ARR) associated with colonoscopy use was 0.52% in an unadjusted model, 0.53% in a multivariate logistic regression model, 0.54% in a propensity score-weighted outcome model, 0.56% in propensity score-matched model, and 0.60% using instrumental variable analysis. For CRC mortality, the ARR was 0.08% in the unadjusted model, multivariate logistic regression model and for a propensity score- weighted outcome model, 0.10% using propensity score matched model and 0.17% using the IVA model. CONCLUSIONS: Colonoscopy use reduced the risk of CRC incidence and mortality in the restricted cohort. The study highlights the importance of appropriate selection of study subjects and use of analytic methods for the evaluation of screening methods using observational data.

Effect of colonoscopy on colorectal cancer incidence and mortality: an instrumental variable analysis.

BACKGROUND: Using population-based health services information to estimate the effectiveness of colonoscopy on colorectal cancer (CRC) outcomes is prone to selection bias. OBJECTIVE: To determine the effect of colonoscopy on CRC incidence and mortality. DESIGN: Population-based retrospective cohort study. SETTING: Ontario provincial health data information. PATIENTS: This study involved average-risk persons aged 50 to 74 years from 1996 to 2000 who were alive and free of CRC on January 1, 2001. INTERVENTION: Colonoscopy between 1996 and 2000. MAIN OUTCOME MEASUREMENTS: CRC incidence and mortality from 2001 to 2007. RESULTS: The study cohort contained 1,089,998 persons, 7.9% of whom had undergone a colonoscopy between 1996 and 2000. Using primary care physician rate of discretionary colonoscopy as an instrumental variable, the receipt of colonoscopy was associated with a 0.60% (95% confidence interval [CI], 0.31%-0.78%) absolute reduction in the 7-year colorectal cancer incidence and a 0.17% (95% CI, 0.14%-0.21%) absolute reduction in the 5-year risk of death caused by CRC. This corresponds to a 48% relative decrease in CRC incidence (risk ratio [RR] 0.52; 95% CI, 0.34-0.76) and 81% decrease in mortality caused by CRC (RR 0.19, 95% CI, 0.07-0.47). In subgroup analyses, the reduction in the risk of death due to CRC was larger in women than men. The reduction in CRC incidence was larger for complete colonoscopies and for left-sided cancers. LIMITATIONS: Instrumental variable methods estimate only the marginal effect on the population studied. CONCLUSION: Increased use of colonoscopy procedures is associated with a reduction in the incidence and mortality of CRC in the population studied.

Social disparities in the use of colonoscopy by primary care physicians in Ontario.

BACKGROUND: It is unclear if all persons in Ontario have equal access to colonoscopy. This research was designed to describe long-term trends in the use of colonoscopy by primary care physicians (PCPs) in Ontario, and to determine whether PCP characteristics influence the use of colonoscopy. METHODS: We conducted a population-based retrospective study of PCPs in Ontario between the years 1996-2005. Using administrative data we identified a screen-eligible group of patients aged 50-74 years in Ontario. These patients were linked to the PCP who provided the most continuous care to them during each year. We determined the use of any colonoscopy among these patients. We calculated the rate of colonoscopy for each PCP as the number of patients undergoing colonoscopies per 100 screen eligible patients. Negative binomial regression was used to identify factors associated with the rate of colonoscopy, using generalized estimating equations to account for clustering of patients within PCPs. RESULTS: Between 7,955 and 8,419 PCPs in Ontario per year (median age 43 years) had at least 10 eligible patients in their practices. The use of colonoscopy by PCPs increased sharply in Ontario during the study period, from a median rate of 1.51 [inter quartile range (IQR) 0.57-2.62] per 100 screen eligible patients in 1996 to 4.71 (IQR 2.70-7.53) in 2005. There was substantial variation between PCPs in their use of colonoscopy. PCPs who were Canadian medical graduates and with more years of experience were more likely to use colonoscopy after adjusting for their patient characteristics. PCPs were more likely to use colonoscopy if their patient populations were predominantly women, older, had more illnesses, and if their patients resided in less marginalized neighborhoods (lower unemployment, fewer immigrants, higher income, higher education, and higher English/French fluency). CONCLUSIONS: There is substantial variation in the use of colonoscopy by PCPs, and this variation has increased as the overall use of colonoscopy increased over time. PCPs whose patients were more marginalized were less likely to use colonoscopy, suggesting that there are inequities in access.

Betel quid without tobacco as a risk factor for oral precancers.

The IARC monographs recently classified chewing betel quid without tobacco as a human carcinogen. Several studies in Taiwan have reported that betel quid without tobacco may increase the risk of oral precancers such as oral leukoplakia and oral submucous fibrosis. However in India, since most betel quid chewers prefer to add tobacco to the quid, the independent effect of betel quid on the risk of oral precancers is difficult to assess and has not yet been fully explored. We conducted a large case-control study in Kerala, India, including 927 oral leukoplakia cases, 170 oral submucous fibrosis cases, 100 erythroplakia cases, 115 multiple oral precancer cases and 47,773 controls. The focus of this reanalysis is on the minority of individuals who chewed betel quid without tobacco. Among nonsmokers and nondrinkers, chewing betel quid without tobacco conferred ORs of 22.2 (95%CI = 11.3, 43.7) for oral leukoplakia, 56.2 (95%CI = 21.8, 144.8) for oral submucous fibrosis, 29.0 (95%CI = 5.63, 149.5) for erythroplakia and 28.3 (95%CI = 6.88, 116.7) for multiple oral precancers, after adjustment for age, sex, education and BMI. Dose-response relationships were observed for both the frequency and duration of betel quid chewing without tobacco on the risk of oral precancers. In conclusion, our study supports the hypothesis that chewing betel quid without tobacco elevates the risks of various oral precancers.

Risk factors for multiple oral premalignant lesions.

Oral leukoplakia, oral submucous fibrosis and erythroplakia are 3 major types of oral premalignant lesions. Multiple oral premalignant lesions may possibly develop due to field cancerization, where carcinogenic exposures can cause simultaneous genetic defects to the upper aerodigestive tract epithelium, putting the epithelium at high risk for development of premalignant lesions at different stages of carcinogenesis. There have been no epidemiological studies on risk or protective factors of the disease. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. A total of 115 subjects with multiple oral premalignant lesions (8-10% of oral premalignant lesions in our case series) were included: 64 subjects with oral leukoplakia and oral submucous fibrosis, 19 subjects with oral leukoplakia and erythroplakia, 22 subjects with oral submucous fibrosis and erythroplakia and 10 subjects with all 3 lesions. Individuals without oral lesions were considered controls (n=47,773). The odds ratio (OR) for ever tobacco chewers was 37.8 (95% confidence interval (CI)=16.2-88.1) when adjusted for age, sex, education, BMI, smoking, drinking and fruit/vegetable intake. Dose-response relationships were seen for the frequency (p<0.0001) and duration of tobacco chewing (p<0.0001) with the risk of multiple oral premalignant lesions. Whereas alcohol drinking may possibly be a risk factor for multiple oral premalignant lesions, smoking was not associated with the risk of multiple oral premalignant lesions (OR=0.9, 95%CI=0.5-1.7). The results suggest that tobacco chewing was the most important risk factor for multiple oral premalignant lesions and may be a major source of field cancerization on the oral epithelium in the Indian population.