Leah J. Martin

Disposition of perfluorinated acid isomers in sprague‐dawley rats; Part 1: Single dose

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.

Disposition of perfluorinated acid isomers in Sprague-Dawley rats; part 2: subchronic dose.

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.

Quality of Life of HIV Patients in a Rural Area of Western Uganda: Impact of a Community-Based Antiretroviral Treatment Program

OBJECTIVEnCommunity-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.nnnMETHODSnWe 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, treatment-naïve, 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.nnnRESULTSnAfter 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.nnnCONCLUSIONSnThe 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.

Improving Google Flu Trends estimates for the United States through transformation.

Google Flu Trends (GFT) uses Internet search queries in an effort to provide early warning of increases in influenza-like illness (ILI). In the United States, GFT estimates the percentage of physician visits related to ILI (%ILINet) reported by the Centers for Disease Control and Prevention (CDC). However, during the 2012–13 influenza season, GFT overestimated %ILINet by an appreciable amount and estimated the peak in incidence three weeks late. Using data from 2010–14, we investigated the relationship between GFT estimates (%GFT) and %ILINet. Based on the relationship between the relative change in %GFT and the relative change in %ILINet, we transformed %GFT estimates to better correspond with %ILINet values. In 2010–13, our transformed %GFT estimates were within ±10% of %ILINet values for 17 of the 29 weeks that %ILINet was above the seasonal baseline value determined by the CDC; in contrast, the original %GFT estimates were within ±10% of %ILINet values for only two of these 29 weeks. Relative to the %ILINet peak in 2012–13, the peak in our transformed %GFT estimates was 2% lower and one week later, whereas the peak in the original %GFT estimates was 74% higher and three weeks later. The same transformation improved %GFT estimates using the recalibrated 2013 GFT model in early 2013–14. Our transformed %GFT estimates can be calculated approximately one week before %ILINet values are reported by the CDC and the transformation equation was stable over the time period investigated (2010–13). We anticipate our results will facilitate future use of GFT.

Estimating the Burden of Recurrent Events in the Presence of Competing Risks: The Method of Mean Cumulative Count

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.

Rates of initial virological suppression and subsequent virological failure after initiating highly active antiretroviral therapy: the impact of aboriginal ethnicity and injection drug use.

Objectives: To compare rates of initial virological suppression and subsequent virological failure by Aboriginal ethnicity after starting highly active antiretroviral therapy (HAART). Methods: We conducted a retrospective cohort study of antiretroviral-naïve HIV-patients starting HAART in January 1999-June 2005 (baseline), followed until December 31, 2005 in Alberta, Canada. We compared the odds of achieving initial virological suppression (viral load <500 copies/mL) by Aboriginal ethnicity using logistic regression and, among those achieving suppression, rates of virological failure (the first of two consecutive viral loads > 1000 copies/mL) by Aboriginal ethnicity using cumulative incidence curves and Cox proportional hazards models. Sex, injection drug use as an HIV exposure category (IDU), baseline age, CD4 cell count, viral load, calendar year, and HAART regimen were considered as potential confounders. Results: Of 461 study patients, 37% were Aboriginal and 48% were IDUs; 71% achieved initial virological suppression and were followed for 730.4 person-years. After adjusting for confounding variables, compared to non-Aboriginals with other exposures, the odds of achieving initial virological suppression were lower for Aboriginal IDUs (odds ratio (OR)=0.33, 95% CI=0.19-0.60, p=0.0002), non-Aboriginal IDUs (OR=0.30, 95% CI=0.15-0.60, p=0.0006), and Aboriginals with other exposures (OR=0.38, 95% CI=0.21-0.67, p=0.0009). Among those achieving suppression, Aboriginals experienced higher virological failure rates ≥1 year after suppression (hazard ratio=3.35, 95% CI=1.68-6.65, p=0.0006). Conclusions: Future research should investigate adherence among Aboriginals and IDUs treated with HAART and explore their treatment experiences to assess ways to improve outcomes.

Google Flu Trends in Canada: a comparison of digital disease surveillance data with physician consultations and respiratory virus surveillance data, 2010–2014

The 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.

Replication data for: Improving Google Flu Trends estimates for the United States through transformation

These files include: (a) the SAS program to create the transformed GFT estimates and conduct the analysis, (b) the R program to plot the figures in the publication, and (c) csv files with the transformed GFT estimates (national and regional) created using the SAS program. Original GFT estimates and ILINet values are available online.

Antimicrobial resistance among Salmonella and Shigella isolates in five Canadian provinces (1997 to 2000).

OBJECTIVEnTo describe rates of antimicrobial resistance (AMR) among Salmonella and Shigella isolates reported in five Canadian provinces, focusing on clinically important antimicrobials.nnnMETHODSnThe authors retrospectively investigated AMR rates among 6219 Salmonella and 1673 Shigella isolates 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% of Salmonella cases and 72% of Shigella cases reported by the study provinces.nnnRESULTSnAmong Salmonella isolates, 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. Among Shigella isolates, 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.nnnCONCLUSIONSnHigher rates of resistance to clinically important antimicrobials (including ciprofloxacin) were observed among both Salmonella and Shigella isolates than has previously been reported. Current Canadian data on rates of AMR for these pathogens are required.

Influenza-like illness-related emergency department visits: Christmas and New Year holiday peaks and relationships with laboratory-confirmed respiratory virus detections, Edmonton, Alberta, 2004–2014

Emergency department (ED) visit volumes can be especially high during the Christmas–New Year holidays, a period occurring during the influenza season in Canada.