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Background: Epidemiological studies suggest that Bisphenol-A (BPA) is a developmental neurotoxicant, but the modifying effects of maternal nutrient status or neurotoxicant metal co-exposures have not been reported. Bisphenol-S (BPS) is being used as a BPA-alternative, but few epidemiological studies have evaluated its effects. Objectives: To examine if prenatal maternal BPA or BPS exposure are associated with children’s neurodevelopment at two years of age while adjusting for effect-measure modification by sex, maternal nutrients, and co-exposure to neurotoxic metals. Methods: Total BPA and BPS concentrations were analyzed in spot maternal urine from the second trimester; metals and maternal nutrient status were analyzed in blood. Child neurodevelopment was evaluated with the Bayley Scales of Infant Development-III (Bayley-III) at age 2 (394 maternal-child pairs) and linear regression was used to investigate associations. Results: Among nutrients and neurotoxic metals, selenium (Se) and cadmium (Cd) were the most significant predictors of Bayley-III scale scores. Higher maternal Cd was significantly correlated with poorer motor performance (p

To reach the WHO goal of hepatitis C elimination, it is essential to identify the number of people unaware of their hepatitis C virus (HCV) infection and to investigate the effect of interventions on the disease transmission dynamics. In many high-income countries, one of the primary routes of HCV transmission is via contaminated needles shared by people who inject drugs (PWIDs). However, substantial underreporting combined with high uncertainty regarding the size of this difficult to reach population, makes it challenging to estimate the core indicators recommended by the WHO. To support progress toward the elimination goal, we present a novel multi-layered dynamic transmission model for HCV transmission within a PWID population. The model explicitly accounts for disease stage (acute and chronic), injection drug use status (active and former PWIDs), status of diagnosis (diagnosed and undiagnosed) and country of disease acquisition (domestic or abroad). First, based on this model, and using routine surveillance data, we estimate the number of undiagnosed PWIDs, the true incidence, the average time until diagnosis, the reproduction numbers and associated uncertainties. Second, we examine the impact of two interventions on disease dynamics: (1) direct-acting antiviral drug treatment, and (2) needle exchange programs. As a proof of concept, we illustrate our results for a specific data set. In addition, we develop a web application to allow our model to be explored interactively and with different parameter values. Keywords: Dynamic modeling, Hepatitis C, Treatment, Needle exchange programs, Surveillance data, Inference, Shiny app

Objectives Neighbourhood-level deprivation is associated with hospitalization related to respiratory infections; however, hospitalizations exclude many who seek care with less severe respiratory illnesses. Another major seasonal contributor to respiratory illness-associated healthcare burdens are influenza-like illness (ILI)–related emergency department (ED) visits. We investigated associations between area-level social and material deprivation and ILI-related ED use. Study design This is a retrospective ecological study. Methods We linked ILI-related ED visit data (2004–2014) for Edmonton, Alberta to a Canadian area-level material and social deprivation index, categorizing deprivation into quintiles. Using a multivariable Poisson model with log population as the offset, we modelled the relationship between visit rates and material and social deprivation adjusting for week and season, age, sex and the interaction between age and sex. Results We included 67,585 ILI-related ED visits, representing 1075.5 (95% confidence interval (CI) = 1067.4–1083.6) visits per 100,000 person-years. ILI-related visit rates increased as each of material and social deprivation increased; increases were slightly greater for material deprivation. Comparing the most deprived quintile to the least deprived quintile: for material deprivation, ILI-related ED visit rates were two times higher (rate ratio (RR) = 2.00, 95% CI = 1.96–2.05); and, for social deprivation, one-and-a-half times higher (RR = 1.47, 95% CI = 1.44–1.51). Conclusions Higher area-level material and social deprivation were associated with higher ILI-related ED visit rates. These findings can be used to identify areas that may need additional public health and healthcare resources and to improve targeting of prevention strategies. Understanding differentials in healthcare use such as this may be especially relevant to ensuring equity of outcomes for pandemic preparedness planning.

Tick-borne encephalitis (TBE) is a vaccine-preventable, high-priority disease in Sweden, with increasing incidence. However, surveillance is limited to case reports. We investigated relationships between reported TBE incidence and syndromic surveillance data to determine if these novel data sources could provide earlier indications of disease activity. We retrospectively compared national, weekly (2010-2017) reported TBE incidence to the percentage of TBE-related a) searches on the main Swedish healthcare information website and b) calls to its telehealth service using Spearman's ρ to determine the most strongly correlated lags. We conducted a sub-analysis (2012-2017) of TBE-related Google Trends queries and compared the number of TBE-related media stories to each novel surveillance dataset. Healthcare website searches for "tbe" and "vaccine" combined, "tbe", "tick", and "tick bite" led case data by 12, 8, 7, and 6 weeks, respectively (ρ = 0.87-0.89); telehealth calls led by 4 weeks (ρ = 0.92; all p0.001). Correlations and lags for Google Trends and healthcare website searches were fairly similar to each other. In comparison, correlation between the different syndromic surveillance datasets and the number of media stories was lower (ρ = 0.25-0.56). We observed volume discrepancies between TBE incidence and the novel surveillance datasets during some years, particularly for web searches. Syndromic surveillance data were strongly correlated with and preceded case data by 4-12 weeks. Syndromic data may provide advanced awareness and earlier indications of TBE activity, which can improve timing and specificity of public health communications. The use of these data as supplements to notifiable disease data for national planning and preparedness in real-time should be investigated.

Background Emergency department (ED) visit volumes can be especially high during the Christmas–New Year holidays, a period occurring during the influenza season in Canada. Methods Using daily data, we examined the relationship between ED visits for the chief complaint “cough” (for Edmonton, Alberta residents) and laboratory detections for influenza A and respiratory syncytial virus (RSV) (for Edmonton and surrounding areas), lagged 0–5 days ahead, for non-pandemic years (2004–2008 and 2010–2014) using multivariable linear regression adjusting for temporal variables. We defined these cough-related visits as influenza-like illness (ILI)-related ED visits and, for 2004–2014, compared Christmas–New Year holiday (December 24–January 3) and non-holiday volumes during the influenza season (October–April). Results Adjusting for temporal variables, ILI-related ED visits were significantly associated with laboratory detections for influenza A and RSV. During non-pandemic years, the highest peak in ILI-related visit volumes always occurred during the holidays. The median number of holiday ILI-related visits/day (42.5) was almost twice the non-holiday median (24) and was even higher in 2012–2013 (80) and 2013–2014 (86). Holiday ILI-related ED visit volumes/100 000 population ranged from 56.0 (2010–2011) to 117.4 (2012–2013). In contrast, lower visit volumes occurred during the holidays of pandemic-affected years (2008–2010). Conclusions During non-pandemic years, ILI-related ED visit volumes were associated with variations in detections for influenza A and RSV and always peaked during the Christmas–New Year holidays. This predictability should be used to prepare for, and possibly prevent, this increase in healthcare use; however, interventions beyond disease prevention strategies are likely needed.

Predicting the magnitude of the annual seasonal peak in influenza-like illness (ILI)-related emergency department (ED) visit volumes can inform the decision to open influenza care clinics (ICCs), which can mitigate pressure at the ED. Using ILI-related ED visit data from the Alberta Real Time Syndromic Surveillance Net for Edmonton, Alberta, Canada, we developed (training data, 1 August 2004–31 July 2008) and tested (testing data, 1 August 2008–19 February 2014) spatio-temporal statistical prediction models of daily ILI-related ED visits to estimate high visit volumes 3 days in advance. Our Main Model, based on a generalised linear mixed model with random intercept, incorporated prediction residuals over 14 days and captured increases in observed volume ahead of peaks. During seasonal influenza periods, our Main Model predicted volumes within ±30% of observed volumes for 67%–82% of high-volume days and within 0.3%–21% of observed seasonal peak volumes. Model predictions were not as successful during the 2009 H1N1 pandemic. Our model can provide early warning of increases in ILI-related ED visit volumes during seasonal influenza periods of differing intensities. These predictions may be used to support public health decisions, such as if and when to open ICCs, during seasonal influenza epidemics.

To reach the WHO goal of hepatitis C elimination, it is essential to identify the number of people unaware of their hepatitis C virus (HCV) infection and to investigate the effect of interventions on the disease transmission dynamics. In many middle- and high-income countries, one of the primary routes of HCV transmission is via contaminated needles shared by people who inject drugs (PWIDs). However, substantial underreporting combined with high uncertainty regarding the size of this difficult to reach population, makes it challenging to estimate the core indicators recommended by the WHO. To help enable countries to monitor their progress towards the elimination goal, we present a novel multi-layered dynamic transmission model for HCV transmission within a PWID population. The model explicitly accounts for disease stage (acute and chronic), injection drug use status (active and former PWIDs), status of diagnosis (diagnosed and undiagnosed) and country of disease acquisition (domestic or abroad). First, based on this model, and using routine surveillance data, we estimate the number of undiagnosed PWIDs, the true incidence, the average time until diagnosis, the reproduction numbers and associated uncertainties. Second, we examine the impact of two interventions on disease dynamics: 1) direct-acting antiviral drug treatment, and 2) needle exchange programs. To make the model accessible to relevant users and to support communication of our results to public health decision makers, the model and its output are made available through a Shiny app. As a proof of concept, we illustrate our results for a specific data set; however, through the app our model can be easily adapted to other high-income countries with similar transmission patterns among PWIDs where the disease is endemic.

Background/Aim: Bisphenol A (BPA) is an endocrine disruptor that is ubiquitous worldwide. Evidence suggests that it is a neurodevelopmental toxicant with sex-specific effects. Bisphenol S (BPS), an...

SUMMARYThe value of Google Flu Trends (GFT) remains unclear after it overestimated the proportion of physician visits related to influenza-like illness (ILI) in the United States in 2012–2013. However, GFT estimates (%GFT) have not been examined nationally in Canada nor compared with positivity for respiratory viruses other than influenza. For 2010–2014, we compared %GFT for Canada to Public Health Agency of Canada ILI consultation rates (%PHAC) and to positivity for influenza A and B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and rhinoviruses. %GFT correlated well with %PHAC (ρ= 0·77–0·90) and influenza A positivity (ρ= 0·64–0·96) and overestimated the 2012–2013 %PHAC peak by 0·99 percentage points. %GFT peaks corresponded temporally with peaks in positivity for influenza A and rhinoviruses (all seasons) and RSV and hMPV when their peaks preceded influenza peaks. In Canada, %GFT represented traditional surveillance data and corresponded temporally with patterns in circulating respiratory viruses.

OBJECTIVE: We compared the health-related quality of life (HRQL) of Aboriginal and non-Aboriginal HIV patients after they started highly active antiretroviral therapy (HAART) in Edmonton, Alberta and investigated whether clinical status (CD4 cell count and viral load) might explain any observed differences. METHODS: In 2006-2007, eligible patients who started HAART in 1997-2005 completed the MOS-HIV to measure HRQL. Using multiple linear regression models, we compared physical (PHS) and mental (MHS) health summary scores across four groups: Aboriginals infected with HIV via injection drug use (AB/IDUs); Aboriginal non-IDUs (AB/non-IDUs); non-Aboriginal IDUs (non-AB/IDUs); and non-Aboriginal non-IDUs (non-AB/non-IDUs). To assess whether clinical status could explain any observed group differences, we fitted a model adjusting for socio-demographics (age and sex) and years since starting HAART only and then additionally adjusted for current clinical status. RESULTS: Ninety-six patients were eligible (35% Aboriginal, 42% IDU). Adjusting for socio-demographics and years since starting HAART, AB/IDUs (p=0.008), AB/non-IDUs (p=0.002), and non-AB/IDUs (p=0.002) had lower PHS scores than non-AB/non-IDUs. After additionally adjusting for clinical status, these relationships remained significant for AB/non-IDUs (p=0.027) and non-AB/IDUs (p=0.048) but not for AB/IDUs (p=0.12). AB/IDUs and non-AB/IDUs tended to have worse MHS scores than non-AB/non-IDUs, but these relationships were not statistically significant and weakened after adjusting for current clinical status. CONCLUSIONS: AB/IDU, AB/non-IDUs, and non-AB/IDUs had significantly poorer physical HRQL than non-AB/non-IDUs. These differences appear to be partially explained by poorer clinical status, especially for AB/IDUs, which suggests that observed inequalities in physical HRQL may be diminished by improving patients’ clinical status; for example, through improved adherence to HAART.

Objective: Community-based antiretroviral treatment (CBART) programs should aim to achieve positive quality of life outcomes. The purpose of this study was to investigate changes in the health related quality of life (HRQOL) outcomes of patients in a CBART program supported by community volunteers in one sub-county in western Uganda located 50 km from the nearest urban centre. Methods: We administered a translated version of the MOS-HIV survey and collected clinical data at baseline and after one year from 130 patients. Inclusion criteria included residency in the sub-county, eighteen years of age or, treatmentnaive, eligible for ART based on CD4 cell count < 200 cells/mm3 or WHO clinical stage 3 or 4, and willing to accept daily treatment support by family/friends and to be visited by a community volunteer weekly. We assessed changes in physical health (PHS) and mental health (MHS) summary scores and examined associations between patient characteristics and changes in HRQOL. Results: After one year, we observed significant increases in mean PHS (42.7 to 50.1; p < 0.01) and MHS (43.5 to 49.5; p < 0.01) scores. Lower age (p < 0.01) and lower baseline PHS scores (p < 0.01) were associated with increases in PHS scores and lower age (p=0.03) and lower baseline MHS scores (p < 0.01) were associated with increases in MHS scores. Fifteen patients (12%) had reductions in their HRQOL after one year which were not associated with patient or clinical characteristics, including virological suppression. Conclusions: The observed improvements in HRQOL demonstrate that positive treatment outcomes can be achieved in CBART programs in rural Uganda. However, some patients appear to experience declines in their overall well-being, despite achieving virological suppression. HRQOL surveys can be useful in identifying these patients, who may require additional attention and support to achieve the full benefits of ART.

Cumulative incidence has been widely used to estimate the cumulative probability of developing an event of interest by a given time, in the presence of competing risks. When it is of interest to measure the total burden of recurrent events in a population, however, the cumulative incidence method is not appropriate because it considers only the first occurrence of the event of interest for each individual in the analysis: Subsequent occurrences are not included. Here, we discuss a straightforward and intuitive method termed “mean cumulative count,” which reflects a summarization of all events that occur in the population by a given time, not just the first event for each subject. We explore the mathematical relationship between mean cumulative count and cumulative incidence. Detailed calculation of mean cumulative count is described by using a simple hypothetical example, and the computation code with an illustrative example is provided. Using follow-up data from January 1975 to August 2009 collected in the Childhood Cancer Survivor Study, we show applications of mean cumulative count and cumulative incidence for the outcome of subsequent neoplasms to demonstrate different but complementary information obtained from the 2 approaches and the specific utility of the former.

This study investigated the burden of illness associated with 440 cases of Salmonella enterica serotype Typhimurium infection identified in Canada between December 1999 and November 2000. We categorized case subjects' infections by definitive phage type 104 (DT104) and antimicrobial-resistance patterns. These variables were then investigated as risk factors for hospitalization. Hospitalization was more likely to occur among case subjects whose infections were resistant to at least ampicillin, chloramphenicol and/or kanamycin, streptomycin, sulphamethoxazole, and tetracycline (R-type AK/CSSuT; odds ratio [OR], 2.3; P=.003), compared with case subjects with AK/CSSuT-susceptible infections, and among case subjects with non-DT104 R-type AKSSuT infections (OR, 3.6; P=.005), compared with case subjects with non-DT104 AKSSuT-susceptible infections. In contrast, hospitalization rates did not differ between case subjects with DT104 infections and case subjects with non-DT104 infections or between case subjects with DT104 R-type ACSSuT infections and case subjects with DT104 ACSSuT-susceptible infections. We estimated that 57% of the hospitalizations among AK/CSSuT case subjects and 72% of the hospitalizations among non-DT104 AKSSuT case subjects were attributable to the resistance patterns of the infections.

Background: Aboriginals are over-represented in Canada’s HIV epidemic and are commonly infected with HIV via injection drug use (IDU); however, little is known about the impact of Aboriginal ethnicity on mortality after starting highly active antiretroviral therapy (HAART). Therefore, we compared mortality rates between Aboriginal and non-Aboriginal HIV patients and between IDU and non-IDU HIV patients after they initiated HAART. Methods: We conducted a retrospective cohort study of antiretroviral-naïve patients starting HAART January 1999–June 2005 (baseline), followed until December 2005. We constructed two Cox proportional hazards models, one to estimate all-cause and one to estimate HIV-related mortality hazard ratios (HRs), considering sex, and baseline age, CD4 cell count, HIV RNA level, calendar year, and HAART regimen as potential confounders. Results: The 548 study patients were followed for 1,889.8 person-years; 194 (35%) were Aboriginal, 255 (46%) were IDUs. We observed 55 deaths; 47% were HIV-related. In multivariable models, Aboriginals experienced higher all-cause (HR=1.85, 95% CI=1.05-3.26, p=0.034) and HIV-related (HR=3.47, 95% CI=1.36-8.83, p=0.009) mortality rates compared to non-Aboriginals; and, compared to patients with other exposures, IDUs experienced higher all-cause (HR=2.45, 95% CI=1.31-4.57, p=0.005) but similar HIV-related (p=0.27) mortality rates. Conclusions: Compared to non-Aboriginals, Aboriginal HIV patients suffer higher all-cause and HIV-related mortality rates after starting HAART. The strongest and most significant predictor of higher all-cause mortality was IDU. Future research should examine reasons for the observed poorer survival of Aboriginal and IDU HIV patients after initiating HAART to develop interventions to improve the prognosis for these vulnerable populations.

Two major industrial synthetic pathways have been used to produce perfluorinated acids (PFAs) or their precursors: Telomerization and electrochemical fluorination (ECF). Products of telomer and ECF origin can be distinguished by structural isomer profiles. A mixture of linear and branched perfluoroalkyl isomers is associated with ECF. Telomer products characteristically consist of a single perfluoroalkyl geometry, typically linear. In biota, it is unclear if the isomer profile is conserved relative to the exposure medium and hence whether PFA isomer profiles in organisms are useful for distinguishing environmental PFA sources. A companion study suggested isomer-specific disposition following a single oral gavage exposure to rats. To confirm these findings under a more realistic subchronic feeding scenario, male and female rats were administered PFA isomers by diet for 12 weeks, followed by a 12-week depuration period. The diet contained 500 ng/g each of ECF perfluorooctanoate (PFOA, approximately 80% n-PFOA), ECF perfluorooctane sulfonate (PFOS, approximately 70% n-PFOS), and linear and isopropyl perfluorononanoate (n- and iso-PFNA). Blood sampling during the exposure phase revealed preferential accumulation of n-PFOA and n-PFNA compared to most branched isomers. Female rats depurated all isomers faster than males. Both sexes eliminated most branched perfluorocarboxylate isomers more rapidly than the n-isomer. Elimination rates of the major branched PFOS isomers were not statistically different from n-PFOS. Two minor isomers of ECF PFOA and one branched PFOS isomer had longer elimination half-lives than the n-isomers. Although extrapolation of these pharmacokinetics trends in rats to humans and wildlife requires careful consideration of dosage level and species-specific physiology, cumulative evidence suggests that perfluorocarboxylate isomer profiles in biota may not be suitable for quantifying the relative contributions of telomer and ECF sources.

Formula chem.A very efficient synthesis of (2R,3S) and (25,3R)-4-aminobutane-1,2,3-triol has been developed using either D- or L-glucose as the starting material. A key step is the one-pot conversion of an aldehyde to an amide, the scope of which has been extended to include other carbohydrate-derived aldehydes.

BACKGROUND: This study was conducted to describe the geographical and seasonal distributions of reported human SalmonellaTyphimurium (ST) definitive type 104 (DT104) cases, to compare these characteristics to those of non-DT104 cases, and to investigate specific antimicrobial resistance (AMR) patterns in four Canadian provinces. METHODS: All laboratory-confirmed ST cases originating from passive reporting in Alberta, British Columbia, and Saskatchewan, and every second case in Ontario identified from December 1999 through November 2000 were investigated. RESULTS: A total of 470 human Salmonella Typhimurium cases were identified during the study period. DT104 was the most common phage type, although its incidence varied by province. The proportion of DT104 cases living in urban Ontario, British Columbia and Saskatchewan did not differ from the general population, but in Alberta, the DT104 cases were more likely to live in rural areas. Overall, DT104 isolates were more often R-type ACSSuT compared to non-DT104 cases, and R-type AKSSuT was often associated with DT208. DT104 cases displayed no seasonality whereas non-DT104 cases were more frequent in the summer than in the winter. INTERPRETATION: Our results suggest that DT104 and non-DT104 cases vary by province, urban vs. rural residential status and by resistance patterns. Lack of seasonality in the DT104 cases may indicate a lesser influence of the agro-environmental route (i.e., farm–manure–water and direct contact) compared to the agro-food route (i.e., farm–animals–food) for these infections. Strain characterization and integration of surveillance information related to ST from animal, food and humans is warranted.

OBJECTIVE:To describe rates of antimicrobial resistance (AMR) amongSalmonellaandShigellaisolates reported in five Canadian provinces, focusing on clinically important antimicrobials.METHODS:The authors retrospectively investigated AMR rates among 6219Salmonellaand 1673Shigellaisolates submitted to provincial public health laboratories in Alberta, Newfoundland and Labrador, Ontario, Prince Edward Island and Saskatchewan from 1997 to 2000; these isolates were estimated to represent 41% ofSalmonellacases and 72% ofShigellacases reported by the study provinces.RESULTS:AmongSalmonellaisolates, 27% (1704 of 6215) were resistant to ampicillin, 2.2% (135 of 6122) to trimethoprim/sulfamethoxazole, 1.5% (14 of 938) to nalidixic acid, 1.2% (one of 84) to lomafloxacin and 0.08% (five of 6163) to ciprofloxacin. AmongShigellaisolates, 70% (1144 of 1643) were resistant to trimethoprim/sulfamethoxazole, 65% (1079 of 1672) to ampicillin, 3.1% (eight of 262) to nalidixic acid, 0.49% (eight of 1636) to ciprofloxacin, 0.14% (one of 700) to ceftriaxone and 0.08% (one of 1292) to ceftazidime.CONCLUSIONS:Higher rates of resistance to clinically important antimicrobials (including ciprofloxacin) were observed among bothSalmonellaandShigellaisolates than has previously been reported. Current Canadian data on rates of AMR for these pathogens are required.

Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 microg/kg body weight perfluorooctane sulfonate (C(8)F(17)SO(3)(-), PFOS), perfluorooctanoic acid (C(7)F(15)CO(2)H, PFOA), and perfluorononanoic acid (C(8)F(17)CO(2)H, PFNA) and 30 microg/kg body weight perfluorohexane sulfonate (C(6)F(13)SO(3)(-), PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m-PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure-property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples.