Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years: an analysis for the Global Burden of Disease Study 2017

Background Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates. Methods We used four strategies to model LRI burden: the mortality due to LRIs was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive ensemble modelling tool; the incidence of LRIs was modelled using population representative surveys, health-care utilisation data, and scientific literature in a compartmental meta-regression tool; the attribution of risk factors for LRI mortality was modelled in a counterfactual framework; and trends in LRI mortality were analysed applying changes in exposure to risk factors over time. In GBD, infectious disease mortality, including that due to LRI, is among HIV-negative individuals. We categorised locations based on their burden in 1990 to make comparisons in the changing burden between 1990 and 2017 and evaluate the relative percent change in mortality rate, incidence, and risk factor exposure to explain differences in the health loss associated with LRIs among children younger than 5 years. Findings In 2017, LRIs caused 808 920 deaths (95% uncertainty interval 747 286–873 591) in children younger than 5 years. Since 1990, there has been a substantial decrease in the number of deaths (from 2 337 538 to 808 920 deaths; 65·4% decrease, 61·5–68·5) and in mortality rate (from 362·7 deaths [330·1–392·0] per 100 000 children to 118·9 deaths [109·8–128·3] per 100 000 children; 67·2% decrease, 63·5–70·1). LRI incidence declined globally (32·4% decrease, 27·2–37·5). The percent change in under-5 mortality rate and incidence has varied across locations. Among the risk factors assessed in this study, those responsible for the greatest decrease in under-5 LRI mortality between 1990 and 2017 were increased coverage of vaccination against Haemophilus influenza type b (11·4% decrease, 0·0–24·5), increased pneumococcal vaccine coverage (6·3% decrease, 6·1–6·3), and reductions in household air pollution (8·4%, 6·8–9·2). Interpretation Our findings show that there have been substantial but uneven declines in LRI mortality among countries between 1990 and 2017. Although improvements in indicators of sociodemographic development could explain some of these trends, changes in exposure to modifiable risk factors are related to the rates of decline in LRI mortality. No single intervention would universally accelerate reductions in health loss associated with LRIs in all settings, but emphasising the most dominant risk factors, particularly in countries with high case fatality, can contribute to the reduction of preventable deaths

Oral rehydration therapies in Senegal, Mali, and Sierra Leone: A spatial analysis of changes over time and implications for policy

Background: Oral rehydration solution (ORS) is a simple intervention that can prevent childhood deaths from severe diarrhea and dehydration. In a previous study, we mapped the use of ORS treatment subnationally and found that ORS coverage increased over time, while the use of home-made alternatives or recommended home fluids (RHF) decreased, in many countries. These patterns were particularly striking within Senegal, Mali, and Sierra Leone. It was unclear, however, whether ORS replaced RHF in these locations or if children were left untreated, and if these patterns were associated with health policy changes.Methods: We used a Bayesian geostatistical model and data from household surveys to map the percentage of children with diarrhea that received (1) any ORS, (2) only RHF, or (3) no oral rehydration treatment between 2000 and 2018. This approach allowed examination of whether RHF was replaced with ORS before and after interventions, policies, and external events that may have impacted healthcare access.Results: We found that RHF was replaced with ORS in most Sierra Leone districts, except those most impacted by the Ebola outbreak. In addition, RHF was replaced in northern but not in southern Mali, and RHF was not replaced anywhere in Senegal. In Senegal, there was no statistical evidence that a national policy promoting ORS use was associated with increases in coverage. In Sierra Leone, ORS coverage increased following a national policy change that abolished health costs for children.Conclusions: Children in parts of Mali and Senegal have been left behind during ORS scale-up. Improved messaging on effective diarrhea treatment and/or increased ORS access such as through reducing treatment costs may be needed to prevent child deaths in these areas

Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017

Background Although the burden of influenza is often discussed in the context of historical pandemics and the threat of future pandemics, every year a substantial burden of lower respiratory tract infections (LRTIs) and other respiratory conditions (like chronic obstructive pulmonary disease) are attributable to seasonal influenza. The Global Burden of Disease Study (GBD) 2017 is a systematic scientific effort to quantify the health loss associated with a comprehensive set of diseases and disabilities. In this Article, we focus on LRTIs that can be attributed to influenza. Methods We modelled the LRTI incidence, hospitalisations, and mortality attributable to influenza for every country and selected subnational locations by age and year from 1990 to 2017 as part of GBD 2017. We used a counterfactual approach that first estimated the LRTI incidence, hospitalisations, and mortality and then attributed a fraction of those outcomes to influenza. Findings Influenza LRTI was responsible for an estimated 145 000 (95% uncertainty interval [UI] 99 000–200 000) deaths among all ages in 2017. The influenza LRTI mortality rate was highest among adults older than 70 years (16·4 deaths per 100 000 [95% UI 11·6–21·9]), and the highest rate among all ages was in eastern Europe (5·2 per 100 000 population [95% UI 3·5–7·2]). We estimated that influenza LRTIs accounted for 9 459000 (95% UI 3 709000–22 935000) hospitalisations due to LRTIs and 81 536 000 hospital days (24 330 000–259851 000). We estimated that 11·5% (95% UI 10·0–12·9) of LRTI episodes were attributable to influenza, corresponding to 54481 000 (38465000–73864000) episodes and 8172000 severe episodes (5 000 000–13 296000). Interpretation This comprehensive assessment of the burden of influenza LRTIs shows the substantial annual effect of influenza on global health. Although preparedness planning will be important for potential pandemics, health loss due to seasonal influenza LRTIs should not be overlooked, and vaccine use should be considered. Efforts to improve influenza prevention measures are needed

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000–18: a geospatial modelling study

Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000–257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution.This study was funded by the Bill & Melinda Gates Foundation. L G Abreu acknowledges support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (Capes; finance Code 001), Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Fundação de Amparo à Pesquisa do Estado de Minas Gerais. D A Bennett acknowledges support from the Oxford National Institute for Health Research (NIHR) Biomedical Research Centre (BRC). The views expressed are those of the author and not necessarily those of the NHS, the NIHR, or the UK Department of Health and Social Care. Z A Bhutta acknowledges support from the Institute for Global Health & Development at the Aga Khan University. F Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. J-W De Neve is supported by the Alexander von Humboldt Foundation. S Dey acknowledges the support from the Centre of Excellence for Research on Clean Air, IIT Delhi. M Ausloos and C Herteliu are partly supported by a grant of the Romanian National Authority for Scientific Research and Innovation (project number PN-III-P4-ID-PCCF-2016-0084). C Herteliu is partly supported by a grant of the Romanian National Authority for Scientific Research and Innovation (project number PN-III-P2-2.1-SOL-2020-2-0351), the Romanian Ministry of Research Innovation and Digitalization (project number ID-585-CTR-42-PFE-2021), and the Romanian Ministry of Labour and Social Justice (30/PSCD/2018). M Jakovljevic acknowledges partial support through Grant OI 175 014 of the Ministry of Science Education and Technological Development of the Republic of Serbia. J S John acknowledges support from the Kunshan Government and China Center for Disease Control and Prevention. W Mendoza is a program analyst in population and development at the United Nations Population Fund country office in Peru, an institution that does not necessarily endorse this study. M N Khan acknowledges the support of Jatiya Kabi Kazi Nazrul Islam University, Bangladesh. K Krishan is supported by UGC Centre of Advanced Study (CAS II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar acknowledges support (FIC/NIH funded K43 TW010716-04 study). B Lacey acknowledges support from UK Biobank, the NIHR Oxford Biomedical Research Centre, and the British Heart Foundation Oxford Centre of Research Excellence. B R Nascimento acknowledges support in part by CNPq (Bolsa de produtividade em pesquisa, 312382/2019-7), by the Edwards Lifesciences Foundation (Every Heartbeat Matters Program 2020) and by FAPEMIG (grant APQ-000627-20). A M Samy acknowledges the support from the Egyptian Fulbright Mission Program. M M Santric-Milicevic acknowledges the support of the Ministry of Education, Science and Technological Development of Serbia (contract 175087). A Sheikh acknowledges the support of Health Data Research UK. I N Soyiri acknowledges support from the University of Hull internal QR Global Challenges Research Fund. S B Zaman acknowledges receiving a scholarship from the Australian Government research training program in support of his academic career. Y Zhang was supported by Science and Technology Research Project of Hubei Provincial Department of Education (grant Q20201104) and Outstanding Young and Middle Aged Technology Innovation Team Project of Hubei Provincial Department of Education (grant T2020003).publishedVersio

Does gamma-aminobutyric acid (GABA) influence the development of chronic inflammation in rheumatoid arthritis?

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK) in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 – agents implicated in the pathogenesis of rheumatoid arthritis (RA). Genetic studies have also associated RA with members of the p38 MAPK pathway.</p> <p>Hypothesis</p> <p>We propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.</p

Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the global burden of disease study 2017

Although the burden of influenza is often discussed in the context of historical pandemics and the threat of future pandemics, every year a substantial burden of lower respiratory tract infections (LRTIs) and other respiratory conditions (like chronic obstructive pulmonary disease) are attributable to seasonal influenza. The Global Burden of Disease Study (GBD) 2017 is a systematic scientific effort to quantify the health loss associated with a comprehensive set of diseases and disabilities. In this Article, we focus on LRTIs that can be attributed to influenza. Methods: We modelled the LRTI incidence, hospitalisations, and mortality attributable to influenza for every country and selected subnational locations by age and year from 1990 to 2017 as part of GBD 2017. We used a counterfactual approach that first estimated the LRTI incidence, hospitalisations, and mortality and then attributed a fraction of those outcomes to influenza. Findings: Influenza LRTI was responsible for an estimated 145 000 (95% uncertainty interval [UI] 99 000–200 000) deaths among all ages in 2017. The influenza LRTI mortality rate was highest among adults older than 70 years (16·4 deaths per 100 000 [95% UI 11·6–21·9]), and the highest rate among all ages was in eastern Europe (5·2 per 100 000 population [95% UI 3·5–7·2]). We estimated that influenza LRTIs accounted for 9 459 000 (95% UI 3 709 000–22 935 000) hospitalisations due to LRTIs and 81 536 000 hospital days (24 330 000–259 851 000). We estimated that 11·5% (95% UI 10·0–12·9) of LRTI episodes were attributable to influenza, corresponding to 54 481 000 (38 465 000–73 864 000) episodes and 8 172 000 severe episodes (5 000 000–13 296 000). Interpretation: This comprehensive assessment of the burden of influenza LRTIs shows the substantial annual effect of influenza on global health. Although preparedness planning will be important for potential pandemics, health loss due to seasonal influenza LRTIs should not be overlooked, and vaccine use should be considered. Efforts to improve influenza prevention measures are needed. Funding: Bill & Melinda Gates Foundation

Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years: an analysis for the Global Burden of Disease Study 2017

Background: Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates.Research reported in this publication was supported by the Bill & Melinda Gates Foundation. AA acknowledges support by the Department of Science and Technology, Government of India (New Delhi, India) through the INSPIRE Faculty program. SA acknowledges the International Centre for Casemix and Clinical Coding, the Faculty of Medicine, National University of Malaysia, and the Department of Health Policy and Management, Faculty of Public Health, Kuwait University for the approval and support to participate in this research project. ABad acknowledges support from the Public Health Agency of Canada. ABar acknowledges support for research from the Project of Ministry of Education, Science and Technology of the Republic of Serbia (number III45005). FC acknowledges funding support from Foundation for Science and Technology/Minister of Science, Technology, and Higher Education through national funds (UID/MULTI/04378/2019 and UID/QUI/50006/2019). AJC acknowledges support by the Health Effects Institute, Boston, MA, USA. MMSM acknowledges the support from the Ministry of Education, Science and Technological Development, Republic of Serbia (Contract number 175087). AMS was supported by the Egyptian Fulbright Mission Program (EFMP). RS-S acknowledges support from Applied and Environmental Sciences University (Bogota, Colombia). AS acknowledges support from Health Data Research UK

Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years: an analysis of the Global Burden of Disease Study 2017

Background Many countries have shown marked declines in diarrhoeal disease mortality among children younger than 5 years. With this analysis, we provide updated results on diarrhoeal disease mortality among children younger than 5 years from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) and use the study’s comparative risk assessment to quantify trends and effects of risk factors, interventions, and broader sociodemographic development on mortality changes in 195 countries and territories from 1990 to 2017. Methods This analysis for GBD 2017 had three main components. Diarrhoea mortality was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive, Bayesian, ensemble modelling tool; and the attribution of risk factors and interventions for diarrhoea were modelled in a counterfactual framework that combines modelled population-level prevalence of the exposure to each risk or intervention with the relative risk of diarrhoea given exposure to that factor. We assessed the relative and absolute change in diarrhoea mortality rate between 1990 and 2017, and used the change in risk factor exposure and sociodemographic status to explain differences in the trends of diarrhoea mortality among children younger than 5 years. Findings Diarrhoea was responsible for an estimated 533 768 deaths (95% uncertainty interval 477 162–593145) among children younger than 5 years globally in 2017, a rate of 78·4 deaths (70·1–87·1) per 100000 children. The diarrhoea mortality rate ranged between countries by over 685 deaths per 100000 children. Diarrhoea mortality per 100000 globally decreased by 69·6% (63·1–74·6) between 1990 and 2017. Among the risk factors considered in this study, those responsible for the largest declines in the diarrhoea mortality rate were reduction in exposure to unsafe sanitation (13·3% decrease, 11·2–15·5), childhood wasting (9·9% decrease, 9·6–10·2), and low use of oral rehydration solution (6·9% decrease, 4·8–8·4). Interpretation Diarrhoea mortality has declined substantially since 1990, although there are variations by country. Improvements in sociodemographic indicators might explain some of these trends, but changes in exposure to risk factors—particularly unsafe sanitation, childhood growth failure, and low use of oral rehydration solution—appear to be related to the relative and absolute rates of decline in diarrhoea mortality. Although the most effective interventions might vary by country or region, identifying and scaling up the interventions aimed at preventing and protecting against diarrhoea that have already reduced diarrhoea mortality could further avert many thousands of deaths due to this illness.SMA acknowledges the International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia and Department of Health Policy and Management, Faculty of Public Health, Kuwait University for their approval and support to participate in this research project. AsA acknowledges funding support from the Department of Science and Technology, Government of India through the INSPIRE faculty scheme. AlaB acknowledges support from the Public Health Agency of Canada. AleB acknowledges support for research from the Project of Ministry of Education, Science and Technology of the Republic of Serbia (number III45005). FC acknowledges funding support from Foundation for Science and Technology/Minister of Science, Technology, and Higher Education through national funds (UID/MULTI/04378/2019 and UID/ QUI/50006/2019). AMS was supported by the Egyptian Fulbright Mission Program. MMSM acknowledges the support from the Ministry of Education, Science and Technological Development, Republic of Serbia (Contract No. 175087). AS acknowledges support from Health Data Research UK

Dynamics of social class contempt in contemporary British television comedy

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.British television comedy has often ridiculed the complexities and characteristics of social class structures and identities. In recent years, poor white socially marginalised groups, now popularly referred to as “chavs”, have become a prevalent comedy target. One of the most popular and controversial television “comedy chavs” is Little Britain's fictional teenage single mother, Vicky Pollard. This article examines the representation of Vicky Pollard in light of contemporary widespread abuse of the white working class. Highlighting the polysemic and ambivalent nature of Vicky Pollard's representation, the article argues that whilst Little Britain's characterisation of Vicky Pollard largely contributes to contemporary widespread demonisation of the working class, there are moments within Little Britain when a more sympathetic tone towards the poor working class may be read, and where chav identities are used to ridicule the pretensions, superficiality, and falsity of middle-class identities. The article concludes that television comedy has been, and continues to be, a significant vehicle through which serious concerns, anxieties, and questions about social class and class identities are discursively constructed and contested