Bacillus Calmette-Guerin vaccination and multiple sclerosis: A population-based birth cohort study in Quebec, Canada.

BACKGROUND AND PURPOSE: The bacillus Calmette-Guerin (BCG) vaccine could reduce the incidence of multiple sclerosis (MS) through immunomodulation. Previous studies, presenting some limitations, reported no association. We re-examined this association in a large cohort focusing on relapsing-remitting MS (RRMS). METHODS: The cohort included 400,563 individuals, and was linked with the Quebec provincial BCG vaccination registry and administrative health data. Individuals were followed up from 1983 to 2014 and then within Period 1 (1983-1996) and Period 2 (1997-2014), for the occurrence of MS. Incident MS cases were defined as those with ≥3 hospital or physician claims for MS. Subjects with ≥1 drug reimbursement for MS disease-modifying therapies were classified as RRMS. Cox proportional hazards regression was used to estimate hazard ratios (HRs) over the follow-ups, adjusting for potential confounders. Possible effect modification due to sex was assessed. RESULTS: A total of 178,335 (46%) individuals were BCG vaccinated. There were 274 (0.06%) incident MS cases identified in 1983-1996, and 1433 (0.4%) in 1997-2014. No association was found with RRMS, either in Period 1 (adjusted HR [HRadj ] = 0.96, 95% confidence interval [CI] = 0.63-1.45; 96 cases) or in Period 2 (HRadj  = 1.02, 95% CI = 0.85-1.23; 480 cases). The remaining MS cases, for whom the phenotype was unknown, were positively associated with BCG over the entire follow-up (HRadj  = 1.25, 95% CI = 1.10-1.41; 1131 cases) and in Period 2 (HRadj  = 1.33, 95% CI = 1.17-1.52; 953 cases). No interaction with sex was found. CONCLUSIONS: Findings suggest that BCG vaccination does not decrease the risk of RRMS, and that future studies should consider phenotypes of MS.

Association between Bacillus Calmette-Guerin vaccination and type 1 diabetes in adolescence: A population-based birth cohort study in Quebec, Canada.

The Bacillus Calmette-Guerin (BCG) vaccine could reduce the incidence of type 1 diabetes through non-specific immunomodulation. Previous epidemiological studies, presenting some limitations, report no association. We examined this association of early life BCG vaccination and age at vaccination with type 1 diabetes incidence in adolescence in a large representative cohort in Quebec. The cohort included 387,704 individuals born in Quebec between 1970 and 1974 whose BCG vaccination status was determined from a provincial registry. Individuals were followed up from 1985 to their 19th birthday (maximum to 1993) for their use of physician services. Individuals were defined as type 1 diabetes cases if they had ≥4 related physician claims over a 2-year period, with at least 30 days between two claims. Cox proportional hazards regression was used to estimate the association of BCG vaccination and age at vaccination with type 1 diabetes. Covariates were selected based on a directed acyclic graph. Interaction according to sex was evaluated. A total of 178,133 (45.9%) individuals were vaccinated and 442 (0.11%) incident cases of type 1 diabetes were identified. The risk of type 1 diabetes was similar in vaccinated compared with unvaccinated individuals (adjusted hazard ratio = 1.06 [95% CI: 0.88-1.29]). There was no association with age at vaccination, and results did not differ by sex (Interaction, p = 0.60). Our results suggest that BCG vaccination does not prevent type 1 diabetes in adolescence.

An epidemiological study to assess the true incidence and prevalence of rheumatic heart disease and acute rheumatic fever in New Caledonian school children.

AIM: To provide in New Caledonian school children (i) the prevalence of rheumatic heart disease (RHD) detected by annual screening program using new World Heart Federation diagnostic criteria; (ii) the point prevalence of acute rheumatic fever (ARF); and (iii) to investigate socio-demographic risk factors associated with RHD. METHODS: This study linked data from national ARF/RHD programs by combining ARF incidence data from the register with RHD prevalence data from echocardiographic screening data for a single age year of the population for overall point prevalence ARF/RHD rates. For the analysis, cases of echocardiographic detection of RHD are presumed to be synonymous with undiagnosed ARF. All results were weighted to minimise the bias introduced from absent pupils of each annual screening program. Incidence and prevalence were age-standardised to the WHO World Standard Population. Each 2013 cumulative prevalence of definite and borderline RHD was studied using a multivariate logistic regression adjusted for socio-demographic factors. RESULTS: The overall age-standardised incidence of clinical and undiagnosed ARF (i.e. echocardiographic-detected RHD) was combined as point prevalence and estimated to be 99/10 000 cases in 2012 and 114/10 000 cases in 2013. This included 40/10 000 prevalent cases of asymptomatic RHD detected by screening each year. Being Melanesian, OR 23.2 (95% CI: 3.4-157.3), or Polynesian, OR 21.5 (95% CI: 2.9-157.7), was associated with a higher prevalence of having definite RHD compared with being Caucasian. Being a girl was associated with a higher risk of having borderline RHD, OR 1.9 (95% CI: 1.03-3.3). CONCLUSION: Without echocardiographic screening, ARF/RHD burden is substantially underestimated.

2D:4D digit ratio as a potential marker for prostate cancer risk.

BACKGROUND: The second-to-fourth digit ratio (2D:4D) is thought to reflect prenatal exposure to sex steroids. We investigated the relationship between 2D:4D and odds of prostate cancer. METHOD: Data were collected in PROtEuS, a population-based case-control study conducted in Montréal, Canada (2005-2012), including 1931 incident prostate cancer cases aged < 76 years and 1994 population controls. In-person interviews elicited information on potential risk factors. Digit lengths were measured by interviewers applying a standard protocol. Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders. RESULTS: The OR of prostate cancer for a standard deviation increase in 2D:4D was 0.91 (95 % CI: 0.85-0.98). For less and more aggressive cancers, ORs were 0.93 (95 % CI: 0.87-1.00) and 0.85 (95 % CI: 0.77-0.93), respectively. There was an interaction with ancestry (p=0.04), whereas the OR among men of African descent was 1.23 (95 % CI: 0.96-1.57, based on 128 cases). CONCLUSION: Findings suggest an inverse association between 2D:4D and odds of overall prostate cancer, more pronounced for aggressive cancers. This supports the notion that high levels of testosterone in utero, estimated by a low 2D:4D ratio, are associated with a higher risk of prostate cancer. Contrastingly, a high digit ratio was associated with greater cancer odds among participants of African descent. Upon replication, 2D:4D could prove to be an easily measured marker of prostate cancer risk.

Early life Bacillus Calmette-Guerin vaccination and incidence of type 1, type 2, and latent autoimmune diabetes in adulthood.

AIMS: Bacillus Calmette-Guerin (BCG) vaccination limits blood sugar elevations and autoimmunity. Previous studies focused on type 1 diabetes among children, despite possible effects on other phenotypes later in life. We studied associations between BCG vaccination and type 1, type 2 and latent autoimmune diabetes (LADA) in adulthood. METHODS: A 1970-1974 birth cohort was linked with the BCG vaccination registry and administrative health data of Quebec. 396,118 people aged 22-44 years were followed-up for diabetes mellitus (DM) onset. Incident DM cases were subjects with ≥1 hospitalization or ≥2 physician claims related to DM over a 2-year period. Type 1 diabetes, type 2 diabetes, and LADA cases were individuals with ≥1 reimbursement of insulin, oral antidiabetic agent, or both. Cox proportional regressions were used to estimate hazard ratios (HR), adjusting for potential confounders. RESULTS: Forty-four percent of subjects were BCG vaccinated, 88% of these before age 1. For type 1 diabetes, no association was found before 30 years old, but vaccinated subjects had a lower risk of this phenotype after age 30 (HRadj= 0.65, 95% CI: 0.44-0.95). BCG vaccination was associated with a lower risk of type 2 diabetes (HRadj=0.85, 95% CI: 0.79-0.92), whereas no association was observed for LADA (HRadj=1.30, 95% CI: 0.71-2.38). Results did not differ by sex. CONCLUSIONS: Early life BCG vaccination was associated with lower risks of both type 1 and type 2 diabetes from early to middle adulthood, but not of LADA. Future studies should explore these long-term associations, while distinguishing diabetes phenotypes.

Overweight and obesity in New Caledonian adults: Results from measured and adjusted self-reported anthropometric data.

AIMS: To estimate the overweight (OW) and obesity (Ob) prevalence and associated socio-demographic risk factors in New Caledonian adults aged 18-67years. METHODS: From a randomly selected cross-sectional population survey, self-reported (n=2513) and measured (n=736) height and weight data were collected. Separate linear regression analyses for measured weight and height were performed, using cases with both self-reported weight and height and socio-demographic variables. The final weight and height assigned to each case was either measured or predicted from the regression (n=2075). OW prevalence was defined as: Body Mass Index (BMI) ≥25 and <30kg/m-2; and Ob: BMI ≥30kg/m-2. Samples were weighted to the general adult population. Prevalence and Odds ratios (ORs) were calculated by gender, and adjusted for socio-demographic variables, to assess differentials in OW, Ob and OW-Ob, using multinomial and logistic regressions. RESULTS: Male (M) OW was 35% (95% CI: 31-38), Ob 29% (95% CI: 26-32) and OW-Ob 64% (95% CI: 60-67); female (F) OW was 26% (95% CI: 23-28), Ob 34% (95% CI: 31-37) and OW-Ob 60% (95% CI: 57-63). Compared to Melanesians (OR=1.0) for male/female: Polynesians had the highest prevalence of OW (1.7/1.5), Ob (4.7/3.5), and OW-Ob (3.0/2.5); New Caledonian-born Europeans had greater OW, Ob and OW-Ob (0.3/0.4) than immigrant Europeans (0.2/0.2). CONCLUSIONS: Findings contribute to obesity comparisons with other Pacific Islands, and they establish trends in New Caledonia for targeting policies and strategies of prevention.

Prevalence and sociodemographic risk factors of chlamydia, gonorrhoea and syphilis: a national multicentre STI survey in New Caledonia, 2012.

OBJECTIVES: To estimate prevalence and identify sociodemographic risk factors for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Treponema pallidum infections in New Caledonia. METHOD: A national cross-sectional survey was undertaken using a three-stage random sampling of general practice surgeries and public dispensaries. Participants were included through opportunistic screening and using a systematic step for selection. The study sample was weighted to the general population aged 18-49 years. Prevalence and risk factors were calculated by logistic regression. RESULTS: CT was the most common sexually transmitted infection, with a prevalence of 9% (95% CI 6.6% to %11.4), followed by NG 3.5% (95% CI 1.9% to 5.1%), previous or latent syphilis 3% (95% CI 1.7% to 4.3%), NG and CT co-infection 2.1% (95% CI 0.8% to 3.3%) and active syphilis 0.4% (95% CI 0.0% to 0.9%). Being from a young age group (18-25 years), being single, having a low level of education and province of residence were all associated with higher prevalence of all three STIs. Being of Melanesian origin was associated with higher prevalence of both CT and NG. There was a significant interaction between ethnic group and province of residence for prevalence of CT. Female gender was associated with higher prevalence of CT. CONCLUSIONS: The prevalence of CT was similar to estimates from other healthcare-based surveys from the Pacific, but higher for NG and lower for active syphilis infection. All sexually transmitted infections estimates were much higher than those found in population-based surveys from Europe and the USA. The sociodemographic risk factors identified in this study will help guide targeted prevention and control strategies in New Caledonia.

Screening for rheumatic heart disease: evaluation of a focused cardiac ultrasound approach.

BACKGROUND: Rheumatic heart disease (RHD) remains a major public health problem worldwide. Although early diagnosis by echocardiography may potentially play a key role in developing active surveillance, systematic evaluation of simple approaches in resource poor settings are needed. METHODS AND RESULTS: We prospectively compared focused cardiac ultrasound (FCU) to a reference approach for RHD screening in a school children population. FCU included (1) the use of a pocket-sized echocardiography machine, (2) nonexpert staff (2 nurses with specific training), and (3) a simplified set of echocardiographic criteria. The reference approach used standardized echocardiographic examination, reviewed by an expert cardiologist, according to 2012 World Heart Federation criteria. Among the 6 different echocardiographic criteria, first tested in a preliminary phase, mitral regurgitation jet length≥2 cm or any aortic regurgitation was considered best suited to be FCU criteria. Of the 1217 subjects enrolled (mean, 9.6±1 years; 49.6% male), 49 (4%) were diagnosed with RHD by the reference approach. The sensitivity of FCU for the detection of RHD was 83.7% (95% confidence interval, 73.3-94.0) for nurse A and 77.6% (95% confidence interval, 65.9-89.2) for nurse B. FCU yielded a specificity of 90.9% (95% confidence interval, 89.3-92.6) and 92.0% (95% confidence interval, 90.4-93.5) according to users. Percentage of agreement among nurses was 91.4%. CONCLUSIONS: FCU by nonexperts using pocket devices seems feasible and yields acceptable sensitivity and specificity for RHD detection when compared with the state-of-the-art approach, thereby opening new perspectives for mass screening for RHD in low-resource settings.

Road traffic crashes and prescribed methadone and buprenorphine: a French registry-based case-control study.

BACKGROUND: Opioids have been shown to impair psychomotor and cognitive functioning in healthy volunteers with no history of opioid abuse. Few or no significant effects have been found in opioid-dependant patients in experimental or driving simulation studies. The risk of road traffic crash among patients under buprenorphine or methadone has not been subject to epidemiological investigation so far. The objective was to investigate the association between the risk of being responsible for a road traffic crash and the use of buprenorphine and methadone. METHODS: Data from three French national databases were extracted and matched: the national health care insurance database, police reports, and the national police database of injurious crashes. Case-control analysis comparing responsible versus non responsible drivers was conducted. RESULTS: 72,685 drivers involved in an injurious crash in France over the July 2005-May 2008 period, were identified by their national health care number. The 196 drivers exposed to buprenorphine or methadone on the day of crash were young, essentially males, with an important co-consumption of other substances (alcohol and benzodiazepines). Injured drivers exposed to buprenorphine or methadone on the day of crash, had an increased risk of being responsible for the crash (odds ratio (OR)=2.02, 95% confidence interval (CI): 1.40 and 2.91). CONCLUSIONS: Users of methadone and buprenorphine were at increased risk of being responsible for injurious road traffic crashes. The increased risk could be explained by the combined effect of risky behaviors and treatments.