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Journal article (peer-reviewed)
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- Afshin, Ashkan, et al.
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Health effects of dietary risks in 195 countries, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
- 2019
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 393:10184, s. 1958-1972
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Journal article (peer-reviewed)abstract
- Background: Suboptimal diet is an important preventable risk factor for non-communicable diseases (NCDs); however, its impact on the burden of NCDs has not been systematically evaluated. This study aimed to evaluate the consumption of major foods and nutrients across 195 countries and to quantify the impact of their suboptimal intake on NCD mortality and morbidity.Methods: By use of a comparative risk assessment approach, we estimated the proportion of disease-specific burden attributable to each dietary risk factor (also referred to as population attributable fraction) among adults aged 25 years or older. The main inputs to this analysis included the intake of each dietary factor, the effect size of the dietary factor on disease endpoint, and the level of intake associated with the lowest risk of mortality. Then, by use of diseasespecific population attributable fractions, mortality, and disability-adjusted life-years (DALYs), we calculated the number of deaths and DALYs attributable to diet for each disease outcome.Findings: In 2017, 11 million (95% uncertainty interval [UI] 10-12) deaths and 255 million (234-274) DALYs were attributable to dietary risk factors. High intake of sodium (3 million [1-5] deaths and 70 million [34-118] DALYs), low intake of whole grains (3 million [2-4] deaths and 82 million [59-109] DALYs), and low intake of fruits (2 million [1-4] deaths and 65 million [41-92] DALYs) were the leading dietary risk factors for deaths and DALYs globally and in many countries. Dietary data were from mixed sources and were not available for all countries, increasing the statistical uncertainty of our estimates.Interpretation: This study provides a comprehensive picture of the potential impact of suboptimal diet on NCD mortality and morbidity, highlighting the need for improving diet across nations. Our findings will inform implementation of evidence-based dietary interventions and provide a platform for evaluation of their impact on human health annually.
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- Gurung, SC, et al.
(author)
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The role of active case finding in reducing patient incurred catastrophic costs for tuberculosis in Nepal
- 2019
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In: Infectious diseases of poverty. - : Springer Science and Business Media LLC. - 2049-9957. ; 8:1, s. 99-
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Journal article (peer-reviewed)abstract
- BackgroundThe World Health Organization (WHO) End TB Strategy has established a milestone to reduce the number of tuberculosis (TB)- affected households facing catastrophic costs to zero by 2020. The role of active case finding (ACF) in reducing patient costs has not been determined globally. This study therefore aimed to compare costs incurred by TB patients diagnosed through ACF and passive case finding (PCF), and to determine the prevalence and intensity of patient-incurred catastrophic costs in Nepal.MethodsThe study was conducted in two districts of Nepal: Bardiya and Pyuthan (Province No. 5) between June and August 2018. One hundred patients were included in this study in a 1:1 ratio (PCF: ACF, 25 consecutive ACF and 25 consecutive PCF patients in each district). The WHO TB patient costing tool was applied to collect information from patients or a member of their family regarding indirect and direct medical and non-medical costs. Catastrophic costs were calculated based on the proportion of patients with total costs exceeding 20% of their annual household income.The intensity of catastrophic costs was calculated using the positive overshoot method. The chi-square and Wilcoxon-Mann-Whitney tests were used to compare proportions and costs. Meanwhile, the Mantel Haenszel test was performed to assess the association between catastrophic costs and type of diagnosis.ResultsNinety-nine patients were interviewed (50 ACF and 49 PCF). Patients diagnosed through ACF incurred lower costs during the pre-treatment period (direct medical: USD 14 vs USD 32,P = 0.001; direct non-medical: USD 3 vs USD 10,P = 0.004; indirect, time loss: USD 4 vs USD 13,P < 0.001). The cost of the pre-treatment and intensive phases combined was also lower for direct medical (USD 15 vs USD 34,P = 0.002) and non-medical (USD 30 vs USD 54,P = 0.022) costs among ACF patients. The prevalence of catastrophic direct costs was lower for ACF patients for all thresholds. A lower intensity of catastrophic costs was also documented for ACF patients, although the difference was not statistically significant.ConclusionsACF can reduce patient-incurred costs substantially, contributing to the End TB Strategy target. Other synergistic policies, such as social protection, will also need to be implemented to reduce catastrophic costs to zero among TB-affected households.
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- Kessler, Thorsten, et al.
(author)
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Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention
- 2019
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In: Cardiovascular Research. - : OXFORD UNIV PRESS. - 0008-6363 .- 1755-3245. ; 115:10, s. 1512-1518
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Journal article (peer-reviewed)abstract
- Aim A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. Methods and results The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91-209) vs. 134 (85-194) AU.min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203AU.min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08-2.68; P = 0.02). Bleeding risk was not altered. Conclusion We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.
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- Robson, T. Matthew, et al.
(author)
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A perspective on ecologically relevant plant-UV research and its practical application
- 2019
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In: Photochemical and Photobiological Sciences. - : Royal Society of Chemistry. - 1474-905X .- 1474-9092. ; 18:5, s. 970-988
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Journal article (peer-reviewed)abstract
- Plants perceive ultraviolet-B (UV-B) radiation through the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8), and initiate regulatory responses via associated signalling networks, gene expression and metabolic pathways. Various regulatory adaptations to UV-B radiation enable plants to harvest information about fluctuations in UV-B irradiance and spectral composition in natural environments, and to defend themselves against UV-B exposure. Given that UVR8 is present across plant organs and tissues, knowledge of the systemic signalling involved in its activation and function throughout the plant is important for understanding the context of specific responses. Fine-scale understanding of both UV-B irradiance and perception within tissues and cells requires improved application of knowledge about UV-attenuation in leaves and canopies, warranting greater consideration when designing experiments. In this context, reciprocal crosstalk among photoreceptor-induced pathways also needs to be considered, as this appears to produce particularly complex patterns of physiological and morphological response. Through crosstalk, plant responses to UV-B radiation go beyond simply UV-protection or amelioration of damage, but may give cross-protection over a suite of environmental stressors. Overall, there is emerging knowledge showing how information captured by UVR8 is used to regulate molecular and physiological processes, although understanding of upscaling to higher levels of organisation, i.e. organisms, canopies and communities remains poor. Achieving this will require further studies using model plant species beyond Arabidopsis, and that represent a broad range of functional types. More attention should also be given to plants in natural environments in all their complexity, as such studies are needed to acquire an improved understanding of the impact of climate change in the context of plant-UV responses. Furthermore, broadening the scope of experiments into the regulation of plant-UV responses will facilitate the application of UV radiation in commercial plant production. By considering the progress made in plant-UV research, this perspective highlights prescient topics in plant-UV photobiology where future research efforts can profitably be focussed. This perspective also emphasises burgeoning interdisciplinary links that will assist in understanding of UV-B effects across organisational scales and gaps in knowledge that need to be filled so as to achieve an integrated vision of plant responses to UV-radiation.
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- Turner, Lucy M., et al.
(author)
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Toxic Algae Silence Physiological Responses to Multiple Climate Drivers in a Tropical Marine Food Chain
- 2019
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
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Journal article (peer-reviewed)abstract
- Research on the effects of climate change in the marine environment continues to accelerate, yet we know little about the effects of multiple climate drivers in more complex, ecologically relevant settings - especially in sub-tropical and tropical systems. In marine ecosystems, climate change (warming and freshening from land run-oft) will increase water column stratification which is favorable for toxin producing dinoflagellates. This can increase the prevalence of toxic microalgal species, leading to bioaccumulation of toxins by filter feeders, such as bivalves, with resultant negative impacts on physiological performance. In this study we manipulated multiple climate drivers (warming, freshening, and acidification), and the availability of toxic microalgae, to determine their impact on the physiological health, and toxin load of the tropical filter-feeding clam, Meretrix meretrix. Using a structural equation modeling (SEM) approach, we found that exposure to projected marine climates resulted in direct negative effects on metabolic and immunological function and, that these effects were often more pronounced in clams exposed to multiple, rather than single climate drivers. Furthermore, our study showed that these physiological responses were modified by indirect effects mediated through the food chain. Specifically, we found that when bivalves were fed with a toxin-producing dinoflagellate (Alexandrium minutum) the physiological responses, and toxin load changed differently and in a non-predictable way compared to clams exposed to projected marine climates only. Specifically, oxygen consumption data revealed that these clams did not respond physiologically to climate warming or the combined effects of warming, freshening and acidification. Our results highlight the importance of quantifying both direct and, indirect food chain effects of climate drivers on a key tropical food species, and have important implications for shellfish production and food safety in tropical regions.
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- Pfeifer, H., et al.
(author)
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Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph plus ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1
- 2019
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In: Leukemia. - : NATURE PUBLISHING GROUP. - 0887-6924 .- 1476-5551. ; 33:8, s. 1910-1922
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Journal article (peer-reviewed)abstract
- Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation. Standardised use of EAC primer/probe sets and of centrally prepared plasmid standards had the greatest impact on reducing interlaboratory variability. In QC1 the proportion of analyses with BCR-ABL1/ABL1 ratios within half a log difference were 40/67 (60%) and 52/67 (78%) at 10(-3) and 36/67 (53%) and 53/67 (79%) at 10(-4)BCR-ABL1/ABL1. Standardized RNA extraction, cDNA synthesis and cycler platforms did not improve results further, whereas stringent application of technical criteria for assay quality and uniform criteria for data interpretation and reporting were essential. We provide detailed laboratory recommendations for the standardized MRD analysis in routine diagnostic settings and in multicenter clinical trials for Ph + ALL.
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