PLoS Medicine

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Age at puberty and risk of asthma: A Mendelian randomisation study

Ma, 07/08/2018 - 22:00

by Cosetta Minelli, Diana A. van der Plaat, Bénédicte Leynaert, Raquel Granell, Andre F. S. Amaral, Miguel Pereira, Osama Mahmoud, James Potts, Nuala A. Sheehan, Jack Bowden, John Thompson, Debbie Jarvis, George Davey Smith, John Henderson

Background

Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males.

Methods and findings

MR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (<12), normal (12–14), or late (>14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10−5) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10−4), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking.

Conclusions

This large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide.

Choices in vaccine trial design in epidemics of emerging infections

Ma, 07/08/2018 - 22:00

by Rebecca Kahn, Annette Rid, Peter G. Smith, Nir Eyal, Marc Lipsitch

In a Policy Forum, Marc Lipsitch and colleagues discuss trial design issues in infectious disease outbreaks.

A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health

Gi, 02/08/2018 - 22:00

by Muin J. Khoury, W. Gregory Feero, David A. Chambers, Lawrence E. Brody, Nazneen Aziz, Robert C. Green, A. Cecile J.W. Janssens, Michael F. Murray, Laura Lyman Rodriguez, Joni L. Rutter, Sheri D. Schully, Deborah M. Winn, George A. Mensah

In a Policy Forum, Muin Khoury and colleagues discuss research on the clinical application of genome sequencing data.

Metabolic and lifestyle risk factors for acute pancreatitis in Chinese adults: A prospective cohort study of 0.5 million people

Me, 01/08/2018 - 22:00

by Yuanjie Pang, Christiana Kartsonaki, Iain Turnbull, Yu Guo, Ling Yang, Zheng Bian, Yiping Chen, Iona Y. Millwood, Fiona Bragg, Weiwei Gong, Qinai Xu, Quan Kang, Junshi Chen, Liming Li, Michael V. Holmes, Zhengming Chen

Background

Little prospective evidence exists about risk factors and prognosis of acute pancreatitis in China. We examined the associations of certain metabolic and lifestyle factors with risk of acute pancreatitis in Chinese adults.

Methods and findings

The prospective China Kadoorie Biobank (CKB) recruited 512,891 adults aged 30 to 79 years from 5 urban and 5 rural areas between 25 June 2004 and 15 July 2008. During 9.2 years of follow-up (to 1 January 2015), 1,079 cases of acute pancreatitis were recorded. Cox regression was used to estimate adjusted hazard ratios (HRs) for acute pancreatitis associated with various metabolic and lifestyle factors among all or male (for smoking and alcohol drinking) participants. Overall, the mean waist circumference (WC) was 82.1 cm (SD 9.8) cm in men and 79.0 cm (SD 9.5) cm in women, 6% had diabetes, and 6% had gallbladder disease at baseline. WC was positively associated with risk of acute pancreatitis, with an adjusted HR of 1.35 (95% CI 1.27–1.43; p < 0.001) per 1-SD-higher WC. Individuals with diabetes or gallbladder disease had HRs of 1.34 (1.07–1.69; p = 0.01) and 2.42 (2.03–2.88; p < 0.001), respectively. Physical activity was inversely associated with risk of acute pancreatitis, with each 4 metabolic equivalent of task (MET) hours per day (MET-h/day) higher physical activity associated with an adjusted HR of 0.95 (0.91–0.99; p = 0.03). Compared with those without any metabolic risk factors (i.e., obesity, diabetes, gallbladder disease, and physical inactivity), the HRs of acute pancreatitis for those with 1, 2, or ≥3 risk factors were 1.61 (1.47–1.76), 2.36 (2.01–2.78), and 3.41 (2.46–4.72), respectively (p < 0.001). Among men, heavy alcohol drinkers (≥420 g/week) had an HR of 1.52 (1.11–2.09; p = 0.04, compared with abstainers), and current regular smokers had an HR of 1.45 (1.28–1.64; p = 0.02, compared with never smokers). Following a diagnosis of acute pancreatitis, there were higher risks of pancreatic cancer (HR = 8.26 [3.42–19.98]; p < 0.001; 13 pancreatic cancer cases) and death (1.53 [1.17–2.01]; p = 0.002; 89 deaths). Other diseases of the pancreas had similar risk factor profiles and prognosis to acute pancreatitis. The main study limitations are ascertainment of pancreatitis using hospital records and residual confounding.

Conclusions

In this relatively lean Chinese population, several modifiable metabolic and lifestyle factors were associated with higher risks of acute pancreatitis, and individuals with acute pancreatitis had higher risks of pancreatic cancer and death.

Quantifying excess deaths related to heatwaves under climate change scenarios: A multicountry time series modelling study

Ma, 31/07/2018 - 22:00

by Yuming Guo, Antonio Gasparrini, Shanshan Li, Francesco Sera, Ana Maria Vicedo-Cabrera, Micheline de Sousa Zanotti Stagliorio Coelho, Paulo Hilario Nascimento Saldiva, Eric Lavigne, Benjawan Tawatsupa, Kornwipa Punnasiri, Ala Overcenco, Patricia Matus Correa, Nicolas Valdes Ortega, Haidong Kan, Samuel Osorio, Jouni J. K. Jaakkola, Niilo R. I. Ryti, Patrick G. Goodman, Ariana Zeka, Paola Michelozzi, Matteo Scortichini, Masahiro Hashizume, Yasushi Honda, Xerxes Seposo, Ho Kim, Aurelio Tobias, Carmen Íñiguez, Bertil Forsberg, Daniel Oudin Åström, Yue Leon Guo, Bing-Yu Chen, Antonella Zanobetti, Joel Schwartz, Tran Ngoc Dang, Dung Do Van, Michelle L. Bell, Ben Armstrong, Kristie L. Ebi, Shilu Tong

Background

Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of climate change on heatwave-related mortality at a global scale is limited.

Methods and findings

We collected historical daily time series of mean temperature and mortality for all causes or nonexternal causes, in periods ranging from January 1, 1984, to December 31, 2015, in 412 communities within 20 countries/regions. We estimated heatwave–mortality associations through a two-stage time series design. Current and future daily mean temperature series were projected under four scenarios of greenhouse gas emissions from 1971–2099, with five general circulation models. We projected excess mortality in relation to heatwaves in the future under each scenario of greenhouse gas emissions, with two assumptions for adaptation (no adaptation and hypothetical adaptation) and three scenarios of population change (high variant, median variant, and low variant). Results show that, if there is no adaptation, heatwave-related excess mortality is expected to increase the most in tropical and subtropical countries/regions (close to the equator), while European countries and the United States will have smaller percent increases in heatwave-related excess mortality. The higher the population variant and the greenhouse gas emissions, the higher the increase of heatwave-related excess mortality in the future. The changes in 2031–2080 compared with 1971–2020 range from approximately 2,000% in Colombia to 150% in Moldova under the highest emission scenario and high-variant population scenario, without any adaptation. If we considered hypothetical adaptation to future climate, under high-variant population scenario and all scenarios of greenhouse gas emissions, the heatwave-related excess mortality is expected to still increase across all the countries/regions except Moldova and Japan. However, the increase would be much smaller than the no adaptation scenario. The simple assumptions with respect to adaptation as follows: no adaptation and hypothetical adaptation results in some uncertainties of projections.

Conclusions

This study provides a comprehensive characterisation of future heatwave-related excess mortality across various regions and under alternative scenarios of greenhouse gas emissions, different assumptions of adaptation, and different scenarios of population change. The projections can help decision makers in planning adaptation and mitigation strategies for climate change.

Climate change and health: Moving from theory to practice

Ma, 31/07/2018 - 22:00

by Jonathan A. Patz, Madeleine C. Thomson

In an Editorial discussing the Special Issue on Climate Change and Health, guest editors Jonathan Patz and Madeleine Thompson summarize key issues in the field and describe the significance of research studies included in the issue.

Prioritizing the needs of children in a changing climate

Ma, 31/07/2018 - 22:00

by Lawrence R. Stanberry, Madeleine C. Thomson, Wilmot James

In a Perspective, Lawrence Stanberry and colleagues discuss impacts of climate change on children.

Reducing the opioid overdose death toll in North America

Ma, 31/07/2018 - 22:00

by Wayne D. Hall, Michael Farrell

In this Perspective, Wayne D. Hall & Michael Farrell discuss the current need for alternative strategies in the rising opioid crisis in the US and the necessity to fund evidence-based treatment initiatives to reduce the death toll.

Methadone maintenance treatment and mortality in people with criminal convictions: A population-based retrospective cohort study from Canada

Ma, 31/07/2018 - 22:00

by Angela Russolillo, Akm Moniruzzaman, Julian M. Somers

Background

Individuals with criminal histories have high rates of opioid dependence and mortality. Excess mortality is largely attributable to overdose deaths. Methadone maintenance treatment (MMT) is one of the best evidence-based opioid substitution treatments (OSTs), but there is uncertainty about whether methadone treatment reduces the risk of mortality among convicted offenders over extended follow-up periods. The objective of this study was to investigate the association between adherence to MMT and overdose fatality as well as other causes of mortality.

Methods and findings

We conducted a retrospective cohort study involving linked population-level administrative data among individuals in British Columbia (BC), Canada with a history of conviction and who filled a methadone prescription between January 1, 1998 and March 31, 2015. Participants were followed from the date of first-dispensed methadone prescription until censoring (date of death or March 31, 2015). Methadone was divided into medicated (methadone was dispensed) and nonmedicated (methadone was not dispensed) periods and analysed as a time-varying exposure. Hazard ratios (HRs) with 95% CIs were estimated using multivariable Cox regression to examine mortality during the study period. All-cause and cause-specific mortality rates were compared during medicated and nonmedicated methadone periods. Participants (n = 14,530) had a mean age of 34.5 years, were 71.4% male, and had a median follow-up of 6.9 years. A total of 1,275 participants died during the observation period. The overall all-cause mortality rate was 11.2 per 1,000 person-years (PYs). Participants were significantly less likely to die from both nonexternal (adjusted HR [AHR] 0.27 [95% CI 0.23–0.33]) and external (AHR 0.41 [95% CI 0.33–0.51]) causes during medicated periods, independent of sociodemographic, criminological, and health-related factors. Death due to infectious diseases was 5 times lower (AHR 0.20 [95% CI 0.13–0.30]), and accidental poisoning (overdose) deaths were nearly 3 times lower (AHR 0.39 [95% CI 0.30–0.50]) during medicated periods. A competing risk regression demonstrated a similar pattern of results. The use of a Canadian offender population may limit generalizability of results. Furthermore, our observation period represents community-based methadone prescribing and may omit prescriptions administered during hospital separations. Therefore, the magnitude of the protective effects of methadone from nonexternal causes of death should be interpreted with caution.

Conclusions

Adherence to methadone was associated with significantly lower rates of death in a population-level cohort of Canadian convicted offenders. Achieving higher rates of adherence may reduce overdose deaths and other causes of mortality among offenders and similarly marginalized populations. Our findings warrant examination in other study centres in response to the crisis of opiate-involved deaths.

From advocacy to action: Projecting the health impacts of climate change

Ma, 31/07/2018 - 22:00

by Hannah Nissan, Declan Conway

In a Perspective, Hannah Nissan and Declan Conway discuss the implications of uncertainty about projected impacts of climate change on health.

Life cycle environmental emissions and health damages from the Canadian healthcare system: An economic-environmental-epidemiological analysis

Ma, 31/07/2018 - 22:00

by Matthew J. Eckelman, Jodi D. Sherman, Andrea J. MacNeill

Background

Human health is dependent upon environmental health. Air pollution is a leading cause of morbidity and mortality globally, and climate change has been identified as the single greatest public health threat of the 21st century. As a large, resource-intensive sector of the Canadian economy, healthcare itself contributes to pollutant emissions, both directly from facility and vehicle emissions and indirectly through the purchase of emissions-intensive goods and services. Together these are termed life cycle emissions. Here, we estimate the extent of healthcare-associated life cycle emissions as well as the public health damages they cause.

Methods and findings

We use a linked economic-environmental-epidemiological modeling framework to quantify pollutant emissions and their implications for public health, based on Canadian national healthcare expenditures over the period 2009–2015. Expenditures gathered by the Canadian Institute for Health Information (CIHI) are matched to sectors in a national environmentally extended input-output (EEIO) model to estimate emissions of greenhouse gases (GHGs) and >300 other pollutants. Damages to human health are then calculated using the IMPACT2002+ life cycle impact assessment model, considering uncertainty in the damage factors used. On a life cycle basis, Canada’s healthcare system was responsible for 33 million tonnes of carbon dioxide equivalents (CO2e), or 4.6% of the national total, as well as >200,000 tonnes of other pollutants. We link these emissions to a median estimate of 23,000 disability-adjusted life years (DALYs) lost annually from direct exposures to hazardous pollutants and from environmental changes caused by pollution, with an uncertainty range of 4,500–610,000 DALYs lost annually. A limitation of this national-level study is the use of aggregated data and multiple modeling steps to link healthcare expenditures to emissions to health damages. While informative on a national level, the applicability of these findings to guide decision-making at individual institutions is limited. Uncertainties related to national economic and environmental accounts, model representativeness, and classification of healthcare expenditures are discussed.

Conclusions

Our results for GHG emissions corroborate similar estimates for the United Kingdom, Australia, and the United States, with emissions from hospitals and pharmaceuticals being the most significant expenditure categories. Non-GHG emissions are responsible for the majority of health damages, predominantly related to particulate matter (PM). This work can guide efforts by Canadian healthcare professionals toward more sustainable practices.

Development of the Impacts of Cycling Tool (ICT): A modelling study and web tool for evaluating health and environmental impacts of cycling uptake

Ma, 31/07/2018 - 22:00

by James Woodcock, Ali Abbas, Alvaro Ullrich, Marko Tainio, Robin Lovelace, Thiago H. Sá, Kate Westgate, Anna Goodman

Background

A modal shift to cycling has the potential to reduce greenhouse gas emissions and provide health co-benefits. Methods, models, and tools are needed to estimate the potential for cycling uptake and communicate to policy makers the range of impacts this would have.

Methods and findings

The Impacts of Cycling Tool (ICT) is an open source model with a web interface for visualising travel patterns and comparing the impacts of different scenarios of cycling uptake. It is currently applied to England. The ICT allows users to visualise individual and trip-level data from the English National Travel Survey (NTS), 2004–2014 sample, 132,000 adults. It models scenarios in which there is an increase in the proportion of the population who cycle regularly, using a distance-based propensity approach to model which trips would be cycled. From this, the model estimates likely impact on travel patterns, health, and greenhouse gas emissions. Estimates of nonoccupational physical activity are generated by fusing the NTS with the English Active People Survey (APS, 2013–2014, 559,515 adults) to create a synthetic population. Under ‘equity’ scenarios, we investigate what would happen if cycling levels increased equally among all age and gender categories, as opposed to in proportion to the profile of current cyclists. Under electric assist bike (pedelecs or ‘e-bike’) scenarios, the probability of cycling longer trips increases, based on the e-bike data from the Netherlands, 2013–2014 Dutch Travel Survey (50,868 adults).Outcomes are presented across domains including transport (trip duration and trips by mode), health (physical activity levels, years of life lost), and car transport–related CO2 emissions. Results can be visualised for the whole population and various subpopulations (region, age, gender, and ethnicity). The tool is available at www.pct.bike/ict. If the proportion of the English population who cycle regularly increased from 4.8% to 25%, then there would be notable reductions in car miles and passenger related CO2 emissions (2.2%) and health benefits (2.1% reduction in years of life lost due to premature mortality). If the new cyclists had access to e-bikes, then mortality reductions would be similar, while the reduction in car miles and CO2 emissions would be larger (2.7%). If take-up of cycling occurred equally by gender and age (under 80 years), then health benefits would be marginally greater (2.2%) but reduction in CO2 slightly smaller (1.8%). The study is limited by the quality and comparability of the input data (including reliance on self-report behaviours). As with all modelling studies, many assumptions are required and potentially important pathways excluded (e.g. injury, air pollution, and noise pollution).

Conclusion

This study demonstrates a generalisable approach for using travel survey data to model scenarios of cycling uptake that can be applied to a wide range of settings. The use of individual-level data allows investigation of a wide range of outcomes, and variation across subgroups. Future work should investigate the sensitivity of results to assumptions and omissions, and if this varies across setting.

Correction: Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis

Ve, 27/07/2018 - 22:00

by Antoine Bouquegneau, Charlotte Loheac, Olivier Aubert, Yassine Bouatou, Denis Viglietti, Jean–Philippe Empana, Camilo Ulloa, Mohammad Hassan Murad, Christophe Legendre, Denis Glotz, Annette M. Jackson, Adriana Zeevi, Stephan Schaub, Jean–Luc Taupin, Elaine F. Reed, John J. Friedewald, Dolly B. Tyan, Caner Süsal, Ron Shapiro, E. Steve Woodle, Luis G. Hidalgo, Jacqueline O’Leary, Robert A. Montgomery, Jon Kobashigawa, Xavier Jouven, Patricia Jabre, Carmen Lefaucheur, Alexandre Loupy