Jeffrey C. Kwong

Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study

BACKGROUND Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinsons disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. METHODS In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20-50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55-85 years (about 2·2 million; dementia or Parkinsons disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individuals proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinsons disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinsons disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers. FINDINGS Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinsons disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06-1·08), 1·04 (1·02-1·05) for 50-100 m, 1·02 (1·01-1·03) for 101-200 m, and 1·00 (0·99-1·01) for 201-300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10-1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10-1·14 for people living <50 m from a major traffic road). No association was found with Parkinsons disease or multiple sclerosis. INTERPRETATION In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinsons disease or multiple sclerosis. FUNDING Health Canada (MOA-4500314182).

Risk of Incident Diabetes in Relation to Long-term Exposure to Fine Particulate Matter in Ontario, Canada

Background: Laboratory studies suggest that fine particulate matter (≤ 2.5 µm in diameter; PM2.5) can activate pathophysiological responses that may induce insulin resistance and type 2 diabetes. However, epidemiological evidence relating PM2.5 and diabetes is sparse, particularly for incident diabetes. Objectives: We conducted a population-based cohort study to determine whether long-term exposure to ambient PM2.5 is associated with incident diabetes. Methods: We assembled a cohort of 62,012 nondiabetic adults who lived in Ontario, Canada, and completed one of five population-based health surveys between 1996 and 2005. Follow-up extended until 31 December 2010. Incident diabetes diagnosed between 1996 and 2010 was ascertained using the Ontario Diabetes Database, a validated registry of persons diagnosed with diabetes (sensitivity = 86%, specificity = 97%). Six-year average concentrations of PM2.5 at the postal codes of baseline residences were derived from satellite observations. We used Cox proportional hazards models to estimate the associations, adjusting for various individual-level risk factors and contextual covariates such as smoking, body mass index, physical activity, and neighborhood-level household income. We also conducted multiple sensitivity analyses. In addition, we examined effect modification for selected comorbidities and sociodemographic characteristics. Results: There were 6,310 incident cases of diabetes over 484,644 total person-years of follow-up. The adjusted hazard ratio for a 10-µg/m3 increase in PM2.5 was 1.11 (95% CI: 1.02, 1.21). Estimated associations were comparable among all sensitivity analyses. We did not find strong evidence of effect modification by comorbidities or sociodemographic covariates. Conclusions: This study suggests that long-term exposure to PM2.5 may contribute to the development of diabetes.

Obesity and Respiratory Hospitalizations During Influenza Seasons in Ontario, Canada: A Cohort Study

Evidence from the 2009 H1N1 pandemic suggests that severe obesity was a risk factor for serious complications from influenza infection. Our study identifies severe obesity as a risk factor for respiratory hospitalizations during seasonal influenza epidemics.

The determinants of 2009 pandemic A/H1N1 influenza vaccination: A systematic review

BACKGROUND Pandemic A/H1N1 influenza vaccine coverage varied widely across countries. To understand the factors influencing pandemic influenza vaccination and to guide the development of successful vaccination programs for future influenza pandemics, we identified and summarized studies examining the determinants of vaccination during the 2009 influenza pandemic. METHODS We performed a systematic literature review using the PubMED electronic database from June 2009 to February 2011. We included studies examining an association between a possible predictive variable and actual receipt of the pandemic A/H1N1 influenza vaccine. We excluded studies examining intention or willingness to receive the vaccine. RESULTS Twenty-seven studies were identified from twelve countries. Pandemic influenza vaccine coverage varied from 4.8% to 92%. Coverage varied by population sub-group, country, and assessment method used. Most studies used questionnaires to estimate vaccine coverage, however seven (26%) used a vaccination registry. Factors that positively influenced pandemic influenza vaccination were: male sex, younger age, higher education, being a doctor, being in a priority group for which vaccination was recommended, receiving a prior seasonal influenza vaccination, believing the vaccine to be safe and/or effective, and obtaining information from official medical sources. CONCLUSIONS Vaccine coverage during the pandemic varied widely across countries and population sub-groups. We identified some consistent determinants of this variation that can be targeted to increase vaccination during future influenza pandemics.

Spatial association between ambient fine particulate matter and incident hypertension

Background— Laboratory studies suggest that exposure to fine particulate matter (⩽2.5 &mgr;m in diameter) (PM2.5) can trigger a combination of pathophysiological responses that may induce the development of hypertension. However, epidemiological evidence relating PM2.5 and hypertension is sparse. We thus conducted a population-based cohort study to determine whether exposure to ambient PM2.5 is associated with incident hypertension. Methods and Results— We assembled a cohort of 35 303 nonhypertensive adults from Ontario, Canada, who responded to 1 of 4 population-based health surveys between 1996 and 2005 and were followed up until December 31, 2010. Incident diagnoses of hypertension were ascertained from the Ontario Hypertension Database, a validated registry of persons diagnosed with hypertension in Ontario (sensitivity=72%, specificity=95%). Estimates of long-term exposure to PM2.5 at participants’ postal-code residences were derived from satellite observations. We used Cox proportional hazards models, adjusting for various individual and contextual risk factors including body mass index, smoking, physical activity, and neighbourhood-level unemployment rates. We conducted various sensitivity analyses to assess the robustness of the effect estimate, such as investigating several time windows of exposure and controlling for potential changes in the risk of hypertension over time. Between 1996 and 2010, we identified 8649 incident cases of hypertension and 2296 deaths. For every 10-µg/m3 increase of PM2.5, the adjusted hazard ratio of incident hypertension was 1.13 (95% confidence interval, 1.05–1.22). Estimated associations were comparable among all sensitivity analyses. Conclusions— This study supports an association between PM2.5 and incident hypertension.

Optimal Pandemic Influenza Vaccine Allocation Strategies for the Canadian Population

Background The world is currently confronting the first influenza pandemic of the 21st century. Influenza vaccination is an effective preventive measure, but the unique epidemiological features of swine-origin influenza A (H1N1) (pH1N1) introduce uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and mortality. Methodology/Principal Findings We developed a deterministic, age-structured compartmental model of influenza transmission, with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and mortality. In all scenarios, prioritization of high-risk individuals (those with underlying chronic conditions and pregnant women), regardless of age, markedly decreased the frequency of severe outcomes. When individuals with underlying medical conditions were not prioritized and an age group-based approach was used, preferential vaccination of age groups at increased risk of severe outcomes following infection generally resulted in decreased mortality compared to targeting vaccine to age groups with higher transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the epidemic peak. Conclusions/Significance Our model simulations suggest that vaccine should be allocated to high-risk groups, regardless of age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable morbidity and mortality, but the benefits are dependent on epidemic dynamics, time for program roll-out, and vaccine uptake.

The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study

Background Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. Methodology/Principal Findings We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. Conclusions/Significance Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Economic appraisal of Ontario's Universal Influenza Immunization Program: a cost-utility analysis.

Beate Sander and colleagues assess the cost-effectiveness of the program that provides free seasonal influenza vaccines to the entire population of Ontario, Canada.

Telaprevir in the Treatment of Acute Hepatitis C Virus Infection in HIV-Infected Men

BACKGROUND There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal. METHODS We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment. RESULTS In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received ≤12 weeks of treatment and there were no relapses after treatment. The overall safety profile was similar to that known for telaprevir-based regimens. CONCLUSIONS Incorporating telaprevir into treatment of acute genotype 1 HCV in HIV-infected men halved the treatment duration and increased the SVR rate. Larger studies should be done to confirm these findings. Clinicians should be alert to detect acute HCV infection of HIV-infected men to take advantage of this effective therapy and decrease further transmission in this epidemic.

Influenza Morbidity and Mortality in Elderly Patients Receiving Statins: A Cohort Study

Background Statins possess immunomodulatory properties and have been proposed for reducing morbidity during an influenza pandemic. We sought to evaluate the effect of statins on hospitalizations and deaths related to seasonal influenza outbreaks. Methodology/Principal Findings We conducted a population-based cohort study over 10 influenza seasons (1996 to 2006) using linked administrative databases in Ontario, Canada. We identified all adults older than 65 years who had received an influenza vaccination prior to the start of influenza season and distinguished those also prescribed statins (23%) from those not also prescribed statins (77%). Propensity-based matching, which accounted for each individuals likelihood of receiving a statin, yielded a final cohort of 2,240,638 patients, exactly half of whom received statins. Statins were associated with small protective effects against pneumonia hospitalization (odds ratio [OR] 0.92; 95% CI 0.89–0.95), 30-day pneumonia mortality (0.84; 95% CI 0.77–0.91), and all-cause mortality (0.87; 95% CI 0.84–0.89). These protective effects attenuated substantially after multivariate adjustment and when we excluded multiple observations for each individual, declined over time, differed across propensity score quintiles and risk groups, and were unchanged during post-influenza season periods. The main limitations of this study were the observational study design, the non-specific outcomes, and the lack of information on medications while hospitalized. Conclusions/Significance Statin use is associated with a statistically significant but minimal protective effect against influenza morbidity that can easily be attributed to residual confounding. Public health officials and clinicians should focus on other measures to reduce morbidity and mortality from the next influenza pandemic.