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Sökning: WFRF:(Marklund J.) > (2020-2024)

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1.
  • Needham, E. J., et al. (författare)
  • Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
  • 2022
  • Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:11, s. 4097-4107
  • Tidskriftsartikel (refereegranskat)abstract
    • COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible. Needham et al. reveal elevations in blood biomarkers of brain injury in patients hospitalised with COVID-19. The changes, which were severity-dependent, were associated with dysregulated immune responses including increases in pro-inflammatory cytokines and autoantibodies. Ongoing active brain injury could still be seen months after infection.
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  • Picetti, Edoardo, et al. (författare)
  • Early management of adult traumatic spinal cord injury in patients with polytrauma : a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS)
  • 2024
  • Ingår i: World Journal of Emergency Surgery. - : BioMed Central (BMC). - 1749-7922. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies.Methods: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted.Results: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak).Conclusions: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.
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  • Laguzzi, F., et al. (författare)
  • Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease : Pooled De Novo Results From 15 Observational Studies
  • 2024
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 149:4, s. 305-316
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
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4.
  • Ramonet, M., et al. (författare)
  • The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO 2 measurements : Atmospheric CO 2 anomaly
  • 2020
  • Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
  • Tidskriftsartikel (refereegranskat)abstract
    • During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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  • Gómez, M. J., et al. (författare)
  • Analysis of Vibration Signals of Drivetrain Failures in Wind Turbines for Condition Monitoring
  • 2021
  • Ingår i: Experimental techniques (Westport, Conn.). - : Springer. - 0732-8818 .- 1747-1567. ; 45:1, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • In the last years, the wind industry has increased in a large scale. A wind turbine out of service leeds to high costs due to both maintenance and repair costs and the incapability of producing electricity. A substantial part of the wind turbine failures are in the drivetrain, mainly in generator and gearbox. Several recent works focuses in the study of benefits of the integration of condition monitoring with current maintenance techniques, that would drive to the reduction of costs. For condition monitoring, vibration analysis has been widely accepted as the technique that gives most information about faults in a rotating machine, thus vibration sensors are often used in wind turbine applications. In this work, data from several vibration sensors installed in 18 wind turbines in cold climate were analysed using the Wavelet Packets Transform energy. Signals were acquired for more than four years (from 2011 to 2015), registering failures in gearboxes and generators of the wind turbines. Data were obtained under varying conditions of load and speed as well as varying weather conditions. Signals were analysed with the aim of finding parameters that indicate the presence of a fault. This would be useful to predict a failure with enough time to plan a stop of the wind turbine in the proper moment for similar faults in the future.
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10.
  • Harris, WS, et al. (författare)
  • Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2329-
  • Tidskriftsartikel (refereegranskat)abstract
    • The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15–18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20–22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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11.
  • Sahin, Cagla, et al. (författare)
  • Structural Basis for Dityrosine-Mediated Inhibition of α-Synuclein Fibrillization
  • 2022
  • Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 144:27, s. 11949-11954
  • Tidskriftsartikel (refereegranskat)abstract
    • α-Synuclein (α-Syn) is an intrinsically disordered protein which self-assembles into highly organized β-sheet structures that accumulate in plaques in brains of Parkinson’s disease patients. Oxidative stress influences α-Syn structure and self-assembly; however, the basis for this remains unclear. Here we characterize the chemical and physical effects of mild oxidation on monomeric α-Syn and its aggregation. Using a combination of biophysical methods, small-angle X-ray scattering, and native ion mobility mass spectrometry, we find that oxidation leads to formation of intramolecular dityrosine cross-linkages and a compaction of the α-Syn monomer by a factor of √2. Oxidation-induced compaction is shown to inhibit ordered self-assembly and amyloid formation by steric hindrance, suggesting an important role of mild oxidation in preventing amyloid formation.
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  • Sendker, Franziska L., et al. (författare)
  • Emergence of fractal geometries in the evolution of a metabolic enzyme
  • 2024
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 628:8009, s. 894-900
  • Tidskriftsartikel (refereegranskat)abstract
    • Fractals are patterns that are self-similar across multiple length-scales1. Macroscopic fractals are common in nature2,3,4; however, so far, molecular assembly into fractals is restricted to synthetic systems5,6,7,8,9,10,11,12. Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpiński triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution.
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  • Yin, Xuejun, et al. (författare)
  • Effects of salt substitutes on clinical outcomes : a systematic review and meta-analysis
  • 2022
  • Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 108:20, s. 1608-1615
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.METHODS: We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.RESULTS: There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was -4.61 mm Hg (95% CI -6.07 to -3.14) and of diastolic blood pressure (DBP) was -1.61 mm Hg (95% CI -2.42 to -0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a -1.53 mm Hg (95% CI -3.02 to -0.03, p=0.045) greater reduction in SBP and a -0.95 mm Hg (95% CI -1.78 to -0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).CONCLUSIONS: The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.TRIAL REGISTRATION NUMBER: CRD42020161077.
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  • Aronsson, Gunnar, et al. (författare)
  • Health and motivation as mediators of the effects of job demands, job control, job support, and role conflicts at work and home on sickness presenteeism and absenteeism
  • 2021
  • Ingår i: International Archives of Occupational and Environmental Health. - : Springer Nature. - 0340-0131 .- 1432-1246. ; 94:3, s. 409-418
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The first objective was to contribute to a better understanding of the contrasting and paradoxical results in studies of work environment factors and sickness presence and sickness absence. A second objective was to examine if, and under what conditions, employees choose to replace sickness absence with sickness presence, i.e., so-called substitution.Methods: The study utilizes a large body of cross-sectional questionnaire data (n = 130,161) gathered in Sweden from 2002 to 2007 in connection with a comprehensive health promotion initiative. Health and motivation were analyzed as mediators of the effects of five job factors, job control, job support, job demand, role conflict and “work to family conflict” on sickness presence and absence.Results: The results concerning job demands indicate substitution in that increased job demands are associated with increased presenteeism and reduced absenteeism. The direct effect of higher job support was increased absenteeism, but via the health and motivation paths, the total effect of more social support was health-promoting and associated with a reduction in sickness absence and sickness presence. High job control emerged as the most pronounced health-promoting factor, reducing sickness presenteeism as well as absenteeism. More role conflicts and work-to-family conflicts were directly and indirectly associated with decreased health and increased absenteeism as well as presenteeism. earlier research.Conclusion: The mediation analyzes shed light on some of the paradoxes in research on sickness presenteeism and sickness absenteeism, especially regarding job demands and job support. The substitution effect is important for workplace policy and occupational health practice.
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  • Baer, David J, et al. (författare)
  • Targeting the Dietary Na : K Ratio-Considerations for Design of an Intervention Study to Impact Blood Pressure.
  • 2021
  • Ingår i: Advances in nutrition (Bethesda, Md.). - : Oxford University Press. - 2156-5376 .- 2161-8313. ; 13:1, s. 225-233
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite medical, dietary, and lifestyle recommendations and drug advancements, hypertension persists as among the most prevalent noncommunicable diseases in the US population, and control remains elusive. Uncontrolled hypertension may increase the risk of serious illness from various other health challenges, including cardiovascular and renal responses. Adoption of a healthy diet is a consistent core element of lifestyle modifications that are recommended for mitigation of hypertension. The dietary sodium-to-potassium ratio is recognized as having promising potential in the regulation of blood pressure. In fact, the understanding of the relation between this ratio and blood pressure was documented as a key evidence gap in the 2019 National Academies of Sciences, Engineering, and Medicine report that revised recommended intake levels for both sodium and potassium. Although notable animal and human evidence supports this point, fundamental to developing a specific dietary recommendation for a sodium-to-potassium ratio is a well-designed human intervention trial. The successful translatability of such a trial will require careful consideration of study elements, including the study population, duration, blood pressure measurement, and dietary intervention, among other factors. This paper addresses these decision points and serves as supporting documentation for a research group or organization with the interest and means to address this important data gap, which will undoubtedly be foundational for advancing dietary guidance and would inform the next iteration of Dietary Reference Intakes for sodium and potassium.
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  • Bernabe-Ortiz, Antonio, et al. (författare)
  • The potential scalability of salt substitutes as an intervention to lower population sodium levels
  • 2022
  • Ingår i: Salud pública de México. - : Instituto Nacional de Salud Publica. - 0036-3634 .- 1606-7916. ; 64, s. S6-S13
  • Tidskriftsartikel (refereegranskat)abstract
    • Reducing salt intake is one of the most cost-effective interventions to improve population health due to the subsequent reductions in blood pressure. Countries are introducing programs to lower salt consumption. Such programs usually focus on reducing salt in packaged foods and meals alongside campaigns to change consumer behavior. Thus, this paper provides an overview of the rationale for and evidence supporting the use of salt substitutes. Cur-rent approaches to salt reduction are insufficient, and more innovative solutions need to be identified. There is good evidence that salt substitutes, where some of the sodium is replaced with potassium, are effective to lower sodium total intake. The main challenge is to understand the pathways to market for salt substitutes. How do we implement programs to promote salt substitutes in different countries? What levels of government intervention are required? With more research and government investment, salt substitutes could be a game changer for increasing the impact of strategies to reduce population salt intake.
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  • Bhat, Saiuj, et al. (författare)
  • A Systematic Review of the Sources of Dietary Salt Around the World.
  • 2020
  • Ingår i: Advances in nutrition (Bethesda, Md.). - : Elsevier BV. - 2156-5376 .- 2161-8313. ; 11:3, s. 677-686
  • Tidskriftsartikel (refereegranskat)abstract
    • Excess salt intake contributes to hypertension and increased cardiovascular disease risk. Efforts to implement effective salt-reduction strategies require accurate data on the sources of salt consumption. We therefore performed a systematic review to identify the sources of dietary salt around the world. We systematically searched peer-reviewed and gray literature databases for studies that quantified discretionary (salt added during cooking or at the table) and nondiscretionary sources of salt and those that provided information about the food groups contributing to dietary salt intake. Exploratory linear regression analysis was also conducted to assess whether the proportion of discretionary salt intake is related to the gross domestic product (GDP) per capita of a country. We identified 80 studies conducted in 34 countries between 1975 and 2018. The majority (n = 44, 55%) collected data on dietary salt sources within the past 10 y and were deemed to have a low or moderate risk of bias (n = 75, 94%). Thirty-two (40%) studies were judged to be nationally representative. Populations in Brazil, China, Costa Rica, Guatemala, India, Japan, Mozambique, and Romania received more than half of their daily salt intake from discretionary sources. A significant inverse correlation between discretionary salt intake and a country's per capita GDP was observed (P < 0.0001), such that for every $10,000 increase in per capita GDP, the amount of salt obtained from discretionary sources was lower by 8.7% (95% CI: 5.1%, 12%). Bread products, cereal and grains, meat products, and dairy products were the major contributors to dietary salt intake in most populations. There is marked variation in discretionary salt use around the world that is highly correlated with the level of economic development. Our findings have important implications for the type of salt-reduction strategy likely to be effective in a country.
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  • Blackburn, Thomas, 1989, et al. (författare)
  • Self-absorption of synchrotron radiation in a laser-irradiated plasma
  • 2021
  • Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 28:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Electrons at the surface of a plasma that is irradiated by a laser with intensity in excess of 1 0 23 W c m - 2 are accelerated so strongly that they emit bursts of synchrotron radiation. Although the combination of high photon and electron density and electromagnetic field strength at the plasma surface makes particle-particle interactions possible, these interactions are usually neglected in simulations of the high-intensity regime. Here we demonstrate an implementation of two such processes: photon absorption and stimulated emission. We show that, for plasmas that are opaque to the laser light, photon absorption would cause complete depletion of the multi-keV region of the synchrotron photon spectrum, unless compensated by stimulated emission. Our results motivate further study of the density dependence of quantum electrodynamics phenomena in strong electromagnetic fields.
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  • Blaschke, Stefan J., et al. (författare)
  • Early Blood–Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice
  • 2024
  • Ingår i: International Journal of Molecular Sciences. - 1661-6596. ; 25:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood–brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [18F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R2 = 0.29, p < 0.01), even detectable by a significant increase in hippocampal uptake of [18F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.
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  • Cardenas, Daniel, et al. (författare)
  • Electron bunch evolution in laser-wakefield acceleration
  • 2020
  • Ingår i: Physical Review Accelerators and Beams. - : American Physical Society. - 2469-9888. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on systematic and high-precision measurements of the evolution of electron beams in a laser-wakefield accelerator (LWFA). Utilizing shock-front injection, a technique providing stable, tunable and high-quality electron bunches, acceleration and deceleration of few-MeV quasimonoenergetic beams were measured with cutting-edge technology sub-5-fs and 8-fs laser pulses. We explain the observations with dephasing, an effect that fundamentally limits the performance of LWFAs. Typical density dependent electron energy evolution with 57–300  μm dephasing length and 6–20 MeV peak energy was observed and is well described by a parabolic fit. This is a promising electron source for time-resolved few-fs electron diffraction.
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  • Cornelius Chukwu, Eugenia, et al. (författare)
  • Engineered Aldolases Catalyzing Stereoselective Aldol Reactions Between Aryl-Substituted Ketones and Aldehydes
  • 2023
  • Ingår i: Catalysis Science & Technology. - : Royal Society of Chemistry. - 2044-4753 .- 2044-4761.
  • Tidskriftsartikel (refereegranskat)abstract
    • An A129G/R134V/S166G triple mutant of fructose 6-phosphate aldolase (FSA) from Escherichia coli was further engineered with the goal to generate new enzyme variants capable of catalyzing aldol reactions between aryl substituted ketones and aldehydes. Residues L107 and L163 were subjected to saturation mutagenesis and the resulting library of FSA variants was screened for catalytic activity with 2-hydroxyacetophenone and phenylacetaldehyde as substrates. A selection of aldolase variants was identified that catalyze the synthesis of 2,3-dihydroxy-1,4-diphenylbutanone. The most active enzyme variants contained an L163C substitution. An L107C/L163C variant was further tested for activity with substituted phenylacetaldehydes, and was shown to afford the production of the corresponding diphenyl substituted butanones with good diastereoselectivities (anti : syn dr of 10 to 30) and reasonable to good enantioselectivities of syn enantiomers (er of 5 to 25).
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  • Fahlstrom, A., et al. (författare)
  • A grading scale for surgically treated patients with spontaneous supratentorial intracerebral hemorrhage: the Surgical Swedish ICH Score
  • 2020
  • Ingår i: Journal of Neurosurgery. - 0022-3085. ; 133:3, s. 800-807
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE The authors aimed to develop the first clinical grading scale for patients with surgically treated spontaneous supratentorial intracerebral hemorrhage (ICH). METHODS A nationwide multicenter study including 401 ICH patients surgically treated by craniotomy and evacuation of a spontaneous supratentorial ICH was conducted between January 1, 2011, and December 31, 2015. All neurosurgical centers in Sweden were included. All medical records and neuroimaging studies were retrospectively reviewed. Independent predictors of 30-day mortality were identified by logistic regression. A risk stratification scale (the Surgical Swedish ICH [SwICH] Score) was developed using weighting of independent predictors based on strength of association. RESULTS Factors independently associated with 30-day mortality were Glasgow Coma Scale (GCS) score (p = 0.00015), ICH volume >= 50 mL (p = 0.031), patient age >= 75 years (p = 0.0056), prior myocardial infarction (MI) (p = 0.00081), and type 2 diabetes (p = 0.0093). The Surgical SwICH Score was the sum of individual points assigned as follows: GCS score 15-13 (0 points), 12-5 (1 point), 4-3 (2 points); age >= 75 years (1 point); ICH volume >= 50 mL (1 point); type 2 diabetes (1 point); prior MI (1 point). Each increase in the Surgical SwICH Score was associated with a progressively increased 30-day mortality (p = 0.0002). No patient with a Surgical SwICH Score of 0 died, whereas the 30-day mortality rates for patients with Surgical SwICH Scores of 1, 2, 3, and 4 were 5%, 12%, 31%, and 58%, respectively. CONCLUSIONS The Surgical SwICH Score is a predictor of 30-day mortality in patients treated surgically for spontaneous supratentorial ICH. External validation is needed to assess the predictive value as well as the generalizability of the Surgical SwICH Score.
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  • Greer, Raquel C, et al. (författare)
  • Potassium-Enriched Salt Substitutes as a Means to Lower Blood Pressure : Benefits and Risks.
  • 2020
  • Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 75:2, s. 266-274
  • Tidskriftsartikel (refereegranskat)abstract
    • Use of salt substitutes containing potassium chloride is a potential strategy to reduce sodium intake, increase potassium intake, and thereby lower blood pressure and prevent the adverse consequences of high blood pressure. In this review, we describe the rationale for using potassium-enriched salt substitutes, summarize current evidence on the benefits and risks of potassium-enriched salt substitutes and discuss the implications of using potassium-enriched salt substitutes as a strategy to lower blood pressure. A benefit of salt substitutes that contain potassium chloride is the expected reduction in dietary sodium intake at the population level because of reformulation of manufactured foods or replacement of sodium chloride added to food during home cooking or at the dining table. There is empirical evidence that replacement of sodium chloride with potassium-enriched salt substitutes lowers systolic and diastolic blood pressure (average net Δ [95% CI] in mm Hg: -5.58 [-7.08 to -4.09] and -2.88 [-3.93 to -1.83], respectively). The risks of potassium-enriched salt substitutes include a possible increased risk of hyperkalemia and its principal adverse consequences: arrhythmias and sudden cardiac death, especially in people with conditions that impair potassium excretion such as chronic kidney disease. There is insufficient evidence regarding the effects of potassium-enriched salt substitutes on the occurrence of hyperkalemia. There is a need for additional empirical research on the effect of increasing dietary potassium and potassium-enriched salt substitutes on serum potassium levels and the risk of hyperkalemia, as well as for robust estimation of the population-wide impact of replacing sodium chloride with potassium-enriched salt substitutes.
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  • Huang, Liping, et al. (författare)
  • The impact of baseline potassium intake on the dose-response relation between sodium reduction and blood pressure change : systematic review and meta-analysis of randomized trials.
  • 2021
  • Ingår i: Journal of Human Hypertension. - : Springer Nature. - 0950-9240 .- 1476-5527. ; 35:11, s. 946-957
  • Tidskriftsartikel (refereegranskat)abstract
    • Sodium and potassium appear to interact with each other in their effects on blood pressure with potassium supplementation having a greater blood pressure lowering-effect when sodium intake is high. Whether the effect of sodium reduction on blood pressure varies according to potassium intake levels is unclear. We carried out a systematic review and meta-analysis to examine the impact of baseline potassium intake on blood pressure response to sodium reduction in randomized trials in adult populations, with sodium and potassium intake estimated from 24-h urine samples. We included 68 studies involving 5708 participants and conducted univariable and multivariable meta-regression. The median intake of baseline potassium was 67.7 mmol (Interquartile range: 54.6-76.4 mmol), and the mean reduction in sodium intake was 128 mmol (95% CI: 107-148). Multivariable meta-regression that included baseline 24-h urinary potassium excretion, age, ethnicity, baseline blood pressure, change in 24-h urinary sodium excretion, as well as the interaction between baseline 24-h urinary potassium excretion and change in 24-h urinary sodium excretion did not identify a significant association of baseline potassium intake levels with the blood pressure reduction achieved with a 50 mmol lowering of sodium intake (p > 0.05 for both systolic and diastolic blood pressure). A higher starting level of blood pressure was consistently associated with a greater blood pressure reduction from reduced sodium consumption. However, the nonsignificant findings may subject to the limitations of the data available. Additional studies with more varied potassium intake levels would allow a more confident exclusion of an interaction.
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29.
  • Hussain, Tasfia, et al. (författare)
  • Quality assessment of consumer-facing websites on sodium reduction
  • 2022
  • Ingår i: The Journal of Clinical Hypertension. - : Wiley-Blackwell. - 1524-6175 .- 1751-7176. ; 24:10, s. 1285-1292
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this paper is to evaluate the quality of information and guidance on dietary sodium reduction available on consumer-facing websites. Google Trends was used to identify the five most-used search terms related to dietary sodium reduction. For each term, websites on the first two pages were collected (n = 18-20). Of 93 websites collected, 24 were excluded due to defective links, duplicate websites, or not being consumer-focused. The remaining 69 websites were evaluated using a novel instrument, JHU-SALT, that includes 14 questions on topics related to salt reduction. The questions are grouped into three domains ("information," "guidance," and "accuracy"). For each question, websites were scored using a 3-step ordinal scale ("topic not addressed," "topic somewhat addressed," or "topic addressed adequately"). Only three of 14 JHU-SALT questions were addressed adequately by a majority of websites. Many websites provided information on the adverse health effects of a high sodium diet (74%, n = 51) or mentioned intake recommendations (64%, n = 44). Information on fundamental concepts was largely missing. The majority of websites (80%, n = 55) provided information on lifestyle strategies to reduce blood pressure, but most did not provide guidance to help implement those strategies. While missing information was common, misinformation was uncommon. The DISCERN questionnaire was utilized as well. Consumers seeking information and guidance on dietary sodium reduction will find that most available websites provide accurate but limited information, and insufficient guidance on how to lower sodium intake. Websites that provide both relevant information and guidance are needed to help consumers effectively reduce dietary sodium.
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30.
  • Imamura, Fumiaki, et al. (författare)
  • Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes : A pooled analysis of prospective cohort studies
  • 2020
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:6
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDe novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).Methods and findingsSeventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.ConclusionsConcentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.
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31.
  • Johnson Curtis, Christine, et al. (författare)
  • Considerations for modelling a broad food tax in the Philippines and other low-income and middle-income countries
  • 2023
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 8:SUPPL_8
  • Tidskriftsartikel (refereegranskat)abstract
    • Fiscal policies to improve diet are a promising strategy to address the increasing burden of non-communicable disease, the leading cause of death globally. Sugar-sweetened beverage taxes are the most implemented type of fiscal policy to improve diet. Yet taxes on food, if appropriately structured and applied across the food supply, may support a larger population-level shift towards a healthier diet. Designing these policies and guiding them through the legislative process requires evidence. Equity-oriented cost-effectiveness analyses that estimate the distribution of potential health and economic gains can provide this critical evidence. Taxes on less healthy foods are rarely modelled in low-income and middle-income countries.We describe considerations for modelling the effect of a food tax, which can provide guidance for food tax policy design. This includes describing issues related to the availability, reliability and level of detail of national data on dietary habits, the nutrient content of foods and food prices; the structure of the nutrient profile model; type of tax; tax rate; pass-through rate and price elasticity. Using the Philippines as an example, we discuss considerations for using existing data to model the potential effect of a tax, while also taking into account the political and food policy context. In this way, we provide a modelling framework that can help guide policy-makers and advocates in designing a food policy to improve the health and well-being of future generations in the Philippines and elsewhere.
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32.
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33.
  • Kimblad, H., et al. (författare)
  • Adult cardiac arrest in the emergency department - A Swedish cohort study
  • 2022
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 175, s. 105-112
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cardiac arrests occurring in emergency departments (ED) represent 10-20% of all in-hospital cardiac arrests (IHCA). Yet few studies have examined the characteristics and outcomes of IHCA occurring in the ED. The aim was to describe this population in a nationwide registry covering all EDs in Sweden. Methods: Patients >= 18 years with an IHCA in the ED reported to the Swedish Registry for Cardio-Pulmonary Resuscitation (SRCR) during 2007-2018 were included. Descriptive statistics were calculated. Results: We identified 2,604 (10 % of all IHCA in SRCR) ED arrests; 902 (35%) survived to hospital discharge and 672 (75%) had good neurological outcomes (Cerebral Performance Category 1-2). The national incidence rate 2016-2018 was 1.6 (range 1.60-1.70) cardiac arrests per 10,000 ED visits. Over 90% were witnessed and 26% had a shockable first rhythm. Three presumed aetiologies together explained half of the cases; myocardial ischaemia (30%, n = 789), primary arrhythmia (12%, n = 327) and respiratory insufficiency (10%, n = 265). At a subset of ED arrest at Karolinska University Hospital, half of the cardiac arrests occurred within one hour from arrival to the ED. Conclusion: About 10% of all IHCA occurs in ED, however, from an ED perspective it is a rare event. Cardiac arrests in the ED generally occur within an hour from arrival to the ED. One in three survive to discharge from hospital and the majority of survivors have a good neurological outcome.
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34.
  • Lai, Heidi T. M., et al. (författare)
  • Trans Fatty Acid Biomarkers and Incident Type 2 Diabetes : Pooled Analysis of 12 Prospective Cohort Studies in the Fatty Acids and Outcomes Research Consortium (FORCE)
  • 2022
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:4, s. 854-863
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.RESEARCH DESIGN AND METHODS: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged >= 18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by prespecified between-study and within-study characteristics.RESULTS: During a mean follow-up of 13.5 years, 2,843 cases of incident T2D were identified. In multivariable-adjusted pooled analyses, no significant associations with T2D were identified for trans/trans-18:2, relative risk (RR) 1.09 (95% CI 0.94-1.25); cis/trans-18:2, 0.89 (0.73-1.07); and trans/cis-18:2, 0.87 (0.73-1.03). Trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated with T2D (RR 0.81 [95% CI 0.67-0.99], 0.86 [0.75-0.99], and 0.84 [0.74-0.96], respectively). Findings were not significantly different according to prespecified sources of potential heterogeneity (each P >= 0.1).CONCLUSIONS: Circulating individual trans-18:2 TFA biomarkers were not associated with risk of T2D, while trans-16:1n-9, total trans-18:1, and total trans-18:2 were inversely associated. Findings may reflect the influence of mixed TFA sources (industrial vs. natural ruminant), a general decline in TFA exposure due to policy changes during this period, or the relatively limited range of TFA levels.
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35.
  • Marklund, A., et al. (författare)
  • Efficacy and safety of controlled ovarian stimulation using GnRH antagonist protocols for emergency fertility preservation in young women with breast cancer-a prospective nationwide Swedish multicenter study
  • 2020
  • Ingår i: Human Reproduction. - 0268-1161 .- 1460-2350. ; 35:4, s. 929-938
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY QUESTION: How efficacious and safe are the current approaches to controlled ovarian stimulation (COS) aimed at fertility preservation (FP) in women with breast cancer (BC)? SUMMARY ANSWER: In women with BC undergoing COS aiming at egg/embryo cryopreservation, letrozole-based protocols and those randomly started were equally effective compared with conventional COS, and the overall survival was similar between the women that proceeded to FP and those who did not. WHAT IS KNOWN ALREADY: Cryopreservation of oocytes and embryos is an established method for FP in women with BC. Recent improvements to COS protocols include concomitant use of letrozole, random-cycle start day of stimulation and the use of GnRHa for the egg maturation trigger. To date, limited sample size of the available studies has not allowed investigation of differences in the efficacy of the different approaches to COS for FP in this patient population. STUDY DESIGN, SIZE, DURATION: A prospective multicenter study with national coverage including 610 women with BC counseled between 1 January 1995 and 30 June 2017 at six Swedish FP regional programs. PARTICIPANTS/MATERIALS, SETTING, METHODS: After counseling, 401 women elected to undergo COS. Treatments differed in the use or not of concomitant letrozole, a conventional or random-cycle day COS initiation and the use of hCG versus GnRHa trigger for oocyte maturation. Numbers of cryopreserved oocytes and embryos were defined as primary outcome. Pregnancy attempts, reproductive outcomes and long-term survival, investigated by the linking of individuals of the cohort to the total population register of the Swedish Tax Agency (up to 25 November 2018), were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Using letrozole or not resulted in similar numbers of oocytes and embryos cryopreserved (meanoocytes=9.7 versus 10 and meanembryos 4.0 versus 5.3, respectively), similar to COS with random versus conventional start (meanoocytes 9.0 versus 10.6 and meanembryos 4.8 versus 4.8). In COS with letrozole, a GnRHa trigger was associated with a higher number of oocytes retrieved (P<0.05) and embryos cryopreserved (P<0.005), compared with conventional hCG trigger. Of 99 women who returned to fertility clinics after cancer treatment, 32 proceeded to thawing of oocytes or embryos and 10 of them had live births. The all-cause survival between the women that underwent COS and those who did not was similar and did not differ between the two groups. LIMITATIONS, REASONS FOR CAUTION: Data on tumor characteristics and estrogen receptor (ER) status were not known for all women at the time of FP counseling and planning of COS, thus protocols with letrozole have been used for both estrogen-sensitive and non-estrogen-sensitive BC. For the same reason, subsequent adjustment for ERs in the BC or tumor characteristics as potential confounders were not performed as these parameters were not available and did not influence the provision of FP through COS. WIDER IMPLICATIONS OF THE FINDINGS: The results of our study support the premise that recently introduced potential improvements to COS protocols for FP in women with BC are efficacious and safe. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by research grants from the Swedish Cancer Society, the Stockholm County Council, the Percy Falk Stiftelsen, Radiumhemmets Forskningsfonder, The Swedish Breast Cancer Association and Karolinska Institutet to K.A.R.W. J.B. reports grants from Amgen, AstraZeneca, Pfizer, Roche, Sanofi-Aventis and Merck, outside the submitted work, and payment from UpToDate to Asklepios Medicine HB for a chapter on BC prediction and prognostication. All the other authors have no competing interests to report. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
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36.
  • Marklund, A, et al. (författare)
  • Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis
  • 2022
  • Ingår i: JAMA oncology. - : American Medical Association (AMA). - 2374-2445 .- 2374-2437. ; 8:10, s. 1438-1446
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis.ObjectiveTo investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis.Design, Setting, and ParticipantsThis Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022.Main Outcomes and MeasuresRelapse and disease-specific mortality after a diagnosis of BC.ResultsThe final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference).Conclusions and RelevanceIn this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.
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37.
  • Marklund, Matti, et al. (författare)
  • Estimated Benefits and Risks of Using a Reduced-Sodium, Potassium-Enriched Salt Substitute in India : A Modeling Study
  • 2022
  • Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 79:10, s. 2188-2198
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Salt substitution (ie, replacement of table and cooking salt with potassium-enriched salt substitutes) is a promising strategy to reduce blood pressure and prevent cardiovascular disease, particularly in countries like India where there is high sodium intake, mainly from discretionary salt, and low potassium intake. Life-threatening hyperkalemia from increased potassium intake is a postulated concern for individuals with chronic kidney disease.Methods: We used comparative risk assessment models to estimate the number of (1) cardiovascular deaths averted due to blood pressure reductions; (2) potential hyperkalemia-related deaths from increased potassium intake in individuals with advanced chronic kidney disease; and (3) net averted deaths from nationwide salt substitution in India. We evaluated a conservative scenario, based on a large, long-term pragmatic trial in rural China; and an optimistic scenario informed by our recent trial in India. Sensitivity analyses were conducted to assess the robustness of the findings.Results: In the conservative scenario, a nationwide salt substitution intervention was estimated to result in approximate to 214 000 (95% uncertainty interval, 92 764-353 054) averted deaths from blood pressure reduction in the total population and approximate to 52 000 (22 961-80 211) in 28 million individuals with advanced chronic kidney disease, while approximate to 22 000 (15 221-31 840) hyperkalemia-deaths might be caused by the intervention. The corresponding estimates for the optimistic scenario were approximate to 351 000 (130 470-546 255), approximate to 66 000 (24 925-105 851), and approximate to 9000 (4251-14 599). Net benefits were consistent across sensitivity analyses.Conclusions: Modeling nationwide salt substitution in India consistently estimated substantial net benefits, preventing around 8% to 14% of annual cardiovascular deaths. Even allowing for potential hyperkalemia risks there were net benefits estimated for individuals with chronic kidney disease.
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38.
  • Marklund, Matti, et al. (författare)
  • Estimated health benefits, costs and cost-effectiveness of eliminating dietary industrial trans fatty acids in Kenya : cost-effectiveness analysis
  • 2023
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 8:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To model the potential health gains and cost-effectiveness of a mandatory limit of industrial trans fatty acids (iTFA) in Kenyan foods.Design Multiple cohort proportional multistate life table model, incorporating existing data from the Global Burden of Disease study, pooled analyses of observational studies and peer-reviewed evidence of healthcare and policy implementation costs.Setting Kenya.Participants Adults aged ≥20 years at baseline (n=50 million).Intervention A mandatory iTFA limit (≤2% of all fats) in the Kenyan food supply compared with a base case scenario of maintaining current trans fat intake.Main outcome measures Averted ischaemic heart disease (IHD) events and deaths, health-adjusted life years; healthcare costs; policy implementation costs; net costs; and incremental cost-effectiveness ratio.Results Over the first 10 years, the intervention was estimated to prevent ~1900 (95% uncertainty interval (UI): 1714; 2148) IHD deaths and ~17 000 (95% UI: 15 475; 19 551) IHD events, and to save ~US$50 million (95% UI: 44; 56). The corresponding estimates over the lifespan of the model population were ~49 000 (95% UI: 43 775; 55 326) IHD deaths prevented, ~113 000 (95% UI: 100 104; 127 969) IHD events prevented and some ~US$300 million (256; 331) saved. Policy implementation costs were estimated as ~US$9 million over the first 10 years and ~US$20 million over the population lifetime. The intervention was estimated to be cost saving regardless of the time horizon. Findings were robust across multiple sensitivity analyses.Conclusions Findings support policy action for a mandatory iTFA limit as a cost-saving strategy to avert IHD events and deaths in Kenya.
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39.
  • Marklund, Matti, 1981-, et al. (författare)
  • Estimated health benefits, costs, and cost-effectiveness of eliminating industrial trans-fatty acids in Australia : A modelling study.
  • 2020
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: trans-fatty acids (TFAs) are a well-known risk factor of ischemic heart disease (IHD). In Australia, the highest TFA intake is concentrated to the most socioeconomically disadvantaged groups. Elimination of industrial TFA (iTFA) from the Australian food supply could result in reduced IHD mortality and morbidity while improving health equity. However, such legislation could lead to additional costs for both government and food industry. Thus, we assessed the potential cost-effectiveness, health gains, and effects on health equality of an iTFA ban from the Australian food supply.METHODS AND FINDINGS: Markov cohort models were used to estimate the impact on IHD burden and health equity, as well as the cost-effectiveness of a national ban of iTFA in Australia. Intake of TFA was assessed using the 2011-2012 Australian National Nutrition and Physical Activity Survey. The IHD burden attributable to TFA was calculated by comparing the current level of TFA intake to a counterfactual setting where consumption was lowered to a theoretical minimum distribution with a mean of 0.5% energy per day (corresponding to TFA intake only from nonindustrial sources, e.g., dairy foods). Policy costs, avoided IHD events and deaths, health-adjusted life years (HALYs) gained, and changes in IHD-related healthcare costs saved were estimated over 10 years and lifetime of the adult Australian population. Cost-effectiveness was assessed by calculation of incremental cost-effectiveness ratios (ICERs) using net policy cost and HALYs gained. Health benefits and healthcare cost changes were also assessed in subgroups based on socioeconomic status, defined by Socio-Economic Indexes for Areas (SEIFA) quintile, and remoteness. Compared to a base case of no ban and current TFA intakes, elimination of iTFA was estimated to prevent 2,294 (95% uncertainty interval [UI]: 1,765; 2,851) IHD deaths and 9,931 (95% UI: 8,429; 11,532) IHD events over the first 10 years. The greatest health benefits were accrued to the most socioeconomically disadvantaged quintiles and among Australians living outside of major cities. The intervention was estimated to be cost saving (net cost <0 AUD) or cost-effective (i.e., ICER < AUD 169,361/HALY) regardless of the time horizon, with ICERs of 1,073 (95% UI: dominant; 3,503) and 1,956 (95% UI: 1,010; 2,750) AUD/HALY over 10 years and lifetime, respectively. Findings were robust across several sensitivity analyses. Key limitations of the study include the lack of recent data of TFA intake and the small sample sizes used to estimate intakes in subgroups. As with all simulation models, our study does not prove that a ban of iTFA will prevent IHD, rather, it provides the best quantitative estimates and corresponding uncertainty of a potential effect in the absence of stronger direct evidence.CONCLUSIONS: Our model estimates that a ban of iTFAs could avert substantial numbers of IHD events and deaths in Australia and would likely be a highly cost-effective strategy to reduce social-economic and urban-rural inequalities in health. These findings suggest that elimination of iTFA can cost-effectively improve health and health equality even in countries with low iTFA intake.
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40.
  • Marklund, Matti, et al. (författare)
  • Estimated health benefits, costs and cost-effectiveness of eliminating industrial trans-fatty acids in Nigeria : cost-effectiveness analysis
  • 2024
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Nigeria is committed to reducing industrial trans-fatty acids (iTFA) from the food supply, but the potential health gains, costs and cost-effectiveness are unknown.Methods: The effect on ischaemic heart disease (IHD) burden, costs and cost-effectiveness of a mandatory iTFA limit (≤2% of all fats) for foods in Nigeria were estimated using Markov cohort models. Data on demographics, IHD epidemiology and trans-fatty acid intake were derived from the 2019 Global Burden of Disease Study. Avoided IHD events and deaths; health-adjusted life years (HALYs) gained; and healthcare, policy implementation and net costs were estimated over 10 years and the population's lifetime. Incremental cost-effectiveness ratios using net costs and HALYs gained (both discounted at 3%) were used to assess cost-effectiveness.Results: Over the first 10 years, a mandatory iTFA limit (assumed to eliminate iTFA intake) was estimated to prevent 9996 (95% uncertainty interval: 8870 to 11 118) IHD deaths and 66 569 (58 862 to 74 083) IHD events, and to save US$90 million (78 to 102) in healthcare costs. The corresponding lifetime estimates were 259 934 (228 736 to 290 191), 479 308 (95% UI 420 472 to 538 177) and 518 (450 to 587). Policy implementation costs were estimated at US$17 million (11 to 23) over the first 10 years, and US$26 million USD (19 to 33) over the population's lifetime. The intervention was estimated to be cost-saving, and findings were robust across several deterministic sensitivity analyses.Conclusion: Our findings support mandating a limit of iTFAs as a cost-saving strategy to reduce the IHD burden in Nigeria.
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41.
  • Marklund, Matti, et al. (författare)
  • Estimated population wide benefits and risks in China of lowering sodium through potassium enriched salt substitution : modelling study
  • 2020
  • Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 369
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To estimate the effects of nationwide replacement of discretionary salt (used at table or during cooking) with potassium enriched salt substitute on morbidity and death from cardiovascular disease in China.DESIGN: Modelling study.SETTING: China.POPULATION: Adult population in China, and specifically individuals with chronic kidney disease (about 17 million people).INTERVENTIONS: Comparative risk assessment models were used to estimate the effects of a nationwide intervention to replace discretionary dietary salt with potassium enriched salt substitutes (20-30% potassium chloride). The models incorporated existing data and corresponding uncertainties from randomised trials, the China National Survey of Chronic Kidney Disease, the Global Burden of Disease Study, and the Chronic Kidney Disease Prognosis Consortium.MAIN OUTCOME MEASURES: Averted deaths from cardiovascular disease, non-fatal events, and disability adjusted life years from a reduction in blood pressure were estimated after implementation of potassium enriched salt substitution. In individuals with chronic kidney disease, additional deaths from cardiovascular disease related to hyperkalaemia from increased intake of potassium were calculated. The net effects on deaths from cardiovascular disease were estimated as the difference and ratio of averted and additional deaths from cardiovascular disease.RESULTS: Nationwide implementation of potassium enriched salt substitution could prevent about 461 000 (95% uncertainty interval 196 339 to 704 438) deaths annually from cardiovascular disease, corresponding to 11.0% (4.7% to 16.8%) of annual deaths from cardiovascular disease in China; 743 000 (305 803 to 1 273 098) non-fatal cardiovascular events annually; and 7.9 (3.3 to 12.9) million disability adjusted life years related to cardiovascular disease annually. The intervention could potentially produce an estimated 11 000 (6422 to 16 562) additional deaths related to hyperkalaemia in individuals with chronic kidney disease. The net effect would be about 450 000 (183 699 to 697 084) fewer deaths annually from cardiovascular disease in the overall population and 21 000 (1928 to 42 926) fewer deaths in individuals with chronic kidney disease. In deterministic sensitivity analyses, with changes to key model inputs and assumptions, net benefits were consistent in the total population and in individuals with chronic kidney disease, with averted deaths outweighing additional deaths.CONCLUSIONS: Nationwide potassium enriched salt substitution in China was estimated to result in a substantial net benefit, preventing around one in nine deaths from cardiovascular disease overall. Taking account of the risks of hyperkalaemia, a substantial net benefit was also estimated for individuals with chronic kidney disease.
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42.
  • Marklund, Matti, et al. (författare)
  • Hypertension treatment capacity in India by increased workforce, greater task-sharing, and extended prescription period : a modelling study
  • 2023
  • Ingår i: The Lancet Regional Health - Southeast Asia. - : Elsevier. - 2772-3682. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The worldwide control rate for hypertension is dismal. An inadequate number of physicians to treat patients with hypertension is one key obstacle. Innovative health system approaches such as delegation of basic tasks to non-physician health workers (task-sharing) might alleviate this problem. Massive scale up of population-wide hypertension management is especially important for low-and middle-income countries such as India. Methods Using constrained optimization models, we estimated the hypertension treatment capacity and salary costs of staff involved in hypertension care within the public health system of India and simulated the potential effects of (1) an increased workforce, (2) greater task-sharing among health workers, and (3) extended average prescription periods that reduce treatment visit frequency (e.g., quarterly instead of monthly).Findings Currently, only an estimated 8% (95% uncertainty interval 7%-10%) of -245 million adults with hypertension can be treated by physician-led services in the Indian public health system (assuming the current number of health workers, no greater task-sharing, and monthly visits for prescriptions). Without task-sharing and with continued monthly visits for prescriptions, the least costly workforce expansion to treat 70% of adults with hypertension would require -1.6 (1.0-2.5) million additional staff (all non-physicians), with -INR 200 billion (approximate to USD 2.7 billion) in additional annual salary costs. Implementing task-sharing among health workers (without increasing the overall time on hypertension care) or allowing a 3-month prescription period was estimated to allow the current workforce to treat -25% of patients. Joint implementation of task-sharing and a longer prescription period could treat -70% of patients with hypertension in India.Interpretation The combination of greater task-sharing and extended prescription periods could substantially increase the hypertension treatment capacity in India without any expansion of the current workforce in the public health system. By contrast, workforce expansion alone would require considerable, additional human and financial resources.
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43.
  • Mehanna, Hisham, et al. (författare)
  • Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC) : a multicentre, multinational, individual patient data analysis
  • 2023
  • Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:3, s. 239-251
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: p16(INK4a) (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications.Methods: In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors.Findings: Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74middot7%) of 7654 patients were male and 1940 (25middot3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10middot9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=-0middot744, p=0middot0035). The proportion of patients with p16+/HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29middot7% vs 9middot0%, p<0middot0001). 5-year overall survival was 81middot1% (95% CI 79middot5-82middot7) for p16+/HPV+, 40middot4% (38middot6-42middot4) for p16-/HPV-, 53middot2% (46middot6-60middot8) for p16-/HPV+, and 54middot7% (49middot2-60middot9) for p16+/HPV-. 5-year disease-free survival was 84middot3% (95% CI 82middot9-85middot7) for p16+/HPV+, 60middot8% (58middot8-62middot9) for p16-/HPV-; 71middot1% (64middot7-78middot2) for p16-/HPV+, and 67middot9% (62middot5-73middot7) for p16+/HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort.Interpretation: Patients with discordant oropharyngeal cancer (p16-/HPV+ or p16+/HPV-) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16-/HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions.
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44.
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45.
  • Moran, Andrew E, et al. (författare)
  • Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries.
  • 2022
  • Ingår i: Revista panamericana de salud pùblica. - 1020-4989 .- 1680-5348. ; 46, s. e140-
  • Tidskriftsartikel (refereegranskat)abstract
    • Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in low- and middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$ 18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average
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46.
  • Ong, Kwok Leung, et al. (författare)
  • Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease : pooled analysis of 19 cohorts
  • 2023
  • Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 380
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived a linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).DESIGN: Pooled analysis.DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis.MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/ min/1.73 m(2). In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m(2) and <75% of baseline rate.RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I-2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I-2=0.0%). Plant derived a linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I-2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (=60 v <60 years), estimated glomerular filtration rate (60-89 v =90 mL/min/1.73 m(2)), hypertension, diabetes, and coronary heart disease at baseline.CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.
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47.
  • Qian, Frank, et al. (författare)
  • Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation
  • 2023
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 82:4, s. 336-349
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial.OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosa-pentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF.METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and sub-groups. Associations were pooled using inverse-variance weighted meta-analysis.RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively.CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.
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48.
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49.
  • Scharf, Lydia, et al. (författare)
  • Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen specific clones.
  • 2023
  • Ingår i: JCI insight. - : American Society for Clinical Investigation. - 2379-3708. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from severe COVID-19 patients every third to seventh day during hospitalization and every third month after recovery. We profiled the antigen-specific immune cell dynamics by combining single cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE)-Seq, B cell receptor (BCR)-Seq with oligo-tagged antigen baits. While the proportion of Spike Receptor Binding Domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen specific cells, which was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to one year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen specific B cell responses in longitudinally sampled COVID-19 infected patients.
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50.
  • Trieu, Kathy, et al. (författare)
  • Estimated Dietary and Health Impact of the World Health Organization's Global Sodium Benchmarks on Packaged Foods in Australia : a Modeling Study.
  • 2023
  • Ingår i: Hypertension. - 0194-911X .- 1524-4563.
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In 2021, the World Health Organization (WHO) set sodium benchmarks for packaged foods to guide countries in setting feasible and effective sodium reformulation programs. We modeled the dietary and health impact of full compliance with the WHO's sodium benchmarks in Australia and compared it to the potential impact of Australia's 2020 sodium reformulation targets.METHODS: We used nationally representative data on food and sodium intake, sodium levels in packaged foods, and food sales volume to estimate sodium intake pre- and post-implementation of the WHO and Australia's sodium benchmarks for 24 age-sex groups. Using comparative risk assessment models, we then estimated the potential deaths, incidence, and disability-adjusted life years averted from cardiovascular disease, chronic kidney disease, and stomach cancer based on the reductions in sodium intake.RESULTS: Compliance with the WHO's sodium benchmarks for packaged foods in Australia could lower mean adult sodium intake by 404 mg/day, corresponding to a 12% reduction. This could prevent about 1770 deaths/year (95% uncertainty interval 1168-2587), corresponding to 3% of all cardiovascular disease, chronic kidney disease, and stomach cancer deaths in Australia, and prevent some 6900 (4603-9513) new cases, and 25 700 (17 655-35 796) disability-adjusted life years/year. Compared with Australian targets, the WHO benchmarks will avert around 3 and a half times more deaths each year (1770 versus 510).CONCLUSIONS: Substantially greater health impact could be achieved if the Australian government strengthened its current sodium reformulation program by adopting WHO's more stringent and comprehensive sodium benchmarks.
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