Effectiveness of inactivated influenza vaccines in preventing influenza-associated deaths and hospitalizations among Ontario residents aged ≥ 65 years: estimates with generalized linear models accounting for healthy vaccinee effects.

BACKGROUND: Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications. METHODS: We conducted a retrospective cohort study among Ontario residents aged ≥ 65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥ 65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations. RESULTS: During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥ 65 years was 22% (95% confidence interval [CI], -6%-42%) for all influenza-associated deaths, 25% (95% CI, 13%-37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%-31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively. CONCLUSIONS: By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ~4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario

It Takes Two–Skilled Recognition of Objects Engages Lateral Areas in Both Hemispheres

Our object recognition abilities, a direct product of our experience with objects, are fine-tuned to perfection. Left temporal and lateral areas along the dorsal, action related stream, as well as left infero-temporal areas along the ventral, object related stream are engaged in object recognition. Here we show that expertise modulates the activity of dorsal areas in the recognition of man-made objects with clearly specified functions. Expert chess players were faster than chess novices in identifying chess objects and their functional relations. Experts' advantage was domain-specific as there were no differences between groups in a control task featuring geometrical shapes. The pattern of eye movements supported the notion that experts' extensive knowledge about domain objects and their functions enabled superior recognition even when experts were not directly fixating the objects of interest. Functional magnetic resonance imaging (fMRI) related exclusively the areas along the dorsal stream to chess specific object recognition. Besides the commonly involved left temporal and parietal lateral brain areas, we found that only in experts homologous areas on the right hemisphere were also engaged in chess specific object recognition. Based on these results, we discuss whether skilled object recognition does not only involve a more efficient version of the processes found in non-skilled recognition, but also qualitatively different cognitive processes which engage additional brain areas

Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines – Multi-country assessment

Background: In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines. Methods: We used electronic health databases to conduct a dynamic retrospective cohort study to assess narcolepsy incidence rates (IR) before and during pH1N1 virus circulation, and after pH1N1 vaccination campaigns in Canada, Denmark, Spain, Sweden, Taiwan, the Netherlands, and the United Kingdom. Using a case-control study design, we evaluated the risk of narcolepsy following AS03- and MF59-adjuvanted pH1N1 vaccines in Argentina, Canada, Spain, Switzerland, Taiwan, and the Netherlands. In the Netherlands, we also conducted a case-coverage study in children born between 2004 and 2009. Results: No changes in narcolepsy IRs were observed in any periods in single study sites except Sweden and Taiwan; in Taiwan incidence increased after wild-type pH1N1 virus circulation and in Sweden (a previously identified signaling country), incidence increased after the start of pH1N1 vaccination. No association was observed for Arepanrix-AS03 or Focetria-MF59 adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the case-control study nor for children born between 2004 and 2009 in the Netherlands case-coverage study for Pandemrix-AS03. Conclusions: Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study

Physical activity and influenza-coded outpatient visits, a population-based cohort study.

Although the benefits of physical activity in preventing chronic medical conditions are well established, its impacts on infectious diseases, and seasonal influenza in particular, are less clearly defined. We examined the association between physical activity and influenza-coded outpatient visits, as a proxy for influenza infection.We conducted a cohort study of Ontario respondents to Statistics Canada's population health surveys over 12 influenza seasons. We assessed physical activity levels through survey responses, and influenza-coded physician office and emergency department visits through physician billing claims. We used logistic regression to estimate the risk of influenza-coded outpatient visits during influenza seasons. The cohort comprised 114,364 survey respondents who contributed 357,466 person-influenza seasons of observation. Compared to inactive individuals, moderately active (OR 0.83; 95% CI 0.74-0.94) and active (OR 0.87; 95% CI 0.77-0.98) individuals were less likely to experience an influenza-coded visit. Stratifying by age, the protective effect of physical activity remained significant for individuals <65 years (active OR 0.86; 95% CI 0.75-0.98, moderately active: OR 0.85; 95% CI 0.74-0.97) but not for individuals ≥ 65 years. The main limitations of this study were the use of influenza-coded outpatient visits rather than laboratory-confirmed influenza as the outcome measure, the reliance on self-report for assessing physical activity and various covariates, and the observational study design.Moderate to high amounts of physical activity may be associated with reduced risk of influenza for individuals <65 years. Future research should use laboratory-confirmed influenza outcomes to confirm the association between physical activity and influenza

Sensitivity analyses.

<p>OR  =  Odds Ratio; CI  =  Confidence Interval.</p>a<p>– All models adjusted for the variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039518#pone-0039518-t001" target="_blank">Table 1</a>.</p

Baseline characteristics by physical activity level.

<p>MET  =  resting metabolic rate.</p>a<p>– Data are presented as Number (%) of patients unless otherwise specified.</p

Odds ratios and 95% confidence intervals for associations between physical activity level and influenza-coded outpatient visits (adjusted and unadjusted analyses).

a<p>– All models adjusted for the variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039518#pone-0039518-t001" target="_blank">Table 1</a>.</p

Improved Survival in Patients with Viral Hepatitis-Induced Hepatocellular Carcinoma Undergoing Recommended Abdominal Ultrasound Surveillance in Ontario: A Population-Based Retrospective Cohort Study.

The optimal schedule for ultrasonographic surveillance of patients with viral hepatitis for the detection of hepatocellular carcinoma (HCC) remains unclear owing to a lack of reliable studies. We examined the timing of ultrasonography in patients with viral hepatitis-induced HCC and its impact on survival and mortality risk while determining predictors of receiving surveillance before HCC diagnosis. A population-based retrospective cohort analysis of patients with viral hepatitis-induced HCC in Ontario between 2000 and 2010 was performed using data from the Ontario Cancer Registry linked health administrative data. HCC surveillance for 2 years preceding diagnosis was assigned as: i) ≥ 2 abdominal ultrasound screens annually; ii) 1 screen annually; iii) inconsistent screening; and iv) no screening. Survival rates were estimated using the Kaplan-Meier method and parametric models to correct for lead-time bias. Associations between HCC surveillance and the risk of mortality after diagnosis were examined using proportional-hazards regression adjusting for confounding factors. Overall, 1,483 patients with viral hepatitis-induced HCC were identified during the study period; 20.2% received ≥ 1 ultrasound screen annually (routine surveillance) for the 2 years preceding diagnosis. The 5-year survival of those receiving routine surveillance was 31.93% (95% CI: 25.77-38.24%) and 31.84% (95% CI: 25.69-38.14%) when corrected for lead-time bias (HCC sojourn time 70 days and 140 days, respectively). This is contrasted with 20.67% (95% CI: 16.86-24.74%) 5-year survival in those who did not undergo screening. In the fully adjusted model, compared to unscreened patients, routine surveillance was associated with a lower mortality risk and a hazard ratio of 0.76 (95% CI: 0.64-0.91) and 0.81 (95% CI: 0.68-0.97), corrected for the respective lead-time bias. Our findings suggest that routine ultrasonography in patients with viral hepatitis is associated with improved survival and reduced mortality risk in a population-based setting. The data emphasizes the importance of surveillance for timely intervention in HCC-diagnosed patients