Use of the prevented fraction for the population to determine deaths averted by existing prevalence of physical activity: a descriptive study

Abstract Background: The disease or mortality burdens of unhealthy lifestyle behaviours are often reported. The positive side of the story, the burden that existing levels have averted, is rarely discussed. We present what we believe to be global application of the Prevented Fraction for the Population to obtain estimates of the percentage of premature mortality and number of premature deaths averted by total physical activity levels for 168 countries. Methods: We combined previously published activity prevalence data (2001-2016) and relative risks of mortality in Monte-Carlo simulations to estimate country-specific Prevented Fractions for the Population (percentage of mortality averted) and their 95% confidence intervals. Higher Prevented Fractions indicate a greater proportion of deaths averted due to physical activity. Using mortality data for 40-74 year olds, we estimated the number of premature deaths averted due to activity levels for all adults and by sex. We presented the median and range of the Prevented Fractions globally, by region, and by income classification. Results: The global median Prevented Fraction for the Population was 15.0% (range 6.6-20.5%), conservatively equating to 3.9 million (95% confidence interval: 2.5-5.6) premature deaths averted annually. The African region had the highest median (16.6%, range 12.1-20.5%), the Americas had the lowest (13.1%, range 10.8-16.6%). Low income countries tended to have higher median Prevented Fractions (17.9%, range 12.3-20.5%) than high income countries (14.1%, range 6.6-17.8%). Globally, the median Prevented Fraction was higher for men than women (16.0% (range 7.8-20.7% and 14.1% (range 5.0-20.4%), respectively). Interpretation: Existing physical activity levels have contributed to averting premature mortality across all countries. The Prevented Fraction for the Population has utility as an advocacy tool to promote healthy lifestyle behaviours as, by making the case of what has been achieved, it could demonstrate the value of current investment and services. This may be more conducive to political support.TS, SJS, and SB are funded by the UK Medical Research Council (MC_UU_12015/1 and MC_UU_12015/3). DD is funded by a Future Leader Fellowship by Heart Foundation Australia (No. 101234). At the time of this work, MT was a member of the Centre for Diet and Activity Research (MR/K023187/1), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, National Institute for Health Research (NIHR), and Wellcome Trust, under the auspices of the UKClinical Research Collaboration, is gratefully acknowledged. MT was also funded on the METAHIT project (Medical Research Council grant MR/P02663X/1)

CMS physics technical design report : Addendum on high density QCD with heavy ions

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Association between vaccination and the risk of central demyelination: results from a case-referent study

International audienceBackground: Few studies documented the potential association between vaccination and the risk of central demyelination (CD). Specifically, anti-hepatitis B and anti-human papillomavirus (HPV) vaccines have been the subject of distrust with regard to their implication to trigger CD. Methods: From a systematic national registry, patients with first signs of CD (cases) were identified and documented for their exposure to vaccination up to 24 months before the first signs occurred. This exposure was compared to that of a representative sample of general practice patients without a history of CD, randomly selected from a national registry (referents). CD cases were 2:1 matched on age, sex, index date (ID), and region of residence. Vaccines against influenza, HPV, hepatitis B and diphtheria–tetanus–pertussis–poliomyelitis–haemophilus (DTPPHae) were considered. Associations between vaccination and CD were assessed using multivariate conditional logistic regressions, controlled for confounding factors. Findings: 564 CD cases were matched to 1,128 randomly selected referents (age range: 2–79 years old). Overall, 123 (22%) CD cases and 320 (28%) referents had received at least one vaccine within 24 months before ID. Adjusted odds ratios (ORs) for any vaccination were 0.69, 95% confidence interval (CI) [0.54–0.88] with respect to any CD first signs, 0.68 [0.51–0.90] for myelitis and 0.70 [0.42–1.17] for optic neuritis. Adjusted ORs for any CD first signs were 1.02 [0.71–1.47] for influenza vaccine (administered in 9.6% of cases and 10.4% of referents) and 0.72 [0.53–0.99] for DTPPHae vaccine (administered in 10.8% of cases and 14.5% of referents). Vaccines against hepatitis B and HPV were only administered in 1.1% and 1.2% of cases and in 2.9% and 3.2% of referents respectively, which statistically explained the point estimates < 1 (ORs of 0.39 [0.16–0.94] and of 0.32 [0.13–0.80]). Interpretation: No increased risk of CD incidence was observed amongst vaccinated patients. Lower rates of vaccination against hepatitis B and HPV observed in patients with CD compared to referents may be due to the reluctance of physicians to vaccinate patients considered at risk of CD

Comparison of cohort and nested case-control designs for estimating the effect of time-varying drug exposure on the risk of adverse event in the presence of ties

International audienceCohort and nested case-control (NCC) designs are frequently used in pharmacoepidemiology to assess the associations of drug exposure that can vary over time with the risk of an adverse event. Although it is typically expected that estimates from NCC analyses are similar to those from the full cohort analysis, with moderate loss of precision, only few studies have actually compared their respective performance for estimating the effects of time-varying exposures (TVE). We used simulations to compare the properties of the resulting estimators of these designs for both time-invariant exposure and TVE. We varied exposure prevalence, proportion of subjects experiencing the event, hazard ratio, and control-to-case ratio and considered matching on confounders. Using both designs, we also estimated the real-world associations of time-invariant ever use of menopausal hormone therapy (MHT) at baseline and updated, time-varying MHT use with breast cancer incidence. In all simulated scenarios, the cohort-based estimates had small relative bias and greater precision than the NCC design. NCC estimates displayed bias to the null that decreased with a greater number of controls per case. This bias markedly increased with higher proportion of events. Bias was seen with Breslow's and Efron's approximations for handling tied event times but was greatly reduced with the exact method or when NCC analyses were matched on confounders. When analyzing the MHT-breast cancer association, differences between the two designs were consistent with simulated data. Once ties were taken correctly into account, NCC estimates were very similar to those of the full cohort analysis