Ascertaining asthma status in epidemiologic studies: a comparison between administrative health data and self-report.

BACKGROUND: Studies have suggested that agreement between administrative health data and self-report for asthma status ranges from fair to good, but few studies benefited from administrative health data over a long period. We aimed to (1) evaluate agreement between asthma status ascertained in administrative health data covering a period of 30 years and from self-report, and (2) identify determinants of agreement between the two sources. METHODS: We used administrative health data (1983-2012) from the Quebec Birth Cohort on Immunity and Health, which included 81,496 individuals born in the province of Quebec, Canada, in 1974. Additional information, including self-reported asthma, was collected by telephone interview with 1643 participants in 2012. By design, half of them had childhood asthma based on health services utilization. Results were weighted according to the inverse of the sampling probabilities. Five algorithms were applied to administrative health data (having ≥ 2 physician claims over a 1-, 2-, 3-, 5-, or 30-year interval or ≥ 1 hospitalization), to enable comparisons with previous studies. We estimated the proportion of overall agreement and Kappa, between asthma status derived from algorithms and self-reports. We used logistic regression to identify factors associated with agreement. RESULTS: Applying the five algorithms, the prevalence of asthma ranged from 49 to 55% among the 1643 participants. At interview (mean age = 37 years), 49% and 47% of participants respectively reported ever having asthma and asthma diagnosed by a physician. Proportions of agreement between administrative health data and self-report ranged from 88 to 91%, with Kappas ranging from 0.57 (95% CI: 0.52-0.63) to 0.67 (95% CI: 0.62-0.72); the highest values were obtained with the [≥ 2 physician claims over a 30-year interval or ≥ 1 hospitalization] algorithm. Having sought health services for allergic diseases other than asthma was related to lower agreement (Odds ratio = 0.41; 95% CI: 0.25-0.65 comparing ≥ 1 health services to none). CONCLUSIONS: These findings indicate good agreement between asthma status defined from administrative health data and self-report. Agreement was higher than previously observed, which may be due to the 30-year lookback window in administrative data. Our findings support using both administrative health data and self-report in population-based epidemiological studies.

Association Between Markers of Vulnerability for Cannabis-Related Harms and Source of Supply: Secondary Analysis of a Representative Population Survey.

OBJECTIVE: In 2018, the sale of non-medical cannabis was authorized in the province of Quebec in Canada, within a public monopoly under the Société Québécoise du Cannabis (SQDC). The objective of this study was to offer a description of the cannabis-using population regarding the sources of cannabis supply and to explore whether at-risk individuals are purchasing cannabis at SQDC. METHOD: We used data from a cross-sectional, representative population survey (age >18 years, n = 1799), the Enquête Québécoise sur le Cannabis, which was completed between February and June 2019. Analyses involved adjusted binary logistic regressions, incorporating population weights, to assess 7 potential indicators of harm. RESULTS: The vulnerability profiles of SQDC consumers (47.8%) and those acquiring their cannabis elsewhere (52.2%) were similar in terms of frequency of cannabis use (adjusted odds ratio [aOR] = 0.46; 95% confidence interval [CI] = 0.12-1.67), motivation to use (aOR = 0.62; 95% CI = 0.16-2.46), concomitant consumption of other substances (aOR = 0.80; 95% CI = 0.14-4.75), cannabis-impaired driving behaviours (aOR = 0.93; 95% CI = 0.26-3.36), psychological distress (aOR = 0.99; 95% CI = 0.26-3.79), and problematic cannabis use (aOR = 0.46; 95% CI = 0.13-1.64). However, SQDC consumers were more likely to be aware of the cannabinoid content of the product purchased compared to those who acquired their cannabis from other sources (aOR = 4.12; 95% CI = 1.10-15.40). CONCLUSIONS: No association was detected between the source of cannabis supply and potential vulnerability indicators of cannabis-related harms, but SQDC consumers were more aware of the cannabinoid content of the products purchased. These results suggest that the regulated government supply in Quebec is reaching a substantial portion of those with potential high vulnerability to harm. Whether this knowledge translates into a reduction in the negative consequences related to consumption is still to be determined.

Association between Bacillus Calmette-Guerin (BCG) vaccination and lymphoma risk: A systematic review and meta-analysis.

Lymphoma etiology remains ill-defined, but immune factors seem to play a major role. The Bacillus Calmette-Guérin (BCG) vaccine, a non-specific stimulator of the cellular immune response, could influence lymphoma risk. Previous studies addressing this issue showed conflicting results. In this study, we performed a systematic review and meta-analysis to synthesize the epidemiological evidence. We conducted a systematic search of all relevant articles in PubMed, Embase, Library and Archives Canada, and Cochrane databases, up to November 1st 2018. A total of 11 studies were included. Each study was summarized, methodological quality was assessed by independent evaluators, and a consensus score was generated. Heterogeneity and publication bias were evaluated. Summary odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated separately for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) by either a fixed effect (FE) or a random effect (RE) model depending on heterogeneity. In this meta-analysis, BCG vaccination was not associated with HL (FE summary OR = 1.10; 95 % CI 0.93-1.30), but positively associated with NHL (RE summary OR = 1.20; 95 % CI 1.01-1.43). However, when restricting to higher quality studies, no association was found between BCG vaccination and either HL (RE summary OR = 0.97; 95 % CI 0.67-1.43) or NHL (RE summary OR = 1.15; 95 % CI 0.84-1.59). Overall, our findings do not support that BCG vaccination is associated with lymphoma risk. Yet, lack of statistical power and relatively high heterogeneity among studies prevent us from making definitive conclusions. Future studies investigating this issue are needed, using robust methodology.

Bacillus Calmette-Guérin (BCG) vaccination patterns in the province of Québec, Canada, 1956-1974.

BACKGROUND: In the province of Québec, Canada, the Bacillus Calmette-Guérin (BCG) vaccine was offered to newborns and school-age children from the 1950s to mid-1970s in an organized tuberculosis prevention program. OBJECTIVE: We aimed to describe the annual rates of skin test administration, proportion of skin tests that were positive, and rates of BCG vaccination from 1956 to 1974 according to age, sex, and administrative region. METHODS: For rates, numerators were extracted from the Québec BCG Vaccination Registry whereas population denominators were obtained from the Canadian Census and governmental publications. Time trends were assessed with linear regression. RESULTS: A total of 2,755,336 skin tests and 2,531,366 BCG vaccinations were administered. Yearly rates of skin tests, routinely administered before vaccination among all except newborns, were highest among children aged 5-9 (9.3 per 100) and 10-14years (7.9 per 100). The proportion of positive skin tests varied greatly by age, ranging from 10.2% among children <1year to 67.2% among adults ≥20years. The vast majority of individuals who had a negative skin test were subsequently vaccinated, whereas those with a positive result were not, as per recommended guidelines. The average annual vaccination rate was highest among children aged <1year (43.8 per 100) and 5-9year-olds (6.9 per 100). There were salient differences in immunization rates, including positive skin tests and vaccinations, across administrative regions but no difference by sex. CONCLUSION: This is the first comprehensive description of the tuberculosis prevention program in Québec which offered free, non-mandatory BCG vaccination. Our results confirm that the targeted groups, newborns and school-age children, were preferentially reached. Socioeconomic, demographic, and organizational factors may explain regional differences in immunization rates. Beyond presenting a historical context for this vaccination campaign, our findings are relevant to contemporary uses of the Québec BCG Vaccination Registry in epidemiological research.

Association Between Bacillus Calmette-Guérin Vaccination and Childhood Asthma in the Quebec Birth Cohort on Immunity and Health.

We estimated the association between bacillus Calmette-Guérin (BCG) vaccination and childhood asthma in a birth cohort using administrative databases, and we determined the impact of adjusting for potential confounders collected from a subset of the cohort members. Data were collected in 2 waves: 1) Administrative data for 76,623 individuals (stage 1) was gathered from the Quebec Birth Cohort on Immunity and Health (1974-1994), including BCG vaccination status, perinatal and sociodemographic characteristics, and use of health services for asthma; and 2) self-reported asthma risk factors were collected in 2012 by telephone interviews with 1,643 participants (stage 2) using a balanced 2-stage sampling design. We estimated odds ratios and 95% confidence intervals for asthma using logistic regression and correcting for the known sampling fractions from stage 1 to stage 2, overall and sex-stratified. In total, 35,612 (46.5%) individuals were BCG vaccinated, and 5,870 (7.7%) had asthma. The final odds ratio, integrating results from both stages of sampling, was 0.95 (95% confidence interval: 0.87, 1.04). Results did not differ according to sex (P for interaction = 0.327). To our knowledge, this is the largest study ever conducted on this topic, and using the best possible comprehensive adjustment for confounders, we found no association between BCG vaccination and asthma.

Bacillus Calmette-Guérin (BCG) Vaccination in Infancy and Risk of Childhood Diabetes.

BACKGROUND: A narrow time window in infancy may be relevant for the aetiology of immune-mediated type 1 diabetes. We investigated whether a non-specific immune stimulation in the first year of life, as resulting from Bacillus Calmette-Guérin (BCG) vaccination, was associated with childhood diabetes. METHODS: Using data from a birth cohort assembled through linkage of administrative databases, 78,492 subjects born in 1974 were the object of the present analysis. Information was extracted from the birth, death, and BCG vaccination registries. Diabetes-related health services were obtained from administrative health databases (physician billing claims and hospitalisation data) until 1994. Subjects were classified as having diabetes according to two validated definitions: (1) ≥2 diabetes-related medical visits within 2 years or ≥1 hospitalisation for diabetes; and 2) ≥4 diabetes-related medical visits within 2 years. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HR) and 95% confidence interval (CI), adjusted for potential confounders. RESULTS: Forty-four per cent of subjects were BCG vaccinated in the first year of life. According to the first and second definition, respectively, 293 (0.37%) and 230 (0.29%) subjects were classified as having diabetes. There was no association between BCG vaccination in the first year of life and risk of diabetes with either definition (HR(def1) = 0.92, 95% CI 0.73, 1.17; HR(def2) = 1.04, 95% CI 0.80, 1.37), and results did not differ by sex. CONCLUSIONS: Given the potentially critical importance of the exposure window and paucity of studies addressing BCG vaccination timing in relation to diabetes risk, this question deserves further investigation.

Evaluating the Validity of a Two-stage Sample in a Birth Cohort Established from Administrative Databases.

BACKGROUND: When using administrative databases for epidemiologic research, a subsample of subjects can be interviewed, eliciting information on undocumented confounders. This article presents a thorough investigation of the validity of a two-stage sample encompassing an assessment of nonparticipation and quantification of the extent of bias. METHODS: Established through record linkage of administrative databases, the Québec Birth Cohort on Immunity and Health (n = 81,496) aims to study the association between Bacillus Calmette-Guérin vaccination and asthma. Among 76,623 subjects classified in four Bacillus Calmette-Guérin-asthma strata, a two-stage sampling strategy with a balanced design was used to randomly select individuals for interviews. We compared stratum-specific sociodemographic characteristics and healthcare utilization of stage 2 participants (n = 1,643) with those of eligible nonparticipants (n = 74,980) and nonrespondents (n = 3,157). We used logistic regression to determine whether participation varied across strata according to these characteristics. The effect of nonparticipation was described by the relative odds ratio (ROR = ORparticipants/ORsource population) for the association between sociodemographic characteristics and asthma. RESULTS: Parental age at childbirth, area of residence, family income, and healthcare utilization were comparable between groups. Participants were slightly more likely to be women and have a mother born in Québec. Participation did not vary across strata by sex, parental birthplace, or material and social deprivation. Estimates were not biased by nonparticipation; most RORs were below one and bias never exceeded 20%. CONCLUSIONS: Our analyses evaluate and provide a detailed demonstration of the validity of a two-stage sample for researchers assembling similar research infrastructures.

The Québec BCG Vaccination Registry (1956-1992): assessing data quality and linkage with administrative health databases.

BACKGROUND: Vaccination registries have undoubtedly proven useful for estimating vaccination coverage as well as examining vaccine safety and effectiveness. However, their use for population health research is often limited. The Bacillus Calmette-Guérin (BCG) Vaccination Registry for the Canadian province of Québec comprises some 4 million vaccination records (1926-1992). This registry represents a unique opportunity to study potential associations between BCG vaccination and various health outcomes. So far, such studies have been hampered by the absence of a computerized version of the registry. We determined the completeness and accuracy of the recently computerized BCG Vaccination Registry, as well as examined its linkability with demographic and administrative medical databases. METHODS: Two systematically selected verification samples, each representing ~0.1% of the registry, were used to ascertain accuracy and completeness of the electronic BCG Vaccination Registry. Agreement between the paper [listings (n = 4,987 records) and vaccination certificates (n = 4,709 records)] and electronic formats was determined along several nominal and BCG-related variables. Linkage feasibility with the Birth Registry (probabilistic approach) and provincial Healthcare Registration File (deterministic approach) was examined using nominal identifiers for a random sample of 3,500 individuals born from 1961 to 1974 and BCG vaccinated between 1970 and 1974. RESULTS: Exact agreement was observed for 99.6% and 81.5% of records upon comparing, respectively, the paper listings and vaccination certificates to their corresponding computerized records. The proportion of successful linkage was 77% with the Birth Registry, 70% with the Healthcare Registration File, 57% with both, and varied by birth year. CONCLUSIONS: Computerization of this Registry yielded excellent results. The registry was complete and accurate, and linkage with administrative databases was highly feasible. This study represents the first step towards assembling large scale population-based epidemiological studies which will enable filling important knowledge gaps on the potential health effects of early life non-specific stimulation of the immune function, as resulting from BCG vaccination.

Characteristics of metabolically obese normal-weight (MONW) subjects.

The existence of a subgroup of normal-weight individuals displaying obesity-related phenotypic characteristics was first proposed in 1981. These individuals were identified as metabolically obese but normal weight (MONW). It was hypothesized that these individuals might be characterized by hyperinsulinemia and (or) insulin resistance, as well as by hypertriglyceridemia and high blood pressure despite having a body mass index (BMI) < 25 kg/m2. Such characteristics could confer upon MONW subjects a higher cardiovascular risk; however, scientific data on MONW subjects are scarce since only 9 publications are directly related to this topic. Despite differences in the criteria for identifying MONW subjects and the small number of subjects involved in most of these studies, their consistent results indicate that: (i) the prevalence of the MONW syndrome ranges between 5% and 45%, depending on the criteria used, age, BMI, and ethnicity; (ii) when compared with control subjects, MONW subjects display an altered insulin sensitivity, a higher abdominal and visceral adiposity, a more atherogenic lipid profile, a higher blood pressure, and a lower physical activity energy expenditure; and (iii) MONW subjects are at higher risks for type 2 diabetes and cardiovascular diseases.

Relationship between ghrelin and energy expenditure in healthy young women.

Ghrelin is a novel peptide that has been isolated from human and rat stomach tissues. Despite its known stimulatory effects on appetite and eating behavior, little information is available regarding its relationship with energy expenditure in normal-weight humans. To address this issue, we examined the relationship between serum ghrelin and resting metabolic rate (RMR), the thermic effect of food (TEF), fasting and postprandial respiratory quotient, physical activity level, peak aerobic capacity (VO(2 peak)), energy intake, and psychological measures of feeding behavior. We recruited 65 young healthy women and determined RMR and TEF by indirect calorimetry after a 12-h fast. Physical activity was determined by a leisure time physical activity questionnaire; VO(2 peak) was determined by bicycle ergometer test to exhaustion; energy intake was determined by a 24-h dietary recall; and food behavior was determined by a three-factor eating questionnaire. Our cohort showed a broad range of body mass index (range, 16.8-28.3 kg/m2), RMR (range, 820-1550 kcal/d), TEF (range, 74.4-136.5 kcal/d), and percent body fat (range, 14.0-37.7%). We noted significant inverse correlations between ghrelin and RMR (r = -0.350, P = 0.004) and TEF (r = -0.396, P = 0.001). These inverse correlations persisted after statistical control for both fat-free mass and fat mass (ghrelin vs. RMR partial, r = -0.284, P = 0.024; and ghrelin vs. TEF partial, r = -0.329, P = 0.01) and insulin levels (ghrelin vs. RMR partial, r = -0.255, P = 0.046; and ghrelin vs. TEF partial, r = -0.287, P = 0.024) using partial correlation analysis. We also observed a significant inverse correlation between ghrelin and daily caloric intake (r = -0.266, P = 0.032), but ghrelin levels were not significantly correlated with fasting (r = -0.002), postprandial respiratory quotient (r = -0.016), leisure time physical activity (r = 0.104), VO(2 peak) (r = 0.138), dietary disinhibition (r = -0.071), dietary restraint (r = 0.051), or feeling of general hunger (r = -0.028). These results suggest that higher levels of ghrelin are associated with low levels of resting and postprandial thermogenesis, which is independent of individual differences in fat-free mass and fat mass. Although speculative, serum ghrelin may play a role in the regulation of energy homeostasis by acting as a hormonal marker of increased energy efficiency.

Metabolic and behavioral characteristics of metabolically obese but normal-weight women.

A unique subset of individuals termed metabolically obese but normal weight (MONW) has been identified. These young women are potentially at increased risk for development of the metabolic syndrome despite their young age and normal body mass index. We seek to determine metabolic and behavioral factors that could potentially distinguish MONW women from young women with a normal metabolic profile.Ninety-six women were classified as MONW (n = 12) or non-MONW (n = 84) based on a cut point of insulin sensitivity (as estimated by the homeostasis model assessment). Potentially distinguishing phenotypes between groups measured included serum lipids, ghrelin, leptin, adiponectin, body composition and body fat distribution, resting and physical activity energy expenditure, peak oxygen uptake, dietary intake, dietary behavior, and family history and lifestyle variables. Despite a similar body mass index between groups, MONW women showed higher percent body fat, lower fat-free mass, lower physical activity energy expenditure, and lower peak oxygen uptake than non-MONW women. Plasma cholesterol level was higher in MONW women, whereas no differences were noted for other blood lipids, ghrelin, leptin, adiponectin, and resting energy expenditure. MONW women had lower dietary restraint scores than non-MONW women, but no differences were noted in disinhibition, hunger, and dietary intake. Stepwise regression analysis performed on all subjects showed that 33.5% of the unique variance of the homeostasis model assessment was explained with the variables of percentage of body fat (17.1%), level of dietary restraint (10.4%), and age (6%). Both metabolic and dietary behavioral variables contribute to the deleterious metabolic profile of MONW women. They display lower insulin sensitivity due potentially to a cluster of sedentary behavior patterns that contribute to their higher adiposity. Furthermore, cognitive attitudes toward food (i.e. dietary restraint) and concomitant lifestyle behaviors may play a role in regulating insulin sensitivity in MONW women.

Metabolic and body composition factors in subgroups of obesity: what do we know?

Obesity is thought to be a heterogeneous disorder with several possible etiologies; therefore, by examining subtypes of obesity we attempt to understand obesity's heterogeneous nature. The purpose of this review was to investigate the roles of metabolic, body composition, and cardiovascular disease risk in subtypes of obesity. We briefly consider two subtypes of obesity that have been identified in the literature. One subset of individuals, termed the metabolically healthy, but obese (MHO), despite having large amounts of fat mass compared with at risk obese individuals shows a normal metabolic profile, but remarkably normal to high levels of insulin sensitivity. Preliminary evidence suggests that this could be due at least in part to lower visceral fat levels and earlier onset of obesity. A second subset, termed the metabolically obese, but normal weight (MONW), present with normal body mass index, but have significant risk factors for diabetes, metabolic syndrome, and cardiovascular disease, which could be due to higher fat mass and plasma triglycerides as well as higher visceral fat and liver content. We also briefly consider the potential role of adipose and gastrointestinal hormonal profiles in MHO and MONW individuals, which could lead to a better understanding of potential factors that may regulate their body composition. This information will eventually be invaluable in helping us understand factors that predispose to or protect obese individuals from metabolic and cardiovascular disease. Collectively, a greater understanding of the MHO and MONW individual has important implications for therapeutic decision making, the characterization of subjects in research protocols, and medical education.