The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides ...an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country.
Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures.
In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries.
Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.
The highly studied metal–organic framework (MOF), UiO-66, has been touted for its high surface area, stability, and tunability of structural defects for particular applications in catalysis and gas ...storage. However, atomic-level characterization and quantification of defects remain challenging for traditional methods. Motivated by this knowledge gap, coordinatively unsaturated zirconium (Zrcus) defect sites within UiO-66 have been determined through infrared spectroscopic studies of the highly sensitive probe molecule, carbon monoxide. A characteristic blue shift of the vibrational frequency for CO adsorbed at nodes within the MOF was used to identify the presence of Zrcus defects. The identification of these coordinatively unsaturated metal sites was further corroborated via exposure of the MOF to the Lewis base, D2O, which was shown to block CO binding to the Lewis acidic Zrcus sites. The infrared spectroscopic signature for CO binding at the Zrcus sites was further employed to track the emergence of missing linker defects that develop upon thermal treatment of the MOF. The concentration of missing linker defects could be characterized over a range from less than 1% (nominally a defect-free MOF) to over 30% with this relatively simple spectroscopic probe.
Carbon dioxide (CO2) capture and separation in sorbent materials relies on the interactions that take place between guest molecules and topological or chemical features of the sorbent. Although ...researchers have developed an immense library of metal–organic framework (MOF) designs, which range in shape, size, and chemical functionality, a molecular-level understanding of how MOF structure and functionality affect capture and transport has yet to be fully achieved. In this work, in situ infrared spectroscopic techniques, coupled with density functional theory, were used to provide insights into the binding locations and energetics of CO2 on the zirconium-based MOF, UiO-66. Two unique CO2 binding motifs in UiO-66 were identified through differing vibrational frequencies of the asymmetric OCO stretching mode. One configuration is established through hydrogen bonding with μ3-OH groups on the MOF nodes, and a second binding mode exists where CO2 is stabilized through dispersive interactions. Variable temperature infrared spectroscopy revealed adsorption enthalpies of −38.0 ± 1.5 and −30.2 ± 1.3 kJ/mol for the hydrogen-bonded and dispersion-stabilized complexes, respectively. The techniques and results from this study can be extended to other gas–MOF systems to reveal how topological features affect gas sorption and to provide insight into the next-generation sorbent material designs.
Laboratory diagnostics are a core component of any pneumonia etiology study. Recent advances in diagnostic technology have introduced newer methods that have greatly improved the ability to identify ...respiratory pathogens. However, determining the microbial etiology of pneumonia remains a challenge, especially in children. This is largely because of the inconsistent use of assays between studies, difficulties in specimen collection, and problems in interpreting the presence of pathogens as being causally related to the pneumonia event. The laboratory testing strategy for the Pneumonia Etiology Research for Child Health (PERCH) study aims to incorporate a broad range of diagnostic testing that will be standardized across the 7 participating sites. We describe the current status of laboratory diagnostics for pneumonia and the PERCH approach for specimen testing. Pneumonia diagnostics are evolving, and it is also a priority of PERCH to collect and archive specimens for future testing by promising diagnostic methods that are currently under development.
Although a positive association has been established, it is unclear whether lower respiratory tract infections (LRTIs) with respiratory syncytial virus (RSV) cause chronic wheezing illnesses. If ...RSV-LRTI were causal, we would expect RSV-LRTI prevention to reduce the incidence of chronic wheezing illnesses in addition to reducing acute disease. We aimed to evaluate the strength of evidence for a causal effect of RSV-LRTI on subsequent chronic wheezing illness to inform public health expectations for RSV vaccines.
We did a systematic review and meta-analysis of observational studies evaluating the association between RSV-LRTI and subsequent wheezing illness (exposure studies) and studies evaluating the association between RSV immunoprophylaxis and subsequent wheezing illness (immunoprophylaxis studies). Exposure studies were included if the exposure group members had an LRTI with laboratory-confirmed RSV and if the exposure ascertainment period began before 2 years of age and ended before 5 years of age. We required a wash-out period of more than 30 days between the index RSV-LRTI and the outcome measurement to allow for resolution of the acute illness. Comparisons between RSV-LRTI and non-RSV-LRTI were not included. Immunoprophylaxis studies were included if they measured the association with subsequent wheezing illness relative to a control group, either in a randomised controlled trial (RCT) or an observational design. For the immunoprophylaxis drugs in question, we required evidence of efficacy in targeting RSV-LRTI from at least one RCT to ensure biological plausibility. All variations of wheezing illness were combined into a single outcome that refers broadly to asthma or any other respiratory illness with wheezing symptoms. Ovid MEDLINE and Embase databases were searched from inception up to Aug 28, 2018. We evaluated whether data from exposure studies could provide evidence against the most viable non-causal theory that RSV-LRTI is a marker of respiratory illness susceptibility rather than a causal factor. Additionally, we tested whether RSV immunoprophylaxis reduces the odds of subsequent wheezing illnesses. We used a random-effects modelling framework and, to accommodate studies providing multiple correlated estimates, robust variance estimation meta-regressions. Meta-regression coefficients (b) quantify differences between exposure and comparator groups on the loge odds ratio (loge OR) scale.
From 14 235 records we identified 57 eligible articles that described 42 studies and provided 153 effect estimates. 35 studies estimated the direct effect of RSV-LRTI on wheezing illnesses (exposure studies) and eight evaluated the effect of RSV immunoprophylaxis (immunoprophylaxis studies). Exposure studies that adjusted for genetic influences yielded a smaller mean adjusted OR estimate (aOR+ 2·45, 95% CI 1·23–4·88) compared with those that did not (4·17, 2·36–7·37), a significant difference (b 0·53, 95% CI 0·04–1·02). Infants who were not protected with RSV immunoprophylaxis tended to have higher odds of subsequent wheezing illness, as we would expect if RSV-LRTI were causal, but the effect was not significant (OR+ 1·21, 95% CI 0·73–1·99). There was generally a high threat of confounding bias in the observational studies. Additionally, in both the observational studies and immunoprophylaxis RCTs, there was high risk of bias due to missing outcome data.
Our findings, limited to exposure and immunoprophylaxis studies, do not support basing policy decisions on an assumption that prevention of RSV-LRTI will reduce recurrent chronic wheezing illnesses.
Bill & Melinda Gates Foundation.
The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing ...countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery.
Recently, RSV-LRTI prevention trials for a long-acting, monoclonal antibody (mAb) and a maternal RSV F protein (RSV-F) vaccine were published 4,5, as was a systematic review and meta-analysis ...assessing the risk of recurrent wheeze given early childhood RSV-LRTI 2. While public health programs for prevention of RSV-LRTI would be major accomplishments, the impact of such programs on chronic respiratory illness is unknown, but would likely be small.Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Acknowledgements There was no specific funding for this study. Product Product efficacy1 Medically-attended, respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) attack rate2 Relative risk for recurrent wheeze in RSV-LRTI vs. non-RSV-LRTI children3 Baseline risk of recurrent childhood wheezing illness4 Relative risk of recurrent wheeze in intervention vs. control groups5 Trial sample size, both arms (1:1 randomization)5 Number needed to treat5 Maternal RSV F protein vaccine 44.4% 9.5% 2.45 4.9% 0.95 179,353 334 44.4% 9.5% 2.45 9.5% 0.95 87,526 172 44.4% 9.5% 2.45 20.0% 0.95 36,172 82 Long-acting, monoclonal antibody 70.1% 9.5% 2.45 4.9% 0.92 70,865 212 70.1% 9.5% 2.45 9.5% 0.92 34,615 110 70.1% 9.5% 2.45 20.0% 0.92 14,343 52 Table 1 Total sample sizes for efficacy trials of RSV-LRTI prevention to demonstrate a significant effect on recurrent childhood wheezing outcomes and number needed to treat.
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an ...association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12–13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies.
The molecular mechanisms governing γ-globin expression in a subset of fetal hemoglobin (α2γ2: HbF) expressing red blood cells (F-cells) and the mechanisms underlying the variability of response to ...hydroxyurea induced γ-globin expression in the treatment of sickle cell disease are not completely understood. Here we analyzed intra-person clonal populations of basophilic erythroblasts (baso-Es) derived from bone marrow common myeloid progenitors in serum free cultures and report the level of fetal hemoglobin production in F-cells negatively correlates with expression of BCL11A, KLF1 and TAL1. We then examined the effects of hydroxyurea on these three transcription factors and conclude that a successful induction of γ-globin includes a reduction in BCL11A, KLF1 and TAL1 expression. These data suggests that expression changes in this transcription factor network modulate γ-globin expression in F-cells during steady state erythropoiesis and after induction with hydroxyurea.
•Respiratory syncytial virus (RSV) is an important pathogen globally.•The burden of RSV illness is highest in low/middle-income countries (LMICs).•In April 2022, WHO convened a meeting to discuss the ...economics of RSV prevention.•We reviewed cost-effectiveness analyses of RSV prevention in LMICs.•We provided recommendations for future data gathering to address data limitations.
Policymakers often rely on impact and cost-effectiveness evaluations to inform decisions about the introduction of health interventions in low- and middle-income countries (LMICs); however, cost-effectiveness results for the same health intervention can differ by the choice of parameter inputs, modelling assumptions, and geography. Anticipating the near-term availability of new respiratory syncytial virus (RSV) prevention products, WHO convened a two-day virtual consultation in April 2022 with stakeholder groups and global experts in health economics, epidemiology, and vaccine implementation. The objective was to review methods, parameterization, and results of existing cost-effectiveness analyses for RSV prevention in LMICs; identify the most influential inputs and data limitations; and recommend and prioritize future data gathering and research to improve RSV prevention impact estimates in LMICs. Epidemiological parameters identified as both influential and uncertain were those associated with RSV hospitalization and death, specifically setting-specific hospitalization rates and RSV-attributable death rates. Influential economic parameters included product price, delivery costs, willingness-to-pay for health on the part of potential donors, and the cost of RSV-associated hospitalization. Some of the influential parameters identified at this meeting should be more precisely measured by further research. Other influential economic parameters that are highly uncertain may not be resolved, and it is appropriate to use sensitivity analyses to explore these within cost-effectiveness evaluations. This report highlights the presentations and major discussions of the meeting.
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